Open Collections

UBC Theses and Dissertations

UBC Theses Logo

UBC Theses and Dissertations

The effect of intermittent hyperbaric oxygen on short term recovery from grade II medial collateral ligament… Soolsma, Serge Jurgen 1996

Your browser doesn't seem to have a PDF viewer, please download the PDF to view this item.

Item Metadata


831-ubc_1996-0490.pdf [ 5.8MB ]
JSON: 831-1.0077081.json
JSON-LD: 831-1.0077081-ld.json
RDF/XML (Pretty): 831-1.0077081-rdf.xml
RDF/JSON: 831-1.0077081-rdf.json
Turtle: 831-1.0077081-turtle.txt
N-Triples: 831-1.0077081-rdf-ntriples.txt
Original Record: 831-1.0077081-source.json
Full Text

Full Text

THE EFFECT OF INTERMITTENT H Y P E R B A R I C O X Y G E N O N SHORT T E R M R E C O V E R Y F R O M G R A D E II M E D I A L C O L L A T E R A L L I G A M E N T INJURIES, by SERGE J U R G E N SOOLSMA B.Sc., Simon Fraser University, 1988  A THESIS SUBMITTED I N P A R T I A L F U L F I L L M E N T OF THE REQUIREMENTS FOR THE D E G R E E OF M A S T E R OF SCIENCE  in THE F A C U L T Y OF G R A D U A T E STUDIES School of Human Kinetics We accept this thesis as conforming to the required standard  THE UNIVERSITY OF BRITISH C O L U M B I A August 1996 © Serge Jurgen Soolsma, 1996  In presenting this thesis in partial fulfilment of the  requirements  for an advanced  degree at the University of British Columbia, I agree that the Library shall make it freely available for reference and study. I further agree that permission for extensive copying of this thesis for scholarly purposes may be granted by the head of my department  or  by his or  her  representatives.  It  is understood  that  copying or  publication of this thesis for financial gain shall not be allowed without my written permission.  Department of j~jQflnAfJ  fafSffTtf^  The University of British Columbia Vancouver, Canada  •ate  DE-6 (2/88)  boQi/ST 7% I  G  ABSTRACT Objective: To examine the hypothesis that intermittent exposure to hyperbaric oxygen (HBO) will increase the rate of recovery from a grade II medial collateral complex injury.  Design: A double blinded controlled study of a treatment group and control group of patients who experience an initial clinical assessment, a magnetic resonance imaging scan of the knee (MRI), two weeks of either H B O or sham treatment, a second M R I post-treatment and six weekly follow up visits after the injury.  Setting: Allan McGavin Sports Medicine Clinic, University of British Columbia, Vancouver, B C , Canada.  Patients: Nineteen patients entered; 14 completed the clinical assessment portion, 9 of the fourteen completed pre and post treatment MRIs.  Interventions: Treatment group: ten H B O treatments consisted of 2 atmospheres absolute (ATA) for one hour with 100% oxygen (0 ) in ten out of fourteen days in 2  the first two weeks of recovery. Control group: ten H B O treatments consisted of  ii  1.2 A T A with air for one hour in ten out of fourteen days in the first two weeks of recovery  Main Outcome Measures: M R I pre-post treatment volumetric analysis; weekly assessments and comparisons of the injured and uninjured knee of: 1) a subjective questionnaire, 2) pain, 3) thigh girth, 4) knee girth, 5) range of motion, 6) maximum flexion, 7) one legged jump test. During the last three weeks a comparison of times straight running to a figure of eight course was made.  Results: Significant findings were found during the treatment period (thefirsttwo weeks) specifically. A more rapid decrease in the volume of edema in patients treatment with H B O as measured by M R I was observed. Patients treated with H B O also experienced less muscle wasting, greater range of motion and maximum flexion improvements. Comparisons of the running tests suggest a greater mobility during the 4th, 5th and 6th week of recovery.  Analysis of variables measured  throughout all the trials did not show any significance. Length of the study may have contributed to their insignificance.  Conclusions: Early intervention with H B O after a sports injury may be beneficial in increasing the rate of recovery. Possible mechanisms are discussed.  T A B L E OF CONTENTS Abstract  ii  Table of Contents  iv  List of Tables  vii  List of Figures  ix  Acknowledgement  x  INTRODUCTION  1  LITERATURE REVIEW  3  Hyperbaric Oxygen and Tissue Injuries  3  Theories for Increased Rate of Recovery  14  Inflammation  16  Edematous Changes  18  Enhanced Collagen Metabolism  20  Neovascularization  21  Medial Collateral Ligament Complex and Injury  23  Knee Rating Systems  26  Visual Analog Scales  28  Objective Functional Knee Tests  30  Magnetic Resonance Imaging  30  R A T I O N A L E FOR S T U D Y  33  iv  METHODOLOGY  34  Subjects  34  Procedures  34  Statistical Analysis  39  Statistical Power  40  HYPOTHESES  41  RESULTS  42  Subjects  42  Analysis of the Subjective Recovery Questionnaire(LS),  45  Pain (VAS), Knee Girth Difference (KG), Range of Motion Difference (ROM), Maximum Flexion Difference (MF), and One Legged Jump Test Difference (OLJ) for trials 1-7 Analysis of the LS, Pain, K G , R O M , M F , and OLJ for trials 1-3  46  Individual Variables  49  Subject Recovery Questionnaire  49  Pain  52  Knee Girth Difference  54  Thigh Girth Difference  56  Range of Motion Difference  59  Maximum Flexion Difference  62  One Legged Jump Test Difference  65  Running Test Ratio  67  Pre-post M R I Difference  69  DISCUSSION  70  Significant Findings  72  Magnetic Resonance Imaging (MRI) determined Edema Difference  72  Thigh Girth Difference  74  Range of Motion and Maximum Flexion Differences  75  Running Test Ratios  76  Non-significant Findings  77  Subjective Questionnaire  77  Pain  79  Knee Girth Difference  81  One Legged Jump Test  82  Comparison of Findings  83  Human Trials  84  Animal Studies  86  Practical Applications of Findings  87  LIMITATIONS OF THE STUDY  89  CONCLUSION AND FURTHER RECOMMENDATIONS  90  REFERENCES  92  APPENDICES A: Timeline for Protocol  110  B: Subject Questionnaire  111  C: Reliability Data  112  vi  LIST OF T A B L E S Table 1  Changes to arterial blood oxygen levels at various pressures and gas mixtures.  8  Table 2a  Anthropometric data.  44  Table 2b  Subject Data.  44  Table 3  Week 0-6 repeated measures multiple analysis of variance ( R M M A N O V A ) for the variables of L S , V A S , TG, K G , R O M , MF. (Trials 1-7)  46  Table 4  Week 0-2 R M M A N O V A for the variables of L S , 47 V A S , TG, K G , R O M , MF. (Trials 1-3)  Table 5  Epsilon Values for the R M M A N O V A calculations.  Table 6  Week 0-2 Follow-up repeated measures analysis of 48 variance ( R M A N O V A ) for Group by Time Interaction.  Table 7  Subjective recovery questionnaire scores at initial assessment and the following six weeks during recovery.  50  Table 8  Pain score (cm.) at initial assessment and the following six weeks during recovery.  52  Table 9  Knee girth difference at initial assessment and the following six weeks during recovery.  54  Table 10  Thigh girth difference (cm.) at initial assessment and the following six weeks during recovery.  57  Table 11  Range of motion difference (deg.) at initial assessment and the following six weeks during recovery.  60  vii  48  Table 12  Maximum flexion difference (deg.) at initial assessment and the following six weeks during recovery.  63  Table 13  One legged jump test difference scores (cm.) during the following six weeks of recovery.  65  Table 14  Running test ratios during weeks 4, 5 and 6 of recovery.  67  Table 15  Edema difference scores (ml.) obtained from MRI.  69  Table 16  Summary of Statistical Findings.  70  Table 17  Summary of pearson product moment correlations  113  for test/retest conditions. Table 18  Variable Measurements for test/retest correlations  viii  114  LIST OF FIGURES Figure 1  Subjective recovery questionnaire versus trials.  51  Figure 2  Pain versus trials.  53  Figure 3  Knee girth difference versus trials  55  Figure 4  Thigh girth difference versus trials.  58  Figure 5  Range of motion difference versus trials.  61  Figure 6  Maximum flexion difference versus trials.  64  Figure 7  One legged jump test difference versus trials.  66  Figure 8  Running test ratio versus trials.  68  ix  ACKNOWLEDGMENT  Projects and accomplishments like this one can only be achieved through the support and encouragement of many individuals. I would like to thank all those who contributed and assisted me in this endeavour, specifically:  Dr. Douglas Clement My advisor, who helped develop, positively criticize, let me follow my ideas to fruition and left a lasting impression. My Committee Dr. Don McKenzie, Dr. Jack Taunton, Dr. Doug Connell, and Dr. Ross Davidson who made this thesis possible. My Parents Who each in their own unique way supported and believed in me. Natalie, Jamie, Marcia and Cheryl. Whose help allowed me to coordinate many of the activities throughout this study.  I N T R O D U C T I O N  Hyperbaric oxygen (HBO) has been utilized as a therapeutic modality for over one hundred years. Only in the last 15-20 years has H B O been recognized as a significant adjunct in the treatment of soft tissue wounds. It has been recognized during recovery that many of these injured tissues experience changes in their availability to oxygen secondary to the wound itself (Lavan and Hunt, 1990). Investigations have shown that wound metabolism and outcomes can be improved with the application of H B O by increasing the availability of oxygen at the wound site (Hunt, Niinikoski and Zederfeldt, 1977; Sadegani, Gottlief, Van Meter et al et al., 1989). This in turn improves wound healing (Uhl et al., 1994)  Increased participation in sport and leisure activity has led to an increased number of sports related injuries. H B O may provide another form of therapy to allow a speedier resumption of pre-injury activity and/or improve the short and long term prognosis of the injury. The application of H B O towards sports injuries was suggested nearly twenty years ago, (Oriani, Barmini et al., 1987) however, no direct studies had been performed. Administration of H B O had until recently been limited to large hospitals with multi-place chambers.  1  These units were large,  labour intensive and expensive to operate. With the development of monoplace H B O chambers, costs and time associated with treatment have decreased.  Although, H B O has shown dramatic effects in a variety of injuries, no conclusive benefits have been shown for sports injuries.  Professional athletic  teams currently rely solely on anecdotal evidence suggesting that utilization of H B O as an adjuvant therapy has a significant effect.  Recently, preliminary  research has been completed on the effects of H B O on sports related injuries. However, the outcomes have been questioned due to the limitations of the experimental designs. It became evident that a study which evaluates H B O on a proven specific sports injury utilizing a double blinded study protocol was needed.  2  LITERATURE REVIEW  Hyperbaric Oxygen and Tissue Injuries Hyperbaric oxygen (HBO) therapy is the administration of 100% oxygen at a pressure greater than one atmosphere absolute (ATA).  Initial study of the  therapeutic effects of this pressure therapy were first seen in the study of diving medicine. Currently, H B O therapy is used in difficult to treat infections, wounds and fractures. These difficult to treat injuries include crush injuries, compartment syndromes, traumatic ischemias, refractory wound healing, exceptional blood loss, necrotizing soft  tissue infections,  osteomyelitis,  radiation  tissue damage,  compromised skin grafts and flaps, and thermal burns (Jain, 1990).  Injury to soft tissues is accompanied by an associated degree of hypoxia (Hunt, Niinikoski, Zederfeldt et al., 1977; Hunt, Zederfeldt, and Goldstitch, 1969; Sheffield, 1985). After tissue injury, there is a influx of fibrin and platelets to the injured area.  Accompanying these events, like in burns, is an increase in  extracellular fluid caused by biochemical mediators and vascular dilation in the area of insult (Hunt, Zederfeldt and Goldstitch, 1969, Niinikoski, 1977). This response is immediately followed by an influx of cells to remove injured cells and  3  reconstruct the wound including neutrophils, macrophages, fibroblasts, smooth muscle cells, and endothelial cells (Lavan and Hunt, 1990).  Lactic acid  production, hypoxia and the production of cytokines after this influx stimulate angiogenesis and the production of collagen (Knighton, Hunt, Scheuenstuhl, et al., 1983, Lavan and Hunt, 1990).  With the maturation of new cells normally  associated with the injured area, the wound is considered healed.  Oxygen plays a critical role in wound healing (Hunt, Niinikoski, Zederfeldt et al, 1977; Pal and Hunt, 1972; Kivisaari and Niinikoski, 1975; Niinikoski, 1977; Niinikoski, Grislis, and Hunt, 1972).  Knighton et al. (1990) has shown that  oxygen plays a prominent role in bacterial clearance and host defense. Oxygen mediates the activity of fibroblasts (Anderson, Watson, Herring and Mehm, 1992; Criswell and Mehm, 1992a; Criswell and Mehm, 1992b; Storch and Talley, 1988). It is also required for the hydroxylation of proline and lysine, a precursory step in the synthesis of collagen (Hunt, Niinikoski, Zederfeldt et al, 1977; Juva, 1968; Pal and Hunt, 1972). It is noteworthy that the synthesis of collagen is stimulated by physiological levels of hypoxia (Pal and Hunt, 1972; Hunt, Zederfeldt and Goldstitch, 1969; Lavan and Hunt, 1970).  Explanations of this phenomenon  include the accompanying increase in lactate at these physiological levels of hypoxia (Kivisaari and Niinikoski, 1975; Knighton, Hunt Scheuenstuhl et al,  4  1983). Collagen that has been formed at lower than normal physiological oxygen levels differs from those produced at normoxic or superoxic levels (Metzler and Myers, 1986). Fibers developed in a hypoxic environment have a lower tensile strength. Raising the oxygen tension in tissues, increases the ratio of ribonucleic acids to deoxyribonucleic acids (RNA/DNA) long term (Penttinen, Niinikoski, and Kulonen, 1972).  The change in this ratio indicates increased formation of the  rough endoplasmic reticulum by the cells of the wounded area and a higher degree of cellular differentiation (Mehm, Pimsler, Becker et al, 1988). In an early study by Pal and Hunt (1972), an increase of 150% above the normal physiological range for oxygen ( P O 2 = 40 mmHg) increased the rate of collagen production by seven times. More recent work by Sadigani, Gottief, Van Meter et al, (1989) and Uhl et al, (1994) have more clearly demonstrated HBO's benefits in surgical wound healing.  The objective in hyperbaric oxygen therapy is to increase the amount of available oxygen to tissue that is experiencing hypoxic or anoxic conditions. Increased availability is achieved by two methods. The first is by increasing the oxygen dissolved in plasma. By increasing the partial pressure of oxygen in the available air, a significant amount of oxygen becomes dissolved in blood plasma (0.03 to 4.2 vol. %) (Bird and Telfer, 1965; Hunt, Zederfeldt and Goldstitch,  5  1969, Jain, 1990).  The second is the complete saturation of hemoglobin by  shifting the oxygen dissociation curve. The benefits of this are however minimal. At 2 A T A and 100% oxygen, the increase in dissolved oxygen is twelve fold while the increase in hemoglobin saturation is at most only 3% (see table 1.) (Jain, 1990). This increase in blood plasma oxygen steepens the gradient from blood to tissue and is sufficient to sustain homeostasis without dissociation of oxygen from hemoglobin (Jain, 1990). Increased plasma oxygen concentrations also improves the elasticity of the erythrocyte which improves blood perfusion in small capillaries (Jain, 1990). These facts are significant in situations where the microcirculation of an area is impaired and/or the distance the oxygen must travel across, from blood to tissue, is increased (i.e. by extracellular fluid, swelling.).  Another  effect  of  increased  plasma  oxygen  concentrations  is  vasoconstriction (Adameic, 1977; Basset and Bennett, 1977; Carnochan, Abbott, Spence et al, 1989, Nida et al, 1995; Nylander, Noordstrom, Eriksson, 1984; Nylander et al, 1987). Vasoconstriction leads to a decreased blood pressure and therefore aids reabsorption of the extracellular fluid into the circulation. Removal of the extra fluid decreases the distance oxygen must diffuse in order to act at the site of injury. Although, there is a decrease in blood flow to the affected area, the amount of oxygen dissolved in the blood plasma is sufficient to more than  6  adequately compensate for this decrease in blood flow (Carnochan, Abbott, Spence et al, 1989; Jain, 1990; Wells et al, 1977). See page 8, table 1: Changes to arterial blood oxygen levels at various pressures and gas mixtures.  Increased availability of oxygen has been shown to be significant at the cellular level (Carnochan, Abbott, Spence et al, 1989; Wells et al, 1977). Normal cellular function requires an oxygen tension of 30 mmHg in and around the cell (Sheffield, 1985). At the mitochondrial level, a minimum of 0.5-3.0 mmHg must be present for oxidative metabolism to occur (Sheffield, 1985). Many enzymes have been shown to lose their effectiveness at lower than normal partial pressures of oxygen (Hunt, Niinikoski, Zederfeldt et al, 1977; Pal and Hunt, 1972; Hunt, Zederfeldt and Goldstitch, 1979, Jain, 1990; Lavan and Hunt, 1990). As a result, it has been suggested that a P O 2 as high as 80 mmHg may need to be present in the circulatory system to achieve the optimal cellular activity (Pal and Hunt, 1972, Kivisaari and Niinikoski, 1975; Webster et al, 1996).  7  CN  S3 a 93 OX)  •o s «  •c  cu  t:  <  L.  S cn cn V i_  CQ  cn  ©  a 3  O  *C  a  a  es 3 > C8  O  o  S a es  s  o CA 9 O a  CU  1  "3D  -o o o  O O  in O  ON  u  o o  |  VO 0 O  S  O  in  ON  o o  ml/1  s  X) _©  ml/1  o o  cn  VO  vo m  in O  o  ON  O  o  ON  O O  o o VO  VO  o  x  O  O  in  ON  <-  1  o  x  O  O  m  ON  > — 1  o a cu  H  *Q  cu a  § o  cu  o o •a .2  ^ cu  € '59 cn Of) C  NH  8Q O  CA  cu  u  =5  </) CA CU iU  s H  0-  CA C3  O  o  5  o  5  o o  3  < CN  O o i-H  (N  < CN  o O O  < CO  O 0  S  CN  3  <  5  O  o  The effects of oxygen with respect to pressure and concentration exist on an inverted parabolic curve, being detrimental at the extremes and beneficial in only a narrow range. The detrimental effects are well documented and are only present at pressures greater than 2 atmospheres absolute (ATA) with 100% 0 for 2  extended periods of time (Clark and Fischer, 1977; Foster, 1992; Jain, 1990). The phenomenon has been termed oxygen toxicity.  Problems experienced with  prolonged H B O exposure include grand mal seizures, pulmonary edema, hepatic damage, renal damage, and fetal ocular changes (Clark and Fischer, 1977; Foster, 1992; Jain, 1990).  Those detrimental effects become significant at pressures  approaching 3 A T A and two hours of exposure (Clark and Fischer, 1977; Jain, 1990).  No clinical effects have been shown on healthy patients using 2 A T A and  120 minutes per treatment session. The currently suggested clinical protocol for non-life threatening injuries of 2 A T A and sixty minutes is within the therapeutic range (Jain, 1990; Peterson and Allen, 1995).  The effect of hyperbaric oxygen on thermal injuries to tissues was first documented in 1970's (Grossman, 1978; Hart, Greilly, Broussard et al, 1974; Korn, Wheeler and Miller, 1977; Niccole, Thornton, Danet et al, 1977). The authors noted that serous exudate diminished more rapidly, there were fewer infections and faster healing in patients exposed to HBO. More recent controlled  9  studies with burns have shown a 30% decrease in the healing time (Atroshenko, et al, 1983; Cianci, 1985; Cianci, Petrone, Shapiro et al., 1990a; Cianci and Sato, 1994; Hammarlund et al, 1992). Other studies have demonstrated increased rates of epithelialization, decreased fluid requirements, decreased conversions from partial to full thickness burns, decreased edema and inflammatory responses; a 48% decrease in grafting and surgical procedures, a 41% decrease in hospital time, and a 45% decrease in cost (Basset and Bennett, 1977, Cianci, 1985; Cianci, Petrone, Shapiro etal., 1990b; Niccole, Thornton, Danet et al., 1977; Niu, Chao, Lee et al, 1990; Stewart, Mason, Kemp et al, 1992; Waisbren et al, 1982). Nylander (1986) demonstrated a decrease in tissue edema, maintenance of phosphorylation metabolism, substrate levels and decreased lactate levels.  Investigations on effects of H B O on fracture healing have also had positive results. Early investigations in rats showed that increased oxygen fractions and H B O will accelerate healing in fractured femurs (Coulson et al, 1966; Makley, Helple, Chase and Herndon, 1967). Evidence leading to the conclusion that H B O speeds the recovery of fractures includes findings of increases in: osteoblastic D N A and RNA, callus formation, the callus nitrogen content, the capacity for protein synthesis, collagen formation, mineralization, osteoblastic activity, capillary budding, fibroblastic activity and proliferation, and osteogenesis (Hammarlund et  10  al,  1992; Hunt, Niinikoski, Zederfeldt et al,  1977, Malnous, 1982; Malnous,  1977; Zusman, 1986).  The benefits of H B O are not limited to boosting tissue repair.  Research  has shown alterations in the inflammatory response after an insult to tissue. Inflammation has shown to lead to hyperemia, edema and increase influx of Tlymphocytes and macrophages (Beck et al,  1986; Gibbs et al,  1984).  Inflammation studies using tuberculin reaction on human skin indicate that oxygen consumption of infiltrating cells may be regulated by oxygen (Harrison et al, 1994).  Administration of H B O has demonstrated increases in overall tissue  oxygen consumption (Silver, 1978). In a study by Abbott et al. (1994), H B O was shown to counteract decreases in tissue P O 2 and increases in P C O 2 associated with inflammation.  The edema in tissues accompanying an injury and inflammation can exacerbate the effect of hypoxia or may make a normoxic situation hypoxic because of the increased distance the oxygen must diffuse. A significant amount of research has been done with post-ischemic muscle.  Post-ischemic muscles  produce a large amount of extra cellular fluid and studies indicate H B O will counter its production (Hill, 1993; Jain, 1990; Nylander, Noordstrom, Franzen et  11  al, 1988; Nylander etal, 1987; Sirsjo etal, 1993). Improved tissue oxygenation in situations where such edematous fluid limits the diffusion of oxygen has been demonstrated with H B O therapy (Atroshenko, 1983; Basset and Bennett, 1977; Nylander, Noordstrom and Ericksson, 1984; Skyhar, Hargens, Strauss, et al, 1986).  Monitoring of tissue perfusion using laser doppler confirms increased blood flow in vessels during and after H B O treatment (Zamboni et al, 1992). Patients with a pre-existing vascular disease have been shown to benefit from H B O (MonisChass et al, 1977).  These people are very susceptible to ischemia in their  periphery and risk possible loss o f limb secondary to infection causing gas gangrene. Using H B O in combination with other therapies has shown a significant decrease in the number of limbs lost.  The success of H B O therapy in various injuries lead to consideration in injuries suffered in sport (Oriani, Barmini et al, 1987). Initial studies in Scotland, demonstrating an accelerated recovery from sports injury have prompted further investigation (James, Scott and Allen, 1993).  12  Using a Glasgow soccer team, an extensive study was completed. Researchers estimated the time to recovery of various injuries sustained during practice and match play by players from their previous experience. These players were then subjected to repeated sessions of hyperbaric oxygen therapy. The overall results were a reduction in the predicted time of recovery of 62.7% (James, Scott and Allen, 1993). Although carefully performed, this study was very subjective in nature with only a few of the controls necessary to consider this as a validation. Also, no standardized injury was compared. Controls are required for time between injury and first treatment and severity of the injury.  Subjects and  researchers need to be blinded and research needs to be limited to a single uniform injury.  A follow up study was attempted at Temple University.  Researchers  narrowed the type of injury to ankles. The time to recovery was estimated for subjects in the treated and untreated groups. No significant differences were found between treated and untreated subjects. During a discussion, researchers admitted that variability in the types of ankle injuries treated  and the inability to blind  subjects  communication,  may  have  limited  findings  unpublished).  13  (Personal  findings  Recently, completion of a human delayed onset soreness study at the University of British Columbia has yielded significant results. The study used an eccentric model muscle injury and determined that there may be some benefit in the recovery of strength gained from the intermittent application of H B O after the injury. (Staples, 1996) A surgically lacerated ligament study with rats also yielded positive results, however study results have not yet been published (Webster et al, 1996).  Theories for Increased Rate of Recovery  Wound repair follows a pattern of inflammation, angiogenesis, fibroplasia and matrix deposition and maturation as well as epithelialization if it involves the epidermis (Lavan and Hunt, 1990). Inflammation is largely due to the infiltration of leukocytes and the creation of free radicals for clearance of bacteria and necrotic tissue (Zamboni et al., 1992, Zamboni et al, 1993). The accumulation of leukocytes to a injured area is a double edged sword. The phagocytotic processes of clearing bacteria and tissue debris also place a great strain on the oxygen supply in the local area. The oxygen debt experienced in the centre of the wound leads to the initiation of angiogenesis and collagen synthesis (Lavan and Hunt, 1990; Knighton et al, 1993). This is exacerbated by the influx of edema into the area of the insult.  14  Wells and co-workers (1977) suggested that it takes approximately thirty minutes for PO2 to plateau in muscle tissue and remain so for only thirty minutes after treatment.  These times may be longer in tissues which are not as heavily  perfused such as ligaments. It is during this time that H B O would appear to have an effect on the physiological systems of the body.  However, Thorn (1990)  demonstrated that changes in neutrophil adherence last 8-12 hours after H B O treatment.  It is therefore possible that the increases in oxygen may have longer  duration effects on these physiologic processes greater than the time of elevated P0 . 2  Assuming that the changes caused by the alterations in PO2 are not significantly longer in duration, timely application of H B O would be important. It would suggest that the benefit of H B O is greater in the initial post injury period. This idea is supported by research in burn, reperfusion, crush, spinal cord, and eccentric model muscle injuries which suggest that treatment should commence in the first 8 hours. However, results from this author's study do not agree with that conclusion, supporting ideas put forth by Peterson and Allen (1995) indicating that H B O treatment is multi-faceted in its benefits.  15  In the opinion of this author, the rationale for any positive findings will be related with four possible effects of H B O 1) the limitation of any inflammation, 2) more rapid reabsorption in edema, 3) enhanced neovascularization, 4) the enhancement of collagen matrix rebuilding and restructuring.  It is hypothesized  that changes to enzyme kinetics related to these reactions is largely responsible but are not clearly identifiable in this study.  Inflammation Inflammation at the site of injury is largely dependent on the amount of activated neutrophils and factors that they release. It is these neutrophils that localize to the injury site through the circulatory system then marginate and adhere to the vessel walls of the area (Zamboni et al, 1993). The effect of altering the adherence properties of these neutrophils is the proposed mechanism by which H B O may alter the inflammatory response (Zamboni et al, 1993). Inhibition of the leukocyte adherence factor (CD 18) limits the cascading inflammatory response and thus any excessive damage. This would largely account for or explain the success achieved by earlier research in muscle physiology (Staples, 1996).  Eliminating the normal neutrophilic response would not allow for normal cleansing and reparative processes to occur. Had H B O eliminated the response,  16  no healing or persistent infection may have occurred. It has been shown H B O prevents excess but not all neutrophils from becoming involved in the injury reaction (Zamboni et al, 1994). This idea was supported by studies completed at U B C in 1996 which showed that myeloperoxidase activity, largely associated with neutrophil presence, for H B O treated rats after muscle damage was halved but not eliminated (Staples, Clement, McKenzie et al., 1996).  Thorn (1990) suggested that oxidative damage via free radical formation may be another cause of the detrimental effects from inflammation. Free radicals such as superoxide (SO2), hydroxyl (OH"), peroxide (H 0 ") and perferryl (Fe") 2  2  can lead to many oxidative-reduction type reactions which can lead to damage of cellular tissue or interfere with cellular metabolism. A n example of this is the oxidation of sulfhydryl groups of the ATPase pump paralleled decreases in calcium ion uptake (Thorn and Elbuken, 1991). Free radicals are largely a result of the activated neutrophils (Jain, 1990). This process was suggested as the prime cause in the model eccentric muscle injury (Staples, 1996).  Studies in skin flaps and  post ischemic muscle reperfusion injury indicate that H B O has indirectly been shown to limit free radical damage (Stewart et al, 1994). This finding led to the theory that hyperoxic environments may prime free radical scavengers systems to more rapidly eliminate any free radicals exposed to a system.  17  Hyperbaric oxygen as a scavenger of free radicals at first appears to be contradictory. Studies have shown that the superoxide dismutase is increased in response to intermittent exposure to H B O (Kaelin et al, 1990). Thom and Elbkin (1991) and Haapaniemi (1995) demonstrated H B O produces alterations favouring less damaging free radical pathways and increases in endogenous antioxidants. There remains a question of how long this inflammatory response actually lasts. Smaller scale inflammatory responses caused by movement during recovery may occur. H B O may have a moderating effect on these as well. Decreases in edema observed in this study infer that H B O does exert some effect on the inflammatory processes. These findings are further supported by anecdotal evidence witnessed with use in professional sports. Although, alterations in the inflammatory response mechanism may play a part in the increased rate of recovery of the subjects used in this study, it might only be small one. The inflammatory process occurs primarily in the first 48 hours after injury or insult.  Edematous Changes An increase in edema is a natural result of inflammation. It is due to vasodilation, changes in the structure of the vascular walls from injury and infiltration of leukocytes as well as changes in the osmolarity. H B O has been shown to decrease the amount of edema following experimental injuries in a  18  number of animal studies. Studies by Bird and Telfer (1965) in humans showed decreases in limb circulation of approximately 20% observed when H B O was applied. Research has shown decreases in edematous volumes following a variety of injuries (Jain, 1990). Skyhar et al. (1986) showed that H B O reduces edema in skeletal  muscles  involved  with  compartment  syndromes  associated  with  hemorrhagic hypotension in dogs. Nylander et al. has demonstrated a reduction in post-ischemic edema in rats and dogs.  The effects of decreased edema are accomplished by a direct action of the increased partial pressure of oxygen on the local vasculature. This increase leads to a vasoconstriction resulting in a decrease in blood flow to the area. The decrease in blood flow to the area is at first intuitively undesirable. However, a fifteen fold increase in the oxygen content of the blood at 2.0 A T A breathing oxygen more than adequately compensates.  Vasoconstriction leads to a reduced capillary  pressure and a shift in the transcappillary flow of fluid to promote greater reabsorption of fluid. The net effect is a maintained or positive increase in oxygen supply to the damaged tissues and a decrease in the interstitial fluid pressure.  19  Enhanced Collagen Metabolism Oxygen is necessary for the hydroxylation of the proline and lysine molecules in the growing collagen alpha chains (Juva, 1968). Juva (1968)  also  showed that an anoxic wound with a small oxygen gradient will cause fibroblasts to continue to form precursors to collagen but not release mature collagen. Other research indicates that collagen maturation (hydroxylation) and cross-linking increase almost linearly when ambient oxygen concentrations are  increased  (Sadegani et al, 1989; Pal and Hunt, 1972; Lavan and Hunt, 1990).  Therefore,  the rate of production of collagen increases as oxygen tensions in and about the wound increase.  The strongest support for improved collagen synthesis comes from in vitro fibroblast cell proliferation and collagen biosynthesis studies. Mehm et al. (1988) treated mouse fibroblast cell cultures to one of six different partial pressures of oxygen for one to four days. Fibroblast cultures were assessed daily. It reported that fibroblast growth and collagen biosynthesis are maximal at oxygen levels twice that of normal.  The study concluded that treatment need be in the range of 80  mmHg P O 2 for maximal benefit.  Hunt et al, (1977) has shown that increased  oxygen tensions during rebuilding of tissues by the body are related to greater tensile tissue strength, total collagen deposition, total protein and total D N A .  20  This increase in fibroblastic activity and collagen synthesis is believed to account largely for the differences to be seen between the control and treatment groups in this study.  The increases in collagen content would account for a  stronger ligament and the ability to deal with the medial and lateral stresses about the knee when used in a maneuvering manner demonstrated in the figure of eight test.  Neovascularization The newly developed basic collagen matrix will support new developing blood vessels (Sheffield and Dunn, 1977; Lavan and Hunt, 1990).  Increased  vascularization will allow for a greater oxygen gradient. Although, it may not be possible to entirely counteract the hypoxic conditions near the center of the wound, an increased oxygen gradient in and about the area of the wound will accelerate the activity of the various processes allowing for a quicker repair (Hunt et al, 1977; Pal and Hunt, 1972; Kivisaari and Niinikoski, 1975; Lavan and Hunt, 1990). Intermittent HBO treatment leads to the phasic changes in P 0 required 2  for angiogenesis (Sheffield, 1988; Wells et al, 1977).  The wound site center because of the interruption of the local vasculature and influx of inflammatory cells, is hypoxic (Abbot et al, 1994). This hypoxic  21  environment leads macrophages to work in an anaerobic state producing lactate. Lactate stimulates fibroblasts to make collagen precursor molecules. Fibroblasts, however, will not release these precursors nor form the complex cross-linking structures necessary to form the alpha-helix strands without the presence of sufficient oxygen (Juva ,1968). Increased oxygen availability is accomplished by angiogenesis which is stimulated by the gradient that exists from the center of the wound out towards healthy normal tissues.  Knighton et al., (1983) has showed that angiogenesis is driven by an oxygen gradient. High arterial tensions drive the process, while when the center of the wound is oxygenated the process stops.  This has been attributed to an  angiogenesis factor being released by macrophages when exposed to hypoxic conditions or high concentrations of lactate  (Jensen, Hunt, Banda and  Scheuenstuhl, 1986). As new vasculature is formed and tissue P 0 levels rise, 2  formation and deposition of collagen occurs toward the center of the wound. With a possible increase in angiogenesis due to a greater diffusion gradient, the repair process can go on uninhibited instead of waiting until edema dissipates and greater availability of oxygen occurs.  22  Medial Collateral Ligament (MCL) Complex and Injury The medial collateral ligament complex is made of three structures.  The  medial collateral ligament, the patellar retinaculum and the posterior oblique ligament (Garvin, Munk and Vellet, 1993, Mirowitz and Shu, 1994; Ruiz and Erickson, 1994; Warren, Marshall and Girgis, 1974). The latter two structures are primarily used to stabilize the ligament throughout the knee's range of motion. The complex's primary function is to stabilize the knee medially but it also has been shown to resist anterior-posterior translation (Frank et al, 1994; Mirowitz and Shu, 1994; Ruiz and Erickson, 1994; Warren, Marshall and Girgis, 1974; Silver, 1978).  Some researchers suggest that it may provide some proprioceptive  feedback (Frank et al, 1994; Ruiz and Erickson, 1994).  The medial collateral  ligament consists of superficial and deep fibres (Ruiz and Erickson, 1994; Warren, Marshall and Girgis, 1974). Different portions of this medial collateral ligament exhibit different tensions throughout the normal range of motion of the knee (Cameron and Sandpan, 1994; Warren, Marshall and Girgis, 1974; Ruiz and Erikson, 1994).  Injury to the M C L complex occur primarily two ways: by the application of force medially at the knee when the foot is fixed or by a lateral application of force to the lower extremity when the foot is not fixed. Both mechanisms result in a  23  varus force being transmitted to the knee. M C L complex injuries occur in a wide variety of sports. A large number of M C L injuries are seen in contact sports such as football and rugby, as well as, skiing where forces about the knee can be increased due to the presence of equipment which increases the lever forces on the knee (Hohn, 1977; Marshall, Fetto and Botero, 1977). M C L injuries are divided clinically into three increasing degrees of injury, grade I, II and III. (Frank et al, 1983; Hughston et al, 1976; Marshall, Fetto, Botero, 1977) Grade I and II level injuries are associated with stretching and partial tears of the structures in the complex. Grade III is a complete full thickness tear and often is accompanied by associated injuries to other structures within the knee. Injury to the ligament also has a profound effect on the musculature around the knee (Young, Stokes and lies, 1987). The associated pain and edema leading to inhibition of extensor musculature and in turn reflex muscle wasting.  Clinical examination and diagnosis of M C L injuries are based on a careful assessment of history and physical testing of the integrity of the joint. Valgus stress tests are the primary method of testing the medial collateral ligament complex in the examining room. The degree of valgus instability provides indication of the severity of damage (Hughston et al, 1976).  24  Treatment of Grade I and II injuries to the M C L complex is non operative since there is an incomplete disruption of the medial knee structures and usually there are no other significant intra articular injuries (Woo et al, 1987). Grade III injuries are usually treated operatively because of complete tissue disruption and resultant instability and since there are often associated significant intra articular injuries. Conservative treatment regimes are governed by the following principles: 1) protect the injured part, 2) reduce the inflammation, 3) promote remodeling of healed tissue by application of adequate stress and strain at appropriate stages and 4) strengthen the muscles which support the joint to prevent re-injury (Hastings, 1980; Marshal, Fetto, Botero, 1977; Tegner, Lysholm, Lysholm and Oberg, 1984; Woo et al, 1987). Differences in the relative importance placed on the individual principles have led to varying regimes.  Ligament healing is similar to wound healing in that the process is basically one of initial inflammation followed by cell proliferation and subsequent scar remodeling and maturation (Frank et al, 1985; Frank et al, 1983; Loitz and Frank, 1987). Maturation of the scar may take from 24 to 40 weeks. At 3-6 weeks, the scar can withstand up to 50% of the original load (Frank et al, 1985; Frank et al, 1983; Kannus, 1988). Return to activity in a controlled manner and with some protection is often recommended at this point. Re-injury occurs at a higher rate  25  with previously injured ligaments for two reasons: 1) the scar has not fully matured and 2) even after it has fully matured the ligament can only sustain 70-80% of the force of the original uninjured ligament (Kannus, 1988).  Histological changes in healed mid-substance tears of the M C L have been analyzed in rabbits (Frank et al, 1994). The scar initially consists of inflammatory cells and fibroblasts, which clear debris and creating a new but disorganized collagen matrix (Frank et al, 1985; Frank et al, 1994; Loitz and Frank, 1987). With time, the matrix organization improves but does not equal that of a normal ligament (Frank et al, 1994; Loitz and Frank, 1987; Tegner and Lysholm, 1985). Decreases in collagen mass, concentration, types, turnover rate and cross-linkages are seen in healed ligaments (Frank et al, 1994; Tegner and Lysholm, 1985).  Knee Rating Systems Assessment of patients who have suffered ligamentous injuries to their knees has been the topic of much controversy. Many subjective rating systems have been developed to compare surgical procedures and rehabilitation programs (Tegner and Lyshlom, 1985; Zairns and Adams, 1988). The systems have been termed subjective because they measure perception of recovery by the doctor and/or patient instead of more objective measures. Most researchers have focused  26  on three subjective questionnaires for an injured or rehabilitating knee; the Marshall scale, the Lysholm scale and the Cincinnati scale (Bollen and Seedhom, 1991; Lysholm and Gillquist, 1982; Tegner, Lysholm, Lysholm and Oberg, 1984).  These systems are based on a quantitative assessment of a group of subjective and objective criteria having to do with pain, function, swelling and 'giving way'. The scales usually total 100 points with the individual criteria taking up varying percentages.  The Lysholm scale has shown to be equally effective in  comparison to the Marshall and Cincinnati scales in subjectively measuring patient knee function (Bollen and Seedhom, 1991; Tegner, Lysholm, Lysholm and Oberg, 1984). Results from these studies have shown that on average the Lysholm knee scoring scale produces higher scores than the Cincinnati and Marshall scales. Differences have been attributed to the latter two scales' insensitivity to medial/lateral injuries versus cruciate injuries and the over reliance of functional tests (Tegner et al, 1986; Fonseca et al, 1992). Many researchers and clinicians now recommend that objective functional testing should be separated from knee scoring scales (Bollen and Seedhom, 1991, Fonseca et al, 1992; Lysholm and Gillquist, 1982; Tegner, Lysholm, Lysholm and Oberg, 1984).  27  Visual Analog Scales The subjective nature of pain has limited any objective measurements used in attempting to quantify this sensation.  Without invasive techniques the only  measures available are that of the subject's perception.  Perception of similar  information has been shown to have high intra-subject variability (Miller and Ferris, 1993). Validation of pain scales has proven difficult due to the lack of a clearly objective comparison. Several rating scales for pain have been devised and tested (Carlsson, 1983; Downie et al, 1978; Huskisson, 1974; Huskisson, 1983, Price et al, 1983). These include a simple numerical rating scale and a five point descriptive scale, however, they have been often described as insensitive (Downie etal, 1978).  Currently one of the best measures for pain is the visual analog scale (Dixon and Bird, 1981; Langley and Shepperd, 1985; Price et al, 1983; Zusman, 1986). The scale consists of a line 10 cm long with marked endings indicating no pain and the worst ever experienced. This line may be horizontal or vertical with both having been shown to be highly correlated (r=0.99) (Scott and Huskisson, 1979). Subjects are asked to place a mark along this line and the distance from the no pain end is measured objectifying the sensation.  28  There is debate regarding the linearity of this test as well as the parametric versus non-parametric techniques used to analyze the data that it produces (Langley and Shepperd, 1985; Miller and Ferris, 1993; Zusman, 1986).  It has  been suggested that the assumption of linearity should hold if the explanation to the subject is that the scale represents a linear representation of pain (Zusman, 1986).  Clear definitions of the end of the scales assists in a subjects use of the  scale as well as improving its linearity. Vague terms such as 'worst pain ever' can vary greatly between subjects depending on experience and perception.  By  describing the ends of the scale as 'no pain' and the 'worst pain experienced with this injury or event' instead of 'no pain' and 'worst pain experienced ever', this ambiguity can be avoided.  Comparisons with other scales and tests, physicians assessments and experimental pain have shown correlations with other measurement systems of 0.60 or higher (Price et al, 1983; Zusman, 1986). Reliability testing has also been performed on visual analog scales.  Several studies have shown the test/re-test  correlation to be greater than 0.9 with some as high as 0.99 (Langley and Shepperd, 1985; Miller and Ferris, 1993; Price etal, 1993; Zusman, 1986).  29  Objective Functional Knee Tests Objective measures of patients recovering from ligamentous knee injuries have been discussed recently (Tegner and Lysholm, 1985; Tegner, Lysholm, Lysholm and Oberg, 1984). Several clinicians and researchers have used strength and performance specific tests as such measures often in combination with passive measures such as thigh girth, knee girth and range of motion. The importance of these measures however, may change through the rehabilitation process. Therefore, none of these should be relied on solely.  Determining when an athlete is ready to return to activity has always been difficult. Testing of recovery needs to be done in a controlled manner. Recent comparisons between figure of eight versus straight running, straight running alone, slalom circuit, hop test, stair climbing and slope running have shown straight running, figure of eight and hop tests to be useful in knee rehabilitation assessments (Fonseca et al, 1985; Tegner, Lysholm, Lysholm and Gillquist, 1986). The success is aided by their simplicity and ease to conduct.  Magnetic Resonance Imaging (MRI) New technology has allowed accurate visualization of structures within the body and has obviated the need for invasive procedures.  30  Magnetic resonance  imaging (MRI) has been used to assess soft tissue pathology since the 1970s. The accuracy of magnetic resonance imaging in knee assessment has been validated by comparative studies with arthroscopy as well as in outcome analysis studies (Gavin, Munk and Vellet, 1993; Kelly et al, 1991; Ruiz and Erikson, 1994; Rowe, Wright, Randall, Lynch, Jokl, and McCarthy, 1992; Schweitzer et al, 1995).  The limitations of non-invasive clinical knee examination are also well known. Magnetic resonance (MR) imaging allows an accurate determination of the anatomical abnormality undergoing treatment ensuring that similar injuries are randomized to treatment and excludes unexpected associated injuries which are not uncommon (Gavin, Munk and Vellet, 1993; Ruiz and Erikson, 1994; Schweitzer et al, 1995).  Investigations indicate M R I findings correlate highly with clinical findings (Gavin, Munk and Vellet, 1993).  There has been some discussion regarding  correlations with severity (Mirowitz and Shu, 1994; Schwietzer et al, 1995). M R imaging has shown that M C L tears may involve the patellar retinaculum and subsequent lateral femoral condyle and patellar bone bruising (Mirowitz and Shu, 1994; Quinn, Brown and Demlow, 1993; Schwietzer et al, 1995). Comparisons of various types of sequences suggest fat saturated T2-weighted images provide  31  the most conspicuous results (Mirowitz and Shu, 1994).  MRI is extremely  sensitive to soft tissue edema. Volumetric measurement of tissue and edema involved can be made allowing an objective measure of initial injury as well as response to treatment (Mirowitz and Shu, 1994).  32  RATIONALE FOR STUDY  The recent availability of a portable hyperbaric oxygen monoplace chamber provides an excellent opportunity to assess this form of treatment in combination with a standardized program of rehabilitation in a single clinical setting. Previous studies on HBO and sports injuries have not been adequately controlled and subjected to double blind evaluation. Only clinical assessment of injury has been undertaken in the past therefore researchers have not with certainty studied an uniform clinical injury. Previous studies have not utilized objective measures of outcome analysis (MRI) in addition to clinical assessment. This study should allow a more scientific and less biased assessment of HBO in sports injuries and should aid in establishing its eventual usefulness in treatment of such injuries.  33  METHODOLOGY  Subjects This study was conducted on patients referred to the Allan McGavin Sports Medicine Clinic at the University of British Columbia for grade II ligament injury of the medial ligament complex of the knee suffered during participation in a sport. Diagnosis was confirmed through clinical assessment and MRI.  Further  subject requirements for inclusion into the study were 1) the subject was between the age of 18-45, 2) had not experienced any previous injury or surgery to the either knee before this injury, 3) was seen by a participating physician within 72 hours of the injury, 4) was willing to receive a M R I of the knee and undergo the first H B O treatment within 96 hours of the injury, 5) was not diabetic and 6) had no claims regarding this injury at the Worker's Compensation Board or Insurance Corporation of British Columbia or any other insurance plan that may be covering the patient for time lost at work. The requirement regarding no previous surgery was important because the uninjured knee was used to provide control parameters for the injured knee.  Procedures After clinical diagnosis of the injury, subject's height, weight, age, side of injury and time of injury, were recorded. All subjects were evaluated with a M R I  34  of their knee at the Heather Pavilion or U B C site of the Vancouver Hospital as soon as possible following the first visit with a participating physician. Subjects were evaluated within 66 +/- 3.8 hours after injury. All knees were imaged in a supine position with a G E Signa 1.5 Tesla system (General Electric, Milwaukee, Wisconsin) using 3.x software and a linear extremity coil.  Contiguous 5 mm  images with 1 mm spacing were obtained using 16 cm field of view and  the  images were reconstructed on a 256 x 256 pixel matrix. The images utilized were axial fast spin echo T2 weighted with an repetition time (TR) of 4000 ms, an excitation time (TE) of 76 ms, a radio frequency flip angle of 90 degrees and 2 excitations (NEX/n).  The images were assessed and analyzed for volumes of edema by the two musculoskeletal radiologists and the author and decisions were reached by consensus. The patella, patellar retinaculum, femoral condyles, tibia to the fibular notch, menisci, cruciates, collateral ligament complexes, as well as bursae and tendons located in the area were visualized. Notes of any pathology were made. Subjects with injuries other than a grade II M C L were eliminated from the study. Subjects with suspected but not confirmed injuries were kept in the study (see table 2). Fifteen days after the first M R I , a second M R I was performed.  35  A  comparison of the total volume of soft tissue edema between the first and second set of scans was performed. Volume analysis of the edema associated with the medial collateral complex was performed on a Sun Microsystems (Mountain View, California) computer and 20 inch screen using P - V Wave Visual Numerics release 6.0 (Boulder, Colorado) software.  Scores recorded were the difference between pre  and post treatment volume of edema.  Any subject with injury to the M C L complex on M R I evaluation was included in the study group. Subjects, after the first MRI, were randomly divided into a control or experimental group and blinded to their specific treatments. A l l subjects were placed individually in a monoplace hyperbaric unit (Hyox, Scotland) for 1 hour ( + 14 minutes for compression and decompression) every day for five out of seven days per week for two weeks as soon as possible after the injury. Time and date of first treatment were recorded. While in the chamber, the control group was pressurized to 1.2 A T A and did breath air (P02= 0.25 A T M ) through a demand regulator and a Scott (Atlanta, Georgia) type mask.  The experimental  group was pressurized to 2.0 A T A and did breath 100% oxygen through the same apparatus. A l l subjects and researchers administering tests or doing clinical or M R I evaluations were blinded to the specific treatments the subjects received.  36  Subjects, on the initial and weekly follow-up clinical visits to the initial examining physician, completed the subjective recovery questionnaire based on the Lysholm knee scale, and were asked to express their current sensation of pain on a visual analog scale (see appendix B).  Subjects were then assessed for the  following: knee girth with a tape measure and using the superior condylar ridges and the centre of the patella as markers, thigh circumference 10 cm above the patella with a tape measure, range of motion of the knee with a goniometer especially noting extension and maximum flexion, and a one legged hop test for distance. Thigh girth, knee girth, range of motion, maximum flexion and the one legged jump test were conducted on both legs for comparison. Thigh girth, knee girth, range of motion, maximum flexion were performed three times during each visit.  The average score of the three measurements for each variable was  recorded. The one legged hop tests were done in a 2.5 metre area with a line serving as the starting point.  Standing on one leg on the middle of the line,  patients hopped once to determine distance when landing on the same leg. The tests was performed three times. Best performances were recorded.  All subjects did also participate for 6 weeks in a standardized program of home rehabilitation. Compliance was verbally assessed during the weekly followup visits. This included ice twice a day and series of stretching and strengthening  37  exercises. While unable to tolerate weight-bearing, exercises consisted of 3 sets of 10 isometric contractions of the quadriceps followed by 3 sets of 10 knee flexions and extensions within their existing range of motion. Subjects, when able, were to move to 3 sets of 10 free standing eccentric squats twice daily as can be tolerated. Upon achieving 100 degrees range of motion, subjects were asked to perform 20 minutes of cycling 3 times per week on a stationary cycle ergometer against 2 kilograms of resistance.  Four weeks after the date of the injury, a 20 metre figure of eight test and 10 metre straight running test were conducted. The 10 metre test had a space of 10 metres after the finish to allow for deceleration. The figure of eight tests had a diameter of both curves of 4 metres and the distance between the centre of each curve 10 metres apart. Patients were asked to complete 1 lap of the figure of eight circuit. These tests were conducted either in a gymnasium or outdoor tennis courts, using cones and a stop watch. Individual subjects performed all their tests on the same surface. Each subject had three opportunities at each trial. Score were recorded as the average of the three trials. This was repeated every week until the end of the sixth week, (see appendix A for overview of timeline)  Pre-  study analysis demonstrated variable test/re-test correlations range from 0.840.99.  38  Statistical Analysis  General descriptive summaries of the data were done. Specific analyses to test the hypotheses stated included: •  A time (7) by knee variable (6) by group (2) repeated measures multiple analysis of variance ( R M M A N O V A ) for the variables of subjective recovery, knee girth, thigh girth, range of motion, maximum flexion, and pain for significance over the entire study period.  •  A time (3) by knee variables (6) by group (2) R M M A N O V A for the variables of subjective recovery, knee girth, thigh girth, range of motion, maximum flexion, and pain for the treatment period (trials 1-3).  •  A time (6) by group (2) repeated measures analysis of variance ( R M A N O V A ) for the variable of running test ratio.  •  A time (3) by group (2) R M A N O V A for the variable of the ratio of the timed straight versus figure of eight running tests.  •  A t-test for the variable of edematous change as measured with the pre- and post-treatment MRIs.  The P<0.05 level of significance was used for all statistical procedures.  39  Statistical Power The statistical power in this study for the various statistical procedures is developed from calculations of Cohen's Dc . Calculations are based on the 0.05 a  level of significance, a 20% expected change, correlations of 0.6 and standard deviations of 33% of the individual variables. These values were determined from a delayed onset muscle soreness study (DOMS) pilot study performed the previous summer,  literature values and what would be considered clinically significant.  Power is estimated to be 0.76. b  Cohen's Dc = delta / s (1-r)" = (magnitude of the difference to be detected) / (expected standard deviation x the square root of 1 - the correlation of the dependent variable) The use of MANOVA as a statistical tool limits the calculation of power due to the intercorrelation of the dependent variables to an estimate based on isolated correlations alone. a  2  b  40  HYPOTHESES  The following hypotheses were tested:  1. The application of H B O will increase the reduction of edema during recovery. 2. The application of HBO will increase the overall perception of recovery. 3. The application of H B O will lead to a decreased perception of pain during recovery. 4. The application of H B O will allow greater range of motion and flexibility during recovery. 5. The application of H B O will significantly decrease muscle wasting during recovery. 6. The application of H B O will significantly improve overall function and stability of the knee during recovery.  These hypotheses were tested for all (1-7) as well as the treatment (1-3) trials specifically.  41  RESULTS  Subjects Forty-two (37 male, 5 female) subjects were screened for possible participation in this study.  Fifteen subjects were eliminated during the initial  clinical exam. Reasons for exclusion of these subjects based on clinical findings include the subject: had actually experienced a previous injury (3), showed signs of a muscle insertion tear (1), showed signs of meniscal tear (1), anterior cruciate tear (2) large thigh contusion (2) and not willing to complete the study (6). Eight subjects were excluded based on M R I evaluations. Reasons for exclusion of these subjects based on M R findings include: anterior cruciate tear (5) and meniscal tear (3). Nineteen (16 male, 3 female) subjects were chosen as suitable. Fourteen (12 male, 2 female) of those completed the clinical portion and nine (7 male, 2 female) of those completing clinical trials, received both initial and follow up MRI's.  Anthropometric data for both groups can be found in table 2a. There was no significant difference found between the groups in terms of height, weight and age. Sports that were the causes of the injuries were hockey, skiing and one case involving soccer.. The primary mechanism of injury was catching of an extremity. The second cause of injury was a collision. Both of these lead to a valgus stress of  42  the knee causing the injury. Bone contusions were found on the MRI's of 7 subjects (4 in the H B O group and 3 in the control group). Four other pathologies were suspected clinically however, M R I did not demonstrate any anatomic abnormality (3 in the treatment group and 1 in the control group) (see table 2b). Subjects were placed in the chamber 74.3 +/- 2.5 hours after their injury. Compliance with the home rehabilitation exercises was easily completed by all subjects.  43  Subject 1 2 3 4 5 6 7 8 9 10 11 12 13 14  Sex M M M M F M F M M M M M M M  Knee R L R L R L L L R L L L R L  Age_ 33 38 34 30 30 44 28 30 22 35 31 34 33 24 31.9 32.0 31.8  Mean HBO Control  Height (cm.) 178 175 178 173 166 188 160 175 175 174 178 181 173 183 175 174.5 175.8  Weight (k 86 79 90.5 71.5 145 65.5 65.5 74 74.5 78 76 95 68 70 76.7 77.2 76.2  Table 2b: Subject Data.  Subject 1 2 3 4 5 6 7 8 9 10 11 12 13 14  Sport in which injury occurred Hockey Soccer Hockey Hockey Skiing Skiing Skiing Hockey Hockey Hockey Skiing Skiing Skiing Skiing  Pre and Post MRI? Yes Yes No No Yes No Yes Yes Yes Yes Yes Yes No No  44  Group? HBO HBO HBO HBO HBO Control Control Control Control HBO Control Control Control HBO  Bone Contusion? Yes No No No Yes Yes No Yes No No Yes No Yes Yes  It is interesting to note that in the process of investigation a new dimension was added in our understanding of grade II M C L complex injuries. The subjects in this study were a sub-population of another study which compared clinical diagnoses with M R I findings. Preliminary results from Vancouver Hospital have shown that this type of injury may have patellar retinacular involvement has high as 75% of the time (unpublished). This was true for all of the subjects in the H B O study.  Analysis of the L S , Pain, K G , T G , R O M , M F , and O L J for trials 1-7 A group (2) by variables (6) by time (7) repeated measures M A N O V A was performed for the variables of the subjective recovery, pain, knee girth, thigh girth, range of motion and maximum flexion.  The results are summarized in table 3.  Significant differences were shown for the group and time main effects (df=6,7; F=12.84; p=0.0018, df=36,297; F=9.17; p<0.001 respectively), however no significant difference was found for group by time interaction (df=36,297; F=1.09; p=0.33).  This finding suggests that although the groups are different averaged  over all the trials and variables and the trials are different averaged over the groups and variables, the groups do not respond differently over the trials averaged over the variables.  The key result is that the negative findings of group by trial  interaction indicate that the rate of change of all the variables summed together are  45  not different between the groups over from trials 1-7. This suggests that there is no difference in the response to treatment over the entire time between the two groups. No further follow up procedures were done for this M A N O V A .  Table 3: Week 0-6 RM MANOVA for the variables of LS, VAS, TG, KG, ROM, MF. (Trials 1-7) Source  df  Test Statistic  F  P  Group Time Group x Time  6,7 36,297 36,297  TSQ* LRatio** LRatio**  12.84 9.17 1.09  0.0018 <0.0001 0.3351  * Hotelling's T- squared ** Wilk's Lambda  Analysis of the LS, Pain, KG, TG, ROM, MF, and OLJ for trials 1-3 A group (2) by variables (6) by trials (3) repeated measures M A N O V A was also performed for those variables looking specifically at the treatment period (trials 1-3). The results are summarized in table 4. Significant differences were found for the group and time main effect (df=6,7; F=11.17; p=0.0028, df=12,38; F=15.54; pO.OOOl respectively), as well a significant difference was found for group by time interaction (df=12,38; F=12.91; p=0.006).  This suggests that  groups are different averaged over the trials and variables, the trials are different averaged over the groups and variables and the groups respond differently over the trials averaged over the variables. The key result is that the significant group by time interaction indicates that the rate of change of the sum of the variables is  46  different for the treatment and control groups over trials 1-3. This suggests that there is a difference during the treatment portion of the study between the two groups. A follow up analysis looking at which variables during this period that were involved with the M A N O V A was conducted. These findings indicate that during the treatment period, the rate of recovery is faster in the treatment than the control group.  Table 4: Week 0-2 M A N O V A for the variables of L S , V A S , TG, KG, R O M , MF.  (Trials 1-3) Source  df  Test Statistic  F  P  Group Time Group x Time  6,7 12,38 12,38  TSQ* LRatio** LRatio**  11.17 15.54 2.91  0.0028 <0.0001 0.006  * Hotelling's T- squared **Wilk's Lambda  The trial 1-7 R M M A N O V A indicates some possible serious violations in the assumptions of the repeated measures M A N O V A . when looking only at trials 1-3. (see table 5)  47  This improved greatly  Table 5: Epsilon Values for the RM MANOVA calculations. Week Epsilon Correction  0-6 GGI*  LS 0.34 VAS 0.29 KG 0.41 TG 0.41 ROM 0.33 MF 0.33 * Greenhouse-Geiser-Ingham ** Huynh-Feldt  HF**  0 -2 GGI*  HF**  0.45 0.36 0.56 0.57 0.44 0.44  0.83 0.68 0.99 0.63 0.70 0.74  1.00 0.80 1.00 0.73 0.83 0.90  The follow up R M A N O V A s for group by time interaction during the treatment period indicate that the variables of thigh girth (TG), range of motion (ROM), and maximum flexion (MF) are significantly different, (see table 6) This indicated that the treatment and control groups respond differently with respect to these variables.  Table 6: Week 0-2 Follow-up Repeated Measures ANOVA's for Group by Time Interaction Variables  SS  MS  df  F  P.  LS VAS KG TG ROM MF  96.4 10.7 0.076 1.17 326.6 241.7  48.2 5.4 0.038 0.58 163.3 120.8  2,24 2,24 2,24, 2,24 2,24 2,24  0.76 3.14 0.44 5.8 6.42 3.71  0.48 0.061 0.651 0.008* 0.0059* 0.0394*  * significant at the 0.05 level  48  Individual Variables  Subjective Recovery Scores showed rapid improvement initially as subjects progressed in their rehabilitation then began to plateau as scores approached the top of the scale. This suggests that an improvement overall was made by the subjects during the trials. There was no significant difference in the initial scores between the groups indicating the two groups started from relatively the same state with respect to this variable. Variability declined over the trials overall and was noted to be consistently less in the treatment group. There was no significant difference in the group by time interaction follow up analysis (df=2, 24; F=0.76; p=0.48) for the significant week 0-2 R M M A N O V A . This indicates that there is no difference in the rate of change of subjective recovery between the treatment and control groups, (see table 7)  49  Table 7: Subjective recovery questionnaire scores at initial assessment and the following six weeks during recovery.  Initial  Week 1 Week 2  Week 3  Week 4  Week 5  Week 6  Control Mean SD  44.71 18.14  63.29 15.07  76.71 15.42  91.14 7.63  93.43 7.85  95.86 4.81  97.71 3.59  HBO Mean SD  37.71 9.34  60.86 12.58  76.86 7.49  90.00 5.03  91.29 5.96  93.57 3.64  98.00 1.91  Overall Mean SD  41.21 14.33  62.07 13.40  76.79 11.65  90.57 6.24  92.36 6.79  94.71 4.27  97.86 2.77  50  o p O CM  o o O O  o o O 00  O  .  o  0  CO 9J03S  51  ,  0  o O •>*•  o O CM  O  o O O  Pain Pain scores overall decreased in a curvilinear manner (rapidly initially then slowly towards the end) as the subjects progressed during recovery. This suggests that the subjects overall experienced less pain with time. Initial scores were found to not be significantly different between the two groups (p=0.44). Variability declined over the trials overall and was noted to be consistently less in the treatment group. This may be in part due to the absolute nature of the ends of the scale. There was no significant difference in the follow up group (2) by time (3) R M A N O V A (df=2, 24; F=3.14; p=0.061) for the treatment period.  Table 8: Pain score (cm.) at initial assessment and the following six weeks during recovery. Initial  Week 1  Week 2  Week 3  Week 4  Week 5  Week 6  Control Mean SD  5.51 2.74  3.07 2.06  1.63 1.39  0.81 0.76  0.51 0.75  0.49 0.65  0.36 0.73  HBO Mean SD  6.63 2.56  1.94 1.62  0.43 0.76  0.29 0.44  0.39 0.61  0.21 0.36  0.03 0.05  Overall Mean SD  6.07 2.61  2.51 1.88  1.03 1.24  .55 0.66  0.45 0.66  0.35 0.52  0.19 0.53  52  o o d  o o o>  o o 00)  o p  o o CO  o o iri  o o  (lUO) 9 J O 0 S  53  o o co  o o CN  o o  o o d.  o o  Knee Girth Difference Scores overall were found to decrease over time indicating the difference in knee girth between the injured and uninjured knee was decreasing. This suggests a decrease in swelling about the injured knee compared to the uninjured knee with time. Initial scores were found to be significantly different between the groups (p=0.007). Variability overall declined with time and was found to be greater in the treatment group.  N o significant difference was found in the knee girth  difference group by time interaction follow up analysis (df=2,24; F=0.44; p=0.65) of the treatment period..  Table 9: Knee girth difference at initial assessment and the following six weeks during recovery.  initiar^^vVeek 1  WeekT"lv^^  WeeTtT"  Control Mean SD  1.27 0.30  1.00 0.29  0.77 0.45  0.59 0.40  0.43 0.44  0.43 0.37  0.41 0.31  HBO Mean SD  0.70 0.35  0.53 0.53  0.29 0.22  0.17 0.22  0.11 0.12  0.03 0.16  0.07 0.11  Overall Mean SD  0.99 0.43  0.76 0.48  0.53 0.42  0.38 0.38  0.31 0.37  0.23 0.34  0.24 0.29  54  J2  (0 (A  3  £  > O  c £  5 £ o  (0 To  o a> c  CO  £ 3 ii  (tin) aouajauia 55  Thigh Girth Difference Overall, thigh girth difference scores were found to first increase then decrease, (see table 10) This suggests that after an initial loss of girth in the injured leg's thigh, a recovery and rebuilding process had begun. This followed the expected thigh wasting of the muscle around the injured knee and increase in size with rehabilitation. There was no significant difference in the initial trials (p=0.17).  Variability was found to be greater in the control group than in the  treatment group. Follow up analysis of the group by time interaction showed there was a significant difference between the groups (df=2, 24; F=5.8; p=0.008). The graph (figure 4) indicates that the control group difference increased over the first two weeks while the treatment group remained consistent.  This finding  indicates that the control experienced muscle wasting while the treatment group did not.  56  Table 10: Thigh girth difference (cm.) at initial assessment and the following six weeks during recovery. Initial  Week 1  Week 2  Week 3  Week 4  Week 5  Week 6  Control Mean SD  0.14 1.08  0.67 1.12  0.83 0.96  0.57 0.93  0.56 0.60  0.40 0.59  0.41 0.31  HBO Mean SD  0.83 0.53  0.86 0.52  0.77 0.39  0.60 0.44  0.50 0.47  0.57 0.50  0.51 0.34  Overall Mean SD  0.49 0.86  0.76 0.84  0.80 0.71  0.59 0.70  0.53 0.52  0.49 0.53  0.46 0.32  57  o o csi  o  in  o o  -r^  o  m  d  o  (uio) aouajau.iQ 58  o o  o 10 p  Range ofMotion Difference Scores overall decreased as the trials progressed, (see table 11)  This  showed that the injured knee was becoming more like the uninjured knee, suggesting greater movement and an improvement with time.  Initial scores  demonstrated no significant difference between the two groups (p=0.51). Variability was similar between the groups. There was a significant difference found in the group by time interaction follow up analysis (df=2,24; F=6.42; p=0.0059) of the treatment period. The graph (figure 5) indicates that the rate of decrease in the difference between the amount of R O M between a subject's injured and uninjured knee is greater for the control than the treatment group.  This  suggests that the treatment groups had better range of motion about the injured knee.  59  Table 11: Range of motion difference (deg.) at initial assessment and the following six weeks during recovery. Initial  Week 1  Week?  Week 3  Week 4  Week 5  Week 6  Control Mean SD  31.00 13.11  21.14 9.44  10.14 6.91  5.00 4.83  4.71 4.07  2.29 2.43  2.14 2.85  HBO Mean SD  35.00 8.58  14.71 10.70  8.86 10.17  7.14 6.57  4.00 4.58  3.00 3.61  2.29 2.50  Overall Mean SD  33.00 10.85  17.93 10.25  9.50 8.38  6.07 5.65  4.36 4.18  2.64 2.98  2.21 2.58  60  o  o  in  o  p d  o  o iri CO  o  o  CO  iri CM  p d  o  p  p d  CM  o  p iri  (saaj6ap) aouaianjrj 61  O  O d  o  o iri  o  o d  o  o iri  1  Maximum Flexion Difference Maximum flexion difference scores mirrored much of what was found in the range of motion difference scores, (see table 12) The scores were found to steadily decrease over the trials. This indicated that the difference between the injured and uninjured knee decreased, suggesting greater flexibility in the injured knee with time.  There was no significant difference found in the initial trials  between the groups (p=0.36).  Variability was equal between the groups.  A  significant difference was found in the follow up analysis of group by time interaction (df=2, 24;F=3.71; 0.0394) for the treatment period. The graph (figure 6) indicates that the differences in the control group decreased slower than the treatment group over the first two weeks of the study. This indicates that the treatment group were able to flex their injured knee to a greater extent than the control group.  62  Table 12: Maximumflexiondifference (deg.) at initial assessment and the following six weeks during recovery. Initial  Week 1  Week 2  Week 3  Week 4  Week 5  Week 6  Control Mean SD  21.57 11.41  17.71 9.03  10.14 6.41  4.86 4.10  4.00 3.42  1.57 2.15  1.57 2.51  HBO Mean SD  27.14 10.70  12.57 9.98  7.43 8.92  5.86 4.41  3.00 3.00  2.43 2.51  1.43 1.99  Overall Mean SD  24.36 11.01  15.14 9.53  8.79 7.60  5.36 4.13  3.50 3.13  2.00 2.29  1.50 2.18  63  o o d  o o  TJ-  CO  iri  o  o d CO  o o  iri  CM  o  o  d  o m  CM  to  o o o  1-  T -  (saaj6ap) aouajauja 64  o q m  o  q o  o q tf)  One Legged Jump Test Difference Many of the subjects were not able to complete the initial trial. Only the last six trials were used for calculations of significance. The scores showed a decline in the difference between the injured and uninjured legs with time (see table 13).  Trial #2 (week 1) showed no significant difference between the groups  (p=0.41). Variability of the last 6 trials between the groups was similar. A group (2) by time (6) R M A N O V A analysis was performed and found no significant difference in the group by time interaction between the groups (df=5, 72; F=0.495; p=0.77).  Table 13: One legged jump test difference scores (cm.) during the following six weeks of recovery. Week 1  Week 2  Week 3  Week 4  Week 5  Week 6  Control Mean SD  25.71 10.63  24.00 11.99  14.29 7.50  11.43 8.77  10.29 7.95  9.86 7.71  HBO Mean SD  20.29 13.33  19.71 13.46  15.00 8.45  6.14 4.85  3.14 2.54  0.43 1.40  Overall Mean SD  23.00 11.92  21.86 12.45  14.64 7.68  8.79 7.34  6.71 6.78  5.14 7.23  65  It Mia,..,no-  •c H (0 3  UIUI  p  S2 > o  o  t  c  a> E H  i  to  tt K-  w To  a E 3  -J  TJ a>  CO  O) a>  —I  a c O  £ 3  O) +  o o  d  •4-4-4o o in co  o o d co  CM  O  o in (LU3) 93U3J9J4!a  66  Running Test Ratio The mnning test ratios showed a decline overall. Both the straight running and the figure of eight course times improved as the trials progressed. However, the figure of eight time progressed more rapidly leading to a decline in the straight running to figure of eight ratio. The variability between the two groups was equal. Initial trials in week 4 showed that the groups were not significantly different (p=0.058).  A group (2) by time (3) R M A N O V A revealed that there was a  significant difference for group by time interaction (df=2, 36; F=3.467; p=0.041). The graph (figure 8) reveals that the treatment group declines more rapidly than the control group.  Table 14: Running test ratios during weeks 4, 5 and 6 of recovery. Week 4  Week 5  Week 6  Control Mean SD  3.65 0.24  3.51 0.15  3.47 0.20  HBO Mean SD  3.90 0.21  3.60 0.13  3.37 0.11  Overall Mean SD  3.78 0.22  3.56 0.14  3.42 0.18  67  68  MRI-Determined Edema Difference  Nine subjects completed pre- and post-treatment imaging. Eight subjects were used for statistical purposes (four in each group) and one subject was eliminated for being an outlier (4.5 standard deviations from the overall mean). A significant difference was found between the treatment and control groups (20.91 +/- 2.23 ml and 15.45 +/- 1.50 ml, p-0.033). This indicates that the treatment and control groups were different.  Table 15: Edema difference scores (ml.) obtained from M R images. Subject  HBO  Control  1 2 3 4  14.8 20.3 24.6 24.0  11.3 15.4 17.2 17.9  Mean SD  20.91 2.23  15.45 1.50  69  DISCUSSION  This research project is the first controlled double blinded human H B O study to show significant efficacy when applied to a clinical sports injury. Specifically, benefits were observed during HBO treatment of the injury. Variables analyzed during the treatment period as well as the running tests ratios and MRIdetermined pre-post treatment edema differences provide evidence that H B O does alter tissue edema and recovery when used for treatment of M C L soft tissue injury. Table 16 summarizes the statistical findings.  Table 16: Summary of Statistical Findings. Statistical Test  p value  Significance  Week 0-6 R M M A N O V A for the variables of LS, V A S , TG, K G , R O M , MF. (Trials 1-7)  0.33  No  Week 0-2 R M M A N O V A for the variables of LS, V A S , TG, K G , R O M , MF. (Trials 1-3, the treatment period)  0.006  Yes  0.48 0.061 0.65 0.008 0.039 0.0059  No No No Yes Yes Yes  0.77  No  0.041 0.033  Yes Yes  R M A N O V A Follow up of Individual Variables (Trials 1-3) Subjective Questionnaire (LS) Pain (VAS) Knee Girth Difference (KG) Thigh Girth Difference (TG) Range of Motion Difference (ROM) Maximum Flexion Difference (MF) One legged Jump Test Difference (Week 1-6) Running Tests Ratio (Week 4-6) M R I Pre - Post Difference (Week 0-2)  70  At the onset of the study, it was hypothesized that the groups would differ over the treatment period as well as over all the trials.  The findings of non-  significance for variables measured over all trials is not surprising, however. The injury used in this study has an overall positive prognosis and all patients were expected to eventually recover full function. The study showed that with all the variables, the groups appear to reach the same point of recovery over the test period (6 weeks). This level was attained early to midway in the study (trial 3-4) potentially masking any significant rate of change differences between the groups over the entire trial period.  This anticipated no significant findings over all the trials prompted specific analysis of the treatment period alone. Analysis of the treatment period suggests that the response to treatment by the groups are different.  It was during this  period that many of the variables did show a different rate of change of recovery when comparing the control and treatment groups. This is evident in many of the graphs of the variables.  While, the groups initially appear to diverge with the  treatment group recovery being more rapid then plateauing, the control group eventually achieves the same plateau in the recovery. This phenomenon occurred as the groups begin to converge midway through the study.  71  Specifically, the variables of thigh girth difference, range of motion difference, maximum flexion and MRI-determined pre-post treatment edema difference were found to be significantly different during the treatment period. The variable of running test ratios showed a significant difference in the final three weeks of the trials.  It is also important to note that while not significantly  different, pain during the treatment period and one legged jump test differences overall showed trends.  Significant Findings MRI-determined edema difference  Research findings confirmed expectations that the difference between the pre and post treatment images would be greater in the treatment group than in the control group. What effects on recovery are evident in the other findings of this study.  Although used consistently in sports injury analysis research, no other  studies are known that have used magnetic resonance technology to standardize the study group and assess soft tissue recovery in patients treated with HBO.  Significant findings were considered limited by the clinical assessment and necessitated by study design. Application of H B O had started (mean = 74.3 +/-  72  2.5 hours) after injury. Time required for initial clinical assessment and obtaining pre-treatment M R I necessitated this delay.  If M R I had not been utilized a  significant number of patients who had clinically unrecognized significant associated injuries would have inadvertently been included in the study group. Earlier research has indicated that early application would give the more significant effects because of the timing of the inflammation phases (Jain, 1990; Staples, 1996; Borromeo et al, 1996). Inflammation become noticeable approximately 6-8 hours after injury with the effects being the most apparent 24-48 hours after injury (Lavan and Hunt, 1990; Hunt, Zederfeldt and Goldstich, 1969; Perrins, 1983). Given this information, it would have been ideal to start treatment as early as possible to interrupt or mediate theses cascades. However, problems with logistics and ethical considerations did not permit it in this study. Some of the benefits found in this study may have been attributed to controlling any further inflammation subjects had elicited in an effort to continue on with their daily activities.  Possible sources of error in M R analysis can be attributed to a lack of a gold standard, and the problems of consensus analysis. In consensus analysis, a disagreement may occur between analysts. It can be argued that the strongest character of the group will prevail independent of the number of opinions and  73  people who have them. However, consensus analysis is the primary method by which most M R research is done currently and is accepted as the norm for most clinical evaluations.  All cases were treated in an emergency fashion in Vancouver Hospital Center, a major metropolitan hospital in Vancouver, British Columbia.  It was  logistically not possible to calibrate the M R I equipment prior to each individual imaging. M R I equipment was calibrated monthly with less than a 0.5% difference in the strength of the field generated during the study. It was also hoped that researchers would be able to correlate images by imaging a standard (i.e. a small water sac) for comparison prior to examining each subject. Unfortunately, this did not occur. This was the reason for a subjective analysis of the images in an attempt to counter this problem. A subjective analysis could account for some slight variations. Since analysis was done in a blinded manner, no bias based on treatment knowledge could occur.  Thigh Girth Difference  Young et al, 1987 demonstrated that with a mild to severe knee injury and the subsequent inflammation and reduced activity, there is a noticeable and disproportionate amount of muscular wasting about the lower thigh. The wasting  74  is caused by inhibition of the extensor mechanism allowing the knee to remain in a flexed position. This phenomenon has been termed reflex muscle wasting. The net result is a decrease in strength. A decrease of one centimeter in circumference about a 36 cm thigh will lead to a decrease of approximately 6% in volume. Findings in this study suggest strongly that the rate of change of muscle wasting is limited if not eliminated during the early phases of recovery when H B O is applied. A decreased inhibition of the extensor group is hypothesized as a possible mechanism.  Potential sources of error in the measurement of thigh wasting include: the tension with which the tape measure was held and measurement of a circumference about a non-perfect cylindrical thigh. Three measurements were made per trial. The results were then averaged.  This minimized any extreme readings and  skewing of data.  Range of Motion and Maximum Flexion Differences  Significant findings during the early phases of recovery with these variables corroborate the findings of MRI-determined edema difference. Measurements of range of motion and maximum flexion were to pain free limits. That is, subjects were asked to move their knees as far as possible while experiencing no pain. Pain  75  occurring beyond this point was hypothesized to be due to excess edema placing pressure on nociceptors and stretching of incompletely developed new collagen fibres. Subjects who had treatment with H B O showed greater range of motion and maximum flexion about the injured knee.  It would therefore suggest that the  increase has to do with the elimination of edema in about the knee caused by the injury and possibly the earlier and stronger formation of new collagen links. Biopsy would be required to substantiate this hypothesis.  Running Test Ratios  This test was to demonstrate overall functional capability of the injured knee compared to the uninjured knee, specifically, the ability to change direction compared to straight running.  It was hypothesized that with an injured knee  certain movements through the figure-of-eight course would limit performance by straining the recovering M C L . The injury considered in this study however, is not an anterior-posterior destabilizer. It should have had no effect on straight running therefore, producing a larger value in the figure of-eight to straight running ratio when the injury is less healed. Findings indicate that the ratio declined over time more quickly in the H B O group as opposed to the control group, supporting this hypothesis.  76  The significant results in the running test ratio during weeks four, five and six of this study are different from the results of the findings of other variables. While most of the other variables appear to plateau and the groups converge to a similiar point during this phase of the study, the running test ratio continues to diverge.  The difference is also noticeable in the one legged jump test.  The  explanation may be that these more objective functional tests are active not passive in nature. They are longer in duration and account for a combination of factors such as pain, range of motion and maximum flexion, strength (limited muscle wasting) and ligament integrity.  The finding of a significant difference in the  running test ratio scores suggest that H B O effects the rate of improvement of functional mobility.  Non-Significant Findings  Subjective Questionnaire The Lysholm scale based questionnaire was a combined subject and researcher assessment of the subject's current state during his recovery. Expected results for recovery were that subjects would achieve scores at or near the maximum in four to six weeks after the injury. This was shown to be the case in almost all subjects showing a plateau at week four of the trials (mean=92.36 +/6.79) and only marginal increases afterwards (5.5 points over the last two trials).  77  The Lysholm knee scale based questionnaire employed in this study showed that the treatment and control groups did not differ over time.  This suggests that  neither subjects or physicians perceived any greater benefit from this type of therapy.  It is important to note that any subjective analysis is easily swayed by personal opinion independent of actual fact. Researchers and subjects alike may answer questions on the questionnaire based on what they believe 'ought' to be and not what actually is. Reports published in the media as well as subjects' desire to please the researcher may have swayed or 'poisoned' the data sufficiently to limit any significant findings.  The effect on the subjects is known as the  Hawthorne Effect and has been demonstrated in many studies.  Anecdotal evidence supports this contention. One of the subjects noted to the author that his recovery was progressing in a similar manner as a notable hockey player with the same injury who was being treated with H B O independent of any knowledge of whether or not the subject was actually in the H B O or control treatment.  It is also possible that this form of questionnaire is insensitive to  changes associated with this type of treatment or injury.  78  Pain  As stated earlier, pain experienced in the subjects participating in this study is assumed to have come from: 1) the initial insult to the structural integrity of the tissue, 2) the primary inflammatory cascade as a result of the injury, 3) secondary inflammation as a result of the recovery process. It was expected that the pain would be at a peak in the initial trial and largely diminish during the recovery period. Pain scores decreased rapidly at first followed by a slow secondary phase approaching zero by the end of the trials. It may have been helpful if more measurements were made earlier in the study during which the largest amount of change in pain perception may have occurred.  Overall the subjects followed the expected trends with most participants feeling little or no pain by the end of the trials. Of those that did experience pain at the end of the trials, they indicated it was only marginal at best. No difference was shown between the groups overall and during the treatment trials in the rate of pain relief, however a very strong divergent trend similiar to the significant variables was noted. The trend indicated that a possible difference in the rate of pain relief may be underlying. It is apparent that variability limited any significant findings with respect to pain. A second possible explanation may be related to the relative late application of H B O (mean = 74.3 hours after injury). Late application  79  of H B O may not have countered the pain largely associate with the inflammatory stages of an injury.  Assessment of pain is difficult in nature. Physiologically, the constant signal intensity from nociceptors will result in a variety of responses of pain perception (Melzack, 1983).  Studies have shown that a large variability is inherent in all  measuring devices of pain (Melzack, 1983; Miller and Ferris, 1993).  It is  suggested that pain has a cognitive as well as physiologic component when expressed by an individual. (Melzack, 1983) Previous studies at U B C recently have successfully used visual analog scales for pain but with much larger subject participation. It is possible that the small number of subjects, variability, and lack of sufficient sampling frequency limited the findings of pain in this study.  The application of H B O was expected to have had a significant effect on pain during the recovery period. Increases in plasma levels of beta-endorphins and adrenocorticotrophic hormones were shown after a single and multiple H B O treatments over five days (Vezzani, Pizzola, Stefanini etal, 1991; Casti, Orlandini, Troglio et al, 1993). These findings coincides with the largest amount of change observed in this study. It is important to note that investigations by Vezzani and Casti used 2.8 A T A pressures versus the 2 A T A used in this research. Pain has  80  also been shown to have decreased when treated with H B O in studies looking at patients recovering from serious burn and vascular diseases (Hammarlund et al., 1992; Tufano, 1988). Patients who suffered from vascular disease felt less pain with HBO. The Tufano study used psychometric tests as well as plasma levels of endorphins and A C T H to measure pain. Although a trend was present, this M C L H B O study concurs with the findings of the U B C delayed onset muscle soreness findings in which no pain difference was noted for HBO, delayed exposure to H B O and a placebo group similar to the control group in this study. (Staples, 1996)  Knee Girth Difference  At the onset of this study, it was anticipated that with the second degree M C L complex injury to the knee, there would be a noticeable amount of swelling in the medial compartment of the knee. The expectation was supported by M R I investigations. However, no difference in the rate of decline in the knee girth between injured and uninjured knees was shown to be present during the treatment and overall periods even though there was a significant difference in the amounts of edema between the groups from M R I evaluation.  Like thigh girth measurements, possible sources inconsistent measuring about the knee.  81  of error include  It is possible that the circumference  measured did not include the portion of edema present because of the injury. Findings in the study were largely associated with patellar retinacular tears which are found in the anterior-medial section of the knee.  The shape of the  circumference of the knee may have led to missed observations of edema. The amount of tension used when holding the tape measure about the knee may also be another source. Compression and displacement of the possible edema by excessive tension on the part of the researcher would also limit any significant findings. It would appear that the use of M R I is a more sensitive means of assessing swelling.  One Legged Jump Test  The rate of change in the improvement of scores on one legged jump test of all available trials did not prove to be significantly different between the groups. This suggests that H B O has no benefit in the recovery process as measured by this variable. A divergent trend similar to the running test ratio findings was evident when analyzing the graph however (see figure 6).  A possible reason for non  significance, particularly in and around the treatment period, may largely be due to the patients unwillingness to attempt the task.  This was  evident on initial  evaluations where only 3 of 14 subjects completed or even attempted the test. The idea of landing on the recently injured leg was largely an unknown to the subjects. This made them hesitant. Most of the anterior-posterior stability is inherent in the  82  cruciates and muscle structure about the knee. It was hypothesized that this task should have been completed with relative ease after the initial inflammation had subsided. Many patients were unwilling to give a good effort for fear of having the knee 'give' again.  Overall, it is possible that the low number of participants available for this study and the large amount of variability contributed to the lack of significance of some of the variables. Increasing the size of a studies 'n' is the number one way to increase its power. The other factor may have been that because of the relative late application of treatment following injury when much of the primary inflammatory process having subsided, a larger -significant difference may have been seen.  Comparison of Findings Although H B O has met with many successes in areas outside sports medicine, conclusive evidence for its benefits has still eluded many researchers within this field. Much of the problem has to do with the standardization of injury and timing of its application. This study has addressed these problems.  By  carefully screening patients with guidelines established in advance and the use of consistent clinical specialists for assessment and confirming diagnosis with a MRI,  83  this study has controlled the inherent variability in the investigation of a soft tissue injury.  Human Trials  Two human trials looking specifically at sports injuries have been reported. One project was research in Scotland with football players. increase in the rate of recovery  (James et al., 1993).  They found an  As expressed earlier,  concern regarding a lack of objective measures and experimental controls meant that this Scottish study did not provide any conclusive evidence for H B O benefits in that study. Findings of the study by the author include improvements in design suggested by the Scottish study including standardization of the injury, blinding of subjects and researchers, and the recording of objective measures.  A research project recently conducted at Temple University does not support our findings (Borromeo et al, 1996) In their study, ankle injuries of varying severity and possibly varying underlying anatomic injuries were assessed and prognosed for recovery time and treated with HBO. prognosis and actual recovery time were made.  Comparisons with the  No significant difference was  found. The study's author concluded that the problem of injury variability with respect to the ankle limited their findings. Ankle injuries compromise a large  84  spectrum of underlying anatomic  derangements with expected  significant  differences in recovery times. It may be that failure to control for this variable in their study lead to no significant difference being apparent.  By utilizing M R I as well as clinical assessment, this M C L study was able to better assess a uniform anatomic injury. It has clearly indicated the significant limitation of clinical evaluation in establishing the underlying anatomic abnormality. Clearly, recovery time for patients with associated cruciate ligament and meniscal tears would differ from those with an isolated injury to the M C L . It is likely that had these other injuries not been excluded that a significant difference would have not been apparent.  Recently, a study completed at U B C (Staples, 1996) showed that strength recovered quicker when H B O was applied after a model eccentric muscle injury. In that project, subjects were asked to perform a large number of eccentric contractions.  The subjects were then treated with H B O for the following five  days. They were divided into a five day treatment, three day treatment and sham groups. Tests for strength using a Kin-Corn dynamometer were performed two and four days after exercise. Pain scores on a visual analog scale were measured daily.  85  Significant findings were only made for strength recovery comparing five day H B O to the sham group.  It is interesting to note that the D O M S and this  M C L study both suffered from excess variability in pain measurement as well as witnessing trends. However, any conclusions need be taken in context due to the difference in muscle and ligament physiology. Enzymatic processes and circulation greatly differ in the two environments.  Animal Studies  In a recent study completed by Webster and colleagues (1996), rats whose M C L was surgically lacerated were treated with H B O treatments were 2.8 A T M , 1.5 hours per day for five days. Rats were sacrificed at two, four, six and eight weeks after laceration. Both lacerated ligament and unlacerated ligament legs were amputated and cleaned leaving only the femur and tibia, M C L and adjacent capsule. Comparisons of the stiffness and force to failure were made between the lacerated M C L and unlacerated M C L of each leg.  Results showed that at four weeks, in non-HBO treated rats, unlacerated ligaments on the same rat had a higher force to failure and stiffness than lacerated MCLs. At four weeks, H B O treated rats had higher force to failure on unlacerated to lacerated M C L ' s but not greater stiffness. It is also interesting that the strength  86  of the lacerated ligament in the treatment group was 33% stronger than that of the lacerated ligament in the control group.  A difference in inflammation,  neovascularization, rate of collagen synthesis and the strength of collagen formation were attributed as causes (Paul Horn, personal communication, May 15, 1996).  Practical Applications of Findings The practical implications of this study are far reaching.  This study  suggests that HBO therapy promotes a more rapid recovery from injury beyond conditions created by a normal environment. Specifically, soft tissue injuries will experience less swelling, less muscle wasting as measured by changes in thigh girth, greater range of motion and maximum flexion, and greater opportunity to return to normal function as measured by the running tests. As a result, a patient will experience less time away from daily activities and/or sports. With less muscle wasting and thus less loss of strength, there is also a decreased opportunity for reinjury. This allows H B O to be applied to a number of sports or activity related injuries such repetitive strain or repetitive use injuries such as seen in the work place.  87  The financial benefits are readily apparent to professional sports.  Rapid  return of an athlete to competition will allow that player to contribute to a teams' performance or compete for monetary gains. The apparent financial benefit of quicker recovery is not limited to professional athletes.  Worker Compensation  Boards will be able to benefit from this form of therapy for those injuries obtained at work which may have been slow to respond to conventional treatment.  88  LIMITATIONS OF THE STUDY  The population from which we are selecting tended to be highly motivated athletic individuals. These subjects had a high drive to return to function as soon as possible. Although thorough analyses of the knees presented was performed and M R I ruled out many other associated injuries, exact standardization of the degree of injury was not possible. The study was limited to the observations made in the first six weeks of recovery during which complete healing of the ligament complex would not have occurred. The study was also limited by the time at which various subjects presented to the clinic and how fast they were able to become integrated into the study. Limitations were also involved in the subjects willingness to be compliant, punctual and timely throughout the study. Subjective analyses of any variables was always dependent on the subjects perceptions and therefore and can always be questioned as being less than an ideal tool. Conclusions drawn from the objective measures may only be limited to those activities measured.  89  CONCLUSION A N DFURTHER  RECOMMENDATIONS  Findings of this study suggest that grade II medial collateral ligament injuries when intermittently exposed to H B O appear to recover more rapidly. This means that people who are dependent on a quick recovery may benefit from H B O treatment. At the moment, this treatment is not readily available. With further research, the application of this technology may become a practical alternative for a wide variety of soft tissue injuries where the reduction of the recovery time is critical.  Our study also suggests that anatomic imaging in addition to clinical assessment is essential in order to ensure that patients with similiar anatomic injuries are studied. A surprising 50% of the subjects screened had unsuspected but significant associated injuries which would have likely significantly affected findings and which would have made finding a treatment difference difficult. H B O studies are likely to involve small overall numbers and this is therefore of critical importance in future studies.  Further study needs to focus attention on the significant individual variables presented. In particular, further review of the effects on pain, functional recovery and edema will prove beneficial in our understanding of the benefit during the  90  recovery process. Strength measurements by Kin-Corn may more clearly elaborate the effects on muscle wasting.  MRI spectroscopy might be a vehicle to assess  biochemical markers of recovery. MRI may also be useful in measuring volume changes about the thigh experienced with reflex muscle wasting.  Further studies using a larger number of subjects need also be done. It has been shown that many ligament injuries are prone to re-injury. This is largely due to the fact the strength of the structure only approaches 80% of the original uninjured part. Interesting studies could be developed on the long term affects of HBO using variables such as the recurrence of injury and wound strength.  91  REFERENCES  Abbott N.C. et al. (1994a). Daily HBO does not increase the severity of inflammation in tuberculin reaction in healthy humans volunteers. Journal of Hyperbaric Medicine. 5: (3), 91-102.  Abbott N.C. et al. (1994b). Effect of hyperoxia at 1 and 2 ATA on hypoxia and hypercapnia in human skin during experimental inflammation. Journal of Applied Physiology. 77(2): 767-773. Adameic L. (1977). Effect of hyperbaric oxygen therapy on some basic vital functions. Acta Physiologica Polandia. 28:215-224.  Adameic L. (1979). Influence of hyperbaric oxygen on pulmonary functions in man. in Smith G. (ed.), Proceedings of the 5th International Congress on  Hyperbaric Medicine. Aberdeen, University Press; pp.60-68. Anderson L.H., Watson B, Herring R.F., and Mehm W.J. (1992). Influence of intermittent hyperoxia on hypoxic fibroblasts. Journal of Hyperbaric Medicine. 7(2): 103-114. Atroshenko Z.B. et al. (1983). Hyperbaric oxygenation in traumatic tissue edema. Soviet Medicine. 9:59-61. Baiter S. (1987). An introduction to physic of magnetic resonance imaging. Radiographics. 7(2): 371-383. Basset B.E. and Bennett P.B. (1977). Introduction to the physical and physiological bases of hyperbaric therapy. In: Davis JC and Hunt TK (eds.) Hyperbaric Oxygen Therapy. Undersea Medical Society, Bethesda MD. pp. 11-24 Beck J.S. and Spence V.A. (1986). Patterns of blood flow in the microcirculation of the skin during the course of the tuberculin reaction in normal human subjects. Immunology. 58: 209-215. Bird A.D. and Telfer A B M . (1965). Effect of hyperbaric oxygenation on limb circulation. Lancet. 1:355-356.  92  Boerema I., Meyne N.G., Brummelkamp W.K., et al. (1959). Life without blood. Journal of Cardiovascular Surgery. 13: 133-146. Bollen S. and Seedhom B . B . (1991). A comparison of the Lysholm and Cincinnati knee scoring questionnaires. The American Journal of Sports Medicine. 19(2): 189-190. Borromeo C.N., Ryan J.L., Marchetto P.A., Peterson R.E., and Bove A.A. (1996) A randomized trial of hyperbaric oxygen therapy for acute ankle sprains. Submitted to the American Journal of Sports Medicine. Cameron J.C. and Sandipan S. (1994). Management of medial collateral ligament laxity. Orthopaedic Clinics of North America. 25(3): 527-532. Carlsson A . M . (1983) Assessment of Chronic Pain. Pain 16: 87-101. Carnochan F.M.T., Abbott N.C., Spence V.A., et al. (1989). Blood flow and respiratory gas measurements over normal and inflamed skin and their modification by oxygen supplementation. In: Proceedings 14th Annual Meeting of EUBS. Aberdeen, Sept. 5-9; pp. 3740. Casti A . , Orlandini G., Troglio M . G . et al. (1993) Acute and chronic hyperbaric oxygen exposure in humans: effects on blood polyamines, adrenocorticotropin, and B-endorphin. Acta Endricrinologica. 129: 436-441. Cianci P. (1985). Thermal burns: preliminary observations with adjunctive hyperbaric oxygen therapy. In: Programs and Abstracts, 1st Winter Symposium on Baromedicine. Snowmass, CO, Jan. 15-17; 17-30. Cianci P., Petrone G., Shapiro R. et al. (1990a). Adjunctive hyperbaric oxygen therapy in treatment of severe burns. In: Joint Meeting on Diving and Hyperbaric Medicine, Undersea and Hyperbaric Medical Society, supplement to Vol. 17, Bethesda, M D , Aug. 11-18; p. 44. Cianci P., Petrone G., Shapiro R. et al. (1990b). Adjunctive hyperbaric oxygen reduces need for grafting in burned hands. In: Joint Meeting in Diving and Hyperbaric Medicine, Undersea and Hyperbaric Medical Society, supplement to Vol-61 7, Bethesda, M D , Aug. 11-18; p. 42.  93  Cianci P. and Sato R. (1994). Adjunctive hyperbaric oxygen therapy in treatment of thermal burns: a review. Burns. 20(1): 5-14. Clark J.K. and Fischer A . B . (1977). Oxygen toxicity and extension of tolerance in oxygen therapy. In: Davis JC and Hunt T K (eds.) Hyperbaric Oxygen Therapy, Undersea Medical Society, BethesdaMD. pp. 11-24 Clark J.K. Gelfard R., Stevens W.L. et al. (1991). Pulmonary function in men after oxygen breathing at 3.0 A T A for 3.5 hours. Journal of Applied Physiology. 71(3): 878-885. Clark J.M., Gelfard R , Stevens W.L. et al. (1990). Extension of pulmonary oxygen tolerance in man at 2.0 A T A by intermittent exposure on a 60: 15 oxygen: normoxic pattern in predictive studies VI. In: Joint Meeting on Diving and Hyperbaric Medicine, Undersea and Hyperbaric Medical Society, supplement td Vol. 17, Bethesda, M D , Aug. I 1 - 1 8; p. Colignon M . , Carlier A.B., Khuc T. et al. (1987). Hyperbaric oxygen therapy in acute ischemia and crush injuries. In: Baroni A, Oriani G (eds.) Proceedings of 13th annual meeting of European Undersea Biomedical Society. Palermo, Italy, Sept. 9-12; pp. 4-9. Connell D., Janzen D., Logan M . and Sooslma S.J. (1996) M R and clinical findngs of suspected grade II medial collateral injuries: a comparative analysis. (In progress). Coulson D.B. et al. (1966). Effect of hyperbaric oxygen on healing femur of rat. Surgical Forum. 17: 449. Criswell D.W. and Mehm W.J. (1992a). Effects of hypoxia and epidermal growth factor on fibroblast infiltration in mice. Undersea Biomedical Research. 19(5): 19-31. Criswell D.W. and Mehm W.J. (1992b). Effects of hypoxia and epidermal growth factor on fibroblast infiltration in rats. Undersea Biomedical Research. 19(5): 155-164. Davidkin N.F. (1977). Experience with clinical use of hyperbaric oxygenation in cases of trauma and their complications. Orthopediia Traumatologicia Protezirovanie. 9: 33-35.  94  Dixon J.S. and Bird H A . (1981). Reproducibility along a 10 cm vertical visual analog scale. Annals of Rheumatic Diseases, 40: 87-89. Doctor N . , Pandys S., and Supe A. (1992). Hyperbaric oxygen therapy in the diabetic foot. Journal of Postgraduate Medicine. 38(3): 112-114. Down J. (1994). Treatment studies: efficacy vs. effectiveness comment]. Journal of Neurosurgery. 80(5): 956. Downie W.W. et al. (1978) Studies with Pain Rating Scales. Rheumatic Diseases, 38: 558-559.  [letter,  Annals of  Favalli A . , Zottola V . , and Lovisetti G. (1990). External fixation and hyperbaric oxygen therapy in the treatment of open fractures of the tibial shaft. Undersea Biomedical Research. 17(suppl.): 172. Fonseca S. et al. (1992). Validation of a performance test for outcome evaluation of knee function. Clinical Journal of Sports Medicine 2(4): 251256. Foster J.H. (1992). Hyperbaric oxygenation treatment- contraindications and complications. Journal of Oral and Maxillofacial Surgery. 50(10): 10811086. Frank C. et al. (1983). Medial collateral ligament healing. The American Journal of Sports Medicine. 11(6): 379-389. Frank C. et al. (1985). Normal Ligament Properties and Ligament Healing. Clinical Orthopaedics and Related Research. 196: 15-25. Frank C. et al. (1994). Abnormality of the contralateral ligament after injuries of the medial collateral ligament: an experimental study in rabbits. The Journal of Bone and Joint Surgery. 76A(3): 403-412. Frigerio D., Lovisetti G., Lovisetti L. (1990). Effect of hyperbaric oxygen on survival of experimental skin flaps in rats. In: Joint Meeting on Diving and Hyperbaric Medicine, .Undersea and Hyperbaric Medical Society, supplement to Vol. 17, Bethesda, M D , 150.  95  Fullerton G.D. (1987). Magnetic resonance imaging signal concepts. Radiographics. 7(3): 579-596. Garvin G.J, Munk P.L. and Vellet A.D. (1993). Tears of the medial collateral ligament: magnetic resonance imaging findings and associated injuries. Canadian Association of Radiologists Journal. 44(3) 199-204. Geofert H. et al. (1992). Controversy over the benefit of hyperbaric oxygen to wound healing and angiogenesis in radiation-damaged tissue [letter, comment]. American Journal of Surgery. 163(4): 457. Gibbs J.H. et al. (1984). Histometric study of the localization of lymphocyte subsets and accessory cells in human Mantoux reactions. Journal of Clinical Pathology. 37:1227-1230. Goldhaber P. (1958). The effect of hyperoxia on bone resorption in tissue culture. Archives of Pathology. 66: 635. Gray D.K. Hamblin DL. (1976). The effects of hyperoxia upon bone organ culture. Clinical Orthopedics and Related Research. 119:225-230. Gregory E . M . and Fridovich I. (1973). Introduction to superoxide dismutase by molecular oxygen. Journal of Biotechnology. 114: 543-548. Grossman A.R. (1978). Hyperbaric oxygen in treatment of burns. Annals of Plastic Surgery. 1(2): 163-171. Haapaniemi T. (1995). Hyperbaric oxygen treatment attenuates glutathione depletion and improves metabolic restitution in postischemic skeletal muscle. Free Radical Research. 23 (2): 91 -101. Hammarlund C. et al. (1992). Hyperbaric oxygenation treatment of healthy volunteers with u.v.-irradiated blister wounds. Burns. 17(4): 296-301. Hammarlund C. and Sundberg T. (1994). Hyperbaric oxygen reduced size of chronic leg ulcers: a randomized double blind study. Plastic and Reconstructive Surgery. 93:829-834.  96  Harrison D.K. et al. (1994). Protective regulation of oxygen uptake as a result of reduced oxygen extraction during chronic fatigue. Advances in Experimental Medicine and Biology. 345: 789-796. Hargens A.R., Strauss M B . , Gershuni D.H. et al. (1983). Delayed hyperbaric oxygen reduces edema and necrosis of skeletal muscle following compartment syndrome. In: 8th Annual Conference of Clinical Applications of Hyperbaric Medicine. Long Beach, CA. June 8- 1 0. Hart G.B., Greilly R.R., Broussard N.D. et al. (1974). Treatment of burns with hyperbaric oxygen. Surgery, Gynecology and Obstetrics 139: 693-696. Hartup G.R., Bifaro C.A., Bifaro S. et al. (1992). The effect of hyperbaric oxygenation and fibrin sealant on wound healing. In: Annual Science Meeting, Undersea and Hyperbaric Medical Society, supplement to Vol. 18, Bethesda, M D , June 19-23; p. 56. Hastings D.E. (1980). The non-operative management of collateral ligament injuries of the knee joint. Clinical Orthopaedics and Related Research. 147: 22-28. Hill R.K. (1993). Is more better?: a comparison of different clinical hyperbaric treatment pressures- a preliminary report. In: Annual Science Meeting of the Undersea and Hyperbaric Medical Society, supplement to Vol. 20, Halifax, NS, July 7- 1 0; p. 12. Hohn D.C. (1977). Oxygen and leukocytic microbial killing. In: Davis JC and Hunt T K (eds.) Hyperbaric Oxygen Therapy, Undersea Medical Society, Bethesda M D . pp. 101-110. Holt J A G . (1980). Hyperbaric oxygen therapy in acute trauma. Annals of the Royal College of Surgeons of England 62(4):307-30S. Hughston J.C. et al. (1976). Classification of knee ligament instabilities. Journal of Bone and Joint Surgery. 58A(2): 159-172. Hunt T.Y., Niinikoski J., Zederfeldt J. et al. (1977). Oxygen in wound healing enhancement: cellular effects of oxygen. In: Davis JC, Hunt T K (eds.) Hyperbaric Oxygen Therapy, Undersea and Hyperbaric Medicine Society, Bethesda. p.p. 111-122.  97  Hunt T.K., Zederfeldt B., Goldstich T. (1969). American Journal of Surgery. 118: 521.  Oxygen and healing.  HuskissonE.C. (1974). Measurement of Pain. The Lancet, 11:9 1127-1131. Huskisson E.C. (1983). Visual Analog Scales. In Melzack R, Pain Measurement and Assessment. Raven Press, New York. Iapicca M . , Turrati A., Longoni C , Paul U . (1990). Necrosis of the femoral head and H B O : a therapeutical approach. In: Proceedings of the 10th International Conference on Hyperbaric Medicine. 167-170. Jain, K . K . (1990). Toronto.  Textbook of Hyperbaric Oxygen. Hogrefe and Huber,  James P.B., Scott B. and Allen M.W. (1993). Hyperbaric oxygen therapy in sports injuries. Physiotherapy 79(8): 571-2. Jensen J.A., Hunt T.K., Banda M.J., and Scheuenstuhl H , (1986). Effect of lactate, pyruvate and pH on secretion of angiogenesis and mitogenesis factors by macrophages. Laboratory Investigations. 54:574-578. Jones R.F., Unsworth LP. and Marosszeky J.E. (1978). Hyperbaric oxygen and acute spinal cord injuries in humans. Medical Journal of Australia. 2: 573574. Juva K. (1968). Hydroxylation of proline in the biosynthesis of collagen. Acta Physiologica Scandinavia. Suppl.: 308. Kaelin C M . , Im M.J., Myers R A M . et al. (1990). The effects of hyperbaric oxygen on free flaps in rats. Archives in Surgery. 123: 607: Kannus P. (1988). Long term results of conservatively treated medial collateral ligament injuries of the knee joint. Clinical Orthopaedics and Related Research. 226: 103-112. Kaplan E.Y., Demurov E.A., Fyodorova E.V. et al. (1981). Antioxidants and enhancement of an organism's resistance to oxygen intoxication. In: Abstracts, 7th International Congress of Hyperbaric Medicine. Moscow, Sept. 2-6; p.415.  98  Kataoka Y . et al. (1992). Effects of hyperbaric oxygen on femoral head osteonecrosis in spontaneously hypertensive rats. Acta Orthopedica Scandinavica. 63(5): 527-530. Kelly M . A . et al. (1991). M R imaging of the knee: clarification of its role. The Journal of Arthroscopic and Related Surgery. 71(1): 78-85. Kivisaari J. and Niinikoski J. (1975). Effects of hyperbaric oxygenation and prolonged hypoxia on healing of open wounds. Acta Chirigica Scandinavica. 141(1): 14-19. Knighton D.R., Hunt T.K., Scheuenstuhl H et al.. (1983). Oxygen tension regulates the expression of angiogenesis factor by macrophages. Science. 221:1283-5. Knighton D.R., Fiegel V.D., Halverston T. et al. (1990). antibiotic. Archives of Surgery. 125:97-100.  Oxygen as a  Knighton D R . , Silver I.A., and Hunt T K . (1981). Regulation of wound healing and angiogenesis - effects of oxygen gradients and inspired oxygen concentrations. Surgery. 90(2): 262. Korn H.N., Wheeler E.S., Miller T.A. (1977). Effect of hyperbaric oxygen on second degree burn wound healing. Archives of Surgery. 12:732-737. Langley G.B. and Shepperd H . (1985). The visual analog scale: its use in pain measurement. Rheumatology International. 24, 475-478. Lavan F.B. and Hunt T.K. (1990) Oxygen and wound healing. Plastic Surgery. 17(3): 463-72.  Clinics in  Loitz B.J. and Frank C.B. (1987). Biology and mechanics of ligament healing. Exercise Sport Reviews, p. 33-64. Lysholm J. and Gillquist J. (1982). Evaluation of knee ligament surgery results with special emphasis on the use of a scoring scale. The American Journal of Sports Medicine. 10(3): 150-154.  99  Maclntyre D L . etal. (1995). The presence of leukocytes, decreased strength and delayed soreness in muscle after eccentric exercise (dissertation). University of British Columbia. (In press). Mader J.T. (chair). (1989). Hyperbaric oxygen therapy: a committee report. Undersea and Hyperbaric Medical Society, Bethesda M D . Makley J.T., Helple K . G . , Chase S.W., Herndon C.H. (1967). The effect of reduced barometric pressure on fracture healing in rats. Journal of Bone and Joint Surgery. 49A: 903-14. Malnous E . G . (1977). Hyperbaric Oxygen in maxillofacial osteomyelitis, osteonecrosis and osteogenesis enhancement. In: Hyperbaric Oxygen Therapy. Bethesda, M D : Undersea Medical Society, Inc. 191-216. Malnous E.G. (1982). Osteogenesis enhancement utilizing hyperbaric oxygen therapy. HBO Review 3(3): 181. Marshall J.L., Fetto I F . and Botero P . M . (1977). Knee ligament injuries. Clinical Orthopaedics and Related Research. 123: 115-129. Mathieu D., Wattel F., Bouachour G. (1989). Prediction of final outcome post traumatic limb ischemia by transcutaneous oxygen measurements in hyperbaric oxygen. In: Schmutz J, Bakker D (eds.) Proceedings of 2nd Swiss Symposium on hyperbaric medicine. Foundation for Hyperbaric Medicine, Basel. 239-240. Matsuda T. et a/.(1993). The effect of hyperbaric oxygen on bone healing in spontaneously hypertensive rats. Acta Orthopedica Scandinavia. 6(1): 41-43. Mehm W.J., Pimsler K , Becker R.L. et al.. (1988). in vitro fibroblast proliferation and biosynthesis. Medicine. 3(4): 340-346.  The effect of oxygen on Journal of Hyperbaric  Melzack R. (1983). Pain Measurement and Assessment. Raven Press, New York. Merola L . and Picitelli F. (1978). Considerations on the use of hyperbaric oxygenation in treatment of burns. Annals of Navy Medicine. 83(3): 515-526.  100  Metzler T., Myers B. (1986). The effect of hyperbaric oxygen on the bursting strength and rate of vascularization of skin wounds in the rat. The American Surgeon 56(12):659-62. Miller M . and Ferris D. (1993). Measurement of Subjective Phenomena in Primary Care research: The Visual Analog Scale. Family Practice Research Journal, 13(1): 15-24. Mirowitz S.A. and Shu H . H . (1994). M R I evaluation of knee collateral ligaments and related injuries: comparisons of Tl-weighted, T2-weighted and fat-saturated T2 weighted sequences - correlations with clinical findings. Journal ofMagnetic Resonance Imaging. 4:725-732. Monies-Chass I. et al. (1977). Hyperbaric oxygen treatment as adjuvant to reconstructive vascular surgery in trauma. Injury. 8: 274-277. Muller W. et al. (1988). O A K knee evaluation, a new way to assess knee ligament injuries. Clinical Orthopaedics and Related Research. 232: 37-50. Narkowicz B . et al. (1993). Hyperbaric oxygen therapy increases free radical levels in the blood of humans. Free Radical Research Communications. 19(2): 71-78. Nelson A.G. et al. (1993). Skeletal muscle metabolic enzymes are altered by hyperbaric oxygenation treatment. Undersea Hyperbaric Medical Society. 20(3): 187-196. Niccole M.W., Thornton J.W., Danet R.T. et al. (1977). Hyperbaric oxygen in burn management: a controlled study. Surgery. 82(5): 727-733. Nida T.Y. et al. (1995). Effect of hypoxia on hyperbaric oxygen on cerebral edema following moderate fluid percussion of cortical impact injury on rats. Journal of Neurotrauma. 12(1): 77-85. Niinikoski J.R. (1977). Oxygen and wound healing. Clinical Plastic Surgery. 4: 361-374 Niinikoski J.R. and Hunt T K . (1972). Oxygen tensions in healing bone. Surgery, Gynecology and Obstetrics. 134: 746-750.  101  Niinikoski J.R., Grislis G., Hunt T.K. (1972). Respiratory gas tensions and collagen in infected wounds. Annals of Surgery. 175:588-593. Niinikoski JR., Pentinnen R, Kulonen E. (1970). Effects of H B O on fracture healing in rats, a biochemical study. Calcified Tissue Research. 4: 115-116, Nilsson L.P., Granstrom G., Rockert H.O.E. (1987). Accelerated bone healing of mandibular osteotomies by use of hyperbaric oxygen. In Maroni A Orrinni G (Eds.) Proceedings of the Thirteenth Annual Meeting of the European Undersea Biomedical Society. Palermo, Sicily. 190-4. Nilsson L.P., Albrektston T., Granstrom G., Rockert H.O.E. (1987). Accelerated bone mineralization utilizing H B O therapy: an experimental study in the rabbit using a bone harvest chamber (BHC). In Maroni A Orrinni G (eds.) Proceedings of the Thirteenth Annual Meeting of the European Undersea Biomedical SocietyPalermo, Sicily. 183-189 Niu A.K.C., Chao C , Lee A.C. et al. (1990). Burns treated with adjunctive hyperbaric oxygen therapy: a comparative study in humans. In: Joint Meeting on Diving and Hyperbaric Medicine, Undersea and Hyperbaric Medical Society, supplement to vol. 17, Bethesda, M D , Aug. 11-18; p. 43. Noyes F.R., McGinniss G H . and Mooar L.A. (1984). Functional disability in the anterior cruciate insufficient knee syndrome: review of knee rating systems and projected risk factors in determining treatment. Sports Medicine. 1: 278302. Nylander G. (1986). Tissue ischemia and HBO: an experimental study. Acta Chirgica Scandinavica 533: 109-110. Nylander G., Nordstrom H . and Eriksson E. (1984). Effects of hyperbaric oxygenation on edema formation after a scald burn. Burns, 10:193-196 Nylander G., Nordstrom H , Franzen L. et al. (1988). Effects of H B O therapy on post-ischemic muscle. Scandinavian Journal of Plastic and Reconstructive Surgery. 22: 31-39. Nylander G., Nordstrom H , Larsson J. et al. (1985). Reduction of post ischemic edema with hyperbaric oxygen. Journal of Plastic and Reconstructive Surgery. 76: 596-603.  102  Nylander G. et al. (1987). Metabolic effects of hyperbaric oxygen in postischemic muscle. Journal of Plastic and Reconstructive Surgery. 79: 9196. Orianni G , Barmini C. et al. (1987). H B O therapy in treatment of various orthopaedic injuries. Minerva Medicine. 73: 2983-2988. Pal M.P. and Hunt T.K. (1972). The effect of varying ambient oxygen tensions on wound metabolism and collagen synthesis. Surgery, Gynecology and Obstetrics 135: 561-567. Pellitteri P.K. etal. (1992). Influence of insensitive hyperbaric oxygenation on skin flap survival in a swine model. Archives of Otolaryngology and Head and Neck Surgery. 188(10): 1050-1054. Pentinnen R., Niinikoski J.R., Kulonen E. (1972). Hyperbaric oxygenation and fracture healing. Acta Chirigica Scandinavia. 138: 39-44. Peterson R.E. and Allen M.W. (1995) The adjunctive use of hyperbaric oxygen therapy for the treatment of sports injuries. Hyperbaric Medicine 1995, Columbia, South Carolina, March 20-22. Perrins I D . (1983). H B O and wound healing. In: Schmutz J (ed.) Proceedings of the 1st Swiss Symposium of Hyperbaric Oxygenation. Foundation for Hyperbaric Medicine, Basel, p.p. 119-132. 233: 31-50. Price P. et al. (1983). The validation of visual analog scales as ratio measures for chronic and experimental pain. Pain, 17: 45-46. Quinn S.F., Brown T.R. and Demlow T.A. (1993). M R imaging of patellar retinacular ligament injuries. Journal of Magnetic Resonance Imaging. 3: 843-847. Quirinia A. and Viidik A. (1995). The effect of hyperbaric oxygen on different phases of healing of ischemic flap wounds and incisional wounds in skin. British Journal of Plastic Surgery. 48(8): 583-589. Roth R.N. and Weiss L.D. (1994). Hyperbaric oxygen and wound healing [review]. Clinics in Dermatology. 12(1): 141-156.  103  Rowe P.A., Wright J., Randall R.L., Lynich J.K., Jokl P. and McCarthy F. (1992) Can M R I imaging effectively replace diagnostic arthroscopy. Radiology. 183: 335-339. Ruiz M . E . and Erickson S.J. (1994). Medial and lateral supporting structures of the knee: normal M R imaging anatomy and pathologic findings. M R I Clinics of North America. 2(3): 381-399. Sadegani K, Gottlief S.F., Van Meter K. et al. (1989). The effects of increased oxygen on surgical wounds. Undersea Biomedical Research. 16:42. Scher D . M . et al.. (1993). Effects of hyperbaric oxygenation on reperfusion of skeletal muscle. Undersea Hyperbaric Medical Society. 20(suppl.): 10. Schweitzer M . E . et al . (1995). Medial collateral ligament injuries: evaluation of multiple signs, prevalence and location of associated bone bruises, and assessment with M R imaging. Radiographics. 194: 825-829. Scott J. and Huskisson E.C. (1979). Vertical and Horizontal Visual Analog Scales. Annals of Rheumatic Diseases, 38: 560. Shafer M R . (1993). Use of hyberbaric oxygen as adjunct therapy to surgical debridement of complicated wounds. Seminars in Perioperative Nursing. 2(4): 256-262. Sheffield P.J. (1985). Tissue oxygen measurements with respect to soft tissue wound healing with normobaric and hyperbaric oxygen. Hyperbaric Oxygen Review. 6(1): 18-25. Sheffield P.J. (1988). Tissue oxygen measurements. In: Davis JC, Hunt T K (eds.) Problem wounds, the role of oxygen. Elsevier, New York, pp 17-5 1. Silver I S . (1978). Tissue P 0 2 changes in acute inflammation. Advances in Experimental Medical Biology. 94: 169-11 A. Sirsjo A. et al. (1993). Hyperbaric oxygen treatment enhances the recovery of blood flow and functional capillary density in postischemic striated muscle. Circulatory Shock. 40(1): 9-13.  104  Skyhar M.J., Hargens A.R., Strauss M B . et al. (1986). Hyperbaric oxygenation reduces edema and necrosis of skeletal muscles in compartment syndromes associated with hemorrhagic hypotension. Journal of Bone and Joint Surgery (Am). 68A: 1218-1224. Staples J.R. (1996). The effects of intermittent hyperbaric oxygen on pain perception and eccentric strength in a human injury model. Masters Thesis, University of British Columbia. (In Press) Staples J.R, Clement D.B., McKenzie D C . et al. (1996) The effects of intermittent hyperbaric oxygen on biochemical muscle metabolites of eccentrically exercised rats. Presented at 3rd Scientific Congress of Canadian Society of Exercise Physiology. Quebec City, Quebec. Oct. 26-28. Steer D . M . , Canada A . , Sashes R. et al. (1993). Effects of hyperbaric oxygenation on reperfusion of skeletal muscle. In: Annual Science Meeting, undersea and Hyperbaric Medical Society, supplement to Vol. 20, Halifax, NS, July 7-10; p. 10. Stewart R.J., Mason S.W., Kemp M . et al. (1992). Hyperbaric oxygen treatment of burn wounds: effect on ATP, phosphocreatine, and collagen synthesis in an animal model. In: Annual Science Meeting of the Undersea and Hyperbaric Medical Society, supplement to Vol. 19, Bethesda, N M , June 23-27; p. 55. Stewart R.J., Moore T. et al. (1994). Effects of free-radical scavengers and hyperbaric oxygen on random-pattern skin flaps. Archives of Surgery. 129(9): 982-987; discussion 987-988. Stoller D.W. (1993). Magnetic Resonance Imaging in Orthopaedics and Sports Medicine. Lippincott, Philadelphia, Penn. Storch T.G. and Talley G.D. (1988). Oxygen concentration regulates the proliferative response of human fibroblasts to serum growth factors. Experimental Cell Research. 175:317-325. Strauss M . B . (1981). Role of hyperbaric oxygen therapy in acute ischemias and crush injuries- an orthopaedic perspective. Hyperbaric Oxygen Review. 2(2): 87-106.  105  Strauss M B . , Hargens A.R., Gershuni D.G. et al. (I 983). Reduction of skeletal muscle necrosis using intermittent H B O in a model compartment syndrome. Journal of Bone and Joint Surgery. (Am). 65 A: 656-662. Strauss M . B . , Hart G.B. (1977). Clinical experience with hyperbaric oxygenation in fracture healing. In: Smith G (ed.) Proceedings of the 7th International Congress on Hyperbaric Medicine, University of Aberdeen Press, Aberdeen. 329-332. Strauss M . B . , Snow K., Greenberg D. et al. (1987). Hyperbaric oxygenation in management of skeletal muscle compartment syndrome. Presented at 9th International Congress of Hyperbaric Medicine. Sydney, Australia. March 14. Szelkely O., Szanto G. and Takats A. (1973). Hyperbaric oxygenation therapy in injured subjects. Injury. 4(4): 294-300. Targ G. et al.. (1993). Polyethylene glycol-conjugated superoxide dismutase protects against oxygen toxicity. Journal of Applied Physiology. 74(3): 14251431. Tegner Y . and Lysholm J. (1985). Rating systems in the evaluation of knee ligament injuries. Clinical Orthopaedics and Related Research. 198: 43-49. Tegner Y., Lysholm J., Lysholm M . , Gillquist J. (1986). A performance test to monitor and evaluate anterior cruciate ligament injuries. The American Journal of Sports Medicine. 14(2): 156-159. Tegner Y., Lysholm G , Lysholm J., Oberg B. (1984). Two year follow-up of conservative treatment of knee ligament injuries. Acta Orthopaedica Scandanavia. 55: 176-180. Tenenhaus M . et al. (1994). Treatment of burned mice with hyperbaric oxygen reduces mesenteric bacteria but not pulmonary neutrophil deposition. Archives of Surgery. 129(12): 1338-1342. Thorn S.R. (1990). Molecular mechanism for the antagonism of lipid peroxidation by hyperbaric oxygen. (Abstract.) Undersea Biomedical Research. 17(suppl.): 52.  106  Thorn S.R. and Elbukin M . E . (1991). Oxygen dependent antagonism of lipid peroxidation. Free Radical Biological Medicine. 10: 413-420. Thorn S.R. (1993). Leukocytes and carbon monoxide-mediated brain oxidative injury. Toxicology and Applied Pharmacology. 123:234-247. Thorn S.R. (1993). Functional inhibition of leukocyte b2 integrins by hyperbaric oxygen in carbon monoxide-mediated brain injury in rats. Toxicology andApplied Pharmacology. 123: 248-256. Tufano R., Del Gaudio A., and De Cillies P. (1988). Hyperbaric oxygen effects on pain relief in patients with vascular disease. Journal of Hyperbaric Medicine, Vol. 3. No. 1, 29-33. Uhl E. et al. (1994). Hyperbaric oxygen improves wound healing in normal and ichemic tissue. Plastic and Reconstructive Surgery. 93: 835-841. Van Opstal M . (1982). Treatment of a complicated, refractory femur fracture by surgery and hyperbaric therapy. In: Programs and abstracts, 7th Annual Conference on Clinical Applications Of Hyperbaric Oxygen Therapy, June 911. Vezzani G., Pizzola A., Stefanini H . et al. (1991) Polyamines, B-endorphins, adrenocorticotrophic hormone, and prolactin levels in prolonged exposure to hyperbaric oxygen. Journal of Hyperbaric Medicine. 6(3): 199-213. Vujnovic D. (1983). The influence of oxygen on fracture healing. In: Dekleva N (ed.), Symposium on Hyperbaric Medicine, Belgrad. pp. 57-61. Waisbren B.A. et al. (1982). Hyperbaric Oxygen in severe burns. Burns and Thermal Injury. 8(3): 176-179. Warren L.F., Marshall, J.L. and Girgis F. (1974). The prime static stabilizer of the medial side of the knee. The Journal of Bone and Surgery. 56A(4): 665674. Webster D.A. et al. (1996). Effect of hyperbaric oxygen on ligament healing in a rat model. Undersea Hyperbaric and Medical Society Annual Meeting: 23 (Suppl.); 13.  107  Wells C.H. et al. (1977). Tissue gas measurements during hyperbaric oxygen exposure. In: Proceedings of the 6th International Congress on Hyperbaric Medicine. Aberdeen, Scotland: Aberdeen University Press; pp. 118-124. Williamson J.A., Webb R.K., Leitch 1.0. et al. (1993). Preliminary report: a prospective, randomized, controlled trial of hyperbaric oxygen therapy in the management of adult thermal burns. In: Annual Science Meeting of the Undersea and Hyperbaric Medical Society, supplement to Vol. 20, Halifax NS, July 7-10; p. 24. Wilmeth J.B. and Gazani A. (1982). Hyperbaric oxygen as a adjunct to treatment of orthopaedic injuries with full thickness of skin grafts. In: Programs and Abstracts, 7th Annual Conference of Clinical and Applied Hyperbaric Oxygenation. Sydney, Australia.. June 9-11. Windsor R.E. et al. (1988). The hospital for special surgery knee ligament rating form. The American Journal of Knee Surgery 1 (2): 140-145. Woo S.L. et al. (1987). Treatment of the medial collateral ligament injury. The American Journal of Sports Medicine. 15(1): 22-29. Yeo J.D. et al. (1978). A preliminary report on ten patients with spinal cord injuries treated with HBO. Medical Journal of Australia. 2: 572-573. Young A., Stokes M . and lies J. (1987). Effects of joint pathology on muscle. Clinical Othopaedics and Related Research. 219:21-7. Young T. (1995). Hyperbaric oxygen in wound management [review]. British Journal of Nursing. 4(14): 796, 798-803. Yung N.C. and K o Chi N . (1982). Burns treated by adjunctive hyperbaric oxygenation in Taiwan ROC. In: Programs and Abstracts of 7th Annual Conference on Clinical and Applied Hyperbaric Oxygenation. Sydney, Australia. June 9-11. Zairns B. and Adams M.D. (1988). Knee injuries in sport. The New England Journal of Medicine. 318(15): 950-961. Zamboni W . A , Roth A.C., Bergmann B . A . et al. (1992). Experimental evaluation of oxygen in treatment of ischemic skeletal muscle. In: Annual  108  Science Meeting of the Undersea and Hyperbaric Medical Society, supplement to Vol. 18, Bethesda, M D , June 19-23; pp.56. Zamboni W.A., Roth A.C., Russell R.C. et al. (1990). Acute effects of hyperbaric oxygen in laser doppler flow in ischemic axial flaps. In: Joint Meeting on Diving and Hyperbaric Medicine, Undersea and Hyperbaric Medical Society, supplement to Vol. 17, Bethesda, N M , Aug. 11-18; pp.37. Zamboni W.A. et al. (1992). The effect of hyperbaric oxygenation on reperfusion on ischemic axial skin flaps: a laser doppler analysis. Annals of Plastic Surgery. 28(4): 339-341. Zamboni W.A. et al. (1993). Morphological analysis of microcirculation during reperfusion of ischemic muscle and the effect of hyperbaric oxygen . Plastic and Reconstructive Surgery. 91(6): 1110-1123. Zavesa P.Z., Shvabe J.J. and Abdushukorov A. (1977). Effect of hyperbaric oxygen therapy on reparative regeneration of the bone. Orpopediia Travmatyologiia I Protezirovanie. 11: 71-72. Zonis Z. et al. (1995). Salvage of severely injured limbs in children; a multidisciplinary approach. Pediatric Emergency Care. 11(3): 76-78. Zusman M . (1986). The absolute visual analog scale as a measure of pain intensity. Australian Journal of Physiology. 32(4): 244-246.  109  Appendix A Timeline for Protocol Day 1-3 following the injury • visit participating physician • complete Subject Questionnaire • physician completes objective tests • receive M R I #1 • begin physiotherapy Day 1-7 after the initial physicians visit • H B O treatments #1-5, 60 minutes per day at 2 A T A Day 7 after the initial physicians visit • follow-up visit #1 • complete Subject Questionnaire • physician to complete objective tests Day 7-14 after initial physician visit • H B O treatments #6-10, 60 minutes per day at 2 A T A Day 14 after initial physician visit • follow-up visit #2 • complete Subject Questionnaire • physician to complete objective tests Day 21 after initial clinical visit • follow up visit #3 • complete Subject Questionnaire • physician to complete objective tests • functional tests conducted Day 15 after initial M R I • follow-up M R I Every seven days after 3rd follow-up visit (till return to sport) • functional tests conducted  110  Appendix B Subject Questionnaire Name: Date of Injury: Date of Testing: Category Limp none (5) slight or periodical (3) severe or constant (0) Support full support (5) stick or crutch (3) weight-bearing impossible (0) Stair-climbing no problems (10) slightly impaired (4) one step at a time (2) unable to climb (0) Squatting no problems (5) slightly impaired (4) not past 90 degree (2) unable to squat (0) Walking, Runriing, and Jumping Instability never giving way (30) rarely during exertion (25) frequently during athletic or other severe exertion or unable to participate (20) occasionally in daily activities (10) every step (0)  111  Subject Knee Profile (cont'd) Walking , Riuining, and Jumping (cont'd) Pain none(30) inconstant and slight during sever exertion (25) marked on giving way (20) marked on severe exertion (15) marked on or after walking more than 2 km (10) marked on walking less than 2 km (5) constant and severe (0) Swelling none(10) with giving way (7) on severe exertion (5) on ordinary exertion (2) constant and severe (0) Atrophy of the thigh none (5) 1-2 cm (3) more than 2 cm (0) Total:  Have you returned to you pre-injury sport? YES If so, what was the date exactly?  NO  Please describe indicate your current level of pain along this line:  No pain  Worst Pain Experienced With This Injury  112  Appendix C Reliability Data Five subjects without injuries and five subjects with grade II M C L injuries participated in data collection for 2 weeks. Measurements for variables without established correlations found in literature were conducted as outlined in the methodology section. A pearson-product moment correlation was used to obtain the degree of correlation between the variables.  A summary of findings is  presented in table 17. Values obtained are presented in table 18.  Table 17 : Summary of pearson product moment correlations for test/re-test conditions. Measurement  Correlation r = 0.99 r = 0.98 r = 0.92 r = 0.84 r = 0. 98 r = 0.97  Knee Girth (KG) Thigh Girth (TG) Range of Motion (ROM) Maximum Flexion (MF) One Legged Jump Test (OLJ) Running Test Ratios (RTR)  Correlation values are considered high. This indicate good test reliability. These results suggest that measurements of these variables are reliable among males and females between the ages of 23 and 32.  113  Table 18: Variable Measurements for test/re-test correlations Subject  Test  KG  TG  ROM  MF  OLJ  RTR  146 145 153 152 147 147 148 146 146 147  34 34 27 29 33 33 34 32 31 33  168 171 134 139 150 152 158 156 162 165  3.81 3.83 4.03 3.99 4.05 4.06 3.96 4.01 3.92 3.89  .......(?.?},) 1 2 3 4 5  1 2 1 2 1 2 1 2 1 2  35.3 35.2 29.0 28.9 33.7 33.7 34.2 34.3 35.0 34.8  57.2 56.8 41.3 41.3 47.6 47.4 50.1 49.8 53.4 53.7  114  


Citation Scheme:


Citations by CSL (citeproc-js)

Usage Statistics



Customize your widget with the following options, then copy and paste the code below into the HTML of your page to embed this item in your website.
                            <div id="ubcOpenCollectionsWidgetDisplay">
                            <script id="ubcOpenCollectionsWidget"
                            async >
IIIF logo Our image viewer uses the IIIF 2.0 standard. To load this item in other compatible viewers, use this url:


Related Items