Field monitoring of sprinting power-force-velocity profile before, during and after hamstring injury: two case reports.

Very little is currently known about the effects of acute hamstring injury on over-ground sprinting mechanics. The aim of this research was to describe changes in power-force-velocity properties of sprinting in two injury case studies related to hamstring strain management: Case 1: during a repeated sprint task (10 sprints of 40 m) when an injury occurred (5th sprint) in a professional rugby player; and Case 2: prior to (8 days) and after (33 days) an acute hamstring injury in a professional soccer player. A sports radar system was used to measure instantaneous velocity-time data, from which individual mechanical profiles were derived using a recently validated method based on a macroscopic biomechanical model. Variables of interest included: maximum theoretical velocity (V0) and horizontal force (F(H0)), slope of the force-velocity (F-v) relationship, maximal power, and split times over 5 and 20 m. For Case 1, during the injury sprint (sprint 5), there was a clear change in the F-v profile with a 14% greater value of F(H0) (7.6-8.7 N/kg) and a 6% decrease in V0 (10.1 to 9.5 m/s). For Case 2, at return to sport, the F-v profile clearly changed with a 20.5% lower value of F(H0) (8.3 vs. 6.6 N/kg) and no change in V0. The results suggest that the capability to produce horizontal force at low speed (F(H0)) (i.e. first metres of the acceleration phase) is altered both before and after return to sport from a hamstring injury in these two elite athletes with little or no change of maximal velocity capabilities (V0), as evidenced in on-field conditions. Practitioners should consider regularly monitoring horizontal force production during sprint running both from a performance and injury prevention perspective.

Recovery of gait pattern after medial patellofemoral ligament reconstruction for objective patellar instability.

Gait pattern alterations were previously reported in association with objective patellar instability (OPI). Gait pattern comparison between a series of patients having undergone medial patellofemoral ligament (MPFL) reconstruction and a sample of control subjects. Thirty patients at 6 months postoperatively after MPFL reconstruction and thirty control subjects were enrolled in the study for a clinical and biomechanical assessment including gait analysis at three selected walking rates using the GAITRite(®) system. The mean raw IKDC score was 73 (± 19), and the mean Kujala knee function was 84 (± 17.5). The study of gait did not demonstrate any significant difference between the two groups at a normal and fast walking rate. At a 10 km/h running speed, the single-support phase was significantly shortened by a mean 2.33% (p < 0.05), the swing phase by a mean 2.64% (p < 0.05) and the double-support phase by a mean 3.49% (p < 0.05) on the operated side. MPFL reconstruction reported good midterm functional and clinical results in the management of OPI. At 6 months postoperatively, the patient gait pattern was similar to that observed in healthy subjects at a normal and fast walking speed. However, our study revealed persistent gait abnormalities at a 10 km/h running speed. These gait alterations seemed to be related to the ligament reconstruction in itself due to the higher strain applied on the reconstructed MPFL during running cycle (10 km/h). Level of evidence IV.

Effects of hamstring-emphasized neuromuscular training on strength and sprinting mechanics in football players.

The objective of this study was to examine the effects of a neuromuscular training program combining eccentric hamstring muscle strength, plyometrics, and free/resisted sprinting exercises on knee extensor/flexor muscle strength, sprinting performance, and horizontal mechanical properties of sprint running in football (soccer) players. Sixty footballers were randomly assigned to an experimental group (EG) or a control group (CG). Twenty-seven players completed the EG and 24 players the CG. Both groups performed regular football training while the EG performed also a neuromuscular training during a 7-week period. The EG showed a small increases in concentric quadriceps strength (ES = 0.38/0.58), a moderate to large increase in concentric (ES = 0.70/0.74) and eccentric (ES = 0.66/0.87) hamstring strength, and a small improvement in 5-m sprint performance (ES = 0.32). By contrast, the CG presented lower magnitude changes in quadriceps (ES = 0.04/0.29) and hamstring (ES = 0.27/0.34) concentric muscle strength and no changes in hamstring eccentric muscle strength (ES = -0.02/0.11). Thus, in contrast to the CG (ES = -0.27/0.14), the EG showed an almost certain increase in the hamstring/quadriceps strength functional ratio (ES = 0.32/0.75). Moreover, the CG showed small magnitude impairments in sprinting performance (ES = -0.35/-0.11). Horizontal mechanical properties of sprint running remained typically unchanged in both groups. These results indicate that a neuromuscular training program can induce positive hamstring strength and maintain sprinting performance, which might help in preventing hamstring strains in football players.

Force-velocity profile: imbalance determination and effect on lower limb ballistic performance.

This study sought to lend experimental support to the theoretical influence of force-velocity (F-v) mechanical profile on jumping performance independently from the effect of maximal power output (P max ). 48 high-level athletes (soccer players, sprinters, rugby players) performed maximal squat jumps with additional loads from 0 to 100% of body mass. During each jump, mean force, velocity and power output were obtained using a simple computation method based on flight time, and then used to determine individual linear F-v relationships and P max values. Actual and optimal F-v profiles were computed for each subject to quantify mechanical F-v imbalance. A multiple regression analysis showed, with a high-adjustment quality (r²=0.931, P<0.001, SEE=0.015 m), significant contributions of P max , F-v imbalance and lower limb extension range (h PO ) to explain interindividual differences in jumping performance (P<0.001) with positive regression coefficients for P max and h PO and a negative one for F-v imbalance. This experimentally supports that ballistic performance depends, in addition to P max , on the F-v profile of lower limbs. This adds support to the actual existence of an individual optimal F-v profile that maximizes jumping performance, a F-v imbalance being associated to a lower performance. These results have potential strong applications in the field of strength and conditioning.

De novo designed proteins neutralize lethal snake venom toxins.

Snakebite envenoming remains a devastating and neglected tropical disease, claiming over 100,000 lives annually and causing severe complications and long-lasting disabilities for many more1,2. Three-finger toxins (3FTx) are highly toxic components of elapid snake venoms that can cause diverse pathologies, including severe tissue damage3 and inhibition of nicotinic acetylcholine receptors (nAChRs) resulting in life-threatening neurotoxicity4. Currently, the only available treatments for snakebite consist of polyclonal antibodies derived from the plasma of immunized animals, which have high cost and limited efficacy against 3FTxs5,6,7. Here, we use deep learning methods to de novo design proteins to bind short- and long-chain α-neurotoxins and cytotoxins from the 3FTx family. With limited experimental screening, we obtain protein designs with remarkable thermal stability, high binding affinity, and near-atomic level agreement with the computational models. The designed proteins effectively neutralize all three 3FTx sub-families in vitro and protect mice from a lethal neurotoxin challenge. Such potent, stable, and readily manufacturable toxin-neutralizing proteins could provide the basis for safer, cost-effective, and widely accessible next-generation antivenom therapeutics. Beyond snakebite, our computational design methodology should help democratize therapeutic discovery, particularly in resource-limited settings, by substantially reducing costs and resource requirements for development of therapies to neglected tropical diseases.

Injuries and illnesses during the 2011 Paris European Athletics Indoor Championships.

This study aimed to record and analyse incidence and characteristics of injuries and illnesses incurred during the Indoor Athletics Championships. During the 2011 European Indoor Athletics Championships in Paris, incidence and characteristics of new injuries and illnesses were recorded prospectively by physicians and physiotherapists from national teams and local organizing committee in 631 registered athletes. Around 70% of athletes were covered by the medical teams (response rate: 84%). Thirty injuries, including eight time-loss injuries, were reported, representing an incidence of 47.5 injuries and 29.4 time-loss injuries per 1000 registered athletes. Injury and time-loss injury risk were highest in heptathlon and hurdles. Three-quarters of injuries affected the lower extremity. Thigh strain was the most common diagnosis (n = 7; 23%). Noncontact trauma (n = 9; 30%) was the predominant cause. A total of 18 illnesses were reported. Incidence of illnesses was 28.5 per 1000 registered athletes, with 17% resulting in time lost from sport. Upper respiratory tract infection was the most common diagnosis (n = 8; 44%) followed by upper respiratory tract allergy (n = 3; 17%) and gastroenteritis (n = 3; 17%). Injury and illness incidence and severity were lower during the 2011 European Indoor Athletics Championships than during outdoor championships, probably due to the shorter duration, the fewer number of events, and shorter sprint distances.

Isokinetic rotator muscles fatigue in glenohumeral joint instability before and after Latarjet surgery: a pilot prospective study.

We aimed to analyze the changes in isokinetic internal (IR) and external (ER) rotator muscles fatigue (a) in patients with non-operated recurrent anterior instability, and (b) before and after shoulder surgical stabilization with the Bristow-Latarjet procedure. Thirty-seven patients with non-operated unilateral recurrent anterior post-traumatic instability (NG) were compared with 12 healthy subjects [control group (CG)]. Twenty patients with operated recurrent anterior instability group (OG) underwent isokinetic evaluation before and 3, 6, and 21 months after Bristow-Latarjet surgery. IR and ER muscles strength was evaluated with Con-Trex® dynamometer, with subjects seated and at a 45° shoulder abduction angle in scapular plane. IR and ER muscle fatigue was determined after 10 concentric repetitions at 180° · s(-1) through the fatigue index, the percent decrease in performance (DP), and the slope of peak torque decrease. There were no differences in rotator muscles fatigue between NG and CG. In OG, 3 months post-surgery, IR DP of operated shoulder was significantly (P < 0.001) higher than presurgery and 6 and 21 months post-surgery. Rotator muscles fatigability was not associated with recurrent anterior instability. After surgical stabilization, there was a significantly higher IR fatigability in the operated shoulder 3 months post-surgery, followed by recovery evidenced 6 months post-surgery and long-term maintenance over 21 months.

Shoulder strength imbalances as injury risk in handball.

This study was conducted to analyze whether internal (IR) and external (ER) rotator shoulder muscles weakness and/or imbalance collected through a preseason assessment could be predictors of subsequent shoulder injury during a season in handball players. In preseason, 16 female elite handball players (HPG) and 14 healthy female nonathletes (CG) underwent isokinetic IR and ER strength test with use of a Con-Trex® dynamometer in a seated position with 45° shoulder abduction in scapular plane, at 60, 120 and 240°/s in concentric and at 60°/s in eccentric, for both sides. An imbalanced muscular strength profile was determined using -statistically selected cut-offs from CG values. For HPG, all newly incurred shoulder injuries were reported during the season. There were significant differences between HPG and CG only for dominant eccentric IR strength, ER/IR ratio at 240°/s and for IRecc/ERcon ratio. In HPG, IR and ER strength was higher, and ER/IR ratios lower for dominant than for nondominant side. The relative risk was 2.57 (95%CI: 1.60-3.54; P<0.05) if handball players had an imbalanced muscular strength profile. In youth female handball players IR and ER muscle strength increases on the dominant side without ER/IR imbalances; and higher injury risk was associated with imbalanced muscular strength profile.

Injuries in Youth and National Combined Events Championships.

In major track and field competitions, the most risky discipline is the combined event. Therefore, we aimed to record and analyze the incidence and characteristics of sports injuries incurred during the Youth and National Combined Events Championships. During the French Athletics Combined Events Championships in 2010, all newly occurred injuries were prospectively recorded by the local organising committee of physicians and physiotherapists working in the medical centres at the stadium, in order to determine incidence and characteristics of newly occurred injuries. In total, 51 injuries and 9 time-loss injuries were reported among 107 registered athletes, resulting in an incidence of 477 injuries and 84 time-loss injuries per 1,000 registered athletes. Approximately 72% of injuries affected lower limbs and 60% were caused by overuse. Thigh strain (17.6%) was the most common diagnosis. 14 dropouts were recorded, 8 were caused by an injury (57.1%). During the National and Youth Combined Events Championships, over one third of the registered athletes incurred an injury, with an injury incidence higher than in international elite track and field competitions. Interestingly, this higher injury risk concerned the younger population affecting immature musculoskeletal structures. In combined events, preventive interventions should mainly focus on overuse and thigh injuries.

Recovery of rotators strength after Latarjet surgery.

The purposes of this study were to prospectively determine changes in rotator cuff strength before and after surgical shoulder stabilization by Bristow-Latarjet procedure and to better estimate time needed for rotator cuff strength recovery. 20 patients with recurrent anterior posttraumatic shoulder dislocation underwent internal (IR) and external (ER) rotator isokinetic evaluation before and 3, 6 and 21 months after Bristow-Latarjet surgery. In a seated position with 45° of shoulder abduction in the scapular plane, both shoulders were evaluated concentrically with a Con-Trex® isokinetic dynamometer at 180°âˆ™s (- 1), 120°âˆ™s (- 1) and 60°âˆ™s (- 1). 3 months post-surgery, IR and ER strength of the operated shoulder were significantly lower than before surgery (- 28 ± 20% for IR, - 17 ± 17% for ER) (P<0.05). At 6 and 21 months post-surgery, IR and ER strength were comparable to strength before surgery; strength recovery is seen at 6 months post-surgery with long-term maintenance at 21 months. Given the weakness 3 months post-surgery, return to sports (including overhead and contact sports) should be discussed, and 6 months post-surgery may be a better point for an athlete to resume practicing sports. Isokinetic rotator cuff strength evaluation appears to be relevant in helping to determine the need of continuing strength rehabilitation. Pre-surgical evaluation contributes to the relevance of later comparisons.

Proteomics and histological assessment of an organotypic model of human skin following exposure to Naja nigricollis venom.

Snakebite envenoming was reintroduced as a Category A Neglected Tropical Disease by the World Health Organization in 2017. Since then, increased attention has been directed towards this affliction and towards the development of a deeper understanding of how snake venoms exert their toxic effects and how antivenoms can counter them. However, most of our in vivo generated knowledge stems from the use of animal models which do not always accurately reflect how the pathogenic effects of snake venoms manifest in humans. Moreover, animal experiments are associated with pain, distress, and eventually animal sacrifice due to the toxic nature of snake venoms. Related to this, the implementation of the 3Rs principle (Replacement, Reduction, and Refinement) in the use of experimental animals in snakebite envenoming research is recommended by the World Health Organization. Therefore, more humane experimental designs and new in vitro/ex vivo alternatives for experimental animals are sought after. Here, we report the use of an organotypic model of human skin to further elucidate the pathophysiology of the dermonecrotic effects caused by the venom of the black-necked spitting cobra, Naja nigricollis, in humans. The goal of this study is to expand the repertoire of available models that can be used to study the local tissue damages induced by cytotoxic venoms.

Thymus-independent development and negative selection of T cells expressing T cell receptor alpha/beta in the intestinal epithelium: evidence for distinct circulation patterns of gut- and thymus-derived T lymphocytes.

We demonstrate that mouse intestinal intraepithelial lymphocytes (IEL) can be divided into subsets based on the differential expression of functional T cell receptor alpha/beta (TCR-alpha/beta) signaling complexes. Two subsets, CD4+ 8 alpha + beta - and CD8 alpha + beta -, are refractory to stimulation with anti-TCR-alpha/beta and contain high frequencies of potentially self-reactive cells. In contrast, the CD4+ and CD8 alpha + beta + IEL subsets are responsive to anti-TCR-alpha/beta and depleted of potentially self-reactive cells. The analysis of fetal liver radiation chimeras using adult thymectomized recipients demonstrates that the four TCR-alpha/beta + IEL subsets are generated in normal numbers in the absence of the thymus. Moreover, expression of the major histocompatibility complex class II-encoded I-E molecule and Mls1a in the gut of the athymic host results in the negative selection of potentially self-reactive T cells expressing V beta 11 and V beta 6, respectively, from those IEL subsets that express functional TCR-alpha/beta signaling complexes. Neither the spleen nor the Peyer's patches of athymic recipients contain T cells of donor origin. In contrast, normal numbers of phenotypically and functionally mature CD4+ and CD8 alpha + beta + T cells of donor origin are found in the lamina propria of chimeric animals. The phenotypic analysis of lymphocytes obtained from Ly5 congenic parabionts reveals that peripheral T cells migrate rapidly to the Peyer's patches and lamina propria, but not to the intestinal epithelium. Taken together, these results demonstrate that the intestinal epithelium is a thymus-independent site of T lymphopoiesis, where selection of the T cell repertoire involves the deletion of potentially self-reactive cells in situ. Moreover, the appearance of donor-derived, phenotypically mature T cells, exclusively in the lamina propria of athymic radiation chimeras, suggests that mature IEL expressing functional TCR-alpha/beta migrate to this site.

Influence of rugby practice on shoulder internal and external rotators strength.

Shoulder injuries are frequent in rugby, and muscular deficiency and/or imbalance of the internal (IR) and external (ER) shoulder rotators are considered as probable mechanisms of shoulder injuries. The purpose of this study was to investigate whether the rotators strength imbalances occur in rugby players by comparing IR and ER strength and ER/IR ratios between rugby players (RP) and nonathletic subjects. Fourteen RP and 19 healthy nonathletic subjects were evaluated in this cross-sectional controlled study with a Con-Trex ((R)) dynamometer. IR and ER isokinetic strength were performed at 60 degrees . s (-1) and 240 degrees . s (-1) in concentric, and 60 degrees . s (-1) in eccentric, for both sides. Strength values were higher for RP than nonathletic ones ( P<0.05), but if peak torque was normalised to body weight, there were no significant differences. There was no significant effect of laterality on the IR and ER peak torque, and no significant influence of rugby and/or laterality on the ER/IR ratio. In conclusions, our results reported no rotators muscles imbalance in RP as a possible risk factor of glenohumeral injury.

Reduced fibre size, capillary supply and mitochondrial activity in constitutional thinness' skeletal muscle.

AIM: Constitutional thinness (CT) is a rare condition of natural low body weight, with no psychological issues, no marker of undernutrition and a resistance to weight gain. This study evaluated the skeletal muscle phenotype of CT women by comparison with a normal BMI control group. METHODS: Ten CT women (BMI < 17.5 kg/m2 ) and 10 female controls (BMI: 18.5-25 kg/m2 ) underwent metabolic and hormonal assessment along with muscle biopsies to analyse the skeletal muscular fibres pattern, capillarity, enzymes activities and transcriptomics. RESULTS: Constitutional thinness displayed similar energy balance metabolic and hormonal profile to controls. Constitutional thinness presented with lower mean area of all the skeletal muscular fibres (-24%, P = .01) and percentage of slow-twitch type I fibres (-25%, P = .02, respectively). Significant downregulation of the mRNA expression of several mitochondrial-related genes and triglycerides metabolism was found along with low cytochrome c oxidase (COX) activity and capillary network in type I fibres. Pre- and post-mitochondrial respiratory chain enzymes levels were found similar to controls. Transcriptomics also revealed downregulation of cytoskeletal-related genes. CONCLUSION: Diminished type I fibres, decreased mitochondrial and metabolic activity suggested by these results are discordant with normal resting metabolic rate of CT subjects. Downregulated genes related to cytoskeletal proteins and myocyte differentiation could account for CT's resistance to weight gain.

Training programs for children: literature review.

INTRODUCTION: Training programs are increasingly being prescribed for occupational therapy for adults affected by chronic illness and/or handicap, but their use is more recent for children and teenagers. OBJECTIVE: A review of the literature to synthesize information concerning training programs for children, whether healthy or with disease or handicap, considering the target population, methodology, the results and limitations. METHODS: We searched the Medline database with use of the key words retraining, training, training programs, physical activity, physical training, fitness program, sport, children, disability, and handicap. We also searched references of the selected articles for appropriate studies. DISCUSSION/CONCLUSION: Physical activity seems to be a good means of primary preventing adverse health in the healthy child and secondary prevention in children with chronic disease or handicap. Thus, training programs could be adapted and integrated into the global treatment of sick or handicapped children in the health care situation or in the home. These programs are feasible and do not undermine children's health, but few studies have shown clear data on the methods of the programs. The suggested training programs, not always validated, included two to five sessions from 30 to 60 min/week, for 6-16 weeks, of variable activity and intensity, adapted to the condition and the objectives of therapy. Training programs adapted to children should be validated to allow their accessibility by health care professionals dealing with children with chronic disease and/or handicap.

Translation and validation of the French version of the Western Ontario Shoulder Instability Index (WOSI): WOSI-Fr.

INTRODUCTION: The Western Ontario Shoulder Instability Index (WOSI) is a specific self-administered questionnaire measuring the functional impact on patients with chronic glenohumeral instability. In its English version, it is valid, reliable, and sensitive to change. The objective of the present study was to provide a linguistic and cross-cultural adaptation of the original version of the WOSI to French and to assess the metrologic properties of this version in patients with chronic shoulder instability. MATERIAL AND METHODS: The WOSI was translated and adapted both linguistically and culturally to French (WOSI-Fr) according to current guidelines. The metrologic properties of the WOSI-Fr were analyzed in the following groups - unoperated patients with chronic shoulder instability (UOG), operated patients with chronic shoulder instability (OG), patients with instability (TotG=UOG+OG), and control patients (ContG) - through analysis of the construct validity by comparing the WOSI-Fr with the Rowe, Walch-Duplay, QuickDASH, and VAS pain scores, and through analysis of reliability through the reproducibility of internal consistency. RESULTS: The WOSI-Fr version was established and then accepted by an expert group (n=7). There was a statistically significant correlation between the WOSI and the different pain and function scores for TotG, OG, and UOG (except with the VAS pain score and the QuickDASH for UOG). Reproducibility (n=27) was good: the ICC value for the total score was 0.88 (95% CI, 0.47-0.98), varying from 0.80 to 0.94 according to the four domains of the WOSI-Fr, and from 0.70 to 0.94 for the different items separately. For TotG, Cronbach's alpha was 0.953, the SEM and the MDC were 120.2 (5.7%) and 333 (15.9%), respectively. CONCLUSION: The French version of the WOSI (WOSI-Fr) is available, adapted linguistically and culturally, valid, and reliable. We recommend using it in following up patients with shoulder instability. LEVEL OF EVIDENCE: Prospective, level 2.

Ground-reactive forces after hallux valgus surgery: comparison of Scarf osteotomy and arthrodesis of the first metatarsophalangeal joint.

AIMS: The purpose of this study was to analyse the biomechanics of walking, through the ground reaction forces (GRF) measured, after first metatarsal osteotomy or metatarsophalangeal joint (MTP) arthrodesis. PATIENTS AND METHODS: A total of 19 patients underwent a Scarf osteotomy (50.3 years, standard deviation (sd) 12.3) and 18 underwent an arthrodesis (56.2 years, sd 6.5). Clinical and radiographical data as well as the American Orthopaedic Foot and Ankle Society (AOFAS) scores were determined. GRF were measured using an instrumented treadmill. A two-way model of analysis of variance (ANOVA) was used to determine the effects of surgery on biomechanical parameters of walking, particularly propulsion. RESULTS: Epidemiological, radiographical and clinical data were comparable in the two groups and better restoration of propulsive function was found after osteotomy as shown by ANOVA (two way: surgery × foot) with a surgery effect on vertical forces (p < 0.01) and a foot effect on anteroposterior impulse (p = 0.01). CONCLUSION: Patients who underwent Scarf osteotomy had a gait pattern similar to that of their non-operated foot, whereas those who underwent arthrodesis of the first (metatarsophalangeal) MTP joint did not totally recover the propulsive forces of the forefoot. TAKE HOME MESSAGE: The main findings of this study were that after surgical correction for hallux valgus, patients who underwent scarf osteotomy had a gait pattern similar to that of their non-operated foot in terms of forefoot propulsive forces (Fz3, Iy2), whereas those who underwent arthrodesis of the first MTP joint had not. Cite this article: Bone Joint J 2016;98-B:641-6.

Isokinetic muscle strengthening for knee osteoarthritis: A systematic review of randomized controlled trials with meta-analysis.

OBJECTIVE: To assess the level of scientific evidence and the place in the rehabilitation framework of isokinetic muscle strengthening (IMS) for knee osteoarthritis (OA). METHODS: A systematic review of the English literature in MEDLINE via PubMed, the Cochrane Library, and PEDro databases for only randomized comparative trials. Data that were sufficiently homogeneous underwent comprehensive meta-analysis. Methodological assessment was done by using the CLEAR scale for non-pharmacologic trials. RESULTS: We identified articles for 9 trials (696 patients). All trials were of low to moderate quality. Tolerance of IMS was considered good. Improvement in muscle strength was better with an IMS program than no treatment or an isometric exercise but did not differ with an aerobic program. We found an important effect for pain (standardized mean difference 1.218 [95% CI 0.899-1.54], P<0.001) and functional Lequesne index (1.61 [0.40-2.81], P=0.009) and a moderate effect for the Western Ontario and McMaster Universities Osteoarthritis Index subscore C for disability (0.58 [0.04-1.11], P=0.03). CONCLUSIONS: IMS is an effective way to propose dynamic muscle strengthening for knee OA rehabilitation and has a significant effect on pain and disability. Because of the weak methodology and the great heterogeneity of studies, particularly in IMS protocol and outcome measures, insufficient data are available to provide guidelines about efficacy and strategy. Future clinical trials are needed, but more attention should be paid to the methods of such studies to clarify the role of IMS in the therapeutic armamentarium of knee OA.

Polygenic nature of spontaneous diabetes in the rat. Permissive MHC haplotype and presence of the lymphopenic trait of the BB rat are not sufficient to produce susceptibility.

We describe the phenotypic characteristics of animals in the fifth backcross-intercross generation of a breeding program in which the RT1 u haplotype and the phenotypic trait responsible for the T-lymphopenia of BB rats have been transferred to the ACI background. In this generation of animals, 24% were lymphopenic with decreased numbers of PBL expressing CD5, TCR alpha, and RT6. The PBL of the lymphopenic animals had a decreased mitogenic response to ConA. All of the nonlymphopenic animals were homozygous for RT6.2. Phenotypic analysis of intestinal IEL revealed that this was also the case for the lymphopenic animals. Moreover, IEL of the lymphopenic animals exhibited a pattern of staining (increased numbers of TCR alpha beta+CD4+CD8+ and decreased numbers of TCR alpha beta+CD4-CD8+) similar to that of BB DP animals. The ACI.1U(BB)-lymphopenic animals, although having two of the genetic traits associated with the expression of spontaneous diabetes mellitus, uniformly fail to develop diabetes. Breeding studies in which these animals were crossed with BB and hBB rats suggest that other genes are necessary for development of overt diabetes.