Knee varus-valgus motion during gait--a measure of joint stability in patients with osteoarthritis?

OBJECTIVE: To determine the validity of varus-valgus motion as a measure of knee joint stability by establishing the relationship of varus-valgus motion with muscle strength, joint proprioception, joint laxity and skeletal alignment in patients with knee osteoarthritis (OA). METHODS: Sixty-three patients with OA of the knee were tested. Varus-valgus motion was determined with a video-based optoelectronic gait analysis system. Muscle strength was measured using a computer-driven isokinetic dynamometer. Proprioceptive acuity was assessed by establishing the joint motion detection threshold in the anterior-posterior direction. Laxity was assessed using a device which measures the passive angular deviation of the knee in the frontal plane. Alignment was assessed using a goniometer. Regression analyses were performed to assess the relationship between varus-valgus motion, muscle strength, joint proprioception, joint laxity and skeletal alignment. RESULT: Varus-valgus motion was not related to muscle strength, joint proprioception, joint laxity and skeletal alignment. CONCLUSIONS: Knee joint stability cannot be measured as varus-valgus motion. Rather, a number of independent factors seem to contribute to the process of stabilization of the knee joint.     

Contrast in the efficacy of hDAF mouse hearts between ex vivo perfusion and transplantation into primates

Abstract: In recent experiments, in which we compared hDAF transgenic rat hearts perfused with 15% human serum in the Langendorff device and hDAF rat hearts transplanted into cynomolgus monkeys, we demonstrated that in the ex vivo heart perfusion model both homozygous and heterozygous hDAF hearts survived longer as nontransgenic controls. Surprisingly, we found that only homozygous hDAF hearts were protected against hyperacute rejection in vivo. The first aim of this study was to determine whether perfusion of mouse hearts with higher human serum concentrations or human blood might explain some of the differences found in survival time of the recently performed experiments with rat heart xenografts. Secondly, we investigated whether the observed differences in survival times of rat xenografts between in vivo and ex vivo transplantation would also hold for mouse hearts transgenic for hDAF. An ex vivo model was used to perfuse hDAF mouse hearts and controls with human serum or blood, and hDAF transgenic hearts and controls were transplanted into cynomolgus monkeys. hDAF transgenic mouse hearts survived significantly longer than their controls when perfused with 15% human serum, but no difference was found when 30% human serum was used, or when these hearts were transplanted into cynomolgus monkeys. However, in both the in vivo and ex vivo models the amount of PMNs adhering to the vascular endothelium was significantly lower in hDAF transgenes as compared with their controls. In conclusion, in the ex vivo situation, the efficacy of hDAF transgenesis in preventing HAR is limited by serum complement concentration.     

State of the art of where we are at using stem cells for stress urinary incontinence

AIMS: This review aims to discuss: 1) the neurophysiology, highlighting the importance of the middle urethra, and treatment of stress urinary incontinence (SUI); 2) current injectable cell sources for minimally-invasive treatment; and 3) the potential of muscle-derived stem cells (MDSCs) for the delivery of neurotrophic factors. METHODS: A PUB-MED search was conducted using combinations of heading terms: urinary incontinence, urethral sphincter, stem cells, muscle, adipose, neurotrophins. In addition, we will update the recent work from our laboratory. RESULTS: In anatomical and functional studies of human and animal urethra, the middle urethra containing rhabdosphincter, is critical for maintaining continence. Cell-based therapies are most often associated with the use of autologous multipotent stem cells, such as the bone marrow stromal cells. However, harvesting bone marrow stromal stem cells is difficult, painful, and may yield low numbers of stem cells upon processing. In contrast, alternative autologous adult stem cells such as MDSCs and adipose-derived stem cells can be easily obtained in large quantities and with minimal discomfort. Not all cellular therapies are the same, as demonstrated by the differences in safety and efficacy from muscle-sourced MDSCs versus myoblasts versus fibroblasts. CONCLUSIONS: Transplanted stem cells may have the ability to undergo self-renewal and multipotent differentiation, leading to sphincter regeneration. In addition, such cells may release, or be engineered to release, neurotrophins with subsequent paracrine recruitment of endogenous host cells to concomitantly promote a regenerative response of nerve-integrated muscle. The dawn of a new paradigm in the treatment of SUI may be near.     

Comparison between the C-leg microprocessor-controlled prosthetic knee and non-microprocessor control prosthetic knees: a preliminary study of energy expenditure, obstacle course performance, and quality of life survey

This study investigated energy expenditure and obstacle course negotiation between the C-leg and various non-microprocessor control (NMC) prosthetic knees and compared a quality of life survey (SF-36v2) of use of the C-leg to national norms. Thirteen subjects with unilateral limb loss (12 with trans-femoral and one with a knee disarticulation amputation) participated in the study. The mean age was 46 years, range 30-75. Energy expenditure using both the NMC and C-leg prostheses was measured at self-selected typical and fast walking paces on a motorized treadmill. Subjects were also asked to walk through a standardized walking obstacle course carrying a 4.5 kg (10 lb) basket and with hands free. Finally, the SF-36v2 was completed for subjects while using the C-leg. Statistically significant differences were found in oxygen consumption between prostheses at both typical and fast paces with the C-leg showing decreased values. Use of the C-leg resulted in a statistically significant decrease in the number of steps and time to complete the obstacle course. Scores on a quality of life index for subjects using the C-leg were above the mean for norms for limitation in the use of an arm or leg, equal to the mean for the general United States population for the physical component score and were above this mean for the mental component score. Based on oxygen consumption and obstacle course findings, the C-leg when compared to the NMC prostheses may provide increased functional mobility and ease of performance in the home and community environment. Questionnaire results suggest a minimal quality of life impairment when using a C-leg for this cohort of individuals with amputation.     

A ten-year experience with laparoscopic treatment of splenic cysts.

BACKGROUND AND OBJECTIVES: The management of symptomatic splenic cysts lacks clear, evidence-based guidelines due to its low incidence. Recently, laparoscopic treatment has been described. We present our experience with the laparoscopic management of solitary splenic cysts with a review of the existing literature, and recommendations for therapy. METHODS: All patients who underwent laparoscopic treatment of splenic cysts over a 10-year period were identified. The medical records of these 9 patients were reviewed. RESULTS: All surgeries were performed laparoscopically, with no conversions. Two patients underwent cyst decapsulation, and 7 patients underwent cyst unroofing. No major complications occurred. Recurrence occurred in 33.3% of patients; unroofing had a recurrence rate of 42.9% compared with 0% after decapsulation. Pseudocysts were found in 66.7% of patients and true cysts on final pathology were found in 33.3%. CONCLUSIONS: Laparoscopic decapsulation and unroofing of splenic cysts are safe procedures that confer the advantages of both splenic preservation and minimally invasive surgery. Cyst unroofing has a high recurrence and should be selectively used. Laparoscopic cyst decapsulation is associated with longer operative time, but should be considered as first-line therapy.     

Combination of anti-CD4 with anti-LFA-1 and anti-CD154 monoclonal antibodies promotes long-term survival and function of neonatal porcine islet xenografts in spontaneously diabetic NOD mice

Type 1 diabetes mellitus (T1DM) is caused by the autoimmune destruction of pancreatic islet beta-cells, which are required for the production of insulin. Islet transplantation has been shown to be an effective treatment option for TIDM; however, the current shortage of human islet donors limits the application of this treatment to patients with brittle T1DM. Xenotransplantation of pig islets is a potential solution to the shortage of human donor islets provided xenograft rejection is prevented. We demonstrated that a short-term administration of a combination of anti-LFA-1 and anti-CD154 monoclonal antibodies (mAbs) was highly effective in preventing rejection of neonatal porcine islet (NPI) xenografts in non-autoimmune-prone B6 mice. However, the efficacy of this therapy in preventing rejection of NPI xenografts in autoimmune-prone nonobese diabetic (NOD) mice is not known. Given that the current application of islet transplantation is for the treatment of T1DM, we set out to determine whether a combination of anti-LFA-1 and anti-CD154 mAbs could promote long-term survival of NPI xenografts in NOD mice. Short-term administration of a combination of anti-LFA-1 and anti-CD154 mAbs, which we found highly effective in preventing rejection of NPI xenografts in B6 mice, failed to promote long-term survival of NPI xenografts in NOD mice. However, addition of anti-CD4 mAb to short-term treatment of a combination of anti-LFA-1 and anti-CD154 mAbs resulted in xenograft function in 9/12 animals and long-term graft (>100 days) survival in 2/12 mice. Immunohistochemical analysis of islet grafts from these mice identified numerous insulin-producing beta-cells. Moreover, the anti-porcine antibody as well as autoreactive antibody responses in these mice was reduced similar to those observed in naive nontransplanted mice. These data demonstrate that simultaneous targeting of LFA-1, CD154, and CD4 molecules can be effective in inducing long-term islet xenograft survival and function in autoimmune-prone NOD mice.     

As time goes by: temporal constraints on emotional activation of inferior medial prefrontal cortex

To investigate the influence of stimulus duration on emotional processing, we measured changes of regional cerebral blood flow (rCBF) in 14 healthy subjects who viewed neutral or emotional images presented for 3 or 6 s. Presentation for 3 s reproduced the previous result of higher rCBF in inferior medial prefrontal cortex (IMPC) during neutral than emotional stimulation. Six-second presentation reverted this relationship, with activity in IMPC being higher during emotional stimulation. Prolonged stimulus presentation attenuated the rise of rCBF associated with emotions in left parietal cortex and cerebellar hemisphere. We speculate that the different rCBF during neutral and emotional stimulation for 6 s is a consequence of attention divided between the emotional stimuli and their associations. Thus, prefrontal activity rises when a cognitive task accompanies emotional stimulation because several cognitive processes compete for attention. The IMPC may serve the mechanism of attention underlying the concept of a default mode of brain function, selecting among competitive inputs from multiple brain regions rather than just processing emotions. The results emphasize the importance of implicit cognitive processing during emotional activation, however, unintended.     

Routine Laboratory Testing Every 4 Versus Every 6 Weeks for Patients on Maintenance Hemodialysis: A Quality Improvement Project

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