Differences in Hip Muscle Strength and Static Balance in Patients with Transfemoral Amputations Classified at Different K-Levels: A Preliminary Cross-Sectional Study.

BACKGROUND: Following amputation, patients with lower limb amputations (LLA) are classified into different functional mobility levels (K-levels) ranging from K0 (lowest) to K4 (highest). However, K-level classification is often based on subjective criteria. Objective measures that are able to differentiate between K-levels can help to enhance the objectivity of K-level classification. OBJECTIVES: The goal of this preliminary cross-sectional study was to investigate whether differences in hip muscle strength and balance parameters exist among patients with transfemoral amputations (TFA) assigned to different K-levels. METHODOLOGY: Twenty-two participants with unilateral TFA were recruited for this study, with four participants assigned to K1 or K2, six assigned to K3 and twelve assigned to K4. Maximum isometric hip strength of the residual limb was assessed in hip flexion, abduction, extension, and adduction using a custom-made diagnostic device. Static balance was investigated in the bipedal stance on a force plate in eyes open (EO) and eyes closed (EC) conditions. Kruskal-Wallis tests were used to evaluate differences between K-level groups. FINDINGS: Statistical analyses revealed no significant differences in the parameters between the three K-level groups (p>0.05). Descriptive analysis showed that all hip strength parameters differed among K-level groups showing an increase in maximum hip torque from K1/2-classified participants to those classified as K4. Group differences were also present in all balance parameters. Increased sway was observed in the K1/2 group compared to the K4 group, especially for the EC condition. CONCLUSION: Although not statistically significant, the magnitude of the differences indicates a distinction between K-level groups. These results suggest that residual limb strength and balance parameters may have the potential to be used as objective measures to assist K-level assignment for patients with TFA. This potential needs to be confirmed in future studies with a larger number of participants.

The Trp64Arg polymorphism of the beta 3-adrenergic receptor gene is not associated with obesity or type 2 diabetes mellitus in a large population-based Caucasian cohort.

The beta3-adrenergic receptor (3-BAR) is assumed to play a role in the regulation of energy balance by increasing lipolysis and thermogenesis. A recently detected allelic polymorphism (Trp64Arg polymorphism) has been suggested to contribute to the development of obesity and non-insulin-dependent diabetes mellitus. We examined the prevalence of the two 3-BAR alleles in Germany and looked for associations between 3-BAR genotype and metabolic disorders (obesity and type 2 diabetes mellitus). From over 6450 participants in the Diabetomobile Study, a nationwide epidemiologic study on the prevalence of metabolic disorders (carried out from 1993 to 1996 in Germany), 1259 participants were randomly chosen. The 3-BAR genotype status was determined by 3-BAR gene-specific genomic PCR and consecutive restriction fragment length polymorphism analysis. The frequencies of the different genotypes in the examined cohort were as follows: Trp64/Trp64, 88.3%; Trp64/Arg64, 10.8%; and Arg64/ Arg64, 0.8%. No significant differences between the different genotypes were found when comparing age, body mass index, weight, total and high-density lipoprotein (HDL) cholesterol, fasting insulin, HbA11, and blood pressure; neither did the type 2 diabetes mellitus participants in the different genotype groups differ significantly in terms of age of diabetes onset or HbA11. This is the largest population-based study on the Trp64Arg polymorphism reported yet. The Arg64 allele of the 3-BAR gene was found commonly in Germany. In our cohort, no significant associations between the Arg64 allele and metabolic disorders (e.g. obesity, type 2 diabetes mellitus, dyslipidemia, or hypertension) were detected.

RAPD analysis reveals low genetic variability in the endangered light-footed clapper rail.

Numbers of light-footed clapper rails Rallus longirostris levipes, an endangered bird inhabiting southern California salt marshes, have substantially declined from historic levels. RAPD (randomly amplified polymorphic DNA) analysis was employed to assess the genetic variability within and among four of the largest remaining light-footed clapper rail populations. A single, larger population of the endangered Yuma clapper rail Rallus longirostris yumanensis was used for comparison. A total of 325 RAPD primers were tested on DNA from a subset of five clapper rails composed of a single representative for each of the four light-footed clapper rail populations and a representative for the single Yuma clapper rail population. Of the 1338 amplified bands (loci) surveyed in these five representative birds, approximately 1% were polymorphic, indicating the level of differentiation across all loci is quite low. Nine primers yielding these 16 polymorphic bands were used to analyse 48 individuals from five populations. Five of these bands were polymorphic in both subspecies, six were polymorphic only within the light-footed clapper rails, and five were polymorphic only within the Yuma clapper rail samples. Considering the few bands that were polymorphic among the light-footed clapper rail populations, a surprisingly high level of population differentiation (GST = 0.28) was found. This is in accord with the results of AMOVA analyses which show that a fairly high percentage of the limited variability among the rails is due to either differences between subspecies or differences between the light-footed rail populations. Because inbreeding depression is suspected and overall genetic distances between populations are low, movement of light-footed clapper rails from larger populations into smaller ones might be considered as a management strategy. Employing RAPDs as one of a series of assays is useful in revealing the population structure of genetically depauperate species.

Diabetic neuropathy 3 years after successful pancreas and kidney transplantation.

Twenty-seven patients with successful transplantation and a control group of 14 patients with early rejection of the pancreas graft but functioning kidney graft were examined in a prospective study for 3 yr. Before transplantation, all patients had long-standing type I diabetes with advanced secondary complications, including end-stage diabetic nephropathy. After transplantation in the patients of both groups, kidney function was almost normal. Mean HbA1 levels were normal in the group with pancreas graft survival. In the control group, HbA1 levels were, on average, 1.5% higher compared with the group with pancreas survival (P = 0.00005). After 3 yr, the patients with functioning pancreas graft showed fewer symptoms (mean difference 1.0 in a symptom score ranging from 0 to 16, P = 0.004) compared with the control group. No statistically significant difference between both groups concerning clinical signs of polyneuropathy could be observed. In the pancreas and kidney transplantation group, peroneal and median nerve conduction velocities increased 7.2 m/s (P < 0.01) and 3.5 m/s (P < 0.05), respectively, whereas no increase was registered in the control group. The change of median and sural sensory nerve conduction velocities, peroneal and median compound muscle action potentials, and sural and median sensory action potentials was insignificant. In conclusion, although the improvement of clinical symptoms and neurophysiological signs of polyneuropathy was modest in the pancreas and kidney transplantation group, our data suggest that successful pancreas transplantation is able not only to halt the progression of diabetic polyneuropathy but also to improve it to some extent even at a far advanced stage.

Cross-sectional study of peripheral microcirculation in diabetic patients with microangiopathy: influence of pancreatic and kidney transplantation.

Diabetic vascular lesions and peripheral autonomic neuropathy are both closely linked to long-term metabolic control of diabetes. Transcutaneous oxygen tension (PtcO2) measurements were made to elucidate whether autonomic neuropathy disturbs the cutaneous microcirculatory blood flow, and whether long-term glucose normalization ameliorates such impairment. Twenty-eight type 1 (insulin-dependent) diabetic patients in whom clinically significant macroangiopathy had been excluded by angiography were studied, subdivided into group A (n = 14; before simultaneous pancreas/kidney transplantation (SPKT); mean age 35 years, range 22-51 years; mean duration of diabetes 24 years, (range 15-32) years and group B (n = 14; mean 31 months, range 2-101 months, after successful SPKT; mean age 35 years, range 19-56 years; mean duration of diabetes 22 years, range 14-29 years). On addition there was a group (group C) of age- and sex-matched healthy control subjects (n = 14; mean age 35 years, range 23-62 years). PtcO2 measurements included basal recordings at 44 degrees C on the leg and the foot, functional recordings at 44 degrees C after arterial occlusion of the limb for 4 min, measurements during breathing 5 l oxygen per minute and finally while standing up (stand up dP20/dt). All subjects underwent extensive cardiac autonomic testing. In this cross-sectional study the recordings of basal values and of the functional parameters after arterial occlusion and during breathing oxygen did not differ significantly between groups A, B and C.(ABSTRACT TRUNCATED AT 250 WORDS)

High incidence of carpal tunnel syndrome in diabetic patients after combined pancreas and kidney transplantation.

Fifty-eight patients with long-standing type 1 (insulin-dependent) diabetes were studied prospectively after combined pancreas and kidney transplantation for a mean observation period of 47.9 months (range 17-116 months). Thirty-three per cent of these patients (19/58) developed carpal tunnel syndrome after a mean interval of 1.7 years (range 3 months-5 years). This rate is about twice that in type 1 diabetic patients. The manifestation of carpal tunnel syndrome was not significantly associated with worsening of diabetic polyneuropathy or with deterioration of kidney or pancreas function. In all but one patient symptoms improved without surgical intervention. This study suggests that patients after combined pancreas and kidney transplantation have an increased risk of carpal tunnel syndrome for which the etiology and pathophysiology are unknown. In most patients no surgical intervention is necessary.

Follow-up study of sensory-motor polyneuropathy in type 1 (insulin-dependent) diabetic subjects after simultaneous pancreas and kidney transplantation and after graft rejection.

The influence of successful simultaneous pancreas and kidney transplantation on peripheral polyneuropathy was investigated in 53 patients for a mean observation period of 40.3 months. Seventeen patients were followed-up for more than 3 years. Symptoms and signs were assessed every 6 months using a standard questionnaire, neurological examination and measurement of sensory and motor nerve conduction velocities. While symptoms of polyneuropathy improved (pain, paraesthesia, cramps, restless-legs) and nerve conduction velocity increased, there was no change of clinical signs (sensation, muscle-force, tendon-reflexes). Following kidney-graft-rejection there was a slight decrease of nerve conduction velocity during the first year, which was not statistically significant. Following pancreas-graft rejection there was no change of nerve conduction velocity during the first year. Comparing the maximum nerve conduction velocity of the patients with pancreas-graft-rejection to the nerve conduction velocities of these patients at the end of the study, there was a statistically significant decrease of 6.5 m/s. In conclusion, we believe that strict normalization of glucose metabolism alters the progressive course of diabetic polyneuropathy. It may be stabilized or partly reversed after successful grafting even in long-term diabetic patients.

Effect of pancreatic and/or renal transplantation on diabetic autonomic neuropathy.

Thirty-nine Type 1 (insulin-dependent) diabetic patients were studied prospectively after simultaneous pancreas and kidney (n = 26) and kidney grafting alone (n = 13) by measuring heart rate variation during various maneuvers and answering a standardized questionnaire every 6 to 12 months post-transplant. While age, duration of diabetes, and serum creatinine (168.1 +/- 35.4 vs 132.7 +/- 17.7 mumol/l) were comparable, haemoglobin A1 levels were significantly lower (6.6 +/- 0.2 vs 8.5 +/- 0.3%; p less than 0.01) and the mean observation time longer (35 +/- 2 vs 25 +/- 3 months; p less than 0.05) in the pancreas recipients when compared with kidney transplanted patients. Heart rate variation during deep breathing, lying/standing and Valsalva manoeuver were very similar in both groups initially and did not improve during follow-up. However, there was a significant reduction in heart rate in the pancreas recipient group. Autonomic symptoms of the gastrointestinal and thermoregulatory system improved more in the pancreas grafted subjects, while hypoglycaemia unawareness deteriorated in the kidney recipients. This study suggests that long-term normoglycaemia by successful pancreatic grafting is able to halt the progression of autonomic dysfunction.

Long-term results in pancreatic transplantation with special emphasis on the use of prolamine.

Our pancreatic transplantation programme was initiated in 1979. Since then a total of 102 pancreas transplantations have been performed, blocking exocrine secretion using the duct occlusion technique with prolamine. Early non-immunological complications are frequent. The long-term results (9 years) in combined pancreas and kidney transplanted patients are satisfying: the survival rate for pancreas is 38% and 54% for kidney. Patient survival rate in this period is 85%. Beyond the first year post-transplant the exocrine activity disappears whereas the endocrine function remains well preserved.

Quality of life in type 1 (insulin-dependent) diabetic patients prior to and after pancreas and kidney transplantation in relation to organ function.

Improvement of the quality of life in Type 1 (insulin-dependent) diabetic patients with severe late complications is one of the main goals of pancreas and/or kidney grafting. To assess the influences of these treatment modalities on the different aspects of the quality of life a cross-sectional study in 157 patients was conducted. They were categorized into patients pretransplant without dialysis (n = 29; Group A), pretransplant under dialysis (n = 44; Group B), posttransplant with pancreas and kidney functioning (n = 31; Group C), post-transplant with functioning kidney, but insulin therapy (n = 29; Group D), post-transplant under dialysis and insulin therapy again (n = 15; Group E) and patients after single pancreas transplantation and rejection, with good renal function, but insulin therapy (n = 9; Group F). All patients answered a mailed, self-administered questionnaire (217 questions) consisting of a broad spectrum of rehabilitation criteria. The results indicate a better quality of life in Groups C and D as compared to the other groups. In general the scores are highest in C, but without any significant difference to D. Impressive significant differences between C or D and the other groups were found especially in their satisfaction with physical capacity, leisure-time activities or the overall quality of life.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic and hormonal studies of type 1 (insulin-dependent) diabetic patients after successful pancreas and kidney transplantation.

Long-term normalization of glucose metabolism is necessary to prevent or ameliorate diabetic complications. Although pancreatic grafting is able to restore normal blood glucose and glycated haemoglobin, the degree of normalization of the deranged diabetic metabolism after pancreas transplantation is still questionable. Consequently glucose, insulin, C-peptide, glucagon, and pancreatic polypeptide responses to oral glucose and i.v. arginine were measured in 36 Type 1 (insulin-dependent) diabetic recipients of pancreas and kidney allografts and compared to ten healthy control subjects. Despite normal HbA1 (7.2 +/- 0.2%; normal less than 8%) glucose disposal was normal only in 44% and impaired in 56% of the graft recipients. Normalization of glucose tolerance was achieved at the expense of hyperinsulinaemia in 52% of the subjects. C-peptide and glucagon were normal, while pancreatic polypeptide was significantly higher in the graft recipients. Intravenous glucose tolerance (n = 21) was normal in 67% and borderline in 23%. Biphasic insulin release was seen in patients with normal glucose tolerance. Glucose tolerance did not deteriorate up to 7 years post-transplant. In addition, stress hormone release (cortisol, growth hormone, prolactin, glucagon, catecholamines) to insulin-induced hypoglycaemia was examined in 20 graft recipients and compared to eight healthy subjects. Reduced blood glucose decline indicates insulin resistance, but glucose recovery was normal, despite markedly reduced catecholamine and glucagon release. These data demonstrate the effectiveness of pancreatic grafting in normalizing glucose metabolism, although hyperinsulinaemia and deranged counterregulatory hormone response are observed frequently.

Diabetic retinopathy and pancreas transplantation: a 3-year follow-up.

The effect of simultaneous pancreas and kidney transplantation on diabetic retinopathy was studied in a prospective study with 30 patients (57 eyes) and 15 control subjects (26 eyes), patients who lost the pancreas, but preserved kidney function. There was no significant difference between the groups after a mean observation time of more than 35 months (a range of 12 to 96 months). Both populations had a stable retinopathy during follow-up. This seems to be a consequence of the far advanced retinopathy (mean duration of type 1 diabetes was 22 years) and the high percentage of coagulated eyes (81% and 85%, respectively), but is not related to the organ transplantation. A closer look at the few patients who did not receive laser coagulation (14 patient and 6 control eyes), produced a different result. Four control eyes experienced a significant deterioration of the retinopathy which had been stable before rejection. It is the most important and so far never mentioned aspect of this study, that periods of destabilisation are a definite threat for the retinopathy. Nevertheless, it seems questionable whether we will ever be able to make a definite statement on the pancreas-eye relation, as long as the transplantation must be restricted to carefully selected late-stage diabetic subjects.

[Pancreas transplantation in Type I diabetic patients]. / Pankreastransplantation bei Typ-I-Diabetikern.

Successful pancreas transplantation can result in the longterm normalization of glucose metabolism. Since most pancreas recipients already have severe diabetic complications, and the observation period after transplantation is rather short, an assessment of the effect of complete glucose normalization on these diabetic changes is problematic. It has, however, been shown that the development of diabetic nephropathy can be prevented, peripheral microcirculation improved, and autonomic and peripheral neuropathy and retinopathy stabilized. These positive effects are, possibly, in part due to the elimination of uremia, since most patients receive both a pancreas and a kidney. The aim must be to perform pancreas transplantation in an early stage of diabetes, even though remarkable improvements have also been reported in terminal stages of the disease, and the quality of life of these patients has been significantly improved.

[Significance and diagnosis of autonomic neuropathy in diabetes]. / Bedeutung und Diagnostik der autonomen Neuropathie bei Diabetes.

The results of studies performed to date would appear to show that autonomic neuropathy (ANP) in diabetics can involve any organ system. The earliest and most common manifestation is seen in the cardiovascular system, and finds expression as orthostatic phenomena, resting tachycardia, and "rigid pulse". Simple, non-invasive tests permit accurate quantification and follow-up. ANP in the gastrointestinal tract manifests as a motility disturbance, and the resulting delay in absorption might be the cause of inexplicable blood sugar fluctuations. A phenomenon of decisive importance for the diabetic is the lowering of his awareness of a hypoglycemic state. For this reason, intensive training of the diabetic in the self-determination of blood sugar and requirement-matched insulin dosage are thus of extreme importance. Disturbances of sexual function, which are all too rarely mentioned, usually put a heavy strain on the diabetic. Medical care of diabetics prior to, during and after surgery should give due consideration to cardiac, pulmonary and gastrointestinal ANP involvement. In view of the limited therapeutic possibilities, prevention of ANP should receive top priority.

Metabolic control and effect on secondary complications of diabetes mellitus by pancreatic transplantation.

After successful pancreatic transplantation blood glucose can be normalized without exogenous insulin, although oral and intravenous glucose tolerance remains impaired in 10-45% of the patients. There is no significant deterioration of glucose control with time in most patients. Since most recipients of pancreatic grafts have far advanced secondary diabetic lesions and the observation time after grafting is rather short, the effects of pancreatic transplantation on these complications are difficult to interpret. However, the development of diabetic nephropathy can be prevented, skin microcirculation improves significantly, while autonomic and peripheral neuropathy and diabetic retinopathy remain stable or improve slightly in most patients. But these ameliorations may be in part due to elimination of uraemia, since in almost all patients combined pancreas/kidney transplantations were performed. It is concluded that pancreas grafting probably has to be performed much earlier in the course of diabetes, although the improvement in the quality of life is striking even in the end-stage diabetics studied so far.