BMP-2 gene polymorphisms and osteoporosis: the Rotterdam Study.

After reported associations of variations in the BMP-2 gene with osteoporosis in small populations, we studied the association of the BMP-2 gene polymorphisms Ser37Ala and Arg190Ser with osteoporosis in 6353 men and women from the Rotterdam Study. We did not observe an association of these variants with BMD, bone loss, hip structural analysis parameters, and fracture risk. INTRODUCTION: Bone morphogenetic protein 2 (BMP-2) plays a role in osteoblast differentiation. BMP-2 gene variation has previously been associated with osteoporosis in various small populations, but current evidence remains inconclusive about the exact association with osteoporosis. Therefore, we studied the association of two polymorphisms located in the BMP-2 gene (Ser37Ala and Arg190Ser) and haplotypes defined by these polymorphisms with BMD, rates of bone loss, parameters of hip structural analysis (HSA), and fractures in the Rotterdam Study, a large prospective cohort study of diseases in the elderly. MATERIALS AND METHODS: Databases were searched for polymorphisms and haplotype blocks in the BMP-2 gene region. Allele frequencies for Ser37Ala and Arg190Ser were determined in 60 blacks and 110 Chinese from Coriell panels. Genotype data on Ser37Ala and Arg190Ser were available for 6353 individuals from the Rotterdam Study population. Haplotype alleles defined by Ser37Ala and Arg190Ser were inferred using PHASE software. Genotype and haplotype analyses for BMD (measured at the lumbar spine and femoral neck), bone loss per year (measured at the femoral neck), and HSA were performed using AN(C)OVA. Fractures were analyzed using a Cox proportional-hazards model and logistic regression. All outcomes were adjusted for age, height, and weight. RESULTS: Allele frequencies were 2.5% for Ala37 and 40.2% for Ser190, whereas haplotype allele frequencies were 57.28% (Ser37Arg190), 40.19% (Ser37Ser190), 2.50% (Ala37Arg190), and 0.02% (Ala37Ser190). For BMD, bone loss, HSA outcomes, and (incident) fractures, no differences could be seen between genotype and haplotype groups. Conclusions: In this large population-based cohort of Dutch whites, we conclude that the BMP-2 Ser37Ala and Arg190Ser polymorphisms or haplotypes thereof are not associated with parameters of osteoporosis.     

Sleep and recovery in physicians on night call: a longitudinal field study

Background  

It is well known that physicians' night-call duty may cause impaired performance and adverse effects on subjective health, but there is limited knowledge about effects on sleep duration and recovery time. In recent years occupational stress and impaired well-being among anaesthesiologists have been frequently reported for in the scientific literature. Given their main focus on handling patients with life-threatening conditions, when on call, one might expect sleep and recovery to be negatively affected by work, especially in this specialist group. The aim of the present study was to examine whether a 16-hour night-call schedule allowed for sufficient recovery in anaesthesiologists compared with other physician specialists handling less life-threatening conditions, when on call.     

Long-term results of above knee femoro-popliteal bypass depend on indication for surgery and graft-material.

OBJECTIVE To determine the long-term results of above-knee femoro-popliteal bypass with autologous saphenous vein (SV) or expanded polytetrafluoroethylene (ePTFE) in routine surgical practice. METHODS: Data from the Swedish vascular registry, Swedvasc, was reviewed retrospectively. Patients with bypass surgery in 1996 and 1997 were assessed 5-7 years later. Data were gathered from the case-records and from clinical follow-up. The composite endpoint of graft failure included death within 30 days, occlusion, major amputation, extension of the graft to below-knee position and removal of an infected graft. Kaplan-Meier curves and Cox' proportional hazard ratios were calculated. RESULTS: Four hundred and ninety-nine patients undergoing bypass for critical limb ischemia (CLI) (56%) or claudication (44%), SV (28%) or ePTFE (72%), were included. There were no significant differences in patient characteristics between patients with SV or ePTFE. CLI and ePTFE were risk factors for graft failure. For patients with both claudication and CLI SV grafts yielded better long-term results than ePTFE grafts ( p <0.03) and ( p <0.003), respectively. Symptom aggravation after graft occlusion was almost exclusively restricted to ePTFE grafts. CONCLUSIONS: Femoro-popliteal bypass above-knee with SV gives good long-term results, especially for claudication. ePTFE grafts cannot be recommended in claudicants, since occlusion occurs often and frequently leads to CLI.     

Renal sensitivity to angiotensin II in type 1 diabetes

The role of the renin angiotensin system for the regulation of kidney function in diabetes mellitus is uncertain. Results from studies in diabetic animals suggest that a reduced activity in this system contributes to the renal hyperperfusion and hyperfiltration in diabetes. The renal sensitivity to angiotensin II in diabetic patients is also unknown. Changes in renal hemodynamics were measured after infusion of two low doses of angiotensin II in ten young type 1 diabetic patients without complications and in ten healthy controls. The renin and angiotensin II levels were found to be the same in both groups. The baseline glomerular filtration rate was higher in the diabetics. During the highest angiotensin II dose, the 51Cr-EDTA and PAH clearance decreased 14 +/- 15 and 157 +/- 118 ml/min in the diabetics and 14 +/- 15 and 146 +/- 109 in the controls respectively. The changes in blood pressure and renal vascular resistance or sodium excretion did not differ between the groups. A malfunction of the renin angiotensin system is thus unlikely as a cause of the glomerular hyperfiltration in type 1 diabetes.     

Is obesity still a risk factor in renal transplantation?

At our center, since 1982, a body mass index (BMI) of less than 30 has been a prerequisite for placing a patient on the waiting list for renal transplantation. This decision was made because obese transplant recipients seemed to have a less than favorable post-transplant outcome. The aim of this study was to evaluate whether this requirement is still justified. Forty-six patients with a BMI above 30 underwent primary cadaveric renal transplantation between 1972 and 1993. For each of these obese patients, five consecutive non-obese (BMI 20–25) control patients were selected. Patient and graft survival, causes of graft loss, and acute rejection rate were evaluated for the two patient groups before and after the year 1982. Within the first 30 post-transplant days, one patient (2 %) and 11 grafts (24 %) were lost in the group of obese patients whereas seven patients (3 %) and 36 grafts (16 %) were lost in the control group. Among the obese patients, renal circulatory complications were a major cause of graft loss. In the period 1973–1981, the 1-year patient survival rate was 65 % among obese patients versus 75 % among controls from 1982 to 1993, this was 90 % versus 93 %. From 1973 to 1981, the 1-year graft survival rate was 25 % among obese patients versus 53 % among controls (P < 0.05); from 1982 to 1993, it was 68 % versus 84 % (P = NS). Multivariate analysis showed that the immunosuppressive regimen, age of the patient, BMI, and cold ischemia time of the graft had a significant influence on graft survival. The acute rejection rate within the first 30 days was 28 % among obese patients and 35 % among controls (P = NS). We conclude that a BMI below or equal to 30 is still justified as a prerequisite for placement on the waiting list for renal transplantation, for despite an overall improvement, the outcome of renal transplantation in obese patients remains worse than that in non-obese patients. Received: 3 February 1997 Received after revision: 4 April 1997 Accepted: 8 April 1997     

The Influence of a New Timing Strategy of Band Adjustment on the Vomiting Frequency and the Food Consumption of Obese Women Operated with Laparoscopic Adjustable Silicone Gastric Banding (LAP-BAND)

Objective: To evaluate the effects of a new timing strategy of band adjustment on the short-term outcome of obese women operated with adjustable silicone gastric banding. Subjects: The outcome of 30 women without binge-eating disorder operated with laparoscopic adjustable silicone gastric banding with a wider intraoperatory band calibration (LAP-BAND) was compared to that of 30 body mass index-matched women without binge-eating disorder previously operated with adjustable silicone gastric banding (ASGB) applied by laparotomy with the usual intraoperatory band calibration. The patients were evaluated 3, 6 and 12 months after surgery. Measurements: (1) weight loss; (2) total daily energy intake; (3) percent as liquid, soft or solid food; (4) vomiting frequency; (5) rate of postoperative percutaneous band adjustments; (6) rate of band-related complications. Results: Both the weight loss and the daily energy intake did not differ between patients with LAP-BAND and patients with ASGB. After surgery, the patients with LAP-BAND ate more solid food and less liquid food than the patients with ASGB. Vomiting frequency was higher in patients with ASGB than in patients with LAP-BAND. The total number of percutaneous band adjustments was higher in women with LAP-BAND than in women with ASGB. Band inflation because of weight stabilization was performed in six (20.0%) women with ASGB and in 19 (63.3%) women with LAP-BAND. Neostoma stenosis occurred in one women with ASGB, but in none of the women with LAP-BAND. One patient with LAP-BAND presented band slippage. Conclusions: The wider intraoperatory band calibration performed in patients with LAP-BAND did not reduce the short-term efficacy of adjustable silicone gastric banding. This new timing strategy of band adjustment required more postoperative percutaneous band inflations, but it improved the eating pattern of the patients (low vomiting frequency and high intake of solid food).     

Human fetal dopamine neurons grafted into the striatum in two patients with severe Parkinson's disease. A detailed account of methodology and a 6-month follow-up

By using stereotaxic surgical techniques, ventral mesencephalic tissues from aborted human fetuses of 8 to 10 weeks' gestational age were implanted unilaterally into the striata in two patients with advanced Parkinson's disease. The patients were treated with a cyclosporine, azathioprine, and steroid regimen to minimize the risk for graft rejection. They were examined for 6 months preoperatively and 6 months postoperatively and continued to receive the same doses of antiparkinsonian medication. There were no significant postoperative complications. No major therapeutic effect from the operation was observed. However, in the clinical tests, both patients showed small but significant increases of movement speed for repeated pronation-supination, fist clenching, and foot lifting. The rate of walking also increased in the one patient tested. For both patients, there was an initial worsening postoperatively, followed by improvement vs preoperative performance at 1 to 3 months. Both patients also showed significant improvement in the magnitude of response to a single dose of levodopa (L-dopa), but there was no increase in the duration of drug action. The motor readiness potential increased in both patients postoperatively, primarily over the operated hemisphere. Neurophysiological measurements also showed a more rapid performance of simple and complex arm and hand movements on the side contralateral to transplantation in one patient at 5 months postoperatively. Positron emission tomography demonstrated no increased uptake of 6-L-(18F)-fluorodopa in the transplanted striatum at 5 and 6 months. Taken together, these results suggest that the fetal nigral implants may have provided a modest improvement in motor function, consistent with the presence of small surviving grafts. Although our results support further scientific experimentation with transplantation in Parkinson's disease, widespread clinical trials with this procedure are probably not warranted at this time.     

Echocardiographic assessment of left ventricular function in left ventricular volume load and the immediate changes after operation

Cardiac function and changes following surgery was studied with computerized M-mode echocardiography in 12 patients with volume load of the left ventricle. Half of them had congenital lesions, the other half aortic regurgitation. Left ventricular (LV) shortening fraction and LV ejection time were significantly reduced postoperatively and came close to normal mean values. Also cardiac output and LV diameters normalized or at least started its normalization. The computerized values for rates of decrease and increase of left ventricular diameter were reduced postoperatively (p less than 0.01 and p less than 0.05 respectively) compared to elevated preoperative values. The study shows that relief of volume load on the left ventricle immediately leads to normalization of left ventricular function, especially if the myocardium was intact preoperatively.