Responses of the skin microcirculation to acetylcholine and to sodium nitroprusside in chronic uremic patients

The aim of the present study was to assess the endothelial function of the microcirculation in chronic renal failure. We investigated the responses of the cutaneous blood flow to locally delivered acetylcholine and sodium nitroprusside in uremic patients. The study included 60 chronic uremic patients: 40 patients with a creatinine clearance of 4-25 ml/min were on conservative treatment and 20 patients were on maintenance hemodialysis. The changes in skin blood flow following iontophoretic delivery of acetylcholine (an endothelium-dependent vasodilator) and sodium nitroprusside (an endothelium-independent vasodilator) were measured by laser Doppler flowmetry. Acetylcholine induced a progressive increase in blood flow in both groups, reaching approximately 100% of the maximal hyperemic response obtained by sodium nitroprusside delivery. The percent increase in blood flow from baseline was lower in hemodialysis patients than in patients on conservative treatment, after both acetylcholine (550 +/- 44 vs. 718 +/- 61%, P < 0.05) and sodium nitroprusside (553 +/- 46 vs. 735 +/- 69%, P < 0.05) delivery. In the hemodialysis group, the hyperemic responses to acetylcholine and sodium nitroprusside did not improve after the hemodialysis session. Hence, the hyperemic responses of the skin microcirculation are lower in hemodialysis patients than in patients on conservative treatment, and did not ameliorate after hemodialysis. It seems to be independent of endothelial dysfunction, and associated with the severity of uremia and with the maintenance hemodialysis treatment. This microcirculatory abnormality is in keeping with the arterial stiffness and vascular wall damages described in dialysis patients, which contribute to the cardiovascular morbidity of chronic uremia.     

Polymorphisms in estrogen metabolism and estrogen pathway genes and the risk of miscarriage

Purpose  This study investigated genetic variations in the estrogen pathway and their association with miscarriages. Methods  A total of 483 patients were recruited from a comprehensive control group for case–control studies. Three variants of the CYP19A1 gene (rs10046, rs4646 and rs700519) and one variant each of the estrogen (ESR1) and progesterone (PGR) receptor genes (rs3020314 and rs1042838) were investigated using polymorphism genotyping. The chi-squared test and one-way analysis of variation (ANOVA) were used for statistical analysis. Results  For rs10046 (CYP19A1), the C/C genotype was associated with a greater frequency of miscarriages (P = 0.017). The other genotypes were not found to be associated with recurrent miscarriage. Conclusions  This is the first study that has identified a single-nucleotide polymorphism in the aromatase gene that suggests a significant association between genotypes and miscarriage. As aromatase is an essential enzyme in the estrogen pathway, it may be speculated that variations in the aromatase gene in some way give rise to different conditions in the endocrine environment that can lead to impaired fertility. S. Cupisti and P. A. Fasching contributed equally to this work.     

“Cherry Picking”, a Multiple Non-anatomic Liver Resection Technique, as a Promising Option for Diffuse Liver Metastases in Patients with Neuroendocrine Tumours

Introduction

Liver metastases of GEP-NETs are a known major prognostic factor with a strong effect on patients’ survival. To date, various treatment options are available, whereas surgery remains the only curative option. Because large liver resections often cannot be performed due to insufficient remnant liver volume, a special operative technique, “cherry picking” (multiple nonanatomic liver resections), can be used as a tissue-preserving procedure.

Methods

Of 91 patients with various GEP-NETs, 16 patients were identified with synchronous or metachronous multifocal, bilobular liver metastases (>10). All were treated with “cherry picking.” Patient records were reviewed retrospectively and clinical data and pathology results were analyzed.

Results

Mean survival after primary tumour resection was 82.8 versus 41.2 months after liver surgery. All 16 patients are still alive. Mean recurrence-free survival after primary tumour operation was 49.8 versus 24.6 months after liver surgery. Complications of cherry picking included two postoperative biliary leakages and three small hepatic abscesses (conservative/interventional approach 25 % (n = 4), surgical approach 6.25 % (n = 1). There was no postoperative mortality. Initial hormonal symptoms (5/16 patients) completely disappeared postoperatively in 2 patients and were significantly decreased in 3 patients.

Conclusions

The tissue-preserving surgical technique “cherry picking” has developed due to improved imaging techniques and increased knowledge in liver anatomy, which has helped to make this approach safer and easier. Highly selected patients with multiple bilobular liver metastases of GEP-NET can benefit from this special surgical approach, also applicable for recurrent metastases.     

Early postoperative tissue harmonic sonography of the thyroid gland

PURPOSE: Fundamental gray-scale imaging (FGI) is known to be unuseful for thyroid imaging in the early postoperative setting. Thus, we evaluated the feasability of tissue harmonic imaging (THI) early after thyroid resection. MATERIAL AND METHODS: FGI and THI of the neck were performed in 48 consecutive patients 4 days after surgery. The examiner was blinded to patient diagnoses and types of surgery. FGI and THI examinations were stored on videotape and reviewed offline by two different readers who rated the quality of delineation of the organ borders and presence or absence of focal lesions. The results were compared to neck US performed 12 weeks after surgery. RESULTS: Delineation of the thyroid remnants in THI/FGI was rated to be excellent in 22/2, good in 11/9, poor in 3/16 and not visible at all in 4/13 patients. The correlation between THI-volumetry and control-volumetry was very high (r=0.81; p<0.0001). THI but not FGI depicted presence or absence of solid thyroid nodules with 100% accuracy. CONCLUSION: THI is a feasible method for thyroid US in the early postoperative setting. It permits volumetry of the residual thyroid tissue and accurately depicts nodules within the thyroid remnant.     

Skeletal muscle and nutritional assessment in chronic renal failure patients on a protein-restricted diet

BACKGROUND: The close relationship between protein-energy malnutrition and quality of life, morbidity and mortality, makes mandatory a careful evaluation of the nutritional status and muscle mass in chronic renal failure (CRF) patients. METHODS: Nutritional and skeletal muscle data were obtained from 28 nondiabetic patients with severe CRF (glomerular filtration rate, GFR < 15 mL min-1) on conservative treatment. Of them, 14 (8 males, 4 females) were on a conventional low-protein (0.6 g kg-1 body weight) diet (LPD) and 14 (8 males, 4 females) were on a very low-protein (0.3 g kg-1 body weight) diet supplemented with essential amino acids and ketoacids (Ketodiet); 28 healthy sex- and age-matched subjects served as controls. We evaluated biochemistry, anthropometry, bioelectrical impedance vector analysis, and three noninvasive tests investigating some skeletal muscle features: (a) myoelectrical fatigue phenomenon was studied using a surface electromyography technique that provides data on conduction velocity (CV), median frequency of power spectrum (MDF) and average rectified value (ARV) of myofibre action potential, at 15 and 35 Hz stimulation frequency; (b) muscle oxidative metabolism was studied by serum lactate following aerobic exercise; and (c) muscle strength of the legs was studied using an isokinetic exercise test at two different angular velocities (60 degrees and 180 degrees s-1). RESULTS: No difference between patients and controls was detected regarding CV, MDF and ARV, at 35 and 15 Hz testing. Serum lactate was higher in patients than in controls at 1, 5, 10 and 30 min recovery. A decreased knee extension and flexion strength was detected in CRF patients both at low (60 degrees s-1) and at high (180 degrees s-1) angular velocity; muscle strength deficit negatively correlated to serum albumin (r = -0.52, P < 0.01), but no relationship was found with protein intake or residual renal function. No difference was found between LPD and Ketodiet patients regarding the studied muscular tests as well as the anthropometry and bio-impedance data. CONCLUSIONS: Implementation of a proper dietary regimen, including severe restriction of protein intake can preserve lean body mass and nutritional status of advanced CRF patients. Skeletal muscle shows unchanged sarcolemma excitability but abnormal oxidative metabolism and reduced segmental strength. Regular physical activity and a close clinical and dietary monitoring should be recommended for the predialysis patient care.     

A special, supplemented 'vegan' diet for nephrotic patients.

High dietary protein intake, in the past recommended for nephrotic syndrome, does not improve hypoproteinemia and may accelerate progressive renal damage. In contrast, low-protein diets reduce proteinuria and preserve renal function in experimental renal models of nephrotic syndrome. In this study, 20 steroid-resistant, nephrotic patients were treated with a pure vegetarian, low-protein diet, supplemented with essential amino acids and ketoanalogues (supplemented vegan diet, SVD) for 4.6 +/- 3.1 months. Before the study, these patients followed an unrestricted protein, low-sodium diet (LSD). Proteinuria, daily urea nitrogen excretion and creatinine clearance decreased significantly on SVD. A similar lowering effect of SVD was observed on serum total cholesterol. Seven of the 20 patients changed from LSD to SVD and vice-versa on 3 occasions, and in all cases, we found an increase of proteinuria during the LSD period. Serum albumin, HDL cholesterol, triglycerides and anthropometric measurements did not change on SVD. Our data suggest that SVD exerts a favorable effect on proteinuria and hypercholesterolemia in nephrotic patients, without inducing clinical or laboratory signs of malnutrition.