Serum ionic fluoride levels in haemodialysis and continuous ambulatory peritoneal dialysis patients

High serum fluoride (F-) in patients with chronic renal failure (CRF) and end-stage renal disease (ESRD) is associated with risk of renal osteodystrophy and other bone changes. This study was done to determine F- in normal healthy controls and patients with ESRD on haemodialysis (HD) or peritoneal dialysis (PD). Seventeen healthy controls (12 males, 5 females) and 39 ESRD patients on dialysis (17 males, 22 females) were recruited in the study in a community with 47.4 +/- 3.28 microM/l (range 44-51 microM/l) of F- content in drinking water. Control subjects showed a mean serum F- concentration of 1.08 +/- 0.350 microM/l. Males in control group showed slightly higher F- levels (1.15 +/- 0.334, range 0.55-1.9 microM/l) than females (0.92 +/- 0.370, range 0.6-1.5 microM/l). Mean serum F- concentration did not correlate significantly with age and sex among control subjects, whereas such correlation was observed in patients with ESRD on dialysis. Mean serum F- concentration was significantly higher in patients on dialysis (2.67 +/- 1.09, range 0.8-5.2 microM/l) than normal controls. When grouped according to sex, the mean serum F- concentration in males (3.05 +/- 1.04, range 1.8-5.2 microM/l) was significantly higher than females (2.38 +/- 1.08, range 0.8-5.2 microM/l). When patients were grouped according to age, it was observed that F- concentration was significantly higher in patients with age groups 21-70 (2.86 +/- 1.05) than those with age group 13-20 years (1.42 +/- 0.531). Thus F- concentration correlated with age and sex, being higher in males and above 20 years. Despite appreciable clearance of F- (39-90%) across the peritoneum, patients on CAPD showed higher serum F- concentration than those on HD (3.1 +/- 1.97 vs 2.5 +/- 1.137 microM/l). Of the total 39 patients on dialysis 39% had their serum F- concentration above 3.0 microM/l, posing the risk of renal osteodystrophy.      

Disposition of oral and intravenous pravastatin in MRP2-deficient TR- rats.

The aim of this study was to characterize the role of the efflux transporter Mrp2 (Abcc2) in the pharmacokinetics of orally and intravenously administered pravastatin in rats. Eight Mrp2-deficient TR- rats and eight wild-type rats were given an oral dose of 20 mg/kg pravastatin. Four TR- animals and four wild-type animals were studied after intravenous administration of pravastatin (5 mg/kg). The TR(-) rats showed a 6.1-fold higher mean area under the plasma concentration-time curve (AUC) of pravastatin (p < 0.001) after oral administration and a 4.7-fold higher AUC (p < 0.01) after intravenous administration of pravastatin as compared with the wild-type animals. The mean systemic (total) clearance of pravastatin was 4.6-fold higher (39.2 versus 8.50 l/h/kg, p < 0.001) and the mean V 4.3-fold higher (14.1 versus 3.29 l/kg, p < 0.01) in the wild-type rats. The mean renal clearance of pravastatin in the TR(-) rats was 16.5-fold increased as compared with the wild-type animals (0.695 versus 0.042 l/h/kg, p < 0.05). The increased systemic exposure to oral pravastatin in the TR- rats was associated with a greater inhibitory effect on 3-hydroxy-3-methylglutaryl CoA reductase, as shown by smaller lathosterol to cholesterol concentration ratios. These results suggest that the reduced biliary pravastatin excretion in the Mrp2-deficient TR- rats is partly compensated for by increased urinary excretion of pravastatin. Furthermore, intestinal Mrp2 does not appear to play a major role in the oral absorption of pravastatin in normal rats.     

Deep venous thrombosis: rate of spontaneous lysis and thrombus extension.

AIM: Although recanalization occurs after an episode of venous thrombosis, the exact timing for this process, the rate of clearing at the different venous segments and the nature of the mechanisms involved and their progression are not well known. Recognition of these competing events is important in understanding the natural history and the mechanisms responsible for lysis of the thrombus and for the development of the post-thrombotic syndrome METHODS: During the course of 5 consecutive years, 110 patients (126 legs) with deep vein thrombosis (DVT) were prospectively followed using ultrasonic duplex. Follow-up studies were performed at intervals of 1 and 7 days, 1 month, every 3 months for the 1(st) year, and yearly thereafter. Mean duration of follow-up was 329 days. RESULTS: When only legs with initial complete occlusion are considered, the prevalence of occlusion progressively decreases to 33% after 6 months, 17% after the 1(st) year, and 0% after 3 years. Recanalization of individual segments occurred even more rapidly. After 3 months, recanalization of completely occluded segments was present in 93% of common femoral veins, 79% of superficial femoral veins (proximal segment), 84% of popliteal veins, and 72% of posterior tibial veins. The rate of recanalization was highest for multisegmental disease. Propagation of thrombi to adjacent venous segments occurred in 15% of the limbs. Propagation was usually limited to 1 or 2 adjacent segments. CONCLUSION: Lysis occurred early and was progressive. After 1 year most legs have recanalized. After 3 years recanalization occurred in all legs although residual thrombosis (partial obstruction) was still present in 50% of the limbs. Propagation of the thrombus was a limited process.     

新疆家畜蠕形蚤病病原研究

本文详细介绍了在新疆发现的花蠕形蚤、叶氏蠕形蚤、北山羊蠕形蚤、羊长喙蚤和狍长喙蚤的形态学特点、地理分布和某些生物学特性。     

Mammalian nuclear transfer.

During development, the genetic content of each cell remains, with a few exceptions, identical to that of the zygote. Differentiated cells, therefore, retain all the genetic information necessary to generate an entire organism (nuclear totipotency). Nuclear transfer (NT) was initially developed to test experimentally this concept by cloning animals from differentiated cells. It has, since then, been used to study the role of genetic and epigenetic alterations during development and disease. In this review, we highlight some of the milestones in mammalian NT reached in the 50 years after the first nuclear transplantations in frogs. We also address problems associated with mammalian nuclear transfer and provide a survey on current NT and stem cell technology. In the long term, nuclear transfer or alternative strategies aim to generate customized pluripotent cells, which would be invaluable to medical research and therapy.     

Hazards of thrombolytic therapy in deep vein thrombosis

From 1965 to 1985, 64 deep vein thrombosis (DVT) patients were treated with streptokinase (SK). In 26 cases 'high-dose SK' (IV 100,000 units/h for 4 days) was used and in 38 patients a 'low-dose SK' regime (IV 250,000 units every 12 h for 4 days) was employed. The clinical signs of DVT subsided in 78 per cent of treated patients within 30 days of completing SK treatment. A repeat phlebography was performed immediately after SK therapy in 29 patients (45 per cent) and a total recanalization or partial thrombolysis was achieved in 80 per cent of the studied cases. In 15 patients minor and major haemorrhagic complications occurred. There were five fatalities, all in the high-dose SK group (three intracranial haemorrhages and two major bleeds). Three patients developed pulmonary embolism and none of them died. The post-treatment clinical and phlebographic evaluation did not reveal any significant difference between the two methods of SK administration, but more haemorrhagic complications (P less than 0.02, chi=5.50825) occurred in the high-dose SK patients. This report emphasizes the risk of bleeding complications during thrombolytic therapy. If SK is to be used, therefore, careful selection of patients and meticulous monitoring are mandatory.     

Subcutaneous low molecular weight heparin versus subcutaneous unfractionated heparin in the treatment of deep vein thrombosis: a Polish multicenter trial.

In a prospective multicenter trial, 149 consecutive patients with phlebographically proven proximal and/or distal deep vein thrombosis of the leg were randomly allocated to receive subcutaneously for 10 days either low molecular weight heparin CY 216 (Fraxiparine) in a fixed dose or unfractionated heparin (UFH) in doses adjusted according to the activated partial thromboplastin time. Pre- and post-treatment phlebograms were assessed blindly using the Arnesen's score system in 134 patients available for analysis of the treatment efficacy. The mean phlebographic score after 10 days of treatment was significantly decreased in both groups (p less than 0.001) in comparison with the baseline score but the difference in score changes between the two groups was not statistically significant. There was an improvement in 45/68 patients (66%) in the Fraxiparine group and in 32/66 patients (48%) in the UFH group, and an increase in the thrombus size in 10/68 (15%) and 12/66 (18%), respectively. One symptomatic non-fatal pulmonary embolism and one major bleeding episode were observed in the UFH group. During a follow-up period of 3 months, two rethromboses had occurred in the UFH group and none in the Fraxiparine group. It is concluded that subcutaneous fixed dose Fraxiparine is safe and at least as effective as subcutaneous adjusted UFH in the treatment of deep vein thrombosis.