尿毒症出血性疾病的治疗

尿毒症出血性疾病是肾衰竭患者常见的并发症之一。早在100年前Reisman就曾描述过肾衰竭患者严重而广泛出血的临床表现。目前该病的病理生理机制尚未完全阐明，但一般认为由多种因素所致，其中血小板异常是引起尿毒症出血性疾病的主要因素。此外，贫血、药物及代谢产物在体内蓄积、血管功能异常及通透性增加、血液透析抗凝剂的使用等都可加重出血倾向。本文在回顾引起尿毒症患者出血可能的病理生理机制的基础上，重点对尿毒症出血性疾病的治疗作一综述。     

Calcific uremic arteriolopathy in association with low turnover uremic bone disease.

We report seven cases (out of 100 dialysis patients) at the University of Kentucky who were diagnosed with calciphylaxis syndrome between 1993 and 1998. Of note is the fact that five of these patients had bone biopsy-proven adynamic renal bone disease, rather low intact PTH, and relatively low calcium-phosphorus product. This is in contrast to the previous view that calciphylaxis is usually seen in patients with excessive parathyroid activity. The reemergence of calciphylaxis with renal bone disease is an intriguing finding and does not correspond to earlier reports associating calciphylaxis with hyperparathyroid bone disease. This report reviews the clinical, biochemical, and bone histology findings of these patients, and provides a review of the literature.     

Oral zeranol shortens the prolonged bleeding time of uremic rats

Intravenous conjugated estrogens reduce the prolonged bleeding time in uremic patients and in a rat model of uremia. However, estrogens have major side effects related to their hormonal activity. We investigated whether a beta-resorcylic acid lactone, zeranol (a compound with close spatial similarity to estrogens but with a weak estrogenic activity), improves primary hemostasis in uremic rats and whether the effect is mediated by estrogen receptors. The results showed that single oral administration of zeranol significantly (P less than 0.01) shortened the bleeding time of uremic rats, 20 mg/kg being the minimum effective dose. This effect was long-lasting (72 hours). The dose of 30 mg/kg zeranol reproduced the pattern observed after 20 mg/kg but bleeding time values were still significantly (P less than 0.01) shortened 96 hours after the administration. No changes in hematocrit, platelet and leukocyte count, and serum creatinine were detected after zeranol administration. When uremic rats were pre-treated orally with two estrogen receptor antagonists, tamoxifen and clomiphene (3 mg/kg), zeranol did not shorten the bleeding time, thus suggesting that the hemostatic effect of zeranol was due to an estrogen receptor-mediated mechanisms. These results might have important future implications for the management of uremic bleeding in humans.     

The Bernard-Soulier syndrome: hereditary giant platelet disease.

A patient with the Bernard-Soulier or hereditary giant platelet syndrome, in whom the characteristic morphological features were present and the in vitro abnormalities of platelet aggregation were demonstrated, is reported. Although rare, this syndrome is important, since surgical procedures may be carried out under cover of infused allogeneic platelets.     

Potentiation of warfarin by trimethoprim-sulfamethoxazole

Potentiation of warfarin by trimethoprim-sulfamethoxazole (TMP-SMX) has been reported occasionally but not in the urologic literature. Three cases are presented in which significant bleeding developed when TMP-SMX was added for the patient already on warfarin anticoagulants. The mechanism of this interaction is uncertain but probably involves competitive protein binding by the two drugs.     

Potentiation of the hepatic action of insulin by chlorpropamide.

In perfused livers of fed rats, chlorpropamide inhibits glucagon-stimulated glucose production by augmenting the action of insulin. This effect is associated with a decrease in cyclic AMP accumulation in liver and perfusate. Alterations in glucose production appear to correlate more closely with changes in the amount of cyclic AMP in the perfusate than with changes in intrahepatic concentration of nucleotide. Potenitation by chlorpropamide of the hepatic action of insulin does not require administration of the drug prior to perfusion. Further, it is demonstrable at concentrations of insulin and glucagon (10(-11M) that approximate the normal plasma levels of these hormones.     

Potentiation of hypoglycemic effect of chlorpropamide and phenfromin by halofenate.

The potentiation of oral hypoglycemic drugs by the antilipemic agent halofenate is reported. Forty-seven diabetic patients were treated for 48 weeks with halofenate, clofibrate, or placebo. Five patients in the halofenate group were taking phenformin plus either chlorpropamide or tolbutamide. Their average initial fasting plasma glucose was 160 mg./dl. All five patients experienced a slow but but substantial fall in fasting plasma glucose. The mean fasting plasma glucose for the five patients after 80 days of halofenate treatment was 63 mg./dl. As oral treatment for diabetes was reduced, the fasting plasma glucose returned to prehalofenate levels. In this study, we did ont detect an effect of halofenate on the fasting plasma glucose of diabetic patients treated with insulin or on the fasting plasma glucose levels of patients treated with diet alone.     

Potentiation of neuromuscular blockade by verapamil

The effects of intravenous (iv) verapamil (0.01 to 1.0 mg/kg) on the constant neuromuscular block produced by an iv infusion of either pancuronium or succinylcholine were studied on the indirectly stimulated gastrocnemius and tibialis-anterior muscles of the rabbit anesthetized with halothane in oxygen. Verapamil alone (n = 6) had no significant effect. However, the drug did significantly potentiate the 50% twitch depression of the gastrocnemius muscle produced by a constant iv infusion of either pancuronium (n = 5) or succinylcholine (n = 5) to 36 +/- 6% and 45 +/- 1% of control, respectively. This effect of verapamil occurred with doses of 0.1 mg/kg for pancuronium and 0.01 mg/kg for succinylcholine; these doses of verapamil were the lowest which produced a significant effect. In contrast, verapamil had no significant effect on the progression of the neuromuscular blockade of either the gastrocnemius or tibialis-anterior muscles produced by alpha-bungarotoxin (n = 5). Verapamil also significantly prolonged the P-R interval of the ECG from a control value of 71 +/- 2 ms to 78 +/- 3 ms at a dose of 0.1 mg/kg and to 93 +/- 6 ms at a dose of 0.3 mg/kg. The possible mechanisms of the neuromuscular actions of verapamil are discussed and it is concluded that verapamil can produce potentiation of either pancuronium- or succinylcholine-induced neuromuscular block at doses within the therapeutic range.     

Thermal injury in von willebrand disease. Management of burn wound bleeding.

A 51-year-old woman sustained a 40% third-degree burn. After five grafting procedures that were unsuccessful due to uncontrolled bleeding, the diagnosis of von Willebrand disease was established. Skin grafting was subsequently accomplished without difficulty using cryoprecipitate as a source of antihemophilic factor (factor VIII). Serial clinical and laboratory investigations demonstrated that using the level of factor VIII procoagulant activity alone as an in vitro index of hemostasis was insufficient as a guide to the control of pathologic burn wound bleeding in this patient.