ABSTRACT
Fluid status in the brain-dead donor is often difficult to assess. We hypothesized that using base deficit as a measure of tissue perfusion will facilitate fluid management in these donors, thereby improving renal allograft function. Consecutive donors over a 12-month period were prospectively studied. In Group I, resuscitation was based on maintaining normal blood pressure and urine output. In Group II, additional parameters of resuscitation included the correction of base deficit. Immediate renal allograft function was examined in the 48 recipients. Delayed graft function occurred in 48% of Group I, and in 19% of Group II recipients. Creatinine clearance on day 7, calculated by the Cockroft-Gault formula, was 29 +/- 6 mL/min in Group I versus 41 +/- 8 mL/min in Group II. We conclude that correcting base deficit is an extremely useful approach to expedite organ recovery and potentially improve function of transplanted kidneys.
Subject(s)
Brain Death , Kidney Transplantation/physiology , Tissue Donors , Cadaver , Creatinine/metabolism , Humans , ResuscitationABSTRACT
Labial fusion is a common condition seen most frequently in infants and young children. While most cases are "physiological," we believe it can occasionally be the presenting feature of genital lichen sclerosus.
Subject(s)
Lichen Sclerosus et Atrophicus/diagnosis , Vulva/abnormalities , Vulvar Diseases/etiology , Administration, Topical , Anti-Inflammatory Agents/administration & dosage , Biopsy, Needle , Child, Preschool , Clobetasol/administration & dosage , Diagnosis, Differential , Female , Follow-Up Studies , Glucocorticoids , Humans , Lichen Sclerosus et Atrophicus/complications , Lichen Sclerosus et Atrophicus/drug therapy , Lichen Sclerosus et Atrophicus/pathology , Treatment Outcome , Vulvar Diseases/drug therapyABSTRACT
The hypocholesterolemic activity for novel ureido fibrate analogues was found to be over 100-fold greater than for any "second-generation" fibrate in cholesterol-fed rats. A comparison of 12 related analogues revealed that the optimal configuration for a urea-bridging region located between two aromatic rings consisted of a trisubstituted nitrogen, optimally substituted with a C7 alkyl chain and linked by dimethylene to a phenoxyisobutyrate moiety found in most fibrate analogues. The hypocholesterolemic potency of these compounds was found to correlate with their increased intrinsic fibrate activity as determined by the ability to induce omega-hydroxylase activity either in rat hepatocyte cultures or in vivo, and not with their 10-fold increased ACAT inhibitory potency when compared to other fibrates. The most active compound, 2-(4-(2-(N'-(2,4- difluorophenyl)-N-heptylureido)ethyl)phenoxy)-2-methylpropionic acid, referred to as (2), was found to induce omega-hydroxylase activity in hepatocytes at concentrations between 5 and 100 nM compared to 1-20 microM concentrations for bezafibrate, and lower serum VLDL+LDL cholesterol in rats at doses between 0.1 and 0.5 mg/kg per day compared to doses of 25-100 mg/kg per day for bezafibrate. Single-dose pharmacokinetic studies with 2 indicated that total drug exposure will be much lower at hypocholesterolemic doses due to the enhanced intrinsic activity, and may result in an improved safety profile for these novel trisubstituted ureido fibrate analogues in rats and humans compared to other fibrates.
Subject(s)
Bezafibrate/chemistry , Bezafibrate/pharmacology , Hypolipidemic Agents/chemistry , Hypolipidemic Agents/pharmacology , Sterol O-Acyltransferase/antagonists & inhibitors , Animals , Bezafibrate/pharmacokinetics , Butyrates/chemistry , Butyrates/pharmacology , Cells, Cultured , Dose-Response Relationship, Drug , Humans , Hypolipidemic Agents/pharmacokinetics , Liver/cytology , Liver/enzymology , Liver/metabolism , Male , Osmolar Concentration , Phenylurea Compounds/chemistry , Phenylurea Compounds/pharmacology , Rats , Rats, Sprague-Dawley , Sterol O-Acyltransferase/metabolism , Structure-Activity RelationshipABSTRACT
The hypothesis that mitochondrial sterol 27-hydroxylase plays a role in the sterol-mediated down-regulation of LDL receptor activity was evaluated in HepG2 cells. 27-Hydroxycholesterol was found to be more potent at suppressing LDL receptor activity than cholesterol (IC50 values of 8 mu M and 142 mu M for 27-hydroxycholesterol and cholesterol, respectively) when the sterols were delivered to cells from 2-hydroxypropyl-beta-cyclodextrin (beta-CD)-solubilized solutions. Cyclosporin, an immunosuppressant which has been shown to inhibit the 27-hydroxylation of sterols, was used to assess whether the formation of endogenous 27-hydroxycholesterol was required for the cholesterol-induced suppression of LDL receptor activity. Cyclosporin dose-dependently inhibited the 27-hydroxylation of cholesterol by HepG2 mitochondria (Ki = 0.25 mu M) and HepG2 cell cultures (IC50 = 1 mu M). At 1 mu M, cyclosporin had no effect on LDL receptor activity, and did not prevent the suppression of LDL receptor activity caused by: 1) the addition of beta-CD-solubilized cholesterol, 2) the receptor-mediated uptake of beta-VLDL, or 3) the inhibition of cholesterol esterification. In contrast, 10 mu M cyclosporin was found to inhibit the esterification of cholesterol and to increase the cellular level of free cholesterol resulting in suppression of LDL receptor activity. These results suggest that if mitochondrial sterol 27-hydroxylase plays a role in the regulation of LDL receptor activity, it is not through the formation of potent regulatory oxysterols, but through its effects on the availability and/or size of the free cholesterol pool regulating LDL receptor activity.
Subject(s)
Cyclosporine/pharmacology , Cytochrome P-450 Enzyme Inhibitors , Enzyme Inhibitors/pharmacology , Lipoproteins, LDL/metabolism , Liver/metabolism , Receptors, LDL/drug effects , Steroid Hydroxylases/antagonists & inhibitors , Biological Transport/drug effects , Cholestanetriol 26-Monooxygenase , Dose-Response Relationship, Drug , Humans , Mitochondria/drug effects , Mitochondria/metabolism , Solubility , Tumor Cells, CulturedSubject(s)
Keloid/therapy , Silicones/therapeutic use , Administration, Topical , Adult , Female , Gels , Humans , Silicones/administration & dosageABSTRACT
The clinical and morphologic features of a pigmented squamous cell carcinoma of the bulbar conjunctiva in a 57-year-old black man are reported. The tumor resembled the more usual epibulbar squamous cell carcinoma but had many melanin containing cells within it. Transmission electron microscopy disclosed melanosomes within squamous epithelium, melanocytes, and macrophages. The only cells within the tumor with morphologic features of a malignant neoplasm were squamous in type. The literature on this rare conjunctival tumor, which has a good prognosis following complete excision, is reviewed. Pigmented squamous cell carcinomas need to be distinguished from the more common nodular melanomas, which have a more ominous outlook.
Subject(s)
Carcinoma, Squamous Cell/ultrastructure , Conjunctival Neoplasms/ultrastructure , Conjunctiva/ultrastructure , Diagnosis, Differential , Epithelium/ultrastructure , Humans , Male , Melanocytes/ultrastructure , Microscopy, Electron , Middle AgedABSTRACT
The alcohol swab is a very reliable and easily obtained substitute for the alcohol lamp in performing a routine culture.
Subject(s)
Microbiological Techniques , Sterilization/methods , Alcohols , Humans , Microbiology/instrumentation , Sterilization/instrumentationABSTRACT
A 33-year-old man had a unique lens capsular cyst that became clinically evident eight years after a penetrating ocular injury in which the lens capsule was disrupted. Microscopic examination indicated that the cyst may have arisen from displaced lens capsule and epithelial cells that became separated from the lens.
