Effective strategy for decreasing blood culture contamination rates: the experience of a Veterans Affairs Medical Centre.

Contaminated blood cultures constitute diagnostic challenges and place a burden on healthcare services. An observational retrospective study was undertaken to evaluate the effect of routine labelling of blood culture bottles with the initials of the healthcare worker who drew them, followed by individualized feedback, on blood culture contamination rates. The contamination rate of the entire facility was 2.6% before the procedural change, and this decreased significantly to 1.5% after the procedural change (P < 0.001) over the first 12 months of the intervention. Routine labelling of blood culture bottles with the initials of the healthcare worker who drew them, followed by individualized feedback, was effective in reducing blood culture contamination rates.

Design and in vivo analysis of potent non-thiol inhibitors of farnesyl protein transferase.

Inhibitors of farnesyl protein transferase (FPTase) based upon a pseudotripeptide template are described that comprise an imidazole group substituted with a hydrophobic substituent. (1, 5)-Disubstitution of the imidazole group is shown to be the optimal array that leads to potent and selective inhibitors of FPTase. A variety of aryl and isoprenyl substituents are shown to afford effective inhibitors, and the mechanism by which these compounds inhibit FPTase has been investigated. The biochemical behavior of these compounds suggests that they bind to FPTase at the site usually occupied by the protein substrate. In experiments in cell culture, the methyl ester prodrugs of these inhibitors are cell permeant and potently inhibit the posttranslational modification of H-Ras protein. Additionally, these molecules revert the phenotype of ras transformed cells as evidenced by their ability to slow the growth of ras transformed cell lines in soft agar. One of the inhibitors, as its methyl prodrug, was evaluated in two in vivo models of tumor growth. The compound selectively inhibited the growth of tumors derived from H-ras transformed cells, in nude mice, and caused the regression of preexisting tumors in an H-ras transgenic animal model.

Fabry's disease presenting as syncope, angiokeratomas, and spoke-like cataracts in a young man: discussion of the differential diagnosis.

A 44-year-old male with a remote history of skin lesions and cataracts presented with subacute onset of syncope. The presentation and the differential diagnosis in this case of Fabry's disease are discussed. The pathophysiology, diagnosis, clinical manifestations, and treatment of this disorder are discussed, with a review of the literature. Fludrocortisone acetate therapy resulted in a reduction in the patient's syncopal event frequency. Serum enzymatic assay and skin biopsy are useful in the diagnosis of Fabry's disease. We advocate a conservative approach to the oculocutaneous symptoms and suggest appropriate interventions for the renovascular and autonomic nervous system complications of this disorder.

Successful twin pregnancy after renal transplant maintained on cyclosporine A immunosuppression.

Cyclosporine A has recently been reported to be an effective immunosuppressant agent for use in renal allograft recipients. Questions have been raised regarding its effects during pregnancy, in light of an increased life span and return of fertility in renal transplant patients. A preterm delivery is reported in a cadaveric renal allograft recipient chronically immunosuppressed with cyclosporine A and methylprednisolone. Dizygotic twins were delivered at 35 weeks' gestation, weighing 2452 and 2386 g. Maternal cyclosporine A levels were determined weekly by whole blood radioimmunoassay, with little increase in requirement found before delivery. No indication of maternal renal compromise was apparent, as evidenced by stable weekly creatinine clearance studies. Cyclosporine A, at the doses used, was passed transplacentally, with cord blood values of 34 and 57% of the maternal cyclosporine A level found at delivery. No adverse effects were noted at birth in the average for gestational age neonates, nor at nine-month follow-up evaluation. Given careful monitoring, cyclosporine A may be an effective immunosuppressant agent for use in pregnancies complicated by renal transplantation.

The role of high-energy phosphate in norepinephrine-induced acute renal failure in the dog.

Previous studies have demonstrated that pretreatment with mannitol, furosemide, or bradykinin can attenuate the severity of norepinephrine-induced renal functional impairment. The present studies were designed to evaluate the possibility that these agents are protective, in part, by preserving cellular metabolic integrity. The renal cortex was repetitively biopsied during the course of this study, and high-pressure liquid chromatography was used to analyze the tissue content of adenine nucleotides (expressed in nanomoles per gram of wet tissue). The adenine nucleotide charge ratio (CR) and total adenine nucleotide (TAN) content were calculated as indices of cellular metabolic integrity. In addition to the above-established protective agents, phenoxybenzamine was used to evaluate a direct toxic effect of norepinephrine on renal tissue. Inulin clearance at 3 hours post infusion (expressed as a percent of control) was 7% with norepinephrine alone and, in the protected groups, 36% with bradykinin, 61% with furosemide, 51% with mannitol, and 100% with phenoxybenzamine. There was no change in CR or TAN with phenoxybenzamine. In contrast, during norepinephrine administration CR fell significantly in all other groups. Three hours after stopping norepinephrine, CR had returned toward control values and the level of CR was significantly better in all protected groups when compared with norepinephrine alone. Similarly, the levels of TAN were significantly diminished in the norepinephrine-alone group when compared to all protected groups, and there was significantly more tubular necrosis as well. The maintenance of higher levels of TAN and the preserved ability to regenerate adenosine triphosphate in the protected groups, when compared to the norepinephrine-alone group, support the contention that these agents offer protection, at least in part, by preserving cellular metabolic integrity.

Metoclopramide kinetics in patients with impaired renal function and clearance by hemodialysis.

Metoclopramide kinetics were examined in 24 adult patients with diminished renal function and in eight healthy subjects with normal renal function. Creatinine clearance correlated with metoclopramide plasma clearance, renal clearance, nonrenal clearance, and elimination t1/2. Regardless of renal function, renal clearance accounted for less than or equal to 21% of total plasma clearance. Nonrenal clearance was reduced in patients and accounted for most of the reduction in plasma clearance. The comparatively small plasma clearances in patients imply that maintenance doses should be reduced accordingly to avoid drug cumulation. Metoclopramide clearance by hemodialysis was also assessed in four patients. Metoclopramide losses from hemodialysis were relatively small compared to estimates of total body metoclopramide stores. Compensatory dosage increases are probably unnecessary for most patients. These data also suggest that hemodialysis is not likely to be effective in metoclopramide overdose.

Eustatic sea level 120,000 years ago on oahu, hawaii.

Extensive dating of the fossil corals associated with the Waimanalo shoreline on Oahu has shown that 120,000 years ago the ocean was approximately 7.6 meters above its present level. Corals grown during that time constitute a major portion of the subaerial reef-derived material on the island, with exposures ranging from about 10 meters to near sea level. This evidence corroborates the notion that 120,000 years before the present was the last time during which the sea stood significantly higher than it does today. The reported benches at 3.7, 1.5, and 0.6 meters, if not of Recent origin, could be features created by brief halts of the sea during rapid regression shortly after the Waimanalo high stand.