Consequences of electroencephalographic-suppressive doses of propofol in conjunction with deep hypothermic circulatory arrest

BACKGROUND: Some patients who undergo cerebral aneurysm surgery require cardiopulmonary bypass and deep hypothermic circulatory arrest. During bypass, these patients often are given large doses of a supplemental anesthetic agent in the hope that additional cerebral protection will be provided. Pharmacologic brain protection, however, has been associated with undesirable side effects. These side effects were evaluated in patients who received large doses of propofol. METHODS: Thirteen neurosurgical patients underwent cardiopulmonary bypass and deep hypothermic circulatory arrest to facilitate clip application to a giant or otherwise high-risk cerebral aneurysm. Electroencephalographic burst suppression was established before bypass with an infusion of propofol, and the infusion was continued until the end of surgery. Hemodynamic and echocardiographic measurements were made before and during the prebypass propofol infusion and again after bypass. Emergence time also was determined. RESULTS: Prebypass propofol at 243 +/- 57 micrograms.kg-1.min-1 decreased vascular resistance from 34 +/- 8 to 27 +/- 8 units without changing heart rate, arterial or filling pressures, cardiac index, stroke volume, or ejection fraction. Propofol blood concentration was 8 +/- 2 micrograms/ml. Myocardial wall motion appeared hyperdynamic at the end of cardiopulmonary bypass, and all patients were weaned therefrom without inotropic support. After bypass, vascular resistance decreased further, and cardiovascular performance was improved compared to baseline values. Nine of the 13 patients emerged from anesthesia and were able to follow commands at 3.1 +/- 1.4 h. Three others had strokes and a fourth had cerebral swelling. CONCLUSIONS: Propofol infused at a rate sufficient to suppress the electroencephalogram does not depress the heart or excessively prolong emergence from anesthesia after cardiopulmonary bypass and deep hypothermic circulatory arrest.     

Clostridium difficile-associated diarrhea: epidemiology, risk factors, and infection control

OBJECTIVES: To evaluate the effectiveness of specific infection control measures on the incidence of Clostridium difficile-associated diarrhea (CDAD) and to identify risk factors for its development. SETTING: 370-bed, tertiary-care teaching hospital with approximately 12,000 to 15,000 admissions per year. METHODS: Several infection control measures were implemented in 1991 and 1992, and the attack rates of CDAD were calculated quarterly. Antibiotic use for 1988 through 1993 was analyzed. A case-control study was conducted from January 1992 to December 1992 to identify risk factors for acquisition of CDAD. RESULTS: From 1989 to 1992, the attack rate of CDAD increased from 0.49% to 2.25%. An increase in antibiotic use preceded the rise in the incidence of CDAD in 1991. Despite implementation of various infection control measures, the attack rate decreased to 1.32% in 1993, but did not return to baseline. Ninety-two cases and 78 controls (patients with diarrhea but with negative toxin assay) were studied. By univariate analysis, history of prior respiratory tract infections (odds ratio [OR], 3.6; 95% confidence interval [CI95], 1.2-10.4), the number of antibiotics, and the duration of exposure to second-generation cephalosporins (OR, 3.55; CI95, 1.47-9.41) and to ciprofloxacin (OR, 7.27; CI95, 1.13-166.0) were related significantly to the development of CDAD. By stepwise logistic regression analysis, only exposure to antibiotics and prior respiratory tract infections (P = .0001 and .0203, respectively) were found to be significant. CONCLUSION: Antibiotic pressure might have contributed to failure of infection control measures to reduce the incidence of CDAD to baseline.     

Prediction of the helix/strand content of globular proteins based on their primary sequences

Population screening for hemochromatosis done by using the transferrin saturation test has been advocated by experts to permit the initiation of therapeutic phlebotomy before the onset of clinical disease. The discovery of a gene associated with hemochromatosis has made DNA testing another option for screening and diagnosis. In this paper, U.S. Preventive Services Task Force criteria are used to evaluate the evidence for the usefulness of population screening done by using iron measures or genetic testing. Published clinical research offers little evidence to suggest that population screening for hemochromatosis done by using genetic testing improves clinical outcomes. Although one recently discovered mutation, C282Y, accounts for 60% to 92% of cases of the disease in series of patients with hemochromatosis, uncertainties remain about the clinical penetrance of various genotypes; the accuracy of genetic testing; and the ethical, legal, and social effects of genetic testing. Before population screening for hemochromatosis done by using transferrin saturation testing can be recommended, laboratory standardization needs to be addressed and questions about risk for clinical disease in asymptomatic persons with mutations or early biochemical expression of disease require resolution. Evidence from case series suggests that hemochromatosis may be associated with liver cancer, other liver disease, diabetes, bradyarrhythmias, and arthritis. In all studies but one, however, estimation of the magnitude and significance of this risk is limited by lack of adequate comparison groups. The need for population data to answer questions about penetrance among asymptomatic persons should not impede efforts to increase the detection and treatment of hemochromatosis in persons found to have elevated iron measures a family history of hemochromatosis, or consistent early signs and symptoms of the disease.     

Renal effects of guanabenz: a new antihypertensive

In order to determine the effects of guanabenz upon renal function, clearance studies were performed on hypertensive volunteers during sustained steady-state water diuresis. The data reveal an acute fall in renal hemodynamics and a marked reduction in sodium excretion during the 3rd and 4th hour after administration. Tha antinatriuresis was due to decreased filtration and enhanced distal nephron reabsorption of sodium, principally in association with secretion of potassium. Chronic administration of guanabenz for one week produced a sustained reduction in blood pressure, but there was no change in either body weight or 24-hour urinary sodium excretion. Repeat clearance studies revealed no change with either renal hemodynamics or sodium clearance. The data suggest that the acute antinatriuresis is a transient hemodynamic event and chronic therapy with guanabenz will not be complicated by sodium retention, a feature characteristic of other antihypertensive agents.     

Overexpression of hepatic lipase in transgenic mice decreases apolipoprotein B-containing and high density lipoproteins. Evidence that hepatic lipase acts as a ligand for lipoprotein uptake

To determine the mechanisms by which human hepatic lipase (HL) contributes to the metabolism of apolipoprotein (apo) B-containing lipoproteins and high density lipoproteins (HDL) in vivo, we developed and characterized HL transgenic mice. HL was localized by immunohistochemistry to the liver and to the adrenal cortex. In hemizygous (hHLTg+/0) and homozygous (hHLTg+/+) mice, postheparin plasma HL activity increased by 25- and 50-fold and plasma cholesterol levels decreased by 80% and 85%, respectively. In mice fed a high fat, high cholesterol diet to increase endogenous apoB-containing lipoproteins, plasma cholesterol decreased 33% (hHLTg+/0) and 75% (hHLTg+/+). Both apoB-containing remnant lipoproteins and HDL were reduced. To extend this observation, the HL transgene was expressed in human apoB transgenic (huBTg) and apoE-deficient (apoE-/-) mice, both of which have high plasma levels of apoB-containing lipoproteins. (Note that the huBTg mice that were used in these studies were all hemizygous for the human apoB gene.) In both the huBTg,hHLTg+/0 mice and the apoE-/-,hHLTg+/0 mice, plasma cholesterol decreased by 50%. This decrease was reflected in both the apoB-containing and the HDL fractions. To determine if HL catalytic activity is required for these decreases, we expressed catalytically inactive HL (HL-CAT) in apoE-/- mice. The postheparin plasma HL activities were similar in the apoE-/- and the apoE-/-,HL-CAT+/0 mice, reflecting the activity of the endogenous mouse HL and confirming that the HL-CAT was catalytically inactive. However, the postheparin plasma HL activity was 20-fold higher in the apoE-/-,hHLTg+/0 mice, indicating expression of the active human HL. Immunoblotting demonstrated high levels of human HL in postheparin plasma of both apoE-/-,hHLTg+/0 and apoE-/-,HL-CAT+/0 mice. Plasma cholesterol and apoB-containing lipoprotein levels were approximately 60% lower in apoE-/-,HL-CAT+/0 mice than in apoE-/- mice. However, the HDL were only minimally reduced. Thus, the catalytic activity of HL is critical for its effects on HDL but not for its effects on apoB-containing lipoproteins. These results provide evidence that HL can act as a ligand to remove apoB-containing lipoproteins from plasma.