ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1995.tb04364.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

We prospectively identified predictors of future antihypertensive use in untreated persons age 18–65 years who had elevated diastolic blood pressures of 90–104 mm Hg or systolic blood pressures of at least 140 mm Hg. Data were derived from two independent cohorts completing household surveys conducted in 1981–1984 and 8 years later, as part of the Pawtucket Heart Health Program. Demographics, self‐reported health behaviors and beliefs, and physiologic measurements were obtained. Drug use was determined through structured interviews. Analysis of covariance and logistic regression were performed. In the 492 subjects, independent baseline predictors of future antihypertensive use (p<0.05) included female gender, older age, diastolic blood pressure elevation, self‐perceived high blood pressure, and self‐reported salt limitation. Antihypertensive use for previously untreated mild hypertension is diverse. Older women with diastolic elevations who are health conscious are most likely to

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1995.tb04365.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

The incidence of emergent resistance and clinical factors affecting its development were evaluated by retrospective review of 173 studies encompassing over 14,000 patients. Eight antibiotic classes and 225 individual treatment regimens were evaluated. Emergent resistance occurred among 4.0% of all organisms and 5.6% of all infections treated. It appeared to be significantly more frequent with penicillin and aminoglycoside monotherapy, with significantly lower rates associated with imipenem‐cilastatin, aztreonam, and combination therapy. Clinical failure also appeared to be significantly more likely to occur after emergence of resistance among organisms treated with fluoroquinolones or aminoglycosides. Infections associated with higher resistance rates were cystic fibrosis, osteomyelitis, and lower respiratory tract infections. Resistance was most common in patients in intensive care units or receiving mechanical ventilation. It was also significantly frequent among studies performed in university or teaching hospitals. Organisms associated with high resistance rates werePseudomonas aeruginosa, Serratia, Enterobacter, andAcinetobactersp. Factors such as infection type, underlying diseases, type of institution, and specific pathogens warrant consideration when examining emergent resistanc

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1995.tb04366.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

We compared the effectiveness of selectively screening pharmacy data bases to identify patients with hypercholesterolemia with that of mass cholesterol screening. Screening data bases of four community pharmacies yielded 426 patients filling prescriptions for β‐blockers, thiazide diuretics, oral hypoglycemics, insulin, sublingual nitroglycerin, nicotine gum, or nicotine patches. They were invited to attend a cholesterol screening. Eighty‐eight of the contacted patients attended, as did 97 walk‐in persons. Cholesterol readings were higher in the contacted group (p=0.017). Borderline‐high cholesterol levels (200–239 mg/dl) were reported in 36.3% of the contacted group and 29.8% of the walk‐in group. High cholesterol levels (>239 mg/dl) were reported in 31.8% and 18.6%, respectively Targeting certain drugs that directly contribute to raising cholesterol or indicate other risk factors for coronary artery disease (e.g., diabetes mellitus) was an effective method of identifying patients with hypercho

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1995.tb04367.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

To evaluate the rationale behind dosing aminoglycosides as a single daily dose versus traditional dosing approaches, we conducted a MEDLINE search to identify all pertinent articles, and also reviewed the references of all articles. Single daily dosing of aminoglycosides is not a new concept, having been examined since 1974. The advantages of this regimen include optimum concentration‐dependent bactericidal activity, longer dosing intervals due to the postantibiotic effect (PAE), and prevention of bacterial adaptive resistance. Because of longer dosing intervals, toxicity may also be delayed or reduced. Costs may be reduced due to decreased monitoring and administration. Clinically, the regimen has been implemented in various patient populations with reported success. Questions remain, however, about optimum dose, peak and trough serum concentrations, and dose adjustment in patients with renal impairment or neutropenia. More clinical experience with this method in large numbers of patients has to be published. Pharmacists can be instrumental in monitoring patients receiving once‐daily therapy and by educating health care professionals as to the rationale behind the ther

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1995.tb04368.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

To characterize the lipid and lipoprotein abnormalities in patients with diabetes mellitus and evaluate the risks and benefits of marketed pharmacologic therapies, a MEDLINE search of the National Library of Medicine data base was performed of studies published from January 1966 to March 1994. Clinical trials assessing effects on lipids and lipoproteins, and adverse effects of marketed lipid‐lowering agents were extracted. Reviews and other relevant articles were included if they provided information regarding lipid and lipoprotein metabolism or guidelines on the treatment of dyslipidemias in patients with diabetes mellitus. An extensive review of clofibrate was not included. The most common dyslipidemia in patients with poorly controlled insulin‐dependent diabetes mellitus (IDDM) is combined elevated triglyceride and cholesterol levels, with reduced high‐density lipoprotein (HDL) cholesterol (mixed hyperlipidemia). Hypertriglyceridemia combined with a reduced HDL cholesterol is the most common dyslipidemia in patients with noninsulin‐dependent diabetes mellitus, but essentially any pattern of dyslipidemia may be present. Small and dense low‐density lipoprotein (LDL), glycosylation of lipoproteins, and increased oxidized lipoproteins may be present in patients with diabetes mellitus; all contribute to accelerated atherosclerotic cardiovascular disease. Insulin therapy generally corrects quantitative lipid abnormalities in patients with IDDM, so drug treatment is seldom indicated. Diet, exercise, and insulin or oral sulfonylureas will improve hypertriglyceridemia and low HDL concentrations, but do not always return them to normal. Drug therapy is indicated when nonpharmacologic measures are inadequate. It is administered based on the effects of each agent on lipids and lipoproteins, patient age, adverse effect profile, patient tolerability, and drug‐disease and drug‐drug interactions. A fibric acid derivative is the drug of choice for marked hypertriglyceridemia in patients with diabetes mellitus. Niacin can worsen glycemic control, but it may be required in severe hypertriglyceridemia, hypercholesterolemia, or mixed hyperlipidemia. Bile‐acid binding resins may accentuate hypertriglyceridemia but may be useful in selected patients with marked hypercholesterolemia and normal triglycerides. Hydroxymethylglutaryl coenzyme A reductase inhibitors are preferred in patients with elevated LDL cholesterol and mild hypertriglyceridemia. Patients with marked lipid abnormalities or mixed hyperlipidemias may require carefully dosed combinations of lipid

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1995.tb04369.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

In humans and various animal species, 3′‐azido‐3′‐deoxythymidine (AZT) is in part eliminated by the kidneys, where it undergoes significant tubular secretion. The goal of this project was to develop, in a continuous renal epithelial cell line (LLCPK1), a model of AZT transport in which mechanisms of drug interactions could be investigated. Transport properties of H3‐AZT were studied in LLCPK1cells grown as monolayers on permeable filters. This system provides access to the basolateral and apical surfaces of the epithelium and allows the determination of substrate transepithelial flux from the basolateral side to the apical side (B → A/secretory direction) and apical to basolateral side (A → B/reabsorptive direction). The B → A flux of AZT was significantly greater than B → A flux of mannitol (a nontransported substrate) and was temperature dependent (37°C>4°C). The AZT A → B flux was significantly smaller than the B → A flux, indicating that the drug is predominantly secreted in this renal epithelium. The B → A flux was significantly inhibited by the organic bases cimetidine, quinine, quinidine, and trimethoprim. Log concentration dose studies indicate that quinine is a weak inhibitor (IC50= 9.61 mM) of AZT B → A flux, and that AZT is a moderate inhibitor (IC50= 0.69 mM) of the organic base cimetidine. These results suggest that AZT may share the organic base transporter in the renal epithelium, and that this model can be used successfully to study transport properties and renal

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1995.tb04370.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

We evaluated the absorption disturbance of the gastrointestinal tract in patients with familial amyloidotic polyneuropathy (FAP). Ursodeoxycholic acid (UDCA) 300 mg was administered orally to 10 patients with FAP and 11 control subjects. Serum levels of total bile acid were determined as an indicator of absorption. The patients had lower serum levels of total bile acid than controls, suggesting an absorption disorder. To attempt to treat the diarrhea commonly associated with FAP, l‐threo‐3,4‐dihydroxyphenylserine (l‐threo‐DOPS), a synthetic precursor of norepinephrine, was administered 100 mg/dose by the oral and 8 mg/0.4 ml by the intranasal route and their effects on the elevation of serum norepinephrine levels were compared. The 3–0‐monohemiphthalate salt of glycyrrhizinic acid and sodium ascorbate were used as vehicles for the intranasal preparation to enhance drug absorption and prevent oxidation. Increased serum levels of norepinephrine, the converted metabolite of l‐threo‐DOPS in serum, was observed 2 hours after intranasal administration, but not after administration of the oral preparation or vehicle alone. Intranasal administration of 8 mg 3 times/day for 1 week resulted in reduction of the daily frequency of diarrhea as well as a decrease in the severe orthostatic hypotension in three patients with FAP. Thus, an intranasal delivery system for l‐threo‐DOPS, which acts by stimulating adrenergic receptors, may be considered in treating patients with FAP

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1995.tb04371.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Jejunoileal bypass reportedly inhibits the absorption of cyclosporine. In patients with malabsorption syndromes, bile acid replacement has been given to enhance the absorption of cyclosporine. A candidate for heart transplantation with New York Heart Association class IV heart failure and a jejunoileal bypass received cyclosporine alone and with concomitant ursodiol administration to determine whether therapeutic cyclosporine plasma concentrations would be attainable after heart transplantation. There were no differences in peak concentration, time to peak, area under the serum concentration versus time curve, or bioavailability of oral cyclosporine when administered alone or with ursodiol. Plasma cyclosporine concentrations were consistent with those in the general population.

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1995.tb04372.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

This study documents a pharmacokinetic interaction between carbamazepine and cyclosporine (CsA) in pediatric renal transplant recipients. Noncompartmental steady‐state CsA pharmacokinetics were determined in three pediatric renal transplant recipients who were receiving both CsA and carbamazepine as long‐term therapy (carbamazepine group) and in three matched renal transplant subjects who were not receiving carbamazepine (control group). Even though the mean daily dosage of CsA was consistently higher in the carbamazepine group than in the control group (16.2 mg/kg/24 hrs vs 10.8 mg/kg/24 hrs, respectively), the predose trough CsA blood concentrations were significantly lower in the carbamazepine group (57 ng/ml vs 162 ng/ml, respectively; p=0.0023). Mean average steady‐state blood concentrations of CsA (Cav) per mg of CsA administered were less than 50% in the carbamazepine group compared with the control group. This reflects either an induction of CsA hepatic metabolism or a reduced systemic bioavailability (possible induction of pre‐hepatic metabolism) by concurrent use of carbam

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1995.tb04373.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY