摘要:

We reviewed the spectrum of activity, pharmacokinetics, clinical efficacy, adverse effects, and relative advantages of piperacillin‐tazobactam, a new β‐lactam‐β‐lactamase inhibitor. Piperacillin‐tazobactam has a wide spectrum of activity that includes gram‐positive organisms such as staphylococci and streptococci, as well as many gram‐negative aerobic and anaerobic bacteria. The combination distributes rapidly after parenteral administration and penetrates well into skin, lung, and intestinal mucosa. Compared with other β‐lactam‐β‐lactamase inhibitor combinations, piperacillin‐tazobactam has comparable efficacy in the treatment of intraabdominal infections, skin and soft tissue infections, and upper and lower respiratory tract infections. It may have better in vitro activity than the currently available combinations against selective bacteria that produce class I β‐lactamases (Richmond‐Sykes classification). The combination is well tolerated, with diarrhea being the most common reported adverse effect. Additional controlled trials and clinical experience are required to define

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1996.tb02933.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Patients infected with human immunodeficiency virus (HIV) are at risk for various viral and bacterial infections. Active immunization with currently available vaccines may reduce the risk of some vaccine‐preventable diseases in this population. Based on available data, most vaccines used in the United States are safe in HIV‐infected adults and children. Their clinical efficacy in these individuals is not well defined, although it appears that patients in the earlier stages of infection are more likely to mount a protective antibody response than those in the later stages. Current guidelines for vaccination in HIV‐infected children and adults in the United States have been recommended by the Advisory Committee on Immunization Prac

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1996.tb02934.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Atypical mycobacteria that cause disseminated disease result in significant morbidity and mortality among patients with advanced human immunodeficiency viral infection. Although significant progress has been made with respect to our understanding of the epidemiology, microbiology, and pathogenesis ofMycobacterium aviumcomplex (MAC) infections in patients with the acquired immunodeficiency syndrome (AIDS), treatment and prevention strategies are still emerging. A series of case‐controlled studies and clinical trials evaluated various combinations of traditional and investigational antimycobacterial agents, and demonstrated modest clinical and microbiologic success in the treatment of disseminated MAC infection. Prevention studies proved rifabutin and clarithromycin to be rational prophylaxis agents. Continued identification of optimum combination regimens remains essential to curtail the increasing frequency of disseminated MAC disease in patients with AID

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1996.tb02935.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Life expectancy has dramatically increased in industrialized countries since the 1900s due to advances in disease prevention and treatment, and improvements in nutrition and infant mortality. Thus, as a society we are living longer and experiencing more of the changes and declines associated with aging. Although the factors that cause our bodies to age are unknown, various medical interventions have been proposed and explored to prevent the process. Published research on aging conducted during the past 10 years was retrieved through MEDLINE and critically evaluated. Animal and human studies suggest potential benefits of dietary modification, exercise, antioxidants, hormones, and deprenyl. Due to the interrelationships between disease and older age and the limitations of existing research in this area, most life extension strategies are untested hypotheses. Many strategies merit scientific inquiry, but they cannot be recommended for use. More extensive research is necessary to assess their safety, effectiveness, and socioeconomic impact, and to resolve ethical controversies before they can be considered applicable in humans.

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1996.tb02936.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

To enhance knowledge in the area of in vitro testing of antibiotics and to understand the limitations of available methods for susceptibility testing, we conducted a MEDLINE literature search in the English language to accumulate relevant articles. Headings searched included microbial sensitivity tests; Kirby‐Bauer; laboratory tests; antiinfective agents; antibiotics, combined; microbiological techniques; blood bactericidal assay; and pharmacology, clinical. The management of patients with serious life‐threatening infections can be complicated by recent changes in organism nomenclature, newly marketed antibiotics, and new isolation and sensitivity testing methods. With the addition of formulary constraints, many problems and controversies arise regarding interpretation of antibiotic sensitivity results. Comprehensive care for infected patients requires assessment of current antibiotic therapy and options for alternative therapy. By applying pharmacodynamic and pharmacokinetic knowledge to known limits of in vitro testing results, the clinician is able to select the most efficient antibiotic or antibiotic combinat

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1996.tb02937.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Study Objective. To assess the accuracy of five creatinine clearance equations in predicting measured creatinine clearance in hospitalized patients with human immunodeficiency viral (HIV) infection.Design. Prospective evaluation over a 6‐month period.Setting. Erie County Medical Center, a 550‐bed teaching institution.Patients. Forty‐seven HIV‐positive patients (39 men, 8 women) who were admitted for a variety of HIV‐related illnesses and judged clinically to have stable renal function. Of the 47 original patients, 44 were evaluable based on exclusion criteria.Interventions. Serum creatinine and 24‐hour measured creatinine clearance were performed in each patient.Measurements and Main Results. The estimated creatinine clearance from each of the equations (Cockcroft‐Gault, two Jeliffe equations, Mawer et al, and Hull et al) was compared with the measured creatinine clearance. Statistical analysis of these comparisons was performed and all of the equations were found to overestimate the measured creatinine clearance (mean error 34–45%).Conclusions. Many HIV‐infected patients have a decreased creatinine clearance despite a serum creatinine concentration within the normal range. Each of the equations overestimated the measured cre

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1996.tb02938.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

The performance of a digital data‐acquisition and ‐analysis system in measuring cardiac complex intervals was compared with manual measurements in 10 healthy subjects. A data set of 500 cardiac complexes was created from lead II electrocardiographic samples from each subject. Intervals were measured to the nearest 5 msec by hand and to the nearest 1 msec by the analysis system. Automated measurements of the RR interval and QRS duration exhibited no bias and median absolute errors of 3 msec. Measurements of the PR interval exhibited a significant bias (18 msec) that accounted for the majority of the imprecision (19 msec). A small but significant bias (4 msec) was found in the measurement of the QT duration with a median absolute error of 12 msec. The traditional method of averaging the values of 10 consecutive complexes provided results similar to individual complex measurements. The automated analysis of cardiac intervals can produce data that are suitable for pharmacodynamic stud

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1996.tb02939.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

We evaluated the antiangiogenic activity of shark cartilage, tumor necrosis factor‐α (TNF‐α), and a combination of the two using a human umbilical vein endothelial cell proliferation assay. Proliferation of endothelium is a hallmark of angiogenesis, and inhibition of endothelial cell proliferation indicates potential antiangiogenic activity. Shark cartilage produced a concentration‐dependent decline in endothelial cell3H‐thymidine incorporation. This activity was heat stable and was found in molecular weight fractions of less than 10 kd. The antiproliferative effect of shark cartilage was specific for vascular endothelium and did not affect the proliferative rate of human astrocytoma cells or human skin fibroblasts. Shark cartilage at a concentration of 500 μg/ml and TNF‐α at a concentration of 10 ng/ml reduced endothelial cell proliferation by 32% and 29%, respectively. Treatment of endothelial cells with the combination of shark cartilage and TNF‐α resulted in a 44% reduction in endothelial cell proliferation. The isolation and identification of the active components of shark cartila

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1996.tb02940.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Study Objectives. To evaluate the safety, tolerability, and pharmacokinetics of single, escalating doses of oral dolasetron mesylate, a new 5‐HT3receptor antagonist.Design. Double‐blind, placebo‐controlled, dose‐escalating phase I study.Setting. A clinical research center.Patients. One hundred twenty healthy male volunteers.Interventions. Subjects received either placebo or oral dolasetron mesylate 50, 100, 150, 200, 250, 300, or 400 mg.Measurements and Main Results. Compared with placebo, subjects receiving dolasetron mesylate reported a greater frequency of headache, lightheadedness, dizziness, increased appetite, and nausea. There were no clinically significant changes in mean laboratory values from before to after treatment. Adverse events were transient, mild or moderate, and similar to those after single intravenous doses of the drug. No clinically significant electrocardiographic changes occurred, but lengthening of the QRS complex duration and dose‐dependent lengthening of PR and QTcintervals were observed 1–2 hours after dosing. These effects were asymptomatic and were mainly associated with higher doses (≥ 300 mg).Conclusion. Dolasetron mesylate is well tolerated when administered in single oral doses up to 400 mg to healthy volunteers. Clinical trials are under way to evaluate the agent's efficacy in preventing chemotherapy‐induced and postoperative nausea and vomiting with dos

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1996.tb02941.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Study Objectives. To evaluate the safety, tolerability, and pharmacokinetics of increasing dose levels of oral dolasetron mesylate, a new 5‐HT3antagonist.Design. Double‐blind, placebo‐controlled, dose‐ranging phase I study.Setting. A clinical research center.Patients. Forty healthy male volunteers.Interventions. Eight subjects at each dose level were randomized in a ratio of 3:1 to receive either dolasetron mesylate 25, 50, 100, 150, or 200 mg in a single oral dose on days 1 and 9, and twice/day on days 2–8, or placebo for 9 days.Measurements and Main Results. Dolasetron was well tolerated at all dose levels. The adverse event rates for dolasetron‐ and placebo‐treated subjects who experienced at least one adverse event were 80% and 50%, respectively. Most frequently reported by subjects receiving dolasetron were headache, constipation, flatulence, and lightheadedness. They generally were mild, and none was severe. No dose‐response relationship was apparent for any adverse event. There were no clinically significant changes in mean laboratory values or vital signs. Asymptomatic treatment‐related electrocardiographic changes were consistent with the drug's electrophysiologic properties. These changes have been well characterized and have thus far been clinically unimportant. Pharmacokinetics of the reduced metabolite were dose independent, and multiple‐dose exposure of this metabolite can be predicted from its single‐dose values.Conclusion. Oral dolasetron mesylate was well tolerated when administered in doses up to 200 mg/day for 9 days

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1996.tb02942.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY