ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1993.tb02694.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

The curative potential of chemotherapy for a number of tumor types has been obscured by the fact that many patients initially have striking remissions but later relapse and die. At the time of relapse many patients manifest resistance to a wide array of structurally unrelated antineoplastic agents, hence the term multidrug resistance (MDR). Other tumor types, such as those arising in the colon, kidneys, liver, and lungs, tend to exhibit poor response to available cytotoxic drugs. The MDR phenomenon includes cross‐resistance among the anthracyclines (doxorubicin, daunorubicin), the epipodophyllotoxins (etoposide, teniposide), the vinca alkaloids (vinblastine, vincristine), taxol, and other compounds. In vitro studies in cell culture indicate that this form of resistance is associated with amplification or overexpression of themdrl gene. Themdrl gene codes for the expression of a cell surface protein, P‐glycoprotein (P‐gp), which acts as an energy‐dependent efflux pump that transports drugs associated with MDR out of the cell before cytotoxic effects occur. The protein is expressed in normal human tissues such as the gastrointestinal tract, liver, and kidneys, where it is thought to serve as an excretory pathway for xenobiotic drugs and toxins. Preliminary studies demonstrated the presence of P‐gp in tumor samples from patients with acute leukemia, multiple myeloma, lymphomas, and a variety of solid tumors. A number of drugs are able to reverse MDR, including calcium‐channel blockers, phenothiazines, quinidine, antimalarial agents, antiestrogenic and other steroids, and cyclosporine. Limited results from clinical trials with small numbers of patients suggest that the addition of verapamil, diltiazem, quinine, trifluoperazine, or cyclosporine to chemotherapeutic regimens has the potential to reverse MDR; however, toxicities limit their clinical usefulness. A number of trials are under way to identify more active and less toxic modula

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1993.tb02695.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Despite its prevalence, the significance of candiduria remains uncertain. The pathogenesis of candidal urinary tract infections has been relatively well characterized and many risk factors have been identified. The disorders lack consistent diagnostic criteria, however, such as the presence of pyuria or a colony count above which is predicative of presence, location, or severity of infection. Treatment is unclear due to lack of data defining the natural progression of the disease. Although often recommended, it may not always be possible to remove risk factors. Amphotericin B, fluconazole, 5‐flucytosine, and other antifungal agents are important agents for managing candidal urinary tract infection

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1993.tb02696.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Gram‐negative sepsis is a common event in hospitalized patients and is a leading cause of death in the United States. Endotoxin (lipopolysaccharide, LPS), a component of the cell wall of gram‐negative microorganisms, is responsible for the cascade of events leading to the sepsis syndrome consisting of fever, tachycardia, tachypnea, and evidence of organ hypoperfusion. The lipid A region of endotoxin produces most of these biologic and toxic effects. Monoclonal IgM antibodies directed against the lipid A portion of endotoxin (anti‐LPS MoAb) have been developed for the treatment of gram‐negative sepsis. Results of two large‐scale clinical trials suggest that these antibodies offer clinically and statistically significant reductions in mortality by a factor of about one‐third. However, in both trials, this apparent beneficial effect was limited to particular subsets of patients, and no overall benefit was seen. These considerations, in addition to the likely high cost of the agents, pose questions about their ultimate use in the treatment of patients with gram‐negative sepsis. Nevertheless, the logic of the approach, the demonstration of efficacy in disease models, and the advances in modern techniques of molecular biology all suggest that these or other closely related products will play a significant role in the treatment of

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1993.tb02697.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

The accuracy of 2‐ and 8‐ hour urine collections for estimating creatinine clearance was compared with that of the standard 24‐hour procedure in 45 hospitalized elderly patients (age ≥ 65 yrs) with indwelling urethral catheters. Urine was collected at blocked intervals from 0–2, 2–8, and 8–24 hours and then added together to determine the 8‐ and 24‐hour clearances. The mean 8‐hour creatinine clearance was not significantly different from the 24‐hour value, whereas the mean 2‐hour creatinine clearance was significantly different. The 8‐hour value was less biased (2.2 and 10.7 ml/min, respectively) and more precise (11.7 and 25.3 ml/min, respectively) than the 2‐hour value. Regardless of age, renal function, serum creatinine level, or diuretic use, the 8‐hour value was less biased, usually more precise, and clinically more accurate. Thus it can be used in stable, hospitalized, elderly patients with indwelling catheters to determine degrees of renal impairment an

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1993.tb02698.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

To determine the renovascular effects of nonprescription ibuprofen in the maximum labeled over‐the‐counter (OTC) dosage for 7 days, and to compare these effects with those of two other available OTC analgesics, aspirin and acetaminophen, we evaluated 25 elderly patients with mild thiazide‐treated hypertension and mild renal insufficiency. Under double‐blind conditions, patients were randomly allocated to one of three treatment groups: ibuprofen 400 mg 3 times/day, aspirin 650 mg 3 times/day, or acetaminophen 650 mg 3 times/day. Blood pressure and indexes of renal function (blood urea nitrogen, creatinine clearance, serum electrolytes) were measured over 7 days in a clinical research center. None of the treatments had a clinically significant effect on blood pressure. Renal function indexes also remained unchanged during all three treatments. We conclude that elderly patients with mild thiazide‐treated hypertension and mild renal insufficiency seem not to be at risk of developing additional renal compromise or of having their hypertension control diminished by treatment with these OTC analgesics f

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1993.tb02699.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

The effects of isradipine 2.5 mg and 5 mg on the disposition of theophylline were investigated in a placebo‐controlled, randomized, three‐way, crossover trial. Eleven healthy, nonsmoking men each received a treatment of placebo, and isradipine 2.5 mg and 5 mg every 12 hours for 6 consecutive days. On the morning of day 6, 2 hours after the isradipine dose, theophylline (solution) 5.0 mg/kg was administered orally, and blood samples were collected over 24 hours. A 2‐week washout period separated treatment sequences. Plasma samples were analyzed for theophylline using high‐performance liquid chromatography. Using a two‐way analysis of variance, no significant changes in apparent theophylline clearance were observed between placebo, and isradipine 2.5 and 5 mg (0.815 ± 0.164, 0.870 ± 0.212, and 0.827 ± 0.164 ml/min/kg, respectively; p=0.136). Similarly, no significant change in volume of distribution was noted. These findings suggest that isradipine at recommended dosages does not impair theophyllin

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1993.tb02700.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1993.tb02701.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1993.tb02702.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1993.tb02703.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY