Biomedical subjects
Publications and source records attributed to J D Cleary.
Fluconazole concentrations in the serum and prostate of human volunteers undergoing transurethral resection for benign prostatic hypertrophy were measured. There was a high correlation (r = 0.783) between serum (mean = 6.6 micrograms/ml) and tissue (mean = 1.9 micrograms/g) fluconazole concentrations, and these data were used to construct a model for local tissue concentrations.
OBJECTIVE: To update readers on the significant changes in infectious diseases pharmacotherapy. DATA SOURCES: An Index Medicus and Iowa Drug Information Service search (1993-1994) of English-language literature pertaining to the selected topic areas was performed. Additional information from abstracts presented at scientific meetings were identified by the authors. STUDY SELECTION AND DATA EXTRACTION: All identified studies were screened and those judged relevant to the update were evaluated. DATA SYNTHESIS: New or clinically significant data since 1992 that related to peptic ulcer disease, microbial resistance (e.g., Enterococcus spp., Streptococcus pneumoniae, Mycobacterium tuberculosis, Candida albicans), immunomodulators, and AIDS were evaluated and compared with previous data. CONCLUSIONS: There have been several exciting and significant changes in infectious diseases pharmacotherapy evident from this review.
Explore the source record for details and available documents.
Since metronidazole is a mutagen in vitro, there is concern about the widespread systemic use of this drug in women with trichomoniasis, particularly those who are pregnant. A randomized, double-blind, placebo-controlled trial compared a single 2-g intravaginal dose of metronidazole cream with a single 2-g oral dose of metronidazole in patients with a culture positive for Trichomonas organisms. Of the 302 preenrollment cultures completed, 94 (31%) were positive. Sixty-one patients were enrolled in the study. Each received either oral placebo and intravaginal metronidazole or intravaginal placebo and oral metronidazole. Follow-up cultures were done on posttreatment day 3-5. Of the 53 evaluatable patients, 14 (50%) of 28 in the intravaginal group and 22 (88%) of 25 in the oral group were microbiologically cured (P = .0037). Single-dose intravaginal metronidazole is inferior to single-dose oral metronidazole and cannot be relied on as an alternative therapy.
OBJECTIVE: To summarize the practice of pharmacy in Iceland. DATA SOURCES: Human resources were the primary sources of data for this publication. Personal observation by Cleary is the basis of this publication. DATA EXTRACTION AND SYNTHESIS: Data on areas related to Icelandic history, practice of pharmacy, Icelandic health system, and the European Economic Community and Education were obtained through interviews. Information is presented to give an appreciation of pharmacy practice in a Nordic country. CONCLUSIONS: Pharmacy education and practice is progressive and flourishing in Iceland's National Health Service. Clinical pharmacy services are in their infancy; however, the potential for growth is immense. The Fulbright experience was educational and beneficial for all parties involved.
Explore the source record for details and available documents.
OBJECTIVE: To report the first five cases of amphotericin B overdose with secondary cardiac complications in a pediatric population. Treatment is also presented. SETTING: Hospital. PATIENTS: Two infants and three children inpatients receiving amphotericin B. INTERVENTIONS AND RESULTS: Cardiac complications were observed in five pediatric patients who received between 4.6 and 40.8 mg/kg/d of amphotericin B. Cardiac arrest occurred in all patients, and four patients died. A detailed description of the cardiac event is provided for one patient who was on a cardiac monitor during the adverse reaction. Hydrocortisone prophylaxis and verapamil therapy were the primary therapies used in patient 1 (the only survivor). Evaluation of the literature provides substantial evidence for the use of hydrocortisone in prevention of cardiac arrhythmias. CONCLUSIONS: Amphotericin B overdose can be fatal in children and infants. The presentation in humans appears similar to that in dogs where cardiac arrhythmias occurred at doses of 5-15 mg/kg. Hydrocortisone may decrease the incidence of mortality associated with cardiac arrhythmias in children receiving amphotericin B overdoses. Animal studies are necessary to evaluate this observation and potential disadvantages of hydrocortisone usage.
Fever and chills occur frequently with amphotericin B (AB) administration, but the mechanism that causes these reactions has not been definitively established. A variety of proinflammatory cytokines, including interleukin-1 (IL-1) and tumor necrosis factor, have been shown to be important mediators of fever. In order to clarify the cellular and biochemical responses associated with AB-induced fever, the experiments described sought to (i) establish whether human mononuclear cells exposed to AB in vitro expressed IL-1 beta, (ii) evaluate whether clinically used premedications for fever prophylaxis in AB-treated patients were effective in down-regulating IL-1 beta expression in vitro, (iii) evaluate whether methylxanthine agents with immunomodulatory actions effected in vitro IL-1 beta expression, and (iv) define the dose and time dependency of the modulating effects. Peripheral blood mononuclear cells were isolated by density centrifugation and resuspended to 10(6) cells per ml in culture wells of Linbro plates. When cocultured for 2 h with human mononuclear cells, both Escherichia coli lipopolysaccharide and AB stimulated IL-1 beta expression in a dose-related fashion. AB-induced IL-1 beta expression was suppressed by hydrocortisone (HC), pentoxifylline, and an investigational theobromine, A81-3138, in a linear, dose-related manner. In contrast, indomethacin, meperidine, and diphenhydramine had no effect on IL-1 beta expression. Our in vitro data indicate that serum HC concentrations of greater than 1 to 2 micrograms/ml may be sufficient to modulate IL-1 beta expression. Pentoxifylline and A81-3138 may also be effective in modulating IL-1 beta expression by mononuclear cells at concentrations achievable in serum. These new agents may prove to be effective alternatives to HC or may be added with HC to suppress febrile reactions secondary to AB administration. Clinical studies with pentoxifylline as a premedication for AB seem warranted.
OBJECTIVE: This overview compares and contrasts the pharmacotherapy of itraconazole with that of other antifungal agents. DATA SOURCES: Primary literature on itraconazole was identified through a medical literature search from 1976 through 1991. This search included journal articles, abstracts, conference proceedings, and reports of animal and human research published in the English language. STUDY SELECTION: All primary literature was reviewed regardless of the study design or outcome. Literature evaluations of efficacy were ranked using a literature rating scale (Dalen JE, Hirsh J. Arch Intern Med 1986;146:462-72), which was slightly modified to include case reports and observations. DATA EXTRACTION: All data were collected and represented with a primary focus on itraconazole's mechanism of action, pharmacokinetics, clinical efficacy in systemic mycotic infections, drug interactions, and adverse reactions. All articles were referenced in the final data presentation unless grouped data had been accurately reviewed and published. DATA SYNTHESIS: Despite the paucity of controlled comparative trials with itraconazole in patients with deep mycoses, results on efficacy are encouraging. It is still unclear what role itraconazole will have in the prophylaxis of fungal infections in immunocompromised hosts. The favorable pharmacokinetic profile permits once- or twice-daily administration and itraconazole appears to be safe and well tolerated. CONCLUSIONS: Itraconazole should prove to be a useful replacement for ketoconazole on hospital formularies. This recommendation is based on itraconazole's greater apparent safety and efficacy. Reevaluation of this agent will be necessary upon the release of newer imidazoles and triazoles.
Explore the source record for details and available documents.
Fungal infections range from superficial mycoses involving skin or mucous membranes to severe opportunistic infections that may be fatal. The selection of chemotherapeutic agents useful for the treatment of fungal infections includes many topical or systemic imidazoles and triazoles. This overview compares and contrasts the pharmacology and therapeutic use of these agents. This review will focus primarily on these agents' mechanism of action, pharmacokinetics, clinical studies, and adverse reactions.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Our objective was to prospectively study febrile and chill reactions associated with two amphotericin B (AB) infusion rates, slow (2-hour) versus rapid (45 minute). Seventeen consenting bone marrow transplant recipients in whom AB was to be initiated for documented or suspected fungal infections were recruited. After standardized premedication, patients received eight daily AB infusions (0.5 mg/kg/d, concentration 0.25 mg/ml). Rate was assigned using a randomized, crossover pair design. Axillary temperature, chills, and meperidine dose required to resolve chills were monitored for each infusion. For the first pair of infusions, fever (defined as a rise of 1 degree C) occurred frequently, in 12 of 17 (70.5 percent) and 13 of 17 patients (76.4 percent), with a mean rise of 1.7 degrees C (range 1.1-3.7) and 1.7 degrees C (1.1-3.5) degrees for the 45-minute and 2-hour infusions, respectively (p greater than 0.10). Chills were observed in 15 of 17 (88.2 percent) and 14 of 17 (82.3 percent) recipients of the 45-minute and 2-hour infusions, respectively. The time of onset (p greater than 0.10) and the duration of chills (p = 0.08) were similar for both infusion rates. Meperidine requirements for rapid and slow infusions were similar as well (p = 0.12). These data suggest that for patients free of preexisting renal and cardiac disease, rapid AB infusions are well tolerated and produce adverse reactions (fever and chills) similar in nature and severity to slower infusions.
Enalapril maleate is a new angiotensin converting enzyme inhibitor marketed in the U.S. by Merck Sharp and Dohme. It has been demonstrated to actively interfere with the renin-angiotensin-aldosterone system. This is reflected by both hemodynamic (decreased blood pressure) and humoral (increased plasma renin, angiotensin I, and decreased angiotensin II) responses to enalapril therapy. Activity in the kallikrein-bradykinin system is still controversial. Enalapril maleate is a prodrug which is quickly absorbed, hydrolyzed by the liver to the active metabolite enalaprilic acid, and excreted 33 percent in the bile and 61 percent in the urine. The therapeutic dosage range is 10-40 mg/d, maximum of 40 mg, given once or twice daily. The onset and duration of action are dose related. Vertigo and headache have been the most commonly reported side effects. Clinical comparison of enalapril to hydrochlorothiazide, beta-adrenergic blockers, and captopril find it efficacious in the treatment of essential hypertension. Efficacy in treating congestive heart failure and hypertension secondary to renal artery stenosis has also been demonstrated for both angiotensin converting enzyme inhibitors. The overall efficacy and safety of enalapril and captopril appear equivalent when used at low doses in patients with uncomplicated hypertension.