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Biomedical subjects

T J Ives

Publications and source records attributed to T J Ives.

At least 19 recordsLinked to original sources

In vitro susceptibilities of Bartonella and Rickettsia spp. to fluoroquinolone antibiotics as determined by immunofluorescent antibody analysis of infected Vero cell monolayers.

The in vitro susceptibilities of Bartonella and Rickettsia spp. to different concentrations of ciprofloxacin, levofloxacin, ofloxacin and sparfloxacin in Vero cell cultures, were determined by enumeration of immunofluorescent-stained bacilli. After incubation in a CO(2)-enriched atmosphere, inocula were replaced and tested with media containing 12 different concentrations of each antibiotic in replicate for each species and the monolayers were re-incubated. Growth status was determined by evaluation of immunofluorescent staining bacilli. Effective inhibitory antibiotic dilution endpoints were determined by counting Bartonella- and Rickettsia-specific fluorescent foci across a range of antibiotic dilutions with an epi-fluorescent microscope, and were compared with an antibiotic-negative control. Based upon the use of C(max):MIC and AUC:MIC data, levofloxacin exhibited activity against Bartonella elizabethae and B. quintana.

Animals↗

Disposition and functions of clarithromycin in human THP-1 monocytes during stimulated and unstimulated conditions.

The macrolide antibiotics are bacteriostatic agents interfering with protein synthesis but they are taken up by phagocytic cells, e.g. macrophages, neutrophils and fibroblasts which take up infectious organisms into phagosome-lysosomal vaculoes. Recent studies have suggested that these macrolide antibiotics block the spread of infections by mechanisms associated with the inflammation process. Herein is a study with clarithromycin using human THP-1 monocytes, a phagocytic cell which has not been studied to date. Clarithromycin was rapidly taken up by the monocytes (approximately 1%) utilizing both saturable carrier and passive processes at pH 7.4 but was exclusively passive at pH 6.8 and 5.0. The carrier process was energy and temperature dependent and appeared to be linked to certain ion channels. Efflux of the drug was rapid and complete in 1 hr. Intracellular disposition showed 74% in the cell sap and 11% in the nucleus. Upon stimulation with zymogen A or bacteria significant increases of uptake occurred in the isolated lysosome-phagosomes. Examination showed that initially clarithromycin treatment triggered the release of NO, H2O2, IL-1 and TNFalpha from the monocytes, known mediators of inflammation, but also mediators which cause bacterial cell death or apoptosis. The activity of the monocyte marker hydrolytic enzyme NAG was elevated at this time as well as protein kinase C activity. Treatment from 2-4 hr with clarithromycin appeared to reverse this process in that the chemical mediator release was reduced along with the activities of hydrolytic enzymes, e.g. NAG and cathepsin D with no evidence of lipid peroxidation and protective SOD enzyme activity elevation. The latter effects of the antibiotic would be useful in blocking the spread of infection or inflammation from the original site. The normal bacterial static killing effects of clarithromycin was evident at 24 but not 2 hr in both extracellular free bacteria and those bacteria phagocytosed by the THP-1 monocytes.

Clarithromycin↗

In vitro susceptibilities of Rickettsia and Bartonella spp. to 14-hydroxy-clarithromycin as determined by immunofluorescent antibody analysis of infected vero cell monolayers.

The in vitro susceptibilities of Rickettsia akari, Rickettsia conorii, Rickettsia prowazekii, Rickettsia rickettsii, Bartonella elizabethae, Bartonella henselae and Bartonella quintana to different concentrations of clarithromycin, 14-hydroxy-clarithromycin (the primary metabolite of clarithromycin) and tetracycline in Vero cell cultures, were determined by enumeration of immunofluorescently-stained bacilli. The extent of antibiotic-induced inhibition of foci was recorded for each dilution of antibiotic and compared with an antibiotic-negative control. Based upon MIC data, clarithromycin alone is highly active against all three Bartonella spp., R. akari and R. prowazekii, while 14-hydroxy-clarithromycin is active against R. conorii, R. prowazekii and R. rickettsii. Further testing is warranted in animal models and human clinical trials, to examine the activity of both clarithromycin and its primary metabolite and to define further the role of clarithromycin in therapy, particularly of infections caused by obligate intracellular bacteria such as Rickettsia and Bartonella spp.

Animals↗

Mycotic infections. Effective management of conditions involving the skin, hair, and nails.

Superficial mycotic infections of the skin, hair, or nails are recurring presentations in the geriatric primary care setting. The most common infections are those caused by dermatophytes. The genus Trichophyton gives rise to most of the tinea dermatophytoses, including tinea capitis, tinea pedis, and tinea unguium (onychomycosis). Part of the diagnostic challenge lies in distinguishing the mycotic lesions from those caused by cutaneous diseases such as psoriasis, eczema, dyshidrosis, and contact dermatitis. Because environmental conditions play a major role in fungal infection onset, clinical management should include patient education about conditions conducive to fungal propagation. Oral agents are the primary mode of treatment for fungal infections of the scalp and nails, whereas topical treatments are frontline agents for other superficial skin conditions.

Antifungal Agents↗

In vitro susceptibilities of Bartonella henselae, B. quintana, B. elizabethae, Rickettsia rickettsii, R. conorii, R. akari, and R. prowazekii to macrolide antibiotics as determined by immunofluorescent-antibody analysis of infected Vero cell monolayers.

The in vitro susceptibilities of Bartonella (Rochalimaea) henselae, B. quintana, B. elizabethae, Rickettsia akari, R. conorii, R. prowazekii, and R. rickettsii to different concentrations of azithromycin, clarithromycin, dirithromycin, erythromycin, and roxithromycin in Vero cell cultures were evaluated. Bartonella and Rickettsia spp. were allowed to initiate infection of the antibiotic-free Vero cell monolayers, which were maintained in 16-chamber microscope slides in the absence of antibiotics at 32 degrees C in a CO2-enriched atmosphere. The monolayers were then incubated for 3 h to allow for initial host cell intracellular penetration by infecting species. After inoculation, inocula were replaced and tested with media containing 12 different concentrations of each antibiotic in replicate (10 wells of each antibiotic dilution) for each species, and the monolayers were reincubated. Tetracycline served as the control. Growth status of Bartonella spp. and Rickettsia spp. was determined by evaluation of immunofluorescent staining bacilli. Five days later, when antibiotic-free, control-infected cell monolayers demonstrated significant fluorescence, media were removed for all cell monolayers, the monolayers were fixed, and all specimens were stained with standard indirect immunofluorescent antibody reagents. Fluorescent foci were enumerated by counting such foci on random fields visualized with an epifluorescence microscope. The extent of antibiotic-induced focus inhibition was recorded for each dilution of antibiotic and compared with that of an antibiotic-negative control. Effective antibiotic dilution endpoints for inhibition of Bartonella and Rickettsia proliferation, as judged by absence of increase of significant fluorescence (as compared with no-growth controls), were enumerated by determining the number of cell culture chambers at various antibiotic dilutions that were negative or positive for significant Bartonella- or Rickettsia-specific fluorescence. All of the macrolide agents tested were readily active against all three Bartonella organisms, and azithromycin, clarithromycin, and roxithromycin may have potential in the treatment of Rickettsia infections. Animal model-based clinical trials are warranted to define the specific treatment role of the newer macrolide antibiotics.

Animals↗

Dermatologic adverse drug reactions in a family medicine setting.

To determine the prevalence of dermatologic adverse drug reactions in a family medicine outpatient practice setting, identify associated drug classes, and describe associated patient demographics and risk factors, we reviewed the charts of 557 patients in a university-based family medicine center who were diagnosed with a dermatologic condition. The study population included all patients diagnosed during a 1-year period. Thirty-five patients (6.3%) were identified as having dermatologic adverse drug reactions, of which the two most common types were exanthematous eruptions (n = 18 [51.4%]) and generalized erythroderma (n = 6 [17.1%]), with antibiotic use accounting for the majority (n = 21 [60.0%]) of reactions. Patient characteristics most commonly associated with a dermatologic adverse drug reaction were race (African-American), gender (female), and age (70 years and older). These data should provide insight into the types of cutaneous drug reactions commonly seen in community practice. Educational programs in all health-care disciplines, particularly medicine, pharmacy, and public health, that incorporate pharmacoepidemiologic strategies into their curricula are necessary to improve the overall process of monitoring and reporting of adverse drug reactions.

Academic Medical Centers↗

Benzoyl peroxide.

Explore the source record for details and available documents.

Acne Vulgaris↗

Pharmacokinetic dosing of phenobarbital in the treatment of alcohol withdrawal syndrome.

We used a pharmacokinetically derived phenobarbital dosing protocol to treat alcohol withdrawal syndrome in patients admitted to a family medicine inpatient service. We describe the protocol and include two case reports documenting its efficacy. Although benzodiazepine agents are considered by many to be the primary agents of choice, based upon our experience and its ease of administration, relative safety, therapeutic efficacy, and lower cost, phenobarbital should be reconsidered as a promising alternative. Comparative trials between these two therapeutic classes will clarify their roles in the treatment of alcohol withdrawal syndrome.

Administration, Oral↗

Drug use in pregnancy and lactation.

When prescribing drugs for patients who are pregnant or lactating, a clinician needs to ask the following questions: (1) Is pharmacotherapy necessary? (2) What drug can be used that has the lowest potential toxicity according to current knowledge? (3) What pharmacokinetic parameters does the drug follow during pregnancy? (4) What are the major risks inherent to this particular drug treatment? (5) Do the benefits outweight the risks? and (6) How can the risks be minimized by adjusting the drug dosage and duration? It is important to inform the patient of the possible risks and have her participate in making treatment decisions. If possible, the fetus or neonate should be monitored for adverse reactions during the course of treatment, and if any serious problems occur, the medication can be discontinued. Although it is true that no drug is totally without risk when used during pregnancy or lactation, if proper precautions are taken, then treatment can be rendered with minimal risks to both mother and child.

Decision Making↗

Pharmacy practice in a chemical-dependency treatment center.

The role of a pharmacist in a chemical-dependency treatment center is described. A pharmacist joined the staff of an outpatient methadone maintenance and chemical-dependency clinic at the request of the clinic's medical staff. In addition to the standard dispensing role, the pharmacist provides drug information, counsels staff and patients, and serves as the medical clinic coordinator. The pharmacist is also responsible for taking medical and drug-use histories, initially evaluating the degree of chemical dependency, assisting in the development of drug therapy plans for chemically dependent patients, and monitoring the effect of prescribed regimens. Other duties include serving as a health educator within the community and as a preceptor for baccalaureate and Doctor of Pharmacy students during substance abuse clerkships, and consulting on the management of chemically dependent patients who are hospitalized for other illnesses or specific conditions. The pharmacist's knowledge of pharmacotherapy and drug products and skill in assessing and managing problems related to substance abuse allowed physicians and nurses more time for other patient-care activities and helped the behavioral counselors develop a better understanding of the pharmacologic aspects involved in the health care of chemically dependent patients. The inclusion of a pharmacist in the chemical-dependency health-care team in this outpatient setting was accepted, valued, and recommended by the rest of the clinic staff.

Alcoholism↗

Mexiletine use in pregnancy and lactation.

Treatment of arrhythmias during pregnancy is complicated by insufficient information on the effects of the drug on the fetus or possible alterations of the drug's pharmacodynamics in the mother. The use of mexiletine, a newly introduced antiarrhythmic agent, during the entire course of pregnancy and subsequent lactation is presented.

Adult↗

Effect of an educational intervention on oral cephalosporin use in primary care.

The prescribing of oral cephalosporin antibiotics in an ambulatory setting was evaluated before and after an educational intervention. A drug utilization review used previously developed criteria to study the indications, processes, complications, and outcome for oral cephalosporins in the outpatient setting. Baseline data were collected for one year in the initial phase of the study. Only one prescription (1.4%) in the initial phase (0.96% of the total) met the criteria for appropriate use. However, during the year after an educational intervention by a clinical pharmacist explaining the proper use of oral cephalosporins, the prescribing of these agents decreased substantially. Educational strategies in medical schools and residency programs that seek to improve drug-prescribing behavior should combine drug utilization review programs with specific education about the appropriate use of pharmacologic agents.

Administration, Oral↗