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Biomedical subjects

J L Howe

Publications and source records attributed to J L Howe.

12 recordsLinked to original sources
PubMed2001

Educational approaches for preparing social work students for interdisciplinary teamwork on geriatric health care teams.

Interest in teamwork has fluctuated over the last several decades, with recent renewed interest. As social workers become more involved in working with older people in the coming years, their success will hinge on collaboration with other health providers. Schools of social work and clinical sites must address this through the development of educational curricula and clinical programs which prepare social workers to work on interdisciplinary geriatric health care teams. Based on the experience of the national Geriatric Interdisciplinary Team Training (GITT) Program, this article presents an overview of the necessary team skills for social workers, educational methods for teach ing teamwork developed at the GITT sites, and some teaching challenges.

Cooperative Behavior↗
PubMed1998

A screen for genes involved in the anaphase proteolytic pathway identifies tsm1(+), a novel Schizosaccharomyces pombe gene important for microtubule integrity.

The growth of several mitotic mutants of Schizosaccharomyces pombe, including nuc2-663, is inhibited by the protease inhibitor N-Tosyl-L-Phenylalanine Chloromethyl Ketone (TPCK). Because nuc2(+) encodes a presumptive component of the Anaphase Promoting Complex, which is required for the ubiquitin-dependent proteolysis of certain proteins during exit from mitosis, we have used sensitivity to TPCK as a criterion by which to search for novel S. pombe mutants defective in the anaphase-promoting pathway. In a genetic screen for temperature-sensitive mitotic mutants that were also sensitive to TPCK at a permissive temperature, we isolated three tsm (TPCK-sensitive mitotic) strains. Two of these are alleles of cut1(+), but tsm1-512 maps to a novel genetic location. The tsm1-512 mutation leads to delayed nuclear division at restrictive temperatures, apparently as a result of an impaired ability to form a metaphase spindle. After shift of early G2 cells to 36 degrees, tsm1-512 arrests transiently in the second mitotic division and then exits mitosis, as judged by spindle elongation and septation. The chromosomes, however, often fail to segregate properly. Genetic interactions between tsm1-512 and components of the anaphase proteolytic pathway suggest a functional involvement of the Tsm1 protein in this pathway.

Anaphase↗
PubMed1995

Bacteria, viruses, yeasts and protozoans associated with diarrheal disease in Singapore.

Labile toxin producing enterotoxic E. coli (ETEC) were the commonest pathogen isolated from diarrheal stools of hospitalized children (21%) and adults (26%) in Singapore. Salmonellas ranked a close second in children (19%). Other bacterial pathogens were isolated from less than 5% of subjects. Blastocystis hominis was detected in 4.3% of diarrheal stools when a simple sedimentation technique was used. Cryptosporidium was not detected at all. An analysis of yeast counts in smears of diarrheal and non-diarrheal stools suggested they were etiologically associated with at least 6% of diarrhea in children and 19% in adults. Testing for rotaviruses by Latex agglutination and for adenovirus by electronmicroscopy showed an association with 6 per cent and 3 per cent diarrhea respectively. The study highlighted a need for: case control studies on ETEC and B. hominis; studies on the epidemiology of diarrhea by yeasts; establishing the true incidence of adenovirus diarrhea; studies on the prevalence and seasonality of rotavirus infection in Singapore.

Adenovirus Infections, Human↗
PubMed1994

The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine.

The characterization of the enzymatic step(s) involved in the reduction of 3'-azido-3'-deoxythymidine (zidovudine)(ZDV) to 3'-amino-3'-deoxythymidine (AMT) was pursued. AMT formation by human liver microsomes was NADPH dependent, enhanced under anaerobic conditions, and increased by flavin adenine dinucleotide (FAD) and FMN. Carbon monoxide inhibited AMT formation by up to 80%. The effect of theophylline (CYP1A substrate), tolbutamide (CYP2C substrate), chlorzoxazone, thiobenzamide, p-nitrophenol, mercaptoethanol, isoniazid (CYP2E substrates), cortisol (CYP3A substrate), ketoconazole, itraconazole, fluconazole, cimetidine, micronazole (CYP inhibitors), methimazole (flavin-containing mono-oxygenase inhibitor), chloramphenicol (undergoes nitroreduction), allopurinol (xanthine oxidase inhibitor) and dicoumarol (DT-diaphorase inhibitor) on AMT formation were studied to see if the reduction reaction was mediated by a particular isozyme. The greatest inhibition was observed with ketoconazole (concentration producing 50% inhibition = 78.0 microM). At this concentration ketoconazole acted as a non-selective inhibitor of several CYP isozymes. Overall, these data suggested that ZDV reduction was probably mediated by both cytochrome P450 isozymes and NADPH-cytochrome P450 reductase. Formation of AMT, as measured by intrinsic clearance (Clint), was significantly increased in microsomes from rats pre-treated with phenobarbitone, dexamethasone and clofibrate (inducers of CYP2B, CYP3A and CYP4A, respectively). Pre-treatment of rats with beta-naphthoflavone and ethanol (CYP1A and CYP2E1 inducers, respectively) had no effect on AMT formation.

Animals↗
PubMed1994

Effect of 3'azido-2',3'-deoxythymidine (AZT) on experimental feline immunodeficiency virus infection in domestic cats.

The compound 3'azido-2',3'-deoxythymidine (AZT) inhibits the replication of feline immunodeficiency virus (FIV) in cell culture, and treatment with the compound has been reported to induce some clinical improvement in some cases of feline FIV infection. In order to determine the effect of prophylactic treatment with AZT on experimental FIV infection, cats were treated with the compound at 0.2, 1.0, 5, 25 or 50 mg kg-1 day-1 for 29 days. One day after the treatment was started, they were inoculated with 150 cat infectious doses of FIV. All the cats became viraemic, seroconverted and developed lymphadenopathy, although the onset of each was delayed in the cats given higher doses of AZT. Anaemia developed in the cats given high doses of AZT. Virus re-isolated from the cats given 50 mg kg-1 day-1 was as susceptible to AZT in cell culture as the inoculated virus. Thus AZT is much less effective in cats than might have been expected from the results of in vitro studies.

Animals↗
PubMed1994

Zidovudine pharmacokinetics in zidovudine-induced bone marrow toxicity.

1. The major adverse effect of zidovudine (ZDV) is haematological toxicity which results in anaemia and granulocytopenia. The aim of the present study was to investigate if HIV-positive patients developing erythroid aplasia/hypoplasia are exposed to higher plasma concentrations of ZDV owing to impaired hepatic metabolism to the major metabolite, 3'-azido-3'-deoxy-5'-beta-D-glucopyranuronosylthymidine (GZDV). 2. Twelve HIV-positive male patients were studied, six having developed bone marrow aplasia/hypoplasia within the first 6 months of ZDV therapy. Each of the patients exhibiting toxicity were matched for age, weight, risk factors for HIV infection and disease stage with patients who had no evidence of early bone marrow toxicity. 3. ZDV was administered orally in doses of 3-10 mg kg-1 and blood samples taken at intervals to 6 h. Urine was collected over the whole 6 h period. ZDV and GZDV were assayed by h.p.l.c. 4. There were no significant differences in the pharmacokinetic parameters between the two groups of patients. For patients with early bone marrow toxicity the elimination half-life of ZDV was 1.10 +/- 0.16 h with an oral clearance of 2752 +/- 1031 ml min-1 compared with values of 1.06 +/- 0.18 h and 2843 +/- 730 ml min-1 seen in the control group. Similarly there was no significant difference in the pharmacokinetics of GZDV or the urinary ratio of GZDV to ZDV. 5. Therefore, despite the fact that ZDV toxicity to haematopoietic progenitor cells has been previously shown to be dose related, there was no indication from this study that it is directly related to plasma concentrations of ZDV.

Administration, Oral↗
PubMed1994

Pharmacokinetics of zidovudine and dideoxyinosine alone and in combination in patients with the acquired immunodeficiency syndrome.

1. Zidovudine (ZDV) has proved unsuccessful in controlling disease progression over extended periods of time in patients with AIDS. Combination of ZDV with another reverse transcriptase inhibitor, dideoxyinosine (ddI) may improve the duration of effectiveness of antiretroviral therapy. The aim of this study was to investigate the possibility of a pharmacokinetic drug interaction between ZDV and ddI. 2. The pharmacokinetics of ZDV and ddI were determined in eight patients with AIDS who were randomised to receive ZDV 250 mg orally, ddI 250 mg orally or a combination of ZDV 250 mg plus ddI 250 mg orally on 3 study days separated by 1 week. 3. The administration of ZDV did not significantly alter ddI pharmacokinetics. The mean AUC was 6.8 +/- 2.0 s.d. and 7.6 +/- 2.5 s.d. mumol l-1 h and oral clearance was 2766 +/- 686 and 2660 +/- 1297 ml min-1 in the presence and absence of ZDV, respectively. 4. In the presence of ddI the elimination half-life of ZDV was increased significantly by 18% from 1.1 +/- 0.3 to 1.3 +/- 0.3 h (P < 0.05) and the mean AUC increased significantly by 35% from 4.8 +/- 1.5 to 6.5 +/- 1.5 mumol l-1 h (P < 0.05). The clearance was decreased by 29% from 3518 +/- 1123 to 2505 +/- 575 ml min-1, but this difference was not significant. The renal clearance of ZDV was not altered by ddI. 5. Administration of ddI also resulted in a significant 22% increase in the AUC of GZDV, from 28.5 +/- 15.7 to 34.9 +/- 12.8 mumol l-1 h (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1992

Extrahepatic metabolism of zidovudine.

The metabolism of zidovudine (3'-azido-3'-deoxythymidine; AZT) has been studied in human renal, gut and hepatic microsomes. Metabolism of AZT to the ether glucuronide (3'azido-3'-deoxy-5'-beta-D-glucopyranosyl thymidine; GAZT) occurred in the kidney with Km and Vmax values of 1.50 +/- 0.49 mM and 14.5 +/- 2.6 nmol h-1 mg-1 respectively (mean +/- s.d.; n = 3 batches of microsomes from a single kidney). Comparative values obtained in liver were 2.19 +/- 0.6 mM and 43.0 +/- 9.5 nmol h-1 mg-1, respectively. Morphine caused inhibition of AZT conjugation in kidney microsomes. Metabolism of AZT by the kidney could contribute significantly to the overall elimination of AZT. In contrast to the kidney findings, AZT was not metabolised to GAZT by either non-activated (Brij-58) or activated gut microsomes.

Adolescent↗
PubMed1992

Studies of hospital social stays in the frail elderly and their relationship to the intensity of social work intervention.

The elderly frequently suffer long lengths of hospital stay (LOS). These long stays are often associated with long social care stays which occur when patients no longer require acute care and are awaiting post-discharge services. In this study, actual acute care LOS and social care LOS were studied specifically in hospitalized frail elderly. Our data demonstrate that frail elderly receiving only acute care do not suffer markedly prolonged total LOS (TLOS). However, in hospitalized frail elderly patients who experience acute care and social care stays, social care LOS accounts for over half of all hospital days. When patients were grouped and studied according to the type of post-discharge services being sought by the health care team, significant differences in acute LOS and social care LOS were noted. Subgroups of patients were also identified among the various groups which differed significantly in their LOS parameters. Patients who required more than one discharge plan during the course of hospitalization experienced the longest hospital stays of all groups, and spent almost 70% of these days receiving non-acute social care. In a study of the relationship between the intensity of social work intervention and social care LOS in the frail elderly, a statistically significant relationship was noted between the timing and frequency of social work intervention and the actual length of social care stays. Early and frequent social work interventions were associated with significantly shorter social care LOS. We conclude that the study of TLOS should include acute LOS and social care LOS to obtain a reliable measure of the course and cost of hospital care for the frail elderly. The study of social care subgroups may facilitate future investigations to define the social care problems which contribute most to TLOS, and the patient populations which should be most heavily targeted for early and intensive social work intervention.

Aged↗