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Biomedical subjects

C Shipman

Publications and source records attributed to C Shipman.

At least 37 records · Page 2Linked to original sources
PubMed1996

Creating a shared vision of out of hours care: using rapid appraisal methods to create an interagency, community oriented, approach to service development.

OBJECTIVES: To undertake a district wide review of out of hours primary health care services and identify the views of users and providers about current arrangements and options for development. DESIGN: A range of qualitative and quantitative survey methods based on rapid appraisal methods, modified to apply to an inner city district. SETTING: Socially deprived, multiethnic district in south east London with a population of over 700,000. MAIN OUTCOME MEASURES: Strengths and weaknesses of current out of hours services and suggestions for developments. RESULTS: Widespread dissatisfaction with current arrangements was identified, with specific problems relating to access, availability, demand for services, and interagency communication. Several areas for development were identified, including the establishment of an out of hours cooperative, multiagency primary care emergency centres, and telephone advice-triage. Many of these are now being planned or piloted. CONCLUSIONS: Rapid appraisal provided a helpful method, enabling partnerships to be established between local agencies and users in relation to service development. The shared understanding and commitment to improving services that resulted is now having a major impact on out of hours care in the district.

Attitude of Health Personnel↗
PubMed1993

Inhibitors of thymidylate synthase and dihydrofolate reductase potentiate the antiviral effect of acyclovir.

In cells infected with herpes simplex virus type 1, intracellular dNTP pools increased markedly. Treatment of these cells with 3 microM acyclovir resulted in an additional expansion in pyrimidine deoxyribonucleoside triphosphate pools with dTTP increasing 32-fold and dCTP 8-fold. Both thymidine and deoxycytidine, however, compete with acyclovir for phosphorylation by the viral pyrimidine deoxyribonucleoside kinase and thus reduce the amount of drug that is anabolized to the active form. Theoretically, agents which inhibit thymidylate synthase or dihydrofolate reductase should reduce intracellular pools of thymidine, resulting in the potentiation of the antiviral effects of acyclovir. We explored this strategy by quantitating the synergy produced by combinations of acyclovir and other drugs using three-dimensional dose-response surface methodology (MacSynergy II). Significant synergy was seen with both 5-FdUrd and methotrexate whereas BrVdUrd, 5-CldUrd, 5-IdUrd, and 5-BrdUrd exhibited little to no synergistic activity. It is suggested that inhibitors of thymidylate synthase and dihydrofolate reductase warrant further exploration as potentiators of acyclovir.

Acyclovir↗
PubMed1993

Strategic design and three-dimensional analysis of antiviral drug combinations.

The development of new drugs effective against human viral diseases has proven to be both difficult and time-consuming. Indeed, there are but 10 drugs licensed for such applications in the United States today. An attractive solution to this problem may be to optimize the efficacy and selectivity of existing antiviral drugs by combining them with agents that strategically block carefully selected metabolic pathways. This approach was used in the rational design of a three-drug combination to increase the apparent potency of acyclovir against herpes simplex virus. Recent advances in analytical techniques have made the evaluation of this complex drug strategy both possible and practical. A modified version of a previously described analytical method was used to identify optimal drug concentrations and to quantitate statistically significant synergy. Concentrations of 0.25 microM 5-fluorodeoxyuridine, 3.6 microM 2-acetylpyridine thiosemicarbazone, and 0.3 microM acyclovir were determined to be optimal in terms of antiviral activity. The volume of synergy produced was nearly 2,000 microM3% at a 95% level of confidence (corresponding to a 186-fold decrease in the apparent 50% inhibitory concentration of acyclovir with the addition of 0.25 microM 5-fluorodeoxyuridine and 3.6 microM 2-acetylpyridine thiosemicarbazone). We anticipate that this strategic approach and the supporting three-dimensional analytical method will prove valuable in designing and understanding multidrug therapies.

Acyclovir↗
PubMed1991

Inhibition of cell growth and DNA, RNA, and protein synthesis in vitro by fentanyl, sufentanil, and opiate analgesics.

We have studied the cytotoxic nature of two groups of narcotic analgesics. Group 1 consists of the opioids, morphine, codeine, hydromorphone, thebaine, and etorphine. Group II contains but two phenylpiperidine-type narcotics, fentanyl and sufentanil. To measure cytotoxicity, three different bioassays were employed using an established line of human cells. Specifically, the effects of narcotic analgesics on DNA, RNA, and protein synthesis were measured by following the uptake and incorporation of radiolabeled thymidine, uridine, and amino acids, respectively. Inhibition of cell growth also was studied by measuring population doubling times of logarithmically growing cells in the presence (or absence) of the test compounds. Lastly, cloning efficiencies of cells were determined in the presence of both groups of compounds. Group I compounds were significantly less inhibitory than Group II compounds by all three bioassays. Moreover, flow cytometric DNA analysis of cells treated with 100 and 320 microM etorphine HCl showed essentially no effects on cell cycle distribution. These in vitro results thus suggest that (1) fentanyl and sufentanil are inherently more cytotoxic than the opioid narcotics in Group I, and (2) the highly potent morphinoid drug etorphine HC1 appears to have special promise as a transdermal narcotic to control pain.

Cell Division↗
PubMed1991

Three-dimensional analysis of the synergistic cytotoxicity of ganciclovir and zidovudine.

The combined cytotoxicity of zidovudine and ganciclovir in three cell lines of human origin was examined. The data were generated by a new rapid cell proliferation assay and a more sensitive plating efficiency assay. A three-dimensional analytical approach was used to evaluate the drug-drug interactions, and the results were compared with those obtained by two conventional methods of analysis. Synergistic cytotoxicity was observed in all cell lines examined and by both assays. Moreover, this synergistic cytotoxicity was statistically significant at physiologically relevant concentrations. It is not known whether these drug-drug interactions manifest themselves in vivo as granulocytopenia or other untoward side effects. These results, however, indicate that further investigation is warranted and that the coadministration of zidovudine and ganciclovir may be contraindicated.

Cell Division↗
PubMed1990

A microtiter virus yield reduction assay for the evaluation of antiviral compounds against human cytomegalovirus and herpes simplex virus.

Although the virus yield reduction assay is a powerful technique for evaluating the efficacy of antiviral compounds, it is not routinely utilized due to its labor-intensive nature. This procedure was modified, developed, thereby reducing greatly the time and effort required to perform yield reduction assays. Monolayer cultures of mammalian cells were grown in 96-well microtiter tissue culture plates and infected with virus. Test compounds were added and serially diluted directly with the plates. Following a cycle of virus replication, culture lysates were made and serially diluted in a separate set of uninfected cultures grown in microtiter plates. The cultures were incubated, plaques were enumerated in wells containing 5 to 20 plaques, and virus titers were calculated. To illustrate the use of the assay the known antiviral drugs acyclovir and ganciclovir were evaluated using this procedure. Ninety percent inhibitory concentrations for the respective drugs were 3 microM and 0.7 microM against herpes simplex virus type 1 and 60 microM and 1 microM against human cytomegalovirus.

Acyclovir↗
PubMed1990

Influence of vehicle on topical efficacy of 2-acetylpyridine thiosemicarbazone and related derivatives on in vivo type 2 herpes simplex virus infections.

2-Acetylpyridine semicarbazone (APSC), 2-acetylpyridine thiosemicarbazone (APTSC) and 2-acetylpyridine-4-methyl-3-thiosemicarbazonoe (APMTSC) were evaluated against type-2 herpes simplex virus (HSV-2)-induced genitalis and encephalitis in mice and guinea pigs. The antiviral activity of these compounds was compared with that of acyclovir. With 1,3-butanediol as a topical treatment vehicle, 1% APSC and APTSC showed significant activity against the genital infection in mice, as evidenced by increased survivors and decreased severity of vaginal lesions. Reduced titers of virus recovered from the lesions were also observed with APTSC treatments. Eight different commercially available vehicles were compared to determine in which topically administered 1% APTSC would be most efficacious against the vaginal disease induced in mice. Significant results were observed with Squibb cream base, Eucerin base, and K-Y jelly; these effects were essentially equivalent to using 1,3-butanediol Unibase, Aquaphor, polyethylene glycol, polyvinyl alcohol and petrolatum were less effective as carrier vehicles. The herpesvirus genital infection in guinea pigs was treated with 1% APMTSC and APTSC comparing Squibb cream, Eucerin and K-Y jelly bases; while neither compound exerted striking effects against this infection in any vehicle, 1% APMTSC in Squibb cream was effective in increasing mean survival time and reducing lesion score and titers of recoverable virus. In this experiment, treatments with 1 and 5% acyclovir in polyethylene glycol base were effective in reducing titers of virus from the vaginal area. Orally administered APTSC (12.5, 25, 50 mg/kg/day given twice daily for 7 days) caused moderate prevention of death of mice infected intraperitoneally with HSV-2; subcutaneous injection of the compound was markedly effective with efficacy comparable to that of acyclovir at 120 mg/kg/day.

Administration, Intravaginal↗
PubMed1989

Acceptance of hepatitis B vaccine among dental health care workers.

Participation in hepatitis B vaccination programs by dental health care workers (DHCWs) has been low. Following a vaccination program at the University of Michigan School of Dentistry, a survey was conducted to determine the relation of sociodemographic status, health beliefs, amount of patient contact, and perceived barriers to participation or nonparticipation in the program by 618 students, faculty, and staff. Stepwise logistic regression revealed that a respondent's age, perceptions about susceptibility to hepatitis B, amount of patient contact, and perceptions about the cost of the vaccine were significant determinants of participation. Findings from this study suggest that a highly structured program format is necessary to lower barriers and facilitate access to vaccination, while also cueing the DHCW to appropriate preventive behavior. knowledge appears to be but one factor that may affect decisions regarding acceptance of hepatitis B vaccine; health beliefs, motivational factors, barriers, and program organization all have a significant impact on the DHCW's decision.

Attitude of Health Personnel↗
PubMed1989

Topical delivery of liposomally encapsulated interferon evaluated in a cutaneous herpes guinea pig model.

The topical delivery of liposomally encapsulated interferon was evaluated in the cutaneous herpes simplex virus guinea pig model. Application of liposomally entrapped interferon caused a reduction of lesion scores, whereas application of interferon formulated as a solution or as an emulsion was ineffective. The method of liposomal preparation rather than the lipid composition of the bilayers appeared to be the most important factor for reducing lesion scores. Only liposomes prepared by the dehydration-rehydration method were effective. This finding implied that the dehydration and subsequent rehydration of the liposomes facilitate partitioning of the interferon into liposomal bilayers, where the drug is positioned for transfer into the lipid compartment of the stratum corneum. Liposomes do not appear to function as permeation enhancers but seem to provide the needed physicochemical environment for transfer of interferon into the skin.

Administration, Topical↗
PubMed1989

Fluorescein dye evaluation of glove integrity.

Several methods of defect detection in disposable latex and vinyl examination gloves were evaluated. Results of this research support other findings that glove integrity cannot be completely assured by the use of new gloves. The use of the fluorescein dye technique was superior, in terms of efficiency and accuracy in the clinical setting, when compared with other methods of defect detection, including the air inflation-water submersion technique.

Air↗
PubMed1988

7-Aminoquinolines. A novel class of agents active against herpesviruses.

A series of 7-aminoquinoline derivatives was synthesized and evaluated for their capacity to produce cytotoxicity in KB cells and to inhibit the replication of herpes simplex virus (HSV) type 1. All compounds tested inhibited the replication of HSV-1 with 50% inhibitory concentrations in the range of 2-50 micrograms/mL. The antiviral activity of many compounds, however, was separated from cytotoxicity to replicating uninfected cells by only two- to fivefold higher than those required for antiviral activity. Nonetheless, six compounds (10, 28, 29, 32, 34, and 36) were identified in which the separation was greater than fivefold. All compounds examined were more potent inhibitors of viral DNA synthesis than the cellular DNA synthesis.

Aminoquinolines↗