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Biomedical subjects

C L Clark

Publications and source records attributed to C L Clark.

At least 19 recordsLinked to original sources
PubMed2005

Drug resistance and neurotransmitter receptors of nematodes: recent studies on the mode of action of levamisole.

Here we review recent studies on the mode of action of the cholinergic anthelmintics (levamisole, pyrantel etc.). We also include material from studies on the free living nematode Caenorhabditis elegans. The initial notion that these drugs act on a single receptor population, while attractive, has proven to be an oversimplification. In both free living and parasitic nematodes there are multiple types of nicotinic acetylcholine receptor (nAChR) on the somatic musculature. Each type has different (sometimes subtly so) pharmacological properties. The implications of these findings are: (1) combinations of anthelmintic that preferentially activate a broad range of nAChR types would be predicted to be more effective; (2) in resistant isolates of parasite where a subtype has been lost, other cholinergic anthelmintics may remain effective. Not only are there multiple types of nAChR, but relatively recent research has shown these receptors can be modulated; it is possible to increase the response of a parasite to a fixed concentration of drug by altering the receptor properties (e.g. phosphorylation state). These findings offer a potential means of increasing efficacy of existing compounds as an alternative to the costly and time consuming development of new anthelmintic agents.

Adenosine Triphosphate↗
PubMed2002

Single- and multistep selection study of the antipneumococcal activity of BMS-284756 compared to ciprofloxacin, levofloxacin, trovafloxacin and moxifloxacin.

Single- and Multi-step selection studies were used to test the ability of BMS-284756, ciprofloxacin, levofloxacin, trovafloxacin and moxifloxacin to yield resistant clones from 12 quinolone-susceptible and -resistant Streptococcus pneumoniae strains. Although all quinolones selected, to a greater or lesser degree, for resistant clones with mutations usually in parC or gyrA, BMS-284756 tended to select for resistant clones at a lower rate than other quinolones studied.

Anti-Infective Agents↗
PubMed2001

The use of recombinant baculoviruses for sustained expression of human cytomegalovirus immediate early proteins in fibroblasts.

The isolation of viruses with mutations in essential genes requires that they be propagated in cells expressing the wild-type proteins. This has been a particularly challenging problem for studying mutations in the human cytomegalovirus (HCMV) immediate early (IE) gene, IE2 86. In the past, we tried a number of approaches to derive human fibroblasts expressing wild-type IE2 86, but were unable to maintain expression of a fully functional protein. To overcome this obstacle, we developed a strategy whereby recombinant baculoviruses were used as vectors for the expression of HCMV IE proteins in primary human fibroblasts (FFs). The IE2 86 and IE1 72 cDNAs, as well as the genomic fragment of the UL122-123 region under the control of a chicken actin promoter, were introduced into the baculovirus genome by site-specific transposition in Escherichia coli. Recombinant "bacmid" DNAs were then transfected into Sf9 cells to generate recombinant baculoviruses. FFs infected at high m.o.i. with these baculoviruses expressed high levels of the HCMV protein for at least 1 week, as determined by immunofluorescence assays and Western blots. Moreover, the IE2 86 protein was found to be fully functional with respect to its ability to activate the HCMV UL112-113 early promoter. Recombinant baculoviruses expressing IE1 72 were also able to efficiently complement HCMV ie1 mutants. These data demonstrate the potential of using recombinant baculoviruses as vectors for the expression of toxic viral genes in human cells and for subsequent isolation of mutant HCMV lacking these essential genes.

Animals↗
PubMed2001

Peri-operative management of patients having external anal sphincter repairs: temporary prevention of defaecation does not improve outcomes.

OBJECTIVE: To determine whether there was any detectable difference in outcomes of external anal sphincter repair depending on whether patients were managed routinely with a covering stoma, a constipating dietary regimen or a laxative dietary regimen in the early postoperative period. PATIENTS AND METHODS: A consecutive retrospective series of 299 anal sphincter repairs undertaken on 286 patients within a single institution was studied. Patients were divided into three groups depending on the peri-operative regimen followed: routine use of a covering stoma (group 1), routine use of a postoperative constipating dietary regimen (group 2) and routine use of a laxative dietary regimen (group 3). Choice of peri-operative regimen depended on surgeon preference alone. Short-term outcomes (length of stay, complications) and long-term outcomes (functional reported degree of continence, anal ultrasound and physiology test results) were assessed in relation to peri-operative group as well as aetiology of sphincter damage. RESULTS: Short-term results (complications of surgery) were obtainable in all patients; long-term results were available for 89% of patients. Length of stay was similar for all 3 groups (excluding re-admission for stoma closure). Complication rates were not significantly different between the three groups. Functional improvement in continence was reported by 68% of group 1, 69% of group 2 and 79% of group 3 (differences not statistically significant). An anatomical sphincter defect was detected postoperatively in 8% of patients in group 1, 9% in group 2 and 7% of group 3. Poorer outcomes were achieved in older patients and in patients with previous ileo-anal pouch formation. Early faecal impaction and repair breakdown were independently associated with poor long-term outcomes. CONCLUSIONS: Neither routine use of a covering stoma nor a postoperative constipating regimen produced better results following external anal sphincter repair than did the use of a postoperative laxative regimen which encouraged early passage of loose stool without the need for straining.

Journal Article↗
PubMed2001

Neurotransmitter release from bovine adrenal chromaffin cells is modulated by capacitative Ca(2+)entry driven by depleted internal Ca(2+)stores.

Two potential mechanisms by which the intracellular Ca(2 stores might modulate catecholamine release from bovine adrenal chromaffin cells were investigated: (i) that the cytosolic Ca(2+)transient caused by Ca(2+)release from the intracellular stores recruits additional chromaffin granules to a readily releasable pool that results in augmented catecholamine release when this is subsequently evoked, and (ii) that the Ca(2+)influx that follows depletion of intracellular stores (i.e. store-operated Ca(2+)entry) triggers release per se thereby augmenting evoked catecholamine release. When histamine or caffeine were applied in Ca(2+)-free perfusion media, a transient elevation of intracellular free Ca(2+)occurred owing to mobilization of Ca(2+)from the stores. When Ca(2+)was later readmitted to the perfusing fluid there followed a prompt and maintained rise in intracellular Ca(2+)concentrations of magnitude related to the degree of store mobilization. In parallel experiments, increased catecholamine secretion was measured under the conditions when Ca(2+)influx following store-mobilization occurred. Furthermore, the size of the catecholamine release increment correlated with the degree of Ca(2+)influx. Store-operated Ca(2+)entry evoked by mobilization with histamine and/or caffeine did not augment nicotine-evoked secretion per se; that is, it augmented evoked catecholamine release only to the extent that it increased basal catecholamine release. The nicotine-evoked catecholamine release was sensitive to cytosolic BAPTA, which, at the concentration used (50 microM BAPTA-AM), reduced release by approximately 25%. However, the increment in basal catecholamine release which followed Ca(2+)influx triggered by Ca(2+)store mobilization was not reduced by intracellular BAPTA. This finding is inconsistent with the hypothesis that the elevated cytosolic Ca(2+)from store mobilization recruits additional vesicles of catecholamine to the sub-plasmalemmal release sites to augment subsequently evoked secretion. This position is supported by the observation that histamine (10 microM) in Ca(2+)-free medium caused a pronounced elevation of cytosolic free Ca(2+), but this caused no greater catecholamine release when Ca(2+)was re-introduced than did prior exposure to Ca(2+)-free medium alone, which caused no elevation of cytosolic free Ca(2+). It is concluded that intracellular Ca(2+)stores can modulate secretion of catecholamines from bovine chromaffin cells by permitting Ca(2+)influx through a store-operated entry pathway. The results do not support the notion that the Ca(2+)released from intracellular stores plays a significant role in the recruitment of vesicles into the ready-release pool under the experimental conditions reported here.

Adrenal Medulla↗
PubMed2000

Hispanics, Blacks and White driving under the influence of alcohol: results from the 1995 National Alcohol Survey.

OBJECTIVE: To report nationwide survey data on patterns of driving under the influence of alcohol among Whites, Blacks and Hispanics. METHOD: Data were obtained from a probability sample consisting of 1582 Blacks, 1585 Hispanics and 1636 Whites in the US household population. Interviews averaging 1 h in length were conducted in respondents' homes by trained interviewers. RESULTS: Self-reported rates of driving a car after having drunk enough 'to be in trouble if stopped by the police' were highest among White and Hispanic men (22 and 21%, respectively), as were lifetime arrest rates for driving under the influence of alcohol (13% for White men, 19% for Hispanic men). Additionally, our analyses suggest that drinkers who drive under the influence of alcohol are more likely to be men (regardless of ethnicity), consume more alcohol, and be alcohol dependent than drinkers who do not engage in alcohol-impaired driving.

Adult↗
PubMed2000

Intimate partner violence and drinking patterns among white, black, and Hispanic couples in the U.S.

PURPOSE: Using reports from both partners, this study estimated prevalence rates of intimate partner violence (IPV) among white, black, and Hispanic couples in the U.S., and assessed the contribution of drinking patterns, psychosocial, and other sociodemographic factors to the risk of partner violence. METHODS: A multistage area probability sample consisting of 555 white, 358 black, and 527 Hispanic couples in the U.S. household population was interviewed in 1995. Logistic regression analyses revealed that predictors of IPV vary by ethnicity. RESULTS: Rates of male-to-female (MFPV) and female-to-male partner violence (FMPV) were highest among black couples (23% and 30%), followed by Hispanic (17% and 21%), and white couples (12% and 16%). Between 27 percent and 41 percent of the men, and 4 percent and 24 percent of the women were drinking at the time of the violent incident. IMPLICATIONS: Black and Hispanic couples are at higher risk for IPV than white couples and should be targeted for prevention intervention. The interrelationships among IPV, alcohol consumption, and ethnicity are complex. These findings suggest that future attempts at modeling IPV should be ethnically sensitive and, ideally, include separate analyses of each ethnic group.

Adolescent↗
PubMed2000

Couples' drinking patterns, intimate partner violence, and alcohol-related partnership problems.

PURPOSE: Past research has revealed a strong correspondence between alcohol use and family dysfunction (e.g., Straus and Gelles in 1986 and 1990). Unfortunately, much of this research has relied on reports from only one family member. METHODS: Here, we present the results from a recent, nationwide study of alcohol-consumption patterns, alcohol-related partnership problems, and intimate partner violence (IPV) based on reports from both romantic partners of 1,615 married and cohabiting couples. RESULTS: Using the "drinking partnerships" construct developed by Roberts and Leonard in 1997, we found that despite considerable concordance between couple members' drinking behaviors, discrepant drinking patterns were strongly predictive of relational distress and the incidence of physical violence. IMPLICATIONS: These findings suggest that the interaction between couple members' alcohol-related behaviors has crucial implication for the health and well-being of the entire family.

Adolescent↗
PubMed2000

Activities and postantibiotic effects of gemifloxacin compared to those of 11 other agents against Haemophilus influenzae and Moraxella catarrhalis.

The activity of gemifloxacin against Haemophilus influenzae and Moraxella catarrhalis was compared to those of 11 other agents. All quinolones were very active (MICs, </=0.125 microgram/ml) against 248 quinolone-susceptible H. influenzae isolates (40.7% of which were beta-lactamase positive); cefixime (MICs, </=0.125 microgram/ml) and amoxicillin-clavulanate (MICs </=4.0 microgram/ml) were active, followed by cefuroxime (MICs, </=16.0 microgram/ml); azithromycin MICs were </=4.0 microg/ml. For nine H. influenzae isolates with reduced quinolone susceptibilities, the MICs at which 50% of isolates are inhibited (MIC(50)s) were 0.25 microgram/ml for gemifloxacin and 1.0 microgram/ml for the other quinolones tested. All strains had mutations in GyrA (Ser84, Asp88); most also had mutations in ParC (Asp83, Ser84, Glu88) and ParE (Asp420, Ser458), and only one had a mutation in GyrB (Gln468). All quinolones tested were equally active (MICs, </=0.06 microgram/ml) against 50 M. catarrhalis strains; amoxicillin-clavulanate, cefixime, cefuroxime, and azithromycin were very active. Against 10 H. influenzae strains gemifloxacin, levofloxacin, sparfloxacin, and trovafloxacin at 2x the MIC and ciprofloxacin at 4x the MIC were uniformly bactericidal after 24 h, and against 9 of 10 strains grepafloxacin at 2x the MIC was bactericidal after 24 h. After 24 h bactericidal activity was seen with amoxicillin-clavulanate at 2x the MIC for all strains, cefixime at 2x the MIC for 9 of 10 strains, cefuroxime at 4x the MIC for all strains, and azithromycin at 2x the MIC for all strains. All quinolones except grepafloxacin (which was bactericidal against four of five strains) and all ss-lactams at 2x to 4x the MIC were bactericidal against five M. catarrhalis strains after 24 h; azithromycin at the MIC was bactericidal against all strains after 24 h. The postantibiotic effects (PAEs) against four quinolone-susceptible H. influenzae strains were as follows: gemifloxacin, 0.3 to 2.3 h; ciprofloxacin, 1.3 to 4.2 h; levofloxacin, 2.8 to 6.2 h; sparfloxacin, 0.6 to 3.0 h; grepafloxacin, 0 to 2.1 h; trovafloxacin, 0.8 to 2.8 h. At 10x the MIC, no quinolone PAEs were found against the strain for which quinolone MICs were increased. Azithromycin PAEs were 3.7 to 7.3 h.

Anti-Bacterial Agents↗
PubMed2000

Impact on medical students of incorporating GALS screen teaching into the medical school curriculum.

OBJECTIVE: To assess the impact of GALS locomotor screen teaching to all 3rd year medical students, at a British medical school. METHOD: In 1998, during their 3rd year, all students were taught the GALS screen in a one hour small group session. At the end of this year, 242 medical students undertook a 16 station Objective Structured Clinical Examination (OSCE). One station assessed the locomotor screening examination, while six stations assessed the examination of other systems. The students completed a five point likert scale, self rating their confidence in each of the skills assessed at this time. Pre-registration house officers (PRHOs) at two London hospitals were invited to undertake the same OSCE and self rating. RESULTS: The students performed the locomotor screen well (mean station score 80%). Three body systems were examined better and one significantly worse (p<0.05). 22/40 PRHOs undertook the assessment. Compared with the students they examined the locomotor system (mean score 20%, p<0.001), but not other systems, less well. The PRHOs felt less confident (p<0.05) examining the locomotor system (mean rating 3.6/5) than the other systems (mean rating 4.6/5), while no significant difference in confidence ratings was seen for the students. CONCLUSION: Students who are taught the GALS screen as part of the curriculum, perform it well in an end of year OSCE, as confidently as other systems, and to a higher standard than PRHOs. Further study is required to determine whether this benefit persists, overcoming the poor skills and confidence in locomotor examination of existing PRHOs, not previously taught a GALS screen.

Clinical Competence↗
PubMed2000

Education provision for surgical senior house officers.

The provision of formal education in surgical SHO training is a requirement for posts to be accredited by postgraduate deans. We carried out a questionnaire survey of surgical SHOs attending a Royal College of Surgeons of England study day to quantify the amount of time given to formal education and supervised operating. We found that 79% of SHOs at district general hospitals and 87.5% at teaching hospitals were provided with a formal education programme. Of these SHOs, 77% were able to attend the teaching on a regular basis. In an average week, 8% of SHOs received no supervised operating experience and 37% had no operations supervised by a consultant. These results suggest that many hospitals fall short of the accepted guidelines on basic surgical training. This issue must be addressed by the Royal Colleges.

Education, Medical, Graduate↗
PubMed1999

Trends in situational norms and attitudes toward drinking among whites, blacks, and hispanics: 1984-1995.

The purpose of this study was to explore trends in situational norms and attitudes toward drinking and to assess the associations of norms and attitudes with current drinking and frequent heavy drinking patterns among whites, blacks, and hispanics between 1984 and 1995. Data were obtained from two nationwide probability samples of US households. Results indicated that there were no broad trends in situational norms and attitudes toward drinking between 1984 and 1995 among whites, blacks, and hispanics in the US. The variations in norms and attitudes detected between 1984 and 1995 were ethnic and gender-specific. For all of the groups studied, situational norms and attitudes were highly predictive of both current drinking and frequent heavy drinking patterns.

Adolescent↗
PubMed1999

Activities of clinafloxacin, alone and in combination with other compounds, against 45 gram-positive and -negative organisms for which clinafloxacin MICs are high.

Time-kill studies indicated that clinafloxacin showed synergy after 24 h with ceftazidime, amikacin, and imipenem against 12, 8, and 10 of 33 gram-negative rods, respectively; with vancomycin, teicoplanin, cefotaxime, and amikacin against 3, 3, 1, and 1 of 9 staphylococci and enterococci, respectively; and with vancomycin, penicillin, and cefotaxime against 0, 2, and 2 of 3 pneumococci, respectively. The MICs of clinafloxacin alone for most strains were >/=1 microg/ml.

Anti-Bacterial Agents↗
PubMed1999

Alcohol-related problems and intimate partner violence among white, black, and Hispanic couples in the U.S.

OBJECTIVES: This study analyzes gender and ethnic/racial differences in the prevalence of alcohol-related problems among white, black and Hispanic couples in the United States, and assesses their contribution to the risk of intimate partner violence (IPV). METHODS: Our study population consisted of 1440 white, black, and Hispanic couples obtained through a multistage area household probability sample from the 1995 National Alcohol Survey. Alcohol-related problems (i.e., drinking consequences and alcohol dependence symptoms in the last 12 months) were assessed among respondents and their partners. Male-to-female and female-to-male partner violence (MFPV, FMPV) were measured separately using the Conflict Tactics Scale. RESULTS AND CONCLUSIONS: Alcohol-related problems were more prevalent among men than women. Our bivariate analysis demonstrated a significant positive association between male alcohol-related problems and IPV across racial/ethnic groups, and a similar association between female alcohol-related problems and IPV for white and black couples. In the multivariate logistic regression analyses, however, many of these associations were attenuated. After controlling for sociodemographic and psychosocial covariates, male alcohol-related problems were no longer significantly associated with an increased risk of MFPV among white or Hispanic couples. Female alcohol-related problems predicted FMPV, but not MFPV, among white couples. Among black couples, however, male and female alcohol-related problems remained strong predictors of intimate partner violence. SIGNIFICANCE: Alcohol-related problems are important predictors of intimate partner violence, and the exact association between problems and violence seems to be ethnic-specific. Alcohol-related problems, rather than level of alcohol consumption, may be the more relevant factor to consider in the alcohol-partner violence association. Future research is needed to explore the temporal relationships between the development of alcohol-related problems and the occurrence of partner violence.

Black or African American↗
PubMed1998

Antipneumococcal activities of levofloxacin and clarithromycin as determined by agar dilution, microdilution, E-test, and disk diffusion methodologies.

The activities of levofloxacin and clarithromycin against 199 penicillin- and macrolide-susceptible and -resistant pneumococci were tested by agar and microdilution methods in air and by disk diffusion and E-test methods in air and CO2. For levofloxacin, >/=99. 0% of strains were susceptible at </=2.0 microgram/ml with zone diameters of >/=17 mm, regardless of incubation in air or CO2. Although zone sizes were smaller and E-test MICs were higher for clarithromycin in CO2 than those in air, category differences were minor, and susceptibility rates for clarithromycin were similar to those obtained by agar and microdilution in air (range, 76.9 to 80.9% by all methods). For clarithromycin, adjustment of breakpoints based upon distribution of results resulted in susceptibility rates which were similar by all methods (75.8 to 76.9% susceptible, 0 to 1.5% intermediate, 22.6 to 23.1% resistant). Minor discrepancies were obtained with levofloxacin for one strain (0.5%) by microdilution and two strains (1.0%) by disk diffusion in CO2. For clarithromycin, minor discrepancies were found in three strains (1.5%) by microdilution, seven strains (3.5%) by agar dilution, four strains (2.0%) by E-test in air, six strains (3.0%) by disk diffusion in air, and five strains (2.5%) by disk diffusion in CO2. Major discrepancies occurred with levofloxacin in one strain (0.5%) by microdilution but were not found with clarithromycin. Very major discrepancies were not seen with levofloxacin, but occurred with clarithromycin in five strains (2.5%) by microdilution, three strains (1.5%) by agar dilution, two strains (1.0%) by E-test in air, eight strains (4.0%) by disk diffusion in air, and one strain (0.5%) by disk diffusion in CO2.

Anti-Bacterial Agents↗