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Biomedical subjects

R Clayton

Publications and source records attributed to R Clayton.

At least 19 recordsLinked to original sources
PubMed2006

The interval from surgery to chemotherapy in the treatment of advanced epithelial ovarian carcinoma.

BACKGROUND: To study the effect of the interval between surgery and the start of chemotherapy in the treatment of patients with advanced ovarian cancer. METHODS: We stratified patients according to the start of platinum-based chemotherapy in group 1 (within 4 weeks from surgery), group 2 (between 4 and 8 weeks) and group 3 (between 8 and 12 weeks). RESULTS: Three hundred and ninty-four stage III ovarian cancer patients were analysed. In the multivariate analysis there were no differences in survival according to the interval between surgery and chemotherapy among the three groups. The independent prognostic variables were type of procedure (p = 0.014), performance status (p = 0.040) and post-chemotherapy CA-125 (p < 0.0001). CONCLUSIONS: The interval between surgery and chemotherapy does not affect outcome.

Adult↗
PubMed2006

Defining the dermatological content of the undergraduate medical curriculum: a modified Delphi study.

BACKGROUND: Dermatological problems are common, but in undergraduate medical courses time for learning dermatology and teaching dermatology is limited. The Delphi technique has been used in other specialties to define undergraduate and postgraduate curricula and to reach consensus on what is important. OBJECTIVES: To identify the core dermatological content of the undergraduate medical curriculum. METHODS: Modified Delphi technique. A questionnaire was designed after review of previous recommendations made by dermatologists. Items were written as explicit learning outcomes. A multidisciplinary panel of 66 individuals responded. Outcomes were rated using a Likert scale (1-5). RESULTS: Fifty-three learning outcomes were rated 'very important'. We recommend that these are included in the content of U.K. undergraduate medical core curricula. CONCLUSIONS: A multidisciplinary panel identified dermatological learning outcomes that should be achieved by all medical graduates. Undergraduate medical curricula must provide sufficient resources for learning, teaching and assessment of dermatology so that graduates achieve these outcomes.

Clinical Competence↗
PubMed2002

Matrix metalloproteases and their inhibitors are produced by overlapping populations of activated astrocytes.

Matrix metalloproteases (MMPs) and tissue inhibitors of metalloproteases (TIMPs) are involved in many cell migration phenomena and produced by many cell types, including neurons and glia. To assess their possible roles in brain injury and regeneration, we investigate their production by glial cells, after brain injury and in tissue culture, and we investigate whether they are capable of digesting known axon-inhibitory proteoglycans. To determine the action of MMPs, we incubated astrocyte conditioned medium with activated MMPs, then did western blots for several chondroitin sulphate proteoglycans. MMP-3 digested all five proteoglycans tested, whereas MMP-2 digested only two and MMP-9 none. To determine whether MMPs or TIMPs are produced by astrocytes in vitro, we tested both primary cultures and astrocyte cell lines by western blotting, and compared them with Schwann cells. All cultures produced at least some MMPs and TIMPs, with no obvious correlation with the ability of axons to grow on those cells. Both MMP-9 and TIMP-3 were regulated by various cytokines. To determine which cells produce MMPs and TIMPs after brain injury, we made lesions of adult rat cortex, and did immunohistochemistry. MMP-2 was seen to be induced in activated astrocytes through the whole thickness of the cortex but not deeper, but MMP-3 was not seen in the injured brain. TIMP-2 and TIMP-3 immunoreactivities were induced in activated astrocytes in deep cortex and the underlying white matter. In situ hybridisation confirmed induction of TIMP-2 in glia as well as neurons, but showed no expression of TIMP-4. These results show that both MMPs and TIMPs are produced by some astrocytes, but TIMP production is particularly strong, especially in deep cortex and white matter which is more inhibitory for axon regeneration. Conversely the MMPs produced may not be adequate to promote migration of cells and axons within the glial scar.

Animals↗
PubMed2001

Ethanol sensitivity of recombinant human N-methyl-D-aspartate receptors.

In this study, the ethanol sensitivity of human N-methyl-D-aspartate (NMDA) receptors stably expressed in L(tk-) cells, or transiently expressed in HEK 293 cells and Xenopus oocytes was determined. NMDA receptor function was measured using fura-2 calcium imaging for L(tk-) cells, whole cell voltage-clamp for HEK 293 cells, and two-electrode voltage clamp for oocytes. Ethanol inhibited NMDA receptor function in all three expression system, but was less potent for receptors expressed in L(tk-) cells. NMDA receptors composed of NR1a/2B subunits were inhibited to a greater extent by ethanol than NR1a/2A receptors when expressed in L(tk-) cells and HEK 293 cells, but not in oocytes. These results suggest that the method of receptor expression and assay system used may influence the degree of ethanol inhibition of recombinant NMDA receptors.

Animals↗
PubMed2001

Factors limiting the rate of living-related kidney donation to children in an inner city setting.

A recent review of our center experience revealed that only 38% of our pediatric renal transplants come from living-related donors (LRD), which is 11% lower than the national average. The present study was designed to identify factors that limit the availability of LRD in our population pool. Retrospective chart reviews and subsequent telephone interviews were conducted with parents of all children who received renal replacement therapy (RRT) at our institution from 1990 to 1999. The availability of parents and their willingness to donate a kidney were noted. Self-reported willingness was defined as the verbal expression of a desire to donate. Firm willingness was defined as the completion of the steps necessary for donation, unless excluded by the medical team. Factors that may impact the ability to donate, such as donor age, ethnicity, religion, educational attainment, employment, and presence of other siblings younger than 18 yr of age, were evaluated. Statistical analyses were performed using the Student's t-test and chi-square analysis. Significant results were entered into a single-step multiple regression analysis. Sixty children were identified with RRT, of whom 60% were Blacks, 30% Hispanics, 7% Caucasians, and 3% Asian. Fifty-five mothers were available for interview. Forty-four mothers reported a desire to donate, nine were unwilling to donate, and two were undecided. However, only 35 attended for screening. Only 30 fathers were available and, of these, 27 reported willingness to donate, yet only 20 attended for screening. Seventy-four per cent (26 out of 35) of mothers screened and 55% (11 out of 20) of fathers screened were medically unsuitable for kidney donation. Nineteen potential donors had hypertension, diabetes and/or obesity, seven had renal disease, four had anemia, two had hepatitis C, and five had other conditions. Expressed unwillingness to donate was associated with a greater number of children (3.1 compared to 1.5 children in addition to the child with end-stage renal disease [ESRD]) (odds ratio 2.91, p < 0.05) and employment (26.3% vs. 4.0%, p < 0.05) (odds ratio 31.2, p = 0.05). Comparing mothers who were firmly willing to donate with mothers who did not complete screening and evaluation, unwilling mothers had, likewise, a greater number of children (2.9 vs. 1.2 in addition to the child with ESRD) (odds ratio 3.23, p < 0.01) and a greater number of years of education (12.4 vs. 10.4) (odds ratio 2.14, p < 0.05). Hence, the availability of living kidney donors for our inner city children is severely limited by a high rate of single parenthood and a high rate of comorbid conditions in the parental donor pool. Furthermore, there is a diminished capacity of the available parent, particularly the mother, to donate as she tends to have numerous other dependents.

Black or African American↗
PubMed2001

Gambling as an addictive disorder among athletes: clinical issues in sports medicine.

This article examines the role of gambling as an addictive disorder experienced by athletes, both college and professional. Gambling may often be seen as a comorbid factor with other addictions and with depression among athletes. The focus on addictions among athletes has gained considerable attention among sports medicine clinicians. Diagnostic indicators, risk and protective factors, and a stage model of addiction among athletes are addressed. An algorithm and pathway of care for athletes with an addictive disorder is offered as are recommendations that sports physicians, sports medicine specialists, coaches and counsellors need to address athletes who have an addictive disorder.

Behavior, Addictive↗
PubMed2001

Hypopituitarism and atherosclerosis.

In the last decade, retrospective cohort data has provided evidence of premature atherosclerosis in patients with hypopituitarism which may account for the recently observed increased death rate from vascular events in these patients. The exact mechanism(s) for such propensity to atherosclerotic vascular disease is not yet completely clear. It is possible that hormonal factors may be the initiating mechanisms with subsequent secondary metabolic abnormalities acting as risk factors for development of atherosclerosis. This seems to be more evident in female hypopituitary patients compared with their male counterparts. Female patients have higher frequency and more pronounced abnormalities of various risk factors as well as surrogate markers of early vascular disease. This may explain why morbidity and mortality in women is in excess of men in retrospective epidemiological studies. Addressing abnormal hormonal factors, especially in females, is a primary objective in managing these patients both in the clinical arena as well as in trials designed to reduce the risk of atherosclerotic vascular disease in these patients. While short-term growth hormone treatment may ameliorate some of the vascular risk factors and improve endothelial function, it remains to be shown whether this translates into long-term reduction in morbidity and mortality from vascular, especially cerebrovascular, disease.

Adult↗
PubMed2000

Effects of ethanol on three endogenous membrane conductances present in Xenopus laevis oocytes.

The Xenopus oocyte expression and recording system has allowed a detailed analysis of the physiology and pharmacology of neuronal ion channels including their sensitivity to ethanol. It is important however, to ascertain the effects of a particular drug on the channels inherently expressed by oocytes to ensure that drug effects ascribed to the expressed recombinant receptors are manifested solely through those receptors. In this study, the effects of ethanol were determined on three endogenous currents that can be elicited in oocytes and other cells by various manipulations. The inward cation current, IC, was activated by perfusing naive oocytes with a divalent-free recording solution. Ethanol (25-100 mM) modestly inhibited IC with 100 mM ethanol producing a 7-8% inhibition of steady state currents. The store-operated or capacitative calcium current (I(SOC)) was activated in thapsigargin-treated oocytes by switching from a calcium-free solution to one containing 10 mM calcium. In thapsigargin-treated oocytes also injected with EGTA to block calcium-activated chloride currents, ethanol (100 mM) had no effect on the store-operated calcium current. In contrast, ethanol (10-100 mM) dose-dependently inhibited the calcium-dependent chloride current (I(Cl(Ca)) in thapsigargin-treated oocytes. A voltage-jump protocol was used to separate the two components of I(Cl(Ca)), I(Cl-1) and I(Cl-2). Under these conditions, ethanol (100 mM) inhibited I(Cl-1) currents to a greater extent (38%) than it did I(Cl-2) currents (14%). These results show that Xenopus oocytes express endogenous ion channels that are differentially sensitive to ethanol.

Animals↗
PubMed2000

Differences in young adult psychopathology among drug abstainers, experimenters, and frequent users.

Shedler and Block offered the provocative proposal that individuals who experiment with drugs are psychologically healthier than either those who abstain completely or those who are frequent users. Not all studies have come to such conclusions, however. In an effort to specify under what conditions Shedler and Block's conclusions might hold, the present study examined three groups of drug users (abstainers, experimenters, frequent users) classified according to three different criteria: (a) marijuana use at age 20; (b) alcohol use during 10th grade; and (c) alcohol use at age 20. The three groups were compared at age 20 in terms of personality, deviant behavior, and psychopathology. The results revealed that abstainers were never more psychologically impaired, and were occasionally healthier, than experimenters. Frequent users of marijuana were consistently more imparied than both the abstainers and experimenters, in terms of both internalizing and externalizing disorders. Classification according to marijuana use appeared to be more related to psychopathology than did classification according to alcohol use.

Adolescent↗
PubMed2000

Violence in the schools: clinical issues and case analysis for high-risk children.

School violence in rural communities has gained considerable attention nationally. Examined are theoretical considerations involving escape theory, the risk and protective factors for school violence, case analyses of recent case studies, and discussion of recent school violence involving fatal injuries to others. Also discussed are diagnostic issues in understanding children who are at-risk for school violence and ways school violence maybe managed in the schools. Suggestions and recommendations including recommendations provided by the National School Safety Center for school personnel are offered, as are steps to be taken in creating a safe school environment. This information may be helpful to child psychiatry and clinical personnel who provide services to school aged children.

Adolescent↗
PubMed2000

The effect of endometriosis and its radical laparoscopic excision on quality of life indicators.

OBJECTIVE: To assess the effect of endometriosis and radical laparoscopic excision on the quality of life of women with this condition. DESIGN: A prospective study. SETTING: The Northern Endometriosis Centre at South Cleveland Hospital, Middlesbrough and St. James's University Hospital, Leeds. POPULATION: Fifty-seven consecutive patients undergoing laparoscopic excision of invasive endometriosis. METHODS: Questionnaires, both pre-operatively and four-month post-operatively, for a number of different symptoms associated with endometriosis were completed by patients. Details of fertility, previous treatments and quality of life as measured by SF12 and EuroQOL (EQ-5D) and sexual activity questionnaire, as well as linear pain scores for several symptoms, were recorded. Details of intra-operative findings was also collected. MAIN OUTCOME MEASURES: Effect of laparoscopic excision on pain scores and quality of life, operative findings, type of surgery, length of surgery and incidence of intra- and post-operative complications. RESULTS: Patients with endometriosis were severely ill with significant pain and impairment of quality of life and sexual activity. Four months after radical laparoscopic excision for deep endometriosis there was significant improvement in all the parameters measured including their quality of life based on EuroQOL evaluation: EQ-5D (0 x 595:0 x 729, P = 0 x 002) and EQ thermometer (68 x 9:77 x 7, P = 0 x 008); SF12 physical score (44 x 8:51 x 9, P = 0 x 015); sexual activity (habit P = 0 x 002, pleasure P = 0 x 002 and discomfort P < or = 0 x 001). Only the mental health score of SF12 failed to show any statistical improvement (47 x 1:48 x 4, P = 0 x 84). Symptomatically, there was a significant reduction in dysmenorrhoea (median 8 x 0:4 x 0, P < or = 0 x 001), pelvic pain (median 7 x 0:2 x 0, P < or = 0 x 001), dyspareunia (median 6 x 0:0 x 0, P < 0 x 001) and rectal pain scores (median 4 x 0:0 x 0, P < 0 x 001). Complications were noted, but were deemed to be acceptable for the extent of the surgery. CONCLUSIONS: This is an early analysis of the first 57 cases studied, but structured evaluation suggests that meaningful improvements in clinical symptoms and quality of life can be obtained with this approach with acceptable levels of operative morbidity. Further follow up of this series is required, but early evidence would suggest that the technique should be further evaluated as part of a randomised trial.

Endometriosis↗
PubMed1999

Comparison of long-term outcomes of atrial repair of simple transposition with implications for a late arterial switch strategy.

BACKGROUND: We report the single-institution, long-term results of 358 patients with simple transposition of the great arteries surviving >30 days after a Mustard (n=226, 1965 to 1980) or Senning (n=132, 1978 to 1992) procedure. METHODS AND RESULTS: Outcome measures included late death, reintervention, ECG and ambulatory ECG rhythm, new arrhythmia, and functional status. Average follow-up was 13.4 (range 0.32 to 17.9) years for the Senning group and 11.7 (range 0.04 to 23.9) years for the Mustard group. The Senning group had a better survival rate at 5, 10, and 15 years (95% versus 86%, 94% versus 82%, and 94% versus 77%, respectively). In both groups, the majority of late deaths were sudden, without preceding ventricular dysfunction. Survival and survival free of reintervention were significantly better in the Senning group (relative risk [RR] 0.34, P=0.06 versus RR 0.39, P=0.027). Loss of sinus rhythm was comparable and unrelated to death. After era correction, the incidence of atrial flutter was similar and strongly associated with late death in both groups. Clinical systemic ventricular failure was uncommon, and at last follow-up, 92% of the Senning group and 89% of the Mustard group were in New York Heart Association class I. In a model exploring the implications of elective arterial switch conversion, this would only be beneficial if the hazard late after switch was markedly reduced and/or the hazard after the Senning procedure increased with time. CONCLUSIONS: Late outcomes after the Senning procedure are superior to those after the Mustard procedure. Both groups had late sudden deaths that were not associated with clinical systemic ventricular failure. Good functional status after the Senning procedure suggests that a strategy of elective switch conversion cannot be justified for patients with isolated transposition.

Cardiac Surgical Procedures↗
PubMed1999

Identification of a vibrio cholerae RTX toxin gene cluster that is tightly linked to the cholera toxin prophage.

We identify and characterize a gene cluster in El Tor Vibrio cholerae that encodes a cytotoxic activity for HEp-2 cells in vitro. This gene cluster contains four genes and is physically linked to the cholera toxin (CTX) element in the V. cholerae genome. We demonstrate by using insertional mutagenesis that this gene cluster is required for the cytotoxic activity. The toxin, RtxA, resembles members of the RTX (repeats in toxin) toxin family in that it contains a GD-rich repeated motif. Like other RTX toxins, its activity depends on an activator, RtxC, and an associated ABC transporter system, RtxB and RtxD. In V. cholerae strains of the classical biotype, a deletion within the gene cluster removes rtxC and eliminates cytotoxic activity. Other strains, including those of the current cholera pandemic, contain a functional gene cluster and display cytotoxic activity. Thus, the RTX gene cluster in El Tor O1 and O139 strains might have contributed significantly to their emergence. Furthermore, the RTX toxin of V. cholerae may be associated with residual adverse properties displayed by certain live, attenuated cholera vaccines.

Amino Acid Sequence↗
PubMed1999

Project DARE: no effects at 10-year follow-up.

The present study examined the impact of Project DARE (Drug Abuse Resistance Education), a widespread drug-prevention program, 10 years after administration. A total of 1,002 individuals who in 6th grade had either received DARE or a standard drug-education curriculum, were reevaluated at age 20. Few differences were found between the 2 groups in terms of actual drug use, drug attitudes, or self-esteem, and in no case did the DARE group have a more successful outcome than the comparison group. Possible reasons why DARE remains so popular, despite the lack of documented efficacy, are offered.

Adolescent↗
PubMed1999

Risky sex behavior and substance use among young adults.

Many young adults, despite widespread prevention and education efforts that target this age group, engage in behaviors that place them at risk of HIV infection. These behaviors include frequent experimentation with alcohol and other drugs before sex, sexual activity with different partners, and inconsistent safe-sex practices. The combination of these risky behaviors causes increased concern about the spread of HIV among this age group. The study discussed in this article examined the relationship between substance use during adolescence and HIV risk behavior among young adults ages 19 to 21 with and without a college education. Results indicated that increased use of alcohol and marijuana at younger ages is related to riskier sexual activity and increased use of alcohol and marijuana as young adults. Recommendations for interventions are made.

Adolescent↗
PubMed1999

Laparoscopic-assisted Doderlein hysterectomy: retrospective analysis of 300 consecutive cases.

OBJECTIVE: To assess the clinical outcomes of the Doderlein laparoscopic-assisted hysterectomy. DESIGN: A retrospective study. SETTING: Women's Endoscopic Laser Foundation at South Cleveland Hospital, Middlesbrough and St James's University Hospital, Leeds. POPULATION: Three hundred consecutive women who had a laparoscopic-assisted Doderlein hysterectomy. METHODS: Patients were identified from the laparoscopic hysterectomy theatre log at both sites. Case notes were requested and examined. MAIN OUTCOME MEASURES: Operative time, uterine weight, associated pelvic pathology, blood loss, hospital stay, intra-operative and post-operative complications. RESULTS: The operations were performed by eight different surgeons, seven of whom were laparoscopic trainees. The mean operating time was 102 minutes (SD 30). Additional surgery including unilateral or bilateral salpingo-oophorectomy, was carried out in 247 patients (82%). The mean uterine weight was 140 g (SD 74). One hundred and thirty-two women (44%) had a normal pelvis at hysterectomy. The mean drop in haemoglobin and haematocrit was 1.46 g (SD 0.95) and 4.4% (SD 2.8), respectively. The overall complication rate was 18%, of which 6.2% were classed as major. The major complications included four cystotomies, five unscheduled laparotomies, seven post-operative blood transfusions, one pulmonary embolus and two re-operations (within six weeks). The mean hospital stay was three days. CONCLUSIONS: Laparoscopic-assisted Doderlein hysterectomy is an alternative to standard laparoscopic hysterectomy techniques. It has the advantage of being easy to learn and is associated with low complication rates, compared with other laparoscopic and traditional techniques for hysterectomy.

Blood Loss, Surgical↗
PubMed1998

Chromosome 2 sequence of the human malaria parasite Plasmodium falciparum.

Chromosome 2 of Plasmodium falciparum was sequenced; this sequence contains 947,103 base pairs and encodes 210 predicted genes. In comparison with the Saccharomyces cerevisiae genome, chromosome 2 has a lower gene density, introns are more frequent, and proteins are markedly enriched in nonglobular domains. A family of surface proteins, rifins, that may play a role in antigenic variation was identified. The complete sequencing of chromosome 2 has shown that sequencing of the A+T-rich P. falciparum genome is technically feasible.

Amino Acid Sequence↗