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Biomedical subjects

A Scott

Publications and source records attributed to A Scott.

At least 127 records · Page 7Linked to original sources
PubMed1997

Plasma leptin concentrations and OB gene expression in subcutaneous adipose tissue are not regulated acutely by physiological hyperinsulinaemia in lean and obese humans.

OBJECTIVES: To determine the effects of obesity on fasting plasma leptin levels and assess the effects of feeding on plasma leptin and OB gene expression in subcutaneous adipose tissue in non-diabetic subjects. DESIGN: Blood and subcutaneous adipose tissue needle biopsy samples were obtained after an overnight fast and 1, 2 and 3 h following a mixed meal (606 kcal). SUBJECTS: Eighteen female subjects: eight lean with a mean age of 40.1 yr (range 20-65) and mean body mass index of 22.24 kg/m2 (range 18.6-26.6) and ten obese subjects with a mean age of 48.6 yr (range 29-71) and body mass index of 33.53 kg/m2 (range 28.7-41.7). RESULTS: Apart from obesity the only significant difference between groups was a 2.6 fold higher fasting plasma leptin concentration in obese subjects compared to leans (26.9 +/- 2.9 vs 10.2 +/- 2.22 (P < 0.05) respectively). Adipose tissue OB mRNA levels were not significantly higher in the obese group. Plasma leptin correlated with BMI and visceral fat weight in lean subjects only. No significant association between plasma leptin and adiposity was evident in obese patients. In addition, there was no association between plasma leptin and the insulin: glucose ratio (an index of insulin sensitivity). Following a mixed meal, post-prandial plasma insulin levels were significantly increased, with a concomitant significant reduction in plasma NEFA levels in both groups. Despite the large increase in plasma insulin, there were no post-prandial changes in either plasma leptin concentrations or subcutaneous adipose tissue OB mRNA levels in either lean or obese subjects. CONCLUSIONS: The data indicate that plasma leptin levels are correlated with the degree of adiposity, especially in lean subjects, and confirm that circulating leptin levels are greater in obese subjects than lean subjects. The present study also failed to show a significant association between plasma leptin and insulin sensitivity in lean and obese women. Furthermore, plasma leptin and subcutaneous adipose tissue OB gene expression are not under short term regulation following feeding in fasted lean or obese female subjects.

Adipose Tissue↗
PubMed1997

Immunotherapy of melanoma: targeting defined antigens.

The clinical experience that spontaneous anti-melanoma immune reactivity can occur has stimulated the search for methods to induce this in patients diagnosed with melanoma. Non-specific approaches using a variety of immune stimulants such as BCG or cytokines have met with limited success, as have vaccines derived from tumour cells. More recently, melanoma antigens have been identified that can act as specific targets for immune recognition. Cell surface glycolipids such as the gangliosides GM2 and GD3, can be targeted by antibodies. This has provided the basis for clinical trials with ganglioside vaccines and monoclonal antibody infusions. Antigens recognized by cytotoxic lymphocytes have also been described in the last 5 years. These are peptide antigens derived from intracellular proteins which are present on the cell surface in association with HLA molecules. These antigens include MAGE 1 and 3, tyrosinase, MelanA/MART-1 and gp100. Clinical trials with these have commenced and novel treatment strategies are being developed. Since tumours can be typed for specific antigens and specific immune responses can be measured, the reasons for treatment success or failure can be analysed more effectively than in the past. For example, the emergence of antigen-negative tumour variants can be assessed. This should enable a more systematic approach for developing new immunotherapies for melanoma.

Antigens, Neoplasm↗
PubMed1997

Prevalence of dementia and depression among elderly people in black and ethnic minorities.

BACKGROUND: This study was designed to identify all elderly people of ethnic minorities living in a defined geographical area in inner-city Liverpool and to identify psychiatric morbidity and barriers to use of services. This paper reports the prevalence of dementia and depression. METHOD: A survey of the community was carried out using the Geriatric Mental State Examination, AGECAT and ethnically matched interviewers. The sampling frame consisted of Family Health Services Authority lists as a basis, with additional information from community lists, 'snow-balling' and a door-to-door survey. RESULTS: 418 people were interviewed, with a high percentage (55%) of young elderly (65-74) men. The prevalence of dementia ranged from 2 to 9% and of depression from 5 to 19%, and there were no significant differences in levels between English-speaking ethnic groups and the indigenous population. Higher levels of dementia were found among non-English-speaking groups. CONCLUSIONS: A complete enumeration of the elderly in ethnic minority groups is best achieved by using several different methods. Diagnosis of dementia may be misleading among those who do not speak the dominant language.

Africa↗
PubMed1997

Can fetal fibronectin testing improve the management of preterm labour?

The detection of fetal fibronectin (Ffn) in cervico-vaginal secretions has been proposed as a method to differentiate true from false threatened preterm labour. This study evaluates the impact of tocolysis in the management of threatened preterm labour and compares actual practice in our department with a hypothetical management strategy based upon fetal fibronectin (Ffn) testing. Over a 12 month period, 41 women were admitted in threatened preterm labour with intact membranes before 34 weeks gestation. In "actual practice", 13 received tocolysis but only three cases were considered to have benefitted from it (ratio 4.3:1). In the Ffn strategy, 34 women would receive tocolysis with 12 potentially benefitting (ratio 2.8:1). If tocolysis was given to all eligible women ("non-selective" policy) 41 women would receive tocolysis with 12 potentially benefitting (ratio 3.4:1). The majority of women receiving tocolysis do not benefit from this treatment regardless of whether tocolysis is based upon clinical judgement. Ffn testing or a non-selective administration policy. Administering tocolysis on the basis of a positive Ffn result would be expected to increase the number of women receiving tocolysis but would make a small improvement in the treatment: potential benefit ratio when compared to "actual practice".

Adrenal Cortex Hormones↗
PubMed1997

Endogenous IL-2 production by natural killer cells maintains cytotoxic and proliferative capacity following retroviral-mediated gene transfer.

Interleukin (IL)-2 therapy given at tolerable doses is insufficient to induce maximum activation of natural killer (NK) cells. We recently demonstrated that NK cells expanded in vivo can be maximally activated by short-term ex vivo incubation with 1000 U/mL IL-2. However, IL-2 withdrawal, which would occur with reinfusion, may lead to a rapid loss of cell viability and function. We hypothesized that retroviral transduction could provide an endogenous source of IL-2 to maintain NK function as measured by proliferation and cytotoxicity. Enriched NK cells were transduced with supernatants containing an MFG-based retrovirus designed to express murine IL-2 cDNA. Several supernatant transduction strategies were evaluated. NK cells were initially cultured in 1000 U/mL of huIL2 for 7-8 days, harvested, and replated prior to transduction (4 hours at 37degrees C); this proved insufficient to sustain NK proliferation or maintain cytotoxicity after exogenous human IL-2 (huIL-2) withdrawal. An alternative transduction procedure using phosphate-depleted medium, centrifugation, and transduction for 16 hours at 32degrees C was then evaluated. NK cells transduced under these conditions maintained significant NK proliferation in the absence of exogenous IL-2 compared with sham-transduced controls. Two consecutive daily transductions resulted in less proliferation, suggesting that several exposures to retroviral supernatant may inhibit subsequent NK proliferation. Cytotoxicity of the transduced NK cells against K562 and Raji was maintained under these conditions without exogenous IL-2. Sham-transduced NK cells produced 8.3+/-2.6 U/mL of murine IL-2 (muIL-2) by ELISA (background) after 7 days without exogenous IL-2. In contrast, 109+/-23 U/mL muIL-2 was produced by NK cells transduced with supernatant from the MFG/muIL-2 producer line. These experiments demonstrate that NK cells can be successfully transduced with retroviruses and induced to express sufficient IL-2 to maintain their proliferative and cytotoxic functions. Transduction of IL-2 genes into NK cells may offer advantages over exogenous IL-2 administration in maintaining maximum function for use in antitumor immunotherapy.

Adult↗
PubMed1996

Transfer of PCBs via lactation simultaneously induces the expression of P450 isoenzymes and the protooncogenes c-Ha-ras and c-raf in neonates.

At the first day of lactation, maternal rats were injected with a single i.p. dose of 100 or 250 mg/kg body weight of a mixture of polychlorinated biphenyls (Aroclor 1254). This treatment caused significant increases in both material and neonatal hepatic cytochrome P-450, cytochrome b5, and cytochrome-c-(P-450) reductase. Transfer of PCBs via lactation resulted in significant increases in hepatic enzyme activities catalysed by neonatal CYP1A1, CYP1A2, CYP2B1, CYP3A1, and CYP2E1 using a variety of substrates. In contrast, the metabolism of dimethylnitrosamine and aminopyrine was only marginally (up to 2-fold) increased in maternal animals four days post treatment. Further measurements showed significant increases in maternal and neonatal epoxide hydrolase, glutathione-S-transferase, and UDP-glucuronyl transferase activities, thus suggesting a coordinated response for an induction of CYP1A1, CYP1A2, CYP2A1, CYP2B1, CYP2E1, CYP3A1, and CYP4A1 in both maternal and neonatal CYP2C6, and at the higher dose the expression of neonatal CYP2E1 was significantly reduced. Northern blot analysis provided further evidence for significant increases in maternal and neonatal hepatic CYP1A1, CYP1A2, CYP2B1, and CYP2E1 mRNA, but reduced amounts of CYP2C7 and CYP4A1 mRNA. Additional Northern blot hybridization experiments may suggest an increased expression of the protooncogenes c-Ha-ras and c-raf in the mother and the neonate upon treatment of maternal rats with Aroclor 1254. Lactation itself may result in an increased expression of the latter protooncogenes, but the mRNA of the protooncogenes c-erb A and c-erb B was not detected in any of the tissues examined.

Animals↗
PubMed1996

Is general practitioner decision making associated with patient socio-economic status?

This paper presents a preliminary exploration into the relationship between decisions made by general practitioners (GPs) and the socio-economic status (SES) of patients. There is a large literature on the association between SES, health state and the use of health services, but relatively little has been published on the association between SES and decisions by clinicians once a patient is in the health system. The associations between GP decision making and the patient's SES, health status, gender and insurance status are examined using logit analysis. Three sets of binary choices are analysed: the decision to follow up; to prescribe; and to perform or to order a diagnostic test. Secondary data on consultations for a check up/examination were used to explore these relationships. The results suggest that SES is associated independently with the decision to test and the decision to prescribe but not with the decision to follow up. Patients of high SES are, ceteris paribus, more likely to be tested and less likely to receive a prescription compared with patients of low SES. Women are more likely to be tested and to receive a prescription than men. These findings have implications for the pursuit of equity as a goal of health services policy.

Adolescent↗
PubMed1996

Erythromycin stimulates gastric emptying after esophagectomy with gastric replacement: a randomized clinical trial.

UNLABELLED: Delayed gastric emptying after esophagogastrectomy can pose a significant early postoperative problem. Because erythromycin, which stimulates the gastric antral and duodenal motilin receptor, has been shown to significantly increase gastric emptying in patients with diabetic gastroparesis, we decided to evaluate its effect on gastric emptying after esophagogastrectomy. METHODS: Twenty-four patients (18 men and six women, age range 41 to 79 years, median 66 years) were randomized to receive either erythromycin lactobionate (200 mg in 50 ml normal saline solution intravenously) (n = 13) or placebo (50 ml normal saline solution intravenously (n = 11) 11 days after esophagogastrectomy (with pyloric drainage procedure). After erythromycin or placebo had been infused over a 15-minute period, patients ingested a solid meal (scrambled egg with bread) labeled with technetium 99m sulfur colloid (500 microCi) over approximately 15 minutes. Dynamic images of the stomach were then acquired over 90 minutes in the supine position by gamma imaging. Results were expressed as percentage of counts retained in the stomach (percent gastric retention) over time. RESULTS: There were no side effects of erythromycin. In the placebo group, the mean percent of radiolabeled meal retained in the stomach after 90 minutes was 88%, which was significantly greater than in the erythromycin group, 37% (p < 0.001). In addition, analysis of covariance demonstrated that the rate of gastric emptying (slope of the line) was significantly greater in the erythromycin-treated group than in the placebo group (p < 0.0001). CONCLUSION: Early satiety after esophagogastrectomy may be due to delayed gastric emptying and not due to a decrease in the gastric reservoir. Intravenous erythromycin significantly improves gastric emptying in patients after esophagogastrectomy by stimulating gastric motility.

Adult↗
PubMed1996

Primary or secondary care? What can economics contribute to evaluation at the interface?

BACKGROUND: The substitution of primary for secondary care is progressing at a fast pace, yet there has been little evaluation of the appropriateness of such a fundamental change in health service organization. The aim of this paper is to raise some issues for discussion about the contribution of economics to future research on the substitution of primary for secondary care. Given the central role general practitioners (GPs) will play in a "primary care led' National Health Service, the paper concentrates on the replacement of secondary care by GP-based services. METHODS: The existing empirical evidence relevant to the replacement of secondary care by GP-based services is summarized. From this, issues for further research from an economic perspective are identified and discussed. RESULTS: The evidence comprises studies examining the efficiency or cost-effectiveness of substituting GP-based care for secondary care and studies examining the effects of incentives on the mixture and range of services provided. Cost-effectiveness evidence is scarce and inconclusive. The evidence on incentives suggests that new services are being provided in local areas which need them least. Several avenues of further research are suggested. As well as more economic evaluation, future research should concentrate on developing methods to elicit patients' and communities' preferences for GP-based care versus secondary care. Research into incentives should concentrate on assessing those factors, beyond practice characteristics, that influence GP's decisions about whether to provide services and how much to provide. This would help to design more appropriate incentives for GPs. CONCLUSIONS: The appropriate balance between primary and secondary care is unknown. The transfer of services from secondary care to general practice (and other primary care providers) should be based on empirical evidence on cost-effectiveness, as should the incentives given to GPs. Although the research agenda is challenging, it is necessary in ensuring that a "primary care led' health system is the right way forward for the NHS.

Adult↗
PubMed1996

General practice on a new housing estate. 1956.

An analysis has been carried out of the records kept for the year 1953 by six doctors practising on a new housing estate near London. The population of the estate is described in terms of age, sex, and social class. 76 per cent. of the registered patients consulted a doctor at some time during the year, the consultation rate per person being 4.1 based on the average registered population; females had more consultations than males; 80 per cent. of all consultations were made by people under the age of 45. One-sixth of the patients accounted for about half of the consultations, and 30 per cent. of the consultations were made by the 7 per cent. of registered patients who consulted twelve or more times in the year. The consultation rates showed a slight, but statistically significant, social gradient, with more consultations among patients in the lower social classes. The illness rate was 26 per person, and was higher among males in infancy and old age, and among females between the ages of 5 and 64. A method of estimating the duration of sickness in terms of the period under medical care was employed. This showed that 70 per cent. of all illnesses were dealt with in single consultations, and that only 3 per cent. of illnesses were under care for more than 90 days. Over half of the practice population were under care for less than 5 days, and only 8 per cent. for more than 90 days. The proportion of patients having more than 30 days sickness generally increased with age, but there was a slight fall among the women aged 65 and over. Certificates were issued at the rate of about one for every five consultations, two-thirds of these being necessitated by the requirements of the National Insurance regulations. Prescriptions were issued at the rate of about one per consultation, the prescription rate being 41 per person. Only 5 per cent. of the practice population consulted the doctor but did not obtain a prescription. About 30 per cent. of the patients who consulted a doctor were referred outside the practices, 80 per cent. of all referrals being to hospitals, either as inpatients or as out-patients. The person-hospital referral rate was 20 per 100, and there were 31 referrals for every 100 registered patients. Males over 65 had the highest rates for consultations, illnesses, prescriptions, and referrals. The reason for this is discussed. The value of record-keeping by general practitioners is stressed, together with the need for a generally accepted method of expressing rates in studies of this kind.

Family Practice↗
PubMed1996

Enhancement of radiation dose to the nucleus by vesicular internalization of iodine-125-labeled A33 monoclonal antibody.

UNLABELLED: In radioimmunotherapy, the emission characteristics of the radioisotope is critical in determining the radiation dose to the tumor compared to normal organs. If antibodies internalize and transport low-energy electron emitting isotopes close to the tumor cell nucleus, an improved therapeutic advantage is achieved. METHODS: Using fluorescent microscopy, we studied the subcellular distribution of an internalizing antibody, A33, which detects a restricted determinant on colon cancer cells. We developed a physical model to assess the dose deposited on the nucleus by electrons emitted from radiolabeled A33 accumulated inside vesicles. This model is based on the energy-range relationship of electrons in water. Similarly, another model was developed to calculate the radiation dose to the nucleus from electrons emitted from extracellular space. The percentage of A33 bound to membrane and internalized was determined in vitro at various time points. Cytotoxicity experiments were performed with 125I- and 131I-labeled A33 at various concentrations and specific activities. RESULTS: A33 accumulates in cytoplasmic vesicles (40% of total bound) which transport the activity close to the nucleus. This increases the radiation dose to the cancer cell nucleus by a factor of 3 compared to the average dose calculated based on the assumption of a uniform distribution on the cell membrane. The cytoplasm of antigen-negative normal cells shields the nucleus from the electrons emitted from extracellular 125I. This shielding is 30 times less for 131I. Cytotoxicity data show 10% cell survival with 10 microCi/ml of 125I-A33, but 90% survival with up to 100 micro/Ci/ml of 125I-A33 in the presence of a blocking dose of 100-fold excess of cold A33. Similar experiments with 131I showed cytotoxicity in both cases. CONCLUSIONS: The results of the cytotoxicity experiment are in agreement with the physical model and suggest a basis for improved tumor-to-marrow radiation dose by clinical use of 125I-A33.

Antibodies, Monoclonal↗