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Biomedical subjects

A Green

Publications and source records attributed to A Green.

At least 253 records · Page 14Linked to original sources
PubMed1996

Tolerance of nicotinamide and carbogen with radiation therapy for glioblastoma.

Nineteen patients with glioblastoma were treated with nicotinamide and carbogen and radiotherapy. Eight patients did not complete the protocol because of hepatic toxicity from phenytoin/nicotinamide drug interactions, persistent nausea or vomiting with nicotinamide, intolerance of the carbogen breathing apparatus, or other reason. In addition, early radiation neurotoxicity appeared increased.

Administration, Inhalation↗
PubMed1996

Prevention of IDDM: the genetic epidemiologic perspective .

Rational prevention of insulin-dependent diabetes mellitus (IDDM) requires knowledge about the aetiology and pathogenesis of the disease. The causation of IDDM is complex, involving genetic susceptibility as well as non-genetic determinants. The evidence of a genetic component to IDDM is based on the high concordance rate in monozygotic twins as compared with dizygotic twins, the higher recurrence risk among relatives of patients with IDDM as compared with the general population risk, and the well-established associations with genetic markers, including specific alleles from the HLA-locus. The evidence of a non-genetic component to IDDM is primarily based on the fact that the concordance rate in monozygotic twins is far from unity; the huge geographical variation in the incidence of IDDM, even between genetically similar populations, and the increasing incidence in many populations provide further support; associations between the risk of developing IDDM and exposure to several non-genetic determinants, including nutrients and viral infections, have been established and serve as additional evidence. In general, the relative risks conferred by the non-genetic determinants are rather small, and it is unknown how these factors initiate the autoimmune-mediated process that destroys the beta-cells of the pancreas. Recent findings suggest that non-genetic factors interact with genetic susceptibility genes in the causation of IDDM. Firstly, it appears that the increase in the incidence of IDDM has predominantly been observed in populations with high frequency of susceptibility genes. Secondly, it seems that the risk of IDDM among relatives of patients with IDDM is positively correlated with the general population risk level. All these lines of evidence considered together suggest that IDDM may develop from several different combinations of susceptibility genes acting together with non-genetic exposures. If so, prevention of IDDM will require assessment of disease risk at individual rather than at population level. Since genetic screening is neither feasible nor ethically acceptable in the population at large, possible prevention of IDDM will be restricted to individuals who, by means of a positive family history, may be classified as being at high disease risk.

Causality↗
PubMed1996

An exploratory study of patients' memory recall of their stay in an adult intensive therapy unit.

This study carried forward an exploration to determine if there is a need to visit patients in a ward following discharge from an adult intensive therapy unit (ITU), by ascertaining what patients remember of their stay and their ability to cope with this experience. Data were collected during interviews 48 hours following subjects' discharge from the ITU, and collated using an adaptation of thematic content analysis as described by Burnard (1991). Twenty-six subjects were studied over a 6-month period. The findings suggest that patients have vivid recollections of their stay in an ITU, and are consistent with previous research in respect of patients continuing to experience dreams, pain, sleep deprivation and worries about transfer out of an ITU to a ward. New themes suggest that ITU patients do not recall their "named nurse", but do recall detailed explanations given to them by nurses in the ITU. Patients also believe they would benefit from a follow-up visit to discuss and clarify aspects of their stay which were unclear or are causing them concern.

Adaptation, Psychological↗
PubMed1996

Unrelated donor bone marrow transplantation for children with relapsed acute lymphoblastic leukaemia in second complete remission.

Allogeneic sibling bone marrow transplantation (BMT) is the recommended treatment for relapsed childhood acute lymphoblastic leukaemia (ALL), but appropriate donors are only available in 30% of cases. Unfortunately, BMT from unrelated donors (UD) has been associated with high rates of severe graft-versus-host disease (GvHD) and transplant-related mortality (TRM). In an attempt to improve outcome in UD-BMT we have assessed the impact of T-cell depletion using CAMPATH-1 (anti-CD52) monoclonal antibodies in 50 consecutively referred patients with relapsed ALL in second remission. All were previously treated according to MRC protocols UKALL X and XI, and then given chemotherapy on MRC R1 from relapse until UD-BMT, 19 patients had relapsed on and 31 off therapy. Patients and donors were fully matched at HLA-A, -B, -DR and -DQ loci in 29 cases and mismatched in 21 (four mismatched for more than one antigen). Pre-transplant conditioning comprised CAMPATH-1G, cyclophosphamide and total body irradiation. Bone marrow was T-cell depleted in vitro using CAMPATH-1 antibodies. Additional GvHD prophylaxis consisted of cyclosporin A (42 cases), cyclosporin plus methotrexate (four) or none (four). 47 patients engrafted. The incidence of acute GvHD was very low: two patients with grade II disease in the matched group, four with grade II-IV in the mismatched group. Only four patients have chronic GvHD. The actuarial event-free survival (EFS) at 2 years is 53%, with no significant difference between the matched and mismatched group. Further leukaemic relapse was the most important cause of failure. These results are similar to the most favourable published reports for HLA-matched sibling BMT in relapsed ALL.

Acute Disease↗
PubMed1996

Reliability and validity of the Opiate Treatment Index among a sample of opioid users in the United Kingdom.

To validate the Opiate Treatment Index (OTI) for use in the United Kingdom, 72 subjects attending two methadone clinics in London completed confidential interviews with two researchers at two points in time, 1-2 weeks apart. About half the interviews were conducted by the same interviewer on both occasions, and the remaining by different interviewers. These research designs enabled an estimation of the test-retest and inter-rater reliability of the instrument. Subjects' responses were validated against key worker reports and self-reported drug use against urinalysis results. The majority of the respondents were males (65%) and their mean age was 34.2 years (range 21-52; SD 8.5). Test-retest reliability coefficients were high for all the scales (range 0.77-0.86) in both the same and different interviewer situations. The internal reliability of the scales was generally high (Cronbach's alpha: range 0.34-0.93). The correlation with key workers' reports was high with the percentage agreement on the items ranging 74-100 (mean 87). The percentage agreement of self-reported drug use with urinalysis results was high (range 69-95; mean 89). These findings are similar to those obtained among Australian subjects and suggest a high cross-cultural validity for the OTI. Minor changes to the OTI have been incorporated into a modified version for use in the UK.

Journal Article↗
PubMed1996

Opening the debate on DALYs (disability-adjusted life years).

The 1993 World Development Report is proving to be an influential document for the development of the health sector policies in developing countries. One important aspect of the Report concerns its proposals for Disability Adjusted Life Years as a measure of health change and hence effectiveness of interventions. This article comments on the use of such measures in the health policy arena.

Cost of Illness↗
PubMed1996

Learning a partial-weight-bearing skill: effectiveness of two forms of feedback.

BACKGROUND AND PURPOSE: Partial weight bearing (PWB) is a skill commonly taught by physical therapists. This study compared the effects of practice with either augmented feedback provided during the task (concurrent feedback) or augmented feedback provided after the task (postresponse feedback) for the learning of PWB with crutches. SUBJECTS: Sixty young adults without known impairment of the neuromusculoskeletal system volunteered for the study. METHODS: Subjects practiced supporting 30% of body weight while stepping onto a floor scale. Augmented feedback was provided during each trial for the concurrent feedback group and either following each trial or after every five trials for the postresponse feedback groups. Subjects returned 2 days later for a no-feedback retention test. RESULTS: During practice, the concurrent feedback group was more accurate and consistent than either of the postresponse feedback groups. During retention, however, the postresponse feedback groups were the most accurate; all groups were equally consistent during retention. CONCLUSION AND DISCUSSION: These results suggest that practice with concurrent feedback is beneficial for the immediate performance but not for the learning of this sensorimotor skill.

Adult↗
PubMed1996

Accuracy of case-reported family history of melanoma in Queensland, Australia.

A positive family history is used in clinical practice as an indication of increased melanoma risk, yet there are no data on the accuracy of reported family histories of melanoma. The validity of case-reported family history of melanoma was assessed in the course of a family and twin study of melanoma in Queensland, Australia, conducted among the families of 2,118 melanoma cases diagnosed in Queensland between 1982 and 1990. A total of 913 melanoma cases made 1,267 reports of melanoma among their first-degree relatives. A total of 1,040 of these reports were checked, first through relatives themselves and then, if the relative also said they had had melanoma, through the relative's medical records. Medical confirmation of melanoma as the diagnosis was obtained for 623 reports (59.9%; 95% confidence interval 56.9-62.9): a false-positive reporting rate by cases of 40.1%. The level of false-positive reporting was lower for cases under 70 years of age, for women, for cases whose own diagnosis of melanoma was more than 5 years earlier, and for cases with three or more relatives with melanoma. Media campaigns in Queensland aimed at increasing skin cancer awareness, and confusion between melanoma and other more common actinic neoplasma (basal and squamous cell carcinomas), may partly explain the high false-positive reporting rate observed here. For this reason, It is difficult to generalize these findings to northern hemisphere populations where skin cancer is not such an important public health issue.

Adolescent↗
PubMed1996

Occurrence of melanomas on the upper and lower limbs in eastern Australia.

In view of the changing trends in the incidence of melanoma at different body sites and in particular on the limbs, the detailed distributions of over 10,000 invasive melanomas diagnosed on the upper and lower limbs in residents of mainland eastern Australia between 1987 and 1993 were examined. Cancer notifications and histopathology reports from the cancer registries of Queensland, New South Wales and Victoria were searched manually, and subsites when specified were recorded as shoulder, upper arm, forearm, elbow, wrist or hand, and thigh, leg, knee, ankle or foot. On the upper limbs relative tumour densities were highest on the shoulder, approximately equal on the upper arm and forearm and least on the hand in both men and women; on the lower limbs melanomas occurred more than twice as often on the leg than on the thigh or the foot, taking account of surface area. There was a clear inverse gradient of incidence of melanoma with latitude in the three eastern Australian states studied, but little difference between the states or between sexes in distribution of histological type: the majority specified being specified as superficial spreading melanomas. In contrast to predictions based on apparent frequency of sun exposure at subsites on the upper limbs, the relative concentration of melanomas on the shoulder suggests that wearing sleeveless garments outdoors in the sun should be avoided whenever possible. Also, the similar densities of leg and forearm melanomas seems inconsistent with the relative degree of exposure of each and further suggests that women's adoption of ankle-length skirts or trousers, in preference to knee-length skirts would be a worthwhile modern control measure.

Adolescent↗
PubMed1996

Chronic sun exposure and age are inversely associated with nevi in adult renal transplant recipients.

In 126 adult renal transplant recipients who had survived their transplantation for at least 8 years, we determined whether numbers of nevi and the presence of clinically atypical nevi were related to chronic sun exposure. On the basis of a skin examination, three groups were defined: patients with at least one clinically a typical nevus; patients with only clinically normal nevi: and patients without any nevi. The prevalence odds ratio of having any clinically atypical nevi as compared to having only clinically normal nevi was calculated in a logistic model, in relation to gender, skin type, age, sun exposure, and number of keratotic skin lesions present. Similarly, the prevalence odds ratio of having 30 or more nevi compared to fewer than 30 nevi was calculated. We found an inverse association between chronic sun exposure and age with numbers of nevi in adult renal transplant recipients. The presence of clinically atypical nevi was also inversely associated with chronic sun exposure, but this association disappeared after adjustment for age. We did not observe an association of nevi with the number of keratotic skin lesions, nor with humoral immune responses against human papillomavirus and the presence of certain HLA antigens, which are factors associated with nonmelanoma skin cancer in renal transplant recipients. Chronic sun exposure and age appeared to be strong determinants for decreased numbers of nevi in adult renal transplant recipients. Infection with human papillomaviruses does not appear to play an important role.

Adult↗
PubMed1996

Narcolepsy in a 2-year-old boy.

This report describes the prospective follow-up of a 2-year-old child with narcolepsy. The initial clinical diagnosis was confirmed by the onset of cataplexy when the child was 5 years old. He does not have the HLA genotype characteristic of narcolepsy or an identifiable brain lesion, although he has megalencephaly and mild learning difficulties. Treatment with dietary tyrosine supplements who are to young to use stimulants safely. The morbidity of narcolepsy is high and early diagnosis is therefore important, as treatment is effective.

Cataplexy↗
PubMed1996

Tumor suppressor p53 down-regulates tissue-specific expression of tyrosinase gene in human melanoma cell lines.

Tyrosinase, the key gene in melanin pigment synthesis, is tissue-specifically expressed in melanocytic cells. Expression of this gene is regulated by various hormones, carcinogens, and environmental factors. The molecular basis underlying tyrosinase gene regulation is still not clear. In this report, we present the effects of tumor suppressor p53 protein in tyrosinase gene expression and melanin synthesis in human melanoma. After stable transfection of wild type p53 expression plasmid into a highly pigmented melanoma cell line, overexpression of wt p53 suppressed the pigmentation of the melanoma cells. The loss of pigmentation was associated with the loss of endogenous tyrosinase expression at the activity and mRNA levels. In order to determine whether the p53 repression of tyrosinase mRNA involved modulation of tyrosinase promoter activity, transient transfection approaches involving p53 expression plasmid and construct containing chloramphenicol acetyl transferase (CAT) reporter gene linked to 270 bp tissue-specific tyrosinase promoter have been used. p53 specifically repressed CAT gene expression from the tyrosinase promoter and not from the Rous sarcoma virus promoter. These data suggest that in human melanoma p53 down-regulates the tissue-specific expression of tyrosinase gene and subsequent melanin synthesis.

Chloramphenicol O-Acetyltransferase↗
PubMed1996

An animal model for human melanoma.

Experimental animal models that are directly relevant to human melanoma are lacking. We propose the Angora goat as a potentially useful field model with experimental potential and to this end have examined the prevalence and site distribution of all skin cancers in 28 Angora goat herds in Queensland, Australia. The prevalence of benign melanocytic lesions (lentigines) and their experimental induction by sunlight were also investigated. Among 1731 goats over 2 years of age, 139 malignant skin tumors were excised from 95 affected animals. The prevalence of squamous cell carcinoma (SCC) was 3.8% and of melanoma, 2.2%. Main site of occurrence of melanoma (83%) was the dorsal surface of the ear; in contrast SCC occurred mostly (84%) on the perineum. Lentigines were darker and more prevalent on the exposed compared with the unexposed surface of the ear in Angoras, analogous to the higher prevalence of nevi on the exposed compared with the less exposed inner surface of the arm in humans. Lentigines, which were also found on the perineum though lighter in color than on the dorsal ear, were absent in young animals under 3 months but were numerous in 1-3 year olds. Furthermore in an experimental substudy eight goats, having one flank repeatedly shorn and the contralateral flank left unshorn, revealed consistently more solar lentigines on the shorn flank (P < 0.05) when both sides were examined after 9 months. Histopathological examination of paired skin biopsies from five of these goats also showed more abundant pigmentation in skin from the exposed, as compared with the unexposed flank. These findings indicate that sunlight induces tumors and lentigines in goats in a highly site-specific manner. The Angora goat model may suggest paradigms for explaining the site differences observed for human melanoma and may also be useful in the future clarification of molecular changes following carcinogenic levels of sun exposure.

Animals↗
PubMed1996

Lens thickness and insulin dependent diabetes mellitus: a population based twin study.

AIM: To investigate the relation between lens thickness and duration of insulin dependent diabetes mellitus (IDDM). METHODS: From the new population based Danish twin register, containing 20,888 twin pairs born between 1953 and 1982 (inclusive), all twin pairs having one or both partners affected with IDDM were searched. Among the 45 twin pairs available for clinical eye examination there were 15 monozygotic pairs, 14 dizygotic pairs of same sex, and 16 dizygotic pairs of opposite sex. Lens thickness was measured by ultrasonography. Using a twin control design, the relation between lens thickness and duration of IDDM was assessed by estimating the correlation between the intrapair difference in lens thickness and the intrapair difference in diabetes duration. RESULTS: In monozygotic twin pairs a statistically highly significant correlation between duration of diabetes and lens thickness was found (right eye: r = 0.88, p < 0.0001; left eye: r = 0.90, p < 0.0001). In dizygotic twin pairs of the same sex the correlations were r = 0.58 (p = 0.029) and r = 0.53 (p = 0.053) for right eye and left eye, respectively. For dizygotic twin pairs of opposite sex the correlations were r = 0.58 (p = 0.018) and r = 0.69 (p = 0.005) for right eye and left eye, respectively. The slope in regression analysis were similar for monozygotic twin pairs (0.025, common for both eyes) and dizygotic twin pairs grouped (0.024, common for both eyes). CONCLUSIONS: There is a statistically significant positive correlation between duration of IDDM and lens thickness, as assessed by the twin control method. The higher correlation in monozygotic twins compared with dizygotic twins suggests that genetic factors play an additional role in the determination of lens thickness. The similar slopes in regression analysis indicate that the effect of diabetes duration on lens thickness is independent of zygosity.

Adolescent↗
PubMed1996

Screening for tyrosinaemia type I.

AIMS: To assess the incidence of tyrosinaemia type I in the West Midlands Region, and the value of current neonatal screening programmes for phenylketonuria (PKU) for its detection. METHODS: Retrospective study of results from the PKU neonatal screening programmes in Birmingham (using plasma amino acid chromatography) and in the rest of the West Midlands (using the Guthrie microbiological assay for blood spot phenylalanine) was carried out between January 1985 and March 1994. Patients with tyrosinaemia I born in the region during the same period were identified from a regional database of patients with confirmed inherited metabolic disease. The study was carried out in a specialist children's hospital; the regional centre in the West Midlands for neonatal screening and investigation of inborn errors, and a supraregional centre for liver transplantation and management of paediatric liver disease. RESULTS: Amino acid chromatography showed increased tyrosine in 447 of 145,444 neonates born in Birmingham; this was still increased at 6 weeks of age in six cases. Five had tyrosinaemia I; the sixth had tyrosinaemia type III. Two others in whom amino acid chromatography was considered normal have since presented with tyrosinaemia I. Outside Birmingham, 525,151 children were screened using the Guthrie test. Five have presented clinically with tyrosinaemia I; screening did not contribute to diagnosis in any case. The incidence of tyrosinaemia I was 1 in 20,791 live births within Birmingham and 1 in 105,037 outside. Of the total 12 patients in the West Midlands with tyrosinaemia I, 10 (83%) were of non-oriental Asian ethnicity; the incidence of tyrosinaemia I was 3.7/10(6) head of population in this group and 0.04/10(6) in the rest of the population. CONCLUSIONS: Asians in the West Midlands have a high incidence of tyrosinaemia I. Neonatal PKU screening using amino acid chromatography may contribute to diagnosis and early treatment.

Amino Acid Metabolism, Inborn Errors↗
PubMed1996

Effect of weight loss on whole body and cellular lipid metabolism in severely obese humans.

We evaluated the effect of diet-induced weight loss on whole body and cellular lipid metabolism in persons with severe upper body obesity in two study protocols. In protocol 1, palmitate and glycerol rates of appearance (Ra) in plasma were determined during basal conditions in seven subjects [initial body mass index (BMI) = 41.3 +/- 2.2 kg/m2] before and after 20.4 +/- 3.0 kg weight loss. Total glycerol and palmitate Ra decreased from 231.0 +/- 19.4 and 166.2 +/- 16.6 mumol/min, respectively, before weight loss to 162.7 +/- 9.5 and 105.0 +/- 9.7 mumol/min, respectively, after weight loss (P < 0.01). However, glycerol and palmitate Ra expressed per kilogram fat mass were similar both before and after weight loss. In protocol 2, subcutaneous abdominal adipose tissue was obtained before and after 14.4 +/- 2.1 kg weight loss in five subjects (initial BMI = 41.6 +/- 2.6 kg/m2). Weight loss caused a 38 +/- 8% decrease in adipocyte hormone-sensitive lipase concentration (P < 0.05) but was not associated with any consistent changes in the concentrations of GTP-dependent regulatory proteins, Gi1 alpha, Gi2 alpha, and G3 alpha. We conclude that diet-induced weight loss ameliorates the increase in basal lipolytic rates in persons with severe upper body obesity. These alterations are associated with changes in cellular hormone-sensitive lipase but not GTP-dependent regulatory protein concentrations.

Adult↗
PubMed1996

Desensitization of beta-adrenergic receptors in adipocytes causes increased insulin sensitivity of glucose transport.

To determine the effect of desensitization of adipocyte beta-adrenergic receptors on insulin sensitivity, rats were continuously infused with isoproterenol (50 or 100 micrograms.kg-1.h-1) for 3 days by osmotic minipumps. Epididymal adipocytes were isolated. The cells from treated animals were desensitized to isoproterenol, as determined by response of lipolysis (glycerol release). Binding of [125I]iodocyanopindolol was decreased by approximately 80% in adipocyte plasma membranes isolated from treated rats, indicating that beta-adrenergic receptors were downregulated. Cellular concentrations of Gn alpha and Gi alpha were not altered. Insulin sensitivity was determined by measuring the effect of insulin on glucose transport (2-deoxy-[3H]glucose uptake). Cells from the isoproterenol-infused rats were markedly more sensitive to insulin than those from control rats. This was evidenced by an approximately 50% increase in maximal glucose transport rate in cells from the high-dose isoproterenol-treated rats and by an approximately 40% decrease in the half-maximal effective concentration of insulin in both groups. 125I-labeled insulin binding to adipocytes was not altered by the isoproterenol infusions, indicating that desensitization of beta-adrenergic receptors results in tighter coupling between insulin receptors and stimulation of glucose transport.

Adipocytes↗