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Biomedical subjects

A Green

Publications and source records attributed to A Green.

At least 37 records · Page 2Linked to original sources

The epidemiology of Type 1 diabetes mellitus is not the same in young adults as in children.

AIMS/HYPOTHESIS: This prospective study examined the epidemiology of Type 1 diabetes in young adults in Europe. METHODS: We ascertained incident cases of Type 1 diabetes in the 15 to 29 years (both inclusive) age group throughout Europe over a period of 2 years. Diabetes registries in nine countries, in which incidence rates for Type 1 diabetes in the 0 to 14 age group were available, took part. Incidence rates were estimated per 100000 person years and standardised for sex and age. Cumulative incidences per 1000 from birth to age 30 were estimated. Heterogeneity between centres was tested with a Poisson regression model. RESULTS: A total of 2112 diabetes cases were ascertained in 1996 and 1997, of which 61.4% were considered to be Type 1 diabetes. Completeness of ascertainment varied from 70 to 90%. Standardised incidence varied from 4.8 per 100000 person years to 13.4 per 100000 person years. The male-female ratio was estimated to be one or more, and in the 25 to 29 age group 1.5 or more in all countries. Cumulative incidences for males and females indicate that the former exceeds the latter from age 24. In the two centres with highest childhood incidence, this applied already from 14 years of age. CONCLUSIONS/INTERPRETATION: The incidence of Type 1 diabetes in adults is lower than in children and the range of incidence is also reduced, with a less than threefold variation in adults, against an eightfold variation in children. There is a male excess in incidence, especially in the age group 25 to 29 years.

Adolescent↗

Role of a mixed type, moderate intensity exercise programme after peripheral blood stem cell transplantation.

OBJECTIVES: To evaluate the effect of peripheral blood stem cell transplantation on functional capacity, and to determine the role of a mixed type, moderate intensity exercise programme in the recovery of patients after intensive cancer treatment. METHODS: Peak aerobic capacity and muscular strength (upper body, lower body, and handgrip strength) measures were assessed before (PI) and after (PII) transplant and after a 12 week intervention period (PIII). After PII, 12 patients aged 16-64 years were allotted in equal numbers to a control group or exercise intervention group. RESULTS: Mean peak aerobic capacity and muscular strength were reduced after the transplant, with significant (p<0.05) decreases for upper body strength. No change was found in aerobic capacity and muscular strength between PII and PIII for the control group. In contrast, participation in the exercise programme led to significant improvements in peak aerobic capacity (p<0.05) and upper and lower body strength (p<0.01). In addition, values recorded after the three month intervention period were significantly higher than before treatment for peak aerobic capacity (litres/min (p<0.05) and ml/kg/min (p<0.01)) and lower body strength (p<0.01). CONCLUSION: Intensive treatment for cancer can adversely affect aerobic capacity and muscular strength. A mixed type, moderate intensity exercise programme can help patients to regain fitness and strength within three months. No exercise can exacerbate physical losses resulting from treatment.

Adolescent↗

Declining prevalence of STI in the London sex industry, 1985 to 2002.

OBJECTIVES: To describe major changes in the London sex industry between 1985 and 2002 and assess the implications for sexually transmitted infection (STI) risk. METHOD: A descriptive study comparing women who first attended a sex work clinic between 1996 and 2002 and those first attending from 1985 to 1992; a nested case-control study. 1050 female sex workers took part. The setting was a specialist clinical service for sex workers based in a London genitourinary medicine (GUM) clinic, and fieldwork in west London. The main outcome measures were reported condom use and prevalent STI. RESULTS: Over the period of the study there was a significant increase in the proportion of sex workers not born in the United Kingdom (from 25% to 63%, p < 0.001), and women entered sex work at an older age (median 24 years compared with 20 years, p < 0.001). Condom use increased (with the exception of oral sex). There was a significant decline in the proportion of participants reporting a previous STI (32% compared with 80%, p < 0.001) and the prevalence of acute STI declined from 25% to 8% (p < 0.001). Acute STI was associated with younger age, younger age at first sex work, being new to sex work, and inconsistent condom use. In a multivariate analysis unprotected sex with clients was the only significant risk. CONCLUSION: Major restructuring of the sex industry, including the shift to a primarily migrant workforce, has been associated with a steep decline in acute STI, undermining popular assumptions that migrant sex workers are central to the ongoing STI epidemic. We attribute the decline in acute STI to an increase in safer sex.

Adolescent↗

Autoantibodies and self-reported health complaints in relatives of systemic lupus erythematosus patients: a community based approach.

First-degree relatives (FDRs) and spouses to a population-derived cohort of lupus patients were investigated for the occurrence of selected autoantibodies and self-reported health complaints. A healthy reference population was included. The lupus population consisted of 103 index cases. A total of 275/375 available relatives accepted to enter the study. Two hundred and twenty-six/315 (72%) were FDRs and 49/60 (82%) were spouses. Serum was analysed for ANA using indirect immunofluorescence on Hep-2 cells at the following dilutions: 1:40, 1:80 and 1:160 and in addition sera were tested for anti-dsDNA, IgM RF, ACA (IgM, IgG), anti-beta2GPI (IgM, IgG) and antibodies to prothrombin. ANA positivity occurred more frequently in FDRs compared with spouses and controls at serum dilution 1:160 (10 versus 0% and 2.5%, respectively, P = 0.04 and P < 0.01), 1:80 (24 versus 4% and 5%, respectively, P = 0.003 and P < 0.001) and 1:40 (31 versus 10% and 10%, respectively, P = 0.006 and P < 0.0001). ANA positivity in FDRs occurred randomly, irrespective of family relationship. Fifty-three/184 versus 2/32 FDRs to patients with definite SLE (D-SLE) and incomplete SLE (I-SLE), respectively, tested ANA positive at 1:80 (P < 0.05). FDRs with ANA titer at 80 were affiliated to lupus probands with high SLICC scores (P < 0.05). Self-reported health complaints, cardiovascular/thromboembolic events in particular, were more frequent among FDRs than in spouses. The population-based approach adopted in the present study supports previous clinic-based evidence of an increased propensity for autoantibody occurrence in relatives to SLE patients. In FDRs, present ANA positivity was associated with increased prevalence of health complaints and ANA positivity in FDRs was related to the criterial burden and cumulated damage in corresponding lupus probands. The low ANA frequency among spouses of SLE patients argues against a significant autoantibody triggering effect of shared environment in adult life.

Adult↗

Gestational diabetes mellitus in India.

BACKGROUND: Glucose intolerance during pregnancy predisposes the offspring for increased risk of developing glucose intolerance in the future. This vicious cycle is likely to influence and perpetuate the incidence and prevalence of glucose intolerance in any population. AIM: No data is available about the prevalence of glucose intolerance during pregnancy in our country and hence a study was undertaken on this aspect. METHODS: This study was performed in the antenatal clinic of Government Maternity Hospital, Chennai, India. As a pregnant woman in second or third trimester checks into the antenatal clinic, she was given 50 gm oral glucose load and blood sample was collected after one hour. This test was performed on 1251 pregnant women. They were requested to come after 72 hours for the 75 gm OGTT recommended by WHO. Among the 1251 women, 891 responded. The blood sample was taken in the fasting state and at 2 hours after 75 gm of oral glucose. Diagnosis was based on the WHO criteria for gestational diabetes mellitus (GDM). RESULTS: The mean age of these pregnant women was 23+/-4 years. There was a significant increase in the prevalence of GDM in relation to gravida. The effect of BMI did not quite reach statistical significance (chi2 (df=1) = 3.659, P = 0.055), but a model of linear trend was significant. Of the 1251 women who underwent the 50 gm oral glucose challenge test, 670 (53.55%) had one hour plasma glucose > or = 130 mg/dl. Among the 891 pregnant women who had 75 gms OGTT, 168 (18.9%) were diagnosed as GDM, taking both FPG > or = 126 mg/dl and/or 2 hr PPG > or = 140 mg/dl as cut-off values. Taking only 2 hr plasma glucose for analysis, 144 (16.2%) had a value > or = 140 mg/dl. A similar study was conducted in different parts of the country taking only the 2 hr 75 gm post-glucose value of > or = 140 mg/dl as diagnostic criteria for GDM. Of the total number of pregnant women (n = 3674) screened, 16.55% of them found to have GDM. CONCLUSION: Our study has documented the increased prevalence of GDM in our population necessitating universal screening for glucose intolerance in pregnancy. Using 2 hr plasma glucose > or = 140 mg/dl as a one step procedure is simple and economical, particularly for the countries ethnically more prone to high prevalence of diabetes.

Adult↗

The Duchenne muscular dystrophy population in Denmark, 1977-2001: prevalence, incidence and survival in relation to the introduction of ventilator use.

Mechanical ventilation of patients with Duchenne muscular dystrophy continues to be a subject of study. The purpose was to estimate prevalence, incidence, mortality and use of mechanical ventilation in the total Duchenne muscular dystrophy population in Denmark between 1977 and 2001 and further, to reconstruct the introduction of mechanical ventilation to assess the role of the patient organization. Study objects were collected from five sources and verifiable cases identified. Negotiations between health authorities and the patient organization constituted main empirical data for the reconstruction. While overall incidence remained stable at 2.0 per 10(5), prevalence rose from 3.1 to 5.5 per 10(5), mortality fell from 4.7 to 2.6 per 100 years at risk and prevalence of Duchenne muscular dystrophy ventilator users rose from 0.9 to 43.4 per 100. We conclude that survival of Duchenne muscular dystrophy patients has increased and ventilator use is probably a main reason. The patient organization exercised a key role but acted upon preconditions created by other players.

Adult↗

ESTs from the basidiomycete Schizophyllum commune grown on nitrogen-replete and nitrogen-limited media.

Lambda phage cDNA libraries were constructed using mRNAs from the basidiomycete Schizophyllum commune grown on media with high or low nitrogen concentrations. A total of 440 clones were sequenced, representing 373 distinct transcripts. Of these, 166 showed significant similarity to annotated genes in GenBank. Those that could be tentatively identified using BLAST searches were classified by function using the Gene Ontology (GO) database. Genes with products involved in cell-cycle processes were more frequent in the nitrogen-limited libraries, while genes with products involved in protein biosynthesis were more frequent in the nitrogen-replete library. Overall, clones showed much greater similarity to the one publicly available basidiomycete genome, Phanerochaete chrysosporium, than to any of the ascomycete genomes.

Bacteriophage lambda↗

Mutation analysis of the RET gene in total intestinal aganglionosis by wave DNA fragment analysis system.

BACKGROUND/PURPOSE: Total intestinal aganglionosis (TIA) extending from the duodenum to the rectum is the most rare form of Hirschprung's disease (HSCR) and usually is fatal. RET is the major gene associated with HSCR, and germline mutations of this gene account for up 50% of familial and up to 15 to 20% of sporadic cases in HSCR. The aim of this study was to investigate DNA variants in the RET gene in TIA patients using the WAVE DNA Fragment Analysis System. METHODS: Genomic DNA was extracted from whole blood samples from 6 patients with TIA. Polymerase chain reaction (PCR) amplification of the 21 exons of RET was performed using published oligonucleotide primers. Heteroduplexes were followed by the WAVE DNA Fragment Analysis System with the DNASep cartridge. RESULTS: WAVE system technology detected 16 variants in the RET gene in the 6 patients with TIA. Three patients had a significant mutation in exon 8, 11, and 15, respectively. Thirteen RET polymorphic variants also were detected in the 6 patients, with L746L variant in exon 13 occurring in 4 patients. CONCLUSIONS: WAVE system technology is an efficient method for the detection of DNA sequence variants. Our findings suggest that not only RET mutations but also RET polymorphic variants may contribute to the occurrence of TIA.

Amino Acid Substitution↗

Predictive testing for BRCA1 and 2 mutations: a male contribution.

BACKGROUND: Management strategies for women carrying BRCA1 and 2 mutations are becoming clearer and predictive testing for a known family mutation is commonly undertaken. Implications for men are not as clear and they participate less frequently. PATIENTS AND METHODS: Twenty-six men from 10 extended families underwent predictive testing. Their motivation, reaction and outcome were studied. Subjects had appropriate pre- and post-test counselling. Informed consent was obtained before predictive testing for known deleterious mutations. DNA analysis followed standard procedures. RESULTS: Eighteen tested positive and eight negative. Four had adverse psychological reactions and three reneged on their commitments to impart results. The spouse of another man had an adverse psychological reaction to the disclosure of his positive result. Two, already suffering from prostate cancer, were phenocopies and paternal lineage transmission was unexpectedly determined in another. Risk was removed from 33 offspring and confirmed for 56. CONCLUSIONS: Complex themes associated with genetic testing are confirmed and the spectrum extended. Men appear to understand the importance of participating in this process. Methods of avoiding adverse reactions merit further study along with other aspects of the process.

Adult↗

Complex chimeras to map ligand binding sites of GPCRs.

Family 1a GPCRs are thought to bind small molecule ligands in a pocket comprising sequences from non-contiguous transmembrane helices. In this study, receptor-ligand binding determinants were defined by building a series of complex chimeras where multiple sequences were exchanged between related G-protein coupled receptors. Regions of P2Y(1), P2Y(2) and BLT(1) predicted to interact with nucleotide and leukotriene ligands were identified and receptors were engineered within their transmembrane helices to transpose the ligand binding site of one receptor on to another receptor. Ligand-induced activation of chimeras was compared with wild-type receptor activation in a yeast reporter gene assay. Binding of ligand to a P2Y(2)/BLT(1) chimera confirmed that the ligand binding determinants of BLT(1) are located in the upper regions of the helices and extracellular loops of this receptor and that they had been successfully transferred to a receptor that normally binds unrelated ligands.

Amino Acid Sequence↗

A comparison of drug effects in latent inhibition and the forced swim test differentiates between the typical antipsychotic haloperidol, the atypical antipsychotics clozapine and olanzapine, and the antidepressants imipramine and paroxetine.

Current animal models of antipsychotic activity that have the capacity to dissociate between typical and atypical antipsychotic drugs (APDs) have two drawbacks: they require previous administration of a psychotomimetic drug, and they achieve the dissociation by demonstrating effectiveness of atypical but not typical APDs, thus losing specificity and selectivity for APDs. The present experiments were designed to solve these problems by using two non-pharmacological tests: latent inhibition (LI), in which potentiation of the deleterious effects of non-reinforced stimulus pre-exposure on its subsequent conditioning served as a behavioral index for a common action of typical and atypical APDs (antipsychotic), and the forced swim test (FST), in which reduction of immobility served as a behavioral index for a dissimilar action of these drugs (antidepressant). The typical APD haloperidol (0.1 mg/kg), the atypical APDs clozapine (2.5 mg/kg) and olanzapine (0.6 mg/kg), and the antidepressants imipramine (10 mg/kg) and paroxetine (7.0 mg/kg), produced distinct patterns of action in the two tests: haloperidol potentiated LI and increased immobility in the FST, clozapine and olanzapine potentiated LI and decreased immobility in the FST, and imipramine and paroxetine decreased immobility in the FST and did not potentiate LI. Thus, the comparison of drug effects in LI and FST enabled a discrimination between typical and atypical APDs without losing selectivity for APDs.

Animals↗

Prevalence of impaired left ventricular systolic function and heart failure in a middle aged and elderly urban population segment of Copenhagen.

OBJECTIVE: To assess the prevalence of impaired left ventricular systolic function and manifest heart failure in a general population aged 50-89 years. DESIGN: In this cross sectional survey, participants filled in a heart failure questionnaire. ECG, blood tests, and echocardiography were performed. SETTING: The study population was recruited from general practitioners situated in the same urban area and examined in a university hospital in Copenhagen, Denmark. PARTICIPANTS: 764 participants (432 women and 332 men, median (SD) age 66 (11) years) participated. The study population was stratified to include a minimum of 150 persons in each age decade. MAIN OUTCOME MEASURES: Prevalence of impaired systolic function and manifest heart failure. RESULTS: The prevalence of systolic dysfunction (left ventricular ejection fraction < or = 40%) was more than twice as high among men (7.6%) as among women (2.6%). In the male population systolic heart failure (left ventricular ejection fraction < or = 40% and symptoms) was found in 1.8% of the 50-59 years age group and approximately doubled for each age decade to reach 13.9% in octogenarians. Among women systolic dysfunction increased from 0.8% to 4.3% in the same age groups. Asymptomatic cases accounted for 44.0% of all cases of systolic dysfunction in the male population and only 9.1% in the female population. CONCLUSIONS: In this age controlled population study impaired left ventricular systolic function and heart failure increased substantially with age and was more than twice as frequent among men as among women. Asymptomatic left ventricular dysfunction occurred more frequently in men than in women and was less prevalent with increasing age.

Age Factors↗

Nail patella syndrome: a review of the phenotype aided by developmental biology.

Nail patella syndrome (NPS) is an autosomal dominant condition affecting the nails, skeletal system, kidneys, and eyes. Skeletal features include absent or hypoplastic patellae, patella dislocations, elbow abnormalities, talipes, and iliac horns on x ray. Kidney involvement may lead to renal failure and there is also a risk of glaucoma. There is marked inter- and intrafamilial variability. The results of a British study involving 123 NPS patients are compared with previously published studies and it is suggested that neurological and vasomotor symptoms are also part of the NPS phenotype. In addition, the first data on the incidence of glaucoma and gastrointestinal (GI) symptoms in NPS are presented. NPS is caused by loss of function mutations in the transcription factor LMX1B at 9q34. The expansion of the clinical phenotype is supported by the role of LMX1B during development.

Adolescent↗

Population screening for neonatal liver disease: potential for a community-based programme.

OBJECTIVES: To evaluate a community-based screening programme for detecting neonatal liver disease by the quantitation of conjugated bilirubin in blood. SETTINGS AND METHODS: Prospective cohort/observational study using spare plasma from routinely collected liquid neonatal screening specimens from babies born in Birmingham over a two-year period. Babies with a conjugated bilirubin above 18 mumol/l and comprising more than 20% of the total bilirubin were followed up. A total of 27654 neonates were tested in the community, with a further 2425 samples from babies hospitalised at the time of the test. RESULTS: In the community-based series, 84.7% of the specimens received were analysed, the remainder being unusable mainly because of gross haemolysis (8.6%) or insufficient sample (5.8%). In 107 neonates the results were above the cut-off limits (0.46% of the number analysed). Of these, 12 had persistently abnormal results, 11 of whom had confirmed liver disease. The liver diseases detected included neonatal hepatitis (n=6), extra-hepatic biliary atresia (n=2), hypopituitarism (n=1), alpha-1-antitrypsin deficiency (n=1) and Alagille syndrome (n=1). The sensitivity and specificity of the test for babies in the community were 100% and 99.6%, respectively. CONCLUSIONS: Conjugated bilirubin in plasma measured at 6-10 days is a reliable marker for neonatal liver disease, and a population screening programme based on this method has the potential to improve the survival and quality of life of infants born with liver disease. However, testing as part of the neonatal screening programme will prove practical only if the method can be adapted to use dried blood spots.

Bilirubin↗

A pooled analysis of 10 case-control studies of melanoma and oral contraceptive use.

Data regarding the effects of oral contraceptive use on women's risk of melanoma have been difficult to resolve. We undertook a pooled analysis of all case-control studies of melanoma in women completed as of July 1994 for which electronic data were available on oral contraceptive use along with other melanoma risk factors such as hair colour, sun sensitivity, family history of melanoma and sun exposure. Using the original data from each investigation (a total of 2391 cases and 3199 controls), we combined the study-specific odds ratios and standard errors to obtain a pooled estimate that incorporates inter-study heterogeneity. Overall, we observed no excess risk associated with oral contraceptive use for 1 year or longer compared to never use or use for less than 1 year (pooled odds ratio (pOR)=0.86; 95% CI=0.74-1.01), and there was no evidence of heterogeneity between studies. We found no relation between melanoma incidence and duration of oral contraceptive use, age began, year of use, years since first use or last use, or specifically current oral contraceptive use. In aggregate, our findings do not suggest a major role of oral contraceptive use on women's risk of melanoma.

Adolescent↗

Skeletal muscle mitochondrial ATP production rate and walking performance in peripheral arterial disease.

This study tested the hypotheses that skeletal muscle mitochondrial ATP production rate (MAPR) is impaired in patients with peripheral arterial disease (PAD) and that it relates positively to their walking performances. Seven untrained patients, eight exercise-trained patients and 11 healthy controls completed a maximal walking test and had muscle sampled from the gastrocnemius medialis muscle. Muscle was analysed for its MAPR in the presence of pyruvate, palmitoyl-L-carnitine or both, as well as citrate synthase (CS) activity. MAPRs were not different between untrained PAD and controls. In contrast, MAPRs (pyruvate) were significantly higher in trained PAD vs. controls. MAPR (pyruvate combinations) was also significantly higher in trained than untrained PAD muscle. MAPR and CS activity were highly correlated with walking performance in patients, but not in controls. These data do not support the hypothesis that isolated mitochondria are functionally impaired in PAD and demonstrate that the muscle mitochondrial capacity to oxidize carbohydrate is positively related to walking performance in these patients.

Adenosine Triphosphate↗

Scapular position: the validity of skin surface palpation.

The assessment of the resting position of the scapula forms part of the examination of upper quadrant posture. The purpose of this study was to determine if surface palpation is a valid indicator of actual scapular position. Twelve embalmed shoulders were examined and the actual location of three bony scapular landmarks and three bony thoracic landmarks were compared with surface palpation of these locations. The results, based on the upper value for a distance (with 95% confidence), suggested that the difference between the surface location of the root of the spine of the scapula, the acromial angle and the inferior angle would be less than 0.67 cm, 0.98 cm and 0.46 cm respectively from the centre of the bony locations. The difference between the twelfth thoracic spinous process (SP), the SP corresponding with the root of the spine of the scapula, and the SP corresponding with the inferior angle and the surface points would be 1.46 cm, 1.09 cm and 1.01 cm respectively. The results of this study suggest that surface palpation of scapular location is a valid method for determining the actual location of the scapula. The findings also suggest that surface palpation can determine the location of thoracic landmarks, which may serve as reference points for scapular position.

Aged↗