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Biomedical subjects

A Scott

Publications and source records attributed to A Scott.

At least 181 records · Page 10Linked to original sources
PubMed1993

Expression of P450 isoenzymes during rat liver organogenesis.

1. The expression of P450 isoenzymes in foetal and neonatal hepatic microsomes was determined by measuring the metabolism of marker substrates and by studying the expression of P450 isoenzymes at the protein and mRNA level. 2. Monooxygenase activities were not measurable at day 10 of gestation, but shortly before birth (day 20 of gestation) and thereafter a surge in monooxygenase activities was observed using ethoxyresorufin, aniline, nitroanisole, aminopyrine, dimethylnitrosamine and aldrin as substrates. 3. In contrast, as early as day 10 of gestation, post oxidative drug metabolism was measurable, when assessed for reactions catalysed by UDP-glucuronyltransferase, glutathione S-transferase and epoxide hydrolase. 4. Microsomal proteins isolated from foetal/perinatal rats did not crossreact with antibodies raised to CYP1A1, CYP1A2, CYP2A1, CYP2B1, CYP2E1, CYP3A1 and CYP4A1 at a protein loading of 3 micrograms total protein/well. 5. With the exception of CYP2E1 mRNA and CYP4A1 mRNA there was little evidence to suggest the expression of CYP1A1, CYP1A2 and CYP2A1 mRNA. 6. The mRNA of CYP2B1, CYP2C7 and CYP3A1 was not detectable in foetal/perinatal rat liver extracts at a loading rate of 10 micrograms total RNA. 7. Microsomal proteins isolated from neonatal rats crossreacted with antibodies raised to CYP2C6, CYP2E1, CYP3A1 and CYP4A1, albeit at varying intensities. 8. Concomitantly, CYP2A1, CYP2E1 and CYP4A1 mRNA transcripts were detectable in Northern blot hybridization experiments using neonatal rat liver RNA extracts.

Animals↗
PubMed1993

Treatment of lactating rats with PCBs induces CYP1A1 and enhances the formation of BP 7,8-dihydrodiol, the proximate carcinogen of benzo(a)pyrene.

1. Treatment of pregnant and lactating rats with a single i.p. dose of 250 mg/kg body weight produced 5-fold and 2-fold increases, respectively, in hepatic P-450 concentrations using microsomes isolated from pregnant, neonatal, lactating and foetal rats. 2. Concomitantly, 26-fold, 20-fold and 14-fold increases in neonatal, maternal and foetal ethoxyresorufin-O-deethylation (EROD), respectively were found, but only 2.5-fold increases could be determined using microsomes isolated from lactating rats. 3. The metabolism of [3H]benzo(a)pyrene was increased 9-fold and 2-fold in pregnant and foetal rats, respectively, but only 2-fold increases were measured for lactating rats. 4. Western blot analysis of microsomal proteins obtained from lactating rats showed significant CYP1A1 and CYP1A2 induction and for the same hepatic tissue 62-fold and 44-fold increases in cDNA hybridized CYP1A1 and CYP1A2 mRNA, respectively, were found. 5. Treatment of lactating rats with PCBs resulted in enhanced formation of all BP-metabolites, but the ratio of diol to total BP-metabolites was more than 3-fold greater. 6. The formation of the proximate carcinogen BP-7,8-dihydrodiol was 5-fold increased and a similar 3-fold increase in epoxide hydrolase activity was estimated for lactating rats. 7. The results of the present study indicates that lactation protects, in part, against the inductive effect of PCBs, possibly by enhanced clearance of these chemicals via lactation.

Animals↗
PubMed1993

The value of early discharge: dispelling some myths.

Our objective in this paper is to assess the value of early discharge schemes following the economic evaluation of three such schemes in New South Wales, Australia. An early discharge programme for obstetric patients, a fractured hip management programme and a continuing community cancer care programme were evaluated. The results of the economic evaluation of these schemes are discussed in the light of four commonly held beliefs about the value of early discharge: that early discharge schemes succeed in reducing length of stay, that early discharge schemes save money, that the welfare of patients is not reduced by early discharge and that early discharge schemes are cost-effective. The caution expressed by previous authors about the perceived advantages of early discharge schemes is still warranted.

Aged↗
PubMed1993

The prevalence of dementia, depression and neurosis in later life: the Liverpool MRC-ALPHA Study.

Prevalence rates for psychiatric disorders in the elderly are presented from the initial cross-sectional stage of a longitudinal community study of the incidence of dementia in the city of Liverpool. Together with five other centres in the UK the MRC-ALPHA project forms part of the MRC multicentre incidence study of dementia and cognitive decline. An age- and sex-stratified random sample of 5222 subjects aged > or = 65 was interviewed at home using the Geriatric Mental State-AGECAT package to provide computer diagnoses. The overall age-standardized prevalence rates for organic disorder (4.7%) depressive illness (10.0%) and the neuroses (2.5%) are consistent with levels found in previous smaller studies that have used GMS-AGECAT. Each of these diagnoses is more common in females than males. A rise in organic disorder with age is confirmed as continuing into the oldest age groups for both sexes. An apparent decline with age observed for depression and neurosis diagnoses disappears when organic cases are excluded from the analysis.

Age Distribution↗
PubMed1993

Effects of dilevalol (R,R-labetalol) compared with nifedipine on heart rate, blood pressure and muscle blood flow at rest and on exercise in hypertensive patients.

1. Dilevalol (R,R-labetalol) is a non-selective beta-adrenoceptor antagonist with beta 2-adrenoceptor agonist activity. Its effects after 1 month's administration on heart rate, blood pressure and muscle blood flow were studied in a double-blind crossover comparison with nifedipine in 16 hypertensive patients. 2. Dilevalol and nifedipine were similarly effective in lowering systolic and diastolic blood pressure at rest, but dilevalol limited the rise in systolic blood pressure induced by exercise more than nifedipine (rise of 27 vs 53 mm Hg respectively, P < 0.01). 3. Dilevalol decreased resting heart rate compared with nifedipine (73 vs 92 beats min-1 respectively, P < 0.01). Dilevalol limited the exercise induced rise in heart rate more than nifedipine (36 vs 48 beats min-1 respectively, P < 0.01). 4. Muscle blood flow (measured by strain gauge plethysmography) was not affected by either dilevalol or nifedipine at rest. After exercise, dilevalol caused an increase in excess blood flow compared with placebo (10.8 vs 5.1 ml min-1 dl-1 respectively, P < 0.01). The difference between dilevalol and nifedipine did not reach statistical significance (10.8 vs 6.5 ml min-1 dl-1 respectively, P > 0.05). 5. On blood pressure and heart rate, dilevalol demonstrated beta-adrenoceptor blocker activity at rest and on exercise. On muscle blood flow, dilevalol appeared to have no effect at rest, but may have acted as a beta-adrenoceptor blocker rather than as a beta 2-adrenoceptor agonist during exercise.

Adolescent↗
PubMed1993

Prospective data on the prevalence of abnormal involuntary movements among elderly people living in the community.

Trained raters from the Liverpool Continuing Health in the Community study interviewed 1070 people over the age of 65 in 1982-1983 using the Geriatric Mental State (GMS) examination. Three years later the cohort was re-interviewed, this time by psychiatrists trained in the GMS, who used the GMS and the History and Aetiology Schedule (HAS). The cohort had fallen in size to 875, because of mortality; 701 were re-interviewed. The cohort was followed up again 6 years after the first interview by trained nurse raters using the GMS (A3) and the Mini-Mental State Examination. Cases of mental disorder identified by the computer diagnostic program AGECAT were re-interviewed by psychiatrists along with a number of controls using the GMS and the HAS on the remaining 450 individuals. Observational behavioural ratings from the GMS and summary sheets were analysed along with AGECAT diagnoses and data on medication gained at the 3 assessments. The community prevalence of tardive dyskinesia and other movement disorders in elderly people over a 6-year follow-up appears to be very low (the community prevalence of tardive dyskinesia being 0.22% and akathisia 1.57%), is usually associated with organic mental disorder (and consequently higher mortality) and is furthermore not usually associated with antipsychotic medication.

Aged↗
PubMed1993

Methotrexate osteopathy in rheumatic disease.

OBJECTIVE: To determine whether two adults with stress fractures receiving low weekly doses of methotrexate had methotrexate osteopathy. CASE REPORTS: Two adult patients developed features consistent with methotrexate osteopathy while receiving low weekly doses of methotrexate. METHODS: Iliac crest biopsy samples were taken and bone histomorphometry carried out. RESULTS: Symptoms resolved when the methotrexate was discontinued. Bone histology showed changes consistent with osteoblast inhibition by methotrexate. CONCLUSIONS: When given in low doses for prolonged periods, methotrexate may have adverse effects on bone, particularly in post-menopausal women.

Aged↗
PubMed1993

Core and peripheral temperature response to exercise in patients with impaired left ventricular function.

OBJECTIVE: Exercise induced hypotension is a specific but insensitive indicator of severe coronary artery disease. Skin blood flow is subject to control by baroreceptor mediated reflexes as well as thermoregulatory reflexes. Monitoring skin temperature or the skin to central temperature gradient may be a more sensitive indicator of impaired cardiac output response to exercise than hypotension. DESIGN AND PARTICIPANTS: Central and skin temperature changes associated with exercise were studied in 10 normal volunteers and eight patients with impaired resting ventricular function due to ischaemic heart disease. Patients exercised according to a modified Bruce protocol. The two sample independent t test was applied to compare the central and peripheral temperatures in the two groups at three minute intervals during exercise and at two minute intervals after exercise. RESULTS: A significant decrease was found in mean (1 SEM) central temperature on exercise in our patient group (98.2(0.2) degrees F to 97.2(0.3) degrees F), compared with the normal increase in central temperature (97.7(0.2) degrees F to 98.3(0.3) degrees F). Mean (1 SEM) skin temperature changes reflected the expected skin blood flow changes with exercise in normal subjects. In the patient group skin temperature declined during exercise (89.7(2.1) degrees F to 86.6(1.7) degrees F) and was significantly lower than normal from six minutes onwards. CONCLUSIONS: The abnormal peripheral temperature changes of patients with impaired resting ventricular function is an early and sensitive indicator of an abnormal haemodynamic response to exercise. It is possible that skin temperature measurement during exercise could help detect exercise induced ventricular dysfunction due to ischaemia or impaired cardiac output due to valvar heart disease.

Aged↗
PubMed1993

A review of dysphagia in four cases of motor neurone disease.

Dysphagia is a common and distressing problem in motor neurone disease. This paper examines some of the strategies available for managing patients with dysphagia, and illustrates these with four contrasting case histories. The factors which influence the decision making process in patients with dysphagia are also discussed.

Aged↗
PubMed1993

Functional gastrointestinal disorders in unselected patients with non-cardiac chest pain.

Patients with non-cardiac chest pain (NCCP) (n = 387) and cardiac chest pain (CCP) (n = 93) were compared with community controls (n = 81), using a symptom questionnaire that assessed the presence of irritable bowel syndrome (IBS), functional dyspepsia, and oesophageal dysfunction and chest pain characteristics. A significantly (p < 0.05) increased prevalence of symptoms compatible with IBS occurred in NCCP patients when compared with those with CCP and with controls. Dysphagia was more frequent in both those with non-cardiac and cardiac chest pain than in controls; this was not apparent, however, when patients with concomitant IBS were excluded. The presence of oesophageal or gastrointestinal symptoms did not enable discrimination with regard to the chest pain characteristics. We conclude that unselected referred patients with documented NCCP are more likely to have IBS and that the presence of oesophageal symptoms such as dysphagia may merely reflect the spectrum of the 'irritable gut'.

Angina Pectoris↗
PubMed1993

Long term follow-up of treated hyperthyroid and hypothyroid patients.

The objective was to assess the success rate in patients receiving surgery or radioactive iodine for primary hyperthyroidism and the incidence of subsequent hypothyroidism. A long term follow up of patients on L-thyroxine has also been performed from a cohort of patients on the Tayside Thyroid Register. The case series has been followed-up for up to 21 years. 2,038 patients were registered of whom 90.1% were female. 1,045 had had previous hyperthyroidism and 993 had hypothyroidism. Treatment for thyrotoxicosis varied with age, 80.4% of patients under the age of 40 being treated by thyroidectomy and 72.6% of patients over 50 being given the iodine. Overall 9% of patients required medical therapy alone (carbimazole), and this varied little with age. Compared to radioactive iodine, thyroidectomy was more successful (90.2% vs 82.9%, p < 0.01) and had a lower rate of subsequent hypothyroidism (22.0% vs 47.6% at 5 years, p < 0.001). Of patients treated with radioactive iodine, those who were unsuccessful had received a lower dose (mean 354MBq vs 489MBq, p < 0.001). Of patients receiving L-thyroxine (n = 1,180), 58.5% had a suppressed level of thyroid stimulating hormone, 38% had a detectable but not elevated level, and 3.5% had an elevated level (> 4.0 mU/l). Patients with a suppressed level were taking a higher dose of L-thyroxine than those with a detectable level (114.2 +/- 56.9 micrograms vs 100.4 +/- 45.9 micrograms, p < 0.01), but those with an elevated level were prescribed an even higher mean L-thyroxine dose (137.1 +/- 58.8 micrograms)); many were probably poorly compliant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Evaluation of the obstetric significance of some pelvic characters in an 18th century British sample of known parity status.

The excavations at Christ Church, Spitalfields (1984-86) produced a sample of 968 human skeletons which were interred between 1729 and 1859. Of these, 387 were recovered in association with coffin plates stating name, age at death, and date of death. There are 138 adult females in the named sample and the obstetric histories of 94 have been reconstructed from historical documentation. Such variables as birth spacing, number of children, and age at first and last births are known for the majority of this sample. Any individual about whose history there is any doubt has been excluded from the analysis. A middle-class group, they were largely of high nutritional status and, by the standards of the day, lived in sanitary and comfortable conditions. Both males and females have a mean age at death of 56 years. The presence or absence, the typology, the severity, the width and the length of the preauricular sulcus, the presence or absence and the number of pits on the dorsal aspect of the pubic body, sulci along the anterior sacrum adjacent to the auricular facet, and the extension of the pubic tubercle were evaluated in relation to the obstetric histories of these females. Statistical analysis has demonstrated a relationship between the presence of pubic tubercle extension and parity status and between the degree of extension and the number of children borne (P < .02). Statistically there is no significant relationship (P > .05) between either the preauricular sulcus or pubic pitting and parity status. Sacral scarring is significantly associated (P < .05) with parity status, but as it was evident in only eight females it has little practical application. Sample sizes are small, and it must be considered that statistical evaluation of larger samples might detect associations between variables not demonstrated here. There is no significant relationship between any of the cortical variants under consideration and age at death.

Adult↗
PubMed1992

Expression of human alpha 1 antitrypsin in transgenic sheep.

We have recently described the production of large amounts (< or = 65 grams per litre) of enzymatically active human alpha 1 antitrypsin in the milk of transgenic sheep (Wright et al., 1991). Here, we describe in more detail the expression of the human protein in the milk of these animals throughout the lactation period. Human alpha 1 antitrypsin is also found at much lower levels in the plasma of transgenic ewes before, during and after lactation. It is also detected in male plasma at very low levels. We have previously shown human alpha 1 antitrypsin purified from transgenic sheep milk to be indistinguishable from commercially available human plasma derived alpha 1 antitrypsin in terms of gross sugar content and in vitro activity. Here we extend this comparison to more detailed analyses of glycosylation state, amino-terminal sequence, pI value, and molecular weight determination by mass spectrometry.

Amino Acid Sequence↗