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Biomedical subjects

M Griffin

Publications and source records attributed to M Griffin.

At least 145 records · Page 8Linked to original sources
PubMed1996

An international investigation of an outbreak of Legionnaires disease among UK and French tourists.

Five cases of legionnaires disease and one death were associated with four members of a tour group from the United Kingdom (UK) and one French tourist who all visited Spain in the spring of 1993. The UK group stayed at four hotels, one of which was also used by the French tourist. Phenotypic and genotypic comparison of isolates of Legionella pneumophila obtained from one of the UK cases and the French patient demonstrated that they were indistinguishable from each other and from environmental isolates obtained from the water supply of the hotel at which all five cases had stayed. A cohort study of the UK tour group was carried out to determine the extent of the outbreak and showed that three further members of the group had respiratory illness but were serologically negative to legionella infection. International participation in this investigation has highlighted the value of a European surveillance scheme and the benefit of microbiological collaboration between legionella reference laboratories in Europe.

Aged↗
PubMed1996

Lipoprotein composition in NIDDM: effects of dietary oleic acid on the composition, oxidisability and function of low and high density lipoproteins.

Oxidation of low density lipoprotein (LDL) plays an important role in the pathogenesis of atherosclerosis and is related to the fatty acid composition which is altered in diabetes mellitus. This study examines the relationship between the fatty acid composition of LDL and high density lipoprotein (HDL) and lipoprotein oxidation. A group of nine non-insulin-dependent diabetic (NIDDM) patients were compared to seven healthy control subjects before and after a high monounsaturated diet. Lipoproteins were isolated and oxidisability was measured by conjugated diene formation and lipid peroxide analysis. Serum HDL cholesterol was significantly lower in the diabetic patients. LDL cholesteryl ester linoleic acid in the diabetic patients was significantly higher at baseline and decreased after diet (p < 0.05) while oleic acid increased in both diabetic and non-diabetic subjects (p < 0.05). HDL cholesteryl ester oleic acid was lower in the diabetic patients compared with control subjects (p < 0.05) before diet and it increased significantly after diet (p < 0.05). LDL lipid peroxides and conjugated diene formation were related to LDL glycation (r = 0.46, p < 0.05 and r = 0.49, p < 0.05, respectively). Both decreased following diet (lipid peroxides for diabetic patients from 476 +/- 30 to 390 +/- 20 nmol/mg protein p < 0.05 and for control subjects from 350 +/- 36 to 198 +/- 30 nmol/mg protein p < 0.05). HDL conjugated diene formation decreased in both groups after diet but only significantly in the control group (55.4 +/- 7.5 to 53.2 +/- 6.7 nmol/mg protein for diabetic patients and 45.8 +/- 6.4 to 31.6 +/- 4.8 nmol/mg protein p < 0.05 for control subjects). There was a positive correlation between LDL lipid peroxide formation and percentage of cholesteryl ester linoleic acid in LDL from diabetic patients (r = 0.61, p < 0.05) and control subjects (r = 0.91, p < 0.01). Fatty acid composition of LDL was reflected in the composition of HDL. In the presence of HDL lipoprotein peroxidation decreased. This decrease in lipoprotein peroxidation was positively related to the percentage of linoleic acid in LDL (r = 0.71, p < 0.05). This study confirms the close relationship between the fatty acid composition of LDL and HDL and demonstrates the importance of the fatty acid composition of the cholesteryl ester fraction in relation to LDL oxidation in diabetes. Linoleic acid in HDL appears to be a protecting factor against oxidation.

Adult↗
PubMed1996

Enhanced apoptosis in transformed human lung fibroblasts after exposure to sodium butyrate.

Simian virus-transformed human cells, WI-38 VA13A, showed a dose-dependent induction of apoptosis and reduction in cell numbers after exposure to sodium butyrate. Apoptosis was confirmed by ApopTag staining, isolation of apoptotic envelopes, and immunofluorescent staining with an antibody specific for apoptotic envelopes. Examination of the cell cultures by phase contrast and fluorescent microscopy revealed the presence of enlarged cells that displayed a more flattened morphology and morphological changes in the nucleus of cells exposed to sodium butyrate. Cell proliferation assays showed control and sodium butyrate cultures were synthesizing DNA and excluded any cytotoxic effects of sodium butyrate. Flow cytometry results indicated an increase in the number of aneuploid cells following sodium butyrate treatment. There was a decrease in the percentage of cells in G2/M in the diploid populations, but an increase in the percentage of cells in G2/ M in aneuploid populations. This human in vitro model system suggests a mode of action for the therapeutic effects of sodium butyrate, which have been observed in the topical treatment of neoplastic cells and reversal of symptom in ulcerative colitis, namely, the induction of apoptosis.

Aneuploidy↗
PubMed1996

The Second National Prevalence Survey of infection in hospitals--overview of the results.

This study was designed to assess the overall prevalence of infection among the patients in hospitals in the UK and the Republic of Ireland. Patient data were collected and entered directly into a portable Olivetti (A12 notebook) computer with a custom-designed program (Epi-Info version 5.01). The statistical analysis was performed using the Statistical Package for Social Sciences software (SPSS). In all, 37,111 patients from 157 centers were studied, and a mean hospital acquired infection (HAI) prevalence rate of 9.0% (range 2-29%) was calculated. HAI rates were higher in teaching hospitals (11.2%) than in non-teaching hospitals (8.4%) P < 0.001. Four major sites of infections--infections of the urinary tract (23.2%), surgical-wound infections (10.7%), lower-respiratory tract (22.9%) and skin infections (9.6%)--accounted for 66.5% (2559 of 3848) of the total infections identified.

Adolescent↗
PubMed1996

Assesssment of the effect of pretreatment with neoadjuvant therapy on primary breast cancer.

Patients with invasive cancer of the breast (T1-4, N0-2, M0) were assigned to pretreatment based on oestrogen receptor (ER) status; patients with ER-negative tumours received chemotherapy [mitozantrone, methotrexate and mitomycin C (MMM)] for 3 months, patients with ER-positive tumours underwent endocrine therapy [luteinising hormone releasing hormone (LHRH) agonist goserelin (leuprolide-premenopausal) or 4-hydroxyandrostenedione (formestane-post-menopausal)] for 3 months. Of the first 100 patients assessed at 3 months, 47 with ER-positive tumours had a 40.4% response (premenopausal 53.8%; post-menopausal 35%) and 53 with ER-negative tumours had a 60% response (premenopausal 57%; post-menopausal 63%). Patients with early breast cancer (T1/T2) had a complete clinical resolution in 41% (16/39) of cases after MMM and in 20% (7/35) of cases following endocrine therapy compared with 14% (2/14) advanced tumours (T3/T4) following MMM and (0/12) following endocrine therapy. However, in those patients achieving a complete clinical response, subsequent appropriate surgery showed that 16 of 19 patients (84%) had evidence of residual viable tumour on histological examination.

Adult↗
PubMed1996

The standard primipara as a basis for inter-unit comparisons of maternity care.

OBJECTIVE: To assess the suitability of the standard primipara (a subset of the obstetric population that has relatively low risk or intervention and of adverse outcome) for making inter-unit comparisons of indicators of the process and outcome of maternity care. DESIGN: Inter-unit comparison of 10 indicators of obstetric intervention and adverse outcome derived from routinely collected computerised data held on the St Mary's Maternity Information System. SETTING: Fifteen maternity units in the former North West Thames Region. PARTICIPANTS: 15,463 primiparae who were delivered in 1992. MAIN OUTCOME MEASURES: Proportion of primiparae within the standard definition; degree to which standard primiparae are associated with lower rates of intervention and adverse outcome, as compared to other primiparae. RESULTS: Within the database, 42.6% of all primiparae were found to be standard, with rates varying between units from 25.9% to 57.7%. As expected, the standard primiparous woman is at less risk of intervention or adverse outcome than other primiparae. All but one component variable of the standard definition is a significant risk factor for at least four of the 10 indicators. Statistically significant differences in indicator rates are seen between standard and nonstandard primiparae within units. Within the standard group, significant differences in rates of intervention and adverse outcome are seen between units. Units with relatively high levels of intervention within the higher risk nonstandard group also have relatively high levels of intervention within the standard group. CONCLUSIONS: Use of the standard primipara, rather than the whole obstetric population, as the basis for inter-unit comparisons of maternity care will control for the substantial difference in case mix seen in different units, thereby increasing the validity of those comparisons. The technique has the additional benefit of clarifying the relationship between everyday clinical decision making and a unit's performance in comparative indicator reports. The approach must be combined with a separate study of the other groups in the case mix, such as multiparae and high risk primiparae. Additional nonoverlapping groups, homogeneous in terms of risk factors, should be defined and used to extend the basis on which comparisons may be made.

Adult↗
PubMed1996

Evidence that cyclic AMP phosphodiesterase inhibitors suppress TNF alpha generation from human monocytes by interacting with a 'low-affinity' phosphodiesterase 4 conformer.

1. We have investigated the inhibitory effects of RP 73401 (piclamilast) and rolipram against human monocyte cyclic AMP-specific phosphodiesterase (PDE4) in relation to their effects on prostaglandin (PG)E2-induced cyclic AMP accumulation and lipopolysaccharide (LPS)-induced TNF alpha production and TNF alpha mRNA expression. 2. PDE4 was found to be the predominant PDE isoenzyme in the cytosolic fraction of human monocytes. Cyclic GMP-inhibited PDE (PDE3) was also detected in the cytosolic and particulate fractions. Reverse transcription polymerase chain reaction (RT-PCR) of human monocyte poly (A+) mRNA revealed amplified products corresponding to PDE4 subtypes A and B of which the former was most highly expressed. A faint band corresponding in size to PDE4D was also observed. 3. RP 73401 was a potent inhibitor of cytosolic PDE4 (IC50: 1.5 +/- 0.6 nM, n = 3). (+/-)-Rolipram (IC50: 313 +/- 6.7 nM, n = 3) was at least 200 fold less potent than RP 73401. R-(-)-rolipram was approximately 3 fold more potent than S-(+)-rolipram against cytosolic PDE4. 4. RP 73401 (IC50: 9.2 +/- 2.1 nM, n = 6) was over 50 fold more potent than (+/-)-rolipram (IC50: 503 +/- 134 nM, n = 6) ) in potentiating PGE2-induced cyclic AMP accumulation. R-(-)-rolipram (IC50: 289 +/- 121 nM, n = 5) was 4.7 fold more potent than its S-(+)-enantiomer (IC50: 1356 +/- 314 nM, n = 5). A strong and highly-significant, linear correlation (r = 0.95, P < 0.01, n = 13) was observed between the inhibitory potencies of a range of structurally distinct PDE4 inhibitors against monocyte PDE4 and their ED50 values in enhancing monocyte cyclic AMP accumulation. A poorer, though still significant, linear correlation (r = 0.67, P < 0.01, n = 13) was observed between the potencies of the same compounds in potentiating PGE2-induced monocyte cyclic AMP accumulation and their abilities to displace [3H]-rolipram binding to brain membranes. 5. RP 73401 (IC50: 6.9 +/- 3.3 nM, n = 5) was 71 fold more potent than (+/-)-rolipram (IC50: 490 +/- 260 nM, n = 4) in inhibiting LPS-induced TNF alpha release from monocytes. R-(-)-rolipram (IC50: 397 +/- 178 nM, n = 3) was 5.2-fold more potent than its S-(+)- enantiomer (IC50: 2067 +/- 659 nM, n = 3). As with cyclic AMP, accumulation a closer, linear correlation existed between the potency of structurally distinct compounds in suppressing TNF alpha with PDE4 inhibition (r = 0.93, P < 0.01, n = 13) than with displacement of [3H]-rolipram binding (r = 0.65, P < 0.01, n = 13). 6. RP 73401 (IC50: 2 nM) was 180 fold more potent than rolipram (IC50: 360 nM) in suppressing LPS (10 ng ml-1)-induced TNF alpha mRNA. 7. The results demonstrate that RP 73401 is a very potent inhibitor of TNF alpha release from human monocytes suggesting that it may have therapeutic potential in the many pathological conditions associated with over-production of this pro-inflammatory cytokine. Furthermore, PDE inhibitor actions on functional responses are better correlated with inhibition of PDE4 catalytic activity than displacement of [3H]-rolipram from its high-affinity binding site, suggesting that the native PDE4 in human monocytes exists predominantly in a 'low-affinity' state.

Benzamides↗
PubMed1996

Angiographic and duplex grading of internal carotid stenosis: can we overcome the confusion?

The stroke risk reduction benefit of surgical intervention in carotid occlusive disease has been validated in multicenter trials for various angiographically defined lesion severity categories. The two divergent angiographic grading methods used for internal carotid artery stenosis in these trials have caused confusion in the clinical application of their recommendations. Moreover, while today's highly accurate carotid duplex scanning can obviate the need for preoperative angiography in many cases, the duplex criteria must be tailored to achieve sufficiently reliable results on which therapeutic decisions can be made. This review offers a clarification of the discrepancies between the angiographic grading techniques and how their measurements of percent stenosis correlate to the duplex criteria needed to support the treatment decision-making process for carotid obliterative disease.

Angiography↗
PubMed1996

Specificity and variability of practice with young children.

It has previously been suggested that paradigms investigating schema theory should include tests of the effects of variability of practice on tasks experienced during the acquisition of learning. The present aim was to test this effect using a sports-related task. Two groups of children (n = 13 each) aged between 3 and 5 yr. old were pretested on an aiming task. They then received ten practice trials per day for ten days. One group (designated the specific group) practised only at the specified target distance, while another group (designated the specific plus variable group) practised at the target distance and at distances around the target. At the end of the practice period both groups were again tested. The data were analysed for distance and lateral errors, using two-way (group x time) analyses of covariance with one repeated measure on the latter factor. The interaction of groups x time was significant for the distance errors, indicating that at the end of the practice period the specific plus variable group had improved more than the specific group. This finding extends previous work on a similar variability paradigm to a sports-related setting.

Child Development↗
PubMed1996

Vasa vasorum visualised by power-Doppler in normal and arteriosclerotic carotid arteries.

Vasa vasorum and the perfusion of the carotid wall in normal arteries and in arteries with arteriosclerotic plaques was evaluated in-vivo using power-Doppler. Two types of arteries were studied using high-resolution ultrasound. These were arteries with a normal wall (intima, media and adventitia clearly separated) and arteries with intima-media thickening and plaques without calcification. In 10 normal subjects and in 10 patients with early plaques vasa vasorum were visualised. On power-Doppler they appeared as distinct, glomerular-like perfusion units, regularly placed along the course of normal arteries and at similar distance (2 to 4 mm from the lumen-wall interface, within the adventitia and periadventitia layers). In arteriosclerotic vessels the distribution of vasa vasorum units was more irregular, often concentrated in one spot with some perfusion units more distant from the lumen (between 2.5 and 5 mm) and their pulsatility was reduced. Flow velocity complex in most vasa vasorum was comparable, in lower scale to the pattern observed in the carotid lumen without significant differences between normal and arteriosclerotic arteries. The average peak systolic flow velocity was 15: +/-4 cm/sec and the average diastolic velocity was 6 +/- 4 in normal arteries with a median pulsatility index of 1.8 (range 2.2-1.05); in arteriosclerotic arteries velocities were 13 +/- 4 (peak systolic) and 3 +/- 2 (end diastolic) with a median pulsatility index of 1.71 (range 2.1-1.1). In conclusion a different, apparent distribution of vasa vasorum was observed in normal carotids and in carotids with arteriosclerotic lesions.

Adult↗
PubMed1995

The importance of the GTP-binding protein tissue transglutaminase in the regulation of cell cycle progression.

Tissue transglutaminase (tTgase) is a GTP-binding Ca(2+)-dependent enzyme which catalyses the post-translational modification of proteins via epsilon(gamma-glutamyl) lysine bridges. Recent evidence suggests that the GTP-binding activity of tTgase may be important in intracellular signaling thus explaining some of the diverse suggested roles for the enzyme. In the following work a malignant hamster fibrosarcoma (Met B) has been stably transfected with both the full length tTgase cDNA (wild type) and a mutant form of the cDNA whereby the active site cysteine (Cys 277) has been replaced by serine. Expression of this mutant cDNA leads to a protein with GTP binding activity which is deficient of protein crosslinking activity. When synchronised into S-phase and allowed to progress through the cell cycle tTgase transfected clones (both mutant and wild type), when compared to transfected controls, show a delayed progression from S-phase to G2/M when analysed by flow cytometry which appears to be elicited by the G-protein activity of the tTgase.

Animals↗
PubMed1995

Oxidation of low-density lipoprotein in NIDDM: its relationship to fatty acid composition.

The increased risk of atherosclerotic disease in diabetic subjects may be due to enhanced foam cell formation following an increased susceptibility of low density lipoprotein to oxidative modification. This study has compared fatty acid content and lipoprotein oxidisability in 10 non-insulin-dependent diabetic subjects with that in 10 control subjects. Both groups were normocholesterolaemic and the diabetic subjects had higher triglyceride levels (2.2 +/- 0.4 vs 1.2 +/- 0.2 mmol/l, p < 0.05). The fatty acid composition was compared in low density lipoprotein following Folch extraction, separation by thin layer chromatography (for the lipid classes) and analysis by gas liquid chromatography. Low density lipoprotein oxidisability was assessed by conjugated diene and thiobarbituric acid reacting substance formation in the presence of copper ions. The esterified/free cholesterol ratio was higher in the low density lipoprotein from patients compared to control subjects (2.9 +/- 0.1 vs 1.9 +/- 0.3, p < 0.05). Linoleic acid in the cholesteryl ester fraction of the lipoprotein was higher in the patients than in the control subjects (48.2 +/- 2.2% vs 42.4 +/- 3.4%, p < 0.05) as was the total quantity of linoleic acid in the cholesteryl ester fraction (317.8 +/- 68.0 vs 213.2 +/- 28.0 micrograms/mg protein, p < 0.05) and in the low-density lipoprotein as a whole (443.2 +/- 70.0 vs 340.2 +/- 28.2 micrograms/mg protein, p < 0.05). Lipoprotein oxidisability was also increased in the diabetic group with increased formation of thiobarbituric acid reacting substances (35.6 +/- 7.2 vs 22.3 +/- 3.5 nmol/mg protein, p < 0.05, increased total diene formation (502 +/- 60 vs 400 +/- 30 nmol/mg protein, p < 0.05) and increased rate of diene formation (7.2 +/- 0.6 vs 5.1 +/- 0.9 nmol diene.mg protein-1.min-1, p < 0.05). This study indicates that low-density lipoprotein from diabetic subjects is more susceptible to oxidation. This could, in vivo, accelerate foam-cell formation thereby increasing atherosclerotic risk in diabetic subjects.

Aged↗
PubMed1995

The impact of preadmission approval and continued stay review on hospital stay and outcome among children and adolescents.

Managed care has emerged as the centerpiece of the health care industry's efforts to control costs and ensure appropriate use of hospital services. This study assesses the impact of managed care by preadmission approval and/or continued stay review on length of psychiatric hospitalization and clinical outcome of children and adolescents. The sample included 277 cases hospitalized in nine psychiatric specialty hospitals in 1990. Demographic and clinical characteristics, hospital ownership type, and preadmission approval or continued stay review were used as independent variables in a multiple regression model to predict length of stay and clinical outcome. Results indicate that the model accounted for 27% of the variance in length of stay. Previous psychiatric hospitalization and for-profit hospital status predicted longer hospitalization. Clinical outcome was not significantly predicted by the model. Managed care did not predict either length of stay or clinical outcome. Implications for health care reform are discussed.

Adolescent↗
PubMed1995

A comparison of conventional culture and three rapid methods for the detection of Salmonella in poultry feeds and environmental samples.

Three rapid methods, an impedance method (Malthus 2000 Analyzer), a colorimetric DNA hybridization method (Gene-Trak) and a post-enrichment enzyme-linked immunosorbent assay (Salmonella-Tek) were compared with conventional culture for the detection of Salmonella in poultry feeds, and in fluff and dust samples from poultry housing. The percentage positive samples for Salmonella by each of the methods were 25.5% for conventional culture, 38.4% for the Malthus, 28.9% for the Gene-Trak and 28.5% for the Salmonella-Tek. By any method 60/153 (39.2%) of the samples tested were positive on confirmed culture.

Animal Feed↗