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Biomedical subjects

G Manning

Publications and source records attributed to G Manning.

At least 19 recordsLinked to original sources
PubMed2005

Contrasting effects of varicose vein surgery on endothelial-dependent and -independent cutaneous vasodilation in the perimalleolar region.

OBJECTIVES: To evaluate the effects of varicose vein surgery on cutaneous microvascular perfusion and vasodilator responses to acetylcholine (Ach) and sodium nitroprusside (SNP) in the gaiter area of patients with great saphenous vein insufficiency. METHODS: Twenty-nine patients with isolated great saphenous vein incompetence attended three study mornings (before surgery, and 6-8 weeks and 6 months after sapheno-femoral ligation+partial stripping) during which cutaneous microvascular responses were measured in the supine and standing positions using laser Doppler fluximetry (LDF) combined with incremental-dose iontophoretic administration of endothelial-dependent (Ach) and -independent (SNP) vasodilators. RESULTS: Varicose vein surgery had no significant effect on baseline cutaneous perfusion or the microvascular response to Ach: e.g. peak vasodilator responses to the 1000 microC stimulus were mean 58 SEM 7, 64 SEM 6 and 65 SEM 7PU on the pre-operative, 6-8 weeks and 6 months assessments. In contrast, the corresponding responses to SNP were significantly increased following surgery: e.g. at 2000 microC, mean 63 SEM 9, 142 SEM 4 and 157 SEM 9PU (p<0.0001) in the upright position. CONCLUSIONS: Sapheno-femoral ligation and partial stripping in patients with great saphenous vein insufficiency improves endothelial-independent cutaneous vasodilator function at the gaiter area, which may at least partly explain the benefits of surgery in reducing the risk of venous ulceration.

Acetylcholine↗
PubMed2004

Comparison of the biotypes of Yersinia enterocolitica isolated from pigs, cattle and sheep at slaughter and from humans with yersiniosis in Great Britain during 1999-2000.

AIMS: To investigate the relationship between livestock carriage of Yersinia enterocolitica and human disease. The biotypes/serotypes of strains recovered from the faeces of pigs, cattle and sheep at slaughter during a national survey in Great Britain in 1999-2000, were compared with those of strains isolated from human cases of yersiniosis during the same period. METHODS AND RESULTS: The faecal carriage of Y. enterocolitica by cattle, sheep and pigs at slaughter was 6.3, 10.7 and 26.1%, respectively. Yersinia enterocolitica biotype (BT) 1a was the most frequently isolated biotype from livestock (58%) and was the predominant biotype (53%) isolated from human cases over the same period. The main recognized pathogenic Y. enterocolitica biotype isolated from livestock was BT3 (O:5,27) (35% of sheep, 22% of pigs and 4% of cattle) but this biotype was not detected in any of the human isolates investigated. The major pathogenic biotypes of strains isolated from humans were BT3 (O:9) (24%) and BT4 (O:3) (19%) whereas of the veterinary isolates investigated, only pigs (11%) carried BT3 (O:9) strains. CONCLUSIONS: Because of significant overlaps in phenotypes of the veterinary and human strains it is not possible to comment on the correlation between host and pathogenicity, especially of biotype 1a. SIGNIFICANCE AND IMPACT OF THE STUDY: The data suggest that further investigations using methods with greater discriminatory power are required. However the data also suggests that pigs may be the primary reservoir for human pathogenic Y. enterocolitica infection.

Abattoirs↗
PubMed2003

Effects of posture and venous insufficiency on endothelial-dependent and -independent cutaneous vasodilation in the perimalleolar region.

OBJECTIVES: To assess the effects of posture, endothelial function and venous insufficiency on cutaneous microvascular vasodilator function in the gaiter area, in particular defining factors which may affect microangiopathy and ulcer formation. METHODS: Endothelial-dependent and -independent vasodilator responses to incremental-doses of acetylcholine (Ach) and sodium nitroprusside (SNP) were evaluated in the perimalleolar region in the supine and standing positions in middle-aged patients with isolated superficial venous insufficiency (ISVI) (n = 25) and healthy controls (n = 28) using laser Doppler fluximetry (LDF) and iontophoresis of vasodilators. RESULTS: The venoarteriolar reflex (vasoconstriction on standing) was equally present in both groups, and reduced the vasodilator responses to SNP in the upright position (e.g., for patients with ISVI, peak SNP response was 82 +/- 11 PU [standing] vs 123 +/- 15 PU [supine]). The presence of ISVI had no effect on endothelial vasodilator function in the supine position, but on standing cutaneous reactivity to Ach was significantly reduced (e.g., peak Ach response 69 +/- 8 PU [ISVI] vs 109 +/- 11 PU [controls], p < 0.003). CONCLUSIONS: Upright posture impairs cutaneous endothelial-dependent vasodilation in the gaiter area of patients with ISVI. This may be of clinical and prognostic utility in identifying which patients with uncomplicated ISVI are at highest risk of tissue breakdown and ulcer formation in the gaiter area.

Acetylcholine↗
PubMed2002

The protein kinase complement of the human genome.

We have catalogued the protein kinase complement of the human genome (the "kinome") using public and proprietary genomic, complementary DNA, and expressed sequence tag (EST) sequences. This provides a starting point for comprehensive analysis of protein phosphorylation in normal and disease states, as well as a detailed view of the current state of human genome analysis through a focus on one large gene family. We identify 518 putative protein kinase genes, of which 71 have not previously been reported or described as kinases, and we extend or correct the protein sequences of 56 more kinases. New genes include members of well-studied families as well as previously unidentified families, some of which are conserved in model organisms. Classification and comparison with model organism kinomes identified orthologous groups and highlighted expansions specific to human and other lineages. We also identified 106 protein kinase pseudogenes. Chromosomal mapping revealed several small clusters of kinase genes and revealed that 244 kinases map to disease loci or cancer amplicons.

Animals↗
PubMed2002

Does the angiotensin-converting enzyme (ACE) gene polymorphism affect rate of abdominal aortic aneurysm expansion?

OBJECTIVES: the tissue renin-angiotensin system (RAS), which plays an important role in vascular structure and function, is regulated in part by an insertion-deletion polymorphism of the angiotensin converting enzyme (ACE) gene. We hypothesised that ACE genotype might affect rate of AAA expansion via modulating long-term structural changes associated with RAS activation. METHODS: fifty-eight patients (50 M, mean age 70 years, mean initial aneurysm size 4.3 cm) with current or previous AAA and serial (>3) annual ultrasound measurements of antero-posterior AAA size provided a sample of leucocyte DNA for ACE genotyping. AAA expansion rate (cm per year) for individual subjects was calculated by linear regression. RESULTS: median AAA expansion rate was 0.28 cm/year (range 0-1.8 cm/year), and the genotype distribution included DD (n=14), DI (n=29) and II (n=15). Corresponding median AAA expansion rates for each of the three genetic subgroups were 0.22, 0.32 and 0.30 cm/year, respectively (p=0.6, nonparametric). CONCLUSIONS: the wide inter-individual variability in AAA expansion rate is likely to reflect complex genetic and environmental interactions, but the lack of any relationship with ACE genotype suggests that differences in vascular ACE activity in aortic tissue are not major determinants of the variability in rate of AAA dilatation.

Aged↗
PubMed2001

Role of ambulatory blood pressure monitoring in the assessment and prognosis of patients with borderline hypertension.

The role of ambulatory blood pressure (ABP) monitoring in the assessment of mild/borderline hypertension (BHT) is unclear. The aim of this study was to test the hypothesis that measurement of ABP in borderline hypertensives differentiates patients with true mild hypertension from those with isolated clinic hypertension (raised office BP but normal ABP) and that a raised ABP identifies a subgroup who are more likely to progress to and require treatment over 1 year. Consecutive untreated patients with BHT (n = 127, 44 +/- 13 years, 45% male) were divided into two groups according to awake ABP: Group 1 (normal ABP < or = 136/86, n = 48), and Group 2 (abnormal ABP > 136/86, n = 79). Left ventricular mass index (LVMI) was greater (116 +/- 30 vs 101 +/- 25 g/m2, p < 0.01) and the proportion of patients with an increased LVMI was significantly higher (34% vs 17%, p = 0.05) in Group 2. During 1 year of follow-up, significantly more patients in Group 2 (34%) required antihypertensive treatment compared with Group 1 (8%, p = 0.01). ABP monitoring usefully discriminates between patients with true BHT and those with isolated clinic hypertension. An elevated awake ABP on initial assessment is associated with a higher LVMI and a greater likelihood of progression to moderate hypertension requiring pharmacological treatment.

Adult↗
PubMed2001

Evidence for a genetically stable strain of Campylobacter jejuni.

The genetic stability of selected epidemiologically linked strains of Campylobacter jejuni during outbreak situations was investigated by using subtyping techniques. Strains isolated from geographically related chicken flock outbreaks in 1998 and from a human outbreak in 1981 were investigated. There was little similarity in the strains obtained from the different chicken flock outbreaks; however, the strains from each of three chicken outbreaks, including strains isolated from various environments, were identical as determined by fla typing, amplified fragment length polymorphism (AFLP) analysis, and pulsed-field gel electrophoresis, which confirmed the genetic stability of these strains during the short time courses of chicken flock outbreaks. The human outbreak samples were compared with strain 81116, which originated from the same outbreak but has since undergone innumerable laboratory passages. Two main AFLP profiles were recognized from this outbreak, which confirmed the serotyping results obtained at the time of the outbreak. The major type isolated from this outbreak (serotype P6:L6) was exemplified by strain 81116. Despite the long existence of strain 81116 as a laboratory strain, the AFLP profile of this strain was identical to the profiles of all the other historical P6:L6 strains from the outbreak, indicating that the genotype has remained stable for almost 20 years. Interestingly, the AFLP profiles of the P6:L6 group of strains from the human outbreak and the strains from one of the recent chicken outbreaks were also identical. This similarity suggests that some clones of C. jejuni remain genetically stable in completely different environments over long periods of time and considerable geographical distances.

Animals↗
PubMed2000

Variability of diurnal changes in ambulatory blood pressure and nocturnal dipping status in untreated hypertensive and normotensive subjects.

An absent or diminished blood pressure (BP) fall during sleep (so-called "nondipping") has been associated with a higher risk of cardiovascular complications, but the long-term reproducibility of dipper status and the relationship between diurnal changes in BP and perceived sleep quality have not been previously documented in untreated hypertensive patients. Ambulatory BP (ABP) and dipping status were examined in 79 subjects (69 hypertensives and 10 normotensives) at 0, 6, and 12 months. Fifty-six percent of subjects had no change in their dipping status, the majority (53%) dipping normally on all three occasions. However, 44% of patients had variable dipping status, and normal nighttime dipping in BP was observed more often when patients perceived their sleep quality to be good during the period of ABP recording. These results highlight significant intrasubject variability in the diurnal fluctuations in ABP and dipper status, which may in part reflect day-to-day variations in sleep disturbance during ABP monitoring. Classifying hypertensive patients into dippers or nondippers on the basis of a single ABP recording is unreliable and potentially misleading.

Adult↗
PubMed1999

Clinical implications of white coat hypertension: an ambulatory blood pressure monitoring study.

Within routine clinical practice, white coat hypertension (where blood pressure is persistently higher in the presence of the doctor or nurse but normal outside the medical setting) makes the diagnosis and management of hypertension difficult. There are conflicting data regarding the prevalence and significance of white coat hypertension. This study has used ambulatory blood pressure monitoring to detect the presence of white coat hypertension in 186 patients referred to an out-patient hypertension unit. The presence of white coat hypertension was defined as an average office blood pressure (measured on three occasions over a 2-month period) of >140/90 mm Hg and an ambulatory awake blood pressure < or = 136/86 mm Hg. The prevalence of white coat hypertension in those patients with borderline hypertension (diastolic blood pressure 90-99 mm Hg) and those with mild-to-moderate hypertension (diastolic blood pressure > or = 100 mm Hg) was determined. Echocardiography was used to assess left ventricular mass index in patients with and without white coat hypertension. The prevalence of white coat hypertension in the total group was 23%. However, the prevalence was higher (33%) in those patients with borderline hypertension compared to 9% of those patients with mild-to-moderate hypertension. There was a statistically significant increase in left ventricular mass index in patients with no evidence of white coat hypertension (125 gm/m2) compared to those with white coat hypertension (102 gm/m2). We conclude that, if office blood pressure is used to identify patients with hypertension who may require treatment, some patients will be incorrectly diagnosed and may be treated inappropriately. We recommend that ambulatory blood pressure monitoring is used in the routine assessment of all newly diagnosed hypertensive patients. Furthermore, we recommend echocardiography in patients with borderline hypertension as some will already have an increased left ventricular mass index.

Adolescent↗
PubMed1998

Twenty-four hour ambulatory blood pressure: a sample from a normal British population.

The aims of this study were to determine 24 h blood pressure (BP) levels in a sample taken from a normal British population, and to investigate factors contributing to variation within the sample. Two hundred and eighty-two Caucasian subjects, with no known hypertension or cardiovascular disease were recruited from local light industry and a general practice population. Office and 24 h BPs were measured. The mean office BP was 120/75, ambulatory mean awake 115/72 and mean asleep 97/58 mm Hg. Males had a small but significantly higher mean office and awake BP but there were no differences in asleep BP. Multiple step-wise regression with age, gender, weight and height showed age to be the best predictor of variation in office BP and awake and asleep diastolic BP. However, age accounted for only a small amount of the variation and did not contribute towards the variation in systolic BP. The two standard deviation upper limits for this population for awake, asleep and overall BP were 136/86, 121/73 and 131/82 mm Hg, respectively. In conclusion, these data providing information on 24 h BP in a healthy British population may be of value in the clinical interpretation of 24 h ambulatory BP recordings in patients with suspected hypertension.

Adolescent↗
PubMed1996

Trainee teachers' attitudes to inclusive education for children with Down's syndrome.

The attitudes of 231 trainee teachers towards inclusive education for children with Down's syndrome were surveyed in two UK colleges of education, one in Scotland and one in Northern Ireland. While the right to educational integration for children with special educational needs was widely endorsed, considerable reservations were expressed about its implementation in practice. Only 13% of respondents indicated that they would welcome the opportunity to teach in an integrated setting and 96% felt that their professional training did not prepare them to meet this challenge. Many underestimated potential levels of achievement in children with Down's syndrome and over half wrongly associated the condition with very short life expectancy.

Attitude↗
PubMed1996

Genetic control of epithelial tube fusion during Drosophila tracheal development.

During development of tubular networks such as the mammalian vascular system, the kidney and the Drosophila tracheal system, epithelial tubes must fuse to each other to form a continuous network. Little is known of the cellular mechanisms or molecular control of epithelial tube fusion. We describe the cellular dynamics of a tracheal fusion event in Drosophila and identify a gene regulatory hierarchy that controls this extraordinary process. A tracheal cell located at the developing fusion point expresses a sequence of specific markers as it grows out and contacts a similar cell from another tube; the two cells adhere and form an intercellular junction, and they become doughnut-shaped cells with the lumen passing through them. The early fusion marker Fusion-1 is identified as the escargot gene. It lies near the top of the regulatory hierarchy, activating the expression of later fusion markers and repressing genes that promote branching. Ectopic expression of escargot activates the fusion process and suppresses branching throughout the tracheal system, leading to ectopic tracheal connections that resemble certain arteriovenous malformations in humans. This establishes a simple genetic system to study fusion of epithelial tubes.

Animals↗
PubMed1996

Development of the Drosophila tracheal system occurs by a series of morphologically distinct but genetically coupled branching events.

The tracheal (respiratory) system of Drosophila melanogaster is a branched network of epithelial tubes that ramifies throughout the body and transports oxygen to the tissues. It forms by a series of sequential branching events in each hemisegment from T2 to A8. Here we present a cellular and initial genetic analysis of the branching process. We show that although branching is sequential it is not iterative. The three levels of branching that we distinguish involve different cellular mechanisms of tube formation. Primary branches are multicellular tubes that arise by cell migration and intercalation; secondary branches are unicellular tubes formed by individual tracheal cells; terminal branches are subcellular tubes formed within long cytoplasmic extensions. Each level of branching is accompanied by expression of a different set of enhancer trap markers. These sets of markers are sequentially activated in progressively restricted domains and ultimately individual tracheal cells that are actively forming new branches. A clonal analysis demonstrates that branching fates are not assigned to tracheal cells until after cell division ceases and branching begins. We further show that the breathless FGF receptor, a tracheal gene required for primary branching, is also required to activate expression of markers involved in secondary branching and that the pointed ETS-domain transcription factor is required for secondary branching and also to activate expression of terminal branch markers. The combined morphological, marker expression and genetic data support a model in which successive branching events are mechanistically and genetically distinct but coupled through the action of a tracheal gene regulatory hierarchy.

Animals↗
PubMed1996

Review: calcium antagonists and diuretics; a useful combination in the management of hypertension?

The use of the combination of a calcium antagonist with a thiazide diuretic for the treatment of hypertension has been the subject of much debate over a number of years. Early studies, with few subjects, demonstrated little benefit, but more recent research using larger numbers of subjects has shown quite clear additional antihypertensive effects of this combination. Combination therapy has an important role in the treatment of patients who do not respond to monotherapy, and the combination of a calcium antagonist and thiazide diuretic may be useful in the successful treatment of these patients.

Calcium Channel Blockers↗
PubMed1996

Double-blind, parallel, comparative multicentre study of a new combination of diltiazem and hydrochlorothiazide with individual components in patients with mild or moderate hypertension.

OBJECTIVE: To compare the antihypertensive efficacy and tolerability of a new combination preparation of diltiazem (150 mg) and hydrochlorothiazide (12.5 mg) with the individual constituents in patients with mild/moderate hypertension. DESIGN: Multi-centre, double-blind, randomised parallel group study. PATIENTS: Seventy-one patients with essential hypertension were recruited to the study. TREATMENT: Following completion of the placebo run-in period 63 patients fulfilled the prerandomisation criteria and entered the 10 week treatment period. Patients were randomised to receive either the combination preparation (D 150 mg/H 12.5 mg), diltiazem (150 mg) or hydrochlorthiazide (12.5 mg). The dosage was increased in three patients who had not attained target blood pressure (BP) control after 6 weeks. OUTCOME MEASURES: Response to treatment assessed by change from baseline in clinic and 24 h ambulatory BP. RESULTS: The proportion of patients achieving target BP (a reduction in resting supine diastolic blood pressure (DBP) to below 90 mm Hg or a reduction of 10 mm Hg from baseline) was 80% in the combination group, 55% in the diltiazem group, and 38% in the hydrochlorothiazide group. The respective figures for reduction in supine DBP from baseline were 13.5 mm Hg, 11.2 mm Hg and 5.9 mm Hg. A similar treatment order appeared throughout each of the efficacy variables. BP control throughout the 24 h dosing interval was demonstrated by ambulatory BP monitoring. Each treatment was well tolerated. CONCLUSION: This study provides clear evidence of the efficacy of combination therapy with diltiazem and hydrochlorothiazide in the management of patients with hypertension.

Adolescent↗
PubMed1994

Raised ambulatory blood pressure in type 1 diabetes with incipient microalbuminuria.

Whether raised blood pressure precedes, follows or develops in parallel with the onset of microalbuminuria, remains unclear. Previous studies, using conventional blood pressure recordings, have yielded discrepant results. Ambulatory blood pressure (ABP) monitoring detects borderline hypertension more reliably, and correlates more closely with end-organ damage. We have therefore compared ABP and left ventricular dimensions in normotensive insulin-dependent diabetic patients with or without microalbuminuria, and matched nondiabetic control subjects. Those diabetic patients with microalbuminuria, and to a lesser extent those without, had higher 24 h mean arterial blood pressure than matched non-diabetic control subjects, with corresponding increases of left ventricular mass, interventricular septal width and posterior wall thickness. These observations suggest that raised arterial blood pressure is present at an early stage of 'incipient' microalbuminuria.

Adult↗