Biomedical subjects

M Small

Publications and source records attributed to M Small.

At least 19 recordsLinked to original sources

PubMed2007

Effects of low-dose continuous combined hormone replacement therapy on glucose homeostasis and markers of cardiovascular risk in women with type 2 diabetes.

BACKGROUND: Low-dose hormone replacement therapy (HRT) has attracted interest for the treatment of postmenopausal symptoms in diabetes because of concerns about increased risk of coronary heart disease (CHD) and stroke with conventional HRT containing conjugated equine oestrogens (CEEs) and medroxyprogesterone acetate (MPA). OBJECTIVES: We assessed the effects on glucose homeostasis and cardiovascular risk factors of continuous oral 17beta oestradiol (1 mg) and norethisterone (0.5 mg) in postmenopausal women with type 2 diabetes. DESIGN: Double-blind, randomized placebo-controlled trial. ASSESSMENTS: Hyperinsulinaemic isoglycaemic clamp and cardiovascular risk factors were assessed before and after 3 months of treatment. RESULTS: Twenty-eight women completed the study. HRT decreased fasting glucose compared with placebo [-9.4% with HRT vs.+2.3% for placebo, 95% confidence interval (CI) -23.2 to -0.3] and total cholesterol (-13.7 vs.+1.0%, 95% CI -22.4 to -3.1%) No significant effect was seen on metabolic clearance rate of glucose, glycated haemoglobin (HbA1c), triglycerides, high density lipoprotein (HDL)-cholesterol or C-reactive protein (CRP). CONCLUSIONS: In women with type 2 diabetes, low-dose HRT decreased fasting glucose and total cholesterol without detectable adverse effects on glucose clearance, triglycerides and CRP as reported with conventional HRT.

Blood Glucose↗

PubMed2006

Complex network from pseudoperiodic time series: topology versus dynamics.

We construct complex networks from pseudoperiodic time series, with each cycle represented by a single node in the network. We investigate the statistical properties of these networks for various time series and find that time series with different dynamics exhibit distinct topological structures. Specifically, noisy periodic signals correspond to random networks, and chaotic time series generate networks that exhibit small world and scale free features. We show that this distinction in topological structure results from the hierarchy of unstable periodic orbits embedded in the chaotic attractor. Standard measures of structure in complex networks can therefore be applied to distinguish different dynamic regimes in time series. Application to human electrocardiograms shows that such statistical properties are able to differentiate between the sinus rhythm cardiograms of healthy volunteers and those of coronary care patients.

Biological Clocks↗

PubMed2006

Detecting chaos in pseudoperiodic time series without embedding.

A different method is proposed to detect deterministic structure from a pseudoperiodic time series. By using the correlation coefficient as a measure of the distance between cycles, we are exempt from phase-space reconstruction and further construct a hierarchy of pseudocycle series that, in turn, preserve less determinism than the original time series. Appropriate statistics are then devised to reveal the temporal and spatial correlation encoded in this hierarchy of the pseudocycle series, which allows for a reliable detection of determinism and chaos in the original time series. We demonstrate that this method can reliably identify chaos in the presence of noise of different sources for both artificial data and experimental time series.

Journal Article↗

PubMed2006

The social shaping of childhood vaccination practice in rural and urban Gambia.

Improving childhood vaccination coverage is a key health policy objective in Africa, and as availability increases, it will depend on addressing issues of demand and timely schedule completion. This paper explores vaccination demand in urban and rural areas of The Gambia as shaped by prevailing local vaccination cultures (comprising maternal knowledge and understandings, socio-cultural contexts and interactions with health providers). A survey of 1,600 mothers constructed on the basis of prior ethnography finds a high level of social demand for vaccination, based on lay theories of the general value of immunization in complementing traditional child protection practices. For most rural mothers, strong social networks encourage routine clinic attendance and vaccination 'default' arises only through day-to-day problems and contingencies. However, more pervasive patterns of schedule non-completion are found amongst poorer urban mothers, including recent immigrants, who experience social exclusion at infant welfare clinics. These findings point to the need for health education dialogue grounded in mothers' own understandings and for particular policy attention to improving the clinic experiences of vulnerable social groups in rapidly expanding urban areas.

Data Collection↗

PubMed2006

Blunted response to systemic nitric oxide synthase inhibition in the cerebral circulation of patients with Type 2 diabetes.

AIMS: Diabetes is a major risk factor for stroke, but the mechanisms that impart the excess risk are unclear. Endothelial dysfunction, which has been demonstrated in the coronary and peripheral vasculature of diabetic patients, is an important early marker of vascular disease. However, the effect of diabetes on cerebrovascular endothelium has not been examined. We sought to investigate the effect of diabetes on basal cerebrovascular endothelial function as assessed by response to the nitric oxide synthase (NOS) inhibitor NG-monomethyl-L-arginine (L-NMMA). METHODS: Fourteen men with Type 2 diabetes and 15 age-matched male control subjects were recruited. The participants had no clinically evident vascular disease and were taking no vasoactive or lipid-lowering medication. Each received a single 15-min intravenous infusion of L-NMMA (0.8 mol/kg/min). Cerebral blood flow was assessed by colour Doppler imaging of the internal carotid artery (ICA) at 10-min intervals for 20 min prior to and following the infusion. Middle cerebral artery velocity (MCAv) was assessed by transtemporal Doppler ultrasound at the same time points. RESULTS: L-NMMA produced a mean reduction in ICA flow area under curve (AUC) in the control group of 12.8 +/- 17.8% compared with a 2.1 +/- 21.7% reduction in the group with diabetes (P < 0.05), indicating blunted basal cerebrovascular response to NOS inhibition in the diabetic group. There was no significant change in MCAv following L-NMMA in either group. Mean +/- sd MAP rose 6.4 +/- 4.2 mmHg in the control group vs. 8.8 +/- 3.5 mmHg in the diabetic group [P = not significant (NS)]. No adverse event or symptom was reported. CONCLUSIONS: Response to NOS inhibition is impaired in the cerebral circulation of patients with diabetes. This observation is consistent with the elevated cerebrovascular risk reported in this population, and may represent a future therapeutic target in stroke prevention.

Adult↗

PubMed2004

Higher carotid-radial pulse wave velocity in healthy offspring of patients with Type 2 diabetes.

AIMS: To determine whether carotid-radial pulse wave velocity (crPWV), a simple non-invasive measurement of muscular artery structure and function, is increased in offspring of patients with Type 2 diabetes compared with well-matched controls with no family history of diabetes. Serum levels of intercellular adhesion molecule-1 (sICAM-1) were also examined. METHODS: Offspring (n = 19, M = 8) were recruited via contact with patients attending clinics. Controls (n = 19, M = 8) were recruited by advertisement. crPWV was measured using COMPLIOR. Blood pressure and heart rate were determined and fasting blood taken for measurement of metabolic and endothelial parameters. RESULTS: Offspring and controls were well matched [mean (sd)] for age [33.1 (9.6) vs. 32.8 (9.5) years], body mass index [24.8 (4.9) vs. 24.3 (3.4) kg/m2], waist circumference [78.3 (2.3) vs. 76.3 (2.5) cm], and systolic blood pressure [120 (9.3) vs. 119 (14.2) mmHg]. crPWV was 10% higher in the offspring [9.94 (1.3) m/s] compared with controls [9.01 (1.2) m/s, P = 0.02] despite similar pulse pressure [52 (10.5) vs. 53.5 (9.3) mmHg] and resting heart rate [71 (8.7) vs. 69 (14.0) beats/min]. They also showed a trend toward higher sICAM-1 [217 (55) vs. 188 (40) ng/ml, P = 0.07] concentrations which were also strongly correlated to crPWV in offspring (r = 0.63, P = 0.004). CONCLUSIONS: Vascular dysfunction in the form of increased muscular artery stiffness is present from an early stage in subjects at higher risk of developing diabetes. This may be secondary to impaired activation of endothelial signalling pathways in the context of inherited insulin resistance.

Adult↗

PubMed2004

Use of quantitative 16S ribosomal DNA detection for diagnosis of central vascular catheter-associated bacterial infection.

Many central vascular catheters (CVCs) are removed unnecessarily because current diagnostic methods for CVC-associated infection are unreliable. A quantitative PCR assay using primers and probe targeted to bacterial 16S ribosomal DNA was used to measure the levels of bacterial DNA in blood samples drawn through the CVC in a population of patients receiving intravenous nutrition. Bacterial DNA concentrations were raised in 16 of 16 blood samples taken during episodes of probable bacterial CVC-associated infection. Bacterial DNA concentrations were raised in 4 of 29 episodes in which bacterial CVC-associated infection was unlikely. The use of this technique has the potential to substantially reduce the unnecessary removal of CVCs.

Bacterial Infections↗

PubMed2003

Clinical aspects of a phase I trial of 5,6-dimethylxanthenone-4-acetic acid (DMXAA), a novel antivascular agent.

The antitumour action of 5,6-dimethylxanthenone-4-acetic acid (DMXAA) is mediated through tumour-selective antivascular effects and cytokine induction. This clinical phase I trial was conducted to examine its toxicity, maximum tolerated dose, pharmacokinetics (PK) and pharmacodynamics (PD). A secondary objective was to assess its antitumour efficacy. DMXAA was administered every 3 weeks as a 20-min i.v. infusion. Dose escalation initially followed a modified Fibonacci schema but was also guided by PK and toxicity. A total of 63 patients received 161 courses of DMXAA over 19 dose levels ranging from 6 to 4900 mg m(-2). DMXAA was well tolerated at lower doses and no drug-related myelosuppression was seen. Rapidly reversible dose-limiting toxicities were observed at 4900 mg m(-2), including confusion, tremor, slurred speech, visual disturbance, anxiety, urinary incontinence and possible left ventricular failure. Transient prolongation of the corrected cardiac QT interval was seen in 13 patients evaluated at doses of 2000 mg m(-2) and above. A patient with metastatic cervical carcinoma achieved an unconfirmed partial response at 1100 mg m(-2), progressing after eight courses. The results of PK and PD studies are reported separately. DMXAA has antitumour activity at well-tolerated doses.

Adult↗

PubMed2003

Internal jugular vein thrombosis following ovarian hyperstimulation.

Superovulation therapy with in vitro fertilization (IVF) treatment may result in ovarian hyperstimulation syndrome and a hypercoaguable state. The site of thrombus formation is commonly in the upper venous extremities. One case of bilateral internal jugular vein thrombosis following ovarian hyperstimulation is described. The clinical presentation, investigations and management are discussed.

Adult↗

PubMed2002

Hormone replacement therapy can augment vascular relaxation in post-menopausal women with type 2 diabetes.

BACKGROUND: Diabetes is a major risk factor for coronary heart disease in women and event rates increase substantially after the menopause. Observational studies have suggested that estrogens may provide cardioprotection by regulating endothelial nitric oxide synthase. METHODS: In order to examine the effect of hormone replacement therapy (HRT) on endothelium-dependent and -independent vascular relaxation in post-menopausal women with type 2 diabetes, an open study was conducted in which gluteal biopsies were collected from 17 women before and after 6 months of transdermal 17 beta-estradiol (80 microg twice weekly) in combination with oral norethisterone (1 mg daily). Small arteries (<550 microm) were dissected from fat and mounted on a wire myograph for assessment of relaxation in response to acetylcholine (ACh), bradykinin (BK) and sodium nitroprusside (SNP). RESULTS: Maximal relaxation responses to ACh, BK and SNP in women with diabetes and non-diabetic control subjects were 52 +/- 8 versus 96 +/- 2% (P < 0.05), 76 +/- 7 versus 97 +/- 1%, (P < 0.05) and 91 +/- 2 versus 98 +/- 1% (P < 0.05) respectively. After 6 months of HRT, maximal relaxation responses to ACh, BK and SNP in women with diabetes (compared with pre-HRT) were: 88 +/- 4 (P < 0.05), 93 +/- 3 (P < 0.05) and 98 +/- 1% (P < 0.05) respectively. At baseline and after HRT, EC50 (concentration required to obtain 50% of maximum response) data exhibited similar changes. CONCLUSIONS: HRT had potentially beneficial effects on vascular relaxation. Data were consistent with improvements in endothelial function, vascular smooth muscle function, or both. Controlled studies are required to confirm and extend these findings.

Acetylcholine↗

PubMed2001

Variation in the dominant period during ventricular fibrillation.

Time-varying periodicities are commonly observed in biological time series. In this paper, we discuss three different algorithms to detect and quantify change in periodicity. Each technique uses a sliding window to estimate periodic components in short subseries of a longer recording. The three techniques we utilize are based on: 1) standard Fourier spectral estimation; 2) an information theoretic adaption of linear (autoregressive) modeling; and 3) geometric properties of the embedded time series. We compare the results obtained from each of these methods using artificial data and experimental data from swine ventricular fibrillation (VF). Spectral estimates have previously been applied to VF time series to show a time-dependent trend in the dominant frequency. We confirm this result by showing that the dominant period of VF, following onset, first decreases to a minimum and then rises to a plateau. Furthermore, our algorithms detect longer period correlations which may indicate the presence of additional periodic oscillations or more complex nonlinear structure. We show that in general this possibly nonlinear structure is most apparent immediately after the onset of VF.

Algorithms↗

PubMed2001

The effects of transdermal estradiol in combination with oral norethisterone on lipoproteins, coagulation, and endothelial markers in postmenopausal women with type 2 diabetes: a randomized, placebo-controlled study.

People with type 2 diabetes have a substantially increased risk of coronary heart disease (CHD). Short-term studies with unopposed oral estradiol in women with diabetes have suggested potentially beneficial effects on lipids, thrombotic factors, and insulin sensitivity. However, most (nonhysterectomized) postmenopausal women require combined estrogen-progesterone preparations. We randomized 43 women with type 2 diabetes either to continuous transdermal estradiol (80-microg patches) in combination with oral norethisterone (1 mg daily) or to identical placebos. Blood samples were taken before and after 6 months for measurement of lipoproteins, coagulation factors, and endothelial markers. Total cholesterol and triglyceride concentrations decreased by 8% and 22%, respectively, in those receiving hormone replacement therapy (P < 0.05 relative to change in placebo group after adjustment for baseline concentrations). There was a trend toward a reduction in high density lipoprotein cholesterol concentration (P = 0.06). Factor VII activity decreased by 16% (P < 0.001), and von Willebrand factor antigen decreased by 7% (P = 0.014) with active treatment. Levels of fibrinogen, tissue plasminogen activator, fibrin D dimer, very low density lipoprotein cholesterol, low density lipoprotein cholesterol, lipoprotein(a), and leptin were not significantly altered. No change in glycemic control was detected. Overall, lipid changes may be considered slightly beneficial with respect to CHD risk. The significant decrease in factor VII activity in this study is notable, because elevated factor VII activity has been associated with an increased risk of coronary thrombosis and normally increases with administration of oral estrogen-containing preparations. In addition, a reduction in von Willebrand factor antigen is consistent with an improvement in endothelial function. We suggest that the regimen used in this study may have the potential to reduce CHD risk in women with type 2 diabetes.

Administration, Cutaneous↗

PubMed2001

Neurofibromatosis type 1 of the head and neck: dilemmas in management.

Neurofibromatosis type 1 (NF 1) or Von Recklinghausen's disease is an autosomal dominant condition characterized by multiple skin café-au-lait lesions and multiple neurofibromas. In the head and neck neurofibromas have a predilection to arise in th deep planes of the neck. Surgical management is nearly always required for functional or cosmetic reasons or to exclude the possibility of malignant transformation. We present four cases of neurofibroma of the head and neck and illustrate the difficulties inherent in managing this condition, particularly the age range in which it may occur, the risk of malignant transformation, the possibility of abnormal bleeding and the morbidity that may be associated with the surgical resection. The role of magnetic resonance (MR) scan in the assessment and monitoring of these lesions is highlighted. We also report a unique association of a pharyngeal pouch with NF 1 in a young (25-year-old) patient.

Adolescent↗

PubMed2000

Determinants of raised C-reactive protein concentration in type 1 diabetes.

As a marker of systemic inflammation, raised C-reactive protein (CRP) concentrations which are still within the normal range have been associated with an increased incidence of coronary heart disease (CHD) in non-diabetic subjects. This study aimed to establish potential determinants of raised CRP concentrations in type 1 diabetic patients. We used a sensitive assay to measure 'low-level' CRP concentrations in 167 type 1 patients (93M, 74F, median age 30 years, range 13-67). Stepwise multivariate analysis was used to relate these CRP levels to known cardiovascular risk factors and demographic data. Only six patients had established CHD (median CRP 3.34 mg/l vs. 0.83 mg/l, p=0.032). In subjects without overt CHD, multivariate analysis showed increases in subject age (p=0.0025), BMI (p=0.001) and HbA(1) (p=0.012) to be associated with a higher CRP concentration, as was female sex (p=0.026) and a history of CHD in a first-degree relative (p=0.018, n=57). The duration of diabetes, current smoking status, presence of microvascular complications, lipid status and presence of hypertension were unrelated. This study suggests that some of the risk factors associated with CHD in type 1 patients are also independently predictive of high CRP concentrations. The reasons for this, and whether intervention would prove useful, require further investigation.

Adolescent↗

PubMed2000

Efficient implementation of the gaussian kernel algorithm in estimating invariants and noise level from noisy time series data

We describe an efficient algorithm which computes the Gaussian kernel correlation integral from noisy time series; this is subsequently used to estimate the underlying correlation dimension and noise level in the noisy data. The algorithm first decomposes the integral core into two separate calculations, reducing computing time from O(N2xN(b)) to O(N2+N(2)(b)). With other further improvements, this algorithm can speed up the calculation of the Gaussian kernel correlation integral by a factor of gamma approximately (2-10)N(b). We use typical examples to demonstrate the use of the improved Gaussian kernel algorithm.

Journal Article↗

PubMed2000

Insulin action is associated with endothelial function in hypertension and type 2 diabetes.

A primary defect in the vascular action of insulin may be a key intermediate mechanism that links endothelial dysfunction with reduced insulin-mediated cellular glucose uptake in metabolic and cardiovascular disorders. The present study was designed to characterize more fully the relations between insulin action and endothelial function in male patients with essential hypertension (H, n=9) or type 2 diabetes (D, n=9) along with healthy control subjects (C) matched for age, body mass index, and lipid profile. They attended for measurement of whole-body insulin sensitivity (MCR) by the hyperinsulinemic clamp technique (day 1) and forearm vasoreactivity in response to intra-arterial infusions of insulin/glucose (day 2) and N(G)-monomethyl-L-arginine (L-NMMA) and norepinephrine (day 3) by bilateral venous-occlusion plethysmography. Results expressed as mean+/-SE MCR (mL/kg per minute) were 7.22+/-0. 99 (C), 6.32+/-0.78 (H), and 5.06+/-0.53 (D). Insulin/glucose-mediated vasodilation (IGMV) was 17.1+/-5.6% (C), 17. 2+/-5.5% (H), and 12.3+/-6.4% (D). L-NMMA vasoconstriction (LNV) was 37.9+/-5.1% (C), 37.5+/-2.3% (H), and 33.6+/-2.8% (D). There were no significant differences among groups for these parameters. Pooled correlation analyses revealed associations between MCR and IGMV (r=0. 46, P<0.05), MCR and LNV (r=0.44, P<0.05), and IGMV and LNV (r=0.52, P<0.01). This study supports functional coupling between insulin action (both metabolic and vascular) and basal endothelial nitric oxide production in humans.

Age Factors↗

PubMed2000

Trandolapril does not improve insulin sensitivity in patients with hypertension and type 2 diabetes: a double-blind, placebo-controlled crossover trial.

Angiotensin-converting enzyme (ACE) inhibitors are increasingly used as first-line therapy for hypertension in type 2 diabetes mellitus and are widely believed to improve insulin sensitivity (M). However, the evidence for the latter effect does not stand close scrutiny. We have assessed the effect of the ACE inhibitor trandolapril on M in 16 patients (mean +/- SD age, 58 +/- 10.6 yr) with mild-to-moderate essential hypertension (initial blood pressure, 173 +/- 14.5/93 +/- 8.0 mm Hg), obesity (body mass index, 30 +/- 5.4 kg/m2), and impaired glucose intolerance (n = 4) or type 2 diabetes (n = 12) in a double-blind, placebo-controlled crossover design. All patients underwent three 3-h euglycemic hyperinsulinemic clamp studies (soluble insulin, 1.5 mU/kg x min) after a 2-week placebo run-in and at the end of two 4-week periods of treatment with 2 mg trandolapril or placebo (2-week washout). M (mean +/- SD) did not change with trandolapril: placebo (run-in), 5.2 +/- 1.98 mg/kg x min; placebo, 5.3 +/- 1.70 mg/kg x min; trandolapril, 5.1 +/- 1.65 mg/kg x min; P = 0.58; 95% confidence intervals, -0.74, 0.43 (trandolapril vs. placebo); 95% power to exclude an 8% increase in M. In conclusion, trandolapril had no clinically relevant effect on M in patients with hypertension and type 2 diabetes. Previous reports of improved M during ACE inhibitor treatment may be attributable to suboptimal study design and/or use of surrogate measures of M.

Adult↗

PubMed2000

Amyloidosis of Waldeyer's ring and larynx.

Amyloidosis of the upper aerodigestive tract is relatively rare. A case of localized amyloidosis involving all components of Waldeyer's ring with added laryngeal involvement is described. This has not been previously reported. A literature review of this conditions is presented.

Amyloidosis↗