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G Hook

Publications and source records attributed to G Hook.

At least 19 recordsLinked to original sources
PubMed2005

Developing the public health practitioner workforce in England: lessons from theory and practice.

FOCUS: The paper focuses on public health practitioners who collectively represent one of three key workforce groups identified by England's Chief Medical Officer as critical to the successful delivery of national public health policy priorities. QUESTION: We report on two areas of work which attempt to address the following two-part question: in developing the public health practitioner workforce in England, what is needed, and how do we do it? APPROACH: First, we describe a five-component conceptual framework for developing the public health workforce which is grounded in data derived from a national Open Space event hosted by the University of the West of England in March 2005. The five components are (i) strategic support and oversight; (ii) national technical and professional support; (iii) national career building; (iv) local organisational development, and (v) sub-regional skills development. Key elements of each component are described in the paper. Second, we describe in some detail a new multidisciplinary skills development programme which illustrates one of the framework components (sub-regional skills development). The programme, established in January 2005, is aimed at three key groups of public health practitioners: health visitors (specialist community public health nurse), school nurses and environmental health officers. Its main features and some initial evaluation findings are presented. CONCLUSIONS: To be effective, activities aimed at supporting the development of the public health practitioner workforce should, where possible, aim to be congruent with core public health principles of self-determination and collective responsibility. We also conclude that leadership and vision at a national level, combined with local implementation of evidence-based training programme such as the one described could help to achieve much greater and more rapid progress in skilling up the existing public health practitioner workforce than has been possible up to now. But we note that this requires sustained investment, robust sector-wide delivery frameworks, and a group of committed local public health champions.

Humans↗
PubMed2001

Polycystic ovary syndrome is associated with endothelial dysfunction.

BACKGROUND: We recently reported endothelial dysfunction as a novel cardiovascular risk factor associated with insulin resistance/obesity. Here, we tested whether hyperandrogenic insulin-resistant women with polycystic ovary syndrome (PCOS) who are at increased risk of macrovascular disease display impaired endothelium-dependent vasodilation and whether endothelial function in PCOS is associated with particular metabolic and/or hormonal characteristics. METHODS AND RESULTS: We studied leg blood flow (LBF) responses to graded intrafemoral artery infusions of the endothelium-dependent vasodilator methacholine chloride (MCh) and to euglycemic hyperinsulinemia in 12 obese women with PCOS and in 13 healthy age- and weight-matched control subjects (OBW). LBF increments in response to MCh were 50% lower in the PCOS group than in the OBW group (P:<0.01). Euglycemic hyperinsulinemia increased LBF above baseline by 30% in the PCOS and 60% in OBW group (P:<0.05 between groups). Across all subjects, the maximal LBF response to MCh exhibited a strong inverse correlation with free testosterone levels (r=-0.52, P:<0.007). This relationship was stronger than with any other parameter, including insulin sensitivity. CONCLUSIONS: PCOS is characterized by (1) endothelial dysfunction and (2) resistance to the vasodilating action of insulin. This endothelial dysfunction appears to be associated with both elevated androgen levels and insulin resistance. Given the central vasoprotective role of endothelium, these findings could explain, at least in part, the increased risk for macrovascular disease in women with PCOS.

Adult↗
PubMed2001

Repeatability characteristics of simple indices of insulin resistance: implications for research applications.

The objectives of this study were to evaluate test characteristics, such as normality of distribution, variation, and repeatability, of simple fasting measures of insulin sensitivity and to use the results to choose among these measures. Duplicate fasting samples of insulin and glucose were collected before 4 h of euglycemic hyperinsulinemic clamping using insulin infusion rates ranging from 40-600 mU/m2 x min. Currently recommended estimates of insulin sensitivity, including the fasting insulin, 40/insulin, the homeostasis model assessment, the logarithmic transformation of the homeostasis model assessment, and the Quantitative Insulin Sensitivity Check Index, were evaluated. The normality of distribution and the variability of the tests (coefficient of variation and discriminant ratio) were compared between the measures and against the "gold standard" hyperinsulinemic clamp. Data from 253 clamp studies in 152 subjects were examined, including 79 repeated studies for repeatability analysis. In subjects ranging from lean to diabetic, the log transformed fasting measures combining insulin and glucose had normal distributions and test characteristics superior to the other simple indices (logarithmic transformation of the homeostasis model assessment coefficient of variation, 0.55; discriminant ratio, 13; Quantitative Insulin Sensitivity Check Index coefficient of variation, 0.05; discriminant ratio, 10) and statistically comparable to euglycemic hyperinsulinemic clamps (coefficient of variation, 0.10; discriminant ratio, 6.4). These favorable characteristics helped explain the superior correlations of these measures with the hyperinsulinemic clamps among insulin-resistant subjects. Furthermore, therapeutic changes in insulin sensitivity were as readily demonstrated with these simple measures as with the hyperinsulinemic clamp. The test characteristics of the logarithmic transformation of the homeostasis model assessment and the Quantitative Insulin Sensitivity Check Index are superior to other simple indices of insulin sensitivity. This helps explain their excellent correlations with formal measures both at baseline and with changes in insulin sensitivity and supports their broader application in clinical research.

Adult↗
PubMed2000

Type II diabetes abrogates sex differences in endothelial function in premenopausal women.

BACKGROUND: Obesity is a more potent cardiovascular risk factor (CVRF) in men than in women. Because traditional CVRFs cannot fully account for this sex difference, we tested the hypothesis that compared with men, women exhibit more robust endothelial function independent of obesity and that this sex difference is abrogated by diabetes. METHODS AND RESULTS: We studied leg blood flow (LBF) responses to graded intrafemoral artery infusions of the endothelium-dependent vasodilator methacholine chloride (Mch) and the endothelium-independent vasodilator sodium nitroprusside (SNP) in groups of lean, obese (OB), and type II diabetic (DM) premenopausal women and age- and body mass index-matched men. LBF response to intrafemoral administration of L-NMMA, an inhibitor of nitric oxide synthase, was also assessed in normal men and women. Maximum LBF increments in response to Mch were 347+/-57% versus 231+/-22% in lean women versus men (P<0.05) and 203+/-25% versus 111+/-17% in OB women versus men (P<0.01), respectively. In DM, maximum LBF increments in response to Mch were 104+/-24% and 138+/-33% in women and men, respectively, (P=NS). LBF decrements in response to L-NMMA were 34.9+/-4.1% and 17.1+/-4.2% in women and men, respectively (P<0.01). The response to SNP was not different between sexes and groups. CONCLUSIONS: Premenopausal nondiabetic women exhibit more robust endothelium-dependent vasodilation owing to higher rates of nitric oxide release than men. Given the protective vascular action of nitric oxide, this difference may partially explain the lower incidence of macrovascular disease in women. In premenopausal women, DM causes impairment of endothelial function beyond that observed with obesity alone and leads to endothelial dysfunction similar to that observed in DM men. These findings may help explain the similar rates of coronary artery disease and mortality in diabetic men and women.

Adult↗
PubMed2000

Evidence for physiological coupling of insulin-mediated glucose metabolism and limb blood flow.

We hypothesized that the vasodilation observed during insulin stimulation is closely coupled to the rate of glucose metabolism. Lean (L, n = 13), obese nondiabetic (OB, n = 13), and obese type 2 diabetic subjects (Type 2 DM, n = 16) were studied. Leg blood flow (LBF) was examined under conditions of euglycemic hyperinsulinemia (EH) and hyperglycemic hyperinsulinemia (HH), which produced a steady-state whole body glucose disposal rate (GDR) of approximately 2,000 micromol. m(-2). min(-1). At this GDR, under both conditions, subjects across the range of insulin sensitivity exhibited equivalent LBF (l/min EH: L, 0.42 +/- 0.03; OB, 0.43 +/- 0. 03; Type 2 DM, 0.38 +/- 0.07; P = 0.72 by ANOVA. HH: L, 0.44 +/- 0. 04; OB, 0.39 +/- 0.05; Type 2 DM, 0.41 +/- 0.04; P = 0.71). The continuous relationship between LBF and GDR did not differ across subject groups [slope x 10(-5) l/(micromol. m(-2). min(-1)) by ANOVA. EH: L, 8.6; OB, 9.2; Type 2 DM, 7.9; P = 0.91. HH: L, 4.2; OB, 2.5; Type 2 DM, 4.1; P = 0.77], although this relationship did differ between the EH and HH conditions (P = 0.001). These findings support a physiological coupling of LBF and insulin-mediated glucose metabolism. The mechanism(s) linking substrate delivery and metabolism appears to be intact in insulin-resistant states.

Adult↗
PubMed2000

Interaction between insulin sensitivity and muscle perfusion on glucose uptake in human skeletal muscle: evidence for capillary recruitment.

Insulin and glucose delivery (muscle perfusion) can modulate insulin-mediated glucose uptake. This study was undertaken to determine 1) to what extent insulin sensitivity modulates the effect of perfusion on glucose uptake and 2) whether this effect is achieved via capillary recruitment. We measured glucose disposal rates (GDRs) and leg muscle glucose uptake (LGU) in subjects exhibiting a wide range of insulin sensitivity, after 4 h of steady-state (SS) euglycemic hyperinsulinemia (>6,000 pmol/l) and subsequently after raising the rate of leg blood flow (LBF) 2-fold with a superimposed intrafemoral artery infusion of methacholine chloride (Mch), an endothelium-dependent vasodilator. LBF was determined by thermodilution: LGU = arteriovenous glucose difference (AVGdelta) x LBF. As a result of the 114+/-12% increase in LBF induced by Mch, the AVGdelta decreased 32+/-4%, and overall rates of LGU increased 40+/-5% (P < 0.05). We found a positive relationship between the Mch-modulated increase in LGU and insulin sensitivity (GDR) (r = 0.60, P < 0.02), suggesting that the most insulin-sensitive subjects had the greatest enhancement of LGU in response to augmentation of muscle perfusion. In separate groups of subjects, we also examined the relationship between muscle perfusion rate and glucose extraction (AVGdelta). Perfusion was either pharmacologically enhanced with Mch or reduced by intra-arterial infusion of the nitric oxide inhibitor N(G)-monomethyl-L-arginine during SS euglycemic hyperinsulinemia. Over the range of LBF, changes in AVGdelta were smaller than expected based on the noncapillary recruitment model of Renkin. Together, the data indicate that 1) muscle perfusion becomes more rate limiting to glucose uptake as insulin sensitivity increases and 2) insulin-mediated increments in muscle perfusion are accompanied by capillary recruitment. Thus, insulin-stimulated glucose uptake displays both permeability- and perfusion-limited glucose exchange properties.

Adult↗
PubMed2000

Free fatty acid elevation impairs insulin-mediated vasodilation and nitric oxide production.

The effect and time course of free fatty acid (FFA) elevation on insulin-mediated vasodilation (IMV) and the relationship of FFA elevation to changes in insulin-mediated glucose uptake was studied. Two groups of lean insulin-sensitive subjects underwent euglycemic-hyperinsulinemic (40 mU x m(-2) x min(-1)) clamp studies with and without superimposed FFA elevation on 2 occasions approximately 4 weeks apart. Groups differed only by duration of FFA elevation, either short (2-4 h, n = 12) or long (8 h, n = 7). On both occasions, rates of whole-body glucose uptake were measured, and changes in leg blood flow (LBF) and femoral vein nitric oxide nitrite plus nitrate (NOx) flux in response to the clamps were determined. Short FFA infusion did not have any significant effect on the parameters of interest. In contrast, long FFA infusion decreased rates of whole-body glucose uptake from 47.7 +/-2.8 to 32.2 +/- 0.6 micromol x kg(-1) x min(-1) (P < 0.01), insulin-mediated increases in LBF from 66 +/- 8 to 37 +/- 7% (P < 0.05), and insulin-induced increases in NOx flux from 25 +/- 9 to 5 +/- 9% (P < 0.05). Importantly, throughout all groups, FFA-induced changes in whole-body glucose uptake correlated significantly with FFA-induced changes in insulin-mediated increases in LBF (r = 0.706, P < 0.001), which indicates coupling of metabolic and vascular effects. In a different protocol, short FFA elevation blunted the LBF response to NG-monomethyl-L-arginine (L-NMMA), which is an inhibitor of NO synthase. LBF in response to L-NMMA decreased by 17.3 +/- 2.4 and 9.0 +/- 1.4% in the groups without and with FFA elevation, respectively (P < 0.05), which indicates that FFA elevation interferes with shear stress-induced NO production. Thus, impairment of shear stress-induced vasodilation and IMV by FFA elevation occurs with different time courses, and impairment of IMV occurs only if glucose metabolism is concomitantly reduced. These findings suggest that NO production in response to the different stimuli may be mediated via different signaling pathways. FFA-induced reduction in NO production may contribute to the higher incidence of hypertension and macrovascular disease in insulin-resistant patients.

Adult↗
PubMed1999

Dual energy X-ray absorptiometry assessment of fat mass distribution and its association with the insulin resistance syndrome.

OBJECTIVE: To determine which dual energy X-ray absorptiometry (DXA)-derived indices of fat mass distribution are the most informative to predict the various parameters of the metabolic syndrome. RESEARCH DESIGN AND METHODS: A total of 87 healthy men, 63 lean (% fat < or =26) and 24 obese (% fat >26), underwent DXA scanning to evaluate body composition with respect to the whole body and the trunk, leg, and abdominal regions from L1 to L4 and from L3 to L4. These regions were correlated with insulin sensitivity determined by the euglycemic-hyperinsulinemic clamp, insulin area under the curve after oral glucose tolerance test (AUC I); triglyceride; total, HDL, and LDL cholesterol; free fatty acids; and blood pressure. The analyses were performed in all subjects, as well as in lean and obese groups separately. RESULTS: Among the various indices of body fat, DXA-determined adiposity in the abdominal cut at L1-4 level was the most predictive of the metabolic variables, showing significant relationships with glucose infusion rate ([GIR], mg kg(-1) lean body mass x min(-1)), triglyceride, and cholesterol, independent of total-body mass (r = -0.267, P<0.05; r = 0.316, P<0.005; and r = 0.319, P<0.005, respectively). Upon subanalysis, these correlations remained significant in lean men, whereas in obese men, only BMI and the amount of leg fat (negative relationship) showed significant correlations with triglyceride and cholesterol (r = 0.438, P<0.05; r = 0.458, P<0.05; r = -0.439, P<0.05; and r = -0.414, P<0.05, respectively). The results of a multiple regression analysis revealed that 47% of the variance in GIR among all study subjects was predicted by AUC I, fat L1-4, diastolic blood pressure (dBP), HDL, and triglyceride as independent variables. In the lean group, fat L1-4 alone accounted for 33% of the variance of GIR, whereas in obese men, AUC I and dBP explained 68% of the variance in GIR. CONCLUSIONS: The DXA technique applied for the evaluation of fat distribution can provide useful information regarding various aspects of the insulin resistance syndrome in healthy subjects. DXA can be a valid, accurate, relatively inexpensive, and safer alternative compared with other methods to investigate the role of abdominal body fat distribution on cardiovascular risk factors.

Absorptiometry, Photon↗
PubMed1998

Recommendations for statistical designs of in vivo mutagenicity tests with regard to subsequent statistical analysis.

A workshop was held on September 13 and 14, 1993, at the GSF, Neuherberg, Germany, to start a discussion of experimental design and statistical analysis issues for three in vivo mutagenicity test systems, the micronucleus test in mouse bone marrow/peripheral blood, the chromosomal aberration tests in mouse bone marrow/differentiating spermatogonia, and the mouse dominant lethal test. The discussion has now come to conclusions which we would like to make generally known. Rather than dwell upon specific statistical tests which could be used for data analysis, serious consideration was given to test design. However, the test design, its power of detecting a given increase of adverse effects and the test statistics are interrelated. Detailed analyses of historical negative control data led to important recommendations for each test system. Concerning the statistical sensitivity parameters, a type I error of 0.05 (one tailed), a type II error of 0.20 and a dose related increase of twice the background (negative control) frequencies were generally adopted. It was recommended that sufficient observations (cells, implants) be planned for each analysis unit (animal) so that at least one adverse outcome (micronucleus, aberrant cell, dead implant) would likely be observed. The treated animal was the smallest unit of analysis allowed. On the basis of these general consideration the sample size was determined for each of the three assays. A minimum of 2000 immature erythrocytes/animal should be scored for micronuclei from each of at least 4 animals in each comparison group in the micronucleus assays. A minimum of 200 cells should be scored for chromosomal aberrations from each of at least 5 animals in each comparison group in the aberration assays. In the dominant lethal test, a minimum of 400 implants (40-50 pregnant females) are required per dose group for each mating period. The analysis unit for the dominant lethal test would be the treated male unless the background frequency of dead implants (DI) is so low that multiple males would need to be integrated to meet the minimum observation of one adverse outcome (DI) per analysis unit. A three-step strategy of data analysis was proposed for the cytogenetic assays. Use of negative historical controls was allowed in certain circumstances for interpretation of results from micronucleus tests and chromosomal aberration tests.

Animals↗
PubMed1997

Endothelial dysfunction is associated with cholesterol levels in the high normal range in humans.

BACKGROUND: The purpose of this study was to test the hypothesis that cholesterol levels in the high normal range are associated with impaired endothelium-dependent vasodilation. METHODS AND RESULTS: We studied leg blood flow (LBF) responses to graded intrafemoral artery infusions of the endothelium-dependent vasodilator methacholine chloride (MCh) or the endothelium-independent vasodilator sodium nitroprusside (SNP) in normal volunteers exhibiting a wide range of total cholesterol levels within the normal range (<75th percentile). LBF increased in a dose-dependent fashion in response to the femoral artery infusions of MCh and SNP (P<.001). LBF responses to MCh were significantly blunted (P<.001) in subjects with high normal cholesterol (195+/-6 mg/dL, n=13) compared with subjects with low normal cholesterol (146+/-5 mg/dL, n=20). Maximal endothelium-dependent vasodilation in the high normal group was decreased by nearly 50% compared with the low normal group (146+/-13% versus 268+/-34%, P<.01). There was a negative correlation between total cholesterol levels and maximal endothelium-dependent vasodilation (total cholesterol, r=-.41, P<.02; LDL cholesterol, r=-.42, P<.02). On the other hand, LBF responses to the endothelium-independent vasodilator SNP did not differ between groups. CONCLUSIONS: These data suggest that an inverse and continuous relationship exists between the prevailing cholesterol level and endothelium-dependent vasodilation. Moreover, cholesterol levels even in the normal range may be associated with endothelial dysfunction, thus potentially contributing to the increased risk of macrovascular disease conferred by cholesterol elevations.

Adult↗
PubMed1997

Elevated circulating free fatty acid levels impair endothelium-dependent vasodilation.

We have recently shown that insulin-resistant obese subjects exhibit impaired endothelial function. Here, we test the hypothesis that elevation of circulating FFA to levels seen in insulin-resistant subjects can impair endothelial function. We studied leg blood flow responses to graded intrafemoral artery infusions of the endothelium-dependent vasodilator methacholine chloride (Mch) or the endothelium-independent vasodilator sodium nitroprusside during the infusion of saline and after raising systemic circulating FFA levels exogenously via a low- or high-dose infusion of Intralipid plus heparin or endogenously by an infusion of somatostatin (SRIF) to produce insulinopenia in groups of lean healthy humans. After 2 h of infusion of Intralipid plus heparin, FFA levels increased from 562+/-95 to 1,303+/-188 micromol, and from 350+/-35 to 3,850+/-371 micromol (P < 0.001) vs. saline for both low- and high-dose groups, respectively. Mch-induced vasodilation relative to baseline was reduced by approximately 20% in response to the raised FFA levels in both groups (P < 0.05, saline vs. FFA, ANOVA). In contrast, similar FFA elevation did not change leg blood flow responses to sodium nitroprusside. During the 2-h SRIF infusion, insulin levels fell, and FFA levels rose from 474+/-22 to 1,042+/-116 micromol (P < 0.01); Mch-induced vasodilation was reduced by approximately 20% (P < 0.02, saline vs. SRIF, ANOVA). Replacement of basal insulin levels during SRIF resulted in a fall of FFA levels from 545+/-47 to 228+/-61 micromol, and prevented the impairment of Mch-induced vasodilation seen with SRIF alone. In conclusion, (a) elevated circulating FFA levels cause endothelial dysfunction, and (b) impaired endothelial function in insulin-resistant humans may be secondary to the elevated FFA concentrations observed in these patients.

Adult↗
PubMed1997

Germ-line effects of a mutator, mu2, in Drosophila melanogaster.

A mutator, mu2a, in Drosophila melanogaster potentiates terminal deficiencies. In the female germ line the gamma mutant frequency induced by irradiation of mature oocytes with 5 Gy increases approximately twofold in heterozygotes and 20-fold in homozygotes compared with wild type. The recovery of terminal deficiencies is not limited to breaks close to chromosome ends; high frequencies of deficiencies can be recovered with breakpoints located in centric heterochromatin or near the middle of a chromosome arm. Lesions induced by gamma-rays are repaired slowly in mu2a oocytes, but become "fixed" as terminal deficiencies upon fertilization. A few lesions induced in wild-type females also produce terminal deficiencies. Mutator males do not exhibit an increase in terminal deletions, regardless of the germ cell stage irradiated. In addition, there is no increase in the mutant frequency when mature sperm are irradiated and fertilize eggs produced by mu2a females. The data are consistent with the hypothesis that lesions induced in sperm chromosomes are repaired after fertilization, while lesions induced in oocyte chromosomes are shunted instead to a mechanism that stabilizes broken chromosome ends. We propose that mu2 affects chromosomal structure during oogenesis, thereby modulating DNA repair.

Animals↗
PubMed1986

Comparison of two methods for determination of magnesium concentration of mononuclear blood cells.

We describe and compare two methods for the determination of magnesium concentration in lymphocytes from cell cultures. The magnesium concentration of lymphocytes was 36 +/- 4 mmol/kg dry weight by atomic absorption spectroscopy analysis and 39 +/- 19 mmol/kg dry weight with electron probe X-ray microanalysis. We found no significant difference between the results for the two methods. The coefficient of variation was 30% for magnesium concentration among individual cells with electron probe X-ray microanalysis.

Burkitt Lymphoma↗
PubMed1984

Imaging of calcium and aluminum in neurofibrillary tangle-bearing neurons in parkinsonism-dementia of Guam.

We report the distribution and imaging of calcium and aluminum in neurofibrillary tangle (NFT)-bearing neurons within Sommer's sector of the hippocampus in Guamanian patients with parkinsonism-dementia, using a method of computer-controlled electron beam x-ray micro-analysis and wavelength dispersive spectrometry. Calcium and aluminum were distributed in cell bodies and axonal processes of NFT-bearing neurons. The elemental images show that both calcium and aluminum deposits occur within the same NFT-bearing hippocampal neuron in this dementing disease, suggesting that these elements are involved in NFT formation. No prominent concentrations of calcium and aluminum were imaged in non-NFT-containing regions within the pyramidal cell layer of the parkinsonism-dementia cases or in the control cases. These findings support the hypothesis that secondary hyperparathyroidism resulting from low environmental calcium and magnesium in the high-incidence focus of amyotrophic lateral sclerosis and parkinsonism-dementia on Guam had led to abnormal deposition of calcium and aluminum in the central nervous system.

Aged↗