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Biomedical subjects

R O Gans

Publications and source records attributed to R O Gans.

At least 37 records · Page 2Linked to original sources
PubMed2000

Insulin-mediated increases in renal plasma flow are impaired in insulin-resistant normal subjects.

BACKGROUND: Impaired vasodilatation in skeletal muscle is a possible mechanism linking insulin resistance to blood pressure regulation. Increased renal vascular resistance has been demonstrated in the offspring of essential hypertensives. We assessed whether insulin-mediated renal vasodilatation is impaired in insulin-resistant normal subjects. DESIGN: In two groups of 10 insulin-resistant and 10 insulin-sensitive normal subjects, we compared the effects of sequential physiological and supraphysiological insulin dosages (50 and 150 mU kg(-1) h(-1)) on renal plasma flow (RPF) and leg blood flow using the euglycaemic clamp technique, 131I-labelled Hippuran clearances and venous occlusion plethysmography. Time-control experiments were performed in the same subjects. RESULTS: Whole-body glucose uptake amounted to 4.9 +/- 2.1 and 11.0 +/- 2.4 mg kg(-1) min(-1) in the insulin-resistant and to 12.7 +/- 2.3 and 17.4 +/- 2.6 mg kg(-1) min(-1) in the insulin-sensitive subjects during physiological and supraphysiological hyperinsulinaemia, respectively. RPF increased more in insulin-sensitive compared to insulin-resistant subjects during physiological hyperinsulinaemia (13.7 vs. 6.8%, P < 0.05). RPF increased to comparable levels during supraphysiological hyperinsulinaemia. Insulin-mediated changes in leg blood flow did not differ between groups. In the combined group, we found a positive correlation between insulin-mediated glucose uptake and changes in RPF during physiological hyperinsulinaemia (r = 0.57, P = 0.009), whereas insulin-mediated glucose uptake correlated with changes in leg blood flow during supraphysiological hyperinsulinaemia (r = 0.54. P = 0.017). CONCLUSIONS: Our results suggest that the sensitivities of the skeletal muscle and renal vascular bed differ for insulin's vasodilatory action. Insulin-mediated increases in RPF are impaired in insulin-resistant but otherwise normal subjects during physiological hyperinsulinaemia.

Adult↗
PubMed2000

Antiproteinase 3- and antimyeloperoxidase-associated vasculitis.

Antiproteinase 3- and antimyeloperoxidase-associated vasculitis. Wegener's granulomatosis, microscopic polyangiitis, and idiopathic pauci-immune necrotizing crescentic glomerulonephritis (NCGN) are strongly associated with antineutrophil cytoplasmic autoantibodies (ANCAs) directed against either proteinase 3 (anti-PR3) or myeloperoxidase (anti-MPO). This has led some investigators to prefer combining these diseases under the common heading of ANCA-associated vasculitides. However, it is increasingly recognized that there are characteristic differences between patients with anti-PR3 and those with anti-MPO-associated vasculitis. This review focuses on the clinical, histopathologic, and possibly pathophysiologic differences between anti-PR3- and anti-MPO-associated vasculitis. Although there is considerable overlap, the anti-PR3- and anti-MPO-associated vasculitides are each characterized by particular clinical and histopathological findings. Extrarenal organ manifestations and respiratory tract granulomas occur more frequently in patients with anti-PR3 than in those with anti-MPO. Anti-PR3-positive patients with NCGN generally have a more dramatic deterioration of their renal function compared with anti-MPO-positive patients. The term "ANCA-associated vasculitis" is considered as a useful concept in the presence of systemic vasculitis. Likewise, in the presence of vasculitis, the terms "anti-PR3-associated vasculitis" and "anti-MPO-associated vasculitis" are useful concepts.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2000

Thiamine supplementation to prevent induction of low birth weight by conventional therapy for gestational diabetes mellitus.

Conventional treatment for gestational diabetes mellitus increases the proportion of infants born with a low birth weight, a risk factor for cardiovascular disease and diabetes mellitus in later life. Thiamine supplementation during pregnancy may be shown to be a safe preventive measure. During pregnancy, approximately 50% of the women develop a biochemical thiamine deficiency, whereas the thiamine status falls, but remains within normal limits, in most other women. Thiamine is essential for glucose oxidation, insulin production by pancreatic beta-cells and cell growth. It is therefore likely that thiamine supplementation in pregnant women not only improves their glucose tolerance but also stimulates the intra-uterine growth, thereby preventing a low birth weight to ensue from conventional therapy which only improves glucose tolerance.

Diabetes, Gestational↗
PubMed2000

Birth weight relates to blood pressure and microvascular function in normal subjects.

OBJECTIVE: The relationship between low birth weight and elevated blood pressure in adult life is well established but presently unexplained. Both microvascular dysfunction and insulin resistance have been proposed as a possible explanation. We have examined the relation between birth weight and blood pressure in 30 healthy subjects exhibiting a wide range of insulin sensitivity, and assessed whether microvascular function and/or insulin resistance may underlie this relationship. METHODS: Birth weight data were obtained from birth announcements. Blood pressure was measured with an ambulatory blood pressure monitor and insulin sensitivity was assessed by the hyperinsulinaemic, euglycaemic clamp technique. Microvascular function, i.e. capillary recruitment and endothelium-dependent and -independent vasodilatation in the skin, was evaluated by videomicroscopy and iontophoresis of acetylcholine and sodium nitroprusside. RESULTS: Birth weight was significantly associated with blood pressure (r= -0.50; P< 0.05), capillary recruitment (r= +0.52; P< 0.05), acetylcholine-mediated vasodilatation (r= +0.40; P< 0.05), insulin sensitivity (r= +0.62; P< 0.01) and waist-to-hip ratio (r= -0.42; P< 0.05). Regression analysis showed a significant association of birth weight with 24 h systolic blood pressure (regression coefficient: -7.6 mmHg/kg; 95% confidence interval: -13.0 to -1.0). Adjustment for capillary recruitment and waist-to-hip ratio decreased the regression coefficient by 39 and 41%, respectively. The results were similar after adjustment for age, sex or body mass index. CONCLUSION: These results suggest that capillary recruitment and body fat distribution may partly explain the relationship between birth weight and blood pressure.

Adult↗
PubMed2000

Effects of insulin and atrial natriuretic peptide on renal tubular sodium handling in sickle cell disease.

We assessed the effect of insulin and atrial natriuretic peptide (ANP) on renal sodium handling in eight patients with sickle cell disease (SCD), who are characterized by loss of vasa recta and long loops of Henle, and matched control subjects. During insulin infusion (50 mU. kg(-1). h(-1)), fractional sodium excretion decreased by 0.44 +/- 0.72% (P = 0.13) in patients with SCD and by 0. 57 +/- 0.34% (P = 0.002) in control subjects, whereas fractional distal sodium reabsorption increased by 4.1 +/- 1.5% (P < 0.001) and 3.0 +/- 1.5% (P < 0.001), respectively. Low-dose (0.3 pmol. kg(-1). h(-1)) ANP infusion did not affect renal sodium handling in patients with SCD but increased fractional sodium excretion by 0.34 +/- 0.22% (P = 0.003) in control subjects. High-dose (2 microg/min) ANP increased natriuresis to a similar extent in both groups. Insulin's antinatriuretic effects predominated over the natriuretic effects of low-dose, but not high-dose, ANP. These data suggest that insulin's antinatriuretic effect is localized at a distal tubular site other than the long loops of Henle and that the long loops are involved in the natriuretic effect of low-dose ANP, possibly mediated by changes in medullary blood flow.

Absorption↗
PubMed1999

[Clinical thinking and decision-making in the practice. A patient with thrombophlebitis].

A 55-year-old man presented with deep venous thrombosis of his left leg. Laboratory evaluation disclosed macrocytic anaemia and leukocytosis. In the clinical decision process it was not verified whether all symptoms fitted in with the presumptive diagnosis of pernicious anaemia and stomach carcinoma. The ultimate diagnosis was acute lymphocytic leukaemia. A proper evaluation of a peripheral blood smear would have led to this diagnosis earlier.

Anemia, Macrocytic↗
PubMed1999

[Myositis in the presence of slightly elevated creatine kinase values].

The clinical picture with, among other things, muscular swelling, fever and nocturnal sweating in three males aged 30, 37 and 52 years, suggested a neoplasm and sepsis. Ultimately, they were found to suffer from focal myositis, localized nodular myositis and polymyositis, respectively. The ESR and leukocyte counts were increased, the serum creatinine kinase (CK) activity was normal or slightly increased. The symptoms decreased after prednisone treatment. Both localized and generalized inflammatory muscular diseases may be present without the serum CK activity being raised.

Adult↗
PubMed1999

[Clinical thinking and decision-making in practice. A patient with episodes of flushing].

A 74-year-old woman had an 8-year history of spells consisting of facial flushing and swelling, itching and erythema of the hands, rhinorrhoea and gastrointestinal complaints. The ultimate diagnosis was systemic mastocytosis without urticaria pigmentosa. In the clinical decision process the treating physicians used clinical axioms to try to establish a diagnosis, but these axioms were sometimes used inappropriately. In particular, spells accompanied by flushing inappropriately elicited a possible diagnosis of phenochromocytoma. Generalised mastocytosis can occur in the absence of urticaria pigmentosa and is probably an underestimated cause of spell-like complaints.

Aged↗
PubMed1999

Microvascular function relates to insulin sensitivity and blood pressure in normal subjects.

BACKGROUND: A strong but presently unexplained inverse association between blood pressure and insulin sensitivity has been reported. Microvascular vasodilator capacity may be a common antecedent linking insulin sensitivity to blood pressure. To test this hypothesis, we studied 18 normotensive and glucose-tolerant subjects showing a wide range in insulin sensitivity as assessed with the hyperinsulinemic, euglycemic clamp technique. METHODS AND RESULTS: Blood pressure was measured by 24-hour ambulatory blood pressure monitoring. Videomicroscopy was used to measure skin capillary density and capillary recruitment after arterial occlusion. Skin blood flow responses after iontophoresis of acetylcholine and sodium nitroprusside were evaluated by laser Doppler flowmetry. Insulin sensitivity correlated with 24-hour systolic blood pressure (24-hour SBP; r=-0.50, P<0.05). Capillary recruitment and acetylcholine-mediated vasodilatation were strongly and positively related to insulin sensitivity (r=0.84, P<0.001; r=0.78, P<0.001, respectively), and capillary recruitment was inversely related to 24-hour SBP (r=-0.53, P<0.05). Waist-to-hip ratio showed strong associations with insulin sensitivity, blood pressure, and the measures of microvascular function but did not confound the associations between these variables. Subsequent regression analysis showed that the association between insulin sensitivity and blood pressure was not independent of the estimates of microvascular function, and part of the variation in both blood pressure (R2=38%) and insulin sensitivity (R2=71%) could be explained by microvascular function. CONCLUSIONS: Insulin sensitivity and blood pressure are associated well within the physiological range. Microvascular function strongly relates to both, consistent with a central role in linking these variables.

Adult↗
PubMed1999

[Hypertension in the Negro patient].

Essential hypertension appears to be more prevalent among blacks than among whites and has an earlier onset in blacks. Many data in this field come from studies in the African-American population. Hypertension-related complications, e.g. ischaemic heart disease, (end stage) renal failure and cerebrovascular disease, are encountered more often among blacks and frequently run a more severe course. Factors that might explain the racial difference in prevalence of hypertension and hypertensive complications include both genetic and environmental variables. Hypertension in blacks is characterized by salt sensitivity, a tendency towards expanded plasma volume and low plasma renin levels. Socioeconomic factors, the higher prevalence of obesity and insulin resistance may contribute to the high prevalence of hypertension in blacks. Aggressive antihypertensive therapy appears mandatory in the black hypertensive, possibly with lower goal blood pressures than the 140/90 mmHg generally recommended. Diuretic monotherapy proves to be the first-line therapy, calcium channel blockers are an attractive alternative. Black patients are frequently less responsive to monotherapy with angiotensin-converting enzyme (ACE) inhibitors and beta-blocking agents. This black/white difference in therapeutic response can, however, be eliminated by addition of a diuretic.

Adolescent↗
PubMed1999

Baroreflex sensitivity is depressed in microalbuminuric Type I diabetic patients at rest and during sympathetic manoeuvres.

AIMS/HYPOTHESIS: To evaluate baroreflex sensitivity (BRS) in microalbuminuric and normoalbuminuric Type I (insulin-dependent) diabetic patients without autonomic neuropathy and in healthy control subjects. METHODS: Microalbuminuric Type I diabetic patients (n = 15) were matched for age, sex, body mass index (BMI) and smoking habits with 15 normoalbuminuric patients and with 15 healthy control subjects. All subjects had a blood pressure less than 160/95 mmHg, a BMI less than 30 kg/m(2) and normal autonomic function on standard tests. Blood pressure and heart rate were measured non-invasively (Finapres) at rest and during sympathetic activation (handgrip, mental stress, standing). The baroreflex sensitivity was defined as the mean gain between blood pressure variability and heart rate variability in the 0.07-0.15 Hz frequency band. RESULTS: Resting baroreflex sensitivity was decreased in the microalbuminuric patients (3.5 +/- 0.4 ms/mmHg) compared with the normoalbuminuric patients and the healthy subjects (7.6 +/- 1.6 and 9.5 +/- 1.1 ms/mmHg, respectively, p < 0.001). The sympathetic tests reduced baroreflex sensitivity similarly in the groups without changing the between group differences. CONCLUSION/INTERPRETATION: Baroreflex sensitivity is reduced in Type I diabetic patients with microalbuminuria but without autonomic neuropathy. A prospective study should indicate whether this early abnormality in cardiovascular reflex function is a risk factor of cardiovascular mortality in these patients. [Diabetologia (1999) 42: 1345-1349]

Albuminuria↗
PubMed1999

Salt sensitivity correlates positively with insulin sensitivity in healthy volunteers.

BACKGROUND: The aim of the study was to assess the relationship between insulin sensitivity and salt sensitivity in healthy subjects who display a wide range of insulin sensitivity. As a secondary objective, we assessed the relationship between salt sensitivity and the other characteristics of the insulin resistance syndrome. STUDY DESIGN: Forty-seven normotensive volunteers (age 34 +/- 15 years) with a normal glucose tolerance test were selected. We measured insulin sensitivity using the hyperinsulinaemic euglycaemic clamp (50 mU kg-1 h-1), blood pressure, waist-to-hip ratio, fasting insulin levels, serum lipids and uric acid levels. In a subset of 21, representing a wide range of insulin sensitivity, salt sensitivity was determined as the difference in mean arterial blood pressure (MAP) at the end of a high-salt diet (10 g of NaCl per day for 1 week) vs. a low-salt diet (2 g of NaCl per day for 1 week). RESULTS: Insulin sensitivity (M/I value, range 0.49-4.41 mg kg-1 min-1 per pmol L-1 x 100) was negatively correlated with MAP (r = -0.54, P < 0. 001) and waist-to-hip ratio (r = - 0.59, P < 0.001) but positively correlated with salt sensitivity (r = 0.47, P = 0.03). Salt sensitivity also correlated with high-density lipoprotein (HDL)-cholesterol (r = 0.46, P = 0.038) but not with waist-to-hip ratio, fasting insulin levels, low-density lipoprotein cholesterol, serum triglycerides or serum uric acid. CONCLUSIONS: In healthy normotensive subjects who display a wide range of insulin sensitivity, as measured with the euglycaemic clamp technique, salt sensitivity correlates positively with insulin sensitivity and HDL-cholesterol, but not with the other characteristics of the insulin resistance syndrome.

Adult↗
PubMed1999

Risk factors for premature atherosclerosis.

OBJECTIVES: to investigate the prevalence of risk factors in patients with premature atherosclerosis. DESIGN: retrospective controlled study. MATERIALS: 135 consecutive patients with premature atherosclerosis </= 55 years (group I) were investigated. A control group comprised 107 consecutive patients >/= 65 years (group II) with atherosclerosis. Statistical analysis was performed with Chi-squared test and logistic regression analysis. RESULTS: group I versus group II: diabetes 11% vs. 27% (p=0.001), smoking 84% vs. 67% (p=0.002), hypertension 36% vs. 58% (p=0.001), hypercholesterolaemia 47% vs. 34% (p=0.04), family history of cardiovascular disease 53% vs. 42% (p=0.08). In group I hyperhomocysteinaemia was present in 24 of the 108 patients tested, anticardiolipin antibodies were present in four of the 34 tested and coagulation abnormalities were found in four of the 22 patients tested. CONCLUSION: the difference in the prevalence of the different risk factors between the two groups suggests that either certain risk factors are more likely to cause premature atherosclerosis, or that other risk factors must be present in addition to the known risk factors in order to induce premature atherosclerosis.

Adult↗
PubMed1999

Insulin's acute effects on glomerular filtration rate correlate with insulin sensitivity whereas insulin's acute effects on proximal tubular sodium reabsorption correlation with salt sensitivity in normal subjects.

BACKGROUND: Insulin induces sodium retention by increasing distal tubular sodium reabsorption. Opposite effects of insulin to offset insulin-induced sodium retention are supposedly increases in glomerular filtration rate (GFR) and decreases in proximal tubular sodium reabsorption. Defects in these opposing effects could link insulin resistance to blood-pressure elevation and salt sensitivity. METHODS: We assessed the relationship between the effects of sequential physiological and supraphysiological insulin dosages (50 and 150 mU/kg/h) on renal sodium handling, and insulin sensitivity and salt sensitivity using the euglycaemic clamp technique and clearances of [131I]hippuran, [125I]iothalamate, sodium, and lithium in 20 normal subjects displaying a wide range of insulin sensitivity. Time-control experiments were performed in the same subjects. Salt sensitivity was determined using a diet method. RESULTS: During the successive insulin infusions, GFR increased by 5.9% (P = 0.003) and 10.9% (P<0.001), while fractional sodium excretion decreased by 34 and 50% (both P<0.001). Distal tubular sodium reabsorption increased and proximal tubular sodium reabsorption decreased. Insulin sensitivity correlated with changes in GFR during physiological (r = 0.60, P = 0.005) and supraphysiological (r = 0.58, P = 0.007) hyperinsulinaemia, but not with changes in proximal tubular sodium reabsorption. Salt sensitivity correlated with changes in proximal tubular sodium reabsorption (r = 0.49, P = 0.028), but not in GFR, during physiological hyperinsulinaemia. Neither insulin sensitivity or salt sensitivity correlated with changes in overall fractional sodium excretion. CONCLUSIONS: Insulin sensitivity and salt sensitivity correlate with changes in different elements of renal sodium handling, but not with overall sodium excretion, during insulin infusion. The relevance for blood pressure regulation remains to be proved.

Absorption↗
PubMed1999

Triiodothyronine: a link between the insulin resistance syndrome and blood pressure?

OBJECTIVE: Overall obesity is associated with elevated serum triiodothyronine concentrations and insulin resistance. Oral triiodothyronine is known to induce hypertension in laboratory rats, while triiodothyronine also increases the expression of genes encoding for enzymes involved in the synthesis and secretion of insulin by pancreatic beta cells. We investigated the hypothesis that central obesity and insulin resistance are linked with an increased blood pressure and insulin production through elevated free serum triiodothyronine concentrations. DESIGN: A cross-sectional study of 47 healthy euthyroid subjects (17 men, 30 women; 34 +/- 15 years, mean +/- SD). METHODS: The waist:hip ratio was used as measure of central obesity, and insulin-stimulated glucose disposal during a hyperinsulinaemic euglycaemic clamp was used as measure of insulin sensitivity. Insulin production was calculated from the insulin clearance during the clamp and fasting insulin concentrations. RESULTS: Free serum triiodothyronine concentrations correlated, independent of age and gender, positively with systolic and diastolic blood pressure, insulin production and fasting insulin. There was only a borderline significant correlation of free serum triiodothyronine with the waist-to-hip ratio, and no correlation with insulin sensitivity as assessed during the clamp. The correlations of free serum triiodothyronine with blood pressure, insulin production and fasting insulin were independent of the waist:hip ratio and insulin sensitivity. CONCLUSION: Our hypothesis of free serum triiodothyronine as an intermediate factor in the insulin resistance syndrome is refuted by these data, but we identified free serum triiodothyronine concentrations as a new determinant of blood pressure, insulin production, and fasting insulin in healthy euthyroid subjects.

Adolescent↗
PubMed1998

[A painful inflammation of the thyroid].

Four women aged 30, 29, 52 and 43 years presented with what appeared to be subacute thyroiditis (De Quervain's thyroiditis). This disease is characterized by fatigue, a painful thyroid gland and thyrotoxic manifestations. The diagnosis is further based on a high erythrocyte sedimentation rate and low tracer uptake during thyroid scintigraphy. Only the first patient showed a typical course. In the second and third ones the painful thyroid was associated with nodular enlargement. Fine needle aspiration cytology was at first consistent with subacute thyroiditis but a repeated aspiration showed papillary carcinoma in the second and anaplastic carcinoma in the third patient. In the fourth one, subacute thyroiditis was accompanied by normochromic anaemia, a low serum albumin concentration and liver function disorders. She made a full recovery without treatment. Thyroid malignancies can mimic subacute thyroiditis. Persistent nodular enlargement of the thyroid is suspicious and requires careful investigation.

Adult↗
PubMed1998

The association of dietary fibres with glucose tolerance is partly explained by concomitant intake of thiamine: the Hoorn Study.

Epidemiologic studies have shown an association between the intake of dietary fibres and 2-h glucose values. Food rich in dietary fibres is often also rich in thiamine. Animal studies have shown that thiamine deficiency can induce glucose intolerance. Our aim was to investigate the association between fibre consumption and thiamine intake on the one hand and glucose tolerance on the other hand. We used data from the Hoorn Study, a study of glucose tolerance among 1008 men and 1188 women, aged 50-75 years, without diabetes. In linear regression analyses, fibre intake was inversely associated with fasting glucose. There was also an inverse association between fibre intake and 2-h glucose but it disappeared for the greater part after adjustment for fasting glucose. Fibre intake appeared to be strongly correlated with thiamine intake, and this correlation explained the remaining part of the association between fibre intake and 2-h glucose. Thiamine intake appeared to have a strong and relevant association with 2-h glucose, which was independent of fibre intake and fasting glucose. This association was borderline after adjustment for potential confounders. In women, but not in men, the effect of thiamine intake, independent of potential confounders. In conclusion, part of the association between fibre intake and glucose tolerance is possibly attributable to concomitant thiamine intake.

Aged↗