| 1. |
- Lindqvist, A, et al.
(författare)
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Artery blood pressure oscillation after active standing up: an indicator of sympathetic function in diabetic patients
- 1997
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Ingår i: Clinical Physiology. - : Wiley. - 1365-2281 .- 0144-5979. ; 17:2, s. 159-169
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Tidskriftsartikel (refereegranskat)abstract
- Dynamic artery blood pressure (Finapres) response to active standing up, normally consisting of initial rise, fall and recovery above the baseline (overshoot), was compared with the early steady-state artery blood pressure level to measure sympathetic vasomotor function in healthy subjects (n = 23, age 35 +/- 9 years; mean +/-SD) and in type I diabetic patients without autonomic neuropathy (AN) (group 1: n = 18, 38 +/- 13 years), with AN but no cardiovascular drugs (group 2a: n = 7, 44 +/- 11 years) and with both AN and cardiovascular drugs (group 2b: n = 10, 47 +/- 7 years). Systolic and diastolic overshoot were similar in the control (15 +/- 13/15 +/- 11 mmHg) and group 1 subjects. Systolic overshoot disappeared in 57% of patients in group 2a (-1 +/- 9 mmHg; P < 0.03), whereas artery blood pressure still overshot in diastole (8 +/- 7 mmHg; NS). Systolic overshoot disappeared in all patients in group 2b (-22 +/- 22 mmHg; P < 0.0006) and diastolic overshoot disappeared in 60% of these patients (-6 +/- 16 mmHg; P = 0.0006). Systolic early steady-state level was not lower in group 2a than in group 1 (NS), but it was impaired in group 2b (P < 0.006), in which six diabetic patients had a pathological response beyond the age-related reference values. There was a strong association between the overshoot and steady-state levels (P for chi 2 < 0.001, n = 58). Overshoot of the control subjects and patients in group 2b correlated to their respective steady-state blood pressure levels (r > or = 0.76; P < or = 0.001). In conclusion, baroreceptor reflex-dependent overshoot of the artery blood pressure after active standing up diminishes with the development of AN and it is associated with the early steady-state level of the artery blood pressure.
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| 2. |
- Torffvit, Ole, et al.
(författare)
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The association between diabetic nephropathy and autonomic nerve function in type 1 diabetic patients
- 1997
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - 1502-7686. ; 57:2, s. 183-191
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Tidskriftsartikel (refereegranskat)abstract
- Diabetic cardiovascular autonomic neuropathy increases the risk of deterioration in renal function and is associated with increased mortality in patients with renal failure. Type 1 diabetic patients with long diabetes duration, matched for age (38 +/- 9 years) and diabetes duration (28 +/- 8 years) were studied regarding the association between cardiovascular autonomic nerve function and different degrees of diabetic nephropathy. Eighteen patients were normo- (< 30 mg/l), six micro- (30-300 mg/l), and 13 macroalbuminuric (> 300 mg/l) based on urinary albumin concentrations in three separate morning samples. They were compared with 33 control subjects with similar age. Autonomic nerve function was evaluated by measuring the response of heart rate to deep breathing and active standing. Beat-to-beat finger artery blood pressure (Finapres) was tested during active standing. During deep breathing both change in heart rate (17 +/- 11, 9 +/- 7 and 4 +/- 3 beats/min) and ratio between expiratory and inspiratory R-R intervals (1.32 +/- 0.24, 1.14 +/- 0.15 and 1.05 +/- 0.04) decreased from normo- over micro- to macroalbuminuria (p < 0.05 vs normoalbuminuric and control subjects [17 +/- 5 beats/min and 1.28 +/- 0.10, respectively]). Similar results were obtained during active standing with respect to change in systolic arterial blood pressure (3 +/- 8, 2 +/- 13 and -6 +/- 11 mmHg; p < 0.05 vs control subjects [8 +/- 11 mmHg]). However, the response of diastolic arterial blood pressure or mean heart rate to standing up did not differ between any of the groups. The ratio of maximum to minimum R-R interval during the dynamic response of heart rate to active standing decreased with the degree of nephropathy (1.27 +/- 0.17, 1.11 +/- 0.11 and 1.05 +/- 0.06) with significantly higher values in patients with normo- compared with patients with macroalbuminuria (p < 0.05). All patients groups had significantly lower values than control subjects (1.46 +/- 0.22, p < 0.05). The overshoot of the blood pressure after an initial fall during active standing decreased with the degree of diabetic nephropathy. In conclusion, type 1 diabetic patients with long duration of diabetes have signs of cardiovascular autonomic neuropathy, the severity of which is related to the degree of nephropathy.
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| 3. |
- Tisell, Lars-Eric, 1931, et al.
(författare)
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Somatostatin receptor scintigraphy in medullary thyroid carcinoma.
- 1997
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Ingår i: The British journal of surgery. - 0007-1323. ; 84:4, s. 543-7
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Tidskriftsartikel (refereegranskat)abstract
- 111In-radiolabelled (DTPA-D-Phe1)-octreotide scintigraphy can be used to localize neuroendocrine tumours expressing somatostatin receptors (SSTRs). The aim of this paper was to analyse the importance of tumour volume and growth for the visualization by SSTR scintigraphy of metastases from medullary thyroid carcinoma (MTC).
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| 4. |
- Torffvit, Ole, et al.
(författare)
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Lack of association between cystopathy and progression of diabetic nephropathy in insulin-dependent diabetes mellitus
- 1997
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Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 31:4, s. 365-369
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Tidskriftsartikel (refereegranskat)abstract
- Whether an association exists between cystopathy and progression of diabetic nephropathy has never been clarified. The aim of the present study was to measure the degree of cystopathy in relation to the rate of progression of diabetic nephropathy. To that end, 17 insulin-dependent diabetic patients with diabetic nephropathy but without voiding symptoms were investigated urodynamically. The median age of the patients was 45 years (range 27-67 years), diabetes duration 23 years (range 14-44 years) and the serum creatinine level was 162 mumol/L (median, range 65-449 mumol/L) at the time of the study. The progression rate of diabetic nephropathy was analysed retrospectively by measuring changes in yearly mean values of Log10 serum creatinine for a period of 13 years (3-15 years) before the investigation. The progression rate was 0.028 mumol/L/year (median). Patients with a progression rate above and below the median rate were considered to be rapid (n = 8) and slow (n = 9) progressors, respectively. More women than men had a rapid progression rate of nephropathy. Rapid progressors were found to have smaller volume or residual urine (90 vs 165 ml; p < 0.05), larger volume voided (440 vs 270 ml; p < 0.05), lower opening pressure (18 vs 48 cm H2O; p < 0.05) and lower pressure at maximum flow (37 vs 64 cm H2O; p < 0.05) compared to slow progressors. However, these variables were not related to the progression rate of nephropathy (MANOVA). Furthermore, these results should be interpreted with caution because of the natural gender differences in pressure conditions. In conclusion, rapid progression of diabetic nephropathy does not seem to be associated with dysfunction of the urinary bladder measured with cystometry and pressure flow.
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| 5. |
- Johannsson, Gudmundur, 1960, et al.
(författare)
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Growth hormone and the metabolic syndrome.
- 1999
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Ingår i: Journal of endocrinological investigation. - 0391-4097. ; 22:5 Suppl, s. 41-6
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Forskningsöversikt (refereegranskat)abstract
- The association of several risk factors, obesity, dyslipoproteinemia, hepatic steatosis, insulin resistance and hypertension with Type 2 (non-insulin-dependent) diabetes mellitus and myocardial infarction has long been known and has been termed the "metabolic syndrome". In 1988 Reaven introduced syndrome X as the link between insulin resistance and hypertension. It has been suggested that a critical factor in the association between obesity, Type 2 diabetes and cardiovascular morbidity is the mass of intraabdominal fat. Striking similarities exist between the metabolic syndrome and untreated growth hormone (GH) deficiency in adults. The central findings in both these syndromes are abdominal/visceral obesity and insulin resistance. Other features common to both conditions are premature atherosclerosis and increased mortality from cardiovascular diseases. These similarities indicate that undetectable and low levels of GH may be of importance in the metabolic aberrations observed in both these conditions. Recent investigations have found that abdominal/visceral distribution of adipose tissue is associated with endocrine disturbances including increased activity of the hypothalamic-pituitary-adrenal axis and a blunted secretion of GH and sex steroids. Theoretically, these endocrine perturbations can be a consequence of obesity, but the endocrine aberrations may have causal effects. We studied moderately obese, middle-aged men with a preponderance of abdominal body fat. As a group, they had slight to moderate metabolic changes known to be associated with abdominal/visceral obesity. Nine months of GH treatment reduced their total body fat and resulted in a specific and a marked decrease in both abdominal subcutaneous and visceral adipose tissue. Moreover, insulin sensitivity improved and serum concentrations of total cholesterol and triglyceride decreased. Diastolic blood pressure also decreased. The finding that GH replacement in men with abdominal obesity can diminish the negative metabolic consequences of visceral obesity suggests that low levels of this hormone are of importance for the metabolic aberrations associated with visceral/abdominal obesity.
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| 6. |
- Johannsson, Gudmundur, 1960, et al.
(författare)
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Serum leptin concentration and insulin sensitivity in men with abdominal obesity.
- 1998
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Ingår i: Obesity research. - 1071-7323. ; 6:6, s. 416-21
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Tidskriftsartikel (refereegranskat)abstract
- We have examined the association between generalized adiposity, abdominal adiposity, insulin sensitivity, and serum levels of leptin in a cross-sectional study of abdominally obese men.Thirty men, 48 to 66 years of age with a body mass index (BMI) of between 25 kg/m2 and 35 kg/m2 and a waist hip ratio of >0.95, were included in the study. Serum leptin concentration was measured using radioimmunoassay. Total body fat percentage was determined from total body potassium, abdominal adiposity was measured by computed tomography, and the glucose disposal rate (GDR) was measured during an euglycemic, hyperinsulinemic glucose clamp.Significant correlations were found between serum leptin concentration and BMI, percentage body fat, abdominal subcutaneous adipose tissue, serum insulin, GDR, and 24-hour urinary-free cortisol. In a multiple regression analysis, it was shown that abdominal subcutaneous adipose tissue, GDR, and BMI explained 72% of the variability of serum leptin concentration. GDR demonstrated an independent inverse correlation with serum leptin concentration.In abdominally obese men with insulin resistance, it was demonstrated that most of the individual variability in serum leptin concentration was explained by the amount of subcutaneous abdominal adipose tissue, insulin sensitivity, and BMI.
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| 7. |
- Torffvit, Ole, et al.
(författare)
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Urinary excretion of the carboxy terminal domain of type IV collagen is associated with kidney size and function in IDDM
- 1990
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Ingår i: Journal of Diabetic Complications. - 0891-6632. ; 4:4, s. 166-169
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Tidskriftsartikel (refereegranskat)abstract
- We evaluated whether urinary excretion of the carboxy terminal domain (NC1) of Type IV collagen is associated with glomerular filtration rate and kidney size in Type I (insulin-dependent) diabetes mellitus (IDDM). Urinary excretion rate of NC1, glomerular filtration rate (GFR), and kidney size were measured in 16 men with Type I diabetes. Their mean age was 33.3 +/- 6.1 years with a duration of diabetes of 14.9 +/- 3.7 years (mean +/- SD). The urinary excretion rate of NC1 was higher in the diabetic patients than in 18 healthy control subjects. Urinary excretion of NC1 was associated with both kidney size, parenchymal width, and GFR (r = 0.73, p = 0.001; r = 0.63, p = 0.009; r = 0.53, p = 0.04, respectively). The exact relationship between these factors and basement membrane turnover/synthesis remains to be elucidated.
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| 8. |
- Torffvit, Ole, et al.
(författare)
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Urine and serum levels of the carboxyterminal domain (NCl) of collagen IV in membranous glomerulonephritis and diabetic nephropathy
- 1991
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Ingår i: Nephron. - 0028-2766. ; 59:1, s. 15-20
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Tidskriftsartikel (refereegranskat)abstract
- Serum and urinary concentrations of NCl, the non collagenous globular domain of collagen IV, were used as markers for turnover of basement membranes. NCl levels were studied in membranous glomerulonephritis and diabetic nephropathy. Thirteen patients with membranous glomerulonephritis and 8 insulin-dependent diabetic patients with diabetic nephropathy were compared to 16 apparently healthy control subjects. The patients with membranous glomerulonephritis had lower levels of NCl in serum and urine compared to the control subjects. In comparison, the patients with diabetic nephropathy had similar levels of NCl in serum and urine as the control subjects. Furthermore, among patients with membranous glomerulonephritis, those with hypertension had higher serum levels of NCl than those without, which may indicate that hemodynamic factors influence the basement membrane collagen metabolism. It is suggested that there are differences in basement membrane turnover in membranous glomerulonephritis and diabetic nephropathy although there are similarities in glomerular histopathological features. Other possible mechanism are discussed. Further studies are needed to confirm the suggested mechanism.
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| 9. |
- Nilsson, Bengt-Olof, et al.
(författare)
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Effects of polyamine synthesis inhibition on polyamines, growth and mechanical properties in hypertrophic rat urinary bladder
- 1998
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Ingår i: Pharmacology and Toxicology. - 1600-0773. ; 82:6, s. 287-294
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Tidskriftsartikel (refereegranskat)abstract
- The polyamines putrescine, spermidine and spermine, are ubiquitous intracellular metabolites associated with growth and protein synthesis. In this study effects of polyamine synthesis inhibition on bladder growth, polyamine levels and mechanical properties were investigated in rat urinary bladder subjected to partial outflow obstruction that causes bladder hypertrophy. The S-adenosyl methionine decarboxylase inhibitor CGP-48664 (5 and 20 mg kg-1) was administered alone or in combination with the ornithine decarboxylase inhibitor DFMO (500 mg kg-1), starting one day before creation of partial outflow obstruction and then daily for 7 days. The bladder muscle level of putrescine was increased 38 times and that of spermine reduced by 4 times while spermidine was unchanged after treatment with CGP-48664 (20 mg kg-1). The increase in putrescine was abolished in animals receiving CGP-48664 in combination with DFMO. Treatment with polyamine synthesis inhibitors could not prevent or reduce the hypertrophy of the bladder as judged by bladder wet weight and protein contents. The effects on polyamine quantities were not associated with changes in Ca(2+)-force relationship or in agonist and electrically stimulated force. In summary, treatment of rats with polyamine synthesis inhibitors resulted in changes in polyamine levels in the growing urinary bladder but did not affect growth or mechanical properties.
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| 10. |
- Lehto, Markku
(författare)
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Search for MODY and Type 2 diabetes genes
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Diabetes is a heterogeneous disease influenced by both environmental and genetic factors. Maturity-onset diabetes of the young (MODY) is considered as a subform of Type 2 diabetes, which is inherited in an autosomal dominant fashion and expressed at childhood or early adult life. The aims of the study was to a) search for susceptibility loci for Type 2 diabetes in 26 Finnish families with late-onset diabetes by using a genome scan approach, b) clone and search for mutations in the genes causing maturity-onset diabetes of the young (MODY) in Scandinavian families with early-onset diabetes, and c) perform phenotypic characterization of MODY families. As a result of the genome wide scan, a subset of Type 2 diabetic families, presenting with an insulin secretory defect, were positively linked to the MODY3 region on chromosome 12, which was named NIDDM2. In the search for MODY-mutations in Scandinavian families with early-onset diabetes, we identified 2 families with mutations in the hepatocyte nuclear factor (HNF) -4a (MODY1) gene, 4 families with mutations in the glucokinase (MODY2) gene and 12 families with a mutations in the HNF-1a (MODY3) gene. Notable, a mutational hot spot was identified in exon 4 of the HNF-1a gene. In addition, three families with early-onset diabetes were found to carry a specific mutation (A3243G) in the mitochondrial tRNALeu(UUR) gene. Both MODY1 and MODY3 mutation carriers had impaired insulin secretion suggesting defects in pancreatic b-cell function. Distinct from common Type 2 diabetes, MODY mutation carriers had no signs of dyslipidemia or insulin resistance. Of note, patients with MODY1 exhibit also low triglyceride and apoCIII concentrations even after long duration of diabetes. Therefore, mutations in the HNF-4a gene could also affect lipid metabolism. Absence of antibodies against glutamic acid decarboxylase (GAD) suggests that autoimmunity does not play a major role in the development of MODY diabetes. Conclusions: In Scandinavian populations, the MODY3 locus on chromosome 12 is associated with both early- and late-onset forms of diabetes. The underlying genetic defect in NIDDM2 remains to be determined. Among the Scandinavian families with early-onset diabetes, mutations in the HNF-1a (MODY3) gene were the most common cause of MODY.
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