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Biomedical subjects

Michael Brändle

Publications and source records attributed to Michael Brändle.

14 recordsLinked to original sources
PubMed2006

Health economic implications of irbesartan plus conventional antihypertensive medications versus conventional blood pressure control alone in patients with type 2 diabetes, hypertension, and renal disease in Switzerland.

OBJECTIVES: The aim of this health economic modelling study was to investigate the effect of irbesartan combined with conventional antihypertensive medications compared to conventional antihypertensive therapy alone on the progression of nephropathy in patients with hypertension, type 2 diabetes and microalbuminuria in a Swiss setting. METHODS: In simulated patients with hypertension and type 2 diabetes, treatment of microalbuminuria with irbesartan 300 mg daily plus conventional antihypertensive medications was compared to a control regimen (conventional medications excluding angiotensin converting enzyme inhibitors, other angiotensin-2-receptor antagonist and dihydropyridine calcium channel blockers). Progression from microalbuminuria to nephropathy, doubling of serum creatinine, ESRD, and all-cause mortality was simulated over a 25-year time horizon using a published Markov model adapted to a Swiss setting. Transition probabilities were based on the Irbesartan in Reduction of Microalbuminuria-2 Study, Irbesartan in Diabetic Nephropathy Trial and other sources. Costs and clinical outcomes were discounted at 5% annually according to Swiss guidelines, and a third party payer perspective was taken. RESULTS: Treatment with irbesartan was projected to improve mean life expectancy by 0.57 years compared to conventional antihypertension treatment (undiscounted 1.22 years). Irbesartan treatment was associated with cost savings of CHF 21,488 per patient over the 25-year time horizon. Sensitivity analysis showed that irbesartan therapy remained dominant to conventional antihypertension treatment over a range of plausible assumptions. CONCLUSIONS: Addition of irbesartan to conventional antihypertension therapy was projected to improve life expectancy and reduce costs in hypertensive patients with type 2 diabetes and microalbuminuria in a Swiss setting.

Albuminuria↗
PubMed2006

Increased prevalence of high Body Mass Index in patients presenting with pituitary tumours: severe obesity in patients with macroprolactinoma.

INTRODUCTION: Prolactinoma has been associated with obesity. As opposed to ACTH- and GH-secreting adenoma, the mechanism by which macroprolactinoma causes obesity has not been fully understood. Having seen patients with both prolactinoma and obesity and more recent literature on brain dopamine, dopamine 2 receptors and obesity, we re-evaluated the potential relationship between prolactinoma and obesity. METHODS: Data of patients with pituitary adenomas were collected retrospectively over a period of 20 years. 399 patients with well-documented pituitary adenomas and information about pre-treatment body mass index (BMI), age, sex, and tumour type were analysed. RESULTS: Elevated BMI (> or = 30 kg/m2) was observed in 8/36 patients (22.2%) with ACTH-producing tumours, in 15/70 (21.4%) with GH-producing tumours, in 25/100 (25%) with macroprolactinoma, in 8/81 (9.9%) with microprolactinoma, and in 18/105 (17.1%) with inactive macroadenomas. Macroprolactinoma patients had a mean BMI value (27.5 +/- 7.7 kg/m2) similar to that of patients with Cushing's disease (27.2 +/- 5.9 kg/m2) and acromegaly (27.4 +/- 4.4 kg/m2) and on average a significantly higher BMI value compared to that of patients with inactive macroadenomas (25.8 +/- 4.4 kg/m2) (95% CI 1.2, 4.4; p-value <0.001). Compared to the general population, the proportion of BMI > or = 30 kg/m2 in patients with macroprolactinoma was significantly higher (95% CI 0.1, 0.29; p-value <0.001). CONCLUSIONS: Average BMI in macroprolactinoma patients is significantly higher than BMI in patients with inactive adenomas. Macroprolactinoma is associated with increased frequency of obesity compared to the general population. We propose that in a subgroup of individuals obesity and macroprolactinoma may share a common basis, namely decreased dopamine 2 receptor-mediated actions.

ACTH-Secreting Pituitary Adenoma↗
PubMed2006

Effect of thyroxine replacement on serum IGF-I, IGFBP-3 and the acid-labile subunit in patients with hypothyroidism and hypopituitarism.

OBJECTIVE: To describe the effect of T4 replacement in patients with primary and central hypothyroidism on components of the IGF binding protein complex: IGF-I, the acid-labile subunit (ALS) and IGFBP-3. PATIENTS AND METHODS: We determined IGF-I, ALS and IGFBP-3 (by 125I-IGF-II ligand blots and immunoblots) in serum of 19 patients with primary and 11 patients with central hypothyroidism. RESULTS: Mean (+/- SD) free T4 (fT4) increased from 4.4 +/- 2.4 pmol/l at baseline to 18.6 +/- 5.2 pmol/l following T4 therapy. In patients with primary hypothyroidism, IGF-I concentrations increased from 101 +/- 57 to 158 +/- 60 microg/l (P < 0.001) and ALS from 12.6 +/- 4.7 to 15.6 +/- 5.2 mg/l (P = 0.001). IGFBP-3 levels (in arbitrary units, AU), assessed by 125I-IGF-II ligand blot and by Western blot (the intensity of the 45/42-kDa doublet following T4 replacement defined as 1 AU) increased from 0.74 +/- 0.47 to 1 (P = 0.029) and from 0.76 +/- 0.42 to 1 (P = 0.018), respectively. In patients with hypopituitarism, IGF-I and ALS concentrations increased on T4 therapy from 49 +/- 23 to 97 +/- 36 microg/l (P < 0.001) and from 7.8 +/- 4.1 to 11.0 +/- 2.7 mg/l (P = 0.010), respectively. IGFBP-3 remained unchanged during T4 replacement. CONCLUSIONS: T4 replacement increases the serum levels of IGF-I and ALS in patients with primary as well as central hypothyroidism. IGFBP-3 levels increase in response to T4 replacement in patients with primary hypothyroidism but not in those with central hypothyroidism, suggesting that thyroid hormones increase IGF-I and ALS but not IGFBP-3 in patients with GH deficiency.

Acromegaly↗
PubMed2005

Effect of pituitary surgery in patients with acromegaly on adiponectin serum concentrations and alanine aminotransferase activity.

BACKGROUND: Thiazolidinediones increase adiponectin concentrations, improve insulin sensitivity and fatty liver disease (reflected by decreased alanine aminotransferase [ALT] activity) in type 2 diabetes. This study was performed to test the effect of neurosurgery in acromegaly (sharing at baseline insulin resistance but not increased visceral fat with type 2 diabetes) on insulin sensitivity, adiponectin concentrations and ALT activity. METHODS: Sixteen patients with acromegaly undergoing pituitary surgery (and 16 patients with type 2 diabetes treated with pioglitazone) were included. Insulin sensitivity, adiponectin concentrations and ALT activity were determined at baseline and after 4 months. RESULTS: Pituitary surgery in acromegalic patients increased adiponectin concentrations from mean (+/-S.D.) 9.3+/-3.8 to 10.2+/-4.4 mg/L (p<0.05). HOMA scores fell from 6.8+/-4 at baseline to 3.5+/-0.9 following neurosurgery (p<0.005) and ALT activity decreased from median (range) 21 (13-30) to 13 (10-42) U/L (p<0.05). In type 2 diabetics, pioglitazone treatment increased adiponectin concentrations; HOMA scores and ALT activity fell significantly. CONCLUSION: Pituitary surgery in patients with acromegaly led to a marked increase in insulin sensitivity and a slight increase in adiponectin serum concentrations, whereas ALT activity significantly decreased.

Acromegaly↗
PubMed2004

Assessment of hyperinsulinaemia at the termination of the prolonged fast.

BACKGROUND: Traditional criteria to diagnose hyperinsulinaemic hypoglycaemia are based on insulin measurements by unspecific insulin assays. This study was performed to test whether these traditional criteria can be applied when insulin is measured by specific immunoassays. METHODS: 29 consecutive patients undergoing a prolonged fast were included; 11 patients with insulinoma and 18 healthy individuals. We determined plasma glucose, insulin, C-peptide, proinsulin, and beta-hydroxybutyrate concentrations at the termination of the fast. Insulin was measured by an unspecific radioimmunoassay (RIA) and a specific enzyme-linked immunosorbent assay (ELISA). RESULTS: In 11 insulinoma patients, insulin concentrations at median plasma glucose concentration of 2.1 (range 1.3-2.5) mmol/l were 170 (76-340) pmol/l measured by RIA and 61 (11-156) pmol/l by ELISA. Insulin concentrations measured by RIA confirmed hyperinsulinaemia (i.e., >36 pmol/l, the proposed cut-off value for traditional insulin assays) in all insulinoma patients, whereas insulin concentrations measured by ELISA were <36 pmol/l in four patients. In three insulinoma patients, insulin concentrations measured by ELISA were <18 pmol/l, a proposed cut-off level to diagnose hyperinsulinaemia for specific insulin assays. CONCLUSION: When insulin concentrations are measured by specific immunoassays in patients evaluated for fasting hypoglycaemia, traditional reference values cannot be applied.

3-Hydroxybutyric Acid↗
PubMed2004

Selective arterial calcium stimulation and hepatic venous sampling in the evaluation of hyperinsulinemic hypoglycemia: potential and limitations.

PURPOSE: To describe the potential and limitations of selective arterial calcium stimulation and hepatic venous sampling (ASVS) in the evaluation of patients with hyperinsulinemic hypoglycemia. MATERIALS AND METHODS: Twenty-seven consecutive adult patients with documented hyperinsulinemic hypoglycemia undergoing an ASVS test and histologically confirmed diagnosis were included. RESULTS: By histology, 24 patients were found to have an insulinoma, two had islet cell hyperplasia, and one had insulin-secreting neuroendocrine carcinoma of the liver. ASVS correctly predicted the source of excessive insulin secretion in 26 of 27 (sensitivity, 96%) patients. In two patients with an insulinoma, ASVS had to be repeated for correct diagnosis; in one patient with a glucose-sensitive insulinoma, ASVS was falsely negative. In one patient, a falsely negative ASVS test was caused by diazoxide treatment; in another patient a falsely negative ASVS test occurred because of extraordinarily high baseline insulin levels when the calcium stimulation was performed. CT and/or MR imaging correctly predicted the source of excessive insulin secretion in 59% of patients, the sensitivity of the intraoperative exploration was 88%. CONCLUSIONS: In the authors' experience, the ASVS test is superior to CT/MR imaging and even the intraoperative exploration in identifying the source of excessive insulin secretion in patients with hyperinsulinemic hypoglycemia. To prevent false negative ASVS tests, medications with an influence on insulin secretion have to be discontinued prior to ASVS and two baseline blood samples should be obtained before the calcium stimulation is performed.

Adult↗
PubMed2004

A novel succinate dehydrogenase subunit B gene mutation, H132P, causes familial malignant sympathetic extraadrenal paragangliomas.

We report a family with malignant sympathetic paragangliomas (PGL) exhibiting a new type of germline mutation in the succinate dehydrogenase subunit B (SDHB) gene. Two affected brothers, presenting with symptoms at the ages of 25 and 52 yr, suffered from malignant abdominal extraadrenal sympathetic PGL. They died of their disease at ages 43 and 61 yr. Their mother had the same history of signs and symptoms, suggesting a catecholamine-producing tumor at the age of 55 yr. Analysis of the germline DNA from these three patients revealed a novel mutation in exon 4 (H132P) of the SDHB gene. This mutation was absent in 160 control chromosomes. Loss of heterozygosity analysis of the tumors showed a loss of one SDHB allele, and RT-PCR-based expression analysis confirmed the exclusive expression of the mutated allele in both tumors. A review of the published PGL families revealed malignant tumors in seven of 12 well-documented families with SDHB mutation-associated extraadrenal PGL. These findings, as well as findings of the family reported here, suggest a strong causal relationship of SDHB germline mutations with malignant extraadrenal abdominal PGL and imply the necessity of a close follow-up of affected individuals and family members.

Abdominal Neoplasms↗
PubMed2004

Insulin determination by specific and unspecific immunoassays in patients with insulinoma evaluated by the arterial stimulation and venous sampling test.

OBJECTIVE: The aim of this study was to compare insulin concentrations measured by a traditional radioimmunoassay (RIA) and a more specific enzyme-linked immunosorbent assay (ELISA) in blood samples obtained during the arterial stimulation and venous sampling (ASVS) test in patients with insulinoma. DESIGN: Prospective case series. METHODS: In 14 patients with an insulinoma undergoing an ASVS test, blood samples were obtained from the hepatic vein at baseline and 60 s after calcium injection into an artery supplying the tumour and a control artery (supplying pancreatic tissue without tumour). A selective arterial calcium stimulation was performed in five additional patients without evidence for an insulinoma. We measured insulin by a traditional RIA and a specific immunoassay. RESULTS: In patients with insulinoma, insulin concentrations increased between 2.3- and 24.2-fold (median 8.2-fold) when measured by RIA and between 7.3- and 59.4-fold (median 16) when measured by ELISA following calcium injection into the artery supplying the tumour. Following calcium injection into the control artery, insulin concentrations were 0.6 to 1.3 times (median 1.0) the baseline values by RIA and 0.5 to 2.5 times (median 1.1) the baseline values by ELISA. In patients without insulinoma, insulin concentrations increased following calcium stimulation between 0.7- and 2.1-fold (median 1.3-fold) when measured by RIA and between 0.6- and 4.7-fold (median 1.3-fold) when measured by ELISA. CONCLUSIONS: When insulin is measured by specific immunoassays, a higher cut-off (i.e. five- to sixfold increase) rather than the traditional criterion of a twofold increase should be used to localise an insulinoma during the ASVS test. The increase in insulin concentrations following calcium stimulation is significantly higher when insulin is measured by a specific assay compared with results obtained with traditional RIAs.

Adult↗
PubMed2003

Impact of thyroid dysfunction on serum cystatin C.

BACKGROUND: Serum cystatin C (CysC) is a novel marker for kidney function that has been claimed to be superior to serum creatinine. Thyroid dysfunction may alter creatinine, which has been found to be increased in hypothyroidism and decreased in hyperthyroidism. This study was performed to evaluate whether changes in CysC and creatinine are parallel during the treatment of hypo- and hyperthyroidism, respectively. METHODS: Prospective case series of 22 consecutively referred patients with thyroid dysfunction. Creatinine and CysC were determined at the time of diagnosis of hypo- and hyperthyroidism, and when free thyroxine (fT4) returned into the normal range. Hypothyroid patients were treated with levothyroxine. Hyperthyroid patients were treated with antithyroid drugs, surgery, or radioiodine. RESULTS: Nine patients with hypothyroidism and 13 patients with hyperthyroidism were included. In patients with hypothyroidism mean fT4 (+/-SD) was 4.9 +/- 2.5 pmol/L (reference, 12 to 22) at diagnosis and increased to 16.6 +/- 3.6 pmol/L when patients were treated with levothyroxine. Creatinine decreased from 86 +/- 13 micromol/L (reference, 70 to 105) in the hypothyroid state to 76 +/- 16 micromol/L when fT4 normalized (P = 0.062), whereas CysC increased from 0.84 +/- 0.17 mg/L (reference, 0.63 to 1.33) to 1.1 +/- 0.28 mg/L (P < 0.001). In patients with hyperthyroidism, mean fT4 was 54.6 +/- 22.7 pmol/L (reference, 12 to 22) at diagnosis and decreased to 15.8 +/- 3.6 pmol/L following treatment with antithyroid drugs, thyroid surgery, or radioiodine. Creatinine increased from 67 +/- 15 micromol/L at diagnosis of hyperthyroidism to 75 +/- 9 micromol/L when fT4 normalized (P = 0.004), whereas CysC declined from 1.32 +/- 0.17 mg/L to 0.95 +/- 0.19 mg/L (P < 0.001). CONCLUSION: Thyroid dysfunction has a major impact on CysC levels. Therefore, thyroid function has to be considered when CysC is used as a marker of kidney function. In contrast to creatinine concentrations, CysC levels are lower in the hypothyroid and higher in the hyperthyroid state as compared with the euthyroid state.

Adolescent↗