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Biomedical subjects

M Hofmann

Publications and source records attributed to M Hofmann.

At least 73 records · Page 4Linked to original sources
PubMed1999

Small and large unilamellar vesicle membranes as model system for bile acid diffusion in hepatocytes.

Uptake of bile acids into the liver cell occurs via active transport or passive diffusion. In a model system, passive diffusion was studied in liposomes using pyranine fluorescence. Rate constants for the diffusion of diverse more polar or more apolar bile acids were examined. Hydrophobic lithocholic acid (LCA) revealed a maximal rate constant of 0.057 s(-1); with the polar ursodeoxycholic acid (UDCA), the value was 0.019 s(-1). UDCA (3 mol%) effectively decreased the rate constant of 0.1 mM chenodeoxycholic acid (CDCA), whereas cholesterol reached a similar decrease only between 5 and 10 mol%. At higher concentrations of CDCA (above 1 mM) or LCA (0.3-0.4 mM), breaking up of liposomal structure was confirmed by light-scattering decrease and increase of carboxyfluorescein fluorescence. Changes in lipid composition of phosphatidylcholine (PC)- small unilamellar vesicles (SUVs) or large unilamellar vesicles (LUVs) also caused decreasing rate constants. For a cardiolipin (CL):PC ratio of 1:20 the CDCA (0.1 mM) rate constant was 71% lower (0.015 s(-1)) and for a sphingomyelin (SM):PC ratio of 2:1 the rate constant was 50% lower (0.026 s(-1)). Changes in membrane fluidity were detected using membrane anisotropy measurements with the 1,6-diphenyl-1,3, 5-hexatriene (DPH) method. Membrane fluidity was reduced with cholesterol- but not with CL- or SM-containing SUVs (ratio: cholesterol, CL, SM:PC of 1:5). This model system is currently used for the analysis of more complex lipid vesicles resembling the plasma/hepatocyte membrane, which is either stabilized or destabilized by appropriate conditions. The results should become clinically relevant.

Animals↗
PubMed1999

The effect of bile salts and calcium on isolated rat liver mitochondria.

Intact mitochondria were incubated with and without calcium in solutions of chenodeoxycholate, ursodeoxycholate, or their conjugates. Glutamate dehydrogenase, protein and phospholipid release were measured. Alterations in membrane and organelle structure were investigated by electron paramagnetic resonance spectroscopy. Chenodeoxycholate enhanced enzyme liberation, solubilized protein and phospholipid, and increased protein spin label mobility and the polarity of the hydrophobic membrane interior, whereas ursodeoxycholate and its conjugates did not damage mitochondria. Preincubation with ursodeoxycholate or its conjugate tauroursodeoxycholate for 20 min partially prevented damage by chenodeoxycholate. Extended preincubation even with 1 mM ursodeoxycholate could no longer prevent structural damage. Calcium (from 0.01 mM upward) augmented the damaging effect of chenodeoxycholate (0.15-0.5 mM). The combined action of 0.01 mM calcium and 0.15 mM chenodeoxycholate was reversed by ursodeoxycholate only, not by its conjugates tauroursodeoxycholate and glycoursodeoxycholate. In conclusion, ursodeoxycholate partially prevents chenodeoxycholate-induced glutamate dehydrogenase release from liver cell mitochondria by membrane stabilization. This holds for shorter times and at concentrations below 0.5 mM only, indicating that the different constitution of protein-rich mitochondrial membranes does not allow optimal stabilization such as has been seen in phospholipid- and cholesterol-rich hepatocyte cell membranes, investigated previously.

Animals↗
PubMed1999

Characterisation of the murine gene encoding the intracellular hyaluronan receptor IHABP (RHAMM).

We have recently shown that the published cDNA sequence encoding the murine cell surface receptor for hyaluronan-mediated motility (RHAMM) in fact represents a partial sequence of the cDNA encoding a new intracellular hyaluronic acid binding protein (IHABP). Here we publish the genomic organisation, including 700bp sequences of the promoter region, of the IHABP gene. The IHABP gene consists of 18 exons and spans more than 25kb. Part of the IHABP gene is identical with the published data on RHAMM. The IHABP gene apparently possesses one promoter region with one major transcriptional start point. IHABP is ubiquitously expressed at the mRNA and the protein level in all murine tissues, suggesting that the function of this intracellular hyaluronan binding protein is not restricted to migrating cells.

5' Untranslated Regions↗
PubMed1999

Octreotide (somatostatin analog) treatment reduces endothelial cell dysfunction in patients with diabetes mellitus.

Octreotide is a long-acting somatostatin analog that has been shown to have various effects in diabetes. This study was performed to evaluate whether octreotide affects the vascular complications of diabetes mellitus. Albuminuria and serum thrombomodulin were used as markers of vascular and renal dysfunction. We studied the effect of octreotide in 27 patients with insulin-dependent diabetes mellitus (IDDM). They received 200 microg octreotide per day over a period of 6 months. As a marker of endothelial cell damage, we measured the serum thrombomodulin level. We also measured urinary albumin excretion, hemoglobin A1c (HbA1c), insulin-like growth factor-1 (IGF-1), and other parameters. IGF-1 decreased from 123 ng/mL before treatment to 114 ng/mL after 6 months of octreotide treatment (P = .009), while no significant change was observed in the unblinded control group (from 103 ng/mL to 102 ng/mL after 6 months of treatment). Urinary albumin excretion in patients with macroalbuminuria declined from 1,124 mg/L before octreotide treatment to 556 mg/L after 6 months of treatment (P < .05), whereas no change was observed in the control group. There was also a reduction of the plasma thrombomodulin level from 61.8 ng/mL to 46.1 ng/mL (P < .07) after 6 months of treatment. Furthermore, HbA1c decreased from 8.75% +/- 1.27% to 8.12% +/- 1.23% (P < .07) after octreotide treatment.

Adult↗
PubMed1999

alpha-Lipoic acid decreases oxidative stress even in diabetic patients with poor glycemic control and albuminuria.

In the present cross-sectional study, the influence of alpha-lipoic acid on markers of oxidative stress, assessed by measurement of plasma lipid hydroperoxides (ROOHs), and on the balance between oxidative stress and antioxidant defence, determined by the ratio ROOH/(alpha-tocopherol/cholesterol), was examined in 107 patients with diabetes mellitus. Patients receiving alpha-lipoic acid (600 mg/day for > 3 months) had significant lower ROOHs and a lower ROOH/(alpha-tocopherol/cholesterol) ratio than those without alpha-lipoic acid treatment [ROOH: 4.76 +/- 2.49 vs. 7.16 +/- 3.22 mumol/l; p < .0001] and [ROOH/(alpha-tocopherol/cholesterol): 1.37 +/- 0.72 vs. 2.16 +/- 1.17; p < 0.0001]. In addition, the influence of glycemic control and albuminuria on ROOHs and on the ratio of ROOH/(alpha-tocopherol/cholesterol) was examined in the presence and absence of alpha-lipoic acid treatment. Patients were subdivided into three groups based on (1) their HbA1 levels (< 7.5, 7.5-9.5, and > 9.5%) and (2) their urinary albumin concentrations (< 20, 20-200, and > 200 mg/l). Neither poor glycemic control, nor the presence of micro- or macroalbuminuria prevented the antioxidant effect of alpha-lipoic acid. Using stepwise multiple regression analysis, alpha-lipoic acid was found to be the only factor significantly predicting low ROOHs and a low ratio of ROOH/(alpha-tocopherol/cholesterol). These data provide evidence that treatment with alpha-lipoic acid improves significantly the imbalance between increased oxidative stress and depleted antioxidant defence even in patients with poor glycemic control and albuminuria.

Albuminuria↗
PubMed1999

Congenital diaphragmatic hernia: ultrasonic measurement of fetal lungs to predict pulmonary hypoplasia.

OBJECTIVE: The purpose of this study was to assess the value of biometric lung measurements for the prediction of severe fetal pulmonary hypoplasia in congenital diaphragmatic hernia and to determine whether a correlation between lung measurements and autopsy findings or neonatal outcome could be established. DESIGN: Prospective study, between 1991 and 1997. SUBJECTS: Nineteen fetuses with congenital diaphragmatic hernia. METHODS: In addition to standard biometry, sonographic measurement of the transverse thoracic diameter, sagittal thoracic diameter, fetal lung diameters at the level of the four-chamber view and lung/thoracic circumference ratio were performed. These were compared with the standard curves defined by Merz and colleagues. Autopsy examinations were performed to determine lung weight, lung weight/body weight ratio and radial alveolar count. RESULTS: Five fetuses (26%) were terminated before 24 weeks of gestation. All of these fetuses had lung measurement values below the 5th centile. Eleven of 14 fetuses (78.6%) with pulmonary hypoplasia diagnosed after 24 weeks of gestation died postnatally. The mortality rate was 70% (7/10) in the fetuses without associated anomalies. The sonographic diagnosis of fetal pulmonary hypoplasia was made in all fetuses who died postnatally. All fetuses with a lung diameter/thoracic circumference ratio below 0.09 died. Three fetuses, which had values within the normal range, survived. In contrast, measurements of the bony thorax (transverse and sagittal thoracic diameters, thoracic circumference) did not provide an indication of the presence of fetal pulmonary hypoplasia. Pulmonary hypoplasia was confirmed at autopsy in all fetuses on the basis of lung weight, lung/body weight ratio or radial alveolar count. Concomitant with pulmonary hypoplasia was polyhydramnios in ten fetuses (71.4%), mediastinal shift in 11 fetuses (78.6%), intrathoracic herniated stomach in six fetuses (42.9%) and associated malformations in four fetuses (28.6%). Postnatal mortality for these conditions was 80%, 78.6%, 100% and 100%, respectively. Postnatal mortality was 75%, 70% and 100% in the fetuses with an isolated diaphragmatic hernia. CONCLUSION: The results of this investigation suggest that the assessment of fetal lung diameter and the use of the lung diameter/thoracic circumference ratio are further useful prognostic parameters in the management of congenital diaphragmatic hernia.

Biometry↗
PubMed1999

Semi-closed femoropopliteal thromboendarterectomy: a prospective study.

OBJECTIVE: to study the primary patency rates of angioscopically controlled thromboendarterectomies of the superficial femoral artery. DESIGN: prospective open study. METHODS: between 1990 and 1995, femoropopliteal thromboendarterectomies were performed in 63 patients (41 male, 22 female). Postoperative follow up was performed at 3- to 6-month intervals using non-invasive pressure measurements plus IVDSA at 1 year. RESULTS: eight patients were not evaluable, leaving 55 patients eligible for follow-up analysis. Postoperative complications (arteriovenous fistulas, false aneurysms) were observed in 5.4% of patients. Immediate perioperative occlusions occurred in 7.3%, early occlusions in 21.8% and late occlusions in 16.4% of all cases. The mean follow-up was approximately 57 months. The mean primary patency rate at 5 years was 44.5% (28 patients with the superficial femoral artery still open). Six patients died during the follow-up period. CONCLUSIONS: in contrast to the very positive reports found in recent literature, this prospective study shows a lower five-year patency rate for semi-closed femoropopliteal thromboendarterectomy than for bypass grafting. Thromboendarterectomy cannot be considered as a standard procedure in revascularisation of the femoropopliteal region.

Aged↗
PubMed1999

The effects of high-intensity and low-intensity cycle ergometry in older adults with knee osteoarthritis.

BACKGROUND: People with osteoarthritis (OA) of the knee experience pain and deconditioning that lead to disability. This study challenged the clinical belief that repetitive lower extremity exercise is not indicated in persons with knee OA. The effects of high-intensity and low-intensity stationary cycling on functional status, gait, overall and acute pain, and aerobic capacity were examined. METHODS: Thirty-nine adults (71+/-6.9 years old) with complaints of knee pain and diagnosis of OA were randomized to either a high-intensity (70% heart rate reserve [HRR]) or low-intensity (40% HRR) exercise group for 10 weeks of stationary cycling. Participants cycled for 25 minutes, 3 times per week. Before and after the exercise intervention they completed the Arthritis Impact Measurement Scale 2 for overall pain assessment, underwent timed chair rise, 6-minute walk test, gait, and graded exercise treadmill tests. Acute pain was reported daily with a visual analog scale and the Western Ontario and McMaster Universities Osteoarthritis Index scale. RESULTS: Analysis of variance revealed that participants in both groups significantly improved in the timed chair rise, in the 6-minute walk test, in the range of walking speeds, in the amount of overall pain relief, and in aerobic capacity. No differences between groups were found. Daily pain reports suggested that cycling did not increase acute pain in either group. CONCLUSIONS: Cycling may be considered as an alternative exercise modality for patients with knee OA. Low-intensity cycling was as effective as high-intensity cycling in improving function and gait, decreasing pain, and increasing aerobic capacity.

Activities of Daily Living↗
PubMed1999

Spectrotemporal mapping of high-resolution ECGs in experimental myocardial infarction: comparison with time-domain analysis and epicardial electrograms.

The study was undertaken to evaluate the relationship of signal-averaged ECG (SA-ECG) readings in the frequency domain (STM) and epicardial electrograms (EE) recorded before and after acute myocardial infarction (AMI) in pigs and to compare the changes with findings in time-domain analysis (TDA). In 20 pigs the left anterior descending artery (LAD) was ligated. Prior to ligation, a SA-ECG was recorded (method of Simson) and bipolar electrodes were used to register EE in the areas supplied by the LAD and the circumflex artery (CIRC). Five minutes after LAD ligation, all measurements were repeated. Time-domain parameters were QRS duration (QRS D) and the duration of the signal below 30 microV (LAS 30). Beginning at a point of 20 ms before the QRS end, the frequency spectra (0-200 Hz) of 25 segments of 80-ms duration at the QRS end were analyzed. The volumes below the 25 curves were analyzed separately for 0-50 Hz, 51-100 Hz, 101-150 Hz, and 151-200 Hz. After AMI, five pigs died within 7 minutes. In 15 pigs, QRS D as well as LAS 30 lengthened significantly (P<0.05; P<0.001). Spectrotemporal mapping (STM) showed a significant decrease of the frequencies above 50 Hz (51-200 Hz) in the entire group and in the animals with late potentials (P<0.05). EE of the LAD area were significantly prolonged (P<0.01); this did not correlate with the changes in STM parameters. In pigs acute myocardial infarction causes a shift towards lower frequencies in the STM which most likely reflects the slowed depolarisation in the ischemic area.

Animals↗
PubMed1999

Cell specific effects of glucocorticoid treatment on the NF-kappaBp65/IkappaBalpha system in patients with Crohn's disease.

UNLABELLED: BACKGROUND/AIMS/PATIENTS: Glucocorticoid treatment is known to reduce nuclear factor-kappa B (NF-kappaB)p65 binding activity and activation in lamina propria cells of patients with Crohn's disease. However, lamina propria cells of glucocorticoid treated patients did not show increased expression of IkappaBalpha, and the hypothesised upregulation of IkappaBalpha by glucocorticoid treatment has not yet been shown in vivo. To investigate whether cells other than lamina propria localised mononuclear cells contribute to increased IkappaBalpha, resection gut specimens from patients matched for Crohn's disease activity index (CDAI) with or without glucocorticoid treatment were studied, and changes in the NF-kappaB/IkappaBalpha system were determined in the lamina propria as well as in underlying submucosal and endothelial cells. METHODS: Changes in the NF-kappaB/IkappaBalpha system were determined by immunohistochemistry, electrophoretic mobility shift assay, and western blot analysis in resected gut specimens from patients matched for CDAI and van Hees index with or without long term glucocorticoid treatment. RESULTS: Resection gut specimens from patients with Crohn's disease under glucocorticoid treatment had significantly lower nuclear NF-kappaBp65 levels in mononuclear, epithelial, and endothelial cells than samples from CDAI and van Hees index matched patients not having glucocorticoid treatment. Nuclear NF-kappaBp65 showed a strong positive correlation with both the CDAI (r = 1 for both groups) and the van Hees index (r = 0.605 for untreated and r = 0.866 for glucocorticoid treated specimens). Lower nuclear translocation of NF-kappaBp65 in the glucocorticoid treated group was paralleled by higher IkappaBalpha levels in vascular endothelial cells, but not in infiltrating mononuclear cells. CONCLUSION: A comparison of resection gut specimens from untreated and treated CDAI matched patients with Crohn's disease showed downregulation of NF-kappaB binding activity and NF-kappaBp65 expression and cell specific induction of endothelial IkappaBkappa expression in the glucocorticoid treated group. As the two groups showed similar disease activity (CDAI, van Hees index), the activation of the NF-kappaBp65/IkappaBalpha system must be only part of the inflammatory cascade leading to the clinical appearance of Crohn's disease.

Adult↗
PubMed1999

[Value of p53, urokinase plasminogen activator, PAI-1 and Ki-67 in vulvar carcinoma].

OBJECTIVE: The present study was to measure new prognostic factors including the plasminogen activator urokinase and the plasminogen inhibitor PAI-1, as well as p53 and Ki-67, a marker of proliferation and to compare the clinical value of these in relation to the classic histopathological prognostic factors. MATERIAL AND METHODS: The patient collective included 45 patients with vulvar carcinoma, both primary tumors and recurrences. RESULTS: Highly significant correlations were found for tumor diameter and thickness. According to Kaplan-Meier estimations, the influence of thickness on the prognosis had a p-value of 0.048, while the influence of diameter had a p-value of 0.029. The variable grading was also significantly associated to the probability of survival (p = 0.01). There was no statistically significant correlation between p53 and the parameters grading, degree of keratinization and Ki-67 color index. The correlation between p53 and PAI-1 as well as between UPA and PAI-1 was highly significant. According to the Kaplan-Meier estimations, Ki-67, UPA and PAI-1 had no influence on survival in our group of patients. CONCLUSIONS: For p53, the median value could be used as a divider with the median survival of patients with a p53 below 122 pg/mg protein being 151 months and with a p53 above 122 pg/mg being only 61 months. The corresponding p-value was significant at 0.0201.

Adult↗
PubMed1998

[Multiple endocrine neoplasia associated with multiple lipomas].

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN-1) is characterized by tumors of the parathyroids, the neuroendocrine pancreas-duodenum and the anterior pituitary, but shows also a wide clinical variety of other symptoms. CASE REPORT: We present a case of a 68-year-old woman with a 18 year history of MEN-1 consisting of gastrinoma and primary hyperparathyroidism. Beside these typical symptoms, the patient suffered from thyroid adenoma, malignant kidney tumor and multiple subcutaneous lipomas. RESULT: While the number of autopsies declined from 113 in 1977 to 66 in 1984, the number of diagnostic techniques used increased continuously (94, 107, 118 and 140, amounting to 0.83, 1.34, 1.76 and 2.12 per patient). The premortal detection of abdominal abnormalities increased globally from 16.8 to 32.5%. This increase was largely due to better diagnosis of liver and gallbladder abnormalities which were in most cases of little relevance. CONCLUSION: Whether these non-endocrine tumors are associated to MEN-1 is unclear and has to be tested by examining the chromosomal regions 11q13 and 11q24/25 of the tumors sample, in which the possible MEN-1 involved tumor suppressor genes are located.

Aged↗
PubMed1998

[Reversible dementia].

A 65 year old woman, referred for differential diagnosis of dementia, presented with cognitive and mnestic deficits. Typical signs and symptoms of hypothyroidism led to the diagnosis of severe autoimmune thyroiditis. After six months of treatment with thyroid hormone, dementia, myopathy and ataxia had disappeared. The neurologic and neuropsychologic manifestations of hypothyroidism are discussed. In dementia the diagnosis of secondary and reversible forms is of great importance with regard to prognosis and treatment. Hypothyroidism is known to be a common and treatable cause of pseudodementia. Early diagnosis and adequate treatment are important to prevent further permanent deterioration of cerebral function.

Aged↗
PubMed1998

A novel technology for packing and unpacking pilot and production scale columns.

A new method of packing and unpacking large scale chromatography columns is described. This involves use of a 3-position valve that can inject chromatography media into a closed column thereby packing it. This same valve in another state is then used to unpack the column. Heights equivalent to a theoretical plate and asymmetry factors of packs on columns from 280 to 800 mm diameter are discussed.

Chromatography, Liquid↗