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Biomedical subjects

G Stein

Publications and source records attributed to G Stein.

At least 109 records · Page 6Linked to original sources
PubMed1999

Alteration of thiamine pharmacokinetics by end-stage renal disease (ESRD).

OBJECTIVE: In a comparative study with 20 end-stage renal disease (ESRD) patients the pharmacokinetics of two therapeutically used thiamine (vitamin B1) preparations were assessed. SUBJECTS, MATERIAL AND METHODS: After a single oral dose of either 100 mg benfotiamin (S-benzoylthiamine-o-monophosphate, BTMP) or 100 mg thiamine mononitrate (TN), blood levels of thiamine phosphate esters were analyzed by HPLC after precolumn derivatization to thiochrome phosphate esters for a 24-hour period. RESULTS: The pharmacokinetic parameters AUC0-24h, Cmax and tmax of the benfotiamin group in whole blood and plasma exceeded significantly those in the TN group. Only 1.0 vs. 0.6% of the administered dose were excreted in urine in the BTMP group and TN group, respectively. A high cellular efficacy, as was concluded from the short-term stimulation of the thiamine-dependent transketolase activity in erythrocytes (ETKA), was assessed for BTMP as well as TN. The activation coefficient (ETK-AC) decreased significantly from 1.10 to 1.04 vs. 1.12 to 1.07 in both the BTMP as well as TN groups, respectively. In addition, a high transfer rate to thiamine diphosphate (TDP) was observed in the patients after ingestion of BTMP. The TDP concentration in whole blood increased by 2.6 and 1.4 times from baseline levels to Cmax in the BTMP and TN groups, respectively. The AUC0-24h of TDP in whole blood after BTMP ingestion exceeded those after TN ingestion by 420%. CONCLUSION: These findings justify the therapeutic application of BTMP in ESRD, because a high intracellular concentration of TDP may protect against numerous adverse effects of uremia in the long run.

Chromatography, High Pressure Liquid↗
PubMed1999

The "point of no return" and the rate of progression in the natural history of IgA nephritis.

BACKGROUND: Based on the observation of 7 patients with chronic IgA nephritis and on a course to end-stage renal failure after several years, D'Amico et al. [1993] reported on a "point of no return" at 2.5 to 3 mg/dl serum creatinine. After exceeding this limit all 7 patients exhibited an irreversible progressive renal failure. PATIENTS AND METHODS: Therefore, 115 patients with IgA nephritis from the "German Glomerulonephritis Therapy Study" were examined in order to look for the existence of such a "point of no return". RESULTS: Three different courses could be distinguished: a stable chronic course with constantly normal or only minor elevated serum creatinine lasting for years (91 patients), a progressive course with continuously increasing serum creatinine (22 patients), and a rare (only 2 patients) early acute course with a short-term increase of serum creatinine followed by a rapid return to the normal range. After exceeding 3 mg/dl serum creatinine no remissions were observed in the progressive cases. Sixteen patients showed a rapid, continuously progressive course until end-stage renal failure with exactly the same progression as the 7 patients of D'Amico et al. Six patients of the 22 progressors were not observed long enough. The serum creatinine level doubled on average from 3 to 6 mg/dl within 10 months. CONCLUSION: Our study confirmed the existence of a "point of no return" at 3 mg/dl (265 micromol/l) during the natural course of chronic IgA nephritis.

Adolescent↗
PubMed1998

Modulation of the cellular and humoral immune responses of tumor patients by mistletoe therapy.

There is evidence from recent data that mistletoe extracts exert immunostimulatory properties which could explain their therapeutic effects observed in some tumor patients. Aim of our study was, therefore, to investigate the effect of a subcutaneous 16-weeks therapy with a mistletoe extract (ABNOBAviscum Mali, AM) on the cellular and humoral immune responses in eight breast cancer patients. Mistletoe therapy induced a strong initial proliferation of peripheral blood mononuclear cells (PBMC) in all individuals, which, however, decreased in six patients during the observation period, indicating that not only activating but also inhibitory mechanisms have been induced. In all supernatants of AM-stimulated cell cultures TNF-alpha or IL-6 were found, indicating the activation of cells of the monocyte-/macrophage lineage by mistletoe extracts. Further analyses revealed, that AM induced in vitro also the release of low amounts of IFN-gamma and IL-4 with individual variations. At the end of the therapy, a shift to Th1- related cytokines could be observed in the in vitro cell culture system. All patients produced anti-mistletoe lectin 1 antibodies of the IgG-type during therapy and in four of them additionally antibodies of the IgE-type were found. It, therefore, seems that AM can influence the Th1/Th2 balance and, in case of a Th1 shift, this may favourably influence the tumor growth.

Adjuvants, Immunologic↗
PubMed1998

PICP as bone formation and NTx as bone resorption marker in patients with chronic renal failure.

UNLABELLED: Renal bone disease which develops in patients with chronic renal failure (CRF) is not a uniform metabolic disorder. Although bone histomorphometry is accepted to be the gold standard for characterizing the state of disease progression, the techniques involved are cumbersome and expensive so that it cannot be used routinely. As a result, numerous biochemical markes have been developed to measure bone formation and resorption. The purpose of this study was to evaluate the suitability of procollagen type-I C-terminal peptide (PICP) in serum as an indicator of bone formation and cross-linked amino-terminal telopeptide of type I collagen (NTx) in urine as an indicator of bone degradation processes, and to investigate their relation to histomorphometric and other biochemical parameters. 77 patients with CRF and 49 patients on intermittent hemodialysis treatment (DT) were investigated. PICP was measured in serum and NTx in urine. In addition, iPTH, phosphate, calcium, alkaline phosphatase (APH), osteocalcin and creatinine in serum were determined. Bone biopsies were obtained from the anterior, superior iliac crest, and the histomorphometric parameters were measured and expressed according to the standardized nomenclature. Patients with CRF and DT had significantly higher PICP and NTx levels as compared to controls. In the CRF group significant correlations could be obtained between PICP and histomorphometric parameters of bone formation as well as between NTx and histomorphometric indices of bone resorption. In this group, PICP levels were positively correlated to iPTH, phosphate and creatinine levels and negatively to calcium concentrations. Furthermore, there were significant correlations between NTx values and those of both iPTH and APH. In the group of dialysis patients, levels of PICP and NTx did not correlate with any of the histomorphometric parameters or the classical humoral markers. CONCLUSIONS: The results suggest that PICP as bone formation and NTx as bone resorption markers are of potential use for screening bone turnover in predialysis chronic renal failure patients. But in patients undergoing dialysis, neither PICP nor NTx yielded any substantial information as noninvasive markers of bone histology.

Adult↗
PubMed1998

Functional comparison of the yeast scERV1 and scERV2 genes.

The yeast scERV1 gene is the first representative of a new emerging gene family. Its gene product is essential for the yeast cell and is involved in the biogenesis of mitochondria and the regulation of the cell cycle. Recently the general importance of the gene for the eukaryotic cell was shown by the identification of a structural and functional human homologue. The homologous mammalian ALR (augmenter of liver regeneration) genes from man, mouse and rat are important for different developmental stages of the organism as for example in spermatogenesis and the regeneration of damaged liver organs. Latest research identified an intron with an unusual 3' branch site in the 5' region of the yeast scERV1 gene. Analysis of the now available complete genome sequence from Saccharomyces cerevisiae identified a second yeast gene with homologies to scERV1 on chromosome 16. The corresponding gene product has a length of 196 amino acids similar to the 189 residues of the scERV1 protein and exhibits 30% identical amino acid residues in the highly conserved carboxy-terminal part of the polypeptides. Because of the structural similarities the new gene will be termed scERV2 from now on. For the scERV1 gene product it has just been shown that it is associated with yeast mitochondria. Analysis of the amino-terminal part of the putative scERV2 protein also identifies a typical leader sequence for import into mitochondria. The comparison of cDNA and genomic DNA from the scERV2 gene shows that no intron is present in this gene. To investigate the functional relation between the two yeast genes disruption experiments and complementation studies of mutants from scERV1 were performed. In addition the expression of messenger RNA under 15 different growth conditions was investigated by detailed Northern hybridization studies. Both genes show a complex and distinct expression pattern for their transcripts and are highly regulated under different physiological conditions. Moreover correct and efficient splicing of the transcript from the scERV1 gene was found to vary with the physiological state of the yeast cell, as further verified by reverse transcription-polymerase chain reaction analysis of transcripts from galactose-grown yeast cells.

Blotting, Northern↗
PubMed1998

Relationship between disease activity and serum levels of vitamin D metabolites and PTH in rheumatoid arthritis.

In several studies on patients with rheumatoid arthritis, an association of bone loss with a persistently high disease activity has been found. The aim of our study was to investigate the relation between disease activity and serum levels of vitamin D metabolites, parathyroid hormone (PTH), and parameters of bone turnover in patients with rheumatoid arthritis. A total of 96 patients (83 women and 13 men) were divided into three groups according to disease activity measured by serum levels of C-reactive protein (CRP). In the whole group, serum levels of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) (P < 0.001) and PTH (P < 0.05) were negatively correlated to disease activity. The urinary excretion of collagen crosslinks--pyridinoline (Pyd) (P < 0.001) and deoxypyridinoline (Dpd) (P < 0.05)--showed a positive correlation with disease activity. The inverse correlation between serum 1,25(OH)2D3 and disease activity was separately evident in patients with (P < 0.001) and without (P < 0.01) glucocorticoid treatment, in pre- (P < 0.01) and postmenopausal (P < 0.001) women, and in men (P < 0.01). 1,25(OH)2D3 and PTH serum levels were positively correlated to serum bone alkaline phosphatase (ALP) (P < 0.01). The results indicate that high disease activity in patients with rheumatoid arthritis is associated with an alteration in vitamin D metabolism and increased bone resorption. The decrease of 1,25(OH)2D3 levels in these patients may contribute to a negative calcium balance and inhibition of bone formation. Furthermore, low levels of 1,25(OH)2D3 as an endogenous immunomodulator suppressing activated T cells and the proliferation of cells may accelerate the arthritic process in rheumatoid arthritis.

Adolescent↗
PubMed1998

A comparison of the antihypertensive efficacy and safety of felodipine IV and nifedipine IV in patients with hypertensive crisis or emergency not responding to oral nifedipine.

OBJECTIVE: A clinical definition of a hypertensive emergency is excessively high blood pressure in the presence of symptoms indicating end organ damage. Equally high blood pressure without symptoms is called a hypertensive crisis. Patients with hypertensive crisis or emergency need prompt, effective, and specific therapy and a controlled reduction of blood pressure. METHODS: We performed a randomized, double-blind multi-centre study, to compare the safety, efficacy and tolerability of an intravenous (i.v.) infusion of two dihydropyridine calcium channel blockers (either nifedipine or felodipine) in 122 patients, of whom 63 were diagnosed as hypertensive emergencies and 59 as hypertensive crisis, who had not reacted adequately (diastolic blood pressure <115 mmHg) to 5 mg of nifedipine PO. RESULTS: Both drugs lowered blood pressure adequately in more than 90% of the patients and were well tolerated. Only one patient had to be withdrawn, because of an excessive decrease in blood pressure. CONCLUSION: Patients with excessively high blood pressure who do not react to oral nifedipine can be treated equally effectively with felodipine and nifedipine IV. Felodipine is easier to handle because of its lack of light sensitivity.

Administration, Oral↗
PubMed1998

Are patients with chronic renal failure (CRF) deficient in Biotin and is regular Biotin supplementation required?

In 23 patients with chronic renal failure (CRF), 23 patients on chronic intermittent hemodialysis treatment (DP), 22 patients after renal transplantation (RT) and 40 normal persons (NP), Biotin plasma levels and the urinary excretion were analysed and compared to the dietary Biotin intake. Unsupplemented DP had lower intake of Biotin than the CRF, RT, NP and DP with supplementation. DP excreted only 1.6-6.3% of the daily intake as compared to 39.7% in NP, 27.6% in CRF and 24.3% in RT. In unsupplemented DP patients, Biotin plasma levels were elevated by 4 times and in supplemented patients by 6 times compared to NP. During hemodialysis treatment, the Biotin plasma level dropped by about 30% in DP with and by 33% in DP without vitamine supplementation. However, after 44 hours, the initial concentration was reached again in those receiving vitamine supplementation (99% of basal level) and in DP without substitution (97% of basal level). Only in male DP significantly higher Biotin plasma levels before HD were detected irrespective of the supplementation dose as compared to female patients (30 micrograms and 300 micrograms Biotin after each dialysis session). Biotin plasma concentration did not vary with respect to the underlying renal disease, the serum creatinine concentration and the length and frequency of dialysis treatment, including the type of dialyzer (low- vs high flux) used and the blood flow rate (QB 180-260 vs 270-280 vs 300 ml/min). There were no major effects of the age of the patients (< 60 years vs > 60 years), the BMI, nicotine abuse, or alcohol intake on Biotin blood concentration. Our results showed normal Biotin plasma levels which reflect a normal functional status and exclude a functional deficit, therefore there is no reason for a regular Biotin supplementation in patients with chronic renal failure.

Age Factors↗
PubMed1998

Is there a beneficial effect of the calcium channel blocker diltiazem on cyclosporine A nephrotoxicity in rats?

To investigate whether or not there is a beneficial effect of diltiazem (D) on cyclosporine A (CsA) nephrotoxicity, renal function, CsA blood levels, and effects of CsA on biotransformation in the liver and on lipid peroxidation were characterized in rats. A single administration of D (60 mg/kg b.wt.) reduced urinary volume (UV), GFR and excretion of Na+ and K+, whereas a single dose of CsA (60 mg/kg b.wt.) alone had no respective effects. P-aminohippurate excretion was almost equal in all groups. Lower doses of D (and CsA) were without effects. After repeated CsA treatment a retardation in body weight gain was seen, with little effect of a co-administration with D hereon. In all tests, thymus mass was reduced by CsA, the weight of spleen, liver, adrenal glands, and kidney were not generally affected by any of the treatments. Furthermore, after repeated administration of CsA and/or D, urinary volume, GFR and Na+ excretion were reduced by CsA, too. Electrolyte concentrations in plasma showed no evident changes by any of the treatments for Na+ and Ca2+. After long time treatment, CsA and CsA + D quite similarly led to higher K+ but lower Mg2+ concentrations in plasma. Only with 7 days highest dosage treatment PAH excretion was reduced significantly by CsA and CsA + D treatment. Surprisingly, CsA levels measured in blood and in kidney tissue, showed lower values after co-administration with D compared to CsA treatment alone. This could be caused by higher activities of monooxygenase functions revealed after pretreatment with D alone. Reduced glutathione (GSH) contents in kidney were elevated in CsA and CsA + D treated groups. In general no significant differences were to be observed concerning lipid peroxidation and stimulated H2O2 formation. Altogether evident protective effects of diltiazem on CsA nephrotoxicity in rats could not be proven.

Animals↗
PubMed1998

Angiographic Morphology Following Heparin and Aspirin Therapy in Patients with Acute Coronary Syndromes and Intracoronary Thrombus.

This series included 26 patients with acute myocardial infarction (15 patients) or unstable angina (11 patients), with thrombotic lesions identified by angiography and treated with intravenous heparin (mean 8 +/- 3 days, aPTT 1.5-2.5 times baseline) and aspirin (250 mg/day). A quantitative angiographic analysis was performed, and comparison of the lesion morphology before and after the antithrombotic treatment was conducted, using a computer-based analysis of the lesion contour. On average, minimal lumen diameter increased by 15.6% (1.15 +/- 0.5mm to 1.33 +/- 0.5mm, P = 0.02), percent diameter stenosis decreased by 10.7% (60.0 +/- 18% to 53.6 +/- 19%, P = 0.009), percent area stenosis decreased by 6.5% (80.0 +/- 14% to 74.8 +/- 16%, P = 0.05), and TIMI flow increased by 8% (2.5 +/- 0.9 to 2.7 +/- 0.7, P = 0.02). A significant improvement in the lesion morphology was more often observed in the right coronary artery (n = 9), than the left coronary artery (n = 16). We conclude that heparin and aspirin therapy improves the angiographic morphology and TIMI flow of thrombotic lesions in patients sustaining the acute coronary syndrome. This improvement was primarily found when the lesion was located in the right coronary artery.

Journal Article↗
PubMed1998

Conformation of replicated segments of chromosome fibres in human S-phase nucleus.

Recent statistical analysis of the folding of G0/G1 chromosomes using fluorescence in situ hybridization (FISH) allowed development of a random walk/giant loop model of chromosome structure. According to this model there are two levels of organization of G0/G1 chromosome fibres. On the first level, the fibres are arranged in giant loops several Mbp in size, and within each loop the fibres are randomly folded. On the second level, the loop attachment sites form a chromosome backbone that also shows random folding. Newly replicated segments of mammalian chromosomes may be directly visualized at high resolution in S-phase nuclei using immunofluorescent methods and appear as worm-like fibres. In our earlier study, we analysed conformation of the fibres in human cells blocked for 16 h at the G1/S boundary with 5-fluorodeoxyuridine (FdU) and then released into S-phase by the addition of a DNA precursor. However, long treatment of cells with FdU induces very short replicons and may promote apoptosis. In this study we analysed conformation of the fibres in normally proliferating human cells that had not been blocked with FdU for a long time. It has been found that replicated chromosome fibres visualized just after 2 h of incubation of the cells with a non-radioactively labelled DNA precursor behave as flexible polymer chains without major constraints, and that their local conformation in the range of several microns of their contour length may be considered as random. Confocal analysis of human X chromosomes visualized in HeLa cells using FISH with a specific painting probe shows that in S-phase the chromosomes occupy distinct nuclear territories and their apparent size does not differ from that in non-S-phase cells. This observation indicates that the second level of chromosome organization also exists in S-phase chromosomes. It appears, therefore, that the random walk/giant loop model developed earlier for G0/G1 chromosomes is also valid for S-phase chromosomes.

Cell Nucleus↗
PubMed1998

Dysregulation of insulin-like growth factors in a case of generalized acquired lipoatrophic diabetes mellitus (Lawrence Syndrome) connected with autoantibodies against adipocyte membranes.

We report on a 33-year-old male patient with generalized acquired lipodystrophy, insulin resistant diabetes mellitus and acanthosis nigricans (Lawrence Syndrome). First probable symptoms of lipodystrophy (weight loss, shrinkage of subcutaneous fatty tissue, and loss of muscular strength) became evident three years ago, with the onset of diabetes mellitus occurring about six months later. The patient suffered from the following clinical symptoms: IDDM with increasing insulin-requirement, extreme reduction of fatty tissue, fatty liver hepatitis with elevated liver enzymes, glomerulopathy, muscular and neuropathic pains, as well as hypertriglyceridaemia. A basal C-peptide concentration is rather high. Definitely, the endogenous insulin secretion is increased. In other words, insulin resistance is documented. In an effort to identify the pathogenetic mechanisms of lipoatrophic diabetes mellitus in this patient and to develop a therapeutic strategy, antibodies against different tissues and endocrinologic regulation were investigated. It was possible to demonstrate the presence of serum autoantibodies against lipocytes of the subcutis and other tissues, against hepatic stellate cells, together with autoantibodies against different endocrine organs. By studying the basis of diabetic abnormalities relating to the growth hormone (GH), the insulin-like growth factor (IGF) dynamics in this patient, i.e. reductions of GH, IGF-I, IGF-II, IGF-Binding protein (IGF-BP) 2 and IGF-BP 3, were detected. An immunosuppressive treatment strategy was not beneficial.

Adipocytes↗
PubMed1998

[Flare measurement and albuminuria in type I diabetics].

BACKGROUND: Chronic hyperglycaemia causes microangiopathy with manifestations in different organ systems. The purpose of this study was to investigate whether anterior chamber protein concentrations and albuminuria in patients with diabetes mellitus type 1 have any correlation. PATIENTS AND METHODS: 23 patients with type 1 diabetes were examined in both eyes by the use of the laser flare-cell meter (LFCM). After clinical exclusion of urinary tract infection urine-samples were taken on the examination-day. Patients were divided into two groups: group 1 consisted of 13 patients with albuminuria (8x microalbuminuria, 5x macroalbuminuria), group 2 comprised 10 controls with normal urine albumin concentrations. RESULTS: Both groups were identical according to age and gender. The flare values in the group with albuminuria were significantly elevated (10.7 +/- 7.1 counts/msec) in comparison to those of the control group (3.7 +/- 1.9 counts/msec)(p = 0.042). The duration of the diabetes was as well significantly different in both groups (7.9 +/- 6.9 yrs. vs. 23.9 +/- 13.4 yrs.)(p = 0.02). A correlation was found between albuminuria and flare values (r = 0.67; p = 0.003). CONCLUSIONS: Our results demonstrate a correlation between protein concentration in aqueous and albuminuria. In future flare measurements could possibly offer a non-invasive diagnosis of diabetic nephropathy.

Adult↗
PubMed1998

Measurement of platelet activation and adhesion to leukocytes during haemodialysis.

In this study we used fluorescent-labelled antibodies to measure the extent of platelet adhesion to polymorphonuclear leukocytes (PMNLs), monocytes and lymphocytes. The activation of platelets, PMNLs and monocytes were also measured during the course of haemodialysis treatment using flow cytometric techniques established in our laboratory. Twenty patients were treated with either a cellulose membrane (TFU) or a polycarbonate filter (Pro 500). Blood samples were taken from the output line of the dialyser 2, 15, 30 and 180 min after commencing dialysis and just before starting treatment. Compared with the pre-dialysis sample, there was a marked increase in platelet-PMNL conjugate formation at 2 min, followed by a decrease in conjugates at 15 and 30 min, and a slight increase at 180 min. During extracorporeal circulation PMNLs become activated as measured by a CD11b upregulation at 15, 30 and 180 min, but not at 2 min. Platelet binding to monocytes was increased above 15 min after starting dialysis, and monocyte activation was slightly increased above basal levels during the same period. The activation state of circulating free platelets, as measured by surface P-selectin exposition, initially decreased slightly, but then returned to basal levels over the 3-h period. Changes in cell counts were also detected: there was a massive decrease in circulating PMNLs and monocytes, and a small decrease in circulating platelets, at 15 and 30 min. These reverted to basal values by the end of the 3-h period. There was no change in the number of circulating lymphocytes or erythrocytes. These results show that flow cytometric studies on whole blood samples may provide important information on the behaviour of circulating blood cells, which could supplement conventional clinical measurements, to give a better insight into changes that occur in the circulation during haemodialysis.

Journal Article↗
PubMed1998

31P-magnetic resonance spectroscopy (31P-MRS) of human allografts after renal transplantation.

BACKGROUND: 31P-Magnetic resonance spectroscopy (31P-MRS) can be used as a non-invasive tool for measuring the relative intracellular concentrations of several phosphorus metabolites in different organs. Various pathological conditions are characterized by different metabolic patterns. We studied the value of 31P-MRS after renal transplantation with both an uneventful and a clinically complicated course. METHODS: We determined the relative concentrations of phosphate-containing metabolites in renal allografts of humans with 31P-MRS (1.5 Tesla) in the first few weeks after transplantation; 18 patients with an uneventful clinical course and 10 patients who required dialysis after transplantation were examined. Six patients with a stable allograft function 2-3 months after transplantation served as controls. RESULTS: In patients with primary allograft function, we found a significant correlation between the phosphomonoester/phosphodiester-ratio (PME/PDE) (r = 0.66, r < 0.01) and the time after transplantation, but no correlation between the nucleoside triphosphate (beta-NTP)-concentration (r = -0.11) and the time course. In the patients with primary or early allograft dysfunction caused by histologically proven rejection (n=5), we found a low beta-NTP compared to patients with an uncomplicated clinical course (0.09+/-0.01 vs 0.15+/-0.03), but no differences in the PME/PDE ratio (0.73+/-0.21 vs 0.80+/-0.21). In contrast, the PME/PDE ratio was lowered in three patients with delayed graft function caused by acute tubular necrosis (0.45+/-0.07 vs 0.80+/-0.21), but the beta-NTP concentration was not reduced (0.15+/-0.003 vs 0.15+/-0.03). The 31P-MR spectrum of two patients with cyclosporin A damage was not altered compared to the controls. CONCLUSIONS: 31P-MRS can be used in patients in the early period after renal transplantation. A significant correlation between the PME/PDE ratio and the time course but no change in the beta-NTP concentration was found in patients with primary allograft function in the first 4 weeks after renal transplantation. Different patterns of 31P-MR spectra were observed depending on the different causes of primary and early transplant dysfunction.

Adult↗