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Biomedical subjects

G Stein

Publications and source records attributed to G Stein.

At least 127 records · Page 7Linked to original sources
PubMed1998

Altered instantaneous and calcium-modulated oscillatory PTH secretion patterns in patients with secondary hyperparathyroidism.

The relative contributions of increased parathyroid cell mass and altered control mechanisms of parathyroid hormone (PTH) secretion in secondary hyperparathyroidism are still controversial. In this study, endogenous pulsatile PTH secretion was analyzed by the multiparameter deconvolution technique to differentiate alterations in cell mass-dependent (PTH burst mass) and regulation-dependent (frequency, synchrony, calcium responsiveness) PTH release in uremic patients. PTH concentration versus time profiles were obtained in 13 uremic and 16 healthy adults under baseline conditions and during acute hypo- and hypercalcemia. Plasma PTH half-life was increased in patients compared with control subjects (4.7+/-1.9 versus 2.6+/-0.1 min, P < 0.005). The baseline PTH secretion rate was elevated eightfold in the patients as a result of an increased PTH mass secreted per burst (17.1+/-4.7 versus 2.0+/-0.4 pM, P = 0.0001), higher burst frequency (8.0+/-0.3 versus 6.8+/-0.3 h(-1), P < 0.01), and a higher tonic secretion rate (343+/-99 versus 30+/-4 pM/h, P = 0.0001). Acute hypocalcemia elicited an immediate, frequency- and amplitude-mediated selective increase in the pulsatile secretory component, which was fractionally weaker in patients (+595%) than control subjects (+1755%, P < 0.001). The acceleration and the amplification of PTH bursts were 35 and 60% lower in the patient group. Acute hypercalcemia suppressed total PTH secretion by 79% in control subjects but only by 63% in patients (P < 0.002). PTH burst frequency was reduced during hypercalcemia by 30% in control subjects, but remained unchanged in patients. In conclusion, uremic hyperparathyroidism is mediated by a marked increase in glandular secretion, but also by reduced PTH elimination. The increased spontaneous PTH burst frequency and the blunted responsiveness to changes in Ca2+ indicate partial uncoupling of hyperplastic parathyroid glands from the physiologic regulatory mechanisms that direct pulsatile PTH release.

Adolescent↗
PubMed1998

High throughput analysis of differential gene expression.

Elucidation of the changes in gene expression associated with biological processes is a central problem in biology. Advances in molecular and computational biology have led to the development of powerful, high-throughput methods for the analysis of differential gene expression. These tools have opened up new opportunities in disciplines ranging from cell and developmental biology to drug development and pharmacogenomics. In this review, the attributes of five commonly used differential gene expression methods are discussed: expressed sequence tag (EST) sequencing, cDNA microarray hybridization, subtractive cloning, differential display, and serial analysis of gene expression (SAGE). The application of EST sequencing and microarray hybridization is illustrated by the discovery of novel genes associated with osteoblast differentiation. The application of subtractive cloning is presented as a tool to identify genes regulated in vivo by the transcription factor pax-6. These and other examples illustrate the power of genomics for discovering novel genes that are important in biology and which also represent new targets for drug development. The central theme of the review is that each of the approaches to identifying differentially expressed genes is useful, and that the experimental context and subsequent evaluation of differentially expressed genes are the critical features that determine success.

Animals↗
PubMed1997

Interleukin-6, soluble interleukin-2-receptor and soluble interleukin-6-receptor in sera of patients with rheumatoid arthritis: influences of disease activity and drug therapy.

Cytokines and their receptors play a fundamental role in the development and maintenance of the inflammatory process in rheumatoid arthritis (RA). The purpose of this study was to evaluate sIL-2R, sIL-6R and IL-6 levels in the sera of 48 RA patients and to correlate them with disease activity, indicators of inflammatory process as ESR and CRP, and drug treatment modalities. IL-6 and sIL-2R levels were positively correlated with disease activity, ESR and CRP. No correlation between sIL-6R levels and these markers were observed. Our results suggest that different drug therapies have a decisive influence on the levels of selected cytokines. All investigated disease-modifying antirheumatic drugs (DMARDs) were able to reduce the IL-6 level significantly. Non-immunosuppressive DMARDs decreased the amount of circulating sIL-2R more than immunosuppressive drugs. Treatment with methotrexate resulted in a significant reduction of circulating levels of sIL-6R compared to azathioprine therapy. Under low dose glucocorticoid therapy, significantly lower levels of sIL-6R were found than in patients without glucocorticoids. In conclusion, the results provide some arguments in favour of combined drug therapies, which might possibly enhance the effectiveness of RA therapy.

Adult↗
PubMed1997

[Still's syndrome in the adult. A report of 8 cases with special reference to diagnostic value of ferritin].

BACKGROUND: Adult onset Still's disease (AOSD) is an uncommon, systemic, inflammatory disorder of unknown etiology, characterized by the triad of fever, arthritis and rash. PATIENTS AND RESULTS: We describe 8 cases of AOSD (3 male, 5 female) diagnosed and treated in the Department of Rheumatology from 1980 to 1996. The delay in reaching a firm diagnosis was between 2 and 86 months, due to both lack of specific serum markers and the abundance of possible differential diagnoses. Our therapeutic strategies and results are presented and the value of obtaining serum ferritin levels for both diagnosis and follow-up studies is discussed. The patients data are compared to those of the world's literature on AOSD. CONCLUSION: The differential diagnosis of fever of unknown origin should always include AOSD, because these patients could be spared from invasive and unnecessary diagnostic measures. Increased serum ferritin levels are of particular value in the diagnosis of acute AOSD and the normalization of the serum ferritin value is a reliable indicator of therapeutic success.

Adolescent↗
PubMed1997

Uvulopalatopharyngoplasty vs laser-assisted uvulopalatoplasty. Anatomical considerations.

OBJECTIVE: To assess and compare anatomical changes in the velopharynx produced by conventional uvulopalatopharyngoplasty and by laser-assisted uvulopalatoplasty. DESIGN: A before-after trial of patients who underwent conventional or laser-assisted palatal surgical procedures. PATIENTS AND INTERVENTIONS: A total of 174 patients (157 men and 17 women; age range, 22-71 years; mean age, 48 years) who were suffering from heavy snoring (n = 16) or obstructive sleep apnea. The first 100 consecutive patients underwent conventional uvulopalatopharyngoplasty, and the remaining 74 underwent 1 of 2 surgical variations of laser-assisted uvulopalatoplasty. MAIN OUTCOME MEASURES: Preoperative and postoperative examinations included peroral photographs of the oropharynx and nasopharyngoscopic examination of the velopharyngeal valve. In 10 randomly selected patients, postoperative lateral and frontal cephalometric radiographs, enhanced with contrast media, were compared with routine preoperative radiographs. RESULTS: Uvulopalatopharyngoplasty results in an enlargement of the oropharynx and an increased velopharyngeal air space. Laser-assisted uvulopalatoplasty, by producing a raw surface, involves circumferential scarring, the severity of which depends on the velopharyngeal axial configuration; therefore, it can result in a diminished velopharyngeal air space and decreased distensibility. CONCLUSIONS: From an anatomical viewpoint, laser-assisted surgery of the palate is significantly inferior to conventional uvulopalatopharyngoplasty and may even be deleterious. The results of preoperative and postoperative polysomnographic comparisons in patients who undergo laser-assisted operations should be evaluated to determine whether future laser-assisted surgery is an adequate option, even for snoring as an isolated symptom.

Female↗
PubMed1997

The determination of pyridinium crosslinks in urine and serum as a possible marker of cartilage degradation in rheumatoid arthritis.

The determination of the collagen crosslinks pyridinoline (Pyd) and deoxypyridinoline (Dpyd) seems to be a successful way of characterizing topic destructive processes in rheumatoid arthritis (RA). Dpyd is a specific marker of collagen I resorption in bone, whereas Pyd is released from types I and II collagen in bone and cartilage. Both crosslinks were examined in 38 RA patients concurrently by RP-gradient-HPLC in urine and serum. A positive correlation was found between the inflammatory activity (measured by CrP) and the level of collagen crosslinks in urine. A correlation between serum and urine concentrations was demonstrable for Pyd, but not for Dpyd. Different elimination kinetics for fragments containing either Pyd or Dpyd are a possible explanation for this observation. The ratio of Pyd/Dpyd is known to be a useful marker to distinguish between destruction of cartilage and bone collagen. Because the Pyd/Dpyd ratio in urine does not necessarily correspond to that in serum, probably as a result of metabolic or elimination processes, the usefulness of the relationship between the crosslinks in urine as a method of differentiating between cartilage and bone degradation must be questioned.

Adult↗
PubMed1997

Kidney function in rats after 5/6 nephrectomy (5/6 NX); effort of treatment with vitamin E.

In adult female rats various kidney functions were measured 3 weeks after 5/6 nephrectomy (5/6 NX). The distinct rises in blood urea nitrogen and in renal excretion of proteins indicate the impairment of the kidney. In 5/6 NX rats, the renal excretion of creatinine, glucosaminoglycan, and of p-aminohippurate was diminished. The concentrations of hydroxypyroline and of free hydrogen ions were distinctly increased in urine samples from 5/6 NX rats. The concentration of lipid peroxides was enhanced in kidney tissue whereas 3 weeks after 5/6 NX the concentration of GSH and GSSG in the remnant kidney tissue was unchanged. Long-term administration of vitamin E increased its concentration in plasma, kidney, and liver. Nevertheless, daily treatment with vitamin E (1 or 10 mg/100 g b.w. s.c. for 5 weeks) did not reduce the degree of impairment of kidney function following 5/6 NX.

Animals↗
PubMed1997

Human renin binding protein: complete genomic sequence and association of an intronic T/C polymorphism with the prorenin level in males.

The role of renin binding protein (RnBP) in human (patho)physiology, despite its biochemical characterization, is as yet unclear. RnBP has been shown to bind and inactivate renin, a key player of the blood pressure regulating renin-angiotensin system. This renders the RnBP gene a promising candidate gene in human hypertension. Herein, a molecular genetic approach was employed to investigate if RnBP might affect renin, prorenin and/or blood pressure levels. Sequencing of the human Xq28 chromosomal region provided the precise chromosomal location and full genomic sequence of the RnBP gene. All 11 exons, adjacent intronic splice sites and the promoter region were sequenced in 20 patients with essential hypertension of early onset and possible X-linked inheritance and in four normotensive individuals. The only variant found was a single base exchange polymorphism 61 base pairs upstream of the intron 6/exon 7 boundary (T61C). Several cardiovascular parameters, the renin, and prorenin levels and the T61C allele status were determined in 505 Caucasian individuals. Male individuals without medication who were hemizygous for the C allele were characterized by lower prorenin levels (196 +/- 15 versus 256 +/- 12 mU/l, P = 0.05) and a significantly higher renin/prorenin ratio (10.7 +/- 1.5 versus 7.7 +/- 0.3%, P = 0.002), whereas no variations in circulating renin, blood pressure, heart rate and left ventricular mass index were associated with the C allele. No significant association was observed in women. The data do not exclude a role of RnBP in essential hypertension. The complete genomic structure of the RnBP gene, including the identified repetitive sequence elements, provides an essential tool for further studies of the RnBP gene in hypertensive patients with a different genetic background.

Base Sequence↗
PubMed1997

Impact of membrane choice and blood flow pattern on coagulation and heparin requirement--potential consequences on lipid concentrations.

BACKGROUND: We reasoned that procoagulant activity, and by implication heparin requirement, during haemodialysis are influenced, amongst other factors, by the type of membranes and the geometry of the blood line system. In addition, there are indications that heparin has dose-dependent effects on the lipid status of chronic haemodialysis patients. METHODS: In a parallel group design we compared patients treated with cuprophane (CU) and polycarbonate-polyether (PC-PE) plate dialysers. In both groups, blood line geometry was varied by including in a first phase and omitting in a second phase drip chambers in the arterial blood line. End-points were changes in coagulation parameters, i.e. thrombin-antithrombin III complex (TAT), plasmin-anti-plasmin complex (PAP), and prothrombin fragment (F1 + 2) concentrations measured by sandwich ELISA. Subsequently all patients were switched to PC-PE dialysers for 6 months and the heparin dose was reduced in a stepwise fashion. Lipid levels and coagulation parameters were monitored. Finally, in an ancillary study, the correlation between heparin dose and LDL/HDL ratio was assessed in patients chronically exposed to PC-PE membranes and low doses of heparin. RESULTS: Post-dialytic concentrations of coagulation and fibrinolysis parameters were significantly lower in the PC-PE group (TAT 31.0 +/- 4.4 micrograms/l; PAP 1180 +/- 148 micrograms/l; F1 + 2 4.2 +/- 0.4 nmol/l) compared to the CU group (TAT 57.3 +/- 10.8 micrograms/l; PAP 1789 +/- 185 micrograms/l; F1 + 2 8.8 +/- 1.0 nmol/l), independently of the use of an arterial drip chamber. Omission of the arterial drip chamber led to lower TAT in the CU group (42.2 +/- 5.8 micrograms/l, P < 0.05), but not in the PC-PE group. In contrast, PAP and F1 + 2 concentrations did not change significantly in either group. Down-titration of heparin dose (from 20.4 +/- 1.1 to 9.4 +/- 0.9 IU/kg/h) was associated with a significant decrease in serum triglycerides (from 2.9 +/- 0.9 to 2.0 +/- 0.6 mmol/l, P < 0.05), LDL-cholesterol (from 3.4 +/- 0.2 to 2.7 +/- 0.4 mmol/l, P < 0.05) and LDL/HDL-ratio (from 3.2 +/- 0.3 to 2.0 +/- 0.3, P < 0.05) with no significant change of total or HDL-cholesterol after 6 months. In an ancilliary analysis, a correlation between lipid parameters (LDL/HDL ratio) and heparin dose was confirmed in 24 patients chronically exposed to PC-PE membranes (r = 0.473, P < 0.05). CONCLUSIONS: In a prospective exploratory study (i) heparin requirement is lower with the use of a polycarbonate-polyether membrane compared to a cuprophane membrane, (ii) heparin requirement is influenced by blood line geometry (decreased with omission of an arterial drip chamber), and (iii) in patients on polycarbonate-polyether membranes down-titration of heparin is associated with a reduction of serum triglycerides, LDL cholesterol, and LDL/HDL ratio. Our data suggest that reduction of heparin dose improves lipid profile. These preliminary observations require confirmation by parallel group controlled studies with controlled dietary intake.

Aged↗
PubMed1997

Pathogenetic aspects of uncomplicated urinary tract infection: recent advances.

Urinary tract infections mostly are caused by Enterobacteriaceae; E. coli dominating in 80-90% for uncomplicated diseases. Microorganisms possessing the ability to colonize the uroepithelium (fimbriae/pili) and to cytotoxically damage cells and tissue (hemolysin) may initiate acute infection. Properties such as serum resistance, iron sequesteration, hydroxamate production and the presence of K-antigen are found in strains which persist in the host without initiating clinical symptoms. The ability of bacteria to adhere to cells of the epithelial boundary layer of the host organisms is of initial importance in the origin and progress of an infection. A variety of specific factors, e.g. glycolipids on the surface of the uroepithelium as well as cellular and humoral disorders of immunoreactions in the host determine the course of a disease. The immune response may ameliorate clinical symptoms and select urovirulent characteristics of the causative microorganism in recurrent diseases.

Adhesins, Escherichia coli↗
PubMed1997

[Enthesopathies--diagnosis and therapy].

Problems are frequently encountered regarding the terminology, diagnosis, differential diagnosis, and therapy of diseases of thes tendons insertion point (enthesis): Terms such as tendinosis, tenopathy, tendinitis, tendovaginitis, tendoperiostitis, insertions tenopathy, tendomyosis, etc. often are used interchangeably even through they describe anatomically and pathophysiologically different conditions. The term enthesiopathy is used as a generic term in this overview article irrespective of the causality.

Combined Modality Therapy↗
PubMed1997

Vitamin C status of patients with chronic renal failure, dialysis patients and patients after renal transplantation.

The vitamin C status of patients with chronic renal failure (CRF), dialysis patients (DP) and patients after renal transplantation (RT) was the object of this investigation. Levels of vitamin C intake from dietary records were estimated at mean values of 93.5 mg/d (CRF), 65.5 mg/d (DP) and 163.9 mg/d (RT). Compared to the recommendation of the German Society of Nutrition (75 mg/d), this indicated a normal range of supply for all groups except the group of DP. The corresponding mean plasma concentrations were 62.2 mumol/l (CRF), 80.3 mumol/l (DP) and 68.8 mumol/l (RT). Supplements of 60 or 100 mg vitamin C given to patients of the DP-group after each dialysis session showed slightly, but not significantly higher concentrations of vitamin C in plasma. During dialysis treatment, plasma vitamin C concentrations dropped to approximately 50% of the basal value, but almost reached initial levels again 44 hours later, both with and without supplementation. During one treatment period, vitamin C loss in the dialysate of three patients ranged between 92.5 and 333.6 mg. The amount of vitamin C in plasma, however, dropped to approximately 50% of the basal value for these patients, too.

Adult↗
PubMed1997

[Pathogenetic aspects of urinary tract infection].

Most urinary tract infections are caused by Enterobacteriaceae; E. coli-strains dominating in 50 to 80% of primary infections. Microorganisms possessing the ability to colonize the uroepithelium (fimbriae/pili) and to cytotoxically damage of cells (hemolysin) may initiate acute infections. On the other hand, properties favouring the survival of these strains in the tissue (K-antigen, iron sequestering/aerobactin) tend to produce relapse and/or chronic infection. A variety of host-specific factors, especially glycosphingolipids, on the surface of epithelial cells determine the virulence of pathogenic microorganisms in the urinary tract and the course of a disease. Structural damages resulting from intra- or extrarenal obstructions, disturbances of the urinary flow and metabolic disorders are essential, predisposing factors of a host organism. These different factors and interactions of these mechanisms determine the manifestation and course of urinary tract infections.

Bacteriuria↗