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Biomedical subjects

G Stein

Publications and source records attributed to G Stein.

At least 181 records · Page 10Linked to original sources

Changes in the kinetics and biopotency of luteinizing hormone in hemodialyzed men during treatment with recombinant human erythropoietin.

To investigate the effect of recombinant human erythropoietin (rh-EPO) on the hypothalamo-pituitary-gonadal axis in end-stage renal failure, plasma luteinizing hormone (LH) concentration release was assessed by frequent blood sampling (every 10 min), both during an 8-h baseline period and after stimulation with an iv bolus of gonadotropin-releasing hormone (GnRH). Seven adult hemodialyzed men were studied before and after partial correction of anemia by rh-EPO treatment. LH was determined by an in vitro Leydig cell bioassay (bio-LH) and a highly sensitive immunoradiometric assay. Pulsatile bio-LH secretion and clearance characteristics were assessed by multiple-parameter deconvolution analysis. Although the rh-EPO treatment did not lead to a change in average concentrations of plasma bio-LH, the mass of hormone released per secretory burst more than doubled, and the estimated bio-LH production rate increased from 8.8 +/- 2.3 to 15.6 +/- 5.2 IU/L per hour (P = 0.05). The lack of change in mean plasma bio-LH is explained by a simultaneous decrease in plasma half-life from 106 +/- 27 to 67 +/- 19 min (P < 0.02). The decrease in the plasma half-life of bio-LH was closely associated with the rise in hematocrit, suggesting an effect of the increased red blood cell mass on LH distribution space and elimination kinetics. As a consequence of the changes in hormone kinetics, the incremental amplitudes of the plasma concentration pulses of bio-LH increased from 112 to 121% of nadir levels (P < 0.05), resulting in a more distinctly pulsatile pattern of hormone signals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Workers' compensation proves the brain and body are connected: lessons for managed care.

Workers' compensation is not only the last frontier for managed care, but also it is the area where somatization is the most apparent to the trained clinician. Because with workers' compensation laws the presumption is always with the injured employee, the incentive can be to see disability as the solution to psychological, social, and economic problems. In many workers' compensation cases, behavioral health issues are more important than the physical injury.

California↗

Dysmorphic erythrocytes in glomerulonephritis. 1. Electron microscopical and histochemical investigation.

Dysmorphic erythrocyte malformation in urine is characteristic of glomerulonephritis. The mechanisms leading to this phenomenon are still unknown. To obtain evidence of the site as well as of the process of erythrocyte damage, electron microscopical and histochemical investigations of renal biopsy materials from 19 patients with histologically defined glomerulonephritis were performed. The results suggest that the initial damage of erythrocytes in the glomerular area is reasoned by enzymatic glycocalyx destruction. On passage through the tubular system the osmotically sensitized surface altered cells undergo rapid hemolysis and losses of membrane skeletal proteins leading to dysmorphic shape transformations.

Adult↗

Dysmorphic red cell formation in glomerulonephritis. 2. In vitro generation of dysmorphic erythrocytes.

In the present study influences leading to in vitro formation of dysmorphic erythrocytes were studied. Fresh and surface altered erythrocytes pretreated with several proteases were passed through different solutions representing distinct nephronís fluids. After passage of intact erythrocytes only 12-15% dysmorphic cells were observed. In case of protease treated cells the number of dysmorphic cells rose to 35-80%. The hemoglobin content was decreased. PAGE and electron microscopical findings demonstrated substantial losses of transmembrane and membrane skeleton proteins. It is assumed that surface protein degradation, loss of membrane skeleton proteins and hemolysis seem to be closely associated with dysmorphic malformation of urinary erythrocytes characteristical for glomerulonephritis.

Anisotropy↗

Initial management of recurrent vulvovaginal candidiasis with oral ketoconazole and topical clotrimazole.

In a randomized study, 151 women with a history of recurrent vulvovaginal candidiasis and suffering from an acute episode of candidal vaginitis were assigned to receive either oral ketoconazole, 400 mg daily for 14 days, or clotrimazole vaginal suppositories, 100 mg daily for 7 days. One week after completion of therapy, evaluation revealed a clinical cure or improvement in 86.4% of ketoconazole- and 81.7% of clotrimazole-treated patients (P > .5), with a mycologic response in 80.3% and 81.7%, respectively. In the absence of maintenance suppressive antimycotic therapy, further follow-up for two months revealed an extremely high rate of clinical and mycologic failure in both groups, reaching 52.5% after ketoconazole and 62.6% after clotrimazole (NS). Adverse effects were significantly more common with systemic ketoconazole than accompanying topical clotrimazole therapy. Although both forms of antifungal therapy were highly successful in inducing clinical and mycologic remission in patients with recurrent vulvovaginal candidiasis, this study emphasized the need for immediate initiation of maintenance therapy following an initial clinical improvement.

Acute Disease↗

Pharmacokinetics of spirapril and spiraprilat in patients with chronic renal failure.

In this single-blind trial with a 2-week placebo run-in followed by a 4-week active-treatment period, patients were given 6 mg of spirapril once daily. Forty-nine hypertensive men and women were recruited; all had pretreatment diastolic blood pressures (DBP) of 95-115 mmHg with varying degrees of renal impairment. Regression analysis of pharmacokinetic parameters C(max)ss (the maximum steady-state drug concentration in plasma during a dosing interval), Cl/f (total plasma clearance) and k (elimination rate constant) of spirapril on creatinine clearance (Clcr) showed that the pharmacokinetics of spirapril were not significantly influenced by the degree of renal impairment. C(max)ss values of spiraprilat, however, increased with decreasing Clcr, and AUC(l)ss (area under the concentration-time curve during a dosing interval) values also increased. Regression analysis of the pharmacokinetic parameters C(max)ss, Clm/fm (total plasma clearance) and lambda 1 (rate constant of the first disposition phase) of spiraprilat on Clcr showed that Clm/fm as well as lambda 1 were linearly correlated with Clcr (p < 0.01). However, the results indicate that, even when renal elimination is completely blocked, there is significant elimination of spiraprilat through a non-renal pathway. In conclusion, the risk of drug accumulation after multiple dosing is minimal as the presence of a substantial non-renal spiraprilat elimination was consistently demonstrated.

Adult↗

Spirapril in chronic renal failure.

In a single-blind trial with a 2-week placebo run-in phase and a 4-week active-treatment period, spirapril at 6 mg once daily was administered to 49 consecutive hypertensive patients (34 men and 15 women). All had pretreatment diastolic blood pressures (DBP) of 95-115 mmHg and varying degrees of renal impairment. At the end of the placebo run-in and at the end of active treatment, renal function was assessed using the following procedures: technetium 99m-DTPA clearance [for glomerular filtration rate (GFR)]; radioiodine (131I)-labelled sodium iodohippurate (Hippuran) clearance [for renal plasma flow (RPF)]; creatinine clearance (Clcr). No statistically significant differences were found in GFR or Clcr during spirapril treatment. In renally impaired patients, RPF remained virtually unchanged whereas, in patients with normal Clcr, there was an increase of around 10% during active treatment. At the end of the study, 48% of the patients with renal failure achieved normalization of DBP (< or = 90 mmHg) and/or a DBP reduction of > or = 10 mmHg; the corresponding rate for patients with normal renal function was 31%. In conclusion, in patients with mild-to-moderate essential hypertension and varying degrees of renal impairment, spirapril at 6 mg once daily is an efficacious and well tolerated antihypertensive therapy.

Adult↗

Treatment with high doses of loop diuretics in chronic renal failure.

In the late 60s, A. Heidland and his collaborators were amongst the first to characterize the renal action of frusemide in preterminal renal failure by giving quantitative information on dose requirements, fractional Na and K excretion, effects on renal haemodynamics, and by recognizing reversible inner ear dysfunction as the major dose-limiting side-effects. These early studies have been largely reconfirmed. They have been extended by more clearly characterizing (a) altered pharmacokinetics of frusemide, e.g. the importance of altered transepithelial transport in the proximal tubule and intratubular protein binding, and (b) the mechanisms underlying altered pharmacodynamics, particularly high baseline fractional Na rejection and increased absolute distal Na reabsorption. Apart from increasing the dose of frusemide, continuous administration by infusion and combination of frusemide with thiazide diuretics have emerged as rational therapeutic strategies in chronic renal failure.

Animals↗

Haemodialysis-associated beta 2M amyloidosis: current controversies.

Beta 2M amyloidosis is a major complication of long-term haemodialysis. Beta 2M, the precursor molecule of amyloid fibrils, accumulates in renal failure because of diminished renal excretion. Whether, in addition, a minor increase of synthesis occurs in dialysed patients is still controversial. Beta 2M amyloidosis differs from most other forms of amyloid by its preferential osteoarticular location. This points to some peculiar role of the microenvironment in the synovial space, which is currently poorly defined. A finding which remains so far unexplained is the more delayed appearance of beta 2M amyloidosis in patients dialysed with polyacrylonitrile membranes. In principle, however, beta 2M amyloidosis is seen with all dialysis modalities and possibly even before maintenance dialysis. Differences between treatment modalities relate either to removal of beta 2M or some aspect of bioincompatibility, e.g. proteolytic processing. Finally, the exact chemical nature of amyloid fibrils, i.e. whether they constitute native beta 2M molecules or processed molecules, is currently controversial.

Amyloid↗

Three-dimensional ultrasonography in maxillofacial surgery. A new diagnostic tool.

Three-dimensional (3-D) ultrasonography is introduced as a new diagnostic method for soft-tissue lesions. This method is based on the production of absolutely parallel brightness (B)-scan tomographies with constant intervals. After adequate preparation, the sonographic primaries are processed into 3-D graphs by a specialized program called EUCLID-IS. This method promises to be useful in the evaluation of tumor patients as well as in the follow-up examination of these patients. The main advantages of the presented method are the capacity to measure accurately the volume of regions of interest and the excellent visualization of the structures examined.

Adult↗

Calcium carbonate (CaCO3): an efficient and safe phosphate binder in haemodialysis patients? A 3-year study.

In an uncontrolled study, 22 dialysis patients (46 +/- 14 years, duration of dialysis 20 +/- 11 months) were treated with CaCO3 over a period of up to 3 years to lower their serum phosphate. The use of 4.5-9 g CaCO3 daily over a period of 9 months led to a reduction of mean serum phosphate from 2.51 to 1.51 mmol/l in 77% of patients, with a simultaneous increase in mean calcium concentration from 2.23 to 2.47 mmol/l, and an improved control of secondary hyperparathyroidism by reduction in mPTH from 1552 to 1032 pg/ml and in APH activity from 6.25 to 4.55 mumol/s/l. In long-term CaCO3 treatment of up to 3 years, however, a constant effective phosphate reduction could not be achieved. There was a progression (77%) of pre-existing microcalcification and a new appearance (42%) of microcalcification in vessels and soft-tissue areas of the hand. The percentage of patients with soft-tissue calcification increased from 43 to 67% during a treatment period of 3 years. We conclude that CaCO3 alone is not suitable on a long-term basis for phosphate reduction in dialysis patients.

Adult↗

Clinical evaluation of a new dialyzer, FLX-12 GW, with a polyester-polymer alloy membrane.

The performance of a membrane in renal failure therapy is determined by its structure, its overall mass transfer properties, and its blood compatibility. In this regard, removal of beta 2-microglobulin (beta 2M) has become a major objective of dialysis therapy. In the present study, a newly developed high-flux membrane composed of a polyester-polymer alloy (PEPA) with the components of polyarylate and polyethersulfone (dialyzer FLX-12 GW; Nikkiso Co., Japan) has been evaluated with regard to both biocompatibility and elimination capacity for beta 2M during hemodialysis of 8 stable chronic uremic patients. The clearance values of low molecular weight solutes were in the same range as those reported for high-flux dialyzers of comparable surface area. There was no drop in leukocyte counts and only a minimal fall in platelet counts nearly in the same range as has been observed by other investigators using polyamide membrane. C3a Des Arg generation was low, and C5a Des Arg formation was not significantly influenced. There was a sharp drop in the serum beta 2M level (-35%) during dialysis with a clearance between 59.7 +/- 5.6 ml/min (QB 200 ml/min) and 70.1 +/- 9.7 ml/min (QB 300 ml/min), respectively. Accordingly, the sieving coefficient was calculated to be 0.2 at 30 min after start of dialysis and 0.6 1 h later. The membrane was able to remove 184.0 +/- 22.3 mg/4 h due to an apparent rate of adsorption during the first hour of treatment in combination with high transmembrane transfer in the following time.

Adult↗

Lithium augmentation therapy in tricyclic-resistant depression. A controlled trial using lithium in low and normal doses.

Thirty-four patients with tricyclic-resistant depressive illness took part in a nine-week, double-blind, placebo-controlled trial of lithium augmentation. In addition to the maximum tolerated doses of their tricyclic antidepressant, the experimental group (n = 16) received 250 mg lithium daily for three weeks, followed by 750 mg lithium daily for six weeks, while the controls (n = 18) received placebo for three weeks followed by three weeks each of 250 mg lithium daily and 750 mg lithium daily. There was no significant difference between placebo and 250 mg lithium for weeks 0-3 of the trial. However, there was a significantly greater improvement on the MADRS for weeks 3-6 for those subjects on 750 mg lithium than for those on 250 mg lithium. In addition, using a 50% fall in the HRSD as a criterion of drug responsiveness, 22% responded to placebo, 18% to 250 mg lithium, and 44% to 750 mg lithium. Thus, lithium in normal, but not in low, dose has a significant antidepressant effect in TCA-resistant depression. Further controlled studies using lithium in normal dose in trials which have a greater duration of placebo exposure are required to confirm the lithium augmentation effect.

Adult↗

Contrasting renal haemodynamic effects of protein in normal subjects and glomerulonephritic patients with impaired renal function.

The effects of a protein load on renal haemodynamics in patients with renal failure are controversial. We measured insulin clearance (Cin) and PAH clearance (CPAH) by constant infusion technique in six healthy subjects and 13 patients with biopsy-confirmed glomerulonephritis and chronic renal failure. The subjects were pre-equilibrated on their usual diet and studied before and 2 h after 1 g protein/kg as cooked red meat. In healthy subjects this caused a significant increase of Cin (from 136 +/- 7.2 (SD) to 148 +/- 7.9 ml/min/1.73 m2) and of CPAH (from 547 +/- 142 to 639 +/- 89). In contrast Cin decreased from 72.7 +/- 7.7 to 60.3 +/- 8.4 in patients with chronic renal failure, whereas CPAH showed no significant change (from 275 +/- 67.8 to 278 +/- 72.7). A similar decrease of Cin was also seen with acute infusion of amino acids (AA). The change in Cin was not related to changes of PRA or concentrations of plasma amino acids. While absolute and fractional Na excretion increased in controls, they decreased in patients in parallel with the decrease of Cin. The decrease of Cin after infusion of AA was amplified by pre-equilibration on low-sodium diet (20 mmol Na/day). The effect of meat ingestion on Cin was not obliterated, however, by pretreatment with captopril (25 mg b.i.d. for 7 days). In conclusion, in patients with chronic renal failure, a paradoxical decrease in Cin is seen both after oral protein and after amino-acid infusion.

Adult↗

The rapid nongenomic actions of 1 alpha,25-dihydroxyvitamin D3 modulate the hormone-induced increments in osteocalcin gene transcription in osteoblast-like cells.

We have previously shown that one of the rapid nongenomic actions of 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25-(OH)2D3), the increase in intracellular calcium (Ca2+), accompanies the increased osteocalcin (OC) mRNA steady-state levels in rat osteosarcoma cells. To determine the functional significance of the nongenomic actions, we have measured changes in intracellular Ca2+ as an indicator of the rapid effects and have assessed the effect of inhibition of the rapid increase in cellular Ca2+ by the inactive epimer, 1 beta, 25-dihydroxyvitamin D3 (1 beta,25-(OH)2D3), on OC mRNA steady-state levels and transcription. 1 beta,25-dihydroxyvitamin D3 inhibited 1 alpha,25-(OH)2D3 induced increases in intracellular Ca2+ and OC mRNA transcription at 1 hr and OC mRNA steady state levels at 3 hr. 1 beta,25-Dihydroxyvitamin D3 did not alter the binding of the vitamin D receptor complex to the vitamin D responsive element of the OC gene. The results demonstrate the functional importance of the rapid, nongenomic actions of 1 alpha,25-(OH)2D3 in the genomic activation of the OC gene by the hormone in rat osteoblast-like cells, perhaps by modifying subtle structural and/or functional properties of the vitamin D-receptor DNA complex or by affecting other protein DNA interactions that support OC gene transcription.

Animals↗

The retrospective diagnosis of postnatal depression by questionnaire.

The Bromley postnatal depression scale is a new screening instrument specifically developed for detecting the presence of both current and previous episodes of postnatal depression. The scale gives a brief description of postnatal depression and respondents are asked to decide whether or not they had experienced such an illness following childbirth. The scale has satisfactory test-retest reliability and a Cohen's Kappa of 0.80 for previous postnatal depressive episodes. Using another scale which measures DSM.III major depression, the Bromley scale has a sensitivity of 62% and a specificity of 94%. The principle advantages of this method are that it provides information about previous postnatal periods and so provides longitudinal information and the method can be also used in postal surveys.

Depressive Disorder↗