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Biomedical subjects

A Schnabel

Publications and source records attributed to A Schnabel.

At least 91 records · Page 5Linked to original sources
PubMed1994

Tolerability of methotrexate starting with 15 or 25 mg/week for rheumatoid arthritis.

The objective of the present study was to assess the rate of side-effects and dose-limiting toxicity in patients with rheumatoid arthritis (RA) receiving methotrexate (MTX) at an initial dose of 15 or 25 mg/week. One hundred and eighty-five patients with active RA were enrolled into a prospective non-blind trial over 12 months and randomized to start at a dose of 15 mg/week with subsequent increases if necessary (group A) or 25 mg/week with subsequent dose reductions according to effect (group B). With 168 patients eligible for evaluation 74% of patient in group A and 73% of patients in group B were on MTX after 12 months. Withdrawal due to side-effects amounted to 16% of patients in group A and 18% in group B, and decreases in dose due to side-effects amounted to 10% in group A and 9% in group B. The higher dose of MTX elicited a significantly higher rate of gastrointestinal side-effects (28% versus 17%, P < 0.05) and a tendency towards a higher rate of liver enzyme elevations (47% versus 39%). The frequencies of other side-effects did not differ significantly between the groups. We concluded that starting MTX treatment at a dose of 25 mg/week was associated with a higher rate of minor but not major toxicity as compared with 15 mg/week. With this profile of tolerability it is possible to examine the therapeutic potential of MTX doses exceeding 15 mg/week.

Aged↗
PubMed1994

Low-dose methotrexate in rheumatic diseases--efficacy, side effects, and risk factors for side effects.

Controlled trials and observational studies have shown low-dose methotrexate (MTX) to be a second-line agent of high potency with a favorable profile of safety and tolerability in the treatment of rheumatoid arthritis (RA). Its risk-benefit ratio in psoriatic arthritis is less well documented. Preliminary reports on its beneficial effects in other disorders, including the systemic manifestations of RA, other spondyloarthritides, and collagen vascular diseases, merit more detailed examination. Gastrointestinal intolerance and hepatic enzyme elevation are the most frequent side effects of MTX; life-threatening events such as severe hemocytopenia and MTX pneumonitis are rare and amenable to prevention by recognizing risk factors and premonitory signs. Hepatotoxicity does not appear to be a major limiting factor in RA patients over the first 2 to 3 years of MTX therapy; its impact on long-term tolerance remains to be clarified.

Arthritis, Rheumatoid↗
PubMed1994

[High-resolution CT (HRCT) of the lung in Wegener's granulomatosis].

HRCT of the lung and plain chest X-ray were performed to reveal pulmonary manifestation in primary diagnostics or reevaluation of 35 patients with Wegener's granulomatosis. Pleural and parenchymal pathology was detected in chest X-ray of 20 (57%) and in HRCT of 30 (85.7%) patients. Granulomas with and without cavitations and with smooth or spiculated margins were deemed pathognomonic. Nonspecific findings were infiltrates, thickened interlobular septae and fibrotic changes of parenchyma and pleura. Ground glass opacities, traction bronchiectasis and small cysts were only visible on HRCT. As expected HRCT proved to be more sensitive in detecting subtle lung alterations than plain film chest X-ray. It helps to differentiate acute inflammatory and thus potentially curable processes from chronic fibrotic changes in Wegener's granulomatosis.

Adult↗
PubMed1993

Effectiveness of cyclophosphamide pulse treatment in Wegener's granulomatosis.

43 patients with Wegener's granulomatosis were studied to evaluate the effectiveness of cyclophosphamide (cyc) pulse treatment. 42% of the patients showed benefits from treatment for at least 6 months after the cessation of cyc pulses. Analysis of clinical and laboratory parameters indicate that this treatment is less effective in patients in whom more than 4 organ systems are involved. Responders to the treatment showed disease manifestations predominantly in the ENT and lower respiratory tract and had lower cANCA titers (< 1:64) prior to treatment.

Adolescent↗
PubMed1993

Treatment of Wegener's granulomatosis with intravenous immunoglobulin.

We report about the treatment of eight patients with Wegener's granulomatosis and one patient with systemic pANCA-associated vasculitis with a single course of high-dose intravenous immunoglobulin (IVIG). In 5 of 9 patients (55%) this resulted in significant clinical improvement, in two patients a decrease of the ANCA-titre was seen.

Adult↗
PubMed1993

The acquired hyperostosis syndrome: a little known skeletal disorder with distinctive radiological and clinical features.

The acquired hyperostosis syndrome (AHS) is a chronic inflammatory disorder of bone of unknown etiology. It is accompanied by circumscribed hyperostosis which can be associated with ossifying lesions at sites of tendinous and ligamentary insertions and erosive or non-erosive arthritis. The predominant location of lesions is the sternocostoclavicular region (approximately 80% of patients), less frequent are involvement of the spine, pelvis, and appendicular skeleton. In 20%-60% of cases AHS is associated with palmoplantar pustulosis, psoriasis, or severe acne (acne fulminans or conglobata). The X-ray appearance of AHS is a more or less homogeneous increase in density with blurred margins, which on scintiscan with labeled phosphate compounds is associated with intense accretion of tracer. These features are associated with a variable increase in the acute phase reactants and a conspicuously low increase, if any, in serum alkaline phosphatase. The therapeutic modalities which have been used so far are entirely symptomatic. Long-lasting improvement has been reported following percutaneous anti-inflammatory radiation therapy.

Acne Vulgaris↗
PubMed1993

Effective sizes for subdivided populations.

Many derivations of effective population sizes have been suggested in the literature; however, few account for the breeding structure and none can readily be expanded to subdivided populations. Breeding structures influence gene correlations through their effects on the number of breeding individuals of each sex, the mean number of progeny per female, and the variance in the number of progeny produced by males and females. Additionally, hierarchical structuring in a population is determined by the number of breeding groups and the migration rates of males and females among such groups. This study derives analytical solutions for effective sizes that can be applied to subdivided populations. Parameters that encapsulate breeding structure and subdivision are utilized to derive the traditional inbreeding and variance effective sizes. Also, it is shown that effective sizes can be determined for any hierarchical level of population structure for which gene correlations can accrue. Derivations of effective sizes for the accumulation of gene correlations within breeding groups (coancestral effective size) and among breeding groups (intergroup effective size) are given. The results converge to traditional, single population measures when similar assumptions are applied. In particular, inbreeding and intergroup effective sizes are shown to be special cases of the coancestral effective size, and intergroup and variance effective sizes will be equal if the population census remains constant. Instantaneous solutions for effective sizes, at any time after gene correlation begins to accrue, are given in terms of traditional F statistics or transition equations. All effective sizes are shown to converge upon a common asymptotic value when breeding tactics and migration rates are constant. The asymptotic effective size can be expressed in terms of the fixation indices and the number of breeding groups; however, the rate of approach to the asymptote is dependent upon dispersal rates. For accurate assessment of effective sizes, initial, instantaneous or asymptotic, the expressions must be applied at the lowest levels at which migration among breeding groups is nonrandom. Thus, the expressions may be applicable to lineages within socially structured populations, fragmented populations (if random exchange of genes prevails within each population), or combinations of intra- and interpopulation discontinuities of gene flow. Failure to recognize internal structures of populations may lead to considerable overestimates of inbreeding effective size, while usually underestimating variance effective size.

Animals↗
PubMed1992

[Oxygen radical formation in pulmonary sarcoidosis. The signs of early macrophage activation].

Oxygen radical formation of alveolar macrophages (by luminogenic substrate-intensified chemiluminescence) and the concentrations of phagocyte products myeloperoxidase, elastase and lactoferrin, as well as alpha-proteinase inhibitor and albumin were measured in bronchoalveolar lavage fluid of 28 patients with pulmonary sarcoidosis. There were 15 men and 13 women (mean age 41 [18-62] years), 10 of them with sarcoidosis I, 10 with clinically active sarcoidosis II and 8 with inactive sarcoidosis II. Six healthy persons served as controls. The purpose of the study was to demonstrate the extent of correlation between macrophage activity and stage of sarcoidosis. Patients in stage I had significantly higher luminescence (346 +/- 253 relative light units [RLU] per second) than the controls (117 +/- 29 RLU/s; P less than 0.02). But the difference between controls and patients in clinically active stage II (294 +/- 75 RLU/s) was not significant and the luminescence in patients with clinically inactive stage II was within normal range (119 +/- 33 RLU/s). The concentrations of proteins measured in the lavage fluid was increased, independent of the site of formation. These data indicate that in pulmonary sarcoidosis there exists, early and independent of stage, a marked activation of alveolar macrophages with increased production of oxygen radicals and a resulting increase in permeability of the alveolo-capillary membrane.

Adolescent↗
PubMed1992

Comparative effects of pollen and seed migration on the cytonuclear structure of plant populations. II. Paternal cytoplasmic inheritance.

We continue our study of the effects of pollen and seed migration on the cytonuclear structure of mixed-mating plant populations by analyzing two deterministic continent-island models under the critical assumption of paternal cytoplasmic inheritance. The major results of this study that contrast with our previous conclusions based on maternal cytoplasmic inheritance are (i) pollen gene flow can significantly affect the cytonuclear structure of the island population, and in particular can help to generate cytonuclear disequilibria that greatly exceed the magnitude of those that would be produced by seed migration or mixed mating alone; (ii) with simultaneous pollen and seed migration, nonzero cytonuclear disequilibria will be maintained not only when there is disequilibrium in the immigrant pollen or seeds, but also through a variety of intermigrant admixture effects when the two pools of immigrants differ appropriately in their cytonuclear compositions; (iii) either immigrant pollen or immigrant seeds can generate disequilibria de novo in populations with initially random cytonuclear associations, but pollen migration alone generally produces lower levels of disequilibrium than does comparable seed migration, especially at high levels of self-fertilization when the overall fraction of immigrant pollen is low; (iv) the equilibrium state of the island population will be influenced by the rate of pollen gene flow whenever there is either allelic disequilibrium in the immigrant pollen or simultaneous seed migration coupled with different cytoplasmic or nuclear allele frequencies in immigrant pollen and seeds or nonzero allelic disequilibrium in either immigrant pool. The estimation of pollen migration should therefore be facilitated with paternal cytoplasmic inheritance relative to the case of maternal cytoplasmic inheritance. These basic conclusions hold whether the population is censused as seeds or as adults, but with simultaneous pollen and seed migration, the relationship between census time and the ability to detect nonrandom cytonuclear associations is complex. When migration is through pollen alone, however, the cytonuclear structure of the island population is independent of the life stage censused.

Alleles↗
PubMed1991

[Tryptophan-induced fasciitis-scleroderma-eosinophilia syndrome].

A fasciitis-sclerodermia-eosinophilia syndrome developed in four female patients, aged between 55 and 75 years, after the ingestion of tryptophan, 1.5-6.0 g daily, for 13 months to 7 years. It began characteristically with hard oedema of the limbs, sometimes also of the trunk. Later there occurred diffuse indurations of the body surface with fixation of the skin to fascial planes. This was associated with mainly sensory peripheral neuropathy. Three of the patients had an eosinophilia (12-30%). Histological examination revealed a cell-poor fasciitis, fibrosis of the cutis and subcutis, perimyositis and epidermal atrophy of varying degree. Erythrocyte sedimentation rate was at most slightly increased. Antinuclear antibodies were demonstrated in one patient (1:80). Serum aldolase concentration was raised (3.4-5.4 U/l), while creatine kinase was normal. The disease progressed even after tryptophan was discontinued, in only one patient there was improvement during glucocorticoid treatment. In two cases the skin induration regressed slowly after administration of methotrexate (15 mg weekly) and hydroxychloroquine (400 mg daily).

Aged↗
PubMed1991

Comparative effects of pollen and seed migration on the cytonuclear structure of plant populations. I. Maternal cytoplasmic inheritance.

We explicitly solve and analyze a series of deterministic continent-island models to delimit the effects of pollen and seed migration on cytonuclear frequencies and disequilibria in random-mating, mixed-mating and self-fertilized populations. Given the critical assumption of maternal cytoplasmic inheritance, five major findings are (i) nonzero cytonuclear disequilibria will be maintained in the island population if and only if at least some migration occurs each generation through seeds with nonrandom cytonuclear associations; (ii) immigrant seeds with no cytonuclear disequilibria can strongly affect the genetic structure of the island population by generating significant and long-lasting transient associations; (iii) with all else being equal, substantially greater admixture disequilibria are generally found with higher rates of seed migration into, or higher levels of self-fertilization within, the island population (with the possible exception of the heterozygote disequilibrium); (iv) pollen migration can either enhance or reduce the cytonuclear disequilibria caused by seed migration, or that due to mixed-mating in the absence of seed migration, but the effect is usually small and appears primarily to make a noticeable difference in predominantly outcrossing populations; and (v) pollen migration alone cannot generate even transient disequilibria de novo in populations with completely random associations. This same basic behavior is exhibited as long as there is some random outcrossing in the island population. Self-fertilized populations represent a special case, however, in that they are necessarily closed to pollen migration, and nonzero disequilibria can be maintained even in the absence of seed migration. All of these general results hold whether the population is censused as adults or as seeds, but the ability to detect nonrandom cytonuclear associations can depend strongly on the life stage censused in populations with a significant level of random outcrossing. We suggest how these models might be used for the estimation of seed and pollen migration.

Cell Nucleus↗
PubMed1989

Definition and properties of disequilibria within nuclear-mitochondrial-chloroplast and other nuclear-dicytoplasmic systems.

We define and determine the interrelationships among five sets of disequilibrium parameters that measure two- and three-locus nonrandom associations in nuclear-dicytoplasmic systems. These assume a diploid nuclear locus and two haploid cytoplasmic loci, with special reference to nuclear-mitochondrial-chloroplast systems. Three sets of two-locus disequilibria measure the association between haplotypes at the two cytoplasmic loci (DMC) and associations between each cytoplasmic locus and nuclear alleles or genotypes (DM, D1M, D2M, D3M; DC, D1C, D2C, D3C). In addition, we present two classes of higher-order disequilibria that measure nonrandom allelic or genotypic associations involving all three loci. The first class quantifies associations between the nuclear locus and the two cytoplasmic loci taken jointly (DA/MC, DAA/MC, DAa/MC, Daa/MC, etc.), whereas the second measures only those associations remaining after all two-locus associations have been taken into account (DA/M/C, DAA/M/C, DAa/M/C, Daa/M/C). Based on combinations of these five sets of measures, we suggest a variety of parameterizations of three-locus, nuclear-dicytoplasmic systems. The dynamics of these disequilibria are then investigated under models of random and mixed mating, either with both cytoplasmic genomes inherited through the same parent or through opposite parents. Except for associations between the cytoplasmic haplotypes, which are constant when the two cytoplasmic genomes are inherited through the same parent, all disequilibria ultimately decay to zero. These randomizations do not necessarily occur monotonically, however, and in some cases are preceded by an initial increase in magnitude or sign change. For both inheritance patterns, the asymptotic decay rates are steadily retarded by increasing levels of self-fertilization. This behavior contrasts with that in the extreme case of complete selfing, for which only the heterozygote disequilibria always decay to zero. For all models considered, the dynamics of the two-locus cytonuclear subsystems are solely a function of the mating system, whereas the dynamical behavior and sign patterns of the cytoplasmic and three-locus disequilibria also depend strongly on the mode of cytoplasmic inheritance.

Cell Nucleus↗
PubMed1984

Metabolic and hormonal responses to exhaustive supramaximal running with and without beta-adrenergic blockade.

The metabolic and hormonal responses to exhaustive short-term supramaximal exercise were studied in 10 male physical education students. The exercise task was a single bout of running on the treadmill at 22 km X h-1 and 7.5% slope. It was performed with single oral doses of 100 mg Bupranolol (non-selective beta-blockade), 100 mg Metoprolol (beta-1-selective blockade), and placebo. Arterialized capillary and venous blood were sampled until 30 min post exercise. Time to exhaustion was 52.0 +/- 2.6, 47.6 +/- 2.0, and 46.0 +/- 1.9 s in the control, Metroprolol, and Bupranolol experiments. At cessation of exercise, adrenaline and noradrenaline were grossly elevated in all three conditions. Lactate and glucose increased markedly, this being accompanied by increasing insulin in the control and Metoprolol, but not the Bupranolol trials. Glycerol increased moderately, while FFA were depressed. Growth hormone showed a delayed increase at 15 and 30 min post exercise. Cortisol was unaffected by exercise. beta-blockade reduced the increases of lactate, glucose, glycerol, insulin, and growth hormone, exaggerated the depression of FFA and had no effect on cortisol. The results demonstrate that the strong sympatho-adrenal response to exercise of this nature is a major determinant of the increase of glucose at cessation of exercise. The hyperglycemia in concert with beta-2-adrenergic stimulation leads to elevation of insulin. Furthermore, lipolysis is controlled by beta-adrenergic stimulation. The delayed increase of growth hormone seems to be triggered by the declining glucose level during recovery.

Adrenergic beta-Antagonists↗