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Biomedical subjects

M Schuler

Publications and source records attributed to M Schuler.

At least 73 records · Page 4Linked to original sources
PubMed1996

Fiber transformation and replacement in low-frequency stimulated rabbit fast-twitch muscles.

The fast-to-slow conversion of rabbit skeletal muscles by chronic low-frequency (10 Hz, 12 h daily) stimulation involves (1) sequential fast-to-slow fiber-type transitions in the order of type IID-->type IIA-->type I, and (2) the replacement of deteriorating fast-twitch glycolytic fibers by new fibers derived from satellite cells and myotubes. These two processes were analyzed in 30- and 60-day stimulated extensor digitorum longus and tibialis anterior muscles. Fast-to-slow transforming fibers were identified by myofibrillar actomyosin histochemistry as type C fibers and immunohistochemically by their reaction with monoclonal antibodies specific to slow and fast myosin heavy chain isoforms. In situ hybridization of mRNA specific to the myosin heavy chain I isoform identified all fibers expressing slow myosin, i.e., type I and C fibers. The fraction of transforming fibers ranged between 35% and 50% in 30-day stimulated muscles. The percentage of type I fibers (20%) was threefold elevated in extensor digitorum longus muscle, but unaltered (3.5%) in tibialis anterior muscle, suggesting that fast-to-slow fiber conversion was more advanced in the former than in the latter. Fiber replacement was indicated by the finding that the fiber populations of both muscles contained 15% myotubes or small fibers with central nuclei. In situ hybridization revealed that myotubes and small regenerating fibers uniformly expressed myosin heavy chain I mRNA. Similarly, high percentages of slow-myosin-expressing myotubes and small fibers were found in 60-day stimulated muscles.

Adenosine Triphosphatases↗
PubMed1996

Immunomodulatory and hematopoietic effects of recombinant human interleukin-6 in patients with advanced renal cell cancer.

Interleukin-6 (IL-6) is a cytokine with pleiotropic biologic activities on B cells, T cells, and hematopoietic progenitors. The present study was undertaken to assess pharmacodynamic effects of subcutaneous administration of IL-6 on blood counts, immunologic parameters, and acute-phase reactants. Blood samples were taken from patients with advanced renal cell cancer participating in a phase II trial of recombinant human IL-6. Multiparameter FACS analyses of peripheral blood mononuclear cells were performed using antibodies against CD3, CD4, CD8, HLA-DR, CD56, CD28, CD38, CD19, sIgM, and sIgG. Serum levels of IL-10, soluble CD23 (sCD23), sCD25, IL-1 receptor antagonist protein (IL-1RA), soluble tumor necrosis factor (TNF) receptors (sTNF-R) p55 and p75, and soluble IL-6 receptor (sIL-6R) were detected by ELISA systems. Levels of C-reactive protein (CRP), neopterin, fibrinogen, beta 2-microglobulin, and immunoglobulins M, G, and A were measured by standard methods. In response to administration of IL-6, a significant increment in platelet counts was observed, reaching peak levels after 21 days of treatment. In contrast, leukocyte subsets remained unaffected. No change in number of immunophenotype of peripheral blood B cells, T cells, or natural killer cells could be detected following IL-6 administration. Blood levels of sCD23, IL-10, sIL-6R, neopterin, beta 2-microglobulin, and immunoglobulin subsets were not influenced by cytokine therapy. However, administration of IL-6 led to a slow increment of acute-phase reactants CRP and fibrinogen. Furthermore, the anti-inflammatory molecules sTNF-R p55 and p75 were induced by IL-6, whereas serum levels of IL-1RA remained unchanged. Finally, an increase in blood levels of sCD25 was observed. In conclusion, IL-6 in vivo predominantly acts as a regulator of inflammation and a megakaryocyte differentiation factor.

Acute-Phase Reaction↗
PubMed1995

Cytokines in the pathophysiology and treatment of chronic B-cell malignancies. A review.

Chronic B-cell malignancies are characterized by accumulation of transformed B cells of low proliferative index in lymphatic and extralymphatic tissues. Cytokines do not appear to play a role in the primary step of transformation. However, proliferation as well as inhibition of apoptosis of malignant B cells can readily be explained by cytokine effects. Clinical trials of interferons (IFN) and interleukin-2 alone or in combination have been performed in patients with hairy cell leukemia (HCL), CLL, and low- and intermediate-grade non-Hodgkin's lymphoma. While IFN alpha became standard therapy of HCL, responses in other entities were variable, ranging from 0 to 70% in selected populations. Combination of IFN and cytotoxic chemotherapy in general revealed no additional benefit as compared to chemotherapy alone. Perspectives for future clinical testing of cytokines in low-grade B-cell lymphomas are discussed.

B-Lymphocytes↗
PubMed1995

Plasma levels of IL-1, TNF alpha, IL-6, IL-8, G-CSF, and IL1-RA during febrile neutropenia: results of a prospective study in patients undergoing chemotherapy for acute myelogenous leukemia.

Plasma levels of IL-1, IL-6, IL-8, IL1-RA, TNF alpha, and G-CSF were prospectively studied during 23 chemotherapy cycles of 20 patients suffering from acute myelogenous leukemia. Increased plasma levels of IL-6, IL-8, and G-CSF were observed in patients with febrile neutropenia and/or major infection. Plasma levels of IL-6, IL-1, TNF alpha and IL-1-RA measured 1 day before and 1 day after the onset of febrile episodes did not accurately predict the development of major infection. In contrast, IL-8 plasma levels were significantly higher in those patients who subsequently developed major infection. The question whether IL-8 plasma levels identify high risk or low risk patients with sufficient specificity and sensitivity has to be answered in large scale clinical trials.

Adolescent↗
PubMed1995

Advantages and limitations of using fluorescence in situ hybridization for the detection of aneuploidy in interphase human cells.

Fluorescence in situ hybridization with chromosome-specific DNA probes is being increasingly utilized for the detection of chromosome aberrations induced in vitro and in vivo by chemical and physical agents. Although potentially a powerful technique, FISH studies for aneuploidy can be heavily influenced by cellular phenomena and hybridization artifacts which make the performance and interpretation of the results difficult. As a consequence, frequently hyperdiploid frequencies are reported in the literature which are substantially higher than one would expect based upon frequencies seen in conventional metaphase analyses. In this article, a number of the potential pitfalls that we have encountered while performing FISH analyses for aneuploidy are discussed and their potential impact on the observed hybridization frequencies is described. After considering these factors, the frequencies of lymphocyte nuclei containing 3 and 4 chromosome copies are compared between metaphase values obtained from published human population studies and interphase values obtained from similar studies using FISH. It is concluded that by using caution in the evaluation of slides, interphase studies using FISH to detect hyperdiploidy and polyploidy can provide estimates of numerical alterations which closely reflect those seen during metaphase analysis using either FISH or conventional approaches. However, due to the inability of interphase analysis to distinguish hyperdiploidy from polyploidy as well as other potential problems, frequencies of aneuploid nuclei obtained using single label FISH should only be considered approximations of absolute frequencies. For additional accuracy, multi-color FISH with two or more different probes should be performed.

Aneuploidy↗
PubMed1994

Interleukins. Clinical pharmacology and therapeutic use.

With interleukins (IL), a new class of potential drugs has been introduced into clinical research. These signal peptides are involved in the regulation of many physiological and pathophysiological processes. IL-1, -2, -3, -4, -6 and -11 have been tested in clinical trials. The growth promoting, growth inhibiting or immunomodulatory activities of interleukins represent the theoretical basis for large scale clinical testing, predominantly in malignant disease. Dose-dependent effects on numbers of peripheral blood cells and recovery from bone marrow failure have been demonstrated for IL-1, -3, -6 and -11. Phase III trials are in progress to determine their value for clinical practice. However, investigations on the immunomodulatory activities proved to be more difficult. This is because key mechanisms for successful treatment of malignant disease by immunomodulation are not clearly defined and the methodology for assessment of immunostimulatory effects is not well established. Besides treatment of renal cell carcinoma and malignant melanoma with IL-2, no successful trials have been reported. However, phase I clinical trials with IL-1, IL-4 and IL-6 have just been completed. Thus, it seems too early to conclude on their therapeutic potential.

Adjuvants, Immunologic↗
PubMed1994

Parenting and early development among children of drug-abusing women: effects of home intervention.

OBJECTIVE: To evaluate the efficacy of home intervention with drug-abusing women on parenting behavior and attitudes, and on children's development. DESIGN: A randomized, clinical trial of 60 drug-abusing women recruited prenatally and randomized into an intervention (n = 31) or comparison (n = 29) group. There were no group differences in gestational age, 1-minute Apgar scores, duration of hospital stay, or neonatal abstinence score. Intervention infants were slightly heavier (P = .098) and had slightly lower 5-minute Apgar scores (P = .089). Most mothers were single, African-American, multiparous, and non-high school graduates from low income families. Approximately 40% of the women were human immunodeficiency virus (HIV)-positive, all admitted to either cocaine and/or heroin use, and 62% had a history of incarceration. Intervention and comparison group women did not differ on any background variables. INTERVENTIONS: All children received primary care in a multidisciplinary clinic. Biweekly home visits were provided by a nurse beginning before delivery and extending through 18 months of life. The intervention was designed to provide maternal support and to promote parenting, child development, the utilization of informal and formal resources, and advocacy. MEASUREMENTS: Behavioral measures included self-reported ongoing drug abuse, compliance with primary care appointments, and an observation of the child-centered quality of the home (HOME Scale). Parenting attitudes were measured by the Child Abuse Potential Inventory (CAPI) and the Parenting Stress Index. The CAPI was administered before initiating the intervention and the Parenting Stress Index was administered when the children were 3 months of age. Both scales were repeated when the children were 18 months of age. Developmental status was measured with the Bayley Scales of Infant Development administered at 6, 12, and 18 months. ANALYSES: Repeated measures multivariate analyses of variance were used to examine changes in parenting attitudes and children's development. Analyses of covariance were used to examine compliance with primary care appointments and the quality of the home. Logistic regression was used to examine ongoing drug abuse. Birth weight and maternal education were used as covariates in all analyses. To control for social desirability, the faking-good index of the CAPI was included as a covariate in analyses involving self-report measures. MAIN RESULTS: Women in the intervention group were marginally more likely to report being drug-free (P = .059) and were compliant with primary care appointments for their children (P = .069). Based on the HOME Scale, women in the intervention group were more emotionally responsive (P = .033) and provided marginally more opportunities for stimulation (P = .065). At 18 months parents reported more normative attitudes regarding parenting and more child-related stress than they had initially, but the differences were not related to intervention status. At 6 months infants in the intervention group obtained marginally higher cognitive scores (P = .099); at 12 and 18 months there were no differences. CONCLUSIONS: The findings suggest a cautious optimism regarding the efficacy of early home intervention among drug-abusing women in promoting positive behaviors. Subsequent investigations of home intervention should include larger sample sizes and more intensive options.

Adult↗
PubMed1993

Prenatal drug exposure: neurodevelopmental outcome and parenting environment.

Examined neurodevelopmental patterns and caregiving environment among 20 infants prenatally exposed to cocaine and 20 drug-free infants. The Brazelton Scale was administered 4 times. Drug-exposed infants had less optimal neurodevelopment than comparison infants at birth, but by 6 weeks only differences in autonomic stability were apparent. Neurodevelopmental performance was related positively to the child-centered quality of the environment. Though support buffered stress in both groups, the effect was more robust among drug-free mothers. Findings support the need to consider neurodevelopmental recovery and the caregiving environment in evaluations of developmental outcome among drug-exposed infants.

Developmental Disabilities↗
PubMed1992

Glycosaminoglycans in thyroid-associated ophthalmopathy.

Glycosaminoglycan (GAG) accumulation in the retrobulbar space of patients with thyroid-associated ophthalmopathy (TAO) has been documented in a number of immunohistochemical studies. In order to gain further insight into possible immunopathogenic mechanisms, the influence of humoral immunity on retrobulbar fibroblasts (RF) as GAG producing cells as well as on GAGs themselves was investigated. The effect of lymphocytes on hyaluronic acid (HA) synthesis of RF as well as in turn the influence of RF on lymphocytes were evaluated. In search of methods which would facilitate management of patients with TAO and allow assessment of disease activity, GAGs were determined in both urine and plasma. Immunoglobulin G (IgG) of patients with TAO were found to markedly stimulate the 3H-GAG secretion of RF. Patients with TAO exhibited significantly greater antibody values directed against HA than controls. Preliminary results concerning the influence of lymphocytes on RF indicate a tendency for patients' lymphocytes to increase the synthesis of HA. Furthermore, these lymphocytes in turn were stimulated more by irradiated autologous RF than by irradiated heterologous RF. Urine and plasma GAG determination proved to be suitable for the routine assessment of disease activity and outcome of therapy. In conclusion, GAGs seem to play an important role in the pathogenesis of the disease and their measurement may provide aid to the endocrinological evaluation of patients with TAO.

Antibody Formation↗
PubMed1992

[The 1980s: demographic trends reversed].

Some recent changes in the spatial distribution of the population of Switzerland are analyzed. The authors suggest that "a new equilibrium is taking shape within the repartition of the Swiss population....Especially the interregional migration flows do not seem to have spatial preferences any longer, if we consider the total figures and not their demographic and socio-economic structure. The dichotomy center-periphery is slowing down, but the explanation of the pattern of population distribution lies in an analysis of micro-processus which seems to show a deep change; the population segregation within agglomerations is growing." (SUMMARY IN ENG AND GER)

Demography↗
PubMed1990

Urinary glycosaminoglycans in Graves' ophthalmopathy.

An increased accumulation of glycosaminoglycans (GAG) in retrobulbar tissues has been reported in patients with thyroid eye disease. We examined the quantitative urinary GAG excretion in 101 patients with Graves' ophthalmopathy of different classes, 36 patients with Graves' hyperthyroidism without ophthalmopathy, 14 patients with toxic nodular goitre and 103 control subjects. Glycosaminoglycans were isolated from 24-h urine collections by precipitation with cetylpyridinium chloride and ethanol followed by photometrical quantification of hexuronic acids after reaction with carbazole. In comparison with the control group (15.8, 10.4, 21.6 mg/24 h; median, 25th, 75th percentile) a significant (P less than 0.005) elevation of urinary GAG excretion was found in patients with ophthalmopathy (19.2, 12.2, 28.7 mg/24 h), whereas patients with Graves' hyperthyroidism and no ophthalmopathy (16.2, 11.9, 21.7 mg/24 h) and patients with toxic nodular goitre (15.8, 11.5, 21.2 mg/24 h) exhibited no markedly increased values. Especially, patients with active, untreated ophthalmopathy showed on average a twofold increase (36.7, 28.1, 48.4 mg/24 h) in urinary GAG excretion. In contrast, high values were not found in patients with inactive ophthalmopathy and elevated values decreased under treatment, which correlated with clinical findings. Further, relapses were also accompanied by high GAG excretion. Thus, using a simple laboratory method, quantitative determination of urinary GAG excretion appears to present an effective parameter for the activity of Graves' ophthalmopathy.

Adolescent↗
PubMed1989

Conceptual development in infancy: the understanding of containment.

In each of 2 experiments, 2 measures were used to assess infants' understanding of the concept of "containment." After being habituated to videotaped episodes of sand being poured into and out of a cylinder, infants saw a "possible" event and then an "impossible" event. Infants who understand containment were expected to look longer at the "impossible" event. In the second test, infants were involved in a game of dropping blocks into a cup. In Experiment 1, 14-month-olds were contrasted with 20-month-olds to establish that the latter but not the former demonstrate an understanding of containment on both tasks. This age effect was obtained. In Experiment 2, we examined whether this understanding could be acquired by 14-month-olds. 50 infants were randomly assigned to 5 training conditions. 1 condition was effective in leading to the development of an understanding of containment: Infants who played with both cans and tubes in their home for 1 month performed in both tests similarly to untrained 20-month-olds.

Child Development↗
PubMed1988

Significance of thrombin-receptors of thrombocytes for the interaction of heparins and low-molecular-weight heparin in human whole blood clotting.

We describe in the present paper the results of the influence of normal and low-molecular-weight heparin on the interaction of human fibrinogen and thrombocytes in human whole blood cotting ex vivo. During the coagulation process sequential measurements of fibrinopeptide A reflect fibrin formation and determination of platelet factor 4 indicate activation of thrombocytes. The data show that low-molecular-weight heparin inhibits plasma thrombin generation in vivo for longer than normal heparin and it affects the fibrinogen platelet binding less. There is good evidence that a lonely factor Xa inhibition mediates this anticoagulant mechanism. Therefore, these data favor the hypothesis that antifactor Xa activity prevents indeed blood clotting.

Blood Coagulation↗
PubMed1988

[DS-1000--a new digital image intensifier film-screen system in thoracic diagnosis].

The characteristics of the DS-1000, a new digital imaging equipment, using an image-intensifier-video-system are described. The digital images are displayed on a monitor with 1024 x 1024 matrix, are stored on a hard disc and can be postprocessed with regard to gray-scale-level and recognition of details. The spatial resolution ist 1,1 Lp/mm, using the 47-cm-image-intensifier. The DS 1000 was employed for chest-examinations. The diagnostic accuracy of 70 selected cases with a great variety of pathologic conditions was verified in comparison to conventional chest films. There was no significant difference in the recognition of normal anatomic structures between the two imaging systems. Pathologic states with low contrast to the surrounding structures (mediastinal and hilar masses, airspace disease, pulmonary nodules) were displayed at least equivalent with the digital technique. The accuracy in recognizing pathologic states with the digital equipment as compared to the conventional technique was inferior for conditions requiring high spatial resolution (subtle interstitial infiltrations, septal lines, scars, subtle calcifications).

Diagnosis, Differential↗
PubMed1987

[Value of high-resolution CT and nuclear magnetic resonance tomography compared to the standard procedures in the diagnosis of meniscal lesions].

The knees of 20 patients with evidence of meniscal tears were examined via high-resolution computed tomography (HRCT); 10 of these were studied by MRI. The HRCT study was performed directly after double-contrast arthrography (AG). For comparison with HRCT, slice orientation for MRI examination was in transverse view; gradient echo sequences using the FISP technique were applied instead of spin echo sequences. All results were correlated to the arthroscopy (AS) findings. In 95% of the cases AG and AS results agreed, HRCT/AS in 85% and MRI/AS in 70%. In certain cases HRCT provided additional information which influenced appropriate surgical treatment. MRI is a noninvasive nonionising method but gives a less exact documentation of the lesion than AG and HRCT. The gradient echo mode is superior to the SE mode in respect of outlining meniscal structures, at least in transverse view.

Adult↗