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Biomedical subjects

M Schmitz

Publications and source records attributed to M Schmitz.

At least 73 records · Page 4Linked to original sources
PubMed1999

Treatment of refractory chronic depression and dysthymia with high-dose thyroxine.

BACKGROUND: An 8-week open trial was conducted to investigate whether patients with treatment-resistant, chronic depression and/or dysthymia could profit from high-dose thyroxine (T4) augmentation. METHODS: Nine patients whose current depressive episode had lasted for a mean of 15.5 +/- 8.6 months (range: 2-30 months) received T4 in addition to their current medication. RESULTS: Two patients dropped out of the study owing to side effects. The remaining 7 patients received a final mean dose of T4 of 235 +/- 58 micrograms/day (range: 150-300 micrograms/day). Their scores on the Hamilton Depression Rating Scale had fallen from a mean of 21.1 +/- 4.1 before inclusion in the study to a mean of 8.0 +/- 2.8 at the end of the 8th week. Five patients were full responders, 1 a partial responder, and 1 a nonresponder. CONCLUSIONS: Augmentation with high-dose T4 proved to have an antidepressant effect in more than 50% of the previously treatment-resistant patients with chronic depression and/or dysthymia.

Adult↗
PubMed1999

Multimodality diagnostics and megatherapy in poor prognosis Ewing's tumor patients. A single-center report.

BACKGROUND: The prognosis of Ewing's tumor patients has been improved gradually through cooperative therapy studies, so that meanwhile 55 to 65% of the patients survive relapse-free in the long term. Patients with multifocal primary, early or multiply-relapsed Ewing's tumors have a dismal prognosis. Megatherapy with subsequent stem cell transplantation seems to improve outcome in this patient cohort. Feasibility of this intense megatherapy regimen is crucially dependent on collaboration and multidisciplinary coordination of radiologists, radiotherapists, surgeons and oncologists. PATIENTS AND METHODS: Since 1988, 25 patients were treated with megatherapy consisting of melphalan, etoposide and total-body irradiation followed by stem cell transplantation. All patients received 6 courses of an induction therapy. Before the fourth therapy block, tumors that were bulky at initial diagnosis (> 200 ml) were excised, as well as lung metastases which could still be detected after the third chemotherapy block. During the fifth and sixth chemotherapy block, patients received local irradiation on all infiltrated sites. Persisting immunosuppression after high-dose treatment may facilitate the incidence of relapse. To improve proliferation and cytotoxic activity of early regenerating NK-cells, adoptive immunotherapy with systemic IL-2 therapy after megatherapy is part of the treatment protocol. RESULTS: Of 25 patients treated with megatherapy, 10 patients are still alive with a follow-up time of 6 months to 9 years after megatherapy. The time up to engraftment was decreased from 15 +/- 6 days down to 9 +/- 2 days through the use of G-CSF and CD34+ selected stem cells. At the same time, erythrocyte and platelet replacement was shortened. Frequently occurring complications were mucositis and infections. One patient died after developing septicemia and multi-organ failure, another patient developed a myelodysplastic syndrome 4.5 years after megatherapy. However, relapse is still the major cause of death. The influence of IL-2 on event-free survival cannot valued because 21 of 25 patients were treated with adoptive immunotherapy. CONCLUSION: The complex diagnostic and therapeutic strategy renders and EFS of 34% for a patient group with otherwise dismal prognosis. To clarify the efficiency of megatherapy in patients with advanced Ewing's tumors, a standardized treatment strategy is necessary to accumulate a sufficient number of patients for large cooperative studies in this subject.

Adolescent↗
PubMed1999

Differential expression of alpha2-6 sialylated polylactosamine structures by human B and T cells.

We found that human peripheral B and T cells differed in the surface expression of alpha2-6 sialylated type 2 chain glycans. In contrast to B cells, T cells expressed only sialoglycans with repeated N-acetyllactosamine (Galss1-4GlcNAc) disaccharides. This finding was based on the specificity of the monoclonal antibodies HB6, HB9 (CD24), HD66 (CDw76), FB21, and CRIS4 (CDw76) with the alpha2-6 sialylated model gangliosides IV6NeuAcnLc4Cer (2-6 SPG), VI6NeuAcnLc6Cer (2-6 SnHC), VIII6NeuAcnLc8Cer (2-6 SnOC), and X6NeuAcnLc10Cer (2-6 SnDC). We found that, in addition to their common requirement of an alpha2-6 bound terminal sialic acid for binding, the antibodies displayed preferences for the length of the carbohydrate backbones. Some of them bound mainly to 2-6 SPG with one N-acetyllactosamine (LacNAc) unit (HB9, HD66); others preferentially to 2-6 SnHC and 2-6 SnOC, with two and three LacNAc units, respectively (HB6 and FB21); and one of them exclusively to very polar alpha2-6 sialylated type 2 chain antigens (CRIS4) such as to 2-6 SnOC and even more polar gangliosides with three and more LacNAc units. These specificities could be correlated with the cellular binding of the antibodies as follows: whereas all antibodies bound to human CD 19 positive peripheral B cells, their reactivity with CD3 positive T cells was either nearly lacking (HD66, HB9), intermediate (about 65%: HB6, FB21) or strongly positive (CRIS4, 95%). Thus, the binding of the antibodies to 2-6 sialylated glycans with multiple lactosamine units appeared to determine their binding to T-cells.

Amino Sugars↗
PubMed1999

ADHD in a school sample of Brazilian adolescents: a study of prevalence, comorbid conditions, and impairments.

OBJECTIVE: To evaluate the prevalence, comorbid conditions, and impairments of attention-deficit/hyperactivity disorder (ADHD) among young adolescents in Porto Alegre, Brazil. METHOD: 1,013 students aged 12 to 14 years were evaluated at 64 state schools, using a screening instrument based on the 18 DSM-IV ADHD symptoms. All positive screened students (n = 99) and a random subset of negative screened subjects (n = 92) had a psychiatric evaluation carried out within a hospital setting or at home. RESULTS: The prevalence of ADHD was estimated to be 5.8% (95% confidence interval = 3.2-10.6), and the comorbidity with other disruptive behavior disorders was high (47.8%). Youths with ADHD (n = 23) had significantly higher rates of school repetitions, suspensions, and expulsions (p < .01) than controls (n = 168). No association was identified between ADHD and alcohol, marijuana, and inhalant use. CONCLUSION: The results extend to adolescents well-documented findings in children, indicating that ADHD is quite prevalent in early adolescence and affected youths are at high risk for impairment and dysfunction in multiple domains.

Adolescent↗
PubMed1999

Cortisol selectively stimulates pituitary gonadotropin beta-subunit in a primitive teleost, Anguilla anguilla.

It has been suggested that in mammals, glucocorticoids, beside their stress-related inhibitory effects on reproductive function, may also play a stimulatory role at the onset of puberty. Using the juvenile female eel as a model, we investigated the potential stimulatory role of cortisol (F) on pituitary gonadotropin (GtH-II). GtH-II levels were measured by RIA, and messenger RNA (mRNA) levels for alpha- and GtH-II beta-subunits were determined by dot blot using homologous probes. F treatment increased eel pituitary GtH-II content in vivo and in vitro. Using a long term, serum-free primary culture of pituitary cells, we studied the direct effect of F on GtH-II production. F increased the GtH-II cellular content in vitro in a dose- and time-dependent manner. The relative potencies of various corticosteroids on GtH-II were: triamcinolone acetonide > dexamethasone > F >> cortisone and aldosterone, indicating a glucocorticoid-specific receptor (GR). F stimulated GtH-II production through a selective increase in mRNA levels for GtH-II beta-subunit; no significant effect was observed on alpha-subunit mRNA levels. This stimulatory effect of F on GtH-II beta, played out directly at the pituitary cell level, recalls that of F on FSHbeta in the rat. The present study, performed in a primitive teleost at the juvenile stage, suggests that the role of F in the positive regulation of gonadotropins at puberty may have arisen early in vertebrate evolution.

Analysis of Variance↗
PubMed1999

[Group B streptococcus, primary cause of life-threatening infections in infants. Epidemiology and prevention strategy].

As soon as the early 70's, group B streptococci (GBS) became clearly predominant in neonatal infections. There was a dramatic increase in the incidence of GBS neonatal sepsis and meningitis throughout developed countries and GBS emerged as the leading cause of severe neonatal infections. Most of these infections, associated with high mortality and morbidity, could be prevented by intrapartum chemoprophylaxis given to risk mothers. AAP, ACOG and the CDC issued guidelines for their prevention. Today, in Belgium, there are still no recommendations for the prevention of GBS early-onset infections.

Antibiotic Prophylaxis↗
PubMed1998

A novel dendritic cell population in human blood: one-step immunomagnetic isolation by a specific mAb (M-DC8) and in vitro priming of cytotoxic T lymphocytes.

Originating from a common progenitor cell, dendritic cells (DC) appear to develop along early branched pathways into various yet ill-defined subpopulations residing at various sites throughout the body where they capture and present antigen in the most professional fashion. Here we give evidence for a unique subpopulation of human DC circulating in blood that account for 0.5-1% of blood leukocytes only, their most specific characteristic being the expression of a cell surface protein recognized by a novel monoclonal antibody (M-DC8) which enables their isolation by a one-step immunomagnetic procedure. The isolated cells (> 97% pure) present morphologically as typical dendritic cells. They express the Fc(gamma)RIII (CD16), so far not found on DC, and avidly phagocytose latex beads as well as opsonized erythrocytes. These cells not only present antigens efficiently to naive T cells but also induce purified CD8+ T cells to become alloantigen-specific cytotoxic cells. Furthermore, when loaded with a tyrosinase-derived peptide they stimulate T cells from normal donors and melanoma patients to exhibit MHC-restricted specific cytotoxicity against melanoma cells.

Antibodies, Monoclonal↗
PubMed1998

Epidemiological study of p53 tumor suppressor gene mutations in patients from Luxembourg and the German Saar region with an advanced colorectal cancer using PCR-SSCP analysis.

Mutations in the p53 tumor suppressor gene are usually associated with an advanced development of colorectal cancer characterized by the transition from the adenoma to the carcinoma stage. We used the polymerase chain reaction (PCR) followed by single-strand conformation polymorphism (SSCP) analysis to screen for the presence of mutations in the p53 gene of patients from Luxembourg and the German Saar region with colorectal cancers at various developmental stages. While we detected no mutations in 16 colic polypi at an early to intermediate stage (adenoma), we revealed seven (13.7%) non-silent point mutations (transitions) in exons 5 to 9 of the p53 gene in 51 colorectal tumors at a late stage (carcinoma). In addition to confirming previous observations, these results show that PCR-SSCP analysis can provide both a sensitive and rapid method for the genetic determination of the histopathological stage of colorectal samples.

Adult↗
PubMed1998

The human autoantigen La/SS-B accelerates herpes simplex virus type 1 replication in transfected mouse 3T3 cells.

Permanently transfected mouse cell lines which expressed different levels of the human autoantigen La/SS-B were infected with different strains of herpes simplex virus type 1, including the strains ANG, HSZP, 17syn+ and HFEM. During infection the localization of the human La protein was followed using an anti-La MoAb, which recognized only the human La protein but did not cross-react with either the endogenous mouse La protein or any viral encoded protein. After infection La protein was transported from the nucleus to the cytoplasm. The time course of translocation was dependent on the amount of human La protein expressed in the respective cell line. Moreover, acceleration of viral replication was dependent on the level of expression of human La protein, suggesting that La protein is a cellular factor that facilitates virus replication.

3T3 Cells↗
PubMed1998

Analysis of epitope spreading over an eleven-year period in a patient with systemic lupus erythematosus.

During a period of more than eleven years serum samples of a patient with Systemic Lupus Erythematosus were collected and analyzed for anti-nuclear autoantibodies. High titer of anti-La/SS-B were detectable in all serum samples. The La/SS-B epitopes remained constant. Besides anti-La/SS-B antibodies all serum samples contained traces of anti-Ro/SS-A including anti-Ro52 and anti-Ro60 antibodies. During disease flares anti-Ro/SS A antibodies were upregulated and anti-dsDNA antibodies appeared, thus supporting the concept of an antigen driven intermolecular epitope spreading to Ro/SS-A and dsDNA.

Adult↗
PubMed1998

[Comparative study for assessing quality of life of patients with exogenous sleep disorders (temporary sleep onset and sleep interruption disorders) treated with a hops-valarian preparation and a benzodiazepine drug].

This randomized, double-blind, controlled clinical trial in parallel group design demonstrated equivalent efficacy and tolerability of a hop-valerian preparation compared with a benzodiazepine preparation in patients suffering from sleep disorders according to DSM-IV criteria. Sleep quality, fitness and quality of life were determined by psychometric tests, psychopathologic scales and sleep-questionnaires at the beginning of the therapy, end of therapy (duration 2 weeks) and then 1 week after cessation of therapy. Patients' state of health (4-point scale) and medication tolerability (occurrence of adverse events) were documented. Using the following as parameters "Alphabetischer Durchstreichtest, Feinmotoriktest, Befindlichkeitsskala, Beschwerdeliste, Schlaffragebögen A and B" the differences between beginning and the end of the therapy were analyzed by simultaneous testing of the equality or superiority of the test preparation. The equivalence of both therapies according to sleep quality, fitness and quality of life was proven by a Mann-Whitney-Statistic of 0.50 with a lower boundary of the 95% confidence interval of 0.46. The patients' state of health improved during therapy while showing a deterioration after cessation with both preparations. Withdrawal symptoms, however, were documented with benzodiazepine. Only one adverse drug reaction was reported during this study, namely stomach complaints from both the test and reference medication. This study shows that the investigated hop-valerian preparation in the appropriate dose is a sensible alternative to benzodiazepine for the treatment of nonchronic and non-psychiatric sleep disorders.

Adult↗
PubMed1997

Androgens stimulate gonadotropin-II beta-subunit in eel pituitary cells in vitro.

Primary cultures of juvenile eel (Anguilla anguilla) pituitary cells were used to study the direct effects of sex steroids on gonadotropin (GtH-II) cell content and release (radioimmunoassay) as well as on mRNAs levels for alpha and GtH-II beta-subunits (dot-blot). Testosterone stimulated GtH-II production in a dose- and time-dependent manner by selectively increasing mRNAs for GtH-II beta-subunit but not alpha-subunit. This positive effect was also induced by non-aromatizable androgens (androstanediol and dihydrotestosterone) but not by estradiol, indicating an androgen-specific effect in the eel. The androgen-specific stimulation of eel GtH-II beta appears closer to the regulation of mammalian follicle stimulating hormone-beta (FSHbeta) than that of salmonid GtH-II beta or mammalian luteinizing hormone-beta (LHbeta)-subunits. Comparison with previous in vivo experiments suggests multiple sites of action of sex steroids on the brain-pituitary gonadotropic axis for the positive feedback on GtH-II synthesis in this juvenile fish.

Androgens↗
PubMed1997

Down-regulation of TSH subunit mRNA levels by thyroid hormones in the European eel.

The effects of 3,5,3'-triiodothyronine (T3) and thyroxine (T4) on alpha and thyroid-stimulating hormone (TSH) beta subunit mRNA pituitary levels were examined in a teleost, the European silver eel. Northern blot analysis showed that the number and length of mRNAs encoding TSH beta varied among individuals, a variability apparently not related to thyroidal status. When several bands were present, their intensities were summed for quantitative analysis. Increasing circulating thyroid hormones (THs) by implantation of T3 or T4 significantly decreased TSH beta mRNA levels. Depression of circulating THs by thiourea treatment increased alpha and TSH beta mRNA levels. In vitro studies showed that T3 and T4 decrease TSH beta mRNA levels in primary cultures of eel pituitary cells. In conclusion, in vivo and in vitro experiments indicate that T3 and T4 exert a negative feedback action on pituitary TSH beta mRNA level in the European eel and that this effect might be exerted, at least partly, through a direct action on the pituitary.

Animals↗
PubMed1997

Sleep quality during alcohol withdrawal with bright light therapy.

1. Alcohol withdrawal is a complex syndrome that ranges from anxiety, insomnia to delirium tremens. Common treatment is the application of sedative medication. Exposure to bright light in the daytime should advance the normal sleep/wake cycle and moreover it should improve the availability of man's adaptive behavior during alcohol withdrawal. 2. This pilot study describes bright light therapy (BL) during alcohol withdrawal in ten alcohol dependent patients (DSM-III-R: 291.80) without any sedative medication. BL (3000 Lux) was administered on day 3 of abstinence between 7.00-9.00 a.m. and 5.00-9.00 p.m. Total-sleep-polysomnography (recordings between 10.30 p.m.-6.00 a.m.) and self-rating scale were performed to compare intraindividual changes during three nights. After one adaptation night (immediately after alcohol withdrawal), one baseline night and one "BL-night" and one "post-BL night" were analysed. 3. At baseline, total sleep time and sleep efficiency were severely deteriorated, but tended to improve in the following nights after BL. Sleep onset latency showed a significant decline after BL. Stages 3 and 4 were reduced at baseline. Latencies to slow wave sleep were significantly shortened after BL. REM increased in the nights after BL. Subjective sleep quality improved after BL. Although the present results, bright light having a possible stabilizing effect on sleep maintenance and sleep architecture during acute alcohol withdrawal, the authors could only derive hypotheses for further ongoing controlled investigations using placebo light, to receive final verification.

Adult↗