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Biomedical subjects

M Schmid

Publications and source records attributed to M Schmid.

At least 307 records · Page 17Linked to original sources
PubMed1994

Weekly 5-fluorouracil and high-dose folinic acid in combination with epidoxorubicin as first-line therapy in advanced breast cancer: a phase II study.

A total of 25 patients with advanced breast cancer were treated weekly with i.v. 5-fluorouracil at 350 mg/m2, folinic acid at 500 mg/m2, and epidoxorubicin at 35 mg/m2 as first-line chemotherapy for a maximum of 18 cycles. In all, 24 patients were evaluable for response. Overall, 1 patient achieved a complete response and 11 patients showed a partial response, for an objective response rate of 50%; the median duration of response was 18.3+ months and median survival amounted to 18.8+ months. Side effects were generally mild, with grade II leukopenia occurring in 10 patients and grade III leukopenia, in 1 patient. Other toxicity included nausea and vomiting (82%), diarrhea (48%), stomatitis (48%), and alopecia (92%), all of which were mainly restricted to WHO grades I and II. Our results suggest that leucovorin modulation of 5-fluorouracil can safely be incorporated into combination chemotherapy with epidoxorubicin on the investigated schedule. The observed response rate appears comparable with that obtained with other first-line regimens.

Adult↗
PubMed1994

A phase I/II study of 4'-O-tetrahydropyranyl-doxorubicin, 5-fluorouracil, and high-dose leucovorin as first-line therapy in advanced breast cancer patients.

A total of 50 patients were treated weekly with 5-fluorouracil (FU), leucovorin (LV), and 4'-O-tetrahydropyranyl-doxorubicin (THP) as first-line chemotherapy for advanced breast cancer (ABC). In phase I the doses of LV (500 mg/m2, day 1) and FU (350 mg/m2, day 1) were held constant, while the dose of THP (day 1) was escalated, from the initial dose of 10 mg/m2 up to the maximum tolerated dose (MTD). Twenty-eight patients entered phase I, and MTD for THP was defined as 35 mg/m2 in this combination. Dose-limiting toxicities were myelosuppression and hepatotoxicity. In phase II, another 22 patients were treated with THP at a dose level of 30 mg/m2. Including 4 patients already treated at this dose in the first part, 25 patients were evaluable for response: 1 patient obtained a complete response (CR) and 13 showed a partial response (PR), giving an objective response rate of 56%. The median duration of response was 9.1+ months and median survival, 15.5+ months. Side effects were generally mild, with ECOG grade I and II leukopenia in 51% of all cycles and grade III in 3% of the courses. Other toxicity included nausea and vomiting (54% and 8%, respectively) and alopecia (24%), all restricted to ECOG grade I and II. Our results suggest that weekly THP/LV-FU represents an active regimen for first-line treatment of ABC with relative low toxicity.

Adult↗
PubMed1994

Male polymorphism in Limia perugiae (Pisces: Poeciliidae).

The male-polymorphic poeciliid fish, Limia perugiae, a small teleostean endemic to the southeast of the Caribbean island Hispañola, consists of three male size morphs with uniform females. Large males differentiate at a size varying between 25 and 38 mm; intermediate males, between 21 and 25 mm. Under competition, large males exhibit an elaborate courtship display, whereas small males show only a sneak-chase behavior. Intermediate males adapt their tactics to the respective competitors. However, all male morphs can switch from courtship display to sneak-chase behavior. In large mating groups with four males of different size and five or six virgin females, large dominant alpha-males as well as small subordinate delta-males did not produce any offspring. Unexpectedly, all progeny were sired exclusively by the intermediate subordinate beta- and gamma-males. Breeding experiments with the three male morphs can best be explained by a model of Y-linked genes for small and large size which are both suspended by the activity of an autosomal recessive repressor responsible for the development of intermediate males. The dominant allele of the recessive repressor, in either its homoorits heterozygous state, activates the Y-chromosomal genes for large or small size, respectively. Accordingly, intermediate males may produce male offspring of all size classes, depending on the presence of either the Y-linked gene or the autosomal repressor.

Agonistic Behavior↗
PubMed1994

Efficacy of steroid withdrawal and low-dose interferon treatment in chronic active hepatitis B. Results of a randomized multicenter trial. Swiss Association for the Study of the Liver.

Fifty-six patients with biopsy-proven, chronic active hepatitis B were included in a multi-center, randomized trial comparing steroid withdrawal followed by 1.5 MU recombinant interferon alpha 2b (Intron) with placebo withdrawal followed by either 1.5 or 5 MU interferon. The patients were equally distributed between the treatment groups with respect to biochemical and histologic activity as well as with respect to DNA levels and quantitative liver function tests. One patient was lost to follow up. After 1 year of treatment, 10/18, 13/19 and 11/18 patients had lost hepatitis B virus DNA in the three groups, respectively (non-significant). Transaminase levels were normal in 27/34 of the responders but in only 4/21 of the non-responders (p < 0.0001). Both galactose elimination capacity and aminopyrine breath test improved significantly in responders, but either did not change (aminopyrine breath test) or deteriorated in non-responders (galactose elimination capacity). Biopsy score improved in both groups but this reached statistical significance only in responders. This effect was due to improvements in both inflammatory and fibrotic activity. Side effects included almost universally a flu-like syndrome, granulocytopenia (1), depression (3) and thyroid dysfunction (2). Two deaths occurred, one due to hepatocellular cancer, and the other to hepatorenal syndrome after spontaneous bacterial peritonitis. A severe cytolytic episode was observed in three patients in the steroid withdrawal group. We conclude that in patients with marked histologic activity, lower doses of interferon may be as effective as the standard dose of 5 MU.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Evaluation of methods for hepatitis C virus detection in archival liver biopsies. Comparison of histology, immunohistochemistry, in-situ hybridization, reverse transcriptase polymerase chain reaction (RT-PCR) and in-situ RT-PCR.

To evaluate reliable methods for detection of hepatitis C virus (HCV) infection in routinely processed liver biopsies we analyzed formaldehyde-fixed and paraffin-embedded liver specimens of 10 patients with serological confirmed HCV infection. We compared (1) conventional histology; (2) indirect immunofluorescence using the mAb TORDJI-22 (Clonatec, Paris, France); (3) RT-PCR using total RNA and Southern blotting with chemiluminescent detection; (4) non-radioactive in-situ hybridization (ISH) with digoxigenin-labeled oligo- and cRNA probes; (5) direct in-situ RT-PCR with incorporation of labeled nucleotides into PCR-products, and (6) indirect in-situ RT-PCR using subsequent ISH for the visualization of intracellular PCR-products. Our results indicate that: (1) using the histological criteria described by Lefkowitch et al. [Gastroenerology 1993;104:595] together with clinical data, most chronic HCV infections can be diagnosed by conventional histology, if liver biopsies specimens are adequate; (2) the commercially available mAb TORDJI-22 appears to crossreact with non-HCV epitopes, resulting in false positives; (3) molecular methods performed on routinely fixed and processed liver biopsies frequently yield false negative results due to sampling problems, low viral copy number and RNA degradation in infected cells; (4) analysis of HCV-RNA by RT-PCR of extracted total RNA is more sensitive than indirect in-situ RT-PCR or ISH; and (5) direct in-situ RT-PCR is not reliable despite the use of modifications such as DNase pretreatment and hot-start procedures. It is concluded, that several molecular methods for HCV detection must await further improvements of protocols to be suitable for routine diagnostics on paraffin-embedded liver biopsies.

Base Sequence↗
PubMed1994

Differential proliferative responses in subsets of human CD28+ cells delineated by BB27 mAb.

We report the identification of a novel 140 kDa disulfide-linked dimer expressed by a subset of peripheral blood T lymphocytes. This molecule, which is recognized by mAb BB27, is also detected on cells of the myelomonocytic lineage. In the T cell lineage, its expression is positively modulated after lymphocyte activation. A series of double-labeling experiments revealed that BB27 mAb identifies new CD4 and CD8 cell subsets different from those defined by CD45RA, CD45RO, CD26, CD29, CD31, and CD38. Finally, BB27 mAb also subdivides the CD28 subset. Of the utmost interest is the finding that a proliferative response to CD28 mAb and phorbol myristate acetate stimulation is exclusively obtained in the CD28+BB27+ cell subset, whereas the CD28+BB27- subset fails to proliferate.

Animals↗
PubMed1994

Two subpopulations of human triple-negative thymic cells are susceptible to infection by human immunodeficiency virus type 1 in vitro.

Some infants infected with human immunodeficiency virus type 1 (HIV-1) rapidly develop a fatal disease characterized by a severe lymphopenia. To explain the immune dysfunction, we proposed a mechanism by which a nongeneration of CD4+ T cells is caused by HIV-1 infection of thymic cells. To examine this hypothesis, we infected primary triple-negative (TN; phenotypically CD3- CD4- CD8-), CD1a- TN, or CD1a+ TN thymic cell subsets. Our data indicate that by flow cytometry, TN, CD1a- TN, and CD1a+ TN cells remain CD4 negative throughout the culture period. We demonstrated that TN and CD1a+ TN thymic cell subsets are susceptible to HIV-1 as is the entire thymic cell population, whereas CD1a- TN cells are not. A limited number of infected TN cells are expressing HIV-1 but the level of transcription is very high in permissive cells, as detected by in situ hybridization. We then performed blocking experiments on TN cells to examine the mechanism of HIV-1 entry into these cells. CD4 (OKT4a) monoclonal antibody blocks their infection. Finally, infection experiments on two subpopulations of TN cells (CD2+ CD7+ and CD2- CD7-) indicate that infected TN cells may correspond to both immature thymocytes and thymic dendritic cells. These data are of particular interest since infection of thymic stromal cells might result in an impairment of T-cell differentiation, which may explain a nongeneration of functional CD4+ T-cell population in the thymus. This phenomenon may play a role in AIDS pathogenesis, in particular in infants born from seropositive mothers.

Antibodies, Monoclonal↗
PubMed1994

Chromosome banding in amphibia. XX. DNA replication patterns in Gastrotheca riobambae (Anura, Hylidae).

Replication banding patterns were induced in the chromosomes of Gastrotheca riobambae by treating cell cultures with 5-bromodeoxyuridine (BrdU) and deoxythymidine (dT). In particular, the time sequence of replication of the highly differentiated XY/XX sex chromosomes was meticulously analyzed throughout the S phase. In the homogametic female, BrdU/dT labeling revealed no evidence of asynchronous replication between euchromatic regions in the XX pair. Minor replication asynchronies between the two X chromosomes were restricted to the heterochromatic C-bands. These results are further proof that dosage compensation in Amphibia for X- or Z-linked genes does not occur by inactivation of one of the two (XX or ZZ) sex chromosomes in the cells of homogametic individuals. In the very large and almost completely heterochromatic Y chromosome of G. riobambae, the various C-bands comprise at least three different structural categories, resulting in a complex pattern of early- and late-replicating bands along the Y chromosome.

Animals↗
PubMed1994

Localization of the telomeric (TTAGGG)n sequence in chicken (Gallus domesticus) chromosomes.

The distribution of the highly conserved eukaryotic telomeric (TTAGGG)n sequence was investigated in chicken metaphase chromosomes using the FISH technique. Besides the expected telomeric locations, interstitial as well as centromeric locations of the (TTAGGG)n repeat were observed on several macrochromosomes. The microchromosomes display three discrete patterns of labeling with this repeat. The significance of this extreme-different distribution of the telomeric related sequence in chicken chromosomes may lie in pointing to structural events that might have occurred during the process of karyotype evolution.

Animals↗
PubMed1994

[High-performance biosignal amplifier for electrophysiologic studies for special safety requirements].

For the recording of minute bioelectric signal voltages in the fields of medical research and diagnostic applications, a high-performance amplifier is needed to provide the signal levels necessary for a significant analysis. Irrespective of the concrete application, the major parameters required for a comparative evaluation of such systems are sensitivity, bandwidth and noise. Some applications also make special demands on electrical safety measures. With the aim of using an amplifier with a particularly powerful magnetic stimulator, and in view of the special requirements for brain voltage recording in a fully conscious patient, a universally applicable amplifier system has been developed that incorporates safety measures that ensure virtually risk-free application. The stimulation artefact can be suppressed completely by means of automatic offset regulation of the preamplifier. The circuit elements in electrical contact with the organism are separated from the rest of the measuring system by a high-voltage insulation barrier. The main innovation and central subject of this article is an active protective system with an extremely short response time, which reliably cuts off the relevant amplifier circuits as soon as the ceiling signal level is exceeded. In accordance with relevant regulations, the user is warned of any first failure by a program-controlled self-test run by the protective unit and done automatically when the amplifier is activated. Exhaustive tests with a prototype have confirmed, among other things, that the integration of the new protective device does not reduce the amplifier output to any measurable extent.

Amplifiers, Electronic↗
PubMed1994

Cyclosporin A inhibits cytokine-induced proliferation in B-chronic lymphocytic leukemia.

We investigated the effects of the immunosuppressant cyclosporin A (CsA) on proliferation of neoplastic B-cells from patients with B-chronic lymphocytic leukemia (B-CLL). Cell growth was induced in vitro by tumor necrosis factor alpha (TNF-alpha (8/16), interleukin 2 (IL-2 (9/16) or both (7/16), in 4 cases spontaneous proliferation was observed. We were able to demonstrate that CsA inhibits cytokine-induced proliferation, as measured by [3H]-thymidine incorporation, in all cases responsive to TNF-alpha or IL-2 as well as in spontaneous proliferation. CsA did not increase the fraction of trypan blue positive cells or apoptosis. Growth inhibition by CsA occurred in a dose dependent manner: 100 ng/ml CsA was the optimal concentration which blocked about 90% of cytokine induced or spontaneous proliferation. We could also demonstrate that the effect of CsA was reversible and that no blocking effect was observed when CsA was added later than 48 hours after stimulation. Cell cycle analysis using propidium iodide as a DNA stain demonstrated that CsA prohibited the progression of B-CLL cells from the G1-phase to the S-phase of the cell cycle. However, we were also able to show that TNF-alpha induced proliferation of hairy cell leukemia (HCL) was not affected by CsA. This observation indicates that the inhibitory activity of CsA seems to be restricted to only a few haematological diseases such as B-CLL.

Apoptosis↗
PubMed1994

Short and longterm fluctuations of generational MS risk.

According to the hypothesis that childhood is an important age stage in view of MS predisposition, alterations of MS risk may be expected in respect of generational succession. Age-period-cohort-analysis in the appropriate statistical analysis model in this connection. After having shown considerable fluctuations of generational MS risk in the long term view we have tried to derive additional informations from corresponding short term fluctuations: descriptive informations as well as results in relation to the short term fluctuations of infectious diseases' mortality. While applying again age-period-cohort-analysis the results are questioned by the fact that the underlying cohort estimates represent 5-years-moving-averages. Computerized individual death records of the Swiss mortality statistics available since 1969 will enable us to check the recent results.

Adolescent↗
PubMed1994

[Comparison of histology, immunohistochemistry, RT-PCR, in situ hybridization, and in situ RT-PCR for demonstration of hepatitis C virus in paraffin-embedded liver biopsies].

To compare immunohistochemical and molecular methods for the detection of hepatitis C virus (HCV) infection in archival liver biopsies we analyzed formalin-fixed and paraffin-embedded liver specimens of 10 patients with serologically confirmed HCV infection. Methods employed included indirect FITC-immunofluorescence, reverse-transcriptase polymerase chain reaction (RT-PCR) using extracted RNA and Southern blotting with chemiluminescence-based detection, non-radioactive in situ hybridization (ISH) with digoxigenin-labeled oligo- and cRNA probes, direct in situ RT-PCR with incorporation of labeled nucleotides into PCR-products, and indirect in situ RT-PCR using subsequent ISH for the visualization of intracellular PCR-products. Our results indicate that: (1) using the histological criteria described by Lefkowitch et al. (Gastroenterology 1993; 104-595) together with clinical data, most chronic HCV infections can be diagnosed by conventional histology, if liver biopsies are representative; (2) the commercially available mAB TORDJI-22 appears to cross-react with non-HCV epitopes; (3) molecular methods performed on routinely fixed and processed liver biopsies frequently yield false negative results due to sampling problems, low viral copy number and RNA degradation in infected cells; (4) analysis of HCV-RNA by RT-PCR of extracted total RNA is more sensitive than indirect in situ RT-PCR or ISH; and (5) direct in situ RT-PCR is not reliable despite the use of modifications such as DNase pretreatment and hot-start procedures. Further studies are required to define both optimal methods for sample processing and improvements of protocols, in order to increase detection sensitivity and specificity of HCV infection by immunohistochemical and molecular methods.

Biopsy↗
PubMed1994

[Detection of human herpesvirus type 6, human herpesvirus type 7, cytomegalovirus and human papillomavirus in cutaneous AIDS-associated Kaposi's sarcoma].

In order to evaluate a possible role of viral infections in the pathogenesis of AIDS-associated Kaposi's sarcoma (KS), we investigated 26 cutaneous AIDS-associated KS by polymerase chain reaction (PCR), in situ hybridization, and immunohistochemistry. By PCR we detected human papilloma viruses (HPV), cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), and for the first time human herpesvirus 7 (HHV-7) in the KS. The prevalence of HPV, HHV-6, and HHV-7 was similar to or lower in KS than in normal skin tissues of AIDS patients without KS, but higher than in normal skin of HIV-seronegative patients. All HHV-6 found in KS were identified as HHV-6 variant B. In addition to the known HPV types 16 and 18 described in KS, we also found HPV types 6 and 33 in KS specimen. By immunohistochemistry HHV-6 could be localized in macrophages in KS, in the adjacent stroma as well as in normal skin of control cases. In situ hybridization for CMV and HPV gave negative results in KS and controls.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Paracrine regulation of B-cell growth in hairy cell leukemia.

There is evidence that the growth of malignant B lymphocytes e.g. hairy cells is regulated by cytokines. Several investigators suggested that the stimulating cytokines are produced by the malignant B cells indicating an autocrine growth regulation. Here we demonstrate that T lymphocyte clones produce soluble mediators which stimulate the growth of malignant B lymphocytes. The incidence of the growth stimulating T cell clones derived from peripheral blood is identical in patients with hairy cell leukemia (HCL) and healthy controls. About 50% of the clones stimulate the growth of hairy cells, but not the growth of purified B-lymphocytes of healthy donors. The stimulating activity of a single clone varies when tested on different hairy cells. Interferon alfa but not antibodies against tumor necrosis factor alfa or interleukin-2 inhibit completely the growth stimulating activity. We propose that interferon alpha inhibits the production of soluble mediators produced by normal T-cells. Our results indicate that a paracrine growth regulation has to be considered in addition to the postulated autocrine loop in the growth regulation of malignant B cells.

B-Lymphocytes↗
PubMed1994

[Breast cancer in the man: a report of 30 patients].

A retrospective review of male patients suffering from breast cancer seen over an 18-year period was carried out at the Department of Clinical Oncology of the University Hospital of Graz. Thirty evaluable cases were analysed. Eight patients had Stage I, 11 had Stage II, 8 had Stage III, and 3 had Stage IV disease. Local control was achieved in the majority, 29/30 (97%), by either surgery alone or combined surgery and radiation therapy. Local recurrence developed in 2 (7%) patients. Further 7 (23%) patients developed distant metastases and were treated in accordance with policies developed for the appropriate stage of the disease in females, with hormonal manipulation for hormone receptor-positive and -unknown patients and chemotherapy for hormone receptor-negative patients. The corrected five-year survival (Kaplan-Meier) is 83% for the entire group, 100% for patients with Stage I disease, 86% in Stage II, and 67% in Stage III and IV disease, respectively. This corresponds well with the results in recently published series. Stage of disease at initial presentation was a significant factor determining survival in our investigation. Our own data as well as recent data from literature suggest that with respect to TNM Stages in mammary carcinoma, there is no prognostic difference between men and women. To what extent improved local control by adequate local therapy or systemic adjuvant treatment modalities may improve overall survival remains to be discussed.

Adult↗
PubMed1993

Reversible inactivation of endothelial nitric oxide synthase by NG-nitro-L-arginine.

NG-Methyl-L-arginine (L-NMA) and NG-nitro-L-arginine (L-NNA) inhibited NO-induced cGMP accumulation in porcine aortic endothelial cells with half-maximally effective concentrations of 15 and 3.4 microM, respectively. The effects of both compounds were reversible, but the L-NNA-induced inhibition was only reversed by wash-out in the presence of 1 mM L-arginine. In short-term incubations (45 s) of membrane fractions, L-NMA and L-NNA exhibited similar potencies to inhibit endothelial NO synthase, but L-NNA was markedly more potent than L-NMA after prolonged incubation periods (> or = 3 min) due to induction of a pronounced, reversible enzyme inactivation.

Amino Acid Oxidoreductases↗