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Biomedical subjects

M David

Publications and source records attributed to M David.

At least 235 records · Page 13Linked to original sources
PubMed1996

Effects of cyclosporin and cremophor on working rat heart and incidence of myocardial lipid peroxidation.

Cyclosporin A (CsA) is widely used as the immunosuppressant of choice for preventing graft rejection. However, its clinical use is hampered by certain side effects, especially its nephrotoxicity and other cardiovascular side effects. CsA for intravenous infusion contains cremophor (Cre) and this vehicle has significant adverse effects on endothelial function and vascular muscle. The present study was aimed at investigating the direct effects of CsA and Cre on isolated and perfused rat hearts in the dosage that closely approximates the peak level achieved for the prevention of graft rejection in the rat. Transplantation is a clinical setting in which the myocardium may be exposed to transient ischemia. In this study, we have shown that the vehicle of CsA, namely Cre, has significant adverse effects on cardiac function. We observed a reduction in coronary flow and aortic output. Addition of CsA appeared to induce a further reduction of aortic flow. We have also shown that a significant increase of thiobarbituric acid reactive substances, considered as an index of lipid peroxidation, occurred in the reperfused heart in the presence of Cre+CsA. Our experimental study shows that Cre turned out to be toxic to myocardium by itself. In the heart, potential Cre-CsA interactions possibly potentiating CsA toxicity could not be excluded. The increase of lipid peroxidation in the heart perfused with CsA suggests that reactive oxygen species may be involved in the detrimental effects of this substance on the heart.

3,4-Methylenedioxyamphetamine↗
PubMed1996

[Emergency angioplasty for total thrombosis of the left main coronary artery. Apropos of a case].

Complete thrombosis of the left main coronary artery is a rare angiographic finding and usually gives rise to cardiogenic shock during unstable angina or myocardial infarction. The prognosis of this condition is very dependent on the collateral coronary circulation and the myocardial protection seems to depend on the rapidity of revascularisation. Two therapeutic approaches may be envisaged; emergency coronary bypass grafting or percutaneous angioplasty, the natural history being particularly disastrous. The authors report the case of a 42-year-old patient with complete occlusion of the left main stem responsible for unstable angina and acute pulmonary oedema. The outcome with angioplasty in the acute phase associated with surgical revascularisation four days later, was good.

Angina, Unstable↗
PubMed1996

[Leg embolisms: treatment via percutaneous thrombo-aspiration].

PURPOSE: Benefits of the local thrombolytic therapy in the treatment of acute peripheral arterial ischemia have been proved (13), but the place of thrombo-aspiration in this percutaneous treatment is not well defined. This study evaluates the results of thromboaspiration with or without local thrombolysis for the treatment of arterial embolism associated with a lower limb arteriopathy. METHODS: From May 1991 to May 1992, ten arterial embolisms (below the common femoral artery) associated with a lower limb arteriopathy have been treated by thromboaspiration with or without local thrombolysis. RESULTS: Nine immediate successes have been obtained. One failure has been operated on with success. On the third day, an occlusion of the popliteal artery occured and a femoroperoneal bypass was performed. But the occlusion of the bypass obligated to an amputation above the knee. This patient died one month later (hospital mortality 10%). During the follow-up (2 months), other procedures were patent. CONCLUSIONS: Thromboaspiration with or without thrombolysis is efficient for the treatment of arterial embolism associated with a lower limb arteriopathy.

Aged↗
PubMed1996

Characterization of the cytochrome P450 enzymes involved in the in vitro metabolism of dolasetron. Comparison with other indole-containing 5-HT3 antagonists.

Dolasetron mesilate [(2 alpha, 6 alpha, 8 alpha, 9a beta)-octahydro-3-oxo-2,6-methano-2H-quinolizin-8-yl-1H-indole-3-c arboxylate monomethane-sulfonate], is a 5-HT3 receptor antagonist, which is in development for the treatment of chemotherapy-induced emesis. The compound is rapidly reduced by carbonyl reductase to form its major pharmacologically active metabolite reduced dolasetron (red-dolasetron), which us further metabolized by cytochrome P450 (CYP450). Studies were conducted, using human liver microsomes, to characterize the CYP450 enzymes responsible for the in vitro metabolism of red-dolasetron. Red-dolasetron underwent oxidation of the indole aromatic ring at positions 5, 6, and 7, and also N-oxidation. Enzyme-selective inhibition and correlation studies showed that hydroxylation of red-dolasetron was CYP2D6-dependent, and N-oxidation was conducted by CYP3A4. The rate of formation of 6-hydroxy red-dolasetron was significantly correlated with that of 5-hydroxy red-dolasetron, which further suggested that these metabolites were formed by the same CYP450 enzyme(s). Inhibition studies also demonstrated that 6-hydroxylation was, to a lesser extent, CYP3A4-dependent. This was confirmed by correlation experiments, wherein formation of this metabolite was significantly correlated with that of N-oxide formation, in quinidine-inhibited microsomes. Results were compared with those obtained with two other indole-containing 5-HT3 receptor antagonists: tropisetron and ondansetron. Tropisetron hydroxylation was CYP2D6-dependent, whereas that of ondansetron was both CYP2D6- and CYP2E1-dependent. Results were further confirmed, when compounds were incubated with microsomes containing recombinant human liver CYP2D6, CYP3A4, and CYP2E1. Red-dolasetron was a competitive inhibitor of CYP2D6, with an IC50 value of 70 microM, which is 2 orders of magnitude above maximum plasma concentrations found in humans. The implications of these in vitro results to the in vivo metabolism of these compounds in humans and their potential pharmacokinetic consequences is discussed.

Cytochrome P-450 CYP2D6↗
PubMed1996

Trichorrhexis nodosa: a manifestation of hypothyroidism.

A 23-year-old woman presented with diffuse white hair nodules, hair fragility, and the inability to grow long hair. Examination of specimens under the light microscope showed the morphologic characteristics of trichorrhexis nodosa. Results of tests revealed hypothyroidism. Treatment with a daily dose of 0.1 mg L-thyroxine sodium for six months restored euthyroidism and concurrently normalization of the hair defect was observed. The corrected hair defect observed after replacement therapy may point toward a causal relationship between hypothyroidism and trichorrhexis nodosa. To the best of our knowledge, this is the first report of trichorrhexis nodosa associated with hypothyroidism.

Adult↗
PubMed1996

[Comments on obstetrics in the 19th century. Joachim Friedrich Henckel (1712-1779): the first cesarean section in a living patient in Berlin 225 years ago].

Dr. Joachim Friedrich Henckel, surgeon at the Charité in Berlin reported in "De sectione caesarea" on probably the first operation of a caesarean section along the linea alba on a living woman. He performed this operation in Berlin in 1769. The child survived. Although the mother's health was good at first, she died probably due to Peritonitis. This operation attracted so much attention in Berlin at that time that king Fredric II. appointed Henckel as professor of surgery and Court Councellor. Later Dr. Henckel became director of the Charité.

Cesarean Section↗
PubMed1996

Beneficial effect of granulocyte-colony stimulating factor in scleromyxoedema associated with severe idiopathic neutropenia.

The treatment of scleromyxoedema is notoriously difficult. We present a patient with long-standing diffuse scleromyxoedema associated with functional impairment who developed chronic idiopathic neutropenia complicated by recurrent life-threatening infections. Treatment with recombinant granulocyte--colony stimulating factor led to normalization of the neutrophil count, prevented further systemic infections, and unexpectedly was associated with a striking clinical improvement of her skin disorder and decrease in mucin deposition in the dermis.

Chronic Disease↗
PubMed1996

[Upright birthing position--more birth canal injuries? Results of a retrospective comparative study].

The maternal birthing position is not only influenced by physical factors but also culture civilization. Nowadays more women prefer to give birth in an upright position (sit, squat, kneel) which is highly supported by some family practitioners. In this retrospective investigation we compared 3 different groups of maternal birthing positions (upright, lateral, mixed birthing position i.e. mainly on the back) concerning the fetal outcome and maternal perineal injury. There was no difference in the APGAR-values and umbilical cord pH. A higher incidence of intermediate and severe laceration as well as higher rates of episiotomy have been found in the mixed group (i.e. mainly on the back birthing position). Regarding our results and considering the literature we conclude that the upright birthing position brings no discredit upon newborn or the maternal perineum.

Apgar Score↗
PubMed1996

Benign and malignant eccrine poroma--a flow cytometric comparison.

Eccrine poroma is a benign, slow growing, solitary adnexal tumor. Malignant degeneration may take place in longstanding solitary lesions; in such cases cutaneous and fatal visceral metastases have occurred. Our goal was to determine whether flow cytometry yields useful diagnostic and prognostic information on benign and malignant eccrine poroma. Flow cytometric analysis of the nuclear DNA ploidy pattern was performed on four samples of eccrine poroma and five samples of malignant eccrine poroma. All the histograms of the eccrine poromas were diploid. Two of five specimens (40%) of the eccrine porocarcinoma were aneuploid, and the other three (60%) were diploid. The diploid pattern represents another expression of the benignancy of eccrine poroma. Since abnormal DNA content is often correlated with tumor grade, the aneuploid DNA histogram of 40% of the patients with malignant eccrine poroma is not a surprising finding in this cytologically malignant neoplasm.

Acrospiroma↗
PubMed1995

Conversion of normal rats into SCID-like animals by means of bone marrow transplantation from SCID donors allows engraftment of human peripheral blood mononuclear cells.

We have recently shown that lethally irradiated normal strains of mice, radioprotected with SCID bone marrow, can be engrafted with human peripheral blood mononuclear cells (PBMC). We now demonstrate that lethally irradiated Lewis rats can also be radioprotected with a transplant of SCID bone marrow cells, administered 1 day after total body irradiation. Split chimerism was found in PBMC, 30 days after transplantation, with predominance of SCID donor-type cells. The average percentages of CD4 and CD8 T cells, of mouse or rat origin, were < 1%. This chimerism status could be maintained for over 3 months. When human PBMC (300-1000 x 10(6) cells) were transplanted intraperitoneally 1 day after the administration of SCID bone marrow, prompt engraftment of human CD4 and human CD8 T cells, as well as human CD20 B cells, was found in the peritoneum and in internal organ (such as liver, lung, spleen, thymus, and lymph nodes). T cell activation was high: about 50% of the cells expressed HLA-DR and almost all expressed CD45RO. High titers of human Ig (> 1 mg/ml) were initially found after 2 weeks; these levels were similar to those found in the irradiated mouse model and in the SCID model. Likewise, marked human anti-tetanus response, predominantly of the IgG type, was recorded 2 weeks after the immunization, reaching maximal levels at 4 weeks. The triple-chimeric SCID-like rats, which accept as much as 1000 x 10(6) human PBMC, can potentially be used to elicit both antibody responses and T cell responses against specific antigens, with the advantages of a larger animal.

Animals↗
PubMed1995

Requirement for MAP kinase (ERK2) activity in interferon alpha- and interferon beta-stimulated gene expression through STAT proteins.

Activation of early response genes by interferons (IFNs) requires tyrosine phosphorylation of STAT (signal transducers and activators of transcription) proteins. It was found that the serine-threonine kinase mitogen-activated protein kinase (MAPK) [specifically, the 42-kilodalton MAPK or extracellular signal-regulated kinase 2 (ERK2)] interacted with the alpha subunit of IFN-alpha/beta receptor in vitro and in vivo. Treatment of cells with IFN-beta induced tyrosine phosphorylation and activation of MAPK and caused MAPK and Stat1 alpha to coimmunoprecipitate. Furthermore, expression of dominant negative MAPK inhibited IFN-beta-induced transcription. Therefore, MAPK appears to regulate IFN-alpha and IFN-beta activation of early response genes by modifying the Jak-STAT signaling cascade.

Binding Sites↗
PubMed1995

Human/mouse radiation chimera are capable of mounting a human primary humoral response.

Lubin et al recently described a new approach that enables the generation of human/mouse chimera by adoptive transfer of human peripheral blood mononuclear cells (PBMC) into lethally irradiated normal strains of mice, radioprotected with bone marrow (BM) from donors with severe combined immune deficiency (SCID). In the present study, we demonstrate in such human/mouse chimera a marked humoral response to recall antigen, such as tetanus toxoid (TT) or hepatitis B surface antigen (HBsAg), as well as a significant primary response to keyhole limpet hemocyanin (KLH). Maximal anti-KLH response in human/Balb chimera was attained 2 to 4 weeks after the immunization and declined thereafter. One week after transplantation, the predominant anti-KLH subtype was IgM, while after 2 weeks, the dominance had shifted to IgG. Similar primary antibody response was also demonstrated against the human immunodeficiency virus (HIV) Nef protein. Comparison between human/Balb and human/SCID chimera showed a major difference in their ability to mount a primary response against KLH. In Balb/c recipients, more than half of the mice exhibited marked IgM titers against KLH, while there was hardly any anti-KLH IgM response in the SCID recipients. From the earliest time point onwards, when anti-KLH antibodies were found in the latter chimera, they were predominantly of the IgG type. We have previously shown that in human/Balb chimera, unlike in SCID recipients, dissemination of transplanted PBMC into the spleen and other internal organs occurs within 24 hours. Therefore, it is likely that the early seeding in the appropriate microenvironment of the lymphoid tissues, is crucial for the maintenance of virgin human B cells.

Animals↗
PubMed1995

Amniocentesis rate and the detection of Down syndrome and other chromosomal anomalies in Israel.

We investigated the contribution of different screening criteria to the prenatal detection of Down syndrome (DS) as well as other chromosomal anomalies in the Jewish population in Israel during 1990 and 1992. There was a significant decrease (P < 0.03) in the incidence of DS live-births during 1992 (40:78 442) compared with 1990 (69:73 751) which paralleled a marked increase in total prenatal testing and in DS cases detected prenatally. Private laboratories, which perform amniocenteses mostly for women with a low risk of DS and without genetic counselling, had a significantly lower detection rate (1:917) compared with that of the genetic institutes, which following genetic counselling test both women > or = 37 years of age (1:91) and women younger than 37 years (1:113). The detection of chromosomal anomalies other than DS was less affected by the reason for amniocentesis. Amniocentesis indicated by maternal serum marker screening of women younger than 37 years identified a greater number of chromosomal anomalies other than DS than amniocentesis based on age (> or = 37 years) alone (111:9604 versus 94:9810; P < 0.06). Prenatal detection of DS is most effective when the indication for amniocentesis follows genetic counselling. The increasing use of maternal serum marker screening leads to a significant improvement in the positive detection rate of chromosomal anomalies other than DS in young women.

Adult↗
PubMed1995

A clinical screening cooperative group phase II evaluation of lobaplatin (ASTA D-19466) in advanced head and neck cancer.

We evaluated the efficacy and tolerability of lobaplatin, a new platinum compound, given at the dose of 50 mg/m2 by i.v. bolus every 4 weeks, in 49 patients with advanced and/or metastatic squamous cell carcinoma of the head and neck (SCCHN). One complete and 2 partial responses were observed in 43 eligible patients for an overall response rate of 7% (95% confidence interval: 1-19%). The duration of responses was 11, 16 and 32 weeks. Toxicities of WHO grade > or = 3 were hematologic: thrombocytopenia in 26%, granulocytopenia in 12% and anemia in 12% of patients. There was no therapy-related death. Nausea/vomiting, diarrhoea and paresthesia were mild and rare. In conclusion, lobaplatin was well tolerated, but its efficacy in advanced SCCHN at the presented dose and schedule, was marginal.

Adult↗
PubMed1995

Transcription factors in interferon signaling.

Interferons (IFNs) comprise a family of polypeptides that exhibit diverse biological effects such as inhibition of cell growth and protection against viral infection. These activities are based mainly on the transcriptional induction of cellular genes by both type I (IFN-alpha and IFN-beta) and type II (IFN-gamma) interferons. Several of these IFN-induced early response genes have been cloned and common elements within their promoters defined. Transcription factors, such as interferon-stimulated gene factor-3, IFN-gamma activation factor and FcRF gamma, that bind to these enhancers subsequently have been isolated and their components identified. This review shall provide an overview of the DNA response elements, the components of the IFN-induced transcription factors and their mechanism of action.

Base Sequence↗
PubMed1995

[Cutaneovisceral leishmaniasis following severe nervous depression].

Leishmania is considered an opportunistic agent during cellular immunodeficiency. The authors report the case of a patient living in the south of France presenting visceral leishmaniasis with cutaneous manifestations in the course of a severe nervous depression. This case report illustrates the possible relationships between stress and immunity.

Adult↗