Hyperactive polymorphonuclear leucocytes migration in patients with Familial Mediterranean Fever.
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Adult↗
Biomedical subjects
M David
Publications and source records attributed to M David.
Human-->mouse radiation chimera do not develop Epstein-Barr virus lymphoma.
It has been shown that engraftment of human peripheral blood lymphocytes (PBL) from Epstein-Barr virus (EBV) seropositive donors in C.B-17/SCID mice is associated with a high incidence of human B cell tumors. More recently, we described a new approach enabling engraftment of human PBL in normal strains of mice or rats receiving lethal split-dose radiation and radioprotected with SCID bone marrow. We now demonstrate that, in contrast to SCID recipients of human PBL, Balb/c and C3H/HeJ recipients of 50-100 x 10(6) human PBL did not develop any EBV lymphoma during a 7-month follow-up period, but were successfully engrafted with human B and T cells. On the other hand, lymphoma developed in 90% of the C.B-17/SCID mice infused with 70 x 10(6) human PBL from the same donor. Likewise, 36% of beige/nude/xid (BNX) mice, exposed to 12 Gy TBI, radioprotected with SCID bone marrow and then transplanted with human PBL developed lymphoma. Similar results were obtained when different strains were infused with PBL of the same donor. Immunohistochemical analysis indicated that the tumor cells were of human B cell origin and expressed the EBV-encoded latent membrane protein-1 and nuclear antigen 2. While further studies are required to understand the mechanisms which suppressed outgrowth of EBV lymphoma in human --> mouse radiation chimera, compared to human --> C.B-17/SCID or human --> BNX chimera, this marked resistance offers new possibilities for transplantation of hematopoietic tissues or cells from EBV-positive donors.
Animals↗
Anticoagulation without catheter removal in children with catheter-related central vein thrombosis.
Catheter-related central venous thrombosis is a serious and common problem among children. The traditional management has been anticoagulation and early catheter removal. Unfortunately, many patients require a new catheter, which is associated with complications that include possible further thrombosis. Although others have used thrombolytic agents in attempts to avoid catheter removal, the authors of the present study believe that the associated complications occur too frequently and are too serious. They have had success with standard anticoagulation in a limited number of patients. Between February 1991 and April 1994, 17 patients (6 weeks to 19 years of age) were treated for catheter-related deep venous thrombosis. Eight patients underwent early catheter removal accompanied by anticoagulation; two of them had intrinsic catheter problems that necessitated removal, and one had hemophilia. Nine others received anticoagulation without catheter removal. Of these, one required catheter removal after 10 days heparin administration failed to diminish the thrombosis. Another patient responded well to anticoagulation but required catheter removal several weeks later because of catheter-site infection. The other seven patients responded well to anticoagulation, and their catheters were retained. For patients with a functional catheter essential to their care, anticoagulation may safely prevent catheter removal.
Adolescent↗
Erythromelanosis follicularis faciei in women.
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Dermatitis, Exfoliative↗
Treatment of Candida nail infection with terbinafine.
BACKGROUND: Terbinafine is a highly potent drug against dermatophytes. Data regarding its effectiveness against Candida species are few and variable. OBJECTIVE: Our purpose was to evaluate the efficacy and safety of oral terbinafine in patients with Candida nail infection. METHODS: In an open-label uncontrolled study, 20 patients completed 16 weeks of treatment with terbinafine, 250 mg/day, and an additional 8 weeks with placebo. Efficacy was assessed clinically and mycologically at weeks 0 (baseline), 4, 8, 16, 24, 36, and 48. Routine laboratory studies were performed at baseline and weeks 4, 8, and 16. RESULTS: At the end of the trial 60% of target nails were cured clinically and mycologically; in 10% there was mycologic cure with residual clinical signs, in 25% a moderate improvement (> 50%), and failure in only 5% (one patient). Most nails were infected by Candida parapsilosis. Two of 28 patients showed mild reversible elevation of liver enzymes 1 month after initiation of terbinafine treatment. CONCLUSION: The administration of terbinafine for 16 weeks is effective in the treatment of Candida nail infection. Liver enzyme values should be determined during the first month of treatment.
Administration, Oral↗
In vivo effects of cytokines on psoriatic skin grafted on nude mice: involvement of the tumour necrosis factor (TNF) receptor.
Following engraftment of human involved psoriatic skin to nude mice there is a partial normalization of pathology associated with a loss of inflammatory leucocytes. However, the epidermis remains hyperproliferative, which may reflect a primary defect. The roles of TNF-alpha, IL-1 and IL-6 in epidermal hyperproliferation of grafted psoriatic lesions were investigated. Before and after treatment, grafts were analysed to determine epidermal thickness and labelling index (LI). HLA-DR, intercellular adhesion molecule-1 (ICAM-1), and TNF receptor (TNF-R; p75 and p55) expression were determined by immunoperoxidase staining. Psoriatic epidermis was found consistently to be negative for p55 TNF-R and p75 TNF-R before grafting. Following engraftment, TNF-R-positive cells (i.e. p55 by keratinocytes; p75 by epidermal dendritic cells) were identified throughout the epidermis. Higher numbers of p75 TNF-R epidermal dendritic cells were found in grafts following a course of TNF-alpha, IL-6 or IL-1 treatment. The p55 form of the TNF-R expressed by keratinocytes was significantly elevated after treatment with TNF-alpha or IL-6. HLA-DR and ICAM-1 were also expressed in these grafts. TNF-alpha, anti-IL-1, and anti-IL-6 treatment induced a marked decrease in the epidermal thickness and LI of psoriatic graft tissue, correcting the hyperproliferation associated with psoriatic epidermis. Supraphysiological levels of TNF-alpha may saturate and consequently down-regulate their own receptors, leading to a paradoxical inhibitory effect.
Animals↗
Inhibition of alpha interferon but not gamma interferon signal transduction by phorbol esters is mediated by a tyrosine phosphatase.
Previous studies have indicated that the expression of viral oncoproteins, cell transformation, or phorbol ester treatment of cells can inhibit alpha/beta interferon (IFN-alpha/beta)-induced gene expression. The mechanisms by which these promoters of cell growth exert their inhibitory effects vary, but in most instances they involve a disruption of the IFN-alpha/beta-induced transcription complex ISGF3 such that the DNA-binding component of this complex (the 48-kDa ISGF3gamma protein) does not bind to the interferon-stimulated response element (ISRE). In this report, we demonstrated that phorbol ester treatment of human peripheral blood monocytes dramatically inhibits activation of IFN-alpha/B-stimulated early response genes but by a mechanism which does not involve abrogation of the ISRE binding of ISGF3gamma. Phorbol ester treatment of monocytes inhibited IFN alpha-stimulated tyrosine phosphorylation of the transcription factors Stat1alpha, Stat2, and Stat3 and of the tyrosine kinase Tyk2 but had no effect on IFN-gamma activation of Stat1alpha. IFNalpha-stimulated tyrosine phosphorylation of Jak1 and the alpha subunit of the IFN-alpha receptor were unaffected by phorbol 12-myristate 13-acetate (PMA). Moreover, PMA caused the dephosphorylation of Tyk2 but not of Jak1, which was activated by IFN. Pretreatment of cells with vanadate prevented the effects of PMA with regard to PMA-induced Tyk2 dephosphorylation. These observations suggest that PMA exerts its inhibitory effects by activation of a tyrosine phosphatase which selectively regulates Tyk2 but not Jak1 activity.
Base Sequence↗
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↗
[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↗
[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↗
John Barnbas Memorial Lecture. Social policy and social movement: the child in independent India.
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Child↗
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↗
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↗
[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↗
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↗
[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↗
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↗
[Welcome, thought, pitfall and grief].
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Adolescent↗