[Endocarditis and arterial embolism in periarteritis nodosa].
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Biomedical subjects
Publications and source records attributed to B Dupont.
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An Intensive Care Unit is noisy. These Noises are made by the Machines and the Staff. Nose must be limited and also the patient isolated.
Congenital adrenal hyperplasia (C.A.H.) with 21-hydroxylase deficiency is an autosomal recessive disease. HLA genotyping of parents and children in six families in which more than 1 child had C.A.H. established that the gene responsible for 21-hydroxylase deficiency is closely linked to HLA. One patient had inherited a maternal HLA-A/B recombinant haplotype and studies in this family indicated that the abnormal gene is close to the HLA-B locus. The findings provide a method for identification of C.A.H. carriers and for prenatal diagnosis of affected children.
A common inherited disorder of steroidogenesis in man, 21-hydroxylase (21-OH) deficiency, is linked to the HLA major histocompatibility complex (MHC), and is associated in particular with certain allotypes of the HLA-linked complement proteins. Recently, this disorder was demonstrated to result from a defective structural gene for the 21-OH enzyme, also termed cytochrome P-450C21. The human (HLA) and murine (H-2) MHCs are homologous in overall organization and in the structures of their component genes. To determine whether 21-OH genes are located in the H-2 complex, we have now used a bovine adrenal complementary DNA clone encoding part of 21-OH to examine a cluster of overlapping cosmid clones derived from the S region of the BALB/c mouse. We found that there are two 21-OH genes in this region, located immediately 3' to the C4 and Slp genes.
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Recent technical achievements allow satisfactory cryopreservation of human platelets that, after thawing and washing, maintain functional viability for therapeutic use. We have now demonstrated that such previously frozen platelets retain full HLA antigenic activity in spite of the combination of freezing, thawing, and washing procedures and the presence of the surface-active cryopreservative DMSO. Platelets stored at 4 C without DMSO and previously frozen platelets from the same donors were tested in parallel for quantitative expression of HLA antigens. In all cases, the previously frozen platelets were quantitatively equal or superior to the platelets stored at 4 C with regard to their capacity to specifically reduce the HLA antibody activities of selected typing sera against a panel of antigen-positive lymphocytes.
Peptidolytic activity was studied in the broken-cell extracts of 17 isolates of pathogenic fungi tested with phenylazobenzyloxycarbonyl-Pro-Leu-Gly-Pro-Arg (PZ-PLGPA) as a substrate. All the fungi studied except Candida spp., Cryptococcus neoformans and two actinomycetes hydrolyzed the substrate and therefore contained a so-called PZ-peptidase activity. Of all the positive strains, Trichophyton schoenleinii, a pathogenic fungus showed the highest activity and was therefore chosen as a source for PZ-peptidase purification. The four chromatographic steps, a 'negative' dye column, a 'positive' dye column, hydroxyapatite Ultrogel, and modified TSK (HW 55), gave a highly purified peptidase with a 12% overall yield. Inhibitor studies suggested that the 82 000 M(r) PZ-peptidase is a metalloproteinase. Moreover it cleaved native rat type I collagen. Partial peptide sequencing showed a strong sequence homology to regions of two metalloproteinases previously identified in the yeast Saccharomyces cerevisiae and in rat.
Congenital adrenal hyperplasia due to 21-hydroxylase (21-OH) deficiency is HLA-linked. The haplotype HLA-(A3);Bw47;DR7 is strongly associated with 21-OH deficiency and always carries a null allele at the complement C4A (Rodgers) locus. It seemed likely that this haplotype carries a deletion encompassing both the C4A and 21-OH loci. We hypothesized that the HLA-linked defect involved a structural gene for the adrenal microsomal cytochrome P-450 specific for steroid 21-hydroxylation. We isolated a plasmid with a 520 bp bovine adrenal cDNA insert encoding the middle third of the P-450 peptide. When human DNA was digested with Taq I restriction endonuclease and hybridized with the cDNA probe, DNA from 13 unrelated normal individuals yielded two hybridizing bands of equal intensity at 3.7 and 3.2 kb. The upper band was not present in DNA from a patient homozygous for Bw47. DNA from six unrelated patients heterozygous for Bw47 yielded, in five, diminished relative intensity of the upper band consistent with a heterozygous deletion, and complete disappearance of the upper band in one. Thus 21-OH deficiency sometimes results from the deletion of a gene and sometimes, presumably, from smaller mutations. This gene is probably located very near the C4A gene encoding the 4th component of complement.
Infections caused by Cryptococcus neoformans cause significant morbidity and high mortality, particularly among immunocompromised patients. Cryptococcal meningitis is an important cause of central nervous system disease and death in patients with AIDS. Although the introduction of amphotericin B has greatly improved the prognosis of patients with cryptococcal meningitis, 30 years of experience have revealed important clinical limitations, including modest efficacy, nephrotoxicity, other clinically significant toxicities, and the inconvenience of intravenous dosing. The discovery of the additive effects of amphotericin B and flucytosine in cryptococcosis resulted in some improvement in efficacy and reduction in amphotericin B-related toxicity. However, approximately 30% of patients with cryptococcal meningitis still fail to respond to therapy. Ketoconazole has not proved useful in treating cryptococcal meningitis. Accumulating evidence suggests that the antifungal triazoles fluconazole, itraconazole, and SCH 39304 represent an advance in the treatment of cryptococcal meningitis, particularly in AIDS patients. Preliminary clinical trials in patients with and without AIDS have indicated that fluconazole and intraconazole are effective and well tolerated as either initial or maintenance therapy. Two large comparative trials of fluconazole and amphotericin B in patients with cryptococcal meningitis (mostly those with AIDS) are under way.
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Four patients with chronic mucocutaneous candidosis from early infancy were treated successfully with ketoconazole given orally. All thrush lesions were clinically and mycologically cured within a few days of treatment with 100-400 micrograms of ketoconazole daily; skin lesions were cured within a few weeks, and nails were cured after about three months of treatment. Delayed cutaneous hypersensitivity to candidin was acquired by the third month. Cellular and humoral immunologic responses were related to the suppression of Candida albicans antigen by ketoconazole. A fifth patient with chronic lingual granuloma due to C. albicans improved considerably. Favorable results also were seen in individual patients with oral and disseminated histoplasmosis due to Histoplasma capsulatum; laryngeal, pulmonary, and hepatic disease with continuous fever also due to H. capsulatum; pulmonary histoplasmosis due to Histoplasma duboisii; cutaneous sporotrichosis; and cutaneous blastomycosis due to Blastomyces dermatitidis and in three patients with favus due to Trichophyton schoenleinii; six of seven patients with tinea capitis due to Trichophyton violaceum (after one month of treatment); and four patients with infections due to Petriellidium boydii, Phialophora pedrosoi, or Beauveria species. All patients responded rapidly to 400 mg of ketoconazole per day given orally. Only the patient with hepatic histoplasmosis required 800 mg per day. Measurements of ketoconazole in the serum during treatment were useful in the evaluation of therapy.
Important progress has been achieved in antifungal chemotherapy in recent years. Two groups of drugs are now used: those produced by various organisms and those made synthetically. In the first group, only amphotericin B (1956) administered systemically is active in numerous deep mycoses. Although toxicity limits the use of amphotericin B, it is still the drug of choice for systemic mycoses. Griseofulvin was the first agent used for oral treatment of dermatophytoses. The introduction of flucytosine began a new era in chemotherapy; however, although flucytosine is orally administered and rapidly distributed, its antifungal activity is limited to cryptococcosis and systemic candidosis. The rapid induction of flucytosine-resistant mutants led to the development of treatment regimens of amphotericin B plus flucytosine. With the development of imidazole derivatives in 1969, a new generation of azole antifungal agents has emerged. Of these, only ketoconazole was orally active. New azole derivatives and triazoles have been synthesized, but only itraconazole has been successful in the treatment of superficial and deep mycoses in humans. Future trends for the development of agents with fungicidal activity, wider spectra, and better distribution are proposed. The association of immunotherapy with antifungal chemotherapy may offer new treatments for fungal infections in immunocompromised patients.
The efficacy of itraconazole, a new triazole antifungal agent, was studied in vitro and assessed in patients. The MICs of itraconazole for 16 strains of Aspergillus fumigatus were in the same range as those of amphotericin B: less than 0.09-0.36 microgram/ml vs. less than 0.09-0.78 microgram/ml, respectively. Eight adult patients with systemic fungal infections were treated orally with 100-200 mg of itraconazole two times a day. A patient with relapsing histoplasmosis (Histoplasma capsulatum var. duboisii) was cleared of the infection; a patient with arthritis of the knee due to Phialophora parasitica did not respond to treatment; four patients with semiinvasive pulmonary aspergillosis improved dramatically and were considered clinically cured; and two patients with aspergilloma improved. The duration of follow-up was one to nine months. Levels of itraconazole in body fluids were measured by a bioassay. Levels of drug in knee fluid were about 30% of the simultaneous levels in plasma. A progressive decrease in the level of itraconazole in plasma occurred in two patients, and a progressive increase in the levels occurred in five patients.
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Six human pathogenic Trichosporon species are described with respect to criteria for routine identification, epidemiology and clinical origin: T. ovoides, T. inkin, T. asahii, T. asteroides (Fissuricella filamenta), T. cutaneum, and T. mucoides. These species are causative agents of white piedra and cutaneous infections and are involved in systemic, localized or disseminated mycoses, particularly in patients with underlying haematological malignancy. Data on in vitro sensitivity to antifungal drugs are provided.
BACKGROUND: Thirteen clustered cases of American histoplasmosis, a deep mycosis caused by Histoplasma capsulatum and acquired through inhalation of airborne spores was reported. Twenty-five persons traveled in Martinique, French West Indies. Thirteen underwent trekking and passed through a mountain tunnel full of bats (tunnel group). The 12 others performed canyoning and did not go through the tunnel (control group). Fifteen days after exposure, 1 patient of the tunnel group developed fever, chills, and cough. METHODS: The index case was diagnosed in the hospital, but 12 cases where initially diagnosed as prolonged influenza. All individuals were contacted and submitted to a phone questionnaire. They were asked about eventual occurrence of influenzalike symptoms, about activities practiced, and the notion of contact with bats. All were invited to have clinical examinations, chest x-ray films, and blood samplings. Serologic testing for histoplasmosis was performed by immunodiffusion. Clinical evidence of infection with H. capsulatum was obtained in all the remaining patients of the tunnel group and in none in the control group. Symptoms occurred with an acute onset in 11 to 23 days: fever and chills, severe asthenia, headaches, digestive tract involvement, and then cough, dyspnea, hepatic involvement. Pulmonary micro- or macronodules and mediastinal adenopathies were seen on radiograph and/or computed tomography scan. RESULTS: H. capsulatum serologic tests were positive in all 13 cases with presence of specific M and or H precipitins, 5 to 13 weeks after exposure, and were negative in control group. All patients were treated with itraconazole 200 mg per day during at least 2 months. Treatment was well tolerated; patients progressively recovered. Clinical and serologic follow-up was obtained for some patients at 1 and 4 years. The present study reports the first large outbreak of histoplasmosis acquired in Martinique. CONCLUSION: Histoplasmosis still occurs and is potentially serious. In patients returning from endemic areas, presenting prolonged influenzalike symptoms, clinicians should look for previous possible exposure to Histoplasma.
In connection with the cases of a group of patients hospitalised in Departments of Infectious Pathology, the authors consider the various general and visceral symptoms caused by the focal infection. In these statistics, fever occupies the first place and in its isolated form poses difficult diagnostic problems which can only be solved by a process of elimination. Repeated biological tests and careful attention to the clinical symptoms are necessary to link what has been observed to an infection which, it should be stressed, is descrete. Articular lesion, very different from acute articular rheumatism, cutaneous, ocular and renal symptoms are each in turn discussed and analyzed. From their personal observations, the authors recall the possibility of serous lesions and, in particular, of recurrent pericarditis. A summing-up of the theories concerning prescription completes this clinical survey which ends by recalling the function of the oto-rhino-laryngologist in the search for the causal infection and the difficulties involved in ascribing responsibility to an almost invariably latent focal infection.