[Atypical forms of AIDS-associated Pneumocystis carinii infection].
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Biomedical subjects
Publications and source records attributed to D Niese.
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Of 686 hemophiliacs who are being treated at our institution, 402 (59%) are HIV-sero-positive. One hundred seventy-eight heterosexual partners of HIV-infected hemophiliacs have been serologically examined; 19 (11%) are HIV-positive. So far none of the seropositive partners suffers from ARC or AIDS. The rate of heterosexual transmission of HIV is statistically significantly correlated with the CD4+ count of the HIV-infected index patient. No such correlation was found with the index patient's clinical stage or the isolation of HIV from the index patient's blood. Of 39 seronegative female partners who were investigated clinically and immunologically, 17 showed pathologically increased numbers of CD8+ counts. In one case, HIV was transmitted from a female patient with von Willebrand's disease to her husband. As compared to other groups at risk for AIDS, the rate of heterosexual HIV transmission is comparatively low in hemophiliacs. The exact reason for this difference is not yet known. The relevance of the immunopathological findings in seronegative sexual partners of hemophiliacs also remains to be determined.
485 HIV-positive patients have been treated at our institution in Bonn during 1985 to 1989. Mycobacterial infections occurred in twelve (2.5%) HIV-positive patients. Of 166 AIDS-manifestations according to CDC, eleven (6.6%) were mycobacterial infections. There occurred one case of miliary tuberculosis, six cases of extrapulmonary, one of disseminated tuberculosis and four cases of atypical mycobacteriosis. Mycobacteriosis other than tuberculosis (MOTT) were caused three times by Mycobacterium kansasii and once by Mycobacterium scrofulaceum. Tuberculosis was seen less often in haemophiliacs. Disseminated tuberculosis and atypical mycobacteriosis developed in late stages of HIV-infection with underlying severe immunodeficiency. The lung was the main target organ of tuberculosis. MOTT most often affected the gastrointestinal tract additionally. Noninvasive materials, first of all sputum and gastric acid, were reliably diagnostic but available with delay in particular cases. In those cases histologic studies proved helpful. Application of five-fold regimen (INH, RMP, EMB, PZA and SM) always succeeded in negative cultures in a mean of 15 days in all cases of tuberculosis. Two cases of atypical mycobacteriosis with Mycobacterium kansasii were treated with a five-fold regimen (one case with ciprofloxacin additionally) and culture-negative after six resp. 28 weeks of therapy.
To determine whether the biological variability of HIV-1 has any clinical significance, the highly variable cytopathogenicity of 153 HIV-1 strains, isolated from 119 hemophiliacs, was related to the number of CD4+ lymphocytes present in the patient's blood at the time of virus isolation. It was shown that the cytopathogenicity of the HIV-1 isolates was inversely correlated with the number of CD4+ lymphocytes. The highest CD4+ cell number were observed in 34 latently infected patients characterized by HIV seropositivity, failure of virus isolation, and detection of viral DNA by the polymerase chain reaction. Cytopathogenicity of the HIV-1 isolates was a reliable prognostic marker and correlated well with other less-sensitive prognostic parameters, including the detection of infectious virus and p24 antigen in the plasma, and the decline of p24 antibody in the serum. The results suggest that the viral isolates - if not subjected to extensive passage - represent in vivo variants selected from a heterogeneous viral population according to the particular immunological conditions of the host.
The course of HIV infection in 53 haemophilic patients aged 5-20 years was evaluated by clinical examination and laboratory tests. During the evaluation time (median 30 months) two patients died of AIDS and 32 patients (60%) deteriorated when assessed by the Brodt-Helm classification. Nineteen patients (37%) had decreased absolute helper cell counts (less than 500 CD4 positive cells/microliters), and 45 patients (87%) had reduced helper cell to lymphocyte ratios (less than 0.35). HIV-1 was isolated from peripheral lymphocytes in 29 of 46 patients. As the disease progressed the number of positive viral cultures increased. Considerable progression of the HIV infection was seen in haemophilic children and adolescents during the median evaluation period of 30 months. The transition from symptomless HIV infection to immunodeficiency was easily recognised. A lowered ratio of helper cells to lymphocytes seems to be a useful marker of the beginning of the deterioration of the immune system.
At our institution 686 hemophiliacs are being treated. Of them 402 (59%) are anti-HIV-seropositive. The general use of heat-treated clotting factor products was begun in July 1983, and from May 1984 all patients exclusively used heat-treated clotting factors. Thus, one can assume that infection occurred no later than early 1984 in our patients. Since December 1985 HIV-positive hemophiliacs have regularly been clinically and immunologically examined. Most of the 306 patients who could be investigated were clinically symptom-free at the time of their first visit. However, 45 patients have developed AIDS from 1982 through August 1988. The mean survival time of hemophiliacs with AIDS is less than 6 months. In 36% of those 274 patients who have been followed for a mean period of 14 months the clinical stage of the disease worsened by at least one stage according to the classification system proposed by the Centers for Disease Control. We did not find a correlation between clotting-factor consumption during the years 1984-1986 and the actual clinical stage of the patients. Virus isolation from peripheral blood lymphocytes (PBIs) answered the question whether anti-HIV seropositive hemophiliacs are not only immunized but really infected in many more cases than those revealed by detection of p24 antigen or decline of p24 antibody. Positive viral culture correlated strongly with a drop in CD4+ lymphocytes under the level of 400/microliters. However, HIV could not be cultured regularly in advanced cases, suggesting that virus replication in PBLs is not necessarily the cause of depletion of T-helper cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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Human immunodeficiency virus (HIV)-seropositive patients show involvement of the central and/or peripheral nervous system. We present here the results of electroencephalographic (EEG) findings in stage WR 1-5 HIV-seropositive hemophiliacs from a total of 184 who attended our clinic prior to October 1987.
As morbidity of thrombopenia in hemophilia A patients is increasing, the pathogenetic influence of the reticuloendothelial system (RES) was measured using autologous anti-Rh0(D)-coated erythrocytes (EA) in 17 patients with or without thrombopenia. Mean survival of EA in patients was reduced to 53% of healthy controls (53.2 +/- 46.1 min vs 100.5 +/- 12.2 min; patients vs controls, mean +/- S.D.). Survival of EA was not significantly different either in thrombopenic vs non-thrombopenic nor anti-HIV (human immunodeficiency virus) positive vs negative patients. Thrombopenia, elevated serum IgG and circulating immune complexes were related to the presence of anti-HIV antibodies. EA survival was also decreased in the absence of anti-HIV antibodies. This indicates activation of RES by a mechanism different from retroviral infection by HIV (1).
A pentapeptide originally isolated by Abiko and coworkers from the ultrafiltrate of a uremic patient was synthesized and studied for its in vitro effects on normal human peripheral blood mononuclear cells. The SRBC-rosette forming capacity of T cells was significantly reduced after preincubation of the cells with the peptide, whereas the viability and the percentage of SRBC-receptor positive cells as determined with a monoclonal antibody remained unchanged. The PHA and ConA induced proliferation of T cells as well as the induction of suppressor cells by ConA were decreased, while the proliferative responses to PWM and specific antigens were enhanced. MLC experiments with separated and reconstituted lymphocyte populations pointed to the T cell as the main target. The data presented demonstrate that at least some of the effects described for so-called middle molecules are reproducible with this peptide at concentrations eventually occurring in patients with chronic renal failure.
Reticuloendothelial system Fc-receptor (FcR) function was measured in 4 healthy controls and 9 patients with immune thrombocytopenia before and after therapy with high dose i.v. gammaglobulin (HDIg). Idiopathic thrombocytopenic purpura (ITP) was diagnosed in 5 patients. 2 patients with hemophilia A, 1 with acute tuberculosis and 1 with psoriasis vulgaris had thrombocytopenia that clinically resembled ITP. 4 out of 9 patients received prednisone prior to or during the study. FcR blockade was observed only in patients with ITP not receiving prednisone. In all other patients, HDIg did not induce a measurable FcR blockade. However, all except 1 patient (with acute tuberculosis) showed a marked rise in platelet counts for 2 to 12 wk. This is consistent with therapeutic efficacy of HDIg in various clinical settings of immune thrombocytopenia. All platelets were fully hemostatic and clinically no difference could be observed. This indicates that the effect of HDIg cannot be due to FcR blockade alone.
The diagnostic classification of arthralgia and non-characteristic neurological deficit is a challenge for the neurologist and the internist if both symptoms arise simultaneously or in combination. Diseases with the combined appearance of both symptoms are grouped into those with early and more or less simultaneous onset, those starting with arthralgias followed by neurological deficits, neurogenic arthropathies, and those presenting both symptoms as complications of ongoing internal disease. A diagnostic procedure is set out and recommended.
Patients who received combination chemotherapy for metastatic nonseminomatous testicular cancer showed a decreased Con A induced suppressor cell function. Additionally 15% of the patients who received ifosfamid had a decreased IgM-serum concentration, an increased number of macrophages and a decreased proliferation rate in MLC.
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52 symptomatic (SPB) and 64 asymptomatic (APB) pigeon breeders were investigated for the HLA-A, -B, -C, -DR; C2, C3, C4 and Bf systems, and C3, C4 and factor B serum concentrations. HLA-DR3 and Bf S frequencies were significantly higher in the SPB than the APB group. Mean factor B concentrations were lower in the SPB than in the APB group. A positive two-way association between HLA-DR3 and the disease was found. It is concluded that a gene or genes responsible for type III and IV allergic reactions leading to the disease is associated with HLA-DR3. The increase of Bf S allotype and low mean factor B concentrations, however, can be explained by the strong linkage disequilibrium between BfS and HLA-DR3.
This study was undertaken to get more insight into the previously suggested heterogeneity of the HLA--DW3 cluster. Preliminary evidence of DW3 heterogeneity was derived from results of intrafamilial mixed lymphocyte culture tests (MLC) where cells of apparently homozygous offspring revealed unexpected stimulations of one of the parents' cells. Therefore, 15 different homozygous typing cells (HTCs) of DW3 specificity were tested against 43 HLA-DW3 heterozygous individuals. The response patterns of the 43 HLA-DW3 heterozygous cells toward 13 HTCs leads to the definition of at least three groups of DW3 stimulating cells. According to these patterns, four groups of responding cells could be classified. These results were confirmed by a MLC checkerboard experiment running all DW3-HTCs against each other. Discussing all possible explanations for these observations, the authors conclude that the existence of DW3 subtypes having some properties in common is the most likely interpretation of the results obtained. Family segregation studies will be needed to define the genotypic situation of the DW3 cluster.
Whereas fifteen pigeon fanciers suffering from extrinsic allergic alevolitis from avian dust had high titres of antibodies against pigeon antigens, antibodies were not demonstrable, even by immunofluorescence, in the serum of a symptomatic individual exposed to minimal amounts of avian dust. Following exposure to larger quantities of pigeon dust inhalation challenges, a low titre of antibodies appeared, but disappeared again after avoidance of the allergen. Cell-mediated immunity was elevated in the lymphocyte transformation test and also decreased after avoidance of allergen contact. Therefore, it seems likely that the antibody is not the only mediator of pigeon breeder's lung. Inhalation challenges and T cell-dependent immune reactivity may reveal more avian dust sensitive individuals suffering from fibrosis without the typical history of extrinsic allergic alevolitis and without detectable antibodies.
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