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Biomedical subjects

M Dietrich

Publications and source records attributed to M Dietrich.

At least 127 records · Page 7Linked to original sources

Interferon alpha in the treatment of AIDS-associated Kaposi's sarcoma.

Twenty-three patients with biopsy-proven Kaposi's sarcoma and HIV infection were treated with recombinant interferon-alpha-2a (Roferon-A). Two dosage regimens were used: 21 patients received 18 X 10(6) units intramuscularly per day for 3 months, followed by injections of 18 X 10(6) units three times a week. The remaining 2 patients were treated with 2 X 18 X 10(6) units i.m. per day for 3 months. Three patients either refused further treatment or were lost to follow-up within the first few weeks. Thus, a median observation period of 7.5 months (range 1.5-17) was available for 20 patients. Within the first 3 months, 6 patients (30%) responded to treatment, 6 patients (30%) showed no progression, whereas in 8 cases (40%) progressive disease was noted. A similar rate of responders versus nonresponders was found after 6 months of observation. In progressive disease, interferon could be effectively combined with cytostatic drugs. Dose-dependent neurological and hematological side effects were observed in a few patients only. Opportunistic infections were diagnosed in 12 patients with a median onset of 6 months (range 1-10) after start of interferon treatment. The total number of lymphocytes expressing the CD4 antigen or the ratio of CD4 to CD8 positive cells were of prognostic value. These data suggest that interferon alpha is an active agent in the treatment of Kaposi's sarcoma, that it shows tolerable side effects and can be combined effectively with cytostatic drugs in case of progression.

Acquired Immunodeficiency Syndrome↗

Effects of systemic and local administration of etomidate on adrenocortical steroidogenesis in male rats.

A method for focal dialysis of the adrenal cortex is introduced allowing determination of adrenal steroid local release rates in conscious, freely moving rats. Etomidate, an anaesthetic drug known to interfere with adrenal steroid synthesis, blocks not only corticosterone but also aldosterone and, to a lesser degree, progesterone release. Intra-adrenal application of the drug via the dialysis system for a defined time resulted in low release rates of corticosterone without inducing sedation of the animals or even anaesthesia. Remaining low steroid concentrations during the next 5 h after cessation of the dialysis with drug-containing medium indicate that the inhibition of steroid synthesis lasted for several hours. It is concluded that the inhibitory effect of etomidate on steroid biosynthesis can be explained on the basis of an interaction of the drug with adrenocortical enzymes without the involvement of hypothalamic or hypophyseal mechanisms.

Adrenal Cortex↗

Monoclonal antibodies to human immunodeficiency virus: their relation to the patterns of lymph node changes in persistent generalized lymphadenopathy and AIDS.

Recently there has been much interest in using immunohistology with monoclonal antibodies (MABs) against different cells of the immune system in lymph nodes (LNs) of patients with HIV infection. The panel of these MABs is becoming increasingly extensive. In this study we report on our finding that by using a limited number of properly chosen MABs, diagnostically and prognostically relevant parameters can be acquired. One hundred and twenty-one LN biopsy specimens from patients with HIV infection were reviewed and classified according to our expanded working classification and a fifth main type of LN lesion, the small lymphocyte follicular type, was added to our earlier classification. We propose that this new type represents a transitional form between the mixed follicular type and the follicular depleted type. In the follicular type of LN lesion there is no marked change in the number of CD4 cells within the follicles and in the extrafollicular parenchyma. The reaction against the major core proteins of HIV is always positive and the number of proliferating cells is very high. The positivity is weaker in the earlier cases and stronger in the older ones. The follicular dendritic cell (FDC) network shows degenerative changes. In the hypervascular follicular type the reaction pattern with these selected MABs is very similar to the one in the follicular type. In the mixed type there are hyperplastic follicles and regressively transformed follicles in the same node. The hyperplastic follicles show a pattern similar to those in the follicular type. However, the reaction with MABs against core proteins of HIV is often markedly stronger. The number of proliferating cells is decreased markedly. Some follicles show extensive FDC network destruction. CD4 cells within the follicles and in the extrafollicular parenchyma are decreased. The regressively transformed follicles contain very few proliferating cells and the reaction with MABs against core proteins is variable, being strong in some follicles and weak in others. The small lymphocyte type contains follicles consisting mainly of small lymphocytes. These lymphocytes are of the same phenotype as those in the primary follicles. In contrast to these, however, the numbers of CD4 and Leu 7+ cells are much decreased. The reaction with MABs to core proteins is weak and limited to the germinal centres (GCs). The number of proliferating cells is strongly diminished. The FDC network, however, is well developed in most follicles. In the follicular depleted LNs there are no follicles; however, in some LNs remnants of FDC can be seen.

AIDS-Related Complex↗

[Kaposi sarcoma within the scope of AIDS].

The disseminated form of Kaposi's sarcoma (KS) is an important cutaneous manifestation of acquired immune deficiency syndrome (AIDS). Since 1983, we observed 5 patients suffering from this rare multifocal cancer associated with AIDS. We report on clinical picture, histopathologic changes, and immunologic parameters.

Acquired Immunodeficiency Syndrome↗

Eosinophil differentiating activity in sera of patients with AIDS under recombinant IL-2 substitution.

An increase in circulating eosinophils was observed in patients with AIDS or ARC who were substituted for a period of 14 days with exogenous recombinant IL-2 in the context of a Phase I/II study. IL-2 exerts a broad range of biological properties and enhances the production of a variety of other cytokines, i.e., factors for haemopoietic cell growth and differentiation. After having excluded a direct effect of r IL-2 on haemopoietic precursor cells in semi-solid agar cultures, we developed a liquid culture system and studied the effect of patients' sera collected at different time intervals before, during and after r IL-2 substitution on cell differentiation of normal human bone-marrow cells in vitro. Patients' eosinophilia was preceded by a detectable activity in the sera which induced light-density, non-adherent bone-marrow cells to differentiate into the eosinophil lineage and was assessed by the presence of eosinophil primary granules or Luxol-fast blue positive granules. Thus, these in vitro data suggest the presence of circulating mediator(s) enhancing eosinophil production and differentiation in response to in vivo substitution of r IL-2.

Acquired Immunodeficiency Syndrome↗

A pathway of coagulation on bovine capillary endothelial cells.

In this report cultured bovine capillary endothelial cells are demonstrated to specifically bind factors IX and X and also their activated forms. Bound factor IXa and cell-associated factor VIII can activate factor X. The product of this reaction, factor Xa, can then interact with a factor V-like molecule expressed by capillary endothelial cells promoting thrombin formation. The thrombin formed can cleave fibrinogen leading to release of fibrinopeptide A and clot formation. Endotoxin-treatment of capillary endothelial cells leads to induction of tissue factor activity which, in the presence of factor VIIa, promotes activation of factors IX and X. The amount of factor Xa formed endotoxin-treated endothelial cells incubated with factors VIIa, IX, VIII and X, is 8 times greater than cells incubated with factors VIIa and X alone. This indicates that on the perturbed endothelial cell surface factors VIII and IX do play an important role in factor X activation by the tissue factor pathway. The perturbed capillary endothelial cell can thus provide a model of the thrombotic state promoting initiation and propagation of a procoagulant pathway leading to thrombin formation. This pathway of coagulation is endothelial cell-dependent, since it requires expression of tissue factor and factor V by capillary endothelial cells, as well as interaction of coagulation factors with the surface of capillary endothelial cells.

Animals↗

HTLV-III/LAV viral antigens in lymph nodes of homosexual men with persistent generalized lymphadenopathy and AIDS.

The presence of core antigens of retrovirus HTLV-III/LAV, referred to as "AIDS-related virus" (AV), has been sought in lymph node samples of patients with persistent generalized lymphadenopathy (PGL, 28 patients), prodromal AIDS (1 patient) and AIDS with Kaposi sarcoma (3 patients). In 30 patients the deposition of viral antigens, detected by monoclonal antibodies to HTLV-III and LAV, could be observed within the germinal centers (GCs) primarily within the extracellular network of immune complexes, and the two patients who were negative were atypical. No AV could be found in normal tonsil or in samples with follicular hyperplasia of unknown etiology (20 cases). These findings, taken together with the ultrastructural identification of typical retrovirus particles in all 9 PGL and 2 AIDS cases studied, indicates that the network of follicular dendritic (FD) cells is an important reservoir of AV virus antigen at this site. The persistence of this retrovirus inside the GCs helps explain how the follicular hyperplasia affecting FD cells and B blasts in PGL may in progressive cases be accompanied by destruction of FD cells and gradual development of T4+ lymphopenia. T4+ T cells may circulate through the GCs and become infected with AV there. In addition, the identification of retrovirus antigen in situ may be of diagnostic value.

Acquired Immunodeficiency Syndrome↗

[Dermatologic diseases in patients with AIDS].

This short review deals with the cutaneous manifestations of the acquired immune deficiency syndrome (AIDS), which comprise Kaposi's sarcoma, as an important marker disease for AIDS, as well as various skin infections caused by bacteria, fungi and viruses. In patients at risk of acquiring AIDS, an extensive immunological investigation should be performed if skin infections are established. In addition, a large number of cutaneous complications encountered in AIDS patients have an immunological background, e.g. an extreme hypersensitivity to trimethoprim-sulfamethoxazole. Therefore, the dermatological investigation of patients at risk of acquiring AIDS is urgently recommended as a regular part of the general check-up.

Acquired Immunodeficiency Syndrome↗

[Fatal complications of tropical malaria in non-immune patients. A retrospective clinico-pathologic analysis of 25 cases].

Clinical and pathological data on 25 fatal cases of tropical malaria were obtained from several hospitals in a retrospective survey. The patients originated, without exception, from non-malaria endemic regions (non-immunes). Death occurred in nine patients despite elimination of the parasitaemia with schizontocides. Life threatening complications were complex and apparently interacting. Manifestations of the disease included (1) initial acute renal failure, (2) disturbance of water and electrolyte balance, (3) cerebral oedema resulting in microhaemorrhages, (4) lung oedema, and increasing respiratory insufficiency even after elimination of the parasitaemia (in 4 cases there was histological evidence of shock lung), (5) myocarditis (histological evidence of cellular myocardial infiltration obtained in 4 cases), (6) hepatocellular damage, (7) complications associated with intensive-care treatment in 2 cases. The data allow no conclusions on the intensity and nature of blood clotting disturbances. According to this analysis the clinical manifestations of advanced malaria resemble protracted shock conditions having other aetiologies. However, specific cerebral and cardiac complications and homeostatic disturbances do apparently occur, the treatment of which requires experience with the clinical syndrome.

Adolescent↗

Detection of coronavirus-like particles in homosexual men with acquired immunodeficiency and related lymphadenopathy syndrome.

Coronavirus-like particles were identified by electronmicroscopy in the feces of homosexual men. The particles banded at a density of 1.21 g/ml after cesium chloride density gradient centrifugation. To determine whether the presence of this virus might be related to clinical symptoms, several patient groups were studied prospectively. In 8 of 16 (50%) homosexual males with acquired immunodeficiency syndrome (AIDS) or unexplained lymphadenopathy syndrome (LAS), coronavirus particles were found. In contrast, such particles were found in none of 18 heterosexual controls and in only 3 of 20 homosexual males without AIDS or LAS. Thus, coronavirus excretion correlated significantly (2 alpha less than 0.01) with the clinical diagnosis of AIDS or with syndromes belonging to the AIDS-related complex. In addition, such particles identified in the serum of one patient with LAS and diarrhea suggest invasion and systemic spread of the agent and underline that this virus behaves differently from "common cold" human coronaviruses.

Acquired Immunodeficiency Syndrome↗

[AIDS fatalities in Hamburg (status: February 1985)--legal medicine aspects].

The registration of patients with acquired immune deficiency syndrome (AIDS) and AIDS deaths is centralized for medical research. A short review of the epidemiological state of AIDS in Hamburg is given (situation as of February 1985), and the autopsy results of seven postmortem examinations are referred to. Kaposi's sarcoma was seen in four patients and opportunistic infections in all cases, especially as a result of Pneumocystis carinii and cytomegalovirus. Due to the constellation of groups with an increased risk of acquiring AIDS--homosexual males, intravenous drug abusers and prostitutes--forensic implications have to be expected.

Acquired Immunodeficiency Syndrome↗

Preliminary clinical observations with recombinant interleukin-2 in patients with AIDS or LAS.

The toxicity of recombinant Interleukin-2 (IL-2) was studied in patients with acquired immunodeficiency syndrome (AIDS) or persistent lymphadenopathy syndrome (LAS). Increasing doses of the drug from 10(3) Units/m2 to 10(6) U/m2 were given as an intravenous bolus injection. At the high-dose levels some minor effects, such as fever up to 39.5 degrees C, chills, malaise or vomiting, were observed. The administration of 10(6) U/m2 as a 4-hour infusion showed identical results. No particular alterations of laboratory parameters were found. At the high-dose level the serum concentration of neopterin, which is released from macrophages after interferon gamma stimulation, was significantly (p less than 0.001) elevated above pretreatment levels. The clinical observation of daily infusions of 10(6)/m2 for 14 days revealed the same side effects. All patients developed lymphocytosis and eosinophilia. Two patients had suffered from severe diarrhoea for several weeks presumably due to cryptosporidiosis. In both cases diarrhoea ceased under the treatment with IL-2 and did not occur in the following two months.

Acquired Immunodeficiency Syndrome↗