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J R Bogner

Publications and source records attributed to J R Bogner.

89 records · Page 5Linked to original sources

Lymphocyte subsets as surrogate markers in antiretroviral therapy.

Efficacy of antiretroviral treatment is evaluated usually according to reduction of serious events (e.g. opportunistic infections while on therapy) and improvement of survival time. In stages of asymptomatic disease treatment trials have to cover very long time periods to fulfil these requirements. In asymptomatic stages, when viremia is commonly absent, monitoring the host's immune response is an indirect means of measuring antiviral efficacy. CD4+ lymphocyte counts are generally accepted as surrogate in all major trials. The subsets of the CD8+ compartment reflect early and late activation and cytotoxic immune response. CD38+, CD57, CD8+ HLA/DR+ subsets reflect the host's vigorous cellular immune response even in early stages. These subsets are candidate surrogate markers in early and late stages of HIV infection. On the other hand, CD3+ CD4- CD8-, CD19/20 (B lymphocytes) and CD16+ (natural killer cells) do not exhibit any properties of candidate surrogate markers. Established and experimental cellular surrogate markers are discussed including own data and a review of the literature.

Evaluation Studies as Topic↗

[Indications for sonography and follow-up studies. Initial results of a prospective study].

Ultrasonic examinations of the abdomen may result in expensive secondary imaging examinations. This prospective study was conducted in collaboration with the Zentralinstitut Köln. The first aim of our study was to compare the results of abdominal sonography in three different patient groups: The first group was comprised of patients referred for a medical check-up, the second group of patients referred because of upper abdominal pain and the third group of patients with generalized atherosclerosis. The second aim was to correlate sonographic findings (classified in three degrees of severity), with subsequently induced diagnostic procedures in the three groups. 2719 patients were enrolled, 2393 (88%) in group 1, 286 (11%) in group 2 and 40 (1%) in group 3. A total of 1792 abnormal findings were diagnosed. 65.6% of the findings in group 1, 65.7% in group 2 and 88% in group 3 were abnormal. Up to now, the findings led to a nearly equal number of subsequent diagnostic procedures in groups 1 and 2. The preliminary results show that abdominal sonography may be as effective in patients for a check-up as in patients referred because of a well-defined indication. Patients with defined abdominal symptoms show more abnormal sonographic findings than patients on a check-up. Higher costs resulting from subsequent examinations deserve critical assessment in the individual patient.

Abdomen↗

[Successful drug therapy in Aspergillus endocarditis].

A 74-year-old man who had a weight loss of 7 kg in three months, with fever up to 38 degrees C and anaemia (Hb 9.4 g/dl) began to have pain and blue discoloration of fingers II-V of the right hand. Echocardiography demonstrated vegetation on the aortic valve cusps and blood culture grew Aspergillus fumigatus, indicating Aspergillus endocarditis. There were no predisposing factors. Valve replacement was contraindicated because of the age of the patient, the presence of peripheral arterial disease, and previous myocardial infarction. Treatment was started with amphotericin B i.v. (dosage increasing to 50 mg daily) and 1.5 g daily of flucytosine by mouth, to a total of 1.1 g amphotericin B and 41.5 g flucytosine in five weeks. During this time there was a gradual decrease in symptoms and the valve vegetations. Nine months later there has been no recurrence.

Aged↗

Erythrocyte antibodies in AIDS are associated with mycobacteriosis and hypergammaglobulinemia.

Positive direct antiglobulin results prior to transfusion in some of our AIDS patients, as well as some reports in the literature on red cell antibodies in AIDS patients, prompted us to investigate the prevalence of erythrocyte antibodies in AIDS patients with transfusion requiring anemia. In addition we studied the question of relevant correlations with clinical diagnosis and with hematological and immunological laboratory parameters. Of 145 consecutive hospitalized AIDS patients (CDC criteria), 34 (23%) presented with anemia requiring transfusion. With each cross-match a routine antibody screening was performed. In cases of positive reaction additional antibody differentiation was done. Diagnoses, hematologic parameters, and therapy were studied retrospectively. Agglutination was positive in at least one test for 41% (14/34) (group 1). C3d, anti I, cold agglutinins, and IgG occurred most frequently (n = 9/8/7/6 out of 14). Seventy-five per cent (12/14) had leukopenia (less than 4000/microliters), 57% (8/14) had thrombocytopenia (less than 150,000/microliters), and 43% (6/14) showed both. Average values for leukocytes, thrombocytes, and CD4-positive lymphocytes did not differ significantly in patients with (group 1) and without (group 2) erythrocyte antibodies. Average gamma globulin levels were significantly increased in group 1 (23.2 g/l versus 16.9 g/l; p less than 0.001). In group 1, 64% (9/14) had proven mycobacteriosis (6 atypical), in contrast to only 15% (3/20) in group 2 (p less than 0.05). There were no significant differences between the two groups in prevalence of other opportunistic infections, malignant lymphoma, and Kaposi's sarcoma. Autoimmune versus infectious pathogenesis of pathologic erythrocyte antibodies in AIDS has been discussed in the literature.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

[Reversible space-occupying lesions of the kidney in HIV infection].

In January 1990 a 32 year old nurse was admitted with fever, weight loss of 9 kilogramms and pain of her right flank. HIV infection due to intravenous drug abuse had been diagnosed in 1986. Ultrasonic imaging revealed a solid tumor of low echogenicity in the cranial part of the right kidney. This finding could be confirmed with computed tomography and magnetic resonance imaging. Angiographic study showed a missing of blood vessels in the same area. A transcutaneous puncture with a thin needle resulted histologically in unspecific findings like detritus, lymphoid cells and neutrophils. Antibiotic treatment with amoxicilline and cefuroxim was without success. Symptoms as well as ultrasonic findings completely disappeared following oral administration of ofloxazine. The clinical course and the successful treatment support the diagnosis of an atypical renal abscess. As a second diagnosis a histologically proven cirrhosis of the liver could be established. Hepatitis C serology proved to be positive.

Abscess↗

Duplex sonography in the diagnosis of renovascular hypertension.

Duplex sonography (DS) has become a well established method for diagnosing peripheral vascular diseases. Technical developments (higher resolution of transducer and deeper penetration) have made also abdominal and retroperitoneal vessels, including renal arteries, accessible for duplex sonography. This method provides the opportunity to recognize renal artery stenoses causing renovascular hypertension without invasive procedures. We therefore examined 86 hypertensive patients with a high likelihood of renovascular hypertension. Due to technical problems (bowel gas, adipositas) we excluded 7 patients. 79 patients (17-79 years) were included in our study. Flow patterns of several renal vascular areas were evaluated while the renal artery was demonstrated on a B-scan. A spectrum analysis included the evaluation of the frequency pattern (widening of the frequency band and loss of a frequency free window below the systolic rise?), the sloping of the diastolic shoulder, and the calculation of different parameters like acceleration index, deceleration index, resistance index, acceleration time, and systolic peak velocity. The accuracy of DS in diagnosing renal artery stenoses was compared with arterial digital subtraction angiography (DSA). Renal artery stenoses was diagnosed in 21 out of 158 renal arteries (13%). Except for the systolic peak velocity no significant correlations could be found of any of the indices from spectrum analysis with hemodynamically significant stenoses (greater than 50%). However, the following 3 criteria proved to be valuable signs of a hemodynamically significant stenoses: 1) Maximal systolic acceleration greater than 3 m/s, 2) Steep sloping diastolic shoulder, and 3) Turbulence of all frequency ranges without a frequency free window below the systolic rise. Compared with DSA the sensitivity of DS was 84.0%, the specificity was 98.5%, and the predictive value 91% in significant stenoses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Expansion of activated T lymphocytes (CD3 + HLA/DR +) detectable in early stages of HIV-1 infection.

The phenotypic characterization of lymphocyte subsets in relation to different clinical stages of HIV infection has mainly focussed on CD4 and CD8 cells. Some reports focus on expansion of activated T lymphocytes in AIDS patients. Yet there is no detailed knowledge whether such changes occur also in earlier stages of HIV infection. In order to describe the kinetics and possible pathogenetic meaning of this subset when related to all distinct chronologic stages, we performed two-color flow cytometric lymphocyte differentiation in 173 HIV-infected patients and 30 healthy controls. All subjects were classified according to the Walter Reed (WR) system. Our results show that a significant increase of activated T lymphocytes (CD3 + HLA/DR +) occurs early, in WR1 and WR2, thus preceding the clinically relevant CD4 depletion. This increase is paralleled by an expansion of CD8 + Leu7 + cytotoxic cells. We conclude, that early changes of lymphocyte subsets are detectable in addition to inversion of the CD4/CD8 ratio. The possible pathogenetic meaning including the question of possible autoimmune mechanisms is discussed.

Acquired Immunodeficiency Syndrome↗

Treatment of secretory diarrhea in AIDS with the somatostatin analogue SMS 201-995.

We have observed two patients with AIDS suffering from severe watery diarrhea refractory to conventional medical treatment. In the first patient the reason for the diarrhea could not be revealed in spite of extensive investigations; however, the clinical picture suggested cryptosporidia infection. In the second patient cytomegalovirus could be shown in colonic biopsy specimens. After failure of several attempts of symptomatic, antibiotic, and antiviral therapy, the long-acting somatostatin analogue SMS 201-995 was administered to the patients subcutaneously in a dose between 2 x 50 micrograms and 3 x 100 micrograms/day. This treatment resulted in a prompt reduction of stool volume and bowel motions. Somatostatin may be a useful addition to the symptomatic treatment of refractory diarrhea in AIDS.

Acquired Immunodeficiency Syndrome↗

Myelin basic protein in the cerebrospinal fluid of patients infected with HIV.

The major pathological abnormalities of HIV encephalopathy are infiltrates of macrophages, multinucleated giant cells, microglial nodules and demyelination. Elevated myelin basic protein (MBP) levels in the cerebrospinal fluid (CSF) provide a marker for central nervous system demyelination. The purpose of this study was to investigate the possible role of CSF MBP as a useful and early marker for HIV encephalopathy. The CSF of 40 consecutive patients with HIV infection of various clinical stages was investigated, including 13 patients with clinical signs of HIV encephalopathy. CSF MBP was elevated in 2 patients (5.0 and 5.3 ng/ml), both of whom had moderate to severe HIV encephalopathy. The course of the disease was rapid in both patients. In the remaining 38 patients, CSF MBP levels were marginally elevated (n = 12) or normal (n = 26). Our results suggest that CSF MBP is not a sensitive marker for the diagnosis and evaluation of HIV encephalopathy, but may be an indicator of prognosis for the course of the disease. There were only few findings of elevated CSF MBP levels in patients with HIV encephalopathy in the current study, and this may be because the disorder progressed slowly in most patients. It is possible that CSF MBP levels in HIV encephalopathy may only be elevated with acute clinical deterioration but are normal in slowly progressive forms of demyelination, as seen in multiple sclerosis.

AIDS-Related Complex↗

Serum neopterin levels as predictor of AIDS.

The reliability of laboratory parameters for the prediction of impending manifestation of AIDS in HIV-1 infected patients was investigated. Over a mean observation period of approximately 1 year (5 to 33 months) 56 patients were studied. Eleven patients progressed to AIDS (group 1) and 45 remained free of AIDS-defining disease (group 2). Eight candidate-predictor variables were measured on each patient at the beginning of the observation period: neopterin, hemoglobin, lymphocytes, CD4 counts, CD8 counts, platelets, gammaglobulins, and erythrocyte sedimentation rate. In a linear discrimination analysis, a stepwise entry of these parameters into the discriminant function was effected according to which variable added most to the separation into groups 1 and 2. Neopterin proved to be most discriminating with no improvement of separation when adding further variables. Thus, a final allocation rule was computed using neopterin alone. This rule assigns neopterin levels above 21.9 nmol/l to group 1 and levels below to group 2. We conclude, tentatively, that in HIV-infected patients neopterin levels of 22 nmol/l and over may indicate the manifestation of AIDS in the year to come.

AIDS-Related Complex↗

Class II (DR) antigen expression on CD8+ lymphocyte subsets in acquired immune deficiency syndrome (AIDS).

In a selected group of human immunodeficiency virus (HIV)-infected patients we confirm the expansion of a CD8+ T-lymphocyte subset, i.e., the CD8+/Leu7+ cells, which account for 30% of the lymphocytes, compared to 3% in the control donors. In addition, a CD8+ T-lymphocyte subset that coexpresses class II (DR) antigens, i.e., CD8+/DR+ cells, is also increased from 1.5% in controls to 27% in the HIV-infected patients. Using three-color immunofluorescence and flow cytometry we can demonstrate that the CD8+/Leu7+ and the CD8+/class II+ cells are not distinct but overlapping subsets. In the HIV-infected patients 42% of the CD8+/Leu7+ cells were strongly positive for class II and these CD8+/Leu7+/class II+ cells accounted for 13% of all lymphocytes. These findings indicate that the expanded CD8+/Leu7+ cells are activated and hence might be actively involved in immune defense in acquired immune deficiency syndrome (AIDS).

AIDS-Related Complex↗

Hyperlipidemia under treatment with proteinase inhibitors.

To define the extent and time course of HIV-proteinase inhibitor (PI) effects on serum lipid levels 148 patients on triple combination therapy including PIs and 91 patients on therapy with two nucleosides as a control group were evaluated. In the PI group there was a significant increase in total cholesterol after 3, 6 and 12 months compared to the baseline level (198, 204 and 203 vs. 176 mg/dl). The increase in triglycerides was 25.5% from the baseline at month 3. Indinavir had a significantly higher impact on cholesterol levels than saquinavir. No changes in lipids were seen in the control group. It was concluded that hyperlipidemia is associated with PI use, becomes evident within 3 months of treatment and seems to be substance specific.

Adult↗

Th1/Th2 shift in HIV lymph nodes: no contribution of CD6o cells.

BACKGROUND: An expansion of CD8+60+ cells with Th2 type helper function has been observed in HIV-infected individuals. A Th1/Th2 shift in late HIV infection might be related to the functional activity of this subset. Our objective was to test the ability of lymph node (LN) lymphocytes to produce cytokines of the Th1 and Th2 type. PATIENTS AND METHODS: LN cells were stimulated with PMA in the presence of ionomycin and brefeldin A. After surface staining for CD4, CD8 and CD60 and intracellular staining for interferon gamma (IFNgamma), interleukin 2 (IL-2) or IL-4 and IL-10, the percentage of cytokine producing lymphocytes (CPL) was determined by flow cytometry. LN of nine individuals in the early stage of HIV infection were compared to late stage patients. RESULTS: CD4+ subset: in early stages of HIV infection the percentage of Th1 CPL was 1.9 times higher than that of Th2 CPL. In late stages of infection the Th1 responding cells were not found more frequently than Th2 ceLLs. CD8+ subset: no Th1/Th2 shift was detected during early or late stages of HIV infection. CD60+ subset: a maximum of 32.1 +/- 7.8% of double positive cells of the CD8+60+ type produced Th2 type cytokines. A small percentage (< 8%) of CD60+ cells also produced Th1 cytokines. No shift in the cytokine production was seen in early or late stages of infection. CONCLUSION: At single cell level a shift in cytokine production in LN cells can only be detected in the CD4+ subset. Thus, the CD60+ subset does not seem to contribute to the putative Th1/Th2 shift attributed to the immunopathogenesis of HIV-induced destruction of the immune system.

Antigens, CD↗

Cost reduction after introduction of a multidisciplinary infectious disease service at a German university hospital.

BACKGROUND: In 1997 an infectious disease service (IDS) similar to those in the US was established at a university hospital in Munich, Germany. PATIENTS AND METHODS: We assessed the economic impact of the new policy by performing a cost comparison analysis. Inpatients with pneumonia, skin infections/cellulitis, urinary tract infections (UTI) and bacteremia/sepsis were assigned to two groups: patients from a 6-month period after the establishment of the IDS (post-IDS group) were compared with similar patients before the implementation of the ID-service (pre-IDS group). Costs of microbiological investigation (MB), antibiotic treatment (AB), clinical imaging (CI), total costs and length of antibiotic therapy were analyzed. RESULTS: Patients with UTIs in the post-IDS group had 39% fewer MBs (p<0.05) than patients in the pre-IDS group, resulting in a 33% decrease in average MB costs (p<0.05). In the total group, in which subgroups with pneumonia, skin infection and UTI were summarized, the post-IDS group had 37% fewer MBs (p<0.05) resulting in MB cost reductions of 34% (p<0.05). There were no significant differences in expenditures for AB and CI and in the average length of antibiotic therapy. CONCLUSION: This study shows that continuous consultation by an IDS does not increase diagnostic and treatment costs, but results in significant cost reductions.

Aged↗

Outlook in oral and cutaneous Kaposi's sarcoma.

We looked at survival of 138 patients with HIV-1-associated Kaposi's sarcoma. Patients with lesions of the oral mucosa had a higher death rate (risk ratio 3.4 [95% CI 1.6-7.1]; p=0.001) than those having exclusively cutaneous manifestations of the disease. Patients with oral Kaposi's sarcoma and a CD4 cell count of at least 150/microL had a similar mortality risk to patients with the cutaneous disease but CD4 cell concentration of no more than 150/microL. Thus, oral Kaposi's sarcoma is an important prognostic marker, at least for patients who do not receive triple antiretroviral therapy.

Germany↗

Liposomal doxorubicin in the treatment of AIDS-associated Kaposi's sarcoma: clinical, histological and cell biological evaluation.

AIDS-associated Kaposi's sarcoma (KS) in eight patients was treated with the systemic application of liposomal doxorubicin (20 mg/m2 per cycle). After six cycles of treatment a significant regression of KS was observed in all patients. Tumour volume was reduced from 556 +/- 635 mm3 before therapy to 42 +/- 134 mm3 after therapy as determined by ultrasonography of selected tumours. Histological examination revealed a reduction of tumour-like structures and the absence of KS spindle cells in involved areas after therapy. In vitro experiments with KS-derived cell cultures, which most likely represent the KS spindle cells, suggested that liposomal doxorubicin may cause regression of KS via two different mechanisms: (i) by highly specific inhibition of KS spindle cell proliferation and (ii) by induction of monocyte chemoattractant protein-1 expression in KS spindle cells, which may result in increased recruitment of phagocytic cells (monocytes/macrophages) into the lesions. A cooperative action of both mechanisms may explain the high efficacy of liposomal doxorubicin in the treatment of AIDS-KS.

Acquired Immunodeficiency Syndrome↗