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Biomedical subjects

H W Pees

Publications and source records attributed to H W Pees.

At least 19 recordsLinked to original sources

Rapid whole blood analysis of virus-specific CD4 and CD8 T cell responses in persistent HIV infection.

OBJECTIVES: Upon HIV infection, strong antiviral cytotoxic and helper T cell responses are generated. They are considered to be an important component in the control of HIV viral load. A simple and rapid whole blood assay was established to quantify and simultaneously characterize HIV-reactive CD4 and CD8 cells. The assay was applied to evaluate the effect of antiretroviral therapy on HIV-specific T cell responses. METHODS: Whole blood of 33 HIV-infected individuals was specifically stimulated by HIV-1 Pr55gag, and activation-induced intracellular cytokine expression in CD4 and CD8 T cells was analysed by flow cytometry. RESULTS: HIV-1-specific CD8 and CD4 T cells can be quantified simultaneously. As specific antigen, HIV-1 Pr55gag virus-like particles were superior to soluble protein, especially for the activation of CD8 T cells. In untreated individuals, a high frequency of HIV-specific T cells was observed. The frequency of CD8 T cells was consistently higher than the respective CD4 T cell response, thus demonstrating a dominance in CD8 T cell expansion in persistent HIV infection. Patients on antiretroviral therapy showed a significant reduction in HIV-specific CD4 and, even more strikingly, CD8 T cells. CONCLUSION: The whole blood assay provides a rapid estimate of the total antiviral T cell resources, and is highly suited for a clinical setting. It may thus have widespread applications for the evaluation of vaccination strategies and immunotherapy. Because antiretroviral therapy significantly reduces both HIV-specific cytotoxic and helper T cell responses, future therapeutic strategies should aim at improving cellular antiviral immunity.

Adult↗

First manifestations of seronegative spondylarthropathy following autologous stem cell transplantation in HLA-B27-positive patients.

Two male patients with non-Hodgkin's lymphoma (NHL, follicular NHL, diffuse large B cell NHL, both in 2nd complete remission) and one female patient with acute myeloid leukemia in 1st complete remission developed arthralgias and enthesopathy following autologous stem cell transplantation. In 2/3 patients, sacroiliitis could be demonstrated on X-ray. In both patients, the rheumatic symptoms were classified as manifestations of a spondylarthropathy. All three patients were subsequently shown to be HLA-B27-positive. The patients were successfully treated with non-steroidal anti-inflammatory drugs. The differential diagnosis of joint pain following autologous stem cell transplantation should include HLA-B27-associated spondylarthropathies in addition to the more commonly seen bone and joint pain due to immobilization and medication.

Adult↗

Kaposi's sarcoma of the pancreas mimicking pancreatic cancer in an HIV-infected patient. Clinical diagnosis by detection of HHV 8 in bile and complete remission following antiviral and cytostatic therapy with paclitaxel.

BACKGROUND: Diagnosis of pancreatic cancer is usually made by endoscopic retrograde cholangiopancreatography (ERCP) and corresponding findings in computed tomography (CT) or magnetic resonance imaging. Kaposi's sarcoma, a frequent tumor in individuals with a late-stage HIV infection, can be located in the gastrointestinal tract and cause identical symptoms to carcinoma of the same site. A close correlation of this tumor to human herpes virus 8 (HHV 8) has been known for several years and there are reports of successful antiproliferative therapy. METHODS: Aspirated pancreatic juice and bile was investigated for the presence of HHV 8 by polymerase chain reaction. The clinical course of the patient under antiviral therapy and treatment with paclitaxel was studied. RESULTS: A 47-yr-old HIV-infected man with a history of Kaposi's sarcoma of skin and lungs caused by obstructive jaundice in the years before was admitted. ERCP showed a typical double-duct sign and CT revealed a tumorous infiltration of the pancreatic head, highly suspicious for pancreatic adenocarcinoma. A mutation of the ki-ras gene could be ruled out and molecular analysis of bile identified HHV 8 by PCR. Intensive antiviral therapy, including foscarnet and treatment with paclitaxel led to a complete remission within 8 m.o. CONCLUSION: Kaposi's sarcoma of the pancreas possibly mimics pancreatic cancer in HIV-infected subjects. Diagnosis may be made by identification of HHV 8 in pancreatic juice or bile, and successful clinical outcome is possible by intensive antiviral and cytostatic treatment with paclitaxel.

Antineoplastic Agents, Phytogenic↗

Anti-EBNA1/anti-EBNA2 ratio decreases significantly in patients with progression of HIV infection.

Reactivation of EBV infection is common in immunocompromised individuals. We determined specific antibodies to EBV-encoded nuclear antigens (EBNA)1 and 2 in 102 sera of HIV-infected individuals. Anti-EBNA1/anti-EBNA2 ratio (E1/E2) is less than 1 in chronic infection and exceeds 1 in healthy EBV-positive carriers. 52% of cases had E1/E2 < 1. E1/E2 decreased remarkably during the progression of HIV infection. Detectable HIV-Antigen, decline of CD4+ cell count and CD4+/CD8+ ratio were correlated with an increasing prevalence of E1/E2 below 1. We conclude that determination of E1/E2 is useful in immunocompromised patients.

Adolescent↗

Active syphilis in HIV infection: a multicentre retrospective survey. The German AIDS Study Group (GASG).

OBJECTIVE: To study syphilis in HIV infection focusing on immunocompromised patients with an atypical or aggressive clinical course of syphilis, inappropriate serological reactions or an unreliable response to therapy. STUDY DESIGN: A multicentre retrospective chart review using a standardised questionnaire for all patients with active syphilis. SETTINGS: Thirteen dermatological and medical centres throughout Germany, all members of the German AIDS Study Group (GASG). PATIENTS: Clinical data of 11,368 HIV infected patients have been analysed for cases of active syphilis requiring treatment. Asymptotic patients with reactive serological parameters indicating latent syphilis without a need for treatment were excluded. RESULTS: Active syphilis was reported in 151 of 11,368 HIV infected patients (1.33%, range per centre 0.3%-5.1%). Most of the 151 syphilis patients were male (93%) and belonged to the homosexual or bisexual exposure category for HIV infection (79%); another 6% were iv drug users. Among the 151 syphilis patients primary syphilis was diagnosed in 17.2%, maculopapular secondary syphilis in 29.1%, ulcerating secondary syphilis in 7.3%, neurosyphilis in 16.6% and latent seropositive syphilis without clinical symptoms but serological abnormalities indicating active syphilis in 25.2%. A history of prior treatments for syphilis was reported in 50%. At the time of syphilis diagnosis 26.5% of the patients were in CDC stage II, 33.8% in stage III and 24.5% in stage IV of HIV disease (CDC classification 1987). CD4 cell count was lowest in those with ulcerating secondary syphilis (mean 307, SD 140/microliters) and neurosyphilis (351, SD 235/ microliters). The highest CD4 count was found in patients with early primary and early secondary syphilis (444, SD 163/microliters and 470, SD 355/microliters). Inappropriate serological response to syphilis infection was found in 81 of 151 patients (54%). Remarkable findings were false negative VDRL titres (11 patients with non primary syphilis), false negative TPHA (1) or 19S-IgM-FTA-ABS-tests (16), and strongly reactive VDRL (> or = 512, 8) or TPHA titres (> or = 10 240, 47). Treatment failures were reported in at least 6 of 151 cases (4%). CONCLUSIONS: Atypical clinical and serological courses of syphilis were observed in HIV infected patients. Ulcerating secondary syphilis with general symptoms ("malignant syphilis") was 60 times more frequent than in historic syphilis series. Neurosyphilis was found in one sixth of those with active syphilis. Therefore lumbar puncture should be considered a routine in coinfections with HIV and syphilis. Treatment efficacy should be monitored carefully.

Adult↗

Molecular and biological characteristics of a novel HIV-2 isolate, HIV-2HOM.

In 1991 a new HIV-2 isolate (HIV-2HOM) was isolated first from a German individual most likely infected in West Africa in the beginning of the 1970s. The virus was isolated from both, the plasma and the peripheral blood lymphocytes of the patient by using OKT-3-stimulated cord blood lymphocytes. The recovered viruses could be further propagated on Jurkat cells and exhibited a broad cell tropism. Biochemical and antigenic properties of HIV-2HOM were examined by radioimmunoprecipitations. For a more detailed molecular characterization, a 1520 bp DNA fragment from the env gene and a 722 bp DNA fragment from the pol gene were amplified by polymerase chain reactions, cloned and sequenced. A comparison of both sequences to prototypic HIV-2 and SIV isolates revealed a close relationship to HIV-2ST. This strain originated from an asymptomatic Senegalese individual and is supposed to be of reduced pathogenicity. Taking into account genetic data, it may be assumed that HIV-2HOM and HIV-2ST are closely related strains with different growth characteristics and pathogenic features.

Base Sequence↗

[Intracellular measurement of anthracyclines with flow cytometry].

The intracellular drug uptake of anthracycline antibiotics, including the anthrachinone analogue mitoxantrone, was investigated. Measurement of drug uptake for each of the white cell subpopulations is possible by Flow cytometry (FCM). Cell separation was carried out by two different methods, using Lysing solution and Ficoll. Ficoll was found to be the best for further investigations in cell kinetics. Stock solutions of each drug, ranging from 0.5-3 micrograms/ml, were incubated with cell suspensions of healthy donors. In the case of doxorubicin, daunorubicin and epirubicin a linear correlation between drug concentration in the incubation medium and intracellular drug level was found. In further studies drug concentration was constant (1 microgram/ml or 3 micrograms/ml) and the intracellular drug uptake was measured at various incubation times. Examinations were carried out with the two different cell separation methods, mentioned above. In healthy donors the reproducibility of FCM measurement was examined. In conclusions of the results observed in experiments, FCM seems to be a suitable, reproducible technique for determination of cellular anthracycline concentrations with the exclusion of aclacinomycin A and mitoxantrone because of their physical properties.

Aclarubicin↗

The BFM-protocol for HIV-negative Burkitt's lymphomas and L3 ALL in adult patients: a high chance for cure.

During a period of 9 years we used the pediatric BFM-NHL protocol for treatment of 14 adult patients with Burkitt's lymphoma or L3 acute lymphoblastic leukemia. Ten of 14 patients obtained a complete remission including 5/8 with stage-IV disease or B-ALL. After a median follow-up of 55 months none of these ten patients relapsed. The projected survival after 8 years is 71%. Toxicity was moderate, with one early death; a tumor lysis syndrome occurred in four patients. From our experience we conclude that the BFM-NHL protocol is very effective in adult patients, with a high cure rate and acceptable toxicity, even in advanced stages of disease.

Adolescent↗

[HIV infection in stage IV C-2 (CDC). Increase in the p24 antigen value before critical decrease in CD4+ lymphocytes].

The Center for Disease Control proposed a classification system of HIV-infection including a symptomatic stage IV C-2 with secondary infections like thrush, oral hairy leukoplakia and herpes zoster. Because the prognostic value of these symptoms for the development of AIDS has been proven and the CDC-classification does not include any immunological parameters we analyzed the numbers of CD4+-lymphocytes and the frequency of HIV-antigen in 65 HIV-infected individuals. When entering stage IV C-2, the incidence of HIV-antigenemia was as high as in full blown AIDS (53% and 60%, respectively). However, we observed no decrease of CD4+-lymphocytes as compared to earlier CDC-stages.--We conclude that in stage IV C-2 the increase of viral protein production proceeds independently from CD4+-status.

CD4 Antigens↗

Effects of human alpha-interferon on granulocyte-macrophage progenitor cells (CFU-GM) in vitro.

Two preparations of human interferon (IFN)-alpha were assessed for their influence on granulocyte-macrophage progenitor cells (CFU-GM) in vitro. Both highly purified human IFN-alpha Ly and recombinant IFN-alpha 2a suppressed CFU-GM colony formation in a dose-dependent manner using low-density bone-marrow target cells. Suppression of CFU-GM colony formation was accompanied by an increase in clusters. However, depletion of monocytes, T lymphocytes and B lymphocytes from low-density bone-marrow cells resulted in insensitivity of progenitor cells to IFN-alpha. These results demonstrate that the effects of human IFN-alpha on myeloid progenitor cells (CFU-GM) are mediated by accessory cells within the bone marrow.

Cell Division↗

[Sequential high-dose cytarabine therapy in combination with asparaginase in acute myeloid leukemia].

Between 1984 and 1987 14 patients with acute non-lymphocytic leukemia were treated with sequential high-dose cytosine arabinoside in combination with asparaginase. Twelve patients were suffering from refractory leukemia; in these patients complete remissions were achieved in 58%. The efficacy of this schedule was much better in patients with substantial leukemia cell reduction due to antecedent conventional therapy and no more than 25% blast cells in the bone marrow. In this subgroup complete remissions were achieved in 75% and 86% respectively, taking into account only the completed treatment courses. Beside the well-known side-effects such as alopecia, nausea, vomiting and hepatotoxicity, we observed an increase in severe infections. Three patients died of pulmonary mycosis.

Adult↗

[Beta interferon therapy in hairy cell leukemia].

Eleven patients with histologically proven hairy-cell leukemia were treated for 2 to 6 months with a natural beta-interferon (beta-IFN) preparation (3 X 4 million units week i.v.). Three of the eight evaluable patients experienced a partial response, two a minor response, and three no improvement. A reduction of the hairy-cell infiltration of the bone marrow was observed in one patient. Typical IFN side-effects with flu-like symptoms were noted. These results demonstrate that IFN-beta has some clinical efficacy in hairy-cell leukemia.

Adult↗

Effective treatment of lymphomas of Burkitt's type and B-ALL in adults.

Malignant lymphomas, Burkitt's type, and B-ALL are rarely encountered in adult patients. Rapid initial responses are usually followed by early relapse and death. In a pilot study four adult patients, two presenting with B-ALL, were successfully treated with an aggressive protocol developed by the BFM study group for childhood lymphomas of B-type. Rapid clearance of tumor masses was achieved in all patients; no relapse occurred during an observation period ranging from 19-33 months of complete remission.

Adolescent↗

[Diagnosis and radio-chemotherapy of the neuroblastoma in adults].

The neuroblastoma in the adult is a rare disease which has a bad prognosis. Until now, there are no generally accepted therapy conceptions. The clinical symptoms of the patient whose case is presented here were above all pains in the pelvic region. The histologic diagnosis was difficult and could be proved only by additional examinations of other metastases. Although the primary tumor was searched for intensively, is was only found 20 months later. Especially radiotherapy, but also chemotherapy (CYVADIC regimen) have proved to be effective. Above all, the quality of life could be largely maintained over a period of 26 months.

Adult↗