Biomedical subjects
Publications and source records attributed to M Dietrich.
We report two cases of benign pleura mesothelioma. We compare our pre-, intra- and postoperative findings with other reports in the literature. This tumor is rare. The patients have few symptoms. Large tumors may cause hypoglycemia. The treatment of choice is complete resection of the tumor. The prognosis is good.
OBJECTIVE: This study compares teacher-reported prevalence rates for disruptive behavior disorders using DSM-IV, DSM-III-R, and DSM-III criteria within the same population of elementary school students and examines the relationships between DSM "subtypes" and academic performance, perceived behavior problems, and demographic variables. METHOD: Teacher rating scales were obtained on 1,077 students in five rural and five urban public schools in Regensburg, Germany. Rating scales included DSM-III-R items (attention-deficit hyperactivity disorder, oppositional defiant disorder, conduct disorder), DSM-IV items (attention-deficit/hyperactivity disorders [AD/HDs], oppositional defiant disorder), and DSM-III items (attention deficit disorder, with and without hyperactivity). Factor analyses of significance were performed. RESULTS: Overall prevalence for attention deficit disorders increased from 9.6% (DSM-III) to 17.8% (DSM-IV) primarily because of new cases identified as AD/HD-AD (inattentive type) and to a lesser degree, AD/HD-HI (hyperactive-impulsive type). Inattention in any subtype was associated with academic problems, and perceived behavior problems were associated with more than 80% of the cases that included hyperactivity-impulsivity. DSM-IV AD/HD subtypes showed significant behavioral, academic, and demographic differences. CONCLUSION: Application of DSM-IV criteria increased total AD/HD prevalence rates by 64% and identified the majority of children with academic and/or behavioral dysfunction. The data show significant heterogeneity between the subtypes and imply that many children screened into these subtypes require further evaluation to ensure appropriate management.
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Serum from patients with P. falciparum malaria at day 1 (pretherapy) induces tissue factor (TF) in cultured endothelial cells. TF induction depends on de novo transcription as shown in Nuclear Run On assays. Electrophoretic mobility shift assays demonstrated binding of AP-1 and NF-kappa B/Rel proteins to their recognition sites in the TF promotor. After therapy (day 28), stimulation of TF antigen by patient serum is reduced by 70%. When serum obtained before and after therapy was compared, a decrease of NF-kappa B activation was evident. Activation of NF-kappa B-like proteins was in part dependent on TNF alpha in patient serum, since a TNF alpha neutralizing antibody reduced induction of TF transcription and translation and induction of NF-kappa B-like proteins. Induction of TF activity was suppressed by pDTC, an inhibitor of NF-kappa B activation. When different promotor constructs of the TF gene were tested, induction was dependent upon the presence of the intact NF-kappa B-like binding site in the TF promotor. A mutant with deleted NF-kappa B, but intact AP-1 sites was not inducible. Mutation of the AP-1 sites did not prevent induction, but reduced inducibility by pretherapy serum. Therefore, NF-kappa B/Rel proteins are responsible for induction of TF transcription by pretherapy serum, but AP-1 is needed for highest inducibility. The effect of antiparasitic therapy on the induction of TF by serum from patients with complicated P. falciparum malaria is dependent on a therapy-mediated loss of activation of NF-kappa B-like proteins in post-treatment patient serum.
During HIV-1 infection, extensive alterations can be observed in the germinal centers (GCs) of lymphatic tissue. The initial hyperplasia of GCs is followed by disintegration and involution of these structures. The process is accompanied by progressive destruction of the network of follicular dendritic cells (FDCs). We investigated whether or not the destruction of GCs is caused by HIV-1 infection of FDCs in vivo. FDCs were purified by FACS or magnetic cell sorter (MACS) from enlarged lymph nodes (LNs) of four asymptomatic HIV-1-infected patients with persistent generalized lymphadenopathy. In situ hybridization demonstrated positive signals for HIV-1 RNA on the cell membrane of FDCs. Virus particles attached to the dendritic network could be demonstrated by electron microscopy, but budding was not seen. Furthermore, proviral DNA was detected by nested PCR (NPCR) in limiting dilution assays of FACS-purified FDCs (up to 1.0 x 10(4) cells) in only one cell fraction. In comparison, proviral DNA could be found in 5.0 x 10(3) to 2.5 x 10(5) FACS-purified Th cells obtained from peripheral blood and in 7.5 x 10(5) to 2.5 x 10(4) Th cells from LN of the same patients. In conclusion, FDCs retain HIV-1 particles on their cell membrane during HIV-1 infection, but the progressive destruction of FDC in vivo is probably not caused by a productive infection of FDCs with HIV-1.
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OBJECTIVE: The aim of the study was to evaluate whether detection of cervical carcinoma or cervical dysplasia is possible with the use of transvaginal sonography (TVS). METHODS: TVS was performed in 215 patients with pathological cervical cytology (PAP III-V), suspicious clinical findings or histologically verified carcinoma of the cervix. RESULTS: Cone biopsy in 54 patients with suspicious cytology and normal cervical features revealed 26 cases of cervical intraepithelial neoplasia (CIN) 0-II and 19 cases of carcinoma in situ. Sonography failed to detect cervical carcinoma in only nine cases (stages Ia, Ib and IIa). False-positive results of TVS were associated in no cases with CIN 0. In 161 cases with suspicious cervical lesions, 133 invasive cancers and 23 carcinomas in situ were detected. The most striking cytological finding was that 92% of patients with PAP III/IIID and abnormal sonographic signs, and 7% with normal sonographic results and suspicious PAP, had cancer of the cervix uteri. CONCLUSION: We conclude that TVS could be usefully applied to the routine pretreatment evaluation of patients with cervical carcinoma.
We performed repeated continuous flow cytaphereses (CFC) on 13 asymptomatic HIV-1-infected patients to study the feasibility of cell separation procedures to recover high yields of peripheral blood T-lymphocytes for adoptive immunotherapy in HIV-infected patients and to determine immunological and virological alterations following such procedures. A mean yield of 6.23 x 10(9) lymphocytes could be obtained by each cytapheresis, containing 1.82 x 10(9) CD4+, 3.23 x 10(9) CD8+ T-lymphocytes and 8.39 x 10(6) CD34+ peripheral progenitor cells. The CD4/CD8 ratio (mean 0.53, SD +/- 0.15) in the cell samples reflected the distribution of the lymphocyte subsets in vivo. Absolute lymphocyte counts decreased at a mean of 404/mm3 (25%) immediately after CFC but were replaced from the extravascular pool within 1 h. The CD4/CD8 ratios, p24-antigenaemia, HLA-DR expression and neopterin levels did not change significantly after cell separation. No alteration of the number of T-cells with integrated proviral DNA copies (1/10(3) to 1/10(6)) could be detected in peripheral T-helper cells by PCR after lymphapheresis. We conclude that high yields of peripheral T-lymphocytes can be obtained by continuous flow lymphapheresis for cell-mediated immunotherapy, without deterioration of virological or immunological parameters in HIV-infected patients. The separated T-cells are fully replaced from extravascular pools after 1 h.
A total of 307 patients with lepromatous leprosy and borderline lepromatous leprosy were randomized to dapsone monotherapy or to one of two types of drug combinations. A 3-year treatment phase was followed by a 5-year observation phase. The evaluation included 233 patients for whom together there were 1,404 years of observation. A total of 1,956 blinded histopathological specimens were processed centrally. When entering the trial isolates from 13 patients (5.6%) showed dapsone resistance in the mouse footpad test, and these patients were evaluated separately. Dapsone monotherapy (68 patients) had the same frequency of cure as the combination of dapsone and rifampin (77 patients) or the four-drug regimen consisting of dapsone, rifampin, isoniazid, and prothionamide (75 patients). We did not find a significant difference in the clearance of bacteria either between the monotherapy and the two-drug combination or the monotherapy and the four-drug combination. Six months after the initiation of treatment, disease in 15% of the patients who received dapsone monotherapy but none of the patients who received combined treatment were clinically progressive. After another 1 to 9 months of treatment the disease in all patients was stable or regressive. There was no difference in the type or frequency of reactions. Only after the end of the scheduled observation phase three relapses were reported. All three treatment regimens well tolerated. Dapsone monotherapy is highly effective in the treatment of multibacillary leprosy under the conditions of well-controlled treatment. Combination regimens seem only to accelerate the regression of the active disease when they are compared with monotherapy with dapsone. The mouse footpad test does not reflect the clinical resistance and cannot be recommended for use in making therapeutic decisions.
To understand at what level hematopoiesis is impaired in AIDS patients, we quantitated bone marrow cells of the myeloid and lymphoid lineages in their different stages of differentiation. The bone marrow aspirates of 20 HIV-infected patients (18 with CDC IV) and 11 controls were analyzed by flow cytometry, using a panel of monoclonal antibodies. The mean percentages of CD34+ and CD10+ hematopoietic precursor cells were not significantly altered in the HIV-infected patients. The values of these patients however scattered in a much wider range than in the control group, some patients showing extremely high values. Patients with high levels of CD34+ and CD10+ precursor cells in the bone marrow had lower blood leukocyte counts and lower blood and bone marrow CD4 cell numbers than patients with a low percentage of CD10+ and CD34+ cells (p < 0.01). The percentages of the CD34+ cell subsets studied (CD34+CD33+, CD34+CD14+, CD34+CD15+) were not altered. Bone marrow CD4+ lymphocytes, especially those of CD45RA-phenotype, were reduced, while the CD8+ cells (especially HLA-DR+/CD45RA+ cells) were increased. These results show that the hematologic disorders in AIDS are not simply caused by an altered number or composition of bone marrow precursor cells. We postulate that hematopoiesis is inhibited due to an imbalance in the bone marrow T lymphocyte populations.
Overhydration can contribute to fatal complications of falciparum malaria, even though renal function may be normal. In this context, the role of inappropriate secretion of antidiuretic hormone (ADH) has been controversial. Therefore, we have analyzed ADH serum concentrations together with serum osmolality and sodium levels in serum and urine of 17 consecutively studied patients with severe falciparum malaria. Serum sodium levels were low in 13 of 17 patients upon admission and returned to normal levels during antiparasitic therapy. Urine sodium levels were low in seven of 13 patients before treatment and increased during therapy. Urine sodium concentrations were high, however, in the remaining six patients. Serum osmolality was lower in these six patients than in the other seven hyponatremic patients (P < 0.002). In relation to serum osmolality, ADH levels were inappropriately high in these six patients, which confirms the presence of inappropriate secretion of ADH. Serum creatinine levels were not higher in these six patients than in those without inappropriate secretion of ADH. Inappropriate secretion of ADH seemed to be a major cause of hyponatremia, since other factors that could lead to this condition were not found in these six patients. In conclusion, we have shown, that human falciparum malaria can be associated with inappropriate secretion of ADH.
We studied seven cases of Kaposi's sarcomas (KS) obtained from patients with AIDS and one KS from a patient without HIV infection. Antigen expression was studied by immunocytochemistry and mRNA expression by in situ hybridisation. The markers tested were endothelial leukocyte adhesion molecule-1, thrombomodulin, and tissue factor. In all tumors (AIDS and non-AIDS associated) these markers reacted positive, indicating transcription and translation of these genes in KS. The synthesis and expression of tissue factor and thrombomodulin suggests that KS is a tumor that has tissue factor-mediated thrombin formation under the control of thrombomodulin. The expression of thrombomodulin and endothelial leukocyte adhesion molecule-1 provides evidence for the vascular origin of KS.
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The prophylaxis of cytomegalovirus retinitis reactivation is effective in reducing the risk of blindness and in prolonging the remission interval and time of survival if given daily throughout life. In this study, a newly developed therapeutic regimen with 3 infusions a week was compared to the conventional maintenance therapy of 5 infusions a week using the same total weekly dose. For this purpose, ten patients were given 10 mg ganciclovir/kg 3 times a week (group A), and 18 received 6 mg ganciclovir/kg once daily for 5 days a week (group B). Only patients with newly diagnosed retinitis were included in this study. Both groups were comparable regarding their general health and ocular state at the beginning of the study. Induction therapy for stabilization of retinitis had to be given for 17.1 and 16.7 days (P = 0.785). Visual acuity was 0.5 and 0.7, respectively, at the beginning (P = 0.128) and 0.5 each at the end of the study (P = 0.875). Fifty-six percent of both groups presented with central retinal involvement at the beginning, whereas it was 56 and 78%, respectively, at the end (P = 0.250). The retinitis was found to have progressed more than 0.5 papilla diameters (pd) after 63.8 and 64.0 days (P = 0.996) and more than 1 pd after 117.6 and 77.8 days (P = 0.350). New induction therapy had to be performed after 147.9 and 131.5 days, respectively (P = 0.598). The maintenance therapy had to be interrupted due to side effects for 1.4 and 8.3 days, respectively (P = 0.185). According to these results, the prophylaxis of retinitis reactivation with 3 x 10 mg ganciclovir/kg per week is as effective as the established one with 5 x 6 mg/kg per week and can thus be recommended for an improvement in the quality of life for the patients concerned. No problems with this therapy were noted.
Yeast has been analysed for its potential to secrete an ovine member of the type-I interferon (IFN) family, trophoblastin (oTP-1). The processing potential of the yeast KEX2 gene product (KEX2p) was evaluated using gene oTP-1 fused to the pre-pro sequence encoding the pre-pro peptide of the yeast alpha-factor precursor. High-level accumulation of nonprocessed (unmatured) recombinant oTP-1 (re-oTP-1) was observed in the medium. In order to short-circuit the limiting activity of KEX2p and to obtain a fully matured re-oTP-1, secretion was directed using a pre::oTP-1 fusion, relying only on signal peptidase-dependent processing. However, secretion of oTP-1 was impaired. High-level secretion was restored when the gene product contained a peptide spacer between oTP-1 and the signal peptidase cleavage site. The oTP-1 variant was shown to have an extended N terminus. An N-extended form was examined further and shown to have the correct size. Surprisingly, the variant retained its in vitro and in vivo biological activities. This system is likely to represent a general method for high-level secretion of type-I IFNs.
Surgery is the therapy of choice in the treatment of infestations with Echinococcus (E.) granulosus and E. multilocularis. Chemotherapy with mebendazole, a benzimidazole derivative, introduced 1976 in the therapy of human echinococcosis, showed good results only in cases of infestation with E. multilocularis. In the cases of liver cysts, caused by E. granulosus, the treatment with mebendazole did not succeed as well. Between 1977 and 1986, 44 patients, suffering from infestations with E. granulosus, were referred to the Clinical Department of the Bernhard-Nocht-Institut. In a retrospective study, the data of seven patients had been evaluated: They had not undergone surgery because of the size of the lesions or because they refused the operative treatment. Receiving mebendazole as the only therapy, they had been treated and followed up for more than four years. Mebendazole was given in a dosage of 50 mg/kg body weight in repeated cycles of one month's duration followed by a treatment-free interval of two months. After a median of 55 months (median 13 effective treatment months) six of the seven patients presented a therapeutical success as demonstrated by ultrasound and computed tomography. The cystic lesions had dissolved or decreased in size considerably. One case showed unaltered findings of the liver lesion. Mebendazole treatment was well tolerated by all patients. If the size of the cystic liver-lesions excludes a curative operative treatment or if the patient refuses surgery, the indication for chemotherapy with mebendazole is given.
Two hundred twenty-four sera were collected from 34 HIV-1 infected patients during an observation period of up to 4.5 years (109 patient years of observation). The sera were tested for the presence of antibodies against the HIV-1 virion infectivity factor (vif) protein. Thirty sera from 6 HIV-1 seronegative individuals served as negative controls. The sera were immunoblotted against a recombinant, prokaryotically expressed vif protein. The prevalence of anti-vif antibodies increased significantly with progression of the disease from 18% to 81% (P less than 0.0001) which suggests a possible role of vif in HIV-1 replication and pathogenicity.