ddc:610

A previously healthy 10-year-old Greek boy born to nonconsanguineous healthy parents developed progressive liver disease after acute infectious mononucleosis. EBV-induced autoimmune hepatitis was suspected and treatment was started with high-dose prednisolone, acyclovir and intravenous immunoglobulins. Despite therapy his liver function continuously deteriorated and the child died 9 months later in profound immune deficiency from candida septicemia. Flow cytometric analysis of his lymphocytes revealed a major subpopulation of atypical cells (20.3%) which were CD3+, fitted into the lymphocyte gate bur showed a very low level of CD4 expression, comparable to that of monocytes. After short-time cell culture, the cells became adherent and developed granules and dendrites; We conclude that these cells may represent strongly activated CD4+ T lymphocytes with downregulated CD4 expression or a subtype of dendritic cells.

Inflammatory reactions are associated with sequestration of leukocytes in the lung. Complement activation leads to accumulation of leukocytes in alveolar septa and alveoli, to lung edema and hemorrhage. Although in organs other than the lung leukocytes interact with the vascular endothelium only in postcapillary venules, alveolar capillaries are considered to be the site of leukocyte sequestration in the lung. However, pulmonary venules and arterioles have not been investigated systematically after complement activation so far, A closed thoracic window was implanted in anesthetized rabbits; leukocytes and red blood cells were stained, and the movement of these cells was measured in superficial pulmonary arterioles, venules and alveolar capillaries using fluorescence video microscopy before and 30 and 60 min after infusion of cobra venom factor (CVF). Erythrocyte velocity and macrohemodynamic conditions did not change after CVF infusion and were not different from the sham-treated controls. The number of sticking leukocytes increased significantly compared to baseline and control: by 150% in arterioles and in venules and by 740% in alveolar capillaries within 60 min after CVF infusion. The width of alveolar septa in vivo was significantly enlarged after CVF infusion, indicating interstitial pulmonary edema. At the end of the experiments, myeloperoxidase activity was higher in the CVF group, showing leukocyte sequestration in the whole organ. It is concluded that complement activation by CVF induces leukocyte sequestration in lung arterioles, venules and alveolar capillaries and leads to mild lung injury.

Many soluble factors of neural, endocrine, paracrine and autocrine origin are present in the thymus and modulate its function. Long-term effects of sex steroids have! been documented for thymocytes and cells of the thymic microenvironment. In this report we examine rapid actions of progesterone upon aspects of epithelial cell physiology. Progesterone (0.1-10 mu M) was applied to cultured thymulin-secreting thymic epithelial cells (TS-TEC) and changes in transmembrane potential, transmembrane current, intracellular calcium levels and thymulin secretion were assessed. Rapid changes in electrophysiology and intracellular calcium provide evidence for a membrane-bound progesterone receptor in these cells, in addition to classical cytoplasmic receptors. Application of progesterone to TS-TEC caused electrophysiological changes in 56% of cells (n = 40), activating an inward current (-24 +/- 9 pA at 1 mu M, n = 7, p < 0.02) and dose-dependent depolarization (7.1 +/- 1.8 mV at 1 mu M, n = 19, p < 0.01). Intracellular calcium levels, monitored by the ratiometric fluorescent calcium indicator fura-2, increased within seconds of progesterone (1 mu M) application. Progesterone(1 mu M) increased thymulin levels in supernatant, as measured by ELISA, above the levels in the preapplication period (142 +/- 16% of the preapplication period, n = 3, p < 0.02). This effect was reduced in the presence of cobalt chloride which blocks voltage-dependent calcium channels. In addition, TS-IEC in culture were immunoreactive to antibody AG7. This antibody was raised to a membrane-bound antigen involved in calcium influx subsequent to progesterone binding in sperm. thus we suggest that progesterone acts upon many aspects of TS-TEC physiology through both cytoplasmic and membrane-bound receptors.

The present review focuses on the current knowledge of the neurochemical processes and neuronal structures involved in the generation of P300. The increasing knowledge in this area facilitates the physiological interpretation of P300 findings as well as the link between P300 research and other research findings in biological psychiatry. Concerning the question of neurochemical substrates, the glutamatergic, GABAergic, cholinergic, noradrenergic, dopaminergic and serotonergic influences on P300 are reviewed. The knowledge of the generating structures of P300 is summarized from intracranial studies, magnetoencephalographic investigations, lesion and animal studies.

The pulmonary capillary microvasculature harbors a large pool of intravascularly marginated leukocytes. In this study, we investigated the interrelationship of leukocyte margination with characteristics of functional capillary geometry and microhemodynamics in alveolar capillary networks. In 22 anesthetized rabbits we assessed functional capillary density, average capillary length, red blood cell velocity and leukocyte kinetics in alveolar capillary networks in vivo by intravital fluorescence microscopy. In alveolar wall areas of 12,800 +/- 1,800 mu m(2), we detected 3.6 +/- 0.5 sticking leukocytes and 21.0 +/- 1.9 functional capillary segments with an average capillary length of 35.7 +/- 2.1 mu m. We calculated that approximately 15% of functional capillary segments are blocked by marginated leukocytes. Leukocyte margination was predominantly observed in capillary networks characterized by a high functional capillary density, short capillary segments and low red blood cell velocities. The multitude of interconnected capillary channels in these networks may allow alveolar blood flow to bypass marginated leukocytes. Hence, this interrelationship may be relevant for maintenance of adequate alveolar perfusion and low capillary network resistance despite excessive leukocyte margination in the pulmonary microvasculature. Local microhemodynamic factors may play a regulatory role in the spatial distribution of leukocyte margination.

Background: With an annual incidence of 0.2% of new cases per 100,000 inhabitants, adrenocortical carcinoma is rare. In advanced tumor only palliative treatment modalities are practicable. Because of scarcity of the tumor, standard treatment has not been defined. The decision on therapy frequently depends on the individual situation. Tumor embolization and chemotherapy are amongst the possible options. Patient and Methods: We report on a case of a 32-year-old female patient with a large-volume hormonally active adrenocortical carcinoma and hematogenous liver metastases. This carcinoma was confirmed histologically by means of liver biopsy. Owing to the large tumor extent and metastatic spreading and also in view of the poor general condition of the patient, curative surgical therapy was not possible. For this reason, a local approach was chosen primarily with transarterial tumor embolization at the capillary level. Systemic chemotherapy was given afterwards. Results: Improvement of the patient's general condition, especially the pronounced pain symptoms, could be achieved for a short time by the embolization: both, the patient's clinical condition and the laboratory test parameters improved. However, a rapid tumor progression occured under chemotherapy, which was started after embolization. Conclusion: In advanced adrenocortical carcinoma, tumor embolization can lead to a stabilization of the disease and improvement of the symptoms as appraised by palliative criteria in some patients.

Few data on the incidence of blindness in Germany are available. We analysed causes of legal blindness for the region Württemberg-Hohenzollern (population 5.5 million) in order to help fill in this gap. Material and Methods: Population-based investigation on the incidence of legal blindness (visual acuity <1/50) based on materials from the social servies. Age-dependent blindness incidences were modelled via logistic regression models. Results: 647 blind persons were newly registered in 1994 (blindness incidence 11.6/100,000). The blindness incidence is moderate in infants (4.5/100,000) and decreases further during childhood. At the age of 20 years, the incidence again rises to the former level and remains relatively constant. After the age of 60 years, the incidence increases sharply: 5-year odds ratios are 1.76 (CI: 1.68-1.85) in women and 1.72 (CI: 1.60-1.84) in men. The blindness incidence is higher in women, 15.6/100,000, compared to 12.2/100,000 in men. The major causes of blindness are: macular degeneration, 3.92/100,000; diabetic retinopathy, 2.01/100,000; glaucoma, 1.6/100,000; high myopia, 0.77/100,000; optic atrophy, 0.68/100,000; central nervous system-triggered blindness; 0.56/100,000, and tapetoretinal degenerations, 0.52/100,000. Discussion: Due to monetary incentives for the blind persons, social service files offer accurate and complete data. Besides macular degeneration, glaucoma and dia betic retinopathy are major causes of blindness. Thus, this study suggests further blindness prevention activities for diabetic retinopathy and glaucoma.

Kaposi's sarcoma (KS), Non-Hodgkin's lymphma (NHL) and invasive cervical cancer are considered AIDS-defining malignancies. The incidence of Kaposi's sarcoma has recently been increased as a secondary manifestation of AIDS. The pathogenesis is not completely understood. Human herpesvirus 8 could be identified as an infectious cofactor. Therapeutic strategies should be based on prognostic factors and tailored to the patient's individual situation. Local treatments widely used are cryotherapy or radiotherapy. Systemic therapies such as interferon-alpha. or single and multiagent chemotherapy are also well established. Based on their high response rates and favorable toxicity profile, liposome-encapsulated anthracyclines may be considered first-line therapy for advanced AIDS-related KS. HIV-associated NHL may increase in frequency as HIV-infected individuals survive longer with improved antiretroviral therapy. There is no advantage for intensive as compared with standard or less intensive chemotherapeutic regimens of the CHOP type. Complete remissions can be achieved in approximately 50% of the patients, but the recurrence rate is high. The therapeutic strategy should include an optimal supportive care and antiretroviral treatment because chemotherapy significantly increases the risk of opportunistic infection. In urban populations at risk, cervical cancer is a common AIDS-related malignancy in women. Patients with cervical carcinoma usually have a more aggressive and more advanced disease. Various malignant diseases, such as Hodgkin's lymphoma, anal cancer or seminoma in patients with AIDS occur at higher frequency in HIV infection.

Alterations in oncogenes are critical steps in the development of endometrial cancer. To investigate the potential clinical relevance of the amplification of the oncogenes c-erbB2, c-myc, and int-2 and the mutation of K-ras in endometrial cancer, 112 tumors were examined using PCR-based fluorescent DNA technology. Amplification of the three oncogenes and the mutation of K-ras were correlated with age, tumor size, lymph node status, metastases, stage, histological types, grade, steroid hormone receptor expression (estrogen receptor, ER; progesterone receptor, PgR), family history of cancer, previous history of cancer or precursor lesions, and previous history of hormone replacement therapy. Oncogene amplification of c-erbB2 was detected in 18.9%, of c-myc in 2.7% and of int-2 in 4.2%, and K-ras mutation in 11.6%. No significant correlations could be detected between amplification of c-erbB2 and any of the other parameters. Mutation of K-ras is associated with positive expression of PgR. This might indicate that mutation and activation of K-ras are involved in the development of hormonal independence in endometrial cancer.

The detection superoxide production in vascular cells is usually limited by a low sensitivity of available assays, We tested the applicability of the luminol derivate L-012 {[}8-amino-5-chloro-7-phenylpyridol{[}3,4-d]pyridazine-l,4(2H,3H)dione] to measure superoxide production in cultured endothelial cells (human umbilical vein endothelial cells) and rat aortic segments. Following stimulation with the protein kinase stimulator phorbol 12-myristate 13-acetate (PMA, 1 mu M) there was an 2,8-fold increase of L-012 chemiluminescence, whereas incubation with angiotensin II (100 nM) did not result in a measurable increase. Addition of vanadate (100 mu M) considerably increased the chemiluminescence (up to 17-fold) after PMA and made possible the detection of an enhanced superoxide production after stimulation with angiotensin II (by 1.7-fold). This was due to a similar to 9-fold increase in signal intensity of L-012 in the presence of vanadate, Prolonged incubation with vanadate also led to a tyrosine phosphorylation-dependent increase in superoxide formation which was predominantly produced by an NAD(P)H oxidase. Short-Term vanadate-enhanced L-012 chemiluminescence represents a highly sensitive assay making it possible to detect small changes of superoxide formation in intact vascular cells. Copyright(C) 1999 S. Karger AG. Basel.

Production of nitric oxide by the inducible NO synthase (iNOS) is known to be enhanced in chronic joint inflammation and osteoarthritis as well as aseptic loosening of joint prostheses. Initial studies yielded promising results after inhibition of the nitric oxide synthase (NOS). However, the effect of NOS inhibition has not been studied at the site of the primary function of NO, the microcirculation of the synovium in vivo. Using our recently developed model for the in vivo study of synovial microcirculation in the mouse knee joint, the effects of selective versus nonselective inhibition of iNOS were investigated by means of intravital fluorescence microscopy. After resection of the patella tendon, the synovial fatty tissue was exposed for intravital microscopy. Diameter of arterioles, functional capillary density (FCD), diameter of venules, venular red blood cell velocity and leukocyte-endothelial cell interaction were quantitatively analyzed before, and 10 and 60 min after intravenous injection of NOS inhibitors {[}selective iNOS inhibitor N-iminoethyl-L-lysine (L-NIL), and nonselective NOS inhibitor N-G-nitro-L-arginine methyl ester (L-NAME)]. Our results demonstrate that L-NAME causes a significant decrease in the arteriolar diameter and FCD associated with an increase in the leukocyte accumulation in the synovium in vivo. In contrast, L-NIL neither altered the microhemodynamics nor the leukocyte-endothelial cell interaction in the synovium, indicating its potential use for selective inhibition of iNOS in joint inflammation. Using our method, further studies will provide new insights into the unknown effect of NOS inhibition on the synovial microvasculature in inflammatory joint disease in vivo. Copyright (C) 1999 S. Karger AG, Basel.

This article provides an impression of the cooperation with interpreters in the treatment of traumatized refugees. After a short presentation of the treatment concept and cultural aspects, which are of concern for therapy, the role of the interpreter as connection between client and therapist is described. Typical conflicts in the therapy with interpreters are exemplified in brief case reports. Facts possibly influencing the efficacy of the cooperation between interpreter and therapist are shown. This can be seen as an attempt to systematize experiences made in practice. A guideline for the therapy with interpreters is presented. The rules and methods considered as being important for the work should assure an effective cooperation and also promote the resources.

Plantar fibromatosis is a rare, benign lesion involving the plantar aponeurosis. Eleven patients (13 feet) underwent 24 operations, including local excision, wide excision, or complete plantar fasciectomy. Clinical results were evaluated retrospectively. There were no differences among the subgroups in postoperative complications. Two primary fasciectomies did not recur. Three of six revised fasciectomies, seven of nine wide excisions, and six of seven local excisions recurred. Our results indicate that recurrence of plantar fibromatosis after surgical resection can be reduced by aggressive initial surgical resection.

The following case report shows a behavioral treatment of a 53-year-old Patient with Alzheimer's Disease (AD), The treatment includes procedures described in the Behavioral Competency Training (VKT) for patients with early-stage AD developed by Ehrhardt and associates. The program consists of about 20 weekly treatment sessions in which the patient's resources are activated and patient's coping is supported. The therapy and the intervention are debated in the light of the ongoing discussion about a state-of-the-art therapy for AD.

Dendritic cells (DC) constitute a heterogeneous leukocyte population having in common a unique capacity to induce primary T cell responses and are therefore most attractive candidates for immunomodulatory strategies. Two populations of blood DC (CD11c+ CD123(dim) and CD11c- CD123(high)) have been defined so far. However, their direct isolation for experimental purposes is hampered by their low frequency and by the lack of selective markers allowing large scale purification from blood. Here we describe the monoclonal antibody (mAb) M-DC8, which was generated by immunizing mice with highly enriched blood DC. This mAb specifically reacts with 0.2-1% of blood leukocytes and enables their direct isolation by a one-step immunomagnetic procedure from fresh mononuclear cells. These cells can be differentiated from T cells, B cells, NK cells and monocytes using lineage-specific antibodies. M-DC8+ cells express HLA class It molecules, CD33 and low levers of the costimulatory molecules CD86 and CD40. Upon in vitro culture M-DC8+ cells spontaneously mature into cells with the phenotype of highly stimulatory cells as documented by the upregulation of HLA-DR, CD86 and CD40; in parallel CD80 expression is induced. M-DC8+ cells display an outstanding capacity to present antigen. In particular, they proved to be excellent stimulators of autologous mixed leukocyte reaction and to activate T cells against primary antigens such as keyhole limpet hemocyanin. Furthermore, they induce differentiation of purified allogeneic cytotoxic T cells into alloantigen-specific cytotoxic effector cells. While the phenotypical analysis reveals similarities with the two known blood DC populations, the characteristic expression of Fc gamma RIII (CD16) and the M-DC8 antigen clearly defines them as a novel population of blood DC. The mAb M-DC8 might thus be a valuable tool to determine circulating DC for diagnostic purposes and to isolate these cells for studies of antigen-specific T cell priming. Copyright (C) 2000 S. Karger AG, Basel.

There is substantial evidence from preclinical data that the antitumor cytotoxicity of selected chemotherapeutic agents either alone or combined with radiation can be enhanced by appropriate heat exposure (40-44 degrees C) of cells or tumor tissues. Based upon these results the integration of hyperthermia as an additional treatment modality, given simultaneously with systemic chemotherapy or in combination with radiochemotherapy, is currently tested at the clinic. Regional hyperthermia combined with chemotherapy or radiochemotherapy showed impressive results (phase II studies) at clinical relevant temperatures in locally advanced tumors of different entities in terms of objective response rate, local tumor control and relapse-free survival. Clinical protocols of well-designed phase III trials on combined treatment modalities integrating hyperthermia are rather limited but for some tumors confirm its clinical benefit. In general, the clinical approach to use hyperthermia has gained much more interest within in the field of medical oncology. One of the major reason is the substantial technical improvements made with the available commercial equipment for local or regional heating, especially in case of deep-seated lesions or systemic heating. Further testing of the potential of hyperthermia combined with chemotherapy or radiochemotherapy in prospective randomized trials are warranted. At this time, hyperthermia as an adjunct to conventional treatment strategies is recommended in the setting of clinical protocols. The results of prospective trials should answer the question for which types of local advanced or metastatic tumors hyperthermia becomes standard as part of a multi-modal treatment strategy.

A 40-week gestational age infant was delivered by cesarean section because of intense contractions and pathological fetal heart rate pattern. The umbilical artery pH was 7.03, Apgar scores were 1/4/7 at 1, 5 and 10 min of age. The 3,250-gram infant had a skull depression of 5 x 7 cm in the left temporal-parietal region with a depth of 1.5 cm. There were no edemas or hematomas in this area; neurological examination was normal. A CT scan did not show a fracture, but the cortex below the depression appeared slightly compressed. At the age of 11 days, the depressed part of the parietal squama was surgically elevated. The child was discharged in good condition 8 days later and remained well at a 6-month follow-up examination.