The Nationwide Austrian Aspergillus Registry: a prospective data collection on epidemiology, therapy and outcome of invasive mould infections in immunocompromised and/or immunosuppressed patients.

A prospective, observational, multicentre study was performed to assess the incidence, diagnosis, epidemiology and outcome of invasive mould infections (IMIs) reported to the Nationwide Austrian Aspergillus Registry. In total, 186 cases were recorded, corresponding to an annual incidence of 42 cases/1000 patients at risk or 2.36 cases/100000 inhabitants. Patients with acute myelogenous leukaemia (34%) and lung transplant recipients (17%) are currently at highest risk for IMI, followed by a mixed population with impaired immunity (14%). In total, 34%, 30% and 36% were proven, probable and possible cases of IMI. Predominant pathogens were Aspergillus spp. (67%), followed by the zygomycetes (28%). Voriconazole was the most frequently administered agent (38%), followed by caspofungin (20%) and posaconazole (19%). Eighty patients (43%) received antifungal prophylaxis for ≥7 days, 30% of whom (24 patients) suffered from a breakthrough infection. The overall crude 12-week mortality was 34%. Multivariate analysis showed that outcome and survival did not correlate with the status of fungal disease, breakthrough infection, fungal species or age (P>0.05). Aspergillosis remains the most commonly identified IMI amongst immunocompromised and/or immunosuppressed patients, but other moulds constitute a significant problem. Survival from IMIs appears to have improved and the main challenge is to overcome breakthrough fungal infections.

In vivo magnetic resonance imaging of embryonic neural grafts in a rat model of striatonigral degeneration (multiple system atrophy).

The effects of embryonic neural transplantation in experimental models of neurodegenerative disorders are commonly assessed by behavioral tests and postmortem neurochemical or anatomical analysis. The purpose of the present study was to evaluate embryonic neuronal grafts in a novel rat model of multiple system atrophy (MSA) with the help of in vivo magnetic resonance imaging (MRI) and to correlate imaging with histological parameters. Striatonigral double lesions were created in male Wistar rats by unilateral intrastriatal injection of 3-nitropropionic acid (3-NP). Seven weeks following lesion surgery animals were divided into four transplantation groups receiving either pure mesencephalic, pure striatal, mesencephalic-striatal cografts, or sham grafts. In vivo structural imaging was performed 21 weeks after transplantation using a whole body 1.5 Tesla MR scanner. The imaging protocol comprised T2-weighted TSE and T1-weighted TIR sequences. Immunohistochemistry using DARPP-32 as striatal marker and tyrosinhydroxylase as marker for nigral neurons was performed for correlation analysis of imaging and histological parameters. The sensitivity of graft detection by in vivo MRI was 100%. The graft tissue was clearly demarcated from the remaining striatal tissue in both T2- and T1-weighted sequences. Morphometrically, cross-sectional areas of the grafts and spared intact striatum as defined by immunohistochemistry correlated significantly with measurements obtained by in vivo MRI. In conclusion, we were able to evaluate in vivo both lesion-induced damage and graft size in a 3-NP rat model of MSA using a conventional whole body 1.5 Tesla MRI scanner. Additionally, we obtained an excellent correlation between MRI and histological measurements.

Potassium permeability of fetal rat pancreatic islets: abnormal sensitivity to glucose.

Potassium channels of fetal rat islets have been recently reported to be inadequately regulated by stimulation with glucose when compared to islets of adult rats. Though in patch clamp experiments the properties of their KATP-channels were shown to be comparable to those from adult rats, until now no closure could be demonstrated with the technique measuring the 86Rb+ efflux. Using this technique, in the presence of a basal (3 mM) glucose concentration the 86Rb+ efflux was completely insensitive to a stimulation with glucose (5.6 mM) or tolbutamide. In contrast, in islets perifused in the absence of glucose the introduction of a low glucose concentration (3 mM) or stimulation with tolbutamide alone inhibited the 86Rb+ efflux, confirming the presence of functioning KATP-channels. The absolute value of the 86Rb+ efflux rate in the absence of glucose was, however, much lower in fetal rat islets as normally observed in adult rat islets. Apart from this, the ATP content of fetal rat islets remained unchanged at either glucose concentration tested. It is suggested that in islets of fetal rats a K+ permeability is present and can be inhibited by glucose and tolbutamide but in contrast to islets of adult rats the K+ efflux is already maximally inhibited in the presence of 3 mM glucose. This may be one reason why pancreatic islets of fetal rats do not respond to glucose-stimulation with an adequate calcium uptake and insulin release.

Treatment of lymphangioleiomyomatosis by ovariectomy, interferon alpha 2b and tamoxifen--a case report.

The gender-specific prevalence of lymphangioleiomyomatosis (LAM) in premenopausal women suggests a hormonal etiology. Despite the antiestrogenic treatment (ovariectomy, tamoxifen) this disease is often refractory to therapy and almost inevitably leads to the patient's death. We describe a case where the antiproliferative effect of systemically applied interferon alpha 2b was successfully employed in addition to ovariectomy and the patient reached complete remission.

[Experiences with acyclovir in herpes virus infections]. / Erfahrungen mit Acyclovir bei Herpesvirusinfektionen.

46 patients suffering from various malignancies (17 non Hodgkin lymphomas, 12 Hodgkin's diseases, 11 acute leukaemias, 4 myelomas, 2 carcinomas), 6 patients with haematological disorders such as ITP, SAA, myeloproliferative disease, LAS and 3 patients without preexisting disease were treated with acyclovir for herpes virus infection diagnosed by clinical means. All but 7 patients had been given intensive treatment with various cytostatic agents and/or irradiation. Most patients were treated with 1500 mg acyclovir daily for 5 to 13 days. Dosage was adjusted according to renal function and clinical response in the remaining 10 cases. 11 patients received intravenous immunoglobulins in addition. Side effects were negligible (local irritation, minimal rise in serum creatinine levels in 5 patients). All patients responded to treatment; 6 patients complained of severe neuralgia lasting for more than one month; 5 patients relapsed.

Tn polyagglutinability occurring in a patient with B cell lymphoma.

A case of polymorphic immunocytoma (B cell lymphoma) coinciding with expression of Tn antigen on a population of erythrocytes is presented. Tn activation was found incidentally by screening blood samples of patients suffering from hematologic malignancies with a Tn specific lectin from Salvia sclarea. So far, Tn activation has been reported only in apparently healthy subjects or in subjects suffering from or developing myeloid leukemia.

[Clinical relevance of the Kiel classification of non-Hodgkin's lymphomas (author's transl)]. / Zur klinischen Relevanz der Kieler Klassifikation von Non-Hodgkin-Lymphomen.

The Kiel classification of non-Hodgkin's lymphomas, based on morphological, cytochemical and functional criteria, differentiates between lymphomas of low-grade malignancy and high-grade malignancy, which are themselves subdivided into several distinct entities. The probability of survival, the symptomatology and some important laboratory parameters are described in 138 cases of malignant non-Hodgkin's lymphomas, classified according to the Kiel classification. The results show that this classification has not only prognostic and clinical relevance, but also explains some uncommon clinical courses of malignant lymphomas. It is to be hoped that this classification will also promote further progress in therapy.

[The clinical significance of the Philadelphia chromosome in acute leukaemia (author's transl)]. / Klinische Bedeutung eines Philadelphia-Chromosoms bei akuter Leukämie.

So-called "Philadelphia-positive acute leukaemias" require varied therapeutic management. Additional chromosome anomalies together with Ph1 indicate an acute transformation of a Philadelphia-positive disease, requiring "non-myelotoxic" treatment and new therapeutic approaches. By contrast, "de novo" acute leukaemias with a Ph1-positive karyotype should be treated with intensive chemotherapy for the induction and maintainance of remission.

Adriamycin cardiotoxicity: a survey of 1273 patients.

Valuable information was collected on the medical history and clinical course of 1273 patients entered in clinical trials with Adriamycin (ADR) carried out in 12 European cancer centers. A coded patient form was used for the data collection carried out in each center by a qualified physician following a guideline which was discussed and accepted by all of the participants. The aim of the study was to define the incidence, characteristics, and possible co-factors of the cardiomyopathy (CMP) in patients treated with combination chemotherapy regimens including ADR. The mean total dose of ADR was 268 mg/m2 (range, 15--1251 mg/m2), and 5.1% of the patients received a total dose of greater than 550 mg/m2. A "definite" ADR-related CMP was observed in 1.7% of the cases; another 3% of the cases were reported as "possible" ADR-CMP since the role played by the drug could not be clearly defined. "Definite" ADR-CMP was fatal in eight patients (0.6%) while "possible" ADR-CMP was fatal in 13 patients (1.0%). Among the possible co-factors examined, the following ones were found to be significantly associated with the occurrence of a "definite" ADR-CMP: (a) total dose of ADR; (b) vincristine when given both before and concomitantly with ADR; (c) bleomycin when given before ADR; and (d) radiotherapy to the mediastinum when given concomitantly with ADR. Furthermore, none of 182 patients receiving ADR by slow infusion developed a "definite" ADR-CMP, while 2% of the patients treated by bolus injection did so. The occurrence of a "possible" ADR-CMP was found to be significantly associated with two pre-existing pathologic conditions (electrocardiogram [ECG] abnormalities and hypertension) but not with the treatment-related co-factors for the "definite" ADR-CMP mentioned above. Other variables examined, such as sex, age, cancer type, baseline liver function, and cyclophosphamide treatment, did not seem to influence the risk of ADR-CMP. Data on ECG changes occurring during ADR treatment were also reported and their incidence was found to be strictly related to the frequency of the ECG monitoring.

[A clinical study of the non-Hodgkin's lymphomas according to the Kiel classification (author's transl)]. / Klinik der Nicht-Hodgkin-Lymphome nach der Kieler Klassifikation.

A study of 138 patients with Non-Hodgkin's lymphomas was performed. The results were compared with retro- and prospective investigations of patients of the Kiel lymphoma study group. The aim of the study is to evaluate the value of the Kiel classification for the therapy and prognosis of malignant lymphomas. The malignant lymphomas of low- and high-grade malignancy differ significantly in their biological behaviour. Especially the clinical progress of the disease and the response to therapy are different. The lymphomas of low-grade malignancy may not need any treatment for long periods in some patients. In contrary, patients with lymphomas of high-grade malignancy need an active treatment immediately after the establishment of the diagnosis. In stages I and II radiotherapy is sufficient, in stages III and IV chemotherapeutic regimens are necessary. Each type of malignant lymphoma may be accompanied by leukemia. Most of the malignant lymphomas, particularly the immunocytomas, may produce monoclonal gammopathies, most of them being macroglobulinemias. Thus the macroglobulinemia Waldenström is just a clinical necessary to evaluate the significance of the subtypes of the Kiel classification for the planning of specific treatment.

[DTIC--one component of ABVD combination therapy in Hodgkin's disease (author's transl)]. / DTIC--Bestandteil einer Therapiekombination (ABVD) bei Morbus Hodgkin.

11 pretreated patients with advanced Hodgkin's disease were treated according to the ABVD schedule. In 6 cases this treatment had to be prematurely terminated due to considerable side effects or due to progression of the disease. The other 6 cases responded favourably, but the improvement was only of short duration.

[Retrospective analysis of the clinical relevance of the Kiel classification of malignant non-Hodgkin's lymphomas (author's transl)]. / Retrospektive Untersuchungen zur klinischen Bedeutung der Kiel-Klassifikation der malignen Non-Hodgkin-Lymphome

405 cases with non-Hodgkin's lymphomas have been diagnosed according to the Kiel classification and analysed retrospectively. 314 patients with non-Hodgkin's lymphomas of low-grade-malignancy (chronic lymphocytic leukemia, lymphoplasmacytoid, centrocytic, centrocytic, centroblastic-centrocytic lymphoma) manifested significantly higher median survival times than the 91 patients with non-Hodgkin's lymphomas of high-grade malignancy (lymphoblastic and immunoblastic lymphoma). Within the group of patients with low-grade malignant lymphomas distinct prognostic differences were found whereas survival times in patients with lymphoblastic or immunoblastic lymphomas were rather similar. The lymphoblastic lymphoma showed a bimodal curve of age distribution whilst all other lymphomas had a maximum of incidence in the seventh decade of life. Increased frequency of B-symptoms did not necessarily represent an unfavorable prognostic factor for the lymphoma entity concerned. Except for chronic lymphocytic leukemia the highest incidence of initial bone marrow involvement was seen in lymphoplasmacytoid, centrocytic and lymphoblastic lymphomas. Centrocytes have been observed in peripheral blood of patients with centrocytic and centroblastic-centrocytic lymphomas, even though lymphocytosis did not exist. Monoclonal hypergammaglobulinemia was found in only 43% of the sera from patients with lymphoplasmocytoid lymphoma. In this disease, it was possible to differentiate between a lymphonodal, a splenomegalic and an extranodal manifestation.