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.

No functional effects of embryonic neuronal grafts on motor deficits in a 3-nitropropionic acid rat model of advanced striatonigral degeneration (multiple system atrophy).

Intrastriatal injection of 3-nitropropionic acid results in secondary excitotoxic local damage and retrograde neuronal cell loss in substantia nigra pars compacta, thus mimicking salient features of striatonigral degeneration, the core pathology underlying Parkinsonism associated with multiple system atrophy. We used 3-nitropropionic acid to create a rat model of advanced striatonigral degeneration in order to assess the effects of embryonic allografts upon rotational and complex-motor behavioural abnormalities. Following stereotaxic intrastriatal administration of 500nmol 3-nitropropionic acid in male Wistar rats we observed consistent amphetamine- and apomorphine-induced ipsiversive rotation. Furthermore, there were marked deficits of contralateral paw reaching. Subsequently, animals received intrastriatal implantations of either E14 mesencephalic or striatal or mixed embryonic cell suspensions. In addition, one group received sham injections. Grafted rats were followed for up to 21 weeks and repeated behavioural tests were obtained during this period. Drug-induced rotation asymmetries and complex motor deficits measured by paw reaching tests were not compensated by embryonic grafts. Persistence of drug-induced rotations and of paw reaching deficits following transplantation probably reflects severe atrophy of adult striatum, additional nigral degeneration as well as glial demarcation of embryonic grafts. We suggest that dopamine rich embryonic grafts fail to induce functional recovery in a novel 3-nitropropionic acid rat model of advanced striatonigral degeneration (multiple system atrophy).

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.

Failure of neuroprotection by embryonic striatal grafts in a double lesion rat model of striatonigral degeneration (multiple system atrophy).

In the present experiment we studied the ability of embryonic striatal grafts to protect against striatal quinolinic acid (QA)-induced excitotoxicity in a previously established double lesion rat model of striatonigral degeneration (SND), the neuropathological substrate of parkinsonism associated with multiple system atrophy (MSA). Male Wistar rats received under halothane inhalation anesthesia a 6-hydroxydopamine 6-OHDA injection into the left medial forebrain bundle. Four to 5 weeks later apomorphine-induced rotation behavior was tested. Rats were divided into two treatment groups receiving either embryonic striatal cell suspensions or sham injections. Apomorphine-induced rotation behavior was retested 2 and 4 weeks after the grafting procedure. Following the rotation test animals of the striatal and sham graft group received a stereotaxic injection of 150 nmol QA. Again rotation behavior was assessed 2 and 4 weeks after lesioning. Brains were then processed to dopamine reuptake ([(3)H]mazindol), dopamine D1 ([(3)H]SCH23390), and D2 ([(3)H]spiperone) receptor autoradiography. Gliosis was detected using [(3)H]PK11195, a marker for peripheral benzodiazepine binding sites. Behavioral and autoradiographic analysis failed to show striatal protection in 6-OHDA prelesioned animals receiving embryonic striatal grafts. These findings indicate that beneficial protective effects of striatal grafts implanted into host striatum prior to excitotoxic insults are abolished in the presence of severe dopaminergic denervation. Our present results are relevant to future applications of neural grafting in MSA-SND.

Towards neurotransplantation in multiple system atrophy: clinical rationale, pathophysiological basis, and preliminary experimental evidence.

Multiple system atrophy (MSA) is a neurodegenerative disorder that occurs sporadically and causes parkinsonism, cerebellar, autonomic, urinary, and pyramidal dysfunction in many combinations. Progressive L-dopa-unresponsive parkinsonism due to underlying striatonigral degeneration dominates the clinical syndrome in the majority of cases (MSA-P subtype). MSA-P is characterized pathologically by degenerative changes in somatotopically related areas of the substantia nigra pars compacta and of the putamen. Furthermore, oligodendroglial cytoplasmic inclusions (GCIs) are observed throughout the cortico-striato-pallidocortical loops and may contribute to the basal ganglia dysfunction. Neurotransplantation strategies are of potential interest in this disease, which causes marked and early disability and dramatically reduces life expectancy. A number of experimental MSA-P models have been employed to evaluate neurotransplantation approaches. Sequential nigral and striatal lesions using 6-hydroxydopamine and quinolinic acid (double toxin-double lesion approach) indicate that apomorphine-induced contralateral rotation is abolished by a secondary striatal lesion. Intrastriatal injection of mitochondrial respiratory chain toxins produces secondary excitotoxic striatal lesions combined with retrograde nigral degeneration and therefore provides an alternative single toxin-double lesion approach. Neurotransplantation in MSA-P animal models has been used to improve functional deficits by replacing lost nigral and/or striatal circuitry (neuroregenerative approach). The available data indicate that embryonic mesencephalic grafts alone or combined with striatal grafts partially reverse drug-induced rotation asymmetries without improving deficits of complex motor function. The potential neuroprotective efficacy of embryonic striatal grafts against striatal excitotoxicity is presently under investigation in the double toxin-double lesion MSA-P rat model. Anecdotal clinical evidence in one MSA-P patient misdiagnosed as Parkinson's disease indicates that embryonic mesencephalic grafts produce incomplete clinical benefit. Striatal co-grafts may increase functional improvement. Further experimental studies are required prior to the clinical application of embryonic neurotransplantation in MSA-P. Future research strategies should explore the effect of neurotransplantation in partial MSA-P rat models with less severe nigral and striatal degeneration, the feasibility of a primate model closely mimicking the human disease, and the replication of oligodendroglial dysfunction.

Innovations in traditional Vietnam.

PIP: In Viet Nam, the 1990 designation of population as a top government concern resulted in a tenfold increase in spending on family planning (FP) and health. The Viet Nam FP Association has developed a number of innovative ways of promoting FP, including a telephone counseling service. The population of Viet Nam has doubled since 1960, and the average per capita income remains very low; thus, condoms and oral contraceptives (OCs) are prohibitively expensive for many families. The FP program provides free condoms, OCs, and IUDs but often runs out of supplies. Need for condoms is estimated at 200 million/year, but the two factories only produce 30 million. OCs are imported from Hungary and have a bad reputation among Vietnamese women. The most commonly used contraceptive is the IUD, but poor quality of care at insertion leads many women to suffer infections. Viet Nam has a high rate of legal abortion, with most procedures occurring in the first month of pregnancy. The FP Association has cautiously introduced sex education in the schools in a pilot program that will be continued nationwide. The Association also opened a special club for young people and one for miliary personnel. These clubs provide contraceptive information along with soft drinks and music. The government's two-child policy is widely accepted but must overcome the obstacles of large family preference in rural areas and of son preference.^ieng

[Experiences with anti-Rhesus-D therapy in pretreated patients with idiopathic thrombocytopenia]. / Erfahrungen mit Anti-Rhesus-D-Therapie bei vorbehandelten Patienten mit idiopathischer Thrombozytopenie.

OBJECTIVE: We tested the effect of anti Rhesus D [anti Rh(D)]-specific IgG in heavily pretreated patients with idiopathic thrombocytopenic purpura (ITP). DESIGN: Retrospective single case studies. SETTING: Clinical department of hematology. PATIENTS: 6 consecutive patients with heavily pretreated therapy-refractory ITP. INTERVENTIONS: 5 patients received one cycle of Anti Rh(D) in doses between 1,200 and 6,000 micrograms in 1 patient 2 consecutive cycles were applied. Treatment effect, durability, and side effects were monitored. RESULTS: Patients after splenectomy and/or immunosuppressive therapy did not respond. Response was short-lived in 2 other patients, one long-term remission could be achieved. Responders showed slight decreases in hemoglobin indicating mild hemolysis. Other major side effects were not observed and the therapy was well tolerated. CONCLUSIONS: Our results suggest that therapy with Anti Rh(D) is safe and comparably inexpensive. No clear dose/effect correlation was found in our investigation. Only patients with platelet sequestration into the spleen might respond to Anti Rh(D) therapy.

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.

Purification and properties of an aryl-alcohol dehydrogenase from the white-rot fungus Phanerochaete chrysosporium.

An intracellular aryl-alcohol dehydrogenase (previously referred to as aryl-aldehyde reductase) was purified from the white-rot fungus Phanerochaete chrysosporium. The enzyme reduced veratraldehyde to veratryl alcohol using NADPH as a cofactor. Other aromatic benzaldehydes were also reduced, but not aromatic ketones. Methoxy-substituted rings were better substrates than hydroxylated ones. The enzyme was also able to reduce a dimeric aldehyde (4-benzyloxy-3-methoxybenzaldehyde). The highest reduction rate was measured when 3,5-dimethoxybenzaldehyde was used as a substrate. On SDS/PAGE the purified enzyme showed one major band with a molecular mass of 47 kDa, whereas gel filtration suggested a molecular mass of 280 kDa. Polyclonal antibodies raised against the gel purified 47-kDa protein were able to immunoprecipitate the aryl-alcohol dehydrogenase indicating that its activity possibly resides entirely in this protein fragment. The pI of the enzyme was 5.2 and it was most active at pH 6.1. The aryl-alcohol dehydrogenase was partially inhibited by typical oxidoreductase inhibitors.

Insulin release from pancreatic islets of fetal rats mediated by leucine b-BCH, tolbutamide, glibenclamide, arginine, potassium chloride, and theophylline does not require stimulation of Ca2+ net uptake.

In pancreatic islets of fetal rats the effect of glucose (3 and 16.7 mM), glyceraldehyde (10 mM), leucine (20 mM), b-BCH (20 mM), tolbutamide (100 micrograms/ml), glibenclamide (0.5 and 5.0 micrograms/ml) arginine (20 mM), KCl (20 mM) and theophylline (2.5 mM) on 45Ca2+ net uptake and secretion of insulin was studied. All compounds tested failed to stimulate 45Ca2+ net uptake. However, in contrast to glucose and glyceraldehyde, leucine, b-BCH, tolbutamide, glibenclamide, arginine, KCl and theophylline significantly stimulated release of insulin. This effect could not be inhibited by the calcium antagonist verapamil (20 microM). Elevation of the glucose concentration from 3 to 5.6 mM did not alter 86Rb+ efflux of fetal rat islets but inhibited 86Rb+ efflux of adult rat islets. Stimulation of 86Rb+ efflux with tolbutamide (100 micrograms/ml), leucine (20 mM) or b-BCH (20 mM) in the presence of 3 mM glucose was also ineffective in fetal rat islets. Our data suggest that stimulation of calcium uptake via the voltage dependent calcium channel is not possible in the fetal state. They also provide evidence that stimulators of insulin release which are thought not to act through their metabolism, initiate insulin secretion from fetal islets by a mechanism which is different from stimulation of calcium influx.

[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.

[A rare cause of septic syndrome]. / Seltene Ursache für septisches Zustandsbild.

The case report is presented of a 18-year old patient, who was admitted to the Haematology Department of the Hanusch Hospital with septic fever, an enlarged spleen and suspected bone marrow failure. Since the patient reported a stay in Sicily prior to the onset of his disease, an infection with Leishmania was suspected. The serological test was highly positive and Leishmania was also isolated from the spleen aspirate. Chemotherapy with Pentostam was successful and the patient made an uneventful recovery. This paper deals with the epidemiology of the disease and discusses the diagnostic approaches.

[Clinical effects of high-dose immunoglobulin therapy in adults with idiopathic thrombocytopenic purpura]. / Klinische Effekte hochdosierter Immunglobulintherapie bei Erwachsenen mit idiopathischer thrombozytopenischer Purpura (ITP).

15 patients suffering from idiopathic thrombocytopenic purpura were treated in our department with high-dosage immunoglobulins. The daily dosage amounted to between 0.13 and 0.4 g/kg body weight, administered for 4 to 15 days consecutively. The platelet count in 10 patients increased within the first week of treatment, but this increase was maintained for more than 4 weeks in only 3 patients. The average age of these 10 patients amounted to 41.2 years and was significantly lower than that of the remaining 5 patients (66.6 years), who failed to respond. Only one of 4 splenectomized patients responded with an increase in platelet count. Two different immunoglobulin preparations were used. No difference in efficacy was found and both preparations were well tolerated.