Control of neuronal branching by the death receptor CD95 (Fas/Apo-1).

The CD95 (Apo-1/Fas)/CD95 ligand (CD95L) system is best characterized as a trigger of apoptosis. Nevertheless, despite broad expression of CD95L and CD95 in the developing brain, absence of functional CD95 (lpr mice) or CD95L (gld mice) does not alter neuronal numbers. Here, we report that in embryonic hippocampal and cortical neurons in vivo and in vitro CD95L does not induce apoptosis. Triggering of CD95 in cultured immature neurons substantially increases neurite branches by promoting their formation. The branching increase occurs in a caspase-independent and death domain-dependent manner and is paralleled by an increase in the nonphosphorylated form of Tau. Most importantly, lpr and gld mutants exhibit a reduced number of dendritic branches in vivo at the time when synapse formation takes place. These data reveal a novel function for the CD95 system and add to the picture of guidance molecules in the developing brain.

Haemostatic abnormalities in lung cancer: prognostic implications.

Both experimental and clinical data have shown that coagulation disorders are common in patients with cancer although clinical symptoms occur rarely. A prethrombotic state is probably involved in the mechanism of metastatic spread. Anticoagulant treatment, with either warfarin or heparin, has been shown to have a positive influence in small cell lung cancer. The purpose of this study was to evaluate the prethrombotic state as a possible marker of the outcome of lung cancer. Pretreatment prothrombin time (PT), partial thromboplastin time (PTT), antithrombin III (AT-III), platelet blood count (P), fibrinogen (F) and D-dimer (DD) were prospectively recorded in a series of 286 consecutive patients with a new primary lung cancer. Other recorded variables (32 in all) consisted of a set of anthropometric, clinical, physical, laboratory, radiological and pathological data. All patients were carefully followed up, and their subsequent clinical course recorded. Spearman rank correlation tests between coagulation factors were weakly significant, or more often non-significant. The best correlation index was that between PT and PTT (ra = -0.25). Univariate analyses of survival showed that a prolonged value of PT (P = 0.00167) and higher values of F (P = 0.00143) and DD (P = 0.0005) were associated with a poor prognosis. A few, weak relationships between well-known prognostic variables and coagulation abnormalities were also found. Because of the weakness of this correlation pattern, coagulation factors emerged in all the Cox's regression analyses as important predictors of survival, regardless of the number and type of cofactors used. A prethrombotic state (depicted by a prolongation of PT and increase of DD) is confirmed in this study as an aggravating condition in lung cancer. Studies attempting to reverse possible haemostatic abnormalities with the use of anticoagulants are justified by the present data.

Spectral versus visual EEG analysis in mild hepatic encephalopathy.

OBJECTIVE: Spectral EEG analysis has been claimed to reduce subjective variability in EEG assessment of hepatic encephalopathy and to allow the detection of mild encephalopathy. METHOD: To test such assumptions, 43 digital EEG were recorded in 32 cirrhotics without overt encephalopathy or with grade 1 overt encephalopathy; 7 patients were re-tested (2-5 times) in their follow up. All patients underwent psychometric assessment. Nineteen controls were considered. EEG were blindly evaluated by two electroencephalographers and by spectral EEG analysis performed according to 3 different techniques. RESULTS: The reliability of the classification based on spectral analysis (biparietal technique) was higher than that based on a three-degree qualitative visual reading (concordance/discordance = 58/4 versus 46/16 P < 0.01) and comparable with that of semiquantitative visual assessment based on posterior basic rhythm (concordance/discordance = 55/7 P = 0.5). The accuracy of spectral EEG analysis was higher than that of qualitative visual EEG readings alone (90 versus 75%) and comparable to semi-quantitative visual assessment (87%), however, statistical significance was not reached. In the follow-up, the variations of theta and delta relative power were found to be significantly correlated with psychometric variations. CONCLUSIONS: In conclusion, spectral EEG analysis may improve the assessment of mild hepatic encephalopathy by decreasing inter-operator variability and providing reliable parameters correlated with mental status.

Long-acting octreotide is effective in controlling rebleeding angiodysplasia of the gastrointestinal tract.

BACKGROUND: Management of bleeding angiodysplasia of the gastrointestinal tract is often a major clinical problem. Lesions are frequently multiple, not detectable or missed during conventional endoscopy and patients are sometimes at high risk for complications because of advanced age and serious concomitant disorders. AIMS: To determine the efficacy of a new formulation of somatostatin analogue (octreotide long-acting) in management of recurrent bleeding angiodysplasia in patients resistant to endoscopic treatment and not suitable for surgery. PATIENTS AND METHODS: Three patients with recurrent bleeding angiodysplasia of gastrointestinal tract were treated with long-acting octreotide administered intramuscularly 20 mg monthly to each individual. The number of admissions for acute bleeding, hospital stay and number of blood units transfused before and after treatment (followup: 15-17 months) were regularly monitored. RESULTS: In each patient, a relevant decrease in number of hospital admissions, duration of hospital stay, number of administered blood units was seen and mean haemoglobin values significantly increased in all of them after introducing long-acting octreotide therapy. CONCLUSIONS: This is the first report on use of long-acting octreotide in bleeding angiodysplasia of gastrointestinal tract. Data suggest that long-acting octreotide is a safe drug and is successful in controlling recurrent gastrointestinal bleeding due to angiodysplasia in elderly patients not eligible for surgical or endoscopic therapy.

Hyperbilirubinemia: does it matter?

Serum bilirubin concentrations are increased in several hematological and hepatic disorders; however, hyperbilirubinemia, often of familial origin, may occur without overt signs of hemolysis or evident liver disease. The authors review briefly the main steps of hepatic bilirubin metabolism, then discuss the pathogenetic mechanisms of the different forms of familial hyperbilirubinemia. The knowledge of these conditions is increasingly important because orthotopic liver transplantation may be a therapeutic choice for some severe forms. Furthermore, early diagnosis is necessary to avoid unnecessary medical investigations for the otherwise relatively common, benign unconjugated hyperbilirubinemia. Finally, individuals with unmasked defective bilirubin handling may be potential liver donors; thus, unexplained jaundice occurring after orthotopic liver transplantation may be related to this disorder.

[The problem of infections in an internal medicine department. Analysis of 312 antibiograms]. / Il problema delle infezioni in un reparto di medicina. Analisi di 312 antibiogrammi.

Following a brief analysis of the problem of hospital infections, the results of a review of 312 antibiograms carried out in the General Medicine Division of Cuneo's S. Croce Hospital in 1979 are reported.

Posterior interosseous nerve neuropathy. Clinical and electromyographical aspects.

A clinical-EMGraphic examination was carried out in 37 patients with posterior interosseous nerve neuropathy: 5 cases had a traumatic origin, 4 iatrogenic, and 28 non-traumatic. One of the non-traumatic cases had a lipoma, and another had chondroma. In the other cases, nerve entrapment at the level of the arcade of Frohse could be presumed. Acute or chronic onset of the deficit was probably due to repeated pronation-supination hand movements. A motor deficit in finger extension together with a radial deviation of the wrist, was typical. Surprisingly about 50% of the non-traumatic cases showed some sensory disturbance at the forearm, wrist or hand. EMG examination was useful to establish the entity and topography of the deficit. Follow-up was carried out in 27 cases (3 traumatic, 2 iatrogenic and 22 non-traumatic). Even if spontaneous recovery is possible, though infrequent, in non-traumatic cases with marked deficit surgery gave the most satisfactory results, especially when onset had been acute and operation was performed within nine months of onset.

VEGF receptor expression decreases during lung development in congenital diaphragmatic hernia induced by nitrofen.

Changes in vascular endothelial growth factor (VEGF) in pulmonary vessels have been described in congenital diaphragmatic hernia (CDH) and may contribute to the development of pulmonary hypoplasia and hypertension; however, how the expression of VEGF receptors changes during fetal lung development in CDH is not understood. The aim of this study was to compare morphological evolution with expression of VEGF receptors, VEGFR1 (Flt-1) and VEGFR2 (Flk-1), in pseudoglandular, canalicular, and saccular stages of lung development in normal rat fetuses and in fetuses with CDH. Pregnant rats were divided into four groups (n=20 fetuses each) of four different gestational days (GD) 18.5, 19.5, 20.5, 21.5: external control (EC), exposed to olive oil (OO), exposed to 100 mg nitrofen, by gavage, without CDH (N-), and exposed to nitrofen with CDH (CDH) on GD 9.5 (term=22 days). The morphological variables studied were: body weight (BW), total lung weight (TLW), left lung weight, TLW/BW ratio, total lung volume, and left lung volume. The histometric variables studied were: left lung parenchymal area density and left lung parenchymal volume. VEGFR1 and VEGFR2 expression were determined by Western blotting. The data were analyzed using analysis of variance with the Tukey-Kramer post hoc test. CDH frequency was 37% (80/216). All the morphological and histometric variables were reduced in the N- and CDH groups compared with the controls, and reductions were more pronounced in the CDH group (P<0.05) and more evident on GD 20.5 and GD 21.5. Similar results were observed for VEGFR1 and VEGFR2 expression. We conclude that N- and CDH fetuses showed primary pulmonary hypoplasia, with a decrease in VEGFR1 and VEGFR2 expression.

VEGF receptor expression decreases during lung development in congenital diaphragmatic hernia induced by nitrofen

Changes in vascular endothelial growth factor (VEGF) in pulmonary vessels have been described in congenital diaphragmatic hernia (CDH) and may contribute to the development of pulmonary hypoplasia and hypertension; however, how the expression of VEGF receptors changes during fetal lung development in CDH is not understood. The aim of this study was to compare morphological evolution with expression of VEGF receptors, VEGFR1 (Flt-1) and VEGFR2 (Flk-1), in pseudoglandular, canalicular, and saccular stages of lung development in normal rat fetuses and in fetuses with CDH. Pregnant rats were divided into four groups (n=20 fetuses each) of four different gestational days (GD) 18.5, 19.5, 20.5, 21.5: external control (EC), exposed to olive oil (OO), exposed to 100 mg nitrofen, by gavage, without CDH (N-), and exposed to nitrofen with CDH (CDH) on GD 9.5 (term=22 days). The morphological variables studied were: body weight (BW), total lung weight (TLW), left lung weight, TLW/BW ratio, total lung volume, and left lung volume. The histometric variables studied were: left lung parenchymal area density and left lung parenchymal volume. VEGFR1 and VEGFR2 expression were determined by Western blotting. The data were analyzed using analysis of variance with the Tukey-Kramer post hoc test. CDH frequency was 37% (80/216). All the morphological and histometric variables were reduced in the N- and CDH groups compared with the controls, and reductions were more pronounced in the CDH group (P<0.05) and more evident on GD 20.5 and GD 21.5. Similar results were observed for VEGFR1 and VEGFR2 expression. We conclude that N- and CDH fetuses showed primary pulmonary hypoplasia, with a decrease in VEGFR1 and VEGFR2 expression.

Depression and neuroticism in multiple sclerosis.

88 subjects (36 males and 52 females) affected by multiple sclerosis (MS), were studied with the CES-D and SRT tests for the evaluation of depressive reactions and neuroticism. Comparing the results with those of the control group, we found a significant score for depression and somatization in the MS patients, whereas the scores for anxiety and inadequacy were normal.

Recurrence of ibuprofen-induced aseptic meningitis in an otherwise healthy patient.

We report the case of a 74-year-old woman who had three episodes of aseptic meningitis in a period of 20 years. These episodes always occurred a few hours after the assumption of a non-steroidal anti-inflammatory drug (NSAID) per os. Nevertheless, the pharmacological anamnesis did not receive proper attention, neither the first nor the second time, and the meningeal syndrome with aseptic liquor was attributed to a viral aggression. However, when the third episode occurred, due to the strict time correlation between the assumption of the drug and the occurrence of symptoms, both the results of the liquoral analysis and the anamnestic records allowed recognition of ibuprofen as the cause of acute meningitis.