[Diagnosis and insurance compensation of occupational diseases in construction industry]. / Malattie professionali segnalate e riconosciute in edilizia.

The aim of this study is to evaluate the outcome of 302 occupational diseases in building workers detected by UOOML Ospedali Riuniti of Bergamo and notified to INAIL from 2000 to 2005. The 41.3% of cases were accepted as work-related. Among remaining cases (58.7%), INAIL rejected 40.9% for lack or absence of documentation. 59.1% for no adhesion to legal medicine criteria. By analysis of occupational diseases detected in the last 5 years, we found an increase of muscle-skeletal disorders, for which, now, diagnostic procedure and insurance evaluation are difficult. This work shows a wide gap between reported occupational diseases of buildings workers and compensation given by INAIL. These results underlines the need of comparison among involved institutions in order to standardize statistical and diagnostic instruments.

Mitochondrial membrane potential and ageing in Podospora anserina.

Some filamentous fungi exhibit a limited vegetative growth with modifications in the mitochondria, suggesting the involvement of mitochondria in the process of ageing. Nevertheless, the relationship between the ability to grow or the fate of these cells relative to their mitochondrial membrane potential (Psi(mt)) level has not been investigated. Using flow cytometric analysis, we have assessed Psi(mt) in young and senescent cultures of wild type strains and mitochondrial or nuclear mutant strains of Podospora anserina that present very long or brief life span. When we compared two distinct populations of cells obtained from the same strain, we can show a correlation not only between Psi(mt) and ageing, but also between Psi(mt) and the frequency of regeneration and/or the life span. However, this relationship is not observed when we compared the cells obtained from different physiological states or mutants strains. These results allow us to suggest that the Psi(mt) modifications during senescence could be only one of the possible consequences of the process and are not the factor driving towards death. We also show that the driving force of Psi(mt) is principally maintained by the alternative pathway during ageing, suggesting a role of the alternative oxidase pathway.

Stereotactic aspiration and drainage of brain abscesses. Experience with 9 cases.

The first-line treatment for brain abscesses is still a much-debated argument. Recently, stereotactic aspiration of these lesions has gained ground as a valid alternative to the traditional medical and/or surgical therapeutical treatments. From 1991 to 1995, 9 patients affected by intracranial abscesses were surgically treated by stereotactic puncture of the lesion and drainage of pus, using the Kelly-Goerss stereotactic system. Multiple abscesses were present in one case. Specific antibiotic therapy was used in the post-operative stage, when possible. One death occurred four weeks after surgery for acute ischemia of the brain stem. Follow-up CT demonstrated gradual resolution of the abscesses in all the cases and a successful return to normal daily life in all the surviving patients. In one case, recurrence of the abscess occurred two months after resolution: a successful result was obtained by steroids and broad-spectrum antibiotic therapy alone. Possible advantages of this technique are discussed and compared with the traditional routes. The literature concerning this argument is reviewed.

Volumetric reconstruction and stereotactic computer assisted resection in intracerebral lesions.

Since 1990 112 patients have undergone stereotactic resection of intra-axial tumoural lesions with volumetric reconstruction, using the Kelly-Goerss system. Stereotactic integration of CT, angiographic and particularly MRI information, together with three-dimensional information of the lesion, provide an innovative evaluation of the most appropriate surgical approach, even for each single patient. The main limitation of this surgical method is in cases where the infiltrating part of the tumour is pre-eminent, while it can allow "macroscopically complete resection" of well circumscribed lesions, almost independently of their location and volume. Some technical aspects of stereotactic resection of brain tumours are discussed in the light of our experience.

[Nontraumatic coma in extramural practice]. / Le coma non traumatique en pratique extrahospitaliére.

After a short review on pathophysiologic mechanisms of comatose states and their complications, a cohort of 392 comatose patients (Glasgow Coma Scale < or = 8) hospitalized in intensive care is analyzed in order to estimate the relative frequency of the different causes of nontraumatic coma. Depending on pathology, the following practical, sequential procedure is recommended: at first, identification and treatment of disorders of vital functions, objective estimate of the severity of the coma and rapid diagnostic orientation with a targeted neurologic investigation; then, simple therapeutic interventions in order to treat reversible causes of a metabolic encephalopathy as well as immediate measures for neuroprotection (anticonvulsive and antihypotensive therapy, oxygen, etc.). An initial, adequate control of the comatose patient is mandatory in order to limit disabling cerebral complications.

Tumor cell kinetics following long-term treatment with antineoplastic ether phospholipids.

Ether phospholipids are analogs of the naturally occurring 2-lysophosphatidylcholine that have been reported to have selective in vitro/in vivo antitumor activity. Their antiproliferative effect has been found against a variety of animal and human tumor cell lines. We have characterized the cytostatic activity of four ether phospholipids, the methoxy-substituted edelfosine (ET-18-OCH 3), the thio-derivative ilmofosine (BM 41.440), and two new aza-alkylphospholipids, BN 52205 and BN 52211, on a human tumor cell line derived from a colon adenocarcinoma, the HT29. A flow cytometric approach has been used and, contrary to previous studies, longer treatment times have been performed to allow multiple cell population doublings. The results confirm that the cytostatic activity of the four ether phospholipids is characterized by multiple "terminal points", as the drugs' action results in a G1 block, a slowdown of the transition from late-S to G2, followed by an accumulation of HT29 cells in the G2 phase of the cell cycle. Tumor cells in late G1 at the time of treatment progressed through S before being blocked in G2. In a similar fashion, tumor cells in late G2 at the time of treatment went through M but were then halted in G1. The long-term treatment studies indicate that the ether phospholipid cytostatic activity is partially reversible, depending on the drug concentration and the duration of the treatment.

Protective effects of somatostatin against gastric damage induced by hemorrhagic shock, stress and PAF in the rat.

Somatostatin is an endogenous cyclic tetradecapeptide which can exert effects on a wide range of gastrointestinal functions, including gastric acid and pepsin secretion, gastric and small intestinal motility, splanchnic blood flow, pancreatic enzyme secretion, intestinal nutrient absorption and gallbladder contractility. Somatostatin has also been shown to reduce the severity of ethanol-induced gastric damage. In this study, we examined the effect of pretreating rats with somatostatin (s.c.) on susceptibility to gastrointestinal damage induced by hemorrhagic shock, stress, platelet-activating factor (PAF), indomethacin or endotoxin. Somatostatin significantly reduced the extent of gastric damage induced by hemorrhagic shock when given at a dose of 20 micrograms/kg or greater (P < 0.05). Somatostatin (20-50 micrograms/kg) also had a dose-dependent protective effect against stress-induced gastric damage. Versus gastric damage induced by intravenous PAF, a dose of 5 micrograms/kg of somatostatin had no effect, while doses of 15-100 micrograms/kg significantly reduced the extent of injury to the stomach. In contrast, somatostatin had no significant effect on gastric or intestinal damage caused by intravenous administration of Salmonella enteritidis endotoxin or by oral administration of indomethacin, despite significantly and dose-dependently (2-10 micrograms/kg) reducing both the volume and titratable acidity of gastric secretion. A protective dose of somatostatin (20 micrograms/kg) had only a small and transient effect on gastric blood flow. The present results demonstrate the effectiveness of somatostatin in protecting the mucosa from injury in a variety of models, and suggest that inhibition of gastric acid secretion is not the sole mechanism underlying these protective effects.

Characterisation of mutations in the Klebsiella pneumoniae nitrogen fixation regulatory gene nifL which impair oxygen regulation.

The nifL gene product of Klebsiella pneumoniae inhibits the activity of the positive activator protein NifA in response to increased levels either of fixed nitrogen or of oxygen in the medium. In order to demonstrate that the responses to these two effectors are discrete we have subjected nifL to hydroxylamine mutagenesis and isolated nifL mutants that are impaired in their ability to respond to oxygen but not to fixed nitrogen. Two such mutations were sequenced and shown to be single base pair changes located in different parts of nifL. The amino acid sequence of NifL shows limited homology to the histidine protein kinases which comprise the sensing component of bacterial two-component regulatory systems. In the light of the location of one of the oxygen-insensitive mutations (Leu294Phe) we have reassessed this homology and we suggest that the Gln273-Leu317 region of NifL may facilitate interactions between NifL and NifA.

Cytostatic activity of new synthetic anti-tumor aza-alkyllysophospholipids.

Alkyllysophospholipids are analogues of the naturally occurring 2-lysophosphatidylcholine which have been reported to have selective in vitro/in vivo anti-tumor activity. Their antiproliferative effect has been found against a variety of animal and human tumor cell lines. We have characterized the cytostatic activity of 2 newly synthetized aza-alkyllysophospholipids (AALPs), the BN52205 and the BN52211, on a human tumor cell line derived from a colon adenocarcinoma, the HT29. We used 3 different flow cytometric approaches to study which phase of the cell cycle was the most sensitive to the antiproliferative activity of the 2 AALPs. By applying the biparametric analysis of 5'-bromo-2-deoxyuridine incorporation vs. DNA content we have been able to demonstrate that the 2 AALPs do not interfere with the S phase of the cell cycle. The simultaneous measurement of total nuclear protein vs. DNA content in isolated HT29 nuclei enabled us to exclude a block in the M phase of the cell cycle. Finally, stathmokinetic analysis enabled us to show that cytostatic activity of the 2 new AALPs is characterized by multiple "terminal points" as the drugs' action results in a G1 block, in a slow-down of the transition from late S to G2 followed by an accumulation of HT29 cells in the G2 phase of the cell cycle.

Tumor cell kinetics following antineoplastic ether phospholipid treatment.

Ether phospholipids are analogues of the naturally occurring 2-lyso-phosphatidylcholine that have been reported to have in vitro/in vivo antitumor activity. Their antiproliferative effect has been found against a variety of animal and human tumor cell lines. We have characterized the cytostatic activity of two ether phospholipids, 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine and 1-hexadecylmercapto-2-methoxymethyl-rac-glycero-3-phosphocholine, on a human tumor cell line derived from a colon adenocarcinoma, HT29. We have used three different flow cytometric approaches to study which phase of the cell cycle was the most sensitive to the antiproliferative activity of the two ether phospholipids. By applying the biparametric analysis, 5'-bromo-2-deoxyuridine incorporation versus DNA content, we have been able to demonstrate that ether phospholipids do not interfere with the S phase of the cell cycle. The simultaneous measurement of total nuclear protein versus DNA content in isolated HT29 nuclei has enabled us to exclude a block in the M phase of the cell cycle. Finally, the stathmokinetic analysis has allowed us to show that the cytostatic activity of the two ether phospholipids 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine and 1-hexadecylmercapto-2-methoxymethyl-rac-glycero-3-phosphocholine is characterized by multiple "terminal points" as the drugs action results in a G1 block and in a slow-down of the transition from late S to G2, followed by an accumulation of HT29 cells in the G2 phase of the cell cycle.

Membrane cholesterol content and sensitivity of human carcinoma-cells to antineoplastic ether phospholipids.

Ether phospholipids represent a new class of anti-cancer drugs which appear to exert their tumoricidal activity through a direct and indirect cytotoxic effect against tumor cells of different origins. The chemotherapeutic interest in these new drugs is based on the finding that, contrary to the majority of anti-cancer drugs, ether phospholipids do not interfere with DNA synthesis, are anti-invasive and induce tumor cell differentiation. There is increasing experimental evidence that the direct cytotoxic effect of these new drugs is mediated by the cell membrane. We have measured the lipid membrane composition of three human carcinoma cell lines that have been found to possess different sensitivity to the tumoricidal activity of four antitumor ether phospholipids. A statistically significant difference has been found in the membrane cholesterol content of the three cell lines and a positive correlation has been established between the membrane cholesterol level and the carcinoma cell sensitivity to ether phospholipids. These findings emphasize previous data obtained with leukemic cells and reinforce the interest in ether phospholipids whose cytotoxic properties may represent a new step towards a more promising anti-cancer chemotherapy.

Platelet-activating factor antagonist, BN-52021 protects against cis-diamminedichloroplatinum nephrotoxicity in the rat.

The protective effect of the platelet-activating factor (PAF) antagonist, BN 52021, was assessed on cis-diammine-dichloroplatinum (CDDP)-induced nephrotoxicity. Wistar male rats were treated with either a single dose of CDDP (10 mg/kg b.w. ip) alone or in association with 7 daily doses of BN 52021 (10 mg/kg b.w. ip). At the end of the experiment, the CDDP-treated rats lost 25% of body weight and serum creatinine and urea increased from 0.041 +/- 0.006 mmol/l and 0.165 +/- 0.007 g/l for the control group to 0.202 +/- 0.019 mmol/l and 1.51 +/- 0.131 g/l versus CDDP respectively. Body weight, serum creatinine, serum urea and creatinine clearances were similar to the control group in animals treated with CDDP and BN 52021. CDDP caused proximal tubular necrosis and dilatation of cortical collecting tubes, changes that were markedly less in the BN 52021-protected animals. The concomitant administration of BN 52021 with CDDP did not modify the plasma pharmacokinetic of CDDP. In addition, BN 52021 did not interfere with the antiproliferative and antitumoral actions of CDDP in cultured human tumor cells. BN 52021 therefore could prevent the nephrotoxicity of CDDP.