Simian virus 40 infection down-regulates the expression of nitric oxide synthase in human mesothelial cells

The cytotoxic effects of asbestos are partly mediated by the production of free radicals, including nitric oxide (NO). SV40 has been suggested to synergize with asbestos in the pathogenesis of malignant mesothelioma. Crocidolite asbestos fibers induced in human mesothelial and malignant mesothelioma cells a significant increase of NO synthase activity and expression, which was absent in SV40-infected cells. Furthermore, SV40 infection prevented the NF kappa B activation elicited by crocidolite in both mesothelial and mesothelioma cells. These data suggest that SV40, by inhibiting the synthesis of NO, could favor the survival of transformed, potentially neoplastic cells.     

BRCA2 germline mutations in primary cancer of the fallopian tube

Germline mutations of BRCA1 and BRCA2 genes confer susceptibility to breast and ovarian cancer. It has been recently reported that BRCA1/2 mutations may also predispose to fallopian tube cancer. We report the presence of germline BRCA2 gene mutations in three out of four subjects with fallopian tube cancer diagnosed in a two-year time span at our clinic. The mothers of two of these women suffered from breast or ovarian carcinoma. These results suggest on one hand that in patients with a history suggestive for a heredofamilial breast/ovarian cancer syndrome fallopian tube carcinoma is associated with high risk of BRCA2 mutation, and on the other hand that in patients/individuals with germline BRCA2 gene mutations in whom a prophylactic oophorectomy is performed, removal of fallopian tubes may be considered.     

Antibiotic therapy in the elderly: features and problems

Bacterial infections cause 30% of deaths in the elderly and are the most frequent cause of hospitalization in elderly patients. Diagnosis of infection can be difficult because aged patients may have neither fever nor leucocytosis; most patients present unusual symptoms such as changes in mental status. The clinician must be cognizant of the frequent noncompliance with drug regimens because lack of elderly adherence to a prescribed antibiotic therapy has the potential to result in treatment failure and to foster the emergence of drug-resistant bacteria. Elderly frequently are taking other drugs such as antiarrhythmics and antihypertensives; ignorance of potential antibiotic-drug interaction can result in ineffective treatment or enhanced toxicity. Aging is associated with changes in physiological processes; the age-related decline in renal function influences the excretion of some antibiotics (aminoglycosides, vancomycin, ofloxacin). The increased potential for toxicity of antimicrobial agents requires a careful drug selection as well as clinical and laboratory monitoring. The most frequent infections occurring in the elderly are pneumonia, urinary tract infection, intra-abdominal infection and soft tissue infection; prevalence and incidence of bacterial meningitis, bacterial endocarditis and bacteraemia are increasing with a mortality rate of 20 to 40%. These bacterial infections have different microbial causes and require different therapeutic approaches according to sites involved, elderly's salient features and overall susceptibility of the bacteria in the ecosystem. Appropriate empirical antibiotic treatment reduces mortality also in bacteraemic old patients.     

Dissociation between respiratory effort and dyspnoea in a subset of patients with stroke

Dyspnoea is not a prominent complaint of resting patients with recent hemispheric stroke (RHS). We hypothesized that, in patients with RHS presenting abnormalities in respiratory mechanics, increased respiratory motor output could translate into an increased perception of dyspnoea. We studied eight wheelchair-bound patients with RHS (mean age 62.4 years), previously evaluated by computerized tomography scanning, and a control group of normal subjects, matched for age and sex. We assessed routine spirometry, inspiratory and expiratory muscle pressures, breathing pattern and dyspnoea using a modified Borg scale. In six patients, we also measured oesophageal pressure during the maximal sniff manoeuvre and tidal inspiratory swing, and mechanical characteristics of the lung in terms of dynamic elastance during both quiet breathing and a hypercapnic/hyperoxic rebreathing test. During room air breathing, ventilation and tidal volume were similar in patients and controls, while tidal inspiratory swings of oesophageal pressure, an index of inspiratory motor output, were greater in patients ( P =0.005). Patients also exhibited a greater dynamic elastance ( P =0.013). During rebreathing, dynamic elastance remained higher ( P =0.01) and a greater than normal inspiratory motor output was found ( P =0.03). Responses of ventilation and tidal volume to carbon dioxide tension were normal, and in all patients but one a lower Borg score for the unit change in carbon dioxide tension and ventilation was found. In conclusion, a higher than normal inspiratory motor output was unexpectedly associated with a blunted perception of dyspnoea in this subset of RHS patients. This is likely to be due to the modulation of the integration process of respiratory sensation.