Reference values for blood benzene in the occupationally unexposed general population

Blood benzene was determined by gas chromatography-mass spectrometry in 431 "normal" subjects, subdivided into 155 rural subjects and 276 urban subjects. Blood benzene (mean value 262 ng/l) was significantly lower in rural (200 ng/l) than in urban (296 ng/l) workers, as well as differing significantly between 293 non-smokers and 138 smokers (205 ng/l and 381 ng/l, respectively). Among non-smokers, values were significantly higher (307 ng/l) in 76 chemical workers. In the total study population, in 95% of cases blood benzene was less than 718 ng/l, the 95th percentile being 514 ng/l in non-smokers vs 901 ng/l in smokers and 576 ng/l in rural vs 822 ng/l in urban subjects. Within each population subgroup, the difference between non-smokers and smokers was statistically significant, except among office workers (non-smokers 234 ng/l, smokers 304 ng/l). Blood benzene (y) was directly proportional to the number of cigarettes smoked (x) (y = 201 + 12x; r = 0.44; n = 431), and inversely proportional to the interval between the last cigarette and the time at which the blood samples was taken (z) (log y = 6.167-0.0015z; r = -0.461; n = 135). The blood half-life of benzene was about 8h. The multiple correlation between blood benzene (Cb), number of cigarettes per day (x) and time since the last cigarette (z) is: Cb = 417 + 7.2x - 0.41z (n = 135; R = 0.20; P less than 0.00001).     

Contribution of computerized tomography to the diagnosis of patients with non-calcified solitary pulmonary nodule, without known neoplasm]

We define a solitary pulmonary noncalcified nodule (NPS) as a single focal rounded or ovoid lesion in the lung parenchyma, less than 4 cm in diameter, without associated adenopathy, atelectasis or pneumonia. An NPS, in the absence of a known primary malignancy, can be lung cancer (NPSM), a metastasis of unknown origin (NPSMT), or a benign lesion (NPSB). The best approach to the management of NPS and the value of CT are still controversial and uncertain. The finding on cross-section CT of a bronchus leading directly to, or contained within, the nodule is called "positive CT bronchus sign" (CT-BS). Our study was aimed at investigating the usefulness of CT bronchus sign, as studied on thin-slice (2 mm thick) CT sections, in order to establish the most appropriate diagnostic sequence in patients with solitary noncalcified pulmonary nodules (NPS). We evaluated 47 NPS (9 NPSB, 34 NPSM and 4 NPSMT) with thin-slice CT to detect the presence of CT bronchus sign. Seventeen cases had CT-BS (15 NPSM; 1 NPSB; 1 NPSMT); of them, 13 were diagnosed by means of transbronchial biopsy and brushing (TBB). Only one case (NPSM) of the 30 (19 NPSM; 3 NPSMT; 8 NPSB) without CT-BS, was diagnosed by TBB. TBB was negative in the 9 NPSB. The CT-BS is not pathognomonic of malignancy; in fact, the sign was observed in NPSB (one tuberculoma) too. Our results suggest that the CT bronchus sign is valuable in predicting the success of TBB in malignant solitary pulmonary nodules. On the other hand, it seems to be useless for NPSB. Therefore, to establish the most appropriate diagnostic sequence, thin-section CT should be performed in each patient with peripheral noncalcified lung lesions to plan whether TBB or transthoracic needle aspiration should come next. If biopsy results are poor, either surgery or the "wait and watch for growth" approaches can be suggested. The choice can be guided by the presence of predisposing factors for cancer or infection.     

Influence of sleep deprivation on neuroactive steroids in major depression.

There is evidence from preclinical and clinical studies that concentrations of neuroactive steroids are altered in depression and normalize after antidepressant pharmacotherapy. However, no data are available concerning the impact of sleep deprivation on the concentrations of neuroactive steroids. A total of 29 drug-free patients (12 men, 17 women) suffering from major depression according to DSM-IV criteria were treated with partial sleep deprivation (PSD). Response to PSD was defined as a reduction of at least 30% according to the six-item version of the Hamilton depression scale (6-HAMD). Plasma samples were taken the day before and after PSD (days 0 and 1) and after one night of recovery sleep (day 2) at 8:00 am. The samples were quantified for neuroactive steroids by means of a highly sensitive and specific combined gas chromatography/mass spectrometry analysis. There was no influence of PSD on the concentrations of neuroactive steroids either in PSD responders (n=20) or in nonresponders (n=9). However, nonresponders showed significantly higher concentrations of 3alpha,5alpha-tetrahydroprogesterone (3alpha,5alpha-THP), 3alpha,5beta-tetrahydroprogesterone (3alpha,5beta-THP), and dehydroepiandrosterone (DHEA) before or after PSD compared to responders. In contrast to antidepressant drugs, which correct the dysequilibrium of neuroactive steroids in major depression within several weeks, PSD does not affect the concentrations of neuroactive steroids either in responders or in nonresponders.     

Hydrocephalus in coccidioidal meningitis: case report and review of the literature

OBJECTIVE AND IMPORTANCE: Coccidioidomycosis was once confined to the southwest United States and northern Mexico. It has become a larger concern because of the concentration of military bases in these areas, the increasing mobility of populations, and the rising population of immunocompromised persons. Outside endemic areas, the diagnosis is rarely considered. Patients with coccidioidomycosis may develop occult basilar meningitis progressing to communicating hydrocephalus and death. CLINICAL PRESENTATION: A 60-year-old white man presented with a 1-month history of vertigo, falls, and vomiting. Computed tomography of the head revealed mild hydrocephalus. Lumbar puncture results were remarkable for 1065 mg/dl protein; acid-fast bacillus stain, Gram's stain, and culture results were negative. Postgadolinium magnetic resonance imaging demonstrated enhancement of basilar and cervical meninges, suggesting inflammation, and communicating hydrocephalus. For 48 hours, the patient's level of consciousness decreased progressively. INTERVENTION: A ventriculoperitoneal shunt was placed, and antifungal agents were initiated on an emergent basis. CONCLUSION: Coccidioidomycosis should be considered in the differential diagnosis of occult basilar meningitis. The diagnosis is established by the discovery of a high (>1:2) titer of complement-fixing antibody in the cerebrospinal fluid. Communicating hydrocephalus is a common complication of untreated coccidioidal meningitis, and it may develop during appropriate treatment (oral fluconazole, 200-400 mg/d, continued indefinitely). Patients with hydrocephalus and evidence of increased intracranial pressure require a shunt.     

Thrombomodulin serum levels in ventilated preterm babies with respiratory distress syndrome

A soluble form of thrombomodulin (TM), an anticoagulant proteoglycan of the endothelial cell membrane, considered a marker of vascular endothelial damage, was measured in plasma of preterm infants with respiratory distress syndrome (RDS). In these patients, lung immaturity leads to endothelial leak of plasma proteins and to surfactant inhibition. In 18 babies with RDS, plasma TM concentration was significantly elevated compared with values of a matched group of babies without pulmonary disease (276.1 ng/ml vs 141.3 ng/ml) (P<0.05). Furthermore, TM levels of mechanical ventilated babies (IPPV) with severe RDS were higher than those of babies with moderate RDS and treated with nasal CPAP (340.9 ng/ml vs 174.2 ng/ml) (P<0.05). Conclusion These data show that TM can be used as marker of pulmonary endothelial damage in preterm babies treated with mechanical ventilation for RDS and suggest early intervention with exogenous surfactant to limit alveolar protein leakage and surfactant inactivation. Received: 20 February 1997 and in revised form: 7 July 1997 / Accepted: 8 July 1997     

Nitric oxide inhibits neonatal hepatocyte oxidative metabolism

BACKGROUND/PURPOSE: Liver function is frequently impaired in neonates with sepsis. Nitric oxide (NO) is thought to be a mediator of organ dysfunction and liver oxidative metabolism during sepsis. The authors developed an in vitro model to investigate the effect of NO and the combined effect of NO plus H2O2 on neonatal hepatocyte oxidative metabolism. METHODS: Hepatocytes were isolated from neonatal rats. Oxygen consumption was measured polarographically. In Study A, cells were exposed to S-Nitroso-N-acetylpenicillamine (SNAP), an NO donor, at various concentrations. In study B, myxothiazol and oligomycin, inhibitors of mitochondrial respiration, were added to investigate the site of action of NO. In study C, hepatocytes were incubated in the presence of both SNAP (300 micromol/L) and H2O2 (1.5 mmol/L). In study D, morphological alterations induced by NO and NO plus H2O2 were investigated by hepatocyte electron microscopy. RESULTS: In study A, SNAP caused a dose-dependent decrease in oxygen consumption. A significant inhibition was reached at 300 micromol/L SNAP. In study B, the lack of further inhibition when SNAP was given together with myxothiazol indicates that NO acts intramitochondrially. Similarly, no further inhibition occurred when the NO donor was given together with oligomycin, suggesting that the effect of NO is mainly at the level of ATP synthase. In study C, concomitant addition of 300 micromol/L SNAP and 1.5 mmol/L H2O2 to hepatocytes caused further inhibition of oxygen consumption compared with either SNAP or H2O2 alone. In study D, mild alterations in hepatocyte morphology were noted in the presence of SNAP or SNAP plus H2O2. CONCLUSIONS: In neonatal hepatocytes, NO significantly inhibits mitochondrial oxygen consumption, possibly at the level of ATP synthase. The effect of NO is additive to that of H2O2. Morphological findings were consistent with these biochemical effects and suggest that NO and H2O2 are important mediators of liver damage during sepsis.     

Reflections on mesenteric infarct

The authors relate their statistic about mesenteric infarction in the last five years and they get out the starting point in order to check the characteristics of a disease, which is today distinguished by an infaust prognosis. After few mentions about etiopathology and pathologic anatomy they keep their attention on clinic manifestations of disease and on diagnostic research. After dealing with medical and surgical therapy they declare how more refined diagnostic technique could help early diagnosis and consequently decrease morbidity and morbidity, which are completely unacceptable.     

Long-term results of a randomized trial on extended use of high dose L-asparaginase for standard risk childhood acute lymphoblastic leukemia.

PURPOSE: Between September 1991 and May 1997, within the International Berlin-Frankfurt-Muenster Study Group (I-BFM-SG), a randomized study was performed aimed at assessing the efficacy of prolonged use of high-dose l-asparaginase (HD-l-ASP) during continuation therapy in children with standard risk (SR) acute lymphoblastic leukemia (ALL), treated with a reduced BFM-type chemotherapy. PATIENTS AND METHODS: The Italian, Dutch, and Hungarian groups participated in this study denominated IDH-ALL-91, and 494 children were enrolled. Treatment consisted of a BFM-type modified backbone with omission of the IB part in induction and elimination of two doses of anthracyclines during reinduction in both arms at the beginning of continuation therapy. Patients were randomly assigned to receive (YES-ASP) or not (NO-ASP) 20 weekly HD-l-ASP (25,000 IU/m2). RESULTS: The event-free-survival and overall survival probabilities at 10 years for the entire group were 82.5% (1.8) and 90.3% (1.3), respectively. Of the 490 patients eligible for random assignment, 355 (72.4%) were randomly assigned (178 YES-ASP and 177 NO-ASP). After a median follow-up of 9 years, the probability of disease-free survival at 10 years was 87.5% (SE, 2.5) for YES-ASP arm versus 78.7% (SE, 3.3) for NO-ASP arm (P = .03). In multivariate analysis, NO-ASP arm (P = .03), male sex (P = .004), and age older than 10 years (P = .0003) had a significantly adverse impact on outcome. CONCLUSION: In this subset of patients, selected with criteria not including monitoring of minimal residual disease, application of extended HD-l-ASP may improve prognosis, compensating reduced leukemia control that results from adoption of a reduced-intensity BFM-backbone for treatment of children with SR ALL.     

In vitro development of engineered muscle using a scaffold based on the pressure‐activated microsyringe (PAM) technique

The development of new human skeletal muscle tissue is an alternative approach to the replacement of tissue after severe damage, for example in the case of traumatic injury, where surgical reconstruction is often needed following major loss of natural tissue. Treatment to date has involved the transfer of muscle tissue from other sites, resulting in a functional loss and volume deficiency of donor sites. Approaches that seek to eliminate these problems include the relatively new solution of skeletal muscle engineering. Here there are two main components to consider: (a) the cells with their regenerative potential; and (b) the polymeric structure onto which cells are seeded and where they must perform their activities. In this paper we describe well‐defined two‐ and three‐dimensional polymeric structures able to drive the myoblast process of adhesion, proliferation and differentiation. We examine a series of polymers and protein adhesions with which to functionalize the structures, and cell‐seeding methods, with a view to defining the optimal protocol for engineering skeletal muscle tissue. All polymer samples were tested for their mechanical and biological properties, to support the validity of our results in the real context of muscle tissue engineering. Copyright © 2014 John Wiley & Sons, Ltd.     

Myocardial Perfusion Single-Photon Emission Tomography (SPET) and Positron Emission Tomography–Computed Tomography (PET-CT) Imaging for Congenitally Corrected Transposition of Great Arteries

Congenitally corrected transposition of great arteries (ccTGA) consists of both atrioventricular and ventriculo-arterial discordance. In patients with ccTGA, the pulmonary artery arises from the left ventricle, whereas the aorta arises from the right ventricle. The burden of the systemic blood pressure on the right ventricle involves an increased risk of coronary artery disease (CAD) and, as a long-term consequence, myocardial hypertrophy and gradual failure. This report describes the case of an adult patient affected by ccTGA who was referred for an episode of atypical chest pain while at rest. First-line diagnostic examinations were inconclusive. Myocardial perfusion single-photon emission tomography (SPET) was performed to exclude CAD, but the congenital abnormalities of the patient??s heart made interpretation of the images particularly difficult. A perfusion positron emission tomography?Ccomputed tomography (PET-CT) scan with ¹³N-ammonia then was suggested, which unmasked an unexpected artifact. The case report demonstrates that hybrid imaging techniques such as SPET-CT and PET-CT should be used systematically when CAD is suspected for patients with abnormal anatomy of the heart, including ccTGA.