Non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that affects a high proportion of the world's population. Insulin resistance and oxidative stress play a critical role in the pathogenesis of NAFLD. Clinical, biochemical and imaging studies are of value in the diagnostic evaluation of patients with NAFLD, but liver biopsy remains the most sensitive and specific means of providing important diagnostic and prognostic information. Simple steatosis has the best prognosis within the spectrum of NAFLD, but NAFLD has the potential to progress to steatohepatitis, fibrosis and even cirrhosis. No effective medical therapy is currently available for all patients with NAFLD. In patients with diabetes mellitus and hyperlipidemia, appropriate metabolic control is always recommended, but rarely effective in resolving the liver disease. Weight reduction, when achieved and sustained, may improve the liver disease, although the results with weight loss have been inconsistent. Pharmacological therapy aimed at the underlying liver disease holds promise. Several medications with different mechanisms of action and potential benefit are currently being evaluated in clinical trials. Liver transplantation is a life-extending therapeutic alternative for patients with end-stage NAFLD, but NAFLD may recur after liver transplantation.     

Prospective Evaluation of New and Old Criteria to Discriminate Between Supraventricular and Ventricular Tachycardia in Implantable Defibrillators

This study was designed to evaluate the ability to distinguish between supraventricular tachycardias (SVTs) and ventricular tachycardias (VTs) based on onset, stability, and width criteria in an implantable defibrillator. Inappropriate detection of atrial fibrillation and sinus tachycardia is a common problem in patients with implantable defibrillators. The onset, stability, and width criteria were studied in 17 patients who underwent implantation of a Medtronic 7218C implantable defibrillator by inducing sinus tachycardia and atrial fibrillation. Additional data on the width criteria was obtained by pacing at separate sites in both the left and right ventricle. Patients were studied at different times for up to 6 months to determine any changes in the criteria. The onset and stability criteria caused inappropriate detections in 36% and 12% of the episodes, respectively. The addition of the width criteria decreased the inappropriate detection using the onset and stability criteria to 5% and 2%, respectively. Pacing from the RV apex, RV outflow tract, and LV apex was appropriately detected as wide in 76%, 41%, and 94%, respectively. The width criteria changed over time in individual patients, but was stable by 6 months in all but one patient. No single criterion is satisfactory for distinguishing between SVT and VT in this patient population, but the combination of criteria seems to provide better discrimination. The width criteria can change dramatically over time and needs to be monitored carefully. Newer algorithms will need to be developed to allow better detection of supraventricular tachycardias.     

Reduced attention-related negative potentials in schizophrenic adults

Event-related potentials were recorded from outpatient adult schizophrenics receiving maintenance doses of neuroleptics and from normal control subjects during performance of a reaction time task and a complex visual discrimination task, the Span of Apprehension. Difference potentials were computed to isolate endogenous activity associated with the processing demands of the Span task. Schizophrenics produce significantly less early endogenous negative activity than do normal subjects. This processing-related negativity reflects pattern matching activity to an attentional trace during the serial scan of the visual icon. We previously reported an identical reduction in processing-related negativity in childhood-onset schizophrenia, suggesting that this deficit is age independent. Both frontal contingent negative variation and an early frontal P3 were larger in the schizophrenics than in normal subjects, suggesting an inappropriate mobilization of nonspecific attentional resources. A later posterior P3 was significantly smaller in schizophrenics than in normal subjects.     

A 90-Day Chloroform Inhalation Study in Female and Male B6C3F1 Mice: Implications for Cancer Risk Assessment

High doses of chloroform induced liver cancer in male and femaleB6C3F₁ mice when administered by gavage, kidney cancer in maleOsborne-Mendel rats when given by gavage or in the drinkingwater, and kidney cancer in male BDF₁ mice when administeredby inhalation. The weight of evidence indicates that chloroformis acting through a nongenotoxic-cytotoxic mode of action. Thepresent study was designed to investigate the dose-responserelationships for chloroform-induced lesions and regenerativecell proliferation in B6C3F₁ mice as the basis for formulationof a biologically based risk assessment for inhaled chloroform.Different groups of female and male B6C3F₁ mice were exposedto atmospheric concentrations of 0, 0.3, 2, 10, 30, and 90 ppmchloroform 6 hr/day, 7 days/week for exposure periods of 4 daysor 3, 6, or 13 consecutive weeks. Some additional exposure groupswere exposed for 5 days/week for 13 weeks or were exposed for6 weeks and then examined at 13 weeks. Bromodeoxyuridine wasadministered via osmotic pumps implanted 3.5 days prior to necropsy,and the labeling index (LI, percentage of nuclei in S-phase)was evaluated iminunohistochemically from histological sections.Complete necropsy and microscopic evaluation revealed treatment-induceddose- and time-dependent lesions only in the livers and nasalpassages of the female and male mice and in the kidneys of themale mice. Large, sustained increases in the liver LI were seenin the 90-ppm groups at all time points. The female mice weremost sensitive, with a no-observed-adverse-effect level (NOAEL)for induced hepatic cell proliferation of 10 ppm. The hepaticLI in the 5 days/week groups were about half of those seen inthe 7 days/week groups and had returned to the normal baselinein the 6-week recovery groups. Induced renal histologic changesand regenerative cell proliferation were seen in the male miceat 30 and 90 ppm with 7 days/week exposures and also at 10 ppmwith the 5 days/week regimen. Nasal lesions were transient andconfined to mice exposed to 10, 30, or 90 ppm for 4 days. Ina previous cancer bioassay, a gavage dose of 477 mg/kg/day produced a 95% liver tumor incidence in female B6C3F₁ mice. Thisgavage dose is equivalent to a daily 6 hr/day inhalation exposureof approximately 80 ppm, based on the observed induced increasesin the LI as an internal dosimeter. The United States EnviromnentalProtection Agency currently uses the linearized multistage modelapplied to the mouse liver tumor data from the chloroform gavagestudy to estimate a virtually safe dose (VSD) as a one in amillion increased lifetime risk of cancer. The resulting valueis an airborne exposure concentration of 0.000008 ppm. Assumingthat chloroform-induced female mouse liver cancer is secondaryto events associated with necrosis and regenerative cell proliferation,then no increases in liver cancer in female mice would be predictedat the NOAEL of 10 ppm or below based on the results reportedhere. Applying an uncertainty factor of 1000 yields an estimateof a VSD at 0.01 ppm. This estimate relies on inhalation dataand is more consistent with the mode of action of chloroform.     

The smell of cancer

An unusual case of lichen sclerosus et atrophicus is described, in which lesions were bullous and haemorrhagic and extended over almost the entire surface of the skin. A marked improvement followed treatment with ACTH.     

Marginal porosity of light activated composites in relation to use of intermediate low-viscous resins

Abstract – The marginal porosity of four light activated restoratives (Command, Durafill, Prismafill and Silux) was investigated in extracted human teeth It was found that the use of a lowviscous resin prior to application of the restorative materials significantly reduced the marginal porosity in both acid etched enamel cavities and EDTA-cleaned dentin cavities.     

Contraction pattern of composite resins in dentin cavities

Abstract – The correlation between the wall-to-wall polymerization contraction close to the surface and the marginal gap in the deeper parts of chemically cured resin fillings was investigated. The investigation was carried out with fillings placed in non-etched dentin cavities in extracted human teeth. A negative correlation was found; i.e. the narrower the marginal gap in the upper part of the cavities, the more pronounced the contraction in the deeper parts of the fillings, and vice versa.     

Predictive value of, and observer variability in, several ways of reporting antepartum cardiotocographs

Summary. Each of three scoring systems, and oscillatory frequency, had significantly poorer correlation with fetal outcome than reporting the cardiotocograph (CTG) as either 'reactive' or 'non-reactive'. There was no significant difference in the intra- and inter-observer variability when the CTG was reported in this way.