Naltrexone-induced alterations in human ethanol intoxication.

OBJECTIVE: Outpatient clinical trials with an opioid antagonist, naltrexone, found that this agent reduces relapse drinking in abstinent alcoholics. It is unknown which aspects of intoxication may be affected by naltrexone. The authors investigated the effects of naltrexone on several subjective and objective measures of ethanol intoxication. METHOD: In a double-blind crossover study, 19 nonalcoholic drinkers received a regimen of naltrexone, 50 mg p.o., or placebo on two different occasions, each time followed by a standard, intoxicating dose of ethanol. Subjective and objective measures of intoxication including mood, physical sensations, performance changes, and ethanol pharmacokinetics were determined. As a control for naltrexone effects, 12 additional subjects received naltrexone or placebo followed by a non-intoxicating, "placebo" dose of ethanol. RESULTS: Naltrexone augmented certain sedative and discriminant effects of ethanol and reduced positive reinforcing effects without affecting psychomotor performance or ethanol pharmacokinetics. Naltrexone had minimal effects in subjects receiving placebo ethanol. CONCLUSIONS: The data are compatible with the clinical findings and suggest that the reduction in ethanol consumption by alcoholics following naltrexone administration may occur because of greater subjective intoxication, greater aversive effects, or less positive reinforcement from ethanol.

Main characteristics of hepatocellular carcinoma and cirrhosis and therapeutic approaches.

Between 1995 and 1997 we studied 100 patients with hepatocarcinoma (HCC) and cirrhosis. Of these 74 were males and 26 females with a mean age of 66 years. 13% patients were only HbsAg positive, 75% only anti-HCV positive, 6% HbsAg and anti-HCV and the etiology in 6% of cases was alcoholic. Alpha-foetoprotein was >400 ng/ml in only 18% of cases and portal thrombosis was present in 12%. Mononodular HCC was observed in 63% of cases (small HCC in only 38%) and in 79% was localized to the right lobe. Of the mononodular types, 70% were shown by echography to be hypoechoic, 6% hysoechoic, 6% hyperechoic and 17% mixed patterns. Histologically, 49% were well-differentiated, 45% moderately-differentiated and 6% poorly-differentiated. No correlation was found between histologic pattern and number of nodules. Well-differentiated HCC was found in 51% of mononodular types and in 46% of multinodular types. Moderately-differentiated HCC was detected in 46% and 43% respectively and poorly-differentiated HCC in 3% and 11% respectively. No correlation was found between number of nodules and the degree of Edmonson.

Protective effect of the cochlear efferent system during noise exposure.

The aim of the present study was to confirm the hypothesis that the cochlear efferent system is involved in the mechanisms underlying the "toughening" effect at high frequencies. The toughening effect is defined as a progressive threshold shift reduction when repeated exposures to the same noise are applied. Vestibular neurectomy was performed through a posterior cranial fossa approach in six healthy pigmented guinea pigs, and it assured the interruption of both crossed and uncrossed olivocochlear bundles to one ear only, before their entrance in the internal auditory meatus. The animals were then implanted with permanent electrodes for the electrocochleographic findings. Ten days after the operation the animals were exposed to octave-band toughening noise, centered at 4 kHz, at 85-dB SPL, for 10 consecutive days, 6 hours on/18 hours off. The hearing threshold was registered before and at the end of each exposure session. The behavior of the hearing threshold in the operated ears was then compared to that of the controlateral, nonoperated ears. Complete recovery from TS in the control ear began after four days of exposure, whereas in the operated ear hearing loss increased to day 7 (55 dB), with only a partial reduction (45 dB) beyond ten days of exposure. The results of the present study clearly demonstrated that sectioning of the OCB in guinea pigs causes persistent hearing loss during noise-exposure conditioning, in comparison to the contralateral, nonoperated ear. Thus, one can assume that the lack of decrease of TS during intermittent noise exposure could be due to the loss of the protective effect of the efferent fibers, perhaps mediated by the lateral OC neurons that synapse beneath the IHCs.

Laser Doppler measurement of cochlear blood flow changes during conditioning noise exposure.

Using laser Doppler flowmetry, cochlear blood flow was assessed in Mongolian gerbils exposed to noise. Anesthetized animals were surgically implanted with permanent electrodes and then exposed for 10 consecutive days (6 h on/18 h off) to an octave band noise centered at 4 kHz (85 dB SPL). The auditory brainstem responses and the blood flow in the basal turn of the cochlea were compared with those of gerbils not exposed to noise. The exposed animals developed an initial threshold shift, followed by a progressive reduction in threshold shift up to complete recovery at the end of the test. In the exposed animals, a reduction in the cochlear blood flow during the first 4 days of exposure was observed, which was then followed by a progressive increase up to the end of the test. The results of this study exclude a possible role of the microvasculature of the lateral cochlear wall in determining the resistance to 4 kHz frequency noise exposure.

[The effect of ursodeoxycholic acid in patients with liver cirrhosis and chronic hypertransaminasemia]. / Effetto dell'acido ursodesossicolico in pazienti con cirrosi epatica ed ipertransaminasemia cronica.

The aim of the study was to evaluate the effect of ursodeoxycholic acid (UDCA) oral administration on alanine aminotransferases (ALT) levels in cirrhotic patients with chronic hypertransaminasemia. Ninety consecutive patients with histologically proven liver cirrhosis and ALT levels higher than twice the upper limit of normal for at least six months, were admitted to the study. All the patients were treated with UDCA 10 mg/kg/day for one year. At the end of this period they were randomized to placebo or to continue UDCA therapy for three further months. ALT levels were evaluated before the beginning of UDCA therapy, at twelve and fifteen months by standard methods. After 12 months of UDCA, ALT decreased significantly (-39 UI, 95% confidence intervals -27 to -52 UI). At the 15 th month ALT did not vary with respect to its values at the 12th month in 36 patients randomized to continue UDCA, while it increased significantly in patients taking the placebo (+11 UI 95% confidence intervals +2 to +19). The results of this study suggest that UDCA is effective in controlling the biochemical activity of the liver disease in cirrhotic patients.

[Humoral and histological correlations in chronic aggressive hepatitis without necrotic bridges]. / Correlazioni umorali ed istologiche in corso di epatite cronica aggressiva senza ponti di necrosi.

By excluding the CALD complicated by B.H.N. we have been left with a range of C.A.H. patterns hardly distinguishable from C.P.H. on one side and from Cirrhosis on the other. We have tried to subdivide this range into three subgroups according to the extension of necrosis, fibrosis, inflammation, regeneration. Furthermore, we compared the biochemical parameters of activity of these subgroups in which we subdivided C.A.H. without B.H.N. to each other and with those of C.P.H. and C.L.H. Results shaw no statistical significative difference in the compared groups. Thus, we conclude for a priority of the histological patterns on biochemical parameters in the management of this disease.

[Partial nodular transformation of the liver. Apropos of a case]. / Trasformazione nodulare parzial del fegato. A proposito di un caso.

Partial nodular transformation is a rare disorder of the liver, that is becoming a very interesting speculative problem, in relation to the nodular regenerative hyperplasia of the liver and cirrhosis. This disease is a cause of non cirrhotic protal hypertension. Clinical and pathological aspects are discussed a propos of a case.

[The risk factors for hepatitis D viral infection in southern Italy]. / Fattori di rischio di infezione da virus dell'epatite delta nel Sud Italia.

The aims of this study were to evaluate the prevalence of hepatitis delta virus (HDV) infection and risk factors associated to it. Three hundred sixty-one HBsAg chronic carriers from southern Italy were studied and 13.8% of them resulted anti-delta positive. 80% of these subjects were less than 50 years old. When anti-delta positive subjects were compared with anti-delta negative ones, a lower number of healthy HDV carriers and a higher frequency of cirrhotics were noted among anti-delta positive. Of lower than 50 years, imprisonment, sexual contacts with drug abusers and male homosexuality were risk factors of HDV infection. No association was found with sex, household contacts with HBV or HDV carriers, number of family members and transfusion of blood products. These data confirm the high prevalence of HDV infection in southern Italy.

Validity of neuropsychological test results in disability evaluations.

A group of 50 disability claimants referred by the Social Security Administration for neuropsychological screening were administered a 36-item, forced-choice, digit-recognition method of detecting malingering to assess effort and motivation to perform well. This abbreviated form of the 1989 Hiscock and Hiscock Forced-choice Procedure has been shown to be quite easy even for individuals with severe organic brain dysfunction. A perfect performance of 36 correct on this digit-recognition task is obtained by most individuals with moderate to severe brain damage. A performance of less than 90% correct is due more likely to poor effort or even malingering rather than brain damage. In this sample, 18% (n = 9) obtained scores of less than 90% correct, i.e., < 33, which calls into question the reliability and validity of test data obtained. An additional 20% (n = 10) obtained intermediate scores of 33 to 35 correct. These intermediate scores are more difficult to interpret although at least some proportion of those scores reflects poor motivation. The results over-all indicate that nearly one-fifth of potential disability claimants produced invalid and uninterpretable neuropsychological test protocols and an additional one-fifth obtained protocols that should be well scrutinized for evidence of poor effort as well. Neuropsychologists conducting disability evaluations are urged to use measures designed specifically to assess effort and motivation.

Order effects in the administration of a forced-choice procedure for detection of malingering in disability claimants' evaluations.

100 disability claimants of the Social Security Administration referred for neuropsychological evaluation and 40 undergraduate college students asked to simulate brain damage were administered a measure for the detection of malingering, an abbreviated version of the Hiscock Forced-choice Procedure, and other neuropsychological tests. Half of each group was administered the Hiscock Procedure at the beginning of the battery; the other half was administered this test last. For both groups, the results indicated poorer performance on the earlier administration of the abbreviated Hiscock Forced-choice Procedure. Formal measures for detection of malingering should be an integral and early part of any neuropsychological evaluation in which the subject has a financial incentive to perform poorly.

[Factors influencing the effect of ursodeoxycholic acid therapy in chronic hypertransaminasemia]. / Studio dei fattori che influenzano l'effetto della terapia con acido ursodesossicolico nelle ipertransaminasemie croniche.

The aim of this work was to detect, in patients with chronic hypertransaminasemia (CH), the factors associated with the changes of ALT serum levels after one year of 10 mg/Kg/die ursodeoxycholic acid (UDCA). One hundred and twenty two consecutive patients with ALT values more than twice the normal upper limit for at least six months were admitted to the study. At the liver biopsy 82 patients were affected by liver cirrhosis (LC), 7 by chronic persistent hepatitis (CPH), and 14 by chronic active hepatitis (CAH). Nineteen patients were classified as unspecified chronic liver disease (UCLD) due to biopsy refusal. Five patients (4 LC and 1 UCLD) did not finish the study. Before and after the beginning of the treatment ALT and the other routine tests of liver function were determined in serum by routine laboratory methods. In all the diagnosis a decrease of ALT was observed after one year UDCA therapy. Particularly, in cirrhotic patients a reduction of 40% in the ALT serum levels was detected (baseline m +/- ds 98 +/- 55 UI, one year transaminase decrease -39 UI with 95% C.I. -27 UI to -52 UI). Furthermore in liver cirrhosis there was an increase of serum albumin (baseline m +/- ds 3.5 +/- 0.6, one year albumin increase +0.2 gr with 95% I.C. +0.1 gr to +0.3 gr). The decrease of ALT showed an inverse association (p < 0.05) with the presence of antibodies to hepatitis C virus and with diagnosis of CAH, and a direct one with the basal values of ALT.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies to hepatitis C virus and chronic hypertransaminasemia in southern Italy.

In an ecographic survey for gallstones, executed on a systematic sample from the municipal electoral roll of a town in Southern Italy, 164 subjects were found with ALT more than twice the upper normal limit (unl). Five years later 138 of these were re-examined; 76 still had ALT greater than 2 unl (group A), 41 still abnormal (group B) and 21 normal (group C). Anti-HCV antibodies were found in 52 subjects of group A (68%). 18 of group B (44%) and 2 of group C (9.5%). The odds ratio of ALT greater than 2 unl (A vs C) in anti-HCV+ was 20.6 and of a still elevated ALT (A + B vs C) was 14.1. Logistic regression was used to eliminate the effect of possible confounding factors (sex, age, alcohol, drugs, HBV markers) on the relationship chronic ALT increase and anti-HCV positivity but the odds ratio was still 18.9 (A vs C) and 11 (A + B vs C). These findings suggest that anti-HCV antibodies are strongly associated with chronic hypertransaminasemia at the population level in Southern Italy.

Impaired awareness of deficits in Alzheimer disease.

This study examined the relation between awareness of memory and functional decline and cognitive function in patients with Alzheimer disease (AD). Twenty-six patients with early AD and 16 nondemented elderly controls were studied. Awareness of deficits was determined by using (a) a discrepancy score between subject's and caregiver's ratings on a memory questionnaire, (b) a discrepancy score between subject's and caregiver's ratings on an activities-of-daily-living scale, and (c) a clinical rating of dementia awareness for patients. Whereas self-ratings of memory and activities of daily living were not significantly different between AD patients and controls, these two measures differed significantly when AD patients' ratings were compared with those of their caregivers. Measures of awareness of deficits correlated with one another and were primarily associated with performance on tests of executive and visuospatial functions but not with depression. Early AD is characterized by a failure of self-monitoring. Deficits in self-monitoring have been proposed to occur after damage to the frontal lobes and other cerebral areas. Impaired awareness of memory and functional deficits in AD is related to cognitive impairments, which may involve frontal and right hemisphere connections.

Hepatitis C virus genotypes and risk of cirrhosis in southern Italy.

Because hepatitis C virus (HCV) genotypes have raised considerable interest as variables that influence chronic hepatitis C progression, a case-control study was conducted to estimate their effects on patients with cirrhosis. Case patients (n = 46) had tested positive for anti-HCV antibody and HCV RNA and were residents of the study area who had cirrhosis recently diagnosed. Controls (n = 138) were drawn randomly from a residents' cohort from the same area. Demographic and other information were recorded. Presence of HCV infection, presence of HCV RNA, and HCV genotypes were assessed. Crude, stratified, and logistic regression analyses were performed. HCV genotype 2a/c occurred in 84 controls (60.9%) and 9 case patients (19.6%); HCV genotype 1b was found in 45 controls (32.6%) and 34 case patients (73.9%). HCV 1b genotype showed an independent effect on the risk of cirrhosis (odds ratio, 7.49; 95% confidence interval, 3.15--17.81). No significant effects related to other variables were observed. These results indicate that the genetic diversity of HCV phylogenetic variants may explain differences in biological behaviors.