Paulo Borini

Possible hepatotoxicity of chronic marijuana usage

CONTEXT Hepatotoxicity is a potential complication from the usage of various illicit drugs, possibly consequent to their liver metabolism, but information on this is scarce in the medical literature. OBJECTIVE To study the occurrence of clinical and laboratory hepatic alterations in chronic marijuana users, from the use of marijuana on its own or in association with other legal or illicit drugs. TYPE OF STUDY transversal study SETTING Hospital Espírita de Marília, Marília, São Paulo, Brazil PARTICIPANTS The study was made among 123 patients interned in the Hospital Espírita de Marília from October 1996 to December 1998, divided into 3 groups: 26 (21%) using only marijuana, 83 (67.5%) using marijuana and crack, and 14 (11.4%) consuming marijuana and alcohol. PROCEDURES AND MAIN MEASUREMENTS: Patients were examined clinically with special emphasis on types of drugs used, drug intake route, age when consumption began, length and pattern of usage, presence of tattooing, jaundice, hepatomegaly and splenomegaly. Serum determinations of total proteins, albumin, globulin, total and fractions of bilirubin, aspartate (AST) and alanine (ALT) aminotransferases, alkaline phosphatase (AP), gamma-glutamyltransferase and prothrombin activity were performed. RESULTS Among users of only marijuana, hepatomegaly was observed in 57.7% and splenomegaly in 73.1%, and slightly elevated AST (42.3%), ALT (34.6%) and AP (53.8%). The three groups did not differ significantly in the prevalence of hepatomegaly, splenomegaly and hepatosplenomegaly. The group using both marijuana and alcohol showed the highest prevalence of alterations and highest levels of aminotransferases. Mean AP levels were above normal in all groups. CONCLUSIONS Chronic marijuana usage, on its own or in association with other drugs, was associated with hepatic morphologic and enzymatic alterations. This indicates that cannabinoids are possible hepatotoxic substances.

ETIOPATHOGENESIS OF PEPTIC ULCER: back to the past?

OBJECTIVES To review some aspects of the etiopathogenesis of peptic ulcerous disease especially on the basis of studies on its correlation with Helicobacter pylori (H. pylori). METHODS A search was made in the data bases MEDLINE, LILACS and PubMed, and in Brazilian and foreign books, referring to the incidence and prevalence of infection by H. pylori and of peptic ulcerous disease in various populations of different countries. RESULTS It was observed that the prevalence of H. pylori infection is similar in individuals with peptic ulcerous disease and the general population. There are differences between countries with respect to the prevalence of infection and of gastric or duodenal peptic ulcers. In many countries the prevalence of infection by H. pylori shows stability while the prevalence of peptic ulcerous disease is declining. The prevalence of peptic ulcerous disease without H. pylori infection varies between 20% and 56% in occidental countries. DISCUSSION The observations might be suggestive of H. pylori being only one more factor to be summed together with other aggressive components in the genesis of peptic ulcerous disease. We would therewith be returning to the classic concept that peptic gastric and duodenal ulcers have multifactorial etiology and would result from imbalance between aggressive and defensive factors. The focus of studies should be enriched with the identification of the defensive factors and of other aggressive factors besides the well known H. pylori and non-steroidal anti-inflammatory drugs, since these two aggressors do not exhaust the full causal spectrum.

Indicators of inflammation and cellular damage in chronic asymptomatic or oligosymptomatic alcoholics: correlation with alteration of bilirubin and hepatic and pancreatic enzymes

Biochemical and hematimetric indicators of inflammation and cell damage were correlated with bilirubin and hepatic and pancreatic enzymes in 30 chronic male alcoholics admitted into psychiatric hospital for detoxification and treatment of alcoholism. Aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, and total bilirubin were altered, respectively, in 90%, 63%, 87%, 23% and 23% of the cases. None of the indicators of inflammation (lactic dehydrogenase, altered in 16% of the cases; alpha-1 globulin, 24%; alpha-2 globulin, 88%; leucocyte counts, 28%) was correlated with alterations of bilirubin or liver enzymes. Lactic dehydrogenase was poorly sensitive for detection of hepatocytic or muscular damage. Alterations of alpha-globulins seemed to have been due more to alcohol metabolism-induced increase of lipoproteins than to inflammation. Among indicators of cell damage, serum iron, increased in 40% of the cases, seemed to be related to liver damage while creatine phosphokinase, increased in 84% of the cases, related to muscle damage. Hyperamylasemia was found in 20% of the cases and significantly correlated with levels of bilirubin, alkaline phosphatase and gamma-glutamyltransferase. It was indicated that injuries of liver, pancreas, salivary glands, and muscle occurred in asymptomatic or oligosymptomatic chronic alcoholics.

Liver synthesis function in chronic asymptomatic or oligosymptomatic alcoholics: correlation with other liver tests

Liver function and its correlation with bilirubin and hepatic enzymes were evaluated in 30 male chronic asymptomatic or oligosymptomatic alcoholics admitted into the psychiatric hospital for detoxification and treatment of alcoholism. Hypoalbuminemia, lowered prothrombin activity, hypotransferrinemia and hypofibrinogenemia were detected in 32%, 32%, 28%, and 24% of patients, respectively. Transferrin was elevated in 8%. Greater prevalence of hyperbilirubinemia was found in patients with lowered prothrombin activity, hypofibrinogenemia, or hypotransferrinemia. No correlation was found between serum bilirubin or aminotransferase levels and normal or elevated albumin levels, time or activity of prothrombin, and fibrinogen levels. Serum alkaline phosphatase was elevated in normoalbuminemics and gamma-glutamyltransferase in patients with lowered prothrombin activity. Hypoalbuminemia was associated with hypofibrinogenemia, hypotransferrinemia with elevated aspartate aminotransferase or gamma-glutamyltransferase, and hypertransferrinemia with elevation of alanine aminotransferase. These data indicated the occurrence of hepatic dysfunction due to liver damage caused directly by alcohol or by alcoholism-associated nutritional deficiencies.

Prevalência do "dedo em baioneta": uma manifestação do distúrbio de hiperatividade e déficit de atenção entre alcoolistas e psicóticos do sexo masculino

The prevalence of Bajonettfinger, a semiologic sign of attention-deficit disorder hyperactivity (ADHD), was determined in male alcoholics and psychotics from a psychiatric hospital. A control group was taken from the hospital staff. The morphologic alteration was observed in 35% of the 200 alcoholics, 45% of the 100 psychotics and 16% of the 50 controls. The difference in prevalence of the sign between the alcoholics and psychotics groups was not significant but the differences between any of these groups and the controls was significant. The observations suggested that: (1) ADHD would be present, as judged through its high correlation with the prevalence of bajonettfinger, in approximately 1/3 of the alcoholics and 1/2 of the psychotics; (2) ADHD would be a vulnerability factor for alcoholism; (3) adolescents with bajonettfinger should deserve special preventive attention with respect to alcoholism.

Histopathologic and biochemical liver test abnormalities in chronic asymptomatic or oligosymptomatic alcoholics: a review

PURPOSE To review the medical literature regarding the histopathologic and biochemical liver test abnormalities in chronic asymptomatic or oligosymptomatic alcoholics. METHODS Review of articles in the MEDLINE and LILACS databases regarding serum levels and prevalence of alterations in aspartate-aminotransferase, alanine-aminotransferase, alkaline phosphatase, and total bilirubin, in relation to liver histopathology, with or without discrimination of types of histopathologic alteration. RESULTS Global mean prevalence rates of aspartate-aminotransferase and alanine-aminotransferase alterations were 86.3% and 51.1%; in cases with steatosis they were 79.1% and 38.5%; and in cases of hepatitis, 90.1% and 58%. In all studies, prevalence rates of aspartate-aminotransferase alterations were significantly higher with lower variability than those of alanine-aminotransferase. Mean aspartate-aminotransferase levels were higher than 2N (N is the upper normal limit of the method employed) in all cases with hepatitis histopathology, while those of alanine-aminotransferase were 1.48N, in the same cases. Prevalence of alkaline phosphatase and total bilirubin abnormalities were 74.5% and 74.9% globally; in cases of steatosis, they were 70.9% and 67.9%; and in cases of hepatitis, 75.9% and 77.7%. Mean alkaline phosphatase levels were above the upper normal limit in all cases, but those of total bilirubin were above normal in 4 of 7 hepatitis studies. CONCLUSIONS Prevalence of aspartate-aminotransferase alteration was consistently related to presence of histopathologic abnormalities; an enzyme level higher than 2N suggests the diagnosis of alcoholic hepatitis.

Alcoolismo e sífilis: prevalência e alterações clínicas e bioquímicas hepáticas

The prevalence of syphilis in chronic alcoholics and the hepatic clinical and biochemical alterations were evaluated in patients with both entities. The prevalence of syphilis in patients with other psychiatric diagnosis was taken as control. The patients were asymptomatic or oligosymptomatic with respect to hepatic alcoholic dysfunction or to any manifestation of the three clinical stages of syphilis. Alcoholics (206 patients) and patients with other psychiatric conditions (228 patients) were submitted to clinical examination and to quantitative serology for syphilis (Wasserman and VDRL), yielding 6.3% and 3.1% of seropositivity, respectively. No statistically significant difference was observed between alcoholics of the seropositive or seronegative groups, as to the frequencies of clinical or biochemical alterations which would indicate hepatic alterations.The prevalence of syphilis in chronic alcoholics and the hepatic clinical and biochemical alterations were evaluated in patients with both entities. The prevalence of syphilis in patients with other psichyatric diagnosis was taken as control. The patients were asymptomatic or oligo-symptomatic with respect to hepatic alcoholic dysfunction or to any manifestation of the three clinical stages of syphilis. Alcoholics (206 patients) and patients with other psichyatric conditions (228 patients) were submitted to clinical examination and to quantitative serology for syphilis (Wasserman and VDRL), yielding 6.3% and 3.1% of seropo-sitivity, respectively. No statistically significant difference was observed between alcoholics of the seropositive or seronegative groups, as to the frequencies of clinical or biochemical alterations which would indicate hepatic alterations.

Alterações clínicas e laboratoriais anteriores ao desenvolvimento do delirium tremens

Duzentos e trinta pacientes alcoolistas cronicos do sexo masculino internados em hospital psiquiatrico para tratamento do alcoolismo foram examinados clinica e laboratorialmente dentro das primeiras 24 horas da internacao. Treze pacientes que desenvolveram delirium tremens (DT) apos a internacao (grupo I) constituem a casuistica deste estudo que visa avaliar a ocorrencia de alteracoes clinicas, hematologicas, bioquimicas hepaticas e eletroliticas que antecedem ao aparecimento das manifestacoes do DT. Para analises comparativas foram estudados dois grupos de 26 pacientes cada um, constituidos de pacientes que nao entraram em DT na internacao atual mas com historia pregressa de DT (grupo II) e pacientes aleatoriamente arrolados - amostra aleatoria simples obtida empregando tabela de numeros aleatorios fornecida por computador - que nunca entraram em DT (grupo III). Os pacientes do grupo I apresentavam media de idade significativamente mais baixa e fisicamente encontravam-se em pior estado geral que os do grupo III. As frequencias de taxas elevadas de aminotransferases e de hipomagnesemia foram significativamente maiores nos grupos I e II que no grupo III. Os valores plasmaticos medios das aminotransferases, especialmente da aspartato-aminotransferase, estavam significativamente mais elevados nos grupos I e II que no grupo III.