[Hepatic and pancreatic disease in patients with acquired immunodeficiency syndrome (AIDS)]. / Patologie epatiche e pancreatiche in pazienti con sindromi da immunodeficienza acquisita (AIDS).

AIDS is frequently expressed through gastrointestinal o abdominal symptoms. In addition, patients with AIDS or ARC frequently have hepatic and biliary symptoms, while pancreatic alterations are found in 4-30% of patients hospitalised for AIDS. Since AIDS patients are immunodepressed, they are subject to opportunistic infection often multifocal and the pathological processes can be present simultaneously. About 2/3 of patients have enlarged liver, steatosis, splenomegaly, lymphoadenopathy, cholecystic and biliary tract abnormalities, alterations of liver function tests, and abdominal discomfort in the upper right quadrant. Jaundice is rare and hepatic failure is not common. Hepatic biopsy is often necessary to establish the diagnosis. The hepatic localisation of an opportunistic pathogenic agent is generally a sign of systemic dissemination which is expressed as granulomatous hepatitis (atypical mycobacteria, frequently mycobacterium avium, or M. tuberculosis representing the reactivation of latent diseases), peliosis hepatis, infection from CMV, HSV, EBV, Pneumocystis carinii, and mycotic infections. Coinfections with the hepatic virus (HBV, HDV, HCV) are also often present. Pharmacological damage may also be present (mainly caused by antibiotic therapies). Neoplasia are rare (hepatic Kaposi's sarcoma associated with cutaneous and gastrointestinal manifestations, or generally metastatic lymphoma). Damage of the biliary tract usually develops after other manifestations of the illness; the most frequent pictures are cholestatic syndromes and cholangitis, while cholecystitis and jaundice are rare. Pancreatic lesions are generally asymptomatic. They are diagnosed during autopsy and are caused principally by opportunistic agents.

Activation of the ornithine decarboxylase-polyamine system and induction of c-fos and p53 expression in relation to excitotoxic neuronal apoptosis in normal and microencephalic rats.

Microencephalic rats obtained by gestational treatment with the DNA alkylating agent methylazoxymethanol, show a remarkable lack of sensitivity to excitotoxic neuropathology caused by systemic injections of the convulsant neurotoxin kainic acid. Taking advantage of this, we have studied in these rats, as well as in normal rats, the relationship between the induction of cellular signals supposedly related to cell death and the neuronal apoptosis consequent to kainic acid administration. While normal rats responded to the excitatory insult with a large and relatively long lasting increase of the activity of the enzyme ornithine decarboxylase and of the concentration of putrescine in some brain regions, these alterations were much smaller in microencephalic rats. Expression of c-fos in brain regions sensitive to kainic acid was quicker but lasted a noticeably shorter time in microencephalic rats as compared to normal animals. A profusion of apoptotic neurons, labeled by an in situ technique, were observed in the olfactory cortex, amygdala and hippocampus of normal rats injected with kainic acid, in particular 48 h and 72 h after drug administration. At corresponding time intervals and with similar topographic localization, neurons expressing p53 protein were observed. By contrast, microencephalic rats displayed only in a few cases and in a small number apoptotic neurons in restricted areas of the ventral hippocampus and entorhinal cortex. Noticeably, in these cases small populations of p53-expressing neurons were also present in the same areas. The present observations clearly show that oncogenes such as c-fos and p53, as well as ornithine decarboxylase which behaves as an immediate-early gene in the brain under certain circumstances, undergo noticeably lower and/or shorter induction in microencephalic rats exposed to excitotoxic stimuli. In these rats, therefore, the cellular signalling pathways studied here and related to excitotoxic sensitivity and commitment to cell death are downregulated as a probable consequence of altered brain wiring.

Serum lipid and lipoprotein patterns in patients with liver cirrhosis and chronic active hepatitis.

BACKGROUND: An impaired lipid metabolism is often found in patients with chronic liver diseases. Unfortunately, few studies are available concerning serum lipid and lipoprotein levels in patients with liver cirrhosis and chronic active hepatitis (CAH). OBJECTIVES: To evaluate low-density lipoprotein (LDL), high-density lipoprotein (HDL), very low-density lipoprotein (VLDL), and total cholesterol serum levels in patients with cirrhosis and CAH and control patients and to relate the findings to the severity of the cirrhosis (Child classification). METHODS: We measured the serum lipid pattern in 34 consecutive patients with liver cirrhosis (15 men and 19 women; mean [+/-SD] age, 55 +/- 14 years; Child classes: 14 in A, 9 in B, 11 in C; patients with biliary cirrhosis were excluded), 34 patients with CAH, and 34 control patients. The 3 groups were matched for sex and age. Total serum, HDL cholesterol, and triglyceride levels were measured by enzymatic methods; serum LDL and VLDL levels were calculated. RESULTS: In patients with cirrhosis, there was a significant decrease in LDL, HDL, and total cholesterol serum levels compared with both the patients with CAH and the control patients, while the VLDL cholesterol level in patients with cirrhosis was significantly lower compared with the control patients alone. A significant decrease in total cholesterol levels was also observed in the CAH group when compared with the control patients. In patients with cirrhosis, levels of LDL, HDL, and total serum cholesterol were progressively lower when comparing patients in Child class A with patients in class C. CONCLUSIONS: In this study, the striking decrease in the level of serum LDL cholesterol in patients with liver disease was related to the increasing severity of the disease. Accordingly, the assessment of the serum LDL cholesterol level is important for an effective treatment and prognostic evaluation of patients with chronic liver disease.

Flutamide-induced toxic hepatitis. Potential utility of ursodeoxycholic acid administration in toxic hepatitis.

Flutamide is a nonsteroidal antiandrogen commonly used in the treatment of prostate cancer. Hepatic toxicity associated with flutamide has been reported with an incidence from less than 1% to about 5%. Ursodeoxycholic acid (UDCA), a hydrophilic bile acid, has been widely used in the treatment of cholesterol gallstones and of several liver diseases, but few data are now available concerning its use in the management of drug-induced hepatitis. The case of a patient who presented severe hepatitis with jaundice following use of flutamide is reported. UDCA treatment was started on admission and, contemporaneously, flutamide was withdrawn. Clinical and biochemical improvement was progressively observed, and the patient was discharged six weeks after the admission. Since fatal flutamide-related hepatitis has been reported, monitoring of serum liver tests is advocated during flutamide administration, and the effectiveness of UDCA in the treatment of drug-induced hepatotoxicity requires further study.