Biomedical subjects
Publications and source records attributed to G Giusti.
A six-month analysis of a controlled trial on the treatment of chronic hepatitis B in children shows that prednisone priming followed by alpha-interferon 2A was effective in 6 of 9 treated patients in reducing HBV replication and disease activity.
Typhoid fever is endemic in the Neapolitan area, where its yearly incidence rate largely exceeds the corresponding national figure. During the period from January to June, 1990, a matched case-control study was carried out in order to identify risk factors of the disease in this area; 51 subjects (mean age 27.2 years) with typhoid fever were compared with 102 controls matched with respect to age, sex and educational level. Consumption of raw shellfish was reported by 76.5% of the cases, as opposed to 19.6% of the controls (P < 0.01). Subjects who had eaten this food item had a 13.3-fold risk (C.I. 95% = 5.5 - 32.8) of contracting typhoid fever. In contrast, no risk was found to be associated with consumption of cooked shellfish, raw vegetables, ice-cream, non-potable water, or unpasteurized milk. The risk factor identified in this study shows that hazardous dietary habits and inadequate sewage treatment facilities, combined with lack of sanitation in the harvesting and marketing of shellfish, play a major role in the endemicity of typhoid fever in the Neapolitan area.
The epidemiology of HDV infection in Italy was assessed in a retrospective study involving 1556 HBsAg chronic carriers on their first presentation at one of the 35 Liver Units in 1987. Total anti-HD was detected in 23.4% of HBsAg carriers and was significantly more frequent in southern than in northern Italy (26.6% vs. 19.1%, p less than 0.01). Age distribution showed that 73% of the anti-HD-positive subjects, but only 56% of the anti-HD-negative subjects, were under 40 years of age (p less than 0.01). Anti-HD prevalence increased with the severity of the liver disease from 3.8% in healthy carriers to 42.5% in cirrhosis. No geographical statistical difference was found among HBsAg healthy carriers or subjects with chronic persistent hepatitis (CPH), while among patients with chronic active hepatitis (CAH) or cirrhosis anti-HD prevalence was much higher in the south (p less than 0.01). The various potential risk factors were evaluated by multiple logistic regression analysis. HDV infection was independently related to young age, residence in the south, i.v. drug abuse, a large family and household contact with an anti-HD-positive carrier. No association was found with blood transfusion or male homosexuality. These findings confirm that HDV infection is endemic in Italy, particularly in some southern areas, where intrafamily contact probably at a young age may favour the spread of the infection.
Hepatitis A is a worldwide disease transmitted by oral-fecal route, the endemicity level is high in developing countries and in the Far East. In northern Europe the endemicity level is low, but it is intermediate in the European Mediterranean area. Seroepidemiological surveys show that in Italy, as in many other European countries, hepatitis type A endemicity is declining. Therefore, immunity to infection shifts towards the older generations, leaving an increasing number of teenagers and young adults susceptible to the infection. Since in adults the infection is associated with higher levels of morbidity and mortality than in children, hepatitis A remains a public health problem. Moreover, travellers visiting an endemic area are at risk of acquiring the disease. Short-term, passive immunization with immune serum globulins is not a satisfactory method of controlling hepatitis A. The best way of controlling HAV endemicity is vaccination and a satisfactory vaccine will be available by 1993. Soon after HAV propagation in cell culture was achieved, three different approaches to HAV vaccine production were investigated: recombinant vaccines, live attenuated vaccines, inactivated vaccines. The production of a recombinant vaccine is, as yet, unavailable, because two HAV surface proteins linked together in a definite three dimensional configuration are needed to stimulate an effective immune response. A satisfactory live attenuated vaccine has not yet been obtained because of difficulties in maintaining a stable level of attenuation. Consequently, attention has shifted towards inactivated vaccines, and the HM 175 strain inactivated vaccine has been produced and widely studied in over 25,000 human volunteers.(ABSTRACT TRUNCATED AT 250 WORDS)
Cefodizime is a stable new beta-lactamase cephalosporin chemically related to cefotaxime and with a long half-life. Its clinical efficacy and tolerability were compared with those of norfloxacin in patients with intercurrent urinary tract infections plus chronic liver diseases. Cefodizime (2 g, once a day, i.v.) and norfloxacin (400 mg, twice a day, p.o.) were randomly given to two groups of 20 patients each with urinary tract infections caused by organisms sensitive in vitro to these drugs. Cultures of midstream bladder urine, urinalysis and blood biochemical tests were performed before and after each antibiotic treatment. Clinical resolution was observed in 100% of the patients at the end of the treatments, but bacteriological eradication was obtained in 90% of the patients treated with cefodizime and 85% of those treated with norfloxacin, because of the development in five patients of asymptomatic bacteriuria (superinfections).
We investigated the effects of the antimycotic agent amphotericin B (AmB) on the phagocytic activity of the isolated perfused rat liver. At a concentration of 5 microM, the drug markedly reduced the clearance of latex beads by the liver as compared to control preparations. Scanning electron microscopy observations showed that latex beads were attached only to Kupffer cells. A liver scan performed infusing 99Tc-colloidal albumin showed that AmB depressed the uptake of the colloid in all hepatic lobes, with no focal defects. Both in control and AmB experiments no trypan blue uptake occurred. The pretreatment of the perfused liver with the calcium antagonist nifedipine prevented the decrease in phagocytosis induced by AmB. In addition, AmB had no effect on livers perfused with a Ca2(+)-free medium. A decrease in the phagocytic capacity of the perfused liver was also observed after the administration of the Ca2(+)-ionophore A23187. The observations suggest that AmB may exert an intrinsic toxicity on the Kupffer cells, which is, at least in part, responsible for the decrease in phagocytosis induced by the drug. This effect may be of relevance to clinical situations and deserves careful consideration.
In the Neapolitan area the prevalence of adult HBsAg carriers ranges from 4-7%. Moreover, hepatitis B virus (HBV) is responsible for most of the chronic hepatitis cases in childhood. Since the chronic carrier state in our area is acquired by early horizontal contact, we investigated the prevalence of HBV infection among 207 pre-school children and of HBsAg carriers among their family members. None of the children was found to be HBsAg positive and 3.9% of them had anti-HBs. HBsAg was positive in 29 out of 892 (3.3%) of the family members. There was a clear age-related distribution of the carriers, their prevalence reaching 6.7% among the elderly members. On the whole, 19 out of the 207 index cases had at least one HBsAg carrier in their family. The results suggest that in our area a decline of HBV endemia may be under way and that early intrafamily contact is no more a common pathway in acquiring an HBsAg carrier state.
Explore the source record for details and available documents.
The prevalence of anti-HCV and anti-HBV antibodies was investigated in a series of 77 adult patients with HBsAg negative, non autoimmune chronic liver disease. Anti-HCV were found in 68% and anti-HBc in 71% of the cases; 68% of the patients carried both antibodies. There was no difference in the proportion of anti-HBc positive cases between the anti-HCV positive or negative patients. The intense circulation of HBV infection in Southern Italy during the past decades might explain the high percentage of subjects with anti-HBc. Whether the co-occurrence of HCV and HBV infection may influence the natural history of the liver disease, remains to be established.
In an attempt to identify some characteristics of HDV infection in the different forms of HBsAg positive chronic hepatitis (CH), we evaluated numerous clinical, biochemical and histological aspects in 203 consecutive HBsAg positive CH patients. The presence of hepatitis delta antigen (HD-Ag) in the liver tissue was the criterion used to identify HDV infection. HD-Ag was observed in none of the 7 patients with non-specific reactive hepatitis, in 14.6% of the 48 with chronic persistent hepatitis (CPH), in 36.4% of the 44 with chronic lobular hepatitis (CLH), in 36% of the 25 with mild chronic active hepatitis (CAH), in 52% of the 36 with severe CAH and in 30.2% of the 43 with inactive or moderately active cirrhosis. Compared with the 139 HD-Ag negative patients in this study, the 64 HD-Ag positive patients more frequently had severe CAH (29.7 vs. 12.2%, p less than 0.01) and less frequently CPH (10.9 vs. 29.5%, p less than 0.01). Of the 139 HD-Ag negative patients, 80 were anti-HD positive and 59 anti-HD negative. The 59 patients with no HD-Ag or anti-HD showed severe CAH less frequently than the 64 HD-Ag positive patients (6.8 vs. 29.7, p less than 0.01) and CPH more frequently (44.1 vs. 10.9, p less than 0.001). Both in CPH and CLH the presence of HD-Ag in the hepatocytes identified subgroups of patients who frequently showed high serum levels of aminotransferases and gammaglobulins and more extended areas of circumscribed lobular necrosis. HD-Ag positive CAH was characterized by a more frequent occurrence of eosinophilic degeneration of hepatocytes without peripolesis (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
We studied the effects of presynaptic dopamine (DA) 2 receptor blockade on the sympathetic-adrenal response to graded exercise in seven normal men. DA2 receptor blockade was achieved by means of domperidone (DMP) administration. The exercise consisted of progressive cycling activity, from 30-80% of the predetermined maximal oxygen consumption for each man. Systolic, diastolic, and mean arterial pressures; heart rate; and plasma norepinephrine (NE), epinephrine (E), PRL, glucose, lactate, FFA, sodium, potassium, cortisol, and PRA were measured at rest, during exercise, and during recovery after placebo or DMP administration. Graded exercise caused significant increases in systolic and mean arterial pressures and plasma NE, E, lactate, sodium, potassium, FFA, cortisol, and PRA. DMP administration before exercise caused a significant increase in plasma PRL (P = 0.0009), a greater increase in plasma NE at the end of the exercise (P = 0.002), and an overall increase in plasma E (P = 0.02) and FFA (P = 0.02) concentrations. These results strongly suggest that endogenous DA limits catecholamine release during sympathetic-adrenal stimulation by activating DA2 receptors.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The role of surgery as an additional risk in transmitting "post-transfusion" hepatitis was investigated in a retrospective study on acute hepatitis occurring in 77 transfused patients, 293 transfused and operated patients and 243 hepatitis cases with history of surgery without transfusion. Hepatitis A patients admitted to the same centres in the same period were utilized as controls. In transfused patients the percentage of NANB hepatitis was higher than that of type B (61.0% vs. 36.4%), while in the operated not transfused group the percentage of type B was twice that of type NANB (63.4% vs. 32.5%). In transfused and operated cases intermediate values were observed. The age-adjusted measures of association between exposures and the different hepatitis types showed a lack of effect of transfusion and a dominant role of surgery in transmitting type B hepatitis. In contrast, NANB "post-transfusional" cases were actually a mixture of post-transfusional and post-surgical cases, since both these exposures were found to be significantly associated with the disease. Our results suggest that studies on the incidence and the etiology of post-transfusion hepatitis should take into account the risk of surgical exposure which might have occurred.
To evaluate whether opioid receptor blockade might modulate sympathetic-adrenal activity, we studied the effects of placebo or naloxone administration on plasma catecholamine (CA) levels in a group of 13 normal subjects and 15 hypertensive patients suspected to have a pheochromocytoma. Diagnostic evaluation confirmed the presence of pheochromocytoma in 9 patients. Among these, 4 had a unilateral epinephrine (E)-secreting tumor, 3 had bilateral E-secreting tumors due to multiple endocrine adenomatosis type IIa, and 2 had a unilateral norepinephrine (NE)-secreting tumor. In each subject studied, CA secretion was evaluated by calculating the area (0-30 min) under the plasma hormone curves after placebo or naloxone administration. In normal subjects naloxone caused a significant increase (P less than 0.005) of E secretion, whereas NE did not change. Similarly, in the group of hypertensive patients, E secretion increased after naloxone (P less than 0.01). In pheochromocytoma patients naloxone caused a significant increase in E (P less than 0.05) and NE (P less than 0.01) secretion from E-producing tumors but no increase in the patients with NE-secreting pheochromocytomas. The study suggests that CA secretion from normal and pathological chromaffin tissue is modulated by endogenous opioids; this modulation seems particularly evident in patients with E-secreting pheochromocytoma.
To investigate the mechanisms of erythromycin cholestasis, the effects of erythromycin estolate (EE) on the excretory function of the isolated perfused rat liver and on liver plasma membrane (LM) preparations were studied and compared to those of erythromycin base (EB) and lauryl sulfate (LS), added alone or in combination. EE (at 125 to 200 microM) caused dose-dependent reductions of bile and perfusate flows, bile acid (BA) excretion, and biliary BA concentration. The alterations of the excretory function were only in part due to the decreased perfusate flow. In contrast, both 200 and 300 microM concentrations of EB elicited similar choleretic responses, which were presumably related to the osmotic activity of the drug excreted in the bile. LS did not affect hepatic excretory functions. However, the simultaneous addition of EB and LS resulted in a rate of bile flow lower than that observed with EB alone. EE, but not EB, increased canalicular permeability to [14C]sucrose as measured by bile to plasma (B:P) ratio. Neither drugs altered [14C]erythritol B:P ratio. In LM preparations both Na+,K+- and Mg2+-ATPase activities were inhibited in a dose-dependent manner by EE, but not by EB. The data suggest that EE could affect bile flow by inhibiting cotransport of Na+ and BA and by altering LM permeability and support the view that the effect of erythromycins on the liver may be related to their surface activity.
The effects of placebo and DA2 antidopaminergic agents on basal and stimulated catecholamine (CA) plasma levels in humans have been evaluated by administration either of domperidone or metoclopramide to separate groups of subjects. The latter group was subjected domperidone to sympathetic stimulation by handgrip coldpressor tests, and standing. Pharmacological DA2 receptor blockade, either peripheral by or central and peripheral by metoclopramide, did not modify plasma CA whilst resting or during acute sympathetic stimulation. It is concluded that endogenous dopamine does not seem to play a significant role in modulating NE release in man, at least not under the physiological conditions examined.
Explore the source record for details and available documents.