Biomedical subjects
Publications and source records attributed to M Chiaramonte.
Only a single case of Graves' disease has been reported so far in Primary Biliary Cirrhosis (PBC), whereas hypothyroidism is a rather common association. We report two cases of hyperthyroidism associated with PBC. A common pathogenic mechanism involving HLA II class antigens is suggested.
Plasma lipids, apoprotein A-I and B in serum and in lipoprotein fractions (VLDL + LDL, HDL2, and HDL3) obtained by preparative ultracentrifugation, as well as postheparin lipoprotein lipase activity (H-TGL and LPL) were evaluated in 17 subjects with primary biliary cirrhosis (stage II and III) subdivided into two groups according to the presence or absence of lipoprotein X (Lp-X). A reduction in total lipoprotein lipase activity was observed in both patient groups, compared to controls (P less than 0.01); the hepatic lipoprotein lipase was significantly reduced (P less than 0.01) only in the Lp-X-positive group. The lipid (477.8 +/- 154.3 vs 239.6 +/- 51.1; P less than 0.01) and protein (147.4 +/- 37.1 vs 83.3 +/- 19.7; P less than 0.01) masses in the VLDL + LDL fraction of the Lp-X-positive group were increased compared to controls. In the same group, the HDL2 fraction also showed an increase in lipid (186.6 +/- 80.0 vs 77.9 +/- 21.6; P less than 0.01) and protein (133.9 +/- 60.0 vs 67.9 +/- 16.5; P less than 0.01) masses; in addition, the HDL2 percent lipid composition was different in the two patient groups, showing a decrease in esterified cholesterol (20.4 +/- 3.6 vs 25.7 +/- 2.2; P less than 0.01) and an increase in phospholipids (59.2 +/- 2.9 vs 54.8 +/- 2.6; p less than 0.01) in the Lp-X-positive group.(ABSTRACT TRUNCATED AT 250 WORDS)
Hepatitis B infection in the aged can be underestimated as the clinical and serological pictures can be rather peculiar in these subjects. Institutions for the elderly carry an increased risk of HBV spread as do many other closed communities. People from lower socioeconomic class and from countries with a high HBV prevalence are less susceptible to infection as they are already immunized by previous infections. However, epidemics have been described in homes for the aged, mostly from those for wealthy people or from those in low prevalence countries. When infected the elderly tend to develop a subclinical hepatitis detected only by serum analysis. These infections are frequently followed by asymptomatic chronic carriage of HBsAg. This phenomenon may be due to alterations of the immune system in the aged, which is also suggested by the finding of very poor antibody responses to hepatitis B vaccines in the aged. Overt acute hepatitis is infrequent. It usually have a benign course, even if occasionally cholestatic. Very active type B chronic hepatitis is very rare, while most elderly patients with HBsAg-positive chronic liver disease have cirrhosis as the end stage of chronic hepatitis acquired previously.
The authors describe a 15-month follow-up of twenty-nine nurse students vaccinated against hepatitis B with Hevac B Pasteur. At three months all subjects were anti-HBs positive, with a geometric mean titre (GMT) of 1187 mIU/ml. At the time of booster dose (T14) GMT had fallen to 380 mIU/ml; after one month (T15) GMT had risen again to 9332 mIU/ml. Such a high antibody level suggests a long lasting protection.
Protein A-bearing Staphylococcus aureus organisms (STA) were used to separate free HBeAg from IgG-bound HBeAg. Free HBeAg was detected in the supernate while IgG-bound HBeAg could be liberated from the pellets using MgCl2 or a glycine buffer. HBeAg was determined by radioimmunoassay and the results expressed as patient's cpm/normal control's cpm ratio (S/N ratio). This ratio was demonstrated to be proportionate to the antigen concentration and used as a titer of HBeAg. Sera of 40 HBsAg-negative healthy volunteers and 82 HBeAg-positive patients who were either asymptomatic HBsAg carriers or had various diseases including chronic persistent hepatitis (CPH), chronic active hepatitis (CAH), and renal disease undergoing hemodialysis, were tested for free HBeAg and IgG-bound HBeAg. Patients with CAH from two different countries were compared. Free HBeAg was detected in all patients but one, IgG-bound HBeAg was detected with similar prevalences (from 56% to 67%) in HBsAg asymptomatic carriers, hemodialysis patients, CPH and Italian CAH patients. In contrast, all CAH patients from New York, who had frequently been exposed to HBV infection, had detectable levels of IgG-bound HBeAg, with the highest S/N ratios observed in the study, and frequently showed an unfavorable outcome. In AVH due to HBV and delta agent co-infection, IgG-bound HBeAg was detected in two of four patients only in the initial stage of the disease. The data reported indicate that a separate determination of free- and IgG-bound HBeAg may have clinical value.
The prevalence of antiHA was assessed in 594 hospital employees and in control groups comprising 932 "healthy" adults not working in the hospital, selected from different socioeconomic classes. Age specific antiHA prevalence which was lower in doctors than in nurses and ancillary staff, was also found to be lower in each group than in the respective controls, matched according to socioeconomic criteria. It is concluded that in our population (i.e. high risk area) the hospital environment does not involve an increased risk of HAV infection for personnel. However, precautions should be taken when working in high risk department, as this study demonstrated that a considerable proportion of health care workers (above all doctors) are still susceptible to Hepatitis A virus infection.
In 35 patients with chronic pancreatitis, C3, C4, s-immunoglobulins, circulating immunocomplexes and T-lymphocytes were assessed in order to verify whether an immunological role may be postulated in the pathogenesis and/or in the maintenance of the disease. A significant increase of serum IgM together with normal values of C3 and C4 and without circulating immunocomplexes was found. A significant decrease in the total number of lymphocytes as well as in the number and percentage of T-lymphocytes was also documented. These results suggest a possible involvement of immunological (humoral and cellular) processes in maintaining the chronic pancreatic damage.
The sera of 722 children and adolescents without overt liver disease were tested for hepatitis B surface antigen (HBsAg), antiHBs and anti-hepatitis B core anti-HBc; 658 of the sera were also tested for anti-hepatitis A virus anti-HAV. Except for the "passive" antibody peak observed in babies, the anti-HAV age-specific prevalence was negligible until the age of 3; it then increased, reaching 35% by the age of 15. Serological evidence of HBV was present in 16% of the subjects: this prevalence was almost constant at all ages. The HBsAg carrier rate was highest in children under 5 years of age (7.6%) and decreased with age. However, only one HBsAg carrier was under 1 year of age. Anti-HBs age-specific prevalence increased progressively from 2.7% to 11.4%. Anti-HBc alone was present in 4.1% of the subjects. No significant sex differences were found in the prevalence of HBV serum markers or in the HBsAg carrier rate. Neither HAV nor HBV infection was significantly influenced by place of residence or socioeconomic status. It is concluded that in this area both HAV and HBV are endemic, but while HAV is mainly acquired at school, most of the HBV infections occur within the household. The results suggest that not only perinatal transmission, but also intrafamilial horizontal infection, plays a role in HBV spread among infants.
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A prospective survey, comprising 623 consecutive upper gastrointestinal endoscopies (in 588 patients) was carried out simultaneously at two endoscopy centres of a Mediterranean country, without altering the routine procedures. Each patient was tested for HBsAg, and sera found to be HBsAg-positive were tested for HBeAg/antiHBe: 40/588 (7.1%) subjects were found to be HBsAg-positive and 6 of them were HBeAg-positive. Sera of the first 5 HBsAg-negative patients in whom the same endoscope and/or biopsy forceps were used after a HBsAg-positive subject, were tested for antiHBc to ascertain antecedent HBV immunity: 77/136 (56.6%) were found to be antiHBc-positive. Forty-eight out of the 59 individuals "at risk" lacking evidence of previous HBV infection were contacted 6 months after endoscopy: none reported symptoms of hepatitis; 40 of them had blood tests for HBsAg and antiHBc: none showed serum markers of HBV infection. It is therefore concluded that, in spite of the high number of HBsAg carriers among endoscopy candidates, the risk of HBV spread during upper G.I. endoscopy is very low, even in high prevalence areas.
A seroepidemiological study was carried out in three different institutions for the aged. Serological evidence of HBV infection and the HBsAg carrier rate were found to be significantly increased in all three institutions with respect to the control group (noninstitutionalized aged). Of the 24 HBsAg asymptomatic chronic carriers 62% were positive for HBeAg. Among 15 patients with acute viral hepatitis, none had a severe course and in three HBsAg was not cleared 4-18 months after transaminase levels became normal. During 12-18 months of followup, two asymptomatic seroconversions to HBsAg were observed. Although no single HBV transmission route was identified, the close cohabitation with this high number of HBsAg/HBeAg-positive asymptomatic subjects could lead to an increased risk of spread of HBV within such institutions. Failure to clear HBsAg and the mild, often subclinical, HBV infection observed in these subjects, may be due to immunological abnormalities present in the elderly.
Prisoners and attending staff from six houses of detention were screened for serum HBsAg, anti HBs, antiHBc and transaminases. Both prisoners and warders showed an increased prevalence of HBV serum markers with respect to age- and sex-matched general population control groups. The HBsAg carrier rate was 6.7% in prisoners and 6.6% in staff. Sixty-five per cent of the HBsAg-positive subjects were antiHBe-positive. When the blood samples were taken, all the HBsAg-positive subjects were asymptomatic; transaminases were normal in 80% and only slightly elevated in 20%. Illicit drug abuse was found to be a relevant risk factor for HBV infection among prisoners under 35 yearts of age, but not in the older group, whereas no correlation emerged between presence of HBV serum markers and tattoos or admitted homosexuality. A high prevalance of HBV serum markers as also found among young warders who had been in service for a short time: most of them, however, come from areas of Italy with a particularly elevated HBV circulation. Although the results suggest that many of the HBV infections are not recently acquired within the institution, this survey confirms that prisons should be regarded as high risk areas for HBV infection, both for prisoners and warders.
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Sera from 3160 subjects without overt liver disease were tested for the presence of HBsAg, anti-HBs, anti-HBc. This group corresponds to a 4%, sample of the population resident in Padova and the surrounding district, selected according to sex and age distribution (in 5 to 5 year classes). The overall prevalence of HBV infection was 23%. The prevalence of HBsAg+ subjects was 3.2% higher in males than in females (3.8% v.s. 2.7%). Children under 5 years of age showed the maximum HBsAg carrier rate (7.3%), which was found to decrease with advancing age. Prevalence of anti-HBs is similar in both sexes (M 15.8% v.s. F 14.2%) and increases with age. Anti-HBc without HBsAg or anti-HBs was found in 4.6%, higher in males than in females (5.8% v.s. 3.6%). These result stress the importance of anti-HBc detection in HBV seroepidemiological surveys and suggest that HBV transmission within the household (both vertical and horizontal) plays a relevant role in HBV spread in our population.
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Acute expansion of extracellular fluid volume during maximal water diuresis was induced in 8 chronic liver disease patients without clinical evidence of fluid retention, and in 8 controls. Fractional reabsorption of sodium was inferred in the proximal tubule, in the ascending limb of Henle's loop, and in the more distal site of the tubule. The results indicate that the significantly reduced increment of sodium excretion in cirrhotic patients was due to its augmented reabsorption in the proximal tubule. To establish whether there was a reduced activity of a natriuretic factor, a biologic assay was performed in 16 albino Wistar rats by using urine samples collected immediately after completion of a saline load and processed with gel filtration. The infusion of this fraction resulted in a significant lowering of the increment of urine output, and absolute and fractional sodium excretion only in the rats infused with urine extracts from cirrhotic patients. The results of this study raise the possibility that a reduced production of a natriuretic factor may play some role in the pathogenesis of sodium retention, which is observed in patients with cirrhosis of the liver.
Sera from 128 drug addicts without overt liver disease living in North-East Italy were tested for HBsAg, antiHBs, antiHBc. HBV infection serum evidence was present in 79.6% of the tested subjects: 14 (10.93%) were found to be HBsAG¿76 (59.3%) antiHBs+ and 12 (9.37%) had antiHBc alone. The overall prevalence of HBV infection was four fold higher than that observed in age matched controls. Our figures are essentially in agreement with those observed in low HBV prevalence countries, indicating that drug addicts are a peculiar group, highly exposed to HBV infection irrespective of the entity of HBV circulation in a given population. However, the risk of HBsAg chronicity is not enhanced in drug abusers.
Twenty patients found LKM antibody positive during the routine screening for autoantibodies, were studied for the association with other autoantibodies. Sixteen sera (80%) were found positive either for ANA (50%) or SMA (50%) or both (20%). Eleven patients (55%) were over 40 years old, 3 patients were HBsAg+ve, 4 have toxic and alcohol-related liver disease. These results provide evidence that the LKM antibody is not confined to young people chronic active hepatitis, but is present also in CALD of adult with various etiology. Its association with other autoantibodies (especially ANA) suggest that also LKM could be a marker of autoimmunity. The presence of ANA may be an expression of more severe stages of the disease.