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Biomedical subjects

G Stagni

Publications and source records attributed to G Stagni.

At least 37 records · Page 2Linked to original sources

Interferon-alpha is effective in the treatment of HIV-1-related, severe, zidovudine-resistant thrombocytopenia. A prospective, placebo-controlled, double-blind trial.

OBJECTIVE: To determine the effect of interferon-alpha for severe, zidovudine-resistant, HIV-1-related thrombocytopenia. DESIGN: Prospective, randomized, double-blind, placebo-controlled, multicenter, crossover trial. SETTING: Outpatient clinics in Central Northern Italy. PATIENTS: 15 sequential patients positive for HIV-1 with platelet counts less than 25 x 10(9)/L who were refractory to 1 month of full-dose (1000 mg/d) zidovudine. INTERVENTION: Interferon-alpha (3 million units) or placebo (1 mL saline) three times a week subcutaneously for 4 weeks, followed by a 4-week washout period. Patients were then switched to the alternative treatment for the next 4 weeks, followed by another 4 weeks of washout, and they were randomly assigned to either sequence of treatment. Patients received zidovudine (200 mg three times daily) throughout the study. MEASUREMENTS: The primary end point was the platelet count (measured weekly). Secondary end points were qualitative assessment of the platelet response; bleeding time; p24 antigen in serum; CD4/CD8 counts; beta 2-microglobulin in serum; and platelet-associated IgG. RESULTS: Interferon-alpha significantly increased platelet counts in the 12 patients who completed the study (baseline level, 15.6 +/- 7.1 x 10(9)/L; after 4 weeks of interferon-alpha therapy, 82.2 +/- 52.2 x 10(9)/L). The estimated increase in the platelet count after interferon-alpha compared with placebo was 60.0 x 10(9)/L (95% CI, 23.2 to 96.8 x 10(9)/L). The increase was already statistically significant after 3 weeks (66.6 +/- 49.7 x 10(9)/L) and remained significantly increased 1 week after discontinuing interferon-alpha therapy (58.2 +/- 45.0 x 10(9)/L). Placebo did not modify the platelet count. The bleeding time was significantly shortened by interferon-alpha. Four of 12 patients who had more serious alterations of some measures reflecting disease severity did not respond to interferon-alpha. No relevant side effects were observed. CONCLUSIONS: Interferon-alpha is a safe and effective treatment for zidovudine-resistant, HIV-related thrombocytopenia.

Acquired Immunodeficiency Syndrome↗

Risk factors for acute parenterally transmitted viral hepatitis: a 20-year study.

In order to verify the relative role of each single risk factor during a long period of observation, and to compare the frequency of risk factors in parenterally and non-parenterally transmitted acute viral hepatitis, we studied 1,251 patients admitted to our Department from 1971 to 1991. Acute hepatitis A cases were considered non-parenterally transmitted, whereas B, C, NANB and Delta hepatitis were grouped together as parenterally transmitted. The two groups were compared for age, sex and the following risk factors: surgical procedures, transfusion, dental procedures, intravenous drug addiction, infected partner, infected relative and hospital admission. There were 243 non-parenterally transmitted and 1,008 parenterally transmitted cases. In univariate analysis, mean age in the two groups was 20 and 37 years (p = 0.000001) for non-parenterally and parenterally transmitted cases respectively; mean ages of patients with different parenterally transmitted hepatitis (B, NANB, C, Delta) did not differ significantly (p = 0.35). The following risk factors were significantly more frequent in the parenterally transmitted hepatitis group: surgical procedure (odds ratio = 8.04, 95% confidence intervals: 3.75, 20.51), transfusion (OR = 18.79, 95% CI: 5.03, 157.72), dental procedures (OR = 2.19, 95% CI: 1.2, 4.06), drug addiction (OR: 11.02, 95% CI: 4.15, 41.34), and infected partner (OR = 17.61, CI: 3.02, 708.65). However, logistic regression showed the following factors as being significant: age (p = 0.00001), transfusion (OR = 3.35, 95% CI: 1.61, 6.94), dental procedures (OR = 1.61, 95% CI: 1.18, 2.2), drug addiction (OR = 4.88, 95% CI: 2.94, 8.1).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Post operative surveillance of human hydatidosis: evaluation of immunodiagnostic tests.

We investigated the kinetics of antibodies detected by indirect hemagglutination (IHA), IgE Elisa and immunoelectrophoresis (IEP) in patients with hydatid disease operated on and continuously followed in the pre-operative and post-operative periods. In the pre-operative phase the IgE Elisa test was found to be adequately sensitive (68.4%) compared with IHA (79%), with a ratio of IgE Elisa/IHA positivity of 87%, while IEP was positive in 55.3% of cases (IEP/IHA ratio = 70%). During post-operative follow-up IHA became negative late in patients who were cured (7 out of 11 were still positive after 4 yrs), whereas IEP and IgE Elisa became negative within 2 yrs of operation (apart from 1 patient with a persisting positive IgE Elisa 3 yrs later). However, IgE Elisa appeared clearly more sensitive in revealing postoperative recurrences (13 out of 13 patients had positive IgE Elisa, vs. 6 out of 13 IEP).

Adult↗

Human pharmacokinetics of betaxolol enantiomers.

Betaxolol is a cardioselective beta-adrenergic antagonist effective in the treatment of hypertension. The pharmacokinetic behavior of betaxolol enantiomers in healthy male subjects is reported. Betaxolol enantiomer concentrations were determined in samples collected up to 48 h after iv administration of a 10-mg dose over a 30-min period by constant-rate infusion in 12 subjects and after oral administration of 40-mg capsules to eight of the same subjects. Betaxolol extracted from whole blood was reacted with (+) or (-)-1-naphthylethyl isocyanate. The resulting diastereoisomeric derivatives were analyzed by reversed-phase HPLC with fluorimetric detection. Following the iv dose, there were no differences in clearance or volume of distribution for the two enantiomers (15.6 +/- 4.4 versus 16.4 +/- 4.1 L/h and 342 +/- 62 versus 340 +/- 65 L, respectively). Likewise, after the oral dose, there were no differences in the maximum concentration, time of maximum concentration, bioavailability, or apparent absorption rate constant (41.0 +/- 8.6 versus 42.0 +/- 7.0 ng/mL, 214 +/- 59 versus 215 +/- 56 min, 0.89 +/- 0.26 versus 0.94 +/- 0.23, and 1.0 +/- 0.6 versus 1.2 +/- 0.6 h-1, respectively). Thus, the pharmacokinetic behavior of racemic betaxolol accurately reflects the behavior of betaxolol enantiomers in this subject group.

Administration, Oral↗

Correlation of preS antigens and clinical status during chronic hepatitis B virus infection.

The serum kinetics of preS1 and preS2 antigens has been evaluated in 38 serial samples from eight patients with chronic active (CAH) or chronic persistent (CPH) hepatitis, followed for 2-7 years (mean 4.4 years) in whom liver biopsy was performed at intervals, and in 46 samples from ten asymptomatic HBsAg carriers followed for 4-5 years (mean 4.6 years). Four patterns of preS behaviour have been observed: (1) persistently positive preS1 and preS2; (2) disappearance of preS2; (3) disappearance of both preS1 and preS2; and (4) persistently negative preS1 and preS2. Pattern 4 has been observed exclusively among healthy carriers, while seven out of eight chronic patients exhibited either pattern 1 or 2. Among the chronic patients, preS2 disappearance was accompanied or followed by alanine aminotransferase (ALT) normalization. The correlation of preS antigens with conventional viral replication markers showed that 100% of hepatitis B virus (HBV)-DNA-positive and 86.6% of HBeAg-positive sera were preS1/preS2 positive, while 61% of HBV-DNA-negative and 64% of HBeAg-negative sera were preS1/preS2 negative. Our data suggest that continuous monitoring of preS antigens in follow-up sera will allow for an improved prognostic evaluation of chronic HBV infection.

Adolescent↗

Thyroid function tests in acute viral hepatitis: relative reduction in serum thyroxine levels due to T4-TBG binding inhibitors in patients with severe liver cell necrosis.

Thyroid function tests were evaluated in 34 patients with acute viral hepatitis (AVH) and in 38 healthy controls (C). As expected, AVH patients displayed a significant increase in T4, rT3 and TBG serum levels with respect to C, while FT4 and TSH concentrations were similar. A positive correlation between TBG and T4 was evident in C, but not in AVH. In this group there was, instead, an inverse correlation between the sum of serum levels of GOT + GPT and T4 concentrations. When AVH patients were divided in "high necrosis" (HN, serum GOT + GPT greater than 2000 UI/l) and "low necrosis" (LN, serum GOT + GPT less than 2000 UI/ml) groups, we found a significant reduction in both T4 and T3 serum concentrations in HN with respect to LN, despite similar levels of TBG, albumin, FT4 and TSH. The hypothesis that thyroid-hormone binding inhibitors (THBI), released during severe liver cell injury, accounted for an impaired serum binding capacity in HN-AVH, was confirmed by the significant increase in FT4/T4 ratio and by the demonstration of THBI activity in pooled sera of these patients, with respect to LN subgroup. Our present finding may clarify the unexplained observation of reduced T4 levels in patients with fulminant hepatitis and the ominous prognostic significance of a "low T4 syndrome" in subjects with severe liver disease and/or other systemic illnesses.

Acute Disease↗

[Study on the presence of Cryptosporidium in Umbria].

Cryptosporidium is an intestinal protozoan parasite belonging to the same family as Isospora and Toxoplasma. Cryptosporidium can cause severe, life-threatening enteritis in immunocompromised patients; he can also cause much less severe diarrhea in immunocompetent humans and in several animal species. Cryptosporidiosis has been diagnosed by identification of characteristic cocysts in fecal smear. In order to detect the small numbers of oocysts excreted, a modified Teleman-Miyagawa concentration technique was used. After, the faecal smears were stained by means of the dimethyl-sulfoxide (DMSO) acid-fast method. During 12 months, 157 specimens of faeces of patients with diarrhoea and 75 stool samples of asymptomatic humans were examined. Cryptosporidium was identified, only, in 2 of 157 stools of patients with diarrhoea. These two patients were less than 2 years of age. Cryptosporidial oocysts not were seen in the faeces of 75 asymptomatic humans and of 35 (only 20 with diarrhoea) immunocompromised patients. Failure to detect the agent in immunosuppressed patients in likely related to poor number of examinated cases. In conclusion, routine laboratory studies to identify Cryptosporidium in the stools of immunocompromised patients seem justified, since the parasite causes in these patients severe opportunistic also extra-intestinal infections.

Adolescent↗

[Prevalence of anti-HTLV III antibodies in detainees at the jail in Perugia].

The Authors studied anti-HTLV III antibodies prevalence in jailed people of Perugia jail. Out of 207 healthy subjects, 10.6% were positive to anti-HTLV III. Prevalence in drug abusers (27.5%) was not apparently different from that observed in a control population of addicts who lived in the community. Prevalence in prisoners who were not intravenous drug abusers (2.2%) was higher, when compared with prevalence in general, "not at risk", population. This result can be explained by the exposition to different risk factors, some of which could depend on prisoner status.

Antibodies, Viral↗

[Bacteriostatic and bactericidal activity, resistance and tolerance of 16 strains of thermophilic Campylobacter to 12 antibiotic drugs].

The majority of gastrointestinal infections due to "thermophilic" Campylobacter is self limiting and does not need antibiotic treatment. Anyhow there are some serious cases (sepsis, persistent and relapsing gastroenteritis, severe immunodeficient patients) which require appropriate therapy. The susceptibility of 15 strains of Campylobacter jejuni and of 1 strain of C. coli, isolated from patients with acute gastroenteritis, has been studied against 12 antibiotics with the broth microdilution method at two different inocula (10(3)-10(4) CFU/ml and 10(7)-10(8) CFU/ml), and with the standard agar disk diffusion test, modified to allow sensitivity testing of Campylobacter. For each antibiotic, the geometric mean of MIC and of MBC and the concentrations of the various drugs needed for inhibition and killing of 50 and 90% of the strains (MIC-MBC50 and MIC-MBC90 respectively) have been calculated. Finally the percentage of resistant strains and the percentage of tolerant strains (ratio MBC/MIC: greater than or equal to 32) at low and high inoculum was determined. Erythromycin and aminoglycosides resulted the most active antibiotics against Campylobacter, being bactericidal as well as bacteriostatic at both low and high inoculum. Among the beta-lactams, cefotaxime was the most active, followed by piperacillin and ampicillin. Ceftazidime, aztreonam and rifampin were inactive. Ciprofloxacin, cotrimoxazole and tetracyclines showed some activity against Campylobacter at low inoculum. The agar disk diffusion method cannot be used for the "routinary" assay of susceptibility of Campylobacter, because it is a "naggy" microaerophilic organism.

Anti-Bacterial Agents↗

Isolation of Chlamydia trachomatis from the prostatic cells in patients affected by nonacute abacterial prostatitis.

To assess the presence of Chlamydia trachomatis in nonacute abacterial prostatitis 30 patients with urethral cultures positive for Chlamydia trachomatis underwent microbiological studies, including cultures of transrectal aspiration biopsies of the prostate. Chlamydia trachomatis was isolated from 10 of the prostatic specimens (33 per cent). In 3 cases a nonspecific cytopathogenic effect caused the destruction of the tissue cultures. Our findings demonstrate that Chlamydia trachomatis may cause ascending infections of the prostate and that this microorganism may have an etiological role in the pathogenesis of nonacute abacterial prostatitis.

Adult↗

Plasma cell generation inhibition in lymphocyte cultures containing cerebrospinal fluid from children with central nervous system viral infections.

Plasma cell generation in pokeweed mitogen-pulsed lymphocyte cultures was markedly suppressed when the experiments were carried out by adding cell-depleted cerebrospinal fluid (CSF) from 5 acute aseptic meningitis or meningoencephalitis children known to have an overexpanded cell population with the suppressor-cytotoxic T-cell surface phenotype in their CSF. In contrast, B-cell terminal differentiation was not affected by the addition of CSF from 5 control children with non-neurological diseases, thereby indicating that CSF from central nervous system virus-infected children contains soluble factors which are themselves capable of exerting regulatory influences on immunocompetent cells.

Adolescent↗

Clinical trials with cyclophosphamide and misonidazole combination for maintaining treatment after radiation therapy of lung carcinoma.

Fifteen patients with inoperable non oat cell lung carcinoma, who had already been treated with telecobalt therapy in the mediastinum-hilar region, were treated with continuing therapy with misonidazole (MISO) and cyclophosphamide (Cy). MISO was administered in single doses of 1000 mg/m2 and 500 mg/m2, orally. Cy was administered in single doses of 500 mg/m2 and 250 mg/m2, i.v. This treatment was given every 4 weeks. All patients (15/15) suffered from hyporexia, nausea and vomiting within 48 hours from administration; furthermore, 2 patients had hemoragic cystitis, 2 had peripheral neurotoxicity, 3 had fever, and 2 had serious nervous depression. Leukopenia occurred in all patients immediately after drug administration, although it was not present in any patient by the time of the next administration. This clinical trial was concluded in December 1981. The follow-up at 18 months shows 7/15 cases of relapse (3 patients dead and 1 patient alive with recurrence, 2 patients dead and 1 patient alive with metastasis without recurrence). Eight of 15 patients are alive with progression of disease from 8 to 18 months.

Adult↗

Pseudomyotonia of the striated urethral sphincter.

Pseudomyotonic discharges of the striated urethral sphincter are infrequent findings. We herein report on 9 patients with dissimilar anatomical-clinical conditions. In some patients a definite neurological lesion was ascertained, whereas in the remaining patients no neurological impairment could be determined clinically and instrumentally. The possibility of spontaneous resolution of the phenomenon is an interesting clinical feature.

Adolescent↗

Serum migration inhibitory activity and monoclonal antibody-defined T-cell phenotypes in patients with acute infectious mononucleosis.

Previous experiments in our laboratory have demonstrated that circulating endogenous leucocyte (migration) inhibitory factor (serum LIF), or a lymphokine with LIF-like activity, may be involved in the impaired cellular immune response observed during the acute phase of the Epstein-Barr virus (EBV) induced infectious mononucleosis (IM). To determine whether serum LIF activity is associated with immunoregulatory IM T-cell subset abnormalities, we analyzed the peripheral blood T-cell populations in a series of acute serum LIF-positive and LIF-negative IM patients by means of T-lymphocyte-specific monoclonal antibodies. Although there was both activation and increase of suppressor/cytotoxic T cells in all IM patients sampled in the acute stage, the relative and absolute numbers of suppressor lymphocytes were found to be significantly higher in those who had LIF activity in their serum. It is postulated that EBV infection can preferentially activate a specific T-cell subpopulation which, in its turn, inhibits the overall host immune response, possibly by a LIF-induced feedback suppression mechanism.

Antibodies, Monoclonal↗