Fausto de Lalla

Insulin-dependent diabetes mellitus during alpha-interferon therapy for chronic viral hepatitis

A 29-year-old man was observed to develop insulin-dependent diabetes mellitus following a 5-month treatment with recombinant alpha-2b-interferon for chronic hepatitis C. After the onset of the disease, serum samples that had, respectively, been collected before therapy commencement, at month 3, and at the onset of insulin-dependent diabetes mellitus were tested for islet-cell (ICA-IgG), glutamic acid decarboxylase (GAD-Abs), IA2 (IA2-Abs) and insulin (IA-Abs) autoantibodies. The following results were obtained: ICA-IgG, 5, >80, and >80 JDF-U, respectively; GAD-Abs: >100 U/ml in all three measurements; IA2-Abs and IA-Abs: negative. During treatment, thyroid microsomal autoantibodies increased markedly (from 1:100 to 25,600 titer); thyroid-stimulating hormone was persistently normal. HLA class II typing revealed a genetic predisposition to insulin-dependent diabetes mellitus as demonstrated by the presence of DRB1* 04/08, DQ A1 52 Arg+/Arg+, and DQB1 57 N-Asp/Asp alleles. One year after the onset of insulin-dependent diabetes mellitus, the patient is still receiving 30 IU insulin daily; the liver function tests are normal and HCV-RNA is negative. These data support the hypothesis that, in predisposed patients, alpha-interferon therapy can enhance an ongoing autoimmune process against pancreatic beta-cells and induce overt insulin-dependent diabetes mellitus. We therefore suggest that, in patients with a documented predisposition to insulin-dependent diabetes mellitus, alpha-IFN therapy should be administered with caution.

Amphotericin B as Primary Therapy for Cryptococcosis in Patients with AIDS: Reliability of Relatively High Doses Administered over a Relatively Short Period

Thirty-one consecutive AIDS patients with cryptococcal disease were enrolled in a study of the efficacy and safety of short-course primary treatment with a relatively high dose of amphotericin B (1 mg/[kg.d] for 14 days); 26 patients also received flucytosine (100-150 mg/[kg.d], given either intravenously or orally). Twenty-five patients had cryptococcal meningitis confirmed by culture, three had presumed cryptococcal meningitis, and three had disseminated extrameningeal cryptococcosis. After successful primary treatment, all patients were given oral itraconazole or fluconazole as suppressive therapy, and their lifelong clinical and mycologic follow-up was planned. Successful primary therapy was defined as the resolution of symptoms and the documentation of negative cultures of cerebrospinal fluid and/or blood 2 months after the initial diagnosis. Therapy was successful in 29 (93.5%) of all 31 cases and in 26 (92.8%) of the 28 cases of culture-proven or presumed cryptococcal meningitis. Nephrotoxicity developed as a result of amphotericin B administration in seven cases; this adverse reaction required a reduction of the dose in two cases and the discontinuation of therapy in five. No deaths due to cryptococcosis were documented during primary therapy. Treatment failed in two cases. During a mean observation period of 10.7 months, three relapses of the underlying infection occurred. Our results indicate that an aggressive approach to the primary treatment of cryptococcosis in AIDS patients, with the administration of a relatively high dose of amphotericin B for a relatively short period, is effective and well tolerated.

Regional Prophylaxis with Teicoplanin in Monolateral or Bilateral Total Knee Replacement: an Open Study

ABSTRACT From January 1991 to June 1997, patients undergoing primary elective monolateral or bilateral total knee replacement (TKR) were consecutively enrolled in a prospective, open clinical study on the efficacy and safety of regional prophylaxis with teicoplanin (TEC). Those scheduled for monolateral TKR (115 patients) received 400 mg of TEC in 100 ml of saline as a 5-min infusion into a foot vein of the leg to be operated on immediately after the tourniquet was inflated to 400 mm Hg (ca. 50 kPa). For patients undergoing bilateral surgery (45 patients), regional administration of TEC was also repeated for the second knee operation. Follow-up ranged from a minimum of 2 years to 8 years. None of the patients experienced local or systemic adverse effects following regional administration of TEC. In the immediate postoperative and 2-year follow-up periods, only one superficial infection of the primary site attributable to intraoperative contamination (prophylaxis failure) out of the 205 prostheses implanted was observed. Deep infections involving the prosthesis did not occur. Infectious complications at distant sites were observed in nine cases (urinary tract infection due to Escherichia coli in eight cases, and Salmonella enteritidis gastroenteritis in one case) in the immediate postoperative period; they all were rapidly cured after antibiotic treatment. A delayed prosthetic infection, related to hematogenous spread of the etiological agent and therefore not considered a prophylactic failure, was observed in a patient who had undergone TKR 5 years before. Regional administration of TEC in monolateral and bilateral TKR appears to be a safe and valuable prophylactic technique.

A multicentre study of patient survival, disability, quality of life and cost of care - Among patients with AIDS in northern Italy

AbstractObjective: To describe the epidemiological, clinical and economic changes that occurred in the HIV epidemic in Italy prior to and after the introduction of highly active antiretroviral therapy (HAART). Design: A prospective, observational, multicentre case-control study was conducted comparing data, collected over 6 months, from an AIDS cohort in 1998 with that of a cohort in 1994. Out of 77 patients with AIDS in the 1998 cohort, 74 survived. These 74 patients were matched for severity of illness with 74 patient survivors from the 1994 cohort to enable valid comparisons of mortality, disability-dependency (DD), health-related QOL (HR-QOL), and direct costs. Results: Overall, a considerable difference was observed in mortality (33.8% in 1994 vs 3.9% in 1998) between unmatched patients of the two cohorts. As for matched patients, the number of hospital admissions was 1.7 in 1994 and 0.8 in 1998; the average length of stay was 28.1 days in 1994 and 12.6 days in 1998. The direct cost per patient per year was €15 390 and €11 465 for the 1994 and 1998 cohorts, respectively (1999 values). The 1998 patient cohort had significantly better HR-QOL at 6 months in two domains of the instrument used (emotional reaction and energy) and the percentage of totally dependent patients was significantly lower compared with the 1994 cohort (1.4% vs 6.8%). Conclusions: This is the first study to present a comprehensive comparison of direct costs, DD and HR-QOL of patients with AIDS between two time periods. The use of a case-control design has enabled changes in costs and outcomes to be linked to the introduction of HAART in Italy in 1997.

HIV, HBV, delta-agent and Treponema pallidum infections in two rural African areas

In order to compare the seroepidemiology of human immunodeficiency virus (HIV), hepatitis B virus, delta agent and Treponema pallidum infections in two rural populations living in north Uganda (Kitgum district) and in central Burundi (Butezi, Ruyigi region), 448 sera were tested for HBS-Ag, HBS-Ab, and anti-HIV antibodies and screened for syphilis using the T. pallidum haemagglutination (TPHA) test. HBS-Ag positive sera were also tested for anti-delta antibodies. Overall seropositivity rates in healthy subjects, outpatients and inpatients (non-AIDS) were 14.2% and 9.5% in Kitgum district and Butezi, respectively. The prevalence of HBS-Ag and HBS-Ab ranged from 10.0% to 15.6% and from 66.2% to 68.9%, respectively. In north Uganda the rates of anti-delta positivity were 3.1% in the overall population and 30.6% in the HBS-Ag positive subjects. No serum obtained in Butezi was anti-delta positive. In Ugandan people, 64.0% of anti-HIV positive and 25.8% of anti-HIV negative patients were also TPHA-positive (P less than 0.01). For Butezi the corresponding figures were 21.4% and 1.6% respectively (P less than 0.04). On the contrary, no correlation was found between either anti-HIV or TPHA positives and seropositivity for B and delta hepatitis serological markers. The study demonstrated an association between seropositivities for HIV and T. pallidum (TPHA), suggesting common patterns of transmission. On the contrary, no association seemed to exist between HBV and HIV infections.

Candidal prosthetic hip infection in a patient with previous candidal septic arthritis

We describe the case of a patient with chronic monocytic leukemia who underwent total hip arthroplasty (THA) for hip arthrosis. The patient has a history of Candida albicans arthritis of the same joint 5 months before THA surgery. Seven months after the prosthetic joint surgery, the patient developed a C albicans prosthetic infection that was successfully treated with amphotericin B and prosthesis removal. At surgery, the patient was believed cured of the candidal infection. Risk of infection after prosthetic joint surgery in patients with previous fungal joint infections has not been fully investigated. A lengthy infection-free follow-up period is probably necessary but may not be sufficient to prevent the occurrence of postoperative infections in these patients.

H. pylori infection in HIV-positive patients : A serohistological study

Sixty-seven consecutive patients infected withthe human immunodeficiency virus (HIV-1), 72% of whichwith overt AIDS, were examinated by upper endoscopy dueto various indications and evaluated for the prevalence of H. pylori infection. Theinfection was studied by performing both histologicalexamination of gastric biopsies and serological testingfor anti-H. pylori IgG antibodies. The H. pyloriprevalence rate was 55% in histology; no significantdifferences were observed in HIV-infected subjects andthose with overt AIDS (52% vs 63%, respectively; P =NS). Positive histological testing appeared to bedirectly related to the peripheral CD4+lymphocyte count (minimum rates of 43% were detected in6 patients with CD4+ < 100 ×106/liter and maximum rates of 78% inpatients with CD4+ > 200 ×106/liter, respectively; P < 0.05) and inversely related to the frequency ofantibiotic treatments performed over the six monthsprior to endoscopy. Low CD4+ counts were alsoapparently associated with low-grade H. pyloriinfection. Serological testing was positive for anti-H. pylori IgGantibodies in 39% of patients; compared to histology,serology displayed a sensitivity of 57% and aspecificity of 81%. The discrepancy between histologicaland serological positive results for H. pylori wasnoted to be higher in the more advanced phases of HIVinfection. Based upon our results, the serologicaltesting for anti-H. pylori IgG antibodies seems to require cautious interpretation in HIV-positivepatients.

A Risk-Benefit Assessment of Teicoplanin in the Treatment of Infections

SummaryTeicoplanin is a glycopeptide antibiotic whose activity is selectively oriented against Gram-positive aerobic and anaerobic bacteria, including Staphylococcus aureus, coagulase-negative staphylococci, Clostridium difficile, Peptostreptococcus spp. and Corynebacterium jeikeium; such activity is affected by neither methicillin resistance nor β-lactamase production.Teicoplanin is not significantly absorbed from the gastrointestinal tract; consequently, it has to be administered intravenously (either by infusion or by rapid injection) or intramuscularly. Its long half-life allows regimens based upon once daily administration.The adverse effects most frequently associated with teicoplanin treatment are local and hypersensitivity reactions, such as itching and drug fever; anaphylactoid reactions (the ‘red man syndrome’) are seldom observed. Teicoplanin also has less potential than vancomycin to cause nephrotoxicity, especially when administered in combination with an aminoglycoside.Teicoplanin has been proven to be effective in the treatment of microbiologically documented Gram-positive infections, including ‘difficult to treat infections’ such as endocarditis and prosthetic infections. Furthermore, recent trials in patients with haematological malignancies or other cancers have clearly demonstrated that teicoplanin is at least as efficacious as vancomycin in the empirical initial antibiotic regimen for febrile neutropenic patients, and is associated with fewer adverse effects. Finally, owing to its good tolerability profile and the advantage of once daily administration by both intravenous and intramuscular routes, teicoplanin has proven to be very useful for the outpatient treatment of serious Gram-positive infections.In conclusion, teicoplanin is potentially an effective alternative to vancomycin both in immunocompetent and immunocompromised patients, with the advantage over vancomycin of single daily dose administration and lower toxicity. Further comparative studies with vancomycin are, however, required to better define the therapeutic role of teicoplanin for particular infections (i.e. infective endocarditis).

Pancreatic hyperamylasemia during acute gastroenteritis: incidence and clinical relevance

BackgroundMany case reports of acute pancreatitis have been reported but, up to now, pancreatic abnormalities during acute gastroenteritis have not been studied prospectively.ObjectivesTo evaluate the incidence and the clinical significance of hyperamylasemia in 507 consecutive adult patients with acute gastroenteritis.MethodsThe clinical significance of hyperamylasemia, related predisposing factors and severity of gastroenteritis were assessed.ResultsHyperamylasemia was detected in 10.2 % of patients studied. Although amylasemia was found over four times the normal values in three cases, the clinical features of acute pancreatitis were recorded in only one case (0.1%). Hyperamylasemia was more likely (17%) where a microorganism could be identified in the stools (p < 0.01). Among patients with positive stool samples, Salmonella spp. and in particular S. enteritidis, was the microorganism most frequently associated with hyperamylasemia [17/84 (20.2 %) and 10/45 (22.2%), respectively], followed by Rotavirus, Clostridium difficile and Campylobacter spp. Patients with hyperamylasemia had more severe gastroenteritis with an increased incidence of fever (80 % vs 50.6 %, O.R. 3.0; P < 0.01), dehydration (18% vs 8.5%; O.R. 2.5; P < 0.05), and a higher mean number of evacuations per day (9.2 vs 7.5; P < 0.05) than those with amylasemia in the normal range. Hyperamylasemia was significantly associated with cholelithiasis, (30.0 % vs 10.7%, O.R. 3.5; P < 0.01) and chronic gastritis or duodenal ulceration (22.0 % vs 10.2%, O.R. 2.4, P < 0.05).ConclusionsHyperamylasemia is relatively frequent, and is associated with severe gastroenteritis. However, acute pancreatitis in the setting of acute gastroenteritis, is a rare event.

Fibrogenesis serum markers in patients with chronic hepatitis C treated with α-IFN

Abstract: The correlation between therapeutic response and liver fibrogenesis was studied in serum and liver specimens taken from 31 patients treated with α-interferon (IFN) (14 sustained responders and 17 non-responders) for chronic hepatitis C. Serum samples, collected before therapy, and at further 6-month intervals over 2 years, were tested for markers of liver neofibrogenesis. Serum N-terminal procollagen III peptide (PIIINP) displayed a significant and persistent decrease (P < 0.05) in sustained responders but not in non-responders; significantly lowered (P < 0.05) mean levels of C-terminal procollagen I peptide (PICP) were transiently observed in both patient groups, apparently as a result of IFN administration. Serum laminin (Lam) levels remained unchanged. One year after the cessation of treatment, liver biopsy re-testing showed an improvement in necro-inflammatory scores only in sustained responders, with the histological fibrosis scores remaining unaltered in both groups. IFN treatment seemed to exert an influence on serum levels of markers of hepatic connective tissue turnover even in patients that did not respond to therapy, while no effect was observed on preexistent liver fibrosis.