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Biomedical subjects

F Chiodo

Publications and source records attributed to F Chiodo.

At least 235 records · Page 13Linked to original sources

Role of fluconazole in the management of AIDS-related cryptococcosis, according to daily dosing.

No unanimous consent has been reached about treatment guidelines of cryptococcosis in the setting of AIDS, as well as about optimal fluconazole dosing in both initial and suppressive therapy. In order to evaluate the relationship between fluconazole dosing and clinical and microbiological outcome of AIDS-related cryptococcosis, a retrospective study was carried out on 30 consecutive patients. Among the 12 subjects treated with fluconazole doses < 400 mg/day, an unfavorable course was significantly more frequent (early mortality, poor clinical and microbiological response, appearance of early relapses) compared with the 18 patients who received daily doses > or = 400 mg, while no differences were observed between the two treatment groups according to known risk factors for a poor prognosis. When assessing maintenance treatment (22 evaluable cases), the 15 patients receiving oral fluconazole at doses < 200 mg/day showed earlier disease relapse and mortality as opposed to the 7 individuals treated with high-dose fluconazole (> or = 200 mg/day), in the absence of significantly different risk factors for disease recurrence. Our experience pointed out a significant difference in clinical activity of fluconazole in AIDS-related cryptococcosis according to its daily dosing, and suggested 400 and 200 mg as the threshold daily dose for an effective initial and suppressive therapy, respectively, since the probability of treatment failure seemed greater with low-dose drug administration, after controlling data for prognostic markers of disease severity. Controlled studies are warranted, comparing high-dose fluconazole with standard regimens containing amphotericin B in the treatment of AIDS-associated cryptococcosis, and identifying the best fluconazole dosing for both acute-phase and maintenance treatment.

AIDS-Related Opportunistic Infections↗

Acinetobacter infections in patients with human immunodeficiency virus infection: microbiological and clinical epidemiology.

BACKGROUND: We evaluated the role of complications caused by Acinetobacter spp. in the setting of HIV infection. METHODS: Clinical records of 1,923 consecutive HIV-infected patients hospitalized in a 9-year period were retrospectively reviewed, in order to identify all cases of Acinetobacter spp. complications, and to assess their occurrence and outcome according to several epidemiological, clinical and laboratory parameters. RESULTS: Ten patients out of 1,923 (0.52%) developed Acinetobacter spp. infections: sepsis in four cases, urinary tract infection in three, pneumonia in two and septicaemic pneumonia in the remaining patient. All patients were severely immunocompromised, as shown by a mean CD4+ lymphocyte count of 122 cells/microl and a frequent prior diagnosis of AIDS. As opposed to other infections, septicaemia was associated with a significantly lower CD4+ cell count and a more frequent occurrence of neutropenia. Hospital-acquired Acinetobacter spp. infections were significantly more frequent than community-acquired ones, and prevailingly involved patients with AIDS and leucopenia, being responsible for frequent blood dissemination. Antimicrobial, corticosteroid and cotrimoxazole treatment were frequently carried out during the month preceding disease onset. Antibiotic susceptibility studies proved the complete resistance of microbial isolates to ampicillin and cephalothin and poor sensitivity to second-generation cephalosporins and gentamicin, while greater susceptibility was shown to ceftazidime, netilmicin and amikacin, followed by piperacillin, cotrimoxazole and quinolones. Appropriate antimicrobial treatment led to clinical and microbiological cure in all cases, with no related mortality or relapses. CONCLUSIONS: Since only 23 episodes of HIV-associated Acinetobacter spp. infections have been described to date in 11 different reports (nine cases of bacteraemia, eight of pneumonia, two of urinary tract involvement, one of intravenous access device infection, one of meningitis and two with unspecified localization), our series represents the largest one dealing with HIV-associated Acinetobacter spp. infections. According to our experience, Acinetobacter spp. may be responsible for appreciable morbidity among patients with HIV infection, above all when a low CD4+ cell count, neutropenia and hospitalization are present. Clinicians and microbiologists who work in the field of HIV infection should consider the potential pathogenic role of Acinetobacter spp. organisms even in the absence of some presumed risk factors, because of the relationship between these infections and immunodeficiency, hospitalization, other infectious complications, prior antibiotic and steroid treatment and extended antimicrobial resistance patterns.

Acinetobacter↗

The use of efavirenz as a part of late rescue antiretroviral treatment.

PURPOSE: Because rescue antiretroviral strategies are increasingly needed, patients' response to a late salvage treatment including efavirenz plus a novel protease inhibitor (PI), with or without at least one novel nucleoside analogue, was assessed. METHOD: 41 consecutive patients, who underwent four or more prior therapeutic failures and received nucleoside analogues alone for > or = 18 months and a PI-based HAART for > or = 15 months, had a 12- to 24-month prospective follow-up. 6 patients who interrupted treatment after 3-8 weeks because of side effects were excluded. In the remaining 35 evaluable participants, the efavirenz-containing rescue regimen included nelfinavir in 23 cases, indinavir in 7, ritonavir in 2, and ritonavir plus hard gel saquinavir in the remaining 3 cases. 17 of 35 patients concurrently introduced one or more novel nucleoside analogues. Initial mean viremia was 4.8 +/- 0.9 log(10) HIV RNA copies/mL, while mean baseline CD4+ lymphocyte count was around 100 cells/microL. Genotyping resistance testing was obtained at the time of treatment modification. RESULTS: The virologic response was both limited and transient. A significant drop of mean viremia was reached at the third month (-0.7 log(10)), but it was not maintained beyond the sixth month; only 4 patients reached viral suppression during the first 6 months. A more evident and sustained benefit on CD4+ cell count was observed throughout the study (p <.007, compared with baseline). The 31 patients who remained evaluable beyond 12 months did not show relevant modifications of laboratory parameters. The patient subgroup that received > or = 1 novel nucleoside analogue at the time of efavirenz adjunct had a significantly more favorable virologic outcome until the ninth month of follow-up and included all cases who reached viral suppression. Antiviral resistance pattern showed frequent mutations of the protease gene, and a cross-resistance with nonnucleoside reverse transcriptase inhibitors (NNRTIs; found in 19 cases of 41), although our patients were not previously exposed to these compounds. CONCLUSION: A late salvage therapy based on efavirenz plus a novel PI is not expected to achieve a complete and sustained virologic success in patients highly experienced with both nucleoside analogues and PIs and with a concurrent elevated viremia, probably due to extensive resistances acquired through time. Our rate of virologic failure proved even greater than that observed in previous studies of salvage therapy including NNRTIs. Prior long-term treatment with isolated nucleoside analogues and HAART, the use of highly sensitive techniques for monitoring of viremia, and a quite prolonged observation period may have played a role. However, the CD4+ response proved to be more evident and sustained than the virologic one, and the concurrent introduction of >/= 1 nucleoside analogue added significantly, especially during the first 9 months of salvage therapy.

Adult↗

Growth hormone (GH) and the immune system: impaired phagocytic function in children with idiopathic GH deficiency is corrected by treatment with biosynthetic GH.

Thirty-seven prepubertal children evaluated for severe growth retardation were studied by assessment of total granulocyte, monocyte and lymphocyte count, lymphocyte subsets CD3+, CD3+Dr+, CD3+Dr-, CD4+, CD8+, CD8+CD57+, CD8+CD57-, CD16+, CD20+ and CD23+, serum immunoglobulin concentrations, and phagocytic activity of circulating neutrophils and monocytes (by a flow cytometric assay). Idiopathic GH deficiency was diagnosed in 21 of 37 patients; the remaining 16 healthy subjects served as controls. Fourteen patients received biosynthetic GH (rhGH), and their immune parameters were assessed at baseline and after 6 months of therapy. Phagocytic function mediated by both polymorphonuclears and monocytes was significantly impaired in GH-deficient subjects compared to controls (p < 0.003 for neutrophils, p < 0.007 for monocytes), while a significant increase of phagocytic activity was obtained during long-term rhGH replacement therapy (p < 0.02 for neutrophils, p < 0.001 for monocytes), thus suggesting that GH may affect the functional activity of circulating phagocyte cells. No significant differences were found in total granulocyte, monocyte and lymphocyte counts, T- and B-lymphocyte subsets and immunoglobulin levels, between GH-deficient patients and controls, and between values observed before and during rhGH substitution treatment.

Adolescent↗

[Prevention and treatment of infections in open heart surgery (author's transl)].

The incidence of bacterial infections in 207 patients who underwent cardiopulmonary bypass surgery is reported. The effectiveness of various prophylactic antibiotic therapies is debated on the basis of performed antibiograms and the results are compared with that obtained by other Authors using different treatments.

Anti-Bacterial Agents↗

[Prion diseases. The association of bovine spongiform encephalopathy with new variant of Creutzfeldt-Jakob disease].

This review summarizes current knowledge of prion diseases and investigates connections between the bovine spongiform encephalopathy epidemic, observed in Great Britain since 1986, and the new variant of human Creutzfeldt-Jakob disease, reported for the first time in 1996. Information from the international literature and results of the most recent experimental studies on prion diseases and transmissible spongiform encephalopathies are evaluated, and particular attention is focused on the possible transmission of the etiological agents of spongiform encephalopathy, the prions, from animals to humans. Epidemiological, clinical, and histopathological data and experimental results seem to confirm the suspected link between bovine spongiform encephalopathy and the new variant of Creutzfeldt-Jakob disease. In this context, transmission of prions from infected cattle to humans by oral intake seems not only possible but also very probable.

Animals↗

[Viral hepatitis A with atypical course. Clinical, biochemical, and virologic study of 7 cases].

The aim of our study was to assess the clinical, biochemical and virological profile of patients with atypical viral hepatitis A (protracted, relapsed and cholestatic forms). Five patients with the relapsed form and 2 patients with the cholestatic form were studied among 95 patients hospitalized in our Division of Infectious Diseases for viral hepatitis A during the years 1988 to 1998. A relapse was defined by a decrease in serum alanine transaminase levels > or = 50% followed by a > or = 50% increase in the minimal value. The protracted form was defined by elevated serum alanine transaminase levels for more than 6 months. The cholestatic form was defined by the highest value of bilirubinemia above 15 mg/dL or by a persistent jaundice for more than 8 weeks. All 5 of the protracted-relapsed forms had a biphasic course: the median time between onset and relapse of the disease was 8 weeks, and serum aminotransferase activities returned to the normal range within an average of 45 weeks after relapse. The two cholestatic forms were characterized by a very high level of bilirubinemia (24.58 and 19.03 mg/dL) and by protracted jaundice with itching (3 and 8 months). All patients were tested for hepatitis B and C, Cytomegalovirus and Epstein-Barr virus, with negative results. In short, viral hepatitis A is a benign, self-limiting disease which usually resolves in a few weeks. In a non-negligible percentage of cases (3-21%), however, it can assume atypical forms, which are more serious in patients with chronic liver diseases.

Adolescent↗

[Viral hepatitis E. Current knowledge and future problems].

Hepatitis E is the principal enterically-transmitted non-A, non-B, non-C hepatitis, responsible for large epidemics of acute hepatitis associated with fecal contamination of drinking water in under-developed and developing countries. In contrast, in the industrialized world, the infection occurs rarely and sporadically, usually in individuals who originated from or traveled to regions of known endemism. However, serological and virological studies have provided evidence that hepatitis E virus may be circulating in geographical areas not previously considered to be endemic. Hepatitis E is a self-limiting, acute disease with an overall mortality rate of 0.4-4%, although a more severe course has been observed in pregnant women, in whom mortality can rise to 20%. Enzyme immunoassays and polymerase chain reaction are available for definitive diagnosis. The immune serum globulins have not evidenced certain beneficial effects during hepatitis E epidemics, and candidate vaccines have not yet reached the clinical trial stage.

Forecasting↗

A new syndrome of long-term idiopathic, severe CD4+ lymphocytopenia: isolated paraparesis and conjunctival ischemic microangiopathy.

An extraordinary case report of an adult patient followed-up for a decade with an extremely severe idiopathic CD4+ T-lymphocytopenia (as expressed by an absolute CD4+ count of 8-25 cells/microL), associated with an isolated paraparesis and a conjunctival ischemic microangiopathy is described, and discussed on the grounds of the available literature. Despite such a severe and prolonged immunodeficiency, no opportunistic disease occurred, in a observation period longer than ever reported to date. The neurological disorder was diagnosed concurrently with idiopathic CD4+ lymphocyte depletion, while the ocular complication occurred two years later, but remained stable thereafter. Both disorders remained stable during the subsequent eight years. Despite extensive and repeated instrumental and laboratory workout, only very limited immunological abnormalities were detected (besides the extremely low CD4+ lymphocyte count), and no apparent explaination was found for the disabling paraparesis syndrome. Idiopathic CD4+ lymphocytopenia, whose pathogenesis deserves careful investigation, has been associated with a very broad spectrum of signs and symptoms, ranging from negligible or no disturbances, to severe lymphoproliferative disorders, different opportunistic infections, and other focal diseases, including neurological pathologies. However, the association of a long-lasting profound peripheral CD4+ lymphocyte depletion in absence of any opportunistic infection or neoplasm, and isolated paraparesis and conjunctival microangiopathy, represents an absolutely unique finding, especially due to the apparently stable course of the above-mentioned syndrome.

Adult↗

AZT+methotrexate in high-grade HIV-related non-Hodgkin lymphomas: interim report on feasibility and tolerance.

BACKGROUND: 3' azido-3' deoxythymidine (AZT) is a thymidine analogue useful in the treatment of AIDS. We have previously demonstrated that AZT can possess significant antineoplastic activity when combined with de novo thymidylate synthesis inhibitors, such as 5-fluorouracil or methotrexate (MTX). We report here on the feasibility and tolerance of the combination AZT+MTX in the treatment of HIV-related non-Hodgkin lymphomas (NHL). PATIENTS AND METHODS: IV-positive patients with high-grade NHL were treated, at weekly intervals, with three consecutive courses of MTX 1 g/m2 plus increasing doses of oral AZT (2, 4 and 6 g/m2) and folinic acid rescue. RESULTS: From July 1992 to June 1994, 16 patients were enrolled in the trial after giving informed consent. Grade III-IV neutropenia was observed after 22% of the courses, but was prevented by G-CSF administration in 34/59 courses. Grade III-IV anemia was observed after 15% of the courses. No non hematological toxicity was observed. CONCLUSIONS: The combination AZT+MTX was extremely well tolerated in this series of HIV-related NHL patients. If these results are confirmed in terms of antineoplastic efficacy, the protocol will deserve wider application.

Adult↗

[The incidence, etiology and clinical significance of visceral mycoses in patients with AIDS].

The incidence, aetiology and clinical significance of visceral mycoses in HIV-infected subjects were evaluated by a retrospective survey of the clinical and microbiological records of 237 consecutive AIDS patients followed-up since 1984. Seventy-four patients out of 237 (31.2%) (56 males, 18 females; 55 IV drug abusers, 7 heterosexuals, 6 homobisexuals, 3 blood recipients and 3 children with congenitally-acquired HIV infection) presented 77 different episodes of visceral fungal infection as a whole, represented by candidiasis in 56 cases (oesophageal 45, pulmonary 5, sepsis 2, eye involvement 2, endocarditis and invasive oropharyngeal infection in the remaining 2 patients), cryptococcosis in 17 cases (meningoencephalitis in all subjects, with disseminated infection in 11 of them), and aspergillosis in 4 cases (pulmonary 2, cerebral and cranio-facial in the remaining 2 patients). In 57 out of 74 patients (77%), visceral mycoses were diagnostic or concurrent with the diagnosis of AIDS. Fungal diseases, as a whole, showed a significantly higher incidence (p < 0.03) among drug abusers, whereas homobisexual men presented a significantly lower frequency (p < 0.001, chi-square test) than AIDS patients with other risk factors for HIV infection. The onset of cryptococcosis was significantly associated with the male sex (p < 0.005, Fisher exact test). All subjects suffering from a visceral mycosis were severely immunosuppressed, with a higher rate of neutropenia in patients developing Candida and Aspergillus spp. infection (23 out of 56 patients with visceral candidiasis and 3 out of 4 cases of aspergillosis had an absolute neutrophil count lower than 1500 cells/mm3), while a severe reduction in CD4+ lymphocyte count was more evident among patients with cryptococcosis (13 out of 17 patients had a CD4+ cell count lower than 50/mm3). After remission of the primary episode of fungal infection (obtained in 80.5% of cases), the incidence of relapse observed in a long follow-up period (mean time 57.6 +/- 39.2 weeks) was elevated both for patients with cryptococcosis (7 cases out of 17) and subjects with candidiasis (19 cases out of 53), with no significant difference among patients receiving a secondary prophylaxis or not (22 relapses observed in 53 patients treated with maintenance antifungals versus 4 episodes in 8 patients followed for a comparable mean time with no antimycotic treatment). Fifty-two out of 74 patients (70.3%) have died up to now; in 21 of them death was due to or associated with the visceral mycosis (cryptococcosis in 11 cases, candidiasis in 8, aspergillosis in 2).(ABSTRACT TRUNCATED AT 400 WORDS)

AIDS-Related Opportunistic Infections↗

[Bacteriuria. Bacteriological diagnosis and sensitivity to chemotherapeutic agents].

In a brief introduction, methods for collecting urine and diagnosis criteria are reviewed. Data relative to a study of about 10,000 samples of urine from patients admitted to various departments of the Milan Ca' Granda Hospital in 1975 are then reported. The frequencies of the various species of bacteria isolated in cases of bacteriuria are reported. Those occurring most frequently were Proteus (40.7%) of whose four species, Proteus mirabilis and Proteus rettgeri cover almost all cases, and Escherichia coli (26.1%). As for individual isolated microrganisms, the sensitivity to 13 chemotherapeutic agents was tested. E. coli, Klebsiella and Enterococcus demonstrated a high degree of sensitivity with respect to the majority of antibiotics considered.

Anti-Bacterial Agents↗