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Biomedical subjects

R Manfredi

Publications and source records attributed to R Manfredi.

At least 37 records · Page 2Linked to original sources
PubMed2001

Lack of change in the distribution of AIDS-defining opportunistic diseases and the related degree of immunodeficiency during the periods before and after the introduction of highly active antiretroviral therapy.

In a retrospective study of 86 patients with AIDS-defining diseases diagnosed from 1997 to June 2000, i.e. following consolidated and large-scale introduction of highly active antiretroviral therapy (HAART), and 342 control patients diagnosed with AIDS from 1985 to 1995, i.e. the decade preceding the HAART era, the etiological spectrum and the related level of immunodeficiency of each individual AIDS-defining opportunistic infection were compared. The results show that, despite the progress attained in the management of HIV infection since the introduction of HAART, clinicians facing newly diagnosed cases of AIDS will likely encounter a spectrum of opportunistic diseases and a level of underlying immunodeficiency similar to those observed during the decade preceding the introduction of HAART. Even in recent years, the large majority of patients newly diagnosed with AIDS have not been able to take advantage of HAART prior to diagnosis of their disease.

AIDS-Related Opportunistic Infections↗
PubMed2001

Limits of deep salvage antiretroviral therapy with nelfinavir plus either efavirenz or nevirapine, in highly pre-treated patients with HIV disease.

The virological and immunological response to an efavirenz-containing rescue regimen was compared with that of a nevirapine-containing one in a prospective, open-label 12-month study performed in patients previously treated with > or = 12 months of nucleoside analogue monotherapy, and > or = 15 months of indinavir- or ritonavir-containing HAART. Pooled laboratory data were assessed according to change or continuation of nucleoside analogues, at the time of start of salvage treatment. An improvement of markers of HIV disease progression occurred in all 59 evaluable patients (with a higher viral load decrease in the efavirenz over the nevirapine group at the third month), but the virological response was neither complete nor sustained at the end of study, irrespective of efavirenz or nevirapine adjunct, and complete viral suppression was attained in only 16.9% of subjects. A progressively increasing mean CD4+ lymphocyte count characterized the immunological response of all patients. The 35 patients who changed at least one nucleoside analogue when introducing salvage therapy had a better outcome, irrespective of the non-nucleoside reverse transcriptase inhibitor chosen. Rescue strategies are increasingly needed in HIV-infected patients treated for a long time with HAART. The association of nelfinavir, a non-nucleoside reverse transcriptase inhibitor, and dual nucleoside analogues, is popular among patients who fail first-line HAART. When prolonged prior treatment with nucleoside analogue monotherapy and HAART are of concern, and a quite elevated viral load is present, this salvage regimen may not allow a complete and sustained virological response in a 1-year period, while a more favourable immunological recovery can be expected. However, the concurrent change of nucleoside analogues significantly improves treatment outcome.

Adult↗
PubMed2001

HIV disease among immigrants coming to Italy from outside of the European Union: a case-control study of epidemiological and clinical features.

The epidemiological, clinical and therapeutic features of HIV disease diagnosed in 41 immigrants from outside of the European Union (EU), were compared with those of 123 Italian and EU patients, in a cross-sectional case-control study, with individuals matched according to age and gender. In total 4.15% of our patients came from outside of the EU (51.2% of them from subsaharan Africa), with a proportional predominance of females, and heterosexual and perinatal transmission of HIV disease (P < 0.0001 and P < 0.02, respectively). Compared with Italian and EU subjects, patients coming from abroad had a shorter duration of known HIV infection (P < 0.001), but only some subjects were aware of their HIV disease prior to immigration, or acquired HIV infection only after coming to Italy (14.6% and 12.2%, respectively). No cases of HIV-2 infection or co-infection were detected in either study group. Compared with controls, patients coming from outside of the EU had a comparable clinical and immunological status, and had similar antiretroviral therapy, which was administered earlier (P < 0.0001), and proved better tolerated (P < 0.04), than in Italian and EU subjects. The apparently more limited virological response (as expressed by a higher mean plasma viral load, and a lower rate of viral suppression at the last visit; P < 0.001 and P < 0.05, respectively), was probably a bias due to the shorter mean overall follow-up time (P < 0.0001), and the shorter mean duration of antiretroviral treatment (11.1 +/- 2.2 months of immigrants vs. 16.2 +/- 6.7 months of controls; P < 0.0001).

Adult↗
PubMed2001

American cutaneous leishmaniasis as a rare imported disease in Europe: a case report favourably treated with antimonial derivatives.

A rare case report of American leishmaniasis imported to Italy after a prolonged journey in Brazil is described, and discussed according to the recent epidemiologic, diagnostic, and clinical literature evidence. Since a delayed diagnosis and treatment of American leishmaniasis outside endemic areas is common (due to a low clinical suspicion), careful and timely consideration of tropical infections is warranted in the differential diagnosis of cutaneous lesions found in a European traveller.

Adolescent↗
PubMed2001

Disorders of lipid metabolism in patients with HIV disease treated with antiretroviral agents: frequency, relationship with administered drugs, and role of hypolipidaemic therapy with bezafibrate.

OBJECTIVES: To assess the correlation between antiretroviral treatment and dyslipidaemia in HIV-infected patients, and the role of bezafibrate as a lipid-lowering agent. METHODS: We retrospectively compared serum lipid levels of five groups of 40 patients, each of them treated with either saquinavir hard gel, indinavir, or ritonavir (associated with two nucleoside analogues), or dual nucleoside reverse transcriptase inhibitors (NRTI) with or without a non-nucleoside reverse transcriptase inhibitor (NNRTI), or not treated with antiretrovirals, randomly selected from nearly 1000 HIV-infected patients followed-up for >or= 12 months, while on the relevant therapy. Hypertriglyceridaemia was defined by triglyceride levels >or= 172 mg/dl, and hypercholesterolaemia by cholesterol levels >or= 200 mg/dl. All patients with triglyceridaemia > 300 mg/dl and cholesterolaemia > 220 mg/dl for at least 6 months, and unresponsive to a >or= 3-month diet, started bezafibrate (400 mg/day), and were prospectively followed-up at a <or= 3-month interval, evaluating both efficacy and tolerability of the hypolipidaemic treatment, provided that they did not change their protease inhibitor treatment for reasons other than metabolic abnormalities. RESULTS: Hypertrygliceridaemia occurred in 75 patients out of 200 (37.5%), but was significantly more frequent and severe with ritonavir vs. indinavir (P<0.001), and in subjects given indinavir vs. all remaining patients (either treated or not) (P<0.001), while isolated saquinavir use was associated with higher tri glyceride levels than NRTI-NNRTI treatment alone, or no antiretroviral therapy (P<0.03). Hypercholesterolaemia was found in 27 subjects (13.5%), and a significantly higher frequency and severity was shown in patients treated with indinavir and ritonavir vs. saquinavir, NRTI-NNRTI, and no anti-HIV therapy (P<0.05 to P<0.001). No appreciable difference was found between patients undergoing NRTI-NNRTI and untreated controls, for all evaluated variables. Bezafibrate was administered once daily for 6-18 months to 49 patients with elevated and diet-resistant hyperlipidaemia due to ritonavir or indinavir (27 and 22 subjects, respectively), and reduced triglyceride and cholesterol levels by 35% and 25%, respectively over 6 months, without differences between the underlying protease inhibitor regimen. Thirty-three patients (67.3%) reached a normal triglyceridaemia after 6-9 months, and normal cholesterol levels were obtained in all subjects. Bezafibrate proved safe and well tolerated. CONCLUSIONS: Careful monitoring of the serum lipid profile is needed during antiretroviral therapy, including protease inhibitors, to identify the need for a diet and/or an hypolipidaemic treatment, and to prevent clinical sequelae related to long-term dyslipidaemia. Specific guidelines for the management of disorders of lipid metabolism in HIV-infected patients are needed.

Bezafibrate↗
PubMed2001

Osteonecrosis and highly active antiretroviral therapy during HIV infection: report of a series and literature review.

Osteonecrosis has shown an increased incidence in HIV-infected patients during the last few years, and has been looked as a side effect of highly active antiretroviral therapy, possibly related to hyperlipidemia. Five cases of osteonecrosis were observed among over 1300 patients with HIV disease. According to our experience, novel antiretroviral regimens do not represent a constant risk factor for avascular necrosis of bone during HIV infection.

Adult↗
PubMed2001

Dual nucleoside analogue treatment in the era of highly active antiretroviral therapy (HAART): a single-centre cross-sectional survey.

Since limited literature exists regarding the outcomes of dual nucleoside analogue reverse transcriptase inhibitor (NRTI) treatment in the highly active antiretroviral therapy (HAART) era, a cross-sectional survey was carried out in a population of around 1000 HIV-infected patients in a single northern Italian university hospital, to assess the frequency, background and long-term evolution of anti-HIV treatment conducted with two NRTIs. An appreciable proportion (20.4%) of the 798 HIV-infected patients currently treated with antiretrovirals at our centre still take a dual NRTI combination, and the great majority of them (68.7%) have a stable disease course (characterized by a viral load <3.7 log(10) HIV RNA copies/mL, a maintained CD4(+) lymphocyte count and absence of HIV disease progression after at least 24 months of follow-up), regardless of the selected regimen, prior antiretroviral therapy use, and baseline virological and immunological situation. Further studies are warranted to establish whether dual NRTI regimens may have residual indications in the HAART era, and whether the shift to a triple antiretroviral combination is expected to lead to long-term advantages in patients with a low risk of disease progression while on dual NRTI treatment.

Anti-HIV Agents↗
PubMed2001

Enterobacter spp. infections complicating the course of HIV disease.

Through a retrospective review of clinical and laboratory data of 2517 consecutive patients with HIV disease hospitalized since 1991, 13 patients were identified (0.52%), who suffered from a confirmed Enterobacter spp. infection (urinary tract disease in 7 cases, sepsis in 4 patients, and pneumonia in 2 cases). A severe immunodeficiency was recognized in all cases, as expressed by a mean CD4+ lymphocyte count <60 cells/microL, and frequently, a prior diagnosis of AIDS. Bloodstream infection proved linked to a lower mean CD4+ cell count, a more frequent occurrence of leukopenia-neutropenia, and nosocomial origin of the infecting pathogen. Hospital-acquired Enterobacter spp. disease was more frequent than community-acquired, and was significantly associated with leukopenia-neutropenia, and a diagnosis of AIDS. Antibiotic susceptibility assays showed a resistance rate to ampicillin and cephalothin involving >90% of tested strains, and a higher (but varied) sensitivity to other beta-lactams, aminoglycosides, fluoroquinolones, and cotrimoxazole. Adequate chemotherapy provided clinical and bacteriological success in all evaluated patients, in the absence of mortality or relapses. Only 34 episodes of HIV-associated Enterobacter spp. infection have been reported to date in 11 different literature studies. Our data point out that also Enterobacter spp. organisms may have an appreciable pathogenic potential in patients with HIV disease, especially in those with a low CD4+ lymphocyte count, leukopenia-neutropenia, who are hospitalized. Despite the unpredictable antibiotic susceptibility profile of these organisms, HIV-related Enterobacter spp. disease may be properly managed through rapid identification and timely and appropriate antimicrobial treatment.

Adult↗
PubMed2001

Role of gancyclovir and HAART administration in the treatment of a rare complication of HIV disease: cytomegalovirus-associated Guillain-Barré syndrome.

Peripheral nerve disorders are very common in patients with HIV infection, including inflammatory demyelinating polyneuropathies, such as Guillain-Barré syndrome. Causes of these neuropathies are probably multiple, and often dictated by the stage of the underlying HIV disease. Acute demyelinating polyneuropathy is usually preceded by infections, generally sustained by cytomegalovirus or Campylobacter jejuni, and a co-infection with HIV may represent the initial etiopathogenetic event leading to the neurological disorder. An extraordinary case report of a cytomegalovirus-associated Guillain-Barré syndrome occurred in one of our patients with advanced HIV infection, who was cured by gancyclovir and HAART administration, and gives us the opportunity to briefly discuss the intriguing pathogenetic and clinical correlations among HIV disease, cytomegalovirus infection, this neurological syndrome, and its specific treatment.

Adult↗
PubMed2001

Pentamidine isethionate as treatment and secondary prophylaxis for disseminated cutaneous leishmaniasis during HIV infection: case report.

Leishmaniasis is emerging as a common and serious opportunistic infection in HIV-infected patients in endemic areas (such as Mediterranean countries), and may occur with various clinical presentations, ranging from typical visceral forms to atypical cases, including cutaneous disease. Although pentavalent antimony compounds have been the mainstay of antileishmanial treatment for half a century, new drugs seem today reliable, including liposomal amphotericin B and pentamidine isethionate. However, the most effective therapy is still unknown. An HIV-infected i.v. drug abuser patient with a very uncommon disseminated cutaneous leishmaniasis, following an initial visceral disease, is described. Primary and recurrent visceral forms of protozoan infection have been treated with liposomal amphotericin B, while pentamidine isethionate was successfully employed as treatment for subsequent cutaneous relapse and as secondary prophylaxis.

AIDS-Related Opportunistic Infections↗
PubMed2001

Switch of protease inhibitor-containing HAART in routine clinical practice: a four-year prospective observational study.

An evaluation was made of the frequency of outcomes, the features, and one-year outcomes of the substitution, carried out because of failure or toxicity, of protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART). Nine hundred and seventy-two HIV-infected patients were prospectively followed up since 1996, with the condition that they had a minimum 80% adherence to prescribed regimens. Four hundred and fifty-two changes occurred in 397 of the 876 evaluable patients (45.3%). Virological and/or immunological failure was of concern in 245 cases (54.2%). Interest in saquinavir had the greatest incidence and earliest occurrence (although the subsequent switch had a significantly better outcome than that of patients failing with other PIs); nelfinavir benefited from a shorter time to change and a worse long-term outcome (probably attributable to its predominant use in indinavir- and ritonavir-experienced patients); while indinavir showed the lowest overall frequency of substitution. Intolerance occurred in the remaining 207 cases (45.8%); with saquinavir being better tolerated than other PIs. A favourable outcome was obtained more frequently when poor tolerability was of concern, compared with therapeutic failure (P<0.008), while no significant differences were found according to prior antiretroviral experience and the subsequently selected HAART regimen. The overall one-year outcome per single substituted compound proved significantly better for patients who stopped using saquinavir and ritonavir, by contrast with those who stopped using indinavir and nelfinavir (P<0.0008). A significantly shorter mean time to substitution was recognized for nelfinavir and saquinavir than with ritonavir and indinavir (P<0.0001). When analysing the subset of patients experiencing HAART failure, a highly significant reverse relationship was demonstrated between mean time to failure, and rate of subsequent response to a modified antiretroviral regimen (P<0.0001). When considering the different patterns of efficacy, durability, resistance induction, expected adherence, and safety of each antiretroviral drug, initial and subsequent therapeutic choices should be carefully balanced against expected benefits and risks.

Antiretroviral Therapy, Highly Active↗
PubMed2001

Gynecomastia associated with highly active antiretroviral therapy.

OBJECTIVE: To report four cases of HIV-associated gynecomastia diagnosed during treatment with nucleoside analogs with or without protease inhibitors. CASE SUMMARY: Four HIV-infected patients developed gynecomastia while taking two nucleoside analogs (stavudine combined with lamivudine in 3 patients, stavudine with didanosine in 1 patient) and protease inhibitors (indinavir, nelfinavir, ritonavir-saquinavir in 3 patients) all patients had received prior treatment with single or associated nucleoside analogs for > or = 21 months. Gynecomastia occurred three to seven months after the start of a triple regimen in the first three patients, and 17 months after initiating the last dual nucleoside analog therapy in the remaining patient. Liver, kidney, and thyroid function were normal; a routine endocrinologic workup showed slight follicle-stimulating hormone and luteinizing hormone abnormalities in one patient only. Other possible causes of drug- or disease-induced gynecomastia were excluded. A concurrent fat redistribution syndrome was present in three patients (including the patient who received nucleoside analogs only), while serum lipid and/or glucose concentration abnormalities were present in all patients. Gynecomastia remained unchanged during the subsequent seven- to 16-month follow-up, even after modification of antiretroviral therapy. DISCUSSION: Gynecomastia has been recently associated with antiretroviral therapy, and all reported cases but one occurred two to 17 months after the start of a protease inhibitor-based regimen. Our experience underlines the possible occurrence of gynecomastia in the absence of protease inhibitor administration, its persistence despite changes of antiretroviral regimen (thus resembling some signs related to lipodystrophy syndrome), and the apparently constant association with prolonged nucleoside analog administration (especially stavudine). CONCLUSIONS: Gynecomastia should be included among emerging adverse effects of antiretroviral therapy, although its etiopathogenesis deserves further investigation.

Adipose Tissue↗
PubMed2001

[Epidemics of bovine spongiform encephalopathy and new variant of Creutzfeldt-Jakob disease in humans. Most recent findings on prion disease].

Prion diseases have been popularized by extensive media coverage of bovine spongiform encephalopathy (BSE) or "mad cow disease" epidemic, observed in Great Britain since 1986, and new variant Creutzfeldt-Jakob disease (nvCJD), reported for the first time in 1996. In contrast to the classical form of the disease, nvCJD affects younger patients, presents a relatively longer duration of illness and is caused by the same agent as BSE. Evidence from laboratory studies now strongly supports the hypothesis that new variant represents human form of animal disease, linked to exposure, probably through food, to bovine prions. Number of BSE reports in the United Kingdom began to decline in 1993, and has continuously decreased year by year since then, but a great worry spread in European countries in association with new BSE reported cases outside of the Great Britain, and increasing incidence of nvCJD. New epidemiological, clinical, histopathological and experimental data on prion diseases are reviewed, focusing our attention on the possible transmission of prion proteins from animals to humans.

Animals↗
PubMed2001

[Cytomegalovirus chorioretinitis in a patient with orthotopic liver transplant. Role of virologic diagnosis and of antiviral chemoprophylaxis].

A case report of cytomegalovirus retinitis in a patient who underwent orthotopic liver transplantation, and suffered from a prior episode of systemic cytomegalovirus disease, is described. Although the diagnosis was obtained only when clinical symptoms prompted ophthalmoscopic evaluation, a successful outcome was attained after ganciclovir treatment. The role of clinical and virologic monitoring of organ transplant recipients, and that of primary and secondary chemoprophylaxis against cytomegalovirus infection are discussed, according to personal observations and to an updated literature review.

Chorioretinitis↗
PubMed2001

[Economic burden and clinical course of HIV infection and AIDS today: how the variation of natural history, available treatments, and strictly related costs play a role in needs of health care].

In order to provide an updated balance of the evolution of the natural history of HIV infection, the major clinical end-points of disease morbidity and mortality were compared with the progressively increasing use of highly active antiretroviral therapy (HAART), in a cohort of patients followed by our tertiary care centre in an eight-year period including both the pre-HAART and the HAART era. Although direct expenditures for antiretroviral agents reached even 99.8% of overall costs related to drugs and blood derivatives at our entire unit in the year 2000, a clear shift towards outpatient assistance of HIV infection was realized during recent years, leading to an increased and greatly varied spectrum of infectious diseases hospitalized at our inpatient and Day-Hospital units. Due to the significant reduction of inpatient expenditures, even the elevated costs of management of HIV disease based on HAART and periodic virological and immunological monitoring are expected to remain cost-effective, at least during the next few years.

Acquired Immunodeficiency Syndrome↗
PubMed2001

[Anthrax].

Anthrax is a serious bacterial infection sustained by Bacillus anthracis and occurring in most mammals, especially grazing herbivors, but it can also involve humans when bacterial endospores enter the body through abrasions in the skin or by inhalation or ingestion. Human disease results from contact with infected animals or contaminated animal products, while there are no known cases of human-to-human transmission. The most common form of human anthrax is the cutaneous infection, usually curable with antimicrobial therapy and rarely leading to systemic and fatal disease; on the other hand, gastrointestinal and inhalatory forms (resulting from inhalation or ingestion of endospores) are very uncommon, but they show a mortality rate approaching 100 percent, usually related to septic and toxic shock. For centuries, anthrax has caused disease in animals and only a few cases in humans, with some outbreaks in developing countries. Today, after the new events in the United States, at least 17 nations are believed to have offensive biological weapon programs, and this old bacterial infection became a modern menace to world safety.

Adult↗