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Biomedical subjects

Roberto Manfredi

Publications and source records attributed to Roberto Manfredi.

At least 19 recordsLinked to original sources
PubMed2006

IL-7 up-regulates TNF-alpha-dependent osteoclastogenesis in patients affected by solid tumor.

BACKGROUND: Interleukin-7 (IL-7) is a potent regulator of lymphocyte development, which has also significant effects on bone; in fact it is a potent osteoclastogenic factor. Some human solid tumors produce high IL-7 levels, suggesting a potential IL-7 role on tumor development and progression. METHODOLOGY: We studied 50 male patients affected by solid tumors, and their blood samples were collected at tumor diagnosis. PBMCs were isolated and cultured with/without IL-7 to study its influence on osteoclastogenesis. Serum and cell culture supernatant IL-7 levels were measured by ELISA. The quantitative analysis of IL-7 expression on T and B cells was performed by Real-Time PCR. PRINCIPAL FINDINGS: Serum IL-7 levels were highest in osteolytic cancer patients, followed by cancer patients without bone lesions, and then healthy controls. We showed the IL-7 production in PBMC cultures and particularly in monocyte and B cell co-cultures. A quantitative analysis of IL-7 expression in T and B cells confirmed that B cells had a high IL-7 expression. In all cell culture conditions, IL-7 significantly increased osteoclastogenesis and an anti-IL-7 antibody inhibited it. We demonstrated that IL-7 supports OC formation by inducing the TNF-alpha production and low RANKL levels, which synergize in promoting osteoclastogenesis. CONCLUSIONS: We demonstrated the presence of high serum IL-7 levels in patients with bone metastasis, suggesting the use of serum IL-7 level as a clinical marker of disease progression and of bone involvement. Moreover, we showed the capability of IL-7 to stimulate spontaneous osteoclastogenesis of bone metastatic patients and to induce osteoclastogenesis in cancer patients without bone involvement. These findings add further details to the disclosure of the mechanisms controlling bone metastasis in solid tumors.

Aged↗
PubMed2006

Nevirapine versus efavirenz in 742 patients: no link of liver toxicity with female sex, and a baseline CD4 cell count greater than 250 cells/microl.

Recent studies have reported increased nevirapine hepatotoxicity in female patients with CD4 lymphocyte counts greater than 250 cells/microl (especially pregnant women). However, our open-label comparison of 742 patients treated with either nevirapine or efavirenz-based HAART as naive patients, experienced subjects, or patients on salvage therapy, found no increased hepatotoxicity in nevirapine-treated subjects, in particular with regard to both sex (females versus males) and T-cell-mediated immunodeficiency (CD4 cell counts above versus below 250 cells/microl).

Alkynes↗
PubMed2006

Long-term statin use does not act on the temporal trend of CD4 cell count in patients on virologically effective HAART.

Pleiotropic features are attributed to statins and fibrates, and effects on laboratory markers of HIV disease progression have been claimed. To assess whether statins/fibrates have long-term effects on the immune recovery of patients on virologically effective HAART, a prospective, comparative study was conducted on 267 dyslipidemic patients treated with either statins, fibrates, or on a dietary exercise programme only. Quarterly assessment of CD4 cell counts showed no differences between groups, thus excluding in-vivo negative immunological effects during effective HAART.

Antiretroviral Therapy, Highly Active↗
PubMed2006

Disseminated, lethal prostate cancer during human immunodeficiency virus infection presenting with non-specific features. Open questions for urologists, oncologists, and infectious disease specialists.

INTRODUCTION: Prostate cancer is a very infrequent occurrence in persons aged 55 years or less, and it has been rarely reported in HIV-infected patients (10 overall cases so far); therefore, an increased incidence compared with the general population has not been established, although a younger age seems more frequent among population with HIV disease. CASE REPORT: We report a case of metastatic prostate cancer occurred in a 53-year-old HIV-infected man, admitted due to non-specific signs, and symptoms: impaired general conditions, fever, weight loss, fatigue, and exertional dyspnea. A remarkable anemia and an aortic systolic murmur were the prominent initial findings, while AIDS-related conditions were not suspected due to a sustained CD4+ count and a contained viremia, which never required antiretroviral therapy. Repeated red blood cell transfusions and an empiric, combined antimicrobial therapy were promptly carried out, under the suspicion of infectious endocarditis, but no appreciable improvement of clinical conditions was achieved. Subsequently, our patient complained not only of an increasingly severe pain at the root of his left thigh, together with overcoming dysuria and urgency, but also urinary tract infection that was rapidly ruled out. During the diagnostic workup for an HIV-associated fever of undetermined origin, a bone marrow biopsy disclosed a metastatic prostatic cancer, with elevated prostate specific antigen (PSA) and acid phosphate levels. An abdominal-pelvic ultrasonography and computerized tomographic scan allowed to detect a dyshomogeneous endopelvic expansive mass with extrinsic compression of the urinary bladder, and involvement of the last lumbar vertebra, large portions of pelvis, and the proximal epiphysis of the right femur. A skeleton scintigraphy pointed out multiple hypercaptation (areas of concentrated traces of radioactivity) areas with involvement of cranial, cervical, dorsal, lumbar, and sacral vertebrae, as well as the pelvis and upper portions of both femurs. Despite therapeutic attempts, our patient deceased after seven weeks due to an overwhelming disseminated intravascular coagulation (DIC). CONCLUSIONS: The non-specific clinical presentation of our case (mimicking other generalized or focal illnesses), and the final, lethal complication (DIC) pose striking problems related to the differential diagnosis during HIV disease, while the rapid evolution into an advanced, complicated, and widely metastatic disease with extensive bone marrow invasion which preceded the appearance of local signs-symptoms, and the lethal overwhelming DIC, deserves attention by specialists who care for HIV-infected subjects.

Biopsy↗
PubMed2006

Reactivation of severe, acute pulmonary tuberculosis during treatment with pegylated interferon-alpha and ribavirin for chronic HCV hepatitis.

The unexpected observation of severe pulmonary tuberculosis after a 7-month combined pegylated interferon-ribavirin for chronic hepatitis C, prompted us to search an eventual immunodeficiency (lymphopenia and/or depletion of CD4+ T-lymphocytes. The retrieval of a chest radiograph incidentally performed 11 y before and showing a probable primary tuberculosis, paralleled a negligible clinical history. The enlargement of interferon indications needs careful evaluation for prior (usually missed) tuberculosis, to prevent or avoid its possible reactivation. Latent tuberculosis is increasingly reported because of extended life expectancy, immigration, and recent availability of cure for multiple chronic disorders, which are often borne by primary-secondary immunodeficiency.

Acute Disease↗
PubMed2006

Multiple, severe lung infiltrates due to Mycobacterium avium-intracellulare in a patient with decompensated liver cirrhosis: Spontaneous resolution after a two-year follow-up.

A unique case of severe, multiple, microbiologically-confirmed pulmonary Mycobacterium avium-intracellulare lesions occurred in a female with decompensated liver cirrhosis, and went to cure after around 2 y despite the impossibility to deliver an effective antimicrobial chemotherapy, owing to the patient's intolerance. From an extensive literature review, we underline a possible mechanism prompting mycobacterial disease during advanced liver disease, while we retrieved only 2 described cases of possible spontaneous resolution of Mycobacterium terrae lung disease, although both were reported in patients without end-organ liver disease, who received a specific combined chemotherapy for an appreciable time period. On the other hand, while decompensated liver cirrhosis is more frequently complicated by a peritoneal localization of bacteria and very infrequently mycobacteria, the reported case represents the first severe pulmonary localization of multiple lesions due to Mycobacterium avium-intracellulare. Moreover, this extraordinary episode resolved spontaneously within the 2-y follow-up, as documented by bronchoalveolar lavage, culture, high-resolution CT scans, and scintigraphic examination.

Aged↗
PubMed2006

Bladder carcinoma and HIV infection during the highly active antiretroviral therapy era: A rare, but intriguing association. Two case reports and literature review.

Two very rare case reports of bladder transitional cell carcinoma associated with HIV infection in patients treated with combined antiretroviral therapy are described, and discussed on the ground of the most relevant and updated literature resources. Only 13 cases of vesical carcinoma have been reported to date in the setting of HIV infection, but only 3 anecdotal single reports (the last in the y 2001) described clinical, therapeutic, and outcome issues of this rare disease association in some detail. In our patients, micro- or macro-haematuria was the clue for in-depth diagnosis and prompt treatment, which was limited to multiple local interventions in 1 case, but finally required a radical cystectomy in the second patient. No relationship was found with the very favourable underlying HIV-related virological and immunological status, and the present 8-12-month follow-up did not show disease relapses.

Antiretroviral Therapy, Highly Active↗
PubMed2006

Severe Candida albicans panophthalmitis treated with all available and potentially effective antifungal drugs: fluconazole, liposomal amphotericin B, caspofungin, and voriconazole.

A severe case of Candida albicans panophthalmitis, probably prompted by an underlying diabetes mellitus, is reported. The course was prolonged (more than 16 weeks), although favourable after treatment with several antifungal agents, all with a predictable activity in this ocular complication and with proven susceptibility in the present case: fluconazole, liposomal amphotericin B, caspofungin, and voriconazole.

Amphotericin B↗
PubMed2006

Emergence of amphotericin B-resistant Cryptococcus laurentii meningoencephalitis shortly after treatment for Cryptococcus neoformans meningitis in a patient with AIDS.

A unique occurrence of two subsequent episodes of HIV-associated Cryptococcus neoformans followed by C. laurentii meningoencephalitis (successfully cured with fluconazole after demonstrated amphotericin B resistance) is presented and discussed. The available literature reported only two cases of HIV-associated C. laurentii infection to date, while a concurrent infection by C. neoformans and C. laurentii has been reported only once in a patient without HIV disease. The absence of prior descriptions of documented central nervous system infection by C. laurentii in non-HIV-infected patients is emphasized as well as the unpredictable in vitro and in vivo antifungal susceptibility of this non-neoformans Cryptococcus spp., and its apparent prevalence in hospitalized patients who received prior antifungal treatments. All epidemiologic, diagnostic, clinical, and therapeutic implications are discussed on the basis of the evolving characteristics of opportunism in the era of highly active antiretroviral therapy (HAART).

AIDS-Related Opportunistic Infections↗
PubMed2006

Fatal long-term immunosuppressive therapy with uncontrolled repeat prescription.

A case of nephrotic syndrome treated with associated cyclophosphamide and corticosteroids came to our attention after over 2 years of self-administered immunosuppressive therapy which remained unchanged and uncontrolled during this period. The self-administered therapy resulted in a severe cell-mediated immunodeficiency (as expressed by a nadir CD4 lymphocyte count of 2 cells/muL). This led to a rapid unfavorable progression of hepatitis B, which was recently acquired and subsequently evolved into a severe cholestatic and fibrosing chronic hepatitis, causing multiple end-organ failure, and ultimately, death. This process was not reversed by lamivudine therapy, hemodialysis, and the use of a Molecular Adsorbent Recirculating System. The role played by repeated drug prescriptions from general practitioners without appropriate clinical and laboratory controls, and that of our patient's depression are discussed. Current literature related to the presented case and the ongoing debate regarding repeated prescriptions are considered in this study.

Drug Administration Schedule↗
PubMed2006

Admission of foreign citizens to the general teaching hospital of Bologna, northeastern Italy: an epidemiological and clinical survey.

BACKGROUND: The emergency regarding recent immigration waves into Italy makes continued healthcare monitoring of these populations necessary. METHODS: Through a survey of hospital admissions carried out during the last five years at the S. Orsola-Malpighi General Hospital of Bologna (Italy), all causes of admission of these subjects were evaluated, together with their correlates. Subsequently, we focused on admissions due to infectious diseases. All available data regarding foreign citizens admitted as inpatients or in Day-Hospital settings of our teaching hospital from January 1, 1999, to March 31, 2004, were assessed. Diagnosis-related group (DRG) features, and single discharge diagnoses, were also evaluated, and a further assessment of infectious diseases was subsequently made. RESULTS: Within a comprehensive pool of 339,051 hospitalized patients, foreign citizen discharges numbered 7,312 (2.15%), including 2,542 males (34.8%) and 4,769 females (65.2%). Males had a mean age of 36.8+/-14.7 years, while females were aged 30.8+/-12.2 years. In the assessment of the areas of origin, 34.6% of hospitalizations were attributed to patients coming from Eastern Europe, 15.3% from Northern Africa, 7.3% (comprehensively) from Western Europe and United States, 6.9% from the Indian subcontinent, 5.9% from sub-Saharan Africa, 5.7% from Latin America, 4.1% from China, 2.5% from the Philippines, and 1.1% from the Middle East. Among women, most hospitalizations (58.8%) were due to obstetrical-gynecological procedures or diseases, including assistance with delivery (27.1%), and pregnancy complications (18.7%), followed by psycho-social disturbances (5.9%), malignancies (5.1%), gastrointestinal diseases (4.7%), and voluntary pregnancy interruption (4.4%). Among men, the most frequent causes of admissions were related to trauma (15.9%), followed by gastroenteric disorders (12%), heart-vascular diseases (8.9%), psycho-social disorders (8.4%), respiratory (7.1%), kidney (6.1%), liver (5.2%), and metabolic (4.9%) diseases, and alcohol or substance abuse (4.2%). Infectious diseases (alone or with concurrent disorders) were reported in 881 discharged individuals, representing 12.1% of the 7,312 DRGs attributed to foreign patients. The comprehensive patient population discharged from our hospital with at least one infectious disease diagnosis had lower rates of respiratory tract infections, followed by chronic viral hepatitis, HIV infection and related diseases, enterocolitis, pulmonary tuberculosis, pyelonephritis, severe skin and soft tissue infection, meningoencephalitis, and malaria, as the most frequently-reported disorders. CONCLUSIONS: Our survey, through a combined analysis of both DRGs and discharge diagnoses, allowed us to conclude that 12.1% of foreign citizens hospitalized at our General teaching Hospital of Bologna (Italy) suffered from at least one infectious disease. Respiratory tract, liver, and gastrointestinal infections, and HIV infection, were found with an appreciable frequency among discharge diagnoses, while the frequency of malaria and meningoencephalitis was lower, compared with other series. Among disorders other than infectious diseases, obstetric-gynecological conditions and post-traumatic episodes (for male patients) were the most frequent causes of hospitalization.

Adolescent↗
PubMed2006

A novel antiretroviral class (fusion inhibitors) in the management of HIV infection. Present features and future perspectives of enfuvirtide (T-20).

Enfuvirtide (Fuzeon, Roche), is the first member of a novel class of antiretroviral agents, the so-called fusion inhibitors, which act against HIV with a completely novel (extra cellular) mechanism of action, and can therefore be easily added to all anti-HIV association therapies including all other antiretroviral agents belonging to nucleoside/nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, and protease inhibitors, since no interactions of any type are expected with enfuvirtide. Despite the need of a twice-daily parenteral (subcutaneous) delivery due to the polypeptide structure of the drug, and its proportionally short elimination lifetime, two extensive multicentre randomized clinical trials and a huge amount of other clinical and laboratory experiences confirmed the elevated potency and the safety profile of enfuvirtide in appropriate samples of HIV-infected patients (both adults and children), who failed and/or became intolerant to all previously available anti-HIV regimens, and had a very restricted choice of antiviral compounds showing residual activity. As a consequence, enfuvirtide is recommended as an adjunct to an "optimized background" containing at least one or two antiretroviral drugs, which are still active against the isolated viral strain, as assessed by resistance testing. The extremely promising profile of this novel anti-HIV drug and the reduced potential for the development of viral resistance (with no possibility of cross-resistance with the other anti-HIV classes) however warrant further pharmacokinetic, pharmacodynamic, pharmacogenomic, and pharmacoeconomic investigation. Also more extensive and prolonged clinical and quality of life studies are strongly needed to establish the best positioning of enfuvirtide in the current therapeutic guidelines of HIV disease and its future role, besides its current approval for salvage therapy of adult and pediatric HIV-infected patients with limited therapeutic options.

Adult↗
PubMed2006

[Screening of adult patients with fever of unknown origin. A prospective study on the role of primary cytomegalovirus infection].

PATIENTS AND METHODS: In a three-year prospective survey of 135 consecutive adult patients referred for fever of unknown origin often associated with a broad spectrum of constitutional signs and symptoms, 21 (15.5%) were found to have a primary Cytomegalovirus infection. RESULTS: In the majority of cases, this syndrome was consistently associated with altered white blood cell count, abnormal T-lymphocyte subsets and hepatosplenomegaly. On the other hand, altered white blood cell differential and serum hepatic enzymes, and constitutional signs and symptoms were absent with a rate ranging from 11.1% to 27.4% of cases, and an initial laboratory cross-reaction with anti-Epstein-Barr IgM antibodies was detected in 48.1% of episodes. Non-specific signs and symptoms were the only features in 27.4% of patients, thus confirming that this disorder may be still clinically underestimated in its real frequency, until virologic assays are carried out. An extensive and varied spectrum of subjective disturbances, sometimes of duration prolonged beyond six months involved nearly 30% of subjects, and lasted for 3-15 months after recovery of acute, primary Cytomegalovirus disease. CONCLUSIONS: In a multidisciplinary (clinical, laboratory, and instrumental) workup for a fever of unknown origin, a rapid recognition of a primary Cytomegalovirus disease is useful to exclude alternative diagnoses, avoid unnecessary exposure to antimicrobial agents, and reassure patients of the benign and self-limiting course of their illness.

Adult↗