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Biomedical subjects

R Manfredi

Publications and source records attributed to R Manfredi.

At least 73 records · Page 4Linked to original sources
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↗
PubMed2001

[Pathogenic role of Acinetobacter spp during HIV infection].

In order to assess the clinical role of bacterial complications due to Acinetobacter spp. during HIV disease, a retrospective survey of clinical and microbiological data of 2221 HIV-infected patients hospitalised during the past 10 years was carried out, evaluating all episodes of Acinetobacter spp. infection according to several epidemiological, clinical and therapeutic variables. Eleven patients of 2221 (0.5%) suffered from Acinetobacter spp. disease: sepsis in 5 cases, and urinary, respiratory tract disease and bacteremic pneumonia in three, two, and one patient respectively. A. calcoaceticus was responsible in 4 cases, A. lwoffii in three, and Acinetobacter spp. in the 4 remaining cases; 4 patients experienced a polymicrobial infection, and 7 had a prior diagnosis of full-blown AIDS. All patients had a severe HIV-related immunodeficiency (mean CD4+ lymphocyte count 118.2 +/- 45.3 cells/microl). Compared with other localizations, sepsis was related to a lower mean CD4+ cell count (p<.001), and a more frequent occurrence of leucopenia-neutropenia (p<.005). Disease episodes diagnosed after the first 72 hours of hospitalisation (deemed no- socomial in origin), proved more frequent than community-acquired ones (9 cases versus 2), affected predominantly patients with AIDS and neutropenia, and were frequent1y associated with bacteremia (p<.04) The use of broad spectrum antibiotics, corticosteroids and cotrimoxazole, was recognized during the month preceding the diagnosis of Acinetobacter spp. disease, in 6, 4, and 8 cases, respectively. One patient only had an indwelling intravascular catheter, while no recent history of surgery, intensive care, or other invasive procedures was found. At in vitro susceptibility studies, bacterial isolates showed complete resistance to ampicillin and cephalothin, and low sensitivity to second-generation cephalosporins, while a higher susceptibility rate was revealed towards ceftazidime, netilmicin, amikacin, and quinolones, followed by cotrimoxazole and piperacillin. A prompt and appropriate antimicrobial therapy (mostly carried out with cephalosporins and aminoglycosides), led all patients to a clinical and microbiological cure within 6-1.3 days, in the absence of mortality or relapses. As opportunist pathogens with a predominant nosocomial origin, Acinetobacter spp. organisms may be responsible for an appreciable morbidity in patients with HIV disease, especially when additional risk factors (immunodeficiency, underlying diseases, and hospitalisation) are present. Notwithstanding the high drug resistance profile of the majority of isolated organisms, a timely diagnosis and a treatment based on in vitro assays, contribute to avoid recurrences and potentially life-threatening complications.

AIDS-Related Opportunistic Infections↗
PubMed2001

[Sexually transmitted diseases (STD) and their relationship with sexual behaviour and condom use, in a cohort of teenagers referring to a STD centre. A nine-year, prospective study].

In order to assess the relationship between a diagnosis of sexually-transmitted disease (STD), sexual behaviour, condom use, and other social, demographic, and epidemiological variables in a cohort of young adults who referred to a STD centre during a 9-year period, all patients aged 13-20 years were prospectively evaluated, with special attention paid to sexual behaviour, and use of condom or other contraceptive techniques. The 284 assessed young adults represented 6.1% of all patients with a diagnosis of STD: an increasing temporal trend was noticed (from 3. % in 1991, up to 10.4% nel 1999: p<.0001). On the whole, 70.1% of subjects aged 20 years or less never used a condom during the 6 months preceding the diagnosis of STD: only 21.8% of patients reported regular condom use, and 4.9% more subjects referred occasional use, while in the remaining 3.2% of cases other contraceptive methods were employed. Among under age patients (10.6% of study population), the rate of condom use was 3.3% only, while male homosexuals always denied the use of barrier methods. Although a progressive increase in condom use was observed through the study time (from 0% encountered in 1991-1994, to 57.6% of 1999: p<.0001), this phenomenon proved linked only to the massive increase of immigrant sex workers, which occurred since 1997. When excluding from analysis any probable female prostitutes, lack of condom use tested related to the male gender (p<.05), and a low education (p<.04). Over 50% of patients reported 0-1 partners during the last 6 months, even though an increase in sexual promiscuity was observed during the last three years, compared with 1991-1996 (p<.02). Among the 297 different STD episodes (mostly nongonococcal cervicitis-vaginitis and urethritis, and HPV infection), an increasing incidence of nongonococcal STD and syphilis was found, but no correlation was observed between the spectrum of diagnosed STD, sexual behaviour, and condom use. In particular, in 69.9% of the 103 episodes nongonococcal disease occurred despite regular (65 cases), or occasional (7 episodes) condom use. Moreover, no significant relationship was disclosed between STD occurrence, condom use, and other analyzed social, demographic, epidemiological, and clinical variables. According to our survey, an increased risk of STD seems to involve young adults, and to be related to the variation of multiple demographic, epidemiological, and behavioral features. While immigration and prostitution had the major impact during the last three years, sexual promiscuity and infrequent condom use represent persistent; risk factors in this age population. Besides their diagnostic and therapeutic role, STD centres are able to carry out permanent monitoring of STD, as a starting point to plan adequate information campaigns and specific prevention strategies.

Adolescent↗
PubMed2001

[Cellulitis and soft tissue infection in patients with HIV disease: epidemiological and microbiological features].

In order to assess the epidemiological, microbiological, and clinical features of cellulitis and soft tissue infection occurring during the course of HIV disease, clinical and laboratory data of 2221 hospitalizations carried out since 1991 were retrospectively examined, and 67 bacteriologically-proven episodes of cellulitis-soft tissue infection were identified (3.02% of overall admissions). Among the 92 cultured pathogens, Staphylococcus aureus was the most frequent (46 cases), followed by Pseudomonas spp., Escherichia coli, and Streptococcus pyogenes; 38.1% of patients had a polymicrobial infection. i.v. drug use (p<.02) and the male gender (p<.05), were significantly associated with the occurrence of these complications, while a great variation in the severity of underlying immunodeficiency was shown. An elevated rate (83.6%) of episodes of cellulitis or soft tissue infection were community-acquired in origin; the comprehensive frequency of these episodes significantly dropped during the highly active antiretroviral therapy (HAART) era (p<.01). Limbs were involved in over 80% of episodes, and an hematogenous dissemination of bacterial infection (which occurred in 25.4% of cases), proved significantly related to a CD4+ lymphocyte count <100 cells/microL (p<.03), and an absolute neutrophil count <1000 cells/microL (p<.05). S. aureus strains showed an elevated in vitro resistance rate to penicillin, ampicillin, and rifampin, and a 21.7% rate of methicillin-resistance, while among the 29 gram-negative microorganisms, resistance to ampicillin and first-generation cephalosporins, and that to amoxycillin-clavulanate and second-generation cephalosporin, occurred in over 90% and 60% of tested strains, respectively. All episodes of HIV-associated cellulitis and soft tissue infection were favorably treated in 5-16 days, in over 60% of cases with associated beta-lactam and aminoglycoside antibiotics; a recurrence of staphylococcal cellulitis occurred in 4 patients only, 6-17 months after the initial episode. Cellulitis and soft tissue infection are underestimated complications of HIV disease, but they have a broad etiological and clinical spectrum, are predominantly community-acquired, and are responsible for an appreciable morbidity, due to the supporting role of i.v. drug addiction, and the frequent hematogenous dissemination (which proved to be significantly related to the progression of immunodeficiency and underlying disease). The frequent polymicrobial etiology requires a combination antimicrobial therapy (to be guided by in vitro susceptibility studies), which may avoid a complicated and recurrent disease course in the great majority of cases.

Adult↗
PubMed2000

Phase I-II trial of preoperative chemoradiation in locally advanced cervical carcinoma.

BACKGROUND: 5-Fluorouracil and cisplatin are characterized by in vitro synergism as well as radiosensitization. A phase I-II study was carried out on patients with invasive cervical carcinoma (FIGO IIB-IIIA) undergoing concomitant chemoradiation with 5-fluorouracil and cisplatin followed by radical surgery. METHODS: Twenty-six patients of 53 years median age, 24 with IIB tumor and 2 with IIIA tumor, all with squamous carcinoma, entered the study. The chemoradiation protocol included external radiotherapy to the pelvis: 39.6 Gy (180 cGy/daily); 5-fluorouracil: 1 g/m(2)/daily, in continuous intravenous infusion days 1-4 and 27-30; cisplatin: 20 mg/m(2)/daily days 1-4 and 27-30. Four weeks after the end of chemoradiotherapy, patients underwent restaging and then radical surgery with pelvic and lumboaortic lymphadenectomy. RESULTS: Twenty-six patients are evaluable for acute toxicity and 24 are evaluable for objective and pathologic response. Grade 3-4 thrombocytopenia or leukopenia was observed in 6 patients and grade 3 acute gastrointestinal toxicity in 3. After chemoradiation CR and PR were observed in 64 and 36% of cases, respectively (CR + PR = 100%). Two patients were excluded from surgery for other diseases. The remaining 24 patients were operated on; 23/24 patients showed negative section margins. The histology of the surgical specimen showed the absence of disease in 13 patients (54.2%), microscopic residual tumor in 4 patients (16.6%), residual disease </=1 cm in 5 patients, and residual disease >1 cm in 2 patients. Median follow up was 33 months. Two-year actuarial local control was 91.7%. CONCLUSIONS: This study showed a particularly high rate of pathologic responses (complete + Tmic: 70.8%) and local control (2 years = 91.7%) in patients with advanced cervical cancer undergoing moderate doses of radiotherapy with concomitant chemotherapy followed by radical surgery.

Adult↗
PubMed2000

Clinical and microbiological survey of Serratia marcescens infection during HIV disease.

Clinical charts of 2,398 consecutive HIV-infected patients hospitalized over an 8-year period were reviewed retrospectively to identify all cases of Serratia infection and to evaluate the occurrence and outcome of these cases according to several epidemiological. clinical, and laboratory parameters. Seventeen of 2,398 (0.71%) patients developed Serratia marcescens infections: nine had septicaemia, six had pneumonia, one had a lymph node abscess, and one had cellulitis. All patients were severely immunocompromised, as evidenced by a mean CD4+ lymphocyte count of < 70 cells/microl and a frequent diagnosis of AIDS (13 patients). When compared with other disease localizations, septicaemia was related to a significantly lower CD4+ cell count and a more frequent occurrence of neutropaenia. Antibiotic, corticosteroid, or cotrimoxazole treatment was frequently carried out during the month preceding disease onset. Hospital-acquired Serratia spp. infection was more frequent than community-acquired infection and was significantly related to AIDS, neutropaenia, and sepsis. Antimicrobial sensitivity testing showed complete resistance to ampicillin and cephalothin but elevated susceptibility to ureidopenicillins, second- and third-generation cephalosporins, aminoglycosides, quinolones, and cotrimoxazole. An appropriate antimicrobial treatment attained clinical and microbiological cure in all cases, in absence of related mortality or relapses. Since only 13 episodes of HIV-associated Serratia spp. infection have been described until now in nine different reports (7 patients with pneumonia, 3 with sepsis, 1 with endophthalmitis, 1 with perifolliculitis, and 1 with cholecystitis), our series represents the largest one dealing with Serratia marcescens infection during HIV disease. Serratia marcescens may be responsible for appreciable morbidity among patients with HIV disease, especially when a low CD4 + cell count, neutropaenia, and hospitalization are present. The clinician and the microbiologist facing a severely immunocompromised HIV-infected patient with a suspected bacterial disease should consider the Serratia spp. organisms. In fact, a rapid diagnosis and an adequate and timely treatment can avoid disease relapses and mortality.

AIDS-Related Opportunistic Infections↗
PubMed2000

Bayesian estimation of relaxation times T(1) in MR images of irradiated Fricke-agarose gels.

The authors present a novel method for processing T(1)-weighted images acquired with Inversion-Recovery (IR) sequence. The method, developed within the Bayesian framework, takes into account a priori knowledge about the spatial regularity of the parameters to be estimated. Inference is drawn by means of Markov Chains Monte Carlo algorithms. The method has been applied to the processing of IR images from irradiated Fricke-agarose gels, proposed in the past as relative dosimeter to verify radiotherapeutic treatment planning systems. Comparison with results obtained from a standard approach shows that signal-to noise ratio (SNR) is strongly enhanced when the estimation of the longitudinal relaxation rate (R1) is performed with the newly proposed statistical approach. Furthermore, the method allows the use of more complex models of the signal. Finally, an appreciable reduction of total acquisition time can be obtained due to the possibility of using a reduced number of images. The method can also be applied to T(1) mapping of other systems.

Bayes Theorem↗
PubMed2000

Sample size calculations for risk equivalence testing in pharmacoepidemiology.

Equivalence testing has been widely discussed and is commonly used in pharmacokinetics (bioequivalence) and clinical trials (therapeutic equivalence). It can also be applied to pharmacoepidemiology, where the aim may be to test with a known risk (one-group design) or with another drug (two-group design). Whether the approach is two-sided or one-sided, predefined equivalence limits are required. The definition of the equivalence region can be based on either risk difference or risk ratio. Risk equivalence testing is complicated by the binary nature of the outcome, its low frequency, and by the absence of commonly defined equivalence limits for differences or ratios. In this context, we consider usable formulae for sample sizes. In most cases, at least when the risk studied is large enough (above 1/1,000), it appears that these formulae result in sample sizes that may be acceptable for practical purposes. For example, demonstrating equivalence with a known risk of 0.01, a 20% maximal risk difference, and a one-sided test (alpha = 0.05 and beta = 0.2) requires: under the one-group design (known risk), 15,309 patients; and under the two-group design, 30,617 patients per group. This approach is the appropriate way to conclude equivalence, rather than the commonly used approach of difference testing and concluding equivalence when the null hypothesis of equality is not rejected.

Clinical Trials as Topic↗
PubMed2000

The effects of alternative treatments for HIV disease on recommended pharmacological regimens.

The use of alternative treatments for HIV disease was assessed before and after the introduction of highly active antiretroviral therapy (HAART) by the use of a standardised questionnaire. These data were related to epidemiological, clinical and laboratory parameters and compliance levels to recommended antiretroviral and anti-Pneumocystis carinii regimens. Compared with the 476 evaluable patients interviewed during the first 9 months of 1996, the 549 evaluable subjects screened in January-September 1998 showed less frequent recourse to alternative treatments (22.8 vs. 35.7% of patients; P < 0.001). A significant correlation between use of alternatives, poor compliance to antiretroviral drugs and anti-P. carinii chemoprophylaxis and clinical and immunological progression of HIV disease was shown in 1996, but was not maintained in 1998. No relevant differences were found in the selection of most non-conventional treatments and in the number of strategies followed and their duration of use. Unorthodox treatments were used by most patients concurrently rather than instead of official therapeutic regimens. No correlation was found between the use of alternative treatment and the patients' age, gender, type of risk for HIV disease and duration of HIV seropositivity. The correlations between alternative and official treatments for HIV disease before and during the HAART era shows that a considerable percentage of patients still resort to alternatives in 1998 compared with 1996 but that this does not interfere with compliance with recommended pharmacological regimens or the progression of the disease.

Anti-HIV Agents↗
PubMed2000

Viral load trend in HIV-1 seropositive patients with different CD4 cell counts before starting HAART.

BACKGROUND: The efficacy of highly active antiretroviral therapy (HAART) was prospectively monitored in HIV-1 seropositive patients by analyzing HIV-1 RNA viral load. OBJECTIVES: The aim of the study was to evaluate the viral load course in two different groups of patients (group 1: CD4>400/mm(3), group 2: CD4<200/mm(3)) during a period ranging from 9 to 25 months. STUDY DESIGN: HIV-1 viral load, at the start and during HAART, was analyzed in 117 patients who had previously been treated only with two anti-transcriptase drugs but were naive for protease inhibitors. RESULTS: The results showed that, after the beginning of therapy, high plasma HIV-1 RNA levels dropped to undetectable values (<50 copies HIV-RNA/ml) in one third of patients over a mean period of about 9 months irrespective of the initial CD4 cell count, even though a viral reduction of at least 2log(s) in a significantly shorter period of time (P<0.001) was observed only among patients who began retroviral therapy with a higher CD4 cell count. CONCLUSION: The response to HAART was not dramatically affected by the initial CD4 count. Though restricted to a small number of subjects, the data support the idea that therapeutic intervention can be effective even in an advanced stage of HIV-1 infection, when patients show a decreased number of CD4 T-lymphocytes.

Anti-HIV Agents↗
PubMed2000

The incidence of cytomegalovirus (CMV) antigenemia and CMV disease is reduced by highly active antiretroviral therapy.

Cytomegalovirus (CMV) infection was one of the most common opportunistic infections in AIDS patients, leading to blindness or life-threatening disease in about 40% of patients in the later stages of AIDS before highly active antiretroviral therapy (HAART). In a retrospective multicenter study we investigated the incidence of CMV retinitis and organ involvement in Northern Italy before (1995 and 1996) and after the introduction of HAART (1997 and 1998) as well as the data regarding CMV antigenemia. We found a sharp drop in the incidence of CMV disease in AIDS patients as well as a decline in the incidence of relapses of CMV-disease after the widespread introduction of HAART. Moreover, there was a decrease in the incidence of antigenemia-positive cases in AIDS patients in the era of HAART and the median CMV viral load was significantly higher in patients who didn't receive HAART than in patients who received HAART (p = 0.001, t test).

AIDS-Related Opportunistic Infections↗
PubMed2000

Pseudomonas spp. complications in patients with HIV disease: an eight-year clinical and microbiological survey.

Two hundred and twenty-four episodes of Pseudomonas spp. complications that occurred in 179 consecutive patients with HIV infection were retrospectively reviewed. Pseudomonas spp. organisms were responsible for 11.6% of 1933 episodes of non-mycobacterial bacterial diseases (5.4% of 1072 episodes of sepsis), observed over an 8-year period; 20.7% of patients experienced disease relapses (45 episodes). These complications mostly involved lower airways (66 cases), urinary tract (53 episodes), and blood (34 cases), with Pseudomonas aeruginosa isolated in 161 episodes, and other Pseudomonas spp. in the remaining 63 cases. An advanced HIV disease was frequently present (as expressed by a prior diagnosis of AIDS, a low CD4+ lymphocyte count, and leukopenia-neutropenia). Indwelling intravascular and urinary catheters were often associated with bacteremia and urinary tract involvement, respectively. More than 60% of patients were given antibiotics and/or cotrimoxazole in the month preceding the onset of Pseudomonas spp. disease. Bacterial strains isolated from our HIV-infected patients showed a favorable sensitivity to piperacillin, ceftazidime, imipenem, amikacin, tobramycin, and ciprofloxacin. An adequate antimicrobial treatment led to clinical and microbiological cure in 73.2% of patients at the first episode, and in 22.3% more subjects after one or more relapses. A lethal outcome occurred in only eight patients of 179 (4.5%), suffering from a far advanced HIV disease; P. aeruginosa infection directly contributed to death in four cases (sepsis, and/or pneumonia). Nosocomial disease occurred in 46.4% of the 224 episodes, and was significantly related to a previous diagnosis of AIDS, concurrent neutropenia, the occurrence of sepsis or urinary tract infection, disease relapses, the involvement of non-aeruginosa Pseudomonas spp., and a lethal outcome, compared with community-acquired infection. Our experience (the largest reported to date) confirms that Pseudomonas spp. (including non-aeruginosa Pseudomonas spp. organisms) is responsible for remarkable morbidity and mortality among patients with HIV infection, and may pose relevant problems to clinicians and microbiologists involved in the care of HIV-infected patients.

AIDS-Related Opportunistic Infections↗
PubMed2000

Management of dyslipidemia in patients with HIV disease.

The epidemiological, etiopathogenetic, laboratory and clinical features of serum lipid abnormalities occurring in the course of HIV disease are still poorly understood (especially when the supporting role of single antiretroviral compounds is considered), while limited literature data are to date available regarding the management of HIV-related dyslipidemia, as well as the efficacy and safety of dietary-exercise programs, and that of selected hypolipidemic agents. At this time, a careful monitoring of serum lipid profile is needed during combination antiretroviral therapy including protease inhibitors, in order to suggest a diet and hypolipidemic treatment when applicable, and to prevent clinical sequelae related to long-term dyslipidemia. The selection of an appropriate hypolipidemic agent is difficult, since no controlled studies are available in this field, and possibly increased risks of pharmacologic interactions, toxicity and impaired patient's adherence should be taken into consideration. Waiting for specific guidelines for the treatment of hypertriglyceridemia and hypercholesterolemia in the setting of HIV infection, all available literature reports dealing with the management of HIV-associated hyperlipidemia are briefly discussed, on the basis of personal clinical experience.

Antiretroviral Therapy, Highly Active↗