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Biomedical subjects

M Moroni

Publications and source records attributed to M Moroni.

At least 163 records · Page 9Linked to original sources

Prevention of symptomatic recurrences of esophageal candidiasis in AIDS patients after the first episode: a prospective open study.

OBJECTIVES: To evaluate the efficacy and safety of low-dose antifungals as prophylaxis of recurrent esophageal candidiasis after the first episode in patients with AIDS. METHODS: After the first episode of esophageal candidiasis, 122 consecutive AIDS patients were randomly assigned to two different regimens of continuous long-term antifungal prophylaxis (ketoconazole 200 mg or fluconazole 50 mg/day p.o.) or no antifungal therapy over a period of 2 yr. Patients were followed up by monthly clinical controls and upper GI endoscopy in the case of recurrence of esophageal symptoms. RESULTS: One hundred and six patients were clinically evaluable over a mean observation time of 7.5 months. Prophylaxis with oral antifungals significantly reduced symptomatic relapses of esophageal candidiasis, the cumulative probability of relapse at 12 months being 38% in the prophylaxis group, compared with 84% in the untreated group. Both antifungals were sufficiently safe and well tolerated. The clinical response of a second episode of candidiasis to the reintroduction of standard oral antifungals was markedly worse in patients on prophylaxis (especially with ketoconazole) than in untreated patients, presumably due to the development of resistance to the antifungal. CONCLUSIONS: Continuous prophylaxis with both-fluconazole and ketoconazole is effective in preventing recurrences of Candida esophagitis in AIDS patients; however, the possible emergence of strains resistant to these antifungals, as well as the high cost of the therapy, should raise doubts as to whether or not this type of prophylaxis should be extended to all AIDS patients with Candida esophagitis, rather than to limit its use to specific subgroups of patients, such as those with frequent symptomatic relapses.

AIDS-Related Opportunistic Infections↗

Effects of adenine nucleotides on low Km 5' nucleotidase from human seminal plasma.

1. Low Km 5' nucleotidase purified from human seminal plasma has been used in this study to investigate the response of the enzyme ot adenine nucleoside di- and triphosphates in the presence of AMP and IMP as substrates. 2. In the presence of AMP, the addition of 0.5 mM ATP to the enzyme Mg-free results into the highest Vmax/Km ratio value and other experimental combinations of effectors tested cause variation of the kinetic parameters of the enzyme, indicating a control of AMP dephosphorylation by adenine nucleotides. 3. In the presence of IMP, ATP and ADP activate the enzyme but the response to various experimental combinations of effectors shows no significant difference in the kinetic properties of the enzyme, indicating a different control of the dephosphorylation of IMP.

5'-Nucleotidase↗

Folinic acid does improve 5-fluorouracil activity in vivo. Results of a phase III study comparing 5-fluorouracil to 5-fluorouracil and folinic acid in advanced colon cancer patients.

We report the results of a phase III trial in which we compared 5-fluorouracil (5-FU) to 5-FU and folinic acid (FA) in 150 previously untreated metastatic colon cancer patients. Patients were randomized in the ratio of 1:2 to receive 5-FU (370 mg/m2, i.v., for 5 days) in arm A or equidose 5-FU plus FA (200 mg/m2, i.v., for 5 days) for arm B, each cycle being repeated every 4 weeks. Five of 49 evaluable arm A patients (10.2%) and 31 of 97 arm B (31.9%) achieved a complete or partial response (p < or = 0.01). Median survival time of arm A patients was 6 months (mean: 6.18), while it was 8 months (mean: 9.01) for arm B cases (p < or = 0.05). In conclusion, our data indicate that FA can enhance 5-FU activity and that this combination is an effective palliative treatment for metastatic colon cancer patients.

Adenocarcinoma↗

The efficacy and safety of zidovudine alone or as cotherapy with acyclovir for the treatment of patients with AIDS and AIDS-related complex: a double-blind randomized trial. European-Australian Collaborative Group.

OBJECTIVE: To evaluate the efficacy and safety of zidovudine (ZDV) at a maintenance dose of 250 mg every 6 h alone or as cotherapy with acyclovir (ACV; 800 mg every 6 h) as treatment for AIDS and AIDS-related complex (ARC). DESIGN: Double-blind, randomized, placebo-controlled clinical trial of up to 1 year's therapy. SETTING: Teaching hospital ambulatory clinics in eight European countries and Australia. SUBJECTS: A total of 131 patients with AIDS and 134 with ARC were enrolled and followed from 1986 to 1988. MAIN OUTCOME MEASURES: Time to development of AIDS-defining opportunistic infections and AIDS-associated neoplasms, survival assessed at 1 year after entry, performance status, body weight, CD4+ cell counts. RESULTS: During the study period, 46 (36%) ZDV recipients and 37 (27%) cotherapy recipients developed opportunistic infections. The probability of an ARC patient progressing to AIDS (1982 Centers for Disease Control criteria) was 0.18 and 0.15 [95% confidence interval (CI) for difference, -0.17 to 0.11] for the ZDV alone and cotherapy recipients, respectively. After excluding patients who experienced an opportunistic infection during the first 4 weeks of therapy, the probability was 0.13 and 0.099 (95% CI for difference, -0.16 to 0.10) for the ZDV and cotherapy recipients, respectively. Thirty-six patients treated with single-agent therapy [28 (41%) AIDS and eight (12%) ARC patients] and 15 cotherapy recipients [13 (21%) AIDS and two (3%) ARC patients] died during the study. There was a significant difference in time to death between the cotherapy and ZDV alone groups for both AIDS (P = 0.014) and ARC (P = 0.045) patients, with cotherapy patients surviving longer. Infections related to herpesviruses, but not cytomegalovirus, were reduced in patients receiving ACV therapy. CD4+ cell counts in both arms generally increased initially and then declined. Forty-six per cent of patients in the ZDV group (59% of AIDS and 31% of ARC patients) and 52% of patients in the cotherapy group (69% of AIDS and 34% of ARC patients) experienced bone-marrow suppression. Red cell transfusions were administered to 33% of ZDV alone recipients and 34% of cotherapy recipients. CONCLUSION: These data show that the addition of high-dose ACV cotherapy to ZDV for patients with AIDS and advanced ARC results in a statistically significant improvement in survival with minimal increase in the risk of toxicity.

AIDS-Related Complex↗

Treatment of AIDS-related refractory diarrhoea with octreotide.

We evaluated the effect of octreotide, a long-acting synthetic analogue of native somatostatin, on bowel frequency in 13 patients with AIDS-associated refractory diarrhoea. Cryptosporidium enteritis and cytomegalovirus colitis were the most common causes of diarrhoea. All patients received 100 micrograms t.i.d. octreotide subcutaneously for 1 week; those who did not improve were given 250 micrograms t.i.d. for a further 7 days. Bowel frequency returned to normal in 1 patient, who was affected with cryptosporidiosis, and decreased by more than 50% in 7 others, another patient improved on the higher dose. In 1 case, the beneficial effect disappeared after 10 days of treatment. No major adverse events due to the therapy were observed. We conclude that octreotide has a potential therapeutic use in severe AIDS-related refractory diarrhoea. How to identify patients who may respond remains unknown at present.

AIDS-Related Opportunistic Infections↗

[The diagnostic difficulties in a case of Behçet's disease].

Behçet's disease is a chronic, heterogeneous, multisystem disorder caused by a vasculitis involving arterial and venous vessels of all sized. In 1990, a new set of diagnostic criteria has been proposed as a guide to diagnosis of Behçet's disease, requiring the presence of oral ulcerations plus two of the following symptoms or signs: genital ulcerations, characteristics eye lesions, typical skin lesions, and a positive pathergy test. Nevertheless, both clinic and pathologic diagnosis of Behçet's disease remains sometimes very difficult. Diagnostic procedures and therapeutic implications in a case of Behçet's disease are reported and discussed.

Aged↗

Survival of zidovudine-treated patients with AIDS compared with that of contemporary untreated patients. Italian Zidovudine Evaluation Group.

OBJECTIVE: To assess the long-term effectiveness of zidovudine (AZT) in patients with acquired immunodeficiency syndrome (AIDS). This assessment has never been adequately done because controlled clinical trials were stopped early and survival comparisons were made with historical controls. DESIGN: Nonrandomized contemporary observational study of patients treated and not treated with zidovudine. SETTING: Twenty-three AIDS treatment centers throughout Italy that reported cases to the National Registry of AIDS Cases between July 1987 and March 1988. PATIENTS: One hundred fifty-nine zidovudine-treated and 112 untreated patients with AIDS, the majority of whom had acquired human immunodeficiency virus (HIV) infection through intravenous drug use. OUTCOME MEASURES: Median survival and 1- and 2-year survival for treated and untreated groups, as estimated using the Kaplan-Meier method. Cox proportional hazards regression analysis was also used to identify independent predictors of survival among the variables studied. RESULTS: Patients were similar with respect to CD4/CD8 ratio, age, sex, clinical and immunological status at diagnosis, and source of HIV infection. After 24 months, survival was 45.9% (95% confidence interval [CI], 36.1% to 55.7%) in the treated group and 20.5% (95% CI, 12.6% to 28.3%) in the untreated group, with median survival of 21.2 and 9.6 months, respectively. CONCLUSIONS: Possible biases of this study include imperfect matching for clinical status and better overall medical care of treated patients. Nevertheless, we believe that the observed differences in survival were primarily due to zidovudine treatment.

Acquired Immunodeficiency Syndrome↗

AIDS-defining diseases in 250 HIV-infected patients; a comparative study of clinical and autopsy diagnoses.

OBJECTIVE: To evaluate the correlation between clinical and autopsy findings in 250 AIDS patients. METHODS: Clinical and autopsy diagnoses of AIDS-defining diseases in 250 AIDS patients who died in Milan between May 1984 and February 1991 were compared. RESULTS: Pneumocystis carinii (PCP) and oesophageal candidiasis were the most frequent clinical diagnoses, while cytomegalovirus (CMV) infection was observed in almost half of the autopsies. Forty-seven per cent of the diseases found at autopsy had not been diagnosed during life; CMV infection, mycoses, HIV-specific brain lesions, cerebral lymphomas and progressive multifocal leukoencephalopathy (PML) had a higher rate of non-diagnosis in life. CMV visceral infection accounted for the majority of the diseases not recognized in life. In contrast, clinically diagnosed PCP, oesophageal candidiasis and, to a lesser degree, brain toxoplasmosis were often not found at autopsy, possibly indicating a significant rate of recovery and prevention of relapse. Finally, bacterial pneumonia and sepsis, although not AIDS indicator diseases, were observed in approximately one-third of the autopsies. CONCLUSION: Considerable differences in the frequency and type of the AIDS-defining diseases diagnosed during life and at post mortem were found.

AIDS-Related Opportunistic Infections↗

Pseudomonas infections in patients with AIDS and AIDS-related complex.

We identified and reviewed retrospectively all the cases of infection by Pseudomonas and related genera in patients with AIDS and AIDS-related complex (ARC) who were hospitalized at our Institution over a 36-month period. We recorded 48 episodes of infection in 34 of 355 patients with AIDS, and in two of 73 patients with ARC: 25 pneumonias (9 community-acquired and 16 of nosocomial origin). 20 urinary tract infections, two soft tissue infections and one sepsis. In 14 of 16 patients with nosocomial pneumonia but in only one of nine patients with community-acquired pneumonia did we find coexisting opportunistic lung diseases. The following micro-organisms were isolated: P. aeruginosa in 41 cases, P. fluorescens in three cases, Xanthomonas maltophilia (P. maltophilia) in two cases, P. putida in one case. Comamonas testosteronis (P. testosteronis) and Comamonas acidovorans (P. acidovorans) in one case. Amikacin and ceftazidime, alone or in combination, appear to be the optimal choice of therapy for severe Pseudomonas infections in HIV-infected patients, although in our study six of 47 isolates were resistant in vitro to amikacin, and nine of 31 isolates were resistant to ceftazidime.

AIDS-Related Complex↗

Cortisol resistance in acquired immunodeficiency syndrome.

This study concerns 9 iv drug abusers with acquired immunodeficiency syndrome (AIDS) who developed hypercortisolism without the clinical signs or metabolic consequences of hypercortisolism. All patients were characterized by an Addisonian picture (weakness, weight loss, hypotension, hyponatremia, and intense mucocutaneous melanosis). An acquired form of peripheral resistance to glucocorticoids was suspected. We, therefore, examined glucocorticoid receptor characteristics on mononuclear leukocytes by measuring [3H]dexamethasone binding and the effect of dexamethasone on [3H]thymidine incorporation, which is one of the effects of glucocorticoid receptor activation. Glucocorticoid receptor density was increased in AIDS patients with an Addisonian picture (group 1; 16.2 +/- 9.4 fmol/million cells) compared to values in 12 AIDS patients without an Addisonian picture (group 2; 6.05 +/- 2.6 fmol/million cells; P less than 0.01) and sex- and age-matched controls (3.15 +/- 2.3 fmol/million cells; P less than 0.01). The affinity of glucocorticoid receptors (Kd) was strikingly decreased (9.36 +/- 3.44 nM in group 1; 3.2 +/- 1.5 nM in group 2; 2.0 +/- 0.8 nM in controls; P less than 0.01). [3H]Thymidine incorporation was decreased dose-dependently by dexamethasone in controls and patients; the effect was significantly blunted (P less than 0.05) in group 1 patients, which suggests that activation of glucocorticoid receptor is impaired as a result of the glucocorticoid receptor abnormality. In conclusion, AIDS patients with hypercortisolism and clinical features of peripheral resistance to glucocorticoids are characterized by abnormal glucocorticoid receptors on lymphocytes. Resistance to glucocorticoids implies a complex change in immune-endocrine function, which may be important in the course of immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗

Anti-HCV antibodies and hepatocellular carcinoma. Relationship in a medium-risk population.

By means of an accurate immunoenzymatic assay, the prevalence was studied of antibodies to hepatitis C virus (HCV) in three different populations: 74 patients affected with hepatocellular carcinoma (HCC) on preexisting cirrhosis, 82 patients with liver cirrhosis but with no apparent neoplasm, and 70 control subjects, hospitalized for various conditions, of internal medicine or geriatric interest. 70.2% of HCC patients exhibited anti-HBC antibodies, versus 47.5% of cirrhotic subjects with no tumor and 7.1% of controls. Such results suggest the possible role of HCV in the etiopathogenesis of HCC, and its possible synergy with other agents-e.g., hepatitis B virus, alcohol--in causing chronically injured hepatocytes to become neoplastic.

Aged↗

Cerebrospinal fluid beta 2-microglobulin in AIDS related central nervous system involvement.

We measured cerebrospinal fluid (CSF) and serum beta 2-microglobulin (beta 2-M) in Acquired Immunodeficiency Syndrome (AIDS) patients with or without clinical evidence of central nervous system (CNS) involvement. The CSF beta 2-M level was significantly higher than the serum level in AIDS patients with neurological symptoms, but not in AIDS without neurological symptoms, suggesting an increased shedding of this protein in CSF, as a result of rapid cellular turnover within CNS. CSF beta 2-M level increases both in Human Immunodeficiency Virus type 1 (HIV-1) related and in opportunistic CNS syndromes, confirming that beta 2-M is a non specific marker of CNS involvement in AIDS. Nevertheless, the highest CSF beta 2-M values were observed in patients with severe dementia and autoptic diagnosis of multifocal giant cells encephalitis (MGCE) without other opportunistic diseases. This observation could have important implications for monitoring AIDS dementia complex in AIDS patients. Finally, 5 out of 7 (71%) AIDS patients with cryptococcal meningitis showed a decline in CSF beta 2-M level well related to the decrease of cryptococcal antigen (Crypto-Ag) titres and the clinical remission. This data suggests that CSF beta 2-M determination could be used as a useful test in monitoring efficacy of therapy of CNS pathologies in AIDS patients.

AIDS Dementia Complex↗

[Correlation between the grade of histological malignancy and nuclear positivity using the AgNOR technique in 6 cases of isolated bone NHL].

Several reports have shown that the degree of positivity for the AgNOR count can be used to evaluate the aggressiveness of malignancies since it express an increased protein-synthesis activity. This technique was applied to six cases of stage I osseous non-Hodgkin's lymphoma--4 intermediate grade (2 diffuse small, non-cleaved cell and 2 diffuse large, non-cleaved cell lymphomas) and 2 high-grade immunoblastic lymphomas--in order to assess the histologic grade and the number of AgNOR-positive regions. It was noted that survival together with the trend to invade the surrounding soft tissues (i.e., the tumour aggressiveness) correlated with the AgNOR granule count. Both factors were also related with Ki-67 cell-proliferation antibody positivity. Such correlations were even higher than those found with the histologic features conventionally evaluated in the Working Formulation, so they seem to convey more reliable indices of neoplastic growth potential.

Antigens, CD↗

[The infusion of high-dose immunoglobulins in a case of idiopathic thrombocytopenic purpura].

Idiopathic thrombocytopenic purpura (ITP) is a disease characterized by the presence of circulating antiplatelet antibodies, which can cause platelet destruction, through the mediation of the reticuloendothelial system (RES). We report on a patient affected with ITP insensible to first line steroid therapy, who achieved a complete response following the administration of high-dose immunoglobulins (HDIgG, 400 mg/kg/die for 5 days), in association with decreasing doses of steroids. At the end of the treatment with immunoglobulins, the patient presented a normal platelet count and, up to date, 5 moths from the end of therapy, he is in good shape and presents normal platelets values.

Adolescent↗