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Biomedical subjects

R Giusti

Publications and source records attributed to R Giusti.

At least 19 recordsLinked to original sources
PubMed2000

ANCA in dialysis patients: a role for bioincompatibility?

UNLABELLED: BACKGROUND. Anti-neutrophil cytoplasmic autoantibodies (ANCA) have been described in patients suffering from systemic vasculitis such as Wegener granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome and other pathological conditions. In this paper we report a greater incidence of ANCA in hemodialysis patients as compared to peritoneal dialysis patients, pre-dialytic uremic patients and non-renal patients; a possible role for dialysis bioincompatibility in ANCA generation was also investigated. METHODS: A total of 335 uremics in substitutive treatment (176 in hemodialytic treatment and 159 in peritoneal dialysis) were examined for ANCA positivity. A total of 189 patients with advanced renal failure in conservative treatment and 100 healthy subjects were used as control. The dialysis techniques were standard hemodialysis (n = 119), low volume hemodiafiltration (n = 26) and hemofiltration (n = 31). ANCA positivity was examined by immunofluorescence (IF): diffuse finely granular staining was considered as classical positive reaction (C-ANCA) and P-ANCA was diagnosed if a perinuclear staining was observed. EIA for proteinase-3 (anti PR-3) and myeloperoxidase-antibodies (anti-MPO) were also performed. RESULTS: In non-renal patients and in patients with pre-dialytic renal insufficiency none were found ANCA positive. In peritoneal dialysis patients all but one were ANCA negative with IF, with all EIA test resulting negative. In hemodialytic patients, a positive IF test was found in 26 (14.7%) for P-ANCA and in 5 (2.8%) for C-ANCA; using the EIA test 23 (13%) patients were positive for MPO and 12 (6.8%) for PR-3. CONCLUSIONS: No correlation with age, primary renal diseases, dialytic age, dialysis membrane materials was found; regarding the different extracorporeal dialytic techniques a higher incidence (p < 0.02) was detected in patients undergoing HDF Backfiltration of contaminated dialysate may induce ANCA via an increased cytokine generation.

Adult↗
PubMed1999

Tamoxifen and fenretinide in women with metastatic breast cancer.

BACKGROUND: Tamoxifen and fenretinide combination therapy has been shown to be an active treatment regimen in metastatic breast cancer patients. This pilot study sought to determine whether the addition of fenretinide to tamoxifen would be associated with antitumor activity in metastatic breast cancer patients who had been previously treated with tamoxifen or who had hormone receptor negative disease. The effect of this therapy on circulating plasma transforming growth factor-beta (TGF-beta) levels and serum lipids was also examined. PATIENTS AND METHODS: Thirty-one patients were treated with tamoxifen (20 mg p.o. daily), and fenretinide (400 mg p.o. daily with a 3-day drug holiday each month). Plasma TGF-beta testing was performed using isoform specific sandwich ELISA. RESULTS: Twenty four of the 31 patients were evaluable for an antitumor response including 14 estrogen receptor (ER) positive patients who had failed prior tamoxifen therapy, seven ER-negative patients, and three hormone therapy naive ER-positive patients. There were no objective antitumor responses; three patients had stable disease for 8, 8, and 24 months. Five patients (16%) discontinued therapy for toxicity (one for grade 3 skin rash and four for abnormal dark adaptation). There was a statistically significant decrease in total cholesterol (median change per patient of -13.5 mg/dl; p = 0.049, a 6.5% decrease), and an increase in HDL levels (median change per patient of +18 mg/dl, p = 0.0001, a 35% increase) with tamoxifen and fenretinide therapy. TGF-beta1 plasma levels were normal in 26 of 28 patients, and no changes in these levels post-treatment were demonstrated. CONCLUSIONS: Tamoxifen and fenretinide therapy is not an active combination in ER negative metastatic breast cancer or in patients whose disease has progressed on tamoxifen. This combination had a beneficial effect on total serum cholesterol and HDL levels with no associated rise in serum triglyceride levels. The 400 mg dose of fenretinide was associated with symptomatic nyctalopia in one-third of patients making it an unsuitable dose for use in breast cancer prevention studies.

Adult↗
PubMed1999

Evidence of exercise-induced myocardial ischemia in patients with primary aldosteronism: the Cross-sectional Primary Aldosteronism and Heart Italian Multicenter Study.

BACKGROUND: Primary aldosteronism (PA) is a disease associated with hypersecretion of aldosterone caused by an aldosterone-producing adrenal adenoma, bilateral adrenal hyperplasia, and, although rarely, by adrenal carcinoma. Arterial hypertension induces several cardiovascular alterations that yield a high cardiovascular risk. It has been shown that reduced myocardial perfusion at rest, assessed by thallium-201 myocardial scintigraphy, was greater in PA than in essential hypertension (EH). However, it is still unknown whether reduced myocardial perfusion at rest and/or regional function abnormalities are present during exercise-induced myocardial stress. PURPOSE: We addressed the impact of PA on myocardial ischemia and sought to identify signs of exercise-induced myocardial ischemia (assessed by MIBI-SPECT and echocardiography) in patients with PA compared to patients with EH. Patients with consistent signs of myocardial ischemia on all of the tests were studied by coronary arteriography. PATIENTS: We studied 72 patients with PA and an age/sex-matched group of 72 patients with EH enrolled in the cross-sectional Primary Aldosteronism and Heart Italian Multicenter Study (PAHIMS). METHODS: Regional function was detected from echocardiographic measurement of wall motion done at baseline and immediately after exercise. Myocardial perfusion was evaluated by SPECT imaging after injecting 99mTc-MIBI with the same-day protocol using the rest-stress sequence. RESULTS: Although the conditions of arterial pressure, duration of hypertension, and target organ damage were equivalent, the patients with PA had greater incidence of both reversible perfusion defects and abnormalities of regional function. Moreover, multiple regression analysis showed that the high plasma aldosterone level was highly predictive for SPECT ischemic score and wall motion index, suggesting that PA contributes to cardiovascular risk over and above that associated with ventricular hypertrophy. Exercise-induced myocardial ischemia in PA was not segmental but widely distributed suggesting that this phenomenon was not related to abnormal coronary perfusion. Accordingly, of the 38 patients with PA who underwent coronarography, there was no presence of significant coronary atherosclerotic lesions in 30 (78.9%) of the patients. CONCLUSIONS: The PAHIMS observed more exercise-induced moderate myocardial ischemic defects (co-detected by SPECT and echocardiograms and not segmental but widely allocated) in patients with PA than in patients with EH. This phenomenon occurred in a greater percentage of patients with PA without significant coronary lesions (78.95%, n = 38), which supports the possible presence of small-vessel intramyocardial disease.

Adult↗
PubMed1998

Is type 2 diabetes a different disease in obese and nonobese patients?

OBJECTIVE: The main purpose of this work was to study the possible differences in insulin secretion in a large group of type 2 diabetic patients in relation to diabetes duration, obesity, and the presence of secondary failure after treatment with oral hypoglycemic agents. RESEARCH DESIGN AND METHODS: There were 147 nonobese and 215 obese type 2 diabetic subjects, aged 35-80 years, investigated in a cross-sectional descriptive study Subjects were grouped according to whether glycemic control was good (mean blood glucose <8.5 mmol/l) or poor. Beta-cell function was assessed by measuring meal-stimulated insulin and C-peptide concentrations, as the mean of the three postprandial increments above the premeal value. RESULTS: Basal C-peptide concentrations were significantly higher in obese than nonobese patients of both groups. The mean of meal-stimulated C-peptide concentrations was also significantly higher in obese than nonobese patients with good glycemic control, but not in the secondary failure groups. In nonobese and obese patients considered separately, a significant negative correlation between the mean of daily blood glucose and meal-stimulated C-peptide was observed (r=-0.705 and r=-0.679, respectively, P < 0.001) and the residual beta-cell function was significantly correlated with the known duration of diabetes and metabolic control, but not with BMI, in both groups. CONCLUSIONS: On average, obese diabetic subjects showed higher meal-stimulated C-peptide than nonobese subjects only in well-controlled groups. In both obese and nonobese patients, an inverse association between meal-stimulated insulin secretion and duration of diabetes was observed. In obese patients, as in nonobese patients, the lower beta-cell function seems likely to be the major pathogenetic factor in the appearance of secondary failure, while being overweight plays only a minor role, thus showing that type 2 diabetes is the same disease in obese and nonobese patients.

Adult↗
PubMed1997

Chronic administration of levosulpiride and glycemic control in IDDM patients with gastroparesis.

OBJECTIVE: We evaluated the effect of chronic administration of levosulpiride, a prokinetic drug that is a selective antagonist for D2 dopamine receptors, on the glycemic control of IDDM subjects. RESEARCH DESIGN AND METHODS: The study was performed on 40 long-standing IDDM subjects with clinical signs of autonomic neuropathy and delayed gastric emptying. Gastric emptying time and glycemic parameters (diurnal glycemic profile and HbA1c) were checked under double-blind conditions before and after the administration of levosulpiride at the dosage of 25 mg t.i.d. orally for 6 months, or placebo. RESULTS: No significant differences were noted in the glycemic and HbA1c values before and after 6 months of placebo administration. In contrast, after 6 months of levosulpiride, glycemic control had improved (HbA1c 6.7 +/- 0.4 and 5.7 +/- 0.3%, P < 0.01; mean daily glycemia 10.9 +/- 0.8 and 8.8 +/- 0.4 mmol/l, P < 0.05, at the start and at the end of the study), while the dosage of injected insulin (0.65 +/- 0.02 IU.kg-1.day-1) and the number of severe hypoglycemic episodes remained unchanged. After 6 months of levosulpiride therapy, the time of gastric emptying was significantly reduced from 321 +/- 14 to 261 +/- 9 min (P < 0.001) and dyspeptic symptoms had improved. CONCLUSIONS: Our results show the importance of gastric emptying in the maintenance of glycemic control and the usefulness of chronic administration of levosulpiride in diabetic subjects with gastroparesis.

Administration, Oral↗
PubMed1996

Prospective, randomized trial of 5-fluorouracil, leucovorin, doxorubicin, and cyclophosphamide chemotherapy in combination with the interleukin-3/granulocyte-macrophage colony-stimulating factor (GM-CSF) fusion protein (PIXY321) versus GM-CSF in patients with advanced breast cancer.

We conducted a prospective randomized trial to evaluate the ability of the interleukin-3/granulocyte-macrophage colony-stimulating factor (GM-CSF) fusion protein, PIXY321, to ameliorate cumulative thrombocytopenia after multiple cycles of 5-fluorouracil, leucovorin, doxorubicin, cyclophosphamide (FLAC) chemotherapy compared with GM-CSF in patients with advanced breast cancer. Fifty-three patients were randomized to receive either PIXY321. 375 microg/m2 twice a day subcutaneously, or GM-CSF, 250 microg/m2 daily subcutaneously after FLAC chemotherapy. PIXY321 was less well tolerated than GM-CSF, with more patients developing chills and local skin reactions and more patients stopping PIXY321 due to intolerance. While no difference in the neutrophil nadirs was seen with the two cytokines, the duration of the absolute neutrophil count less than 1,000/muL for all cycles was significantly longer with PIXY321 than with GM-CSF. Fifty percent of patients treated with multiple cycles of FLAC chemotherapy on both study arms developed dose-limiting thrombocytopenia. No differences in platelet nadirs, duration of thrombocytopenia, or need for platelet transfusions were observed with PIXY321 versus GM-CSF. The average delivered doses of FLAC chemotherapy were somewhat higher in the GM-CSF study arm. PIXY321 was not superior to GM-CSF in ameliorating the cumulative thrombocytopenia observed with multiple cycles of FLAC chemotherapy and was less well tolerated.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Progressive deterioration of beta-cell function in nonobese type 2 diabetic subjects. Postprandial plasma C-peptide level is an indication of insulin dependency.

The purpose of the present study was to characterize secondary failure (SF) to oral hypoglycaemic agents by assessment of threshold insulin-secretion values in relation to diabetes duration. One hundred and forty-seven nonobese diabetic patients, 35 to 80 years of age, with disease duration ranging from 1 to 36 years, were studied. Beta-cell function was assessed by meal-stimulated (delta CP) and glucagon-stimulated (delta aCP) C-peptide concentrations. The quality of glycaemic control was considered good if mean daily blood glucose was less than 8.5 mmol/l. One group with good (NOb-GC) and another with poor control (NOb-SF) were established. Mean daily glycaemia was negatively correlated with delta CP or delta aCP (r = -0.703 vs r = -0.696; p < 0.001) more than with basal C-peptide (r = -0.453; p < 0.001). A close positive correlation between meal-stimulated (delta CP) and glucagon-stimulated (delta aCP) C-peptide concentrations was observed (r = 0.869; p < 0.001). Residual beta-cell function (delta CP and delta aCP) was significantly correlated with known disease duration in both groups (GC: r = -0.693 and SF: r = -0.680; p < 0.001). Nonobese patients with SF showed early impaired secretion during the first years of disease, meal-stimulated delta CP being below 0.350 mmol/l. The most useful result in this study was the incremental value of C-peptide (delta CP), which showed minimal overlapping between the two groups. Basal, postprandial or postglucagon absolute values were less discriminating. The daily profile allowed measurement of both glycaemic control and insulin production after a regular meal. The validity of this measurement was confirmed by the strong correlation between meal-stimulated and glucagon-stimulated delta C-peptide concentrations. This parameter is a useful physiological marker of secondary failure.

Administration, Oral↗
PubMed1995

Evidence for sexual and mother-to-child transmission of human T lymphotropic virus type II among Guaymi Indians, Panama.

Guaymi Indians, a non-intravenous drug-using population in which human T cell lymphotropic virus type II (HTLV-II) is endemic, were studied in Changuinola, Panama, to identify the prevalence and modes of transmission of HTLV-II. A population-based survey showed that 352 (9.5%) of the 3686 participants were seropositive for HTLV-II. Infection rates were the same for male and female subjects and increased significantly with age, beginning in young adulthood. HTLV-II infection status was highly concordant among spouses (P < .001) and between mother and child; of children aged 1-10 years, 36 of 219 born to seropositive mothers were seropositive compared with 3 of 997 born to seronegative mothers (P < .001). The strong associations of HTLV-II infection with age and with an infected spouse in adults and of infection in children with infection in their mothers strongly suggest sexual and mother-to-child transmission of HTLV-II in this population.

Adolescent↗
PubMed1995

Peer review of mammography interpretations in a breast cancer screening program.

Mammograms from a statewide screening program were subjected to a blind review by a panel of expert mammographers. Ninety-five percent (173/182) of original normal mammograms and 53% (164/311) of original abnormal mammograms were reread as normal. In comparison with the expert panel community radiologists were more likely to request a repeat mammogram in 6 months than to interpret a mammogram as normal or address their uncertainty with an immediate diagnostic workup.

Breast Neoplasms↗
PubMed1994

Immunologic disturbances and levels of parathyroid hormone in uremic patients in replacement dialysis therapy.

We studied the changes in cellular immunity in patients in replacement dialysis therapy (RDT) and examined the relationship between T-lymphocyte function and plasma levels of parathyroid hormone (PTH). In a preliminary study we found that increased plasma levels of PTH were associated with a decrease of T-lymphocytes and CD4, an increase in CD8 and a reduction in the ratio of CD4 to CD8. In the present study we examined the relationship between plasma levels of PTH, interleukin 2 receptors (IL-2R) and soluble human CD8 (S-CD8). We studied 54 patients divided into two groups: 26 patients with normal levels of PTH and 28 patients with increased levels of PTH. We found a significant reduction in total T-lymphocytes in both groups as compared to controls, with an inverse correlation between total T-lymphocytes and plasma PTH in the second group (R = -0.52). There was an increase in IL-2R in the group II as compared to the controls and also in the total population of uremic patients with a linear correlation between levels of IL-2R and PTH (R = 0.6). The levels of S-CD8 showed a significant increase in both groups with a linear correlation between levels of SC-D8 and PTH (R = 0.63). No specific differences were seen between patients treated with and without 1,25-dihydroxyvitamin D3. The elevated levels of PTH affect the lymphocyte function and are associated with change in cellular immunity with reduction in total number of T cells, and increases in levels of CD8, S-CD8 and IL-2R.

Adult↗
PubMed1993

Parathyroid hormone and T-cellular immunity in uremic patients in replacement dialytic therapy.

We studied 54 patients in replacement dialytic therapy divided into two groups: Group 1, 26 patients with normal parathyroid hormone (PTH) (10-80 pg/ml): and Group 2, 28 patients with elevated PTH (80-400 pg/ml). Total T lymphocytes, CD4, CD8, and CD4/CD8 ratio were evaluated. We found a reduction of total T lymphocytes in both groups compared with controls. A decrease of CD4 and CD4/CD8 ratio with a rise of CD8 occurred in Group 2 but not in Group 1. In Group 2, PTH presented a linear correlation with CD8 and a reverse correlation with total T cells. CD4, and CD4/CD8 ratio. PTH might act on T-cellular immunity with an immunosuppressive effect from the earlier phases of hyperparathyroidism.

Adult↗
PubMed1992

Comparison between first and second generation tests to determine the frequency of anti-HCV antibodies in uremic patients in replacement dialytic therapy.

Research was carried out on 74 hemodialysis patients to determine the frequency of anti-HCV antibodies; this was done by means of the 1st and 2nd generation screening and control tests. The 1st generation tests showed 9 HCV-seropositive patients, while the 2nd generation tests demonstrated 15 HCV-seropositive patients. It seems evident that the 2nd generation tests are more sensitive than those of the 1st.

Adult↗
PubMed1991

Failure of ciprofloxacin to eradicate convalescent fecal excretion after acute salmonellosis: experience during an outbreak in health care workers.

OBJECTIVE: To determine the efficacy of ciprofloxacin therapy in eradicating convalescent fecal excretion of salmonellae after acute salmonellosis. DESIGN: Randomized, placebo-controlled, double-blind trial of ciprofloxacin, with prospective follow-up of nonparticipants. SETTING: An acute care community hospital experiencing an outbreak of salmonellosis. PATIENTS: Twenty-eight health care workers developed acute infection with Salmonella java; 15 participated in a placebo-controlled trial of ciprofloxacin, beginning on day 9 after infection. INTERVENTIONS: Eight patients were randomly assigned to receive ciprofloxacin, 750 mg, and 7 patients to receive placebo; both were administered orally twice daily for 14 days. Nonparticipants who received therapy were placed on the same ciprofloxacin regimen. MEASUREMENTS AND MAIN RESULTS: Study participants had follow-up stool cultures every 3 days initially and then weekly for 3 weeks; nonparticipants were followed until three consecutive cultures were negative. All eight ciprofloxacin recipients showed eradication of S. java from stool cultures within 7 days of beginning therapy (compared with 1 of 7 placebo recipients), and their stool cultures remained negative up to 14 days after discontinuing therapy (P less than 0.01). However, 4 of 8 relapsed; their stool cultures became positive between 14 and 21 days after therapy. In addition, 3 of 3 hospitalized patients treated with ciprofloxacin who did not participate in the controlled trial also relapsed. Thus, the total relapse rate was 7 of 11 (64%; 95% CI, 31% to 89%). In 4 of these 7 patients, relapse was associated with a longer duration of fecal excretion of salmonellae than that of the placebo group. Relapse could not be explained on the basis of noncompliance, development of resistance, or presence of biliary disease. CONCLUSIONS: Despite its excellent antimicrobial activity against salmonellae and its favorable pharmacokinetic profile, ciprofloxacin at a dosage of 750 mg orally twice daily had an unacceptably high failure rate in patients with acute salmonellosis and may have prolonged fecal excretion of salmonellae. The late occurrence of relapses indicates the need to obtain stool cultures up to 21 days after therapy to document fecal eradication in acute salmonellosis.

Acute Disease↗