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M J Alsar

Publications and source records attributed to M J Alsar.

At least 37 records · Page 2Linked to original sources

Comparison of a monoclonal antibody fluorescent polarization immunoassay with monoclonal antibody radioimmunoassay for cyclosporin determination in whole blood.

We have compared the whole blood concentrations of parent cyclosporin A (CsA) using monoclonal fluorescence polarization immunoassay (FPIA) and radioimmunoassay (RIA) as well as polyclonal FPIA in kidney, heart, and bone marrow transplant patients (n = 89). A good correlation was found between monoclonal FPIA and monoclonal RIA (r = 0.96) and a slightly worse one between polyclonal and monoclonal FPIA (r = 0.90). The interassay coefficient of variation was satisfactory for all the methods-less than 5% for monoclonal FPIA. The monoclonal FPIA assay with Abbott TDx appears to provide rapid, precise, and accurate measurement of parent CsA. It is therefore useful for therapeutic monitoring of CsA in whole blood in kidney, heart, and bone marrow transplant patients.

Antibodies, Monoclonal↗

[Initial dosage of vancomycin in neutropenic hematologic patients].

PURPOSE: To evaluate the percentage of neutropenic patients who reach the therapeutic threshold when vancomycin is given at standard initial doses of 500 mg/6 hr, and to assess the creatinine clearance and body vancomycin clearance in such patients. MATERIAL AND METHODS: The study was performed on 37 haematological patients with normal renal function. They received intravenous vancomycin at an initial 500 mg/6 hr doses. The plasma concentration of the drug was assessed 48-72 hr later, pharmacokinetic parameters being calculated. Creatinine clearance was estimated by two different methods. RESULTS: The concentration attained was beyond the therapeutic threshold in 100% of the patients. The correlations between vancomycin and creatinine clearance were r = 0.42 and r = 0.47 when the Cockroft-Gault's and the Jellife's methods, respectively, were used. Administration of vancomycin at initial doses of 500 mg/6 hr renders a very high percentage of patients with plasma concentration of the drug beyond the therapeutic margin. CONCLUSIONS: 1) The poor correlation between creatinine and vancomycin clearance in the patients with normal renal function does not allow using nomograms based on such values for estimation of the initial doses. 2) The estimation of initial doses based on the patient's weight (20-25 mg/kg) may render a higher percentage of patients with therapeutic concentrations from the beginning of treatment. The maintenance doses can be adjusted at 48-72 hr, after measuring the plasma concentrations. 3) Therefore, it seems advisable to perform further clinical assays on different groups in order to verify an increase of the drug's efficacy with no higher toxicity when the initial vancomycin doses is adjusted according to the patient's weight, as recommended here.

Adolescent↗

[Infectious complications in bone marrow transplantation].

BACKGROUND: Initially, the aim of the present study was to evaluate the incidence and implicated organisms in the infections in patients receiving a bone marrow transplants (BMT). METHODS: 194 febrile episodes (FE) were evaluated in 115 patients having received a BMT between 1980 and 1987. The analysis was carried out at three different moments: during the period of most marked neutropenia (period I) to the 100th day after BMT (period II) and beyond the 100th day (period III). RESULTS: The unequivocal confirmation that FE was infective was found in 62% of cases (confirmation was microbiological in 46% and clinical in 16%), while 31% of FE were considered as possible infections and the remaining 7% as doubtful infections. The causative organisms were bacteria (73%), viruses (10%), fungi (8%), and combinations of them (polymicrobial infections) (9%). Gram negative and Gram positive organisms were more common, respectively, in period I and in periods II and III (p = 0.02). Bacteremia was the commonest cause of confirmed infection. The overall mortality rate due to infection was 18%. There was a remarkably high mortality from pneumonia (54%) and a low mortality in patients with sepsis (6%) (p less than 0.0001). The number of FE was lower in patients with autografts than those with allografts (p = 0.08). 33% of the FE in patients with allografts were coincident with acute or chronic graft-versus-host disease, and in two thirds of them infections was confirmed. CONCLUSIONS: Infection represents a major complication of BMT. The different antimicrobial treatments used in association with bone marrow grafting allowed us to control most FEs. Pneumonia was the most severe infective localization and the leading cause of death. Mortality rate due to sepsis was small.

Adolescent↗

Interference of digoxin-like immunoreactive substances with TDx digoxin II assay in different patients.

The TDx digoxin II immunoassay was used in controls and in patients not taking digoxin or any other cardiac glycoside. We report the frequency of interference thought to be caused by digoxin-like factors (DLFs). We found a high incidence of false-positive results in 15 patients with severe hepatic disease (60% false-positive results). In newborn infants we found false-positive results both when their blood was drawn from a peripheral vein (89% false-positive results) and, more strikingly (100% false-positive results), when it was obtained from an umbilical cord vein (p less than 0.001). Compared to a control group, no statistically significant false-positive results were found in patients with mild to moderate chronic renal failure (n = 21) or in pregnant women (n = 15). In patients with chronic renal failure undergoing hemodialysis six of 25 had false-positive results. These results suggest that digoxin levels must be interpreted carefully in patients with chronic liver disease and chronic renal failure and in newborns until new methods that eliminate the interference caused by DLFs become readily available.

Adult↗

Autologous bone marrow transplantation as consolidation therapy for non-Hodgkin's lymphoma patients with poor prognostic features.

Theoretical considerations and preliminary results of clinical trials support the earlier use of autologous bone marrow transplantation (ABMT) in poor prognosis non-Hodgkin's lymphoma (NHL). A prognostic analysis of 50 patients with intermediate or high grade NHL younger than 60 years, who achieved at least one complete remission and were not treated with BMT, was performed. Patients with bulky tumor at diagnosis and/or serum LDH greater than or equal to 600 U/l do poorly with conventional chemotherapy. Twelve patients with these high-risk initial characteristics in first complete remission (CR) and six patients in second or third CR were treated with cyclophosphamide (60 mg/kg x 2) and total body irradiation (1000-1200 cGy) followed by ABMT. Overall disease-free survival was 65% at a median follow-up of 35 months. No differences were found between the first and later CR patients. The rate of toxic death was 11%. Disease-free survival after first CR was better for 1st CR ABMT patients than for a historical chemotherapy control group with similar poor prognosis features (p = 0.008). These results support the use of ABMT in selected, high-risk NHL patients in first CR.

Adolescent↗

[Bone marrow autotransplantation in patients with acute myeloblastic leukemia in primary remission].

Fifteen bone marrow autotransplants (BMAT) in patients with acute myeloblastic leukemia (AML) were performed after the first remission. The mean age was 37 years (range 12 to 60 years). According to the morphological classification FAB, 8 patients had monocytic leukemia (M4, M5) and 7 myeloid leukemia (M1, M2, M3). The mean interval elapsed between the date of complete remission and the BMAT was 3.9 months (range 1 to 5-9 months). In 8 patients this interval was longer than 6 months and in 7 cases it was shorter than 6 months. After achievement of the complete remission all patients underwent certain cycles of intensification before the BMAT. Eight patients received only a cycle whereas 7 patients received more than one cycle (between 2 and 4). The conditioning protocol consisted of cyclophosphamide (CP) (60 mg/kg x 2) and total body radiotherapy (TBR) (10 Gy) in 9 patients; CP and busulfan in five; and CP, cytarabine at high doses and melphalan in one case. Marrow extraction was performed after completion of chemotherapy of intensification. In 5 cases the bone marrow was depleted of leukemic cells by previous in vitro treatment with ASTA-Z. There are at present 8 alive patients. The survival free of illness was 51.8%. Seven patients died: 3 cases because relapse of the leukemia, 3 due to attachment failure of the transplantation, and one patient suffered a viral myocarditis. The survival free of illness was significantly longer in those patients transplanted after 6 months of the complete remission.

Adolescent↗

[Empirical treatment of febrile episodes in patients with neutropenia in bone marrow transplantation].

The results of therapy of febrile episodes during the pregraft phase in bone marrow transplant was retrospectively evaluated in 84 granulocytopenic patients. Most patients received co-trimoxazole and i.v. ticarcillin as antibacterial prophylaxis. 47 episodes were treated with a third generation cephalosporin plus an aminoglycoside, with a 55% favorable response rate. 37 episodes were treated with a wide spectrum penicillin plus an aminoglycoside, with a 41% response rate (p greater than 0.05). Among the 23 infections caused by gram-negative bacilli the response rate was 89% (8 of 9) with the first regimen, and 21% (3 of 14) with the second one (p = 0.003). The investigation of in vitro sensitivity suggested that prophylactic ticarcillin favors the infections due to bacilli with cross-resistance to wide spectrum penicillins. The antibiotic regimen did not influence the final resolution or the mortality rate of the febrile episode.

Adult↗

Use of salivary caffeine tests to assess the inducer effect of a drug on hepatic metabolism.

OBJECTIVE: To validate the use of successive salivary caffeine tests in evaluating how long inducer drugs affect hepatic metabolism. The time course of the inducer effect of rifampin found in other studies using different methodologies was chosen as the time course of reference. DESIGN: Open-label, prospective, longitudinal study. SETTING: A university hospital. PARTICIPANTS: Five healthy volunteers. MAIN OUTCOME MEASURES: Rifampin 600 mg/d was administered for 21 days. Anhydrous caffeine 300 mg was concurrently administered on each study day. Salivary caffeine tests were carried out on the following days: predose (baseline), and days 1, 5, 9, 13, and 17. Salivary tests were performed for up to 13 days after the last dose of rifampin (study days 21, 25, 29, and 33). RESULTS: The mean systemic caffeine clearance was increased for up to 17 days after the intake of rifampin, reaching the maximum inducer effect between days 5 and 9, and returning to previous values progressively during several days after rifampin was discontinued. CONCLUSIONS: Our results suggest that successive salivary caffeine measurements could be a safe, reliable, noninvasive, and suitable test for exploring the time course of the inducer effect of drugs on hepatic metabolism activity.

Adult↗