Biomedical subjects

M V Bernardo

Publications and source records attributed to M V Bernardo.

7 recordsLinked to original sources

PubMed2001

Sample size calculations for the two-sample problem using the multiplicative intensity model.

In this paper we propose formulae for calculating the expected number of events or, alternatively, the required trial duration, for clinical trials involving two treatment groups in which patients may potentially experience multiple events and the data will be analysed using a multiplicative intensity (MI) model. We use a partial likelihood-based approach and examine in detail two MI models: one that includes a binary treatment variable as the only covariate and a three-state Markov process model in which a binary time-varying covariate is added to the previous model. For the simpler model, our formula coincides with those derived by Cook using full likelihood methods. We present applications of the derived formulae to chronic granulomatous disease and breast cancer data sets.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2000

Is radiation alone adequate treatment to the axilla for patients with limited axillary surgery? Implications for treatment after a positive sentinel node biopsy.

PURPOSE: To estimate the possible efficacy of axillary radiation therapy (AXRT) following a positive sentinel node biopsy (SNB), we evaluated the risk of regional nodal failure (RNF) for patients with clinical Stage I or II, clinically node-negative invasive breast cancer treated with either no dissection or a limited dissection (LD) defined as removal of 5 nodes or less followed by AXRT. MATERIALS AND METHODS: From 1978 to 1987, 292 patients underwent AXRT in the absence of axillary dissection; 126 underwent AXRT following LD. The median dose to the axilla was 46 Gy. The median dose to the supraclavicular fossa was 45 Gy. Among patients found to have positive nodes on LD, adjuvant chemotherapy and tamoxifen were administered to 81% and 7% of subjects, respectively. All patients had potential 8-year follow-up. RESULTS: Six of the 418 patients (1. 4%) developed RNF as a first site of failure within 8 years. Among these 6 patients (1.4%) with RNF as the first site of failure, 4 had simultaneous distant and regional recurrences; and 2 had isolated axillary failures. Three of the 292 patients (1%) with no axillary dissection, none of 84 patients with pathologically negative nodes and 3 of 42 patients (7%) with pathologically involved nodes had RNF as a first site of failure. Radiation pneumonitis developed in 5 patients (1.2%), brachial plexopathy in 5 (1.2%) and arm edema in 4 (1.2%). In all cases, radiation pneumonitis and brachial plexopathy were transient. CONCLUSION: These results imply that AXRT may be an effective and safe alternative to completion dissection for treatment of the axilla following a positive SNB. Further studies comparing these two options in specific patient subgroups are needed.

Aged↗

PubMed2000

Aerosolized pentamidine as pneumocystis prophylaxis after bone marrow transplantation is inferior to other regimens and is associated with decreased survival and an increased risk of other infections.

Pneumocystis carinii pneumonia (PCP) is a life-threatening but preventable infection that may occur after bone marrow transplantation (BMT). Although various prophylactic regimens have been used in this setting to prevent active infection, their efficacy, toxicity profile, and impact on outcomes are poorly described in this patient group. We undertook a retrospective cohort study in which we reviewed the records of 451 adult patients who underwent BMT for hematologic malignancies, aplastic anemia, or myelodysplasia over a 7-year period at the Brigham and Women's Hospital. Post-BMT PCP prophylaxis consisted of aerosolized pentamidine (AP) 150 mg every 2 weeks or 300 mg per month, trimethoprim/sulfamethoxazole (TMP/SMX) 160/800 mg orally b.i.d. 3 times per week, or dapsone 100 mg orally each day. Prophylaxis was continued for 1 year post-BMT in all patients when clinically feasible. One hundred twenty-one patients were unevaluable because of death or relapse <60 days after BMT (n = 89), loss to follow-up upon hospital discharge (n = 20), or other reasons (n = 12). Three eligible patients did not receive any prophylaxis and were not further evaluated. Of the 327 patients analyzed, 133 underwent autologous BMT, 4 syngeneic BMT, 159 related allogeneic BMT, and 31 unrelated allogeneic BMT. Graft-versus-host disease prophylaxis in the 190 patients receiving allogeneic BMT consisted of T-cell depletion with anti-CD5 and complement in 58 patients and cyclosporine/methotrexate or FK506 with or without steroids in 132 patients. Eight of 327 (2.4%) documented PCP cases were identified, 0 of 105 in patients receiving only TMP/SMX. Four cases occurred in patients receiving only AP (4/44, 9.1%; odds ratio [OR] relative to TMP/SMX 23.4, 95% confidence interval [CI] 1.2, 445.2); 1 in patients receiving only dapsone (1/31, 3.2%; OR not significant); 2 in patients receiving more than 1 prophylactic regimen (2/147 1.4%; OR not significant); and 1 >1 year post-BMT in a patient who was off PCP prophylaxis. Although the patients receiving only AP had a significantly lower probability of treatment-related toxicity than those receiving TMP/SMX (OR 0.19 [95% CI 0.04, 0.851), the probability of their acquiring other serious non-PCP infections was increased (OR 2.2 [95% CI 1.0, 4.6]), and the probability of their dying by 1 year post-BMT was significantly higher (OR 5.2 [95% CI 2.4, 26.6]), even when adjusted for variables such as type of BMT (autologous versus allogeneic; high versus low risk) and sex. Although AP is associated with fewer toxicities, the data show that it is inferior to TMP/SMX in preventing PCP in the post-BMT setting and is associated with an increased risk of other infections and a higher mortality at 1 year after BMT.

Administration, Inhalation↗

PubMed1999

Bupivacaine-loaded comatrix formed by albumin microspheres included in a poly(lactide-co-glycolide) film: in vivo biocompatibility and drug release studies.

Bupivacaine-loaded comatrix, formed by bupivacaine-loaded microspheres included in a poly(lactide-co-glycolide) film, was assayed for the controlled release of the drug 'in vivo'. The comatrix, with 66.37 microg of bupivacaine, signifying a dose of 265.5 microg/kg, was subcutaneously implanted in the back of rats. Maximum plasma bupivacaine concentration was 147.6 +/- 5.0 ng/ml 95 h after the device implantation, and the drug was detected in plasma for 17 days. The half-life time of bupivacaine improves by more than 50 times with regard to that of the drug administered in a solution by intraperitoneal injection. After 15 days of implantation the comatrix was included in a thin fibrous capsule and degradation of the microspheres was observed. The histological studies show good biocompatibility of this comatrix. After 50 days the comatrix was degraded and its remains were almost indistinguishable from the surrounding tissue. Small number of microspheres was observed and they were surrounded by conjunctive tissue. Nerve packets and small blood vessels were also observed in the periphery of the implant.

Animals↗

PubMed1998

Poly(acrylamide-co-monoethyl itaconate) hydrogels as devices for cytarabine release in rats.

This study has tested the application of three different copolymeric poly(acrylamide-co-monoethyl itaconate; A/MEI) hydrogels, 90A/10MEI, 75A/25MEI and 60A/40MEI, on the release of cytarabine (ara-C). The drug was incorporated in gels by placing it in the polymerization feed mixture and discs loaded with 5-50 mg ara-C were obtained. The amount of swelling at equilibrium in saline solution (NaCl, 0.9% w/w) was between 78 and 82% w/w, depending on the composition of the copolymer. The diffusion studies followed Fick's second law. The diffusion coefficients for swelling of the gels were between 9.30 x 10(-11) m2 s(-1) and 37.42 x 10(-11) m2 s(-1); those for release of ara-C were between 3.42 x 10(-11) m2 s(-1) and 10.25 x 10(-11) m2 s(-1). The activation energies for swelling were in the range 16.60 +/- 2.59-21.85 +/- 1.78 kJ mol(-1); those for ara-C release were 28.13 +/- 3.1-29.7 +/- 4.6 kJ mo(-1). To determine the applicability of these copolymers, 75A/25MEI gel was subcutaneously implanted in rats and the plasma concentration of the drug was determined by high-performance liquid chromatography. The concentration of ara-C in plasma (range 17.67 +/- 5.68-10.76 +/- 2.15 microg mL(-1)) was maintained during the first stages (2-8 h) and no drug was detected after 32 h. This route of administration was compared with intraperitoneal injection of the drug. In conclusion, ara-C can be incorporated in hydrogels and released in a pharmacologically active form. The concentration of ara-C in plasma is maintained for long enough to improve therapeutic results.

Acrylamides↗

PubMed1995

Acute decreases in serum potassium augment blood pressure.

Potassium depletion is a risk factor for cardiovascular diseases, including hypertension, and frequently is encountered in patients with end-stage renal disease. Since the treatment of end-stage renal disease might result in K+ depletion and postdialysis hypokalemia, we investigated the relationship between acute K+ removal by hemodialysis and changes in blood pressure at the completion of treatment compared with predialysis and 1-hour postdialysis blood pressure. The effects of three different dialysate potassium concentrations ([K+]d; 1.0, 2.0, and 3.0 mmol/L) were investigated in 11 patients. Hemodialysis-induced K+ removal, serum [K+], total body K+, and blood pressure were measured. The use of 1.0, 2.0, or 3.0 mmol/L [K+]d resulted in the removal of 77.0 +/- 6.5, 54.5 +/- 7.9, and 42.5 +/- 9.9 mmol of K+ per treatment, respectively (P < 0.05, [K+]d 1.0 v [K+]d 3.0). Predialysis and postdialysis serum [K+] were 4.9 +/- 0.2 and 3.6 +/- 0.1 mEq/L for 1.0 mmol/L [K+]d, 5.1 +/- 0.3 and 3.9 +/- 0.1 mEq/L for 2.0 mmol/L [K+]d, and 5.3 +/- 0.3 and 4.2 +/- 0.2 mEq/L for 3.0 mmol/L [K+]d, respectively (P < 0.001 for each [K+]d). The baseline total body K+ corrected for gender, age, and race was 92% of predicted normal level and did not change significantly with the use of different [K+]d. Blood pressure decreased during hemodialysis as excess fluid was removed, regardless of [K+]d. Significant increases in blood pressure did occur 1 hour postdialysis compared with levels measured at the completion of treatment ("rebound hypertension") when hemodialysis was performed with 1.0 and 2.0 mmol/L, but not with 3.0 mmol/L [K+]d.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗

PubMedDate not supplied

In vitro controlled release of bupivacaine from albumin microspheres and a co-matrix formed by microspheres in a poly(lactide-co-glycolide) film.

Albumin microspheres cross-linked with glutaraldehyde and loaded with bupivacaine, a local anaesthetic, were synthesized (138 +/- 59 microm diameter). A matrix formed by bupivacaine-loaded microspheres in a poly(lactide-co-glycolide) film was prepared in order to improve the controlled release of the drug. In vitro release of the drug was determined in phosphate buffer at 37 degrees C in the absence and in the presence of protease type VIII to mimic a biological system. The effect of temperature and protease on bupivacaine as a function of time was examined; both of them cause a degradative effect on the drug. A rapid release (60 +/- 8% of the drug) takes place at 1 h, and maximum release is found at 50 +/- 6 h from microspheres with swelling. In the presence of protease, maximum release of bupivacaine from microspheres is found at 28 +/- 2 h; the microspheres disappear at 8 days. Inclusion of bupivacaine-loaded microspheres in a poly(lactide-co-glycolide) film causes a slower release of the drug, up to 18 days, with swelling. In the presence of protease, the polymer protects bupivacaine-loaded microspheres from degradation, which takes place at 20 days.

Animals↗