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Biomedical subjects

G Lawless

Publications and source records attributed to G Lawless.

8 recordsLinked to original sources
PubMed2001

Delivering adjuvant chemotherapy to women with early-stage breast carcinoma: current patterns of care.

BACKGROUND: Variations in practice patterns are markers for the quality of patient care in general medicine, but little is known about variation in care delivered to cancer patients. This study's purpose was to describe chemotherapy use, variations in chemotherapy delivery, and the incidence of complications in community practice settings. METHODS: Data describing adjuvant chemotherapy for patients with early-stage breast carcinoma (ESBC) were collected from an ongoing Oncology Practice Pattern Study at 13 large managed care, academic, and community practices (1111 patients). Data collection included information about diagnoses and adjuvant chemotherapy treatments, laboratory results, supportive care, complications, and treatment modifications. RESULTS: The median patient age was 50 years, and most patients had zero to three positive lymph nodes. Chemotherapy regimens consisting of cyclophosphamide, methotrexate, and 5-fluororacil (CMF) and of doxorubicin and cyclophosphamide (AC) accounted for 76% of the adjuvant therapies used. Overall, 30% of patients had delivered average relative dose intensities </= 85% of the referenced targets. Delivered summation dose intensities (SDIs) frequently were well below targeted SDIs. Neutropenia-related dose modifications occurred for 27.6% of patients and recurred with a 60.7% rate. AC was the regimen delivered with a dose intensity closest to the referenced target. However, patients who were treated with AC regimens and with regimens consisting of cyclophosphamide, doxorubicin, and 5-fluorouracil had significantly higher rates of chemotherapy-related complications compared with patients who were treated with CMF regimens in the most recent treatment years. CONCLUSIONS: Adjuvant chemotherapy for patients with ESBC frequently is not administered as referenced in off-protocol community settings. Variation in the delivered SDI raises concerns about potential treatment outcomes and warrants strategies to identify patients who are at risk for complications early in therapy.

Adult↗
PubMed2001

The impact of age on delivered dose intensity and hospitalizations for febrile neutropenia in patients with intermediate-grade non-Hodgkin's lymphoma receiving initial CHOP chemotherapy: a risk factor analysis.

The purpose of this historical case series study was to evaluate the association of age on delivered dose intensity of initial CHOP (cyclophosphamide/doxorubicin/ vincristine/prednisone) chemotherapy and the occurrence of hospitalizations for febrile neutropenia for patients with intermediate-grade non-Hodgkin's lymphoma (NHL). Findings are reported for 12 managed community and academic practices. Medical records of 930 NHL patients not enrolled on clinical trial protocols were reviewed. We reported on 577 of the study patients (62%) who received initial CHOP chemotherapy. Median age of the patients was 65.1 years. Older patients (age > or = 65 years) had more hospitalizations for febrile neutropenia (28% vs. 16%; P < 0.05) than younger patients (age, 18-64 years). In patients with advanced-stage NHL (stage III/IV), older patients received fewer cycles of CHOP (< 6 cycles, 35% vs. 22%; P < 0.05) than younger patients. Older patients were planned for lower average relative dose intensity (ARDI < or = 80%; P < 0.05) and had more heart disease and comorbid conditions (P < 0.05) than younger patients. Multiple logistic regression models showed that older patients were more likely to receive a lower dose intensity (ARDI < or = 80%; odds ratio = 2.46, 95% confidence interval [CI]: 1.62-3.72) during their first 3 cycles of therapy and to experience more hospitalizations for febrile neutropenia (odds ratio = 2.17, 95% CI: 1.43-3.30). We found the dose intensity of delivered CHOP chemotherapy for elderly patients to be less than standard CHOP therapy and the risk of hospitalizations for febrile neutropenia to be greater than in younger patients. Prospective clinical trials examining supportive care measures, such as colony-stimulating factor, for elderly NHL patients are recommended.

Adult↗
PubMed1999

Recombinant adeno-associated virus (AAV) drives constitutive production of glutamate decarboxylase in neural cell lines.

Many neurological disorders result directly or indirectly from the loss of inhibitory function. Engineering the production of GABA, an inhibitory neurotransmitter, may therefore be able at least partly to restore the lost inhibition seen in epilepsy, Parkinson's disease, or Huntington's disease. In this article, we describe a set of recombinant adeno-associated viruses (AAVs) that can deliver cDNAs encoding the GABA-producing enzyme, glutamate decarboxylase (GAD), directly into neural cells. We have characterized these recombinant AAVs in several cell lines derived from the CNS. These recombinant AAVs effectively transduced all neural cell lines, although with different efficiencies. Transduction occurred in both proliferating and nonproliferating cells, but actively proliferating cell lines had approximately six times greater transduction efficiency than nonproliferating cells. Furthermore, these AAVs maintained long-term expression of GAD in an astrocytic cell line for at least seven passages. These recombinant AAVs are promising vehicles for investigating the potential therapeutic effects of GABA in animal models of epilepsy and neurodegenerative diseases.

Animals↗
PubMed1997

A rapid desktop theophylline assay. Evaluation of use in clinical management.

STUDY OBJECTIVES: To assess the practicality and precision of a simple desktop theophylline assay (Biotrack 516TM) in comparison to a standard laboratory assay system (Abbott TDxTM). DESIGN: A prospective blinded paired sample study. SETTING: The respiratory ward and outpatient clinics, the pulmonary function and biochemistry laboratories of a university teaching hospital. PATIENTS: Sixty patients with asthma or COPD attending the respiratory service. MEASUREMENTS AND RESULTS: Paired specimens for theophylline assay were collected simultaneously for analysis. There was a highly significant (p < 0.001) correlation between the two assay systems for both the total range studied (1.2-39.1 micrograms/mL; r = 0.98), and the clinically important range of 5-15 micrograms/mL (r = 0.95). The limits of agreement for the data by the Bland and Altman method indicated a +/-2 micrograms/mL limit for the 5-15 micrograms/mL range and a +/-2.7 micrograms/mL limit for the total range studied. CONCLUSIONS: The Biotrack 516 is an easy-to-use system, which provides rapid and reasonably precise measurements of serum theophylline levels. The device should be of particular value in smaller centers without an on-site laboratory assay system.

Evaluation Studies as Topic↗
PubMed1995

Role of extracellular calcium influx in EGF-induced osteoblastic cell proliferation.

This study investigated the effects of epidermal growth factor (EGF) on cytosolic calcium ([Ca++]i) levels in rat calvarial osteoblasts, the nature of the regulation of this event, and the role these EGF-induced [Ca++]i changes have in osteoblastic cell proliferation. EGF significantly increased [Ca++]i measured in fura-2-loaded, individual cells. This increase was related to extracellular calcium influx. Activation of protein kinase C(PKC) by pretreating the cells with phorbol esters blocked the EGF-induced increase in [Ca++]i. EGF failed to increase inositol trisphosphate levels measured by high performance liquid chromatographic analysis. However, it did increase inositol bisphosphate and inositol tetrakisphosphate production. The EGF-dependent increase in DNA synthesis was partially blocked by the addition of calcium channel blockers. Therefore, it appears that the mechanism of action of EGF-induced osteoblastic cell proliferation is mediated by changes in [Ca++]i primarily due to extracellular calcium influx.

Analysis of Variance↗
PubMed1990

Direct stereotactic intracerebral injection of monoclonal antibodies and their fragments: a potential approach to brain tumor immunotherapy.

Delivery of monoclonal antibodies (Mab) to brain tumors is restricted by the blood:brain barrier. To circumvent this problem, we studied direct stereotactic injection of the Mab into the brain. An anti-melanoma intact Mab and its Fab fragments, which do not react with normal rat brain, were radioiodinated and injected either intracerebrally (IC) or intravenously (IV) into rats. At 5 days after injection, IC delivery of intact antibody was 101 times higher than IV delivery. The ratio of radioantibody in injected cerebrum:blood was 14:1. With IC delivered Fab fragments, the radioantibody ratio in injected cerebrum:blood was 242:1 at 5 days after IC injection, with a 680-fold delivery advantage over IV injection. These data demonstrate a dramatic regional delivery advantage for intact Mab and especially for Fab fragments injected directly into the brain. This route of Mab delivery may have therapeutic potential for brain tumors.

Animals↗
PubMed1972

Atopic eczema.

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Eczema↗