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Biomedical subjects

L White

Publications and source records attributed to L White.

At least 181 records · Page 10Linked to original sources
PubMed1989

Evaluation of response to chemotherapy in retinoblastoma heterotransplanted to the eyes of nude mice.

The role of chemotherapy in the treatment of retinoblastoma (RB) is unsatisfactory and clinical research is severely limited. A xenograft model for testing chemotherapeutic and other agents has been developed by the heterotransplantation of human RB cells into the anterior chamber of the nude mouse eye. A grading system for visually monitored tumor growth was designed to allow serial observations and documentation of the response to therapy in the model. This method of monitoring compared favorably with histopathologic, photographic, or other criteria in the reproducible, sequential evaluation of tumor status. Six chemotherapeutic agents [vincristine (VCR), doxorubicin (DOX), actinomycin D (ACT-D), dimethyltriazeno-imidazole carboxamide (DTIC), cyclophosphamide (CPM), and diaziquone (AZQ)] were then tested in the model against a patient-derived xenograft line. Results were expressed as the delay in tumor progression judged by serial grading. CPM produced a consistent response in all treated tumors, as did DTIC to a lesser, more variable extent. In 3 of 10 tumors treated with CPM and in 1 of 18 treated with DTIC, complete responses were maintained for at least 20 weeks. VCR, DOX, and ACT-D were ineffective, producing patterns of tumor progression no different from those in the control group. AZQ was most effective, producing responses far exceeding those of conventional agents. The model allows quantitative documentation of the response to therapy in heterotransplanted human RB. Further testing of new agents and combinations is warranted. AZQ may be active against RB.

Animals↗
PubMed1989

Pay for performance. Implementing a financial incentive for excellent work.

Based upon my own experience with the system, both staff and supervisors believe that the advantage of pay for performance outweigh the disadvantages. I frequently encountered issues such as how to get a higher rating, what is the incentive to identify a difficult objective if one can pick an easier objective and still receive a higher rating, and where do individuals fall in the ratings compared to peers. In response to achieving a higher rating, the supervisors reviewed the rating system and developed objectives that would receive higher ratings. The supervisors and administrators put emphasis on improved performance, rather than on points. To convince employees to choose more difficult objectives, we explained that objectives should reflect the skills and goals of each employee. The objective serves as an indicator of how well the employee achieved a goal. In dealing with the ranking problem, we told the staff where they ranked in relation to others (eg, top, middle, bottom), but emphasized that the evaluation is confidential and that the results are not to be shared. In conclusion, pay for performance offers a supervisor a detailed objective format for reviewing an employee's performance. For the employees, it provides a means in which their performance review is based on individual achievement of self-selected objectives. Employees are measured against their own standards rather than being compared with others performing the same job.

Clinical Competence↗
PubMed1989

Antiemetic therapy for chemotherapy-induced vomiting: metoclopramide, benztropine, dexamethasone, and lorazepam regimen compared with chlorpromazine alone.

Twenty-six children aged 4 to 15 years who were to receive cancer chemotherapy were enrolled in a double-blind, randomized, crossover trial that compared the antiemetic efficacy of a four-drug regimen (the MBDL regimen: metoclopramide, 8 mg/kg; benztropine, 0.04 mg/kg; dexamethasone, 0.7 mg/kg; lorazepam, 0.1 mg/kg), given over 24 hours, with the efficacy of chlorpromazine, 3.3 mg/kg, given in four doses over 24 hours. The MBDL regimen was more effective than chlorpromazine in both objective and subjective measures of antiemetic control. Of 26 children, 23 (89%) had less vomiting on the MBDL regimen, and 20 (77%) of 26 patients or parents preferred this regimen (p less than 0.01). The MBDL regimen reduced the number of vomiting episodes by a mean of 4.0 (p less than 0.01) and reduced the duration of vomiting by a mean of 3.7 hours (p less than 0.01). A moderate level of sedation was documented at some stage in the 24-hour period of observation in 27% on the MBDL regimen and in 35% receiving chlorpromazine. Dystonia was seen in 1 (4%) of 26 children. We conclude that the MBDL regimen is safe in children and more effective than chlorpromazine.

Adolescent↗
PubMed1989

Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease.

Interleukin 1, an immune response-generated cytokine that stimulates astrocyte proliferation and reactivity (astrogliosis), was present in up to 30 times as many glial cells in tissue sections of brain from patients with Down syndrome and Alzheimer disease compared with age-matched control subjects. Most interleukin 1-immunoreactive glia in Down syndrome and Alzheimer disease were classified as microglia. The number of interleukin 1 immunoreactive neurons did not appear to differ in Down syndrome and Alzheimer disease compared with control brain. Numerous temporal lobe astrocytes in Alzheimer disease and postnatal Down syndrome were intensely interleukin 1-, S-100-, and glial fibrillary acidic protein-immunoreactive and had reactive structure. Interleukin 1 levels in Alzheimer disease temporal lobe homogenates were elevated, as were the levels of S-100 and glial fibrillary acidic protein, two proteins reportedly elevated in reactive astrocytes. These data suggest that increased expression of S-100 in Down syndrome, resulting from duplication of the gene on chromosome 21 that encodes the beta subunit of S-100, may be augmented by elevation of interleukin 1. As a corollary, the astrogliosis in Alzheimer disease may be promoted by elevation of interleukin 1.

Adult↗
PubMed1989

The association of age-related macular degeneration and lens opacities in the aged.

Data from 3,087 persons age 45 or older in the National Health and Nutrition Survey, 1971-74, showed that subjects with lens opacifying disease had an increased odds for age-related macular degeneration (AMD) compared to those who had no lens opacities. The crude odds ratio for aphakic patients was 4.6 (95% CI = 2.5, 8.6). The association remained after controlling for age, sex, and systolic blood pressure (a common risk factor) in a logistic regression model. These data are consistent with the hypothesis that light-induced damage may contribute to both lens and retinal disease and suggest that cataract extraction without implantation of ultra-violet/blue light absorbing intraocular lens may place subjects at increased risk of AMD.

Aged↗
PubMed1989

Comparison of cyclophosphamide and diaziquone in a retinoblastoma xenograft model.

The benefits and optimal applications of chemotherapy in the management of retinoblastoma remain to be defined. There are major obstacles to its further study in the clinical setting. A xenograft model of human retinoblastoma heterotransplanted directly into the anterior chamber of the nude mouse eye has been adapted for evaluation of therapeutic efficacy. Cyclophosphamide, the most effective conventional drug, and diaziquone, an experimental agent, both produced documented and comparable responses in each of four xenograft cell lines. There was no evidence of rapidly emerging drug resistance or cross-resistance between two agents when sequential chemotherapy courses were given. Diaziquone is an effective chemotherapeutic agent for retinoblastoma in the xenograft model, and may have applications in clinical management.

Animals↗
PubMed1989

Regulation of tyrosine hydroxylase activity in rat PC12 cells by neuropeptides of the secretin family.

Tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, is subject to regulation by the cAMP as well as the calcium and cGMP second messenger systems. Treatment of intact rat PC12 cells with neuropeptides including secretin and vasoactive intestinal polypeptide (VIP) stimulated tyrosine hydroxylase activity 2 to 3-fold in vitro. Secretin (EC50 = 10 nM) was about 3 orders of magnitude more potent than VIP (EC50 = 3 microM). A combination of several protease inhibitors failed to enhance the potency of either peptide. Other members of the secretin family including glucagon and peptide histidine isoleucine (PHI) stimulated tyrosine hydroxylase activity to a lesser extent. Somatostatin, which is not homologous to secretin, was ineffective. The maximal response of tyrosine hydroxylase activation to 1 microM secretin occurred within 6-15 sec. Secretin, VIP, and forskolin also enhanced tyrosine hydroxylase activity (3,4-dihydroxyphenylalanine production) in intact cells, as determined by high performance liquid chromatography and electrochemical detection. Secretin, VIP, PHI, and glucagon increased the levels of cAMP in PC12 cells more than 10-fold, as determined by radioimmunoassay. We also demonstrated that cAMP is released from the cells into the incubation medium following secretin treatment. Secretin and VIP treatment also enhanced the activity of cAMP-dependent protein kinase in a concentration-dependent fashion, as measured subsequently in vitro. Based on the greater potency of secretin in comparison with VIP, PHI, and glucagon, we suggest that the PC12 cells contain a secretin-preferring receptor that increases cAMP levels and brings about an activation of tyrosine hydroxylase activity through the stimulation of cAMP-dependent protein kinase.

Adrenal Gland Neoplasms↗
PubMed1989

Effective therapy for a severe case of the idiopathic hypereosinophilic syndrome.

An 8-year-old boy with idiopathic hypereosinophilic syndrome (HES) is reported. He has been maintained in prolonged hematologic remission with vincristine and mercaptopurine despite an initial eosinophil count of 186 X 10(9)/L and a poor response to prednisone and hydroxyurea. Success with this combination of chemotherapeutic agents has not previously been reported in the management of HES. Progressive endomyocardial fibrosis required cardiac surgery 11 months after diagnosis. The management of this disorder is discussed with a review of the published literature.

Cardiomyopathies↗
PubMed1989

Cancer prevention and detection in nursing practice.

Cancer screening by definition is an organized effort to detect cancer at an early stage when reduced mortality is possible. Cancer screening should not be the exclusive responsibility of cancer centres or large urban medical centres. Rather, every healthcare professional should play a significant role in the early detection and education of patients with cancer. Some of the most common and life-threatening forms of cancer are the most preventable. Practical and inexpensive steps exist for thorough and effective screening. Nurses educated in the early detection of cancer are in a unique position; they are on the front line of patient care in educating patients as to the many benefits of early detection. Nurses can incorporate cancer prevention and detection into clinical practice, and by uniting together in these efforts, we will see progress against cancer.

Health Behavior↗
PubMed1988

A cluster of chromosome 11p13 translocations found via distinct D-D and D-D-J rearrangements of the human T cell receptor delta chain gene.

Human T cell tumours have few consistently occurring translocations which provide markers for this disease. The translocation t(11;14)(p13;q11), however, seems to be an exception, since it has been repeatedly observed in T-ALL. We have analysed a number of T-ALL samples carrying the t(11;14) with a view to assessing the nature of the translocated sequences on chromosomes 11 and 14. Three of the tumours studied have breakpoints, at 14q11, within the T cell receptor delta chain locus, while a fourth appears to break in the J alpha region. The TCR delta sequences involved in the translocation junctions are made from D delta-D delta-J delta joins or from D delta-D delta joins, allowing us to define distinct human D delta and J delta segments. These results allow us to make a comparison between the human and mouse TCR delta loci, both as regards sequence and rearrangement hierarchies. The disparate translocation breakpoints at chromosome 14q11 contrast with the marked clustering of breaks at chromosome 11p13; in all four cases, the breakpoint occurs within a region of less than 0.8 kb of chromosome 11. The analysis of junctional sequences at the 11p13 breakpoint cluster region only shows a consensus heptamer-like sequence in one out of four tumours analysed. Therefore, recombinase-mediated sequence specific recognition is not the only cause of chromosomal translocation.

Animals↗
PubMed1988

Ineffective photodynamic therapy (PDT) in a poorly vascularized xenograft model.

Haematoporphyrin derivative (HPD) photodynamic therapy (PDT) may have clinical application in the management of patients with retinoblastoma. Heterotransplantation of retinoblastoma cells into the anterior chamber of the nude mouse eye and the subsequent growth of small tumour masses has provided a model for evaluation of various therapeutic modalities. Ninety-four evaluable xenograft tumours in 54 nude mice were randomized to receive one of the following treatments: cyclophosphamide (CPM) alone, HPD-PDT alone, CPM followed by HPD-PDT, HPD-PDT followed by CPM, or saline control. Responses were demonstrated after CPM treatment in all three relevant groups. However, HPD-PDT was found to be ineffective either alone or as a contributor in the double modality treatment groups. The small tumour masses treated can be demonstrated histologically to be avascular. It is proposed that although the same retinoblastoma cells in different circumstances are responsive to HPD-PDT, no clinical response is demonstrable utilizing this model, due to the absence of tumor vascularity.

Animals↗
PubMed1988

Staying alive.

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Appointments and Schedules↗