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Biomedical subjects

J Bentley

Publications and source records attributed to J Bentley.

At least 19 recordsLinked to original sources

Granulocyte colony-stimulating factor to prevent dose-limiting neutropenia in non-Hodgkin's lymphoma: a randomized controlled trial.

The effect of granulocyte colony-stimulating factor (G-CSF) on neutropenia, infection, and cytotoxic chemotherapy administration was studied in a randomized trial in patients receiving intensive weekly chemotherapy for non-Hodgkin's lymphoma (NHL). Eighty patients (aged 16 to 71 years) with high-grade NHL (Kiel) of any stage were randomized to receive VAPEC-B chemotherapy alone (39 patients) or with G-CSF administered as a daily subcutaneous dose of 230 micrograms/m2 (41 patients). Prophylactic ketoconazole and cotrimoxazole were administered to all patients throughout treatment. The protocol specified identical dose modification and antibiotic treatment criteria bor both groups. Neutropenia (absolute neutrophil count [ANC] less than 1.0 x 10(9)/L) occurred in 15 of 41 (37%) of the G-CSF-treated patients and in 33 of 39 (85%) of the controls, giving a relative risk for control patients of 2.31 (95% confidence interval [CI], [1.51, 3.54]; P = .00001). Fever (greater than or equal to 37.5 degrees C) with neutropenia (ANC less than 1.0 x 10(9)/L) occurred in 9 of 41 (22%) of the G-CSF group and in 17 of 39 (44%) of the controls (relative risk for control, 2.26; 95% CI [1.01, 5.06]; P = .04). There were fewer treatment delays, with shorter duration (P = .01) in patients receiving G-CSF. Chemotherapy doses were reduced in 4 of 41 (10%) of the G-CSF patients and 13 of 39 (33%) of the controls (P = .01). The dose intensity of cytotoxic chemotherapy was significantly increased in patients receiving G-CSF (median of 95% in G-CSF group compared with 83% in control patients). Three vascular deaths occurred in the G-CSF group. Delays in the control group most commonly resulted from neutropenia (19 patients, compared with 2 patients in the G-CSF-treated group, P = .000007). Severe mucositis was the major dose-limiting toxicity in G-CSF-treated patients, but did not occur more frequently than in controls (15 patients in each group). Overall, patients randomized to receive G-CSF achieved a greater dose intensity than control patients, but this did not result in significant differences in drug toxicity (other than neutropenia), intravenous antibiotic usage, or hospitalization between the two groups.

Adolescent

Reflection electron energy-loss spectroscopy and imaging for surface studies in transmission electron microscopes.

A review is given on the techniques and applications of high-energy reflection electron energy-loss spectroscopy (REELS) and reflection electron microscopy (REM) for surface studies in scanning transmission electron microscopes (STEM) and conventional transmission electron microscopes (TEM). A diffraction method is introduced to identify a surface orientation in the geometry of REM. The surface dielectric response theory is presented and applied for studying alpha-alumina surfaces. Domains of the alpha-alumina (012) surface initially terminated with oxygen can be reduced by an intense electron beam to produce Al metal; the resistance to beam damage of surface domains initially terminated with Al+3 ions is attributed to the screening effect of adsorbed oxygen. Surface energy-loss near-edge structure (ELNES), extended energy-loss fine structure (EXELFS), and microanalysis using REELS are illustrated based on the studies of TiO2 and MgO. Effects of surface resonances (or channeling) on the REELS signal-to-background ratio are described. The REELS detection of a monolayer of oxygen adsorption on diamond (111) surfaces is reported. It is shown that phase contrast REM image content can be significantly increased with the use of a field emission gun (FEG). Phase contrast effects close to the core of a screw dislocation are discussed and the associated Fresnel fringes around a surface step are observed. Finally, an in situ REM experiment is described for studying atomic desorption and diffusion processes on alpha-alumina surfaces at temperatures of 1,300-1,400 degrees C.

Aluminum Oxide

A pharmacokinetic and tolerance study of romazarit in patients with rheumatoid arthritis.

Romazarit is a new drug for which animal pharmacology suggests a disease-modifying action in rheumatoid arthritis (RA). These animal studies predict that plasma romazarit concentrations within the range 50-100 mg l-1 may be required for efficacy in the clinic. Therefore, a pharmacokinetic study was designed to estimate the dosage required to achieve these concentrations in man. Twenty-four patients with RA entered a double-blind controlled assessment receiving either placebo, 100 mg t.i.d., 350 mg b.i.d., or 350 mg t.i.d., for 6 days. Pharmacokinetic profiles were measured after single doses and after the last of the multiple doses. Adverse events were mainly trival and were distributed almost equally between all three treatment and the placebo groups. Plasma romazarit concentrations were not dose-proportional after the single doses. Mean peak plasma drug concentrations were 11.8, 66.7, and 159 mg l-1 at steady state after 100 mg t.i.d., 350 mg b.i.d., and 350 mg t.i.d. The mean urinary recovery of drug-related material (mostly ester glucuronides) was 71 per cent of the dose during the dosage interval. The renal clearance of romazarit glucuronides correlated with creatinine clearance (p less than 0.01). Saturable tubular secretion of glucuronides coupled with reversible glucuronidation would explain these findings. It is predicted that oral doses of 450 mg romazarit given 12-hourly will result in plasma concentrations within the target range of 50-100 mg l-1.

Administration, Oral

Introducing confident midwives: Midwifery Education--Action for Safe Motherhood.

The present crisis in midwifery and the seriousness of maternal mortality and morbidity demands a rethink about the background and training requirements of each level of midwifery worker. This paper describes the background of the present shortage and mal-distribution of midwives. The reduction of maternal mortality by 50% at the turn of this century requires the development of a maternal health care team in which the midwife functions as the linchpin. In order to equip the midwife for the leadership functions in this team, the present educational system needs to be fundamentally improved. The rationale for the acquisition of epidemiological, managerial specialised technical and teaching skills by midwives is discussed. Implications for further education are high-lighted. Collaborative actions taken by the WHO, ICM, UNICEF and other governmental and non-governmental agencies to address the issue of midwifery are outlined. This paper was given at the 1990 ICM, WHO, UNICEF Pre-Congress Workshop on Midwifery Education--Action for Safe Motherhood in Kobe, Japan.

Clinical Competence

Residents' hours and supervision.

One year of graduate medical education, the internship, had become the norm for graduates of most U.S. medical schools by 1920, and subsequently was adopted by most states as a criterion for licensure. The original concept of a "resident physician" carried with it responsibility for patients 24 hours per day, seven days per week. Recent public and media attention to the issues of residents' supervision and working hours has led to governmental efforts to restrict their hours and set minimum requirements for supervision. New York is the first state to impose specific requirements. The New York recommendations have implications for the concept of graded responsibility for residents, for learning the natural course of illness, and for the need to provide service in hospitals. Further, the recommendations raise four objections: they do not recognize differences by type of specialty or year of training; they might affect the length of time needed to acquire aggregate clinical skills; they affect different types of hospitals differently; and they would have a major effect on physician manpower. Hospitals and residency programs will face several difficult choices in responding to the regulations. To provide its members with guidelines for action, the Executive Council of the Association of American Medical Colleges has issued recommendations for residency hours and supervision, including the use of an 80-hour work-week averaged over four weeks, the continued use of graded supervision of residents in emergency rooms and in inpatient and ambulatory settings, and control of housestaff moonlighting.

Emergency Service, Hospital

Stereo-electron microscopy and energy-dispersive x-ray analysis of avian reticulocytes.

Utilizing the techniques of stereo-electron microscopy (stereo-EM) and energy-dispersive x-ray analysis (EDX), we have studied aspects of the ultrastructure of avian reticulocytes. Stereo-EM of thin sections (0.10 to 0.25 mum thick) stained with uranyl and lead revealed the three-dimensional arrangement of 25 nm chromatin fibers on the tangential surfaces of nuclei. Use of the Bernhard staining procedure in combination with stereo-EM permitted a three-dimensional view of the interchromatin spaces and channels leading to the nuclear pores, and of cytoplasmic polyribosomes. With either staining technique we frequently encountered in the cytoplasm clusters and paracrystalline arrays of electron-dense granules with granule diameters approximately 1/2 that of monomer ribosomes. These granules were highly electron-dense in unstained specimens and have been identified as intracellular ferritin on the basis of the similarity of their ultrastructural morphology to that of horse spleen ferritin and their high content of iron as determined by EDX. The possibility that these granules represent toxic products of phenylhydrazine treatment (Heinz bodies) is considered unlikely, since we have demonstrated in this study that Heinz bodies cannot be visualized in unstained preparations, do not reveal the same granular structure, and do not contain significant amounts of iron above background. The occurrence of intracellular ferritin is discussed in light of current concepts of iron transport and storage during erythropoiesis.

Anemia