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Biomedical subjects

A Jones

Publications and source records attributed to A Jones.

At least 685 records · Page 38Linked to original sources
PubMed1968

Clinical factors determining curative tumor dose.

The dominant factor determining treatment policy, when considering radiotherapy of a neoplastic disorder, is the biologic nature of the tumor process in relation to its spatial configuration. This is also the important factor determining curative tumor dose. With the exception of very small tumors and certain important radiosensitive conditions, it is the effect on normal tissues which defines the limits of irradiation and which effectively determines the prescription of dosage. The relationship between dose and volume is basic to this discussion and is considered with particular reference to the integrity of mesenchyme. When comparing the radiosensitivities of tumor and host tissues, it is important to compare like with like. The ultimate effect on a tumor is measured functionally, in terms of suppressing the only function by which the tumour is recognized--its capacity for indefinite proliferation--and reflected in 5- and 10-year cure rates. The effects on normal tissues should therefore be similarly measured in dynamic terms of the final functional state rather than on any transient structural appearance. These features are considered in relation to three different clinical situations: certain radiosensitive tumors, accessible primary tumors of limited sensitivity, and large tumors situated deeply. It is emphasized that curative treatment requires careful clinical appraisal of all the relevant features in each individual patient. The state of both tumor and host reaction may change significantly during the period of treatment and there is no alternative to continuous clinical observation using all the ancillary aids available.

Carcinoma, Squamous Cell↗
PubMed1966

Just people.

Explore the source record for details and available documents.

Humans↗
PubMedDate not supplied

Multilevel models and health economics.

Multilevel analyses have become an accepted statistical technique in the field of education where over the past decade or so the methods have been developed to explore the relationships between pupil characteristics and the characteristics of the schools they attend. More recently, widespread use has extended to other social sciences and health research. However, to date, little use has been made of these techniques within the health economics literature. This paper presents an introductory account of multilevel models and describes some of the areas of health economics research that may benefit from their use.

Adult↗
PubMedDate not supplied

Antibody-combining sites. Extending the natural limits.

The antibody repertoire is very large with at least 10(9) different antibody specificities, yet there are currently only 800 variable-region sequences known and < 23 Fab structures deposited with the Brookhaven Protein Data Bank. To engineer the antibody-combining site rationally, we need to define the rules that govern antibody structure. To understand the process of antibody-antigen recognition, we need not only to predict complementary determining regions accurately, but to simulate accurately the interaction of antibody with antigen. We have made progress in the modeling of antibody-combining sites and in the simulation of antibody complex formation. The combination of these approaches will allow us to extend the natural limits of antibody-combining sites in a more rational manner.

Algorithms↗
PubMedDate not supplied

Pharmacokinetics and safety of escalating single and repeat oral doses of GW420867X, a novel non-nucleoside reverse transcriptase inhibitor.

OBJECTIVE: To assess the pharmacokinetics, safety and tolerability of escalating oral doses of GW420867X, a non-nucleoside reverse transcriptase inhibitor, was investigated in healthy male volunteers in a randomized, double-blind placebo-controlled study. METHODS: Study subjects were divided into four groups of 12 subjects (10, 50, 100 and 200-mg dose groups) with eight subjects from each group receiving active treatment and the remaining four matched placebo. Subjects were initially administered a single dose of GW420867X or placebo, and following a 24- to 28-day washout period, re-exposed to the same treatment for 14 consecutive days. Safety measurements including clinical laboratory evaluations, ECG and vital signs were performed before, during and after dosing. RESULTS: Geometric mean GW420867X peak plasma concentrations (Cmax) following single oral doses of 10, 50, 100 and 200 mg were 160, 608, 1,000 and 1,662 ng/ml, respectively. Time to Cmax (tmax) increased from a median value of 1 h following the 10-mg dose, to 3 h after the 200-mg dose. Geometric mean plasma areas under the curves (AUC) were 4,325 (10 mg), 17,862 (50 mg), 35,295 (100 mg) and 62,338 ng/ml per hour (200 mg) and were proportionally less than the increase in the administered dose. Apparent terminal elimination half-life (t1/2) was approximately 50 h. Following repeat dosing, accumulation ratios based on plasma AUC were: 3.0+/-1.0 (10mg), 2.6+/-0.9 (50mg), 1.8+/-0.3 (100 mg) and 1.9+/-0.8 (200 mg) after 14 days of dosing compared to the corresponding single dose. In general, oral clearance (CL/F) was greater after 14 days and greater with higher doses except for the 10-mg dose group. Steady-state CL/F was 2.2, 3.4, 4.2, and 5.1 l/h for 10, 50, 100, and 200 mg, respectively. Steady-state was generally achieved within 7-10 days. Comparison of single and repeat dosing with GW420867X showed that Cmax increased by a factor of between 1.4 to 1.8, after 14 days of daily dosing to 288 (10 mg), 1,006 (50 mg), 1,401 (100 mg) and 2,613 (200 mg) ng/ml. These increases were proportionally less than the increase in the administered dose. GW420867X was well tolerated by subjects both after single and repeated dosing. Adverse effects reported by subjects on the active drug were similar to those receiving placebo. All episodes were rated as mild to moderate in severity and resolved spontaneously without further intervention. CONCLUSION: The pharmacokinetic findings of this study imply that systemic exposure to GW420867X decreases with increasing dose and displays time-variant pharmacokinetics, which suggests decreased absorption and/or increased clearance of GW420867X. The relatively long plasma half-life, of approximately 50 h, makes it suitable for once-daily dosing.

Administration, Oral↗
PubMedDate not supplied

Noninvasive imaging of intraarterial baffles in infants and children.

Baffles within the lumen of the pulmonary artery are created in (1) the Aubert procedure, a variation of the arterial switch favored by some surgeons when two major coronary ostia arise close to one another or when one coronary artery has an intramural course, and (2) the Takeuchi procedure, a technique applied to patients with anomalous origin of the left coronary from the pulmonary artery. In both operations, coronary artery transplantation is avoided; instead, an aorticopulmonary window is created and aortic blood is redirected by an intrapulmonary artery baffle into the coronary circulation. We imaged five patients with Aubert and 10 patients with Takeuchi procedures by use of ultrasound to assess the sequelae of such intraarterial baffles. All five Aubert patients were < 3 weeks old; the ages of the 10 Takeuchi patients ranged from 2 to 86 months. Two patients died early after surgery; the remaining 13 patients were observed for 3 to 83 months (median 46 months). In all 15 patients, the baffle geometry was visualized and the aorticopulmonary window was identified. In the six who had serial imaging, none developed aorticopulmonary window stenosis. In no patient was any peribaffle shunting detected. Supravalvar narrowing, caused by the baffle partially obstructing the neopulmonary artery, was observed in two of five Aubert patients; in only one of these has reoperation been performed. In one of the 10 Takeuchi patients supravalvar narrowing of the pulmonary artery (related to repair of coexistent tetralogy of Fallot) has developed and the patient has since undergone reoperation.

Child, Preschool↗
PubMedDate not supplied

Women living with drug abuse and HIV disease: drug abuse treatment access and secondary prevention issues.

In collaboration with the National Institute on Drug Abuse, the Health Resources and Services Administration is conducting a multisite, longitudinal study on issues of service needs, service utilization, and access to care for drug abusers with HIV. This article discusses access to drug abuse treatment and HIV secondary prevention for 116 women interviewed during the study's first year in five U.S. cities. Using interview data from 115 service providers in those same cities, it also discusses drug abuse treatment availability and barriers to service expansion for drug users with HIV. Study findings indicate that there are highly significant gaps between the drug abuse treatment services these women feel they need and those they have been able to receive; these were particularly pronounced for drug detoxification and residential and outpatient drug-free treatment. Women who used crack cocaine or injection drugs had particularly high levels of need for residential and outpatient drug abuse treatment, while women who use crack were found to have significantly less experience with the drug abuse treatment system than IDUs. HIV secondary prevention was also found to be a critical need for these women, many of whom were engaging in behaviors that place them at risk for reinfection, infection with other diseases, and transmission to others. Providers indicated that lack of funding was the major barrier to expanding services for this population; other barriers, such as lack of ancillary services and transportation, were also noted. Two positive findings were that many drug abuse treatment agencies in these cities provide a wide range of ancillary services and that many different kinds of agencies offer drug abuse treatment services.

Adolescent↗