Arthur F. Kohrman

Ethical issues in phase I oncology research: A comparison of investigators and institutional review board chairpersons

PURPOSE Phase I research trials assess the safety of agents never before administered to humans. In the field of oncology, this practice raises several important ethical questions. We examined the ethics of these trials by surveying phase I oncology investigators and institutional review board (IRB) chairpersons at major cancer research centers around the country. METHODS Questionnaires were mailed to 78 investigators and 47 chairpersons to obtain their views on the ethical propriety of conducting phase I oncology research, and on institutional practice regarding these trials. The response rate was 68% in each group. RESULTS The majority of each group reported that phase I oncology trials face no more scrutiny or resistance in their institutions IRB process than other research protocols. Nevertheless, IRB chairpersons were more likely than investigators to favor special procedural safeguards to protect subjects in phase I oncology trials. Nearly all respondents agreed that although actual medical benefit was very uncommon, most patients entered for a chance at a therapeutic effect. Investigators were more likely than chairpersons to report that patients obtained psychologic benefit from participation in phase I trials. CONCLUSION Although individual IRB chairpersons and oncology investigators may have important differences of opinion concerning the ethics of phase I trials, these disagreements do not represent a widespread area of ethical conflict in clinical research.

Barriers to Care for Children and Youth With Special Health Care Needs Perceptions of Illinois Pediatricians

Objective. To assess primary care pediatricians’ (PCPs’) perceptions of caring for children and youth with special health care needs (CYSHCN). Methods. Cross-sectional survey of Illinois pediatricians. Results. Thirty-five percent of surveys were returned and 26% were analyzed. The top 3 perceived barriers were insufficient time (72%), insufficient reimbursement (68%), and lack of support services (59%). Insufficient interest was the least cited barrier (19%). Preparedness to perform tasks related to care of CYSHCN ranged from 89% for accessing early intervention services to 24% for billing and coding. The percentage of PCPs somewhat or very comfortable providing primary care to patients with technology dependence ranged from 75% for blood glucose monitoring to 12% for dialysis. Conclusions. The issues of time, reimbursement, billing, and coding are perceived as significant barriers to the care CYSHCN. There is substantial variation in PCPs’ comfort in the care of CYSHCN who require the assistance of medical technologies.

Patterns of development of adenyl cyclase activity and norepinephrine responsiveness in the rat.

Extract: The present studies were done to delineate developmental patterns of the adenyl cyclase system and its responsiveness to norepinephrine. Investigations were performed in four tissues of the rat: brain, brown fat, heart, and liver. The general developmental patterns of adenyl cyclase in brown fat, heart, and liver are similar. In all three tissues, adenyl cyclase activity reaches a nadir at approximately 14 days of age. Heart, brown fat, and liver also show similar responses to norepinephrine, which increases adenyl cyclase activity to 2–4 times that of basal levels at all ages. The adenyl cyclase activities in the late gestational and early infant brain are relatively low compared with later ages, but are comparable to those of the other tissues in the neonatal period. Activity in cerebrum rises steadily until about 21 days of age. There is responsiveness to sodium fluoride stimulation of adenyl cyclase in all tissues examined at all ages, with values 5–20 times basal levels in brown fat, liver, and heart. In cerebrum, sodium fluoride causes stimulation of adenyl cyclase activity to about 2 times basal levels at all ages.Speculation: Adenyl cyclase activity in brown fat in the rat is at high levels in the neonate. This may be related to the high metabolic activity and active lipolysis occurring in that tissue in the perinatal period. In the brain, adenyl cyclase activity is at very low levels in the neonate compared with the adult, rising rapidly in the 2nd and 3rd weeks of life. This pattern of development of the adenyl cyclase system in the rat brain may be related to concurrent biochemical and structural changes.

The Capacity of Primary Care Pediatricians to Care for Children With Special Health Care Needs

Objective. To measure the willingness and ability of primary care pediatricians (PCPs) to accept children and youth with special health care needs (CYSHCN) into their practices. Methods. Surveys were mailed to 1441 members of the Illinois Chapter of the American Academy of Pediatrics practicing primary care. Results. In all, 376 physicians were eligible for analyses. When asked if they would accept additional CYSHCN, 6% selected “yes,” 34% selected “yes, with supports,” and 60% selected “no.” PCPs closer to residency or with intermediate numbers of CYSHCN in their practices were more willing to add additional CYSHCN. PCPs preparedness to care for various conditions ranged from 96% for asthma to 53% for spina bifida. Familiarity with programs ranged from 89% for Early Intervention to 4% to 22% for the state’s waiver programs. Conclusions. Most PCPs did not want additional CYSHCN in their practices. Variation exists in PCP preparation to care for varying conditions and in familiarity with supportive programs.

Re-hospitalization after diagnosis of diabetes varies by gender and socioeconomic status in urban African-American and Latino young people.

Abstract: Purpose: To examine risk factors for re‐hospitalization after diagnosis of diabetes mellitus amongst urban minority children.

Permanent effects of estradiol on cellular metabolism of the developing mouse vagina

Abstract Persistent, hormone-independent vaginal proliferation is produced when estradiol is given to mice during a discrete period following birth. Synthesis of DNA, RNA, and protein in the altered vaginae has been investigated. An increased rate of cell multiplication in vaginae from adult animals, given estradiol in the newborn period, is indicated by increased incorporation of thymidine- 3 H into DNA. Incorporation of labeled amino acids into vaginal protein is accelerated, as is incorporation of uridine- 3 H into total organ RNA. Vaginal RNA, labeled in vivo with 32 P, was fractionated by extraction at three temperatures. The results of thermal fractionation suggest that the permanent estradiol-induced changes in vaginae are accompanied by selective effects on some RNA species, either in terms of relative rates of synthesis or in qualitative differences of RNA moieties. Vaginae from mice, given estradiol in the newborn period, retain selective uptake and prolonged retention of 3 H-labeled estradiol and the capacity to respond to exogenous estradiol with increased incorporation of labeled amino acids into protein. The vaginal epithelium remains capable of both mucin and keratin production. These studies demonstrate that persistent alterations of cellular metabolism accompany the morphological sequelae seen in vaginae from mice given estradiol during a defined neonatal period. Rates of synthesis of DNA, RNA and protein are permanently altered, while some normal characteristics and hormone-specific responses of vaginae are unaffected.

Risks and Benefits of Hormonal Agents in Pregnancy

Concern over the possible teratogenic effects of the hormone 17alpha -hydroxyprogesterone caproate (17alpha OHP-C) when given intrapartum to the mother and the possible effects on the cervix and vagina in later life, was voiced in response to a published report, and advocacy of use of this hormone for the prevention of early abortion questioned. In response, the authors share their concern over possible long-term carcinogenic effects as well as possible effects on the hypothalamic-pituitary-gonadal axis, the mammary apparatus, the male genitalia, and psychosexual behavior.

A new metabolic product of l-homocitrulline

Abstract The appearance of an unidentified compound in rat urine following intraperitoneal injections of l -[ureido-14C]homocitrulline indicated that a previously unreported metabolite was being produced. Under acidic conditions the unknown was converted to a second compound. An apparently identical metabolite of homocitrulline was produced by treating this amino acid with l -amino acid oxidase.

A rapid method for quantitative separation of urea cycle intermediates.

Abstract To our knowledge, there exists no single rapid technique for the quantitative separation of the amino acid intermediates of the Krebs-Henseleit urea cycle. In this cycle, ammonia is converted to urea by a series of reaction beginning with the condensation of l -ornithine with carbamyl phosphate and proceeds sequentially through citrulline, argininosuccinic acid, and, finally, arginine, which is the cleaved to form urea with regeneration of ornithine. This communication describes chromatographic methods which have been found to give satisfactory separation of these compounds in a variety of mixtures. The time required for the separations is slightly over 2 hr which compares favorably with the 12–18 hr needed for papar chromatography or the time required for separations by automatic amino acid analyzers.

Institutional and Professional Attitudes: Dilemmas for the Chronically III Child

A majority of children with chronic illness and handicaps enter the systems of care and services through medical institutions. The organization of health care services, reinforced by institutional practices and social attitudes, can run counter to the goals of independence for the child. This discussion addresses the disease-centered structures of services for disabled children and analyzes their orientation toward institutional imperatives rather than toward the concerns of families.