Biomedical subjects
P C Young
Publications and source records attributed to P C Young.
Environmetric time-series analysis: modelling natural systems from experimental time-series data.
Using the modelling of solute transport in flowing media as an example, this paper outlines the main aspects of a systematic approach to the modelling of natural systems from experimental time-series data. The objective of the approach, which exploits sophisticated methods of recursive parameter estimation, is to produce a parametrically efficient, data-based model which is both physically meaningful and statistically well defined. Although the proposed methodology has its origins in systems and control theory and may be unfamiliar to some natural scientists, it has been developed and refined for use with natural environmental systems over the past 20 years, and has wide application potential in areas such as biology and ecology. In this sense, the paper is intended to introduce the more general reader to the topic, in the hope that the tutorial review and practical examples will stimulate interest and encourage reference to the many publications cited in the paper. The practical examples are concerned with the modelling of pollutant dispersion in stream channels: phloem translocation and carbon partitioning in plants: and rainfall-streamflow modelling in a river catchment.
Infant temperament and school age behavior: 6-year longitudinal study in a pediatric practice.
We conducted a retrospective cohort study in a pediatric practice to assess the association between parents' ratings of temperamental difficulty (observations of specific infant behaviors) and perceptions of temperamental difficulty (impressions of one's infant as compared with other infants) in infancy and behavior problems at school age. Mothers of 129 infants, who had completed the Revised Infant Temperament Questionnaire at the 4-month visit, completed the Child Behavior Checklist when the child was 6 years of age. Teachers of 102 of these children completed the teacher Child Behavior Checklist. Temperamental difficulty was defined by assessments of rhythmicity, approach/withdrawal, intensity, mood, and adaptability. Initial analyses revealed that low socioeconomic status (r = -.29, P = .001), ratings of temperamental difficulty (r = .17, P = .06), and perceptions of temperamental difficulty (r = .22, P = .02) at 4 months of age were associated with increased maternal rating of behavior problems at 6 years of age (all 2-tailed tests). However, a multivariate regression analysis showed only low socioeconomic status (P less than .01) and increased perceptions of temperamental difficulty (P = .02) associated with maternal behavior problem scores. Teacher behavior problem scores were associated only with low socioeconomic status (r = -.27, P = .01). These results suggest that the link between difficult infant temperament and later behavior problems is complex and probably reflects both child factors and parent attitudes about what constitutes typical infant behavior.
Features associated with survival and disease-free survival in early endometrial cancer.
Age, clinical stage, histologic grade, depth of myometrial penetration, adnexal status, peritoneal cytology, and progesterone and estrogen receptor status were available for 139 patients with clinical stage IA, IB, or II endometrial adenocarcinoma who had therapy at Indiana University Hospital or St. Vincent Hospital in Indianapolis. These features were analyzed for their association with survival and disease-free survival. Patients treated at Indiana University Hospital were similar to those from St. Vincent Hospital when comparisons were made by chi 2 test for age, clinical stage, grade, adnexal metastases, peritoneal cytologic results, progesterone receptor status, or estrogen receptor status. However, patients treated at Indiana University Hospital had lesions that were deeper (p = 0.03) than those treated at St. Vincent Hospital. Survival differences were observed for patients with progesterone receptor-rich versus progesterone receptor-poor tumors (p = 0.004), grades 1 and 2 versus grade 3 lesions (p = 0.013), and malignant versus benign peritoneal cytologic results (p = 0.01). Differences in disease-free survival were observed for those patients with adnexal metastases versus those with no adnexal disease (p = 0.002), those with estrogen receptor-rich versus estrogen receptor-poor tumors, outer third myometrial invasion (p = 0.002), and patients with clinical stage I versus clinical stage II disease (p = 0.03). A stepwise Cox proportional hazards model was constructed to determine correlates of disease-free survival. In the final model, grade (p = 0.0002), peritoneal cytologic results (p = 0.0002), progesterone receptor status (p = 0.004), and age as a continuous variable (p = 0.008) were most closely associated with disease-free survival.
Health care of physicians' children.
In anecdotal reports, problems have been cited in the health care of physicians' children, but no systematic study of this issue has been attempted. Pediatricians in a community of high physician density were interviewed to determine whether and how the health care of physicians' children differs from that of children of equivalent socioeconomic status. Of the community's 33 pediatricians, 94% responded to items in a 45-minute structured interview, for which test-retest reliability was demonstrated. Systematic differences in the care of physicians' children included delayed help seeking and increased self-referral to specialists by parents, and poor documentation of psychosocial history, less detailed instruction giving, and a reluctance to discuss problem behavior by pediatricians. Reasons cited by pediatricians for these problems included inappropriate assumptions concerning the medical knowledge of the physician's family, confusion between the roles of healer and help seeker, and embarrassment about discussing personal issues with colleagues. Pediatricians and physician parents need to become aware of and communicate about the potential for problems in the health care of physicians' children.
Steroid receptors and clinical outcome in patients with adenocarcinoma of the endometrium.
Progesterone receptor content was measured in tissue samples from 175 patients with endometrial adenocarcinoma by use of the dextran-charcoal method. The estradiol receptor content was determined in 138 of these samples. Ninety-two tumors (52.6%) tested positive for progesterone receptors (greater than 50 fmol/mg cytosol protein) and 111 (80.4%) tested positive for estradiol receptors (greater than 6 fmol/mg). Median follow-up was 27.3 months (range 1 to 152 months). Progesterone receptor status correlated significantly with grade, histology, adnexal spread, age, and recurrence rate in stage I cancer. There was no correlation between progesterone receptor status and clinical stage, myometrial invasion, peritoneal cytology, retroperitoneal lymph node involvement, or spread to the cervix. Estradiol receptor status correlated with adnexal spread and recurrence rate. Recurrence in patients with stage I disease was significantly more common if tumors were negative for progesterone receptor (16 of 43, 37.2%) than if they were positive (four of 57, 7%; p less than 0.001). Recurrence was also more common if tumors were negative for estradiol receptor (seven of 17, 41.2%) than if they were positive (eight of 63, 12.7%; p = 0.02). In recurrent or advanced disease, response to progestin was independent of estradiol receptor content, but tumors positive for progesterone receptors responded significantly more often than those lacking progesterone receptors. Overall survival was superior for patients with progesterone receptor-positive tumors (p = 0.001). Although survival in clinical stages I and II was also superior in patients with lesions positive for progesterone receptors (p = 0.13), there was no statistical difference in survival between patients with progesterone receptor-positive or -negative cancers and surgical stages I and II disease (p = 0.12). Estradiol receptor status had no apparent correlation with survival.
Parental attitudes about confidentiality in a pediatric oncology clinic.
Children and parents who attend pediatric oncology clinics often develop close relationships with other patients and may question clinic staff about another child's disease, therapy, or status. To assess parental attitudes concerning the dissemination of information by the clinic staff, questionnaires were mailed to the parents of all 154 patients who have attended pediatric oncology clinic since 1972. There were 100 (65%) responses including 77 from 99 living (78%) and 23 from 55 deceased patients (42%). Parents were asked whether clinic staff should respond completely to questions from other clinic parents regarding six aspects of their child's cancer. Percentages of parents who favored complete information sharing without their explicit consent about each of the aspects were as follows: diagnosis, 83%; medication/side effects, 85%; laboratory results, 66%; general status, 87%; occurrence of relapse, 77%; development of terminal phase, 67%. Neither the survival status (living v deceased) nor whether the patient was receiving therapy or not affected responses significantly. Benefit from receiving information about other children from clinic staff was reported by 82% of parents.
Evaluation of the capillary microhematocrit as a screening test for anemia in pediatric office practice.
The capillary microhematocrit test is widely used to screen pediatric patients for anemia. Recently, it has been suggested that this method produces spuriously elevated values compared with venous hematocrits measured by a Coulter electronic counter and might consequently fail to detect children who are truly anemic. To address this issue we studied 66 white children 9 months to 14 years of age whose capillary hematocrits were either below, equal to, or one or two points above the lower limit of normal for age. Venous specimens were obtained simultaneously with the capillary sample; hemoglobin, hematocrit, and mean corpuscular volume results were obtained using a Coulter electronic counter. Using published standards of venous hemoglobin, we determined the sensitivity, specificity, and predictive values of the capillary microhematocrit in this population of patients with low or borderline values. Twenty of the 66 patients had venous hemoglobin values less than the lower limit of normal. The sensitivity of the microhematocrit was 90.0%; the specificity was 43.5%. The predictive values for a normal (negative) hematocrit was 90.1%; the predictive value for a low (positive) hematocrit was 40.9%. We conclude that the microhematocrit method using capillary blood will miss very few patients with significantly low venous hemoglobin values and is thus an acceptable screening test for anemia. Because it does not require expensive equipment or special skill to obtain the specimen or perform the test, it is ideal for physicians' offices or nonhospital-based clinics.
Estrogen and progesterone receptors in uterine sarcomas.
Estrogen and progesterone receptors were measured in tissues from 43 patients with various uterine sarcomas using the dextran-coated charcoal assay. Estrogen receptor was present in 55.5% and progesterone receptor in 55.8% of samples, at median estrogen and progesterone receptor concentrations of 10.7 and 15.8 fmol/mg cytosol protein, respectively. These median values are much lower than those in 30 consecutive endometrial adenocarcinomas and 50 breast carcinomas assayed in our laboratory. Progesterone receptor status correlated strongly with estrogen receptor status in uterine sarcomas (P = .001). Estrogen and progesterone receptor levels were not influenced by stage, grade, or mitotic count. Patients 50 years of age or less had significantly higher progesterone receptor than those over 50. No such age effect was seen for estrogen receptor. Endometrial stromal sarcoma had higher estrogen and progesterone receptor levels than other histologic types. Low-grade endometrial stromal sarcomas had higher median estrogen receptors (238.9 fmol/mg) and better survival (all patients alive at 6-12 months) than did high grade (N = 7) endometrial stromal sarcomas (median ER = 6.6 fmol/mg, all dead of disease at 8-27 months). For all histologic types, evaluable patients with stage I or II disease (N = 16) were more likely to survive longer than one year than those with stage III or IV disease (N = 13, P = .003). Evaluable patients with estrogen receptor-positive sarcomas were more likely to survive longer than one year than those with estrogen receptor-negative tumors (P = .006). With one exception, an endometrial stromal sarcoma, hormonal therapy exerted no beneficial effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Why families change pediatricians. Factors causing dissatisfaction with pediatric care.
Dissatisfaction with their child's physician sometimes causes parents to transfer to a new provider. We studied the reasons for such transfers from four pediatric practices in Chittenden County, Vermont. Personal qualities of the physician, including the parent's perception of the physician's communication skills, his or her clinical competence, and the apparent level of concern were the most important factors that distinguished satisfied from dissatisfied parents. Structural features, including costs, waiting time, and continuity with the same physician, were less often sources of enough dissatisfaction to produce a transfer. Effectiveness and success in pediatric practice are dependent on competence, communication, and caring.
The effect of copper in vivo on specific progesterone binding by human endometrial cytosol.
Copper has been shown to interfere with specific progesterone binding by human endometrial and myometrial cytosol in vitro. These results suggested that one possible mode of action of the copper-bearing intrauterine devices (IUDs) is through interference with the action of progesterone at its target sites. A prospective study was carried out to determine whether the proposed mode of action of copper-bearing IUDs could be demonstrated in vivo. The results of this study revealed a significant difference in specific progesterone-binding capacity between proliferative and secretory endometria (P less than 0.001). However, when secretory endometria of the controlled subjects were compared with those of the copper-bearing IUD wearers, no significant difference was observed in the specific progesterone-binding capacity (P greater than 0.2). These data suggested that copper released from copper-bearing IUDs in vivo may not interfere with the binding of progesterone to its receptors in vitro. It is doubtful that the contraceptive effectiveness of copper-bearing IUDs could be due to the ability of copper to prevent progesterone from exerting its full effects on the endometrium.
Endocrine and metabolic studies in a patient with male pseudohermaphroditism and true agonadism.
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Effect of metal ions on the binding of 17beta-estradiol to human endometrial cytosol.
The influence of zinc and other metal ions on the binding of 3H-17beta-estradiol to human endometrial cytosol was studied. Zn2+ began to interfere with estrogen binding when its concentration in the cytosol exceeded 50 micronM. At a concentration of 5 mM, all of the specific binding of 17beta-estradiol, including more than 50% of the nonspecific binding of the hormone, was destroyed. Analysis of the binding data revealed that one possible site of action of the cations on the binding protein might be the sulfhydryl group(s) of the 17beta-estradiol binding site. The inhibition of 17beta-estradiol binding brought about by Zn2+ was partially abolished by dithiothreitol. Among the metal ions tested, Cu2+ was found to be the most potent inhibitor, followed by Cd2+, Zn2+, and Pb2+. At 1 mM, Mn2+, Ba2+, Ca2+, and Mg2+ had little effect, but at 5 mM, their inhibitory action became more appreciable. K+ and Na+ had no effect on 17beta-estradiol binding. The stimulatory effect of 5 mM Zn2+, Ca2+, Mg2+, and K+ on the binding of 3H-17beta-estradiol to a macromolecular fraction from bovine endometrium was not observed in human endometrial cytosol.
Progesterone binding in human endometrial carcinomas.
By means of dextran-coated charcoal assay, the capacity of various endometrial cytosol preparations for specific binding of 3H-rone was determined. With the use of an arbitrary value of 50 femtomoles of bound 3H-progesterone per milligram of cytosol protein as the breaking point between high and low binding capacities, 19 out of 20 normal endometria had high progesterone-binding capacities. Two out of 11 Grade I, 3 out of 8 Grade II, and 2 out or 4 Grade III endometrial carcinomas showed low binding capacities. All 4 endometrial polyps, 7 out of 9 hyperplastic endometria, and 0 out of 7 nonendometrial gynecologic tumors had high binding capacities. These data suggest a progressive loss of specific progesterone-binding activity from normal endometria to hyperplastic endometria, and from the well-differentiated to the anaplastic forms of endometrial adenocarcinoma. There seemed to be an inverse relationship betweeen age and concentration of progesterone receptors in endometrial adenocarcinomas. All irradiated tumors studied had low progesterone-binding capacity.
The antihypertensive effect of pregnancy in spontaneously hypertensive rats.
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Sequential changes in the renin--angiotensin--aldosterone systems and plasma progesterone concentration in normal and abnormal human pregnancy.
To investigate the role of components of the renin-angiotensin-aldosterone system and plasma progesterone concentrations in the pathophysiology of hypertension in pregnancy, sequential measurements were made throughout pregnancy in 45 normotensive subjects, 41 other pregnant patients in whom hypertension became manifest only during pregnancy and 26 patients with chronic hypertension antedating pregnancy. Among the normotensive subjects plasma renin activity and substrate, plasma aldosterone and progesterone concentrations were elevated as early as the sixth week of gestation. While consistent, progressive, further increases were noted in renin substrate, aldosterone and pregesterone concentrations during pregnancy, plasma renin activity did not continue to rise. In both hypertensive groups, plasma renin activity and aldosterone concentration were significantly suppressed during the last trimester despite levels of renin substrate and progesterone that were not significantly different than those observed in normotensive pregnancy. These observations confirm earlier studies reporting suppression near term of plasma renin activity in toxemia and indicate from these prospective observations that they are secondary effects. These studies, in addition, demonstrate parallel suppression of plasma aldosterone concentration in toxemia. The current report also indicates that this suppression is not due to a decrease in renin substrate concentration and that a hypothesized deficiency of plasma progesterone, which was not observed in the hypertensive subjects, does not play a permissive role in the development of hypertension.
Serum unconjugated estriol in normal and abnormal pregnancy.
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