Dehydrative thiolation of allenols: indium vs gold catalysis.

Intermolecular additions of thiols to allenols via formal S(N)2' selectivity to produce functionalized dienes are described. Although this dehydrative reaction was initially developed using gold(I) catalysis, indium(III) proves to be a far superior catalyst in terms of selectivity and substrate scope.

Novel estrogenic action of the pesticide residue beta-hexachlorocyclohexane in human breast cancer cells.

The estrogenic action of some persistent organochlorine pesticide residues may play a role in the progression of hormonally responsive tumors of the breast and uterus. The prototypical xenoestrogen o,p'-dichlorodiphenyltrichloroethane (o,p'-DDT) acts by binding and activating the estrogen receptor (ER). The present study focuses attention on the mechanisms through which another organochlorine compound, beta-hexachlorocyclohexane (beta-HCH), exerts estrogen-like effects in human breast cancer cells. Both o,p'DDT and beta-HCH stimulated proliferation in a dose-dependent manner in the ER-positive cell lines MCF-7 and T47D but not in the ER-negative lines MDA-MB231, MDA-MB468, and HS578T. Both compounds produced an increase in the steady state level of pS2 mRNA in MCF-7 cells. These responses were equal in magnitude to the maximal effect of estradiol, and they were inhibited by inclusion of the antiestrogen ICI164384. On the other hand, when tested in a competitive binding assay, beta-HCH did not displace 17beta-[3H]estradiol from the ER even at a concentration that was 40,000-fold higher than the tracer steroid. Furthermore, nuclear retention of the ER during homogenization procedures was induced by a 2- or 24-h treatment of MCF-7 cells with o,p'-DDT and 17beta-estradiol but not by treatment with beta-HCH; this indicates that beta-HCH nether activates the ER, nor is it converted intracellularly to an ER ligand. Transcriptional activation by beta-HCH occurs in estrogen-responsive GH3 rat pituitary tumor cells transfected with a luciferase reporter construct driven by a complex 2500-bp portion of the PRL gene promoter; this trans-activation response is inhibited by inclusion of ICI164384. However, beta-HCH is ineffective in stimulating a reporter construct driven only by a consensus estrogen response element and a minimal promoter derived from the herpes simplex virus thymidine kinase gene. Thus, beta-HCH cannot act on a simple, single estrogen response element; rather, it requires the combinatorial regulation found in a complex promoter. These data are consistent with the notion that beta-HCH stimulation of cell proliferation and gene expression is ER dependent, but its action is not through the classic pathway of binding and activating the ER. beta-HCH may represent a new class of xenobiotic that produces estrogen-like effects through nonclassic mechanisms and, therefore, may be of concern with regard to breast and uterine cancer risk.

The management of febrile infants by primary-care pediatricians in Utah: comparison with published practice guidelines.

OBJECTIVE: To determine primary-care pediatricians' management of febrile infants and compare them with published practice guidelines. DESIGN: Case scenarios were sent to 194 primary-care pediatricians in Utah, describing three febrile infants, ages 21 days, 60 days, and 20 months, corresponding to the three age groups: 0 to 28 days; 29 to 90 days, and 91 days to 36 months for which the guidelines suggest different strategies. RESULTS: Ninety-four pediatricians responded (response rate, 48%). Compliance with the guidelines was 39% for the 21 day old, 9.6% for the 60 day old, and 75% for the 20 month old. No respondent followed the guidelines for all three infants. Performance of tests to determine if an infant was low risk varied from 3%, for a stool white cell examination in a febrile 2 month old with diarrhea, to 75% for a complete blood count in a 20 month old with a temperature of 40 degrees C. Compliance did not differ between private and academic practitioners. Those in practice less than 5 years (n = 22) were more likely than those with more experience to follow the guidelines for the 21 day old but not the other two infants. CONCLUSION: Primary-care pediatricians in Utah manage febrile infants with fewer laboratory tests and less hospitalization than recent practice guidelines developed by an expert panel of academic specialists suggest.

The role of the primary care physician in the care of children with serious heart disease.

OBJECTIVE: To determine the roles of primary care physicians and specialists in the medical care of children with serious heart disease. SETTING: Pediatric Cardiology Division; Tertiary Care Children's Hospital. SUBJECTS: Convenience sample of parents, primary care physicians, and pediatric cardiologists of 92 children with serious heart disease. DESIGN: Questionnaire study; questionnaires based on 16 medical care needs, encompassing basic primary care services, care specific to the child's heart disease and general issues related to chronic illness. RESULTS: All children had a primary care physician (PCP), and both they and the parents (P) reported high utilization of PCP for basic primary care services. However, there was little involvement of PCP in providing care for virtually any aspect of the child's heart disease. Parents expressed a low level of confidence in the ability of PCP in general or their child's own PCP to meet many of their child's medical care needs. Both PCP and pediatric cardiologists (PC) were significantly more likely than parents to see a role for PCP in providing for care specific to the heart disease as well as more general issues related to chronic illness. PC and PCP generally agreed about the role PCP should play, although PC saw a bigger role for PCP in providing advice about the child's activity than PCP themselves did. PC were less likely to see the PCP as able to follow the child for long term complications than PCP did. PC were more likely than PCP to believe that PCP were too busy or were inadequately reimbursed to care for children with serious heart disease. Only about one-third of parents reported discussing psychosocial, family, economic, or genetic issues with any provider, and PCP were rarely involved in these aspects of chronic illness. CONCLUSIONS: Primary care physicians do not take an active role in managing either the condition-specific or the more general aspects of this serious chronic childhood illness. With appropriate information and support from their specialist colleagues primary care physicians could provide much of the care for this group of children. Generalists and specialists are both responsible for educating and influencing parents about the role primary care physicians can play in caring for children with serious chronic illness.

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.

Simethicone in the treatment of infant colic: a randomized, placebo-controlled, multicenter trial.

OBJECTIVE: To determine the efficacy of simethicone in the treatment of infant colic. DESIGN: Randomized, double blind, placebo-controlled. SETTING: Three general pediatric practices in distinct geographic regions. PATIENTS: Eighty-three infants between 2 and 8 weeks of age with infant colic. INTERVENTIONS: Treatment with simethicone and placebo in double blind crossover fashion. RESULTS: A total of 166 treatment periods, ranging from 3 to 10 days, were evaluated in the 83 infants. Compared to baseline, improvement in symptoms was reported for 54% of the treatment periods, worsening was reported for 22%, and, for 24%, there was no change. The likelihood of the treatment period being rated as showing improvement, worsening, or no change was the same whether the infant was receiving placebo or simethicone. Twenty-eight percent of he infants responded only to simethicone, 37% only to placebo, and 20% responded to both. No statistically significant differences were noted among these three groups of responders. No difference could be shown even when infants with "gas-related symptoms" (by parental report) were separated out as a group. CONCLUSION: Although both produced perceived improvements in symptoms, simethicone is no more effective than placebo in the treatment of infantile colic.

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.

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.

Usefulness of echocardiography for detection of coronary artery thrombi in patients with Kawasaki disease.

To evaluate the role of echocardiography for predicting and accurately detecting thrombi in patients with abnormal coronary arteries after Kawasaki disease, we reviewed the echocardiograms of 40 consecutive patients and compared echocardiographic findings with angiographic findings when available. Patients with Kawasaki disease who had coronary artery aneurysms > or =5 mm had significantly greater multivessel involvement, thrombi, and persistent coronary abnormalities than those with diameters <5 mm.

Strain differences in vaginal responses to the xenoestrogen bisphenol A.

Bisphenol A (BPA) is the monomer component of polycarbonate plastics and epoxy resins; human exposure derives from leachate in foodstuffs packaged in certain plastics or from epoxy-based dental appliances. BPA stimulates prolactin secretion in Fischer 344 (F344) rats but not in Sprague-Dawley (S-D) rats. The present studies were performed to determine if another classic estrogen target tissue, the rat vagina, responds to BPA in a strain-specific manner. In F344 rats BPA increased DNA synthesis in vaginal epithelium with a median effective dose (ED(50)) of 37.5 mg/kg body weight; DNA synthesis was not stimulated in S-D rats by any dose tested. Clearance of (3)H-BPA from blood followed the same time course in both strains of rats, with a half-life of 90 min. Scatchard analysis of [(3)H]estradiol binding showed no strain differences in concentration or affinity of the vaginal estrogen receptor. BPA increased the level of mRNA for the immediate early gene, c-fos, with similar dose-response curves in both rat strains. Thus, F344 and S-D rats exhibit differences in sensitivity to BPA at the level of cell proliferation in the vaginal epithelium. However, metabolic clearance of BPA and the early events that lead to the proliferative response, receptor-ligand interaction and induction of immediate early genes, show no strain differences. These observations suggest that differences in intermediate effects must account for the difference in sensitivity of the proliferative response to the xenoestrogen. Furthermore, these results point to the need for caution in choosing a suitable end point and animal model when seeking to test the estrogenic effects of xenobiotics.

Progesterone and dexamethasone inhibition of uterine epithelial cell proliferation: studies with antiprogesterone compounds in the neonatal mouse.

Progestins and glucocorticoids inhibit uterine epithelial cell proliferation. Earlier studies showed that in the neonatal mouse, dexamethasone (Dex) was at least 100-fold more potent than progesterone (P) as an inhibitor of epithelial DNA synthesis. Using steroid autoradiography, we now show that the uterine cells of the neonatal mouse have receptors for both progestins (PR) and glucocorticoids (GR). Since it is known that P can interact with the GR it is possible that even a weak interaction might mediate the inhibitory effects of large doses of P. Therefore, we examined the receptor pathway specificity of the P response in neonatal mice using antiP steroids with reportedly strong antiglucocorticoid activity, RU486, or weak antiglucocorticoid activity, ZK98.734 (ZK734). Both RU486 and ZK734 exhibited strong binding activity in a PR assay performed on cytosolic preparations from adult mouse uteri. For murine thymic GR, the relative binding activity of RU486 was 12-fold that of ZK734. The high PR binding activity was reflected by the in vivo dose-response of the antagonists administered in conjunction with P; either antagonist completely blocked the inhibitory effect of P on uterine epithelial DNA synthesis when it was administered at one-tenth the dose of P. On the other hand, blockade of the inhibitory effect of Dex only occurred when the dose of antagonist was 10-fold the dosage of Dex. There were no significant differences between the two antagonists in blocking the effects of either P or Dex. These results indicate that progestins and glucocorticoids act through their own receptor systems to inhibit DNA synthesis in the uterine epithelium of the neonatal mouse. However, because of the considerable antiglucocorticoid activity of ZK734, a potential role for the interaction between P and the GR cannot be ruled out by these experiments.

Exposures and outcomes of children with urticaria seen in a pediatric practice-based research network: a case-control study.

OBJECTIVES: (1) To determine the duration, outcome, and associated findings of urticaria in children seen by general pediatricians; (2) to compare the exposure to foods, medications, insect stings or bites, and the presence of other symptoms in children with urticaria with controls; (3) to determine general pediatricians' management of urticaria. DESIGN: Case-control. PARTICIPANTS: Children with urticaria seen by Utah Pediatric Practice Based Research Network members between August 1, 1999, and August 31, 2000. Control patients were matched for age and sex. MAIN OUTCOME MEASURES: Duration of urticaria; associated symptoms; personal and family history of atopy; medications; ingestion of peanuts, nuts, shellfish, tomatoes, strawberries, or eggs; being stung by an insect; suspected cause, diagnostic studies; treatment. RESULTS: Fifty-two cases and 47 controls were enrolled. The mean duration of urticaria was 8.9 days (range, 1-50 days). Seventeen patients (33%) and 1 control patient were taking antibiotics (odds ratio [OR], 22.3; 95% confidence interval [CI], 2.8-176; chi(2), P<.001). Fourteen patients and 5 controls had gastrointestinal symptoms (OR, 3.1; 95% CI, 1.02-9.4; chi(2), P =.04). There were no differences between cases and controls for other symptoms, personal or family history of atopy, ingestion of the foods listed, insect sting, or other medications. A cause was suspected in 28 patients (54%): a "viral illness" (19%), antibiotics (15%), or a combination (35%). CONCLUSIONS: Patients were more likely than controls to be taking an antibiotic and were more likely to have a personal or family history of atopy or to report ingesting foods commonly associated with urticaria. A viral illness was the most common cause suspected by pediatricians.

Significance of grunting respirations in infants admitted to a well-baby nursery.

OBJECTIVES: (1) To determine the frequency and duration of grunting in term and near-term newborns; (2) to determine the peripartum characteristics associated with grunting; and (3) to compare the short-term outcomes of newborns with and without grunting. DESIGN: Medical record review of all newborns admitted to a well-baby nursery during a 2-month period. SETTING: University well-baby nursery for term infants, with more than 2700 deliveries annually. MAIN OUTCOME MEASURES: Frequency and duration of grunting, maternal and newborn clinical characteristics, clinical course, and length of stay. RESULTS: Grunting respirations beginning during the first 4 hours of life were recorded for 81 (17.4%) of 466 newborns. Fifty-five (68%) stopped grunting within 30 minutes of birth, 69 (85%) by 1 hour, and 75 (93%) by 2 hours. More mothers of grunting infants received intrapartum antibiotics than mothers of nongrunters (33% vs 20%; P =.03). More grunting infants than nongrunters received bag and mask resuscitation (15% vs 5%; P =.01). More chest radiographs, blood cell counts, and blood cultures were ordered for grunting infants, and antibiotics were more often given to grunting than nongrunting infants (11.1% vs 4.6%; P =.04). Grunters' length of stay exceeded that of nongrunters (72 vs 55 hours; P =.01), but only 3 were transferred to a neonatal intensive care unit. CONCLUSIONS: All grunting infants should be carefully observed, but because nearly all otherwise healthy term or near-term infants will stop grunting and have a benign course, other interventions can be postponed for 1 or 2 hours to give the newborn a chance to stop grunting or show other signs of respiratory illness.

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)

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.

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.

MR imaging of the traumatized lumbar spine.

MR imaging is the imaging modality of choice for evaluation of the traumatized lumbar spine, providing critical information for determination of appropriate therapy. It is superior to other modalities for evaluating the supporting ligaments, disc, spinal cord, and the cauda equina. Major fracture patterns are readily discernable. Canal compromise caused by osseous fragments, epidural hemorrhage, or disc fragments is well visualized.

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.

Felodipine-induced gingival hyperplasia.

Felodipine is a calcium channel blocking agent used in the management of hypertension and angina. We report a case of gingival hyperplasia in a patient with chronic use of this drug. Gingival changes occurred soon after initiation of felodipine and improved upon its discontinuation. The clinical characteristics, inciting agents, proposed pathogenetic mechanisms, as well as prevention and treatment of drug-induced gingival hyperplasia are briefly reviewed.