Mental retardation, keratoconus, febrile seizures and sinoatrial block: a previously undescribed autosomal recessive disorder.
Explore the source record for details and available documents.
Abnormalities, Multiple↗
Biomedical subjects
D Kirby
Publications and source records attributed to D Kirby.
Potent and long-acting corticotropin releasing factor (CRF) receptor 2 selective peptide competitive antagonists.
We present evidence that members of the corticotropin releasing factor (CRF) family assume distinct structures when interacting with the CRF(1) and CRF(2) receptors. Predictive methods, physicochemical measurements, and structure-activity relationship studies have suggested that CRF, its family members, and competitive antagonists such as astressin [cyclo(30-33)[DPhe(12),Nle(21),Glu(30),Lys(33),Nle(38)]hCRF((12-41))] assume an alpha-helical conformation when interacting with their receptors. We had shown that alpha-helical CRF((9-41)) and sauvagine showed some selectivity for CRF receptors other than that responsible for ACTH secretion(1) and later for CRF2.(2) More recently, we suggested the possibility of a helix-turn-helix motif around a turn encompassing residues 30-33(3) that would confer high affinity for both CRF(1) and CRF(2)(2,4) in agonists and antagonists of all members of the CRF family.(3) On the other hand, the substitutions that conferred ca. 100-fold CRF(2) selectivity to the antagonist antisauvagine-30 [[DPhe(11),His(12)]sauvagine((11-40))] did not confer such property to the corresponding N-terminally extended agonists. We find here that a Glu(32)-Lys(35) side chain to side chain covalent lactam constraint in hCRF and the corresponding Glu(31)-Lys(34) side chain to side chain covalent lactam constraint in sauvagine yield potent ligands that are selective for CRF(2). Additionally, we introduced deletions and substitutions known to increase duration of action to yield antagonists such as cyclo(31-34)[DPhe(11),His(12),C(alpha)MeLeu(13,39),Nle(17),Glu(31),Lys(34)]Ac-sauvagine((8-40)) (astressin(2)-B) with CRF(2) selectivities greater than 100-fold. CRF receptor autoradiography was performed in rat tissue known to express CRF(2) and CRF(1) in order to confirm that astressin(2)-B could indeed bind to established CRF(2) but not CRF(1) receptor-expressing tissues. Extended duration of action of astressin(2)-B vs that of antisauvagine-30 is demonstrated in the CRF(2)-mediated animal model whereby the inhibition of gastric emptying of a solid meal in mice by urocortin administered intraperitoneally at time zero is antagonized by the administration of astressin(2)-B but not by antisauvagine-30 at times -3 and -6 h while both peptides are effective when given 10 min before urocortin.
Animals↗
Hyponatraemia and selective serotonin re-uptake inhibitors in elderly patients.
Hyponatraemia (serum sodium arbitrarily defined as less than 135 mmol/L) is an increasingly recognised adverse effect of selective serotonin re-uptake inhibitors (SSRIs). Its precise prevalence and incidence in the elderly are hard to determine because of confounding factors including other prescribed medications and medical conditions. Although hyponatraemia has been reported with all SSRIs and venlafaxine, most studies are small, retrospective, limited by confounding variables or are individual case reports. The risk of developing hyponatraemia while on an SSRI seems to increase with age, female, sex, previous history of hyponatraemia and the concomitant use of other medications known to include hyponatraemia. The sodium concentrations of most patients with SSRI associated hyponatraemia return to normal within days to weeks of SSRI withdrawal. A few cases of SSRI rechallenge indicate that hyponatraemia may sometimes be a transient effect with tolerance developing over time. There is an urgent need for controlled, rigorous studies to confirm the extent of the association between SSRIs and hyponatraemia. Older drugs such as tricyclic antidepressants also need systematic study. It remains quite unclear whether any specific SSRI or venlafaxine has a stronger association with hyponatraemia than any other antidepressant drug.
Age Factors↗
Safer choices: reducing teen pregnancy, HIV, and STDs.
OBJECTIVES: This study evaluated the long-term effectiveness of Safer Choices, a theory-based, multi-component educational program designed to reduce sexual risk behaviors and increase protective behaviors in preventing HIV, other STDs, and pregnancy among high school students. METHODS: The study used a randomized controlled trial involving 20 high schools in California and Texas. A cohort of 3869 ninth-grade students was tracked for 31 months from fall semester 1993 (baseline) to spring semester 1996 (31-month follow-up). Data were collected using self-report surveys administered by trained data collectors. Response rate at 31-month follow-up was 79%. RESULTS: Safer Choices had its greatest effect on measures involving condom use. The program reduced the frequency of intercourse without a condom during the three months prior to the survey, reduced the number of sexual partners with whom students had intercourse without a condom, and increased use of condoms and other protection against pregnancy at last intercourse. Safer Choices also improved 7 of 13 psychosocial variables, many related to condom use, but did not have a significant effect upon rates of sexual initiation. CONCLUSIONS: The Safer Choices program was effective in reducing important risk behaviors for HIV, other STDs, and pregnancy and in enhancing most psychosocial determinants of such behavior.
Adolescent↗
Schoolwide effects of a multicomponent HIV, STD, and pregnancy prevention program for high school students.
Few studies have tested schoolwide interventions to reduce sexual risk behavior, and none have demonstrated significant schoolwide effects. This study evaluates the schoolwide effects of Safer Choices, a multicomponent, behavioral theory-based HIV, STD, and pregnancy prevention program, on risk behavior, school climate, and psychosocial variables. Twenty urban high schools were randomized, and cross-sectional samples of classes were surveyed at baseline, the end of intervention (19 months after baseline), and 31 months afterbaseline. At 19 months, the program had a positive effect on the frequency of sex without a condom. At 31 months, students in Safer Choices schools reported having sexual intercourse without a condom with fewer partners. The program positively affected psychosocial variables and school climate for HIV/STD and pregnancy prevention. The program did not influence the prevalence of recent sexual intercourse. Schoolwide changes in condomuse demonstrated that aschool-based program can reduce the sexual risk behavior of adolescents.
Adolescent↗
Identification of potent and selective neuropeptide Y Y(1) receptor agonists with orexigenic activity in vivo.
Neuropeptide Y (NPY) binds to a family of G-protein coupled receptors termed Y(1), Y(2), Y(3), Y(4), Y(5), and y(6). The use of various receptor subtype-selective agonists and antagonists has facilitated identification of the receptor subtypes responsible for mediating many of the biological effects of NPY. For example, the potent orexigenic activity of NPY is believed to be mediated by both the Y(1) and Y(5) receptor subtypes. Several selective Y(5) receptor agonists that stimulate food intake in rodents are available, but no selective Y(1) receptor agonist has been reported. We have identified several NPY analogs that bind the NPY Y(1) receptor with high affinity and exhibit full agonist activity, measured as inhibition of forskolin-stimulated cAMP production in cells expressing the cloned NPY Y(1) receptor. [D-Arg(25)]-NPY, [D-His(26)]-NPY, Des-AA(10--17)[Cys(7,21),Pro(34)]-NPY, Des-AA(11--18)[Cys(7,21),D-Lys(9)(Ac)]-NPY, Des-AA(11--18)[Cys(7,21),D-Lys(9)(Ac),Pro(34)]-NPY, Des-AA(11--18)[Cys(7,21),D-Lys(9)(Ac),D-His(26)]-NPY and Des-AA(11--18)[Cys(7,21),D-Lys(9)(Ac),D-His(26), Pro(34)]-NPY bind the NPY Y(1) receptor with K(i) values of 0.9 +/- 0.2, 2.0 +/- 0.3, 0.2 +/- 0.05, 0.7 +/- 0.1, 0.2 +/- 0.01, 2.2 +/- 0.3, and 1.2 +/- 0.3 nM, respectively, and inhibit forskolin-stimulated cAMP production with EC(50) values of 0.2 +/- 0.02, 0.5 +/- 0.04, 0.3 +/- 0.03, 0.5 +/- 0.05, 0.4 +/- 0.16, 5.3 +/- 0.32, and 5.1 +/- 0.97 nM, respectively. These peptides are highly selective for the NPY Y(1) receptor relative to the NPY Y(2), Y(4), and Y(5) receptors. [D-Arg(25)]-NPY, [D-His(26)]-NPY and Des-AA(11--18)[Cys(7,21), D-Lys(9)(Ac),D-His(26),Pro(34)]-NPY stimulate food intake dose-responsively in Long-Evans rats for at least 4 h after intracerebroventricular administration. Although the involvement of Y(1) receptors in several physiological activities, such as vasoconstriction and anxiolysis, remains to be investigated, adequate tools are now available.
Animals↗
Making condoms available in schools. The evidence is not conclusive.
Explore the source record for details and available documents.
Condoms↗
A novel method of incorporating windows in a cast.
Explore the source record for details and available documents.
Casts, Surgical↗
Psychosocial predictors of delay of first sexual intercourse by adolescents.
This investigation predicted adolescents' delay of intercourse onset from attitudes, social norms, and self-efficacy about refraining from sexual intercourse. Age, gender, ethnicity, and parental education were also examined as predictors and moderators of the relationships among the 3 psychosocial determinants and onset. The participants (N = 827), part of a cohort initially surveyed in the 9th grade, reported at baseline that they had never engaged in intercourse. The multivariable proportional hazards regression model suggested that adolescents with more positive attitudinal and normative beliefs, as well as those with a parent who graduated from college, were less likely to engage in intercourse in the follow-up period (up to approximately 2 years). Interventions that include an objective to delay onset may benefit from addressing psychosocial determinants, especially attitudes and norms about sexual intercourse.
Adolescent↗
Validity of scales measuring the psychosocial determinants of HIV/STD-related risk behavior in adolescents.
We examined the content, construct and concurrent validity of scales to assess beliefs and self-efficacy related to adolescents' sexual risk behavior. We addressed content validity in the scale development process by drawing on literature and theory, and by pre-testing items with focus groups. We used confirmatory factor analysis of two models, an intercourse involvement model and a condom use model, to assess construct validity. The final intercourse involvement model included three scales: norms about sexual intercourse, attitudes about sexual intercourse and self-efficacy in refusing sex. The final condom use model included five scales: norms about condoms, attitudes about condom use, self-efficacy in communicating about condoms, self-efficacy in buying/using condoms and barriers to condom use. After two alterations to the models, the chi 2 and other indices indicated that the data fit the models well. Supporting the concurrent validity of the scales, high school students who had never had sexual intercourse had more negative attitudes toward sexual intercourse among teenagers, perceived norms toward sexual intercourse among teenagers to be more negative and expressed greater self-efficacy in refusing sex than did those who had experienced sexual intercourse. Consistent condom users had more positive attitudes and norms about condoms, had higher self-efficacy in communicating about and buying/using condoms, and perceived fewer barriers to condom purchase and use than did inconsistent condom users.
Adolescent↗
Short-term impact of safer choices: a multicomponent, school-based HIV, other STD, and pregnancy prevention program.
This study evaluated the effectiveness of the first year of Safer Choices, a theoretically based, multicomponent HIV, STD, and pregnancy prevention program for high school youth. The study featured a randomized trial involving 20 schools in California and Texas, with a cohort of 3,869 ninth-grade students. Students who completed both the baseline and the first follow-up survey approximately seven months later were included in the analysis (n = 3,677). Safer Choices enhanced 9 of 13 psychosocial variables including knowledge, self efficacy for condom use, normative beliefs and attitudes regarding condom use, perceived barriers to condom use, risk perceptions, and parent-child communication. Safer Choices also reduced selected risk behaviors. Specifically, Safer Choices reduced the frequency of intercourse without a condom in the three months prior to the survey, increased use of condoms at last intercourse, and increased use of selected contraceptives at last intercourse.
Adolescent↗
Reflections on two decades of research on teen sexual behavior and pregnancy.
During the past 20 years, both researchers and program developers made great progress in their efforts to reduce adolescent unprotected sex and prevent teen pregnancy. Research studies are now more likely to employ experimental designs with random assignments, to have large sample sizes with adequate statistical power, to measure actual sexual and contraceptive behaviors, to measure longer term effects, to employ proper statistical methods, and to report results in an unbiased manner. As a result of this body of research, large advances have occurred in our understanding of: 1) the incidence of teen pregnancy, and its consequences; 2) the effects of improving adolescent knowledge, increasing access to contraception, and improving parent/child communication; and 3) the characteristics of effective programs. The on-going evaluation of sex and HIV education programs coupled with creativity and perseverance on the part of program developers led to two groups of effective programs--sex and HIV education programs that reduce sexual risk-taking behavior, and youth development programs that reduce teen-age pregnancy and childbearing.
Adolescent↗
The impact of condom availability [correction of distribution] in Seattle schools on sexual behavior and condom use.
OBJECTIVES: Ten Seattle high schools made condoms available through vending machines, baskets in school clinics, or both. This study measured the number of condoms that students obtained and subsequent changes in sexual behavior and condom use. METHODS: Schoolwide surveys were administered in spring 1993 and in spring 1995, before and during the condom availability program. These data were compared with data from nationally representative surveys administered at the same time. RESULTS: Seattle students obtained an average of 4.6 condoms per year, the vast majority from baskets and very few from vending machines. Relative to the national samples, the percentage of Seattle students who had ever had sex remained stable after the program began; current sexual activity decreased significantly; and the percentage of sexually experienced students who used a condom the last time they had sex decreased significantly, particularly in the 5 schools with baskets of condoms in clinics. CONCLUSIONS: Making condoms available in Seattle schools enabled students to obtain relatively large numbers of condoms but did not lead to increases in either sexual activity or condom use.
Adolescent↗
Sexually transmitted diseases, unintended pregnancy, and adolescent health promotion.
Adolescence is a critical period in the development of sexual behaviors that may lead to acquiring sexually transmitted diseases (STDs), including human immunodeficiency virus (HIV), and to unintended pregnancy. Understanding adolescent sexual behavior is essential for understanding adolescents' risk of pregnancy and STD/HIV infection and for planning and evaluating health promotion activities. This chapter reviews the sexual behaviors and psychosocial factors associated with STDs and unintended pregnancy among adolescents as well as school-, community-, and clinic-based interventions designed to reduce risk behaviors and promote adolescent sexual health.
Adolescent↗
Sexuality and sex education at home and school.
This article reviews numerous studies of parent-adolescent communication about sexuality and 30 studies of sexuality and HIV education programs. Although parent-adolescent communication about sexuality has increased during the last few decades, both the occurrence and the quality of this communication could still be greatly improved. There does not exist a clear simple relationship between greater parent-adolescent communication and less adolescent risk-taking behavior, but both adults and youth believe it is important anyway. Sexuality and HIV education programs do not increase any measure of sexual activity, but some of them with ten common characteristics do reduce sexual risk-taking, either by delaying or reducing sexual behavior or increasing condom use. Thus, these programs can be an effective component in a larger initiative to reduce HIV, other STDs, and unplanned pregnancy in adolescence.
Adolescent↗
Diagnostic criteria and functional psychosis.
Explore the source record for details and available documents.
Humans↗
Optical Monitoring of Cerebral Hemodynamics and Oxygenation in the Neonatal Piglet
> Objective: Optical spectroscopy can monitor changes in cerebral oxyhemoglobin (HbO), deoxyhemoglobin (Hb), and total hemoglobin (HbT = Hb + HbO). The purpose of this study was to identify which one of these three optical variables would be the best correlate of cerebral hemodynamics and oxygenation accompanying different physiological conditions known to affect cerebral perfusion pressure and oxygenation. Methods: Eleven anesthetized and ventilated newborn piglets were subjected to: 1) hyperoxic hypercapnia, 2) asphyxia from room air, 3) hypertension, 4) hypotension, and 5) cerebral venous congestion. Optical measurements were recorded continuously along with carotid blood flow (CaBF) measured by the transit time Doppler technique and arterial hemoglobin oxygen saturation (SaO2) measured by pulse oximetry. Results: A good positive HbT-CaBF correlation was recorded during hypercapnia (r = 0.816), asphyxia (r = 0.846), hypertension (r = 0.72), and hypotension (r = 0.95), where as negative correlation was recorded during venous congestion (r = -0.91). A good positive correlation HbO-SaO2 was recorded during asphyxia (r = 0.842) and hypotension (r = 0.86), whereas no HbO-SaO2 agreement occurred during hypercapnia (r = 0.23), hypertension (r = 0.19), and venous congestion (r = 0.34), when SaO2 did not change at all. A good positive HbO-SaO2 correlation was recorded during hypercapnia (r = 0.84), hypertension (r = 0.91), and hypotension (r = 0.94), suggesting a high HbO dependence on changes in CaBF. Conclusions: We demonstrated that none of the optical variables (Hb, HbO, HbT) alone can be used as a correlate of cerebral hemodynamics and oxygenation over a broad range of cerebral perfusion pressure and oxygenation. However, all three variables combined (i.e. optical patterns) strongly reflect the changes in cerebral hemodynamics and oxygenation accompanying those physiological conditions. These and similar patterns could potentially serve as a reference model for future studies in the human fetus where "gold standard" correlation methods do not exist.
Journal Article↗
Optical Brain Monitoring of the Cerebrovascular Effects Induced by Acute Cocaine Exposure in Neonatal Pigs.
> Objective: The purpose of this study was to assess the direct effects of cocaine on cerebral blood flow and oxygenation in newborn piglets using optical spectroscopy. Optical spectroscopy is capable of monitoring changes in cerebral oxyhemoglobin, deoxyhemoglobin, and total hemoglobin continuously, noninvasively, and in real time. Methods: Five anesthetized and ventilated newborn piglets were injected intravenously with 1 mg/kg cocaine through a central venous catheter over 60 seconds. Cerebral blood flow and oxygenation were assessed by optical spectroscopy and standard physiologic monitoring: mean arterial pressure, carotid blood flow, cerebrovascular resistance, and arterial hemoglobin oxygen saturation (by pulse oximetry). Results: Cocaine induced a profound increase in cerebrovascular resistance, a decrease in carotid blood flow, and a decrease in mean arterial pressure and heart rate. Cerebrovascular changes were detected readily by optical spectroscopy (i.e. a decrease in cerebral oxyhemoglobin was associated with an increase in deoxyhemoglobin). The hypotensive response augmented the cerebral vasoconstriction effect on carotid blood flow. A good correlation existed between the changes in carotid Doppler blood flow and total hemoglobin in each animal and for all animals combined. Peripheral arterial hemoglobin oxygen saturation measured by pulse oximetry remained normal throughout the experiment. Conclusions: The cause for the apparent idiosyncratic hypotensive response to intravenous injections of cocaine is uncertain and requires further investigation. Our study clearly demonstrates that optical spectroscopy might become an extremely useful tool for monitoring cerebral hemodynamics and oxygenation in cocaine-exposed fetuses and infants.
Journal Article↗