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Biomedical subjects

C Hayward

Publications and source records attributed to C Hayward.

At least 19 recordsLinked to original sources

Is puberty a risk factor for eating disorders?

OBJECTIVE: To examine the association between stage of sexual maturation and eating disorder symptoms in a community-based sample of adolescent girls. PARTICIPANTS: All sixth- and seventh-grade girls (N = 971) enrolled in four northern California middle schools. MAIN VARIABLES EXAMINED: Pubertal development measured using self-reported Tanner stage and body mass index (kg/m2). The section of the Structured Clinical Interview for DSM-III-R Disorders (SCID) discussing bulimia nervosa was used to evaluate symptoms of bulimia nervosa. RESULTS: Girls manifesting eating disorder symptoms, while not significantly older than their peers without such symptoms, were more developmentally advanced as determined with Tanner self-staging. The odds ratio for the association between sexual maturity and symptoms was 1.8 (95% confidence interval, 1.2 to 2.8); ie, at each age, an increase in sexual maturity of a single point was associated with a 1.8-fold increase in the odds of presenting symptoms. The odds ratio for the association between body mass index (adjusted for sexual maturity) and symptoms was 1.02 (95% confidence interval, 1.0 to 1.05). There was no independent effect of age or of the interaction between age and the sexual maturity index. CONCLUSIONS: These results suggest that (1) puberty may be a risk factor for the development of eating disorders, and (2) prevention efforts might best be directed at prepubertal and peripubertal adolescents.

Adolescent

Schizophrenia and rheumatoid arthritis: a review.

Fourteen epidemiologic studies of the relationship of rheumatoid arthritis to schizophrenia have been conducted between 1934 and 1985. Twelve of the studies report a lower-than-expected rate of rheumatoid arthritis in populations of schizophrenics. Methodologic weaknesses in the studies are assessed. Nutritional, hormonal, psychosocial, genetic, and immunologic data and theories are briefly reviewed which might explain the epidemiologic results. There is sufficient evidence for the negative association between the two disorders to justify further research.

Arthritis, Rheumatoid

A linkage map of 10 loci flanking the Marfan syndrome locus on 15q: results of an International Consortium study.

Members of an International Consortium for Linkage Analysis of the Marfan Syndrome (MFS1) have pooled data for joint analysis in an attempt to determine the precise location of the MFS1 gene and the order of 10 DNA markers on 15q. Five laboratories performed a total of 2111 genotypes in 22 families consisting of 225 affected and 248 normal subjects. For each marker a mean of 98 meioses was informative. D15S48 and D15S1 were identified as the closest linked markers with 99% upper confidence intervals of 12% and 13% respectively. We have used the CRI-MAP program to construct the most likely order as: D15S24-D15S25-D15S1-MFS1-D15S48-D15S49+ ++-(D15S45/S51)-(D15S29/S38). Placement of D15S2 in relation to -D15S1-D15S48- cannot be determined with certainty. The genetic map of these markers extends 53.6 cM in males and 65.0 cM in females with a sex averaged map of 60.7 cM. The sex difference was statistically significant (p = 0.005). Linkage heterogeneity between 22 MFS1 families was documented (p = 0.009) necessitating the exclusion of one family from the analysis. However, comparison of the remaining 21 families for two point and multipoint lod scores showed no evidence for linkage heterogeneity of the MFS1 locus.

Chromosome Mapping

Pubertal stage and panic attack history in sixth- and seventh-grade girls.

OBJECTIVE: Although the incidence of first panic attacks appears to peak during adolescence, little is known about which features of adolescence contribute to the risk of a first panic episode. The purpose of this study was to compare the relative importance of age and pubertal stage in explaining the occurrence of panic attacks in adolescents. METHOD: From a school-based sample of sixth- and seventh-grade girls, 754 subjects completed both a structured clinical interview determining history of one or more panic episodes and a self-assessment of Tanner stages of pubertal development. A multiple logistic regression analysis was performed with panic attack history as the dependent variable and pubertal stage, age, and their interaction as the independent variables. RESULTS: A history of one or more four-symptom panic attacks was found in 5.3% of the girls (N = 40). After age was controlled for, pubertal stage was significantly related to panic attack history. At each age, higher rates of panic attacks were found in the more physically mature girls. CONCLUSIONS: Pubertal stage, after adjustment for the effects of age, appears to predict panic attack occurrence in young adolescent girls. Understanding the link between puberty and panic may offer clues regarding the onset and etiology of panic attacks.

Adolescent

Insulin-like growth factor binding protein-3 in normal pubertal girls.

IGFBP-3 concentrations rise in the second decade of life. To test the hypothesis that the stage of pubertal development, independent of chronological age, was associated with these increases we measured serum IGFBP-3 concentrations by radioimmunoassay in 324 sixth and seventh grade girls (12.3 +/- 0.7 years) at the beginning of a multisite school-based health curriculum. The mean (+/- SD) serum IGFBP-3 among the 242 girls with complete data was 4.0 +/- 0.7 mg/l. Pubertal stage was significantly associated with IGFBP-3 (p less than 0.0001, ANOVA). Mean concentrations rose from 3.5 +/- 0.7 mg/l among those with the earliest pubertal stages to 4.2 +/- 0.7 mg/l among the mature girls. IGF-I and IGFBP-3 concentrations were significantly correlated (Spearman's r = 0.43, p less than 0.0001). After controlling for the association between pubertal development and IGFBP-3 concentrations, only the waist/hip ratio, among the various measures of body composition, was significantly associated with IGFBP-3 concentration (Spearman's r = -0.23, p = 0.0002). Likewise, none of the measures of nutrition: intake of total calories, protein, fat and carbohydrate; serum iron; red cell mean corpuscular volume; or cholesterol; were significantly associated with IGFBP-3 concentrations. There was, however, a small, but significant association between IGFBP-3 concentrations and both serum transferrin and blood hemoglobin concentrations. Pubertal stage has a significant impact on IGFBP-3 concentrations and those attempting to utilize IGFBP-3 concentrations during adolescence should be cognizant of the subject's pubertal stage.

Adolescent

Linkage analysis of maturity-onset diabetes of the young (MODY): genetic heterogeneity and nonpenetrance.

We have analyzed the inheritance of maturity-onset diabetes of the young (MODY) on chromosome 20 in a large multigeneration family, the R.-W. family, and in two other MODY families. Of the four branches of the R.-W. pedigree which have been studied, two have documented early onset of non-insulin-dependent diabetes mellitus (NIDDM), while there is no evidence of early onset in the other two branches. The early-onset branches have apparently inherited the same D20S16 allele from the affected parent, while another D20S16 allele was inherited in the two branches without evidence of early onset. A test for homogeneity, the M-test, using the results of two-point linkage analysis with D20S16 indicates heterogeneity between early- and late-onset branches of the R.-W. family (P less than or equal to .014). In addition, analysis strongly suggests that MODY as expressed in the EDI and WIS families is unlinked to loci on chromosome 20 (P less than or equal to .018-.004). Comparable results are seen when the data are analyzed by the HOMOG program. Three polymorphic loci-D20S16, D20S17, and ADA--show no recombination with the MODY locus when two-point linkage analysis is used in the early-onset branches of the family. The multipoint lod score in the early-onset branches of the R.-W. family is 10.16, with the most likely location being between D20S4 and D20S17. Multipoint linkage analysis using the CHROMPICS option of the program CRI-MAP has been used to follow inheritance of the MODY disease locus. This analysis has identified two cases of possible nonpenetrance in the early-onset branches of the family (odds of at least 156:1), as determined by the appearance of apparent isolated double crossovers at the MODY locus in these unaffected individuals.

Adolescent

An exclusion map for pre-eclampsia: assuming autosomal recessive inheritance.

Pre-eclampsia is a common complication of the second half of pregnancy that is associated with substantial fetal and maternal morbidity. Although the genetic basis of the disorder is unclear, epidemiological studies suggest that it occurs predominantly in the first pregnancies of women who are homozygous for a relatively common susceptibility gene. Using this epidemiological model, we have begun to construct an exclusion map by using both candidate genes and random DNA markers on a panel of two-generation families in which pre-eclampsia was rigorously defined. No evidence was found for linkage to the HLA region or to several genes implicated in the pathogenesis of hypertension.

Chromosomes, Human, Pair 1

Oral vaccination of calves against experimental salmonellosis using a double aro mutant of Salmonella typhimurium.

An attenuated derivative of the fully calf virulent Salmonella typhimurium strain ST4/74 was constructed by introducing stable mutations into genes aroA and aroD rendering the strain dependent for growth on aromatic compounds. The strain (BRD562) was used to vaccinate orally ten Friesian calves 7 days after birth with approximately 10(10) live organisms. The only effects of vaccination in the calves was a transient faecal excretion of the organism, mild transient diarrhoea and mild pyrexia in one animal. Two of these animals were tested for the presence of BRD562 at necropsy 56 days after birth but none were shown to be infected. Eight of the vaccinated calves were subjected to an oral challenge infection with ST4/74 28 days after vaccination and seven out of the eight animals survived. The only effect of challenge in the surviving calves was mild pyrexia and transient excretion of ST4/74 in their faeces; only one of the seven animals was found to be infected at necropsy 28 days after challenge. The eighth challenged calf scoured severely and was killed in extremis 7 days after challenge. Four unvaccinated control calves infected orally with ST4/74 28 days after birth all scoured severely and were euthanased for humane reasons 5-7 days later. This study suggests that vaccination with an attenuated strain of S. typhimurium harbouring mutations in two aro genes is a safe and effective way of protecting young calves against experimental S. typhimurium infection.

Administration, Oral

Impact of pubertal development on body fat distribution among white, Hispanic, and Asian female adolescents.

Variation in the waist/hip ratio (WHR) may be related to changes in hormonal secretion associated with pubertal maturation. We therefore studied the effects of race, pubertal development, and body fatness on WHR during adolescence in a multiethnic population. A total of 688 white, Asian, and Hispanic female adolescents (mean (+/- SD) 12.4 +/- 0.7 years), participating in the evaluation of a multisite school-based health education program, were included in these analyses. Self-assessed stage of puberty and measurements of height, weight, waist circumference, and hip circumference were obtained from each participant. The WHR and age-adjusted body mass index were calculated. Analysis of covariance demonstrated that puberty significantly affects hip circumference and WHR but not waist circumference among female adolescents. Age and fatness, as reflected by age-adjusted body mass index, contributed significantly to both circumferences and to the WHR. There was a significant effect of ethnicity on hip circumference but not on waist circumference or the WHR. These results confirm that pubertal stage exerts a significant effect on the hip circumference and WHR in female adolescents, even after the effects of fatness and age are controlled. Studies of body fat distribution during late childhood and adolescence should include assessments of pubertal maturation.

Adipose Tissue

Construction and characterization of Bordetella pertussis mutants lacking the vir-regulated P.69 outer membrane protein.

The Bordetella pertussis P.69 protein is an immunogen with vaccine potential. The role of this protein in pathogenesis is unclear; it has been associated with the toxic adenylate cyclase and adhesion to eukaryotic cells. For further analysis of the role of P.69 in the biology of B. pertussis, we have constructed strains which specifically lack P.69. The cloned P.69 (prn) gene of B. pertussis was insertionally inactivated with a kanamycin-resistance cassette. This inactivated gene was used to construct P.69- mutants of B. pertussis by allelic exchange using plasmid pRTP1. B. pertussis P.69- strains produced normal levels of other vir-regulated factors, including adenylate cyclase. The serotype of B. pertussis, determined by Eldering and Preston typing sera and monoclonal antibodies, was also unaffected by the presence or absence of P.69. The ability of a prn mutant to adhere to and invade HEp2 cells was not significantly different from that of its parent strain. A strain containing a mutation in fhaB was significantly less adhesive and invasive than its parent, and a prn fhaB double mutant exhibited an even greater reduction in adhesiveness and invasiveness down to levels comparable with a Vir- strain. However, strains harbouring mutations in FHA and/or P.69 were able to colonize or multiply in the murine respiratory tract, although a Vir- strain was unable to survive and proliferate in the same infection model.

Adenylyl Cyclases

Role of ompR-dependent genes in Salmonella typhimurium virulence: mutants deficient in both ompC and ompF are attenuated in vivo.

A Salmonella typhimurium strain harboring stable mutations in both ompC and ompF was constructed from the mouse-virulent strain S. typhimurium SL1344. When administered orally to BALB/c mice the strain was attenuated, with the 50% lethal dose (LD50) reduced by approximately 1,000-fold. However, the intravenous LD50 was reduced only by approximately 10-fold. The ompC ompF mutant persisted in murine tissues for several weeks following oral challenge, and mice immunized with this mutant were well protected against challenge with virulent SL1344. A strain harboring a stable mutation in tppB behaved in a manner similar to that of strain SL1344 in vivo, while a strain harboring mutations in ompC, ompF, and tppB behaved as an ompC ompF mutant in vivo, indicating that the tppB operon is not required for virulence in S. typhimurium.

Animals

Insulin-like growth factor-I as a reflection of body composition, nutrition, and puberty in sixth and seventh grade girls.

Large variations in nutritional intake have profound effects on the GH-insulin-like growth factor-I (IGF-I) axis in children and adults, but the effect of normal variations in nutrition on IGF-I concentrations is largely unstudied, particularly during puberty. We measured serum IGF-I concentrations in 325 sixth and seventh grade girls (12.4 +/- 0.7 yr) at the beginning of a multisite school-based health curriculum. The mean serum IGF-I level among the 243 girls with complete data was 573 +/- 244 micrograms/L. Pubertal stage was significantly associated with IGF-I (P less than 0.0001, by analysis of variance). Mean concentrations rose from 427 +/- 198 micrograms/L among those at the earliest pubertal stages to 639 +/- 219 micrograms/L among the mature girls. After adjusting for the association with the stage of pubertal development, serum IGF-I was not significantly associated with measures of body composition (body mass index, triceps skin fold thickness, waist/hip ratio, height, and weight). Additionally, IGF-I concentrations were not associated with nutritional intake (total calories, total protein, total fat, and total carbohydrate) or such measures of nutrition as serum iron, hemoglobin, red cell mean corpuscular volume, white cell count, and cholesterol. IGF-I concentrations, however, were significantly correlated with transferrin concentrations, another possible index of nutritional status (r = 0.29; P less than 0.0001). IGF-I is not a clinically useful index of nutritional status among normal pubertal girls.

Adolescent

Cardiovascular considerations in selection of anti-panic pharmacotherapy.

Patients with panic disorder may be at increased risk for cardiovascular morbidity and mortality. There is also preliminary evidence that some cardiovascular risk factors may be increased in patients with panic disorder. Since anti-panic medications can alter cardiovascular function, the cardiovascular effect of these medications should be considered, particularly when used in patients with cardiovascular disease. This article will review the cardiovascular side effects of anti-panic medications.

Anti-Anxiety Agents

Motor activity and tonic heart rate in panic disorder.

Motor activity and tonic heart rate were monitored in 62 drug-free panic disorder patients and 40 normal control subjects. Mean daily activity, mean waking heart rate controlled for activity, and mean sleeping heart rate were determined. Panic disorder patients without phobic avoidance showed higher activity than control subjects or patients with limited or extensive avoidance. Similarly, an "inverted U", relationship between trait anxiety and activity was observed. On the other hand, neither mean waking nor sleeping heart rate showed significant differences between patients and controls, suggesting that the differences previously reported in laboratory studies result from anticipatory anxiety.

Adult

Evaluation of intense renal parenchymal activity ("hot kidneys") on bone scintigraphy.

The bone scintigrams of 600 patients performed over a 12-month period were reviewed. Thirty-six demonstrated abnormalities of the urinary tract of which six cases of intense renal parenchymal activity ("hot kidneys") were found. Two cases were related to treatment with the new antineoplastic agent mitoxantrone. In one patient it was related to treatment with calcitonin. Neither of these associations has been previously reported. Recognized causes of hypercalcemia and recent radiotherapy were present in two patients. No cause could be found in the final patient.

Adult

Cardiovascular and symptomatic reduction effects of alprazolam and imipramine in patients with panic disorder: results of a double-blind, placebo-controlled trial.

Seventy-nine patients with panic disorder were randomized to an 8-week double-blind treatment with alprazolam, imipramine, or placebo. Patients kept daily records of panic attacks, activity, anxiety, sleep, and medication use. Weekly measures of anxiety, depression, somatic symptoms, fears, avoidance, disability, and improvement were obtained. All patients underwent a symptom-limited exercise treadmill and other cardiovascular measures. By physician and patient global assessment, patients receiving alprazolam or imipramine were significantly better than patients on placebo. The alprazolam effects were apparent by week 1; the imipramine effects by week 4. All groups showed significant reductions in anxiety, depression, somatic measures, and panic attack frequency. At 8 weeks, patients in the alprazolam group reported significantly less fear than patients in the other two groups. Subjects in the imipramine group showed a significant increase in heart rate and blood pressure.

Adult