Neural tube defects and folic acid knowledge and use in Mississippi women.
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Adolescent↗
Biomedical subjects
M Norman
Publications and source records attributed to M Norman.
Impaired endothelial function and increased carotid stiffness in 9-year-old children with low birthweight.
BACKGROUND: Low birthweight (LBW) has been associated with an increased incidence of adult cardiovascular disease. Endothelial dysfunction and loss of arterial elasticity are early markers of hypertension and atherosclerosis. We studied the prevalence of these markers in 44 healthy, prepubertal (age 9+/-1.3 years) children, 22 with LBW for age. METHODS AND RESULTS: Endothelial function in skin was tested with the local application of acetylcholine (inducing endothelium-dependent vasodilation) and nitroglycerin (endothelium-independent vasodilation), and local perfusion changes were measured with the laser Doppler method. The elastic properties of the abdominal aorta and common carotid artery were measured with an ultrasonic vessel-wall tracking system. Endothelium-dependent vasodilation was lower in children with LBW (88+/-33 perfusion units [PU]) than in normal-birthweight controls (133+/-34 PU, P<0.001). There was no difference in aortic or carotid elasticity between the 2 groups, but a negative correlation was found between birthweight and stiffness of the carotid artery wall (r=-0.45, P<0.01). Endothelium-independent vasodilation and blood pressure were similar in the 2 groups. CONCLUSIONS: Schoolchildren with a history of LBW show impaired endothelial function and a trend toward increased carotid stiffness. These findings may be early expressions of vascular compromise, contributing to susceptibility to disease in adult life.
Acetylcholine↗
Identification of a deletion in plakoglobin in arrhythmogenic right ventricular cardiomyopathy with palmoplantar keratoderma and woolly hair (Naxos disease).
BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an autosomal dominant heart muscle disorder that causes arrhythmia, heart failure, and sudden death. Previously we mapped the genetic locus for the triad of autosomal recessive ARVC, palmoplantar keratoderma, and woolly hair (Naxos disease) to chromosome 17q21, in which the gene for plakoglobin is encoded. This protein is a key component of desmosomes and adherens junctions, and is important for the tight adhesion of many cell types, including those in the heart and skin. METHODS: We studied 19 individuals with Naxos disease, as well as unaffected family members and unrelated individuals from the neighbouring Greek islands of Naxos and Milos. Gene sequence was determined by reverse transcriptase PCR from RNA isolated from the skin of an affected individual and mutations in other cases were confirmed by restriction-enzyme analysis. FINDINGS: A homozygous 2 base pair deletion in the plakoglobin gene was identified only in the 19 affected individuals. This deletion caused a frameshift and premature termination of the protein, which was shown by western blot analysis. 29 clinically unaffected family members were heterozygous for the mutation; 20 unrelated individuals from Naxos and 43 autosomal dominant ARVC probands were homozygous for the normal allele. INTERPRETATION: The finding of a deletion in plakoglobin in ARVC suggests that the proteins involved in cell-cell adhesion play an important part in maintaining myocyte integrity, and when junctions are disrupted, cell death, and fibrofatty replacement occur. Therefore, the discovery of a mutation in a protein with functions in maintaining cell junction integrity has important implications for other dominant forms of ARVC, related cardiomyopathies, and other cutaneous diseases.
Alleles↗
Normative data for iliac bone histomorphometry in growing children.
Many insights into normal and pathologic bone development can only be gained by bone histomorphometry. However, the use of this technique in pediatrics has so far been hampered by the lack of reference data. Therefore, we obtained transfixing iliac bone samples from 58 individuals between 1.5 and 22.9 years of age (25 male; tetracycline labeling performed in 48 subjects), who underwent surgery for reasons independent of abnormalities in bone development and metabolism. The results of histomorphometric analyses of cancellous parameters and cortical width are presented as means and standard deviations, as well as medians and ranges in five age groups. In addition, the original data are available from the authors. There were significant age-dependent increases in both cortical width and cancellous bone volume, the latter being due to an increase in trabecular thickness. Osteoid thickness did not vary significantly with age. Bone surface-based indicators of bone formation showed an age-dependent decline, reflecting similar changes in activation frequency. Mineral apposition rate decreased continuously with age. Parameters of bone resorption did not vary significantly between age groups. Paired biopsies from adjacent sites, obtained in eight subjects, were used to examine the reproducibility of histomorphometric parameters in children. The lowest coefficients of variation (<10%) were found for structural measures, as well as mineral apposition rate and wall thickness. The highest variability was found for cellular parameters. The availability of reference material will greatly facilitate the use of histomorphometry in pediatrics.
Adolescent↗
Is it necessary to suture all lacerations after a vaginal delivery?
BACKGROUND: Midwives tend to leave minor perineal lacerations to heal spontaneously, and clinical experience and studies show that women can suffer from their stitched lacerations. The study purpose was to determine any differences in the healing process and experience of minor perineal lacerations when they were sutured or not sutured. METHODS: Eighty term pregnant primiparas with minor perineal lacerations of grades I-II were randomized after childbirth. The experimental group was nonsutured and the control group was sutured. A follow-up examination was performed at 2 to 3 days, 8 weeks, and 6 months after the delivery. Participants were asked about the type of discomfort, and the effect of the laceration on breastfeeding and sexual intercourse. RESULTS: No significant differences were found in the healing process. The type of pain differed between the groups, but the amount of discomfort was the same. The sutured group had to visit the midwife more often because of discomfort from the stitches. Sixteen percent of the women in the sutured group, but none in the nonsutured group (p = 0.0385), considered that the laceration had had a negative influence on breastfeeding. CONCLUSIONS: Minor perineal lacerations can be left to heal spontaneously. The benefits for the woman include the possibility of having a choice, avoiding the discomfort of anesthesia and suturing, providing positive affects on breastfeeding.
Breast Feeding↗
Human cervical ripening, an inflammatory process mediated by cytokines.
An extensive remodelling process, referred to as cervical ripening, takes place in the cervical tissue during pregnancy and labour. It is recognized as softening and dilation of the cervical canal, and starts as a slow process during pregnancy, becoming rapid close to partum. In this study we focus on cytokines as possible mediators of this final remodelling. mRNA levels for interleukin (IL)-8, IL-6 and granulocyte colony-stimulating factor (G-CSF) were upregulated in the ripe postpartum cervical tissue (n = 8) compared to the unripe state (n = 9). Likewise, released cytokine concentrations increased from non-pregnant (n = 11) to the term-pregnant group (n = 13) with a further increase at partum (n = 16). IL-8 concentrations increased 4-fold from non-pregnant to term-pregnant (P<0.01), and a further 10-fold to postpartum state (P<0.0001). Concentrations of IL-6 and G-CSF were similarly increased. Specific IL-8 immunostaining was identified in the epithelia of pregnant cervical tissue (n = 7) and was most pronounced in the epithelia and stroma of postpartum tissue (n = 4). In conclusion, IL-8, IL-6 and G-CSF increase in the human cervix during the ripening process, indicating their important role in the cervical remodelling. These data demonstrate that cervical ripening is similar to an inflammatory process.
Adult↗
Impaired acetylcholine-induced vascular relaxation in low birth weight infants: implications for adult hypertension?
Low birth weight is associated with an increased risk of adult hypertension. To elucidate whether this association reflects altered vascular physiology already at birth, we studied acetylcholine-induced vasodilation. Forty newborn infants and their mothers were studied 3 d after delivery. Vasodilation in skin was induced by local application of acetylcholine and local heating to 44 degrees C. Perfusion changes were measured with the laser Doppler technique. In response to acetylcholine, the mean skin perfusion increased by 240% in low birth weight infants compared with 650% in normal birth weight controls (p < 0.001). In contrast, mothers of low birth weight infants showed a mean increase in perfusion of 1100% after acetylcholine administration compared with 680% in mothers of control infants (p < 0.05). The perfusion increase at 44 degrees C local skin temperature did not differ between the two groups of infants or between their mothers. Blood pressure was normal in all subjects. We conclude that low birth weight infants show signs of endothelial dysfunction at birth. Such findings may help us understand the link between low birth weight and adult hypertension.
Acetylcholine↗
Insertion gain measurements using two low-powered analogue hearing aids.
Differences between insertion gain measurements and coupler measurements were investigated using two different hearing aids, to assess the accuracy of hearing aid fitting methods which involve the use of real-ear-to-coupler differences (RECDs). The hearing aids used were the NHS BE19 and the Lavis X11. They were allocated alternately to 80 new adult hearing aid users, and insertion gain measurement was carried out with the allocated aid on all subjects, and with both hearing aids on 36 subjects. Coupler measurements were also carried out with both hearing aids, at two different gain settings. Comparison of the coupler measurements and the insertion gain measurements suggests that the differences in insertion gain produced by different hearing aids cannot be predicted accurately from the differences in coupler gain measurements produced by the same aids. Although the use of RECDs measured using insert earphones may accurately predict the real-ear performance of some models of hearing aid, this method may not produce equally satisfactory results with other models.
Hearing Aids↗
Inhaled nitric oxide does not influence bleeding time or platelet function in healthy volunteers.
BACKGROUND: Bleeding time has been reported to increase during gaseous nitric oxide (NO) inhalation in healthy volunteers and patients, and it has been speculated that inhaled NO inhibits platelet function. However, results have not been unanimous, and we have been unable to document any effects of inhaled NO on circulating platelets. MATERIALS AND METHODS: We performed a double-blind, placebo controlled cross-over study in which healthy volunteers (n = 15) inhaled NO (30 ppm, 30 min) or control gas. Aspirin (640 mg x 1 orally) was used as positive control on the third occasion (n = 14). Bleeding time was measured, and platelet function was determined flow cytometrically by measuring the expression of P-selectin on circulating platelets and locally activated platelets in wound blood. Skin perfusion close to the site for bleeding time incisions was assessed by laser Doppler flowmetry. RESULTS: Bleeding time was unaffected by NO, as there were slight increases during both NO and control inhalation (+20% and +14% respectively, P = 0.9). Similarly, NO inhalation had no effect on platelet P-selectin expression in either systemic or wound blood, or on skin perfusion. Aspirin pretreatment, on the other hand, prolonged bleeding time (P < 0.001) and decreased P-selectin expression of platelets in wound blood (P = 0.03). CONCLUSIONS: This first placebo-controlled study indicates that inhaled NO does not influence either bleeding time, platelet activity or skin perfusion. Thus, it is unlikely that treatment of critically ill patients with inhaled NO will aggravate haemostatic disturbances, which has previously been feared, by influencing platelet function.
Administration, Inhalation↗
Anal incontinence after vaginal delivery: a prospective study in primiparous women.
OBJECTIVE: To investigate the incidence and degree of anal incontinence after vaginal delivery among primiparous women and to define associated risk factors. DESIGN: Prospective observational study. SETTING: Karolinska Institutet, Danderyd Hospital, Sweden, a university hospital. PARTICIPANTS: Three hundred and forty-nine primiparous women. METHODS: Questionnaires distributed within the first days after delivery and re-distributed five and nine months postpartum. Analysis of delivery records. RESULTS: Eighty percent of the women answered all questionnaires. At five months postpartum, 2% of the women had symptoms of faecal incontinence and 25% had symptoms of involuntary flatus. At nine months postpartum, 1% of the women had symptoms of faecal incontinence and 26% had symptoms of involuntary flatus. The majority of the women had infrequent symptoms and a decrease in severity was noted at nine months. Symptoms of incontinence were more common in women who sustained a sphincter tear at delivery. Risk factors for incontinence at five months included maternal age, duration of the second stage of labour, instrumental vaginal delivery, and clinically diagnosed sphincter tear at delivery. Development of incontinence at nine months was associated with maternal age and clinically diagnosed sphincter tear at delivery. CONCLUSIONS: The present study demonstrates that infrequent involuntary flatus is a common symptom after vaginal delivery in primiparous women. These symptoms of involuntary flatus frequently improved and only a few women suffered from frank faecal incontinence. Factors associated with an increased risk of anal incontinence and sphincter tears should be considered during delivery.
Adult↗
Predicting therapeutic outcome in severe ulcerative colitis by measuring in vitro steroid sensitivity of proliferating peripheral blood lymphocytes.
BACKGROUND: Up to 29% of patients with severe ulcerative colitis (UC) fail to respond to steroid treatment and require surgery. Previous studies have failed to show a clear correlation between failure of steroid treatment in severe UC and measures of disease severity. The reasons for treatment failure therefore remain unknown. AIM: To investigate the hypothesis that patients with severe UC who fail to respond to steroid treatment have steroid resistant T lymphocytes. METHODS: Eighteen patients with severe UC were studied. After seven days' treatment with high dose intravenous steroids they were classified as complete responders (CR), incomplete responders (IR), or treatment failures (TF). Within 48 hours of admission blood was taken and the antiproliferative effect of dexamethasone on phytohaemagglutinin stimulated peripheral blood T lymphocytes was measured. Maximum dexamethasone induced inhibition of proliferation (I(max)) was measured. RESULTS: In vitro T lymphocyte steroid sensitivity of TF and IR patients was significantly less than that of CR patients. Both TF and 3/5 IR patients had an I(max) of less than 60%; all CR patients had an I(max) of greater than 60%. No significant correlation was seen between response to treatment and disease severity on admission. When in vitro T lymphocyte steroid sensitivity was remeasured three months later, there was no difference between the groups. CONCLUSIONS: Results suggest that T lymphocyte steroid resistance is an important factor in determining response to steroid treatment in patients with severe UC and may be more predictive of outcome than disease severity.
Adult↗
Wide variation in lymphocyte steroid sensitivity among healthy human volunteers.
Steroids are frequently used to treat inflammatory conditions in which lymphocytes play a role. We have recently shown that in severe ulcerative colitis, treatment outcome correlates better with in vitro estimates of lymphocyte steroid sensitivity (LSS) than with disease severity. This lead us to examine the range and variability of LSS in the healthy population. Dexamethasone inhibition of lymphocyte proliferation was measured on 54 occasions in 18 volunteers (mean age, 46 yr; range, 23-60 yr) over an 8-month period. Inter- and intra-assay variation in LSS was low when expressed as maximum inhibition achieved, Imax (2.9% and 3.4%, respectively), allowing us to demonstrate a very wide variation in Imax between healthy individuals (-6.7% to 99.7%). In contrast, within-individual variation of Imax was significantly less than between-individual variation (F test, P < 0.0001), consistent with stability of this parameter over time. No correlation was seen between LSS and glucocorticoid receptor density or affinity, suggesting a postreceptor mechanism. Serum cortisol at the time of sampling and skin sensitivity to glucocorticoids also failed to correlate with LSS. This study suggests Imax is a sufficiently stable parameter to categorize healthy individuals according to LSS. The wide range of LSS demonstrated is striking and suggests that up to 30% of the healthy population would fail to respond to steroid therapy for severe inflammatory conditions.
Adult↗
Insertion of an amino acid in the DNA-binding domain of the glucocorticoid receptor as a result of alternative splicing.
When the human glucocorticoid receptor (GR) was first sequenced, a predominant form (GRalpha) and a minor variant (GRbeta) were identified. In the present communication, we describe a new variant of the glucocorticoid receptor (GRgamma) in which, as a result of alternative splicing, three bases are retained from the intron separating exons 3 and 4. These three bases code for an additional amino acid (arginine) in the DNA binding domain of the receptor. Insertion of arginine at this site has previously been shown to decrease transcriptional activation by the GR to 48% that of GRalpha. Analysis of cDNA from different tissues shows that the novel form is widely expressed at a relatively high level (between 3.8 and 8.7% of total GR).
Alternative Splicing↗
Variations in calibration for computerized electronystagmography.
The accuracy of the analyses of vestibular test results obtained from a computerized electronystagmography (ENG) system depends on the accuracy with which the system has been calibrated to record the patient's eye movements. The variability of the calibration sensitivity was investigated by analysing the records of 50 consecutive patients who attended for vestibular testing and a study was carried out using 16 volunteer subjects to examine the contributions that time, changes in lighting and subject movement made to this variability. The effect of calibration frequency on the results obtained from caloric testing was also examined by analysing 16 patient records. The mean percentage change in sensitivity between the first two calibrations carried out on patients was found to be -17%, with a standard deviation of 18%. However, there seems to be little baseline drift over time under constant lighting conditions. Changes in lighting have a marked effect, and the adjustment to lighting changes is slow. Gentle movement has little effect. Repeated calibration does not seem to be an effective method to control the calibration-related errors in caloric test results. Careful control of room illumination and the use of adequate adaptation periods to allow patients to adjust to the lighting should help to improve accuracy but, even in the absence of satisfactory calibration, the use of a computerized ENG system can provide valuable diagnostic information.
Adolescent↗
In vitro measurement of lymphocyte steroid sensitivity: lack of agreement between whole blood culture and separated lymphocyte culture.
The use of a whole blood culture to measure steroid sensitivity has previously been compared to the use of a separated lymphocyte assay. Good correlation between the two methods was reported. However the number of subjects studied appears to have been small and no patients with steroid resistance were studied. We have studied a large number of subjects and compared steroid sensitivity measured by a whole blood culture with an established separated lymphocyte assay. Proliferation was stimulated with phytohaemagglutinin and inhibited by dexamethasone. A wide range of steroid sensitivity was found between individuals. In steroid sensitive subjects, good agreement was seen between the two assays. However in individuals identified as steroid resistant by the separated lymphocyte assay, steroid resistance was not seen using the whole blood assay. This is important because in vitro lymphocyte steroid resistance, as measured by the separated lymphocyte assay has been shown to predict a poor in vivo response to steroid therapy. Using the whole blood culture this steroid resistance would not be demonstrated. Hence the use of a whole blood assay can not be recommended.
Adult↗
Anal sphincter tears at vaginal delivery: risk factors and clinical outcome of primary repair.
OBJECTIVE: To determine risk factors for obstetric anal sphincter tears and to evaluate symptomatic outcome of primary repair. METHODS: Obstetric-procedure, maternal, and fetal data were registered in 845 consecutive vaginally delivered women. Risk factors for anal sphincter tears were calculated by multiple logistic regression. All 808 Swedish-speaking women who delivered vaginally were included in a questionnaire study regarding anal incontinence in relation to the delivery. Questionnaires were distributed within the first few days postpartum, and at 5 and 9 months postpartum. RESULTS: Six percent of the women had a clinically detected sphincter tear at delivery. Sphincter tears were associated with nulliparity (odds ratio [OR] 9.8, 95% confidence interval [CI] 3.6, 26.2), postmaturity (OR 2.5, 95% CI 1.0, 6.2), fundal pressure (OR 4.6 95% CI 2.3, 7.9), midline episiotomy (OR 5.5 95% CI 1.4,18.7), and fetal weight in intervals of 250 g (OR 1.3 95% CI 1.1, 1.6). Fifty-four percent of women with repaired sphincter tears suffered from fecal or gas incontinence or both at 5 months and 41% at 9 months. Most of the symptoms were infrequent and mild. CONCLUSION: Several risk factors for sphincter tear were identified. Sphincter tear at vaginal delivery is a serious complication, and it is frequently associated with anal incontinence. Special attention should be directed toward risk factors for this complication. Symptoms of anal incontinence should explicitly be sought at follow-up after delivery.
Adult↗
Galanin regulates prolactin release and lactotroph proliferation.
The neuropeptide galanin is predominantly expressed by the lactotrophs (the prolactin secreting cell type) in the rodent anterior pituitary and in the median eminence and paraventricular nucleus of the hypothalamus. Prolactin and galanin colocalize in the same secretory granule, the expression of both proteins is extremely sensitive to the estrogen status of the animal. The administration of estradiol-17beta induces pituitary hyperplasia followed by adenoma formation and causes a 3,000-fold increase in the galanin mRNA content of the lactotroph. To further study the role of galanin in prolactin release and lactotroph growth we now report the generation of mice carrying a loss-of-function mutation of the endogenous galanin gene. There is no evidence of embryonic lethality and the mutant mice grow normally. The specific endocrine abnormalities identified to date, relate to the expression of prolactin. Pituitary prolactin message levels and protein content of adult female mutant mice are reduced by 30-40% compared with wild-type controls. Mutant females fail to lactate and pups die of starvation/dehydration unless fostered onto wild-type mothers. Prolactin secretion in mutant females is markedly reduced at 7 days postpartum compared with wild-type controls with an associated failure in mammary gland maturation. There is an almost complete abrogation of the proliferative response of the lactotroph to high doses of estrogen, with a failure to up-regulate prolactin release, STAT5 expression or to increase pituitary cell number. These data further support the hypothesis that galanin acts as a paracrine regulator of prolactin expression and as a growth factor to the lactotroph.
Alleles↗
Differential expressions of mRNA for proteoglycans, collagens and transforming growth factor-beta in the human cervix during pregnancy and involution.
During pregnancy and involution, an extensive remodelling of the human cervical connective tissue occurs. This cervical ripening is one of the most pronounced physiological remodelling processes known in human connective tissue. To investigate how the remodelling is accomplished, the levels of mRNA for collagen I and III, versican and three small proteoglycans, biglycan, decorin and fibromodulin, were evaluated using Northern blots at different stages of cervical ripening. In the corresponding biopsies the concentration of collagen and of small and large proteoglycans were determined. The role of transforming growth factor-beta (TGF-beta) as a mediator of the remodelling process was also investigated. The concentration of collagen decreased and 1 week before partus, 50% of the nonpregnant level was attained. No further decrease was noted after partus. The mRNA for collagen I and III did, however, not decrease in the term pregnant cervix 1 week before partus. Only 20-30% decrease during the final ripening just before partus was recorded. Neither did the mRNA levels of the small proteoglycans change significantly during the ripening, despite an almost 50% decrease in the concentration of the small proteoglycans. The message for versican was, however, 5-fold increased at partus and then gradually returned to nonpregnant levels within 4 days after delivery. These changes corresponded to similar changes in the concentration of the large proteoglycan. Thus, the remodelling of the cervical connective tissue is achieved by two different mechanisms, on one hand an increased turnover of collagen and the small proteoglycans, on the other a changed transcription followed by an increased production of versican. During the involution 2- to 3-fold increases in the messages for collagen I and III, and the small proteoglycans, biglycan and decorin, corresponded to increases in the concentration of the small proteoglycans and non-extractable collagen. The message for TGF-beta was increased 2-fold immediately after delivery compared with the term pregnant state. Thus, TGF-beta may be of importance for the reconstruction of the cervix, which starts immediately after partus.
Adult↗