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Biomedical subjects

J Gregg

Publications and source records attributed to J Gregg.

At least 19 recordsLinked to original sources

Neuropsychological effects of exposure to anticonvulsant medication in utero.

OBJECTIVE: To investigate the long-term differential drug effects on cognitive functioning in school-aged children exposed to antiepileptic drugs (AEDs) in utero. METHODS: Mothers with epilepsy were recruited from specialist epilepsy clinics and obstetric clinics from the Liverpool and Manchester region. The mothers and their children were recruited without prior knowledge of their AED treatment during pregnancy or the health of the offspring. A battery of neuropsychological tests was applied to each mother-child pair in order to obtain a neuropsychological profile for each child. RESULTS: Neuropsychological investigation was performed on 249 children between the ages of 6 and 16. Children exposed to sodium valproate had a significantly lower verbal IQ when compared to children exposed to other antiepileptic drugs or not exposed at all. The same children were more likely to have an IQ below 69 and more likely to have memory impairment when compared to the other groups. The mothers' IQ, exposure to sodium valproate, and the number of tonic-clonic seizures during pregnancy were significant predictors of verbal IQ in this population. CONCLUSIONS: This retrospective study highlights the potential harmful effects of sodium valproate exposure in utero on neuropsychological development.

Adolescent↗

The longer term outcome of children born to mothers with epilepsy.

OBJECTIVES: To determine the prevalence of cognitive delay and possible associated dysmorphic features in children exposed to antiepileptic drugs (AEDs) in utero. DESIGN: Retrospective study of children born to mothers with epilepsy. SETTING: Regional epilepsy clinics in Liverpool and Manchester, UK. PARTICIPANTS: Children aged between 6 months and 16 years born to mothers with epilepsy. MAIN OUTCOME MEASURES: Structured interviews, hospital records, clinical examination, and psychometric tests (Wechsler) were used to assess exposure and intelligence quotient (IQ). Blinded assessment of photographs was used to score children with characteristic dysmorphic features. RESULTS: A total of 249 children aged 6 and over were studied: 41 were exposed to sodium valproate, 52 to carbamazepine, 21 to phenytoin, 49 to polytherapy, and 80 were unexposed. Mean verbal IQ was significantly lower in the valproate group compared to unexposed and other monotherapy groups. Multiple regression analysis showed that both valproate exposure and frequent tonic-clonic seizures in pregnancy were significantly associated with a lower verbal IQ despite adjusting for other confounding factors. There was a significant negative correlation between dysmorphic features and verbal IQ in children exposed to valproate. CONCLUSIONS: This study identifies valproate as a drug carrying potential risks for developmental delay and cognitive impairment and is the first to suggest that frequent tonic-clonic seizures have a similar effect. Our results need to be interpreted with caution given their retrospective nature. Women with epilepsy need careful counselling about individual risk benefit of AED treatment before pregnancy.

Abnormalities, Drug-Induced↗

Mixed blessings: cervical cancer screening in Recife, Brazil.

This study examines the effects of a large-scale cervical cancer prevention campaign in Recife, Brazil between 1994 and 1995. It suggests that while this program effectively motivated women to get pap smears, it reinforced local understandings of the pap smear that ultimately had unintended negative consequences for women's health. It argues that because the campaign connected female sexual activity directly with cervical cancer, the program's message was interpreted by many women to mean that cervical cancer was a sexually transmitted disease and that it would behave like one. Women who were no longer sexually active believed that they did not need to be screened. In addition, women who were sexually active believed that they could use pap smears to diagnose and cure sexually transmitted diseases.

Adolescent↗

The impact of loading on deformation about posteromedial meniscal tears.

To simulate the effects of partial weight bearing on meniscal repair, full-thickness tears were produced in the posteromedial aspect of seven ACL-intact cadaveric knees. Following suture repair, metal markers were imbedded to index the position of the tear. A radiolucent chamber was used to position and load each knee for computed tomography scanning at flexion angles of 0 degrees, 30 degrees, and 60 degrees with and without a load force of 100 lb. Sutures were removed and the tests repeated. Changes in marker distances were obtained for each test condition. Loading produced average dimensional changes of < or =0.5 +/-0.6 mm in either sutured or unsutured menisci. Based on the Friedman test, neither flexion angle, loading, nor suture exerted a significant impact (P> or =.52). These data support clinical accelerated rehabilitation programs previously published. Therefore, partial weight bearing during convalescence is tenable.

Adult↗

Detection of differentially expressed genes in primary tumor tissues using representational differences analysis coupled to microarray hybridization.

The identification of differential gene expressionbetween cells is a frequent goal in modern biological research. Here we demonstrate the coupling of representational difference analysis (RDA) of cDNA with microarray analysis of the output for high throughput screening. Two primary Ewing's sarcoma tissue samples with different biological behavior in vivo were compared by RDA: one which was metastatic and progressed rapidly; the other localized and successfully treated. A modified RDA protocol that minimizes the necessary starting material was employed. After a reduced number of subtractive rounds, the output of RDA was shotgun cloned into a plasmid vector. Inserts from individual colonies from the subtracted library were amplified with vector-specific primers and arrayed at high density on glass slides. The arrays were then hybridized with differentially fluorescently labeled starting amplicons from the two tissues and fluorescent signals were measured at each DNA spot. We show that the relative amounts of fluorescent signal correlate well with the abundance of fragments in the RDA amplicon and in the starting mRNA. In our system, we analyzed 192 products and 173 (90%) were appropriately detected as being >2-fold differentially expressed. Fifty unique, differentially expressed clones were identified. Therefore, the use of RDA essentially provides an enriched library of differentially expressed genes, while analysis of this library with microarrays allows rapid and reproducible screening of thousands of DNA molecules simultaneously. The coupling of these two techniques in this system resulted in a large pool of differentially expressed genes.

3T3 Cells↗

Klinefelter's syndrome as a model of anomalous cerebral laterality: testing gene dosage in the X chromosome pseudoautosomal region using a DNA microarray.

Consistent handedness and language laterality are two of the most striking behavioral and cognitive asymmetries observed in humans. Alterations in the typical pattern of cerebral laterality, termed "anomalous dominance," is observed in left-handers and some patients with verbal learning disabilities. We undertook the study of a genetically distinct group of subjects, XXY males (Klinefelter's syndrome; KS), who demonstrate anomalous dominance in a variety of testing paradigms in order to begin to elucidate the molecular basis of anomalous dominance in this population. KS subjects manifest specific verbal learning disability, evidence of altered functional laterality for phonologic processing, and an increase in left-handedness when measured by skill. It is proposed that an alteration in gene dosage in the pseudoautosomal region (PAR) of the sex chromosomes is the most likely explanation for anomalous dominance in these patients. This is especially intriguing in light of previously described genetic models of cerebral laterality that suggest a contributing locus in the PAR, or adjacent high homology regions of the X chromosome. We have developed an ordered DNA microarray covering the X chromosome PAR at high resolution for hybridization with two-color fluorescently labeled probes. We demonstrate the ability to detect changes in hybridization signal that will facilitate efficient large-scale screening of this region for alterations in gene dosage associated with features of anomalous dominance and other cognitive or behavioral phenotypes.

Case-Control Studies↗

A randomized controlled trial of early physiotherapy for high-risk infants.

The aim of this study was to investigate the hypothesis that infants at high risk of cerebral palsy would benefit from early physiotherapy. In total, 105 infants with abnormal cranial ultrasound scans were randomized at around term to early physiotherapy or standard treatment (delaying physiotherapy until abnormal physical signs became apparent). At 12 and 30 months there were clinical and objective assessments. Nine infants died and nine were lost to follow-up by 12 months when 87 infants were assessed. One other child had died and three others were lost to follow-up by 30 months when 83 children were assessed. Cerebral palsy was only accurately predicted in 45 (54%) infants. There was no difference in outcome. The difficulty of predicting cerebral palsy reliably and the heterogeneity of the condition should be borne in mind when planning treatment and assessing its efficacy.

Cerebral Palsy↗

Explanatory models for cancer among African-American women at two Atlanta neighborhood health centers: the implications for a cancer screening program.

This paper examines cultural models for breast and cervical cancer among low-income African-American women over 40, in order to better understand how those models might affect cancer screening behavior. The study is part of The Community-Based Cancer Screening Project, which is sponsored by Emory University, Grady Memorial Hospital, and the American Cancer Society. The Screening Project attempts to increase the use of mammography, clinical and self-examination of the breast, and cervical Pap smear among women aged 40 or older in a predominantly African-American, low-income, low educational level population that is currently underserved by any screening activities. The study of cultural models of cancer within the project was prompted by the recognition that if screening programs targeted at specific, underserved, populations are to succeed, cultural as well as logistical barriers to screening must be overcome. Patients and clinicians must each understand how the other perceives cancer, its prevention, and its treatment. Only with this mutual understanding as a foundation, can physicians and their clients cooperate to improve cancer screening rates. Our research results indicate that the cancer models held by the patient population differ significantly from those held by clinicians. Women attending the clinics endure cancer screening tests that to them seem to serve only as heralds of a disease that will ultimately kill them. Most women doubt there is a cure for cancer, though some believe a person may live if the disease is caught in time.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Effect of esophageal ligation on the development of fetal rabbit intestinal lactase.

To investigate the effect of normal fetal swallowing and amniotic fluid ingestion on small intestinal disaccharidase development, 13 pregnant New Zealand White rabbits underwent operation on day 24 of a normal 31-day gestation. The right ovarian fetus in the bicornuate uterus underwent esophageal ligation (EL), while the contralateral left fetus underwent cervical exploration only, and served as the control (C). Rabbits were sacrificed on gestational day 31, fetal somatic measurements obtained, and the midjejunum removed for determination of disaccharidase activity and protein content. There was one maternal death, and 9 of 12 fetal pairs survived the entire study period (75%). Results are reported as mean +/- SEM, analyzed by two-tailed Student's t testing with P < .05 being considered significant. Fetal weight was decreased in EL (48.6 +/- 2.7 g) versus C (51.4 +/- 3.2 g) (P = .06). Small intestinal length decreased in EL (49.2 +/- 2.0 cm) versus C (54.9 +/- 1.1 cm) (P = .01). Midjejunal protein content (mg/mL homogenate) was also significantly decreased in EL (38.4 +/- 3.4) versus C (46.2 +/- 3.7) (P = .05). Sucrase activity was not detectable in either group. Lactase activity in jejunal mucosa was not effected when expressed as units of enzyme per milliliter of homogenate (EL = 0.357 +/- 0.03 v C = 0.373 +/- 0.04; P = .70) and units enzyme per gram of protein (EL = 38.8 +/- 4.2 v C = 34.2 +/- 4.6; P = .44). We have confirmed previous studies demonstrating decreases in somatic growth, small intestinal length, and mucosal nutrient transport in rabbit fetuses following esophageal ligation.(ABSTRACT TRUNCATED AT 250 WORDS)

Amniotic Fluid↗

A comparison of three procedures to assess the motor ability of 12-month-old infants with cerebral palsy.

This study compared three methods of assessing motor impairment during infancy. The 77 infants studied were considered to be at high risk of motor impairment because of abnormal neonatal cranial ultrasound scans or abnormal somatosensory responses. The children were assessed at eight and 12 months post-term by the Movement Assessment of Infants, the Griffiths locomotor development quotient and the limb-by-limb approach, and the results were compared with clinical assessment at 12 months post-term. The sensitivity of the limb-by-limb approach was highest, although its specificity was slightly lower than the other tests. It was also the easiest to perform. While giving information about the quality of movement, none of these methods is a quantitative test of movement.

Cerebral Palsy↗

Primary immunisations in Liverpool. I: Who withholds consent?

The association between parents in Liverpool consenting to their children being invited for primary immunisations and five sociodemographic factors, namely sex, position of child in the family, family type, migration into Liverpool since birth, and local deprivation was examined. Rates of consent to invitation were over 97% for each antigen except pertussis, which had a consent rate of 83%. Consent to invitation for pertussis vaccine was least likely to have been given for boys, children with older siblings, those recorded as living with a single parent, and those in the most deprived areas. Local deprivation also had an effect on consent to the measles, mumps, and rubella vaccine. Migration into Liverpool had a significant effect on consent to invitation for all antigens except pertussis. The child's sex, family type, and local deprivation had no effect on consent to diphtheria, tetanus, and polio immunisations. Maximising pertussis vaccine uptake will require more attention to be paid to those parents who have been identified as being less likely to give consent. It is particularly important that consistent and clear advice about immunisations is made available to parents with two or more children, lone parents, and those living in materially deprived areas. Our findings challenge some of the assumptions underlying the principles of 'first parent visiting', at least so far as pertussis is concerned.

Attitude to Health↗

Primary immunisations in Liverpool. II: Is there a gap between consent and completion?

The association between completion of primary dipht eria, tetanus and pertussis, measles, mumps, and rubella and polio immunisation courses in Liverpool and five sociodemographic factors, namely the child's sex, position in the family, family type, migration into Liverpool since birth, and local deprivation was examined. Only 68% of children were fully immunised by their second birthday. The immunisation rate for pertussis was 74%, compared with 85-89% for the other antigens. Children who had older siblings, were recorded as living with one parent, had moved into Liverpool or who lived in areas of high deprivation were less likely to complete the full set of antigens and individual courses. Boys were significantly less likely than girls to be fully immunised against pertussis. Differences in the completion of pertussis immunisation associated with the child's sex and with local deprivation were a direct reflection of differences in rates of parental consent. Parental consent did not wholly account for significantly lower rates among children with older siblings, those living with a lone parent, and those who had moved into Liverpool, however. This may reflect the practical difficulties of attending immunisation clinics. To achieve immunisation targets, a more flexible and targeted approach is required of health professionals. This may include the careful targeting of efforts to increase consent and the improvement of access to immunisations by providing domiciliary services or by opportunistic immunisation of infants when they are in contact with primary and community health care services.

Attitude to Health↗

Trauma to elbows, knees, and ankles.

In summary, the emergency department or office-based physician should distinguish first between inflammation and injury. A clinical diagnosis of fracture should be made before obtaining and reading films. Comparison views help to resolve doubt. A neurologic examination should be documented before undertaking reduction. Finally, if in doubt, a splint for 24 to 48 hours until an orthopedic opinion is available causes no harm.

Ankle Injuries↗

The isolation of identical thyroxine containing amino acid sequences from bovine, ovine and porcine thyroglobulins.

Identical, thyroxine containing tryptic peptides have been isolated from digests of bovine, ovine and procine thyroglobulins. This 19 residue hormone containing sequence, NH2-Asn-Ile-Phe-Glu-T4-Gln-Val-Asp-Ala-Gln-Pro-Leu-Arg-Pro-Cys-Glu-Leu-G in-Arg- COOH, is completely conserved across these three species, and it represents a principal site of thyroxine synthesis. HPLC maps of tryptic digests of the thyroglobulins have been monitored at several wavelengths and suggest that, in each case, only a small number of tryptic peptides are iodinated in vivo and that an even smaller number of tryptic peptides contain thyroid hormone. These data are consistent with a high degree of selectivity in iodination of tyrosines within thyroglobulin and the subsequent coupling of these selected tyrosines to form thyroid hormone.

Amino Acid Sequence↗