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Biomedical subjects

J Stevenson

Publications and source records attributed to J Stevenson.

At least 73 records · Page 4Linked to original sources

Implementation and evaluation of a measles/rubella vaccination campaign in a campus university in the UK following an outbreak of rubella.

An age shift in rubella infection to young adults has occurred in Scotland since the introduction of a first dose measles, mumps and rubella (MMR) vaccination in 1988 and a second dose measles/rubella (MR) vaccination in 1994/95. The Health Board was alerted to an outbreak of rubella at Stirling University by the notification of 6 cases amongst male students aged 18-28 years with dates of onset between 3 March and 21 March 1996. In response, a MR vaccination campaign was conducted to enhance population immunity to rubella within the university population and to reduce the likelihood of further cases. A total of 1795 students, staff and visitors were vaccinated. Vaccine coverage of 46% was estimated to be sufficient to boost rubella immunity in full time male students in university accommodation to 88.7-91.0%, just above the upper critical level of herd immunity for rubella of 85-88%. Students in colleges and universities in the UK will remain at increased risk of outbreaks of rubella and measles until the cohort who have received a two dose schedule of MR form the bulk of the college population. It may be prudent for tertiary education colleges and other institutions in the UK with young adults living in shared residential accommodation to offer MR vaccination to new entrants, targeting those who have not previously received the vaccine, between now and the year 2000.

Adolescent↗

Genetic influence on language delay in two-year-old children.

Previous work suggests that most clinically significant language difficulties in children do not result from acquired brain lesions or adverse environmental experiences but from genetic factors that presumably influence early brain development. We conducted the first twin study of language delay to evaluate whether genetic and environmental factors at the lower extreme of delayed language are different from those operating in the normal range. Vocabulary at age two was assessed for more than 3000 pairs of twins. Group differences heritability for the lowest 5% of subjects was estimated as 73% in model-fitting analyses, significantly greater than the individual differences heritability for the entire sample (25%). This supports the view of early language delay as a distinct disorder. Shared environment was only a quarter as important for the language-delayed sample (18%) as for the entire sample (69%).

Child, Preschool↗

Alpha-ketoisocaproate alters the production of both lactate and aspartate from [U-13C]glutamate in astrocytes: a 13C NMR study.

The present study determined the metabolic fate of [U-13C]glutamate in primary cultures of cerebral cortical astrocytes from rat brain and also in cultures incubated in the presence of 1 or 5 mM alpha-ketoisocaproate (alpha-KIC). When astrocytes were incubated with 0.2 mM [U-13C]glutamate, 64.1% of the 13C metabolized was converted to glutamine, and the remainder was metabolized via the tricarboxylic acid (TCA) cycle. The formation of [1,2,3-(13)C3]glutamate demonstrated metabolism of the labeled glutamate via the TCA cycle. In control astrocytes, 8.0% of the [13C]glutamate metabolized was incorporated into intracellular aspartate, and 17.2% was incorporated into lactate that was released into the medium. In contrast, there was no detectable incorporation of [13C]glutamate into aspartate in astrocytes incubated in the presence of alpha-KIC. In addition, the intracellular aspartate concentration was decreased 50% in these cells. However, there was increased incorporation of [13C]glutamate into the 1,2,3-(13)C3-isotopomer of lactate in cells incubated in the presence of alpha-KIC versus controls, with formation of lactate accounting for 34.8% of the glutamate metabolized in astrocytes incubated in the presence of alpha-KIC. Altogether more of the [13C]glutamate was metabolized via the TCA cycle, and less was converted to glutamine in astrocytes incubated in the presence of alpha-KIC than in control cells. Overall, the results demonstrate that the presence of alpha-KIC profoundly influences the metabolic disposition of glutamate by astrocytes and leads to altered concentrations of other metabolites, including aspartate, lactate, and leucine. The decrease in formation of aspartate from glutamate and in total concentration of aspartate may impair the activity of the malate-aspartate shuttle and the ability of astrocytes to transfer reducing equivalents into the mitochondria and thus compromise overall energy metabolism in astrocytes.

Amino Acids, Branched-Chain↗

Central auditory processing, MRI morphometry and brain laterality: applications to dyslexia.

We review data from our laboratory related to a view of dyslexia as a biological disorder, or deficit, caused by both structural and functional brain abnormalities. The review is focused on central auditory processing in dyslexia, and the possibility that impairments in the auditory or acoustic features of the phonological code may be at the heart of the impairments seen in dyslexia. Three methodological approaches by which to investigate central auditory processing deficits are outlined: dichotic listening (DL) to consonant-vowel syllables; magnetic resonance imaging (MRI), and the use of event-related potentials (ERPs). Consonant-vowel syllable DL is a technique for probing the functional status of phonological processing areas in the superior temporal gyrus, particularly in the left hemisphere. MRI is a corresponding structural, or morphological, measure of anatomical abnormalities in the same brain region, particularly covering the planum temporale area. The ERP technique, and particularly the mismatch negativity (MMN) component, reveals cortical dysfunctions in sensory processing and memory related to basic acoustic events. For all three approaches, the dyslexic children were seen to differ from their control counterparts, including absence of modulation of the right ear advantage (REA), in DL through shifting of attention, smaller left-sided planum temporale asymmetry, and prolonged latency in the MMN ERP complex, particularly in the time-deviant stimulus condition.

Auditory Diseases, Central↗

Cluster survey evaluation of coverage and risk factors for failure to be immunized during the 1995 National Immunization Days in Egypt.

BACKGROUND: In 1995, Egypt continued to experience endemic wild poliovirus transmission despite achieving high routine immunization coverage with at least three doses of oral poliovirus vaccine (OPV3) and implementing National Immunization Days (NIDs) annually for several years. METHODS: Parents of 4188 children in 3216 households throughout Egypt were surveyed after the second round of the 1995 NIDs. RESULTS: Nationwide, 74% of children are estimated to have received both NID doses, 17% one NID dose, and 9% neither NID dose. Previously unimmunized (47%) or partially immunized (64%) children were less likely to receive two NID doses of OPV than were fully immunized children (76%) (P < 0.001). Other risk factors nationwide for failure to receive NID OPV included distance from residence to nearest NID site >10 minute walk (P < 0.001), not being informed about the NID at least one day in advance (P < 0.001), and residing in a household which does not watch television (P < 0.001). Based on these findings, subsequent NIDs in Egypt were modified to improve coverage, which has resulted in a marked decrease in the incidence of paralytic poliomyelitis in Egypt. CONCLUSIONS: In selected situations, surveys can provide important information that is useful for planning future NIDs.

Child, Preschool↗

Functional magnetic resonance imaging of human brain activity in a verbal fluency task.

OBJECTIVES: Functional MRI (fMRI) holds the promise of non-invasive mapping of human brain function in both health and disease. Yet its sensitivity and reliability for mapping higher cognitive function are still being determined. Using verbal fluency as a task, the objective was to ascertain the consistency of fMRI on a conventional scanner for determining the anatomic substrate of language between subjects and between sexes. Comparison was made with previous PET studies. METHODS: Using a 1.5 Tesla magnet and an echoplanar pulse sequence, whole brain fMRI was obtained from 12 normal right handed subjects (6 males and 6 females) as they performed a verbal fluency task. RESULTS: A broadly consistent pattern of response was seen across subjects. Areas showing activation changes included the left prefrontal cortex and right cerebellum, in agreement with previous PET 15O-H2O studies. In addition, significantly decreased responses were seen in the posterior cingulate and over an extensive area of mesial and dorsolateral parietal and superior temporal cortices. The male cohort showed a slight asymmetry of parietal deactivation, with more involvement on the right, whereas the female cohort showed a small region of activation in the right orbitofrontal cortex. There were individual task related regional changes in all 12 subjects with the area showing the most significant change being the left prefrontal cortex in all cases. CONCLUSIONS: Magnetic resonance scanners of conventional field strength can provide functional brain mapping data with a sensitivity at least that of PET. Activation was seen in left prefrontal and right cerebellar regions, as with PET. However, decremental responses were seen over a much larger area of the posterior cortex than had been anticipated by prior studies. The ability to see a response in each subject individually suggests that fMRI may be useful in the preinterventional mapping of pathological states, and offers a non-invasive alternative to the Wada test for assessment of hemispheric dominance. There were no gross differences in the pattern of activation between male and female subjects.

Adult↗

Dual metalloprotease inhibitors: mercaptoacetyl-based fused heterocyclic dipeptide mimetics as inhibitors of angiotensin-converting enzyme and neutral endopeptidase.

A series of 7,6- and 7,5-fused bicyclic thiazepinones and oxazepinones were generated and incorporated as conformationally restricted dipeptide surrogates in mercaptoacyl dipeptides. These compounds are potent inhibitors of angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) both in vitro and in vivo. Compound 1a, a 7,6-fused bicyclic thiazepinone, demonstrated excellent blood pressure lowering in a variety of animal models characterized by various levels of plasma renin activity and significantly potentiated urinary sodium, ANP, and cGMP excretion in a cynomolgus monkey assay. On the basis of its potency and duration of action, compound 1a (BMS-186716) was advanced into clinical development for the treatment of hypertension and congestive heart failure.

Angiotensin-Converting Enzyme Inhibitors↗

Factors determining the rate of referral, transplantation, and survival on dialysis in women with ESRD.

The determinants of referral for transplantation in women have not been well-studied. Similarly, factors determining survival on dialysis and the rate of transplantation in women remain controversial. Women have been reported to have lower rates of transplantation than men, and black women have the lowest rates of all groups. We questioned whether black women were referred at lower rates than whites and if race and other socioeconomic factors predicted referral, rate of renal transplantation, and patient survival on dialysis. All women in Allegheny or Philadelphia counties in Pennsylvania initiating dialysis between January 1, 1990, and December 31, 1992, were eligible for this study. Information was requested by questionnaire from each dialysis unit in these areas. Of the 383 eligible patients, completed questionnaires were obtained for 276 (72%). Ninety-three (54.7%) of the black patients and 57 (53.8%) of the white patients were referred for transplantation (P = 0.8). Declining the transplant option was the most common reason for nonreferral in both races. Patients with high school or greater education were approximately twice as likely to be referred than those with grade school educations (odds ratio [OR], 2.2; P = 0.04). Patients with coexisting illness were 67% (OR, 0.33; P = 0.004) less likely to be referred compared with patients with no other illnesses. Each additional year of age reduced the chances of being referred by 6% (OR, 0.94; P = 0.0001). Homemakers were 83% (P = 0.0008) and others 55% (P = 0.07) less likely to be referred compared with employed patients. Patients in Philadelphia County were 56% less likely to be referred compared with those in Allegheny County (P = 0.024). Race was not significantly associated with referral. Predictors of transplantation included age (RR, 0.96; confidence interval [CI], 0.93 to 0.99; P = 0.13), white race (RR, 2.2; CI, 1.3 to 4.0; P = 0.0053), presence of other illnesses (RR, 0.37; CI, 0.21 to 0.65; P = 0.0006), and employment status. White homemakers were 86% (RR, 0.14; CI, 0.03 to 0.6; P = 0.0082) less likely than those with other employment situations to receive a transplant. Factors predicting patient survival on dialysis included race, educational status, and presence of comorbid illnesses. White patients were approximately four times (RR, 3.7; CI, 1.7 to 8.1; P = 0.002) more likely to die than black patients. Patients with high school or greater education were 56% (RR, 0.44; CI, 0.2 to 0.92; P = 0.008) less likely to die than those with grade school education alone. Patients with at least one coexisting illness were approximately 1.7 times (RR, 1.68; CI, 1.1 to 2.4; P = 0.001) more likely to die than those without other illnesses. In summary, race was not a factor in referral for transplantation, but was predictive of transplantation and patient survival on dialysis. Socioeconomic factors such as educational status, age, and employment status were highly predictive of transplantation and long-term survival on hemodialysis. White homemakers unexpectedly received transplants less than any other group of dialysis patients. Further study is needed to determine why these potential transplant patients have declined or deferred transplantation.

Adolescent↗

Patterns of behaviour problems among pre-school children.

BACKGROUND: Previous research has suggested that behavioural problems displayed during the pre-school years are best understood as undifferentiated difficulties in manageability. The present study explored this issue, by examining the structure of British parents' ratings of their pre-school children's behavioural problems. METHOD: The 19-item Behavioural Checklist (BCL; Richman, 1977) was completed by 1047 parents of 3-year-old children taking part in an epidemiological survey of child development. RESULTS: Factor analysis revealed six factors representing poor social adjustment, poor emotional adjustment, sleep problems, over-activity/inattention, eating problems and soiling. When these scores were used as a basis for cluster analysis, problem types clustered around six centres. The first, and largest, grouping was of children with no problems. Three further large groupings displayed specific but moderate problems (over-active, timid, and naughty children). The final two groupings displayed more extreme problems including anti-social behaviour. In one group these were accompanied by severe emotional problems and in the other by signs of hyperactivity. The reliability and validity of these clusters was supported. Parental ratings of behaviour problems taken when the children were 8-years-old suggested that the children in the hyperactive/conduct group were likely to have continued difficulties. CONCLUSION: This paper argues against the homogeneity of pre-school behaviour problems but supports the idea that problems of a clinically significant level are likely to be co-morbid, with either problems of emotional regulation (neurotic) or those of behavioural regulation (hyperactive) accompanied by problems of conduct.

Analysis of Variance↗

The association between internalizing and externalizing behavior in childhood and early adolescence: genetic of environmental common influences?

This study analyzed the genetic and environmental influences on internalizing and externalizing behavior problems and the nature of their cooccurrence in the national Norwegian twin sample. The sample comprised 526 identical and 389 fraternal same-sexed twin pairs from five to birth cohorts, aged 5-6, 8-9, 12-13, 13-14, and 14-15 years. Behavior problems were assessed by parental ratings on the Child Behavior Checklist. A model of additive genetic, shared, and nonshared environmental influences was fitted to both internalizing and externalizing behavior on four sex and age groups. The considerable covariance, r = .51 to .58, between these traits is accounted for mainly by common environmental components; this effect was most marked in the 5 to 9-year olds. Concordance rates for children scoring above 1 standard deviation from the total sample mean on the internalizing scale only, externalizing problems only than for combined problems.

Adolescent↗

A longitudinal twin study of temperament and behavior problems: common genetic or environmental influences?

OBJECTIVES: To assess the longitudinal covariance between emotionality, activity, and sociability (EAS) temperamental traits and anxious/depressed behavior, attention problems, delinquent behavior, and aggressive behavior and to assess the significance of genetic and common environmental influences on the temperament and behavior relations. METHOD: Parental responses to the Child Behavior Checklist and the EAS Temperament Survey were collected from five national cohorts of Norwegian same-sex twins. The final sample consisted of 759 twin pairs aged 7 through 17 at 2-year follow-up. RESULTS: High emotionality predicted anxious/depressed behavior, attention problems, delinquent behavior, and aggressive behavior. The influence on delinquent and aggressive behavior was stronger in boys. Aggressive behavior was further predicted by high activity scores, especially in younger children. Significant genetic influence was found for the covariance between emotionality and attention problems and emotionality and aggressive behavior. CONCLUSION: Emotionality was the strongest temperamental predictor of behavior problems. The mechanisms involved in the associations between temperament and behavior problems appeared to differ with kind of behavior problems.

Adolescent↗

Are there "autistic-like" features in congenitally blind children?

Twenty-four congenitally blind children between 3 and 9 years of age were studied for the prevalence of "autistic-like" features, as assessed by teacher reports and by systematic observations of the children's behaviour. A comparison between the 15 blind children who had IQs over 70 and 10 sighted children group-matched for age and verbal ability revealed that a number of autistic-like features were more common in the blind. When the nine blind children who had IQs less than 70 were compared with nine group-matched autistic children, the picture that emerged was of substantial overlap in clinical presentation, despite subtle differences on clinical impression. Similar results were obtained when blind subgroups were reconstituted according to the children's nonautistic or autistic-like clinical presentation, rather than IQ. These findings are discussed in relation to competing theories concerning the development of autism and "theory of mind".

Autistic Disorder↗

Development of outcome indicators for monitoring the quality of public mental health care.

OBJECTIVE: The study attempted to develop a brief and integrated set of reliable and valid outcome measures that could be used by both consumers and providers to assess the quality of public mental health care. METHODS: A model of outcomes in four domains-consumer satisfaction, functioning, quality of life, and clinical status-was developed from the literature and from the priorities expressed by members of an advisory group of stakeholders. Based largely on extant measures, a consumer survey and a case manager survey were then created to assess these domains. A total of 236 adult consumers of mental health services from six community mental health centers in Washington State were surveyed. The four-item case manager survey to rate consumers' clinical status was completed by 163 of the participants' case managers. Scores and ratings on the survey were analyzed using correlational analysis and principal components analysis to determine whether the data provided empirical support for the four-domain model. RESULTS: Principal components analysis demonstrated support for the four-domain model. Internal consistency of the outcome indicators was adequate, and their concurrent validity was partly supported. CONCLUSIONS: The described outcome measures provide a practical, empirically supported structure for monitoring and improving public mental health services.

Activities of Daily Living↗