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Biomedical subjects

J Head

Publications and source records attributed to J Head.

At least 19 recordsLinked to original sources
PubMed2001

Ten-year follow-up of three different initial treatments in de-novo PD: a randomized trial.

BACKGROUND: The long-term effectiveness of three different initial drug regimes in patients with early, mild PD was evaluated by the PD Research Group of the United Kingdom (PDRGUK). In 1995, the selegiline arm of the trial was terminated following an interim analysis. METHOD: This was an open, randomized trial. Between 1985 and 1990, 782 patients with de-novo PD were recruited and randomized to one of three treatment arms: levodopa plus dopa decarboxylase inhibitor; levodopa plus decarboxylase inhibitor and selegiline; or bromocriptine. The main endpoints were mortality, disability, and adverse events. Intention-to-treat analysis was used. RESULTS: There was no significant difference in mortality between the bromocriptine and the levodopa arms (hazard ratio 1.15 [95% CI 0.90, 1.47]). Patients initially randomized to bromocriptine had slightly worse disability scores throughout follow-up. This difference was significant during the first years. Patients in the bromocriptine arm returned to pretreatment disability levels one year earlier than those in the levodopa arm. Patients randomized to bromocriptine had a significantly lower incidence of dyskinesias than those randomized to levodopa (rate ratio 0.73 [95% CI 0.57, 0.93]). However, this difference was not significant when only moderate to severe dyskinesias were considered. Patients in the bromocriptine arm had slightly lower rates of dystonias and on-off fluctuations, but moderate and severe forms were equally frequent in both arms. CONCLUSION: Starting treatment with the dopamine agonist bromocriptine does not reduce mortality in PD. A slightly lower incidence of motor complications is achieved at the expense of significantly worse disability scores throughout the first years of therapy.

Antiparkinson Agents↗
PubMed2001

Chronic aircraft noise exposure, stress responses, mental health and cognitive performance in school children.

BACKGROUND: Previous research suggests that children are a high risk group vulnerable to the effects of chronic noise exposure. However, questions remain about the nature of the noise effects and the underlying causal mechanisms. This study addresses the effects of aircraft noise exposure on children around London Heathrow airport, in terms of stress responses, mental health and cognitive performance. The research also focuses on the underlying causal mechanisms contributing to the cognitive effects and potential confounding factors. METHODS: The cognitive performance and health of 340 children aged 8-11 years attending four schools in high aircraft noise areas (16 h outdoor Leq > 66 dBA) was compared with children attending four matched control schools exposed to lower levels of aircraft noise (16 h outdoor Leq < 57 dBA). Mental health and cognitive tests were group administered to the children in the schools. Salivary cortisol was measured in a subsample of children. RESULTS: Chronic aircraft noise exposure was associated with higher levels of noise annoyance and poorer reading comprehension measured by standardized scales with adjustments for age, deprivation and main language spoken. Chronic aircraft noise was not associated with mental health problems and raised cortisol secretion. The association between aircraft noise exposure and reading comprehension could not be accounted for by the mediating role of annoyance, confounding by social class, deprivation, main language or acute noise exposure. CONCLUSIONS: These results suggest that chronic aircraft noise exposure is associated with impaired reading comprehension and high levels of noise annoyance but not mental health problems in children.

Aircraft↗
PubMed2001

The West London Schools Study: the effects of chronic aircraft noise exposure on child health.

BACKGROUND: Previous field studies have indicated that children's cognitive performance is impaired by chronic aircraft noise exposure. However, these studies have not been of sufficient size to account adequately for the role of confounding factors. The objective of this study was to test whether cognitive impairments and stress responses (catecholamines, cortisol and perceived stress) are attributable to aircraft noise exposure after adjustment for school and individual level confounding factors and to examine whether children exposed to high levels of social disadvantage are at greater risk of noise effects. METHODS: The cognitive performance and health of 451 children aged 8-11 years, attending 10 schools in high aircraft noise areas (16 h outdoor Leq > 63 dBA) was compared with children attending 10 matched control schools exposed to lower levels of aircraft noise (16 h outdoor Leq < 57 dBA). RESULTS: Noise exposure was associated with impaired reading on difficult items and raised annoyance, after adjustment for age, main language spoken and household deprivation. There was no variation in the size of the noise effects in vulnerable subgroups of children. High levels of noise exposure were not associated with impairments in mean reading score, memory and attention or stress responses. Aircraft noise was weakly associated with hyperactivity and psychological morbidity. CONCLUSIONS: Chronic noise exposure is associated with raised noise annoyance in children. The cognitive results indicate that chronic aircraft noise exposure does not always lead to generalized cognitive effects but, rather, more selective cognitive impairments on difficult cognitive tests in children.

Aviation↗
PubMed2001

A follow-up study of effects of chronic aircraft noise exposure on child stress responses and cognition.

BACKGROUND: Children are a high-risk group vulnerable to the effects of chronic aircraft noise exposure. This study examines the effects of aircraft noise exposure on children's health and cognition around London Heathrow airport and tests sustained attention as an underlying mechanism of effects of noise on reading and examines the way children adapt to continued exposure to aircraft noise. METHODS: In this repeated measures epidemiological field study, the cognitive performance and health of 275 children aged 8-11 years attending four schools in high aircraft noise areas (16-h outdoor Leq > 66 dBA) was compared with children attending four matched control schools exposed to lower levels of aircraft noise (16-h outdoor Leq < 57 dBA). The children first examined at baseline were examined again after a period of one year at follow-up. Health questionnaires and cognitive tests were group administered to the children in the schools. RESULTS AND CONCLUSIONS: At follow-up chronic aircraft noise exposure was associated with higher levels of annoyance and perceived stress, poorer reading comprehension and sustained attention, measured by standardized scales after adjustment for age, social deprivation and main language spoken. These results do not support the sustained attention hypothesis previously used to account for the effects of noise on cognition in children. The reading and annoyance effects do not habituate over a one-year period and do not provide strong evidence of adaptation.

Adaptation, Psychological↗
PubMed2000

Probing meiosis in hybrids of Lolium (Poaceae) with a discriminatory repetitive genomic sequence.

A moderately repetitive genomic DNA sequence (designated pLPBB2-123) derived from Lolium perenne L. (Poaceae) is considerably more abundant in the genome of this species than in that of the closely related L. temulentum. The repetitive sequence probe is clearly able to discriminate between the genomic DNA of both species in Southern analysis, and effectively 'paints' only the chromosome set of L. perenne in diploid and triploid hybrids with L. temulentum. Fluorescence in situ hybridisation of this sequence onto homologous chromosomes during meiosis I of the hybrids shows that the sequence is evenly distributed along all of the chromosomes of L. perenne and appears to have little effect on the structural integrity or recombination potential of hybrid bivalents. Discrimination between chromatin of different parental origin in hybrid bivalents shows for the first time a progressive relaxation of relational coiling of homoeologues throughout meiotic prophase. It also highlights structural irregularities that can now be unequivocally assigned to the longer chromosomes of L. temulentum. The advantages of the use of specific differentially amplified sequences instead of whole genome probes are discussed within the context of introgression breeding programmes within the Lolium/Festuca complex.

Chromosomes↗
PubMed1998

Investigation by Parkinson's Disease Research Group of United Kingdom into excess mortality seen with combined levodopa and selegiline treatment in patients with early, mild Parkinson's disease: further results of randomised trial and confidential inquiry.

OBJECTIVE: To determine whether the excess mortality observed in patients who received both levodopa and selegiline in a randomised trial could be explained by revised diagnosis of Parkinson's disease, autonomic or cardiovascular effects, more rapid disease progression, or drug interactions. DESIGN: Open randomised trial and blind comparison and reclassification of the cause of death of patients who were recruited from 93 hospitals between 1985 and 1990 and who had died before December 1993 in arms 1 and 2. SETTING: United Kingdom. SUBJECTS: 624 patients with early Parkinson's disease who were not receiving dopaminergic treatment and a subgroup fo 120 patients who died during the trial. INTERVENTIONS: Levodopa and a dopa carboxylase inhibitor (arm 1), levodopa and a dopa decarboxylase inhibitor in combination with selegiline (arm 2), or bromocriptine alone (arm 3). MAIN OUTCOME MEASURES: All cause mortality for 520 subjects in arms 1 and 2 and for 104 subjects who were randomised into these arms from arm 3. Cause specific mortality for people who died in the original arms 1 and 2 on the basis of the opinion of a panel, revised diagnosis and disability ratings, evidence from clinical records of either autonomic or cardiovascular episodes, other clinical features before death, and drug interactions. RESULTS: After extended follow up (mean 6.8 years) until the end of September 1995, when arm 2 was terminated, the hazard ratio for arm 2 compared with arm 1 was 1.32 (95% confidence interval 0.98 to 1.79). For subjects who were randomised from arm 3 the hazard ratio for arm 2 was 1.54 (0.83 to 2.87). When all subjects were included the hazard ratio was 1.33 (1.02 to 1.74) and after adjustment for other baseline factors it was 1.30 (0.99 to 1.72). The excess mortality seemed to be greatest in the third and fourth year of follow up. Cause specific death rates showed an excess of deaths from Parkinson's disease only (hazard ratio 2.5 (1.3 to 4.7)). No significant differences were found for revised diagnosis, disability rating scores, autonomic or cardiovascular events, other clinical features, or drug interactions. Patients who died in arm 2 were more likely to have had possible dementia and a history of falls before death compared with those who died in arm 1. CONCLUSION: The results consistently show excess mortality in patients treated with combined levodopa and selegiline. Revised diagnosis, autonomic or cardiovascular events, or drug interactions could not explain this finding, but falls and possible dementia were more common in arm 2. The results do not support combined treatment in patients with newly diagnosed Parkinson's disease. In more advanced disease, combined treatment should perhaps be avoided in patients with postural hypotension, frequent falls, confusion, or dementia.

Antiparkinson Agents↗
PubMed1998

Explaining social class differences in depression and well-being.

Work characteristics, including skill discretion and decision authority, explain most of the socioeconomic status gradient in well-being and depression in middle-aged British civil servants from the Whitehall II Study, London. Social support explained about one-third of the gradient, life events and material difficulties less than one-third. Socioeconomic status was measured by employment grade. Work characteristics were based on the Karasek model, social support was measured by the Close Persons Questionnaire, depression by the General Health Questionnaire and well-being by the Affect Balance Scale. Despite a small contribution from social selective factors measured by upward mobility, the psychosocial work environment explained most of the cross-sectional socioeconomic status gradient in well-being and depression.

Adult↗
PubMed1998

Socioeconomic and sex differentials in reason for sickness absence from the Whitehall II Study.

OBJECTIVES: Large socioeconomic differences exist in disease and mortality. This paper describes the distribution of specific medical reasons for sickness absence by grade of employment in the Whitehall II study and validates the medical reason by comparison with general practitioners' records. METHODS: Analysis of sickness absence data on 5620 male and female civil servants aged 35-55 years. Data have been collected from 12 of the 20 London based civil service departments participating in the Whitehall II study, where medical reason for absence was available. Rates and distributions of reasons for absence for short spells (< or = 7 days) and long spells (> 7 days) were analysed. RESULTS: Respiratory disorders and gastroenteritis accounted for over half of all spells of absence, with headache and migraine, musculoskeletal disorders, injury, and neurosis accounting for a further 20%-30% of absences. There was an inverse association with employment grade, the lower the grade the higher the rate of absence for both short spells (< or = 7 days) and long spells (> 7 days). In general, women had higher rates of absence than men. Comparison of reason for very long spells of absence (> 21 days) showed moderate agreement between civil service and general practitioner. CONCLUSION: There is a lack of national comprehensive data on sickness absence and medical reason for absence, in particular for women and for spells of different duration. Data from the Whitehall II study show large employment grade and sex differences in the distribution of medical reasons for absence that are similar to socioeconomic differences in morbidity documented in other studies. Possible explanations include the subjective nature of illness and disease; the work/family interface; and the influence of the absence culture. Longer term follow up will provide information on whether sickness absence relates to serious morbidity and mortality.

Absenteeism↗
PubMed1997

Work and psychiatric disorder in the Whitehall II Study.

It is important that the effects of work on mental health are investigated when work practices are changing rapidly and there is decreasing job security. This has been examined in the Whitehall II Study, a cohort study of 6895 male and 3413 female, London-based civil servants, aged 35-55 years at baseline in 1985. Work characteristics were measured by modified Karasek indices in a self-report questionnaire. Psychiatric disorder was measured by the 30-item General Health Questionnaire (GHQ). In longitudinal analyses in men and women, high work social support predicted lower GHQ scores, and high job demands predicted higher GHQ scores at follow-up. High work social support and high skill discretion were protective against taking short spells of psychiatric sickness absence. The protective effects of social support at work and the potential risk of job demands have implications for management, job design, training, and further research.

Adult↗
PubMed1997

Social support and psychiatric sickness absence: a prospective study of British civil servants.

BACKGROUND: Studies on the direct and buffering effects of social support have not examined psychiatric sickness absence and few studies have considered support both at home and at work. This study addresses prospectively the effects of chronic stressors and social supports, at home and at work, on psychiatric sickness absence rates. METHODS: Sociodemographic factors, health and social support were measured at baseline, and short and long spells of sickness absence were measured prospectively over a 5-year period. The participants were a subsample of 4202 male and female civil servants, aged 35-55 years at baseline, from an occupational cohort, the Whitehall II Study, who completed detailed social support questions. RESULTS: Support from colleagues and supervisors at work is related to lower risk of short spells of psychiatric sickness absence, particularly for those also receiving high levels of negative aspects of close relationships from their closest person outside work. Negative aspects of close relationships from the closest person increase the risk of taking long spells of psychiatric sickness absence in men. High levels of material problems increase the risk of short spells of sickness absence. CONCLUSIONS: Negative aspects of close relationships may have an aetiological role in non-psychotic psychiatric disorder. Social support at work appears to protect against short spells of psychiatric sickness absence. This potentially implies that levels of short spells of absence might be reduced by increasing support at work. Conversely, emotional support at home may influenced absence-related behaviour and encourage a person to take absence at a time of illness.

Absenteeism↗
PubMed1996

The inhibition of antigen-induced eosinophilia and bronchoconstriction by CDP840, a novel stereo-selective inhibitor of phosphodiesterase type 4.

1. The novel tri-aryl ethane CDP840, is a potent and selective inhibitor of cyclic AMP phosphodiesterase type 4 (PDE 4) extracted from tissues or recombinant PDE 4 isoforms expressed in yeast (IC50S: 4-45 nM). CDP840 is stereo-selective since its S enantiomer (CT 1731) is 10-50 times less active against all forms of PDE 4 tested while both enantiomers are inactive (IC50S: > 100 microM) against PDE types 1, 2, 3 and 5. 2. Oral administration of CDP840 caused a dose-dependent reduction of interleukin-5 (IL-5)-induced pleural eosinophilia in rats (ED50 = 0.03 mg kg-1). The eosinophils in pleural exudates from CDP840-treated animals contained higher levels of eosinophil peroxidase (EPO) than cells from control animals, suggesting a stabilizing effect on eosinophil degranulation. CDP840 was approximately equi-active with the steroid dexamethasone in this model and was 10-100 times more potent than the known PDE 4-selective inhibitors rolipram and RP73401. The activity of CDP840 was not influenced by adrenalectomy, beta-sympathomimetics or beta-sympatholytics. 3. Antigen-induced pulmonary eosinophilia in sensitized guinea-pigs was reduced dose-dependently by CDP840 (0.01-1 mg kg-1, i.p.) and intracellular EPO levels were significantly higher. CDP840 was more potent in these activities than CT1731 or rolipram and comparable in potency to RP73401. 4. Rolipram or CDP840 were less active than dexamethasone in preventing neutrophil accumulation, or exudate formation in carrageenan-induced pleurisy in rats and thus do not exhibit general anti-inflammatory activity. 5. In sensitized guinea-pigs, aerosols of the antigen ovalbumin caused a dose-dependent bronchoconstriction demonstrated by an increase in pulmonary inflation pressure. Administration of CDP840 (0.001-1.0 mg kg-1, i.p.), 1 h before antigen challenge, resulted in dose-dependent reduction in response to antigen. This activity was not due to bronchodilatation since higher doses of CDP840 (3 mg kg-1) did not significantly change the bronchoconstrictor response to histamine. Rolipram was approximately 10 times less active than CDP840 in preventing antigen-induced bronchoconstriction. 6. These results confirm the observations that selective PDE 4 inhibitors reduce antigen-induced bronchoconstriction and pulmonary eosinophilic inflammation. CDP840 is more potent than rolipram in inhibiting native or recombinant PDE 4. Unlike the recently described potent PDE 4 inhibitor RP73401, CDP840 is more active than rolipram in the rat IL-5 model following oral administration. The novel series of tri-aryl ethanes, of which CDP840 is the lead compound, could be the basis of an orally active prophylactic treatment for human asthma.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1996

Excess mortality and its relation to hypertension and proteinuria in diabetic patients. The world health organization multinational study of vascular disease in diabetes.

OBJECTIVE: To determine the extent that mortality in IDDM and NIDDM patients is in excess of that of the general population and examine its relation to hypertension and proteinuria in diabetic patients. RESEARCH DESIGN AND METHODS: A stratified random sample of 4,714 diabetic patients aged 35-55 years participating in the World Health Organization Multinational Study of Vascular Disease in Diabetes has been followed up from 1975 to 1987. Excess mortality, compared with the background population, was assessed in terms of standardized mortality ratios (SMRs) for each of the 10 international cohorts. The relationship between excess mortality and proteinuria/hypertension was examined by diabetes type and sex. RESULTS: SMRs were in general higher in patients with IDDM (ranging from 188 to 686 for men and from 336 to 790 for women) than with NIDDM (from 138 to 370 for men and from 126 to 435 for women). For both diabetes types and in both sexes, SMRs decreased with increasing age and increased with increasing diabetes duration. Patients with both hypertension and proteinuria experienced a strikingly high mortality risk: 11-fold for men with IDDM and 18-fold for women with IDDM and 5-fold for men with NIDDM and 8-fold for women with NIDDM. Even in the absence of proteinuria and hypertension, SMRs were significantly increased in both IDDM (284 men and 360 women) and NIDDM (192 men and 236 women) patients. CONCLUSIONS: Considerable international differences were found not only in mortality rates for the two types of diabetes but also in the extent of excess mortality among centers. IDDM patients had a high excess mortality in comparison with the general population. The significant excess mortality was demonstrated even in patients without proteinuria and without hypertension for both sexes and diabetes types.

Adult↗
PubMed1995

Sickness absence for psychiatric illness: the Whitehall II Study.

Over the past 20 years, rates of sickness absence have increased and psychiatric disorders have become an important cause of sickness absence. The socio-demographic associations for psychiatric sickness absence are reported from the Whitehall II study, a longitudinal survey of 10,308 London-based male and female civil servants between 35-55 years. Short spells (< or = 7 days), long spells (> 7 days) and very long spells (> 21 days) of sickness absence were examined in 5620 civil servants for whom reason for absence was available in civil service records. Civil service coding of reasons for absence was validated against report of general practitioners' diagnoses. Psychiatric disorder, largely neurosis and neurosis ill-defined, was the third most common cause of long spells of sickness absence in women and the fourth most common in men. For both men and women it was the second most common cause of very long spells of absence. Psychiatric sickness absence for short, long and very long spells was more frequent in lower employment grades than higher employment grades in keeping with the pattern for other illnesses. This partly explains the higher rate of sickness absence in women than men. Widowed and single men, and divorced women had high rates of psychiatric sickness absence. Comparing reason codes based on sickness certificates with general practitioners reports, there appeared to be evidence of under-reporting of psychosis on certificates.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Cancer mortality in Indian and British ethnic immigrants from the Indian subcontinent to England and Wales.

Risk of cancer mortality from 1973 to 1985 in persons born in the Indian subcontinent who migrated to England and Wales was analysed by ethnicity, and compared with cancer mortality in the England and Wales native population, using data from England and Wales death certificates. There were substantial highly significant raised risks in Indian ethnic migrants for cancers of the mouth and pharynx, gall bladder, and liver in each sex, larynx and thyroid in males, and oesophagus in females. There were also substantial raised risks in these migrants of each sex for non-Hodgkin's lymphoma and myeloma. For the mouth and pharynx, and liver in each sex, and gall bladder in females, there were also raised risks of lesser magnitude in British ethnic migrants. For colon and rectal cancer and cutaneous melanoma in each sex, ovarian cancer in women and bladder cancer in men, there were appreciable significantly reduced risks in the Indian ethnic migrants not shared by those of British ethnicity. Appreciable raised risks in British ethnic migrants not shared by those of Indian ethnicity occurred for nasopharyngeal cancer in males, soft tissue malignancy in both sexes and non-melanoma skin cancer in males. In migrants of both ethnicities there were appreciable significantly raised risks in each sex for leukaemia and decreased risks in each sex for gastric cancer, for lung cancer except in females of British ethnicity and in males for testicular cancer. The results suggest the need for public health measures to combat the high risks of oral and pharyngeal cancers and liver cancer in the Indian ethnic immigrant population of England and Wales, by prevention of betel quid chewing and hepatitis transmission respectively. The data also imply that early exposures or early acquired behaviours in India, or exposures during migration, may increase the risk of leukaemia and reduce the risks of gastric and testicular cancers in the migrants irrespective of their ethnicity. Aetiological studies would be worthwhile to investigate the reasons for the sizeable decreased risk of colon and rectal cancer and increased risk of gall bladder cancer in each sex and the increased risk of thyroid and laryngeal cancer in males and oesophageal cancer in females of Indian ethnicity but not of British ethnicity who have migrated from the Indian subcontinent.

Adolescent↗