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Biomedical subjects

M Whitehead

Publications and source records attributed to M Whitehead.

At least 19 recordsLinked to original sources
PubMed2006

Impact of hemoglobin levels on outcomes of adjuvant chemotherapy in resected non-small cell lung cancer: the JBR.10 trial experience.

BACKGROUND: Cisplatin-induced anemia may correlate with adverse events, poor quality of life (QoL), decreased adjuvant chemotherapy (ACT) dose intensity, shorter relapse-free survival (RFS) or overall survival (OS). METHODS: The JBR.10 trial demonstrated significantly longer survival with adjuvant cisplatin and vinorelbine (n=242) compared to observation (n=240) in patients with resected NSCLC [Winton T, Livingston R, Johnson D, Rigas J, Johnston M, Butts C, et al. Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med 2005;352(25):2640-2]. This exploratory analysis evaluates the predictive value of baseline (in all patients) and during-treatment (in ACT arm only) hemoglobin (Hb) levels on OS and RFS when adjusted for prognostic factors. Baseline (in all patients) and during treatment (in ACT arm only) Hb levels were also correlated with adverse events, QoL, morbidity and ACT dose intensity. RESULTS: Baseline Hb did not predict RFS or OS. However, there was a trend to shorter OS (p=0.1) when baseline Hb was <120g/L. Lower baseline Hb predicted increased hospitalization (p=0.04) and worse QoL (SOB item, p=0.03) but had no impact on adverse events or dose intensity. There was a trend to longer RFS (p=0.08) in patients with lower nadir during-treatment Hb and to longer OS (p=0.06) and RFS (p=0.08) in patients with maximum during-treatment Hb drop >30% that was not maintained when ACT dose intensity was included in the model. Maximum during-treatment Hb drop >30% correlated with increased lethargy (p=0.003) and worse QoL (fatigue item, p=0.07). CONCLUSIONS: Lower baseline and during-treatment Hb levels seem associated with poorer QoL, fatigue and increased hospitalization. There is a trend for shorter OS in patients with lower baseline Hb levels.

Anemia↗
PubMed2006

Does sodium hyaluronate- and carboxymethylcellulose-based bioresorbable membrane (Seprafilm) decrease operative time for loop ileostomy closure?

BACKGROUND: Adhesions can result in serious clinical complications and make ileostomy closure, which is relatively simple procedure into a complicated and prolonged one. The use of sodium hyaluronate and carboxymethyl cellulose membrane (Seprafilm) was proven to significantly reduce the postoperative adhesions at the site of application. The aim of this study was to assess the incidence and severity of adhesions around a loop ileostomy and to analyze the length of time and morbidity for mobilization at the time of ileostomy closure with and without the use of Seprafilm. METHODS: Twenty-nine surgeons from 15 institutions participated in this multicenter prospective randomized study. 191 patients with loop ileostomy construction were randomly assigned to either receive Seprafilm under the midline incision and around the stoma (Group I), only under the midline incision (Group II), or not to receive Seprafilm (Group III). At ileostomy closure, adhesions were quantified and graded; operative morbidity was also measured. RESULTS: All 3 groups were comparable relative to gender, mean age and number of patients with prior operations (26, 25 and 19, respectively). Group II patients were significantly more likely to have pre-existing adhesions than Group III patients (30.6% vs. 14.1%, p = 0.025). At stoma mobilization, significantly more patients in Group III than in Group I had adhesions around the stoma (95.2% vs. 82.3%, p = 0.021). Mean operative times were 27, 25, and 28 minutes, respectively (p = 0.38), with significant differences among sites. There was no significant difference in the number of patients needing myotomy or enterotomy (29, 27 and 24 patients, respectively), nor in the number of postoperative complications (7, 9 and 7 patients, respectively). CONCLUSIONS: When consistently applied, Seprafilm significantly decreased adhesion formation around the stoma but not operative times without any increase in the need for myotomy or enterotomy. These findings were not seen in the overall study population possibly due to the large number of surgeons using a variety of application techniques.

Adjuvants, Immunologic↗
PubMed2006

Gender and socio-economic variations in employment among patients with a diagnosed musculoskeletal disorder: a longitudinal record linkage study in Sweden.

OBJECTIVE: To establish whether the employment consequences of musculoskeletal disorder vary by gender and socio-economic group in Sweden. METHODS: Two linked registers, containing diagnostic and socio-economic data for the 1.8 million residents of Stockholm County, were used to investigate the subsequent employment consequences over 5 yr of having a musculoskeletal disorder requiring hospital admission in 1996. Age-standardized employment rates of all patients with musculoskeletal disorder (n = 2185) were compared with patients employed prior to hospital admission (n = 1286) and with the general population of Stockholm. Odds of leaving employment between 1996-2001 were calculated for men, women and patients from different socio-economic groups. RESULTS: Employment rates increased and social differentials narrowed in the general population, while employment declined and social differentials widened among patients with musculoskeletal disorders. These trends were masked when analyses were restricted to individuals employed at baseline. Following hospital admission, the odds of leaving employment increased annually for patients; by 2001, their adjusted odds were over three times greater [odds ratio (OR) = 3.36, 95% confidence interval (CI) 2.89-3.91] than for the general population. Women with musculoskeletal disorders were significantly more likely to leave employment during follow-up than men (OR = 1.95, 95% CI 1.49-2.56). Semi- and unskilled manual workers with musculoskeletal disorders were over three times as likely to leave employment than their professional counterparts (OR = 3.40, 95% CI 2.41-4.81). CONCLUSIONS: People with musculoskeletal disorders, particularly women and semi- and unskilled manual workers, are vulnerable to leaving employment. Health and social policies must do more to protect the employment of people with musculoskeletal disorders.

Adult↗
PubMed2006

The social and economic consequences of childhood-onset Type 1 diabetes mellitus across the lifecourse: a systematic review.

BACKGROUND: The incidence of childhood-onset (Type 1) diabetes is high, and increasing, particularly among the very young. The aim of this review was to determine the longer-term social consequences of having diabetes as a child and to determine whether adverse consequences are more severe for disadvantaged children. METHODS: Results from published and unpublished studies were synthesized narratively to examine the impact of diabetes on education, employment and income in adulthood. The question of whether the impact differed for different social groups was also examined. RESULTS: Case-control studies found that children with diabetes missed more school than healthy children. Most studies of attainment found no differences between children with diabetes and non-diabetic control subjects or the local population, although poor metabolic control, early-onset, longer illness duration and serious hypoglycaemic events were associated with underachievement. People with childhood-onset diabetes may experience disadvantage in employment, and have a lower income in adulthood, although diabetic complications appear to be the most important determinant of social consequences in later life. CONCLUSIONS: Many children with diabetes--especially late-onset--perform equally well at school despite increased rates of absence, but it is not yet clear whether specific subgroups are at greater risk of educational underperformance. People with childhood-onset diabetes, however, do appear to experience some disadvantage in adult employment. Qualitative research and cohort studies are needed to fill key gaps in the existing evidence base. Future research must also examine the impact of diabetes-related risk factors on socio-economic consequences.

Adolescent↗
PubMed2005

Increased cardiac sympathetic nerve activity following acute myocardial infarction in a sheep model.

The time course of cardiac sympathetic nerve activity (CSNA) following acute myocardial infarction (MI) is unknown. We therefore undertook serial direct recordings of CSNA, arterial blood pressure (MAP) and heart rate (HR) in 11 conscious sheep before and after MI, and compared them with 10 controls. Conscious CSNA recordings were taken daily from electrodes glued into the thoracic cardiac nerves. Infarction was induced under pethidine and diazepam analgesia by applying tension to a coronary suture. MI size was assessed by left ventricular planimetry (%) at postmortem, peak troponin T and brain natriuretic peptide levels (BNP). Baroreflex slopes were assessed daily using phenylephrine-nitroprusside ramps. The mean infarcted area was 14.4 +/- 2.9%, troponin T 1.88 +/- 0.39 microg l(-1) and BNP 8.4 +/- 1.3 pmol l(-1). There were no differences in haemodynamic parameters or CSNA between groups at baseline. MAP and HR remained constant following MI. CSNA burst frequency increased from baseline levels of 55.8 +/- 7.1 bursts min(-1) to levels of 77.5 +/- 8.7 bursts min(-1) at 2 h post-MI, and remained elevated for 2 days (P < 0.001). CSNA burst area also increased and was sustained for 7 days following MI (P= 0.016). Baroreflex slopes for pulse interval and CSNA did not change. CSNA increases within 1 h of the onset of MI and is sustained for at least 7 days. The duration of this response may be longer because the recording fields decrease with time. This result is consistent with a sustained cardiac excitatory sympathetic reflex.

Action Potentials↗
PubMed2004

Effect of long-term estrogen therapy on dopaminergic responsivity in post-menopausal women--a preliminary study.

Females have a higher prevalence than men of neuropsychiatric disorders in which dopaminergic abnormalities play a prominent role, e.g. very late-onset schizophrenia and Parkinson's disease (PD). The biological basis of these sex differences is unknown but may include modulation of the dopaminergic system by sex hormones, as there is preliminary evidence that estrogen modulates treatment response in these disorders. Furthermore, sex differences in dopamine-mediated cognitive decline suggest estrogen may also play a role in healthy aging. However, the effects of estrogen on the dopaminergic system are poorly understood, and nobody has examined the effect of long-term estrogen therapy (ET) on this system. We compared dopaminergic responsivity (growth hormone (GH) response to apomorphine) in post-menopausal women on ET to women who were ET-naïve. GH response to subcutaneous apomorphine (0.005 mg/kg) was measured in two groups of healthy post-menopausal women aged between 55 and 70 years: those taking ET (n = 13) and those who had never taken ET (n = 13). Neither group was taking any other medication. GH was measured at 15 min intervals from -30 min before administration of apomorphine to 90 min post-administration. GH response was measured in two ways: area under the curve (AUC) and maximum response over baseline (GH). There were no between-group differences in demographic or baseline variables. The ET treated women had a significantly greater (p = 0.03) AUC than ET naïve women (mean +/- S.D.; 5.3 +/- 4.7 vs. 2.6 +/- 2.3). However, (GH) did not differ significantly between groups (6.1 mU/l +/- 6.2 vs. 2.7 mU/l +/- S.D. = 4.1). Also, analysis of GH response over time revealed a significant main effect of time (p < 0.0005), and a group by time interaction (p = 0.004) , but no significant main effect of group. Our results suggest that ET may enhance dopaminergic responsivity in post-menopausal women. Estrogen deficiency following menopause may partly explain age and gender differences in late-onset neuropsychiatric disorders.

Aged↗
PubMed2004

The social and economic consequences of childhood asthma across the lifecourse: a systematic review.

BACKGROUND: Asthma prevalence rates are high, and may be increasing in the Western world, particularly among children. The aim of this study was to evaluate the longer-term social and economic consequences of having asthma as a child and to determine whether adverse consequences are more severe for poorer children. METHODS: Results from published and unpublished, quantitative and qualitative studies were synthesized narratively to examine the impact of childhood-onset asthma on school attendance, academic achievement and employment in adulthood. The question of whether the impact differed for different social groups was also examined. FINDINGS: Twenty-nine good quality studies were identified, including in total 12 183 children with asthma or wheeze. Compared with asymptomatic children, those with asthma missed more days of school (additional absence as a result of asthma ranged from 2.1 to 14.8 days). Studies of academic achievement found that children with asthma performed as well as their healthy peers. The existing evidence on labour market performance is sparse, but there is an indication that people with asthma during childhood experience disadvantage in later employment. In an examination of consequences by social position, children with asthma from deprived areas were more likely to miss school than their more affluent peers, and minority ethnic children were also more likely to have poor school attendance. The only qualitative study suggested that children with asthma strove to participate fully in every aspect of their daily lives. INTERPRETATION: Although asthma limits children's daily activities and affects their social activities, this research synthesis found little evidence of major, adverse long-term social and economic consequences in studies reviewed. Further longitudinal research using comparison groups is needed to fill key gaps in the existing evidence base.

Age of Onset↗
PubMed2003

A composite chiral pair of rotational bands in the odd-A nucleus 135Nd.

High-spin states in 135Nd were populated with the 110Pd(30Si,5n)135Nd reaction at a 30Si bombarding energy of 133 MeV. Two DeltaI=1 bands with close excitation energies and the same parity were observed. These bands are directly linked by DeltaI=1 and DeltaI=2 transitions. The chiral nature of these two bands is confirmed by comparison with three-dimensional tilted axis cranking calculations. This is the first observation of a three-quasiparticle chiral structure and establishes the primarily geometric nature of this phenomenon.

Journal Article↗
PubMed2003

A neural mechanism for sudden death after myocardial infarction.

By monitoring efferent cardiac sympathetic nerve activity (CSNA) directly in a conscious animal we observed, for the first time, that ventricular fibrillation (VF) following myocardial infarction (MI) was preceded by a paroxysm of CSNA which was not baroreflexmodulated. This observation has potential therapeutic implications.

Animals↗
PubMed2003

Effects of long-term estrogen replacement therapy on growth hormone response to pyridostigmine in healthy postmenopausal women.

OBJECTIVE: There is growing evidence that estrogen may protect against age-related cognitive decline and reduce the risk of developing Alzheimer's disease (AD) in healthy, postmenopausal women. The underlying biological basis for this is not known but may include preservation of cholinergic systems. Cholinergic dysfunction has been implicated in the aetiology of age-related memory impairment and AD. We studied the effect of prolonged use of estrogen replacement therapy (ERT) on central cholinergic tone in healthy postmenopausal women. METHOD: Growth hormone (GH) responses to oral pyridostigmine (120 mg) were measured over a 3 h period in thirty healthy postmenopausal women, 15 on long-term ERT and 15 ERT naïve. RESULTS: GH release following pyridostigmine was significantly larger in ERT treated women than in ERT naïve women. In addition within the ERT treated group there was a significant positive correlation between duration of estrogen treatment and GH response. CONCLUSIONS: Long-term ERT can enhance cholinergic function in postmenopausal women and this may be related to duration of estrogen treatment. Modulation of central cholinergic function may be one mechanism by which long-term ERT could preserve cognitive function in healthy, postmenopausal women.

Aged↗
PubMed2002

Survival of Escherichia coli O157:H7 in traditional African yoghurt fermentation.

Growth and survival of a nontoxigenic strain of Escherichia coli O157:H7 (ATCC 43888) was determined in traditionally fermented pasteurized milk. Preheated milk was inoculated with 1% (v/v) of a mixed culture of Lactobacillus delbrueckii ssp. bulgaricus (NCIMB 11778) and Streptococcus salivarius ssp. thermophilus (NCIMB 110368) and incubated at 25, 30, 37 or 43 degrees C for 24 h. E. coli O157:H7 (10(5) CFU/ml) were introduced into the milk pre- and post-fermentation. Fermented milk samples were subsequently stored at either 4 degrees C (refrigerator temperature) or 25 degrees C (to mimic African ambient temperature) for 5 days. After 24 h of fermentation, the pH of the samples fermented at the higher temperatures of 37-43 degrees C decreased from 6.8 to 4.4-4.0 ( +/- 0.2) whereas at the lower temperature of 25 degrees C, the pH decreased to pH 5.0 +/- 0.1. During this period, viable counts for E. coli O157:H7 increased from 10(5) to 10(8) - 10(9) CFU/ml except in milk fermented at 43 degrees C wherein viability declined to 10(4) CFU/ml. In fermented (25-30 degrees C) milk stored at 4 degrees C for 5 days, E. coli O157:H7 viability decreased from 10(8-9) to 10(6-7) CFU/ml whereas milk fermented at 43 degrees C resulted in loss of detectable cells. In contrast, storage of fermented milk samples at 25 degrees C for 5 days eventually resulted in complete loss of viability irrespective of fermentation temperature. Stationary phase E. coli O157:H7 inoculated post-fermentation (25 and 43 degrees C) survived during 4 degrees C storage, but not 25 degrees C storage. Fermentation temperature and subsequent storage temperature are critical to the growth and survival of E. coli O157:H7 in traditional fermented products involving yoghurt starter cultures.

Colony Count, Microbial↗
PubMed2001

Effects of estrogen replacement therapy on human brain aging: an in vivo 1H MRS study.

Estrogen replacement therapy (ERT) may preserve cognitive function in postmenopausal women, but the mechanism is unknown. Thus, the authors studied aging of parietal lobe and hippocampus using proton MR spectroscopy. ERT naïve postmenopausal women had a significant increase in choline-containing compounds (Cho) compared to long-term ERT users and young women. Cho reflects increased neuronal/glial membrane turnover. Thus, ERT's "neuroprotective" effect may include modulating the effects of age on neural integrity in brain regions involved in cognitive function.

Adult↗
PubMed2001

Prolactin response to d-fenfluramine in postmenopausal women on and off ERT: comparison with young women.

Estrogen is thought to have an impact on both psychological well being and cognitive function. The biological basis to this is not fully understood, but may involve estrogen's interactions with central serotonergic (5-HT) systems. Therefore, we studied the effect of long-term estrogen hormone replacement therapy (ERT) on central 5-HT tone in healthy postmenopausal women and made comparisons with young women. Prolactin (PRL) responses to the specific 5-HT releasing and re-uptake inhibiting agent, d-fenfluramine, were measured in three groups of healthy women: 11 young, 11 postmenopausal on long-term ERT, and 11 postmenopausal ERT naïve. PRL responses were significantly decreased in ERT naïve women compared to young healthy women. In contrast, PRL responses were not different between estrogen-treated and young women. Overall, there was a significant relationship between older age and lower PRL responsivity. These results suggest that central 5-HT tone is reduced in healthy postmenopausal women who are ERT naïve, but not in postmenopausal women who have received prolonged estrogen treatment. Estrogen may modulate age-related changes in 5-HT tone. This may partly explain why estrogen can decrease vulnerability to mood disorders and cognitive changes in postmenopausal women.

Adult↗
PubMed2001

The role of income differences in explaining social inequalities in self rated health in Sweden and Britain.

STUDY OBJECTIVE: To analyse to what extent differences in income, using two distinct measures-as distribution across quintiles and poverty-explain social inequalities in self rated health, for men and women, in Sweden and Britain. DESIGN: Series of cross sectional surveys, the Swedish Survey of Living Conditions (ULF) and the British General Household Survey (GHS), during the period 1992-95. PARTICIPANTS AND SETTING: Swedish and British men and women aged 25-64 years. Approximately 4000 Swedes and 12 500 Britons are interviewed each year in the cross sectional studies used. The sample contains 15 766 people in the Swedish dataset and 49 604 people in the British dataset. MAIN RESULTS: The magnitude of social inequalities in less than good self rated health was similar in Sweden and in Britain, but adjusting for income differences explained a greater part of these in Britain than in Sweden. In Britain the distribution across income quintiles explained 47% of the social inequalities in self rated health among women and 31% among men, while in Sweden it explained, for women 13% and for men 20%. Poverty explained 22% for British women and 8% for British men of the social inequalities in self rated health, while in Sweden poverty explained much less (men 2.5% and women 0%). CONCLUSIONS: The magnitude of social inequalities in self rated health was similar in Sweden and in Britain. However, the distribution of income across occupational social classes explains a larger part of these inequalities in Britain than in Sweden. One reason for this may be the differential exposure to low income and poverty in the two countries.

Adult↗
PubMed2000

Anti-endomysial and anti-gliadin antibodies in screening for coeliac disease in children at greater risk of developing coeliac disease.

AIMS: To determine the prevalence of coeliac disease in selected groups of children presenting to a paediatric department. METHODS: Children presenting to the Paediatric Department at Christchurch Hospital were enrolled upon identification of one or more factors associated with increased risk of coeliac disease. All subjects were screened with anti-endomysial antibody and antigliadin antibody tests. Those children with positive tests underwent small bowel biopsy. RESULTS: 36 of 153 children had abnormal antibody tests. Seven (4.5%) of 34 children who underwent small bowel biopsies were found to have histological findings consistent with coeliac disease. Five of these children had presented with symptoms not classically ascribed to coeliac disease (failure to gain weight or non-specific abdominal pain). CONCLUSIONS: The possibility of coeliac disease should be considered in children with atypical symptoms and the diagnosis excluded by appropriate testing. Recognition of the variable presentations associated with coeliac disease in children is clinically relevant.

Adolescent↗