Biomedical subjects

H Blake

Publications and source records attributed to H Blake.

At least 19 recordsLinked to original sources

PubMed2006

Brain donation for research: who donates and why?

Understanding what influences people to donate or not donate body organs is critical for the future of transplant surgery and medical research. Are people involved with a brain donor program for research influenced by the same factors, and are they also donors for organ transplantation? Using web-based technology, people involved in an Australian brain donation program (for research) were asked to complete a questionnaire designed to elicit demographic information, motivational factors and information about involvement in organ transplantation programs. The response rate was 82%. The majority of people involved in the program are young, well-educated Australian females. Seventy-eight percent are involved in other organ and tissue donation programs. People involved in the 'Using our Brains' program are the same group as those who are organ and tissue donors. An improvement in the overall donation rate might be possible if the resources of the research and transplant organisations were combined.

Adolescent↗

PubMed2005

Distribution of mesorectal lymph nodes in rectal cancer: in vivo MR imaging compared with histopathological examination. Initial observations.

The aim of this work was to determine the distribution of mesorectal lymph nodes using T2-weighted magnetic resonance (MR) imaging compared with histopathological findings in patients with rectal carcinoma. Sixteen patients with rectal carcinoma undergoing primary surgery without pre-operative neoadjuvant treatment were evaluated using 3-mm axial T2-weighted MR imaging. The position of each visible mesorectal node on imaging was localised by measuring its minimum distance from the mesorectal fascia (d(m)), its minimum distance from the rectal wall (d(r)) and its distance from the distal tumour margin (d(v)). Independent assessment of d(m), d(r) and d(v) was made at histopathological examination. Eighty-five mesorectal nodes on in vivo MR imaging were matched to histopathological findings. On imaging, 67/85 mesorectal nodes were found at the level of the tumour and 84/85 were identified at or within 5 cm proximal to the tumour. Only one out of 85 nodes was seen below the inferior tumour margin. The mean difference of d(m) and d(r) obtained on in vivo MR imaging and histopathological examination was 0.7 mm (95% confidence interval, CI, -0.12 to 1.42 mm) and -1.1 mm (95% CI -2.29 to 0.14 mm), respectively. Almost all mesorectal nodes visible on MR imaging were found at the level of tumour or within 5 cm proximal to the tumour. This has implications for the planning of MR imaging and the level of mesorectal transection at surgery.

Adenocarcinoma↗

PubMed2002

Evaluation of cognitive assessment in stroke rehabilitation.

OBJECTIVE: To assess the effect of cognitive assessment on the functional outcome of stroke patients and quality of life for both patients and their carers. DESIGN: A multicentre, single-blind, randomized controlled trial. SETTING AND PARTICIPANTS: Two hundred and twenty-eight stroke patients were recruited from hospital wards in three UK centres. INTERVENTIONS: Patients were screened for cognitive impairment and randomly allocated to either routine care (116 patients) or routine care plus a detailed cognitive assessment (112 patients). MAIN OUTCOME MEASURES: Outcome was assessed three and six months after recruitment by an independent assessor blind to the intervention on Extended ADL, Cognitive Failures Questionnaire, General Health Questionnaire-28 for patients and carers and Carer Strain Index. RESULTS: There was no significant difference between the two groups in patients' functional outcome, perceived cognitive ability, level of psychological distress or satisfaction with care. There was a trend for the assessment group to have lower levels of carer strain (p = 0.06). CONCLUSIONS: The provision of information about cognitive assessment in stroke rehabilitation may decrease carer strain.

Aged↗

PubMed2001

The additive effect of neurotransmitter genes in pathological gambling.

As access to gambling increases there is a corresponding increase in the frequency of addiction to gambling, known as pathological gambling. Studies have shown that a number of different neurotransmitters are affected in pathological gamblers and that genetic factors play a role. Polymorphisms at 31 different genes involved in dopamine, serotonin, norepinephrine, GABA and neurotransmitters were genotyped in 139 pathological gamblers and 139 age, race, and sex-matched controls. Multivariate regression analysis was used with the presence or absence of pathological gambling as the dependent variable, and the 31 coded genes as the independent variables. Fifteen genes were included in the regression equation. The most significant were the DRD2, DRD4, DAT1, TPH, ADRA2C, NMDA1, and PS1 genes. The r(2) or fraction of the variance was less than 0.02 for most genes. Dopamine, serotonin, and norepinephrine genes contributed approximately equally to the risk for pathological gambling. These results indicate that genes influencing a range of brain functions play an additive role as risk factors for pathological gambling. Multi-gene profiles in specific individuals may be of assistance in choosing the appropriate treatment.

Adult↗

PubMed2000

Strain and psychological distress among informal supporters of reflex sympathetic dystrophy patients.

PURPOSE: A study to investigate strain and psychiatric morbidity in informal caregivers of patients with reflex sympathetic dystrophy (RSD). METHOD: Fifty one caregivers of RSD patients in the community, identified from a support group in Leeds or a conference in Eastbourne completed standardized questionnaire measures of strain, mood, adjustment, positive and negative affectivity and social support. RESULTS: Fifty seven percent of caregivers experienced significant strain and 53% had poor mood. Adjusting for age and gender, partial correlations showed that the experience of strain in caregivers was associated with poor mood, poor psychological adjustment to the patient's illness, high levels of negative affectivity, increased handicap and disability of the patient. CONCLUSIONS: A high proportion of caregivers of RSD patients experience poor mood and significant levels of strain. Caregivers who are poorly adjusted to the illness experience the most strain. These findings suggest a need for intervention to alleviate the negative impacts of caregiving and facilitate adjustment.

Adolescent↗

PubMed2000

Comparison of the role of dopamine, serotonin, and noradrenaline genes in ADHD, ODD and conduct disorder: multivariate regression analysis of 20 genes.

The present study is based on the proposal that complex disorders resulting from the effects of multiple genes are best investigated by simultaneously examining multiple candidate genes in the same group of subjects. We have examined the effect of 20 genes for dopamine, serotonin, and noradrenergic metabolism on a quantitative score for attention deficit hyperactivity disorder (ADHD) in 336 unrelated Caucasian subjects. The genotypes of each gene were assigned a score from 0 to 2, based on results from the literature or studies in an independent set of subjects (literature-based scoring), or results based on analysis of variance for the sample (optimized gene scoring). Multivariate linear regression analysis with backward elimination was used to determine which genes contributed most to the phenotype for both coding methods. For optimized gene scoring, three dopamine genes contributed to 2.3% of the variance, p = 0.052; three serotonin genes contributed to 3%, p = 0.015; and six adrenergic genes contributed to 6.9%, p = 0.0006. For all genes combined, 12 genes contributed to 11.6% of the variance, p = 0.0001. These results indicate that the adrenergic genes play a greater role in ADHD than either the dopaminergic or serotonergic genes combined. The results using literature-based gene scoring were similar. An examination of two additional comorbid phenotypes, conduct disorder and oppositional defiant disorder (ODD), indicated they shared genes with ADHD. For ODD different genotypes of the same genes were often used. These results support the value of the simultaneous examination of multiple candidate genes.

Adolescent↗

PubMed2000

Multivariate analysis of associations of 42 genes in ADHD, ODD and conduct disorder.

In a previous study (Comings DE et al. Comparison of the role of dopamine, serotonin, and noradrenergic genes in ADHD, ODD and conduct disorder. Multivariate regression analysis of 20 genes. Clin Genet 2000: 57: 178-196) we examined the role of 20 dopamine, serotonin and norepinephrine genes in attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD), using a multivariate analysis of associations (MAA) technique. We have now brought the total number of genes examined to 42 by adding an additional 22 candidate genes. These results indicate that even with the inclusion of these additional genes the noradrenergic genes still played a greater role in ADHD than any other group. Six other neurotransmitter genes were included in the regression equation - cholinergic, nicotinic, alpha 4 receptor (CHNRA4), adenosine A2A receptor (ADOA2A), nitric oxide synthase (NOS3), NMDAR1, GRIN2B, and GABRB3. In contrast to ADHD and ODD, CD preferentially utilized hormone and neuropeptide genes These included CCK, CYP19 (aromatase cytochrome P-450), ESR1, and INS (p = 0.005). This is consistent with our prior studies indicating a role of the androgen receptor (AR) gene in a range of externalizing behavors. We propose that the MAA technique, by focusing on the additive effect of multiple genes and on the cummulative effect of functionally related groups of genes, provides a powerful approach to the dissection of the genetic basis of polygenic disorders.

Adolescent↗

PubMed2000

A multivariate analysis of 59 candidate genes in personality traits: the temperament and character inventory.

Cloninger (Cloninger CR. Neurogenetic adaptive mechanisms in alcoholism. Science 1987: 236: 410-416) proposed three basic personality dimensions for temperament: novelty seeking, harm avoidance, and reward dependence. He suggested that novelty seeking primarily utilized dopamine pathways, harm avoidance utilized serotonin pathways, and reward dependence utilized norepinephrine pathways. Subsequently, one additional temperament dimension (persistence) and three character dimensions (cooperativeness, self-directedness, and self-transcendence) were added to form the temperament and character inventory (TCI). We have utilized a previously described multivariate analysis technique (Comings DE, Gade-Andavolu R, Gonzalez N et al. Comparison of the role of dopamine, serotonin, and noradrenergic genes in ADHD, ODD and conduct disorder. Multivariate regression analysis of 20 genes. Clin Genet 2000: 57: 178-196; Comings DD, Gade-Andavolu R, Gonzalez N et al. Multivariate analysis of associations of 42 genes in ADHD, ODD and conduct disorder. Clin Genet 2000: in press) to examine the relative role of 59 candidate genes in the seven TCI traits and test the hypothesis that specific personality traits were associated with specific genes. While there was some tendency for this to be true, a more important trend was the involvement of different ratios of functionally related groups of genes, and of different genotypes of the same genes, for different traits.

Adult↗

PubMed2000

Association of the neutral endopeptidase (MME) gene with anxiety.

Enkephalins have been implicated in the regulation of mood, anxiety, reward, euphoria and pain. One of the major enzymes for enkephalin degradation is neutral endopeptidase [enkephalinase, membrane metalloendopeptidase (MME)]. We identified a dinucleotide polymorphism in the 5' region of the MME gene. Subjects were placed into three genotypes, 3/3, 3/x, and x/x since the 3 allele was the most common of the six alleles. Using one-way analysis of variance, we examined the association of these genotypes with the mean SCL-90 scores for anxiety, depression, obsessive-compulsive and phobic anxiety symptoms in 120 Caucasian males from an addiction treatment unit. There was a significant association between the MME genotypes and the SCL-90 scores for phobic anxiety, obsessive-compulsive and anxiety at a Bonferroni corrected alpha value of 0.0125. These results support a role of genetic variants of enkephalin metabolism in anxiety.

Adult↗

PubMed2000

Factors associated with strain in co-resident spouses of patients following stroke.

OBJECTIVE: To identify the factors associated with carer strain following stroke. DESIGN: Co-resident spouses of stroke patients were sent questionnaire measures of their perceptions of strain, stress, mood, handicap, adjustment, social support, life satisfaction and personality, and patient's mood and independence in activities of daily living. SETTING: Stroke spouses were identified from the stroke register at City Hospital, Nottingham. RESULTS: In a sample of 222 carers, 37% had significant strain. Strain was highly correlated with negative affectivity on the Positive and Negative Affectivity Scale, carer mood on the General Health Questionnaire-12 (GHQ-12) and carer's perceptions of patient's independence in activities of daily living on the Extended Activities of Daily Living Scale (EADL). Logistic regression analysis of 96 of these carers supported the correlations and showed three factors, carer GHQ-12, patient EADL and negative affectivity, were independently associated with carer strain. CONCLUSION: The relationship between these factors and strain needs to be tested prospectively. Early identification of carers who may be at risk of strain later on will enable services to be targeted at prevention rather than cure.

Adult↗

PubMed1999

The proenkephalin gene (PENK) and opioid dependence.

We tested the hypothesis that the alleles at the (CA)n repeat of the proenkephalin gene (PENK) might be associated with opioid addiction in 31 non-Hispanic Caucasian subjects with opioid dependence (heroin), 89 ethnically matched subjects with substance dependence other than opioid dependence and 132 controls. Among the subjects with opioid dependence, 66% carried the > or = 81 bp allele compared with 40% of subjects with other types of substance abuse (chi2 = 11.31, p < 0.004) and 49% of controls (chi2 = 6.0, p < 0.015). These results are consistent with a role of the PENK gene in opioid dependence.

Adult↗

PubMed1999

Additive effect of three noradrenergic genes (ADRA2a, ADRA2C, DBH) on attention-deficit hyperactivity disorder and learning disabilities in Tourette syndrome subjects.

Halperin et al. (Halperin JM. Newcorn JH, Koda VH, Pick L, McKay KE, Knott P. Noradrenergic mechanisms in ADHD children with and without reading disabilities: a replication and extension. J Am Acad Child Adolesc Psychiatry 1997: 36: 1688 1696) reported a significant increase in plasma norepinephrine (NE) in attention-deficit hyperactivity disorder (ADHD) children with reading and other cognitive disabilities compared to ADHD children without learning disabilities (LD). We examined the hypothesis that ADHD + LD was associated with NE dysfunction at a molecular genetic level by testing for associations and additive effects between polymorphisms at three noradrenergic genes the adrenergic alpha2A receptor (ADRA2A), adrenergic alpha2C receptor (ADRA2C), and dopamine beta-hydroxylase (DBH) genes. A total of 336 subjects consisting of 274 individuals with Tourette syndrome (TS) and 62 normal controls were genotyped. Regression analysis showed a significant correlation between scores for ADHD, a history of LD, and poor grade-school academic performance that was greatest for the additive effect of all three genes. Combined, these three genes accounted for 3.5% of the variance of the ADHD score (p = 0.0005). There was a significant increase in the number of variant NE genes progressing from subjects without ADHD (A-) or learning disorders (LD-) to A + LD - to A - LD + to A + LD + (p = 0.0017), but no comparable effect for dopamine genes. These data support an association between NE genes and ADHD, especially in ADHD + LD subjects.

Adolescent↗

PubMed1998

Association between the gamma-aminobutyric acid A3 receptor gene and multiple sclerosis.

BACKGROUND: In a prior study we observed an association between the dopamine D2 receptor gene (DRD2) and the age of onset and/or diagnosis of multiple sclerosis (MS). We hypothesized that this effect was mediated through the dopaminergic control of the release of prolactin, a modulator of immune response. Since gamma-aminobutyric acid also modulates the release of prolactin, we examined the possible association between alleles of the GABRA3 (gamma-aminobutyric acid A3 receptor) gene and MS. DESIGN: We examined the GABRA3 alleles of 189 subjects with MS who died of their disease. They were divided into test group 1 (n=64) and retest group 2 (n=56). Each group had a separate set of controls (group 1, n=109; group 2, n=430). All subjects were white. All were tested at a dinucleotide cytosine-adenosine repeat polymorphism with 6 alleles representing 11 to 16 repeats. RESULTS: In the first group there was a significant difference in the frequency of the GABRA3 alleles (P<.002), with the most notable difference being an increase in the frequency of the 16-repeat allele in subjects with MS and a relative decrease in the other alleles. In the replication group there was again a significant difference in the distribution of the GABRA3 alleles (P<.001), and again the greatest difference was an increase in the frequency of the 16-repeat allele in subjects with MS. For both groups combined, a significant difference in the frequency of the 16-repeat allele was noted (chi2=46.30; P<.001). CONCLUSIONS: These results suggest the GABRA3 gene may be a risk factor for MS. As with the DRD2 gene, the effect may be mediated through its regulation of prolactin release.

Alleles↗

PubMed1998

Correlation of length of VNTR alleles at the X-linked MAOA gene and phenotypic effect in Tourette syndrome and drug abuse.

Abnormalities in monoamine oxidase (MAO) levels have been implicated in a wide range of psychiatric disorders. We have examined a VNTR polymorphism at the X-linked MAOA gene to test two hypotheses: (1) Do variants of the MAOA gene play a role in any of the behavioral disorders associated with Tourette syndrome or drug abuse? (2) If so, is there any correlation between the length of the alleles and the phenotypic effect? We examined two independent groups: 375 TS patients, relatives and controls, and 280 substance abusers and controls. The alleles were divided into four groups of increasing size. There was a significant association between the MAOA gene and behavioral phenotypes in both groups, and in both the longest alleles were associated with the greatest phenotypic effect. The strongest effect was for the diagnosis of drug dependence (P=0.00003). The VNTR allele groups were in significant linkage disequilibrium with the Fnu4H1 polymorphism previously shown to be associated with MAO-A activity. While these results are consistent with the possibility that different-sized alleles of the short-repeat polymorphisms themselves may play a role in gene regulation, further studies directly linking these alleles with enzyme levels need to be done.

Alleles↗

PubMed1998

A prospective audit of the usefulness of evacuating proctography.

Fifty-nine evacuating proctograms were performed over a 4 month period. We sought to identify how useful this technique is in diagnosing the cause of various anorectal symptoms and indicating which treatment option may be beneficial to the patient. The main reasons for referral were faecal soiling (60%) and obstructed defaecation (47%). Of the proctograms, 90% revealed some pathology. The most common abnormalities detected were rectocele (56%), rectal intussusception (39%), enterocele (19%) and rectal prolapse (12%). Of the patients, 45% were treated with an operation specific to the pathology detected on the proctogram; 29% did not require any active treatment and the remainder were managed with biofeedback conditioning or injection sclerotherapy. Evacuating proctography is of value in providing a diagnosis in patients with anorectal symptoms and thereby allowing specific treatment, operative or nonoperative, to be directed to the underlying pathology.

Adult↗

PubMed1998

The use of rectosigmoid stents in the management of acute large bowel obstruction.

The management of the acutely obstructed colon is controversial. Initial decompression of the bowel is still favoured by many surgeons, but the resulting colostomy has significant morbidity and mortality. Instead, stenting of the obstruction would permit defunctioning of the bowel, without the need for surgery and stoma formation. In this study we present our experience of the use of stents in the initial management of six patients with acute and sub-acute large bowel obstruction.

Acute Disease↗

PubMed1995

Endoscopic biliary stenting in a district general hospital.

During a 48 month period to December 1990, 367 patients, median age 75 years, with obstructive jaundice caused by common bile duct stones (201), malignant biliary obstruction (148), and benign biliary strictures (18), underwent therapeutic endoscopic retrograde cholangiopancreatography. Endoscopic biliary stenting and drainage was achieved in 343 of 367 patients attempted (93%), seven patients requiring a combined percutaneous endoscopic approach. Endoscopic stenting failed in 24 patients because of malignant duodenal infiltration (10), Billroth 2 gastrectomy (6), tight and extensive biliary strictures (6), peripapillary diverticulum (1), and technical failure (1). Prolonged follow up was available in 91% (311 of 343). The 30 day mortality was 5% (17 of 343), which included two procedure related deaths (0.6%) from fulminant pancreatitis and major sphincterotomy site bleeding. Early complications occurred in 14% (48 of 343) and late complications occurred in 11.9% (35 of 294) patients, as of the original 343, 17 had died within 30 days and another 32 were lost to follow up. Eighty patients with incomplete bile duct clearance and eight patients with benign biliary strictures had biliary stents inserted for 12-48 months (median 30). Endoscopic biliary stenting services are necessary in a district general hospital with technical success, death and morbidity rates comparable to other studies.

Adult↗

PubMed1994

A comparison of the shock index and conventional vital signs to identify acute, critical illness in the emergency department.

STUDY OBJECTIVE: Shock index (SI) (heart rate/systolic blood pressure; normal range, 0.5 to 0.7) and conventional vital signs were compared to identify acute critical illness in the emergency department. DESIGN: Quasi-prospective study. PATIENTS: Two hundred seventy-five consecutive adults who presented for urgent medical care. INTERVENTIONS: Patients had vital signs, SI, and triage priority recorded on arrival in the ED and then their final disposition. RESULTS: Two groups were identified retrospectively by the SI; group 1 (41) had an SI of more than 0.9, and group 2 (234) had an SI of less than 0.9 on arrival in the ED. Although both groups had apparently stable vital signs on arrival, group 1 had a significantly higher proportion of patients who were triaged to a priority requiring immediate treatment (23 versus 45; P < .01) and required admission to the hospital (35 versus 105; P < .01) and continued therapy in an ICU (10 versus 13; P < .01). CONCLUSION: With apparently stable vital signs, an abnormal elevation of the SI to more than 0.9 was associated with an illness that was treated immediately, admission to the hospital, and intensive therapy on admission. The SI may be useful to evaluate acute critical illness in the ED.

Adult↗