Case report: recurrent temporalis muscle swelling and headache.
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Adrenal Cortex Hormones↗
Biomedical subjects
M Hutchinson
Publications and source records attributed to M Hutchinson.
Presenilin-1 mutation (E280G), spastic paraparesis, and cranial MRI white-matter abnormalities.
The authors report unusual presentations of members of an Irish family with familial AD due to an E280G mutation in exon 8 of presenilin-1. One had spastic paraparesis and white matter abnormalities on cranial MRI. A sibling had an internuclear ophthalmoplegia, spastic-ataxic quadriparesis, and "cotton-wool plaques" with amyloid angiopathy on brain biopsy. Another affected sibling also had MRI white matter abnormalities. The MRI findings may reflect an ischemic leukoencephalopathy due to amyloid angiopathy affecting meningocortical vessels.
Adult↗
Molecular analysis of multiple cytochrome P450 genes from the malaria vector, Anopheles gambiae.
Cytochrome P450s are a superfamily of haemoproteins, important in the metabolism of endogenous compounds and xenobiotics. As a first step to elucidating the role of this family in insecticide resistance in the malaria mosquito, Anopheles gambiae, we have cloned and mapped multiple P450 genes. Sixteen cDNAs encoding full-length P450s were cloned and physically mapped to the mosquito's polytene chromosomes. Fourteen of these encode putative CYP6 proteins and two encode P450s belonging to the CYP9 class. Eighteen new A. gambiae Cyp4 P450 genes were identified using degenerate PCR primers, cDNAs were detected for ten and in situ locations for thirteen members of this gene family.
Amino Acid Sequence↗
The prevalence of "pure" autosomal dominant hereditary spastic paraparesis in the island of Ireland.
OBJECTIVES: Hereditary spastic paraparesis (HSP) is clinically and genetically heterogeneous. "Pure" autosomal dominant (AD) HSP is most common and eight genetic loci are identified to date. Previous studies have included autosomal recessive and sporadic cases in prevalence calculations. This study aimed to determine the prevalence and features of pure ADHSP in the island of Ireland. METHODS: Index cases were identified from a 5 year survey of all adult and paediatric neurologists, clinical geneticists, hospital records, and hospital inpatient enquiry system data in Ireland, north and south. Families were examined by two neurologists and classified as affected or unaffected according to specific criteria. The prevalence date was set at 1 June 2000 and the midyear population estimate for the previous year was 5.436 million. RESULTS: Eighty two patients with pure ADHSP and a further 12 obligate carriers from 19 families were identified. In total 69 patients with pure ADHSP were alive and resident in Ireland at the prevalence date. Twenty nine per cent of these were asymptomatic but with signs of paraparesis. CONCLUSIONS: The prevalence of ADHSP in Ireland to estimated to be 1.27/100 000 population. The high proportion of asymptomatic cases and obligate carriers means that this condition is likely to be underdiagnosed.
Adolescent↗
CADASIL imitating multiple sclerosis: the importance of MRI markers.
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) can mimic multiple sclerosis (MS), leading to diagnostic confusion. We report a family with CADASIL in which the index case and the daughter of the index case were initially erroneously diagnosed with MS. Relatively specific magnetic resonance imaging (MPI) markers of CADASIL include involvement of the anterior temporal lobes and external capsules and, as illustrated in this report, these MRI findings may aid in the differentiation of the two conditions.
Adult↗
Willingness to pay for flood and ecological risk reduction in an urban watershed.
Urban watershed managers frequently must address alternative policy goals; flood control and ecological risk reduction. This study combines hydrologic models of flood control and biotic models of ecologic risk with economic models of willingness-to-pay and psychological models of risk processing and planned behavior to evaluate these two alternative policy objectives. The findings reveal that flood risk exposure, especially for those individuals who would remain outside the 100 year flood plain if the project were enacted, does influence the financial support that local residents would be willing to make to a flood control project. Other important determinants include demographic factors such as income, and attitudinal measures of the respondent. Expanding the scope of the project to include ecological risk reduction does not, however, appear to change the average willingness-to-pay for a project.
Demography↗
Interferon-beta1b in the treatment of secondary progressive MS: impact on quality of life.
BACKGROUND: The recent randomized, controlled trial of interferon-beta1b (IFN-beta1b) in 718 patients with secondary progressive MS (SP-MS) demonstrated a significant effect on the development of disability as evaluated by the physician. Its effect on patient-reported health-related quality of life (HrQoL) is reported herein. METHODS: In this multicenter, double-blind, randomized, placebo-controlled trial, outpatients with SP-MS scoring between 3.0 and 6.5 on the Expanded Disability Status Scale received either 8 x 10(6) IU of IFN-beta1b or placebo for up to 3 years. A range of outcomes was measured, including HrQoL, which was assessed using the Sickness Impact Profile (SIP), a self-report questionnaire validated for use in MS. Measurements were undertaken at baseline and at 6-monthly intervals thereafter for 36 months. RESULTS: A slight positive effect on the HrQoL of the IFN group in comparison with the placebo group was found, which reached significance in the physical scale of the SIP at 6 and 12 months and at last visit. There was moderate correlation between physician-assessed evaluation of change and patient-reported change. CONCLUSIONS: IFN-beta1b may delay sustained deterioration in patient-reported HrQoL in SP-MS. Methods of interpreting change in HrQoL are currently insufficiently developed to determine how clinically important these changes are for this population.
Activities of Daily Living↗
SPG15, a new locus for autosomal recessive complicated HSP on chromosome 14q.
The authors studied two families with autosomal recessive hereditary spastic paraplegia (HSP) complicated by the presence of additional symptoms of pigmented maculopathy, distal amyotrophy, dysarthria, mental retardation, and further intellectual deterioration. Evidence was obtained for linkage to a locus on chromosome 14q that is distinct from the SPG3 locus for autosomal dominant HSP (D14S77: lod score of 4.20 at zero recombination). Haplotype construction of nearby markers confirms the existence of this novel HSP locus (SPG15) and narrows it to a 19-cM interval flanked by D14S1038 and D14S61.
Chromosomes, Human, Pair 14↗
HPV co-factors related to the development of cervical cancer: results from a population-based study in Costa Rica.
We examined factors associated with high-grade squamous intraepithelial lesions (HSIL) and cervical cancer among human papillomavirus (HPV)-infected women in a prevalent case-control study conducted within a population-based cohort of 10 077 women in Costa Rica. We compared 146 women with HPV-positive HSIL or cancer (HSIL/CA) against 843 HPV-positive women without evidence of HSIL/CA. Subjects completed a risk factor questionnaire. We evaluated the associations between exposures and HSIL/CA among women positive for any HPV and restricted to those positive for high-risk HPV types. Risk of HSIL/CA increased with increasing number of live births (P(trend)= 0.04). Women who smoked 6+ cigarettes/day had a RR for HSIL/CA of 2.7 (95% CI = 1.1-6.7) compared to non-smokers. Current use of barrier contraceptives was associated with a reduction in risk of HSIL/CA (RR = 0.39; 95% CI = 0.16-0.96). Sexual behaviour and a self-reported history of sexually transmitted diseases (STDs) other than HPV were not associated with HSIL/CA. Oral contraceptive use was associated with HSIL/CA among women with <3 pregnancies. Effects were similar in analysis restricted to women positive for high-risk HPV types. Among women positive for high-risk HPV types, 44% of HSIL/CA could be attributed to multiparity (>/=3 pregnancies) and/or smoking. Among HPV-positive women, multiparity and smoking are risk factors for HSIL/CA. Oral contraceptive use may be associated with HSIL/CA in subgroups of women.
Adolescent↗
Clinical and pathologic findings in hereditary spastic paraparesis with spastin mutation.
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Adenosine Triphosphatases↗
Hemichorea, moya-moya, and ulcerative colitis.
This is a case report linking chorea, colitis, and moya-moya. The clear involvement in the vasculopathy of the basal ganglia offers an obvious substrate for the movement disorder.
Adolescent↗
A multicentre, open, non-comparative phase II study of a combination of fludarabine phosphate, cytarabine and granulocyte colony-stimulating factor in relapsed and refractory acute myeloid leukaemia and de novo refractory anaemia with excess of blasts in transformation.
The primary objective of this study was to determine the complete remission (CR) rate achieved with the FLAG (fludarabine phosphate, cytarabine and granulocyte colony-stimulating factor) regimen in patients with relapsed or refractory acute myeloid leukaemia (AML) or de novo refractory anaemia with excess of blasts in transformation (RAEB-t). Secondary objectives were to evaluate survival and toxicity. Induction treatment consisted of between one and two courses of FLAG. Patients achieving CR received between one and two courses of consolidation treatment. Eighty-three of the 89 patients entering the study were eligible for assessment. CR rates were: 17 out of 21 (81%) in late relapse AML (Group 1), 13 out of 44 (30%) in early relapse/refractory AML (Group 2), and 10 out of 18 (56%) in de novo RAEB-t (Group 3). Thirty-four of the 40 responders (85%) achieved CR after one induction course. Median survival times were 1.4 years, 3 months and 1.6 years in Groups 1, 2 and 3 respectively. Other than myelosuppression, the FLAG regimen was not generally associated with clinically significant toxicity and was well tolerated by most patients including the elderly. The FLAG regimen offers a very effective alternative treatment for CR induction in poor prognosis adult patients with either relapsed or refractory AML or de novo RAEB-t. FLAG delivers high-dose treatment without increasing overall toxicity, an approach which is of particular value in older patients, who constitute the majority in these diseases. It is therefore an important advance in developing new treatment options for these patients.
Acute Disease↗
Doctors' professional values: results from a cohort study of United Kingdom medical graduates.
OBJECTIVES: To examine young doctors' views on a number of professional issues including professional regulation, multidisciplinary teamwork, priority setting, clinical autonomy and private practice. METHOD: Postal survey of 545 doctors who graduated from United Kingdom medical schools in 1995. RESULTS: Questionnaires were returned by 95% of the cohort (515/545). On issues of professional regulation, teamwork and clinical autonomy, the majority of doctors held views consistent with current General Medical Council guidance. The majority supported the right of doctors working in the NHS to engage in private practice. Most respondents thought that public expectations of doctors, medicine and the NHS were too high, and that some form of rationing was inevitable. On many issues there was considerable variation in attitudes on the basis of sex and intended branch of medicine. CONCLUSIONS: The results highlight the heterogeneity of the profession and the influence of specialty and gender on professional values. Doctors' attitudes had also been shaped by broader social changes, especially debates surrounding regulation of the profession, rising public expectations and the need for rationing of NHS care.
Adult↗
Lambert-Eaton myaesthenic syndrome: a possible association with Hodgkin's lymphoma.
Lambert-Eaton myasthenic syndrome is a presynaptic neuromuscular junction disorder typically associated with small cell lung carcinoma. The characterstic electrophysiological abnormality is a low amplitude compound muscle action potential that shows a marked increment after maximal voluntary contraction or brief tetanic nerve stimulation. We describe a patient who had LEMS in association with Hodgkin's disease. A 61 year old woman presented with proximal muscle weakness 6 years following successful treatment of Hodgkin's disease. Her symptoms responded well to treatment with diaminopyridine. 9 additional patients have been described with LEMS in association with lymphoproliferative diseases. A systemic malignancy is usually found within 2 years of LEMS diagnosis but may present later. LEMS should be considered in patients with Hodgkin's disease presenting with muscle weakness.
Female↗
A qualitative study of patients' views on anxiety and depression.
BACKGROUND: In the management of patients with anxiety and depression in general practice, the emphasis has been on improving detection and appropriate use of drug therapies by health professionals. Patients' own perceptions of their problems and what services they would prefer have not often been sought. AIM: To explore patient perspectives in relation to their healthcare needs in anxiety and depression. DESIGN OF STUDY: Semi-structured individual and focus group interviews. SETTING: A total of 27 patients from an urban four-partner group general practice who were identified as having anxiety and depression by a practice population questionnaire survey. METHOD: All interviews were transcribed and the major themes were summarised using grounded theory analysis. RESULTS: Patients seek many different ways of coping with their problems but view their general practice as a focal point for help. Their experiences are dominated by the struggle to control unwelcome and intrusive thoughts and to live in a hostile and threatening world. They also have distinct preferences regarding their health needs and there is universal scepticism about drug therapies. CONCLUSION: Patients describe personal and professional barriers to seeking help and have particular views on the treatment options. This perspective contrasts with the current professional emphasis on detection and drug use. This view is therefore central to informing the debate on management of neurotic disorders in primary care and on improving the care of these patients.
Adolescent↗
Phenotype of AD-HSP due to mutations in the SPAST gene: comparison with AD-HSP without mutations.
BACKGROUND: "Pure" autosomal dominant hereditary spastic paraparesis (AD-HSP) is clinically and genetically heterogeneous. There are at least seven genetic loci with varying ages at onset and disability. The SPAST gene at the SPG4 locus on chromosome 2p is the major disease gene for AD-HSP. OBJECTIVES: To investigate whether there are distinct clinical features among families with AD-HSP due to SPAST mutations compared with families excluded from SPG4. METHODS: Nineteen families with "pure" AD-HSP were identified, and the clinical features of family members were compared using a standard protocol. With use of genetic studies, the families were divided into two groups for comparison: those with mutations in SPAST, the "mutation-positive" group, and those excluded from SPG4 on the basis of linkage studies, the "SPG4-excluded" group. RESULTS: Twenty-nine individuals from four families had mutations in SPAST, whereas 22 individuals from three families comprised the SPG4-excluded group; in 11 families, the pattern of linkage was unknown. In the one remaining family, no mutations were found despite strong linkage to SPG4. Different mutations were identified in the four SPAST pedigrees, but the clinical picture was similar in each. Comparison of the mutation-positive group with the SPG4-excluded group revealed an older age at onset (p = 0.03), more disability (p = 0.001), more rapidly progressive paraparesis (p = 0.044), and more cognitive impairment (p = 0.024) among affected individuals with SPAST mutations, not confounded by disease duration. CONCLUSION: Despite different mutations, SPAST families have a similar phenotype that can be distinguished from other genetic groups.
Adenosine Triphosphatases↗
Should asymptomatic haemochromatosis be treated? Update from Seamark and Hutchinson.
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Female↗
The metabolic topography of essential blepharospasm: a focal dystonia with general implications.
OBJECTIVE: To determine the metabolic topography of essential blepharospasm (EB). BACKGROUND: EB is a cranial dystonia of unknown etiology and anatomic localization. The authors have used 18F-fluorodeoxyglucose (FDG) and PET with network analysis to identify distinctive patterns of regional metabolic abnormality associated with idiopathic torsion dystonia (ITD), as well as sleep induction during PET imaging to suppress involuntary movements, thereby reducing this potential confound in the analysis. METHODS: Six patients with EB and six normal volunteers were scanned with FDG-PET. Scans were performed twice: once in wakefulness and once following sleep induction. The authors used statistical parametric mapping to compare glucose metabolism between patients with EB and control subjects in each condition. They also quantified the expression of the previously identified ITD-related metabolic networks in each subject in both conditions. RESULTS: With active involuntary movements during wakefulness, the EB group exhibited hypermetabolism of the cerebellum and pons. With movement suppression during sleep, the EB group exhibited superior-medial frontal hypometabolism in a region associated with cortical control of eyelid movement. Network analysis demonstrated a specific metabolic covariance pattern associated with ITD was also expressed in the patients with EB in both the sleep and wake conditions. CONCLUSION: These findings suggest that the clinical manifestations of EB are associated with abnormal metabolic activity in the pons and cerebellum, whereas the functional substrate of the disorder may be associated with abnormalities in cortical eyelid control regions. Furthermore, ITD-related networks are expressed in patients with EB, suggesting a functional commonality between both forms of primary dystonia.
Adult↗