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Biomedical subjects

R Harrison

Publications and source records attributed to R Harrison.

At least 73 records · Page 4Linked to original sources

Do experienced diagnosticians agree about the diagnosis of dementia from survey data? The effects of informants' reports and interviewers' vignettes.

Dementia in community settings is often diagnosed by computerized algorithms. This study examines the extent to which independent diagnosticians agreed among themselves in diagnosing dementia, severity and type when presented with data obtained during a population-based incidence study of cognitive decline and dementia. Secondly, it examines how judgements, based initially on respondents' self-reports and cognitive performance, were affected first by informants' reports and then by short case-vignettes written by trained lay interviewers. Thirdly, it compares diagnosticians' diagnosis of dementia with the algorithmic diagnosis (AGECAT). The items presented were selected from two screening interviews at wave 1 and wave 2 separated by an interval of 2 years and from wave 2 assessment and informant interviews, and included medical, psychiatric and ADL items and interviewers' own observations. The sample (N = 42) was derived from the first year of the wave 2 assessments, potential dementia cases entering consecutively while presumed normals were selected randomly. Informants were available in 30. Agreement on diagnosis and type of dementia improved with increasing information, particularly from informants, but remained poor regarding severity. The number of cases of dementia, defined operationally, increased from 10 to 12 and uncertain cases fell from eight to six, but no respondent initially diagnosed as a dementia case was rediagnosed as a non-case, or vice versa. Dementia type changed from agreement about Alzheimer's disease to agreement about vascular dementia in one case. Operational and algorithmic diagnoses showed good agreement. Causes of disagreement, the role of vignettes and the relevance of the results for population surveys are discussed.

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A prospective study of dementia with Lewy bodies.

BACKGROUND: little is known about the longitudinal course of dementia with Lewy bodies (DLB) and how this differs from Alzheimer's disease (AD). METHOD: standardized baseline and annual assessments of cognitive and non-cognitive symptoms are reported in a cohort of 72 patients with DLB or AD. AD was diagnosed using the NINCDS ADRDA criteria and DLB was diagnosed with the criteria of McKeith et al. Cognitive assessment was undertaken using the MMSE schedule and operationalized definitions were used to diagnose non-cognitive symptoms. RESULTS: 42 patients with DLB and 30 patients with AD were assessed. Of the 19 on whom post mortem examinations have been performed, 18 (95%) have had the clinical diagnosis confirmed. DLB patients were significantly more likely to experience visual hallucinations, disturbances of consciousness and parkinsonism at both baseline and at annual assessments. Of DLB patients exposed to neuroleptics, 33% developed sensitivity reactions. The magnitude and pattern of cognitive decline was similar in both groups. CONCLUSION: the importance of the core features highlighted in the newly proposed consensus DLB criteria is supported. These features appear to be stable over time.

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Long-term results of pediatric liver transplantation: an analysis of 569 transplants.

OBJECTIVE: To analyze a single center's 13-year experience with 569 pediatric orthotopic liver transplants for end-stage liver disease. SUMMARY BACKGROUND DATA: Despite advances in medical therapy, liver replacement continues to be the only definitive mode of therapy for children with end-stage liver disease. Innovative surgical techniques and improved immunosuppression have broadened the application of liver replacement for affected children. However, liver transplantation in the child remains challenging because of the scarcity of donor organs, complex surgical technical demands, and the necessity to prevent long-term complications. METHODS: The medical records of 440 consecutive patients younger than 18 years of age undergoing orthotopic liver transplantation for end-stage liver disease from March 20, 1984, to November 15, 1997, were reviewed. Results were analyzed using Cox multivariate regression analysis to determine the statistical strength of independent associations between pretransplant covariates and patient and graft survival. Actuarial patient and graft survival rates were determined at 1, 3, 5, and 10 years. The type and incidence of posttransplant complications were determined, as was the quality of long-term allograft function. The median follow-up period was 4.1 years. RESULTS: Biliary atresia was the most common cause (50.4%) of endstage liver disease in this patient population. The median recipient age was 2.4 years; 239 patients (54%) were younger than 3 years of age and 1 11 patients (25%) were younger than 1 year of age. There were 471 whole organs, 29 were ex vivo reduced size, 33 were living-related donor, and 36 were in situ split-liver allografts. Three hundred forty-three (78%) patients underwent a single allograft, whereas 97 patients required retransplantation; hepatic artery thrombosis was the most common indication for retransplantation (55 patients). The 1-, 3-, 5-, and 10-year actuarial patient survival rates were 82%, 80%, 78%, and 76%, respectively; allograft survival rates were 68%, 63%, 60%, and 54%. Long-term liver function remains excellent: current median follow-up values for total bilirubin and aspartate aminotransferase were 0.5 mg/dl and 54 IU/L, respectively. Cox multivariate regression analysis demonstrated that pretransplant patient age, the era of transplantation, and the number of allografts performed significantly and independently predicted patient survival rates, whereas allograft type and pretransplant diagnosis did not. CONCLUSIONS: Liver transplantation in the pediatric patient is a durable procedure that provides excellent long-term survival. Although there have been overall improvements in patient outcome with increased experience, the effect is most pronounced for patients younger than 1 year of age. Retransplantation, although effective in a meaningful number of patients, continues to carry a progressive decrement in survival with the number of allografts performed. Use of living-related and in situ split-liver allografts has dramatically reduced waiting times for small children and has improved patient survival.

Actuarial Analysis↗

A reappraisal of xanthine dehydrogenase and oxidase in hypoxic reperfusion injury: the role of NADH as an electron donor.

Xanthine oxidase (XO) is conventionally known as a generator of reactive oxygen species (ROS) which contribute to hypoxic-reperfusion injury in tissues. However, this role for human XO is disputed due to its distinctive lack of activity towards xanthine, and the failure of allopurinol to suppress reperfusion injury. In this paper, we have employed native gel electrophoresis together with activity staining to investigate the role human xanthine dehydrogenase (XD) and XO in hypoxic reperfusion injury. This approach has provided information which cannot be obtained by conventional spectrophotometric assays. We found that both XD and XO of human umbilical vein endothelial cells (HUVECs) and lymphoblastic leukaemic cells (CEMs) catalysed ROS generation by oxidising NADH, but not hypoxanthine. The conversion of XD to XO was observed in both HUVECs and CEMs in response to hypoxia, although the level of conversion varied. Purified human milk XD generated ROS more efficiently in the presence of NADH than in the presence of hypoxanthine. This NADH oxidising activity was blocked by the FAD site inhibitor, diphenyleneiodonium (DPI), but was not suppressible by the molybdenum site inhibitor, allopurinol. However, in the presence of both DPI and allopurinol the activities of XD/XO were completely blocked with either NADH or hypoxanthine as substrates. We conclude that both human XD and XO can oxidise NADH to generate ROS. Therefore, the conversion of XD to XO is not necessary for post-ischaemic ROS generation. The hypoxic-reperfusion injury hypothesis should be reappraised to take into account the important role played by XD and XO in oxidising NADH to yield ROS.

Allopurinol↗

The "hidden patient": older relatives raising children orphaned by AIDS.

In the United States today, thousands of grandmothers and other third- and fourth-generation relatives are raising children and adolescents whose primary parent, usually the mothers, has died from acquired immune deficiency syndrome (AIDS) or is too ill to serve as the primary parent. More than 100,000 children below the age of 18 are expected to lose their mothers to AIDS by the year 2000, most in poor communities. Isolated by the demands of caregiving, child care, and the stigma of AIDS on even uninfected family members, this group of older surrogate parents is at risk not only for chronic conditions and stress-related somatic complaints, but for neglected health. Using the gerontological concept of the "hidden patient," this article presents four cases drawn from an exploratory study of the physical and emotional health risks and health behaviors of older adults raising children orphaned by AIDS. External and internal barriers to self-care are described, including lack of child and respite care and health insurance, caregiver depression, and denial of health problems.

Acquired Immunodeficiency Syndrome↗

Pre-admission clinic in an orthopaedic department: evaluation over a 6-month period.

A pre-admission clinic for patients undergoing elective orthopaedic surgery has been used at the Royal Surrey County Hospital, Guildford, for the past 3 years. This report audits the activities of the clinic over a period of 6 months. Data regarding the patients who were invited to the pre-admission clinic during the study period were analysed. In all, 232 patients were asked to attend the clinic and a total of 221 (95.2%) attended. Of these patients, 10 had their operations cancelled and three had their operations postponed in the clinic due to various medical and social reasons. Another 28 operations were cancelled or postponed at a later stage. All of the postponed procedures were eventually performed within 3 months. Of the 232 patients, 180 (77.5%) underwent their operation on the arranged day without any complications. The pre-admission clinic in our orthopaedic department helps us to prevent a significant number of operation cancellations on the day of admission. It also facilitates an extensive pre-operative assessment of the patients and reduces the ward-based workload of the junior medical staff. More extensive use of the pre-admission clinic is recommended.

Adolescent↗

Structure of monellin refined to 2.3 a resolution in the orthorhombic crystal form.

The structure of orthorhombic crystals of monellin, a sweet protein extracted from African serendipity berries, has been solved by molecular replacement and refined to 2.3 A resolution. The final R factor was 0.150 for a model with excellent geometry. A monellin molecule consists of two peptides that are non-covalently bound, with chain A composed of three beta-strands interconnected by loop regions and chain B composed of two beta-strands interconnected by an alpha-helix. The N terminus of chain A is in close proximity to the C terminus of chain B. The two molecules in the asymmetric unit are related by a non-crystallographic twofold axis and form a dimer, similar to those previously observed in other crystal forms of both natural and single-chain monellin. The r.m.s, deviation between the Calpha atoms in the two independent molecules is 0.60 A, while the deviations from the individual molecules in the previously reported monoclinic crystals are 0.50-0.57 A. This result proves that the structure of monellin is not significantly influenced by crystal packing forces.

Journal Article↗

Anionic- and lipophilic-mediated surface binding inhibitors of human leukocyte elastase.

We report the synthesis of a series of diphenylmethane-based oligomers containing anionic and lipophilic functionalities that are potent inhibitors of human leukocyte elastase (HLE). The enzyme inhibition is regulated by the size of the oligomer, as well as, the number of charges. Lipophilicity is an important element in determining potency and specificity against other basic enzymes. Compounds whose scaffolds contain three phenoxyacetic acid groups and three alkyl ethers are competitive and specific inhibitors of HLE with Ki = 20 nM. The mechanism of action of this class of compounds is believed to involve multidendate interactions with the surface of HLE near the active site which prevents substrate access to the catalytic site.

Benzhydryl Compounds↗

NADH oxidase activity of human xanthine oxidoreductase--generation of superoxide anion.

Human xanthine oxidase was purified from breast milk. The dehydrogenase form of the enzyme, which predominates in most mammalian tissues, catalyses the oxidation of NADH by oxygen, generating superoxide anion significantly faster than does the oxidase form. The corresponding forms of bovine enzyme behave very similarly. The steady-state kinetics of NADH oxidation and superoxide production, including inhibition by NAD, by the dehydrogenase forms of both enzymes, are analysed in terms of a model involving two-stage recycling of oxidised enzyme. Established inhibitors of xanthine oxidoreductases (allopurinol oxypurinol, amflutizole and BOF 4272), which block all other reducing substrates, were ineffective in the case of NADH. Diphenyleneiodonium, on the other hand, was a powerful inhibitor of NADH oxidation. The potential involvement of reactive oxygen species arising from NADH oxidation by xanthine oxidoreductase in ischaemia-reperfusion injury and other disease states, as well as in normal signal transduction, is discusssed.

Animals↗

A detailed phenomenological comparison of complex visual hallucinations in dementia with Lewy bodies and Alzheimer's disease.

Visual hallucinations (VH) are a core feature of dementia with Lewy bodies (DLB), but little is known about their phenomenology. A total of 73 dementia patients (42 DLB, 30 Alzheimer's disease [AD], 1 undiagnosed) in contact with clinical services were assessed with a detailed standardized inventory. DLB was diagnosed according to the criteria of McKeith and colleagues, AD was diagnosed using the NINCDS-ADRDA criteria. Autopsy confirmation has been obtained when possible. VH were defined using the definition of Burns and colleagues. Detailed descriptions of hallucinatory experiences were recorded. Annual follow-up interviews were undertaken. The clinical diagnosis has been confirmed in 18 of the 19 cases that have come to autopsy. A total of 93% of DLB patients and 27% of AD patients experienced VH. DLB patients were significantly more likely to experience multiple VH that persisted over follow-up. They were significantly more likely to hear their VH speak but there were no significant differences in the other phenomenological characteristics including whether the hallucinations moved, the time of day that they were experienced, their size, the degree of insight, and whether they were complete. VH may be more likely to be multiple, to speak, and to be persistent in DLB patients. These characteristics could potentially aid accurate diagnosis.

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