Biomedical subjects
Publications and source records attributed to J Murray.
We report a 47-year-old man with myelofibrosis who presented with bilateral nephromegaly secondary to extramedullary haematopoiesis. We discuss diagnosis and treatment of this rare case and review the literature.
OBJECTIVES: To develop and validate a psychometrically rigorous measure of health-related quality of life (HRQoL) for people with dementia: DEMQOL. DATA SOURCES: Literature review. Expert opinion. Interviews and questionnaires. REVIEW METHODS: Gold standard psychometric techniques were used to develop DEMQOL and DEMQOL-Proxy. A conceptual framework was generated from a review of the literature, qualitative interviews with people with dementia and their carers, expert opinion and team discussion. Items for each component of the conceptual framework were drafted and piloted to produce questionnaires for the person with dementia (DEMQOL) and carer (DEMQOL-Proxy). An extensive two-stage field-testing was then undertaken of both measures in large samples of people with dementia (n = 130) and their carers (n = 126) representing a range of severity and care arrangements. In the first field test, items with poor psychometric performance were eliminated separately for DEMQOL and DEMQOL-Proxy to produce two shorter, more scientifically robust instruments. In the second field test, the item-reduced questionnaires were evaluated along with other validating measures (n = 101 people with dementia, n = 99 carers) to assess acceptability, reliability and validity. RESULTS: Rigorous evaluation in two-stage field testing with 241 people with dementia and 225 carers demonstrated that in psychometric terms: (1) DEMQOL is comparable to the best available dementia-specific HRQoL measures in mild to moderate dementia, but is not appropriate for use in severe dementia [Mini Mental State Examination (MMSE) <10]; and (2) DEMQOL-Proxy is comparable to the best available proxy measure in mild to moderate dementia, and shows promise in severe dementia. In addition, the DEMQOL system has been validated in the UK in a large sample of people with dementia and their carers, and it provides separate measures for self-report and proxy report, which allows outcomes assessment across a wide range of severity in dementia. CONCLUSIONS: The 28-item DEMQOL and 31-item DEMQOL-Proxy provide a method for evaluating HRQoL in dementia. The new measures show comparable psychometric properties to the best available dementia-specific measures, provide both self- and proxy-report versions for people with dementia and their carers, are appropriate for use in mild/moderate dementia (MMSE >/= 10) and are suitable for use in the UK. DEMQOL-Proxy also shows promise in severe dementia. As DEMQOL and DEMQOL-Proxy give different but complementary perspectives on quality of life in dementia, the use of both measures together is recommended. In severe dementia, only DEMQOL-Proxy should be used. Further research with DEMQOL is needed to confirm these findings in an independent sample, evaluate responsiveness, investigate the feasibility of use in specific subgroups and in economic evaluation, and develop population norms. Additional research is needed to address the psychometric challenges of self-report in dementia and validating new dementia-specific HRQoL measures.
Granulocyte apoptosis has been proposed as a fundamental, injury-limiting granulocyte-clearance mechanism. As such, inhibition of this process may prevent the resolution of inflammation. Our previous studies have shown that TNFalpha (tumour necrosis factor-alpha) has a bi-modal influence on the rate of constitutive neutrophil apoptosis in vitro, causing early acceleration and late inhibition of this process. The pro-apoptotic effect is uniquely TNFR1 (TNF receptor 1) and TNFR2-dependent and the latter survival process is mediated via phosphoinositide 3-kinase and NF-kappaB (nuclear factor-kappaB) activation. In the present study, we show that, in contrast with GM-CSF (granulocyte/macrophage colony-stimulating factor), the delayed addition (i.e. at 6 h) of TNFalpha increases its survival effect despite substantial loss of neutrophil TNFR1 and TNFR2 at that time. This paradox was resolved using PBMC (peripheral blood mononuclear cell)-deplete and 5% PBMC-replete neutrophil cultures, where the enhanced survival effect observed after delayed TNFalpha addition was shown to be PBMC-dependent. TNFR2-blocking antibodies had no effect on the late survival effect of TNFalpha, implying a TNFR1-dependent process. Finally, I-kappaBalpha (inhibitory kappaB-alpha) and NF-kappaB time-course studies demonstrated that the survival effects of both GM-CSF and TNFalpha could be explained by maintenance of functional NF-kappaB.
This review is based on research-based literature on occupational lung disease in the mining and related industries, focusing on conditions of public health importance arising from asbestos, coal and silica exposure. Both 'traditional' and 'new' concerns about occupational respiratory disease in miners are addressed, with the inclusion of practical evidence-based findings relevant to practitioners working in developed and developing countries. Mining is not a homogeneous industry since current miners work in formal and informal operations with numerous, and often multiple, air-borne exposures. A further occupational health challenge facing primary care practitioners are ex-miners presenting with disease only after long latency. The sequelae of silica exposure remain an occupational health priority, particularly for practitioners who serve populations with concomitant HIV and tuberculosis infection and even when exposure is apparently below the statutory occupational exposure level. Coal workers' pneumoconiosis, asbestos related diseases, lung cancer and other occupational respiratory diseases remain of considerable importance even after mining operations cease. While mining exposures contribute significantly to lung disease, smoking is a major factor in the development of lung cancer and chronic obstructive airways disease necessitating a comprehensive approach for prevention and control of mining-related occupational lung disease.
A 40 year old man presented with abdominal pain, jaundice, weight loss, and hepatosplenomegaly. Liver function tests revealed cholestatic jaundice and a computed tomography scan showed an enlarged liver, with a normal biliary tree. Liver biopsy showed diffuse infiltration by neutrophils, monocytoid cells, and blasts. Peripheral blood film and bone marrow were consistent with acute myeloid leukaemia. After treatment with chemotherapy using an acute myeloid leukaemia protocol (UK Medical Research Council AML-12), there was complete resolution of jaundice and the patient went into complete molecular remission.
BACKGROUND: Patients undergoing total knee replacement (TKR) in the UK usually have either blood cross-matched or have an auto-transfusion of drained blood postoperatively. A previous retrospective audit of blood requirements in patients who had undergone primary TKR showed that a large amount of cross-matched blood was wasted as the CT ratio (ratio of number of units of blood cross-matched to number of units transfused) of 4.9:1 was obtained. The range recommended by the Blood Transfusion Society is 2:1 to 3:1. METHODS: A protocol was introduced to group and save plus antibody screen for all patients and to cross-match 2 units of blood pre-operatively in patients with either a haemoglobin of less than 12.5 g/dl or with multiple red cell antibodies in their blood. The trigger point for blood transfusion postoperatively was also reduced from 9.0 g/dl to 8.0 g/dl, unless the patient was clinically symptomatic. RESULTS: A further prospective study involving 50 patients was carried out using the new protocol. Five patients required cross-matching pre-operatively, three with haemoglobin less than 12.5 g/dl and two with multiple red cell antibodies. Postoperatively, the patients with haemoglobin of less than 12.5 g/dl required blood transfusion of 2 units each, reducing the CT ratio to 1.7:1. The patients with red cell antibodies did not require a blood transfusion. CONCLUSIONS: The benefits from above protocol are 2-fold: patient safety, as risks of transfusion are avoided; and cost saving, in regards to haematology technician time and auto-transfusion sets which cost around pound 70 each.
The case is reported of a retired professional jockey with progressive memory loss. The concern is that he may be suffering from chronic traumatic encephalopathy or the "punch drunk syndrome".
Charcot is often credited as being the first to describe MS and the one who named it sclérose en plaques disseminées. He himself recognized that this was not true, and in turn acknowledged the contribution of others. The history of the disorder can be traced far beyond the first medical observations, however. There are entries in diaries, case reports and other literature documenting symptoms that could now be classified as MS. These all appeared before Charcots leçons in 1868 and although they did not name or frame the disease, contribute to its recognition. In addition, several physicians observed and documented the pathology of the disease and developed new techniques allowing further investigation. This review details the early documentation of patients with what was probably MS and the contribution of physicians to the delineation of MS as a named disease.
Transmission of caprine arthritis-encephalitis virus (CAEV) is not completely understood and the vertical route of infection from the goat to the embryo or to the fetus needs to be investigated. This route of infection involves the presence of CAEV in the genital tract tissues. Prior studies have detected CAEV-infected cells in genital secretions and in flushing media recovered during embryo collection from infected goats. To specify the origin of these cells, we conducted a double-nested polymerase chain reaction (PCR) test on embryo flushing media and on mammary gland, mammary lymph node, synovial membrane, pelvic lymph node, uterus and oviduct tissues from 25 CAEV-infected (blood PCR positive) embryo donor goats for the presence of CAEV proviral DNA. The presence of proviral DNA was found in 22 of 25 mammary gland samples, 14 of 25 uterus samples, and in 16 of 25 oviduct samples. Nineteen of 25 goats had at least one positive genital tract sample. Flushing media from 11 goats were PCR positive. All goats with positive-flushing media were oviduct positive. Of this group of does, except for 1 of the 11, infection of flushing media correlated with infection of almost all the other tissues examined. The frequency of positive tissues for flushing media-positive goats (61/66; 92%) was significantly higher than that for flushing media-negative goats (50/84; 60%) (P<0.01). This study demonstrated the presence of CAEV-infected cells in the goat genital tract. The presence of CAEV-infected cells in the uterus and oviducts suggests potential for vertical transmission of CAEV from doe to embryo or fetus.
BACKGROUND: The role of postoperative computed tomography (CT) in asymptomatic patients with severe liver injury has not been investigated. The aim of the present study was to investigate the nature and incidence of significant liver-related abnormalities detected by postoperative CT in asymptomatic patients with severe liver injury. METHODS: This was a prospective study of survivors with severe liver injury (grades III-V) who were treated surgically. The patients underwent CT to evaluate the liver after operation, irrespective of symptoms. RESULTS: During the study interval there were 181 patients with severe liver injury, of whom 49 fulfilled the criteria for inclusion. The overall incidence of liver-related complications detected by CT was 49 per cent (necrotic areas in the liver in seven patients, seven bilomas, four abscesses, three perihepatic collections and three false aneurysms). In the subgroup of 17 asymptomatic patients CT revealed four abnormalities: two large bilomas, one false aneurysm and one fluid collection. Two of these patients required therapeutic intervention and the other two remained under observation. CONCLUSION: In view of the incidence of asymptomatic significant liver abnormalities following operative management of severe liver injury, it is recommended that these patients undergo routine postoperative CT.
A low-density, male-based linkage map was constructed as one of the objectives of the International Equine Gene Mapping Workshop. Here we report the second generation map based on testing 503 half-sibling offspring from 13 sire families for 344 informative markers using the CRIMAP program. The multipoint linkage analysis localized 310 markers (90%) with 257 markers being linearly ordered. The map included 34 linkage groups representing all 31 autosomes and spanning 2262 cM with an average interval between loci of 10.1 cM. This map is a milestone in that it is the first map with linkage groups assigned to each of the 31 automosomes and a single linkage group to all but three chromosomes.
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OBJECTIVE: To identify what patient and carer characteristics influence transition into residential care for people with dementia. METHOD: Longitudinal study of a cohort of people with dementia and their carers in contact with old age psychiatric services in south London. RESULTS: 100 people with dementia and their main family carer were recruited. At six month follow up 22 were in residential care, 63 in the community, 8 had died, and for 7 there were missing data. Between six and 12 months, 7 of the 63 in the community went into residential care, 4 died, and 12 were lost to follow up. The most striking finding is the 20-fold protective effect of having a co-resident carer (odds ratio 0.05, 95% confidence intervals 0.01 to 0.42, p=0.006). Higher ratings of behavioural problems in the person with dementia were also statistically significantly associated with transition into residential care as was the psychological domain of quality of life of the carer. CONCLUSION: These findings powerfully illustrate the pivotal role carried out by carers of people with dementia; interventions directly targeted at helping them to maintain this role would be supported by these data. These data also suggest that strategies directed at improving carer quality of life and at the resolution of behavioural disorder in the person with dementia may also have particular value.
Activation of the NADPH oxidase system to generate reactive oxygen species (ROS) plays a key role in bacterial killing by human neutrophils. However, the involvement of such radicals in spontaneous and TNFalpha-driven neutrophil apoptosis remains uncertain. While incubation of cells under anoxic conditions attenuated the pro-apoptotic effect of TNFalpha, full activation of the respiratory burst using PAF followed by fMLP, or the addition of physiologically relevant concentrations of H(2)O(2), had no effect on the rate of apoptosis. Furthermore, the phosphoinositide 3-kinase inhibitor, LY294002, which abolishes receptor-mediated activation of the NADPH oxidase, and five discrete anti-oxidants all failed to affect apoptotic thresholds. Thus ROS do not appear to modulate constitutive apoptosis in neutrophils or appear sufficient to mediate the pro-apoptotic effect of TNFalpha.
Knobloch syndrome (KS) is a rare disease characterized by severe ocular alterations, including vitreoretinal degeneration associated with retinal detachment and occipital scalp defect. The responsible gene, COL18A1, has been mapped to 21q22.3, and, on the basis of the analysis of one family, we have demonstrated that a mutation affecting only one of the three COL18A1 isoforms causes this phenotype. We report here the results of the screening of both the entire coding region and the exon-intron boundaries of the COL18A1 gene (which includes 43 exons), in eight unrelated patients with KS. Besides 20 polymorphic changes, we identified 6 different pathogenic changes in both alleles of five unrelated patients with KS (three compound heterozygotes and two homozygotes). All are truncating mutations leading to deficiency of one or all collagen XVIII isoforms and endostatin. We have verified that, in exon 41, the deletion c3514-3515delCT, found in three unrelated alleles, is embedded in different haplotypes, suggesting that this mutation has occurred more than once. In addition, our results provide evidence of nonallelic genetic heterogeneity in KS. We also show that the longest human isoform (NC11-728) is expressed in several tissues (including the human eye) and that lack of either the short variant or all of the collagen XVIII isoforms causes similar phenotypes but that those patients who lack all forms present more-severe ocular alterations. Despite the small sample size, we found low endostatin plasma levels in those patients with mutations leading to deficiency of all isoforms; in addition, it seems that absence of all collagen XVIII isoforms causes predisposition to epilepsy.
To improve the knowledge on the risk of transmission of the caprine arthritis-encephalitis virus (CAEV) during embryo manipulations, we conducted a double-nested polymerase chain reaction (PCR) for CAEV proviral-DNA on flushing media recovered from the oviducts 48 h after the beginning of estrus and on blood from 89 donor does. Sixty-four does had negative blood and flushing media by PCR. Among the 25 CAEV infected goats (blood PCR positive), 11 were PCR flushing media positive (P < 0.01). Cell lysate from flushing media samples that were PCR positive were serially diluted 10 times at 1:100. Starting with the second 1:100 dilution all the cell lysate samples were PCR negative. The mean number of embryos recovered was not significantly different between goats with flushing media PCR positive and goats with flushing media PCR negative (6.0 +/- 5.4 versus 7.8 +/- 4.4, respectively; mean +/- S.D.) nor between goats with blood PCR positive and goats with blood PCR negative (7.0 +/- 5.0 versus 5.9 +/- 5.3; mean +/- S.D.). The presence of CAEV infected cells in oviductal flushing media from infected donor does was indicated for the first time during this study. The absence of flushing media PCR positive for goat blood PCR negative seemed to allow the use of the blood PCR test to confidently predict the absence of CAEV provirus in the oviductal fluid.
BACKGROUND: Despite significant injuries elderly patients (aged 70 years or more) often do not exhibit any of the standard physiological criteria for trauma team activation (TTA), i.e. hypotension, tachycardia or unresponsiveness to pain. As a result of these findings the authors' TTA criteria were modified to include age 70 years or more, and a protocol of early aggressive monitoring and resuscitation was introduced. The aim of the present study was to assess the effect of the new policy on outcome. METHODS: This trauma registry study included patients aged 70 years or more with an Injury Severity Score (ISS) greater than 15 who were admitted over a period of 8 years and 8 months. The patients were divided into two groups: group 1 included patients admitted before age 70 years and above became a TTA criterion and group 2 included patients admitted during the period when age 70 years or more was a TTA criterion and the new management protocol was in place. The two groups were compared with regard to survival, functional status on discharge and hospital charges. RESULTS: There were 336 trauma patients who met the criteria, 260 in group 1 and 76 in group 2. The two groups were similar with respect to mechanism of injury, age, gender, ISS and body area Abbreviated Injury Score. The mortality rate in group 1 was 53.8 per cent and that in group 2 was 34.2 per cent (P = 0.003) (relative risk (RR) 1.57 (95 per cent confidence interval 1.13 to 2.19)). The incidence of permanent disability in the two groups was 16.7 and 12.0 per cent respectively (P = 0.49) (RR 1.39 (0.59 to 3.25)). In subgroups of patients with an ISS of more than 20 the mortality rate was 68.4 and 46.9 per cent in groups 1 and 2 respectively (P = 0.01) (RR 1.46 (1.06 to 2.00)); 12 of 49 survivors in group 1 and two of 26 in group 2 suffered permanent disability (P = 0.12) (RR 3.18 (0.77 to 13.20)). CONCLUSION: Activation of the trauma team and early intensive monitoring, evaluation and resuscitation of geriatric trauma patients improves survival.
Details of service receipt by 132 people diagnosed with dementia and their carers were collected in South London (boroughs of Lewisham, Camberwell, Southwark and Croydon), a geographical area served by several health and social care providers. The data collected included the Caregiver Activity Survey, which details the informal care given. This paper reports the formal and informal services received by the people with dementia at entry to the study. The amount of time spent on specific caring tasks by all informal carers of people with dementia averaged seven hours per week, but was significantly higher for co-resident carers, even when controlling for the level of dependency of the person cared-for. The odds ratios of receipt of formal services are given, according to where people were living: in the community or residential care, with co-resident carers or alone.