Reversal of asymptomatic over-anticoagulation with oral vitamin K.
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Anticoagulants↗
Biomedical subjects
C Morrison
Publications and source records attributed to C Morrison.
Overview of a paediatric renal transplant programme.
INTRODUCTION: Renal transplantation is the therapy of choice for children with end-stage renal failure. There are many challenges associated with a paediatric programme in a developing country where organs are limited. METHODS: A retrospective review was undertaken of 149 paediatric renal transplants performed between 1968 and 2006 with specific emphasis on transplants performed in the last 10 years. Survival of patients and grafts was analysed and specific problems related to drugs and infections were reviewed. RESULTS: On review of the total programme, 60% of the transplants have been performed in the last 10 years, with satisfactory overall patient and graft survival for the first 8 years post transplant. At this point, transfer to adult units with non-compliance becomes a significant problem. Rejection is less of a problem than previously but infection is now a bigger issue--specifically tuberculosis (TB), cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections with related complications. A wide variety of drugs are available for tailoring immunosuppression to minimise side-effects. CONCLUSION: It is possible to have a successful paediatric transplant programme in a developing country. However, to improve long-term outcomes certain issues need to be addressed, including reduction of nephrotoxic drugs and cardiovascular risk factors and providing successful adolescent to adult unit transition.
Adolescent↗
Patients strategies for managing medication for chronic heart failure.
OBJECTIVES: To explore patients views of the management of medication of chronic heart failure (CHF); to explore in what circumstances they have difficulties in managing medication. DESIGN: Qualitative analysis of in-depth interviews using a constant comparative approach. PARTICIPANTS: Patients attending an outpatients clinic with a primary diagnosis of CHF due to left ventricular systolic dysfunction, NYHA Class II or III symptoms, and a history of hospital admission for heart failure. RESULTS: 50 patients were recruited, average age 67.1 years with ranges between 41 and 80 years. 26 were classified as NYHA Class II and 24 Class III. Patients reported developing routines and back up strategies to help with the complex task of medication-taking. They also described circumstances in which they were more likely not to take medication. CONCLUSIONS: This study demonstrates, with a large sample of respondents, the complexities of medication-taking and the difficulties of maintaining constant medication over a long period of time. The study provides examples of patients' strategies for so doing. Health care professionals should recognise that concordance may vary but explore ways in which they can help patients establish routines.
Adult↗
Pre-hospital coronary care and coronary fatality in the Belfast and Glasgow MONICA populations.
BACKGROUND: The aim of this study was to describe and compare coronary event case fatality and care pathways in two defined populations with access to different models of pre-hospital care provision. METHODS: Secondary analysis of MONItoring of Trends and Determinants in CArdiovascular Disease (MONICA) population coronary event registers (1988, 1989, 1990, 1992 and 1993). RESULTS: Case fatality at 28 days following an acute coronary event was 6.5% greater in the Glasgow MONICA Project (GMP) population (46.7%) than in the Belfast MONICA Project (BMP) population (40.2%). Pre-hospital case fatality was 33.9% in the GMP population and 28.3% in the BMP population. These differences could not be fully explained by mobile coronary care unit (MCCU) responses in the BMP area. Initial care was provided in hospital for 28.3% of the BMP events and only 7.7% of the GMP events. Additional data collected by the Belfast and Glasgow MONICA investigators support a large difference between the median delay to main medical care in the BMP events (120 min) and the median delay to ward admission in the GMP area (220 min) at this time. CONCLUSIONS: Our findings suggest that the delay between coronary event onset and access to specialist coronary care was the most likely critical difference, irrespective of hospital-based MCCU provision in the BMP area. An established 'culture of early intervention' in Belfast may have been an important factor. As a large proportion of coronary event fatalities continue to occur outside hospital, there is a need to strengthen the evidence base underpinning the provision of appropriate skilled care and treatment at the earliest possible opportunity.
Adult↗
Melanin concentrating hormone innervation of caudal brainstem areas involved in gastrointestinal functions and energy balance.
Neural signaling by melanin-concentrating hormone and its receptor (SLC-1) has been implicated in the control of energy balance, but due to the wide distribution of melanin-concentrating hormone-containing fibers throughout the neuraxis, its critical sites of action for a particular effect have not been identified. The present study aimed to anatomically and functionally characterize melanin-concentrating hormone innervation of the rat caudal brainstem, as this brain area plays an important role in the neural control of ingestive behavior and autonomic outflow. Using retrograde tracing we demonstrate that a significant proportion (5-15%) of primarily perifornical and far-lateral hypothalamic melanin-concentrating hormone neurons projects to the dorsal vagal complex. In the caudal brainstem, melanin-concentrating hormone-ir axon profiles are distributed densely in most areas including the nucleus of the solitary tract, dorsal motor nucleus of the vagus, and sympathetic premotor areas in the ventral medulla. Close anatomical appositions can be demonstrated between melanin-concentrating hormone-ir axon profiles and tyrosine hydroxylase, GABA, GLP-1, NOS-expressing, and nucleus of the solitary tract neurons activated by gastric nutrient infusion. In medulla slice preparations, bath application of melanin-concentrating hormone inhibited in a concentration-dependent manner the amplitude of excitatory postsynaptic currents evoked by solitary tract stimulation via a pre-synaptic mechanism. Fourth ventricular administration of melanin-concentrating hormone (10 microg) in freely moving rats decreased core body temperature but did not change locomotor activity and food and water intake. We conclude that the rich hypothalamo-medullary melanin-concentrating hormone projections in the rat are mainly inhibitory to nucleus of the solitary tract neurons, but are not involved in the control of food intake. Projections to ventral medullary sites may play a role in the inhibitory effect of melanin-concentrating hormone on energy expenditure.
Animals↗
Neuropsychological assessment of patients with late onset GM2 gangliosidosis.
OBJECTIVE: To characterize cognitive status in a sample of individuals with late-onset GM2 gangliosidosis (commonly referred to as late-onset Tay-Sachs disease). METHODS: Seventeen subjects (13 men, 4 women) diagnosed with GM2 gangliosidosis were evaluated. Subjects ranged in age from 18 to 56 years and were in various stages of disease progression. Subjects underwent comprehensive neuropsychological assessment. Impairment was defined as performance more than 1.6 SD below the normative mean. RESULTS: Group mean performance was within the denoted normal range on all measures except on a task assessing visual sequencing and set shifting. Approximately one-half of the sample scored in the impaired range on measures of processing speed, visual sequencing, and set shifting. One-third of the sample also scored in the impaired range on measures of delayed verbal recall. Impairment tended to be restricted to a subset of the sample, as 5 of the 14 subjects able to undergo formal testing accounted for 70% of the total number of impaired scores. If the three subjects unable to participate in formal testing are also considered impaired, 47% of the current sample exhibited significant cognitive impairment in at least one cognitive domain. CONCLUSION: In late-onset GM2 gangliosidosis, there is a risk of impairment in executive functioning and memory as well as cerebellar dysfunction. Dementia was not present in any subjects in the current sample.
Adolescent↗
Use of the Brief Visuospatial Memory Test-Revised (BVMT-R) in neuropsychological evaluation of epilepsy surgery candidates.
Many commonly used measures of figural reproduction have been found to be relatively insensitive to the effects of right temporal lobe dysfunction. More positive findings are present in studies using measures of figural learning over repeated trials. This study examined the use of a commercially available measure of figural learning in a sample of epilepsy patients undergoing presurgical neuropsychological testing. The Brief Visuospatial Memory Test-Revised (BVMT-R) was administered to 47 subjects undergoing comprehensive presurgical workups with video and EEG monitoring. Groups with left (N = 25) and right (N = 22) temporal lobe seizures did not differ on BVMT-R measures of learning, delayed recall, or yes/no recognition. Approximately 29% of the sample exhibited "impaired" performance in comparison to published norms. The results of receiver operating curve analyses revealed little discrimination in performance between groups. The BVMT-R does not appear to have the sensitivity required for assessing nonverbal memory in this population.
Adult↗
Distribution of TT virus (TTV), TTV-like minivirus, and related viruses in humans and nonhuman primates.
TT virus (TTV) and TTV-like minivirus (TLMV) are small DNA viruses with single-stranded, closed circular, antisense genomes infecting man. Despite their extreme sequence heterogeneity (>50%), a highly conserved region in the untranslated region (UTR) allows both viruses to be amplified by polymerase chain reaction (PCR). TTV/TLMV infection was detected in 88 of 100 human plasma samples; amplified sequences were differentiated into TTV and TLMV by analysis of melting profiles, showing that both viruses were similarly prevalent. PCR with UTR primers also detected frequent infection with TTV/TLMV-related viruses in a wide range of apes (chimpanzees, gorillas, orangutans, gibbons) and African monkey species (mangabeys, drills, mandrills). These findings support the hypothesis for the co-evolution of TTV-like viruses with their hosts over the period of primate speciation, potentially analogous to the evolution of primate herpesviruses.
Animals↗
Evaluation of a dietary targets monitor.
OBJECTIVE: To evaluate a two-page food frequency list for use as a Dietary Targets Monitor in large scale surveys to quantify consumptions of the key foods groups targeted in health promotion. DESIGN: Intakes of fruit and vegetables, starchy foods and fish estimated from a validated food frequency questionnaire (FFQ) were compared with a short food frequency list (the Dietary Targets Monitor) specifically designed to assess habitual frequency of consumption of foods in relation to dietary targets which form the basis of a National (Scottish) Food and Health Policy. SUBJECTS: A total of 1085 adults aged 25-64 y from the Glasgow MONICA Study. RESULTS: : The two questionnaires both collected data on frequencies of food consumption for fruit and vegetables, starchy foods and fish. Comparing the two questionnaires, there were consistent biases, best expressed as ratios (FFQ:Dietary Targets Monitor) between the methods for fruit and vegetables (1.33, 95% CI 1.29, 1.38) and 'starchy foods' (1.08, 95% CI 1.05, 1.12), the DTM showing systematic under-reporting by men. For fish consumption, there was essentially no bias between the methods (0.99, 95% CI 0.94, 1.03). Using calibration factors to adjust for biases, the Dietary Targets Monitor indicated that 16% of the subjects were achieving the Scottish Diet food target (400 g/day) for fruit and vegetable consumption. Nearly one-third (32%) of the subjects were eating the recommended intakes of fish (three portions per week). The Dietary Targets Monitor measure of starchy foods consumption was calibrated using FFQ data to be able to make quantitative estimates: 20% of subjects were eating six or more portions of starchy food daily. A similar estimation of total fat intake and saturated fat intake (g/day) allowed the categorization of subjects as low, moderate or high fat consumers, with broad agreement between the methods. The levels of agreement demonstrated by Bland-Altman analysis, were insufficient to permit use of the adjusted DTM to estimate quantitative consumption in smaller subgroups. CONCLUSIONS: The Dietary Targets Monitor provides a short, easily administered, dietary assessment tool with the capacity to monitor intakes for changes towards national dietary targets for several key foods and nutrients.
Adult↗
Trends and social factors in blood pressure control in Scottish MONICA surveys 1986-1995: the rule of halves revisited.
Time trends and social factors in detection, treatment and control of hypertension in the community were examined in four independent Scottish MONICA cross-sectional surveys in 1986, 1989, 1992 and 1995. Residents aged 25-64 years were recruited randomly from general practice lists in north Glasgow, Scotland with stratification by sex and 10-year age groups. A total of 1262 participated in the first survey, 1397 in the second, 1516 in the third and 1836 in the fourth. Differences and trends in proportions of hypertension undetected, detected but untreated, treated but uncontrolled and controlled across the four surveys were tested by chi(2), and the associations of the poor control of hypertension with social factors were estimated by multivariate logistic regression model to derive odds ratios. Using the cut point of >/=160/95 mmHg, proportion of hypertension undetected across the four surveys was 56.3, 44.6, 32.0 and 38.2%, and of treated controlled hypertension was 15.2, 26.4, 32.0 and 32.8% (both trends P<0.001). Multivariate analysis showed that poor control of hypertension was not related to social deprivation, but significantly related to being male, young, of low body mass index and heavy alcohol drinking. Undetected hypertension was significantly related to full-time employment, and untreated hypertension to high social class and possibly education level. These findings suggest that in this part of Scotland the management of hypertension has improved, so the 'rule of halves' no longer applies. Control of blood pressure is not positively associated with social deprivation, but people at a high risk of poor control of hypertension should be targeted.
Adult↗
Sister chromatid cohesion and genome stability in vertebrate cells.
For successful eukaryotic mitosis, sister chromatid pairs remain linked after replication until their kinetochores have been attached to opposite spindle poles by microtubules. This linkage is broken at the metaphase-anaphase transition and the sisters separate. In budding yeast, this sister chromatid cohesion requires a multi-protein complex called cohesin. A key component of cohesin is Scc1/Mcd1 (Rad21 in fission yeast). Disruption of the chicken orthologue of Scc1 by gene targeting in DT40 cells causes premature sister chromatid separation. Cohesion between sister chromatids is likely to provide a substrate for post-replicative DNA repair by homologous recombination. In keeping with this role of cohesion, Scc1 mutants also show defects in the repair of spontaneous and induced DNA damage. Scc1-deficient cells frequently fail to complete metaphase chromosome alignment and show chromosome segregation defects, suggesting aberrant kinetochore function. Consistent with this, the chromosomal passenger protein, INCENP (inner centromere protein) fails to localize to centromeres. Survivin, another passenger protein and one which interacts with INCENP, also fails to localize to centromeres in Scc1-deficient cells. These results show that cohesin maintains genomic stability by ensuring appropriate DNA repair and equal chromosome segregation at mitosis.
Animals↗
The concomitant occurrence of multiple epidermal cysts, osteomas and thyroid gland nodules is not diagnostic for Gardner syndrome in the absence of intestinal polyposis: a clinical and genetic report.
Gardner syndrome, a phenotypic variant of familial adenomatous polyposis, is characterized by the classical clinical triad of skin and soft tissue tumours, osteomas and intestinal polyposis, but disease patterns with pairs of these findings have also been reported. Different mutations in the adenomatous polyposis coli (APC) gene have been shown to be associated with Gardner syndrome disease phenotypes. A 36-year-old patient presented with multiple epidermal cysts on the face, left ear lobe and neck, and the possible diagnosis of Gardner syndrome was based on the additional findings of two classical osteomas in the left radius and ulna and a cold non-malignant nodule of the thyroid gland. Intestinal polyposis was lacking at the time of examination. Major deletions but not microdeletions were excluded by a cytogenetic analysis with 650 chromosomal bands per haploid set. Systematic sequencing of the entire coding region of the APC gene (> 8500 bp) of the patient and five healthy controls was also performed. As a results, new APC gene polymorphisms were identified in exons 13 [A545A (A/G)] and 15 [G1678G (A/G), S1756S (G/T), P1960P (A/G)]. We also detected D1822V (A/T) which has recently been reported to be potentially related to colorectal carcinoma, and genotyped 194 randomly chosen healthy individuals from the Glasgow area for this as well as for the above variants in exons 13 and 15. Interestingly, of the 194 controls, 112 carried the DD (57.7%), 71 the DV (36.6%), and the remaining 11 (5.7%), including our patient, the VV genotype. It is therefore unlikely that APC D1822V serves as an important marker for colorectal carcinoma. In conclusion, we failed to identify obvious germline candidate mutations in > 8500 bp of the coding region of the APC gene in a patient with multiple epidermal cysts, osteomas and a thyroid gland nodule; major chromosomal deletions were excluded. Therefore, we assume that only the presence of intestinal polyposis is a marker for Gardner syndrome.
Adult↗
Hyperparathyroidism-jaw tumour syndrome.
Amongst hyperparathyroidism-related syndromes, hyperparathyroidism-jaw tumour syndrome is one of the least common and relatively unknown but its clinical and genetic aspects are not less interesting or important. With the recent identification of its genes, we can now better characterize the disease, both clinically and genetically, which will certainly impact the field of endocrinology and oncology. In this article, we review the clinico-pathological features and genetic basis of this syndrome with the hope that it will create awareness and interest in this disease amongst clinicians and basic scientists.
Genes, Tumor Suppressor↗
Clinical findings of a myoclonus-dystonia family with two distinct mutations.
Myoclonus-dystonia has recently been associated with mutations in the epsilon-sarcoglycan gene (SCGE) on 7q21. Previously, the authors reported a patient with myoclonus-dystonia and an 18-bp deletion in the DYT1 gene on 9q34. The authors have now re-evaluated the patient harboring this deletion for mutations in the SGCE gene and identified a missense change. In the current study, the authors describe the clinical details of this family carrying mutations in two different dystonia genes. Further analysis of these mutations separately and together in cell culture and in animal models should clarify their functional consequences.
Adolescent↗
An economic analysis of specialist heart failure nurse management in the UK; can we afford not to implement it?
AIMS: Hospital activity represents the major component of health care expenditure related to heart failure. This study evaluated the economic impact of applying specialist nurse management programmes that limit heart failure-related hospital readmissions within a whole population. METHODS: Using a reliable and validated estimate of the current level and cost of heart failure-related hospital activity in the U.K., we determined the thresholds at which the actual cost of establishing and applying a national service based on three different models of specialist nurse management would be equal to the 'cost' of bed utilization associated with preventable hospital readmissions in the year 2000. The three models of care examined were home-based, clinic-based or a combination of home plus clinic-based, post-discharge follow-up. The potential impact of this service was based on a U.K.-wide caseload of 122,000 patients discharged to home with a discharge diagnosis of congestive heart failure in that year. RESULTS: Based on heart failure-specific patterns of hospital activity, we estimate that 47,000 of these 122,000 patients would normally accumulate a total of 594000 days of associated hospital stay from 49,000 readmissions (for any reason) within 1 year of hospital discharge. The cost of these admissions to the National Health Service was calculated at 166.2 million pounds sterling. Taking into account other costs associated with such hospital activity (e.g. general practice and hospital outpatient visits) each 10% reduction in recurrent bed utilization would be associated with 18.0 million ponds sterling in cost savings. Alternatively, the cost of applying a U.K.-wide programme of home-, clinic- or home plus clinic-based follow-up was calculated to be 69.4 pounds sterling, 73.1 pounds sterling and 72.5 million pounds sterling per annum, respectively. The relative thresholds at which generated 'cost-savings' would equal the cost of applying these programmes of care would therefore be a 38.5%, 40.6% and 40.3% reduction in recurrent bed utilization, respectively. If, as expected, a home-based programme of specialist nurse management reduced recurrent bed utilization by 50% or more, annual savings equivalent to 169,000 pounds sterling per 1000 patients treated would be generated. CONCLUSIONS: This is the first study to examine the economic consequences of applying a specialist nurse-mediated, post-discharge management service for heart failure within a whole population. Our findings suggest that such a service will not only improve quality of life and reduce readmissions in patients with congestive heart failure, but also reduce costs and improve the efficiency of the health care system in doing so.
Community Health Nursing↗
An audit of activity and outcome from a daily and a weekly "one stop" rapid assessment chest pain clinic.
OBJECTIVES: The recent National Service Framework for coronary heart disease advocates the establishment of rapid assessment clinics for chest pain. But how should these clinics be organised and do they fulfil their objectives? The aim of this study was to compare referral patterns to a daily and a weekly "one stop" rapid access chest pain clinic (RACPC), and to examine clinical outcome in patients attending these clinics. DESIGN: Patients were prospectively categorised into one of the following subgroups: "acute coronary syndrome", "stable coronary heart disease", or "low risk/non-coronary chest pain". Fatal and non-fatal outcomes were audited over eight months. SETTING: Both RACPCs were situated within the cardiology departments of two large Glasgow teaching hospitals. Patients were seen by a cardiologist, and underwent non-invasive testing. PARTICIPANTS: A total of 633 patients with chest pain who were referred by their general practitioner; 500 came to the daily and 133 to the weekly clinic. Forty four (7%) were categorised as having an acute coronary syndrome, 267 (42%) as stable coronary artery disease, and 322 (51%) as low risk/non-coronary chest pain. RESULTS: Referral patterns to the two clinics differed significantly. Compared with the weekly clinic, more patients with an acute coronary syndrome (7.8 v. 3.8%) and low risk/non-coronary chest pain (55.2 v. 35.6%), but fewer patients with stable coronary disease (37.0 v. 61.6%) were referred to the daily clinic (p<0.00001). During follow up eight (1.3%) patients died from a cardiac cause, and eight (1.3%) patients suffered a myocardial infarction. None of these patients were classified as low risk/non-coronary chest pain. CONCLUSIONS: (1) RACPCs do provide an effective tool for the early assessment of patients with possible angina. (2) The frequency with which clinics are scheduled may be an important factor in determining how the service is utilised in practice.
Aged↗
The mechano-biology of the epiphysis of the long bones as revealed by photoelastic models.
Stress contours have been generated in photoelastic models simulating cartilaginous and bony epiphyses. According to the findings, the secondary centre of ossification is formed in areas of the cartilaginous epiphysis shown to have reduced mechanical stress. The bony epiphysis appears to have been developed as a more mechanically efficient structure.
Bone and Bones↗
Genetic analysis of the DNA-dependent protein kinase reveals an inhibitory role of Ku in late S-G2 phase DNA double-strand break repair.
Two major complementary double-strand break (DSB) repair pathways exist in vertebrates, homologous recombination (HR), which involves Rad54, and non-homologous end-joining, which requires the DNA-dependent protein kinase (DNA-PK). DNA-PK comprises a catalytic subunit (DNA-PKcs) and a DNA-binding Ku70 and Ku80 heterodimer. To define the activities of individual DNA-PK components in DSB repair, we targeted the DNA-PKcs gene in chicken DT40 cells. DNA-PKcs deficiency caused a DSB repair defect that was, unexpectedly, suppressed by KU70 disruption. We have shown previously that genetic ablation of Ku70 confers RAD54-dependent radioresistance on S-G(2) phase cells, when sister chromatids are available for HR repair. To test whether direct interference by Ku70 with HR might explain the Ku70(-/-)/DNA-PKcs(-/-/-) radioresistance, we monitored HR activities directly in Ku- and DNA-PKcs-deficient cells. The frequency of intrachromosomal HR induced by the I-SceI restriction enzyme was increased in the absence of Ku but not of DNA-PKcs. Significantly, abrogation of HR activity by targeting RAD54 in Ku70(-/-) or DNA-PKcs(-/-/-) cells caused extreme radiosensitivity, suggesting that the relative radioresistance seen with loss of Ku70 was because of HR-dependent repair pathways. Our findings suggest that Ku can interfere with HR-mediated DSB repair, perhaps competing with HR for DSB recognition.
Animals↗