Biomedical subjects
G Morris
Publications and source records attributed to G Morris.
Coagulation and inflammatory markers in Alzheimer's and vascular dementia.
Alzheimer's disease is classified as a degenerative dementia while vascular dementia is known to be associated with atherothrombosis and classical vascular risk factors. However, over the last decade, there is increasing evidence of the role of haemostatic factors and inflammatory mechanisms in the pathogenesis of Alzheimer's disease. Serum markers of hypercoagulability and markers of inflammation could lead to thrombosis, accelerated atherogenesis and resulting dementia of both Alzheimer's and vascular dementia. In this case control study, we studied these serum markers of coagulation and inflammation in patients suffering from dementia.
Local magnetic susceptibility of the positive muon in the quasi-one-dimensional S=1/2 antiferromagnet dichlorobis (pyridine) copper (II).
We report muon spin rotation measurements of the local magnetic susceptibility around a positive muon in the paramagnetic state of the quasi-one-dimensional spin 1/2 antiferromagnet dichlorobis (pyridine) copper (II). Signals from three distinct sites are resolved and have a temperature dependent frequency shift which is significantly different than the magnetic susceptibility. This difference is attributed to a muon induced perturbation of the spin 1/2 chain. The obtained frequency shifts are compared with transfer matrix density-matrix renormalization-group numerical simulations.
Hypoparathyroidism and 22q11 deletion syndrome.
AIMS: To investigate a population of individuals with 22q11 deletion syndrome for hypocalcaemia. METHODS: A detailed clinical history enquiring into symptoms of hypocalcaemia and blood sampling to assess for hypocalcaemia and hypoparathyroidism, of patients outside the neonatal period known to have the 22q11 microdeletion from fluorescent in situ hybridisation studies was taken. RESULTS: Sixty one individuals were identified, of whom 23 were untraceable and one was unable to give informed consent. Biochemical investigations were performed on 27 subjects. Ten subjects had review of notes only. Four subjects had previously identified hypoparathyroidism. A new case of hypoparathyroidism was identified. Three subjects had borderline hypocalcaemia. DISCUSSION: In this population of patients with 22q11 deletion syndrome, 13% of the total or 30% of those biochemically assessed had evidence of reduced serum calcium concentrations. It is likely that 13-30% of patients with 22q11 deletion syndrome have possible hypoparathyroidism outside the neonatal period. Reported symptoms of hypocalcaemia did not correlate with biochemical evidence of persisting hypocalcaemia. We have shown that previously undiagnosed asymptomatic hypoparathyroidism occurs in patients with 22q11 deletion syndrome and conclude that screening of this population should be considered.
Effective environmental regulation to maximise the benefits of integrated wastewater management.
On the 25 November 1999, the Secretary of State for the Environment in England and Wales announced the outcome of the water companies' third Periodic Review. As a result, a major environmental investment programme will be completed during the period 2000/2005. Overall in England and Wales, it is planned that almost 3,600 km of rivers will be protected or improved and 3,800 unsatisfactory CSOs will be improved to allow receiving water objectives to be met. This means that over the next 5-year period an average of nearly 18 discharges will be improved every week. The implementation of the programme will involve a large workload for the Environment Agency in planning and authorising the individual schemes for delivery by the water companies. The paper illustrates how the Urban Pollution Management procedure and associated environmental standards are to be used to underpin the Environment Agency's policy, to encourage the use of integrated wastewater planning and, as a result, ensure that the anticipated environmental improvements will be delivered.
The evaluation of a new standard data set on reported cases of intestinal infectious disease in Scotland, and recommendations for the future.
A national survey of local authorities was carried out to ascertain what information they collected on reported cases of intestinal infectious disease and why. As a result of the survey, and a review of national objectives, two data collection forms designed to satisfy both local and national objectives were piloted. One of the forms was four pages long, and sought much less data than the second form, which was 10 pages long. The outcomes of these investigations were established, and assessed, to see if they could have led to the achievement of the stated local and national objectives. Neither data collection form was entirely successful in fulfilling all local objectives, although the four-page form was no less successful than the ten page form. Neither form succeeded in fulfilling national objectives. The study has shown that our best efforts at fulfilling local and national objectives by the universal administration of either the four-page, or the 10-page form are of limited value. We recommend that the universal collection of such information from reported cases of intestinal infectious disease be discontinued. We recommend a risk-based approach to identify cases whose follow up is more likely to achieve more realistic objectives.
Analysis of wine for penicillin.
This study addresses the question of whether the antibiotic Penicillin, which is produced by the common mold Penicillium notatum, could possibly become a contaminate of wine during the fermentation process. The significance of this study is related to the potential health effects this agent might produce in those consumers who have an allergic response to Penicillin. It has been estimated that between 6% and 8% of the American population is subject to this type of allergic response. A method is developed for the detection of penicillin in wines using high-pressure liquid chromatography. We demonstrate that penicillin G hydrolyzes rapidly in wine with first-order kinetics, and the half-life of this antibiotic is 147 min in a typical commercial wine. An analysis of a number of commercial wines shows no evidence of the presence of penicillin, which should negate the question of any allergic response associated with this potential contaminate.
Viral evolution in response to the broad-based retroviral protease inhibitor TL-3.
TL-3 is a protease inhibitor developed using the feline immunodeficiency virus protease as a model. It has been shown to efficiently inhibit replication of human, simian, and feline immunodeficiency viruses and therefore has broad-based activity. We now demonstrate that TL-3 efficiently inhibits the replication of 6 of 12 isolates with confirmed resistance mutations to known protease inhibitors. To dissect the spectrum of molecular changes in protease and viral properties associated with resistance to TL-3, a panel of chronological in vitro escape variants was generated. We have virologically and biochemically characterized mutants with one (V82A), three (M46I/F53L/V82A), or six (L24I/M46I/F53L/L63P/V77I/V82A) changes in the protease and structurally modeled the protease mutant containing six changes. Virus containing six changes was found to be 17-fold more resistant to TL-3 in cell culture than was wild-type virus but maintained similar in vitro replication kinetics compared to the wild-type virus. Analyses of enzyme activity of protease variants with one, three, and six changes indicated that these enzymes, compared to wild-type protease, retained 40, 47, and 61% activity, respectively. These results suggest that deficient protease enzymatic activity is sufficient for function, and the observed protease restoration might imply a selective advantage, at least in vitro, for increased protease activity.
The kinematics and neural control of high-speed kicking movements in the locust.
The tibiae of locust hind legs can be extended fully in a kick in 3 ms with peak angular velocities of at least 80 degrees ms(-1). If the mass of the distal part of the leg is halved, then the extension is complete in less than 1 ms with angular velocities of more than 200 degrees ms(-1). The high velocities and the associated power are generated by a preceding storage of energy and its sudden release produced by a specific motor pattern and specialisations of the femoro-tibial joints. To understand the dynamics of these rapid movements and the interrelations between joint mechanics and the motor pattern, kicks were analysed with high-speed video images coupled to simultaneous intracellular recordings from identified leg motor neurones. The first movement is a full tibial flexion followed by co-contraction of the extensor and flexor tibiae muscles for 0.3-1 s, during which the distal end of the femur is flattened dorso-ventrally and expanded laterally. The two semi-lunar processes on the distal femur are bent when the fast extensor tibiae motor neurone spikes so that their tips move ventrally by up to 0.6 mm. The inward projections of these processes into the femur form the proximal part of the hinge joint with the tibia, so that the pivot of the joint also changes and the tibia therefore moves proximally and ventrally, widening the gap between it and the femur. Extension of the tibia begins on average 34 ms after the flexor motor neurones are inhibited at the end of the co-contraction phase. The tibia then begins to extend slowly, reaching peak velocities only when it has extended by 60-70 degrees. The semi-lunar processes do not start to unfurl until the tibia has extended by 55 degrees, so they cannot provide the initial energy for extension. An audible click is produced when the semi-lunar processes unfurl. The peak velocity of tibial extension is correlated with the amount of bending of the semi-lunar processes and with the number of fast extensor motor spikes, but the same amount of semi-lunar bending can be produced by both short and long co-contractions. When the tibia reaches full extension, inertial forces may cause it to bend by as much as 33 degrees at a plane of weakness in the proximal tibia, thus allowing further extension of the distal end.
GREAT-ER: a new tool for management and risk assessment of chemicals in river basins. Contribution to GREAT-ER #10.
The GREAT-ER (Geo-referenced Regional Exposure Assessment Tool for European Rivers) project team has developed and validated an accurate aquatic chemical exposure prediction tool for use within environmental risk assessment schemes. The software system GREAT-ER 1.0 calculates the distribution of predicted environmental concentrations (PECs) of consumer chemicals in surface waters, for individual river stretches as well as for entire catchments. The system uses an ARC/INFO-ArcView (ESRI) based Geographical Information System (GIS) for data storage and visualization, combined with simple mathematical models for prediction of chemical fate. At present, the system contains information for four catchments in Yorkshire, one catchment in Italy, and two in Germany, while other river basins are being added. Great-ER 1.0 has been validated by comparing simulations with the results of an extensive monitoring campaign for two 'down-the-drain' chemicals, i.e. the detergent ingredients boron and Linear Alkylbenzene Sulphonate (LAS). GREAT-ER 1.0 is currently being expanded with models for the terrestrial (diffuse input), air and estaurine compartments.
Influenza vaccination coverage in old people's home in Carmarthenshire, UK, during the winter of 1998/99.
A mailed questionnaire survey was undertaken in old people's (nursing and residential) homes in Carmarthenshire, UK to determine the influenza vaccine uptake during the 1998/99 season. Out of the total 60 questionnaires circulated, response was received from 47 homes giving an overall response rate of 78%. Amongst the 1399 residents, 1132 (81%) received influenza vaccine in the winter of 1998/99. Uptake was higher in nursing homes (89%) than in residential homes (79%) or dual registered homes (81%). The most common reason for not receiving influenza vaccination was refusal by the residents themselves, although the vaccine was offered to 99% of residents. This study suggests that strategies to improve communication and provision of educational materials outlining the benefits of influenza vaccine to elderly residents and health professionals may help increase the likelihood of vaccine uptake.
The use of measured boron concentration data from the GREAT-ER UK validation study (1996-1998) to generate predicted regional boron concentrations
The concentrations of boron in the Aire and Calder which have been measured in order to validate the GREAT-ER model have been used to derive a predicted environmental concentration (PEC) for boron in the Aire catchment in Yorkshire. The data have been obtained from 33 sites, with monthly sampling over a 2-year period. The 90th percentile of the means of measured concentrations (242 microg l(-1)) is higher than the 90th percentile predicted by the GREAT-ER model (186 microg l(-1)), if river stretches are normalised by their flow volumes, and unpolluted headwaters are included in the catchment averaging procedure. However, if the river stretches are normalised by the length of the respective stretch, and unpolluted headwaters are included, a lower regional PEC of 28 microg l(-1) is obtained. If normalisation by stretch length is appropriate for regional risk assessment, then the 90th percentile of the means of the measured data will overpredict the regional boron concentration in a catchment such as the Aire, with a low natural level of boron in the headwaters. Monitoring data for boron in the effluents from sewage treatment works in the Aire catchment, and for boron in the Went and Rother catchments, with a higher background boron level, are also given.
A novel infant formula milk with added long-chain polyunsaturated fatty acids from single-cell sources: a study of growth, satisfaction and health.
OBJECTIVE: To evaluate the growth, feeding and health of babies fed a novel infant formula milk with added long chain polyunsaturated fatty acids (LCPs) produced from single-cell sources, at concentrations similar to those found in mature breast milk. DESIGN: Randomized double-blind control trial. SUBJECTS: One-hundred and forty healthy, full-term infants of birth weight 2.5-4.5 kg born at the Maternity Department, East Glamorgan General Hospital, Wales, whose mothers had already decided to bottle feed. INTERVENTIONS: Subjects were randomized to two groups; one (control group) to receive a standard formula milk and the other to receive the trial milk with added LCPs. Milks were supplied in a double-blind fashion and given for the first 12 weeks of life. Anthropometric measurements were made at recruitment, 3 months, 6 months and 1 y. Feeding diaries were completed at 6 weeks and 3 months, and a parental record was kept of any ill health suffered by the subjects during the first year of life. RESULTS: Of 140 infants recruited, 31 did not complete the protocol. Small but statistically significant differences were found only in the subscapular skinfold thickness at 6 weeks and 3 months, that in the trial group being slightly higher, but unlikely to be of any clinical importance. No differences were found in the feeding patterns of the infants in the two groups. Stool patterns were similar, as were the frequencies of illness and allergy. CONCLUSIONS: This study supports the view that LCPs from single-cell sources do not have detrimental effects on the growth, feeding and general health of infants.
Sampling of Aspergillus spores in air.
Nosocomially acquired aspergillosis typically occurs in the setting of treatment for leukaemia or other haematological malignancy. As Aspergillus species can be readily found in the environment, it has been widely believed that aspergillosis occurs as a consequence of exogenous acquisition of the fungus. Stringent environmental controls in transplant units have included high-efficiency air filtration, positive-pressure ventilation and frequent room air changes. Although there have been several well-documented examples of aspergillosis outbreaks as a result of hospital demolition and reconstruction, it has not always been possible to demonstrate elevated spore counts in clinical areas during building work. The sampling of air for Aspergillus is very problematic. Careful attention must be given to the design of air sampler, sampling protocols and an understanding of air sampling data. This review outlines many of the physical and environmental parameters that influence meaningful air sampling and recommends a simple procedure that has been tried and tested in many aspergillosis outbreaks.
Influenza immunization coverage in older hospitalized patients during winter 1998-99 in Carmarthenshire, UK.
OBJECTIVE: to determine the coverage of influenza vaccination in hospitalized elderly patients in view of the 1998 recommendations of the UK Department of Health, and the reasons for refusal in those unvaccinated. DESIGN: questionnaire-based interview. SETTING: acute elderly-care wards in a district general hospital in South Wales, UK. SUBJECTS: 443 consecutive patients aged over 65 hospitalized during December 1998 and January 1999. RESULTS: of 383 patients in whom influenza vaccination was recommended according to Department of Health guidelines, only 48% received it during the winter of 1998-99. The commonest reason given by those unvaccinated was lack of information from the general practitioner (in 26% of cases). Other reasons were concern about vaccine side effects (21%), perceived good health (16%) and concern about vaccine efficacy (11%). CONCLUSIONS: influenza vaccine uptake in high-risk older hospitalized patients is still unsatisfactory. Improved education of the health-care staff and the general public about the benefits of vaccine is necessary to improve uptake.
Major aphthous ulcers induced by nicorandil.
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Effect of radioimmunoscintigraphy on the management of recurrent colorectal cancer.
BACKGROUND: Radioimmunoscintigraphy (RIS) is being used increasingly as a new investigation in the diagnosis of recurrent colorectal cancer. This study assessed the efficacy of 99mTc-radiolabelled PR1A3 scanning in a cohort of patients with possible recurrent colorectal cancer and the effects of scan interpretation on subsequent clinical management. METHODS: The scans and case notes of patients scanned over a 3-year period were reviewed. RESULTS: Forty-seven scans in 40 patients were available for analysis. In 39 instances in which scan interpretation could be verified accurately, sensitivity for recurrent colorectal cancer was 22 of 23 (96 per cent), specificity for recurrent colorectal cancer was eight of 16 (50 per cent), positive predictive value for recurrence was 22 of 30 (73 per cent) and negative predictive value for recurrence was eight of nine (89 per cent). In 16 of the 40 patients, scan interpretation strengthened a management decision or altered management. This was beneficial to ten patients and possibly detrimental to six. CONCLUSION: This study demonstrated that RIS is sensitive in the detection of recurrent colorectal cancer and benefited the patient in one-quarter of cases. For the majority of patients, accurate detection of recurrent disease cannot be followed by curative therapy, but there is an important subgroup of patients in whom RIS alters management beneficially. However, a randomized prospective study is needed to confirm this.
Adding lamotrigine to valproate: incidence of rash and other adverse effects. Postmarketing Antiepileptic Drug Survey (PADS) Group.
PURPOSE: Valproate (VPA) triples the half-life of lamotrigine (LTG), and combined use may be difficult. The adverse effect (AE) profile of this combination needs clarification. METHODS: We prospectively recorded our experience in adding LTG to VPA-containing regimens in 108 patients. Data collected included medications, seizure types and syndromes, and AEs. Patients were followed up to 27 months, until a stable dose was reached, or until LTG was discontinued. Patient management was not altered by this study. There were 60 patients with partial-onset seizures, 30 with generalized onset, and 12 with the Lennox-Gastaut syndrome. In 37, LTG was added to VPA monotherapy, and in 71, to VPA and other drugs. The median starting dose of LTG in our adult patients was 20.8 mg/day. RESULTS: LTG was added successfully in 86 (80%) patients. It was discontinued in 22 (20%): seven because of rash, seven for other AEs, and nine for other reasons. Rash occurred in 14 (13%) but caused discontinuation of LTG in only seven. We found a rash rate of 14.2% and a discontinuation rate because of rash of 8.7% among 310 patients in whom LTG was added to drug regimens not including VPA. Other AEs included fatigue (12%), gastrointestinal (GI) symptoms (9%), dizziness, headache, and insomnia (3% each). Serious AEs were hallucinations (two patients), hepatic enzyme elevations (two patients), irritability (one patient), and low white blood cell count (one patient). Whether LTG was added to VPA monotherapy or polytherapy made no difference in overall AE rate. CONCLUSIONS: LTG can be added to VPA with an acceptable incidence of side effects. LTG-induced rashes are no more common with VPA than with other drugs when LTG is added at very low initial dosages. Rashes are potentially serious and should be evaluated promptly.