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A Murray

Publications and source records attributed to A Murray.

At least 109 records · Page 6Linked to original sources
PubMed2000

Allelic association in the FRAX region.

The sex chromosomes enable direct determination of haplotypes, and the analysis of 8 microsatellite markers from the FRAX region on Xq27-q28 contributes 7219 independent haplotypes from our study in Wessex. Allelic association increases with frequency of alleles, and is less for trinucleotide than dinucleotide repeats. The estimate of epsilon, the exponential decline of association with distance in kb, is 0.0023. The swept radius 1/epsilon estimates the distance at which disequilibrium falls to e(-1) approximately .37 of its initial value. The current study estimates the swept radius of association to be 433 kb, which is surprisingly close to estimates for SNPs, and suggests that a marker density of 1/100 kb should be powerful in regions such as FRAX. An explanation for these results is offered, and some speculations made about what will be found when SNPs are subjected to an equally intensive study in multiple regions.

Alleles↗
PubMed2000

Reproductive and menstrual history of females with fragile X expansions.

FRAXA premutations have been associated with premature ovarian failure (POF) or menopause before the age of 40. We have studied women in families ascertained because of a mentally retarded full mutation relative and determined their age of menopause, serum hormone levels in premenopausal individuals and the outcome of any pregnancies. Survival analysis was used as a measure of menopause and demonstrated a significant decrease in age of menopause in premutation carriers compared with their full mutation carrier and normal relatives. Serum FSH was also raised in premutation carriers, although oestradiol, inhibin A and inhibin B were not significantly different. However, we did not find an excess of dizygous twins or pregnancy loss/trisomies, both of which are associated with aging ovaries. Thus premutation carriers as a group have an earlier menopause and raised serum FSH but do not appear to manifest other features of an aging ovary.

Age Factors↗
PubMed2000

Stability and haplotype analysis of the FRAXE region.

FRAXE full mutations are rare and appear to be associated with mild mental retardation. As part of a screening survey of boys with learning difficulties to determine the frequency of full and premutations, we have collected data on the frequency of instability at FRAXE for about 4000 transmissions and the haplotype for over 7000 chromosomes. The distribution of FRAXE repeats was similar to other English populations but differed from two North American Caucasian series. Observed instability at FRAXE was rare but increased with increasing repeat number, and there were no expansions into the full mutation range, except in pedigrees ascertained through a full mutation. Haplotype analysis suggested division into five groups with each group having a characteristic distribution of FRAXE repeats. Fourteen of the 15 full mutations occurred on a single haplotype and this haplotype also had a significant excess of intermediate-sized alleles, suggesting that full mutations originate from large normal alleles. However, a related haplotype also had a significant excess of intermediates but we observed no full mutations on this haplotype, suggesting either loss or gain of stability determinants on it. We suggest that whilst triplet repeat size is a significant predisposing factor for expansion at FRAXE other genetic determinants are also likely to be important.

Alleles↗
PubMed2000

Patients with neck lumps: can they be managed in a 'one-stop' clinic setting?

The present government has stated its intentions to expand the application of "one-stop" assessments for out-patients. To decide if this is an appropriate strategy for managing patients with neck lumps, we prospectively assessed 110 patients referred to the Neck Lump Clinic of the Otolaryngology Department of a teaching hospital. Patients were assessed clinically and with immediately reported fine needle aspiration cytology (FNAC). The accuracy of immediately reported FNAC was later compared with a final report and histology, when available. A "one-stop" visit was defined as patients who were discharged, or placed on a waiting list, after a single consultation. Eight-three (76%) patients did not have to return to the outpatient department, of which 59 (54%) were discharged. No changes occurred from immediate to final FNAC reports. If certain criteria are met, patients with neck lumps can be successfully managed in a "one-stop" setting.

Adolescent↗
PubMed2000

The clinical value of septal perforation biopsy.

Biopsy from the edge of a septal perforation is performed to diagnose potentially significant aetiological conditions, including malignant pathology and Wegener's granulomatosis. However, it is common for the histological result to be undiagnostic and unhelpful in planning an individual patient's management. To clarify the role of septal perforation biopsy, we reviewed all biopsies performed on our patients over a 13-year period. Of the 65 biopsies performed, in 63 patients, none had a histological result which changed the clinical diagnosis made before biopsy. Forty-three patients had clinically benign perforations biopsied, and no histology other than chronic inflammation was obtained. In 16 patients with a clinical vasculitis, none had this diagnosis confirmed histologically. One positive biopsy was obtained from two patients with clinically malignant perforations yet both were treated for T-cell lymphoma. The subsequent management of all patients was based on their clinical diagnosis rather than their biopsy results. We suggest only clinically malignant perforations are worthwhile biopsying.

Adolescent↗
PubMed2000

Adefovir dipivoxil for the treatment of lamivudine-resistant hepatitis B mutants.

Lamivudine has been shown to be an effective therapy for chronic hepatitis B, but resistance to this nucleoside agent is common after prolonged use. Five patients with chronic hepatitis B virus (HBV) infection developed resistance to lamivudine after 9 to 19 months of treatment. In 4 patients this occurred after liver transplantation and the remaining individual had stable cirrhosis. In each case, resistance was confirmed to be caused by one or more mutations in the HBV-DNA polymerase gene and was associated with active underlying liver disease. The patients were treated with adefovir dipivoxil in a dose of 5 to 30 mg daily. Two to 4 log(10) reductions in HBV-DNA levels were observed in 4 cases, and the fifth patient became negative by quantitative polymerase chain reaction (PCR) after retransplantation in conjunction with hepatitis B immunoglobulin (HBIg). Virologic improvement was associated with stable or declining serum alanine transaminase levels in 4 patients. HBV-DNA suppression has been sustained during a mean treatment period of 13 months (range 11 to 15 months), including 1 patient in whom lamivudine has been discontinued. Mild changes in renal function were observed during treatment in most cases but did not require early discontinuation of the drug. This study provides evidence that adefovir dipivoxil can be an effective treatment for lamivudine-resistant HBV mutants as well as wild-type HBV.

Adenine↗
PubMed2000

Follicular development in vitro.

There has been tremendous interest in recent years in the culture of oocytes and follicles. Although much of the research using follicle culture aims to increase understanding of the regulation of follicle development, an important goal has been to develop a method that will eventually allow maturation of human oocytes from the primordial follicle to the mature Graafian stage. We are still some way from this at present, although it has now been achieved in the mouse. In this article, we consider various methods of follicle culture for primordial, preantral, and antral follicles. In vitro development of primordial follicles has used primarily whole ovaries or ovarian fragments as a source of follicles. Culture of later stages of follicle development uses mainly isolated follicular units, either whole (with an intact basement membrane and, in some cases, attached thecal cells) or nonintact (oocyte-somatic cell complexes, which may or may not have remnants of basement membranes and/or thecal cells attached).

Animals↗
PubMed2000

Premature ovarian failure and the FMR1 gene.

FMR1 is an X-linked gene that codes for an RNA binding protein. Expansion of a triplet repeat within exon 1 of the gene causes the fragile X syndrome, which is characterized by mental retardation and various physical anomalies. The triplet repeat in FMR1 can expand to varying degrees. Only the very large expansions in which there is concomitant methylation of the gene cause the fragile X syndrome. Expansions of between 50 and 200 repeats are premutations. Although premutations were originally perceived to be without phenotypic effect, there is now substantial evidence that female carriers of premutations are at increased risk of having early menopause. The FMR1 premutation is also associated with a significant number of cases ascertained because of idiopathic premature ovarian failure, particularly when ovarian failure is a familial trait. The molecular mechanism to explain the association between ovarian failure and premutations is unknown.

Female↗
PubMed2000

Pulmonary Mycobacterium bovis infection in a dog.

AIM: To describe the clinical course of a dog infected with Mycobacterium bovis causing a granulomatous pneumonia. CLINICAL FINDINGS: The dog initially presented with a persistent cough, inappetence and weight loss. Clinical findings included a fever, dyspnoea and tachypnoea, with haematological evidence of a mild neutrophilia and hypoalbuminaemia. Radiographs of the chest demonstrated a concomitant pneumothorax, pleural effusion, and a consolidated area within the left caudal lung lobe. An exploratory thoracotomy revealed this to be a ruptured granulomatous lesion. Subsequent histopathological, microbiological and genetic studies identified M. bovis as the causal agent. CLINICAL SIGNIFICANCE: Mycobacterium bovis infections should be included in the differential diagnosis of pulmonary disease and pleural effusions in dogs living in regions of New Zealand known to have a high incidence of mycobacterial infection in wildlife and farm animals.

Journal Article↗
PubMed2000

Heart rate and blood pressure variability in normal subjects compared with data from beat-to-beat models developed from de Boer's model of the cardiovascular system.

The objective of this study was to assess the ability of de Boer's model of the cardiovascular system to reproduce the heart rate and blood pressure variability observed in a range of normal subjects, and to make modifications to improve its performance. ECG, blood pressure and chest wall movement were recorded from 12 normal human subjects during controlled breathing. For each beat, systolic pressure, diastolic pressure, arterial time constant and RR interval were extracted. RR interval and systolic pressure spectral power in low and high frequency bands and the baroreflex sensitivity index, alpha, were then determined. For each subject, mean values were input to the model and the beat-to-beat output compared with the actual data for that subject. Finally, the effects of reducing the influence of baroreflex on peripheral vascular resistance and of providing separate sympathetic and vagal baroreflex sensitivities were assessed. Simulations resulted in data which were qualitatively similar to those of each subject's recording. With the modifications, the log ratio of simulated to real data improved from 7.2 to 1.5 (p = 0.003) for low frequency RR, from 0.27 to 0.55 (p = 0.011) for high frequency RR and from 8.5 to 0.9 (p = 0.003) for low frequency systolic pressure. We conclude that de Boer's model reproduces many of the characteristics of heart rate and blood pressure variability, and our modifications to baroreflex sensitivities and the feedback effect on peripheral resistance resulted in significant improvements.

Adult↗
PubMed2000

Similarity in bilateral photoplethysmographic peripheral pulse wave characteristics at the ears, thumbs and toes.

The characteristics of the photoplethysmography (PPG) pulse signal are body site specific, with pulses from the various peripheral sites showing differences in pulse transit time, strength and shape, and variation of each over time. The aim of this study was to determine the similarity in the right-left pulse characteristics for a group of normal subjects with pulses obtained simultaneously from six peripheral sites (cars, thumbs and big toes). A multi-site photoplethysmography pulse measurement and analysis system is described and comprised six sets of pulse probes and amplifiers, arranged and electronically matched in pairs for the right and left side comparisons. Two sets of data were collected: firstly a set of validation data to test the electronic matching of right left channels, and secondly a set of physiological data for pulses from 40 normal subjects. The right-to-left side similarity in pulse waveform shape at the three segmental levels (ears, thumbs and toes) was assessed using two types of analysis: root mean square error (RMSE) providing a measure of differences, and cross correlation analysis providing a measure of the degree of similarity. Very low levels of RMSE and correlation coefficients close to unity were obtained for the system validation data, demonstrating good right-left channel matching. The RMSE was an order of magnitude lower than that calculated for the normative physiological data, where median RMSE levels were between 0.053 and 0.060 relative to a peak-to-peak pulse amplitude of unity. The median correlation coefficients were greater than 0.98 for all three segmental levels studied, with the maximum values approaching those of the validation data. We have shown that pulses from the right and left sides of normal subjects are highly correlated at each segmental level. We have obtained a normative range of pulse data, with which specific (vascular) patient groups can be compared.

Adolescent↗
PubMed2000

Pharmacokinetics of tramadol in children after i.v. or caudal epidural administration.

We have studied the pharmacokinetics of a single bolus dose of tramadol 2 mg kg-1 injected either i.v. or into the caudal epidural space in 14 healthy children, aged 1-12 yr, undergoing elective limb, urogenital or thoracic surgery. Serum concentrations of tramadol and its metabolite O-demethyl tramadol (MI) were measured in venous blood samples at various intervals up to 20 h by non-stereoselective gas chromatography with nitrogen-selective detection. All pharmacokinetic variables were evaluated using a non-compartmental model. After a single i.v. injection (n = 9), the mean elimination half-life of tramadol was 6.4 (SD 2.7) h, with a volume of distribution of 3.1 (1.1) litre kg-1 and total plasma clearance of 6.1 (2.5) ml kg-1 min-1. All of these pharmacokinetic variables were similar to those reported previously in adults. After caudal epidural administration (n = 5), mean elimination half-life was 3.7 (0.9) h, volume of distribution was 2.0 (0.4) litre kg-1 and total clearance was 6.6 (1.9) ml kg-1 min-1. The caudal/i.v. quotient of the AUC was 0.83, which confirms that there is extensive systemic absorption of tramadol after caudal administration. Serum concentrations of MI showed a time course typical of a metabolite after both modes of administration. Serum concentrations of MI after caudal administration were lower than those after i.v. injection.

Analgesia↗
PubMed2000

Do patients with ankylosing spondylitis have poorer balance than normal subjects?

OBJECTIVES: To investigate whether patients with ankylosing spondylitis have poorer balance than normal subjects, and to study the relationship between balance and posture. METHODS: Balance was studied in 30 ankylosing spondylitis subjects using sway magnetometry, making quantitative measurements of movement at the hips with eyes open and eyes closed. The results were compared with data from 58 normal subjects. Balance was also compared with quantitative measurements of posture. RESULTS: The numbers of patients with poor balance, above the 95th percentile for normal, were significantly greater than expected; 18% for eyes open (P = 0. 03) and 23% for eyes closed (P = 0.004). No significant relationships between balance and any of the quantitative descriptions of posture were demonstrated. CONCLUSION: A significant proportion of ankylosing spondylitis patients have poorer balance than normal subjects.

Adult↗
PubMed2000

Relationship of baroreflex sensitivity and blood pressure in an older population.

OBJECTIVES: Ageing and hypertension are associated with reduced baroreflex sensitivity (BRS) in young and middle-aged populations. The effects of blood pressure level on BRS in the older population are unclear. We examined the association between blood pressure and BRS in older persons with blood pressure below 180 mmHg. METHODS: BRS, high (alphaHF 0.15-0.4 Hz) and low (alphaLF 0.04-0.15 Hz) frequency alpha-index, was determined in 75 normotensive subjects (aged 75 +/- 4 years, 41% female, 131 +/- 10/74 +/- 7 mmHg) and 64 untreated hypertensive subjects (aged 76 +/- 5 years, 48% female, 165 +/- 7/ 88 +/- 7 mmHg) by spectral analysis of 20 min continuous blood pressure and heart rate recordings using finger plethysmography. Subjects were recruited from 10 general practices and were taking no cardiovascular medications. RESULTS: High but not low frequency alpha-index was significantly blunted in hypertensive subjects (alphaHF 5.1 +/- 3.1 versus 8.4 +/- 7.4 ms/mmHg, P< 0.001 and alphaLF 4.7 +/- 3.0 versus 5.8 +/- 3.9 ms/mmHg, P= 0.07). Multivariate analysis of the relationship between age and blood pressure demonstrated systolic and to a lesser extent diastolic blood pressure were significant predictors of variance in BRS for alphaHF [systolic blood pressure (SBP) P< 0.0001, diastolic blood pressure (DBP) P< 0.05, r2 = 0.1] and alphaLF (SBP P=0.01, DBP P<0.05, r2 = 0.04). Age was not a significant predictor for either measure, in the 20 year range studied. CONCLUSIONS: In an older population blood pressure is associated with reduced BRS, particularly for the high frequency component. Such a change may place older subjects with hypertension at increased risk of orthostatic hypotension, vasovagal syncope and sudden cardiac death.

Aged↗
PubMed2000

Alpha-melanocyte stimulating hormone can reduce T-cell interaction with melanoma cells in vitro.

This study was undertaken to investigate whether alpha-melanocyte stimulating hormone (alphaMSH) influences the interaction of melanoma cells with T-lymphocytes in the light of previous work from our laboratories showing that alphaMSH can reduce tumour necrosis factor-alpha (TNFalpha) stimulated ICAM-1 upregulation in both normal and transformed melanocytes. Two cutaneous melanoma cell lines--A375-SM and HBL--were examined initially. A375-SM cells gave only a two-fold increase in T-cell proliferation, which was not much improved by the pretreatment of the melanoma cells with cytokines. HBL cells induced a three-fold increase in T-cell proliferation, which was slightly enhanced by the addition of cytokines. Neither cell line expressed B7(1), HBL cells expressed a low level of B7(2), whereas A375-SM cells had little, if any, B7(2) expression. Addition of alphaMSH reduced the interaction between these cutaneous melanoma cells and T-lymphocytes in some, but not all, conditions. An ocular melanoma cell line transfected with B7 showed a modest interaction with T-cells (in two out of three donors) and this response was reduced by the addition of alphaMSH. Pretreatment of the transfected line with cytokines markedly enhanced stimulation of T-cell proliferation by these tumour cells, and alphaMSH reduced the interaction between melanoma cells and T-cells for two out of three donors. In summary, under experimental conditions where melanoma cell stimulation of T-cells occurred (generally pretreatment of the cells with interferon-gamma gave the most convincing response), alphaMSH reduced this response in the majority of experiments, providing preliminary evidence to confirm the hypothesis that MSH may assist melanoma cells to evade interaction with immune cells.

Antibodies, Monoclonal↗
PubMed2000

Dispersion of QT intervals: a measure of dispersion of repolarization or simply a projection effect?

QT interval dispersion may provide little information about repolarization dispersion. Some clinical measurements demonstrate an association between high QT interval dispersion and high morbidity and mortality, but what is being measured is not clear. This study was designed to help resolve this dilemma. We compared the association between different clinical measures of QT interval dispersion and the ECG lead amplitudes derived from a heart vector model of repolarization with no repolarization dispersion whatsoever. We compared our clinical QT interval dispersion data obtained from 25 subjects without cardiac disease with similar data from published studies, and correlated these QT dispersion results with the distribution of lead amplitudes derived from the projection of the heart vector onto the body surface during repolarization. Published results were available for mean relative QT intervals and mean differences from the maximum QT interval. The leads were derived from Uijen and Dower lead vector data. Using the Uijen lead vector data, the correlation between measurements of dispersion and derived lead amplitudes ranged from 0.78 to 0.99 for limb leads, and using the Dower values ranged from 0.81 to 0.94 for the precordial leads. These results show a clear association between the measured QT interval dispersion and the variation in ECG lead amplitudes derived from a simple heart vector model of repolarization with no regional information. Therefore, measured QT dispersion is related mostly to a projection effect and is not a true measure of repolarization dispersion. Our existing interpretation of QT dispersion must be reexamined, and other measurements that provide true repolarization dispersion data investigated.

Adolescent↗