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Biomedical subjects

J Miles

Publications and source records attributed to J Miles.

At least 37 records · Page 2Linked to original sources

d-morphine, but not l-morphine, has low micromolar affinity for the non-competitive N-methyl-D-aspartate site in rat forebrain. Possible clinical implications for the management of neuropathic pain.

A diverse range of opioids and enantiomers were examined for their ability to displace binding at the [(3)H] MK-801-labelled site of the N-methyl-D-aspartate (NMDA) receptor in rat forebrain, displacement which is equitable with non-competitive NMDA receptor antagonist activity. Surprisingly, d-morphine, but not natural l-morphine, has low micromolar affinity for the site, suggesting clinical potential for racemic dl-morphine in the treatment of neuropathic pain with reduced development of tolerance. The opioid mu-receptor agonists: levorphanol, d- and dl-methadone, displayed similar properties. With the exception of the case of d-morphine, the structural requirements for affinity correspond closely with those previously found for the inhibitory effects of opioids on monoamine uptake.

Analgesics, Opioid↗

Characterization of a zebrafish/mouse somatic cell hybrid panel.

We have characterized a collection of zebrafish/mouse somatic cell hybrids with 211 genes and markers chosen from the 25 zebrafish linkage groups. Most of the zebrafish genome is represented in this collection with 88% of genes/markers present in at least one hybrid cell line. Although most hybrids contain chromosomal fragments, there are a few instances where a complete or nearly complete zebrafish chromosome has been maintained in a mouse background, based on multiple markers covering the entire chromosome. In addition to their use in mapping studies, this collection of somatic cell hybrids should constitute an important tool as a source of specific chromosome fragments and for assessing the function of genome regions.

Animals↗

Immunosuppressant effect of gold on IgG subclasses and IgE; evidence for sparing of Th2 responses.

We set out to examine the effect of gold treatment on the Th2-dependent antibodies IgG4 and IgE in relation to other IgG subclasses in patients with rheumatoid arthritis (RA). Eighty-five gold-treated RA patients and 82 RA controls were studied. Serum IgG subclass concentrations were measured by ELISA, IgE was measured by automated enzyme immunoassay. Samples were studied serially in 13 gold-treated patients and in 11 patients with gold-induced adverse events. There was a significant reduction in the concentration of IgG1, IgG2 and IgG3 in gold-treated RA patients compared with RA controls (P 0.004-0.019), whereas IgG4 was less significantly reduced in gold-treated patients (P = 0.044) and there was no difference in IgE. In serial samples there was a significant fall in the concentration of IgG1 (P = 0.001), IgG2 (P = 0.001) and IgG3 (P = 0.026) with time but no change in IgG4 and IgE. The development of gold-induced adverse events was not associated with any change in the concentration of each IgG subclass or IgE. Deficiencies of IgG subclasses were found in 30% of gold-treated RA patients and 8.5% of RA controls, and were associated in gold-treated patients with a longer disease duration (P = 0.003) and with erosive disease (P = 0. 03). IgG2 was affected most frequently and in the majority of these cases subnormal specific IgG2 binding to widespread polysaccharide antigens (Pneumovax II) was found. Gold induces an overall immunosuppressant effect on IgG subclasses, with a deficiency in 21. 5%, adjusted for controls. The effect on the Th2-dependent antibodies IgG4 and IgE is less marked, suggesting a sparing of Th2 responses.

Antirheumatic Agents↗

UK patients with deep-vein thrombosis can be safely treated as out-patients.

Deep-vein thrombosis (DVT) affects approximately 1:1000 people, approximately 750 cases/year in a Health Authority of average size. Prior to 1992, patients presenting with DVT were usually admitted for treatment with unfractionated heparin (UFH) over a 5-day period, but pressures on medical admissions have prompted many hospitals to review conditions which could be managed at home. Three different pilot studies commenced in 1996 at three centres in the UK. After 6 months, the protocols used were integrated into the normal care plan of the hospital. In total, 5191 patients were assessed, of whom 1347 were either venogram or Doppler ultrasound positive. Overall 1138 (82%) were treated as out-patients, 75% presenting during 'working hours'. Only 12 patients were readmitted, one with a clinically significant PE. Success was attributed to three factors: assignment of a key person as the project co-ordinator; referral of patients directly to permanent, dedicated staff, either on the Medical Admissions Unit (MAU) or the Accident and Emergency (A&E) department; and the introduction of dedicated anticoagulation nurses. In the 6-month period following initial therapy, complications were well below those in previously published studies. Most patients with DVT in the UK can be treated safely and effectively without being admitted to hospital.

Ambulatory Care↗

Slimming on the Internet.

The first 50 websites identified on searching the Internet for 'weight loss diets' were assessed systematically and their content compared with published clinical guidelines for management of obesity. The relevance and quality of the sites varied enormously. Only 3 confined themselves to sound dietary advice. Most promoted dietary supplements or other 'slimming aids', often of uncertain composition and based on dubious physiological principles. Potential hazards--for example, those of very low calorie diets--were rarely highlighted and certain regimens on offer were potentially dangerous.

Clinical Protocols↗

Refining the use of inhaled steroids in asthma.

Inhaled corticosteroids remain the most significant aspect of asthma therapy. An increasing number of drugs, devices and formulations are available to health-care professionals. This article aims to address the goals of inhaled steroid therapy and asks how well the available options meet these goals.

Administration, Inhalation↗

Radiation hybrid mapping of the zebrafish genome.

The zebrafish is an excellent genetic system for the study of vertebrate development and disease. In an effort to provide a rapid and robust tool for zebrafish gene mapping, a panel of radiation hybrids (RH) was produced by fusion of irradiated zebrafish AB9 cells with mouse B78 cells. The overall retention of zebrafish sequences in the 93 RH cell lines that constitute the LN54 panel is 22%. Characterization of the LN54 panel with 849 simple sequence length polymorphism markers, 84 cloned genes and 122 expressed sequence tags allowed the production of an RH map whose total size was 11,501 centiRays. From this value, we estimated the average breakpoint frequency of the LN54 RH panel to correspond to 1 centiRay = 148 kilobase. Placement of a group of 235 unbiased markers on the RH map suggests that the map generated for the LN54 panel, at present, covers 88% of the zebrafish genome. Comparison of marker positions in RH and meiotic maps indicated a 96% concordance. Mapping expressed sequence tags and cloned genes by using the LN54 panel should prove to be a valuable method for the identification of candidate genes for specific mutations in zebrafish.

Animals↗

Contaminated aerosol recovery from pulmonary function testing equipment.

Clinically, the spread of infectious agents between subjects undergoing spirometry is quite uncommon. There is almost no documentation in the medical literature on this subject. We studied the retrieval of nonpathogenic Escherichia coli after aerosolizing organisms into standard pulmonary function tubing of a type that is frequently used by volume-sensing spirometers. The arrival of the aerosol at the distal end of the tubing was documented by culture. After delays of 0, 1, 5, and 10 min, respectively, air was forcibly withdrawn from the proximal end of the tubing through a special petri plate assembly. The plates were cultured and the colonies were counted. Immediately after insufflation of organisms, air withdrawn from the proximal tubing had counts similar to the air sampled at the distal end. After a 1-min delay, the proximal samples contained only rare organisms. No organisms were recovered from proximal air samples after a delay of 5 or 10 min after insufflation of organisms. The absence of detectable aerosolized E. coli after delays of 5 and 10 min after insufflation of organisms into spirometry tubing supports the hypothesis that a significant transfer of aerosolized organisms does not occur during routine pulmonary function testing as long as an interval of 5 min or more is allowed between tests.

Aerosols↗

Physiological response to moderate exercise workloads in a pulmonary rehabilitation program in patients with varying degrees of airflow obstruction.

STUDY OBJECTIVES: To investigate whether a 12-week pulmonary rehabilitation program that includes moderately intensive exercise training performed twice weekly can induce a training effect in patients with a wide variation of airflow limitation. PARTICIPANTS: Sixty patients with COPD (38 men) with a mean +/- SD FEV(1) % predicted of 55.1 +/- 19.8 (range, 0.51 to 2.99). All patients performed identical incremental symptom-limited cycle ergometer testing before and after a 12-week study period. MEASUREMENTS AND RESULTS: After 12 weeks, the patients demonstrated a significant (p < 0.05) increase in the peak values for work rate (WR; 77 +/- 30 vs 91 +/- 36 W) and oxygen uptake (1.14 +/- 0.45 vs 1.20 +/- 0.52 L/min). Furthermore, at a given WR during incremental symptom-limited cycle ergometer testing, there were significant (p < 0.05) reductions in minute ventilation (42.4 +/- 16.1 vs 37.0 +/- 13. 6 L/min), carbon dioxide output (1.13 +/- 0.49 vs 1.03 +/- 0.42 L/min), ventilatory equivalent for oxygen (37.6 +/- 8.1 vs 36.0 +/- 6.3), and heart rate (135 +/- 15 vs 128 +/- 16 beats/min). None of the observed physiologic changes correlated with FEV(1) % predicted. CONCLUSIONS: A pulmonary rehabilitation program performed twice weekly with moderate exercise workloads can lead to a physiologic training response irrespective of the degree of airflow limitation.

Exercise↗

Dysaesthetic neck pain with syncope.

Neurogenic dysaesthetic pain in the neck following surgery for tumours in the neck is rare. Rarer still is the combination of pain following surgery with syncope. We looked at four patients who had tumours within the neck excised and then went on to develop neurogenic dysaesthetic neck pain associated with syncope. Distinction is made between neurogenic dysaesthetic pain following neck surgery and glossopharyngeal neuralgia which has been previously reported in association with neck surgery and also glossopharyngeal neuralgia with syncope. Spinal cord stimulation was used successfully to treat the dysaesthetic pain and syncope in three of the patients while the fourth patient died from the effects of his tumour. Medical practitioners may wish to consider spinal cord stimulation in relation to treating neurogenic dysaesthetic neck pain with syncope.

Adult↗

Risk of lung cancer associated with residential radon exposure in south-west England: a case-control study.

Studies of underground miners occupationally exposed to radon have consistently demonstrated an increased risk of lung cancer in both smokers and non-smokers. Radon exposure also occurs elsewhere, especially in houses, and estimates based on the findings for miners suggest that residential radon is responsible for about one in 20 lung cancers in the UK, most being caused in combination with smoking. These calculations depend, however, on several assumptions and more direct evidence on the magnitude of the risk is needed. To obtain such evidence, a case-control study was carried out in south-west England in which 982 subjects with lung cancer and 3185 control subjects were interviewed. In addition, radon concentrations were measured at the addresses at which subjects had lived during the 30-year period ending 5 years before the interview. Lung cancer risk was examined in relation to residential radon concentration after taking into account the length of time that subjects had lived at each address and adjusting for age, sex, smoking status, county of residence and social class. The relative risk of lung cancer increased by 0.08 (95% CI -0.03, 0.20) per 100 Bq m(-3) increase in the observed time-weighted residential radon concentration. When the analysis was restricted to the 484 subjects with lung cancer and the 1637 control subjects with radon measurements available for the entire 30-year period of interest, the corresponding increase was somewhat higher at 0.14 per 100 Bq m(-3) (95% CI 0.01, 0.29), although the difference between this group and the remaining subjects was not statistically significant. When the analysis was repeated taking into account uncertainties in the assessment of radon exposure, the estimated increases in relative risk per 100 Bq m(-3) were larger, at 0.12 (95% CI -0.05, 0.33) when all subjects were included and 0.24 (95% CI -0.01, 0.56) when limited to subjects with radon measurements available for all 30 years. These results are consistent with those from studies of residential radon carried out in other countries in which data on individual subjects have been collected. The combined evidence suggests that the risk of lung cancer associated with residential radon exposure is about the size that has been postulated on the basis of the studies of miners exposed to radon.

Aged↗

Classification of asthma severity: should the international guidelines be changed?

BACKGROUND: International guidelines recommend that, in addition to symptoms and medication requirements, measurements of forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF) are necessary for the objective assessment of asthma severity. The guidelines suggest that parity exists between measurements of FEV1 and PEF when expressed as percentage of predicted normal values, and that asthma severity can be classified as mild, moderate or severe on the basis of FEV and PEF measurements of > 80%, 60-80% and < 60% of predicted values, respectively. OBJECTIVE: To determine the relationship between measurements of FEV1 and PEF when expressed as percentage predicted values. METHODS: A total of 1198 paired measurements of FEV1 and PEF were obtained from the medical records of a random sample of 25 adult asthmatic patients attending a hospital-based chest clinic. Measurements of lung function were expressed as a percentage of predicted normal values, using the European Respiratory Society prediction equations for PEF and FEV1. For the individual paired measurements, the mean differences between PEF and FEV percentage predicted were calculated. Measurements of lung function were used to determine asthma severity with <60%, 60-80%, and >80% predicted FEV1 and PEF values representing severe, moderate and mild asthma, respectively. The proportion of paired measurements in which differences in classification resulted from the use of FEV1 or PEF percentage predicted values was then calculated. RESULTS: In asthma of differing severity, there was considerable variability between measurements of FEV1 and PEF when expressed as percentage predicted values; calculation of the FEV1% predicted resulted in lower values than those of the PEF percentage predicted, with a mean difference of -17.2% (95% CI -16.3%, -18.1%). There was agreement in classification of asthma severity in only 49.9% (598/1198) of paired measurements. Different prediction equations, while variably altering the degree of misclassification, did not correct the basic differences in the assessment of asthma severity dependent on the use of FEV or PEF. CONCLUSION: FEV1 and PEF values, expressed as percentage predicted, are not equivalent. Pending further evaluation, the authors suggest that published asthma guidelines should avoid the assumption of parity between these two measurements.

Adolescent↗

Mapping radon-prone areas by lognormal modeling of house radon data.

Results of radon measurements in houses are generally distributed approximately lognormally, whether large or small areas are considered. The properties of the lognormal distribution allow the proportion of houses above a threshold level to be estimated even when there are insufficient data to calculate the proportion directly. In this paper the properties of the data set of radon measurements made in UK houses with etched-track radon detectors are examined, with the purpose of using them to map radon-prone areas. Individual results are normalized depending on the average outdoor temperature during the measurement to estimate the annual average radon level. For certain types of maps, results may also be normalized to estimate the radon level in a standard house or mixture of house types on the same site. Methods to use the lognormal model to estimate the geometric mean radon concentration and geometric standard deviation for data grouped by area have been developed. These data are then used to map radon-prone areas of England and Wales.

Air Pollutants, Radioactive↗

Impact of the change in Connecticut syringe prescription laws on pharmacy sales and pharmacy managers' practices.

We assessed the impact of the 1992 change in Connecticut syringe prescription laws on pharmacy sales and pharmacy managers' sales practices. A mail survey was conducted in 1994 of all current pharmacy managers in the five largest cities in Connecticut (Hartford, New Haven, Waterbury, Bridgeport, and Stamford) and a random sample of those practicing in all other areas. Of these, 89.3% of the pharmacies in the five largest cities and 85.1% in the other areas had ever sold syringes without a prescription since the July 1992 law went into effect. Most pharmacists identified safety issues as very important in their personal decision about the sale of syringes without a prescription. Although the purpose of the change in the prescription law was to provide expanded access to sterile syringes by injection drug users (IDUs), only 31.4% of the managers who were allowed to sell in all instances and 18.1% of those who sold at their discretion were very willing to sell syringes to IDUs. In the logistic regression model of pharmacies with a sell-in-all-instances policy, the perceived benefit of the sale of syringes on health and community well-being was the only influence independently associated with managers support for nonprescription sales. Overall, managers reported they did not know what other pharmacists thought (40.4%) or did (42.9%) regarding the sale of syringes. When pharmacists had discretion over syringe sales, managers' beliefs about what other Connecticut pharmacists thought and did about the nonprescription sale of syringes remained a significant influence on the degree of support for sales. Most pharmacies implemented and maintained policies permitting the sale of syringes without a prescription. Several issues, including risk of discarded contaminated syringes around pharmacies and in the community and reluctance to sell to IDUs, reduced pharmacists willingness to sell syringes. Efforts to incorporate pharmacists as active partners in HIV prevention in IDUs should promote the sale of syringes without a prescription to IDUs as acceptable public health practice.

Acquired Immunodeficiency Syndrome↗

Recovery of nerve conduction following microvascular decompression for trigeminal neuralgia.

OBJECTIVE: To assess the function of trigeminal nerve before and after microvascular decompression for trigeminal neuralgia. BACKGROUND: To date there is no direct evidence that microvascular decompression of the trigeminal root restores normal conduction in the nerve. METHODS: The authors examined 10 patients with trigeminal neuralgia in whom preoperative MRI and MR angiography demonstrated neurovascular contact. During microvascular decompression, the trigeminal nerve was monitored by recording early scalp trigeminal evoked potentials immediately before, during, and after decompression. Direct recordings from the root entry zone were also performed. RESULTS: In all patients preoperative scalp evoked potentials showed impaired conduction of the trigeminal root. Microvascular decompression was associated with immediate recovery of conduction in seven patients, demonstrated by both scalp evoked potentials and direct root recordings. All 10 patients were pain free postoperatively. CONCLUSIONS: Improvement in trigeminal neuralgia following microvascular decompression is often associated with normalization of neurophysiologic data, suggesting recovery of nerve function. Rapid electrophysiologic recovery and pain relief following microvascular decompression argue that neither phenomenon is linked to remyelination. It is possible that the trigeminal evoked potentials might predict an effective microvascular decompression.

Decompression, Surgical↗