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Biomedical subjects

D James

Publications and source records attributed to D James.

At least 37 records · Page 2Linked to original sources

Malignant hyperthermia associated with exercise-induced rhabdomyolysis or congenital abnormalities and a novel RYR1 mutation in New Zealand and Australian pedigrees.

Malignant hyperthermia (MH) is rarely associated with specific myopathies or musculoskeletal abnormalities. Three clinical investigations of MH associated with either non-specific myopathies or congenital disorders in three separate families are presented. Two of these cases also show evidence of exercise-induced rhabdomyolysis. In each case MH susceptibility was confirmed by in vitro contracture testing of quadriceps muscle. DNA sequence analysis of each kindred revealed the presence of a common novel mutation that results in an arginine401-cysteine substitution in the skeletal muscle ryanodine receptor gene (RYR1). Haplotype analysis using chromosome 19q markers indicated that the three families are likely to be unrelated, providing confirmation that the MH/central core disease region 1 of RYR1 is a mutation hot spot.

Amino Acid Sequence↗

Which patients stop working because of rheumatoid arthritis? Results of five years' follow up in 732 patients from the Early RA Study (ERAS).

OBJECTIVES: To assess the occurrence and prognostic factors for the ability to maintain paid work in patients with rheumatoid arthritis (RA). SETTING: Inception cohort of patients with RA recruited from rheumatology departments in nine NHS Hospital Trusts in England. PATIENTS: All consecutive patients with RA of less than two years' duration, before any second line (disease modifying) drug treatment, and followed up for five years. METHODS: Clinical, laboratory, and radiological assessments, and all treatments were recorded prospectively using a standardised format at presentation and yearly. OUTCOME MEASURES: Changes in, and loss of paid work by five years' follow up. RESULTS: 732 patients completed the five year follow up. 353/721 (49%) were gainfully employed at the onset of RA, 211 (60%) were still working at five years, 104 (29%) stopped because of the disease, and 31 (9%) retired for reasons other than RA. Work disability at five years was more likely in manual workers (odds ratio (OR) 2.3, 95% confidence interval (CI) 1.4 to 3.8) and worse baseline Health Assessment Questionnaire (HAQ>1.5, OR 2.26, 95% CI 1.38 to 3.7). In combination with other baseline variables (erythrocyte sedimentation rate, sex, age of onset, and radiological erosions), employment outcome was predicted in 78% using multivariate analysis. CONCLUSIONS: Nearly half of the patients with RA were in paid employment at onset, work disability was an adverse outcome for a third of these patients by five years, and manual work and high baseline HAQ were important predictors for this. These details are likely to be useful to clinicians, health professionals, and patients in order to plan medical, orthopaedic, and remedial treatments in early RA. Future disease modifying treatments could be compared with this cohort of patients who were treated with conventional second line drugs.

Adult↗

Entonox as an analgesic agent during panretinal photocoagulation.

BACKGROUND/AIMS: Panretinal photocoagulation (PRP) reduces the risk of visual loss in proliferative diabetic retinopathy but some patients cannot tolerate PRP because of pain. Inhaled Entonox was evaluated as an analgesic during PRP. METHODS: A randomised, crossover, double masked pilot study was performed. Patients inhaled either air or Entonox and half the PRP was applied. The treatment was completed with the alternate inhaled gas. Patients graded pain experienced during both stages of the treatment using a visual analogue scale. Pain scores were compared using a paired t test. RESULTS: 20 patients participated. Mean pain scores from the Entonox and air treatments were 2.94 (SD 2.73) versus 3.73 (SD 3.20) respectively (p<0.03). CONCLUSION: Entonox can be used as a safe and effective analgesic agent during PRP treatment.

Administration, Inhalation↗

A confidential enquiry into cases of neonatal encephalopathy.

OBJECTIVES: To assess the quality of care and timing of possible asphyxial events for infants with neonatal encephalopathy; to compare the quality of care findings with those relating to the deaths from the Confidential Enquiry into Stillbirths and Deaths in Infancy (CESDI); and to assess whether the confidential enquiry method is a useful clinical governance tool for investigating morbidity. DESIGN: Independent, anonymised, multidisciplinary case reviews. SETTING: Trent Health Region, UK. PATIENTS: All cases of grade II and III neonatal encephalopathy born in 1997, excluding those due to congenital malformation, inborn error of metabolism, or infection. All CESDI deaths thought to have resulted from intrapartum asphyxia in 1996 and 1997. MAIN MEASURES: Quality of care provided, timing of possible asphyxial episodes, and the source and timing of episodes of suboptimal care. RESULTS: Significant or major episodes of suboptimal care were identified for 64% of the encephalopathy cases and 75% of the deaths. An average of 2.8 and 2.5 episodes of suboptimal care were identified for the deaths and encephalopathy cases respectively. Over 90% of episodes involved the care provided by health professionals. Results were fed directly back to the units concerned on request and changes in practice have been reported. CONCLUSIONS: The findings were very similar for the encephalopathy cases and the deaths. We have demonstrated that with minor adaptations the CESDI process can be applied to serious cases of morbidity. However, explicit quality standards, control data, and a more formal mechanism for the implementation of findings would strengthen the confidential enquiry process as part of clinical governance.

Asphyxia↗

Sequence diversity and virulence in Zea mays of Maize streak virus isolates.

Full genomic sequences were determined for 12 Maize streak virus (MSV) isolates obtained from Zea mays and wild grass species. These and 10 other publicly available full-length sequences were used to classify a total of 66 additional MSV isolates that had been characterized by PCR-restriction fragment length polymorphism and/or partial nucleotide sequence analysis. A description is given of the host and geographical distribution of the MSV strain and subtype groupings identified. The relationship between the genotypes of 21 fully sequenced virus isolates and their virulence in differentially MSV-resistant Z. mays genotypes was examined. Within the only MSV strain grouping that produced severe symptoms in maize, highly virulent and widely distributed genotypes were identified that are likely to pose the most serious threat to maize production in Africa. Evidence is presented that certain of the isolates investigated may be the products of either intra- or interspecific recombination.

Geminiviridae↗

Antenatal determination of fetal brain activity in response to an acoustic stimulus using functional magnetic resonance imaging.

Functional magnetic resonance imaging (fMRI) is now a well-established technique for directly identifying adult brain activity. This study builds on earlier pilot work that showed that fMRI could provide direct evidence of fetal brain cortical activation in response to an auditory stimulus. The new work presented here aims to assess the sensitivity of this technique in a larger sample group. This article includes a specific discussion of the methodology required for fetal fMRI. Sixteen pregnant subjects were scanned between 37 and 41 weeks gestation, 12 had an auditory stimulus applied to the maternal abdomen (study group) and 4 had an auditory stimulus applied to the mother's ears (control group). Two of twelve (2/12) study-group patients experienced back pain so that the experiment was abandoned; 4/12 showed significant activation (P < 0.005) in one or both of the temporal lobes; 1/12 showed significant activation in the frontal lobe. A susceptibility artifact at the interface between the maternal bowel and the fetus affected 3/12 data sets. No significant activation was found in 3/4 of the control cases, and 1/4 could not be analyzed due to a susceptibility artifact.

Acoustic Stimulation↗

Texture detection of simulated microcalcification susceptibility effects in magnetic resonance imaging of breasts.

The presence, size, structure and clustering characteristics of microcalcifications can indicate breast cancer. The magnetic susceptibility of microcalcifications differs from soft biological tissues, leading to directional blurring effects that can be detected by statistical image processing methods. A study of the ability of statistical texture analysis to detect simulated localized blurring in magnetic resonance imaging (MRI) of dense breast is presented. This method can detect localized blurring with sensitivity of 88.89% to 94.44%, specificity of 99.72% to 100%, positive predictive value of 73.91% to 100% and negative predictive value of 99.91% to 99.95%. J. Magn. Reson. Imaging 2001;13:876-881.

Artifacts↗

The relative infectivities and genomic characterisation of three distinct mastreviruses from South Africa.

The genomic nucleotide sequences of the cloned agroinfectious genomes of three South African mastreviruses obtained from Zea mays, a Setaria sp., and Panicum maximum (designated MSV-Kom, MSV-Set, and PanSV-Kar respectively), were determined. Additionally, their relative infectivities and virulence were analysed in a range of differentially susceptible wheat, maize, and barley genotypes. MSV-Kom produced moderate to severe streak symptoms in all maize genotypes tested, but only moderate to very mild symptoms in the wheat and barley genotypes. MSV-Set infected only the susceptible to tolerant maize genotypes, but was generally more severe in the barley and wheat genotypes than MSV-Kom. PanSV-Kar was incapable of infecting any of the wheat and barley genotypes and only produced very mild symptoms on the three most sensitive maize genotypes. Genomic characteristics in common with related mastreviruses were identified. Phylogenetic analysis indicated that while MSV-Kom was closely related to previously sequenced MSV isolates, MSV-Set and PanSV-Kar represented distinctly novel strains of MSV and PanSV respectively. In the case of MSV-Set, this is the most distantly related MSV strain yet characterised.

Animals↗

The design and evaluation of a simulated-patient teaching programme to develop the consultation skills of undergraduate pharmacy students.

OBJECTIVES: This study aimed to identify the key skills and knowledge required for the delivery of an ideal patient consultation in order to develop a training programme (using simulated-patients) to teach consultation skills to undergraduate pharmacy students. METHODS: Participants included all third year undergraduate Pharmacy students (MPharm, level III) at the School of Pharmacy & Biomolecular Sciences, University of Brighton (from October 1999 to March 2000). Working in groups of 12, students participated in two 4 hour seminars. A structured questionnaire was designed to assess students' perceptions of the difficulty of conducting a consultation and their confidence in delivering a structured consultation. MAIN OUTCOME MEASURES: Questionnaires were administered before and after delivery of the teaching programme to assess changes in students' confidence and ability to consult with patients. RESULTS: Twelve volunteers satisfied the criteria set to serve as simulated patients and then received appropriate training. Six scenarios were developed which focused on the key skills and knowledge identified from the adherence and consultation skills literature. A total of 91 students participated in the programme (mean age = 23 years, SD = 4.5). Following participation in the programme students' perceived 'confidence' for conducting an effective consultation significantly increased (t = -5.9, p < 0.01) while a statistically significant decrease was seen in students' perceived level of 'difficulty' when conducting a consultation (t = 4.0, p < 0.01). CONCLUSION: This study has shown that the use of a structured teaching programme improves students' perceptions of their ability and confidence in conducting an effective consultation. Providing skills training around the consultation process, using simulated patients, provides pharmacists with a good framework around which to practice pharmaceutical care.

Adult↗

Academic and non-academic predictors of success on the Nottingham undergraduate medical course 1970-1995.

OBJECTIVES: To identify academic and non-academic predictors of success of entrants to the Nottingham medical course over the first 25 completed years of the course's existence. SETTING, DESIGN AND MAIN OUTCOME MEASURES: Retrospective study of academic and non-academic characteristics of 2270 entrants between 1970 and 1990, and their subsequent success. Analyses were undertaken of two cohorts (entrants between 1970 and 1985 and entrants between 1986 and 1990). RESULTS: Overall, 148 of 2270 (6.5%) entrants left the course, with the highest proportion being from the first 6 years (10.7%). Of the 148 leavers, 58 (39.2%) did so after obtaining their BMedSci degree. Concerning non-academic factors, in the 1970-85 cohort, applicants from the later years and those not taking a year out were more successful. However, these two factors had no influence on outcome in 1986-90. In contrast, ethnicity and gender were highly significant predictors of success in obtaining honours at BMBS in 1986-90 but at no other exam nor in the earlier years. Older, mature or graduate entrants were more successful at obtaining a first-class degree at BMedSci for the whole 21 years. However, they were less likely to be successful at passing the BMBS. With regard to academic factors, overall, A grades at Ordinary level/General Certificate of Secondary Education (O-Level/GCSE) were inconsistent independent predictors of success. However, for 1986-90, high grades at O-Level/GCSE chemistry and biology were strong independent predictors of success at BMedSci and BMBS. Very few Advanced level (A-Level) criteria were independent predictors of success for 1970-85. In contrast, for 1986-90 entrants, achieving a high grade at A-Level chemistry predicted success at obtaining a first-class degree at BMedSci, and a high grade at A-Level biology predicted success at BMBS. Over the 21 years, the majority of entrants achieved significantly lower grades at A-Level than predicted. General Studies A-Level was a poor predictor of achievement. CONCLUSIONS: On balance our current GCSE A-grade requirements should remain. Biology should be added to Chemistry as a compulsory A-Level subject. If predicted A-Level grades are borderline then the lower estimate should be used. General Studies should continue not to be used in selection. Performance of more recent mature entrants at BMBS needs further study. The recent gender and ethnic biases in obtaining honours at BMBS is currently being examined. The motivation of applicants planning to take deferred entry should be carefully explored at interview.

Achievement↗

Persistent right umbilical vein in a fetus with Noonan's syndrome: a case report.

We present a case of persistent right umbilical vein with Noonan's syndrome. Persistence of the right umbilical vein with no intrahepatic portion is an uncommon finding with a review of the literature revealing only five other cases. In these cases drainage was directly into the right atrium, inferior vena cava (IVC) or IVC via the iliac vein. Of the reported cases Noonan's syndrome was confirmed in one case and suspected in a second. This report represents a third case of persistent right umbilical vein with confirmed Noonan's syndrome.

Adult↗

Antimicrobial susceptibility of Pseudomonas aeruginosa: results of a UK survey and evaluation of the British Society for Antimicrobial Chemotherapy disc susceptibility test.

A survey was conducted in 1999, first to establish the prevalence of antibiotic resistance among clinical isolates of Pseudomonas aeruginosa in the UK and secondly to test whether the use of the standardized British Society for Antimicrobial Chemotherapy (BSAC) disc testing method improved the accuracy of routine susceptibility testing for this organism. Twenty-five hospitals were each asked to collect up to 100 consecutive, clinically significant isolates of P. aeruginosa and to test their susceptibility to amikacin, gentamicin, ceftazidime, imipenem, meropenem, ciprofloxacin, piperacillin and piperacillin/tazobactam using the new BSAC disc method. A total of 2194 isolate reports were available for analysis and 10% of the isolates represented, plus those with unusual resistances, were re-tested centrally for quality control purposes. The zone distributions were essentially unimodal, indicating the absence of major populations with acquired resistance. The results indicated that resistance rates to the beta-lactam, aminoglycoside and quinolone agents tested in P. aeruginosa in the UK remain low (<12%), and were mostly unchanged since a previous survey conducted in 1993. High resistance rates were nevertheless reported for isolates from cystic fibrosis patients. The accuracy of susceptibility testing using the new BSAC disc testing method was better than in previous studies, when Stokes' method was most frequently used. Critically, the proportion of resistant isolates incorrectly reported as susceptible was reduced significantly; nevertheless, depending on the antibiotic, up to 49% of the isolates reported as intermediate or resistant were found susceptible on central re-testing.

Anti-Bacterial Agents↗

In vitro reaction of formaldehyde with fenfluramine: conversion to N-methyl fenfluramine.

Embalming is common, and it can create problems for the forensic scientist if a drug has been the cause death and this drug is also reactive toward the embalming fluid. Previous studies have focused on the tricyclic amines nortriptyline and desipramine. In the presence of formaldehyde, a typical component of embalming fluid, either of these two compounds can be rapidly converted to their methylated derivatives amitriptyline and imipramine, respectively. We have begun a larger project designed to determine the reactivity and reactions of a wide range of drugs with formaldehyde. We report here our results from fenfluramine, which, like the tricyclic amines, is reactive towards formaldehyde and is converted into its N-methyl derivative. The rate of conversion is dependent upon pH and formaldehyde concentration. Up to 100% conversion in 24 h was observed. In addition, we have also devised a simplified procedure for monitoring this process that may be useful for others working in this area. Finally, we note that the reactions of fenfluramine studied here and of amines in general with formaldehyde need to be considered when performing postmortem/postembalming forensic analysis.

Embalming↗

In vitro reaction of barbiturates with formaldehyde.

Barbiturates are widely used as sedatives, hypnotics, and antiepileptics, and, when coupled with their narrow therapeutic index, the probability that their use will result in accidental or intentional death is significant. When barbiturates are implicated in a murder or suicide, analysis for their presence is often required. Under certain conditions, barbiturates are quite stable, but conditions found in vivo immediately after death or after embalming may promote barbiturate decomposition. If extensive decomposition occurs, analysis for them may be difficult or impossible. Here, the stability of three representative barbiturates, under conditions that model those likely to prevail in vivo shortly after death and after embalming, have been studied. Solutions of phenobarbital were found to slowly decompose in water over the pH range of approximately 3.5 to 9.5. More rapid decomposition occurred at higher pH, and 2-phenylbutyric acid was the main decomposition product. Formaldehyde (5-20%) accelerated the decomposition rate 3-10-fold such that phenobarbital decomposition could be complete after 30 days. In contrast, pentobarbital decomposed roughly 10 times more slowly and secobarbital did not detectably decompose under any of the conditions studied. Thus, certain barbiturates may partially or completely decompose in vivo after death, especially after embalming, and thus analysis for them may lead to false negatives. However, this work shows that analysis for the parent barbiturate or its predicted decomposition product may provide data that will reduce the likelihood of false negatives.

Barbiturates↗

Spontaneous peritonitis from perforation of the colon in collagenous colitis.

A 37-year-old woman presented with an acute abdomen following the onset of watery diarrhea. Spontaneous peritonitis was detected, along with evidence of a focal sigmoid colon perforation. Subsequent postoperative colonoscopic studies revealed collagenous colitis with a focal, deep, nongranulomatous ulcer in the sigmoid colon. Although the literature suggests that collagenous colitis tends to have a relatively 'benign' clinical course characterized by chronic or episodic watery diarrhea. Potentially serious and life- threatening complications may occur in this microscopic form of inflammatory bowel disease.

Adult↗