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Biomedical subjects

P R James

Publications and source records attributed to P R James.

At least 19 recordsLinked to original sources
PubMed2005

Delayed presentation of traumatic ventricular septal defect and mitral leaflet perforation.

A case of intracardiac stabbing is reported. The victim sustained injuries disproportionate to his initial presentation. These included a ventricular septal defect and mitral valve leaflet perforation. The need for immediate referral to a cardiothoracic unit and the importance of the use of echocardiography is stressed. This enables the safest and most appropriate management of potentially lethal injuries.

Echocardiography, Transesophageal↗
PubMed2004

Morphological features of the microdistribution of naturally occurring 10Pb/2l0Po and 226Ra in the teeth of children and juveniles.

PURPOSE: To examine the microdistribution of natural alpha-radioactivity in deciduous teeth of children and the permanent teeth of juveniles extracted for orthodontic purpose from across the UK. MATERIALS AND METHODS: The microdistribution of 210Pb-supported 210Po and 226Ra in 708 deciduous and permanent teeth and 32 foetal teeth was measured on 1442 TASTRAK alpha-particle track detectors. RESULTS: Of the various findings, a number are of special interest. Around half of the 210Pb activity in the outer enamel of deciduous teeth appears to have been acquired in utero as a result of transplacental transfer. In deciduous and permanent teeth, 226Ra is concentrated mainly in the circumpulpal region, while the highest levels of 210Po are on the highly calcified outer enamel surface. Furthermore, activity concentrations recorded on this surface were In-normally distributed. CONCLUSIONS: 210Pb-supported 210Po activity on the outer enamel surface of permanent teeth constitutes an assay of cumulative environmental exposure with which to assess exposure in bone, both in utero and in childhood. Such assessment can be used to study geographical variations in the alpha-activity in teeth. More work is also required to determine the concentrations of both 210Po and 210Pb in the foetal skeleton.

Adolescent↗
PubMed2004

Aspects of the geographical variations of naturally occurring 210Pb/210Po in permanent teeth of juveniles in the UK.

PURPOSE: To study geographical variations in the level of naturally occurring 210Pb-supported 210Po in permanent teeth of juveniles in the UK. MATERIALS AND METHODS: Permanent teeth extracted from 278 juveniles for orthodontic purposes were obtained from 48 counties in the UK. 210Po activity concentration was measured on the outer enamel surface using TASTRAK alpha-particle-sensitive plastic track detectors. RESULTS: Geometric mean +/- SE activity concentrations in teeth from urban, suburban and rural areas, excluding the high radon area of Devon, were 8.41 + 0.25/-0.24, 7.76 + 0.37/-0.35 and 7.20 +0.49/-0.46 Bq kg(-1), respectively. Overall, there was no significant association between alpha-activity on the outer enamel surface of permanent teeth and proximity to the major UK motorways. However, when the data were considered with respect to the prevailing south-westerly wind on the western side of the UK, a statistically significant association with respect to donors living downwind (on the easterly side) of the motorways was found. This effect was greater for sections of the M5 and M6 motorways that traverse urban areas. 210Po levels in teeth were also associated with domestic radon concentration. This effect was comparable with that from traffic and urban pollution. CONCLUSIONS: Higher levels of 210Pb-supported 210Po are seen in permanent teeth of juveniles near sources of increased exposure in the UK. Inhalation uptake is an important pathway of exposure, especially with respect to domestic radon exposure. The results might be important in assessing integrated exposure to 210Po in the skeleton and consequent high linear energy transfer dose to bone marrow.

Adolescent↗
PubMed2002

Physiological changes in ventricular filling alter cardiac electrophysiology in patients with abnormal ventricular function.

OBJECTIVE: To explore the hypothesis that patients with abnormal ventricular function have an altered electrophysiological response to physiological changes in ventricular filling which is not evident in people with normal ventricles. DESIGN: The influence of an acute alteration in ventricular filling on dispersion of repolarisation, measured as QT dispersion, was examined in subjects with normal (n = 9) and abnormal ventricles (n = 9). A physiological reduction in ventricular filling was achieved using dual chamber atrioventricular (AV) pacing in two different modes-AV pacing: atrial activation 120 ms before ventricular activation such that atrial contraction occurred normally in late diastole; and VA (ventriculoatrial) pacing: atrial activation 50 ms after ventricular activation, such that atrial contraction occurred after closure of the AV valves. The absence of effective atrial contraction was confirmed by echocardiography. Ventricular cycle length and sequence of excitation through the ventricle was constant throughout both VA and AV sequences within each patient. RESULTS: During AV pacing (normal ventricular filling) there was no significant difference in QT dispersion between the two groups. In contrast during VA pacing, when the atrial component to ventricular filling was abolished, there was an immediate and consistent increase in QT dispersion compared with baseline in subjects with abnormal ventricular function (p < 0.001) but not in those with normal ventricles. CONCLUSIONS: An abrupt change in ventricular filling, within the physiological range, increased QT dispersion in subjects with abnormal ventricular function but not in subjects with normal ventricles. The findings suggest an altered electrophysiological response to ventricular load in patients with abnormal ventricular function.

Echocardiography↗
PubMed2001

Drugs in pregnancy. Cardiovascular disease.

This chapter reviews the therapeutic armamentarium available for the treatment of cardiovascular disease during pregnancy. The management does not differ markedly from that of the non-pregnant population. Few drugs are absolutely contraindicated, although, for many, safety data are limited and caution is recommended. The potential risks to the fetus must be weighed against maternal benefit and the well-being of the pregnancy. Women of childbearing age requiring long-term medication should be offered pre-pregnancy counselling, and other non-pharmacological avenues, such as radio-frequency ablation for supraventricular arrhythmias, should be explored.

Anti-Arrhythmia Agents↗
PubMed2000

Acute psychological stress and the propensity to ventricular arrhythmias; evidence for a linking mechanism.

AIMS: This study was designed to test the hypothesis that acute psychological stress is capable of inducing an increase in the dispersion of repolarization in patients with underlying coronary artery disease. METHODS AND RESULTS: Twenty four patients undergoing elective coronary angiography were studied, 17 with significant coronary artery disease and seven with normal coronary arteries. Following coronary angiography they were subjected to a series of timed cognitive tests, well known to induce acute psychological stress. An individual's perception of stress was assessed by visual analogue scales. Serial ECGs were recorded during the cognitive tests and QT, QRS and JT intervals measured from which QT, QRS and JT dispersion were calculated. Psychological stress was reported by the seven patients with normal coronaries and 14 of the 17 with coronary artery disease. In patients who experienced stress a marked increase in QT dispersion, reflecting JT dispersion, was observed in those with coronary artery disease (F=22.4, P=0.0001) but not in those without. At baseline there was no difference in QT dispersion between those with and without coronary artery disease (27-57 ms, 17-53 ms, P > or = 0.5). CONCLUSION: Acute psychological stress induces an increase in QT dispersion in patients with underlying coronary artery disease due to changes in JT dispersion (rather than QRS dispersion). This suggests that psychological stress modifies the dispersion of repolarization through ischaemia related changes in action potential duration.

Acute Disease↗
PubMed1993

Development of an in vitro hepatotoxicity assay for assessing the effects of chronic drug exposure.

We have used the human hepatoma cell line HepG2 to compare the hepatotoxic effects of acute (24 hr) and chronic (up to 10 days) exposure to amitriptyline, paracetamol and ondansetron. In acute exposure studies, hepatotoxicity was assessed by the sulforhodamine B protein staining method, where amitriptyline and paracetamol produced 50% hepatotoxicity at concentration of 30 microM and 7 mM, respectively, while ondansetron was non-hepatotoxic at 100 microM, the highest concentration used. In chronic exposure studies, the morphology of HepG2 cells was assessed by phase microscopy every 2 days and the compounds, at concentrations determined from the acute assay, were added fresh every 2 days. Chronic exposure to amitriptyline and paracetamol produced significant morphological changes in HepG2 cells at 3 microM and 1 mM respectively, concentrations which had no significant effect in the acute assay. Ondansetron (100 microM) produced only slight morphological changes in the cells after 10 days of culture. The combination of acute and chronic drug exposure assays with HepG2 cells represents novel in vitro systems for the hepatotoxicological assessment of drugs intended for human use.

Acetaminophen↗
PubMed1991

Development of a co-culture system with induced HepG2 cells and K562 cells for examining drug metabolism in vitro. Studies with cyclophosphamide, ondansetron and cisplatin.

We have established a cell co-culture system for assessing potential cytotoxic effects of drugs and their metabolites in vitro. Human hepatoma cells (HepG2) were cultured for 7 days in modified Earle's medium in order to induce their drug metabolising (primarily mixed function oxidase) enzymes. K562 human erythroleukemic cells in Transwells, were used as indicator cells for the cytotoxic effects of cyclophosphamide (CYP) and Ondansetron (OND) and/or their metabolites, produced by induced HepG2 cells in the co-cultures. CYP was found to be approximately 1000 times more toxic to K562 cells when cultured in the presence of induced HepG2 cells. OND, a selective 5-HT3 receptor antagonist which is used as an anti-emetic during chemotherapy, was not found to be cytotoxic in the co-cultures at concentrations as high as 100 microM. Since OND has been particularly useful in relieving vomiting induced by cisplatin (cisPt) chemotherapy, we also examined the effect of cisPt on K562 cells in the presence and absence of OND, and found no evidence that OND significantly enhances the cytotoxic effect of cisPt on these cells alone or in co-cultures with induced HepG2 cells. The induced HepG2 co-culture system uses cells of human origin and clearly has considerable potential for examining the effects of drugs and their metabolites on indicator cells derived from a tissue of choice. This system may be particularly useful in the assessment of metabolism and toxicity of new drugs intended for human use.

Antiemetics↗