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Biomedical subjects

J Mitchell

Publications and source records attributed to J Mitchell.

At least 91 records · Page 5Linked to original sources
PubMed1996

d-Sotalol decreases defibrillation energy requirements in humans: a novel indication for drug therapy.

INTRODUCTION: We assessed the effect of d-sotalol on defibrillation voltage and energy requirements in patients undergoing automatic defibrillator implantation. Drugs that primarily prolong cardiac refractoriness generally decrease the energy requirements for defibrillation in animal models. Despite the widespread use of antiarrhythmic drugs in patients with implanted cardioverter defibrillators, the effect of such drugs on defibrillation energy requirements in humans has not been well studied. Sotalol (in the d,l racemic form) is an antiarrhythmic with beta-blocking and cardiac refractoriness prolonging effects. The d-isomer of sotalol is largely devoid of beta-blocking effects; both forms decrease defibrillation energy requirements in animals. We hypothesized that d-sotalol would decrease defibrillation voltage and energy requirements in humans. METHODS AND RESULTS: Fifteen patients undergoing implanted cardioverter defibrillator implantation were studied before and 20 minutes after d-sotalol infusion (2 mg/kg IV in 15 min, followed by 1 mg/kg per hour). The estimated energy (E50) and voltage (V50) for 50% success in defibrillation (estimated from two successive defibrillation "threshold" measurements), ventricular effective refractory period, monophasic action potential duration, and mean cycle length of ventricular fibrillation were measured, along with heart rate, blood pressure, and plasma concentration of d-sotalol. There was a significant decrease in defibrillation energy (E50 = 12.4 +/- 5.0 J before and 8.4 +/- 4.0 J after d-sotalol, P < 0.003) and voltage (V50 = 440 +/- 77 V before and 354 +/- 93 V after d-sotalol, P < 0.001). Consistent with the Class III effect of d-sotalol, ventricular effective refractory period increased from 284 +/- 21 to 330 +/- 24 msec (P < 0.001), and action potential duration was prolonged from 296 +/- 28 to 340 +/- 22 msec (P < 0.001). Following d-sotalol, there was a tendency for induced tachyarrhythmia to self-terminate (23/102 episodes before vs 74/150 after sotalol, P < 0.001), and ventricular fibrillation cycle length was increased from 216 +/- 20 msec before to 274 +/- 23 msec (P < 0.001) after d-sotalol, despite the persistence of a rapid, disorganized rhythm of the surface ECG. No patient suffered adverse effects. CONCLUSIONS: d-Sotalol lowers defibrillation energy by a mean 32% +/- 27% at concentrations producing a 16% +/- 7% increase in ventricular effective refractory period. Along with its other antiarrhythmic effects, d-sotalol may increase the safety margin for defibrillation or allow lower programmed energies in patients with implanted defibrillators.

Adrenergic beta-Antagonists↗
PubMed1996

Antigen recognition during progression from acute to chronic infection with a cagA-positive strain of Helicobacter pylori.

We have previously published two reports on acute infection with Helicobacter pylori, one of an adult male and one of a family of four. In the present study, we have isolated H.pylori from each of twin boys in the family and compared these by use of random amplified polymorphic DNA PCR. In addition, we have monitored the antibody response over time of the family and the adult male by Western blotting (immunoblotting) with two different strains of H. pylori as the antigen and by use of a commercial kit. The acutely infected twin boys were infected by an identical strain of H. pylori. The twin boys responded to antigens of 19, 26.5, and 29 kDa 30 days after the initial diagnosis, with recognition of 43-to 49-, 66-, 69-, and 87-kDa antigens by day 63. One twin responded to the CagA antigen on day 63, whereas the other responded on day 857. Antibody to the CagA antigen was not detected by use of the infecting strain, UNSW-RU1. Investigation of UNSW-RU1 revealed the presence of cagA. In two acutely infected adults (one, the father of the boys), the initial response to a 45-kDA antigen was later followed by responses to 19-, 29-, 49-, 60-, 77-, and 84-kDa antigens. Sera from the twins' younger sister, born 17 months after the twins acute episode, indicated that she also had become infected. This report supports intrafamilial transmission of H. pylori. Initial antibody responses in the children were to small-molecular-size antigens; in the adults, the initial responses were to larger-molecular-size antigens. The pattern of the serological response differs according to the antigen used. This has implications in regard to international data comparisons.

Acute Disease↗
PubMed1996

Effect of land-based and water-based fitness programs on the cardiovascular fitness, strength and flexibility of women aged 65-75 years.

The purpose of this study was to determine the effectiveness of a generalized water-based exercise program (WBE) compared to a land-based exercise program (LBE) on improving cardiorespiratory fitness, body composition, forward trunk flexion and strength measurements of elderly women aged 70 +/- 3.2 years (mean +/- SD). Forty-one healthy, sedentary women were selected to participate in the study and were randomly assigned to the LBE or WBE. The 2 groups exercised for 12 weeks, 3 times/week for 45 min. Fitness testing was done before, during and after training, and included measurements of peak aerobic power (VO2 peak), forward trunk flexion, sum of skinfolds, grip strength, curl-ups and push-ups. Between the tests performed before and after training, there were significant improvements in VO2 peak in both groups (p < 0.05) with no significant differences between the groups (p > 0.05). The LBE group also showed a significant improvement in the total number of curl-ups performed (p < 0.05). There were no significant differences in trunk forward flexion, total (right plus left) grip strength, push-ups, waist to hip ratio, sum of skinfolds or body mass index between the tests performed before and after training over time within groups or between groups (p > 0.05). The results show that general exercise interventions resulted in improvements in cardiovascular fitness (for both groups) and abdominal endurance (in the LBE only), but the two exercise programs used were not specific enough or long enough to cause improvements in muscular strength, flexibility or body composition. Furthermore, except for changes in abdominal endurance, the type of exercise venue (land vs. water) did not have a significant effect on the results obtained.

Aged↗
PubMed1996

Developing quality indicators as educational tools to measure the implementation of clinical practice guidelines.

Our objective was to explore expectations and recommendations for the development of measurable quality indicators as educational tools to implement clinical practice guidelines. A survey using structured personal interviews with a stratified sample of 20 health professionals was made. Questions analyzed preferences in evaluating quality of care, measuring discrepancies between clinical guidelines and actual practice patterns, and the development of quality indicators. All of our participants (100%) reported that the compliance with established and widely accepted clinical guidelines is an important quality indicator. Health professionals indicated 1.8 (+/- 1.1) overall preference of our developed quality indicators for the management of depression. Although most currently used quality indicators focus either on the process or on the outcome of care, health professionals strongly prefer indicators that measure both. Our measurable quality indicators were found to have wide acceptance without major differences among primary care physicians, medical directors, and health benefit managers.

Adult↗
PubMed1996

The hepatopulmonary syndrome: radiologic findings in 10 patients.

OBJECTIVE: The purpose of this study was to review the radiologic manifestations of the hepatopulmonary syndrome. MATERIALS AND METHODS: We retrospectively reviewed clinical records, chest radiographs, 99m Tc-macroaggregated albumin (MAA) perfusion lung scans, chest CT scans, and pulmonary angiograms of 10 patients with proven hepatopulmonary syndrome. RESULTS: Chest radiographs showed basilar, medium-sized (1.5-3.0 mm) nodular or reticulonodular opacities in all cases. CT was done in eight cases and showed basilar dilatation of lung vessels with a larger than normal number of visible branches. The vascular basis for these opacities was best appreciated on conventional CT scans of 10-mm sections. No individual arteriovenous malformations were seen on CT scans. High-resolution CT scans showed no evidence of interstitial fibrosis. 99mTc-MAA perfusion lung imaging, done in seven patients, showed pulmonary arteriovenous shunting in five. Contrast echocardiography confirmed intrapulmonary shunting in these five patients. Pulmonary angiography, done in four cases, showed subtle distal vascular dilatation in two and moderate dilatation with early venous filling in two but did not reveal any individual arteriovenous malformations. CONCLUSION: Chest radiographs in hepatopulmonary syndrome usually show bibasilar nodular or reticulonodular opacities. Conventional CT shows that these opacities represent dilated lung vessels. High-resolution CT is useful in excluding pulmonary fibrosis or emphysema as the cause of these opacities. 99mTc-MMA perfusion imaging or contrast echocardiography can be used to confirm intrapulmonary arteriovenous shunting.

Adult↗
PubMed1996

Aberrant Timm-stained fibres in the dentate gyrus following tetanus toxin-induced seizures in the rat.

The present study addresses whether seizures, which result from the chronic block of inhibition caused by an intrahippocampal injection of tetanus toxin, induce axonal sprouting of the hippocampal mossy fibres. Timm stain was used to identify the mossy fibre terminals. In nine of 15 animals killed at 1 month or later after an injection of tetanus toxin, Timm-stained terminals were observed bilaterally in the inner molecular layer and in seven animals a meshwork of Timm-stained fibres/ terminals was also observed bilaterally in the outer molecular layer of the fascia dentata. None of these changes were observed in any of the 12 saline-injected controls. There was no obvious correlation between the number of motor fits an animal exhibited and the amount of Timm-stained fibre sprouting present in either the inner or outer molecular layer. The Timm-stained axonal sprouting into the outer molecular layer of the fascia dentata may simply reflect the reinnervation of sites on the granule cell dendrites, previously occupied by the terminals of the hilar somatostatin-containing cells. These hilar somatostatin-containing cells which are believed to project to the outer molecular layer are known to succumb to the seizure activity in this animal model of epilepsy.

Animals↗
PubMed1996

Genetic diversity among selected ethnic subpopulations of Australia: evidence from three highly polymorphic DNA loci.

Immigration has been the principal source of population growth in Australia since European settlement began in 1788. As a result, the Australian gene pool has been constantly evolving, particularly over the last 50 years, during which peoples from many European and Asian countries have arrived in large numbers. Three highly polymorphic DNA loci (D1S80, HLA-DQA1, and human THO1) are used to assess the level of diversity among six immigrant subpopulations that compose significant elements in present-day Australia, namely, Asians, Italians, Greeks, Slavs, Middle Easterners, and a "general white" sample. Asian migrants are the most distinctive of the groups at all three loci, possessing the highest frequencies of alleles HLA-DQA1*3 and D1S80*27, *28, and *30, and an exceptionally high frequency of THO1*9. The European-derived groups cluster together separately from Asians, but Greeks are characterized by their frequencies of HLA-DQA1*2 and *4 and THO1*8. Middle Easterners lie on the fringe of the European cluster. When the results of the present study are combined with worldwide data for each of the three DNA markers, these hypervariable loci, especially D1S80 and THO1, are able to differentiate the major groups of humans. The level of population differentiation revealed by RST values for the three DNA markers is similar to or even less than the values recorded for the less polymorphic classical genetic markers. Therefore these three DNA markers are highly suitable for both forensic purposes and the investigation of population relationships.

Adult↗
PubMed1996

Long-term outlook for survivors of congenital diaphragmatic hernia.

CDH patients are critically ill but can expect excellent survival if other serious anomalies are not present; however, significant long-term morbidities exist in the survivors. The most notable of these are developmental delay, poor growth, gastroesophageal reflux disease, hearing loss, and musculoskeletal abnormalities. Patients require careful long-term follow-up for these problems, and caregivers must continue to critically evaluate their medical interventions in the neonatal period to try to minimize these morbidities.

Child, Preschool↗
PubMed1996

Allotypes of complement components C4, C3, C2 and BF in the populations of Tasmania and northeast England.

The distribution of four serum complement component polymorphisms (BF, C2, C3 and C4) were examined in two geographically separated populations, one from Tasmania (Australia) and the other from northeast England. The differences in genotypic frequencies between them at all 4 loci are not statistically significant (p > 0.05). When C4 haplotypes were investigated, only one (C4A4-C4B2) exhibited significant linkage disequilibrium (p = 0.0006 after correction, p = 0.01), and this was only observed in Tasmanians. The English population exhibited a larger number of alleles across the four loci used in this study than the Tasmanian, and this may well reflect a bottle-neck effect and the greater relative isolation of the population of the island State of Australia. Overall, the findings confirm the close relationship between immigrants from the British Isles to Tasmania.

Complement C2↗
PubMed1995

The multidomain structure of Orc1p reveals similarity to regulators of DNA replication and transcriptional silencing.

The origin recognition complex (ORC) is a six protein assembly that binds S. cerevisiae origins of replication and directs DNA replication throughout the genome and transcriptional silencing at the yeast mating-type loci. Here we report the cloning of the genes encoding the 120 kDa (ORC1), 62 kDa (ORC3), and 56 kDa (ORC4) subunits of ORC and the reconstitution of the complete complex after expression of all six subunits in insect cells. Orc1p is related to Cdc6p and Cdc18p, which regulate DNA replication and mitosis, and to Sir3p, a regulator of transcriptional silencing. The N-terminal region of Orc1p is highly related to Sir3p, and studies of Orc1p/Sir3p chimeric proteins indicate that this domain is dedicated to the transcriptional silencing function of ORC.

Amino Acid Sequence↗
PubMed1995

Pulmonary hypoplasia and fetal breathing in preterm premature rupture of membranes.

Forty-eight patients with premature rupture of membranes prior to 24 weeks gestation (PPROM) were studied to investigate whether there was any difference in fetal breathing movements in those fetuses that did or did not develop pulmonary hypoplasia. The diagnosis of pulmonary hypoplasia was made on the basis of ultrasound measurement of fetal lung length. A control group of fetuses with intact membranes and normal pregnancies at the same gestation was also studied. The group that developed pulmonary hypoplasia had significantly less breathing movements than those that did not develop pulmonary hypoplasia and controls. This reduction in breathing movements may contribute to the development of pulmonary hypoplasia.

Female↗
PubMed1995

Purification, characterization, and partial amino acid sequence of a G protein-activated phospholipase C from squid photoreceptors.

Invertebrate visual transduction is thought to be initiated by photoactivation of rhodopsin and its subsequent interaction with a guanyl nucleotide-binding protein (G protein). The identities of the G protein and its target effector have remained elusive, although evidence suggests the involvement of a phospholipase C (PLC). We have identified a phosphatidylinositol-specific PLC from the cytosol of squid retina. The enzyme was purified to near-homogeneity by a combination of carboxymethyl-Sepharose and heparin-Sepharose chromatography. The purified PLC, identified as an approximately 140-kDa protein by sodium dodecyl sulfate-polyacrylamide gels, hydrolyzed phosphatidylinositol 4,5-bisphosphate (PIP2) at a rate of 10-15 mumol/min/mg of protein with 1 microM Ca2+. The partial amino acid sequence of the protein showed homology with a PLC cloned from a Drosophila head library (PLC21) and lesser homology with Drosophila norpA protein and mammalian PLC beta isozymes. Reconstitution of purified squid PLC with an AlF(-)-activated 44-kDa G protein alpha subunit extracted from squid photoreceptor membranes resulted in a significant increase in PIP2 hydrolysis over a range of Ca2+ concentrations while reconstitution with mammalian Gt alpha or Gi 1 alpha was without effect. These results suggest that cephalopod phototransduction is mediated by G alpha-44 activation of a 140-kDa cytosolic PLC.

Amino Acid Sequence↗
PubMed1995

A fundamental problem of consent.

A consultant anaesthetist gave a diclofenac suppository for postoperative pain to a patient having four teeth extracted under general anaesthesia in the dental surgery. He did not seek the patient's specific consent preoperatively for use of the suppository but told her afterwards what he had done. Charged before the professional conduct committee of the General Medical Council with failure to obtain informed consent and assault, the anaesthetist was found guilty of serious professional misconduct and admonished. This decision has far reaching implications and has caused great concern.

Adult↗