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Biomedical subjects

P Morton

Publications and source records attributed to P Morton.

At least 19 recordsLinked to original sources

Mechanism of binding of warfarin enantiomers to recombinant domains of human albumin.

Domain fragments of human serum albumin corresponding to domains 1 and 2 (D12) and domains 2 and 3 (D23) were expressed in yeast. The kinetics of warfarin binding to these fragments were investigated using stopped-flow fluorescence spectroscopy. Binding can be characterized by a two-step process, a rapid diffusion-controlled step and a slower rate-limiting step in which a stable drug-protein complex is formed. The equilibrium constant for step 1 is greater for both D12 and D23 than for albumin, probably as a result of reduced steric hindrance offered by the domain fragments. Binding step 2, thought to be the result of a conformational change as warfarin is accommodated by the protein, is faster for D12 and D23. Albumin and the domain fragments show an increased preference for the R enantiomer, but the preference is particularly enhanced for domain fragment D12. These preferences can largely be explained by the domains having different rates for step 2 of the binding process.

Binding Sites↗

Child health profiles: the viewpoints of adults.

UNLABELLED: THE CHILD HEALTH PROFILE: The teenage years have been identified as an important time to influence attitudes and behaviour likely to affect current and future health. The child health profile was developed partly to provide appropriate health information to young people aged 10 and older, but was also intended to recognize their right to assume greater responsibility for their health records. It was seen as an extension of the popular parent held record for younger children. METHODS: A Scottish child health profile was introduced through schools in three health board areas. Data about usage and views were obtained from children and relevant adults by means of questionnaires. In this paper, the perspectives of parents, health professionals and teachers are reported. FINDINGS: The majority of the adults were keen on the idea of the profile in principle. However, most parents knew little about it, even though all their children had been issued with one. Teachers had little involvement with the profile and the majority of health professionals had some doubts about its application. The adults indicated that a small number of children made effective use of the profile, but information from both adults and children indicated that it was seldom discussed during consultations with health professionals, few of whom routinely asked to see it. CONCLUSIONS: The paper outlines implications for the provision of health information and records for this age group.

Adolescent↗

Positive outcome after preimplantation diagnosis of aneuploidy in human embryos.

usromosomal abnormalities are responsible for a great deal of embryo wastage, which is reflected, at least partially, in decreased implantation and increased miscarriage in older women. To address this problem the transfer of only chromosomally normal embryos previously selected by preimplantation genetic diagnosis (PGD) has been proposed. We designed a multi-centre in-vitro fertilization (IVF) study to compare controls and a test group that underwent embryo biopsy and PGD for aneuploidy. Patients were matched retrospectively, but blindly, for average maternal age, number of previous IVF cycles, duration of stimulation, oestradiol concentrations on day +1, and average mature follicles. All these parameters were similar in test and control groups. Only embryos classified as normal for those chromosomes were transferred after PGD. The results showed that the rates of fetal heart beat (FHB)/embryo transferred between the control and test groups were similar. However, spontaneous abortions, measured as FHB aborted/FHB detected, decreased after PGD (P < 0.05), and ongoing pregnancies and delivered babies increased (P < 0.05) in the PGD group of patients. Two conclusions were obtained: (i) PGD of aneuploidy reduced embryo loss after implantation; (ii) implantation rates were not significantly improved, but the proportion of ongoing and delivered babies was increased.

Aneuploidy↗

Scoring criteria for preimplantation genetic diagnosis of numerical abnormalities for chromosomes X, Y, 13, 16, 18 and 21.

Fluorescence in-situ hybridization (FISH) for application in preimplantation genetic diagnosis (PGD) of aneuploidy has been used successfully, but stringent scoring criteria to score FISH signals have not been developed. In the present study a FISH protocol to simultaneously enumerate chromosomes X, Y, 13, 16, 18, and 21 was used to evaluate two different scoring criteria. The criteria consider hybridization signal size, shape, and vicinity to other signals and nuclear diameter. For this purpose, 74 embryos (412 blastomeres) donated for research had most or all of their cells analysed. The least error-prone criterion (9%) was selected for use in PGD cases. Some probes produced more errors than others, and these criteria may provide clues to improve these probes. The same probe solution was applied to 55 PGD cases and a total of 307 embryos. Of the non-transferred embryos, 67 were fully reanalysed and 1.5% (1/67) of them were falsely diagnosed as normal, while 19% (13/67) were falsely diagnosed as abnormal. Twelve of the patients became pregnant after PGD.

Aneuploidy↗

Effect of noninvasive low intensity ultrasound on bone growth into porous-coated implants.

Noninvasive low intensity ultrasound has been shown to be an effective means of accelerating bone fracture healing in both animal and clinical studies. An in vivo canine study was designed to determine if noninvasive low intensity ultrasound could influence the rate and extent of bone growth into porous-coated implants. Twenty-two pairs of fully porous transcortical implants were inserted bilaterally into the femora of 12 dogs. In each dog, one femur served as a control and the other was subjected to daily ultrasound stimulation for 2, 3, or 4 weeks. Overall, the ultrasound-stimulated implants demonstrated an 18% increase in bone ingrowth compared with their contralateral controls (p = 0.02). Noninvasive low intensity ultrasound had its greatest effect in the first 2-3 weeks of stimulation. At 2 and 3 weeks, the ultrasound-stimulated implants showed 21 and 16% more ingrowth than their respective contralateral controls. Because noninvasive low intensity ultrasound had a positive effect on bone ingrowth in this experimental investigation, further research is suggested to assess the clinical potential for application to noncemented porous-coated total joint replacements.

Animals↗

Preliminary experience with human oocyte cryopreservation using 1,2-propanediol and sucrose.

Feasibility of cryopreservation of mature human oocytes using 1, 2-propanediol and sucrose was studied initially utilizing 1 and 2 day old unfertilized oocytes. Of these 285 aged oocytes 55% survived thawing, and 41% of 128 oocytes inseminated by single sperm intracytoplasmic injection (ICSI) fertilized normally. Limited embryonic development occurred in 51% of these embryos (n = 27) observed for the next 4 days. Cryosurvival of fresh donated oocytes (n = 81) was poorer (n = 20; 24.7%), while fertilization (n = 13; 65%) and embryo development (100%) was good prior to uterine transfer on day 3. Eight oocyte recipient cycles were undertaken, in which cryopreserved donated oocytes were thawed and inseminated by ICSI. Five of these cycles reached embryo transfer, and three pregnancies were initiated though none went successfully to term. Oocyte cryopreservation will ultimately facilitate oocyte donation procedures; however, cryosurvival of fresh frozen oocytes must be improved to at least the degree observed with aged unfertilized oocytes.

Cell Survival↗

A performance study of the Loma Linda proton medical accelerator.

More than three years have passed since Loma Linda treated the first cancer patient with the world's first proton accelerator dedicated to radiation therapy. Since that time, over 1000 patients have completed treatments and the facility currently treats more than 45 patients per day. With a typical intensity of 3 x 10(10) protons per pulse and 27 pulses per minute, dose rates of 90-100 cGy/min are easily achieved on a 20-cm diameter field. In most cases, patient treatment times are 2 min, much less than the patient alignment time required before each treatment. Nevertheless, there is considerable medical interest in increasing field sizes up to 40-cm diameter while keeping dose rates high and treatment times low. In this article, beam measurements relevant to intensity studies are presented and possible accelerator modifications for upgrades are proposed. It is shown that nearly all intensity losses can be ascribed to the large momentum spread of the injected beam and occur at or near the injection energy of 2 MeV. The agreement between calculations and measurements appears quite good. In addition, optimum beam characteristics for a new injector are discussed based upon the momentum acceptance and space charge limits of the Loma Linda synchrotron.

Biophysical Phenomena↗

Hemodynamic effects of different temporary pacing modes for the management of bradycardias complicating acute myocardial infarction.

Twelve patients requiring temporary pacing following acute myocardial infarction (AMI) (10 heart block, 2 junctional bradycardia) had hemodynamic measurements taken with ventricular demand pacing at 80 ppm (VVI80), ventricular demand pacing at the atrial rate (VVIa), physiological pacing (DDD), and spontaneous (intrinsic) rhythm. VVI80 mode did not improve any hemodynamic parameter compared with spontaneous rhythm. VVIa mode improved diastolic and mean arterial pressures only. DDD mode improved most hemodynamic parameters compared with spontaneous rhythm (cardiac output by 29% [P less than 0.0001]; blood pressure: diastolic by 24% [P less than 0.01], systolic by 19% [P less than 0.01], mean by 21% [P less than 0.005]; pulmonary wedge pressure by 10% [P = 0.057] and right atrial pressure by 24% [P less than 0.005]) and also significantly improved some parameters compared with VVIa (cardiac output by 20% [P less than 0.001], systolic blood pressure by 11% [P less than 0.01] and right atrial pressure by 15% [P less than 0.01]). Physiological pacing is hemodynamically superior both to ventricular pacing and spontaneous rhythm for patients requiring temporary pacing following AMI. Ventricular pacing at 80 ppm has little hemodynamic advantage over spontaneous rhythm.

Adult↗

Management of acute coronary occlusion during percutaneous transluminal coronary angioplasty: experience of complications in a hospital without on site facilities for cardiac surgery.

OBJECTIVE: To determine whether percutaneous transluminal coronary angioplasty may be safely performed in cardiology centres in the United Kingdom without immediate on site cardiac surgical cover for complications arising at angioplasty. DESIGN: Retrospective review of coronary angioplasties and complications in a hospital without on site cardiac surgical cover. SETTING: All angioplasties were performed in the catheterisation laboratory of the Belfast City Hospital. Revascularisation surgery for complicated coronary angioplasty was performed in the cardiac surgical unit of the Royal Victoria Hospital, 2.4 km away from the catheterisation laboratory. PATIENTS: 540 Coronary angioplasties were performed on 512 patients between late 1982 and November 1988. Indications included stable angina, unstable rest angina, and suitable coronary disease at coronary arteriography after myocardial infarction. MAIN OUTCOME MEASURES: In hospital mortality after complicated coronary angioplasty and delay to surgical revascularisation after acute coronary occlusion at angioplasty. RESULTS: Coronary angioplasty was successful in 444 cases (82%). Acute coronary occlusion occurred in 35 cases (6.5%). Twelve patients required urgent revascularisation surgery and were transferred safely to the surgical unit; none of these patients died. A mean delay of 268 minutes (range 180-390 minutes) occurred before revascularisation compared with 273 minutes (range 108-420 minutes) in the Royal Victoria Hospital, where on site surgical cover was available. The principal cause of delay was the wait for a cardiac operating theatre to become available and not the transfer time between hospitals. Five deaths occurred after coronary angioplasty, a mortality of 0.9%. Three deaths were related to acute coronary occlusion. The absence of immediate surgical help did not influence the outcome in any patient. CONCLUSION: With careful selection of patients coronary angioplasty may be safely performed in a hospital without on site cardiac surgical facilities, provided that these are available at a nearby centre.

Acute Disease↗

Intravenous streptokinase for acute myocardial infarction reduces the occurrence of ventricular late potentials.

The occurrence of ventricular late potentials in survivors of acute myocardial infarction treated with intravenous streptokinase was compared with that in a conservatively treated group and the relation between ventricular late potentials and patency of the infarct related artery was examined. Of 115 patients admitted with a first infarct, 55 were treated with intravenous streptokinase (streptokinase group) and 60 were treated conservatively (non-streptokinase group). A signal averaged electrocardiogram was recorded in all patients and coronary angiography was performed in 45 (81.8%) of the streptokinase group and in 21 (35%) of the non-streptokinase group. At a 40 Hz filter setting ventricular late potentials were significantly less common in patients treated with streptokinase (9 (16.4%) of 55) than in those who were not (26 (43.3%) of 60). A total of 66 patients underwent angiography. Of the 26 who had closed infarct-related arteries, 17 had ventricular late potentials at a 40 Hz filter setting (sensitivity 65.4%, specificity 95%) and 38 of the 40 patients with a patent infarct-related artery did not have ventricular late potentials (sensitivity 80.9%, specificity 89.5%). Patients with acute myocardial infarction treated with intravenous streptokinase were significantly less likely to have ventricular late potentials than conservatively treated patients and the absence of ventricular late potentials at 40 Hz filter setting was a good non-invasive predictor that the infarct-related artery was patent.

Arrhythmias, Cardiac↗

Oral acyclovir in the treatment of herpes zoster in general practice.

A double-blind, randomised trial evaluated the efficacy of oral acyclovir, 800 mg 5 times daily for 7 days, in acute herpes zoster and postherpetic neuralgia. Forty patients aged 16 years or over, presenting to their general practitioners within 3 days of rash onset, received acyclovir, while 43 patients received placebo. Acyclovir reduced the extent and duration of the rash, the spread of the rash to adjacent dermatomes and the incidence of disseminated lesions. It shortened the period of new lesion formation and reduced the incidence of ulceration. The weekly prevalence of pain was reduced on acyclovir by the fourth week, with a reduction in the monthly prevalence of chronic pain in the second and third months and a reduction in associated local neurological symptoms between months 3-6. Total analgesic use in the first 4 weeks was reduced by acyclovir, but during follow up there was no difference in the prevalence of analgesic use between groups. There were slightly fewer medical events on acyclovir in the second week, but the frequency was the same in each group for the rest of the 6 months. Biochemical and haematological tests showed no adverse effects of treatment.

Acute Disease↗

Pathological changes after intravenous streptokinase treatment in eight patients with acute myocardial infarction.

At necropsy five of eight patients (mean age 57 years) who died after intravenous streptokinase treatment for severe acute myocardial infarction (mean Peel index = 18) were found to have a patent infarct related coronary artery. Coronary artery stenoses were caused by fibrofatty atheromatous plaques; there were no residual thrombi in the lumen or acute intimal lesions. Three of these infarcts were of partial thickness (less than two thirds wall width) with sparing of the outer third of the myocardium and subendocardial zones. In the other three patients the infarct related coronary arteries remained histologically closed with residual lumen thrombi and underlying intimal lesions. Two infarcts were transmural. Six of the eight infarcts were noticeably haemorrhagic. Myocardial haemorrhage was confined to areas of necrotic myocardium and did not affect viable regions. These findings suggest that thrombus overlying a complex lesion may be more difficult to lyse than thrombus overlying a simple fibrofatty plaque. They also suggest that myocardial haemorrhage outside the infarct area, which might lead to cardiac rupture or delayed healing, does not usually occur.

Acute Disease↗

Relation of coronary arterial patency and left ventricular function to electrocardiographic changes after streptokinase treatment during acute myocardial infarction.

One hundred and eighty-eight patients with evolving acute myocardial infarction were treated with intravenous streptokinase. Serial 12-lead electrocardiograms were recorded for 3 hours after treatment and inspected for rapid repolarization changes of the ST segment and T wave. Abrupt electrocardiographic repolarization changes were observed in 106 patients (56%) and were strongly predictive for an open infarct-related coronary artery at a mean of 6 days after treatment (predictive value = 0.92, sensitivity = 0.67). Abrupt electrocardiographic changes were not observed in 82 patients (44%). This absence was not a good predictor of an occluded infarct-related coronary artery (predictive value = 0.4). There was no relation between the presence or absence of abrupt electrocardiographic changes and global or regional left ventricular function after streptokinase treatment. Abrupt repolarization changes after thrombolytic treatment indicate a high probability of an open infarct-related artery. When abrupt repolarization changes do not occur, the patency of the infarct-related coronary artery cannot be predicted with accuracy. Serial electrocardiographic recordings do not provide sufficient information about coronary patency to eliminate the need for coronary arteriography.

Aged↗