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Biomedical subjects

S Evans

Publications and source records attributed to S Evans.

At least 217 records · Page 12Linked to original sources

Characterization of the quaternary structure and conformational properties of the human stem cell inhibitor protein LD78 in solution.

The human LD78 protein (sometimes referred to as human macrophage inflammatory protein-1 alpha) has been shown to protect multipotential hemopoietic stem cells from the effects of cytotoxic agents. Administration of the recombinant stem cell inhibitor molecule LD78 as an adjunct to chemotherapy has potential clinical benefit in reducing or preventing the neutropenia associated with this treatment. At physiological ionic strength, the 8-kDa LD78 molecule exists as soluble, heterogeneous, multimeric complexes of mass ranging from 100 to > 250 kDa. The hydrodynamic and structural properties of LD78 have been determined in various buffer solutions using analytical ultracentrifugation, circular dichroism, and fluorescence spectroscopy. The results demonstrate that defined, homogeneous monomer and tetramer forms of LD78 can be prepared which display distinct conformational properties. The combined use of hydrodynamic and spectroscopic analysis provides an insight into the pathway and molecular mechanics of LD78 self-association.

Acetates↗

Control of thermal runaway and uniformity of heating in the electromagnetic rewarming of a cryopreserved kidney phantom.

Successful cryopreservation of whole organs may require electromagnetic (EM) heating at much faster warming rates than those at which thermal relaxation can smooth out nonuniform power distribution or suppress hot spots which become unstable due to an increase of power absorbtion with temperature in the material being heated. Calculations of the heating distribution for a uniform spherical workpiece in a resonant EM applicator show that the size of a workpiece for which there will be good uniformity of heating has a sharp upper limit given D < or = 0.3 lambda m, where D is the workpiece diameter and lambda m is the EM wavelength in the material. We also introduce three stability factors which indicate whether thermal runaway can occur; they are dependent solely on the material's dielectric properties and the geometry and orientation of any irregularities. These factors provide clear guidelines to the choice of source frequency and applicator geometry that are favorable for intrinsic control of thermal runaway. Experimental results are presented for spherical phantom workpieces of 36- and 45-mm diameter, rewarmed from -90 to above 0 degrees C in 30 to 150 s, in a 434-MHz resonant cavity applicator. The observed spatial temperature distributions for different E-field configurations clearly indicate the effectiveness of the stability factors in predicting uniformity of temperature, and the significance of the workpiece size limit, in practical EM heating situations.

Animals↗

Successful repair of major retrohepatic vascular injuries without the use of shunt or sternotomy.

Injury to the retrohepatic veins and vena cava secondary to blunt abdominal trauma is often fatal. The purpose of this report is to describe the successful isolation and repair of retrohepatic vascular injuries without the use of median sternotomy or vena caval shunt. Two children with both hepatic vein and retrohepatic caval injuries from blunt trauma were treated by the following surgical approach: (1) bilateral subcostal incision with vertical midline extension; (2) packing of the liver and volume resuscitation with the Rapid Infusion System prior to vascular isolation; (3) isolation of the intrapericardial vena cava through a transdiaphragmatic pericardial window; (4) control of the suprarenal vena cava and porta hepatis; and (5) repair of vein lacerations with vascular occlusion and continuous saline irrigation for improved visualization despite continued venous bleeding. This approach was tolerated and allowed successful repair without shunting in these patients despite an average weight of 14 kg and the loss of 3 L and 23 L of blood, respectively. We attribute the success of this technique to rapid control of hemorrhage and volume resuscitation. This success suggests that the routine use of shunt or sternotomy is not necessary in these devastating injuries.

Child, Preschool↗

A comparison of abdominal and vaginal examinations for the diagnosis of engagement of the fetal head.

The diagnosis of engagement of the fetal head is mandatory before operative vaginal delivery is to be attempted. There is widespread belief that the fetal head is engaged in the maternal pelvis when vaginal examination reveals that the bony presenting part has reached the level of the ischial spines. However, it is also claimed that in the presence of moulding the vaginal findings may be misleading and that it may be preferable to make the diagnosis by abdominal examination of the level of the fetal head in relation to the pelvic brim. In order to evaluate the relative merits of each of these 2 systems of physical examination, a retrospective study was made of 104 cases which had been evaluated for possible operative vaginal delivery by both methods. Prediction of successful vaginal delivery was greater by abdominal criteria (94%) than by vaginal criteria (80%) (p < 0.01). When evaluated by maximum likelihood logistic regression analyses, the factor of greatest importance in determining the probability of allocation of a case to each of the engagement groups was moulding (odds ratio 2.17; 95% confidence intervals 0.75-6.27). We conclude that when these 2 methods of assessment produce different diagnoses, the major factor responsible is moulding of the fetal head. Clinical evaluation prior to operative vaginal delivery must include abdominal examination and reliance on vaginal findings alone may prove misleading when moulding is present.

Adult↗

Increasing calorie consumption in children with cystic fibrosis: replication with 2-year follow-up.

Three mildly malnourished children with cystic fibrosis and their parents participated in a behavioral group-treatment program that focused on promoting and maintaining increased calorie consumption. Treatment included nutritional education, gradually increasing calorie goals, contingency management, and relaxation training, and was evaluated in a multiple baseline design across four meals. Children's calorie intake increased across meals, and total calorie intake was 32% to 60% above baseline at posttreatment. Increased calorie consumption was maintained at the 96-week follow-up (2 years posttreatment). The children's growth rates in weight and height were greater during the 2 years following treatment than the year prior to treatment. Increases in pace of eating and calories consumed per minute were also observed 1 year posttreatment. These findings replicated and extended earlier research supporting the efficacy of behavioral intervention in the treatment of malnutrition in children with cystic fibrosis.

Behavior Therapy↗

Perception of need for child psychiatry services among parents and general practitioners.

Previous research has found the prevalence of child psychiatric disorder in the general population to be between 7% and 25%, and higher among attenders at some general practitioners' surgeries. This survey examines the perception of need among general practitioners and parents of general practice attenders, and compares this with the prevalence of disorder found using the Rutter A Questionnaire for Parents. The results support claims that the services for children with psychiatric disorders are inadequate. However, many children with disorders are presented to other professionals by their parents. Ways to extend the service synergistically to meet some of the unmet need are discussed. The need for further research to be undertaken, which would effectively target such scarce resources, is identified.

Adolescent↗

Immunoreactivity, pharmacokinetics and bone marrow dosimetry of intrathecal radioimmunoconjugates.

Ten patients with neoplastic meningitis were treated with a variety of 131I-monoclonal antibody (MAb) conjugates, chosen to bind to their particular malignancy. Pharmacokinetic studies revealed that MAbs leave the ventricular compartment, enter the sub-arachnoid space and then pass into the blood. Once the MAbs enter the blood compartment, their clearance is determined by factors such as circulating anti-mouse Ig and circulating antigens. These lead to complex formations and the clearance of the conjugate by the reticuloendothelial system. In one individual, the anti-mouse Ig response observed systemically was not mirrored within the CSF, which has implications for planning future therapy of this type. In other patients, formation of immune complexes was due to binding to circulating antigen within the blood. The major toxicity associated with the intrathecal administration of 131I-MAbs was bone-marrow suppression. The doses to the bone marrow, resulting from the form of therapy, were calculated but showed no direct correlation with WHO grade 3/4 toxicity. Doses to the ventricular lining were also calculated, but due to the complex geometry of the compartment, calculation of potential tumour doses was not practicable.

Adult↗

Ingested arsenic, keratoses, and bladder cancer.

A cohort of 478 patients treated with Fowler's solution (potassium arsenite) in Lancashire, England, during the period 1945-1969 and previously followed until January 1, 1980, was followed for an additional 11 years. A significant excess of bladder cancer mortality occurred (observed/expected ratio = 5/1.6; p = 0.05). No excess was found for other causes of death. In a subcohort of 142 patients examined for signs of arsenicism around 1970, all 11 subsequent cancer deaths occurred in those with signs of arsenicism (p = 0.0009).

Arsenic↗

Inhibition of human red blood cell glutathione reductase by valproic acid.

Glutathione reductase (GR) one of the enzymes of the glutathione redox cycle, plays a salient role in maintaining appropriate cellular levels of reduced glutathione. The enzyme in human red blood cells is inhibited in vitro by the anticonvulsant drug valproic acid (VPA). The inhibition is dose-dependent, reversible, uncompetitive and does not depend on the redox state of the enzyme. VPA also inhibits red blood cell GR activity in children being treated with the drug. The level of serum VPA correlates significantly with the suppression of GR activity.

Adolescent↗

Synthesis and release of acetylcholine in the rabbit kidney cortex.

Several cholinergic processes were demonstrated and partially characterized in rabbit kidney cortical minces: choline uptake, acetylcholine synthesis and calcium-dependent release. Minces took up labelled choline, acetylated it, and stored it in a pool that was not readily accessible to physostigmine-sensitive cholinesterase activity. [3H]Acetylcholine synthesis but not [3H]choline uptake was inhibited by the removal of sodium ions or incubation at 0 degrees C. The release of newly synthesized [3H]acetylcholine was increased by 300 mOsmol urea in a calcium-dependent manner, but not by potassium depolarization (300 mOsmol), vasopressin (10 microM), or bradykinin (10 microM). These results suggest that acetylcholine may be synthesized by non-neuronal rabbit kidney cortical cells and that this transmitter may be released in response to physiological levels of urea.

Acetylation↗

Generalized allergic reactions during anesthesia.

Twenty-eight adults with a history of a generalized allergic reaction during anesthesia were investigated. The reactions were systemic in 23 adults, urticaria/angioedema in four, and bronchial obstruction in one adult. The study population and an additional 35 subjects with a history of use of thiopental during anesthesia but without reactions were investigated by methods including thiopental skin test, succinylcholine skin test, and IgE RAST for antibodies to thiopental, succinylcholine, or latex. Among the 28 patients with reactions, 17 had positive thiopental skin tests; 14/28 reactors and 1/35 of the control group had an IgE thiopental RAST value greater than 2 SD above the mean for control sera from ragweed-allergic subjects. The one control subject with a positive thiopental RAST also was the only control subject with a positive thiopental skin test. IgE succinylcholine RAST was negative in all 23 reactor sera tested. The IgE latex RAST was strongly positive in one reactor. In conclusion, evidence of allergy, particularly allergy to thiopental as a possible basis for the reactions, was obtained in greater than 50% of the patients who were investigated. No allergy to succinylcholine was found.

Adolescent↗

Experimental results on the rewarming of a cryopreserved organ phantom in a UHF field.

We describe a UHF rewarming system which has been used to measure warming rates, and particularly the uniformity of warming on three orthogonal axes, in a rabbit kidney phantom 36 mm in diameter. The stabilizing effect is demonstrated of using an E-field directed along the temperature gradient (or normal to any surface of dielectric discontinuity). One hot spot remains unaccounted for. The average warming rates and power dissipation are related to the volumetric heat capacity of the phantom material at -30 degrees C.

Animals↗

Analysis of electromagnetic heating patterns inside a cryopreserved organ.

Computer analysis of the induced electromagnetic field and heating distribution inside cryopreserved organs subjected to electromagnetic illumination at frequencies of 84 MHz, 434 MHz and 2.45 GHz were carried out using a spherical model for the organ, with special reference to heating in a single-mode resonant cavity. The interaction between the frequency of the incident field and the size and dielectric properties of the sample was investigated. It is shown that uniform heating of organs is likely to be achieved at lower frequencies, as might be expected. However, the ratio between the power penetration depth for plane waves and the size of the organ is not a sufficient basis on which to judge quantitatively the uniformity of the power absorption. Hot or cold spots can occur within the organ even when this ratio is greater than unity; the wavelength in the material is also an important factor. The results from this study indicate that the use of a resonant cavity as a heating applicator has advantages over plane-wave illumination. A sharp upper limit can be set to the frequency suitable for rapid and uniform heating of a given organ.

Animals↗

Food in chronic heart failure: improvement in central haemodynamics but deleterious effects on exercise tolerance.

Food has been known to have significant central haemodynamic effects for over half a century; it causes an increase in cardiac output and a fall in systemic vascular resistance. These changes are potentially desirable in patients with chronic heart failure but how they relate to exercise tolerance is unknown. This study was designed to examine the haemodynamic effects of food with changes in exercise capability in a group of patients with chronic heart failure. Fifteen patients with chronic heart failure and 10 normal control subjects were studied. They underwent treadmill exercise testing whilst fasting and after a standardized meal. Measurements were made of symptom-limited exercise tolerance, cardiac output, limb blood flow and respiratory gases. Superior mesenteric artery blood flow was measured fasting and postprandially only. Despite an increase in cardiac output, at rest and during exercise, which was not, however, as great as that in the control subjects, the symptom-limited exercise tolerance of the patients fell by 37 s postprandially (P < 0.05). Superior mesenteric artery blood flow increased postprandially by a mean of 133 ml.min-1 (P < 0.05) in the patients and 424 ml.min-1 (P < 0.01) in the control subjects. Calf blood flow increased in both groups during exercise, but there was no change in limb blood flow when comparisons were made between the fasting and postprandial states. The normal postprandial increase in oxygen consumption did not occur in the patients although their minute ventilation was higher than the control subjects (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Design of a UHF applicator for rewarming of cryopreserved biomaterials.

The dielectric properties of cryopreserved biological tissue are discussed in relation to the problems which arise when EM fields are used for rapid rewarming. The UHF band is favored from two aspects: the avoidance of thermal runaway and the uniformity of heating inhomogeneous material. Various resonant cavity applicators are considered for efficient and uniform rewarming. The square-aspect TE 111 cylindrical applicator is favored principally because it allows variation of the E-field orientation as required during the warming profile. An appropriate kidney phantom organ is described. It is used to obtain measured values of the overall efficiency of a TE 111 applicator. The efficiency values are found to fall steadily with increasing temperature from 85% at -40 degrees C to 45% at the phase change, mainly due to the decreasing tan delta value of the phantom material.

Animals↗

Factors predicting success in DC catheter ablation of accessory pathways.

In a series of 33 patients with accessory pathways, 26 had successful catheter ablation (fulguration [23 patients] or modification [3 patients]) of their accessory pathway conduction, and could be considered as a clinical success. One hundred thirteen single discharge or double discharge shocks were delivered, and each shock was studied to reveal which parameters were important to predict the success or failure of catheter ablation. Double discharge shocks resulted in successful accessory pathway modification or ablation twice as often as single discharge shocks (32% vs 16%). This effect was more pronounced in left lateral accessory pathways (48% vs 4%). Shocks in the electrophysiologically defined ventricular zone were more likely to be successful (33%) than shocks delivered in the atrial zone (14%), irrespective of accessory pathway location. The presence of a probable Kent potential was the parameter most strongly associated with success. The parameter most strongly associated with failure, with a 100% negative predictive value, was the absence of earliest activation recorded on the ablating catheter prior to shock delivery. An AV interval of < 60 msec significantly divided the successful from the unsuccessful shocks (P = 0.01). The VA interval during orthodromic reciprocating tachycardia or right ventricular stimulation did not allow for significant division into successful and unsuccessful attempts in this relatively short series. VA intervals, when longer, were predictive of failure but, when shorter, had low positive predictive value. Mean follow-up in 25 successful patients was 15 +/- 6 months. All patients did well in the follow-up period. Neither those patients with ablation nor modification of the accessory pathway had recurrent episodes of tachycardia or required pharmacological treatment for control of arrhythmias.

Adult↗