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Biomedical subjects

A J Walker

Publications and source records attributed to A J Walker.

At least 19 recordsLinked to original sources

Diacylglycerol kinase theta is translocated and phosphoinositide 3-kinase-dependently activated by noradrenaline but not angiotensin II in intact small arteries.

Diacylglycerol (DG) kinase (DGK) phosphorylates the lipid second messenger DG to phosphatidic acid. We reported previously that noradrenaline (NA), but not angiotensin II (AII), increases membrane-associated DGK activity in rat small arteries [Ohanian and Heagerty (1994) Biochem. J. 300, 51-56]. Here, we have identified this DGK activity as DGKtheta, present in both smooth muscle and endothelial cells of these small vessels. Subcellular fractionation of artery homogenates revealed that DGKtheta was present in nuclear, plasma membrane (and/or Golgi) and cytosolic fractions. Upon NA stimulation, DGKtheta translocated towards the membrane and cytosol (155 and 153% increases relative to the control, respectively) at 30 s, followed by a return to near-basal levels at 5 min; AII was without effect. Translocation to the membrane was to both Triton-soluble and -insoluble fractions. NA, but not AII, transiently increased DGKtheta activity in immunoprecipitates (126% at 60 s). Membrane translocation and DGKtheta activation were regulated differently: NA-induced DGKtheta activation, but not translocation, was dependent on transient activation of phosphoinositide 3-kinase (PI 3-K). In addition, DGK activity co-immunoprecipitated with protein kinase B, a downstream effector of PI 3-K, and was increased greatly by NA stimulation. The rapid and agonist-specific activation of DGKtheta suggests that this pathway may have a physiological role in vascular smooth-muscle responses.

Androstadienes↗

Acute effect of exercise on blood glucose and insulin levels in women with gestational diabetes.

OBJECTIVE: To evaluate the effect of a single session of exercise (cycling), at rest (control condition) and at two intensity levels (low- and moderate-intensity exercise conditions), on blood glucose and insulin in pregnancy complicated by gestational diabetes mellitus (GDM). METHODS: A one-group repeated measures design was used. Women aged 18-38 with GDM, no other complications, not on insulin, and not exercising regularly were recruited. The women rested or exercised at the two intensities for 30 min and rested for 2 h after each session. Blood was sampled for blood glucose, insulin and hematocrit at baseline and every 15 min. RESULTS: There was no difference at baseline in blood glucose levels. The blood glucose level was significantly lower for each exercise condition compared to rest, and for moderate compared to low-intensity exercise (5.2 vs. 4.3 vs 3.9 mmol/l) at the end of exercise (30 min), and for the two exercise conditions compared to rest at 15 min after exercise (4.9 vs 4.4 vs. 4.0 mmol/l). By 45 min after exercise, the blood glucose values were nearly identical. The area under the curve for blood glucose was significantly lower for low- and moderate-intensity exercise than for rest (p = 0.01). The slope of change in insulin among the three conditions, from baseline to the 30-min session, approached significance (p = 0.065). The power for that analysis was 0.51. A sample of 23 would have been required to increase the power to 0.80. CONCLUSIONS: Significant declines in blood glucose level were observed during low- and moderate-intensity exercise compared to rest. These differences were gone by 45 min after exercise. Continued research should examine those with high body mass index and more pronounced hyperglycemia for further evaluation of the effect of exercise on blood glucose and insulin levels in women with GDM.

Adolescent↗

Validity and reliability of combining three methods to determine ventilatory threshold.

PURPOSE: This research was undertaken to validate a combination of methodologies to determine ventilatory threshold (VT). METHODS: Three methods were used individually and then combined to determine VT as follows: 1) ventilatory equivalencies, 2) excess CO2 production, and 3) a modified V-slope method. Three groups of participants-endurance athletes (N = 132), healthy, aerobically active adults (N = 31), and healthy, sedentary/low-active adults (N = 22)-were independently evaluated for VT and compared with the criterion standard lactate threshold (LT) defined as the first rise in blood lactate with increasing intensity of exercise. RESULTS: VT and LT were significantly correlated using the combined VT method within each study group (r = 0.98, 0.97, and 0.95, respectively; P < 0.001). Mean VO2 values at VT and LT were not significantly different between the three groups (P > 0.20). The combined method improved the determination rate of VT and reduced the standard deviation of the LT - VT difference by 80-170% over the individual methods. During test-retest procedures VO2lt and VO2vt determined by the combined method met criteria demonstrating further reliability. CONCLUSION: The combined method to determine VT is valid and reliable across a wide fitness range in healthy individuals and improves the determination rate and accuracy of VT determination over the use of single methods.

Adult↗

Lichtenstein patch or Perfix plug-and-patch in inguinal hernia: a prospective double-blind randomized controlled trial of short-term outcome.

BACKGROUND: Open mesh used in anterior inguinal hernia repair can be configured as a flat patch (Lichtenstein operation) or as a cone-shaped preformed plug and supplementary patch (plug-and-patch operation; Perfix Plug; Davol Inc, Cranston, RI). METHODS: One hundred forty-one patients were randomly allocated and blinded to receive either a Lichtenstein patch or a Perfix plug-and-patch. Information before the operation and on postoperative days 3 and 14 was recorded by an independent blinded observer to include operating time, postoperative pain, analgesic medication, return to activity and work, and quality of life assessment. RESULTS: Operating time (32 vs 37.6 minutes) was significantly shorter in the plug-and-patch group (P = .01). During days 1 through 8, patients who had undergone the plug-and-patch operation experienced less pain, and their physical functioning on day 3 was significantly better (P = .013). Days of analgesic medication (4.0 vs 4.6 days), return to normal activity (2.8 vs 3.6 days), return to work (17.0 vs 20.8 days), and total days of work missed (14.3 vs 16.1 days) were similar in both groups (P = NS for all comparisons). CONCLUSIONS: Compared with patients who received the Lichtenstein patch for ambulatory inguinal hernia repair, patients who underwent the Perfix plug-and-patch operation experienced less postoperative pain in the first 8 days after the operation but consumed similar postoperative analgesic medication. The rate of return to normal activity and work is similar in both groups, which indicates no superiority for the plug-and-patch operation in overall rehabilitation and societal costs. Overall hospital costs are greater for the plug-and-patch operation ($120 [US]) compared with the Lichtenstein patch ($20 [US]), with a negligible (5.6 minutes) saving of operating room time for the plug-and-patch operation.

Adult↗

Neuropsychological functioning of adults with attention deficit hyperactivity disorder.

The neuropsychological functioning of adults with Attention Deficit Hyperactivity Disorder (ADHD) was compared to that of healthy controls and individuals with mild psychiatric disorders including attentional complaints. Thirty adults in each group were examined on the Conners' Continuous Performance Test (CPT) and measures of attention, executive function, psychomotor speed, and arithmetic skills. The ADHD group performed lower than healthy controls on most measures. However when compared to the psychiatric group, the performances of the ADHD group were not significantly lower on any of the measures. The predictive power of the tests was poor in discriminating ADHD from psychiatric disorder. Implications for the clinical diagnosis of ADHD are discussed.

Adolescent↗

Visualisation of biomedical datasets by use of growing cell structure networks: a novel diagnostic classification technique.

BACKGROUND: Medical research produces large multivariable datasets that are difficult to visualise and interpret intuitively. We describe a novel growing cell structure (GCS) technique that compresses multidimensional datasets into two dimensional maps with colour overlays that can be visually interpreted. METHODS: The two-dimensional map is self-discovered from the training set by distribution of cases to different nodes according to similarity between the cases at each node. Nodes are added to the map until there is no further significant reduction in error. The Parzen window method is used to estimate the probability distribution of the training cases, and this probability is converted to posterior class probabilities by use of Bayes' theorem. Classification performance can be assessed by means of receiver operating characteristic (ROC) curves. Colour maps of the values of each input variable at each node are constructed, which illustrate the relation between each input variable and the overall distribution of cases in the network map. FINDINGS: From a dataset of 11 input variables from 692 fine-needle aspirate samples from breast lesions, a 32-node network produced an area under the ROC curve of 0.96, which was not significantly different from that for logistic regression (0.98, z=1.09, p>0.05). Colour maps of the input variables showed that some variables had discrete distributions over exclusively benign or malignant areas of the network, and were thus discriminant, whereas others, such as foamy macrophages, covered both benign and malignant regions. INTERPRETATION: This technique produces dimensional compression that allows multidimensional data to be displayed as two-dimensional colour images. This envisioning of information allows the highly developed visuospatial abilities of human observers to perceive subtle inter-relations in the dataset.

Artificial Intelligence↗

Transgenic Arabidopsis leaf tissue expressing a modified oryzacystatin shows resistance to the field slug Deroceras reticulatum (Müller).

Transgenic Arabidopsis thaliana has been developed which expresses the oryzacystatin mutant OC-I delta 86, which is an inhibitor of the major proteinase present in the digestive gland of the slug, Deroceras reticulatum. When fed on leaf tissue from plants expressing this inhibitor the growth of juvenile slugs was significantly reduced by 31% compared with those feeding on control leaf tissue. Furthermore, while surviving slugs did not individually consume less when feeding on leaf tissue expressing OC-I delta 86, the total amount of leaf tissue eaten was 50% less, due to reduced survival of slugs. The synthetic cysteine proteinase inhibitors E-64 and leupeptin also significantly reduced slug weight gain (by at least 40%) and digestive gland cysteine proteinase activity when administered in an artificial diet, indicating that their antimetabolic effects are due to direct inhibition of gut proteolytic activity. These results suggest that transgenic crop plants expressing phytocystatins could be used to suppress the growth rates of slug populations in the field.

Animals↗

Ruptured abdominal aortic aneurysms: selecting patients for surgery.

OBJECTIVES: Mortality from ruptured abdominal aortic aneurysm (RAAA) remains high. Despite this, withholding surgery on poor-prognosis patients with RAAA may create a difficult dilemma for the surgeon. Hardman et al. identified five independent, preoperative risk factors associated with mortality and proposed a model for preoperative patient selection. The aim of this study was to test the validity of the same model in an independent series of RAAA patients. METHODS: A consecutive series of patients undergoing surgery for RAAA was analysed retrospectively by case-note review. Thirty-day operative mortality and the presence of the five risk factors: age (> 76 years), creatinine (Cr) (> 190 mumol/l), haemoglobin (Hb) (< 9 g/dl), loss of consciousness and electrocardiographic (ECG) evidence of ischaemia were recorded for each patient. RESULTS: Complete data sets existed for 69 patients (mean age: 73 years, range: 38-86 years, male to female ratio: 6:1). Operative mortality was 43%. The cumulative effect of 0, 1 and 2 risk factors on mortality was 18%, 28% and 48%, respectively. All patients with three or more risk factors died (eight patients). CONCLUSIONS: These results lend support to the validity of the model. The potential to avoid surgery in patients with little or no chance of survival would spare unnecessary suffering, reduce operative mortality and enhance use of scarce resources.

Adult↗

Exaggerated blood pressure response to exercise: importance of resting blood pressure.

Normotensive individuals who exhibit an exaggerated blood pressure (BP) response to exercise have an increased risk of future hypertension. However, previous studies failed to control for resting BP despite the fact that an elevated resting BP in the normotensive range is also a strong predictor of future hypertension. Therefore, we determined whether maximal systolic BP is associated with resting BP. Resting BP was measured in 68 healthy normotensive men on three separate days. The subjects then performed a graded, maximal exercise test on a Monark cycle ergometer. Maximal systolic BP was strongly correlated with resting systolic BP (r = 0.64, P < 0.0001). Subjects with elevations in systolic BP during maximal exercise (> 220 mmHg) also had higher (P < 0.005) resting BP than those without (< 220 mmHg). When stepwise regression analyses were performed, systolic BP at rest was a significant independent predictor of maximal systolic BP, explaining over 40% of the variability. These results suggest that exaggerated BP response as a predictor of future hypertension reported in previous studies may be little more than a simple reflection of elevated resting BP. Specifically, these studies should not be interpreted as demonstrating that exercise BP is a better predictor of future hypertension than resting BP alone. In the future, defining the BP 'response' to exercise as a change score (i.e. maximal BP minus resting BP) may be advantageous as it permits the effects of exercise to be examined independently of the level of resting BP.

Adult↗

Energy deposition pattern from tritium and different energy photons--a comparative study.

Energy deposition patterns of beta particles from tritium decay have been analyzed in comparison with photon radiation in the energy range from 12 to 1250 keV. Energy deposition was modeled by Monte Carlo means using electron tracks in water vapor with a complete follow up of delta electrons. Ionizations have been used as representative of track structure. Frequencies of clusters on a nanometer scale and their spatial distribution in spherical targets representing cell nuclei have been derived. Cluster analysis has been carried out by implementing a k-means method. Frequencies of ionization clusters from tritium are similar to 60-100 keV photons. Spatial distribution of clusters from tritium closely match approximately 70 keV photons up to 2 microm separation.

Monte Carlo Method↗

Amount of care given and caregiving satisfaction: a latent growth curve analysis.

We examined the wear-and-tear hypothesis using data from 4 annual interviews with 130 (128 White) middle-aged daughters caring for their physically impaired, elderly mothers. We formulated a latent growth curve model hypothesizing that increases in the amount of care given by daughters caused a decrease in caregiving satisfaction, independent of caregiving duration. We found considerable individual variability and change in both caregiving satisfaction and the amount of care given in univariate latent growth curve analyses. Contrary to the wear-and-tear hypothesis, a multivariate latent growth curve analysis revealed duration of caregiving had no effect on either initial caregiving satisfaction or change in satisfaction. An elaborated wear-and-tear model was supported, however. The mechanism for decline in satisfaction is an increase in the amount of care given.

Aged↗

The early morbidity of varicose vein surgery.

The early outcome and morbidity associated with varicose vein surgery were assessed at six months post operation by postal questionnaire. Most cases underwent sapheno-femoral ligation, above-knee stripping of the long saphenous vein and multiple stab avulsions. A 73.8% response rate resulted in 155 replies, and revealed a high incidence (65.8%) of perceived complications within the first two weeks after surgery. The commonest of these were bruising, pain and numbness. Over a third of patients consulted their general practitioner (GP) postoperatively. Half of these required further management or treatment and the rest, reassurance alone. At six months 79.4% were satisfied with the outcome of their surgery, although some still claimed problems with residual veins, skin discoloration, numbness, and ankle or foot discoloration. Eleven percent were referred to hospital for further opinion, mostly because of perceived residual varicose veins. The difference between residual and recurrent varicose veins is discussed. No patient felt that the standard 2.5 day admission was too long, and 12.9% thought it too short. Day case surgery is not a popular option in this population group. Despite high satisfaction rates, there is a considerable morbidity attached to varicose vein surgery. We believe that good pre- and perioperative communication, augmented by a comprehensive information sheet, is important to prepare patients for those postoperative problems and thus reduces their perceived importance.

Adult↗

Experimental experience with a temporary intraluminal heparin-bonded polyurethane arterial shunt.

After vascular injury, intraluminal arterial shunting may be employed if definitive surgery must be delayed. This paper describes use of a heparin-bonded polyurethane shunt to restore distal circulation after ligation of the femoral artery in sheep. In studies to determine tissue viability for 12 h after insertion into the femoral artery, five of seven shunts remained patent. In another series of experiments to study tissue viability after limb ischaemia, the femoral artery was ligated and a tight Esmarch bandage applied to the limb for 6 h before shunt insertion. The shunt remained patent for 12 h in five of six cases. Nearly all shunt failures occurred shortly after placement and were attributable to intimal damage arising from difficulties during insertion.

Anastomosis, Surgical↗

Recurrent varicose veins: assessment of the saphenofemoral junction.

Thirty-six consecutive unselected patients, who had apparently previously undergone saphenofemoral ligation for primary uncomplicated long saphenous varicosities and who had then re-presented with recurrent thigh varices emanating from the groin, underwent preoperative clinical assessment, hand-held Doppler and duplex ultrasonographic examination and varicography to establish the presence or absence of saphenofemoral incompetence as the cause of recurrence. All patients underwent reexploration of the saphenofemoral junction (SFJ) via a lateral approach. Twenty-six patients had an intact SFJ (type I recurrence) and ten had varices arising from either a thigh perforator, or from abdominal or perineal veins (type II recurrence). Clinical examination alone was poor at distinguishing type I from type II recurrence. Doppler ultrasonography was sensitive (88 per cent) but non-specific (40 per cent). In contrast, duplex scanning was insensitive (42 per cent) but extremely specific (100 per cent) and accurate, with a positive predictive value of 100 per cent. Varicography also had a specificity and positive predictive value of 100 per cent, a sensitivity of 73 per cent and in addition provided a precise anatomical 'road-map'. A combination of clinical examination and hand-held Doppler ultrasonography seems to be the most appropriate first-line method of preoperative assessment in these patients. Duplex ultrasonography, if available, will provide additional useful information about both the SFJ and the presence of thigh perforators. Contrast examination may be reserved for patients who have equivocal results on non-invasive investigations, who have had more than one previous groin operation or who have, in addition, deep venous disease.

Adult↗

Abdominal aortic aneurysm: still missing the message.

Over a 7-month period 50 patients presented to the vascular unit with a ruptured or acute symptomatic abdominal aortic aneurysm (AAA). Information regarding the 24 months before acute presentation was obtained from the patient, family doctor and relevant case records to determine whether an asymptomatic aneurysm had previously been diagnosed but the patient not referred to the vascular service, or whether the patient had undergone an examination at which an aneurysm might reasonably have been expected to be diagnosed. Thirteen patients (26 per cent) had previously had an AAA diagnosed but only five had been referred. Thirteen patients (26 per cent) had had a total of 16 inpatient hospital admissions without an asymptomatic aneurysm being diagnosed. Six patients (12 per cent) underwent abdominal examination for an unrelated complaint by the family doctor without an asymptomatic aneurysm being diagnosed. A significant impact on overall mortality from aortic aneurysm may be made by increasing the number of patients undergoing elective aneurysm repair. All doctors should assess aortic diameter in all patients over 50 years of age who undergo abdominal examination for whatever reason. All patients diagnosed as having an asymptomatic AAA should be referred to a vascular surgeon for assessment.

Acute Disease↗