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Biomedical subjects

A Neal

Publications and source records attributed to A Neal.

14 recordsLinked to original sources

A collaborative audit of the management of hypertension in general practice.

We carried out an audit of the management of essential hypertension in general practice, against standards based on current guidelines. We examined the records of 882 hypertensive subjects (on medication) in whom hypertension had been diagnosed between January 1989 and December 1993, from 14 general practices in the Portsmouth and South East Hampshire Health Authority. The overall prevalence of hypertension was 3.5%. Pretreatment blood pressure had been measured on three or more occasions in 87% of patients. Pretreatment blood pressure was equal to or greater than 150/95 mmHg in 96% and 160/100 mmHg in 86.5% of patients. A thiazide diuretic was the initial drug of choice in 30% of patients, with beta-blockers being the most popular initial treatment. Ninety per cent of patients had had their blood pressure measured at least once during the preceding year. In 82.5% of patients, current blood pressure was less than 150/95 mmHg, while 44% achieved a current blood pressure less than 140/90 mmHg. We conclude that the prevalence of hypertension in this population was lower than expected, suggesting the need for improved screening. We also propose that the initial treatment choice should be a thiazide in the majority, which would result in significant cost saving. The blood pressure control was suboptimal compared to current guidelines.

Adrenergic beta-Antagonists

Intraaortic balloon counterpulsation improves right ventricular failure resulting from pressure overload.

BACKGROUND: Right ventricular (RV) dysfunction is common after heart transplantation, and myocardial ischemia is considered to be a significant contributor. We studied whether intraaortic balloon counterpulsation would improve cardiac function using a model of acute RV pressure overload. METHODS: In 10 anesthetized sheep, RV failure was induced using a pulmonary artery constrictor. Baseline measurements included mean systemic blood pressure, RV peak systolic pressure, cardiac index, and RV ejection fraction. Myocardial and organ perfusion were measured using radioactive microspheres. RESULTS: After pulmonary artery constriction, there was an increase in RV peak systolic pressure (32 +/- 2 to 60 +/- 3 mm Hg; p < 0.01) and a decrease in mean systemic blood pressure (68 +/- 4 to 49 +/- 2 mm Hg; p < 0.01), RV ejection fraction (0.51 +/- 0.04 to 0.16 +/- 0.02; p < 0.01), and cardiac index (2.48 +/- 0.04 to 1.02 +/- 0.11; p < 0.01). Blood flow to the RV did not change significantly, but there was a significant reduction in blood flow to the left ventricle. The initiation of intraaortic balloon counterpulsation (1:1) using a 40-mL intraaortic balloon inserted through the left femoral artery resulted in an increase in mean systemic blood pressure (49 +/- 2 to 61 +/- 3 mm Hg; p < 0.01), cardiac index (1.02 +/- 0.11 to 1.45 +/- 0.14; p < 0.05), RV ejection fraction (0.16 +/- 0.02 to 0.23 +/- 0.02; p < 0.01), and blood flow to the left ventricle. CONCLUSIONS: In a model of right heart failure, the institution of intraaortic balloon counterpulsation caused a significant improvement in cardiac function. Although RV ischemia was not demonstrated, the augmentation of left coronary artery blood flow by intraaortic balloon counterpulsation and subsequent improvement in left ventricular function suggest that left ventricular ischemia contributes to RV dysfunction, presumably through a ventricular interdependence mechanism. Therefore, study of the safety and efficacy of intraaortic balloon counterpulsation in the management of patients with acute right heart dysfunction is warranted.

Animals

Accuracy of pelvic radiotherapy: prospective analysis of 90 patients in a randomised trial of blocked versus standard radiotherapy.

The aim of this study was to assess the accuracy of pelvic radiotherapy during a trial of blocked radiotherapy at the Royal Marsden Hospital, UK. Prospective evaluation was performed on 90 patients receiving CT planned pelvic radiotherapy using weekly anterior-posterior and lateral portal films. Field placement errors (FPEs) were calculated by comparing field centres of each film with a designated point of interest. Data was evaluated to calculate the overall treatment simulator differences, the number of error free treatments, and mean treatment-simulator position and to evaluate the role of systematic versus random errors. Age, weight, disease site, position of treatment, fractionation, blocked versus conventional techniques were assessed for their effect on treatment accuracy. The mean absolute error between treatment and simulator films was anterior right-left (ARL) 0.25 cm, anterior superior-inferior (ASI) 0.32 cm, lateral anterior-posterior (LAP) 0.42 cm, and lateral superior-inferior (LSI) 0.28 cm. On average the field centre was displaced by 0.66 cm (standard deviation, S.D. = 0.34) from that intended. On each treatment day 29% of anterior films and 45% of lateral films had at least one 0.5 cm error. Overall 59% of treatments had at least one 0.5 cm error and 9% a 1.0 cm error. The field centre was more than 0.5 cm from the position intended in 66% of treatments and over 1 cm for 14% of treatments. Analysis of variance showed that both random and systematic errors occurred in all directions. Though random errors were of similar magnitude in all direction (variance sigma 2 = 0.06-0.09 cm2); systematic errors showed a 4-fold variation being greatest in the LAP direction (sigma 2 = 0.19 cm2) and least the ARL direction (sigma 2 = 0.048 cm2). No factor consistently predicted for worse outcome in all directions. Hypofractionated treatments were less accurate in the LSI direction (P > 0.05). Systematic errors were associated in the ARL direction with hypofractionation (P < 0.01) and, in the LSI direction with weight (P < 0.03) and age (P < 0.05). We conclude that significant random and systematic errors can occur during pelvic radiotherapy especially in the LAP direction. These results suggest that in the absence of a customised immobilisation device, to cover 95% of errors, margins of 0.6 cm for RL and SI directions and 0.9 cm for AP direction should be allowed between the planning and clinical target volumes. However, ideally, each centre should determine their own margin requirements according to local clinical practice.

Age Factors

A comparison of conventional 'forward planning' with inverse planning for 3D conformal radiotherapy of the prostate.

A radiotherapy treatment plan optimisation algorithm has been applied to 48 prostate plans and the results compared with those of an experienced human planner. Twelve patients were used in the study, and 3-, 4-, 6- and 8-field plans (with standard coplanar beam angles for each plan type) were optimised by both the human planner and the optimisation algorithm. The human planner 'optimised' the plan by conventional forward planning techniques. The optimisation algorithm was based on fast simulated annealing using a cost-function designed to achieve a homogenous dose in the 'planning-target-volume' and to minimise the integral dose to the organs at risk. 'Importance factors' assigned to different regions of the patient provide a method for controlling the algorithm, and it was found that the same values gave good results for almost all plans. A study of the convergence of the algorithm is presented and optimal convergence parameters are determined. The plans were compared on the basis of both dose statistics and 'normal-tissue-complication-probability' (NTCP) and 'tumour-control-probability' (TCP). The results of the comparison study show that the optimisation algorithm yielded results that were at least as good as the human planner for all plan types, and on the whole slightly better. A study of the beam-weights chosen by the optimisation algorithm and the planner revealed differences that increased with the number of beams in the plan. The planner was found to make small perturbations about a conceived optimal beam-weight set. The optimisation algorithm showed much greater showed much greater variation, in response to individual patient geometry, frequently deselecting certain beams altogether from the plan. The algorithm is shown to be a useful tool for radiotherapy treatment planning. For simple (e.g., three-field) plans it was found to consistently achieve slightly higher TCP and lower NTCP values. For more complicated (e.g., eight-field) plans the optimisation also achieved slightly better results with generally less numbers of beams, unfavourable beams being deselected from the plan. Probably the greatest benefit is the reduced time taken by the optimisation to compute optimised beam-weights. This time always < or = 5 min; a factor of up to 20-times faster than the human planner.

Algorithms

Instance-based categorization: automatic versus intentional forms of retrieval.

Two experiments are reported which attempt to disentangle the relative contribution of intentional and automatic forms of retrieval to instance-based categorization. A financial decision-making task was used in which subjects had to decide whether a bank would approve loans for a series of applicants. Experiment 1 found that categorization was sensitive to instance-specific knowledge, even when subjects had practiced using a simple rule. L. L. Jacoby's (1991) process-dissociation procedure was adapted for use in Experiment 2 to infer the relative contribution of intentional and automatic retrieval processes to categorization decisions. The results provided (1) strong evidence that intentional retrieval processes influence categorization, and (2) some preliminary evidence suggesting that automatic retrieval processes may also contribute to categorization decisions.

Adult

Hematocrit modifies the circulatory control of systemic and myocardial oxygen utilization in septic sheep.

OBJECTIVE: To describe the relationship between hematocrit and oxygen utilization before and after the onset of a hyperdynamic septic state. DESIGN: Prospective, observational study. SETTING: Laboratory of a large university-affiliated medical school. SUBJECTS: Thirty mature sheep, each weighing 30 to 40 kg (0.9 to 1.1 m2 body surface area). INTERVENTIONS: After baseline measurements, cecal ligation and perforation were used to establish an intra-abdominal source of infection. The abdominal wound was closed and animals were studied on the second postoperative day. An increase in cardiac output of > or = 30% was used to arbitrarily define the onset of sepsis. Repeat measurements were performed and the animal was killed. RESULTS: The circulatory response to this septic insult included an increase in both cardiac index (change, baseline to sepsis, delta +2.24 +/- 0.75 L/min/m2; p < .01) and myocardial blood flows (delta +76.4 +/- 56 mL/100 g/min; p < .01). We found a negative correlation between the hematocrit and cardiac index (r2 = .21; p < .01) during the septic study, and noted that the amount (p < .01) of this correlation was significantly greater in the septic than the nonseptic study. Concurrently, the negative correlation observed between hematocrit and whole-body oxygen extraction (r2 = .21; p < .01) was significantly lower (p < .01) across the range of hematocrit values examined during the septic study vs. the similar relationship in the nonseptic study (r2 = .27; p < .01). The increase in myocardial oxygen consumption paralleled the relationship between cardiac work and hematocrit in the septic study, and was accompanied by increases in both myocardial blood flows (r2 = .25; p < .01) and myocardial oxygen extraction (r2 = .35; p < .01). CONCLUSIONS: The normal circulatory compensation to anemia in hyperdynamic sepsis includes increases in cardiac index and whole-body oxygen extraction, although greater reliance is likely placed on the use of systemic flow reserve to maintain tissue oxygen uptake in septic vs. healthy study conditions. Furthermore, increased reliance on myocardial oxygen extraction in sepsis suggests that the normal flow-reserve supporting myocardial oxygen availability may be limited in this syndrome.

Animals

Compared with crystalloid, colloid therapy slows progression of extrapulmonary tissue injury in septic sheep.

We tested the hypothesis that the type of fluid infused to chronically maintain intravascular volumes would modify both microvascular integrity and cellular structure in extrapulmonary organs in hyperdynamic sepsis. After cecal ligation and perforation, awake sheep were treated for 48 h with 10% pentastarch (n = 9), 10% pentafraction (Du Pont Critical Care; n = 8), or Ringer lactate (n = 8) titrated to maintain a constant left atrial pressure. After 48 h of fluid therapy, biopsy samples were taken from the left ventricle and gastrocnemius for electron microscopy. At this time, all groups demonstrated a similar hyperdynamic circulatory response, increased systemic O2 utilization and organ blood flows, measured by radioactive microsphere injection. However, greater capillary luminal areas with less endothelial swelling and less parenchymal injury were found in septic sheep treated with pentastarch vs. Ringer lactate infusion in both muscle types. Pentafraction showed few benefits in study end points over pentastarch. Thus, we conclude that chronic intravascular volume resuscitation of hyperdynamic sepsis with pentastarch ameliorated the progression of both microvascular and parenchymal injury. These findings indicate that microvascular surface area for tissue O2 exchange in sepsis may be better preserved with chronically infused colloid, resulting in less parenchymal injury.

Animals

Changes in myocardial blood flow rates during hyperdynamic sepsis with induced changes in arterial perfusing pressures and metabolic need.

OBJECTIVE: To determine whether hyperdynamic sepsis is associated with dysregulation in the control of myocardial blood flow rates unrelated to hypotension or the use of anesthetic agents. DESIGN: Prospective, nonrandomized, controlled trial. SETTING: Experimental laboratory. SUBJECTS: Fifteen mature male sheep (34 to 61 kg). INTERVENTIONS: Data were recorded in study subjects before and after the induction of sepsis following cecal ligation and perforation. Data were then recorded during: a) an infusion of prostaglandin E1 (PGE1), which decreased mean arterial perfusing pressure; and b) an infusion of zymosan-activated plasma, which increased mean pulmonary arterial pressures. MEASUREMENTS AND MAIN RESULTS: Myocardial blood flow rates were measured by the radiolabeled microsphere technique and cardiac index was measured by the thermodilution technique. Cardiac index (change delta) postcecal ligation and perforation minus baseline (+2.3 +/- 1.0 L/min/m2; p < .01) was increased in the septic study. Blood flow rate to the left ventricle was simultaneously increased, and was not further affected when the PGE1 infusion decreased the mean arterial perfusing pressures (-19 +/- 4%). During the infusion of zymosan-activated plasma, mean pulmonary arterial pressures increased (50 +/- 30%) and right ventricular blood flow was increased (zymosan minus postcecal ligation and perforation study: delta 17.8 +/- 50 mL/100 g/min; p < .01). CONCLUSIONS: In this model of hyperdynamic sepsis, increases in blood flow to both the left and right ventricles were positively coupled to changes in respective ventricular work. From the interventional PGE1 and zymosan-activated plasma infusion studies, we found no evidence to support previous suggestions that the regulation of myocardial blood flow rates according to changes in perfusing pressure and/or metabolic oxygen need is significantly altered during hyperdynamic sepsis.

Alprostadil

Low grade glioma presenting as subarachnoid hemorrhage.

During the last 2 years, we treated three cases of brain tumor that presented with intracranial hemorrhage. Two of the three tumors were metastatic. They presented with hemorrhage into the tumor, but no blood in the cerebrospinal fluid. One tumor was a low grade astrocytoma that presented as subarachnoid and intraventricular hemorrhage in a 15-year-old child. It was removed with no neurological sequelae.

Adolescent

Malabsorption of pyridostigmine in patients with myasthenia gravis.

Four patients with myasthenia gravis were under unsatisfactory control while receiving oral pyridostigmine. In each of these patients, the serum levels of this drug were below those observed in patients with myasthenia gravis who are well controlled. The strength of each of these patients improved when the serum pyridostigmine level was increased by intravenous administration of this agent. Furthermore, the rate of disappearance of pyridostigmine from the serum following intravenous administration was the same as that for control subjects and patients under good control. This demonstrates that failure to achieve adequate serum pyridostigmine levels following oral administration is due to malabsorption rather than to increased rates of tissue uptake, degradation, or excretion of the drug.

Administration, Oral