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Biomedical subjects

J Vickers

Publications and source records attributed to J Vickers.

At least 19 recordsLinked to original sources

Assessment of satisfaction with care after inpatient treatment for oesophageal and gastric cancer.

BACKGROUND: Patients' views are becoming increasingly important in the current health system. They provide information on effectiveness of healthcare and how it may be improved. This study aimed to measure patients' satisfaction with care received for treatment of oesophageal and gastric cancer, and to identify areas that contribute most to overall satisfaction scores. METHODS: Consecutive inpatients with oesophageal and gastric cancer treated in one surgical unit were recruited prospectively during a 2-year period. The European Organization for Research and Treatment of Cancer 'satisfaction with in-hospital care' questionnaire (QLQ-SAT32) was completed following discharge. Scores ranged from 0 to 100 for each satisfaction scale. Univariable and multivariable analysis was used to define the relationships between the different dimensions of satisfaction with care and the overall score. RESULTS: Ninety-one patients (mean age 67 years, 60 men) completed the questionnaire a mean of 40 days after treatment. The highest scores were for doctors (mean 72), nurses (mean 67) and overall satisfaction (mean 68). Univariable analysis showed that all dimensions of satisfaction with care contributed significantly to overall satisfaction (P < 0.001). Multivariable analyses, however, showed that most of the variation in overall satisfaction could be attributed to levels of satisfaction with doctors, nurses, and hospital comfort and cleanliness. CONCLUSION: Satisfaction with care in these surgical patients was high and could be measured using a multidimensional instrument. Overall satisfaction was not influenced equally by all aspects of care. The strongest contributors to overall satisfaction in this study were doctors, nurses and hospital cleanliness.

Aged↗

Properties of microtubules assembled from mammalian tubulin synthesized in Escherichia coli.

When isolated from tissues, the alpha beta-dimeric protein tubulin consists of multiple isoforms which originate from the expression and subsequent posttranslational modification of multiple polypeptide sequences. Microtubules studied in vitro consist of mixtures of these isoforms. It is therefore not known whether dimers composed of single sequences of alpha- and beta-tubulin can polymerize to form microtubules, or whether posttranslational modifications may be necessary for microtubule assembly. To initiate investigation of these questions, rabbit reticulocyte lysate, which contains the cytoplasmic chaperonin CCT and its cofactors, was employed to prepare substantial quantities (tens of micrograms) of active tubulin by in vitro folding of mouse alpha- and beta-tubulins recombinantly synthesized in E. coli. This recombinant tubulin is composed of only a single alpha-chain and a single beta-chain. When analyzed after folding by isoelectric focusing, each chain yielded only one band, indicating that neither was detectably posttranslationally modified in the course of the folding reaction. When subjected to assembly-promoting conditions, this tubulin formed microtubules without the addition of any exogenous protein. Electron microscopy showed them to be of normal morphology. Analysis of their protein composition showed that they are composed nearly entirely of recombinant tubulin. These results demonstrate that the naturally occurring mixtures of isoforms are not strictly required for the formation of microtubules. They also open a route to other studies, both biomedical and structural, of fully defined tubulin in vitro.

Animals↗

Inhibition of leukocyte chemiluminescence by platelets: role of platelet-bound fibrinogen.

Tethering of PMNL by platelets via CD62P has been shown to cause PMNL activation. Co-incubation of purified PMNL with platelets that were activated with thrombin and then fixed and washed, resulted in the formation of platelet-PMNL conjugates as well as in a generation of reactive oxygen species that were measured as luminol-enhanced chemiluminescence. When platelets were thrombin activated in the presence of RGDS to prevent binding of fibrinogen to membrane receptors, they had a reduced capacity to adhere to PMNL, but ROS generation was enhanced. In samples of citrated whole blood RGDS as well as the more specific platelet fibrinogen receptor antagonist GR144053F or a dissociation of the platelet glycoprotein IIb/IIIa complex markedly enhanced ROS generation that was induced by stirring the samples for 10 min at 1000 rpm, by 175%, 95% and 138%, respectively. Removal of platelets from the whole blood samples also resulted in an enhancement of stirring-induced ROS generation, which was inversely correlated to the platelet count. These data provide some evidence that platelets are capable of inhibiting ROS generation in PMNL by a mechanism that involves platelet-bound fibrinogen and probably depends on fibrinogen-mediated platelet-PMNL contact.

Blood Platelets↗

Dietary intake at child-care centers and away: are parents and care providers working as partners or at cross-purposes?

OBJECTIVE: To examine how meals and snacks children consume before and after their time at a child-care facility complement the menu at the facility. DESIGN: Dietary intake of children at and away from the child-care center was compared with recommended standards for child nutrition. Registered dietitians observed foods consumed at the center during 3 consecutive days. Parents reported foods consumed away from the center during the same 3 days. SUBJECTS/SETTING: Six nonprofit child-care centers with strong menus (i.e., menus that come close to meeting dietary recommendations) and 6 with menus supplying less than 50% of the Recommended Dietary Allowance were selected for study. Five families at each center were invited to participate. Complete data sets were obtained for 51 children aged 3 to 6 years. STATISTICAL ANALYSES PERFORMED: Descriptive and inferential statistics were calculated to compare the children's dietary intake during center time and family time and over a full day with recommended standards. Energy and nutrient profiles and food frequencies were included in the analysis. RESULTS: Children consumed plenty of foods at the center and away from the following groups: meat, poultry, fish, dry beans, eggs, nuts; milk, yogurt, cheese; and fruit, fruit juice. Most children failed to consume enough vegetables. Nearly all the children failed to consume enough bread, cereal, pasta, and rice, especially while at the center. The majority ate more than sparing amounts of fats, oils, and sweets, especially during family time. Average percentage of energy from fat was 33 +/- 4. Intakes of concern for the full day were energy, iron, sodium, and zinc. APPLICATIONS: Child-care menus are an appropriate target for increasing iron and zinc by serving more cereal and whole grains. Families are an appropriate target for reducing young children's consumption of fats, oils, and sweets. Nutrition education and advocacy are needed to strengthen the partnership between parents and caregivers.

Calcium, Dietary↗

Oesophageal cancer staging using endoscopic ultrasonography.

BACKGROUND: Despite encouraging results from Europe and the USA, endoscopic ultrasonography has yet to become established in the UK for imaging gastrointestinal lesions. The aim of this prospective study was to investigate the accuracy of endoscopic ultrasonography for local tumour (T) and lymph node (N) staging of oesophageal cancer. METHODS: Endoscopic ultrasonography was performed in 50 consecutive patients with operable oesophageal cancer. Its accuracy for locoregional tumour staging was assessed and a detailed analysis of the distribution of ultrasonographically detected lymph nodes performed. RESULTS: Endoscopic ultrasonography was highly accurate for both local tumour (92 per cent correct T stage prediction) and lymph node (86 per cent correct N stage prediction) staging compared with final histology. The procedure was also superior to open surgical staging performed by the surgeon; it had a tendency to overestimate malignant involvement of individual lymph nodes and had only limited ability to identify small benign lymph nodes, particularly in the abdomen. CONCLUSION: Endoscopic ultrasonography was reliable for both local tumour and lymph node staging of oesophageal cancer.

Adenocarcinoma↗

Influence of luminal obstruction on oesophageal cancer staging using endoscopic ultrasonography.

BACKGROUND: Endoscopic ultrasonography is technically limited in patients with obstructing oesophageal cancers if the endoscope cannot pass beyond the lesion. This problem may be overcome by preliminary endoscopic tumour dilatation, or by the use of narrower calibre 'blind' endoscopic ultrasonographic telescopes or fine-bore endoscopic ultrasonographic miniprobes. These alternatives are either potentially hazardous or time consuming and expensive. The aim of this prospective study was to determine the effect of oesophageal obstruction on the locoregional staging accuracy of endoscopic ultrasonography for oesophageal cancer. METHODS: Some 50 patients with oesophageal cancer underwent staging with endoscopic ultrasonography before oesophagectomy and the T and N stage determined by endoscopic ultrasonography was compared with final histology. In 11 cases of luminal obstruction no attempt was made to overcome the blockage and a limited mediastinal scan alone was performed. RESULTS: Malignant obstruction of the oesophagus did not greatly reduce the staging accuracy of endoscopic ultrasonography. It correctly assessed local infiltration in all patients with obstruction, and correctly predicted nodal stage in nine of 11 patients. CONCLUSION: Tumours large enough to cause luminal obstruction are nearly all full thickness (T3), and frequently have mediastinal lymph node metastases (N1) at the time of examination. This can usually be detected from limited endoscopic ultrasonography within the mediastinum.

Diagnostic Errors↗

Measurement of platelet activation and adhesion to leukocytes during haemodialysis.

In this study we used fluorescent-labelled antibodies to measure the extent of platelet adhesion to polymorphonuclear leukocytes (PMNLs), monocytes and lymphocytes. The activation of platelets, PMNLs and monocytes were also measured during the course of haemodialysis treatment using flow cytometric techniques established in our laboratory. Twenty patients were treated with either a cellulose membrane (TFU) or a polycarbonate filter (Pro 500). Blood samples were taken from the output line of the dialyser 2, 15, 30 and 180 min after commencing dialysis and just before starting treatment. Compared with the pre-dialysis sample, there was a marked increase in platelet-PMNL conjugate formation at 2 min, followed by a decrease in conjugates at 15 and 30 min, and a slight increase at 180 min. During extracorporeal circulation PMNLs become activated as measured by a CD11b upregulation at 15, 30 and 180 min, but not at 2 min. Platelet binding to monocytes was increased above 15 min after starting dialysis, and monocyte activation was slightly increased above basal levels during the same period. The activation state of circulating free platelets, as measured by surface P-selectin exposition, initially decreased slightly, but then returned to basal levels over the 3-h period. Changes in cell counts were also detected: there was a massive decrease in circulating PMNLs and monocytes, and a small decrease in circulating platelets, at 15 and 30 min. These reverted to basal values by the end of the 3-h period. There was no change in the number of circulating lymphocytes or erythrocytes. These results show that flow cytometric studies on whole blood samples may provide important information on the behaviour of circulating blood cells, which could supplement conventional clinical measurements, to give a better insight into changes that occur in the circulation during haemodialysis.

Journal Article↗

Role of endoscopic ultrasound in the preoperative assessment of patients with oesophageal cancer.

Despite encouraging results from Europe and America, endoscopic ultrasound (EUS) has yet to become established in the United Kingdom. The aims of this prospective study were to investigate its value in the assessment of patients with benign and malignant oesophageal conditions, and in particular to assess its reliability for local tumour (T) and lymph node (N) staging in patients with oesophageal cancer. EUS was performed in 90 patients: 23 were normal controls, 17 had benign oesophageal diseases and 50 had operable oesophageal cancer. Detailed measurements of the oesophageal wall and regional nodes were made and the accuracy of EUS for locoregional tumour staging was compared with final histology. EUS visualised the normal oesophageal wall as a multilayered structure, thicker distally than proximally. Distal stenotic conditions caused thickening of the proximal wall and loss of this gradient. EUS was highly accurate for both local tumour (92% correct) and lymph node staging (86% correct) and was better than computed tomography, magnetic resonance imaging and open staging performed by the surgeon. Fine needle aspiration biopsy using radial scanning EUS guidance was shown to be feasible. EUS is a valuable technique for investigation of both benign and malignant oesophageal conditions. It provides highly accurate local tumour and regional lymph node staging data in patients with oesophageal cancer.

Endosonography↗

Formation of platelet-leukocyte conjugates in whole blood.

The purpose of this investigation was to obtain information on platelet-leukocyte conjugate formation in whole blood and on factors that affect it. We also measured platelet and leukocyte activation by quantitating the expression of CD62P and CD11b. In both cases a flow cytometric approach was used. The results show that platelet-monocyte and platelet-polymorphonuclear leukocyte (PMNL) conjugate formation is enhanced by simply stirring blood, with optimum conjugate formation occurring after 10 min. In the case of monocytes,conjugate formation was enhanced by adenosine diphosphate (ADP). Both monocyte and PMNL conjugate formation was enhanced by phorbol myristate acetate (PMA), but L-formyl methionyl lysyl proline (FMLP) was either without effect (monocytes) or inhibitory (PMNL). EDTA also inhibited conjugate formation (implying involvement of divalent cations), as did dextran sulphate (implying involvement of P-selectin = CD62P). Interestingly GR144053F, which acts at GpIIb-IIIa on platelets to interfere with fibrinogen binding, and also glycyl prolyl arginyl proline (GPRP), a peptide that interferes with the interaction between CD11c on leukocytes and fibrinogen, did not inhibit platelet-monocyte conjugate formation, but did inhibit the platelet-PMNL interaction; this indicates that GpIIb-IIIa on platelets and CD11c on leukocytes and fibrinogen are involved in mediating the interaction between platelets and PMNL but not platelets and monocytes. Surprisingly arginyl-glycyl aspartyl serine (RGDS) inhibited the formation of both types of conjugate but this may be because it also inhibited both platelet and leukocyte activation as measured by CD62P and CD11b exposure and/or interferes with the binding of adhesion molecules other than fibrinogen. The results show that a flow cytometric procedure can be effective in obtaining rapid information on platelet-leukocyte conjugate formation in whole blood and on factors that are involved in its regulation. It is suggested that the technique may be applicable to the study of platelet-leukocyte conjugate formation in whole blood in disease, and also to study the effects of drugs interfering with conjugate formation.

Journal Article↗

Strategies for diagnosing and managing medication-induced headache.

PROBLEM ADDRESSED: Headache is a common clinical disorder. Nearly 50% of patients with headaches use prescription medications, and 90% regularly use nonprescription drugs. Medication-induced headaches (MIH) are chronic daily headaches caused by overuse of medicine. OBJECTIVES: To summarize the diagnostic criteria for MIH, to determine the investigations necessary to confirm the diagnosis and exclude other possible diagnoses, and to establish recommendations for managing MIH. MAIN FINDINGS: Diagnosis of MIH is based on patient's history and the clinical characteristics of the headache. Treatment includes patient education and support, withdrawal of offending medications, relief of withdrawal symptoms, and specific treatment of residual headache. When migraine and other causes of headache are adequately addressed, patients will not seek additional pain relief. CONCLUSION: Medication-induced headache is preventable. The key to prevention is appropriate drug therapy to relieve the primary headache. All patients with MIH can be treated and most cured.

Analgesics↗

CSF testosterone and 5-HIAA correlate with different types of aggressive behaviors.

We studied the potential roles of testosterone and serotonin in various forms of aggressive and violent behaviors by measuring each biochemical and behaviour in free-ranging adolescent male nonhuman primates. Our results showed that (1) CSF free testosterone concentrations were positively correlated with overall aggressiveness, but not with measures of impulsivity. (2) CSF 5-HIAA concentrations were negatively correlated with impulsive behavior, and severe, unrestrained aggression, but not with overall rates of aggression. High rates of impulsive behavior were positively correlated with severe, unrestrained aggression, but not overall rates of aggression. (3) Dimensional analyses showed that while subjects with low CSF 5-HIAA exhibited high rates of aggression, high CSF testosterone further augmented rates and intensity of aggression in subjects with low CSF 5-HIAA. We conclude that high CSF free testosterone concentrations are associated with competitive aggression, while low CSF 5-HIAA concentrations are associated with severe aggression which results from impaired impulse control, and perseverance.

Aggression↗

Excessive mortality in young free-ranging male nonhuman primates with low cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations.

BACKGROUND: The purpose of this study was to assess the impact of central serotonin turnover rate on survival to adulthood among nonhuman primates living in a large, free-ranging colony. METHODS: The rate of mortality was ascertained over a 4-year period after obtaining blood and cisternal cerebrospinal fluid (CSF) samples from 49 free-ranging, 2-year-old prepubertal male rhesus monkeys. Cerebrospinal fluid was assayed for 5-hydroxyindoleacetic acid (5-HIAA), norepinephrine, 3-methoxy-4-hydroxyphenylgycol, and homovanillic acid. Blood plasma was assayed for adrenocorticotropic hormone, cortisol, and testosterone. Following the sampling of body fluids, records of scars and wounds and aggressive encounters were used to rank the subjects from low to high in aggressiveness. Direct observations of aggressive behavior were collected from 27 of the subjects over a 3-month period. RESULTS: Four years later, 6 of the 49 subjects were known to be dead and an additional 5 had been missing for more than 2 years and were presumed dead. The CSF 5-HIAA concentrations were predictive of which subjects died, with 46% of the subjects with low CSF 5-HIAA concentrations dead or presumed dead. None of the subjects from the highest CSF 5-HIAA concentration quartile were dead or missing. Indeed, 91% of the dead subjects came from the 2 lowest quartiles of CSF 5-HIAA concentrations. Direct observations of aggressive behavior showed that dead or missing subjects had initiated escalated aggression, a measure of unrestrained aggression that has a high probability of trauma or injury, at a higher rate than subjects that were known to be alive. The cause of death could be ascertained for 6 of the 11 missing subjects. The 4 subjects that were known to die as a consequence of aggressive encounters came from the lowest quartile of CSF 5-HIAA concentrations and had been rated as more aggressive during their initial capture. Subjects captured more than once possessed lower CSF 5-HIAA concentrations, were rated as more aggressive, and were more likely to suffer early death than those captured only once. CONCLUSION: These findings suggest that low CSF 5-HIAA concentrations quantified early in life is a powerful biological predictor of future excessive aggression, risk taking, and premature death among nonhuman primate males.

Aggression↗

Studies on the effects of agonists and antagonists on platelet shape change and platelet aggregation in whole blood.

The shape change that occurs when platelets are stimulated with an agonist can be quantitated by monitoring changes in their forward-scatter/side-scatter profile using a flow cytometer. Here we have stimulated platelets in citrated whole blood with several agonists and determined the time-course and extent of the shape change that occurs. In some experiments parallel investigations of shape change and aggregation were performed. Aggregation was measured by monitoring the fall in number of single platelets using a Whole Blood Platelet Counter. Some agents (ADP, PAF, U46619 and 5HT) produced a strong and rapid change in platelet forward-scatter/side-scatter that was maximal within 10 s. Others (A23187 and collagen) produced a strong but slower response. Adrenaline produced only a weak response that was also slow to develop, and PMA did not produce any response. The concentrations of each of ADP, PAF, U46619 and 5HT needed to induce a shape change were lower than those required for aggregation. Selective PAF, TXA2 and 5HT antagonists (WEB 2086, sulotroban and MCI-9042) clearly inhibited both the shape change and the aggregation induced by the appropriate agonist; in each case the effect of the antagonist was to move the dose-response curve to the right. These results are consistent with the shape change and aggregation brought about by each of these agonists being mediated via a single receptor. In contrast, a selective P2T purinoceptor antagonist (ARL 66096) markedly inhibited the aggregation induced by ADP but was found to have little or no effect on shape change. This is consistent with these platelet responses to ADP being mediated by different receptors, with P2T receptors mediating only the aggregation response.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗