Anti-GOR in chronic HCV patients with membranoproliferative glomerulonephritis.
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Epitopes↗
Biomedical subjects
R Wilson
Publications and source records attributed to R Wilson.
Tumour necrosis factor-alpha (TNF-alpha) gene polymorphism and expression in pre-eclampsia.
Pre-eclampsia is an endothelial disorder and TNF-alpha has fundamental effects on endothelial cells by several means, including altering the balance between oxidant and anti-oxidant, changing the pattern of prostaglandin production and affecting expression of several cell surface components. To determine whether TNF-alpha mRNA expression is increased in pre-eclamptic patients, leucocytes from pre-eclamptic patients, normal pregnant women and normal non-pregnant women were studied for TNF-alpha expression using a quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method. Using a model of 373A ABI Sequencer, TNF-alpha gene polymorphism was also analysed by GENESCAN and Genotyper software in order to explain the mechanism of abnormal TNF-alpha expression. Our results show that TNF-alpha mRNA expression is significantly elevated in pre-eclamptic patients compared with the other two control groups. The high expression of TNF-alpha may be associated with the TNF1 allele, whose frequency is markedly increased in pre-eclamptic patients. These observations are consistent with a major role for TNF-alpha in mediating endothelial disturbances, and suggest a key role for TNF-alpha in the development of pre-eclampsia.
Adult↗
Failed intubation revisited: 17-yr experience in a teaching maternity unit.
We have reviewed 5802 Caesarean sections performed during general anaesthesia. Our use of general anaesthesia had decreased from 83% in 1981 to 23% in 1994. Despite this, the incidence of failed intubation has increased from 1 in 1984 to 1 in 250 in 1994. The problems associated with general anaesthesia in the obstetric population are increasing. Asians and African/Afrocaribbeans were represented disproportionately because of the increased use of general anaesthesia in these patients. Exposure of trainees to obstetric general anaesthetics has decreased by one-third.
Adult↗
Clinical studies in chronic bronchitis: a need for better definition and classification of severity.
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Anti-Bacterial Agents↗
Cardiovascular responses during sedation after coronary revascularization. Incidence of myocardial ischemia and hemodynamic episodes with propofol versus midazolam. Institutions of the McSPI Research Group.
BACKGROUND: Propofol sedation offers advantages for titration and rapid emergence in the critically ill patient, but concern for adverse hemodynamic effects potentially limits its use in these patients. The current study compares the cardiovascular effects of sedation with propofol versus midazolam during the first 12 h after coronary revascularization. METHODS: Three hundred fifty-one patients undergoing coronary revascularization were anesthetized using a standardized sufentanil/midazolam regimen, and assigned randomly to 12 h of sedation with either propofol or midazolam while tracheally intubated. The incidence and characteristics of hemodynamic episodes, defined as heart rate less than 60 or greater than 100 beats/min or systolic blood pressure greater than 140 or less than 90 mmHg, were determined using data electronically recorded at 1-min intervals. The presence of myocardial ischemia was determined using continuous three-channel Holter electrocardiography (ECG) and of myocardial infarctions (MI) using 12-lead ECG (Q wave MI, Minnesota Code) or creatine kinase isoenzymes (CK-MB) analysis (non-Q wave MI, peak CK-MB > 70 ng/ml, or CK-MB > 70 IU/I). RESULTS: Ninety-three percent of patients in both treatment groups had at least one hemodynamic episode during the period of postoperative sedation. Propofol sedation resulted in a 17% lower incidence of tachycardia (58% vs. 70%, propofol vs. midazolam; P = 0.04), a 28% lower incidence of hypertension (39% vs. 54%; P = 0.02), and a greater incidence of hypotension (68% vs. 51%; P = 0.01). Despite these hemodynamic effects, the incidence of myocardial ischemia did not differ between treatment groups (12% propofol vs. 13% midazolam; P = 0.66), nor did its severity, as measured by ischemic minutes per hour monitored (8.7 +/- 5.8 vs. 6.2 +/- 4.6 min/h, propofol vs. midazolam; P = 0.19) or ischemic area under the curve (6.8 +/- 4.0 vs. 5.3 +/- 4.2; P = 0.37). The incidence of cardiac death (one per group), Q wave MI (propofol, n = 7; midazolam, n = 3; P = 0.27), or non Q wave MI (propofol, n = 16; midazolam, n = 18; P = 0.81) did not differ between treatment groups. CONCLUSIONS: Hemodynamic episodes occur frequently in the first 12 h after coronary revascularization. Compared with a standard sedation regimen (midazolam), propofol sedation appears to modulate postoperative hemodynamic responses by reducing the incidence and severity of tachycardia and hypertension and increasing the incidence of hypotension. Both sedation regimens appear similarly safe with respect to myocardial ischemia. These findings indicate that propofol infusion provides effective sedation without deleterious hemodynamic effects in patients recovering from cardiac surgery.
Adult↗
Multicenter study of target-controlled infusion of propofol-sufentanil or sufentanil-midazolam for coronary artery bypass graft surgery. Multicenter Study of Perioperative Ischemia (McSPI) Research Group.
BACKGROUND: The use of target-controlled infusions of anesthetics for coronary artery bypass graft surgery has not been studied in detail. The effects of target-controlled infusions of propofol or sufentanil, supplemented by infusions of sufentanil or midazolam, respectively, were evaluated and compared. METHODS: At 14 clinical sites, 329 patients were given a target-controlled infusion of propofol (n = 165) to produce effect-site concentration (Ce) of > or = 3-micrograms/ml or a target-controlled infusion of sufentanil (n = 164). Sufentanil or midazolam, respectively, also were infused. Systolic hypertension, hypotension, tachycardia, and bradycardia were assessed by measuring heart rate and blood pressure every minute during operation. Myocardial ischemia was assessed perioperatively by monitoring ST segment deviation via continuous three-lead Holter electrocardiography, and it was evaluated during operation by monitoring left ventricular wall motion abnormality via transesophageal echocardiography. RESULTS: The measured cardiovascular parameters were satisfactory and usually similar for the patients receiving propofol-sufentanil or sufentanil-midazolam. The primary endpoint of the percentage of patients with intraoperative ST segment deviation (23 +/- 6% vs. 24 +/- 6%, P = 0.86) did not differ significantly between the two groups. The incidence of left ventricular wall motion abnormality shown on transesophageal echocardiography before (19 +/- 4% vs. 26 +/- 4%, P = 0.25) and after (23 +/- 4% vs. 31 +/- 5%, P = 0.32) cardiopulmonary bypass also did not differ significantly for the two groups. Changes in intraoperative target concentration were more frequent with propofol-sufentanil anesthetic than with sufentanil-midazolam (11.7 +/- 7.1 vs. 7.3 +/- 3.6, P < 0.001). The incidence of intraoperative hypotension (77% vs. 55%, P < 0.001), the use of inotropic/vasopressor medications (93% vs. 84%, P = 0.01), and the administration of crystalloids (2.8 +/- 1.4 L vs. 2.4 +/- 1.2 L, P < 0.001) were significantly greater in the propofol-sufentanil group. Conversely, the incidence of intraoperative hypertension (43% vs. 54%, P = 0.05) and the use of antihypertensive/vasodilator medications (70% vs. 90%, P < 0.001) were significantly less in the propofol-sufentanil group. CONCLUSIONS: Target-controlled infusions of propofol or sufentanil, supplemented by infusions of sufentanil or midazolam, respectively, were suitable to provide anesthesia for coronary artery bypass graft surgery. Continuous monitoring revealed a high prevalence of hemodynamic abnormalities. Despite greater hypotension in the propofol-sufentanil group and greater hypertension in the sufentanil-midazolam group, episodes of myocardial ischemia were similar for both groups and were not temporally related to episodes of hemodynamic abnormalities.
Aged↗
The importance of the dura in craniofacial surgery.
The hypothesis of this study is that craniofacial procedures that rely on devascularization of cranial bone are successful largely because of the unique environment that the dura offers. This hypothesis was tested by sequentially labeling animals with tetracycline and studying the healing of cranial bone grafts when replaced immediately and when subjected to room air exposure for 90 minutes and contrasting healing in mature and immature animals. Bilateral parietal bone flaps were harvested from guinea pigs. On one side, the bone was replaced as a control, and on the other side, the dura was resected prior to replacing the bone flap. The animals were divided into four groups of five animals each. The first and second groups were immature animals (3 to 4 weeks of age), and the third and fourth groups were mature animals (4 to 6 months of age). In the first and third groups, the bone flaps were replaced immediately, and in the second and fourth groups, the bone flaps were exposed to room air for 90 minutes, since this has been shown to destroy surface osteocytes and simulates extreme exposure conditions that could occur in clinical situations. Sequential marking with tetracycline was performed to study the mineralization rate and overall matrix formation. Significantly decreased mineralization rates occurred in bone flaps not in contract with dura. In those bone flaps exposed to room air for 90 minutes, healing occurred only on the side where dura was present. The clinical implications of the importance of the dura in craniofacial procedures are discussed.
Aging↗
Generation and analysis of 280,000 human expressed sequence tags.
We report the generation of 319,311 single-pass sequencing reactions (known as expressed sequence tags, or ESTs) obtained from the 5' and 3' ends of 194,031 human cDNA clones. Our goal has been to obtain tag sequences from many different genes and to deposit these in the publicly accessible Data Base for Expressed Sequence Tags. Highly efficient automatic screening of the data allows deposition of the annotated sequences without delay. Sequences have been generated from 26 oligo(dT) primed directionally cloned libraries, of which 18 were normalized. The libraries were constructed using mRNA isolated from 17 different tissues representing three developmental states. Comparisons of a subset of our data with nonredundant human mRNA and protein data bases show that the ESTs represent many known sequences and contain many that are novel. Analysis of protein families using Hidden Markov Models confirms this observation and supports the contention that although normalization reduces significantly the relative abundance of redundant cDNA clones, it does not result in the complete removal of members of gene families.
Adult↗
The quality of prescribing in general practice.
General practitioner prescribing is a subject of legitimate interest to all those concerned with the quality of patient care. The analysis of prescribing and cost data can reveal much about this quality. Suggests that both general practitioners and those who administer and advise on family practitioner services will need to understand the issues involved. Warns that, taken in isolation, prescribing data can be misleading, and it must be compared with other aspects of patient care. Simple calculations can suggest areas of possible under-prescribing and over-prescribing, and in turn lead to consideration of the criteria for diagnosis of common chronic diseases such as asthma and diabetes, as well as their subsequent management. Suggests that the prescribing of both new drugs and those of dubious merit is a subject for particular scrutiny, and those who prescribe these drugs must accept the duty of extra vigilance this imposes on them.
Drug Prescriptions↗
Anti-inflammatory, membrane-stabilizing interactions of salmeterol with human neutrophils in vitro.
1. We have investigated the effects of salmeterol (0.3-50 microM) on several pro-inflammatory activities of human neutrophils in vitro. 2. Oxidant production by FMLP- and calcium ionophore (A23187)-activated neutrophils was particularly sensitive to inhibition by low concentrations (0.3-3 microM) of salmeterol, while the responses of phorbol myristate acetate- and opsonised zymosan-stimulated cells were affected only by higher concentrations (3-50 microM) of the drug. At these concentrations salmeterol is not cytotoxic, nor does it act as a scavenger of superoxide. 3. These anti-oxidative interactions of salmeterol with neutrophils were insensitive to propranolol but could be eliminated by washing the cells, or by pretreatment with low concentrations (1-2 microM) of the pro-oxidative, membrane-destabilizing phospholipids, lysophosphatidylcholine (LPC), platelet activating factor (PAF) and lysoPAF (LPAF). 4. At concentrations of 6.25-50 microM salmeterol interfered with several other activities of stimulated neutrophils, including intracellular calcium fluxes, phospholipase A2 activity and synthesis of PAF. 5. In an assay of membrane-stabilizing activity, salmeterol (25 and 50 microM) neutralized the haemolytic action of LPC, PAF and LPAF. 6. Of the other commonly used beta 2-adrenoceptor agonists, fenoterol, and formoterol, but not salbutamol, caused moderate inhibition of neutrophil oxidant generation by a superoxide-scavenging mechanism. However, unlike salmeterol, these agents possessed only weak membrane stabilizing properties. 7. We conclude that salmeterol antagonizes the pro-inflammatory, pro-oxidative activity of several bioactive lipids implicated in the pathogenesis of bronchial asthma, by a mechanism related to the membrane-stabilizing, rather than to the beta 2-agonist properties of this agent.
Adenosine Triphosphate↗
Soluble adhesion molecules in serum of smokers and non-smokers, with and without periodontitis.
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Adult↗
Mapping of the H7-serospecific domain of Escherichia coli flagellin.
The amino acid sequences responsible for H7 and H23 flagellum serology have been identified by using a genetic approach. The H7-specific domain was located between amino acids 352 and 374 of the H7 flagellin. The sequencing data also demonstrated that the difference between the H7 and H23 flagellins in this region results from a single substitution at amino acid 366 (Ser-->Thr). The common epitopes for H7 and H23 were located between amino acids 284 and 366.
Amino Acid Sequence↗
Comparison of haemophilus influenzae type b interaction with respiratory mucosa organ cultures maintained with an air interface or immersed in medium.
Haemophilus influenzae type b infection of immersed and air interface organ cultures for 24 h caused significant epithelial damage. Bacterial association with mucus, damaged epithelium, and unciliated cells was significantly higher in air interface than immersed organ cultures, and total bacterial association was 55.8 times greater. Bacteria exhibited tropism for mucus only on explants maintained with an air interface. We conclude that immersion of nasopharyngeal tissue in medium may influence bacterial interaction with the mucosal surface.
Culture Media↗
Socioeconomic circumstances and the risk of bowel cancer in Northern Ireland.
OBJECTIVE: To describe the variation in the incidence of colorectal cancer across Northern Ireland and relate it to factors associated with community deprivation. DESIGN: This was a cross sectional descriptive study. SETTING: Incidence data were obtained from a population based register for the period 1990-91. Small areas were characterised by their "affluence", or lack of it, by deriving a Townsend deprivation score for each electoral ward, using information from the 1991 census. PARTICIPANTS, MAIN OUTCOME MEASURES, AND STATISTICAL METHODS: The age standardised incidence was calculated for all colorectal cancer cases diagnosed histologically in 1990-91. Electoral wards were grouped into quintiles of the population after ranking of their Townsend scores and the association with incidence was studied using Poisson regression. RESULTS: The age standardised colorectal cancer incidence ranged from 22.5 (for quintile 1) to 29.9/100,000 (quintile 5) for men but the trend for women was less regular and rates were 18.4, 23.8, 27.3, 26.5, and 23.9/100,000 for quintiles 1-5 respectively (that is, from the most "affluent" to the most "deprived" fifths of the population). After adjusting for age and sex in Poisson regression, there was a significant association between the total colorectal cancer incidence and levels of community deprivation. The rate ratio for the most deprived quintile of the population (compared with the least) was 1.28 (95% CI 1.06,1.53). The effect was stronger for rectal cancer than for colonic cancer. There was no association between community deprivation and the cancer stage at diagnosis. CONCLUSIONS: In this population, the colorectal cancer incidence is associated with the level of material deprivation. The disease stages at the time of diagnosis in patients from more deprived areas seem to be comparable with those of patients from affluent areas. As others have shown, associations such as these are not explicable entirely on the basis of the distribution of known risk factors. Further research is needed to determine plausible mechanisms for the association.
Adolescent↗
Breathlessness in an Afro-Caribbean woman.
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Adult↗
Ciliary disorientation alone as a cause of primary ciliary dyskinesia syndrome.
Ciliary disorientation has been proposed as a variant of primary ciliary dyskinesia (PCD); cilia have normal ultrastructure and normal or near normal ciliary beat frequency (CBF) but lack efficacy because their beat direction is disorientated. We have identified 11 patients, including two siblings, with the clinical features of PCD, who satisfy these criteria. A chest radiograph, pulmonary function tests, nasal mucociliary clearance (NMCC), CBF, ciliary ultrastructure, and orientation were assessed in each subject. One patient had biopsies taken from the nose and both main bronchi. Eight patients had a computed tomography scan (CT) of the thorax; the clinical features were compatible with PCD. Cilia ultrastructure was normal and NMCC was absent in all cases. Mean CBF was normal (11.6-14.9 Hz) in five cases and slow in six (range 8.4-9.7 Hz). Ciliary beat pattern was stiff in seven cases, six of which had slow CBF. The cilia were disorientated when measured by both the central pair (range, 21.8 degrees - 26.4 degrees) and basal feet (range, 20.6 degrees - 28.9 degrees) compared with 16 normal controls (range, 11.0 degrees - 15.5 degrees and 12.3 degrees - 17.6 degrees, respectively). Two siblings had the clinical features of PCD and ciliary disorientation alone on repeated biopsies taken 10 yr apart. Orientation of cilia from the nose and bronchus was similar. Two cases had unchanged ciliary disorientation after 3 mo of treatment with antibiotics and topical corticosteroids. We concluded that ciliary disorientation alone can lead to the clinical syndrome of PCD.
Administration, Topical↗
A human respiratory-tissue organ culture incorporating an air interface.
The immersion of respiratory tissue in organ cultures is unphysiologic and may influence the interactions of the tissue with experimental agents. We have assessed an organ culture of human nasal turbinate tissue with an air interface by light microscopy (LM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM), with and without replacement of culture medium. Without replacement of medium, ciliary beat frequency (CBF) was normal (11.3 +/- 0.5 Hz) at 5 d, but fell significantly (p<0.05) to 7.9 +/- 0.8 Hz at 10 d. The degree of ciliation decreased significantly (p<0.05) at 4 and 10 d. Nuclear heterochromatin in all cell types was significantly (p<0.05) reduced at 5 d. Significant (p<0.05) mitochondrial abnormalities occurred in ciliated cells at 5 d and in both ciliated and unciliated cells at 10 d. With daily replacement of medium, CBF fell significantly (p<0.05) from 11.6 +/- 0.2 Hz at Time 0 to 10.6 +/- 0.3 Hz after 20 d. The proportions of ciliated and nonciliated cells did not change after 20 d, but the proportion of mucus cells was higher at 20 d (26.3 +/- 5.4%) than at Time 0 (9.8 +/- 2.7%). No mitochondrial abnormalities, changes in nuclear heterochromatin levels, or reduction in cilial density on ciliated cells were present. The amount of damaged epithelium was less at 20d (7.2 +/- 3.8%) than at Time 0 (19.0 +/- 5.8%). This model more closely reproduces physiologic conditions in vitro than do models involving the immersion of respiratory tissue in media. Its long viability will permit studies of virus and bacterial infections, and of the effects of pharmacologic agents and environmental factors.
Air↗
Short-term recombinant human DNase in bronchiectasis. Effect on clinical state and in vitro sputum transportability.
We report a double blind placebo-controlled phase II study of the efficacy and safety of nebulized recombinant human DNase (rhDNase) administered for 14 d to adults with bronchiectasis not caused by cystic fibrosis. All were in a stable clinical state at the commencement of the study, and they received (1) rhDNase 2.5 mg twice daily, (2) rhDNase once daily, or (3) placebo (excipient only) inhalation. The outcome measures were spirometry, subjective quality of life/dyspnea, and safety. We also measured the ciliary transportability of the sputum expectorated before and after the treatment period, using the mucus-depleted bovine trachea. The drug was well tolerated, but it produced no significant change in any of the outcome variables or in sputum transportability. When the drug was incubated with bronchiectatic sputum in vitro, a fall in transportability was observed. We discuss possible explanations for the lack of a measurable benefit from rhDNase in this study population, which appears to contrast with the improvements shown in cystic fibrosis using studies of similar design.
Administration, Inhalation↗