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At least 1,081 records · Page 60Linked to original sources
PubMed1996

The structure of organometals determines cytotoxicity and alteration of calcium homeostasis in HL-60 cells.

There is increasing concern about the degradation and metabolisation as well as the biochemical mechanisms of action of organometallic compounds. They are known to be immunotoxic and/or neurotoxic. Because of their different toxic capacities, the development of a reliable correlation between molecular parameters and biochemical effects, which could be helpful in risk assessment, was an aim of this study. The tested organolead and -tin compounds decrease the viability of human cells in culture in a time- and concentration-dependent manner. Parabolic QSAR(1)(1) The abbreviations used are: TMT, trimethyltin chloride; TET, triethyltin bromide; TPT, tripropyltin chloride; TBT, tri- n-butyltin chloride; DBT, di- n-butyltin dichloride; TEL, triethyllead chloride; DEL, diethyllead dichloride; TML, trimethyllead chloride; TPhL, triphenyllead chloride; QSAR, quantitative structure-activity relationships; TSA, total surface area; MW(ion), ionic molecular weight; fMLP, N-formyl-L-methionyl-L-leucyl-L-phenylalanine; fluo-3, fluo-3 free acid; fluo-3 AM, fluo-3 acetoxymethyl ester; Me(2)SO, dimethyl sulfoxide; PLA(2), phospholipase A(2) (EC 3.1.1.4); FCS, fetal calf serum; HEPES, 4-(2-hydroxy-ethyl)-1-piperazineethanesulfonic acid; EGTA, [ethylene-bis(oxyethylenenitrilo)]tetraacetic acid; [Ca(2+)](i), cytosolic free Ca(2+) concentration models yield an adequate correlation between toxicity expressed as LC(50) and structural parameters like ionic molecular weight (MW(ion)) or total surface area (TSA). Two main chemical attributes of the organometals are probably responsible for such a parabolic relationship: the hydrophobic side chain and the polar metal atom. Furthermore, all tested organometal compounds evoke a persistent increase of the cytosolic free calcium concentration [Ca(2+)](i). This effect is mainly due to an influx from the extracellular space. Further results suggest that Ca(2+) enters the cell via opened calcium channels. Based on the essential role of Ca(2+) within cellular signalling, the perturbation of calcium homeostasis appears to be an important event in final cell killing by organometals and it is most likely that other biochemical mechanisms, e.g. activation of phospholipase A(2), are possibly mediated by an increase of [Ca(2+)](i).

Journal Article↗
PubMedDate not supplied

Early presentation of a congenital coronary artery fistula in a neonate.

A neonate developed severe congestive heart failure secondary to a congenital coronary artery fistula requiring emergent surgery. Intraoperative transesophageal echocardiography helped guide successful emergent closure of the fistula without complications.

Coronary Vessel Anomalies↗
PubMed2002

Conservative management of pneumatosis intestinalis and pneumoperitoneum following bone-marrow transplantation.

Pneumatosis intestinalis (PI), with or without pneumoperitoneum (PP), may complicate allogenic bone-marrow transplantation (BMT). The aim of our study was to establish the incidence and outcome of this complication following BMT in children. A departmental database was used to identify children who underwent BMT in the 4-year period up to December 1999. The medical records of children who developed PI with or without PP were obtained for further study. All patients were managed without recourse to surgery. Conservative management included 7 days of intravenous antibiotics and 10 days of intestinal rest supported by parenteral nutrition. In the study period, 138 BMTs were carried out. Six children (4%) with a total of 7 episodes of PI/PP were identified, 1 boy and 5 girls with a median age of 8.5 years (range 0.8-11). Neutropenia was noted in 3 children at the time of presentation. Other risk factors identified included alternative BMT donors (5/6), steroid therapy (6/7), and graft-versus-host disease (5/6). Organisms were isolated from stool cultures sent at the time of diagnosis in 3 out of 7 instances. Diarrhoea was the predominant presenting symptom. All patients recovered from the acute episode, but 5 died at a mean of 12 months from the development of PI/PP (range 6-17 months). This mortality of 83% compares with a mortality of 33% (43 of 132) for the remainder of children who underwent BMT during the study period. Thus, while initial recovery can be anticipated, the medium-term mortality in this group of children is high.

Anti-Bacterial Agents↗
PubMed2005

Antenatally diagnosed duplication cyst of the tongue: modern imaging modalities assist perinatal management.

When a foetal abnormality is detected during routine antenatal screening, further information is required in order to plan the remainder of the pregnancy and perinatal management. If a lesion is detected in the foetal mouth or neck, there may be compromise of the foetal airway. The ex-utero intrapartum (EXIT) procedure has recently been developed to allow lifesaving foetal surgery to be performed during delivery of such cases whilst relying on placental support. Detailed antenatal assessment is essential when planning the EXIT procedure, and modern imaging modalities may be implemented. We illustrate this by reporting a rare case of enteric duplication cyst arising from the base of the tongue, which was detected on routine antenatal ultrasound scan. Subsequent imaging using foetal MRI and colour Doppler ultrasound reassured us that the foetal airway was patent, and an EXIT procedure was avoided.

Cysts↗
PubMed2005

Bacterial contamination of central venous catheters during insertion: a double blind randomised controlled trial.

Static electricity within sterile packaging may result in bacterial contamination of central venous catheters (CVCs) prior to insertion. To prevent this, some surgeons inject saline into the pack before opening it. This trial was designed to determine the effect of this procedure. A double blind randomised controlled trial of 47 CVCs comparing injection of 2 ml of sterile saline into the pack prior to opening with no injection was performed. Five centimetre lengths cut from the tip of the catheter before and after subcutaneous tunnelling were sent for microbiological culture. Eight catheters (17%) showed evidence of bacterial contamination prior to insertion into the vein. Two (4.2%) were contaminated prior to tunnelling and seven (14.9%) afterwards. One catheter was contaminated before and after tunnelling. All but one of the contaminating bacteria were coagulase negative staphylococci. There was no significant difference in the contamination rate between catheters from packs that had been injected (5/25) and those that had not (3/22), P = 0.56. Just under one-fifth of the catheters were contaminated with bacteria prior to insertion into the vein but this was not influenced by prior injection of saline into the pack. We conclude that there is no evidence to support the practice of injecting the catheter pack prior to opening.

Adolescent↗
PubMed2006

Pilot study of new training model for laparoscopic surgery.

The aim of this study was to evaluate whether an assessment exercise performed on a laparoscopic trainer model reliably reflects previous laparoscopic experience and can therefore be used to accurately assess laparoscopic skills in surgical trainees. Subjects were recruited from a cross-section of surgical trainees and students at the Great Ormond Street Hospital for Children and the Institute of Child Health. Subjects were required to complete a baseline laparoscopic surgical skills questionnaire and an exercise on a new laparoscopic trainer model. Nine subjects completed both the baseline questionnaire and the exercise. These subjects exhibited a wide range of previous experience in laparoscopic surgery. Subjects with higher self-assessment scores had the lowest exercise scores (i.e. better scores; P=0.003). Furthermore, the exercise score was strongly negatively correlated with the baseline number of training modalities received (P=0.007) and the laparoscopic experience score (P=0.027). The assessment exercise on a novel laparoscopic trainer was capable of differentiating between subjects with little laparoscopic experience and those with more extensive previous laparoscopic training. The correlation between the exercise score and measured baseline variables suggests that the scoring system used in this model is sensitive and specific to measuring skills relevant to laparoscopic surgery.

Clinical Competence↗
PubMed2006

Surgical skills training in the laparoscopic era: the use of a helping hand.

The aim of this study was to evaluate whether a training programme involving an assessment exercise performed on a laparoscopic trainer model leads to an improvement in the acquisition of laparoscopic skills in surgical trainees. Subjects were recruited from a cross-section of surgical trainees at the Great Ormond Street Hospital, Department of Surgery and the Institute of Child Health. All subjects completed both a baseline laparoscopic surgical skills questionnaire and three exercises on a new laparoscopic trainer model. Thirteen subjects completed both the baseline questionnaire and all three assessment exercises. These subjects exhibited a wide range of previous experience in laparoscopic surgery. Sixty-nine percent of subjects showed a significant improvement in the assessment exercise score with training (ANOVA; P = 0.01). Sixty-two percent of subjects showed a greater improvement between exercises 2 and 3 than between exercises 1 and 2. The difference in score between exercises 1 and 2 was not statistically significant (P = 0.597), whereas the difference in score between both exercises 2 and 3 and exercises 1 and 3 was statistically significant (P = 0.018 and P = 0.005, respectively). The double glove training model is thus a simple, inexpensive, and easily reproducible tool that elicits a significant improvement in laparoscopic surgical skills in surgical trainees with a broad range of previous laparoscopic experience. It can therefore be used as part of a training programme to facilitate the acquisition of laparoscopic skills in a paediatric surgery setting.

Adult↗
PubMed2002

Oesophageal atresia: a simplified approach to early management.

Management following the repair of oesophageal atresia (OA) with tracheooesophageal fistula (TOF) in the past included the routine use of an intercostal chest drain, a gastrostomy, or a transanastomotic tube (TAT) for enteral nutrition and a routine contrast swallow (CS) before oral feeds. There has been a trend towards simplification of the management, but this is not universal. The aim of this study was to evaluate the safety of a simplified management regime in infants undergoing primary repair of OA in a retrospective case note review of infants undergoing surgery for OA with TOF under the care of one consultant over a 12-year period. Intercostal chest drains, TATs, and CSs were not routinely used. Early enteral feeding was initiated and oral feeding was allowed in babies of adequate birth weight (BW) and gestation. A CS was only performed when there were specific anastomotic concerns. Parameters recorded included demographic details, time to first enteral feed by tube or mouth, time to full oral feeds, and complications. Forty patients were studied; 17 were managed without (group 1) and 23 with (group 2) a TAT. Sex distribution, gestational age, and BW were comparable in the two groups. In group 1, the time to the establishment of full oral feeds was 2-8 days (average 3.9). Four infants developed strictures; 2 were managed with dilatation alone and 2 required surgery. In group 2, the time to the establishment of full enteral feeds was 2-12 days (average 5.9). Four patients developed strictures; 2 underwent an anti-reflux procedure and a 3rd resection of a cartilaginous remnant. There was 1 death in a patient with intractable cardiac failure. The majority of infants with OA and TOF can thus be safely managed without routine chest drainage or CS. A sizeable minority do not require a TAT. Early introduction of oral feeds in the non-TAT group is not associated with an increased complication rate.

Birth Weight↗
PubMed2006

Obstetric hysterectomy: changing trends over 20 years in a multiethnic high risk population.

The aim of this study was to determine the demographics, indication and complications of emergency postpartum hysterectomy in a multiethnic high-risk obstetric population and to assess if there is a change in trend between 1983 and 2003. Eighteen women underwent postpartum hysterectomies in the 20 year period (prevalence 0.028%) and there were two maternal deaths. Overall, 77% of the postpartum hysterectomies were performed for intractable haemorrhage following caesarean section (CS). There is a statistically significant threefold increase (Mann-Whitney test, p=0.007) in the prevalence of emergency postpartum hysterectomies between 1994 and 2003 as compared to the previous 10 years between 1983 and 1993 despite the introduction of new pharmacological agents and conservative surgical techniques. Subtotal abdominal hysterectomy appears to be the procedure of choice in the more recent 10 years (60% of cases between 1994 and 2003 compared to 25% of cases between 1983 and 1993). Previous Caesarean section, advancing maternal age, abnormal placentation (including placenta praevia) appear to be risk factors for postpartum hysterectomy. Women of black African origin appear to be more at risk for hysterectomy compared to women of other ethinicity.

Adult↗
PubMed2006

Pin1 levels are downregulated during ER stress in human neuroblastoma cells.

Previously, we showed that pretangle neurons in Alzheimer's disease (AD) brain display unfolded protein stress in the endoplasmic reticulum (ER). Others showed that the peptidylprolyl isomerase Pin1 protects against tangle formation by facilitating tau dephosphorylation, corroborating with the lower expression of Pin1 observed in tangle-bearing neurons. In this study, we investigated Pin1 expression under ER stress conditions. We show that in human, but not mouse neuroblastoma cells, Pin1 is downregulated in response to ER stress, in accordance with the presence of an ER stress response element in the mouse, but not the human Pin1 gene. This study creates a starting point to investigate whether modulation of the ER stress response may prevent or delay tau pathology in AD.

Animals↗
PubMed1998

Culture and characterization of sinusoidal endothelial cells isolated from human liver.

Although most vascular models use large vessel endothelial cells from human umbilical veins, there is marked heterogeneity among endothelial cells from different vascular beds and organs. More accurate modeling of endothelial involvement in liver diseases, including metastasis, may result from the use of human hepatic sinusoidal endothelial cells. Liver resection specimens were sectioned, then treated with a 1.2 U/ml dispase solution. The tissue slurry was mechanically disaggregated and separated by centrifugation on a Percoll density gradient. Cells were then cultured in an endothelial-specific media with growth factors. These techniques resulted in a homogeneous monolayer consistent with endothelial cells by light microscopy. An endothelial origin was further confirmed by the expression of Factor VIII, binding of Ulex lectin, and uptake of acetylated low density lipoprotein. Electron microscopy showed transcellular fenestrations consistent with a sinusoidal origin. These human hepatic sinusoidal endothelial cells were then studied for expression of the adhesion molecules CD31/PECAM, CD34, E-selectin, ICAM-1, L-selectin, LFA-3, P-selectin, and VCAM-1 plus the binding of wheat germ agglutinin lectin. The patterns of adhesion molecule expression and lectin binding by these cells are characteristic of hepatic sinusoidal endothelia. In this paper, we have described a method for isolation and culture of human cells with the morphologic and phenotypic characteristics of hepatic sinusoidal endothelia.

Aged↗
PubMed1990

Cardiopulmonary exercise testing before and after conditioning in older coronary patients.

Cardiac rehabilitation has been demonstrated to improve aerobic capacity in young and middle-aged coronary patients. The effect of an aerobic conditioning program on cardiopulmonary markers of fitness was assessed in 22 older patients (mean age 68 years) following a coronary event compared with 37 younger patients (mean age 52 years). Before conditioning, peak oxygen consumption was lower in the older patients, 16.9 versus 24.3 cm3/kg/min (p less than 0.001), as was exercise duration and maximal ventilation. Older coronary patients were more likely to stop exercise at a respiratory equivalent ratio of less than 1.00 (8 of 22 versus 4 of 37, p less than 0.05) and therefore often did not attain a true maximal cardiopulmonary limitation. Both groups had similar increases in peak oxygen consumption following a 36-session conditioning program, improving 27% in the older group and 23% in the younger group. Duration of treadmill exercise on a Balke treadmill protocol increased similarly in the two groups, 62% in the older group (from 8.9 to 14.3 minutes) and 40% in the younger group (from 12.2 to 17.1 minutes) (p = NS). Thus while older patients following coronary events are substantially less fit than younger patients, they obtain a similar relative improvement of aerobic capacity with a graded conditioning program.

Aged↗
PubMed1992

Cardiac rehabilitation participation predicts lower rehospitalization costs.

The effect of participation in cardiac rehabilitation on medical costs was determined by measuring hospitalization charges for cardiac admissions over a 3-year period in 580 post-coronary event patients (58% after coronary bypass surgery, 42% after myocardial infarction), of whom 230 entered a cardiac rehabilitation program and 350 did not. Baseline left ventricular ejection fraction was similar in entrants and nonentrants (59.9% vs 59.5%). Over the 1 to 46-month follow-up period (mean 21 months), per capita hospitalization charges for participants in cardiac rehabilitation were $739 lower than charges for nonparticipants ($1197 +/- 3911 vs $1936 +/- 5459, p = 0.022). This was due to both a lower incidence of hospitalizations and lower charges per hospitalization. Inasmuch as groups differed with regard to age, sex, diagnostic category, and smoking status, data were adjusted for these baseline differences by means of analysis of covariance. Rehospitalization charges remained significantly higher in nonparticipants (p = 0.015). Because physician charges were not measured, the cost differential between groups is underestimated. Results of this study show an association between participation in comprehensive cardiac rehabilitation and lowered cardiac rehospitalization costs in the years after an acute coronary event.

Aged↗
PubMed1995

Seeding of intracoronary stents with immortalized human microvascular endothelial cells.

Intracoronary stents are effective in decreasing the complications associated with acute closure during coronary angioplasty. A major complication associated with the use of coronary stents is acute thrombotic occlusion. It has been postulated that the stent loses its thrombogenic potential after it becomes covered with a layer of endothelial cells. Human dermal microvascular endothelial cells were transfected with a plasmid containing the simian virus 40 large T-antigen gene. Stents were placed in culture media with cells for 2 weeks. Seeding efficiency of the stent with the endothelial cells was assessed by scanning electron microscopy. Balloon-expandable coronary stents placed in cell culture with immortalized human microvascular endothelial cells showed near-complete coverage after 2 weeks. After balloon inflation, persistence of cells on the stent was noted only on the lateral aspect of the balloon-expanded stents. If these stents were placed in culture, complete recovery of the monolayer was noted after 3 days. Stents were then covered with endothelial cells and frozen for 4 days. After thawing, the cells adhered to the devices and divided to form a monolayer in tissue culture. Seeded balloon-expandable stents were frozen for 4 months, thawed, and then implanted in a pig coronary artery. Human endothelial cells were identified on the stent 4 hours after deployment. These studies demonstrate the feasibility of using a human microvascular endothelial cell line to seed an uncoated metal stent. The cells remain adherent to the stent, are functional after freezing, and remain on the stent at least 3 hours after intracoronary implantation.

Angioplasty, Balloon, Coronary↗
PubMed1987

Effect of metoprolol on the submaximal stress test performed early after acute myocardial infarction.

To determine the effect of beta-adrenergic blockade on the submaximal stress test after acute myocardial infarction (AMI), 36 post-AMI patients performed their treadmill test on 2 separate days, with and without metoprolol, in a double-blind, placebo-controlled, crossover design study. Rest and peak submaximal exercise heart rate was diminished by 100 mg of metoprolol administered twice daily (from 84 +/- 3 to 68 +/- 2 beats/min, p less than 0.001, and from 126 +/- 3 to 97 +/- 2 beats/min, p less than 0.001, respectively) compared with placebo. Rest and peak submaximal systolic blood pressure was also decreased (from 121 +/- 3 to 108 +/- 2 mm Hg, p less than 0.001, and from 151 +/- 4 to 124 +/- 3 mm Hg, p less than 0.001). Exercise-induced ST-segment depression of 1 mm or more from baseline occurred in 12 patients taking placebo. However, only 4 of these patients had ST depression when they exercised while taking metoprolol (p less than 0.05). Angina pectoris occurred in 4 patients taking placebo but in only 1 of these taking a beta-blocking drug. It is concluded that beta-blocking therapy renders the post-AMI submaximal stress test less sensitive for markers of exercise-induced ischemia than if the test is performed without the drug. Therefore, when using the prognostic information of published studies, it is important to define the conditions surrounding the exercise test.

Adult↗
PubMed1989

Usefulness of myocardial ischemia as predictor of training effect in cardiac rehabilitation after acute myocardial infarction or coronary artery bypass grafting.

Exercise capacity increases to a variable degree in coronary patients during cardiac rehabilitation. The effect of baseline exercise-induced ischemia on the response to a 12-week conditioning program was evaluated in 106 coronary patients. The magnitude of exercise conditioning response was greater in nonischemic patients than in ischemic patients, with maximal exercise intensity increasing 69 versus 50% (7.2 to 12.1 vs 7.1 to 10.6 METs) (p less than 0.05) and maximal oxygen consumption increasing 28 versus 10% (23.1 to 29.6 vs 23.0 to 25.4 cc/kg/min) (p less than 0.05). Markers of conditioning during submaximal exercise such as heart rate and heart rate-systolic blood pressure product were similarly reduced in both groups. The groups did not differ by age, diagnosis, resting ejection fraction, incidence of beta-blocker use, maximal exercise capacity, maximal exercise heart rate, blood pressure or intensity of actual exercise training. These results suggest that exercise-induced ischemia alters the stimulus to adapt to exercise training.

Angina Pectoris↗
PubMed1990

Cardiac and skeletal muscle adaptations to training in systemic hypertension and effect of beta blockade (metoprolol or propranolol).

Cardiovascular and peripheral adaptations to an aerobic conditioning program were studied in 30 hypertensive adults taking either placebo, beta 1-selective beta-adrenergic blocker (metoprolol) or beta 1-nonselective beta-adrenergic blocker (propranolol). The placebo group increased aerobic capacity (VO2max) 24% (p less than 0.002), largely explained by an increased peripheral arteriovenous (AV) oxygen difference with minimal changes in cardiac size and function. Resting blood pressure and total systemic resistance also decreased. The group taking a beta 1-selective beta blocker increased VO2max 8% (p less than 0.05), reduced resting blood pressure but had no significant change of AV oxygen difference or cardiac size or function. The group taking the beta 1-nonselective beta blocker propranolol had no increase in VO2max, no decrease in resting blood pressure and no cardiovascular or peripheral adaptations to the exercise program. Thus, beta 1-selective and beta 1-nonselective beta blockers attenuate conditioning in hypertensive patients to differing degrees, in each case by blocking peripheral mechanisms of conditioning.

Adaptation, Physiological↗