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Biomedical subjects

A Leahy

Publications and source records attributed to A Leahy.

At least 37 records · Page 2Linked to original sources

Vitamin C reduces ischaemia-reperfusion-induced acute lung injury.

OBJECTIVES: to evaluate vitamin C supplementation in the prevention of ischaemia-reperfusion (I-R) induced acute lung injury. DESIGN: Sprague-Dawley rats (n =6/group) were randomised into Control, I-R and I-R pretreated with vitamin C (3.3 g over 5 days). Ischaemia-reperfusion injury was induced by 30 minutes infrarenal aortic cross-clamping and 120 minutes reperfusion. METHODS: pulmonary microvascular injury was measured by broncho-alveolar lavage protein concentration, pulmonary neutrophil infiltration by tissue myeloperoxidase activity and bronchoalveolar lavage neutrophil counts. In a second experiment (n =5/group) neutrophil respiratory burst activity was measured in Control and vitamin C groups. RESULTS: ischaemia-reperfusion resulted in a significant increase in both microvascular leakage and pulmonary neutrophil infiltration as measured by bronchoalveolar lavage protein concentration and pulmonary myeloperoxidase activity respectively. Pretreatment with vitamin C significantly attenuated both microvascular leakage and neutrophil infiltration. Neutrophil respiratory burst activity was significantly reduced in the vitamin C group (13.02 m.c.f.+/-0.3) compared with Control (19.04 m.c.f.+/-1. 9),p <0.02. CONCLUSION: these data suggest that oral vitamin C therapy protects against ischaemia-reperfusion-induced acute lung injury, possibly by attenuating neutrophil respiratory burst activity.

Animals↗

Abnormalities of the electrogastrogram in functional gastrointestinal disorders.

OBJECTIVE: Cutaneous electrogastrography records gastric electrical activity and detects gastric arrhythmias. Abnormalities of the electrogastrogram have been described in a variety of disorders, but their specificity and their prevalence in patients with functional gastrointestinal disorders has not been reported. The aim of this study was to assess the specificity of electrogastrography as well as the prevalence and pattern of abnormalities in functional dyspepsia and irritable bowel syndrome. METHODS: Electrogastrography was performed in 170 patients with functional dyspepsia, 70 patients with irritable bowel syndrome, 20 patients with gastroesophageal reflux disease, and 30 asymptomatic controls. The abnormal electrogastrogram was defined as <70% normal electrical activity either before or after a test meal. RESULTS: The electrogastrogram was abnormal in 36% of patients with functional dyspepsia and in 25% with irritable bowel syndrome who complained of concurrent dyspepsia. The electrogastrogram was normal in 93% of asymptomatic controls, 90% of patients with gastroesophageal reflux, and 92% of patients with irritable bowel syndrome who did not complain of dyspepsia. As a group, functional dyspepsia patients had a greater degree of tachygastrias both before (p < 0.02) and after (p < 0.01) a test meal. The electrical frequency after the test meal was also more unstable (p < 0.003). CONCLUSIONS: The electrogastrogram is abnormal in approximately 36% of functional dyspepsia patients and has a specificity of approximately 93%. Electrogastrography defines a subgroup of patients with functional dyspepsia and electrical rhythm disturbance. In irritable bowel syndrome, the electrogastrogram is usually abnormal only if concurrent dyspepsia is present.

Adult↗

Large-scale screening for developmental genes in embryonic stem cells and embryoid bodies using retroviral entrapment vectors.

Mammalian development is orchestrated by a variety of cellular proteins with expression that is regulated precisely. Although some of the genes encoding these factors have been identified, largely by homology to those of simpler organisms, the majority of them presumably remain unknown. We report here on the results of a large-scale genetic screen that can potentially lead to the identification of many of these unidentified genes in mice. The method we developed takes advantage of the fact that many of the factors that regulate early development are expressed at highly specific stages of early embryogenesis. We therefore established a method for tagging candidate developmental genes by virtue of their expression in a stage-specific manner during formation of embryoid bodies without a bias for their expression in undifferentiated embryonic stem (ES) cells. Of 2,400 ES cell clones with random insertions of retroviral vectors carrying a human placental alkaline phosphatase reporter gene (AP), 41 clones exhibited stage-specific reporter gene expression during embryoid body formation. The majority of these insertions were in genes that are not expressed in undifferentiated ES cells. Eleven ES cell clones with characteristic patterns of AP reporter gene expression in vitro were chosen for further examination in vivo for AP expression in developing embryos. Ten ES cell clones exhibited AP expression between day 7.5 and day 10.5 of development. Clones that showed restricted reporter gene expression in vitro also exhibited similar temporally and spatially restricted AP expression in vivo. Sequence analysis of genomic DNA flanking several vector insertions and corresponding cDNAs suggested that several of the insertions identified a previously unidentified gene. Thus, screening for reporter gene expression during embryoid body formation provides an efficient means of enriching clones that contain vector insertions into potentially novel genes that are important for regulating different stages of early postimplantation development.

Alkaline Phosphatase↗

The effects of recombinant human growth hormone on cardiopulmonary function in elective abdominal aortic aneurysm repair.

OBJECTIVES: Cardiorespiratory complications are the predominant source of morbidity in patients undergoing major surgery. Recombinant human growth hormone (rhGH) has previously been shown to be effective in improving respiratory and cardiac function in compromised patients. DESIGN: The aim of this study was to assess the effects of perioperative rhGH on cardiac function in 33 patients undergoing elective infrarenal abdominal aortic aneurysm repair. METHODS: Patients were randomised to one of three groups: placebo for 6 days before and after surgery (control, n = 12); genotropin (GH) 0.3 units/kg/day for 6 days before and after surgery (pre and postop GH, n = 10) and placebo for 6 days before and GH (0.3 units/kg/day) for 6 days after surgery (postop EH, n = 11). Patients were assessed on days 7 and 1 before and days 7, 14 and 50 after operation. Intraoperative cardiac index (CI) was measured after induction of anaesthesia, before and after aortic cross-clamping, after aortic unclamping and at the end of surgery. RESULTS: Pretreatment with GH resulted in a significantly higher heart rate during surgery and was associated with a trend towards higher cardiac index (CI) (p < 0.067) at all stages of surgery. Mean arterial blood pressure at the stage of aortic unclamping was significantly higher in patients treated with GH preoperatively. CONCLUSIONS: Larger studies are required to evaluate the beneficial effects of GH in aortic surgery. However, data from this pilot study suggests that perioperative GH administration may result in improved cardiac performance during aortic surgery.

Aged↗

The effect of cisapride on dyspepsia symptoms and the electrogastrogram in patients with non-ulcer dyspepsia.

BACKGROUND: The electrogastrogram (EGG), which records gastric myoelectrical activity, is abnormal in one-third of adult patients with non-ulcer dyspepsia (NUD). AIM: To observe the effects of cisapride on EGG in adults with NUD. METHODS: Twenty-seven NUD patients who had undergone a pre- and post-prandial EGG were entered into an open study. All patients completed a dyspepsia symptom questionnaire and were then treated with cisapride 10 mg t.d.s. The dyspepsia questionnaire was repeated in all those completing 4 weeks of treatment. Those with an initial abnormal EGG (< 70% of slow wave activity at 2-4 cycles per minute) had a repeat EGG at the end of the study. RESULTS: Treatment with cisapride was associated with a significant improvement in the post-prandial EGG (P = 0.007). After 4 weeks of treatment, 7 of 13 abnormal EGGs normalized. Symptom scores improved significantly in the 13 patients with an abnormal EGG who completed treatment (P < 0.0003), but not in NUD patients with a normal EGG (P = 0.48). CONCLUSION: In this open study, treatment of NUD with cisapride was associated with significant symptom improvement in patients with an abnormal pre-treatment EGG, but not those with a normal EGG, with a significant improvement of the post-prandial EGG.

Adult↗

Thermotolerance induces heat shock protein 72 expression and protects against ischaemia-reperfusion-induced lung injury.

BACKGROUND: Ischaemia-reperfusion injury is mediated by neutrophil-endothelial interaction. Induction of heat shock proteins attenuates neutrophil-endothelial interactions. The aim of this study was to determine whether thermal preconditioning could have a protective effect on neutrophil-mediated lung injury in an animal model of lower torso ischaemia-reperfusion. METHODS: Sprague-Dawley rats were randomized into: control, ischaemia-reperfusion, and ischaemia-reperfusion preconditioned with hyperthermia groups. Ischaemia-reperfusion injury was induced by infrarenal aortic clamping for 30 min and reperfusion for 120 min. Thermotolerance was induced by raising the core body temperature to 40.5-41.5 degrees C for 15 min, 18 h before ischaemia-reperfusion. Wet:dry lung (W:D) weight ratio, bronchoalveolar lavage protein (BALprot) concentration, tissue myeloperoxidase (MPO) activity and bronchoalveolar lavage polymorphonuclear neutrophil (BAL PMN) count were measured. Heat shock protein 72 (hsp72) expression in lung, intestine and mesentery was measured using Western immunoblotting. RESULTS: Ischaemia-reperfusion resulted in a significant increase in tissue oedema (W:D weight ratio) and BALprot concentration. In addition there was a marked increase in tissue neutrophil infiltration (MPO activity, BAL PMN concentration). Preconditioning with hyperthermia resulted in increased expression of hsp72 and significantly reduced tissue oedema and neutrophil infiltration. CONCLUSION: Thermal preconditioning protects against neutrophil-mediated ischaemia-reperfusion-induced lung injury, possibly by increasing the expression of heat shock proteins.

Animals↗

An "all comers" policy for ruptured abdominal aortic aneurysms: how can results be improved?

OBJECTIVE: To review our experience of a non-selective policy for the treatment of ruptured abdominal aortic aneurysm to see if the policy was justified, and to identify any preoperative risk factors that adversely influenced outcome. DESIGN: Retrospective study. SETTING: Teaching hospital, Republic of Ireland. SUBJECTS: 258 patients admitted with abdominal aortic aneurysms between January 1982 and December 1993. INTERVENTIONS: Definitive surgical treatment. MAIN OUTCOME MEASURES: Morbidity, mortality, and risk factors. RESULTS: In-hospital mortality for all patients was 43% (110/258). Overall, women did worse than men (28/44, 64%, died, compared with 96/214, 45%, p=0.03). The mortality among patients over the age of 80 (23/45, 51%) was not significantly different from that among younger patients (97/202, 48%). Blood pressure, platelet count, and haemoglobin concentration were all significantly lower preoperatively among those who died (p < 0.05). CONCLUSIONS: Age alone cannot be used to justify witholding definitive surgical treatment. Treatment should be aimed towards reversing haematological and haemodynamic abnormalities preoperatively to try to improve outcome.

Aged↗

Induction of heat shock protein 72kDa expression is associated with attenuation of ischaemia-reperfusion induced microvascular injury.

Leukocyte-endothelial interaction is a pivotal step in the pathogenesis of ischemia-reperfusion (I/R) injury. Exposure of cells to a subcritical heat stress may protect cells from subsequent I/R injury, through induction of a 72-kDa heat shock protein (HSP72). The aim of this study was to investigate the effect of thermotolerance on leukocyte adherence and migration during an I/R period in rat mesenteric postcapillary venules. Sprague-Dawley rats were randomized into control (sham I/R), I/R, and thermotolerance+I/R groups. Thermotolerance was induced 18 hr prior to I/R, which was in turn established by occlusion of the superior mesenteric vascular pedicle for 10 mins, followed by 60 mins of reperfusion. The blood flow, leukocyte rolling velocity, and the number of adherent and migrated leukocytes in postcapillary venules were measured by intravital microscopy. I/R significantly decreased the rolling velocity of leukocytes; increased the number of adherent leukocytes at 10, 30, and 60 mins after reperfusion; and also increased the number of migrated leukocytes at 60 mins after reperfusion. Thermotolerance induction expression of HSP72 in pulmonary, intestinal, and mesenteric tissues was determined by Western immunoblotting. Thermotolerance significantly prevented the I/R-induced decrease in rolling velocity of leukocytes, the increase in the number of adherent leukocytes at 30 and 60 mins, and the increase in the number of migrated leukocytes at 60 mins. This results suggest that thermotolerance attenuates I/R injury by modulating leukocyte-endothelial interaction in vivo, possibly by increasing tissue expression of HSP72.

Animals↗

Ruptured abdominal aortic aneurysm--can treatment costs and outcomes be predicted by using clinical or physiological parameters?

Mortality rates for patients undergoing surgery for ruptured abdominal aortic aneurysm (RAAA) remain high. The high cost of providing care for these patients mandates that proposed treatment protocols be evaluated for their cost-effectiveness. This study assessed costs related to outcome in different groups of patients with RAAA. From July 1987 to December 1993, 140 patients underwent emergency surgery for RAAA. Complete data on preoperative haemodynamic status, blood transfusion requirements, intensive care unit (ICU) stay and other hospital costs was available for 94 patients. Seventy-seven males (mean age 71.6(6)) and 17 females (mean age 77.2(6)) underwent surgery. Known risk factors including age (< or > 70 years), shock on admission (systolic blood pressure (BP) < or > 90 mm Hg), sex, and acute renal failure were analysed. For the purpose of comparison, costs (Pounds) were assessed by the ESRI (Economic and Social Research Institute of Ireland) based on 1992 prices. The overall survival rate was 48%: 53% among males and 24% among females (p < 0.05, Chi-squared test). In addition to having a significantly worse outcome than males, female patients with RAAA also had longer hospital and ICU stays and this was reflected in significantly greater expenditure. Similarly, male patients > 70 years old presenting with haemodynamic instability had significantly longer hospital and ICU stays than younger male patients. The average cost per RAAA survival (12,945 Pounds) in this series is not prohibitive, and the greater cost in high risk groups should not discourage intervention.

Acute Kidney Injury↗

Selective cholangiography in laparoscopic cholecystectomy.

Laparoscopic cholecystectomy is now the method of choice for removing the diseased gallbladder. Asymptomatic common bile duct stones occur in approximately 6 per cent of patients. Controversy exists, however, as to whether selective or routine peroperative cholangiography should be performed during laparoscopic cholecystectomy. Over a 21-month period 300 consecutive laparoscopic cholecystectomies without routine cholangiography were attempted. There were 28 conversions. In all, 229 patients did not undergo cholangiography and in this group there were two common duct injuries. These were both identified and dealt with by open operation. Five patients underwent peroperative cholangiography, none of whom was found to have common duct pathology. Endoscopic retrograde cholangiopancreatography was performed in 38 patients. Of 27 who had this investigation performed before operation, common duct stones were diagnosed in seven (26 per cent). Two common duct stones were discovered in 11 patients who underwent the investigation after operation. Thus only two of 240 patients (0.8 per cent) who did not undergo preoperative or peroperative cholangiography subsequently had symptomatic duct stones. Peroperative cholangiography may be indicated in selected patients who have had symptoms of common bile duct stones or in those in whom the biliary anatomy is unclear. However, routine preoperative or peroperative cholangiography is unnecessary during laparoscopic cholecystectomy.

Adolescent↗

Asymptomatic carotid stenosis: a benign lesion?

Recent reports of the risk of asymptomatic carotid stenosis have been compromised by flawed patient selection or the performance of a large number of carotid endarterectomies during follow-up. We report the natural history of a randomly selected group of asymptomatic patients (n = 188; 114 males and 74 females) with documented carotid artery disease who were prospectively followed without intervention for up to 8 years. Risk factors included ischaemic heart disease in 17%, diabetes in 10%, hypertension in 46% and 88% were smokers. The degree of internal carotid stenosis was classified by duplex scanning and a total of 259 vessels had evidence of atherosclerosis. Study end-points included TIA, CVA and death. At mean follow-up of 4 years 3% of the 96 patients with internal carotid artery stenosis of less than 50% had died and 2% suffered a stroke. Six per cent of patients with a stenosis of 50-79% had died and 4% and 2% had suffered a CVA and TIA, respectively. In the 59 patients with greater than 80% stenosis 7% had suffered a TIA and an additional 7% a CVA, while 2% had died. None of the patients suffering a stroke had an antecedent TIA. Though the incidence of ischaemic events is significantly higher in patients with greater than 80% stenosis the incidence of unheralded stroke remains low. We therefore continue to recommend a conservative approach to the management of asymptomatic carotid stenosis.

Aged↗

Laparoscopic cholecystectomy in the scarred abdomen.

Laparoscopic cholecystectomy is rapidly becoming the definitive method for treating symptomatic gallbladder stones. Previous upper abdominal surgery is a relative contraindication to this technique. We describe a method for safely placing the trocars in a scarred abdomen, thus facilitating laparoscopic cholecystectomy in a wider group of patients.

Abdomen↗

Laparoscopic cholecystectomy: a hundred consecutive cases.

Laparoscopic cholecystectomy is a new, minimaly invasive technique for removing the gallbladder which has several advantages over the traditional laparotomy cholecystectomy. We reviewed our initial experience with 100 consecutive patients in whom laparoscopic cholecystectomy was attempted. The indications for operation were biliary colic, chronic cholecystitis, acute gallbladder and gallstone pancreatitis. Laparoscopic cholecystectomy was successfully performed in 87 patients. Anaesthesia time was 144 +/- 52 min. There was no mortality while overall morbidity was 14%. One patient had a retained common bile duct stone. Postoperative hospital stay was 4.1 +/- 2.2 days and the mean time to full activity in a random sample of 25 patients was 13.7 +/- 11.7 days. Laparoscopic cholecystectomy is a safe effective procedure which removes the gallbladder. We suggest that this technique be considered in all patients undergoing cholecystectomy.

Adolescent↗

Gallstone clearance: a randomized study of extracorporeal shock wave lithotripsy and chemical dissolution.

Following extracorporeal shock wave lithotripsy it is not known whether gallstone fragments are cleared from the gallbladder without the use of oral dissolution therapy. To assess the efficacy of lithotripsy and dissolution therapy, alone or in combination, 35 patients were randomized to one of three treatment groups: lithotripsy alone, dissolution therapy alone or combined lithotripsy and dissolution therapy. All patients had symptomatic gallstones, functioning gallbladders and comparable stone profiles. Lithotripsy was administered using a piezoelectric lithotripter. Dissolution therapy consisted of combined bile acid and terpene. Clearance was assessed at 6 months using ultrasound and oral cholecystography. Patients with less than 50 per cent stone clearance at the end of 6 months were considered failures. The number of patients with total or partial clearance in the combined group (7/10) was significantly greater than those in the lithotripsy alone group (0/10, P less than 0.002). Gallstone clearance following lithotripsy appears to be dependent upon dissolution therapy.

Adult↗

The patients' view of life in a psychiatric hospital. A questionnaire study and associated methodological considerations.

In any assessment of hospital life, the patients' view is indispensable, but there is no generally accepted way of seeking it. In this study, the views of 258 patients in four 'traditional' English psychiatric hospitals were obtained by a questionnaire of 45 items supplemented by freehand comments. Their experience of fellow patients, the staff and the material and institutional aspects of hospital care were explored. Some of the benefits and problems of questionnaire use in this realm are discussed.

Anxiety↗