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Biomedical subjects

P Curley

Publications and source records attributed to P Curley.

17 recordsLinked to original sources

Identification and characterisation of a gene encoding aminoacylase activity from Lactococcus lactis MG1363.

Analysis of the sequence of a randomly cloned chromosomal DNA fragment (3.2 kb) from Lactococcus lactis revealed the presence of part of an open reading frame, designated amd1, which specifies a protein displaying significant similarity to aminoacylases from various bacteria. The presence of an immobilised copy of an IS982 element immediately upstream of the coding region of amd1 has probably resulted in the displacement of amd1's native promoter. This genetic organisation was shown to be retained in seven other dairy strains, one of which was only slightly different. The amd1 gene was overexpressed in L. lactis NZ9800 under the control of the inducible nisA promoter and the deacetylating capacity of its gene product was measured on a number of substrates.

Amidohydrolases↗

Does the introduction of HDU reduce surgical mortality?

The aim of this study was to assess the change in workload in a general surgery department over 2 consecutive 1-year periods and document the impact of a high dependency unit (HDU) on hospital mortality. Data were collected on all admissions, the number and type of operations performed for a 1-year period before and after a purpose-built HDU was opened. During the study period, the total number of admissions increased by 15%, with a disproportionately large increase (27%) in the number of emergency admissions. This was reflected by increases in the emergency out-of-hours operating by 12%. During the study period, the overall in-patient mortality rose from 2.16% to 3.2%. Introduction of HDU facilities alone does not lead to a reduction in hospital mortality. Alterations in emergency workload and changes in case-mix are important in determining outcome. League tables of hospital mortality are likely to be difficult to interpret without adequate information about facilities and case-mix.

Adult↗

Decreased interleukin-2 production in murine acute pancreatitis: potential for immunomodulation.

BACKGROUND & AIMS: The role of the cytokine interleukin 2 (IL-2) has long been recognized as central to normal immunologic function and defense against infection after burns and trauma, but little effort has been directed towards its role in acute pancreatitis (AP), which also has a high mortality related to sepsis. This study investigated the potential role of IL-2 in mice with diet-induced AP. METHODS: AP was induced in mice by 10 days of feeding a choline-deficient, ethionine-supplemented diet. T-helper (CD4) cells were estimated, and T-cell mitogen-stimulated splenocyte proliferation and IL-2 production in vitro were measured on days 3, 7, and 10. RESULTS: Significant reduction in IL-2 production was found on day 3 (32%; P < 0.05) and day 10 (48%; P < 0.005). Administration of intraperitoneal lipopolysaccharide on day 10 was associated with reduced IL-2 production (P < 0.025) 4 hours later and 90% mortality in animals with AP. In vivo therapy with recombinant IL-2 improved in vitro IL-2 secretion (P < 0.05) and reduced lipopolysaccharide-induced mortality (P = 0.036). CONCLUSIONS: Murine diet-induced AP is associated with impaired immune function and increased susceptibility to sepsis and may be a valuable tool in the investigation of immunomodulation in AP.

Acute Disease↗

Impact of the New Deal on vascular surgical training.

The rapid development and technological advances in vascular surgery have provided the impetus for the establishment of dedicated pure vascular surgical services. It remains unclear whether all vascular surgery will be provided by such units in the future or whether several district general hospitals will combine resources and provide dedicated vascular on-call rotas between surgeons on separate sites. Training in vascular surgery is also changing rapidly. A modular training scheme encompassing three levels of training has been recommended (1). Some of the training will only be performed in large training units, but there remains a requirement for general surgeons to be exposed to some vascular surgery during their training. The "New Deal' for junior doctors has imposed limits on the amount of hours worked during a week. Junior doctors should not on average be contracted for more than 72 hours a week or work more than 56 (2). The maximum on-call rota which fulfils these criteria is a 1 in 4 on-call with no early starts, late finishes and no prospective cover. Allowing for holidays, study leave, early starts and late finishes a 1 in 5 or 1 in 6 rota system is required. Implementation of the Calman report in higher specialist training would reduce the time spent in training at high specialist level to perhaps five years. In a modular training programme in vascular surgery there may be as little as one year Level II training spent in vascular surgery or perhaps two years if the candidate opted to have vascular surgery as their only sub-specialty. In an attempt to assess the impact of the New Deal and the Calman report on vascular surgical training we have assessed the exposure to vascular surgical procedure of hypothetical trainees on a 1 in 6 rota.

Education, Medical, Graduate↗

Long-term immunotherapeutic intervention with pentoxifylline in a mouse model of thermal injury and infection.

Major thermal or traumatic injury often results in abnormalities of immune function, and these abnormalities contribute to the increased susceptibility to infection observed in these patients. Abnormalities of T-cell function, including decreased proliferation and secretion of cytokines are observed following major injury and, conversely, there is markedly increased monokine production. Thus, therapy of this syndrome might logically be aimed at modulating the immune system to upregulate T-cell function and downregulate monocyte hyperactivation. Pentoxifylline (PTX), a methylxanthine derivative, has been shown to be therapeutically effective in several animal models. The purpose of this study was to evaluate PTX and its effect on cytokine production in a mouse model of thermal injury and to study its effect on survival after septic challenge. The results show that PTX therapy after injury can restore T-cell production of IL-2 and downregulate the hyperactive macrophage secretion of proinflammatory cytokines. However, improvement in survival resulting from this therapy following thermal injury and septic challenge depends on timing of dosage.

Animals↗

Multiple system organ failure may be influenced by macrophage hypoactivation as well as hyperactivation--importance of the double challenge.

OBJECTIVE: To find out if an infective challenge caused by a burn followed by caecal ligation and puncture in mice caused more abnormalities of the immune response than burn alone or caecal ligation and puncture alone. DESIGN: Laboratory study. SETTING: University hospital, USA. MATERIAL: 80 male 7-8 week old A/J mice. INTERVENTIONS: Burn followed 10 days later by caecal ligation and puncture (n = 18), caecal ligation and puncture alone (n = 24), burn alone (n = 20), and controls (n = 18). The mice had their spleens removed on day 11 (n = 28; 6, 8, 8, and 6 in the respective groups), day 12 (n = 26; 6, 8, 6, and 6), and day 13 (n = 26; 6, 8, 6, and 6), and splenocytes and adherent cells were harvested for measurement of prostaglandin E2 (PGE2), interleukin 1 (IL-1), interleukin 2 (IL-2), interleukin 6 (IL-6), and tumour necrosis factor alpha (TNF-alpha). MAIN OUTCOME MEASURES: Alterations in the production of the cytokines. RESULTS: After the double challenge (burn followed by caecal ligation and puncture) there were significant reductions in production of TNF-alpha and IL-6 compared with caecal ligation and puncture alone (p < 0.05), burn alone (p < 0.05), and controls (p < 0.05). These findings indicate that activation of macrophages was reduced after infection; production of TNF-alpha, IL-1, and IL-6 by splenocytes stimulated by lipopolysaccharide was reduced. CONCLUSIONS: The differences do not seem big enough to indicate that mortality would be increased after caecal ligation and puncture alone. Only when there has been a previous injury (which resulted in hyperactivation of macrophages followed by a more pronounced hypoactivation) would mortality increase. In view of clinical trials with antiendotoxin and antiTNF antibodies that failed to improve survival in infected patients, we suggest that the mechanisms of the cellular immune response need further clarification.

Animals↗

Minimally invasive treatment for common bile duct stones.

The impact of endoscopic surgery on the management of stones in the common bile duct (CBD) was studied. All patients with proven common duct stones managed by a single consultant during a 21-month period were included. Of a total of 60 patients, 48 were referred because of symptoms or signs of calculi in the CBD and 12 were found to have common duct stones although symptoms were related primarily to the gallbladder. Of the 48 patients referred with common duct stones, 41 (85 per cent) were successfully treated by endoscopic retrograde cholangiography (ERC) and endoscopic sphincterotomy (ES) (complications were cholangitis (one patient), mild acute pancreatitis (one), impacted retrieval basket (one)). Of the remaining seven patients, two underwent open exploration (one after failed laparoscopic exploration) and five had successful laparoscopic duct exploration. One patient underwent laparoscopic exploration of the CBD but subsequently died. Of the patients with primary gallbladder symptoms, eight underwent preoperative ES, one was treated by laparoscopic duct exploration, one by conversion to open operation and in two patients duct stones were removed at postoperative ERC. The overall mortality rate was 2 per cent and the incidence of complications 12 per cent. Open exploration of the CBD was performed in three patients (5 per cent). This experience suggests that open duct exploration will become increasingly infrequent and may be replaced by endoscopic surgery in the majority of patients.

Adult↗

Audit of cranial computerised tomography in a general medical unit.

Over a two year period 108 patients had cranial computerised tomographic (CCT) scans while under the care of a general medical team. Sixty eight scans showed 70 abnormalities. Completed stroke, transient ischaemic attacks (TIA), epilepsy and headache were the most common indications for CTT while infarct, atrophy, haemorrhage and tumour were the most common abnormalities. Eight tumours were identified comprising 12% of epileptics and 9% of stroke patients.

Adult↗

Common peroneal nerve dysfunction after high tibial osteotomy.

We assessed 16 patients before and after high tibial osteotomy by electrophysiological recordings, creatine phosphokinase levels, radiographs and intracompartmental pressure monitoring. We found mild electrophysiological abnormalities pre-operatively in 12 of the 16 patients, but postoperatively these had deteriorated in 11 of the 14 patients studied. Creatine phosphokinase levels, compartment pressure and radiological deformity were not predictive of the development of postoperative common peroneal nerve palsy. Patients who also had a proximal fibular osteotomy had greater electrical abnormalities postoperatively and two of them developed common peroneal palsies. Proximal fibular osteotomy appears to be a causative factor in the development of common peroneal nerve palsy; more work is needed on the blood supply of the nerve.

Adult↗

Prophylactic antibiotic use in four Dublin teaching hospitals.

A retrospective study of 266 surgical patients revealed that 55% received antibiotics. Of these, 71% had prophylactic and 29% therapeutic courses. Twenty-five per cent of prophylactic courses were started post-operatively, 65% were continued for more than 24 hours, 28% were administered by an inappropriate route and 10% were started more than two hours pre-operatively. Of all courses of antibiotics ordered, 67% had no record of intended duration on the prescription. In 4% of courses the surgeon's orders were not followed. This study demonstrates widespread suboptimal use of antibiotic prophylaxis in a variety of surgical specialties.

Anti-Bacterial Agents↗

Clinical application of a new enzyme-linked assay for the estimation of brain-specific creatine kinase in head injured patients.

The clinical value of serum brain specific creatine kinase (CK-BB) was assessed in head injured patients (group A) using a new enzyme-linked immunosorbent assay (ELISA). The results were compared to healthy controls (group B) and patients post-myocardial infarction (group C). None of the head injured patients had undergone a surgical procedure or ventricular puncture. CK-BB was significantly higher in group A than in controls. The level of CK-BB in group A was inversely proportional to the Glasgow Coma Scale on admission. All patients with a CK-BB greater than 100 micrograms/l died. The ELISA technique is a simple and reliable assay with prognostic significance in patients with head injury and has wider clinical application than the previously described radioimmunoassay methods.

Brain Injuries↗

A super active cyclic hexapeptide analog of somatostatin.

The cyclic hexapeptide, cyclo (Pro-Phe-D-Trp-Lys-Thr-Phe), I, has been shown to have the biological properties of somatostatin. We now report structure-activity studies which optimize the potency of this cyclic hexapeptide series with the synthesis of cyclo (N-Me-Ala-Tyr-D-Trp-Lys-Val-Phe), II, which is 50-100 times more potent than somatostatin for the inhibition of insulin, glucagon and growth hormone release. The hydroxyl group of tyrosine is seen to lend a 10-fold enhancement to the potency. Potency also is found to be correlated with hydrophobicity. II is found to improve the control of postprandial hyperglycemia in diabetic animals when given in combination with insulin. The analog is found to be quite stable in the blood and in the gastrointestinal tract, but the bioavailability after oral administration is only 1-3%. The biological properties and long duration of II should allow clinical evaluation of the inhibition of glucagon release as an adjunct to insulin in the treatment of patients with diabetes.

Animals↗