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Biomedical subjects

Andrew Kingsnorth

Publications and source records attributed to Andrew Kingsnorth.

9 recordsLinked to original sources
PubMed2006

Keratin 8 sequence variants in patients with pancreatitis and pancreatic cancer.

Keratin 8 (KRT8) is one of the major intermediate filament proteins expressed in single-layered epithelia of the gastrointestinal tract. Transgenic mice over-expressing human KRT8 display pancreatic mononuclear infiltration, interstitial fibrosis and dysplasia of acinar cells resulting in exocrine pancreatic insufficiency. These experimental data are in accordance with a recent report describing an association between KRT8 variations and chronic pancreatitis. This prompted us to investigate KRT8 polymorphisms in patients with pancreatic disorders. The KRT8 Y54H and G62C polymorphisms were assessed in a cohort of patients with acute and chronic pancreatitis of various aetiologies or pancreatic cancer originating from Austria (n=16), the Czech Republic (n=90), Germany (n=1698), Great Britain (n=36), India (n=60), Italy (n=143), the Netherlands (n=128), Romania (n=3), Spain (n=133), and Switzerland (n=129). We also studied 4,234 control subjects from these countries and 1,492 control subjects originating from Benin, Cameroon, Ethiopia, Ecuador, and Turkey. Polymorphisms were analysed by melting curve analysis with fluorescence resonance energy transfer probes. The frequency of G62C did not differ between patients with acute or chronic pancreatitis, pancreatic adenocarcinoma and control individuals. The frequency of G62C varied in European populations from 0.4 to 3.8%, showing a northwest to southeast decline. The Y54H alteration was not detected in any of the 2,436 patients. Only 3/4,580 (0.07%) European, Turkish and Indian control subjects were heterozygous for Y54H in contrast to 34/951 (3.6%) control subjects of African descent. Our data suggest that the KRT8 alterations, Y54H and G62C, do not predispose patients to the development of pancreatitis or pancreatic cancer.

Acute Disease↗
PubMed2006

The management of incisional hernia.

Many thousand laparotomy incisions are created each year and the failure rate for closure of these abdominal wounds is between 10-15%, creating a large problem of incisional hernia. In the past many of these hernias have been neglected and treated with abdominal trusses or inadequately managed with high failure rates. The introduction of mesh has not had a significant impact because surgeons are not aware of modern effective techniques which may be used to reconstruct defects of the abdominal wall. This review will cover recent advances in incisional hernia surgery which affect the general surgeon, and also briefly review advanced techniques employed by specialist surgeons in anterior abdominal wall surgery.

Abdominal Wall↗
PubMed2004

Association of antioxidant enzyme gene polymorphisms and glutathione status with severe acute pancreatitis.

BACKGROUND & AIMS: Genetic variations in antioxidant metabolism may explain varying biological responses to acute pancreatitis (AP). We studied the contribution of oxidative stress to the pathogenesis of severe pancreatitis by examining the prevalence of functional gene polymorphisms of antioxidant enzymes and evidence of heightened oxidative stress. METHODS: DNA from 320 patients with AP (90 severe) and 263 controls was genotyped for glutathione S-transferase (Mu-1 [M-1], theta-1 [T-1], and pi-1 [P-1: Ile-105Val]), manganese superoxide dismutase (Ala-9Val), and catalase (C-260T) polymorphisms. Erythrocyte reduced glutathione (GSH) concentration was determined 24 and 72 hours after the onset of pain in 46 patients (11 severe). Disease severity was assessed using Atlanta clinical criteria, Acute Physiology Scores (APS), and peak serum C-reactive protein levels. RESULTS: The functional GSTT-1*A genotype was more prevalent in severe (96%) compared with mild attacks of AP (78%; odds ratio [OR], 5.9; 95% confidence interval [CI ], 2-17; P < 0.0001) and controls (76%; OR, 6.6; 95% CI, 2.3-18.7; P < 0.0001). Compared with null genotype, GSTT-1*A was associated with higher peak C-reactive protein levels (184 vs. 94 g/dL; P = 0.0005) and APS (24 hours, P = 0.04; 48 hours, P = 0.015). Reduced glutathione (GSH) at 24 hours was lower in mild (median, 382 nmol/g) and severe attacks (median, 407 nmol/g) compared with controls (median, 3685 nmol/g; P < 0.001). Levels increased at 72 hours in mild (P = 0.012) but not severe attacks and inversely correlated with APS (r = -0.49; P = 0.04). CONCLUSIONS: The functional GSTT-1*A genotype was associated with severe attacks of pancreatitis. Heightened oxidative stress characterized by glutathione depletion may be of importance in mediating the progression from mild to severe pancreatitis.

Acute Disease↗
PubMed2003

Hernias: inguinal and incisional.

In the past decade hernia surgery has been challenged by two new technologies: by laparoscopy, which has attempted to change the traditional open operative techniques, and by prosthetic mesh, which has achieved much lower recurrence rates. The demand by health care providers for increasingly efficient and cost-effective surgery has resulted in modifications to pathways of care to encourage more widespread adoption of day case, outpatient surgery, and local anaesthesia. In addition, the UK National Institute for Clinical Excellence has recommended strategies for bilateral and recurrent hernias. Here, we discuss these strategies and review some neglected aspects of hernia management such as trusses, antibiotic cover, return to work and activity, and emergency surgery. Many of the principles of management apply equally to inguinal and incisional hernias. We recommend that the more difficult and complex of the procedures be referred to specialists.

Age Factors↗
PubMed2002

Pylorus-preserving pancreatoduodenectomy with Billroth I type reconstruction: a viable option for pancreatic head resection.

BACKGROUND/PURPOSE: The aim of this study was to investigate the efficacy of pylorus-preserving pancreatoduodenectomy (PPPD) versus standard pancreatoduodenectomy (PD). METHOD: A cohort of 80 patients were studied for 5 years using prospectively gathered data. PPPD was performed in 48 (60%) patients, and the other 32 (40%) underwent a standard Whipple's operation with partial distal gastrectomy (PD). In all cases, the gastric or duodenal stump was anastomosed with the first loop of jejunum as a Billroth I-type reconstruction. RESULTS: Overall, morbidity in the cohort of patients consisted of 10 with a pancreatic fistula, 5 with postoperative hemorrhage, 5 with sepsis, 3 with delayed gastric emptying, 2 with an anastomotic leak, and 1 each with intraabdominal hematoma or myocardial infarction. Major morbidity associated with PPPD appeared in 8 of the 48 (16.7%) patients compared with 2 of 32 (6.3%) in the PD group. There were two deaths (4.2%) in the PPPD group and one (3.1%) in the PD group. The mean length of hospital stay was 14.6 days for PPPD versus 17.1 days for PD. Of the 48 patients in the PPPD group 7 (14.6%) had a hospital stay of more than 20 days versus 8 of the 32 (25%) in the PD group. CONCLUSIONS: Contrary to recent reports, in our series the PPPD patients had a shorter hospital stay; and overall, 3 of the 80 (3.75%) patients developed delayed gastric emptying, a relatively low rate. The pancreatic fistula rate was almost threefold higher in the PPPD group than in the PD group (but did not prolong the inpatient stay). This may be due to an intact antrum secreting higher quantities of gastrin.

Adult↗