bluuebunny/crossref_metadata_2025 huggingface dataset:
Probing the catalytic mechanism of Escherichia coli amine oxidase using mutational variants and a reversible inhibitor as a substrate analogue
Authors: SAYSELL Colin G. , TAMBYRAJAH Winston S. , MURRAY Jeremy M. , WILMOT Carrie M. , PHILLIPS Simon E.V. , McPHERSON Michael J. , KNOWLES Peter F.
Published: July 2002

Copper amine oxidases are homodimeric enzymes containing one Cu2+ ion and one 2,4,5-trihydroxyphenylalanine quinone (TPQ) per monomer. Previous studies with the copper amine oxidase from Escherichia coli (ECAO) have elucidated the structure of the active site and established the importance in catalysis of an active-site base, Asp-383. To explore the early interactions of substrate with enzyme, we have used tranylcypromine (TCP), a fully reversible competitive inhibitor, with wild-type ECAO and with the active-site base variants D383E and D383N. The formation of an adduct, analogous to the substrate Schiff base, between TCP and the TPQ cofactor in the active site of wild-type ECAO and in the D383E and D383N variants has been investigated over the pH range 5.5–9.4. For the wild-type enzyme, the plot of the binding constant for adduct formation (Kb) against pH is bell-shaped, indicating two pKas of 5.8 and ∼8, consistent with the preferred reaction partners being the unprotonated active-site base and the protonated TCP. For the D383N variant, the reaction pathway involving unprotonated base and protonated TCP cannot occur, and binding must follow a less favoured pathway with unprotonated TCP as reactant. Surprisingly, for the D383E variant, the Kb versus pH behaviour is qualitatively similar to that of D383N, supporting a reaction pathway involving unprotonated TCP. The TCP binding data are consistent with substrate binding data for the wild type and the D383E variant using steady-state kinetics. The results provide strong support for a protonated amine being the preferred substrate for the wild-type enzyme, and emphasize the importance of the active-site base, Asp-383, in the primary binding event.
A single normal ultrasonographic scan at age 65 years rules out significant aneurysm disease for life in men
Authors: Crow P , Shaw E , Earnshaw J J , Poskitt K R , Whyman M R , Heather B P
Published: July 2002

Background

Screening for abdominal aortic aneurysm (AAA) has been carried out in Gloucestershire since 1990. All men in the county are offered aortic ultrasonography in their 65th year. Men with an aortic diameter of less than 26 mm are considered ‘normal’ and no follow-up is arranged. The aim of this study was to ascertain if men with ‘normal’ aortic diameters at age 65 years ever develop a clinically significant aneurysm.

Methods

A cohort study was performed on 223 65-year-old men who had an aorta of less than 26 mm in diameter in 1988. These men had repeat ultrasonography in 1993 and 2000. The causes of death in men who died during this interval were investigated.

Results

Eight men were lost to follow-up. As far as it was possible to ascertain, none of the 86 men who died over the 12-year interval did so from ruptured AAA. There was no clinically significant increase in mean aortic diameter in the remaining 129 men who had three serial ultrasonographic scans over the 12-year interval.

Conclusion

A single, ‘normal’ ultrasound scan at age 65 years effectively rules out the risk of clinically significant aneurysm disease for life in men.
Influence of blood components and faeces on the in vitro cancericidal activity of povidone–iodine
Authors: Basha G , Penninckx F , Yap P
Published: July 2002

Background

Tumoricidal agents have been used to kill viable exfoliated tumour cells following colorectal cancer surgery. Recent in vivo experiments have thrown some doubt on the tumoricidal activity of povidone–iodine.

Methods

The cytotoxic effect of distilled water and of povidone–iodine at 0·04, 0·4, 0·8, 2 and 4 per cent final concentrations on human SW620 colonic cancer cells in the presence of red blood cells, purified haemoglobin and red blood cell (RBC) membranes, plasma, albumin, faeces and bacteria was investigated. Cell viability was assessed using the trypan blue assay and MTT test.

Results

The presence of albumin and plasma decreased the tumoricidal activity of povidone–iodine except for the highest concentration tested. Bacterial suspension did not influence the efficacy of povidone–iodine. Faecal material was found to have an intrinsic tumoricidal effect. Both intact and lysed RBCs very strongly inhibited the tumoricidal activity of all povidone–iodine concentrations tested. This inhibitory effect was due to haemoglobin, but not to RBC membranes.

Conclusions

Low concentrations of povidone–iodine fail to kill all ‘exfoliated’ cancer cells in the presence of proteins, intact or lysed RBCs. Therefore, washing out of these organic materials before application of a relatively high povidone–iodine concentration (e.g. 5 per cent or greater) may be more useful in killing viable exfoliated tumour cells during surgery for colorectal cancer.
Digest
Authors: Castaing D
Published: July 2002

Since the beginning of 1998, Annales de Chirurgie and Lyon Chirurgical have merged into one French language surgical journal. Numbers 1, 2 and 3 of 1998 result from this cooperative collaboration. A reciprocal digest written by our European Editor, Mr Colin Johnson, is published in the French journal.
The missing mammographic abnormality
Authors: Kerin M J , Monson J R T
Published: July 2002

On completion of a diagnostic stereotactic localization excision biopsy and check specimen radiograph, no abnormality to correlate with a preoperative mammogram is found. How should this clinical problem be handled? Mr M. J. Kerin and Professor J. R. T. Monson of the University of Hull reply.
In vitro DNA synthesis in freshly separated human breast cancer cells assessed by tritiated thymidine incorporation assay: relationship to the long-term outcome of patients
Authors: Nio Y , Tamura K , Kan N , Inamoto T , Ohgaki K , Kodama H
Published: July 2002

Background

Tumour growth rate has a significant effect on the clinical course of various malignancies. The present study was designed to assess whether in vitro DNA synthesis in freshly separated breast cancer cells is a useful marker in evaluating growth rates and in predicting the clinical outcome of patients.

Methods

From 1982 to 1992, DNA synthesis was assessed by [3H]thymidine incorporation in 97 samples of primary lesions from 94 patients with breast cancer. The patients were followed for 5–15 years and their outcome was surveyed in January 1998.

Results

The level of DNA synthesis did not correlate with the patients' age, clinical stage or expression of oestrogen receptor. However, it correlated significantly with the histological grade. In 89 patients, whose outcome was reported, the survival rate in the group with a high rate of DNA synthesis (log10c.p.m. 3·0 or more) was significantly lower than that in the low-level group; the 5- and 10-year survival rates were 84 and 74 per cent for the low synthesis group (n = 46), and 60 and 46 per cent for the high synthesis group (n = 43) respectively. This was also noted in patients with stage 1 or 2 cancers, for whom the 5- and 10-year survival rates were 100 and 90 per cent for the low synthesis group (n = 25), and 75 and 70 per cent for the high synthesis group (n = 35). Multivariate analysis supported this significant correlation for DNA synthesis in the prognosis of patients after mastectomy. Furthermore, the level of DNA synthesis was significantly higher in 18 patients who died from a recurrence within 3 years after operation than in 56 survivors, and the level of DNA synthesis also correlated significantly with the survival period in the 33 patients who died.

Conclusion

The level of DNA synthesis in breast cancer was variable, and was independent of the clinical stage or oestrogen receptor status. However, a high level of DNA synthesis was a positive indicator of a high risk of recurrence after operation, especially for stage 1 or 2 breast cancer. In vitro DNA synthesis may account for some of the clinical characteristics of breast cancers.
Radical resection of hilar bile duct carcinoma and predictors of survival
Authors: Todoroki T , Kawamoto T , Koike N , Takahashi H , Yoshida S , Kashiwagi H , Takada Y , Otsuka M , Fukao K
Published: July 2002

Background

Patients with carcinoma of the main hepatic duct have a poor prognosis. This study attempted to identify clinicopathological predictors of survival after resection.

Methods

A retrospective review was performed of 114 patients who presented with hepatic ductal carcinoma between 1976 and 1998. Of the 114 patients, 98 had a radical resection, three underwent palliative resection and 13 were not treated surgically. Forty-six patients with stage IVA disease had microscopic tumour residue after resection. Of these, 28 patients were treated with radiotherapy and the remaining 18 had resection alone.

Results

The overall operative morbidity and mortality rates were 14 and 4 per cent respectively. The overall 5-year survival rate after resection was 28 per cent. Nineteen patients survived for more than 5 years, including ten with stage IVA disease. The main prognostic factors were performance status; jaundice; tumour location; gross appearance; histological grade; T, N and M categories in tumour node metastasis (TNM) classification; TNM stage; and residual tumour. Adjuvant radiotherapy, tumour extension into the hepatic ducts, histological grade, N and residual tumour were independent predictive factors by multivariate Cox analysis.

Conclusion

This study suggests that radical resection provides the best survival rate for patients with hilar bile duct carcinoma. For patients with stage IVA disease, following complete gross resection radiotherapy improved treatment outcome.
Treatment of recurrent colorectal liver metastases by interstitial laser photocoagulation
Authors: Shankar A , Lees W R , Gillams A R , Lederman J A , Taylor I
Published: July 2002

Background

Hepatic resection improves survival in selected patients with colorectal liver metastases. The treatment of recurrent hepatic metastases after resection is controversial. Interstitial laser photocoagulation, performed under local anaesthesia, offers a minimally invasive option to repeat resection. The first series of patients with recurrent colorectal liver metastases treated with photocoagulation is reported.

Methods

Nineteen patients (five women and 14 men, median age 57 (range 44–71) years) who developed recurrent colorectal liver metastases after hepatectomy (five with bilateral disease) were treated with photocoagulation between 1993 and 1997. Fifteen patients also received chemotherapy (14 systemic, one hepatic arterial) before photocoagulation.

Results

There were no major complications or deaths related to the treatment. Six patients developed minor complications related to the procedure but did not require any form of intervention. Median survival from commencement of photocoagulation was 16 (range 4–36) months.

Conclusion

Photocoagulation is a safe, minimally invasive therapy that may be used as an adjunct to chemotherapy and repeat resection in the treatment of recurrent colorectal liver metastases, and may lead to improved survival.
Pain after laparoscopic cholecystectomy
Authors: Wills V L , Hunt D R
Published: July 2002

Background

Although laparoscopic cholecystectomy (LC) results in less pain than open chole-cystectomy, it is not a pain-free procedure. Many methods of analgesia for pain after laparoscopy have been evaluated.

Methods

Forty-two randomized controlled trials assessing interventions to reduce pain after LC are reviewed, as are the mechanisms and nature of pain after this procedure.

Results

Non-steroidal anti-inflammatory drugs, wound local anaesthetic, intraperitoneal local anaesthetic, intraperitoneal saline, a gas drain, heated gas, low-pressure gas and nitrous oxide pneumo-peritoneum have been shown to reduce pain after LC. The clinical significance of this pain reduction is questionable.

Conclusion

Pain after LC is multifactorial. Although many methods of analgesia produce short-term benefit, this does not equate with earlier discharge or improved postoperative function. However, single trials evaluating low-pressure insufflation, heated gas and multimodal analgesia suggest that clinically relevant benefits can be achieved.
Aminoguanidine attenuates endotoxin-induced mesenteric vascular hyporeactivity
Authors: Kavuklu B , Iskit A B , Guc M O , Ilhan M , Sayek I
Published: July 2002

Background

The aim of this study was to investigate the effects of inducible nitric oxide synthase inhibition by aminoguanidine on endotoxin-induced reduction in mesenteric blood flow.

Methods

Twenty Sprague–Dawley rats (180–230 g) allocated into four groups were administered either Escherichia coli endotoxin 1 mg/kg intraperitoneally or its solvent saline and were pretreated with either aminoguanidine (15 mg/kg intraperitoneally 20 min before and 2 h after endotoxin injection) or saline. Some 4 h after endotoxin injection, animals were anaesthetized, arterial blood pressure and mesenteric blood flow were measured and the resistance in the mesenteric vascular beds was then calculated. The effect of phenylephrine (1–30 µg/kg intravenously) on these parameters was also investigated.

Results

Endotoxin did not significantly modify the mean arterial blood pressure but decreased mesenteric blood flow by increasing the vascular resistance (mean(s.e.m.) 7·8(1·0) versus 13·7(1·2) mmHg per min per ml for control versus endotoxin groups; n = 5, P = 0·0099). Aminoguanidine alone had no effect on either the mean arterial blood pressure or mesenteric blood flow, but it completely blocked the effects of endotoxin. On the other hand, endotoxin significantly attenuated the responsiveness to phenylephrine which was restored by aminoguanidine.

Conclusion

The present results indicate that endotoxin decreases the mesenteric vascular blood flow by increasing vascular resistance and decreases responsiveness to phenylephrine. The effects of endotoxin were inhibited by aminoguanidine. The mesenteric vasoconstriction in response to endotoxin might not be explained by the overproduction of nitric oxide; other actions of aminoguanidine may explain its inhibitory effect.
Association of tumour necrosis factor microsatellite haplotypes with chronic pancreatitis
Authors: O'Reilly D A , Sargen K D , Dunlop S , Demaine A G , Kingsnorth A N
Published: July 2002

Aims

Recent evidence implicates the immune system in having a primary pathogenic role in the development of chronic pancreatitis (CP). This study examined the relationship between the tumour necrosis factor (TNF) gene and susceptibility to CP.

Methods

DNA was extracted from the blood of 40 patients with CP, 107 ethnically matched normal controls and 33 patients with alcohol-induced liver disease (alcoholic controls). Three microsatellite polymorphisms at the TNF locus were examined by the polymerase chain reaction, gel electrophoresis and autoradiography.

Results

The TNFa6 allele was significantly over-represented in patients with CP compared with normal controls (χ2 = 4·09, P = 0·043), and in those with alcoholic CP (n = 24) compared with alcoholic controls (χ2 = 4·63, P = 0·031). The three locus haplotypes 6–5−1 and 2–5−2 were significantly over-represented (χ2 = 4·14, P = 0·042) and under-represented (χ2 = 4·63, P = 0·042) respectively in patients with alcoholic CP compared with alcoholic controls.

Conclusions

A TNF haplotype has been defined that is associated with CP. This is consistent with a genetically determined role for TNF in the immunopathogenesis of CP.
Early outcome after laparoscopic and open floppy Nissen fundoplication
Authors: Ferguson J I , Palmer K , Dresner S M , Griffin S M , Paterson-Brown S
Published: July 2002

Aims

There remains debate regarding the best operative procedure for gastro-oesophageal reflux. For those who advocate a full ‘floppy’ Nissen fundoplication there is some scepticism that this can be completed effectively laparoscopically with division of all the short gastric vessels. This study therefore compared the results of patients operated on in two different hospitals in which floppy Nissen fundoplication was carried out either laparoscopically (hospital 1) or by open surgery (hospital 2).

Methods

All patients undergoing antireflux surgery in both hospitals were recorded prospectively and perioperative data were collected retrospectively from the case records. A postoperative questionnaire was sent to each patient to determine the modified DeMeester score and the impact of surgery on daily activities, which were then analysed anonymously by an independent clinician.

Results

Operating time was significantly longer (median 150 versus 75 min; P < 0·001), but postoperative stay (2 versus 4 days; P < 0·001) and return to normal activities (14 versus 25 days; P < 0·002) were shorter for the laparoscopic approach. There was no difference in gas bloat (both groups median 1·0, range 0–3), dysphagia (median 1·0 versus 0·0, range 0–3) or modified DeMeester score (both groups median 1·0, range 0–9) between the two techniques (median follow-up 10 and 15 months).

Conclusions

As the postoperative results were comparable this study confirms that a ‘floppy’ Nissen fundoplication with complete mobilization of the gastric fundus can be performed laparoscopically. The advantages of a shorter hospital stay and earlier return to normal activities are offset by a longer operating time.
Acute severe pancreatitis and multiple organ failure: total parenteral nutrition is still required in a proportion of patients
Authors: Schneider H , Boyle N , McCluckie A , Beal R , Atkinson S
Published: July 2002

Aims

Enteral nutrition (EN) is increasingly advocated as the favoured means of nutritional support in patients with multiple organ failure resulting from acute severe pancreatitis. In a proportion of patients, however, EN may not be feasible either because of gastrointestinal stasis and high nasogastric aspirates or because of superseding complications of pancreatitis such as fistulation. In these cases total parenteral nutrition (TPN) is indicated.

Methods

Patients with acute severe pancreatitis admitted to the intensive care unit (ICU) were commenced on either nasogastric or, where established, jejunostomy EN. Rates of EN were controlled by protocol and volumes of nasogastric aspirate. TPN was commenced when volumes of EN were persistently inadequate or when this route was contraindicated (e.g. high-volume small bowel fistula). Physiological and outcome data were collected prospectively and included severity of illness scoring (Acute Physiology and Chronic Health Evaluation (APACHE) II), length of stay, duration of EN and TPN, and hospital outcome.

Results

Of 69 patients with acute severe pancreatitis, 31 were transferred from other ICUs. The median APACHE II score was 18 (range 4–40) and the overall hospital mortality rate was 39 per cent. Seventeen patients (25 per cent) were managed with EN alone, ten (14 per cent) with TPN alone and 19 (28 per cent) with a combination of both. Twenty-three (33 per cent) did not have any nutritional support during their ICU stay. The mortality rate was worse among patients who received TPN only than in those who had EN (60 versus 24 per cent).

Conclusions

EN is likely to remain the route of choice for nutritional support in the ICU. However, in high-risk patients with acute severe pancreatitis EN may not be feasible and TPN is often required. This may reflect a greater severity of illness.
Need for staging laparoscopy in patients with gastric cancer
Authors: Bhalla R , Formella L , Kerrigan D D
Published: July 2002

Aims

The aim of preoperative staging in gastric cancer is to correctly identify patients with advanced disease who should not be subjected to surgery and to allow the treatment of those who are admitted for operation to be planned accurately. This study assessed the impact of a policy of selective staging laparoscopy in patients deemed suitable for curative or palliative surgery, to ascertain whether the selective approach increased the frequency of abandoned or unplanned surgical procedures.

Methods

Fifty consecutive patients with gastric or type III gastro-oesophageal junction cancer staged by computed tomography (CT) alone, in whom surgery was felt to be appropriate for ‘cure’ or palliative symptom control, were studied. Specific CT, endoscopic and biochemical criteria were applied prospectively to select out a subgroup of 18 patients who also underwent preoperative staging laparoscopy. The overall accuracy of staging and operative outcomes were assessed.

Results

Using this selective approach the resection rate was 98 per cent, although three patients in each group had their planned procedure altered to a less radical (two in each group) or more radical (one in each group) resection (P = 0·23). Overall, 41 of 50 patients were staged correctly (accuracy 82 (95 per cent confidence interval 69–90) per cent) and 86 per cent of patients underwent the planned surgical procedure. The only abandoned operation occurred in the staging laparoscopy group.

Conclusions

It is possible to plan a patient's operation accurately without the need for a staging laparoscopy in all cases.
Current nature and management of cancer of the oesophagus and cardia
Authors: Gillison E W , Powell D J , McConkey C , Spychal R T
Published: July 2002

Aims

To inform the debate about upper gastrointestinal cancer care in the UK, the incidence of cancer of the oesophagus and cardia (OGJ) was determined in the West Midlands, a region covering 10 per cent of England and Wales, with particular reference to the methods of treatment.

Methods

The case-notes of 2776 patients diagnosed with oesophageal and OGJ cancer in the 5 years from 1 January 1992 to 31 December 1996 were scrutinized by one experienced surgeon. Tumour types were classified by histology and site, and treatment modalities assessed for 30-day mortality rate together with life-table analyses.

Results

Oesophageal cancer was identified in 2188 patients (61 per cent lower, 34 per cent middle, 4 per cent upper), including 999 squamous carcinomas (27 per cent lower, 64 per cent middle, 9 per cent upper) and 995 adenocarcinomas (97 per cent lower, 3 per cent middle), while there were 588 cases of OGJ cancer (94 per cent adenocarcinomas). Resection was the commonest treatment (865 cases; 31 per cent), with a mortality rate of 10 per cent for oesophageal and 4 per cent for OGJ cancer. Palliative resection had a higher mortality rate than radiotherapy (9 versus 3 per cent), compared with 22 per cent for endoscopic palliation, while the 30-day mortality rate was 30 per cent for the 308 patients given no treatment.

Conclusions

Squamous carcinomas and adenocarcinomas of the oesophageal body are now equally common; lower-third and OGJ tumours are predominantly adenocarcinomas. This study provides baseline data for critical appraisal of potential changes in the delivery of upper gastrointestinal cancer in the UK.
Development of an EORTC module to improve quality of life assessment in patients with gastric cancer
Authors: Vickery C W , Blazeby J M , Conroy T , Johnson C D , Alderson D
Published: July 2002

Aims

A valid measure of quality of life (QL) that is sensitive to clinically significant changes in health is important for the assessment of patients with gastric cancer. The aims of this study were to examine whether the EORTC (European Organisation for Research and Treatment of Cancer) QLQ-C30 core questionnaire alone could distinguish between two clinically different groups of patients and to design a module, which included relevant patient-defined gastric cancer-specific variables.

Methods

The QLQ-C30 was completed by patients with potentially curable disease and those undergoing palliative treatment, and the results were compared between the two groups. A disease-specific module was then developed in four distinct phases according to EORTC guidelines. Relevant issues were identified from a literature search and structured interviews with patients and healthcare professionals, and worded into a provisional questionnaire which was pretested to determine any problems in its content, before formal validation.

Results

All of the subscales and single items within the QLQ-C30 were scored similarly by 144 patients, 86 with operable disease and 58 having palliative treatment, except constipation (P = 0·001). On the basis of interviews with 58 patients and 24 professionals, from the UK, France, Germany and Spain, 43 issues were reduced to produce a provisional questionnaire consisting of 24 items and pretested in 114 patients undergoing radical gastrectomy, palliative resection or other supportive measures. The resulting questionnaire, containing 22 items divided into five scales (dysphagia, pain, reflux, dietary restrictions and specific emotional problems related to gastric cancer and its treatment) and four single items, is undergoing validation.

Conclusions

The EORTC QLQ-C30 is a valid generic instrument, but does not address all factors constituting QL in patients with gastric cancer. A specific module has been developed, which includes issues volunteered by patients to increase sensitivity and improve the evaluation of treatments for a disease where QL is important.
Functional and morphological changes in the pancreatic remnant following pancreaticoduodenectomy with pancreaticogastric anastomosis
Authors: Lemaire E , O'Toole D , Sauvanet A , Hammel P , Belghiti J , Ruszniewski P
Published: July 2002

Background

The aim was to evaluate pancreatic exocrine and endocrine function, pancreatic atrophy and main pancreatic duct dilatation in the pancreatic remnant following pancreaticoduodenectomy and pancreaticogastrostomy.

Methods

Nineteen patients who underwent pancreaticoduodenectomy and pancreaticogastrostomy for benign or malignant pancreatic tumours with a histologically normal pancreatic resection margin were studied prospectively. The median interval between operation and evaluation was 32 (range 12–120) months. Pancreatic exocrine insufficiency was assessed by measuring 72-h faecal fat concentrations and faecal-1 elastase. Fasting blood glucose, haemoglobin A1c, serum peptide C and insulin levels were used to assess endocrine function. Pancreatic parenchymal thickness and main pancreatic duct diameter were measured before operation and at evaluation using computed tomography (CT).

Results

Faecal fat excretion was raised in 16 of 17 patients; faecal-1 elastase was reduced in all 17 patients. None of the 17 non-diabetic patients had developed diabetes mellitus at follow-up. A significant decrease in pancreatic parenchymal thickness and increased dilatation of the main pancreatic duct were observed on CT at evaluation (P = 0·01 and P = 0·01 respectively). Pancreatic atrophy, assessed by subtracting the diameter of the pancreatic duct from the total gland thickness, tended to develop over time, but at the limit of statistical significance (P = 0·06).

Conclusion

A median of 3 years following pancreaticoduodenectomy and pancreaticogastrostomy, patients remained free from diabetes but developed marked pancreatic exocrine insufficiency.
Influence of allograft size to recipient body-weight ratio on the long-term outcome of renal transplantation
Authors: Nicholson M L , Windmill D C , Horsburgh T , Harris K P G
Published: July 2002

Background

The critical nephron mass needed to meet the metabolic demands of an individual depends on the body-weight. This study evaluated the effect of the kidney transplant ultrasonographic size to recipient body-weight ratio (Tx/W) on the outcome of kidney transplantation.

Methods

A consecutive series of 104 cadaveric renal transplants was studied. Transplant cross-sectional area (TXSA) was measured ultrasonographically in the first week after transplantation as an index of renal size. A ‘nephron dose’ index (Tx/W) was calculated by dividing TXSA by recipient weight and was used to define three groups of patients, with high (more than 0·45), medium (0·3–0·45) or low (less than 0·3) Tx/W ratios. Isotope glomerular filtration rate (GFR) measurements were made at 1, 6 and 12 months after transplantation.

Results

The serum creatinine level was significantly lower in the first 5 years after transplantation in patients with a high Tx/W ratio than in those with a medium or low ratio. GFR measurements were marginally higher in the groups with a high and medium Tx/W ratio compared with the low Tx/W group. A statistically significant association between Tx/W ratio and graft survival was not found.

Conclusion

The renal transplant size to recipient weight ratio was an important determinant of long-term renal allograft function in this study. Extreme mismatching between allograft and recipient size should be avoided where possible, but the findings presented require confirmation in larger studies before clear recommendations can be made about size matching and kidney allocation.
Changes in pancreatic resection for chronic pancreatitis over 28 years in a single institution
Authors: Falconi M , Valerio A , Caldiron E , Salvia R , Sartori N , Talamini G , Bassi C , Pederzoli P
Published: July 2002

Background

Because of advances in knowledge over recent years there is reason to believe that surgical attitudes towards patients with chronic pancreatitis may have changed.

Methods

Some 547 patients were treated surgically for chronic pancreatitis from 1971 to June 1998. Anastomoses were performed in 80 per cent (438 patients) and resections in 20 per cent (109 patients). Indications and type of operation were analysed, as were mortality and morbidity rates and long-term follow-up results, in patients undergoing resection both over the period as a whole and after dividing the series into two subperiods of 14 years.

Results

In the second 14-year period, there was a significant reduction in the percentage of resections compared with anastomoses (28 per cent (69 of 244 patients) versus 13 per cent (40 of 303); P < 0·0001), and a significant change in the type of resection with a substantial increase in resections of the head compared with those of the body and tail. Statistically significant reductions occurred in operating times, number of units of blood transfused (mean(s.d.) 4·7(3·6) versus 1·2(1.6) units; P = 0·0001) and mean hospital stay (18 versus 14 days for pylorus-preserving and 12 versus 8 days for left pancreatectomy with splenectomy; P < 0·01); mortality and morbidity rates also tended to decrease, but not significantly.

Conclusion

A different pattern has emerged over the years as regards both the type and number of resections performed.
Audit of time to emergency trauma laparotomy
Authors: Henderson K I M , Coats T J , Hassan T B , Brohi K
Published: July 2002

Background

An analysis of the process of care may improve quality of care within a trauma system. Early operative control of haemorrhage is vital and any delay before surgery may adversely affect outcome.

Methods

Times from activation of the aeromedical team to arrival in the emergency department and the operating room for patients with liver or spleen injury were analysed to identify factors that delayed laparotomy. These results were compared with those of a national database.

Results

The median time from emergency call to operation was 127 min (140 min for blunt and 86 min for penetrating injuries). Time from arrival in the emergency department to the operating room was 54 min (56 min for blunt and 37 min for penetrating injuries). An audit filter, set at the upper quartile of the emergency call to operating room time, selected 21 patients whose records were examined; five correctable delays were identified. Compared with the national trauma database, these patients had longer on-scene times, but significantly shorter times to operation from the emergency call (127 versus 161 min) and arrival at the emergency department (54 versus 115 min), although the patients were more severely injured (median Injury Severity Score 34 versus 24).

Conclusion

The time to emergency trauma laparotomy may be used effectively as an audit of process for the clinical governance of a trauma system.
Randomized clinical trial of haemorrhoidectomy under a mixture of local anaesthesia versus general anaesthesia
Authors: Ho K S , Eu K W , Heah S M , Seow-Choen F , Chan Y W
Published: July 2002

Background

Application of a topical anaesthetic agent may facilitate infiltration of local anaesthetic at haemorrhoidectomy.

Methods

A randomized clinical trial of 53 consecutive patients requiring elective haemorrhoidectomy was carried out. One group underwent haemorrhoidectomy under general anaesthesia, while the second group had topical anaesthetic cream (containing lignocaine and prilocaine) applied followed by local anaesthetic infiltration for surgical anaesthesia.

Results

There were no differences between the two groups in terms of operating time, postoperative pain, nausea or vomiting, pain-free interval after operation, analgesic requirements or patients' satisfaction with the method of anaesthesia. Postoperative oxygen saturation and pulse rate were similar in the two groups.

Conclusion

Topical anaesthetic and local anaesthesia can be used effectively for haemorrhoidectomy and provide an alternative to general anaesthesia.
Differences in cognitive function and S100 production after carotid endarterectomy under local or general anaesthetic
Authors: Calvey T A J , Bollom P , Cruickshank J , Waterman M , Mavor A I D , Homer-Vanniasinkam S , Gough M J
Published: July 2002

Background

Previous studies reported both improved (enhanced cerebral perfusion after carotid endarterectomy (CEA)) and diminished (intraoperative ischaemic injury) cognitive function (CF) following CEA. These studies were not adequately controlled for anxiety, general health and learning (repeated testing), and the influence of anaesthetic technique was not assessed.

Methods

This study assessed CF (trained psychologist, seven computerized tests) before operation, and at 5 and 90 days after CEA performed under local anaesthesia (LA) (n = 34) or general anaesthesia (GA) (n = 13). Similar measurements in patients undergoing lower limb revascularization (n = 14) and unoperated subjects with asymptomatic carotid stenosis greater than 70 per cent (n = 16) tested twice, 3 months apart, controlled for the effects of anaesthesia, surgery and carotid arteriosclerosis. Additionally, jugular venous S100 levels (neuronal protein released following cerebral injury) were measured (before carotid clamping, and 1, 4 and 24 h after clamp release) in 18 of these patients (nine LA, nine GA).

Results

Compared with controls, test performance in patients who had CEA under GA improved in one (executive CF 90 days; P = 0·028), but deteriorated in another (working memory 90 days; P = 0·038) while patients who had LA improved in three of seven tests (executive function, working memory) at 5 days (P = 0·03, 0·048, 0·036) and 90 days (P = 0·01, 0·05, 0·006). Further, a greater than 25 per cent improvement in one or more tests was more likely 90 days after CEA under LA (22 of 34 versus four of 13; P < 0·04) with improved executive function, speed and accuracy. S100 levels were lower after CEA under LA (1 h: 0 (0–30) versus 29 (8–98) µg ml−1, P < 0·05; 4 h: 0 (0–6) versus 22 (2–95) µg ml−1, P < 0·05; 24 h: 0 (0–1) versus 35 (14–77) µg ml−1, P < 0·01).

Conclusion

This study demonstrated improved CF following CEA under LA which was associated with lower jugular venous S100 levels (marker of cerebral injury). These differences may reflect improved cerebral oxygenation (preservation of cerebral autoregulation).
Intraoperative change in baroreceptor function during carotid endarterectomy
Authors: Gaunt M E , Sigaudo-Roussel D , Panerai R , Evans D H , London N L , Naylor A R , Bell P R F
Published: July 2002

Background

Labile blood pressure following carotid endarterectomy (CEA) is common and is associated with perioperative myocardial infarction and intracranial haemorrhage. Previous studies have identified that alteration in carotid baroreceptor function is responsible for the blood pressure changes although the mechanism remains unclear. This study aimed to identify the mechanism by which CEA affects baroreceptor function.

Methods

Fifty patients were recruited prospectively and underwent estimation of baroreceptor sensitivity (BRS) during a 10-min period of supine bed rest using electrocardiography and Finapres, 2 days before and 2 days to 6 weeks after surgery. During surgery continuous measurements of blood pressure (intra-arterial) and heart rate were recorded on to digital audio tape for postoperative analysis. During analysis the operation was divided into different stages to identify at which stage baroreceptor function altered. Particular attention was paid to initial clamping of the carotid artery, performance of the endarterectomy and final restoration of blood flow. In addition the carotid sinus area was stimulated by stroking the inside of the artery before and after removal of the plaque. Autonomic activity was calculated using power spectral analysis of beat-to-beat blood pressure and the R–R interval from the electrocardiograph. BRS was estimated by calculation of the square root of the ratio of the powers of R–R interval and systolic blood pressure to give the alpha index which has been shown to correlate well with BRS calculated by means of standard pharmacological techniques.

Results

For this cohort of patients BRS was significantly reduced 2 days after surgery compared with the preoperative recordings (2·8(0·4) to 5·6(0·8)). Six weeks after operation BRS had improved but had not achieved preoperative levels (3·8(0·6) to 5·6(0·8)). During surgery, patients with good baroreceptor function identified before operation experienced a rise in blood pressure on initial carotid clamping indicating that dissection had not affected the baroreceptor mechanism. Similarly, intraluminal stimulation of the carotid sinus area with the plaque in situ produced a decrease in blood pressure indicating good baroreceptor function. After removal of the plaque, repeating the intraluminal stimulation did not produce a decrease in blood pressure indicating disruption of the baroreceptor mechanism.

Conclusion

Removal of the atheromatous plaque during CEA adversely affects carotid baroreceptor function. The baroreceptor mechanism is disrupted but not completely destroyed and gradually improves in the weeks following surgery.
Indications of infection with Chlamydia pneumoniae are associated with expansion of abdominal aortic aneurysm
Authors: Scott R A P , Ashton H , Lindholt J S
Published: July 2002

Background

This was a study of the possible association between the progression of abdominal aortic aneurysm (AAA) and indicators of infection with Chlamydia pneumoniae.

Methods

Blood samples were taken from patients with AAA (3 cm diameter or greater detected by an aneurysm screening programme) who had been followed prospectively for up to 11·5 (mean 4·1) years. A sex- and age-matched control group was also recruited. Immunoglobulin (Ig) G and IgA antibodies against C. pneumoniae were measured by a microimmunofixation test. Analysis of variance, multiple linear regression and logistic regression were used for statistical analysis. Ninety men and ten women with a small AAA and 20 age-matched male controls were investigated. Outcome measures studied were AAA expansion, and IgA and IgG titres of antibodies against C. pneumoniae.

Results

Forty-four (95 per cent confidence interval (c.i.) 31–55) per cent of the men with an AAA had IgA greater than 64 or IgA above 28 compared with 10 per cent of the women with an AAA (odds ratio (OR) 7·2 (95 per cent c.i. 1·0–160·8)) and 25 per cent of the controls (OR 2·24 (95 per cent c.i. 0·67–7·93)). IgA greater than 128 was significantly associated with greater expansion (5·3 versus 2·6 mm per year), even after adjustment for initial AAA size and age. A significant dose–response reaction was found between IgA titre and mean annual expansion (R = 0·45 (95 per cent c.i. 0·24–0·62)). The significant positive correlation remained after adjusting for initial AAA size and age. Finally, IgG greater than 128 was present significantly more often in patients with expansion above 1 cm annually (OR 12·6 (95 per cent c.i. 1·4–293)).

Conclusion

A high proportion of men with AAA have signs of infection by C. pneumoniae. The progression of AAAs correlated with the presence of indicators of C. pneumonia infection, and a dose–response reaction between IgA titre and expansion was observed.
Population screening reduces the total community mortality rate from aortic aneurysms
Authors: Shaw E , Poskitt K , Earnshaw J , Whyman M , Heather B
Published: July 2002

Background

Screening of the male population for unsuspected abdominal aortic aneurysm (AAA) has been taking place in a single UK county (population 520 000) since 1990.

Methods

The general practitioner surgery-based programme involves ultrasonographic examination of each year's new batch of 65-year-old men, excluding those who were older than this when the programme started. This method of screening has resulted in a gradually enlarging cohort of screened men, so that by the end of 1998 all men between the ages of 65 and 73 years had been offered an ultrasound scan, with 85 per cent accepting and over 21 000 men examined. Total aneurysm-related deaths in the community have been quantified by examining inpatient records and post-mortem results for the county's hospitals, together with computerized death certificate records held by the health authority (available for 1994 onwards). This figure thus includes deaths at home from ruptured AAA, in-hospital deaths from ruptured AAA with or without emergency surgery and all deaths following elective AAA surgery.

Results

The 65–73-year-old age group has been progressively influenced by AAA screening as new 65 year olds are examined each year. Total aneurysm-related deaths in this age range have shown a progressive, year by year fall between 1994 and 1998, with an overall reduction in deaths by two-thirds during this 5-year period. In contrast, aneurysm-related deaths in men aged below 65 and over 73 years have tended to show a slight increase in the same period.

Conclusion

These figures clearly demonstrate that population screening reduces overall deaths from aortic aneurysms.
Risk factors for postoperative death following elective surgical repair of abdominal aortic aneurysm
Authors: Powell J T
Published: July 2002

Background

In regional and national studies death within 30 days of elective open surgical repair of an abdominal aortic aneurysm has been reported to be 7–8 per cent or even higher. Identification of preoperative factors associated with this mortality risk is important for informing surgical policy and may suggest suitable preoperative interventions.

Methods

During the course of the UK Small Aneurysm trial, 820 patients aged 60–80 years underwent elective open surgical repair of an abdominal aortic aneurysm. The relationship between 30-day mortality rate and 13 prespecified potential prognostic factors (including age, sex, aneurysm diameter, electrocardiographic evidence of myocardial ischaemia, lung function, creatinine level, hospital centre and tube or bifurcated graft) was studied.

Results

The postoperative mortality rate was 5·6 per cent overall (46 deaths in 820 patients). In univariate analyses postoperative mortality risk was associated significantly with higher serum creatinine (P = 0·002), poor lung function with low forced expiratory volume in 1 s (FEV1) (P = 0·003) and older age (P = 0·03). Evidence of the relationship between age and postoperative death was weaker (P = 0·08) after adjustment for creatinine and FEV1. The predicted postoperative mortality risk ranged from 2·7 per cent in younger patients with a low creatinine level and high FEV1 to 7·8 per cent in older patients with above average creatinine levels and below average FEV1. There was no evidence of between-hospital or between-surgeon variability in postoperative risk.

Conclusion

Poor preoperative lung and renal function were associated strongly with postoperative death. Age was less important once these two prognostic indicators were taken into account. The potential for preoperative improvement in lung and renal function to reduce the postoperative mortality rate should be addressed in future studies.
Outcome of 112 consecutive patients with an abdominal aortic aneurysm greater than 5·5 cm turned down for elective repair at a university hospital
Authors: Conway K , Byrne J , Lane I F
Published: July 2002

Background

The UK Small Aneurysm study has demonstrated the low risk of rupture in aneurysms less than 5·5 cm in diameter. However, the natural history of aneurysms greater than 5·5 cm remains unresolved. Questions of equipoise probably preclude another trial in patients with an AAA over 5·5 cm. In this centre, the authors prospectively maintain records of all patients refused elective aneurysm surgery. This study aimed to document the outcome of all patients referred with an AAA greater than 5·5 cm in diameter, and to determine the cause of death and risk of rupture in all patients.

Methods

Details of all patients presenting with an AAA from 1989 to 1999 were recorded and demographic details on all patients with an AAA greater than 5·5 cm were collected. The endpoint was 1 May 1999. Copies of death certificates for deceased patients were obtained from the Office of National Statistics, local in-hospital patient records and general practitioner records. Results of post-mortem examinations were also retrieved. Aneurysms were stratified according to size at presentation (5·5–5·9, 6·0–7·0, more than 7·0 cm) and reasons for non-intervention were documented.

Results

Some 112 patients were turned down over 10 years (11·4 per year). The mean(s.d.) age of this patient group was 77·7(7·7) years; there were 74 men and 38 women. Crude mortality data are shown in the Fig. below (Kaplan–Meier curve). At the end of the study period, 87 patients (76 per cent) were dead, 26 (30 per cent) from a ruptured AAA. Mean survival times were: 23 months (5·5–5·9 cm), 20 months (6·0–7·0 cm) and 15 months (greater than 7·0 cm).

Conclusion

While recognizing the problems with death certification, rupture still seems to be a significant cause of death in patients with untreated AAAs greater than 5·5 cm. While little difference is observed in 5·5–7·0-cm range, patients with an AAA greater than 7·0 cm seem to have a much poorer prognosis.