bluuebunny/crossref_metadata_2025 huggingface dataset:
Does the caseload of the pathologist influence the minimum and extended data set of pathology variables reported for rectal adenocarcinoma?
Authors: Hatzidis  , Solomon  , Schnitzler  , Cartmill  , Loder  , Chapuis
Published: March 2003

Background

The role of adjuvant therapy for rectal carcinoma, both radiotherapy and chemotherapy, remains controversial. Nevertheless, some stages of rectal cancer may benefit from adjuvant therapies. Post‐operative decision making is determined by accurate pathology staging of the tumour which may depend on the experience, expertise and activity of the pathologist and by surgeon variables.

Methods

Pathology reports for consecutive rectal cancer resection specimens at five University of Sydney teaching hospitals were assessed for the presence of important pathology variables. The desired minimum data set included the assessment of six major variables: extent of tumour penetration, distal and circumferential margins, degree of differentiation, number of nodes and identification of an apical node. A multivariate analysis was performed to see if the activity of the pathologist (number of specimens reported in time period) correlated with the number of minimum data set pathology variables reported. Multivariate analysis was also used to determine if the activity (number of resections) or training (colorectal society vs non‐society) of the surgeon were correlated with variables potentially related to adequate surgical clearance of the tumour and to abdominoperineal (APE) resection rates.

Results

Four hundred and forty‐five consecutive rectal cancer pathology reports were reviewed. Of the minimum data set (six variables) only 17% of the reports documented all of these major variables (range 2–6). Apical node identification was reported in only 47% of reports and circumferential margin in only 39%. Circumferential margin was reported significantly more frequently in the higher activity group of pathologists (51% vs 29%, P=0.00001). APE rates were significantly different between some of the hospitals (range 19–31%). Surgeons performing more than 20 resections had lower APE rates (16% vs 37%, P=0.000 001) than those with less than 20 resections. There was no difference in APE rates between society and non‐society surgeons. Distal margins of <2 cm for anterior resections were significantly higher in non‐society surgeons (52% vs 36%, P=0.004).

Discussion

Standardized reporting, template proformas and perhaps dedicated gastrointestinal pathologists may improve reporting of surgical rectal cancer specimens.
Emergency admission for surgery predicts disease progression during adjuvant 5‐Fluouracil (5‐FU)‐based chemotherapy
Authors: Hayman  , James
Published: March 2003

Objective

To determine the prognostic significance of a number of variables in patients that receive adjuvant chemotherapy for colorectal cancer.

Patients and methods

We reviewed the Cancer Centre records of 194 patients who received adjuvant chemotherapy following potentially curative resection of Dukes’ B or C colorectal cancer. Eight variables were examined to determine which factor(s) predicted disease progression during the 6‐month chemotherapy period.

Results

Admission for emergency resection (due to bowel obstruction or perforation) rather than elective resection, and a poorly differentiated tumour rather than moderately/well differentiated were independent significant factors in predicting disease progression (P < 0.001 and P=0.011, respectively). However, sex, age, Dukes’ stage, number of involved lymph nodes, delays in starting chemotherapy and compliance with chemotherapy regime had no significant effect on 6‐month tumour progression.

Conclusion

These preliminary findings confirm data which suggest that emergency admission patients may suffer from intrinsically more aggressive disease than the average population with colorectal cancer.
Plasma TIMP‐1—a marker of metastasis in colorectal cancer
Authors: Simpson  , Hemingway  , Thompson
Published: March 2003

Objective

To assess a potential role for plasma assay of TIMP‐1 and MMP‐9 as markers of disease presence and disease stage in colorectal cancer.

Patients and methods

Plasma concentration of  TIMP‐1 and MMP‐9 was measured in 41 patients with proven colorectal cancer and in 20 age/sex‐matched controls. In the 38 cancer patients who underwent laparotomy, portal plasma samples were collected in addition to peripheral venous samples, to assess whether these might be a more sensitive indicator of disease severity.

Results

In samples taken preoperatively, systemic plasma levels of both TIMP‐1 and MMP‐9 were significantly elevated in cancer patients compared with controls (P < 0.0001 and P < 0.0001), respectively. Systemic and portal plasma TIMP‐1 levels were significantly higher in those with metastatic disease compared with those with localized disease (P=0.0248 and P=0.0382). Elevated levels of TIMP‐1 in systemic blood were seen in those with muscle‐invading tumours compared with more superficial lesions (P=0.0349). Plasma MMP‐9 levels did not correlate with clinicopathological features.

Conclusion

TIMP‐1 and MMP‐9 levels were significantly elevated in the plasma of patients with colorectal cancer. Metastatic disease is associated with significantly higher plasma TIMP‐1 than is localized disease. Sampling of portal blood is of no additional benefit when measuring MMP‐9 enzyme levels in colorectal cancer.
Early flexible sigmoidoscopy in the evaluation of acute left iliac fossa pain
Authors: Tan  , Senapati  , Thompson
Published: March 2003

Objective

To evaluate the feasibility, safety and diagnostic yield of flexible sigmoidoscopy as an early diagnostic tool in the investigation of the colonic causes of acute left iliac fossa pain.

Patients and methods

A 1‐year prospective study was conducted in which flexible sigmoidoscopy was performed as soon as possible by two consultant coloproctologists within their normal theatre sessions on all emergency patients admitted with acute left iliac fossa pain. The clinical details, flexible sigmoidoscopy findings and subsequent outcome were recorded on a proforma.

Results

It was possible to perform early flexible sigmoidoscopy on 86% (62/72) of patients referred during their in‐patient stay at a median delay of 4 days from time of admission. Eighty‐four percent of the examinations resulted in a diagnosis or exclusion of a colonic cause for their acute left iliac fossa pain. There was low morbidity and one unrelated death in the study.

Conclusion

This study has shown that it is feasible to use early flexible sigmoidoscopy as a first line investigation for patients presenting with acute left iliac fossa pain. Flexible sigmoidoscopy is a quick and safe procedure in skilled hands with a high diagnostic yield, although the potential risks involved in performing this procedure in the acute period mandate that it should only be undertaken by experts.
Is laparotomy mandatory for parastomal hernia repair?
Authors: Baig  , Wexner  , Uriburu  , Moscovitz  , Singh  , Weiss  , Nogueras  , Zhao
Published: March 2003

Objective

A parastomal hernia is an incisional hernia at the site of an intestinal stoma. The incidence varies, as do techniques for repair and their associated rates of success. The aim of this study was to evaluate the methods of parastomal hernia repair and their outcome.

Patients and methods

Between 1988 and 1998, 33 patients who underwent elective parastomal hernia repair were identified by the use of a computerized database. Information was collected on the indication and type of reparative procedure, as well as any morbidity or recurrence, post‐operative complications and recurrence. The operative procedures performed included reanastomosis and ipsilateral and contralateral relocation with hernia repair. Additional data were collected on whether a laparotomy was required or mesh was placed.

Results

The commonest operation was relocation without laparotomy or mesh (36%), followed by laparotomy still without mesh (21%); the overall recurrence rate was 9% (3/33) at a mean follow up of 55.2 months (range 10–108 months).

Conclusion

Parastomal hernia repair without laparotomy or mesh is a safe and effective method of repair.
What determines the outcome after total mesorectal excision for rectal carcinoma—15 years experience of a specialist surgical unit
Authors: Marks  , Reid  , Lewis  , Jackson  , Cook
Published: March 2003

Objectives

Outcome after surgery for rectal cancer is often correlated with surgical technique, without detailed pathological examination of the specimen. Measurement of the number of lymph nodes by a fat clearance technique, mesorectal spread and involvement of the circumferential margins together with clinical findings at operation are correlated with outcome in a consecutive series of patients treated by a specialist surgeon.

Patients and methods

The effect of prognostic factors on patients’ survival was analysed using Cox’s proportional hazards regression models. Survival curves and 5‐year survival rates were calculated using Kaplan–Meier analysis.

Results

After curative procedures, 78.6% (95% confidence interval (CI) 72.8–84.3) of patients survived compared with 6.0% (95% CI 0.7–11.4) after palliative procedures; the hazard of dying was 1.5 times higher for patients with Dukes’ B tumours and 6.4 times higher for those with Dukes’ C compared with those with Dukes’ A (P < 0.0001). Patients with four or more lymph nodes involved had a two‐fold increase in the hazard of dying compared with those with three or less involved lymph nodes.

Conclusion

The strongest predictor of 5‐year survival for patients with rectal carcinoma was whether the operation was deemed curative or palliative. Neither the extent of mesorectal spread nor the involvement of the circumferential resection margin had a significant effect on survival, after surgery in a specialist unit, compared with published series after conventional surgery.
A retrospective analysis of palliative colonic stent placement in an elderly population
Authors: Buchanan  , Khawaja  , Okojie  , Rowe  , Saunders  , Stoodley  , Anderson
Published: March 2003

Objective

Self‐expanding metal stents (SEMS) have added a new dimension to the management of colonic malignant obstruction. We present our experience of palliative colonic stent insertion in a group of patients unsuitable for surgery.

Patients and methods

Since 1995 11 patients (median age 82 years) with strictures of the rectosigmoid region underwent SEMS placement at this Hospital. The indications for stent placement were large bowel obstruction (n=6), overflow incontinence (n=4) and faecal fistula (n=1). The selection criteria included five patients with disseminated disease and six who were deemed unfit for surgery. SEMS insertion was performed under fluoroscopic control in all patients, and colonoscopic assistance was required in four patients where fluoroscopy alone failed.

Results

SEMS placement was successful in nine patients with resulting bowel decompression and immediate symptomatic relief, but failed in two patients. Where SEMS placement was unsuccessful, the stricture was impassable in one instance and in the other the patient withdrew consent. Stent migration occurred in three out of nine patients. The median survival time after stent placement was 5 months; one patient is still alive at 14 months.

Conclusion

SEMS placement resulted in the successful palliation of symptoms in patients with obstructive lesions deemed unfit for surgery—however, it is not always successful and there are complications.
Multiplanar anal endosonography – normal anal canal anatomy
Authors: Williams A. B. , Bartram C. I. , Halligan S. , Marshall M. M. , Nicholls R. J. , Kmiot W. A.
Published: March 2003

Introduction

Volume acquisition during anal ultrasound enables multiplanar imaging of the anal canal. The normal ultrasonic multiplanar appearance of the anal canal is described and gender differences in canal anatomy are highlighted.

Methods

Ten male and 12 female normal volunteers (mean ages 31.5 years (s.d. 5.9) and 31.2 (s.d. 6.7)) had three‐dimensional anal endosonography (3‐D AES). Each volume dataset was seeded in the axial plane facilitating multiplanar identification of known anatomical structures.

Results

The anterior external anal sphincter (EAS) was significantly longer in men than women 30.1 mm (3.9) vs 16.9 mm (7.4) (P < 0.001). There was no difference in the length of the puborectalis 24.7 mm (6.4) vs 24 mm (5) (P=0.78) in men compared with women. The cranial extent of the anterior EAS was tilted forward in both sexes. The angle formed by the anterior EAS and the longitudinal axis of the anal canal was more acute in men than in women (11.1°vs 18.6°; P=0.007). Dataset volume seeding of familiar structures in the axial plane allowed the multiplanar endosonographic anatomy to be described.

Conclusions

Multiplanar AES has enabled detailed longitudinal measurement of the components of the anal canal and has revealed important gender differences. The multiplanar ultrasonic appearance of the normal anal canal has been described for the first time.
Life table analysis of hernia following end colostomy construction
Authors: Mylonakis E. , Scarpa M. , Barollo M. , Yarnoz C. , Keighley M. R. B.
Published: March 2003

Objective

To study the long‐term hernia rate and risk factors after end colostomy construction.

Patients and methods

86 patients with a permanent end colostomy constructed over 5 years were examined and interviewed. There were 35 men and the mean age was 56.5 (28–87) years. Risk factors which were analysed included emergency operation, age over 60 years, obesity, steroids, cancer, infection at the stoma site, smoking and chronic obstructive airways disease.

Results

Para‐colostomy hernia occurred in 12/86 cases (13.9%). The cumulative recurrence rose with duration of follow up. Overall 10/45 patients (22%) over 60 years developed hernia vs. 2/41 patients (4.8%) less than 60 years (P=0.02). There were no other risk factors that correlated with para‐colostomy hernia.

Conclusions

These data indicate that the incidence of colostomy related hernia increases with follow up and is significantly higher in patients over the age of 60. Other risk factors, particularly obesity and coexisting cardiorespiratory disease, have no impact.
Long‐term results of subtotal colectomy for severe slow‐transit constipation in patients with normal rectal function
Authors: Aldulaymi B. H. , Rasmussen O. Ø. , Christiansen J.
Published: March 2003

Objective

The outcome of subtotal colectomy for severe constipation may be difficult to predict. One factor, which probably is of major importance for the functional outcome, is rectal function. The aim of the study has been to evaluate long‐term results after subtotal colectomy with ileo‐rectal anastomosis in a group of patients with severe slow‐transit constipation but without evidence of impaired rectal emptying.

Patients and methods

Of 273 patients with constipation referred for surgical evaluation 18 (7%) fulfilled our criteria for subtotal colectomy. Slow‐transit was confirmed by radio‐opaque marker studies and normal rectal function by emptying of viscous fluid and normal emptying at defecography.

Results

At follow up between 3 and 9 years 15 patients had a bowel frequency between 2 and 6 daily. One patient, who had an ileostomy because of anastomotic leak, had not wanted bowel continuity restored. One patient with opiate abuse became less constipated with 2–3 bowel movements a week. One patient was still constipated one year after the operation and subsequently had an ileal pouch–anal anastomosis. This patient who had normal rectal emptying had a very high volume tolerability with a maximum tolerable volume of 700 ml. In 4 of 7 patients abdominal pain persisted after the operation, and 3 developed diarrhoea, which required daily intake of loperamide.

Conclusion

Subtotal colectomy for severe slow‐transit constipation is justified provided anorectal function is normal. In spite of normal rectal emptying very high rectal volume tolerability may be an indicator of functional megarectum and impaired rectal emptying postoperatively.
Objective assessment of morbidity and quality of life after surgery for low rectal cancer
Authors: Camilleri‐Brennan J. , Steele R. J. C.
Published: March 2003

Objective

To determine whether an anterior resection for low rectal cancer is associated with less morbidity and a better quality of life than an abdominoperineal resection.

Patients and methods

Fifty‐three patients who had anterior resection for low rectal cancer were individually matched with 53 other patients, who had an abdominoperineal resection during the same period of time, for gender, age and socioeconomic status. There was no evidence of tumour recurrence in these patients. All patients answered three quality of life questionnaires at least one year after surgery: Short Form 36 version 2, EORTC QLQ‐C30 and EORTC QLQ‐CR38. Details on short‐term and long‐term complications were collected prospectively.

Results

There was no significant difference in both the short‐term and the long‐term complication rates between the two groups of patients. There was also no difference in the global quality of life score on the QLQ‐C30. However, patients who had an anterior resection had a better perception of body image than those who had an abdominoperineal resection, as measured on the QLQ‐CR38 questionnaire (P=0.009), but were more prone to suffer from constipation (P=0.001).

Conclusions

The overall similarities in quality of life between the two groups is probably a reflection of better stoma care, although problems with body image still persist in stoma patients.
Tailgut cyst associated with a pilonidal sinus: an unusual case and a review
Authors: Satyadas T. , Davies M. , Nasir N. , Halligan S. , Akle C. A.
Published: March 2003

Tailgut cysts are rare congenital abnormalities in the retrocaecal/presacral region. Clinical diagnosis is difficult and delayed and they can present in childhood and adult life with a variety of clinical symptoms and complications. Differential diagnoses include, rectal duplication cysts, cystic teratoma, epidermal cyst, anal gland cyst and anal gland carcinoma. Magnetic resonance imaging has recently become the modality of choice to image these cysts. Although Tailgut cysts rarely undergo malignant transformation, early surgical resection is presently considered the treatment of choice. Here we report the case of a 34 year old gentleman with a Tailgut cyst associated with a Pilonidal sinus, and review of the literature. We believe that the high incidence of complications associated with operations in the presacral region should be weighed against the generally benign course of these lesions, especially with the quality of modern imaging technology.
Inhibition of proliferation of a colon cancer cell line by indole‐3‐carbinol
Authors: Frydoonfar H. R. , McGrath D. R. , Spigelman A. D.
Published: March 2003

Objective

To observe the effect of Indole‐3‐carbinol (I3C), a naturally occurring component of cruciferous vegetables, on cell proliferation of a colon cancer cell line.

Methods

Cell proliferation was measured using three different methods; 3H‐thymidine incorporation, cell count and colourimetric assay.

Results

Each method of measurement revealed that I3C significantly reduced cell proliferation at concentrations of > 0.1 mM.

Conclusion

The present study demonstrates for the first time the capacity of indole‐3‐carbinol to inhibit cell proliferation of a colon cancer cell line.
Transanal endoscopic microsurgery – lessons from a single UK centre series
Authors: Lloyd G. M. , Sutton C. D. , Marshall L. J. , Baragwanath P. , Jameson J. S. , Scott A. D. N.
Published: March 2003

Objectives  Transanal endoscopic microsurgery (TEM), a minimally invasive technique has been employed in the excision of benign and selected malignant rectal tumours since 1983. We present a single surgeon's series of 102 procedures.

Patients and methods  A retrospective case note review of 102 procedures performed over a 6‐year period between 1996 and 2001.

Results  One hundred and two TEM procedures were performed on 100 patients. 68 for adenomas, 19 potentially curative excisions for carcinoma, 13 palliative procedures for advanced carcinoma and 2 for solitary rectal ulcer syndrome (SRUS). Four adenomas recurred and were successfully treated by various procedures. None went on to develop malignancy, or a further recurrence. Of the cancers, six T1 and 10 T2 were excised with curative intent. Three T3 cancers were excised before endorectal ultrasound was available in the unit and went on to have definitive procedures. One T1 and two T2 carcinomas were not completely histologically excised. These patients were offered definitive procedure and there have been no recurrences. 11 patients underwent palliative TEM procedures, 2 went on to have a recurrence of symptoms. Both underwent a successful second TEM procedure.

Conclusions  Although longer term follow up is still required, TEM appears to be an effective method of excising benign tumours and T1 carcinomas of the rectum. The role of TEM in the treatment of T2 carcinomas is, as yet, unclear and needs further evaluation although the results of our series and others are encouraging.
Histological changes associated with the use of intravenous cyclosporin in the treatment of severe ulcerative colitis may mimic dysplasia
Authors: Hyde G. M. , Jewell D. P. , Warren B. F.
Published: March 2003

Background  During six years experience of intravenous cyclosporin (iv Cy) for severe ulcerative colitis we have noted that changes of villous architecture and epithelial regeneration occur even when the disease fails to enter clinical remission and colectomy is required.

Objective  To describe the histological changes in patients who received iv Cy and steroids compared with those treated with iv steroids alone.

Patients and methods  Two groups of histological sections were reviewed. The first group was of 23 colectomy specimens from patients who had been treated with iv Cy and steroids. For 11 patients pre‐Cy histological sections were available. The second group was of 10 colectomy specimens from patients who had received iv steroids alone. Biopsies were scored for their histological disease activity (HDAI), villous architecture and epithelial regeneration. The HDAI assesses the degree of acute and chronic inflammation.

Results  The post‐Cy group had higher median scores for villous architecture and epithelial regeneration compared to the pre‐Cy and poststeroid groups. For the patients where both pre‐ and post‐Cy histological sections were available 63% increased their villous score post‐Cy and 82% increased their epithelial regeneration score post‐Cy.

Conclusion  Although villous transformation and epithelial regeneration may be seen in UC they are more frequent and more severe in those patients who received iv Cy and iv steroids, compared to controls who received iv steroids alone. These histological changes may mimic dysplasia. Increased awareness of this potential mimic of dysplasia is crucial for patient management.
Acute rectal obstruction after PPH stapled haemorrhoidectomy
Authors: Cipriani S. , Pescatori M.
Published: March 2003

An unusual case of acute intestinal obstruction following a PPH stapled haemorrhoidectomy is reported: the complication was due to an almost complete interruption of the rectal lumen tightened by a purse‐string suture anchored by staples. The stricture was dilated and the suture released thus restoring intestinal continuity. Surgeons should be aware that such troublesome complication may occur and can be treated successfully by a transanal approach.
Dysplasia in the ileoanal pouch
Authors: Duff S. E. , O'Dwyer S. T. , Hultén L. , Willén R. , Haboubi N. Y.
Published: March 2003

Formation of an ileo‐anal pouch is an accepted technique following colectomy in the surgical management of ulcerative colitis (UC) and familial adenomatous polyposis (FAP). The configuration of pouches and anastomotic techniques has varied over the last two decades. The increased use of stapling devices in formation of the pouch‐anal anastomosis avoids the need for endoanal mucosal stripping and may contribute to improved functional results, but leaves a ‘columnar cuff’ of residual rectal mucosa in situ. Concerns regarding the long‐term safety of the ileo‐anal pouch have been raised by reports of the occurrence of dysplasia in the pouch mucosa and 15 cases of adenocarcinoma. In UC, persistence of underlying disease in the residual rectal mucosa, anal transition zone and columnar cuff provides the site for development of dysplasia and malignancy. Pouchitis is unlikely to be a major cause of dysplasia or malignancy, as long‐term follow‐up of patients with Koch pouches has demonstrated. In FAP, any persistent rectal mucosa and mucosa of the small intestine is at risk of adenomatous dysplasia due to the genetic alterations causing the disease. Long‐term surveillance should focus on all FAP pouch patients, and in UC patients should be directed towards the diagnosis of residual rectal mucosa in the area distal to the pouch anastomosis. Specialist histopathological opinion is essential in the diagnosis of dysplasia in the ileo‐anal pouch.
Health related quality of life in Crohn's proctocolitis does not differ from a general population when in remission
Authors: Andersson P. , Olaison G. , Bendtsen P. , Myrelid P. , Sjödahl R.
Published: March 2003

Objective  All treatment in Crohn's disease, although palliative, aims at restoring full health. The objective of this study was to compare health‐related quality of life and psychosocial conditions in patients with Crohn's proctocolitis with a general population.

Patients and methods  One hundred and twenty‐seven patients with Crohn's proctocolitis (median age 44 years, 44.1% men) were compared with 266 controls (median age 45 years, 50.7% men). A questionnaire consisting of the Short Form‐36 (SF‐36), the Psychological General Well‐Being Index (PGWB) and a visual analogue scale (VAS) evaluating general health as well as questions regarding psychosocial conditions was used. Disease activity was evaluated by Best's modification of the classical Crohn's Disease Activity Index.

Results  Patients in remission had a health related quality of life similar to controls according to the SF‐36 apart from general health where scores were lower (P < 0.01). Patients with active disease scored lower in all aspects of the SF‐36 (P < 0.001 or P < 0.0001) as well as the PGWB (P < 0.0001). In a model for multiple regression including age, gender, concomitant small bowel disease, permanent stoma, previous colonic surgery, disease activity, duration, and aggressiveness, disease activity was the only variable negatively predicting all 8 domains of the SF‐36 in the patient group (P < 0.001). The mean annual sick‐leave for patients and controls were 33.9 and 9.5 days (P < 0.0001), respectively. Sixty‐eight percent of the patients and 78.4% of the controls (P = 0.04) were married or cohabited, 67.7% and 78.0% (P = 0.04), respectively, had children.

Conclusion  The health related quality of life for patients with Crohn's proctocolitis in remission does not differ from the general population. The disease has, however, a negative impact on parenthood, family life and professional performance.
Acarbose vs. bedtime NPH insulin in the treatment of secondary failures to sulphonylurea‐metformin therapy in type 2 diabetes mellitus
Authors: López‐Alvarenga J. C. , Aguilar‐Salinas C. A. , Velasco‐Perez M. L. , Arita‐Melzer O. , Guillen L. E. , Wong B. , Brito G. , Mercado V. , Gómez‐Pérez F. J. , Rull‐Rodrigo J. A.
Published: March 2003

Objective: To evaluate the efficacy of acarbose in the treatment of secondary failures to sulphonylurea‐metformin therapy, its comparison against bedtime NPH insulin, and to measure the changes in postprandial metabolism resulting from both treatments.

Methods: One hundred type 2 diabetic patients in a secondary failure were included. The study begun with a run‐in diet period of 6 weeks, in which an isocaloric diet was prescribed. Only subjects who continued hyperglycaemic were randomly assigned to placebo and acarbose (n = 17) or bedtime NPH insulin (n = 12). Acarbose (300 mg/day) or placebo were administered using a randomized, double blind, crossover design. Treatment periods of 3 months were separated by a

3‐week washout period. Insulin was administered during 3 months. At the beginning and the end of each treatment period, an i.v. glucose tolerance test and a meal test were performed. Safety tests were done every 4 weeks.

Results: Acarbose resulted in a small but significant improvement in fasting plasma glucose (13.5 ± 2.4 vs. 11.3 ± 3.9 mmol/l, p = 0.05), HbA1c (11.1 ± 3.4 vs. 10.3 ± 2.5%, P = 0.3) and in a decreased plasma glucose during the meal test. Bedtime insulin significantly decreased fasting plasma glucose (13.1 ± 2.9 vs. 8.2 ± 2.3 mmol/l, p < 0.01), HbA1c (11.7 ± 2.9 vs. 9.4 ± 2.7%, p < 0.01) and plasma cholesterol. No change in insulin secretion resulted from insulin and acarbose treatment.

Conclusions: Acarbose decreases blood glucose in secondary failure to sulphonylurea‐metformin therapy; however, the decrease is not enough to reach the desired metabolic control. Bedtime NPH insulin is, by far, a more effective alternative.
Testosterone and leptin in a group of Chinese with and without diabetes
Authors: Ng W. Y. , Lui K. F. , Thai A. C.
Published: March 2003

Aim: Leptin levels in the overweight and differences between men and women may be confounded by sex hormones in obesity‐related type 2 diabetes. We carried out a study of leptin and testosterone and the effect of diabetes on this relationship in 71 Chinese subjects (51 with type 2 diabetes and 20 healthy non‐diabetics) of whom 32 were overweight (body mass index (b.m.i.) > 25.0 kg/m2).

Methods and results: Leptin levels were similar in the diabetic (median 7.4, interquartile range 4.2–10.6 ng ml–1) and non‐diabetic (11.3 (6.0–16.3) ng ml–1) subjects. Testosterone and free testosterone in diabetics and non‐diabetics were similar for both gender. Regardless of diabetes status, testosterone and its free form tend to increase in overweight women and decrease in men. Leptin correlated with testosterone in women with diabetes (Pearson correlation coefficient r = 0.495, p = 0.037) but not in diabetic men. Sixty‐eight per cent of leptin variance was affected by b.m.i, insulin, sex (female) and diabetes status in a regression model that excluded testosterone (total and free). However, testosterone and insulin were predictors of leptin changes in the non‐diabetic subjects. In diabetes, b.m.i., sex (female) and insulin remained as predictors of leptin changes.

Conclusions: These results suggest that apart from body adiposity, testosterone also influences leptin levels and that diabetes has a significant effect on this association.
Insulin resistance: an independent risk factor for cardiovascular disease?
Authors: Balkau B. , Eschwège E.
Published: March 2003

Summary. Population‐based studies have shown that patients with type 2 diabetes have a higher cardiovascular morbidity and mortality and an increased all‐cause mortality compared with non‐diabetic subjects. In non‐diabetic subjects, hyperinsulinaemia not only has been associated with an increased cardiovascular risk, but is also related with a number of other cardiovascular risk factors – hyperglycaemia, hypertension, dyslipidaemia, and a central body fat distribution – that constitute the insulin resistance syndrome and are also characteristic of type 2 diabetes. After 23 years of follow‐up in the Paris Prospective Study, both fasting and 2‐h insulin concentrations were related with all‐cause mortality in a U‐shaped fashion, with low and high concentrations being associated with an increased risk, independently of other risk factors; in contrast, while high insulin levels carried an increased risk for cardiovascular and coronary heart disease mortality, this was not independent of other risk factors.
Time‐course changes in plasma endothelin‐1 and its effects on the mesenteric arterial bed in streptozotocin‐induced diabetic rats
Authors: Makino A. , Kamata K.
Published: March 2003

Aim: To examine the mechanisms underlying the elevated plasma endothelin‐1 (ET‐1) in diabetes and its vascular effects.

Results: Relationships between the plasma ET‐1 level and the levels of other plasma constituents (glucose, cholesterol, and triglyceride) were found in 10‐week streptozotocin (STZ)‐induced diabetic rats. In contrast, at 1 week after the STZ injection only plasma ET‐1 and glucose levels were elevated, suggesting that the hyperglycaemia might trigger the excess production of ET‐1. Incubation with high glucose promoted the release of ET‐1 from the isolated mesenteric arterial bed. In STZ‐induced diabetic rats, the maximum contractile response of the mesenteric arterial bed to ET‐1 was significantly reduced, and the vasoconstriction and vasodilation induced by the ETB‐receptor agonist IRL‐1620 in this bed were significantly impaired. The vascular responses induced by these ET receptor agonists were restored to normal by chronic treatment of diabetic rats with insulin for 7 or 4 weeks.

Conclusions: These results suggest: (1) that the marked increase in plasma glucose in STZ‐induced diabetic rats elevates the plasma ET‐1; and (2) that the decreased contractile and vasodilator responses of the mesenteric arterial bed to ET‐1 receptor agonists may be due to desensitization of not only ETA, but also ETB receptors, an effect secondary to the elevation of plasma ET‐1.
Treatment of familial hypertriglyceridaemia with acarbose
Authors: Malaguarnera M. , Giugno I. , Ruello P. , Maugeri D. , Pistone G.
Published: March 2003

Aim: The evaluation of serum triglyceride levels has played an important role as an independent method for assessing the risk factor for coronary atherosclerosis. Fibrates, nicotinic acid, and omega‐3 polyunsaturated fish oils are the pharmacological tools most used today against hypertriglyceridaemia. Acarbose is a pseudotetrasaccharide of microbial origin which exerts a competitive, selective and reversible inhibition of the intestinal α glucoside‐hydrolase. We evaluated the efficacy and side‐effects of acarbose as a new and alternative drug in the treatment of hypertriglyceridaemia in non‐diabetic patients.

Methods: We enrolled 30 non‐diabetic patients (18 men, 12 women; mean age 59.23 ± 6.27 years) without a family history of diabetes mellitus affected by familial hypertriglyceridaemia. The study covered a total period of 6.5 months: half of the patients were on 1.5 months of ‘run in’ diet only followed by 5 months of therapeutic diet plus acarbose; and half were on the therapeutic diet plus placebo. We gave 30 dividable pills to all patients. The administration was as follows: half a pill before lunch and half a pill before dinner while on the ‘run in’ diet. Fifteen patients (group A) took acarbose while the reminder (group B) took a placebo (50 mg of starch); these were distributed randomly and the test was double blind. The 20 weeks of study were divided in five 4‐week periods. Fasting serum concentrations of total cholesterol, triglycerides, HDL‐cholesterol (HDL‐c), LDL‐cholesterol (LDL‐c) and glucose were determined at the starting of the study and after each treatment cycle. Glucose values were determined 2 h after lunch at the beginning of the study and at the end of the first, third and fifth month of treatment. All parameters assessed have been analysed by anova.

Results: The serum total cholesterol, LDL‐c levels observed in the two groups did not change during the course of treatment. We observed a noteworthy progressive reduction of mean baseline triglyceride levels until the fourth month (p < 0.05) in acarbose‐treated patients, with an increase in HDL‐c (p < 0.008).

Conclusions: We maintain that acarbose may be a useful therapeutic tool in addition to the diet in order to reduce triglyceride serum levels in non‐diabetic patients.
Erythrocyte insulin receptor tyrosine kinase activity is increased in glyburide‐treated patients with type 2 diabetes in good glycaemic control
Authors: Santos R. F. , Nomizo R. , Oliveira E. , Ursich M. , Wajchenberg B. , Reaven G. M. , Azhar S.
Published: March 2003

Aim: The goal of this study was to test the hypothesis that insulin receptor tyrosine kinase activity of isolated erythrocytes would be greater in glyburide‐treated patients with type 2 diabetes in good glycaemic control (n = 13) than in untreated patients (n = 12) with significant fasting hyperglycaemia.

Methods: The two groups were similar in age, sex distribution, and body mass index. By selection, glyburide‐treated patients had significantly (p < 0.001) lower (mean ± s.e.m.) fasting glucose (6.9 ± 0.4 vs. 13.9 ± 0.8 mmol/l) and HbAIC (7.4 ± 0.2 vs. 11.8 ± 0.9%) concentrations. In addition, insulin‐stimulated tyrosine kinase activity was increased in erythrocytes from glyburide ‐treated patients (p < 0.01).

Results: Although insulin receptor number was similar in solubilized erythrocytes from the two groups, tyrosine kinase activity per insulin receptor was significantly (p < 0.02) greater in erythrocytes from glyburide‐treated patients with type 2 diabetes.

Conclusions: These findings are quite similar to previously published data in metformin‐treated patients. As such, it is suggested that decreases in insulin receptor tyrosine kinase activity may contribute to the loss of insulin sensitivity in hyperglycaemic subjects (glucotoxicity), and that an improvement in glycaemic control, irrespective of how it is achieved, will help rectify this abnormality.
N‐phenacylthiazolium bromide decreases renal and increases urinary advanced glycation end products excretion without ameliorating diabetic nephropathy in C57BL/6 mice
Authors: Schwedler S. B. , Verbeke P. , Bakala H. , Weiss M. F. , Vilar J. , Depreux P. , Fourmaintraux E. , Striker L. J. , Striker G. E.
Published: March 2003

Summary

Aims  Advanced glycation end products (AGE), which form from the non‐enzymatic reaction of proteins and sugars, have been implicated in the pathogenesis of diabetic nephropathy. Recently, a compound [N‐phenacylthiazolium bromide (PTB)] has been described which cleaves α,β‐dicarbonyl compounds. In the present study we used diabetic C57BL/6 mice to determine if PTB altered renal AGE levels and reduced diabetic glomerulosclerosis.

Methods  Mice with stable hyperglycaemia induced by streptozotocin were given daily subcutaneous injections of either PTB (10 μg/g) or saline for 12 weeks. Renal‐collagen bound AGE and urinary AGE‐peptides were measured by ELISA using an anti‐AGE‐RNase antibody. Renal collagen‐released Nε(carboxymethyl)lysine (CML) and pentosidine were determined by high pressure liquid chromatography (HPLC). Glomerular lesions (volume and mesangial/total surface area) were evaluated by computer‐assisted image analysis. We determined urinary protein/creatinine ratio as a functional parameter. AGE localization was examined by immunohistochemistry using the anti‐AGE‐RNase antibody.

Results  Renal collagen‐bound AGE were decreased and urinary AGE excretion was increased in PTB‐treated diabetic mice. However, collagen‐released CML and pentosidine were similar in both groups. Glomerular histology and morphometric analysis revealed also no differences between PTB‐and saline‐treated diabetic mice. The urinary protein/creatinine ratio was unaffected by PTB‐treatment. AGE staining by anti‐AGE‐RNase antibody was present in Bowman's capsules, glomerular basement membranes and cortical tubules. It was decreased in all structures in PTB‐treated diabetic mice.

Conclusion  In summary, PTB decreased renal AGE accumulation but did not ameliorate glomerular lesions or proteinuria. Thus, cleavage of AGE by PTB is not sufficient to prevent development of diabetic nephropathy in C57BL/6 mice.
Insulin‐sensitizing action of rosiglitazone is enhanced by preventing hyperphagia
Authors: Pickavance L. C. , Buckingham R. E. , Wilding J. P. H.
Published: March 2003

SUMMARY

Aim  We investigated whether pair‐feeding to prevent hyperphagia would potentiate the insulin‐sensitizing effect of rosiglitazone in chow‐fed and insulin‐resistant dietary obese rats, and studied the role of leptin and hypothalamic neuropeptide Y as mediators of weight gain during treatment.

Methods  Dietary obese and chow‐fed rats (575 ± 10 vs. 536 ± 7 g; p < 0.01) were given rosiglitazone (30 mg/kg p.o.) or vehicle daily for 14 days.

Results  Energy intake and weight gain were greater in rosiglitazone‐treated ad‐lib‐fed rats (body weight: chow + 24 ± 2 g, rosiglitazone‐treated + 55 ± 2 g, p < 0.001; dietary obese + 34 ± 2 g, rosiglitazone‐treated + 74 ± 7 g, p < 0.001). Half of each rosiglitazone‐treated group were pair‐fed to vehicle‐treated controls. Rosiglitazone normalized circulating free fatty acids (FFAs) and insulin sensitivity in dietary obese rats (homeostasis model assessment (HOMA): chow‐fed controls, 3.9 ± 0.3; dietary obese controls, 6.7 ± 0.7; rosiglitazone‐treated, ad lib‐fed dietary obese, 4.2 ± 0.5; both p < 0.01). Insulin sensitivity improved further with pair‐feeding (HOMA: 2.9 ± 0.4; p < 0.05 vs. rosiglitazone‐treated, ad lib‐fed dietary obese), despite unchanged FFAs. Qualitatively similar findings were made in chow‐fed rats. Pair‐feeding prevented rosiglitazone‐related weight gain in chow‐fed, but not dietary obese rats (body weight: + 49 ± 5 g, p < 0.001 vs. untreated dietary obese controls). Adipose tissue OB mRNA was elevated in dietary obese rats, reduced 49% (p < 0.01) by rosiglitazone treatment, and further (by 16%) with pair‐feeding (p < 0.0001). Plasma leptin, however, only fell in the pair‐fed group. Hypothalamic neuropeptide Y mRNA was unchanged throughout, suggesting that weight gain associated with high‐dose rosiglitazone treatment is independent of hypothalamic neuropeptide Y.

Conclusions  Food restriction potentiates the insulin‐sensitizing effect of rosiglitazone in rats, and this effect is independent of a fall in FFAs.
Site‐specific regulation of oestrogen receptor‐α and ‐β by oestradiol in human adipose tissue
Authors: Anwar A. , McTernan P. G. , Anderson L. A. , Askaa J. , Moody C. G. , Barnett A. H. , Eggo M. C. , Kumar S.
Published: March 2003

SUMMARY

Aim  To examine the expression of oestrogen receptors α and β (ERα and ERβ) and their regulation by 17β‐oestradiol (E2) in stromal cells and adipocytes from human subcutaneous (s.c.) and omental (o.m.) adipose tissue.

Methods  Subcutaneous and o.m. abdominal adipose tissues were obtained from 10 women (mean age 63.5 ± 4.8 years; mean weight 75.6 ± 6.7 kg) undergoing elective or cosmetic surgery. Immunohistochemistry and RT‐PCR analysis were used to detect the presence of ERα and ERβ. The regulation of ERα and ERβ by E2 (10−7 M to 10−9 M) was examined using Western immunoblotting analysis in both s.c. and o.m. stromal cells and mature adipocytes cultured in serum‐free, phenol red‐free medium.

Results  Immunostaining of s.c. and o.m. adipose tissue showed that the ER subtypes were localized predominantly within the nucleus. Western analysis demonstrated that E2 treatments differentially altered ERα and ERβ expression in s.c. and o.m. adipocytes. In s.c. and o.m. stromal cells, E2 (10−8 M) produced a significant up regulation relative to control of 66 kDa ERα (s.c.:1.87 ± 0.22; o.m.:1.97 ± 0.17; p < 0.05) and 60 kDa ERβ (s.c.:1.66 ± 0.3; o.m.: 1.68 ± 0.16; p < 0.05). In s.c. adipocytes, however, ERα expression significantly decreased with E2 10−8 M relative to control while ERβ expression increased (ERα 0.58 ± 0.06, ERβ: 1.47 ± 0.11; p < 0.05). In o.m. adipocytes, the inhibition of ERα with E2 was not observed (ERα 1.86 ± 0.36, ERβ:1.03 ± 0.15, p < 0.05)

Conclusions  ERα and ERβ are expressed but differentially regulated by E2 in s.c. and o.m. adipocytes and stromal cells. The upregulation of ERβ by E2 suggests that E2 maintains the expression of these receptors. The feed‐back inhibition of ERα expression by E2 in s.c. but not o.m. adipocytes observed in vitro is consistent with the data from ERα knock out mice where s.c. fat is increased. Selective ER modulators may have different effects in different adipose sites.
Blood glucose‐ and triglyceride‐lowering effect of trans‐dehydrocrotonin, a diterpene from Croton cajucara Benth., in rats
Authors: Silva R. M. , Santos F. A. , Rao V. S. N. , Maciel M. A. , Pinto A. C.
Published: March 2003

Aim: The objective of this study was to assess in rats the antidiabetic effects (i.e. reduction of hyperglycaemia and hypertriglyceridaemia) of trans‐dehydrocrotonin (t‐DCTN), a bioactive diterpene isolated from the popular medicinal plant Croton cajucara.

Methods: Hyperglycaemia was induced by intraperitoneal injection of streptozotocin (STZ) and hypertriglyceridaemia by oral administration of ethanol in rats. The blood glucose levels were measured by the glucose oxidase method using commercially available enzyme kits.

Results: Treating rats with t‐DCTN (50 mg/kg) significantly reduced STZ‐induced increases in blood glucose levels as well as ethanol‐induced increases in blood triglycerides.

Conclusion: The results suggest that t‐DCTN has an antidiabetic potential that warrants further research on its mechanism and clinical significance.
The regulation of HSL and LPL expression by DHT and flutamide in human subcutaneous adipose tissue
Authors: Anderson L. A. , McTernan P. G. , Harte A. L , Barnett A. H. , Kumar S.
Published: March 2003

Clinical observations suggest a role for testosterone in the accumulation of central adiposity and with an associated increased risk of disease. To date, no human study has analysed the role of dihydrotestosterone (DHT) on adipose tissue mass regulation in vitro. This study investigated the role of DHT and androgen receptors (AR) in the regulation of lipolysis and lipogenesis by examining the key enzymes hormone sensitive lipase (HSL) and lipoprotein lipase (LPL) respectively. Isolated abdominal subcutaneous adipocytes (Scad) (n = 15) were treated with either DHT (10−7−10−9 m), an antiandrogen, flutamide (FLT: 10−7−10−9 m) or a combination of DHT (10−7−10−9 m) with FLT (10−8 m). Relative protein expression of HSL, LPL and AR was determined. In Scad, DHT inhibited HSL expression maximally at 10−9 m (0.7 ± 0.4**; p < 0.01**) compared with control (control: 1.0 ± (s.e.m.) 0.0), whereas LPL protein expression was stimulated at DHT10−9 m (2.22 ± 0.48*; p < 0.05*). Glycerol release assay results correlated with HSL expression data. LPL expression was reduced at all doses with combinations of DHT + FLT compared with DHT alone. Androgen receptor expression studies showed an inverse correlation with DHT, whereas DHT + FLT reduced AR expression. These studies indicate that DHT may alter HSL and LPL expression, whereas only LPL expression appears mediated by AR. These findings suggest a physiological role for DHT in the control of adipose tissue mass in women, and indicate that androgens may also play an important role in regulating lipid metabolism.