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Background and aim: Postprandial glycaemia and lipaemia are known risk factors for atherosclerosis in type 2 diabetes. Coagulation activation in the postprandial. state also contributes to acceleration of atherosclerosis. Nateglinide is effective in reducing postprandial glycaemia. Its effect on glycaemia may also be beneficial in postprandial lipaemia and coagulation. The aim of this study was to examine the potential effect of a single dose of nateglinide on postprandial triglyceridaemia, coagulation, and fibrinolysis in patients with type 2 diabetes. Methods and results: Ten subjects with type 2 diabetes, treated with diet alone were recruited in a crossover randomized study. In the morning, after a 12- to 14-h fast, each subject received a standard mixed meat (total energy 783 kcal), preceded by one tablet of 120 mg nateglinide or placebo. Venous blood samples were drawn prior to meat consumption and 6 h afterwards for the measurement of plasma glucose, insulin, and C-peptide, lipids, coagulation, and fibrinolysis factors. As expected, there was a significant reduction in postprandial glycaemia after nateglinide administration compared to placebo (P < 0.001). Plasma insulin levels were significantly higher after nateglinide than after placebo (P = 0.002). Nateglinide administration resulted in a lower overall postprandial reduction of tissue-plasminogen activator than placebo (-2.9 ± 1.3 vs. -8.3 ± 3.7 ng/ml h, P = 0.003). In addition, a significant reduction of postprandial plasminogen activator inhibitor-1 was observed in comparison with the baseline values after nateglinide (P = 0.001), although the overall response was not significantly different after nateglinide and placebo (P = 0.31). Plasma concentrations of C-peptide, lipids and the remaining coagulation parameters studied were not different between nateglinide and placebo. Conclusions: Acute nateglinide administration improves postprandial glycaemia and fibrinolytic activity in patients with type 2 diabetes. This combined effect, if confirmed by a long-treatment study, might reduce cardiovascular risk in type 2 diabetes. © 2005 Published by Elsevier Ltd. Nutrition Metabolism and Cardiovascular Diseases

Multiple myeloma (MM) is charecterized by great clinical heterogeneity. Among known prognostic factors the cytogenetic abnormalities are thought to be of major importance. The aim of this study was to correlate certain chromosomal abnormalities with immunoglobulin isotype and survival in MM patients.Forty-nine Greek MM patients, homogeneously treated with conventional-dose chemotherapy, were cytogenetically studied by direct culture of bone marrow cells and G-banding technique.Twenty-four patients had a normal karyotype while the remaining 25 patients presented numerical and structural abnormalities. Recurrent structural abnormalities were observed. Translocations involving the 14q32 region were observed in 8 cases, while 6 cases exhibited a del(1)(p12). We confirmed the negative impact of chromosomal abnormalities on the overall survival of MM patients and we also showed that t(11;14) had a worse impact on disease outcome as compared to t(14q32) with an unidentified partner chromosome. The presence of del(1) (p12) significantly worsened the prognosis in MM patients. No correlations existed between the association of immunoglobulin isotype with survival or certain chromosomal changes.Further studies are indicated at the molecular level to clarify the exact role and the prognostic value of 1p12 involvement in MM patients.

Subclinical hypercortisolism (SH) is detected increasingly in a substantial proportion of patients with incidentally discovered adrenal adenomas. The clinical implications of SH are currently unclear. Osteoporosis is a well-known complication of glucocorticoid excess. So far, the impact of SH on bone mineral density (BMD) has been studied in a limited number of reports with discordant results. In the present study we evaluated the BMD in a large cohort of post-menopausal women with adrenal incidentalomas. : patients and measurements Forty-two post-menopausal women with incidentally discovered adrenal masses and radiological features highly suggestive of benign adrenal adenomas were investigated. All patients underwent a standard low-dose dexamethasone suppression test (LDDST; 0.5 mg 6-hourly for 2 days). The diagnosis of subclinical hypercortisolism (SH) was based on post-LDDST cortisol concentrations of70 nmol/l. According to this criterion patients were subdivided into two groups: with (n = 18; group A) or without (n = 24; group B) SH. There was no significant difference in age, years since menopause and body mass index between these groups. BMD was measured at L2-L4 vertebrae and three sites of the proximal femur by the dual energy X-ray absorptiometry (DEXA) method.Post-menopausal women with SH (group A) exhibited slightly but significantly lower absolute and age-adjusted BMD values compared to group B patients in the femoral neck (BMD g/cm2: 0.72 +/- 0.08 vs. 0.79 +/- 0.09; Z-score: -0.20 +/- 0.82 vs. +0.43 +/- 0.94, P0.05) and trochanter (BMD g/cm2: 0.60 +/- 0.09 vs. 0.69 +/- 0.10; Z-score: -0.32 +/- 1.0 vs. +0.30 +/- 1.05, P0.01). BMD measurements of the Ward's triangle were also lower in group A patients but the difference did not reach statistical significance (BMD g/cm2: 0.60 +/- 0.10 vs. 0.68 +/- 0.13, P = 0.06). There was no difference in the lumbar vertebrae between the two groups (BMD g/cm2: 0.888 +/- 0.13 vs. 0.90 +/- 0.16, P = 0.78; z-score: +0.50 +/- 1.16 vs. +0.11 +/- 1.5, P = 0.36). The number of patients in the osteoporotic range was minimal with no significant difference between the two groups. However, the frequency of osteopenia in group A was significantly greater than in group B patients in the trochanter and Ward's triangle areas. Serum osteocalcin (BGP) levels were significantly lower in group A compared to group B patients (18.6 +/- 8.6 vs. 26.2 +/- 8.1 ng/ml, P0.01); no difference existed regarding parathyroid hormone (PTH) concentrations (43 +/- 15.6 vs. 41.2 +/- 14.8 pg/ml, P = 0.72).In this series, post-menopausal women with subclinical hypercortisolism had lower absolute and age-adjusted BMD values and a higher rate of osteopaenia in the trabecular loaded and mixed cortical-trabecular bone of proximal femur. These data demonstrate that the subtle hypercortisolism of patients with adrenal incidentalomas may have an adverse effect on the bone mass of these patients.

There are no guidelines on second-line therapies for Helicobacter pylori eradication failures of omeprazole-clarithromycin-amoxicillin triple therapy.To compare the efficacy of two second-line therapies for persistent H. pylori infection.Over a 6-year period, patients with persistent H. pylori infection following omeprazole-clarithromycin-amoxicillin eradication therapy were randomized to receive omeprazole, 20 mg twice daily, bismuth, 120 mg four times daily, metronidazole, 500 mg twice daily, and either tetracycline, 500 mg four times daily, or clarithromycin, 500 mg twice daily, given for 7 days. Before therapy, patients underwent endoscopy with biopsies for histology, culture and antibiotic susceptibility tests. H. pylori infection was confirmed by histology.Of the 95 randomized patients, 88 (93%) completed the study. Age, sex, smoking, ulcer/non-ulcer dyspepsia ratio and antibiotic resistance were not significantly different between the treatment groups. On intention-to-treat analysis, eradication was achieved in 41 of the 49 patients (84%; 95% confidence interval, 70.4-92.7%) and 27 of the 46 patients (59%; 95% confidence interval, 43.3-73.0%) of the tetracycline- and clarithromycin-containing groups, respectively (P=0.007). On multivariate regression analysis, the sensitivity of H. pylori to metronidazole had a likelihood ratio of 5.2 (P=0.022), followed by the type of quadruple therapy (likelihood ratio, 4.4; P=0.036).Tetracycline-containing quadruple rescue therapy is highly effective in treating H. pylori eradication failures of the omeprazole-amoxicillin-clarithromycin regimen.

Splenectomy in patients with non-Hodgkin's lymphoma (NHL) is performed for either diagnostic or therapeutic reasons. We report on a series of 29 patients with NHL and splenomegaly who underwent splenectomy during the years 1979-1998 in our hospital. According to the indication for splenectomy our patients were categorized in three groups. Group A: In 20 patients splenectomy was performed for diagnostic reasons. Group B: Three patients were splenectomized for autoimmune haemolytic anaemia (AIHA). Group C: Six patients underwent splenectomy because of hypersplenism. A definitive histopathological diagnosis of NHL was obtained in all patients of group A. Hypersplenism and AIHA were resolved in all patients after splenectomy. One (3.5%) patient died postoperatively because of septicemia complicated by disseminated intravascular coagulation. Six postoperative complications were observed in 4 (14%) patients. Splenectomy, with an acceptable surgical risk, has the potential to establish the diagnosis of NHL in patients with splenomegaly without lymphadenopathy and negative bone marrow findings. Moreover, splenectomy has the capacity to modify the disease course in patients with NHL complicated by AIHA or hypersplenism.

Treating patients with erosive esophagitis and maintaining remission in a cost-effective fashion is a desirable goal in clinical practice. There are no established criteria to identify patients with healed esophagitis who will subsequently remain in remission with low-dose omeprazole therapy. We investigated whether 24-h esophageal-gastric pH monitoring could provide criteria to select patients for low-dose omeprazole maintenance therapy.Seventy consecutive symptomatic outpatients with grade 2-3 reflux esophagitis were prospectively investigated. They were treated with 20 mg/day omeprazole for 2 months. Those with healed esophagitis were given alternate-evening 20-mg omeprazole maintenance therapy for 6 months. Clinical evaluation, endoscopy, and 24-h esophageal-gastric pH were done at the end of each treatment period. Results of pH studies of patients in remission were compared with those with endoscopically documented relapse of esophagitis.In 63/70 patient (intention-to-treat, 90%; 95% confidence interval [CI], 83-97%) esophagitis was healed at 2 months. During the 6-month maintenance period esophagitis remain healed in 28 (G1) (40%; 95% CI, 29-52%), but recurred in 32 patients (G2). During healing with omeprazole 20 mg/day the 24-h gastric pH was below 4 for10% of the time in 96% of the patients, who subsequently remained in long-term remission with low-dose maintenance therapy (G1), but not in any patient with recurrence of esophagitis (G2). The 10% threshold value has a specificity of 1.00 and sensitivity of 0.96.The 24-h intragastric pH monitoring during 20 mg/day omeprazole therapy provides criteria by which to preselect patients with reflux esophagitis who will remain in remission with low-dose omeprazole therapy.

Early menopause, whether it be natural or surgical, is one of the established risk factors for osteoporosis. Surgical menopause, however, differs from natural menopause owing to the abrupt cessation of estrogen secretion. This study attempts to investigate the influence of menopause type on bone mineral density (BMD) changes.Four groups, each consisting of 30 women, were compared: early menopause (EMP), surgical menopause (SUMP) and two groups of natural menopause. The two groups share a similar number of years since menopause (YSM) but have a different chronological age (NMPO), or share a similar age but different YSM (NMPY) to the EMP and SUMP. BMD was measured by the DXA method at L2-L4 vertebrae and proximal femur.Mean vertebral BMD of EMP was lower than that of SUMP (P0.05) and of NMPY (P0.001) women. Femoral neck BMD did not differ between SUMP and EMP women but both exhibited significantly lower BMD than either natural menopause groups. BMD of SUMP and vertebral BMD of NMPY women was inversely correlated to chronological age and to number of YSM. Pertaining to T-score values according to the osteoporotic range, NMPO, EMP and SUMP women being homogeneous exhibited significantly lower values than NMPY in the vertebrae (F-ratio = 7.84, P0.001). Whereas, in the femoral neck and the trochanter major, EMP and SUMP categories presented significantly lower T-score values than the NMPO and NMPY (F = 3.61, P0.01 and 2.8, P0.05 respectively).Women with early menopause exhibit lower vertebral BMD than women of similar age after either surgical or natural menopause. In women of similar age, surgical menopause results in lower vertebral and femoral neck densities compared to natural menopause. Chronological age and the interval after menopause negatively affects bone density in women with similar age whether in surgical or natural menopause.

Follicular gastritis is an important histological entity, because it may progress to overt gastric MALT lymphoma. However, there is no universal agreement on whether there is any correlation of follicular gastritis with histological features of the antral mucosa or on the prevalence of follicular gastritis. To shed further light on these issues, we studied antral biopsies obtained from 735 adult patients, who had participated in six consecutive clinical trials. They included 348 patients with duodenal ulcer, 82 with gastric ulcer, and 305 with nonulcer dyspepsia. The Sydney classification system of gastritis was used, using a score of 0-3 to grade degree and activity of inflammation, gland atrophy, intestinal metaplasia, and H. pylori colonization density. Follicular gastritis was defined as prominent lymphoid follicles with no lymphoepithelial lesion. None of the H. pylori-negative patients (N = 159) had follicular gastritis. Among H. pylori-positive patients, 80/340 (23.5%) with duodenal ulcer, 5/77 (6.5%) with gastric ulcer, and 20/159 (12.6%) with nonulcer dyspepsia had follicular gastritis (P0.001). Multivariate discriminant analysis selected the following four significant predictor variables for follicular gastritis (Wilks lambda = 0.91, chi2 = 70.6, df = 4, P0.001): gastritis sum score, atrophic gastritis, age of the patient, and disease. The prevalence of follicular gastritis was linearly correlated (gamma = 24.55 - 0.98chi, r = -0.62, F1,11 = 6.12, P = 0.03) with the age groups of the 576 H. pylori-positive patients studied. In conclusion, follicular gastritis is highly correlated with H. pylori-caused severe, active gastritis. It is mostly prevalent in the young H. pylori-infected patients with duodenal ulcer.

In a double-blind, randomized study, miglitol (BAY m 1099), an alpha-glucosidase inhibitor, 100 mg tds or placebo was given orally with meals for a period of 24 weeks in 117 patients with Type 2 (non-insulin-dependent) diabetes mellitus (DM) treated with insulin. Fasting and 1 h postprandial plasma glucose and C-peptide were measured at the beginning and at the end of each 4-week interval and glycosylated haemoglobin was determined at day 0 and at the end of the 12th and 24th week. One hour postprandial plasma glucose was significantly lower in the miglitol group at the end of the 24th week (placebo: 11.6 +/- 1.5 vs miglitol: 8.2 +/- 1.5 mmol l-1, mean +/- SD, p = 0.001). Diabetes control improved in the same group as the HbA1 was lowered by 16% (p =0.0001) at the end of the treatment. Mild reversible adverse effects were observed in 37 patients of the miglitol group (mainly flatulence and mild hypoglycaemia) and 2 of the placebo group. Urinary glucose was rendered negative in 41 patients in the miglitol group only. Thus miglitol appears to be a safe and effective adjunct in the management of Type 2 DM, in association with insulin.

Summary OBJECTIVE The few published prospective studies suggest a strong association of colonic tumours with acromegaly, but include small numbers of patients. In addition, the upper gastrointestinal tract of these patients has never been prospectively studied. The aim of the present study was to investigate the incidence of gastric and colonic tumours in a large cohort of acromegalic patients. DESIGN Acromegalic patients consecutively admitted to an Endocrinology Department for diagnosls and follow-up, were submitted to gastroscopy and colonoscopy, to identify those harbouring gastrointestinal tumours. PATIENTS Over a 5-year period, 54 out of 61 patients (78% with active disease) received colonoscopy and 42 out of 61 gastroscopy. No patient had a past history of gastrointestinal malignancy. MEASUREMENTS All polypoid lesion8 found at colonoscopy and gastroscopy were separately recorded and biopsled. RESULTS No case of gastrointestinal cancer or gastric polyp was discovered. Nineteen patients (35%) had 1-8 colonic polyps, including 5 (9·3%) with adenomas. When compared to patients with a normal colon, those with polyps were significantly older (44·±14· vs 52· f 10·9 years, P= 0·47), but the duration of acromegaly (10·±8· vs 10·±7· years, P= 0·9) and the number of patients with active disease were similar in both groups. CONCLUSIONS Acromegalic patients do not have an increased incidence of gastric tumours. The observed significant variation in the prevalence of colonic adenomas (9-35%, P= 0·03) and cancer (0-15%, P= 0·017), between our patients and those of the published prospective studies with similar demographic characteristics, suggest that environmental and hereditary factors may be more important than the presence of acromegaly.

The magnitude of complex carbohydrate malabsorption in exocrine pancreatic insufficiency has not been well quantified in the past. The quantity of carbohydrate malabsorbed after a rice starch (100 g) meal in 20 patients with chronic pancreatitis (n = 10) or pancreatic cancer (n = 10) was therefore estimated. Patients had a three day stool fat collection (80 g/24 hour fat intake), a lactulose (20 g), and a rice flour (100 g) breath hydrogen test. Normal controls (n = 29) had a postprandial H2 increase < or = 14 ppm and malabsorbed (mean (SEM)) 1.12 (0.44) (range 0-11.10) g of the 100 g of carbohydrate ingested. Patients malabsorbed significantly more carbohydrate (11.36 (2.23) (range 8.90-32.60) g, F1.47 = 29.92, p < 0.001). The number of patients with fat (> 7 g, n = 8) or carbohydrate (increase in H2 > or = 20 ppm, n = 10) malabsorption was not different (chi 2 = 0.10, p = 0.75). There was a significant correlation between faecal fat and amount of malabsorbed carbohydrate (r = 0.60, F1.17 = 9.70, p = 0.006) and faecal fat and stool wet weight (r = 0.57, F1.18 = 8.67, p < 0.009), but not between stool wet weight and amount of malabsorbed carbohydrate (r = 0.28, F1.17 = 1.45, p = 0.25). Although patients with exocrine pancreatic insufficiency malabsorb 10%-30% of the ingested complex carbohydrate, the main determinant of stool wet weight could be faecal fat.

The significance of main pancreatic duct width in the diagnosis of pancreatic disease, was studied in 338 endoscopic retrograde pancreatographies. Two hundred and forty patients referred for suspected biliary disease had normal pancreatograms (Group 1), 60 had pancreatic carcinoma (Group 2) and 38 had a history and pancreatogram compatible with chronic pancreatitis (Group 3). After categorizing patients by decade, in group 1 the effect of aging on the pancreatic duct width in the head, body and tail (F5,2343.71, p0.003) was pronounced, especially after the fifth decade. There was a significant difference between groups 1, 2 and 3 in terms of the width of the main pancreatic duct in all three parts of the pancreas (F2,32542.24, p0.001). The upper range of normal pancreatic duct width was 8.0 mm, 4.0 mm and 2.4 mm in the head, body and tail, respectively. Abnormal ductograms were wider than the normal ranges in the head, body and tail of the pancreas in 14%, 49% and 59% (p0.001) of the patients, respectively. Establishing normal ranges of the pancreatic duct width may help in the diagnosis of pancreatic disease. Measurements in the body and tail, as compared with the head, are a more sensitive indicator of pancreatic duct dilation.

In order to investigate the relationship between the in vivo platelet activity and diabetic macroangiopathy we have measured plasma beta-thromboglobulin (beta-TG) concentrations by means of a very sensitive radioimmunoassay in 55 diabetics, aged 47-80 years, and in 27 non-diabetic healthy controls (group A) of respective age and sex. Among diabetics 17 were free of vascular complications (group B) in terms of diabetic micro- or macroangiopathy, while the remaining 38 (group C) suffered from peripheral occlusive arterial disease (POAD) of the lower limbs. All subjects underwent a thorough clinical and laboratory investigation. The diagnosis of POAD was based upon the findings of Doppler ultrasound examination and was confirmed by selective arteriography. The mean plasma beta-TG concentrations were significantly higher in the two groups of diabetics compared to the non-diabetic controls (p0.001), whereas the highest beta-TG levels were found in diabetics with POAD (py 0.001), (beta-TG: mean +/- 1 SD ng/ml; group A: 26.50 +/- 13.14; group B: 55.88 +/- 26.56; group C: 106.50 +/- 52.65). These findings reveal an increased release reaction of platelets in diabetics and an enhanced in vivo platelet activity especially in POAD subjects. However, this may occur not only in cases with prominent macroangiopathy but also in the early stages of diabetic angiopathy when the vascular lesions cannot be traced clinically.