Evaluation of beta cell dysfunction by mixed meal tolerance test and oral L-arginine in patients with newly diagnosed type 2 diabetes mellitus.

BACKGROUND AND AIMS: Defective insulin secretion is required for the development of frank diabetes mellitus. We evaluated the secretory response of pancreatic beta cells after the ingestion of mixed meal plus oral L-arginine in newly diagnosed type 2 diabetic patients. MATERIALS AND METHODS: Twenty-four newly diagnosed type 2 diabetic patients were enrolled in this study. All patients were ingested a mixed meal of 553 kcal. Serum insulin levels were measured at time 0 just before the mixed meal and at 1, 2, 3, 4 and 5 h after the ingestion of the mixed meal. Twenty-four hours later, all patients ingested mixed meal followed by oral 8 g L-Arginine, and insulin levels were again measured at 0, 1, 2, 3, 4 and 5 h after the ingestion of the meal. RESULTS: Insulin levels reached to peak values at the 2 (nd) hour, and decreased to baseline levels at the 5 (th) hour measurements both after the ingestion of mixed meal only and after the ingestion of mixed meal plus oral L-Arginine. First and 2 (nd) hour insulin levels were significantly higher after the ingestion of mixed meal plus oral L-Arginine. CONCLUSION: In this study we used for the first time the combination of oral L-arginine with mixed meal test to evaluate the beta cell dysfunction in type 2 diabetic patients. Increments regarding serum insulin levels after the ingestion of mixed meal plus oral L-Arginine suggest that oral L-Arginine could be benefical for the evaluation of beta cell function and secretory defects.

Association of the angiotensinogen M235T and angiotensin-converting enzyme insertion/deletion gene polymorphisms in Turkish type 2 diabetic patients with and without nephropathy.

OBJECTIVE: Recent studies have suggested an association between a deletion variant of the angiotensin-converting enzyme (ACE) gene and diabetic nephropathy. However, this finding has not been confirmed by all investigators. Furthermore, an M235T variant of the angiotensinogen (AGT) gene has been associated with hypertension, an important risk factor for the development and progression of diabetic nephropathy. RESEARCH DESIGN AND METHODS: We investigated the relationship of the ACE insertion/deletion (I/D) and AGT M235T gene polymorphisms in Turkish patients with type 2 diabetes mellitus (DM) with and without diabetic nephropathy. A total of 102 individuals were screened for the presence of the ACE I/D and AGT M235T polymorphism: 46 individuals who had type 2 DM with diabetic nephropathy and, as controls, 56 individuals who had type 2 DM without diabetic nephropathy. Gene polymorphisms were determined by the specific melting temperature (T(m)) values of the resulting amplicons after real-time online polymerase chain reaction and melting curve analysis. RESULTS: The frequencies of the ACE DD, ID, and II genotypes were 34.8%, 37.0%, and 28.3%, respectively, among type 2 diabetic patients with nephropathy, and 33.9%, 42.9%, 23.2%, respectively (P=.788), in the control subjects without diabetic nephropathy. On the other hand, the frequencies of the AGT MM, MT, and TT genotypes among the same groups were 26.1%, 52.2%, 21.7% and 26.8%, 57.1%, 16.1%, respectively (P=.758). CONCLUSIONS: There were no differences in the frequencies of the AGT M235T and ACE I/D genotypes between Turkish patients with type 2 DM with and without nephropathy.

The prevalence of RET/PTC mutations in papillary thyroid cancers in Turkish population and its relation between tumor histopathology and prognostic factors.

OBJECTIVE: In recent years, thyroid cancer has been at the forefront of molecular pathology as a result of the consequences of the Chernobyl disaster and the recognition of the role of RET/PTC rearrangements in papillary thyroid carcinomas (PTCs). Correlation of RET/PTC expression with clinical outcome is controversial. This study aims to identify the prevalence of RET/PTC oncogene expression in Turkey, and to investigate the correlation between RET/PTC oncogene expression and the known prognostic factors of PTC in 101 patients. METHODS: The RET rearrangements were examined by means of reverse transcriptase-polymerase chain reaction analysis, with primers flanking the chimeric region. Statistical evaluation was performed by using Independent samples t-test, One-sample Chi-square test and Pearson Chi-square or Fisher's Exact Test. RESULTS: RET/PTC was determined positive in 67(66.3%) of totally 101 patients (p<0.001). RET/PTC1 in 32(31.7%), RET/PTC3 in 21(20.8%), RET/PTC1+RET/PTC3 both in 10(9.9%) patients were found to be positive. There was RET/PTC2 positiveness in two patients, RET/PTC2,3 positiveness in one patient, and RET/PTC1,2,3 positiveness in one patient. No statistical difference was found between RET/PTC1 and RET/PTC3. None of genetico-clinical analyses showed any significant association between RET/PTC expression and the clinical and pathological features of the cancers. CONCLUSION: While this prevalence of the RET/PTC is less than RET/PTC frequency seen after Chernobyl in Belarus, its prevalence in our region is also high (66.3%). As a result, no significant correlation was found in between prognosis and RET/PTC frequency.

Demographic and clinical features of patients with subacute thyroiditis: results of 169 patients from a single university center in Turkey.

BACKGROUND: Turkey is an endemic area for thyroid diseases. The Aegean region is well documented for increased prevalence of thyroid disorders. In this study we investigated the demographic and clinical features of subacute thyroiditis (SAT) patients who had been diagnosed and treated in Ege University. METHODS: The hospital files of patients admitted to the endocrinology clinic of Ege University between January 1987 and December 2001 were retrospectively evaluated. Patients who had been diagnosed as having any thyroid disorder were determined. RESULTS: 176 fulfilled diagnostic criteria for SAT. The majority of patients with SAT were diagnosed as having subacute granulomatous thyroiditis (169/176) (134 females, 35 males, mean age 34.0+/-17.8 yr); 69% of the patients were between 30-50 yr of age. Thyroid pain was present in 97.1% of female patients, and in 100% of male patients. High fever was evident in 78 patients (46.2%). Mean erythrocyte sedimentation rate (ESR) was 43.42+/-39.68 mm/h. Anti-thyroglobulin antibody was positive in 20%, and anti-thyroid peroxydase antibody was positive in 4% of patients. Among patients who were treated with non-steroidal anti-inflammatory drugs (NSAD) 10 female patients (10.6%), and 3 male patients (12%) developed recurrence of the disease. Among patients who were treated with prednisolone 7 female patients (17.5%), and one male patient (10%) developed recurrence. There was no significant difference regarding the recurrence rates between patients who were treated with NSAD and patients who were treated with prednisolone. CONCLUSION: With the exception of ESR, demographic, clinical, laboratory, and imaging findings and prognoses of our patients were comparable to the previous reports.

Fas/Fas ligand gene polymorphism in patients with papillary thyroid cancer in the Turkish population.

OBJECTIVE: Fas ligand (FasL) is an apoptotic agent and a member of tumor necrosis factor (TNF) family. FasL exists in cytotoxic T lymphocyte (CTL) and natural killer (NK) cells, and it is increased in tumor cell membrane. On the contrary, CTL and NK are bound to Fas on the surfaces of cell membrane; this triggers apoptosis in cytotoxic cells and leads to their death. This system plays an important role in eliminating viral infections and cancer cells. Malfunction of this system results in the development and spread of the malignancy. This study aims at evaluating the influence of Fas and FasL gene polymorphism in papillary thyroid cancer (PTC) in the Turkish population. RESEARCH DESIGN AND METHODS: Forty-five patients with PTC and 100 healthy controls were included in this study. The diagnosis of PTC was confirmed by histopathologic examination after surgery. The evaluation of genotype for Fas 670 A/G and FasL 843 C/T gene polymorphism was performed using the PCR-restriction fragment length polymorphism (RFLP) method. RESULTS: The evaluation of Fas/FasL genotype and gene allele frequency did not show statistically significant differences between the patient and control group (p>0.05). In addition, the univariate analysis did not reveal a statistically significant relationship between the size of the nodule and the Fas/FasL gene polymorphism in patients with PTC. CONCLUSIONS: As in other types of malignancy, genetic factors in the pathogenesis of PTC may also show changes in different populations. Fas/FasL gene polymorphysms are possible that different mechanisms function in apoptosis balance in PTC development.

Dehydroepiandrosterone and human adipose tissue.

OBJECTIVE: The aim of this study was to investigate whether DHEA alters the proliferation and differentiation of human sc and visceral adipose cells in primary cultures. METHOD: Sc and omental adipose tissue was obtained from 10 female donors aged 36+/-3.6 yr with a body mass index (BMI) of 33+/-3.21 kg/m2. Stromal vascular cells were isolated and cultured using modified procedures described by Entenmann and Hauner. For the proliferation assay, stromal-vascular cells from sc and visceral adipose tissue cultures were fed with proliferation media containing 0, 25 or 100 microM DHEA for 3 days. At the end of this treatment period, two type cultures were prepared for determining their metabolic activity using the sulforhodamine B staining procedure. RESULTS: The metabolic activity of proliferating human visceral adipose tissue was higher than sc adipose tissue. The activity of proliferating human visceral tissue cultures decreased more than the sc tissue as the level of DHEA in the cultures was increased. CONCLUSIONS: These data suggest that DHEA predominantly influences the proliferation and differentiation of human omental adipose tissue.

Preprandial repaglinide decreases exogenous insulin requirements and HbA1c levels in type 2 diabetic patients taking intensive insulin treatment.

In this study, we investigated the effects of combining preprandial repaglinide to the insulin therapy for reducing the exogenous insulin requirements and serum HbA(1c) levels in type 2 diabetic patients whose blood glucose levels were previously regulated by multiple dose intensive insulin therapy. Fifty patients with type 2 diabetes who had been initially treated with oral antidiabetic agents without a satisfactory response were included in this study. After adequate glycemic control was achieved with intensive insulin therapy, the patients were divided into two subgroups. The first group continued with intensive insulin therapy. The second group received a combination of multiple insulin injections and oral repaglinide (1.5 mgr tid). The doses of insulin injections were gradually decreased accordingly in the second group. Both groups were followed-up for 3 months. Repaglinide was well tolerated and had no toxicity. A significant reduction regarding exogenous insulin requirements and serum HbA(1c) levels were demonstrated in patients taking preprandial repaglinide (p<0.01). Combining repaglinide to intensive insulin therapy could be a safe and effective alternative to intensive insulin therapy alone for the glycemic control and for reducing exogenous insulin requirements in type 2 diabetic patients.

Spontaneous rupture of extrahepatic choledochal cyst: two pediatric cases and literature review.

Spontaneous rupture of extrahepatic choledochal cysts is very rare. Neonatal cases generally present with biliary ascites, and older children with acute abdomen. Although the cause is unclear, accumulation of protein plugs in an anomalous pancreaticobiliary junction, irritation of the cyst wall due to reflux of pancreatic juice, and weakness due to a developmental error such as common channel syndrome have all been suggested to play contributing roles. The treatment of choice is complete excision of the cyst and hepatico-jejunostomy. In newborns who are in a poor condition, the primary treatment should be simple peritoneal drainage.

CT findings in skeletal cystic echinococcosis.

PURPOSE: To evaluate the CT findings of skeletal cystic echinococcosis. MATERIAL AND METHODS: CT findings of 7 patients with pathologically confirmed skeletal cystic echinococcosis were evaluated. RESULTS: There were 4 men and 3 women, aged 36-75 years. Hydatid cysts were located in the spine (n=2), a rib (n=3), the pelvis and a vertebra (n=1), the pelvis and the left femur (n=1). The size of the lesions varied from 1 cm to 15 cm. CT showed well defined, single or multiple cystic lesions with no contrast enhancement, no calcification, no daughter cysts, and no germinal membrane detachment. The cystic lesion had a honeycomb appearance in 2 cases; there was pathologic fracture in 2 cases, bone expansion in 5 cases, cortical thinning in 6 cases, cortical destruction in 6 cases, bone sclerosis in 1 case, and soft tissue extension in 6 cases. CONCLUSION: Preoperative differential diagnosis of skeletal cystic lesions should include cystic echinococcosis, especially in endemic areas, since this diagnosis may easily be missed unless kept in mind.

Lumbosacral extrarenal Wilms' tumour: a case report and literature review.

UNLABELLED: Occurrence of extrarenal Wilms' tumour (WT) is very exceptional and the diagnosis is almost always made after surgical intervention. The tumour can be located in the retroperitoneum, uterus, cervix, testes, skin and even in the thorax. The exact mechanism whereby a WT occurs in extrarenal tissues is not known. The presence of ectopic metanephric blastema cells or the WT gene that cause transformation of extrarenal primitive mesonephric or pronephric remnants into WT are both considered in the embryogenesis. Although ultrasonography and CT scan are both helpful in the definition of retroperitoneal tumours, there is no characteristic finding to diagnose an extrarenal WT before surgery. However the histological characteristics are the same as in intrarenal WT, a retroperitoneal teratoma should be clearly investigated for a possible admixture of WT cells. Patients with extrarenal WT are given the same treatment protocol as patients with stage III WT. In this paper, a 5-year-old female patient with an extrarenal WT located in the lumbosacral region is presented. CONCLUSION: as a rule, diagnosis of extrarenal Wilms' tumour is made after surgery. Surgical excision is the treatment of choice and the same general therapeutic rules should be followed as when the kidney were affected. Stage III guidelines for chemotherapy and radiotherapy are appropriate in these patients.

Pictorial essay. Various locations of cystic and alveolar hydatid disease: CT appearances.

Hydatid disease (echinococcosis) is a parasitic infection caused by the larval stage of the tapeworm Echinococcus. In humans, the two main forms are cystic hydatid disease, caused by E. granulosus, and less frequently alveolar hydatid disease, caused by E. multilocularis. They can be found in various sites in the body. The purpose of this essay is to illustrate the CT appearances of cystic and alveolar hydatid disease in various locations.

Various diffuse infiltrative lung diseases: high resolution computed tomography appearances.

High resolution CT (HRCT; 1-2 mm collimation scans reconstructed with a high spatial frequency algorithm) is an established technique for the evaluation of diffuse infiltrative lung diseases. For many of these diseases, the features shown on HRCT correlate well with the histopathological abnormalities. The purpose of this pictorial essay is to illustrate HRCT appearances in various diffuse infiltrative lung diseases.

Evaluation of routine basal serum calcitonin measurement for early diagnosis of medullary thyroid carcinoma in seven hundred seventy-three patients with nodular goiter.

The aims of the study were to identify medullary thyroid cancer (MTC) in its earliest stages by screening patients with basal calcitonin measurements and to determine whether basal serum calcitonin measurements should be a part of the routine evaluation of a nodular goiter. Basal serum calcitonin levels were obtained from 75 patients (female:male 57:18, mean age 42.8 years, range with 18-76 years) with nonnodular thyroid disease as controls. Their mean basal calcitonin level was 7.8+/-0.4 pg/mL with a range of 5-27 pg/mL. Seven hundred seventy-three patients with nodular goiter were included in the study (female:male 586:187) with the mean age of 46.1 years (range 17-78). Four patients had elevated basal serum calcitonin levels ranging between 150-1000 pg/mL. These 4 patients underwent surgery. MTC was confirmed by histopathology in all 4. One patient's mother and brother were also diagnosed as MTC as a result of family screening. Basal serum calcitonin levels were higher than 150 pg/mL in these patients. Fine needle aspiration biopsy (FNAB) of 2 of 4 MTC patients were incorrectly diagnosed as papillary carcinoma; another had malignant cytology and the fourth had benign cytology. None were diagnosed as MTC on the basis of FNAB. In conclusion, calcitonin measurement is an effective method for the diagnosis of MTC. Measurement of basal calcitonin levels in patients with malignant or suspicious FNAB may be a cost-effective approach to screen for MTC. High basal serum calcitonin levels increase the chance of curative therapy by diagnosing MTC in the early stages. It is superior to FNAB for diagnosis of MTC.

Triiodothyronine antibodies in patients with goiter.

OBJECTIVE: To investigate the prevalence of triiodothyronine (T(3)) antibodies in patients with goiter, the influence of these antibodies on the results of thyroid hormone measurements, and the potential relationship between T(3) antibodies and thyroid autoantibodies. METHODS: We undertook a study of 100 healthy control subjects (80 female and 20 male subjects) who had no clinical or biochemical evidence of thyroid disease and 100 patients (81 female and 19 male patients) with goiter. Serum concentrations of total T(3), total thyroxine, free T(3), and free thyroxine were measured by radioimmunoassay kits with a coated tube method. An immunoprecipitation method was used to detect anti-triiodothyronine auto-antibodies. RESULTS: Patients with a T(3) antibody binding ratio +3 standard deviations (SD) above the mean for the normal control group were considered to have T(3) antibodies. Normal control group binding was 2.4 +/- 1.3%. On the basis of +3 SD, seven patients had T(3) antibodies. The mean serum total T(3) level was 1.61 +/- 0.1 nmol/L in patients with binding ratios above +3 SD, whereas the mean serum total T(3) level was 2.23 +/- 0.3 nmol/L in patients without T(3) antibodies. Thus, patients with a binding ratio above +3 SD had a significant decrement in total T(3) levels. No correlation was found between the presence of T(3) antibody and antimicrosomal and antithyroglobulin antibodies. CONCLUSION: When serum thyroid hormone concentrations are measured with a coated tube-radioimmunoassay method, antibodies can result in low T(3) concentrations. T(3) antibodies should be suspected whenever a discordance is noted between the measured thyroid hormone concentrations and the clinical status.

Glycaemic index of different kinds of carbohydrates in type 2 diabetes.

An adequate diet provides good metabolic control in diabetics. Since 1981 when Jenkins showed that complex carbohydrates are digested more slowly and raise blood glucose less than simple sugars, many studies have been performed in this field. In this study, seven kinds of carbohydrate-rich food were compared with glucose in 52 Type 2 diabetic patients and 31 normal volunteers. The subject consumed either macaroni, white rice, potatoes, tarhana soup (tarhana includes wheat flour, yoghurt, tomato and green pepper), noodle soup, white or whole wheat bread, or glucose at one-week intervals after an overnight fast. The glycaemic index (GI) of each food was calculated from the area under its glycaemic response curve (AUC) expressed as a percentage of the mean response to glucose. The results showed that the foods ranked from the highest to the lowest GI as follows: white bread; whole wheat bread; macaroni; tarhana soup; white rice; potatoes; noodle soup.

Acarbose treatment in obesity: a controlled study.

UNLABELLED: Acarbose is an alpha-glucosidase inhibitor which reversibly inhibits oligosaccharidase and disaccharidase at the brush border of the small intestine. The aim of this study was to observe its effectiveness in the treatment of obesity. METHODS: Two groups of 25 obese women were put on a 15 kcal/kg/day low-calorie diet for 12 weeks. One group (the study group) received 150 mg/day acarbose for the first 2 weeks and 300 mg/day acarbose for the remaining 10 weeks. The second group (controls) received no additional treatment. Body weight, BMI, skinfold thickness, serum lipids, OGTT, and insulin and C-peptide responses to OGTT were assessed before and after the study. RESULTS: Body weight, BMI and skinfold thickness decreased significantly in both groups. Basal insulin and triglyceride levels in the study group, total and LDL cholesterol and triglyceride levels in the control group decreased significantly. No difference was found between the two groups when these decrements were compared, but the triglyceride level fell more in the control group. CONCLUSION: Additional acarbose therapy is not more beneficial than low-calorie diet therapy alone.

Long-term treatment with acarbose for the treatment of reactive hypoglycemia.

OBJECTIVE: Acarbose, a potent alpha-glucosidase inhibitor, provides a new concept for the treatment of metabolic disorders, and particularly diabetes mellitus. It reduces the postprandial blood glucose increment and insulin response. For this reason the drug has been successfully used not only in the treatment of type 1 and type 2 diabetes, but also in the management of reactive hypoglycemia and dumping syndrome. The primary aim of the present study is to evaluate the long-term effect of acarbose in reducing hypoglycemic symptoms and influencing laboratory measurements in patients with the diagnosis of reactive hypoglycemia. DESIGN AND METHODS: 21 non-obese (BMI < 27 kg/m2) patients (6 males, 15 females) complaining of postprandial symptoms suggesting hypoglycemia and who showed blood glucose values of < 54 mg/dl on one or more occasions during a 5 h oral glucose tolerance test (OGTT) were selected. RESULTS: Before treatment, ingestion of glucose decreased plasma glucose levels at the 3rd and 4th hours, the lowest levels being 39 mg/dl and 45 mg/dl respectively. Eighteen patients had hypoglycemic symptoms during OGTT. Following 3 months of acarbose treatment, the lowest plasma glucose levels at the 3rd and 4th hours increased to 67 mg/dI and 75 mg/dI respectively. Plasma insulin and c-peptide levels were reduced between the 1st and 5th hours, but only the 1st and 2nd hour decrements were statistically significant. The area under the curve (AUC) between 0-300 minutes for insulin was not significant. Plasma glucose levels were significantly increased during the last 3 hours. The AUC for glucose was not significantly changed. Frequency of hypoglycemic attacks was reduced from 4 times a week to 1. C-peptide levels in 24-hour urine collection did not change significantly: 45 micrograms/I and 56 micrograms/I respectively before and after treatment. CONCLUSIONS: These results confirm that acarbose may be of value in preventing reactive hypoglycemia by reducing the early hyperglycemic stimulus to insulin secretion, and in the treatment of reactive hypoglycemia.

Urothelial hyperplasia complicating use of metal stents in malignant ureteral obstruction.

Self-expandable metal stents (7 mm in diameter) combined with coaxial double-j stents were placed in 10 ureters in ten patients with malignant ureteral obstruction. After 2 and 3 months, when the double-j stents were removed in seven patients, six patients developed hydronephrosis and one patient tolerated removal of the double-j stent and had no signs of urinary obstruction until she died in the fifth month. A double-j stent was inserted again in six patients who developed hydronephrosis. Endoscopy performed during insertion of the double-j stents showed urothelial hyperplasia and incrustations which reduced the lumen of the metal stent. Their double-j stents were exchanged with new ones every 3 months. In the last three patients, double-j stents were not removed, but exchanged with new ones every 3 months. Endoscopy performed regularly during the exchange of the double-j stents in the follow-up of nine patients showed that urothelial hyperplasia, although mild, persisted until the sixth month in three patients. We conclude that urothelial hyperplasia and incrustations limit the use of metal stents in malignant ureteral obstruction. Metal stents, however, when used together with the coaxially placed double-j stents, contributed to the achievement of internal urinary drainage in this study. Since a metal stent provides a buttress for the previously obstructed segment of the ureter, the lumen, although decreased by hyperplasia and incrustations, is held open, which allows an easy exchange of the double-j stent. Regarding the high cost of metal stent, use of it with a coaxial double-j stent should be spared for the malignant ureteral obstructions when a previously placed double-j stent alone fails to achieve efficient drainage.