Pioglitazone and statins lower incidence of Parkinson disease in patients with diabetes mellitus.

BACKGROUND AND PURPOSE: The pharmacologic effects of pioglitazone on the incidence of Parkinson disease (PD) are not clear. No study has examined the interaction between pioglitazone and statin treatment on prevention of PD. This study analyzed the associations between pioglitazone, statins, and the incidence of PD in patients with diabetes mellitus (DM) in Taiwan. METHODS: We used the National Health Insurance database from 1996 to 2013. DM and PD were diagnosed according to the International Classification of Diseases, Ninth Revision, Clinical Modification codes. We used the propensity score-matching method to match the study groups. Cox regression analyses were employed to calculate the relative risk of the incidence of PD. RESULTS: There were 48 828 patients matched and categorized equally into the pioglitazone group and the non-pioglitazone group. The number of PD patients in the pioglitazone group and the non-pioglitazone group was 275 (1.1%) and 417 (1.7%), respectively. The pioglitazone group had a lower incidence of PD, with an adjusted hazard ratio (aHR) of 0.66 [95% confidence interval (CI): 0.57-0.78], and this benefit was dose-dependent. Of note, as compared with either pioglitazone or statin treatment, our results first showed that the combination of pioglitazone and statins further lowered the risk of PD, with an aHR of 0.78 (95% CI: 0.64-0.94; P = 0.010). CONCLUSIONS: Our study results suggested that pioglitazone could be a promising agent for reducing the incidence of PD in patients with DM, and works synergistically with statins.

A Point-based Mortality Prediction System for Older Adults with Diabetes.

The mortality prediction models for the general diabetic population have been well established, but the corresponding elderly-specific model is still lacking. This study aims to develop a mortality prediction model for the elderly with diabetes. The data used for model establishment were derived from the nationwide adult health screening program in Taiwan in 2007-2010, from which we applied a 10-fold cross-validation method for model construction and internal validation. The external validation was tested on the MJ health screening database collected in 2004-2007. Multivariable Cox proportional hazards models were used to predict five-year mortality for diabetic patients ≥65 years. A total of 220,832 older subjects with diabetes were selected for model construction, of whom 23,241 (10.5%) died by the end of follow-up (December 31, 2011). The significant predictors retained in the final model included age, gender, smoking status, body mass index (BMI), fasting glucose, systolic and diastolic blood pressure, leukocyte count, liver and renal function, total cholesterol, hemoglobin, albumin, and uric acid. The Harrell's C in the development, internal-, and external-validation datasets were 0.737, 0.746, and 0.685, respectively. We established an easy-to-use point-based model that could accurately predict five-year mortality risk in older adults with diabetes.

Changes in high-density-lipoprotein cholesterol upon statin treatment in type 2 diabetic patients: a meta-analysis.

BACKGROUND AND AIM: To investigate the diversity of change in high-density-lipoprote in cholesterol (HDL-C) after statin treatment in patients with type 2 diabetes mellitus (T2DM). METHODS AND RESULTS: A systemic review searched for trials that reported a serum change in HDL-C in patients with T2DM after statin treatment, and extracted data for meta-analysis. Of 6709 articles surveyed, 160 articles were identified as eligible articles. In the analysis of simvastatin, serum HDL-C was increased in Non-Asian and Asian patients with T2DM by 2.17 mg/dl (95% CI 1.43 ∼ 2.90 mg/dl, p < 0.001) and 2.31 mg/dl (95% CI 1.37 ∼ 3.25 mg/dl, p < 0.001), respectively. In the analysis of atorvastatin, although significant, serum HDL-C was subtly increased in Non-Asian patients with T2DM by 1.14 mg/dl (95% CI 0.28 ∼ 2.01 mg/dl, p = 0.010) mg/dl; however, atorvastatin treatment did not significantly change the serum HDL-C by 0.12 mg/dl (95% CI -1.04 ∼ 1.27 mg/dl, p = 0.839) mg/dl in Asian patients with T2DM. According to meta-regression analysis, the baseline HDL-C did not affect the change in serum HDL-C in Asian patients with T2DM after either simvastatin or atorvastatin treatment. However, contrary to simvastatin, the coefficient of regression (r) showed a significant negative association (r = -0.18; 95% CI -0.32 to -0.04; p = 0.01) between baseline HDL-C and the change of HDL-C in non-Asian patients with T2DM after atorvastatin treatment. CONCLUSION: We have demonstrated for the first time that there may be a discrepancy in the change of serum HDL-C in Asian patients with T2DM after atorvastatin treatment.

Residual effect of reductions in red blood cell count and haematocrit and haemoglobin levels after 10-month withdrawal of pioglitazone in patients with Type 2 diabetes.

AIM: To investigate the recovery of thiazolidinedione-induced body weight gain and haematopoietic changes after stopping pioglitazone treatment in patients with Type 2 diabetes. METHODS: This retrospective cohort study included 214 patients divided into three groups according to pioglitazone treatment status. The first study arm included patients who received pioglitazone for 38 months then interrupted this for 10 months (pioglitazone-interruption group). The second arm consisted of patients who received pioglitazone throughout the 48 months (pioglitazone-continuous group); the third arm included patients who had never received pioglitazone therapy (control group). RESULTS: Red blood cell count and haematocrit and haemoglobin levels decreased significantly, while body weight increased in the two pioglitazone-treated groups as compared with the control group at 38 months. Multivariate regression analysis showed that the reductions in red blood cell count/haemoglobin levels were associated with pioglitazone use. In the pioglitazone-interruption group, no recoveries of red blood cells, or haematocrit or haemoglobin levels were observed after stopping pioglitazone for 10 months compared with the pioglitazone-continuous group, but body weight gain decreased to a level that was significantly lower than that in the pioglitazone-continuous group and did not differ significantly from the control group. CONCLUSION: In this study, we observed a reversal of body weight gain but no recoveries in red blood cells or haematocrit or haemoglobin levels after stopping pioglitazone for 10 months in patients treated with pioglitazone for 38 months. This finding should prompt a reconsideration of the sustained effect of thiazolidinediones on the haematopoietic system in patients with Type 2 diabetes.

Small ubiquitin-like modifier-4 Met55Val polymorphism is associated with glycemic control of Type 2 diabetes mellitus in Taiwan.

AIM: The development of Type 2 diabetes mellitus (T2DM) has been recognized to be associated with a combination of pancreatic beta-cell dysfunction and insulin resistance. Nuclear factor-kappaB (NF-kappaB) has been recognized as one central mediator in the reaction of inflammation and proapoptotic event in beta-cells. A functional polymorphism at the codon 55 (methionine to valine; A163G) of the small ubiquitin- like modifier-4 (SUMO4) gene may result in higher NF-kappaB activity. This study investigates whether this SUMO4 Met55Val polymorphism also contributes to the development of T2DM. MATERIALS AND METHODS: The study was performed using genomic DNA samples from 574 Type 2 diabetic patients and 323 healthy controls. The SUMO4 Met55Val polymorphism was genotyped using allele-specific real-time PCR. RESULTS: The frequency of the G allele (encoding Val55) was significantly higher in Type 2 diabetic patients and Type 2 diabetic patients with the GG genotype had higher hemoglobin A1c level. Multivariate logistic regression analysis revealed the genotype of GG and GA was an independent risk factor contributing to the development of T2DM. CONCLUSION: This study suggests that in Taiwan the SUMO4 Met 55Val polymorphism is associated with susceptibility to T2DM and Type 2 diabetic patients with GG genotype have worse glycemic control.

The effects of glurenorm on plasma glucose and lipids in patients with type 2 diabetes mellitus.

BACKGROUND: The effects of sulfonylureas on plasma glucose, lipids, and macrovascular complications are of interest. This study was designed to investigate the effects of glurenorm on plasma glucose and lipids in patients with type 2 diabetes mellitus. METHODS: Nineteen patients, 15 men and 4 women, with an age range of 38-69 years, and with type 2 diabetes mellitus, were studied. Plasma glucose, glycated hemoglobin, and lipids were compared before and 3 months after glurenorm treatment. RESULTS: Fasting and postprandial plasma glucose, and HbA1c significantly improved after 3 months of glurenorm treatment. The mean (+/- SD) triglyceride level of 10 patients with mild to moderate hypertriglyceridemia decreased from 279 +/- 66 to 219 +/- 100 mg/dl (p = 0.054). The total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) of 14 hypercholesterolemic patients did not change significantly. Their mean body weight increased significantly from 65.7 +/- 9.6 to 67.2 +/- 9.9 kg (p = 0.002). CONCLUSION: Glurenorm was effective for glycemic control but caused weight gain in type 2 diabetic patients. Triglycerides in hypertriglyceridemic patients, and total cholesterol, LDL-C, and HDL-C in hypercholesterolemic patients did not improve after glurenorm treatment.

Characteristics of thyroid carcinomas in aging patients.

BACKGROUND: To investigate the clinical features of thyroid cancer in aging patients and to present the results of treatment. From this we can provide bases for earlier diagnoses and better treatment of thyroid malignancies in older patients. MATERIALS AND METHODS: In this study a retrospective analysis was performed with 204 thyroid cancer patients aged 60 years or older (132 women, with a mean age of 68.3 +/- 6.6 years; 72 men, with a mean age of 67.0 +/- 5.3 years). RESULTS: Of the 204 patients, 142 had well-differentiated thyroid carcinomas (96 papillary thyroid carcinomas, 43 follicular carcinomas, three Hürthle cell carcinomas) and three medullary carcinomas. Sixty-nine (33.8%) of the 204 patients died after treatment. Of these, three patients died of causes not related to thyroid cancer. For well-differentiated thyroid carcinomas, male gender, follicular carcinoma, and a larger tumour size indicated a poor prognosis. Of the 59 non-well-differentiated thyroid carcinomas, 39 were anaplastic thyroid carcinomas, nine metastatic cancers of the thyroid, seven lymphomas, and four squamous cell carcinomas. After treatment, 40 (67.8%) of the 59 patients died. In multivariant analysis of the differences in clinical parameters between aging and younger thyroid cancer patients, the current status, tumour size, follow-up period, sex, and stage at diagnosis were independent factors. From this data the delayed diagnosis of aging patients with thyroid cancer was of note when compared with younger patients. CONCLUSION: Thyroid cancer in older patients is not a benign clinical disorder. Early diagnosis and urgent aggressive treatment are recommended courses of action for this type of cancer, especially for non-well-differentiated thyroid cancers.

Endocrinological aspects of Langerhans cell histiocytosis complicated with diabetes insipidus.

Langerhans cell histiocytosis (LCH) is a rare disorder and may be complicated with hypopituitarism and diabetes insipidus (DI) due to invasion of the hypothalamic-pituitary area. In this study, 10 patients with complete (4) and partial (6) type central DI were found among 125 LCH patients in our hospital records. The water deprivation test, followed by the pitressin test, was performed to confirm DI. Hypothalamic-pituitary endocrine function tests were carried out on these 10 patients at the initial diagnosis and during follow-up. All patients revealed growth hormone insufficiency in the insulin hypoglycemic tolerance test. Four patients had impairment of cortisol secretion, demonstrated by insulin hypoglycemic stimulating test results. Two patients had poor response in the thyrotropin releasing hormone stimulating test. Two patients had only partial responses in the luteinizing hormone releasing hormone test. Four patients had hyperprolactinemia. All patients underwent surgical treatment followed by chemotherapy and/or radiotherapy. One patient completely recovered from the endocrine disorder, 3 patients required smaller doses of desmopressin, and one patient had normal adrenal, thyroid, and gonadal function. Hypothalamic-pituitary disorders in LCH should not be neglected. Treatment of LCH can partially or completely reverse associated endocrine disorders. Therefore, endocrine studies and hormone replacement should be mandatory for patients with LCH.

The roles of cytokines and retinoic acid in the regulation of human thyroid cancer cell growth.

The purpose of this study was to investigate the effects of cytokines and retinoic acid in human thyroid cancer cell growth. Cellular proliferation studies of the CGTH W-1 and SW 579 cell lines were performed with various cytokines and all-trans retinoic acid (RA). Cell number was determined by cell counting and incorporation of [3H]thymidine into DNA. Inhibitory effects of tumour necrosis factor alpha (TNF-alpha) were found in both cell lines. SW 579 was more sensitive to TNF-alpha. The SW 579 cell line revealed gradually decreased cell proliferation in [3H]thymidine incorporation studies as TNF-alpha concentration increased. In contrast, the CGTH W-1 cell line revealed prominent suppressive effects when the TNF-alpha concentrations increased over 1 ng/ml. An inhibitory effect of interleukin 1 beta (IL-1 beta) on CGTH W-1 cells was noted at the concentration of 1 ng/ml, however, IL-1 beta failed to demonstrate an inhibitory effect in SW 579 cells.

Acute suppurative thyroiditis and aggressive malignant thyroid tumors: differences in clinical presentation.

BACKGROUND AND OBJECTIVES: Aggressive malignant thyroid tumors (AMTT) may mimic the clinical symptoms and signs of acute suppurative thyroiditis (AST) in the early course of the disease process. Our objective was to analyze the clinical features of these two conditions, to assess the best way of early diagnosis, and to propose proper treatment. METHODS: We retrospectively reviewed and analyzed the clinical features of 30 patients, who had similar clinical pictures of AST and were managed at Chang Gung Memorial Medical Center in Linkou, Taiwan, during the period from 1983 to 1996. These patients were consequently diagnosed as either AST or AMTT. The data were analyzed by the Mann-Whitney U, chi-square and Fisher's exact tests. RESULTS: Among the 30 patients, 25 patients (Male/Female (M/F) ratio = 9/16) were diagnosed as having AST and 5 (M/F ratio = 1/4) as AMTT. After statistical analysis we concluded that the presence of the following factors, namely, older age at diagnosis (P = 0.0155), history of dysphonia (P = 0.0325), right thyroid lobe involvement (P = 0.0151), large size of lesions (P = 0.0013), presence of anemia (P = 0.0075), and sterile pus cultures from thyroid aspirates (P = 0.0013) were cause to suspect a malignancy if the condition did not improve after antibiotics. Delay in diagnosis and management of AMTT may result in a poor prognosis (P = 0.0082). CONCLUSION: Due to the high mortality rate of AMTT, we should closely observe the patients with poor prognostic variables of acute thyroiditis. Earlier detection and aggressive surgical intervention for AMTT might improve the outcome.

Clinical presentations and predictive variables of thyroid microcarcinoma with distant metastasis.

BACKGROUND: Thyroid microcarcinoma is not an uncommon disorder. The purpose of this study is to analyze the clinical presentation and predictive factors for patients with thyroid microcarcinomas who have distant metastases. METHODS: We retrospectively reviewed and analyzed the clinical variables of 97 patients with thyroid microcarcinoma during the period from 1977 to 1995. The patients were divided into 2 groups representing patients with and without distant metastases. These data were analyzed by the Mann-Whitney U, chi 2 and Fisher's exact tests. RESULTS: Of the 97 patients with thyroid microcarcinomas, there were 6 (6.2%) cases (F/M = 5/1) with distant metastases. Among them, 4 cases were papillary carcinomas and 2 cases were follicular carcinomas. The parameters: age at diagnosis (P = 0.0137), one month postoperative serum thyroglobulin (Tg) level (P = 0.0215), cervical lymph node metastasis (P = 0.0097), and follicular cell type (P = 0.0079), were determined to be factors predictive for distant metastases by statistical analysis. There were no statistical differences between gender (P = 0.5781), postoperative 131I uptake (P = 0.1238), tumor size (P = 0.0571), preoperative thyroid function (P = 0.4425), fine-needle aspiration cytology (FNAC) (P = 0.9723), preoperative thyroid scan (P = 0.9765), and operative methods (P = 0.1060) between these two groups. CONCLUSIONS: Most thyroid microcarcinomas presented with relatively benign clinical courses, but patients with adverse predictive factors need more aggressive interventions to improve outcome.

Skull metastasis with brain invasion from thyroid papillary microcarcinoma.

Thyroid papillary microcarcinoma has a notably benign clinical course among carcinomas. The occurrence of distant metastases is exceptional, but significantly increases the risk of mortality. We report the case of a 75-year-old woman with a 1.0 cm primary thyroid papillary microcarcinoma with skull metastases and brain invasion. The clinical presentation was a large mass over the occipital area which progressively grew over the course of 1 year. No thyroid nodule or lymph nodes were palpable. The metastatic mass and primary tumor were surgically removed. The serum thyroglobulin level was 163 ng/mL 1 month after surgery. There was no further management because the patient refused follow-up. She returned to the hospital 15 months later due to a seizure. The tumor had further extended into the brain tissue. Her condition progressively deteriorated and she died 2 months later due to uncontrollable seizures.

Percutaneous transcystic cholangioscopy for combined treatment of gallbladder and bile duct stones.

A procedure for percutaneous transcystic cholangioscopy requiring only one percutaneous transhepatic fistulous tract to remove stones located in both the gallbladder and bile ducts is described. The procedure begins with percutaneous transhepatic drainage of the gallbladder or bile duct. Stones in the gallbladder and bile duct can be removed under direct vision on transhepatic cholangioscopy. Larger stones can be fragmented by electrohydraulic lithotripsy before removal. In a preliminary trial the procedure proved to be a feasible method for treatment of 13 patients with both gallbladder and bile duct stones as well as septic cholangitis who either refused operation or were considered poor candidates for surgery. On long-term follow-up (mean period 28 months) stone recurrence was observed in three patients.

The realization of a pulsatile implantable impeller pump with low hemolysis.

A pulsatile implantable impeller pump with low hemolysis was developed without markedly increasing the complexity of the system compared with the nonpulsatile pump. The key to the question is to design a three-dimensional impeller with twisted vanes, compacted by an axial helical spiral and a radial logarithmic spiral so as to reduce the turbulent shear in the pump as the impeller changes its rotations per minute periodically to generate a physiologic pulsatile flow. Both mathematic computation of velocity distribution in the impeller and geometric illustration of the velocity triangle at the top of the vane have demonstrated that the peripheral velocity variation of blood cells in a twisted impeller will be less than that in an untwisted impeller. Thus, the main mechanical factor of hemolysis in the impeller pump, namely, the turbulent shear, should be reduced because it is proportional to the product of velocity variations measured in two perpendicular directions. In the in vitro experiments, the pump delivered 4 L/min mean flow at 100 mm Hg mean pressure (pulsed between 80-120 mm Hg) for more than 3 h in a circulatory model containing 700 ml of fresh citrated porcine blood. Every half hour, the free hemoglobin level in the plasma was tested, and the resulting index of hemolysis was about 0.020, slightly more than that of a nonpulsatile impeller pump developed in Shanghai. To compare hemolysis, the index of hemolysis of this pump is about 1/6 of that of the self-made diaphragm pump and 1/13 of that of the Polystan Pulsatile Pump.(ABSTRACT TRUNCATED AT 250 WORDS)

Structure and synthesis of hemoglobin in marmosets (Saguinus fuscicollis).

Marmoset reticulocytes and bone marrow provide a valuable tissue resource for the study of primate hemoglobin structure and synthesis. The amino acid sequence of the marmoset hemoglobin has been determined, and the close homology between it and that of the human suggest it may be a valuable model for study of the effects of chemical modification on hemoglobin function. Hemoglobin synthesis by fetal bone marrow has been reported to be stimulated by physiologic levels of l-thyroxine. Differences in hormone responsiveness between fetal and adult red cell precursors have tentatively been ascribed to differences in permeability of the fetal and adult clones of cells.

Amino acid metabolism of myeloma cells in culture.

The growth of myeloma cells in Leibovitz medium supplemented with 20% serum was limited by the depletion of glutamine. A simple modification of the Leibovitz medium by increasing the concentrations of glutamine, lysine, isoleucine, leucine, sodium pyruvate, galactose, and vitamins resulted in over 100% increase in cell growth yield. The total myeloma protein produced by the cells was increased by approximately 90% in modified Leibovitz media. Analysis of spent culture media for 19 amino acids showed that the concentrations of 8 amino acids were reduced; those of 5 amino acids were increased and the other 6 did not change significantly.

Primary structure of the marmoset (Saguinus fusicollis) hemoglobin. I. Use of tryptic maleylated peptides in the solubilization and sequence elucidation of the alpha- and beta-chains.

The primary structure of adult marmoset hemoglobin has been determined. The alpha- and beta-chains of HbA were separated on a CM23 column in 8 M urea using a sodium phosphate gradient. Tryptic digest of the alpha- and beta-chains were fractionated on a Dowex 50W-X2 column using a pH and pyridine acetate gradient. Large peptide fragments were obtained by the cyanogen bromide cleavage of the alpha- and beta-chains, as well as by tryptic digestion of the maleylated alpha- and beta-chains. The sequence was derived from the amino acid compositions and sequences of the individual tryptic peptide, automated sequence determination of intact alpha- and beta-chains, as well as automated sequence determination of cyanogen bromide fragments and tryptic maleylated peptides derived from the alpha- and beta-chains. The complete structure of marmoset adult hemoglobin is closely homologous to that of other primate hemoglobins. The sequence of the marmoset alpha-chain differs from the alpha-chian of human HbA at positions 8, 19, 23, 68, and 116. The beta-chain from marmoset HbA differs from the beta-chain of human HbA at positions 5, 13, 21, 50, 87, and 125.