Increased Short-Term Beat-to-Beat QT Interval Variability in Patients with Impaired Glucose Tolerance.

Prediabetic states and diabetes are important risk factors for cardiovascular morbidity and mortality. Determination of short-term QT interval variability (STVQT) is a non-invasive method for assessment of proarrhythmic risk. The aim of the study was to evaluate the STVQT in patients with impaired glucose tolerance (IGT). 18 IGT patients [age: 63 ± 11 years, body mass index (BMI): 31 ± 6 kg/m2, fasting glucose: 6.0 ± 0.4 mmol/l, 120 min postload glucose: 9.0 ± 1.0 mmol/l, hemoglobin A1c (HbA1c): 5.9 ± 0.4%; mean ± SD] and 18 healthy controls (age: 56 ± 9 years, BMI: 27 ± 5 kg/m2, fasting glucose: 5.2 ± 0.4 mmol/l, 120 min postload glucose: 5.5 ± 1.3 mmol/l, HbA1c: 5.4 ± 0.3%) were enrolled into the study. ECGs were recorded, processed, and analyzed off-line. The RR and QT intervals were expressed as the average of 30 consecutive beats, the temporal instability of beat-to-beat repolarization was characterized by calculating STVQT as follows: STVQT = Σ|QTn + 1 - QTn| (30x√2)-1. Autonomic function was assessed by means of standard cardiovascular reflex tests. There were no differences between IGT and control groups in QT (411 ± 43 vs 402 ± 39 ms) and QTc (431 ± 25 vs 424 ± 19 ms) intervals or QT dispersion (44 ± 13 vs 42 ± 17 ms). However, STVQT was significantly higher in IGT patients (5.0 ± 0.7 vs 3.7 ± 0.7, P < 0.0001). The elevated temporal STVQT in patients with IGT may be an early indicator of increased instability of cardiac repolarization during prediabetic conditions.

Improved glycemic control in pancreatic diabetes through intensive conservative insulin therapy.

OBJECTIVE: The aim of this study was to evaluate the effectivity and safety of insulin therapy in patients with DM secondary to underlying chronic pancreatitis with initially inappropriate glycemic control. METHODS: Pancreatic DM patients treated with oral antidiabetics (OAD) or pre-mixed insulin (PMI) with HbA1c ≥7.0% were recruited. Intensive conservative insulin treatment (ICT) (Group A, n = 16) or PMI (Group B, n = 8) was introduced instead of OAD, or the initial PMI therapy was switched to ICT (Group C, n = 10). The changes in HbA1c, fasting plasma glucose, body weight and hypoglycemic events from baseline to 2 years were followed. RESULTS: The patients in Group A and B had been treated with oral antidiabetics for 55 ± 68 months before switching to insulin therapy. The level of HbA1c had worsened from 8.3 ± 1.5% to 9.8 ± 1.7% during this period. The ICT had reduced HbA1c significantly from 9.7 ± 1.8% to 7.6 ± 1.4% after 12 weeks, in Group A, and five patients had HbA1c<7.0%. The introduction of PMI in Group B reduced HbA1c from 10.0 ± 1.4% to 9.0 ± 0.6% by 12 weeks. None of the patients had HbA1c<7.0%. By 12 weeks, the introduction of ICT in Group C had reduced the level of HbA1c from 8.8 ± 1.7% to 7.7 ± 1.2%. Two patients reached HbA1c<7.0%. There were two severe hypoglycemic episodes during the 2 years, one-one case in Group A and B. CONCLUSIONS: Oral medication becomes insufficient early in pancreatic DM. Long-term improvement of glycemic control can be achieved through intensified insulin therapy and in selected cases through PMI with a low risk of hypoglycemia.

Correlations between Arteriograph-derived pulse wave velocity and aortic elastic properties by echocardiography.

INTRODUCTION: There is an increased scientific interest on the evaluation of parameters characterizing aortic elasticity. The current study was designed to compare two characteristics of aortic distensibility: Arteriograph-derived pulse wave velocity (PWV) and augmentation index standardized to 80 per minutes heart rate (AIx80) and aortic elastic properties by echocardiography. METHODS: The study comprised 21 adult healthy volunteers. In all cases, systolic and diastolic ascending aortic diameters were recorded during transthoracic echocardiography in M-mode at a level 3 cm above the aortic valve from a parasternal long-axis view. Using forearm blood pressure values, the following aortic elastic properties were calculated: aortic strain, distensibility and stiffness index. All patients were examined by Arteriograph at the same time, as well. RESULTS: The Arteriograph-derived AIx80 and PWV correlated with aortic strain (R = -0·495, P = 0·023 and R = -0·527, P = 0·014, respectively) and aortic stiffness index (R = 0·454, P = 0·039 and R = 0·608, P = 0·003, respectively). Aortic distensibility did not correlated with AIx80 (R = -0·344, P = 0·127), only with PWV (R = -0·593, P = 0·005, respectively). DISCUSSION: Low to moderate correlations could be demonstrated between Arteriograph-derived PWV and aortic elastic properties by echocardiography.

Correlations between aortic stiffness and parasympathetic autonomic function in healthy volunteers.

Cardiovascular autonomic dysfunction and alterations in vascular elasticity are known complications of several disorders, including diabetes mellitus, hypertension, hypercholesterolemia, aging, and chronic kidney disease. The current study was designed to test whether a relationship existed between pulse wave velocity (PWV), augmentation index (AIx), aortic elastic properties, and cardiovascular autonomic function in healthy volunteers. The study comprised 25 healthy volunteers, whose aortic strain, distensibility, and stiffness index were measured by echocardiography, whereas PWV and AIx were evaluated by Arteriograph (TensioMed, Budapest, Hungary) in all cases. Autonomic function was assessed by means of 5 standard cardiovascular reflex tests. We found that heart rate response to deep breathing, as the most reproducible cardiovascular reflex test to characterize parasympathetic function, showed low to moderate correlations with PWV (r = -0.431, p = 0.032), aortic strain (r = 0.594, p = 0.002), distensibility (r = 0.407, p = 0.043), and stiffness index (r = -0.453, p = 0.023). Valsalva ratio and autonomic neuropathy score (ANS) correlated with PWV (r = -0.557, p = 0.004 and r = -0.421, p = 0.036, respectively) and AIx (r = -0.461, p = 0.020 and r = -0.385, p = 0.057, respectively), while ANS correlated with even aortic stiffness index (r = -0.457, p = 0.022). Cardiovascular reflex tests mainly characterizing sympathetic function had no correlation with aortic stiffness parameters (p = NS for all correlations). Correlations exist between parameters characterizing aortic elasticity and parasympathetic autonomic function, as shown by standard cardiovascular reflex tests in healthy volunteers.

[The first molecular analysis of a Hungarian HNPCC family: a novel MSH2 germline mutation]. / Az elsó magyar hereditaer nem polypoticus colorectalis carcinoma család molekuláris vizsgálata: az MSH2 gén uj mutációja.

BACKGROUND: Hereditary nonpolyposis colorectal cancer is an inherited disease characterized by onset at an early age, an excess of synchronous and metachronous large bowel tumors and a variety of extracolorectal malignancies. Basal and squamous cell carcinomas of the skin are not customarily included in the tumor spectrum of the syndrome. The disease is caused by a germline mutation in one of the DNA mismatch repair genes, most commonly MSH2 or MLH1, and typically presents with microsatellite instability and frequent loss of mismatch repair protein expression in the tumor tissue. PATIENT: The case of a 62-year old woman who had a history of colon cancer at the age of 46 years, endometrial cancer at the age of 56 years, baso-squamous, and squamous cell cancer of the face at the ages of 53, 54, 62 and 58 years, respectively, and rectal cancer at 60 is reported. Her family fulfills the Amsterdam criteria for the diagnosis of hereditary nonpolyposis colorectal cancer. The baso-squamous cell, the squamous cell, the endometrial and the rectal cancers were assessed for the microsatellite instability status and the expression of the MSH2 and MLH1 mismatch repair proteins, and the p53 tumor suppressor protein by immunohistochemistry. Mutational screening using an automated capillary DNA sequencer was performed by the direct genomic sequencing of 17 fragments of the MSH2 gene, which covers promoter, all exons and flanking intronic regions. RESULTS: All cancers displayed microsatellite instability and were positive for the p53 protein. The immunohistochemical staining in the baso-squamous cell, the squamous cell, the rectal and endometrial cancers were negative for MSH2 and positive for MLH1 proteins. DNA sequencing analysis revealed a mutation c.2292G > A in exon 14 of the MSH2 gene, which is altering the 764. amino acid, the tryptophan to STOP codon (p.W764X). Thus the MSH2 protein is presumably truncated by 171 aminoacids. CONCLUSION: To the best of authors' knowledge, this is the first molecular characterization of a Hungarian hereditary nonpolyposis colorectal cancer family. According to the Human Mutation Database and International Collaborative Group of HNPCC Database, this mutation is novel, has not been reported previously. Cutaneous baso-squamous and squamous cell cancers may present as part of the HNPCC phenotype. Detection of the loss of mismatch repair protein expression and mismatch repair gene mutation mapping, represents a significant improvement of the diagnosis of this syndrome in Hungary. These examinations identify the mutation carriers who are at an increased risk of developing cancers.

Cardiovascular autonomic dysfunction in primary Sjögren's syndrome.

OBJECTIVE: To assess the occurrence and clinical significance of a cardiovascular autonomic nervous system dysfunction in primary Sjögren's syndrome (pSS). METHODS: Fifty-one pSS patients participated in this case-control study. Heart rate and blood pressure variability measurements, spontaneous baroreflex sensitivity examinations and cardiovascular reflex tests were performed. RESULTS: The results of the heart rate and blood pressure variability measurements and also the baroreflex sensitivity parameters of the pSS patients peaked in the lowest percentile ranges of a database on 559 healthy control subjects (P < 0.05). In three of the five cardiovascular reflex tests, the frequencies of abnormal results were significantly higher among the patients than among the controls (P < 0.05), and the median autonomic neuropathy score was also elevated (3 vs 0 in the controls; P < 0.0001). CONCLUSION: Signs of an autonomic nervous system dysfunction involving the cardiovascular system can be discerned in the majority of pSS patients.