Sitagliptin Modulates the Electrical and Mechanical Characteristics of Pulmonary Vein and Atrium.

BACKGROUND: The pulmonary veins (PVs) and atria are important foci during that period when atrial fibrillation (AF) is generated and maintained. It is well understood that hypertension and diabetes mellitus (DM) are important risk factors for AF. Dipeptidyl peptidase-IV (DPP-4) inhibitors are new agents in the fight against type 2 DM, though they have been found to have several cardiovascular effects. However, it is not clear whether DPP-4 may modulate the electrical and mechanical characteristics in hypertensive atrium or PVs. METHODS: Conventional microelectrodes were used to record the action potentials (APs) in isolated PVs, right atrium (RA), and left atrium (LA) in Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) with or without sitagliptin (10 mg/kg) for 4 weeks. RESULTS: WKY (n = 5), SHR (n = 7), sitagliptin-treated WKY (n = 5) and sitagliptin-treated SHR (n = 7) had similar PV or sinoatrial spontaneous beating rates. However, the sitagliptin-treated WKY had fewer sinoatrial-PV beating rate differences than WKY, SHR or sitagliptin-treated SHR. WKY and SHR had shorter 90% (APD90) of RA AP duration than sitagliptin-treated WKY or sitagliptin-treated SHR. In contrast, WKY had longer LA APD90 than sitagliptin- treated WKY, but SHR and sitagliptin-treated SHR had similar LA APD90. Sitagliptin-treated WKY or sitagliptin- treated SHR had larger (RA-LA) APD90 differences than WKY or SHR, respectively. Moreover, as compared to WKY the post-rest potentiation of contraction was decreased in SHR, sitagliptin-treated WKY, and sitagliptin-treated SHR. CONCLUSIONS: Sitagliptin significantly affects the electromechanical characteristics of PVs and atria, which can be modulated by hypertension. KEY WORDS: Atrial fibrillation; Atrium; Dipeptidyl peptidase inhibitor-4; Hypertension; Pulmonary vein.

Evaluation of secondary adrenal insufficiency: findings by corticotropin-releasing hormone test and magnetic resonance imaging in parallel.

BACKGROUND: The corticotropin-releasing hormone (CRH) stimulation test is reliable for diagnosing pituitary or hypothalamic adrenal insufficiency. In the present study, we evaluated secondary adrenal insufficiency in patients with pituitary disease by CRH test and magnetic resonance imaging (MRI). METHODS: A total of 12 healthy persons and 20 patients with pituitary disorder were recruited, including 6 with Sheehan's syndrome, 6 with idiopathic panhypopituitarism, 3 with isolated ACTH deficiency, 2 with pituitary apoplexy, 2 with empty sella syndrome and I with postoperative suprasellar tumor. Blood ACTH and cortisol levels were measured after 100 microg ovine CRH (oCRH) intravenous bolus infusion. RESULTS: In patients, basal ACTH was 15.9+/-17.3 pg/ml and basal cortisol was 4.8+/-4.6 microg/dl. These values were significantly lower than those in controls (p = 0.02). In 11 of 20 patients (3 with Sheehan's syndrome, 3 with panhypopituitarism, 2 with empty sella, 2 with isolated ACTH deficiency and 1 with pituitary apoplexy), a delayed and prolonged ACTH response was observed. In the other 9 patients, ACTH showed little change. In all patients, there was no apparent increase in cortisol value. Moreover this value was significantly lower than in healthy persons (6.2+/-5.4 vs. 21.1+/-6.0 microg/dl; p <0.0001). Sellar MRI showed complete empty change in all Sheehan's syndrome, apoplexy and empty sella syndrome patients. The six patients with panhypopituitarism had variable hypoplastic adenohypophysis with or without visible pituitary stalk. The three isolated ACTH deficiency cases demonstrated a normal anatomy. CONCLUSIONS: Our study showed that patients with pituitary disease had significantly lower plasma cortisol response after oCRH than controls. Thus, CRH testing appears useful for the diagnosis of central adrenal insufficiency. The two different functional ACTH responses to CRH observed in each pituitary disorder did not correlate with damage levels shown on MRI.

Diagnosis of thyroid metastasis in cancer patients with thyroid mass by fine needle aspiration cytology and ultrasonography.

BACKGROUND: Thyroid metastasis is generally thought to be infrequent. To evaluate its occurrence, fine needle aspiration cytology and ultrasound of the thyroid gland were performed in nonthyroid cancer patients with thyroid mass. METHODS: A total of 20 nonthyroid cancer patients (6 males and 14 females with a mean age of 55 +/- 7 years) with thyroid mass were examined with thyroid ultrasound and fine needle aspiration cytology. Their underlying malignancies included lung cancer in 10 patients, breast cancer in 7 patients, cervical cancer in 2 patients and colon cancer in 1 patient. RESULTS: Thyroid metastases were diagnosed in 4 patients (20%), 2 with breast cancer and 2 with lung cancer. For 3 of them, thyroid ultrasound showed solitary hypoechoic nodule, and in 1 case, multiple nodular lesions were demonstrated in each lobe. In addition, neck lymph nodes were noted in 3 patients. In the remaining 16 cancer patients, thyroid ultrasound showed either multiple or solitary nodular goiter change with no neck lymph node involvement. Fine needle aspiration cytology (FNAC) yielded nonthyroid adenocarcinoma in 4 metastatic cases. The 2 breast cancer patients received finally total thyroidectomy and were still alive 1 year after operation. While in the other 2 lung cancer cases, only supportive treatment were given due to advanced stages and the patients died within months. CONCLUSIONS: Thyroid metastases could occur at a high frequency in nonthyroid cancer patients with thyroid mass from our small series. By combining FNAC with ultrasound, a clinical diagnosis of thyroid metastasis is attainable in cancer patients with thyroid mass.