Ali Alsafi

Coadministration of Glucagon-Like Peptide-1 During Glucagon Infusion in Humans Results in Increased Energy Expenditure and Amelioration of Hyperglycemia

Glucagon and glucagon-like peptide (GLP)-1 are the primary products of proglucagon processing from the pancreas and gut, respectively. Giving dual agonists with glucagon and GLP-1 activity to diabetic, obese mice causes enhanced weight loss and improves glucose tolerance by reduction of food intake and by increase in energy expenditure (EE). We aimed to observe the effect of a combination of glucagon and GLP-1 on resting EE and glycemia in healthy human volunteers. In a randomized, double-blinded crossover study, 10 overweight or obese volunteers without diabetes received placebo infusion, GLP-1 alone, glucagon alone, and GLP-1 plus glucagon simultaneously. Resting EE—measured using indirect calorimetry—was not affected by GLP-1 infusion but rose significantly with glucagon alone and to a similar degree with glucagon and GLP-1 together. Glucagon infusion was accompanied by a rise in plasma glucose levels, but addition of GLP-1 to glucagon rapidly reduced this excursion, due to a synergistic insulinotropic effect. The data indicate that drugs with glucagon and GLP-1 agonist activity may represent a useful treatment for type 2 diabetes and obesity. Long-term studies are required to demonstrate that this combination will reduce weight and improve glycemia in patients.

Role of US Contrast Agents in the Assessment of Indeterminate Solid and Cystic Lesions in Native and Transplant Kidneys

Ultrasonography (US) is often the initial imaging modality employed in the evaluation of renal diseases. Despite improvements in B-mode and Doppler imaging, US still faces limitations in the assessment of focal renal masses and complex cysts as well as the microcirculation. The applications of contrast-enhanced US (CEUS) in the kidneys have dramatically increased to overcome these shortcomings with guidelines underlining their importance. This article describes microbubble contrast agents and their role in renal imaging. Microbubble contrast agents consist of a low solubility complex gas surrounded by a phospholipid shell. Microbubbles are extremely safe and well-tolerated pure intravascular agents that can be used in renal failure and obstruction, where computed tomographic (CT) and magnetic resonance (MR) imaging contrast agents may have deleterious effects. Their intravascular distribution allows for quantitative perfusion analysis of the microcirculation, diagnosis of vascular problems, and qualitative assessment of tumor vascularity and enhancement patterns. Low acoustic power real-time prolonged imaging can be performed without exposure to ionizing radiation and at lower cost than CT or MR imaging. CEUS can accurately distinguish pseudotumors from true tumors. CEUS has been shown to be more accurate than unenhanced US and rivals contrast material-enhanced CT in the diagnosis of malignancy in complex cystic renal lesions and can upstage the Bosniak category. CEUS can demonstrate specific enhancement patterns allowing the differentiation of benign and malignant solid tumors as well as focal inflammatory lesions. In conclusion, CEUS is useful in the characterization of indeterminate renal masses and cysts.

Combination of Peptide YY3–36 with GLP-17–36 amide Causes an Increase in First-Phase Insulin Secretion after IV Glucose

Context: The combination of peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) has been proposed as a potential treatment for diabetes and obesity. However, the combined effects of these hormones, PYY3–36 and GLP-17–36 amide, on glucose homeostasis are unknown. Objective: This study sought to investigate the acute effects of PYY3–36 and GLP-17–36 amide, individually and in combination, on insulin secretion and sensitivity. Setting and Design: Using a frequently sampled iv glucose tolerance test (FSIVGTT) and minimal modeling, this study measured the effects of PYY3–36 alone, GLP-17–36 amide alone, and a combination of PYY3–36 and GLP-17–36 amide on acute insulin response to glucose (AIRg) and insulin sensitivity index (SI) in 14 overweight human volunteers, studied in a clinical research facility. Results: PYY3–36 alone caused a small but nonsignificant increase in AIRg. GLP-17–36 amide alone and the combination of PYY3–36 and GLP-17–36 amide did increase AIRg significantly. No significant differences in SI were observed with any intervention. Conclusions: PYY3–36 lacks any significant acute effects on first-phase insulin secretion or SI when tested using an FSIVGTT. Both GLP-17–36 amide alone and the combination of PYY3–36 and GLP-17–36 amide increase first-phase insulin secretion. There does not seem to be any additive or synergistic effect between PYY3–36 and GLP-17–36 amide on first-phase insulin secretion. Neither hormone alone nor the combination had any significant effects on SI.

Cerebral Venous Sinus Thrombosis, a Nonenhanced CT Diagnosis?

Purpose. Retrospectively evaluate the density of cerebral venous sinuses in nonenhanced head CTs (NCTs) and correlate these with the presence or absence of a cerebral venous sinus thrombus (CVST). Materials and Methods. Institutional review board approval was obtained and informed consent waived prior to commencing this retrospective study. Over a two-year period, all CT venograms (CTVs) performed at our institution were retrieved and the preceding/subsequent NCTs evaluated. Hounsfield Units (HUs) of thrombus when present as well as that of normal superior sagittal and sigmoid sinuses were measured. HU of thrombus was compared to that of normal vessels with and without standardisation to the average HU of the internal carotid arteries. Results. 299 CTVs were retrieved, 26 with a thrombus. Both raw and standardised HU measurements were significantly higher in CVST (p < 0.0001) compared to normal vessels. Both raw and standardised HUs are good predictors of CVST. A HU of ≥67 and a standardised measurement of ≥1.5 are associated with high probability of CVST on NCT. Conclusion. Cerebral venous sinus HU measurements may help improve sensitivity and specificity of NCT for venous sinus thrombosis and avoid potentially unnecessary follow-up examinations.

Changes in Renal Function in Elderly Patients Following Intravenous Iodinated Contrast Administration: A Retrospective Study

Background. Contrast-induced nephropathy (CIN) is a recognised complication of intravascular administration of iodinated contrast media (ICM). Previous studies suggest a higher incidence in the elderly, but no large study has assessed this to date. We set out to assess changes in creatinine in elderly inpatients following computed tomography (CT) examination and compare those who received intravenous contrast to those who did not. Methods. Using the Radiology Information System in two teaching hospitals, inpatients over the age of seventy who had a CT examination and a baseline creatinine were identified and their follow-up creatinine levels were analysed. Elderly inpatients who underwent a noncontrast CT over the same period were used as controls. Results. 677 elderly inpatients who received ICM were compared with 487 controls. 9.2% of patients who received ICM developed acute kidney injury (AKI) compared to 3.5% of inpatient controls (P < 0.0001). Patients with higher baseline eGFR had a higher incidence of post-CT AKI. Conclusions. The incidence of post-CT AKI is higher in patients who received IV ICM compared to those who did not; the difference may be partly attributable to contrast-induced nephropathy. This suggests that the incidence of CIN in the elderly may not be as high as previously thought.

Acute Aortic Syndromes: Aortic Dissection, Intramural Haematoma and Penetrating Aortic Ulcers

Acute Aortic Syndrome includes three non-traumatic potentially fatal pathologies of the thoracic aorta which commonly present with chest pain.

2015 Myocardial perfusion after percutaneous recanalization of coronary chronic total occlusions: a cardiovascular magnetic resonance study

Methods Sixteen consecutive patients with CTO were recruited in the study and 12 patients underwent a CMR MPI both before (6.3 ± 6.4 days) and after revascularization (56 ± 39 days). CMR MPI study was performed in 1.5 T Siemens Avanto scanner using a 3 slice hybrid-EPI sequence with TSENSE. First-pass stress perfusion imaging was performed after 4 minutes of 140 μg/kg/min adenosine and 0.1 mmol/Kg of Gd-DTPA injected at 7 ml/s, followed by late enhancement imaging with inversion-recovery segmented FLASH sequence. First-pass rest perfusion images were acquired > 20 minutes after stress perfusion imaging. In addition, we obtained multiple SSFP cine images to encompass the left ventricle from base to apex (8 mm slice thickness, 2 mm gap). A visual wall motion, gadolinium and perfusion score (0–4) on a 16-segment model was applied and myocardial perfusion reserve index (MPRI) was calculated in all CTO myocardial territories. Left ventricular end-diastolic (LVDV) and end-systolic volumes (LVSV), ejection fraction (LVEF) and infarcted mass were also calculated.

2056 Quantitative magnetic resonance first-pass perfusion analysis in hypertrophic cardiomyopathy. Intrastudy variability

Aims Microvascular perfusion abnormalities in hypertrophic cardiomyopathy (HCM) are important markers of prognosis and may act as a trigger for arrhythmic events. Magnetic resonance first pass perfusion is a validated noninvasive imaging tool for the assessment of microvascular dysfunction by the quantification of myocardial perfusion reserve indices (MPRI). There are limited data available for the intrastudy and interstudy reproducibility of quantification using commercially available software. We sought to determine the intrastudy variability for MPRI in patients with HCM.

2052 Interstudy reproducibility of the quantification of CMR myocardial late gadolinium enhancement in hypertrophic cardiomyopathy

Aim Myocardial fibrosis is a common finding in patients with hypertrophic cardiomyopathy (HCM) and the amount of fibrosis is closely correlated with known risk factors for sudden cardiac death and adverse left ventricular remodeling. Quantification of fibrosis is challenging owing to the variable patterns and signal intensity of fibrotic regions, variable TI settings and surface coil responses. There are no published data on the interstudy reproducibility of late gadolinium quantification in HCM. This needs to be determined before the significance of longitudinal changes in fibrosis after pharmacologic or therapeutic interventions in defined patient cohorts can be assessed. We sought to assess the interstudy reproducibility of quantification of fibrosis in patients with HCM.