Evaluation of immunogenicity of LY2963016 insulin glargine compared with Lantus® insulin glargine in patients with type 1 or type 2 diabetes mellitus.

AIMS: To compare the immunogenicity profiles and the potential effects on clinical outcomes of LY2963016 insulin glargine (LY IGlar) and Lantus® insulin glargine (IGlar), products with identical primary amino acid sequences, in patients with type 1 or type 2 diabetes mellitus (T1DM or T2DM). METHODS: To assess immunogenicity, anti-insulin glargine antibodies (measured as percent binding) were compared between treatments in 52-week (open-label) and 24-week (double-blind) randomized studies in total study populations of patients with T1DM (N = 535) and T2DM (N = 756), respectively, and two subgroups of patients with T2DM: insulin-naïve patients and those reporting prestudy IGlar treatment (prior IGlar). Relationships between insulin antibody levels and clinical outcomes were assessed using analysis of covariance and partial correlations. Insulin antibody levels were assessed using Wilcoxon rank sum. Treatment comparisons for treatment-emergent antibody response (TEAR) and incidence of detectable antibodies were analysed using Fisher's exact test. RESULTS: No significant treatment differences were observed for insulin antibody levels, incidence of detectable anti-insulin glargine antibodies, or incidence of TEAR [overall and endpoint, by last-observation-carried-forward (LOCF)] in patients with T1DM or patients with T2DM, including the insulin-naïve subgroup. A statistically significant difference was noted in the overall incidence of detectable antibodies but not at endpoint (LOCF) nor in TEAR for the prior IGlar subgroup of patients with T2DM. Insulin antibody levels were low (<5%) in both treatment groups. Insulin antibody levels or developing TEAR was not associated with clinical outcomes. CONCLUSIONS: LY IGlar and IGlar have similar immunogenicity profiles; anti-insulin glargine antibody levels were low for both treatments, with no observed effect on efficacy and safety outcomes.

Efficacy and safety of LY2963016 insulin glargine compared with insulin glargine (Lantus®) in patients with type 1 diabetes in a randomized controlled trial: the ELEMENT 1 study.

AIMS: To compare the efficacy and safety of LY2963016 insulin glargine (LY IGlar) and the reference product (Lantus®) insulin glargine (IGlar) in patients with type 1 diabetes (T1D). METHODS: This phase III, randomized, open-label, 52-week study enrolled patients with T1D [glycated haemoglobin (HbA1c) ≤11%] being treated with basal (once-daily) and bolus insulin. Patients were randomized to receive once-daily LY IGlar (n = 268) or IGlar (n = 267) in combination with mealtime insulin lispro for 52 weeks. The primary efficacy outcome was to test the non-inferiority (0.4% and then 0.3% margin) of LY IGlar to IGlar as measured by change in HbA1c from baseline to 24 weeks. RESULTS: Both treatment groups had similar and significant (p < 0.001) within-group decreases in mean HbA1c values from baseline. LY IGlar met the non-inferiority criteria compared with IGlar for change in HbA1c from baseline to 24 weeks [-0.35 vs -0.46%, least-squares mean difference 0.108% (95% confidence interval -0.002 to 0.219), p > 0.05]. There were no significant (p > 0.05) treatment differences in other efficacy measures, including proportion of patients reaching HbA1c <7%, daily mean blood glucose, and insulin dose at 24 and 52 weeks. At 52 weeks, similar findings were observed between LY IGlar and IGlar for safety outcomes, including adverse events, allergic reactions, hypoglycaemia, weight change and insulin antibodies. CONCLUSIONS: Both LY IGlar and IGlar, when used in combination with mealtime insulin lispro, provided effective and similar glucose control and similar safety profiles.

Similar efficacy and safety of LY2963016 insulin glargine and insulin glargine (Lantus®) in patients with type 2 diabetes who were insulin-naïve or previously treated with insulin glargine: a randomized, double-blind controlled trial (the ELEMENT 2 study).

AIMS: To compare the efficacy and safety of LY2963016 insulin glargine (LY IGlar) and the reference product (Lantus(®)) insulin glargine (IGlar) in combination with oral antihyperglycaemic medications in patients with type 2 diabetes (T2D). METHODS: This phase III, randomized, double-blind, 24-week study enrolled patients with T2D who were insulin-naïve [glycated haemoglobin (HbA1c) ≥7 and ≤11.0%] or previously on IGlar (HbA1c ≤11%) and treated with ≥2 oral antihyperglycaemic medications. Patients were randomized to receive once-daily LY IGlar (n = 376) or IGlar (n = 380) for 24 weeks. The primary efficacy outcome was to test the non-inferiority (0.4% and then 0.3% margin) of LY IGlar to IGlar, as measured by change in HbA1c from baseline to 24 weeks. RESULTS: Both treatment groups had similar and significant (p < 0.001) within-group decreases in mean HbA1c values from baseline. LY IGlar met non-inferiority criteria compared with IGlar for change in HbA1c from baseline [-1.29 vs -1.34%; respectively, least-squares mean difference 0.052% (95% confidence interval -0.070 to 0.175); p > 0.05]. There were no treatment differences (p > 0.05) in fasting plasma glucose, proportion of patients reaching HbA1c <7% or insulin dose at 24 weeks. Adverse events, allergic reactions, weight change, hypoglycaemia and insulin antibodies were similar between treatment groups. Similar findings were observed in patients who were insulin-naïve or previously treated with IGlar at baseline. CONCLUSIONS: Both LY IGlar and IGlar, when used in combination with oral antihyperglycaemic medications, provided effective and similar glucose control with similar safety profiles in patients with T2D.

Zona fasciculata cortical adenoma and adrenal medullary hyperplasia in MEN II patient: unique concurrent presentation.

I-131 MIBG for the localization of pheochromocytoma is a highly specific agent. In this case report, an apparent false-positive finding attributed to the presence of three zona fasciculata cortical adenomata was ultimately deduced to be due to the presence of adrenal medullary hyperplasia in this MEN patient.

Effect of maintenance oral theophylline on dipyridamole-thallium-201 myocardial imaging using SPECT and dipyridamole-induced hemodynamic changes.

To evaluate the effect of maintenance oral theophylline therapy on the diagnostic efficacy of dipyridamole-thallium-201 single photon emission computed tomography (SPECT) imaging for coronary artery disease, dipyridamole-thallium-201 SPECT imaging was performed in eight men with documented coronary artery disease before initiation of theophylline treatment and repeated while these patients were receiving therapeutic doses of oral theophylline. Before theophylline treatment, intravenous dipyridamole caused a significant increase in heart rate, decrease in blood pressure, angina in seven of eight patients, and ST segment depression in four of eight patients. While they were being treated with theophylline, none of the patients had angina or ST segment depression, and there were no hemodynamic changes with intravenous dipyridamole. Before theophylline treatment, dipyridamole-thallium-201 SPECT imaging showed reversible perfusion defects in myocardial segments supplied by stenotic coronary arteries. With theophylline treatment, dipyridamole-thallium-201 SPECT showed total absence of reversible perfusion defects. Treatment with theophylline markedly reduced the diagnostic accuracy of dipyridamole-thallium-201 imaging for coronary artery disease.

Painful spondylolysis or spondylolisthesis studied by radiography and single-photon emission computed tomography.

Planar bone scintigraphy (PBS) and single-photon emission computed tomography (SPECT) were compared in 19 adults with radiographic evidence of spondylolysis and/or spondylolisthesis. SPECT was more sensitive than PBS when used to identify symptomatic patients and sites of "painful" defects in the pars interarticularis. In addition, SPECT allowed more accurate localization than PBS. In 6 patients, spondylolysis or spondylolisthesis was unrelated to low back pain, and SPECT images of the posterior neural arch were normal. The authors conclude that when spondylolysis or spondylolisthesis is the cause of low back pain, pars defects are frequently heralded by increased scintigraphic activity which is best detected and localized by SPECT.

A description of the nuclear medicine service at the VAMC in Wood, Wisconsin.

It is rare for a Nuclear Medicine Service to replace or add four gamma cameras within six months; it is more unusual for a Service to move to a totally renovated facility. And even more remarkable for a Service to add a large sophisticated imaging computer system, which converts the entire Service to an "all digital" image acquisition, interpretation and archiving (PACS) oriented service. At this Medical Center, we have had all three events occur simultaneously in the past year.

Gamma camera energy windows for Tc-99m bone scintigraphy: effect of asymmetry on contrast resolution. Work in progress.

By raising the lower threshold of the Tc-99m energy window, rejection of scattered photons can be made more efficient. Unfortunately, with most gamma cameras significant nonuniformities are produced when the window is changed to an asymmetric setting. Recently introduced designs with gain stabilization of the photomultiplier tubes and improved energy correction maintain field uniformity even for an asymmetric window. To assess the impact of an asymmetric energy window on clinical images, 33 Tc-99m-MDP scintigrams of the lumbar spine were taken with symmetrical (126-154 keV) and asymmetric windows (135-154 keV). Bone:soft tissue ratios improved with the asymmetric window, and the resulting images were preferred by the physicians questioned.

Concentration of In-111-oxine-labeled autologous leukocytes in noninfected and nonrejecting renal allografts: concise communication.

Autologous leukocytes labeled with In-111 oxine (ILL) concentrated in the renal allografts of eight patients for whom transplant rejection, infection, or acute tubular necrosis (ATN) could be excluded. All patients had good-to-adequate renal function at the time of ILL scintigraphy, and none developed rejection or renal transplant failure during a 1-mo follow-up period. It is concluded that normally functioning renal allografts without evidence of rejection, infection, or ATN often will concentrate ILL. When a baseline study is not available for comparison, this phenomenon limits the value of ILL scintigraphy as a diagnostic test for transplant rejection or infection.

Gastric gallium-67 uptake in gastritis.

Even though Ga-67 imaging has been used widely in the diagnosis of malignant as well as inflammatory lesions, its uptake in the stomach has been reported in the literature mainly in gastric lymphoma and carcinoma. As shown in this case, intense gastric uptake of the radionuclide may be seen in common gastritis without malignancy. Perhaps the benign gastric uptake of Ga-67 deserves more emphasis.

An ambulatory ventricular function monitor: validation and preliminary clinical results.

A device for the continuous measurement of left ventricular (LV) function was tested in a series of 34 subjects. The instrument consisted of 2 arrays of radiation sensitive cadmium telluride detectors held in place over the region of the left ventricle and lung by a vest-like garment (hence the name VEST). The VEST electronic instrumentation included analog-to-digital converters, a battery pack, microprocessor and gating device, which were worn in a back pack. Data generated by the VEST, including the digitized average electrocardiogram, RR interval, counts/13 ms in each radiation detector, and time since commencement of data recording, were recorded on a cassette tape recorder every 2 minutes for subsequent analysis. At the conclusion of conventional multigated blood pool imaging, the VEST was positioned and worn by the subjects while supine, standing in place and walking. The correlation of ejection fraction calculated independently from the VEST and scintillation camera data was greater than 0.95. The inter-record reproducibility of the ejection fraction measured by the VEST in sedentary subjects was less than 3%.

A simplified technique for measuring right ventricular ejection fraction using the equilibrium radionuclide angiocardiogram and the slant-hole collimator.

The authors developed and tested a simplified technique for measuring the right ventricular ejection fraction (RVEF). Following in vivo 99mTc red cell labeling, equilibrium (ECG-gated) radionuclide angiocardiography was performed in the modified left-anterior-oblique projection using a 30 degree slant-hold collimator. A single region-of-interest was defined from the ejection fraction image, and background was corrected. In 11 normal patients, the mean RVEF was 0.59 +/- 0.08 (SD). In 20 patients with suspected disease, who had RVEF measured by both equilibrium and first-pass techniques, the correlation between the two methods was excellent (r = 0.95; RVEF [first-pass] = 0.74 RVEF [equilibrium] + 0.03; Sy,x = 0.05). Interobserver correlation was also excellent (r = 0.98; Sy,x = 0.03), as was the correlation between RVEFs measured at least 60 minutes apart (r = 0.98; Sy,x = 0.03). This method was more accurate than alternative techniques, using either a background region-of-interest adjacent to the right ventricle or a fixed right ventricular region-of-interest which included the infundibulum. This simplified technique provides a reproducible method for the sequential quantitative assessment of right ventricular performance.