Patients with non-insulin-dependent diabetes mellitus (NIDDM) who have chronic hyperglycemia lose acute incremental insulin responses to glucose but are able to briskly respond to other p-cell secretagogues. To investigate whether this is a defect specific for glucose or represents a more general phenomenon, we measured the insulin responses to acute intravenous tolbutamide in 10 obese patients with NIDDM both before and during sulfonylurea therapy with tolazamide. Comparable glycemia was achieved with oral dextrose 2 h before intravenous testing. To assess p-cell responsiveness to a nonsulfonylurea secretagogue, 1 mg glucagon was administered intravenously during tolazamide therapy.In seven patients, the mean peak insulin increment 5 or 10 min after intravenous tolbutamide was 54 ± 11 ixU/ml when not receiving tolazamide (0.14 ± 1 . 3 |xU/ ml) with tolazamide (P < .001), even though serum insulin responded rapidly to intravenous glucagon. In four patients tested for reversibility of their refractoriness to intravenous tolbutamide during chronic tolazamide therapy, the mean peak insulin increment 1 wk after discontinuing tolazamide was 79 ± 22 (xU/ml. A relatively rapid development of refractoriness was documented in four patients who were tested only 12 h after beginning tolazamide therapy; the mean peak insulin increments 5-10 min after intravenous tolbutamide were undetectable (-0.5 (xU/ml), yet responses to intravenous glucagon were evident.In these NIDDM patients, exposure of pancreatic pcells to sustained levels of sulfonylureas induces a reversible state of refractoriness to acute stimulation with sufonylureas but not to another secretagogue. This phenomenon has features in common with the effect of sustained hyperglycemia on desensitization of the p-cell response to intravenous glucose with implications regarding the pathogenesis of NIDDM. Moreover, it suggests that the insulinotropic effect of sulfonylureas might be more effective, particularly in cases of NIDDM with "secondary failure" to sulfonylureas, if these drugs are administered either on an intermittent schedule or as "pulse" therapy, using a form with a shorter duration of action. DIABETES 1986; 35:1314-20.

Although the anatomical configuration of the amygdala has been studied a great deal, very little research has been conducted on understanding the precise mechanism by which this emotional regulatory center exerts its control on emotional and sexual behavior. By applying research methodology from the Neuroscience Research Institute, State University of New York, College at Old Westbury, we intended to demonstrate that much of the mediated effects of the amygdala, specifically the regulation of the male and female sexual response cycles, as well as related emotional considerations, exert their effects coupled to nitric oxide (NO) release. Furthermore, by using current anatomical and histological data, we demonstrated that amygdalar tissue rich in endocannabinoid and opiate, as well as catecholamine, receptors could exert its neurochemical effects within an NOmediated paradigm. This paradigm, together with the existence of estrogen and androgen signaling within the amygdala, further lends credence to our theoretical framework. We begin with a brief anatomical and functional review of amygdalar function, and then proceed to demonstrate its relationship with NO.

Background and Purpose— Intravenous tissue-type plasminogen activator (tPA) is a proven treatment for acute ischemic stroke, but there has been limited evaluation among patients aged ≥90 years. Methods— We analyzed data from the Get With The Guidelines–Stroke national quality improvement registry from January 2009 to April 2013. Frequency, determinants, and outcomes of tPA use were compared among patients aged ≥90 and 3 younger age groups (18–64, 65–79, and 80–89 years). Results— Among 35 708 patients from 1178 sites who arrived within 2 hours of time last known well and received tPA, 2585 (7.2%) were ≥90 years. Compared with younger patients, the rate of tPA use among patients without a documented contraindication was lower among patients aged ≥90 years (67.4% versus 84.1% in 18–89-year olds; P <0.0001). Discharge outcomes among individuals aged ≥90 years included discharge to home or acute rehabilitation in 31.4%, independent ambulation at discharge in 13.4%, symptomatic hemorrhage in 6.1%, and in-hospital mortality or hospice discharge in 36.4%. On multivariable analysis, good functional outcomes generally occurred less often and mortality more often among patients aged ≥90 years. The risk of symptomatic hemorrhage was increased compared with patients <65 years but was not significantly different than the risk in 66- to 89-year olds. Conclusions— The use of intravenous tPA among those aged ≥90 years is lower than in younger patients. When fibrinolytic therapy is used, the risk of symptomatic hemorrhage is not higher than in 66- to 89-year olds; however, mortality is higher and functional outcomes are lower.

INTRODUCTION Acute disseminated encephalomyelitis (ADEM) is a rare demyelinating disease of the central nervous system (CNS) that classically occurs in children and adolescents. It characteristically presents with acute inflammation, resulting in demyelination, often following an infectious disease. ADEM has been described in adult patients, but the incidence in the adult and especially elderly population is low. CASES We describe five older adults (age 57 to 85) who presented with acute neurological symptoms. Three patients presented with an infectious illness preceding the event, 4 patients were encephalopathic, and oligoclonal bands (OCBs) were negative in all tested cases. The clinical scenario and imaging studies suggested alternative diagnoses, such as metastasis, primary CNS tumor, or stroke. Two patients had contrast enhancing lesions, two other patients had lesions with restricted diffusion on diffusion-weighted imaging. Neuropathologic diagnostic from biopsy or autopsy was eventually conclusive, showing perivascular zones of myelin loss with relative axonal sparing in all five cases. CONCLUSION Each of these patients was found to have pathological findings of acute demyelination on tissue diagnosis, suggesting ADEM or ADEM-like disease. The initial presentation and imaging was pointing toward other diagnoses. Broad differential diagnosis is important, especially for older patients, and pathological proof might be warranted for a conclusive diagnosis.