The diagnosis of dementias of the Alzheimer type

There are a large number of people with primary degenerative dementia of the Alzheimer type throughout the world. This number will continue to increase during the next century, and will represent a major health problem for future generations. The diagnosis of the dementia is based on the presence of disturbances in higher cortical functions, cognition, language or behaviour, and the presence of apraxia and agnosia. To determine the etiology of the dementia, a number of investigations are required; these include neurological examination, use of diagnostic criteria, assessment instruments and measurement of mental functions, electroencephalography, and imaging techniques. Diagnosis is generally obvious in the middle stages of the disorder, but may be difficult or even hazardous in the early stages. This is a major handicap for research investigations. At present, emission tomography is the only technique which identifies abnormalities in the early stages of the disorder and which differentiates primary degenerative dementia from multi-infarct dementia. For the time being, this technique is still too sophisticated and costly to be used on a regular basis, but it will prove indispensable in the identification, understanding and early treatment of dementia.     

Short-Ti inversion-recovery pulse sequence: analysis and initial experience in cancer imaging

Inversion recovery (IR), commonly considered a pulse sequence capable of producing T1-weighted images with excellent display of normal anatomy, is versatile: The null point and peak time provide a useful, succinct summary of the properties of IR and its capacity for producing both T1- and T2-weighted images. Shortening of the inversion time (TI) and creation of a short-TI inversion-recovery (STIR) pulse sequence increases sensitivity to malignancy and other abnormalities by making the effects of prolonged T1 and T2 on signal intensity additive and by nulling the signal from fat. The authors examined over 300 patients with various malignancies and compared STIR images with T1- and T2-weighted images obtained at 0.5 T. In 43 cases, signal-difference-to-noise ratios (SD/Ns) were calculated between tumor, fat, and muscle. In general, STIR images demonstrated tumor as a conspicuously high-intensity area in a background of muted, discernible anatomic detail. The good contrast achieved with STIR sequences between tumor and fat (SD/N = 18.1) and tumor and muscle (SD/N = 12.9) consolidated into a single image the information contained separately on T1- and T2-weighted images, which facilitates efficient detection and localization of malignancy.     

A randomized trial of a family physician intervention for smoking cessation

We assessed the impact of three conditions on one-year smoking cessation rates. Physicians in 70 community general practices were randomly allocated by practice to one of three groups: In the usual care group, smoking patients were to receive the care they normally would receive. In the gum only group, physicians were asked to speak to patients about smoking cessation and offer nicotine gum. In the gum plus group, physicians were trained in the experimental intervention. This intervention involved advice to stop smoking, the setting of a quit date, the offer of nicotine gum, and four follow-up visits. Smoking cessation was measured by self-report after one year and validated using saliva cotinine measures. Using a criterion of at least three months of abstinence, 8.8% of the patients of the trained physicians had stopped smoking at the one-year follow-up compared with 4.4% and 6.1% of the patients in the usual care and gum only groups, respectively.     

Similar co-stimulation requirements of CD4+ and CD8+ primary T helper cells: role of IL-1 and IL-6 in inducing IL-2 secretion and subsequent proliferation.

Primary murine CD4+ and CD8+ T helper (Th) cells provide help for various immune responses by secreting lymphokines which activate effector cells. The purpose of the present study was to investigate the co-stimulatory signals that, together with T cell receptor (TCR) cross-linking, induce phenotypically distinct primary Th cells to secrete IL-2 and proliferate. We isolated highly purified populations of primary CD4+ or CD8+ T cells and stimulated them in vitro with platebound anti-CD3 mAb. TCR cross-linking by anti-CD3 mAb induced both IL-2 receptor expression and responsiveness to exogenous IL-2, but was not sufficient to induce either IL-2 secretion or T cell proliferation. Rather, for both CD4+ and CD8+ primary Th cells, IL-2 secretion and proliferation required both TCR cross-linking and antigen presenting cell (APC)-derived co-stimulatory signals. Based on G-10 adherence and sensitivity to gamma-irradiation, the APC populations able to induce primary CD4+ Th cells and primary CD8+ Th cells to secrete IL-2 were indistinguishable. In addition, we found that either IL-1 or IL-6 could replace the requirement for APC-derived co-stimulatory signals for IL-2 secretion and proliferation by both primary CD4+ Th cells and primary CD8+ Th cells. Thus, the present study has examined and compared the co-stimulatory requirements of rigorously purified subsets of IL-2-secreting primary CD4+ and primary CD8+ T cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Nervous control of gastric and pancreatic secretory response to 2-deoxy-D-glucose in the dog

The relative contribution of the vagus and splanchnic nerves as mediators of the action of 2-deoxy-D-glucose (2-DG) on the stomach and the pancreas is largely unknown. In conscious dogs with gastric and pancreatic fistulas, the effect of 2-DG (100 mg kg-1, given as an intravenous bolus) on gastric acid and pancreatic exocrine secretion was tested before and after bilateral truncal vagotomy and after truncal vagotomy plus celiac and superior mesenteric ganglionectomy (i.e. extrinsic denervation of the stomach and the pancreas). In another set of dogs, only ganglionectomy was performed and the same experiments were done as in the first set of dogs. With the extrinsic nerves intact, 2-DG caused a rapid (within 15 min) and prolonged increase in gastric acid output as well as in pancreatic flow rate, bicarbonate and protein output. Truncal vagotomy abolished the gastric acid and pancreatic secretory response to 2-DG; additional ganglionectomy had no further effect. Ganglionectomy alone did not significantly alter 2-DG-stimulated gastric acid output, pancreatic flow rate and bicarbonate output; protein output, however, was significantly diminished by 57%. These results indicate that (a) intravenous 2-DG is a potent stimulant of gastric acid and pancreatic bicarbonate and protein output; (b) the vagus nerves are the major mediators of the gastric and pancreatic secretory response to 2-DG; (c) the sympathetic nerve fibers running through the celiac and superior mesenteric ganglia are probably not involved in the mediation of the 2-DG-induced gastric acid and pancreatic bicarbonate secretion. The diminished protein response to 2-DG after ganglionectomy is probably due to cut vagal fibers running through these ganglia.     

Effects of alterations in left ventricular filling, contractility, and systemic vascular resistance on the ascending aortic blood velocity waveform of normal subjects.

OBJECTIVES: To confirm the consistent effects on Doppler-measured aortic blood flow velocity waveform variables of alterations in left ventricular preload, afterload, and inotropy using pharmacologic and physiologic maneuvers. SETTING: Medical school laboratory. SUBJECTS: Healthy volunteers. INTERVENTIONS: Increasing infusion rates of dobutamine (1.25 to 5 micrograms/kg.min), esmolol (1.25 to 5 mg/min), phentolamine (1.25 to 5 mg/min), methoxamine (1.25 to 5 mg/min), metaraminol (1.25 to 5 mg/min), and placebo (1.25 to 5 mL of 0.9% saline/min) and increasing plasma removal (0.5 to 1 L) in awake, rested, supine subjects. MEASUREMENTS AND MAIN RESULTS: Ascending aortic blood flow was measured by the suprasternal Doppler approach allowing calculation of waveform variables of stroke distance and minute distance (linear measures of stroke volume and cardiac output), peak velocity, mean acceleration and flow time corrected for heart rate. An index of systemic vascular resistance was obtained by dividing mean systemic BP by the minute distance. Inotropic changes predominantly affected peak velocity and mean acceleration. Changes in preload mainly affected the flow time corrected for heart rate, whereas afterload changes had an intermediate effect. Unsuspected but subsequently confirmed hemodynamic effects were seen with esmolol and metaraminol. CONCLUSIONS: Aortic blood flow velocity waveform variables measured by Doppler ultrasound can be used to noninvasively follow changes in left ventricular preload, afterload, and inotropy.     

Lectin-like cell adhesion molecule 1 mediates leukocyte rolling in mesenteric venules in vivo

During the inflammatory response, granulocytes and other leukocytes adhere to and emigrate from small venules. Before firm attachment, leukocytes are observed rolling slowly along the endothelium in venules of most tissues accessible to intravital microscopy. The molecular mechanism underlying this early type of leukocyte-endothelial interaction is unknown. Leukocyte rolling was investigated in venules (diameter, 40 microns) of the exposed rat mesentery. Micro-infusion of a recombinant soluble chimera (LEC-IgG) of the murine homing receptor lectin-like cell adhesion molecule 1 (LEC-CAM 1; gp90MEL) into individual venules reduced the number of rolling leukocytes by 89% +/- 2% (mean +/- SEM, n = 20 venules), while a similar CD4 chimera (CD4-IgG) had no effect (inhibition 14% +/- 7%, n = 25). Rolling was also greatly reduced by a polyclonal serum against LEC-CAM 1 (inhibition 84% +/- 3%, n = 35); preimmune serum was ineffective (11% +/- 13% inhibition, n = 28). These findings indicate that LEC-CAM 1 mediates the adhesive interaction underlying leukocyte rolling and thus may play an important role in inflammation and in pathologic conditions involving leukocytes.     

Reconstitution of (BALB/c x B6)F1 normal mice with stem cells and thymus from nonobese diabetic mice results in autoimmune insulitis of the normal hosts' pancreases.

The NOD mouse develops immune-mediated diabetes mellitus characterized by T cell infiltration and destruction of pancreatic islet tissue. We wished to determine whether one contributing factor was an abnormality of the NOD pancreas that caused it to elicit an attack by NOD T cells. Therefore we constructed mice that had an NOD immune system and a non-NOD host pancreas. We found that these animals with only an NOD immune system developed both insulitis and diabetes in their non-NOD pancreas. We conclude that the NOD pancreas is not unique in its ability to elicit an autoimmune attack from NOD T cells.