Scintigraphic assessment of regionalized defects in myocardial sympathetic innervation and blood flow regulation in diabetic patients with autonomic neuropathy

OBJECTIVES: This study sought to evaluate whether regional sympathetic myocardial denervation in diabetes is associated with abnormal myocardial blood flow under rest and adenosine-stimulated conditions. BACKGROUND: Diabetic autonomic neuropathy (DAN) has been invoked as a cause of unexplained sudden cardiac death, potentially by altering electrical stability or impairing myocardial blood flow, or both. The effects of denervation on cardiac blood flow in diabetes are unknown. METHODS: We studied 14 diabetic subjects (7 without DAN, 7 with advanced DAN) and 13 nondiabetic control subjects without known coronary artery disease. Positron emission tomography using carbon-11 hydroxyephedrine was used to characterize left ventricular cardiac sympathetic innervation and nitrogen-13 ammonia to measure myocardial blood flow at rest and after intravenous administration of adenosine (140 microg/kg body weight per min). RESULTS: Persistent sympathetic left ventricular proximal wall innervation was observed, even in advanced neuropathy. Rest myocardial blood flow was higher in the neuropathic subjects (109 +/- 29 ml/100 g per min) than in either the nondiabetic (69 +/- 8 ml/100 g per min, p < 0.01) or the nonneuropathic diabetic subjects (79 +/- 23 ml/100 g per min, p < 0.05). During adenosine infusion, global left ventricular myocardial blood flow was significantly less in the neuropathic subjects (204 +/- 73 ml/100 g per min) than in the nonneuropathic diabetic group (324 +/- 135 ml/100 g per min, p < 0.05). Coronary flow reserve was also decreased in the neuropathic subjects, who achieved only 46% (p < 0.01) and 44% (p < 0.01) of the values measured in nondiabetic and nonneuropathic diabetic subjects, respectively. Assessment of the myocardial innervation/blood flow relation during adenosine infusion showed that myocardial blood flow in neuropathic subjects was virtually identical to that in nonneuropathic diabetic subjects in the distal denervated myocardium but was 43% (p < 0.05) lower than that in the nonneuropathic diabetic subjects in the proximal innervated segments. CONCLUSIONS: DAN is associated with altered myocardial blood flow, with regions of persistent sympathetic innervation exhibiting the greatest deficits of vasodilator reserve. Future studies are required to evaluate the etiology of these abnormalities and to evaluate the contribution of the persistent islands of innervation to sudden cardiac death complicating diabetes.     

Induction of autoimmune arthritis in HLA-DR4 (DRB1*0401) transgenic mice by immunization with human and bovine type II collagen

Although associations between the expression of particular HLA genes and the susceptibility to specific autoimmune diseases has been known for some time, the role that these HLA molecules play in the autoimmune response is unclear. Through the establishment of a chimeric HLA-DR/I-E transgene, we have examined the function of the rheumatoid arthritis (RA) susceptibility allele HLA-DR4 (DRB1*0401) in presenting antigenic peptides derived from the model Ag, type II collagen (CII), and in mediating an autoimmune response. As a transgene, the chimeric DR4 molecule conferred susceptibility to an autoimmune arthritis induced by immunization with human CII or bovine CII. These mice developed an inflammatory, autoimmune arthritis that was similar both histologically and in severity to that previously described for the collagen-induced arthritis model. The DR4-mediated autoimmune arthritis was accompanied by T cell and B cell responses to both the immunogen and the autoantigen, murine CII. The DR4-restricted T cell response to human CII was focused on an immunodominant determinant within CII263-270 and a minor determinant within CII286-300, the same CII determinants recently identified for yet another RA susceptibility allele, HLA-DR1 (DRB1*0101). Thus these data demonstrate that, like HLA-DR1, HLA-DR4 is capable of binding peptides derived from human CII and therefore probably plays a role in the autoimmune response to human CII observed in RA patients.     

Parent-victim agreement in adolescent suicide research

It is known that transcranial magnetic stimulation (TMS) administered over the occipital pole suppresses recognition of visual objects. Our aim was to ascertain whether this suppression can be interpreted as a change in visual contrast threshold. Four subjects detected the orientation of an U-shaped hook flashed for 21 ms. Under control conditions, mean contrast threshold was found at 0.88 log units Weber contrast. Thresholds were raised if TMS was applied 40-200 ms after the visual stimulus. Maximum elevation was 1.67 log units under TMS at 120 ms stimulus onset asynchrony. This phenomenon can be interpreted as a reduction in signal-to-noise ratio of the visual stimuli by TMS, which can be compensated for by increasing the contrast of the stimuli.     

Interaction of a novel GDP exchange inhibitor with the Ras protein

Mutated, tumorigenic Ras is present in a variety of human tumors. Compounds that inhibit tumorigenic Ras function may be useful in the treatment of Ras-related tumors. The interaction of a novel GDP exchange inhibitor (SCH-54292) with the Ras-GDP protein was studied by NMR spectroscopy. The binding of the inhibitor to the Ras protein was enhanced at low Mg2+ concentrations, which enabled the preparation of a stable complex for NMR study. To understand the enhanced inhibitor binding and the increased GDP dissociation rates of the Ras protein, the conformational changes of the Ras protein at low Mg2+ concentrations was investigated using two-dimensional 1H-15N HSQC experiments. The Ras protein existed in two conformations in slow exchange on the NMR time scale under such conditions. The conformational changes mainly occurred in the GDP binding pocket, in the switch I and the switch II regions, and were reversible. The Ras protein resumed its regular conformation after an excess amount of Mg2+ was added. A model of the inhibitor in complex with the Ras-GDP protein was derived from intra- and intermolecular NOE distance constraints, and revealed that the inhibitor bound to the critical switch II region of the Ras protein.     

Naso-temporal asymmetry of spatial interactions in strabismic amblyopia

PURPOSE: Naso-temporal asymmetries of visual acuity and contrast sensitivity have been reported in strabismic amblyopia and attributed to asymmetries of interocular suppression. In this study, we investigated the naso-temporal asymmetry of cortical spatial interactions in two strabismic amblyopes (one esotrope and one exotrope). METHODS: Length and width Westheimer functions were measured on both amblyopes at the 10 deg retinal eccentricity of both nasal and temporal visual fields. RESULTS: Spatial interactions in the two amblyopic eyes were more degraded in the temporal visual fields than in the nasal visual fields. A comparison with results from the preferred eyes suggested that this asymmetry was caused mainly by a loss of spatial interactions in the temporal visual fields of amblyopic eyes, with those in the nasal visual fields being normal. CONCLUSION: Our results suggest that intracortical connections underlying cortical spatial interactions might have been degraded by amblyopia. This degradation exists not only in the areas of the strabismic visual cortex responding to foveal stimuli but also in those responding to stimuli presented in the temporal visual fields.     

Minimally invasive valve operations

BACKGROUND: To reduce the morbidity from valvular heart operations, a right parasternal approach was introduced. We report our initial experience with the procedure. METHODS: From January 1996 through July 1996, 115 patients underwent primary isolated valve procedures. One hundred (85%) patients underwent the operation through a right parasternal incision. RESULTS: There was one hospital death secondary to a stroke on the fifth postoperative day. Three patients (two with aortic valve operations and one having a mitral valve procedure) required conversion to sternotomy. Mean aortic occlusion time was 71 minutes; mean cardiopulmonary bypass time was 93 minutes. Mean stay in the intensive care unit was 27 hours and mean hospital postoperative stay was 5.7 days. Seventy-seven percent of the patients did not receive blood transfusions. Comparison with median sternotomy demonstrated a reduction in both postoperative length of stay and direct hospital costs. CONCLUSIONS: We conclude that this minimally invasive approach is safe for a variety of valve procedures and is effective in reducing surgical trauma and cost.     

A qualitative investigation into an HIV outbreak among injection drug users in Vancouver, British Columbia

The effect of Cd, Cu, Zn, Hg, and Pb solutions at various concentrations, on the restoration potential of the leaves of Portulaca oleracea was tested. All the trace metals completely affected the shoot regeneration. The degree of their effect on root regeneration, however, varied. Early initiation of parental leaf decay was also observed. The order of their relative effect on the regeneration process was: Cd > Cu > Zn > Hg > Pb.