beta-Endorphin-induced hyperglycemia is mediated by increased central sympathetic outflow to adrenal medulla

Synthetic human beta-endorphin increased plasma glucose concentration when administered intracisternally in chronically cannulated, conscious, unrestrained, adult male rats. This hyperglycemic effect of beta-endorphin was blocked by prior systemic administration of naloxone, supporting mediation of the effect at opioid receptors in brain. Adrenal denervation blocked the beta-endorphin-induced increase in plasma glucose, supporting a thesis that this effect is mediated at least in part by increased epinephrine secretion. The hyperglycemic response to intracerebral beta-endorphin was also blocked by either intracerebral hemicholinium-3 or somatostatin, supporting both a cholinergic link and a somatostatin neuron in the brain mechanism regulating endorphin-induced stimulation of sympathetic outflow.     

Surgical repair of type A aortic dissection by the circulatory arrest-graft inclusion technique in sixty-six patients

During an 8-year period (1984 to 1991) 66 patients (mean age 59 years, range 26 to 84 years) with type A aortic dissection (60 ascending aorta tears, 6 arch tears; 35 acute, 31 chronic) had surgical repair by a continuous suture-graft inclusion technique. Hypothermic circulatory arrest (16 degrees C) was used in 58 patients (35/35 acute, 23/31 chronic; mean arrest time 26 minutes, range 10 to 55 minutes). Fifty-two patients had hemiarch repair and 6 had total arch replacement. Aortic valve disease necessitated treatment in 38 patients (1 valved conduit, 20 valve replacements, 17 valve repairs). Recently 11 patients had valve repair by reconstruction of the native aortic root, by means of techniques similar to those used for homograft valve insertion. Operative mortality was 9% (14% acute, 3% chronic). Stroke occurred in 2 patients (3%) and was fatal in both. Variables suggestive of increased operative risk by univariate analysis were acuteness (p = 0.12), visceral ischemia (p = 0.12), and preoperative shock (p = 0.13). No variable was significant by multivariate analysis. Overall actuarial survival at 48 months was 77%, with 3 late deaths from a ruptured distal aneurysm. Late computed tomography or magnetic resonance imaging scan was done in 28 patients at a mean interval of 33 months. These studies identified 1 patient with a pseudoaneurysm requiring reoperation and 3 patients with contained flow between the graft and the wrap. Three patients required late operation: 1 for pseudoaneurysm, 1 for arch dissection, and 1 for repair of a distal aneurysm.     

Protective effects of an aptamer inhibitor of neutrophil elastase in lung inflammatory injury

Neutrophils play an important part in the development of acute inflammatory injury. Human neutrophils contain high levels of the serine protease elastase, which is stored in azurophilic granules and is secreted in response to inflammatory stimuli. Elastase is capable of degrading many components of extracellular matrix [1-4] and has cytotoxic effects on endothelial cells [5-7] and airway epithelial cells. Three types of endogenous protease inhibitors control the activity of neutrophil elastase, including alpha-1 protease inhibitor (alpha-1PI), alpha-2 macroglobulin and secreted leukoproteinase inhibitor (SLPI) [8-10]. A disturbed balance between neutrophil elastase and these inhibitors has been found in various acute clinical conditions (such as adult respiratory syndrome and ischemia-reperfusion injury) and in chronic diseases. We investigated the effect of NX21909, a selected oligonucleotide (aptamer) inhibitor of elastase, in an animal model of acute lung inflammatory disease [11-14]. This inhibitor was previously selected from a hybrid library of randomized DNA and a small-molecule irreversible inhibitor of elastase (a valine diphenyl ester phosphonate, Fig. 1), by the blended SELEX process [15]. We show that NX21909 inhibits lung injury and neutrophil influx in a dose-dependent manner, the first demonstration of efficacy by an aptamer in an animal disease model.     

Vertebral artery injury in C1-2 transarticular screw fixation: results of a survey of the AANS/CNS section on disorders of the spine and peripheral nerves. American Association of Neurological Surgeons/Congress of Neurological Surgeons

OBJECTIVES: The goal of this study was to investigate the possible role of transesophageal echocardiography in the evaluation of patients with clinical pacemaker syndrome. BACKGROUND: Several reports on transthoracic echocardiographic features of ventricular pacing were described; however, no previous study of transesophageal echocardiography has been undertaken in patients at the severe end of pacemaker syndrome who need reprogramming of dual-chamber pacing for symptom relief. METHODS: Twelve patients with ventricular-inhibited pacemakers (VVI) with clinical symptomatic pacemaker syndrome (group I) and 10 patients with VVI without pacemaker syndrome (group II) were prospectively studied. The two groups were pacemaker dependent and had persistent ventriculoatrial conduction. Transesophageal echocardiographic parameters were assessed in group II and within 6 hours before reprogramming to the DDD mode in group I. Follow-up transesophageal echocardiographic study was performed 28+/-5 days after reprogramming in group I. RESULTS: All patients in group I had subjective improvements of symptoms after DDD reprogramming. The atrial reverse flow velocities of pulmonary veins in group I before reprogramming were significantly higher in group II (39.3+/-11.4 versus 15.7+/-13.5 cm/sec, p < 0.0001). Spontaneous echo contrast in the descending aorta was detected in all patients from group I before reprogramming. The prevalence of significant mitral regurgitation (> or = moderate) was significantly higher in group I before reprogramming than in group II (67% versus 8%, p = 0.01). Significant mitral regurgitation and spontaneous echo contrast in the descending aorta in group I disappeared after reprogramming to the DDD mode. CONCLUSIONS: Transesophageal echocardiography provides physiologic, pacemaker-related hemodynamic changes in paced patients. Significantly higher atrial reverse flow velocities of pulmonary veins, increased frequency of spontaneous echo contrast in the descending aorta, and significant mitral regurgitation are peculiar echocardiographic findings in patients with VVI with clinical pacemaker syndrome.     

Effects of short-term treatment of hyperlipidemia on coronary vasodilator function and myocardial perfusion in regions having substantial impairment of baseline dilator reverse

BACKGROUND: We tested the hypothesis that correction of hyperlipidemia improves coronary vasodilator response and maximal perfusion in myocardial regions having substantial impairment of pretreatment vasodilator capacity. METHODS AND RESULTS: Measurements of myocardial blood flow were made with PET [13N]ammonia in 12 patients with ischemic heart disease (11 men; age, 65+/-8 years [mean+/-SD]) at rest and during adenosine at 70 and then 140 microg . kg-1 . min-1 for 5 minutes each before and approximately 4 months after simvastatin treatment (40 mg daily). Simvastatin reduced LDL (171+/-13 before versus 99+/-18 mg/dL after simvastatin, P<0.001) and increased HDL (39+/-8 versus 45+/-9 mg/dL, P<0.05). Myocardial segments were classified on the basis of pretreatment blood flow response to 140 microg . kg-1 . min-1 adenosine as normal (flow >/=2 mL . min-1 . g-1) or abnormal (flow <2 mL . min-1 . g-1). In normal segments, baseline myocardial blood flow (0.95+/-0.32) increased (P<0.001) at both low- (1.62+/-0.81) and high- (2.63+/-0.41) dose adenosine and was unchanged both at rest and with adenosine after simvastatin. In abnormal segments, myocardial blood flow at rest (0. 73+/-0.19) increased at low- (1.06+/-0.59, P<0.02) and high- (1. 29+/-0.33, P<0.01) dose adenosine. After simvastatin, myocardial blood flow increased more compared with pretreatment at both low- (1. 37+/-0.66, P<0.05 versus pretreatment) and high- (1.89+/-0.79, P<0. 01 versus pretreatment) dose adenosine. CONCLUSIONS: Short-term lipid-lowering therapy increases stenotic segment maximal myocardial blood flow by approximately 45%. The mechanism involves enhanced, flow-mediated dilation of stenotic epicardial conduit vessels and may account at least in part for the efficacy of lipid lowering in secondary prevention trials and in reducing ischemic episodes in ambulatory patients.     

Antibiotic therapy for seminal infection. Effect on antioxidant activity and T-helper cytokines

OBJECTIVE: To investigate the effect of antibiotic therapy on seminal infection. STUDY DESIGN: The seminal plasma of 50 men was evaluated in three groups: (1) men with seminal infection (20), (2) men with leukocytospermia only (18), and (3) men of proven fertility (12). The evaluation protocol included semen analysis, culture and antibiotic sensitivity test, total antioxidant activity, alpha-tocopherol and retinol, T-helper cytokines, IL-2, IL-8, IL-4 and antisperm antibodies. RESULTS: Sperm parameters were worse with seminal infection: 25 versus 84 million per milliliter for fertile men. Antioxidant activity, total alpha-tocopherol and retinol were reduced in leukocytospermia (P < .02, .01) and seminal infection (P < .01, .05) as compared to controls. Antisperm antibodies IL-2 and IL-8 were highly expressed, while IL-4 was low in men with leukocytospermia and bacteriospermia. Gram-negative organisms were more associated with expression of T-helper 1 cytokines than T-helper 2 cytokines. Antibiotic therapy significantly improved the sperm parameters, antioxidant activity and IL-4 but reduced IL-2 and IL-8 and had no effect on antisperm antibody titer. CONCLUSION: Antibiotic therapy improves sperm parameters by increasing antioxidant activity and IL-4 and by reducing IL-2 and IL-8.