Effect of dopamine agonists and antagonists on neurotensin-induced antinociception

In previous reports, we have demonstrated that intracisternal (IC) administration of neurotensin (NT), an endogenous tridecapeptide, produces significant antinociception in a variety of analgesic tests, including the hot-plate test. In addition, many of the central nervous system effects of NT (i.e., hypothermia, gastric cytoprotection) appear to be mediated by brain dopamine (DA) systems. In this study, we evaluated the effect of selected DA agonists and antagonists on NT-induced antinociception in the hot-plate test with mice. Doses, route of administration, and pretreatment interval were determined from the available literature to significantly affect the incidence of DA-dependent behaviors. Pretreatment with chlorpromazine but not haloperidol significantly potentiated NT-induced antinociception. This potentiating effect of chlorpromazine appears not to be due to any intrinsic antinociceptive activity of this agent, chlorpromazine had no significant effect on hot-plate latencies when administered alone. The involvement of DA on NT-induced antinociception was further substantiated by the findings that pretreatment with several DA receptor agonists, including methylphenidate, apomorphine, and d-amphetamine, significantly antagonized the antinociceptive response to IC NT. None of these agents significantly altered the animal's response to the hot-plate when administered alone. The data furnished in the present report suggest that central DA circuits may be involved in the expression of NT-induced antinociception.     

Only Hyperuricemia with Crystalluria,but not Asymptomatic Hyperuricemia,Drives Progression of Chronic Kidney Disease

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Bedside diagnosis and follow-up of patients with pleural effusion by a hand-carried ultrasound device early after cardiac surgery

OBJECTIVES: The aim of this study was to assess the potential value of hand-carried ultrasound (HCU) devices in the diagnosis and follow-up of patients with pleural effusion (PE) after cardiac surgery. METHODS: Seventy consecutive patients were evaluated at bedside early after cardiac surgery, in the upright sitting position, using an HCU device on hospital admission and every 3 days until hospital discharge. The posterior chest wall was scanned along the paravertebral, scapular, and posterior axillary lines. For each hemithorax, an effusion index was derived as the sum of the intercostal spaces between the lower and upper limits of the PE along the lines of scanning, divided by 3. A standard chest radiograph was performed in all patients on hospital admission and at hospital discharge, and was qualitatively scored (0, absent; 1, small; 2, large PE). The findings of the HCU device and radiograph were compared using kappa statistics and the Kruskal-Wallis test. RESULTS: A chest ultrasound was feasible in all patients (mean [+/- SD] time, 5 +/- 2 min). Compared with the chest ultrasound, a physical examination showed a sensitivity of 69% and a specificity of 77%. On hospital admission, the HCU device detected a PE in 72 of 140 hemithoraxes. Agreement with the finding of the radiograph was 76% (kappa = 0.52). In 15 hemithoraxes, the HCU device revealed a PE that had not been diagnosed using the radiograph. Conversely, in 18 hemithoraxes a PE that had been diagnosed with a radiograph was not confirmed by the HCU device. The correlation between ultrasound and radiographic scores was statistically significant (p < 0.001). At hospital discharge, a PE was present in 31 of 140 hemithoraxes according to the findings of the HCU device, and in 38 of 140 hemithoraxes according to the findings of the radiograph (agreement, 78%; kappa = 0.44). CONCLUSIONS: In patients early after cardiac surgery, HCU devices allow rapid PE detection and improve the clinical diagnosis. Compared to a radiograph, this method offers the unique advantage of the bedside evaluation of patients without the need for radiation exposure.     

Lack of Borrelia burgdorferi DNA in synovial samples from patients with antibiotic treatment-resistant Lyme arthritis

OBJECTIVE: To determine whether Borrelia burgdorferi DNA may be detected in synovial tissue from patients with Lyme arthritis who have persistent synovial inflammation after antibiotic treatment. METHODS: Synovial specimens obtained at synovectomy from 26 patients with antibiotic treatment-resistant Lyme arthritis and from 10 control subjects were tested for B burgdorferi DNA using 3 primer-probe sets that target genes encoding outer surface proteins A or B or a flagellar protein (P41) of the spirochete. RESULTS: The 26 patients with Lyme arthritis, who had received antibiotic therapy for a mean total duration of 8 weeks prior to synovectomy, and the 10 control subjects each had negative polymerase chain reaction (PCR) results in synovial samples. When the samples were spiked with approximately 1-10 B burgdorferi, all but 1 had positive PCR results, suggesting that spirochetal DNA could have been detected in most of the unspiked samples if it had been present. CONCLUSION: These results indicate that synovial inflammation may persist in some patients with Lyme arthritis after the apparent eradication of the spirochete from the joint with antibiotic therapy.     

Percutaneous coronary intervention of or through saphenous vein grafts or internal mammary arteries: the impact of stents, adjunctive pharmacology, and multicomponent distal protection.

We hypothesized that the use of stents and aggressive adjunctive pharmacotherapies has been associated with lower rates of complicating myocardial infarction (MI) and improved long-term outcomes compared to either previous balloon-only percutaneous coronary intervention (PCI) or atheroablative intervention for lesions of or through saphenous vein grafts (SVGs) and/or internal mammary arteries (IMAs). PCI of SVG has been complicated by relatively high rates of procedural MI and less favorable long-term outcomes than native vessel PCI, stimulating the development and application of an array of technologies. This study was based on retrospective review of stent-era (1999-2004) 5-year experience of a single center with 95 SVG procedures in 85 patients and 20 IMA procedures in 20 patients. These cases were compared with the previously published experience of one of the operators during the balloon-only period and literature review of the application of multiple technologies to SVG intervention, as well as consideration of the reoperation alternative. There was one in-hospital death each in the SVG cohort (1%) and in the IMA cohort (5%). There were SIX procedural MIs (6%), defined by total CK > normal, and 19 procedural MIs (20%) based on troponin-I > 1.0. Follow-up has been from 4 months to 5 years (average, 2.5 years), with 91% survival and one late CABG in the IMA group. SVG PCI with stents and adjunctive pharmacotherapies is associated with relatively low rates of procedural MI and favorable long-term outcomes.     

The MPO Study: just a European HEMO Study or something very different?

Although results from observational and epidemiological studies suggested a survival benefit associated with high-flux hemodialysis, conclusive evidence from prospective randomized clinical trials has been lacking. Both the HEMO Study in the USA and the Membrane Permeability Outcome Study (MPO Study) in Europe are randomized studies investigating the effect of high- and low-flux hemodialysis on patient outcomes, even though there were some significant differences in the design of the two studies. An earlier randomized clinical trial could not show differences on patient survival between patient groups being treated with membranes of different material and permeability, but this trial was not designed specifically to examine this particular endpoint. Based on these previous experiences, the MPO Study addressed a hemodialysis patient population which was considered to be more susceptible to the intervention with high-flux dialysis. To identify these patients with an elevated risk, low serum albumin levels were chosen as an indicator; low serum albumin is associated with malnutrition, inflammation, atherosclerosis, and with increased risk of morbidity and mortality. Together with low serum albumin, patients had to be new to dialysis to be selected for the MPO Study. These particular considerations on patient selection, together with additional methodological refinements in the study design allow the conclusion that the MPO Study is valid on its own rather than being a European version of the HEMO Study.