Is Cerebral Microembolism in Mechanical Prosthetic Heart Valves Clinically Relevant?

BACKGROUND AND PURPOSE: High-intensity transient signals (HITS) are frequently detected by transcranial Doppler (TCD) ultrasound in patients with mechanical prosthetic heart valves (PHVs), but published data about their clinical relevance are controversial. This study was undertaken to determine the clinical relevance of HITS in patients with mechanical PHVs. METHODS: The authors prospectively studied patients with mechanical PHVs using TCD monitoring for microemboli detection with and without O2 inhalation. The cognitive testing of patients included the Mini-Mental State Examination, the Dementia Rating Scale, and MicroCog. RESULTS: The authors studied 36 patients (20 women, aged 58 +/- 13 years). HITS were detected in 72% of patients, with a nonsignificant increase of HITS rate in the aortic valve group (P = .07). There was no significant difference in HITS rate between asymptomatic and symptomatic patients. In a multiple linear regression model, HITS rate was predicted only by younger age (P = .024). No correlation was found between HITS rate and the cognitive performance of patients. There was a significant decrease in HITS rate after 100% O2 inhalation compared to baseline levels (32.8 +/- 40.2 vs 6.1 +/- 11.3, P = .011). Subgroup analysis in asymptomatic patients confirmed this finding (P = .017), but in symptomatic patients, decreased HITS rate was not statistically significant (P = .18). CONCLUSION: Only age was a significant predictor of HITS in patients with mechanical PHVs. The lack of association between HITS, clinical symptoms, and cognitive functioning suggests that most of these signals represent harmless epiphenomena, and only HITS detected after O2 inhalation have any clinical relevance.     

Diagnostic laparoscopy for chronic abdominal pain after gastric bypass.

BACKGROUND: To evaluate, in an observational study, the utility of diagnostic laparoscopy as a tool to evaluate patients with abdominal pain of unknown etiology after gastric bypass surgery. METHODS: A retrospective analysis was performed of data from patients who had undergone laparoscopy for diagnosis or treatment of abdominal pain. This study included 13 patients with negative preoperative radiographic and/or endoscopic findings. RESULTS: A total of 13 patients who had undergone Roux-en-Y gastric bypass underwent diagnostic laparoscopy for abdominal pain. The findings included internal hernia (4), adhesions (3), ventral hernia (2), partial small bowel obstruction (1), and chronic cholecystitis (1). There were 2 negative laparoscopies, while a diagnosis was made in 85%. After an average follow-up of 3.2 months, 7 of 11 patients had unresolved abdominal pain and 4 patients experienced pain resolution (2 patients were lost to follow-up). CONCLUSION: The results from this small retrospective study suggest that significant pathologic findings can be identified in most patients who have negative preoperative evaluation findings; however, the efficacy of diagnostic laparoscopy to eliminate pain in this patient population requires additional study. Despite the potential complications, we believe that diagnostic laparoscopy has a role in the diagnosis and treatment of chronic abdominal pain after gastric bypass.     

Rolling-circle amplification in DNA diagnostics: the power of simplicity

Due to its robustness and simplicity, the rolling replication of circular DNA probes holds a distinct position in DNA diagnostics among other isothermal methods of target, probe or signal amplification. Major rolling-circle amplification approaches to DNA detection via posthybridization probe/signal turn-by-turn enhancement are briefly overviewed here with an emphasis on the new concepts and latest progress in the field, including the single-molecule and single-mutation detection assays as exemplary applications. Underlying mechanisms, current controversies and principal advantages of rolling-circle amplification are also considered. Possible future directions for the further advancement of this diagnostic methodology are outlined.     

Synthetic Cannabinoid Abuse Resulting in ST-Segment Elevation Myocardial Infarction Requiring Percutaneous Coronary Intervention

Background

Synthetic cannabinoids (SC) are recreational designer drugs intended to mimic delta-9-tetrahydrocannabinol while surreptitiously circumventing classification by the Drug Enforcement Administration.

Effects of salvinorin A, a kappa-opioid hallucinogen, on a neuroendocrine biomarker assay in nonhuman primates with high kappa-receptor homology to humans

This study focused on the in vivo effects of the kappa-opioid hallucinogen salvinorin A, derived from the plant Salvia divinorum. The effects of salvinorin A (0.0032-0.056 mg/kg i.v.) were studied in a neuroendocrine biomarker assay of the anterior pituitary hormone prolactin in gonadally intact, adult male and female rhesus monkeys (n = 4 each). Salvinorin A produced dose- and time-dependent neuroendocrine effects, similar to the synthetic high-efficacy kappa-agonist U69,593 ((+)-(5alpha,7 alpha,8beta)-N-methyl-N-[7-(1-pyrrolidiniyl)-1-oxaspiro[4.5]dec-8yl]-benzeneacetamide), but of shorter duration than the latter. Salvinorin A was approximately equipotent to U69,593 in this endpoint (salvinorin A ED50, 0.015 mg/kg; U69,593 ED(50), 0.0098 mg/kg). The effects of i.v. salvinorin A were not prevented by a small dose of the opioid antagonist nalmefene (0.01 mg/kg s.c.) but were prevented by a larger dose of nalmefene (0.1 mg/kg); the latter nalmefene dose is sufficient to produce kappa-antagonist effects in this species. In contrast, the 5HT2 receptor antagonist ketanserin (0.1 mg/kg i.m.) did not prevent the effects of salvinorin A. As expected, the neuroendocrine effects of salvinorin A (0.0032 mg/kg i.v.) were more robust in female than in male subjects. Related studies focused on full-length cloning of the coding region of the rhesus monkey kappa-opioid receptor (OPRK1) gene and revealed a high homology of the nonhuman primate OPRK1 gene compared with the human OPRK1 gene, including particular C-terminal residues thought to be involved in receptor desensitization and internalization. The present studies indicate that the hallucinogen salvinorin A acts as a high-efficacy kappa-agonist in nonhuman primates in a translationally viable neuroendocrine biomarker assay.     

The sphingosine-1-phosphate (S1P) lysophospholipid receptor S1P3 regulates MAdCAM-1+ endothelial cells in splenic marginal sinus organization

Marginal zones (MZs) are microdomains in the spleen that contain various types of immune cells, including MZ B cells, MOMA1(+) metallophilic macrophages, and mucosal addressin cell adhesion molecule 1 (MAdCAM-1)(+) endothelial cells. MAdCAM-1(+) and MOMA1(+) cells line the sinus, that separates MZs from splenic follicles. Here we show that a receptor for the lysophospholipid sphingosine-1-phosphate (S1P), S1P(3), is required for normal numbers of splenic immature and MZ B cells, and for S1P-induced chemotaxis of MZ B cells. S1P(3) is also essential for proper alignment of MOMA1(+) macrophages and MAdCAM-1(+) endothelial cells along the marginal sinus. The lack of cohesion of the marginal sinus in S1P(3)(-/-) mice affects MZ B cell functions, as wild-type (WT) MZ B cells migrate more into S1P(3)(-/-) follicles than into WT follicles after treatment with lipopolysaccharide. Additionally, short-term homing experiments demonstrate that WT MZ B cells home to the S1P(3)(-/-) spleen in increased numbers, suggesting a role for the marginal sinus in regulating MZ B cells numbers. Moreover, S1P(3)(-/-) mice are defective in mounting immune responses to thymus-independent antigen type 2 due to defects in radiation-resistant cells in the spleen. These data identify lysophospholipids and the S1P(3) receptor as essential regulators of the MZ sinus and its role as a barrier to the follicle.