Brain injury and neurofunctional deficit in neonatal mice with hypoxic-ischemic encephalopathy

Birth asphyxia accounts for the majority of developmental motor and cognitive deficits. Studies were undertaken to develop a reproducible murine model of perinatal hypoxic-ischemic encephalopathy (HIE) which would permit both anatomic and neurofunctional quantification of injury. Short-term neurofunctional outcomes consisted of three developmental reflexes (righting, cliff aversion and geotaxis) assessed in 7-day-old mouse pups 24 h after unilateral carotid artery ligation followed by inhalation of 8% oxygen. Cerebral infarct volume was dependent on duration of hypoxia, being approximately 2.5-fold greater with longer (60 min) versus shorter (30 min) hypoxia exposure (P=0.001). All three sensorimotor neonatal reflexes assessed at 24 h after HIE injury correlated significantly with long-term neurofunction evaluated using a water-maze test of navigational learning and memory assessed 8 weeks later in the same animals. Cerebral atrophy, a delayed consequence of HIE in this model, also correlated strongly with water-maze performance (r=0.86, P=0.002). These data demonstrate for the first time that murine neonatal sensorimotor reflex performance can be rigorously quantified in the acute phase of perinatal HIE and has strong predictive value not only for anatomic extent of cerebral injury, but also for long-term neurofunctional outcome.     

"Binge" cocaine differentially alters preproenkephalin mRNA levels in guinea pig brain

Male Hartley guinea pigs were administered i.p. injections of cocaine or saline for 2 or 7 days in a "binge" paradigm. RNA was isolated from dissected brain regions and levels of preproenkephalin mRNA and total RNA were quantified by RNase protection assays. Following 2 days of "binge" cocaine administration, no significant alterations in preproenkephalin mRNA levels were detected in six brain regions. Following 7 days of cocaine administration, however, lower levels of preproenkephalin mRNA were observed in the nucleus accumbens and hypothalamus of cocaine-treated animals and higher levels in the frontal cortex and amygdala. These findings differed from previous studies in the rat, so an additional experiment was performed with animals treated at the 7 day time point. For increased statistical power, data from the two experiments were combined and examined by two-way ANOVAs; in this combined analysis, increases in preproenkephalin mRNA were observed in frontal cortex, amygdala, and hippocampus, decreases were found in the nucleus accumbens and hypothalamus, with no change in thalamus, caudate putamen, or cerebellum. These observed differences between guinea pigs and rats make this species an interesting model for neurobiological studies of cocaine-induced alterations in neuropeptide gene expression in the mammalian brain.     

Basal metabolic rate in the Yakut (Sakha) of Siberia.

Human indigenous circumpolar populations have elevated basal metabolic rates (BMRs) relative to predicted values; this metabolic elevation has been postulated to be a physiological adaptation to chronic and severe cold stress. The present study examines BMR in the Yakut, an indigenous high-latitude population from the Sakha Republic of Russia to determine (1) whether the Yakut show evidence of an elevated BMR, (2) if the Yakut display evidence of age-related changes in BMR, and (3) whether lifestyle differences influence BMR. BMR was measured during the late summer in 75 women and 50 men (ages 18-56 years) from the Siberian village of Berdygestiakh. Measured BMR (+/- SEM) of the entire sample was significantly elevated (+6.5%) compared to predictions based on body mass (6,623.7 +/- 94.9 vs. 6,218.2 +/- 84.7 kJ/day; P < 0.001). Additionally, measured BMR for the entire sample was significantly higher than predictions based on fat-free mass (+20.8%) and surface area (+8.9%). Males and females both showed significant elevations relative to all three standards. The elevated BMR of the Yakut does not appear to be attributable to extreme levels of protein, since the Yakut consume a mixed diet with a substantial proportion of carbohydrates. No significant age-related changes in BMR were found when controlled for body composition. No significant relationship was found between lifestyle variables and BMR, suggesting the possibility of a genetic or developmental mechanism. This study provides additional evidence of metabolic elevation in indigenous circumpolar groups and has important implications for estimating the nutritional requirements of these populations.     

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.