Brain activity and language assessment using event-related potentials: development of a clinical protocol

To test the validity of a new computerized task to assess children's receptive vocabulary, event-related potentials (ERPs) were recorded from 56 typically developing children ranging in age from 5 to 12 years. This ERP-computerized vocabulary task does not require a child to give a verbal or motor (i.e. pointing) response. Single pictures, from an existing standardized test of receptive vocabulary, were presented on a computer screen and simultaneously named either correctly (congruent) or incorrectly (incongruent) via a computer. As predicted, the N400 amplitude was found to be significantly higher to the incongruent picture-word pair (i.e. the child knew it was an incorrect pairing) than to the congruent picture-word pair (i.e. the child knew it was a correct pairing). This effect was found for each of the four age groups (5 to 6 years, 7 to 8 years, 9 to 10 years, 11 to 12 years). This task accurately estimated current receptive vocabulary in typically developing children. Although still in the development stage, it may eventually serve as an adjunct to a thorough neurological and neurodevelopmental assessment of some children presenting with moderate to severe cerebral palsy.     

Lessons from other diseases: granulomatous inflammation in leishmaniasis

The Leishmania granuloma shares some, though not all, properties with that formed following mycobacterial infection. As a simplified, noncaseating granuloma composed of relatively few and largely mononuclear cell populations, it provides a tractable model system to investigate intra-granuloma cellular dynamics, immune regulation, and antimicrobial resistance. Here, the occurrence of granulomatous pathology across the spectrum of leishmaniasis, in humans and animal reservoir hosts, is first described. However, this review focuses on the process of hepatic granuloma formation as studied in rodent models of visceral leishmaniasis, starting from the initial infection of Kupffer cells to the involution of the granuloma after pathogen clearance. It describes how the application of intravital imaging and the use of computational modeling have changed some of our thoughts on granuloma function, and illustrates how host-directed therapies have been used to manipulate granuloma form and function for therapeutic benefit. Where appropriate, lessons that may be equally applicable across the spectrum of granulomatous diseases are highlighted.     

Baclofen: reduction of presynaptic calcium influx in the cat spinal cord in vivo

 In the ventral horn of the lumbar spinal cord of cats anaesthetised with pentobarbitone sodium, microelectrophoretically administered (–)-baclofen, but not (+)-baclofen, reversibly reduced the duration of the orthodromic action potential of muscle group Ia afferent terminations, but not those of muscle group I afferent myelinated fibres. The presumably submicromolar concentrations are already known to reversibly reduce excitatory transmitter release from muscle group Ia afferent terminations. Action potential durations were estimated from threshold recovery curves after an orthodromic impulse using an extracellular microstimulation technique. Both of these presynaptic effects of (–)-baclofen were blocked by baclofen antagonists, and neither appeared to be reduced by the potassium channel blocking agents tetraethylammonium and 4-aminopyridine. Tetraethylammonium and 4-aminopyridine also did not significantly modify the reduction by (–)-baclofen of monosynaptic field potentials in the lumbar cord of rats anaesthetised with pentobarbitone sodium. In the cat the maximum reduction by (–)-baclofen of termination action potentials was considerably less than that produced by cadmium ions, which, unlike (–)-baclofen, also reduced the action potential duration of group I myelinated fibres. These findings are consistent with a reduction by (–)-baclofen of the influx of calcium through voltage-activated channels in the membrane of group Ia terminations, a proposal which also accounts for the reduction by (–)-baclofen of the release of GABA at axo-axonic depolarizing synapses on these terminations. The results are discussed in relation to the mode of action of (–)-baclofen and the different sensitivities of transmitter release at various central synapses. Received: 30 May 1996 / Accepted: 11 September 1996     

Compartment-specific remodeling of splenic micro-architecture during experimental visceral leishmaniasis

Progressive splenomegaly is a hallmark of visceral leishmaniasis in humans, canids, and rodents. In experimental murine visceral leishmaniasis, splenomegaly is accompanied by pronounced changes in microarchitecture, including expansion of the red pulp vascular system, neovascularization of the white pulp, and remodeling of the stromal cell populations that define the B-cell and T-cell compartments. Here, we show that Ly6C/G(+) (Gr-1(+)) cells, including neutrophils and inflammatory monocytes, accumulate in the splenic red pulp during infection. Cell depletion using monoclonal antibody against either Ly6C/G(+) (Gr-1; RB6) or Ly6G(+) (1A8) cells increased parasite burden. In contrast, depletion of Ly6C/G(+) cells, but not Ly6G(+) cells, halted the progressive remodeling of Meca-32(+) and CD31(+) red pulp vasculature. Strikingly, neither treatment affected white pulp neovascularization or the remodeling of the fibroblastic reticular cell and follicular dendritic cell networks. These findings demonstrate a previously unrecognized compartment-dependent selectivity to the process of splenic vascular remodeling during experimental murine visceral leishmaniasis, attributable to Ly6C(+) inflammatory monocytes.     

Calcium antagonists are associated with reduced mortality after cardiac surgery: a propensity analysis

OBJECTIVES: Observational studies have questioned the effectiveness of perioperative calcium channel blockers but failed to correct for selection biases. We therefore performed a prospective observational cohort study of the effects of calcium channel blockers on cardiac surgical mortality. A propensity score technique was used for risk adjustment. METHODS: We identified 6619 patients who underwent nontransplant cardiac surgery at the Toronto General Hospital (Toronto, Ontario, Canada) between May 1999 and December 2001. Propensity scores for calcium channel blocker use were constructed for the entire sample and for the subgroup (n = 5222) that underwent coronary artery bypass grafting. The calcium channel blocker adjusted odds ratio for in-hospital mortality after cardiac surgery was determined by using multiple logistic regression and propensity matched-pairs analyses. A subgroup analysis was performed for patients who underwent coronary artery bypass grafting: the calcium channel blocker adjusted odds ratio for mortality was determined by using propensity score matched-pairs analyses. RESULTS: Calcium channel blockers were associated with significantly reduced cardiac surgical mortality after adjustment with both multiple logistic regression (odds ratio, 0.56; 95% confidence interval, 0.33-0.94; P =.028) and propensity score matched-pairs analyses (odds ratio, 0.56; 95% confidence interval, 0.32-0.98; P =.042). Calcium channel blockers were also associated with reduced mortality (odds ratio, 0.48; 95% confidence interval, 0.23-0.98; P =.044) among patients who underwent coronary artery bypass grafting. CONCLUSIONS: After adjustment for baseline differences, calcium channel blockers were associated with significantly reduced mortality after cardiac surgery. This benefit also extends to the subgroup that underwent coronary artery bypass grafting. A large randomized controlled trial of perioperative calcium channel blockers is therefore warranted.     

Esophageal strictures in children: treatment by serial balloon catheter dilatation

Grüntzig balloon catheters were used to dilate ten esophageal strictures in eight infants and children. Five infants who had anastomotic strictures following esophageal atresia repair gained complete resolution of their strictures, usually after one or two dilatations. Three older children who had strictures following esophageal re-operation or reconstruction required longer courses of dilatations to achieve consistent esophageal patency. The technique failed in two chronic strictures of two and one-half and nine years' duration. Balloon catheter dilatation, begun in the early postoperative period, is a safe, effective method for dilating esophageal strictures.     

Ureteral calculi: percutaneous removal using modified basket extractors and fluoroscopy

Two modified helical basket extractors are described that have increased the success rate of removing ureteral calculi using fluoroscopy from 63% to 92%. Initially a rather stiff and expandable basket with a 20-cm filiform tip is used with coaxial catheters and sheath (stage 1). If this procedure is unsuccessful, a basket with two long cable ends is passed from the nephrostomy out through the urethra (stage 2). When used with coaxial bladder catheters, this technique allows dilatation of the vesicoureteric junction and retrograde catheterization and injection of fluids or gas to dislodge the stone prior to extraction. In a series of 38 patients, stones were removed in all but three (a success rate of 92%). In five cases small stones (less than 5 mm) were not retrieved but subsequent studies were normal. Ureteral stones were found in the abdominal ureter in 28 cases, in the pelvic ureter in seven cases, and in multiple sites in three cases. Stones were larger than 1 cm in 27.7% of cases. Postextraction mucosal edema with reduced ureteral patency was common but usually cleared in 2-3 days. Occasional complications were related to the nephrostomy.     

Zinc Status Alters Alzheimer's Disease Progression through NLRP3-Dependent Inflammation

Alzheimer''s disease is a devastating neurodegenerative disease with a dramatically increasing prevalence and no disease-modifying treatment. Inflammatory lifestyle factors increase the risk of developing Alzheimer''s disease. Zinc deficiency is the most prevalent malnutrition in the world and may be a risk factor for Alzheimer''s disease potentially through enhanced inflammation, although evidence for this is limited. Here we provide epidemiological evidence suggesting that zinc supplementation was associated with reduced risk and slower cognitive decline, in people with Alzheimer''s disease and mild cognitive impairment. Using the APP/PS1 mouse model of Alzheimer''s disease fed a control (35 mg/kg zinc) or diet deficient in zinc (3 mg/kg zinc), we determined that zinc deficiency accelerated Alzheimer''s-like memory deficits without modifying amyloid β plaque burden in the brains of male mice. The NLRP3-inflammasome complex is one of the most important regulators of inflammation, and we show here that zinc deficiency in immune cells, including microglia, potentiated NLRP3 responses to inflammatory stimuli in vitro, including amyloid oligomers, while zinc supplementation inhibited NLRP3 activation. APP/PS1 mice deficient in NLRP3 were protected against the accelerated cognitive decline with zinc deficiency. Collectively, this research suggests that zinc status is linked to inflammatory reactivity and may be modified in people to reduce the risk and slow the progression of Alzheimer''s disease.SIGNIFICANCE STATEMENT Alzheimer''s disease is a common condition mostly affecting the elderly. Zinc deficiency is also a global problem, especially in the elderly and also in people with Alzheimer''s disease. Zinc deficiency contributes to many clinical disorders, including immune dysfunction. Inflammation is known to contribute to the risk and progression of Alzheimer''s disease; thus, we hypothesized that zinc status would affect Alzheimer''s disease progression. Here we show that zinc supplementation reduced the prevalence and symptomatic decline in people with Alzheimer''s disease. In an animal model of Alzheimer''s disease, zinc deficiency worsened cognitive decline because of an enhancement in NLRP3-driven inflammation. Overall, our data suggest that zinc status affects Alzheimer''s disease progression, and that zinc supplementation could slow the rate of cognitive decline.     

Retrorenal colon: implications for percutaneous diskectomy

It has been recommended that computed tomography (CT) with the patient prone be performed in every patient undergoing percutaneous diskectomy; this would enable detection of a retrorenal location of the colon, which could interfere with the percutaneous procedure. In this evaluation of 346 prone CT studies, only one patient (0.29%) was found to have retrorenal or retropsoas bowel that would have been perforated at diskectomy. Because of this extremely low prevalence, the performance of prone CT in every patient undergoing percutaneous lumbar diskectomy is not believed to be necessary.