Target-specific catecholamine elevation induced by anticonvulsant thalamic deep brain stimulation

PURPOSE: Anterior thalamic nucleus (AN) deep brain stimulation (DBS) is effective in raising EEG and clonic seizure threshold in experimental models. Little is known about the specific properties of DBS that afford its anticonvulsant effect. We sought to test the hypothesis that experimental seizures and the anticonvulsant action of AN DBS alter the underlying regional neurochemistry of AN, specifically with facilitation of the serotonergic system to local electrical stimulation. METHODS: Halothane-anesthetized adult Sprague-Dawley male rats underwent stereotactically guided bilateral placement of bipolar stimulating steel electrodes and dialysis probes-guide cannulae in AN and posterior thalamus (PT), and placement of four epidural EEG screw electrodes 48 h before experiments. Both stimulated (AN DBS) and nonstimulated (NO DBS) animals (n=7 per group) were infused with i.v. pentylenetetrazol (PTZ, 5.5 mg/kg/min). Simultaneous thalamic and cortical EEG were recorded, and microdialysis samples were collected from AN and PT in 20-min epochs. AN stimulation was delivered (150 microA; 0.1-ms pulse duration) 40 min before and continued during PTZ infusion. RESULTS: Bilateral AN stimulation delayed the onset of EEG seizures compared with controls: 82+/-8 vs. 58+/-5 min (p=0.02). PTZ infusion alone, or together with stimulation, resulted in a steady increase in norepinephrine (NE), but not dopamine, at AN and PT sites (p<0.001). Although extracellular serotonin was measured at very low levels, the metabolite, 5-hydroxyindoleacetic acid (5-HIAA) increased selectively in AN after stimulation and during preconvulsant infusion of PTZ (p<0.001), returning to baseline after the first generalized seizure. CONCLUSIONS: These data suggest that PTZ and DBS together enhance the nonselective release of NE in thalamic nuclei while specifically stimulating AN-localized serotonin. Low serotonin levels at baseline and during STIM alone or PTZ infusion may indicate efficient reuptake systems for serotonin, with 5-HIAA serving as a surrogate marker for serotonergic activity. Modulation of the AN-specific serotonergic activity may be critical in altering PTZ seizure threshold and be an important neurotransmitter system underlying the efficacy of AN DBS.     

A six year review of odontoid fractures: the emerging role of surgical intervention

BACKGROUND: Traditionally, odontoid fractures have been treated with different bracing techniques resulting in variable degrees of successful healing. Surgical intervention is becoming more widely practiced as a primary intervention. The purpose of this report was to survey our recent experience in southern Alberta to determine potential outcome differences in management strategies. METHODS: We retrospectively reviewed the charts of 520 patients diagnosed with cervical spine fractures over a six-year period from January 1990, through December 1996. Patients were identified through the medical records database of the two Level 1 trauma facilities, on the basis of ICD-9 diagnostic coding. RESULTS: Ninety-three fractures of the odontoid process were identified, of which 85 were acute and eight were chronic. There were 57 Type II (67%) and 27 Type III (32%) acute odontoid fractures. Of these, 64 were managed conservatively (bracing), whereas 20 were treated surgically. Thirteen patients underwent anterior screw fixation, seven patients had posterior cervical fusion. Eleven patients died in the acute phase, two as a result of their high cervical cord injury and nine from unrelated medical causes. Fifty-six of the remaining 82 patients (68%) were located with a minimum of three months follow-up (range three months to eight years). Satisfactory results were obtained in 76% of all acute patients treated by bracing, but only 50% in those over the age of 65. In the surgically managed group, all patients (100%) went on to develop stable fusions. CONCLUSIONS: Our results indicate that while conservative management of odontoid fractures with external bracing results in fracture healing in most cases, surgical fusion may provide superior rates of bony union with acceptable morbidity. This difference in outcome lends itself to formal investigation through a prospective randomized trial.     

Depression and risk of heart failure among the elderly: a prospective community-based study

OBJECTIVE: Although the association between depression and the incidence of coronary heart disease has been established in many studies, the impact of depression on the incidence of heart failure has not been previously investigated. METHODS: We examined the effect of depression (assessed by means of the Center for Epidemiological Studies Depression Scale (CES-D) with a cutoff point of > or =21) on the incidence of heart failure in a community sample of persons aged > or =65 years who were participants in the New Haven cohort of the Established Populations for Epidemiological Studies in the Elderly. RESULTS: At baseline 2501 individuals were free of heart failure. Of these, 188 (132 women and 56 men) scored as depressed. Depressed participants were significantly more likely to have hypertension, diabetes, and mobility-related functional limitations and were less likely to be male or married. During the 14-year follow-up period, 313 participants (146 men and 167 women) developed heart failure, defined as hospital admission for heart failure or mortality with heart failure as the underlying cause of death. After adjusting for baseline differences in demographic and comorbidity factors and functional status using Cox regression, depression tended to be associated with a greater risk of heart failure (hazard ratio (HR) = 1.52, 95% confidence interval (CI) = 0.94-2.43, p =.09). This effect was significant in women (HR = 1.96, 95% CI = 1.11-3.46, p =.02) but not in men (HR = 0.62, 95% CI = 0.23-1.71, p =.05 for the interaction term between sex and depression). CONCLUSIONS: Depression is an independent risk factor for heart failure among elderly women but not elderly men.     

Novel hydrophobic deep eutectic solvent for vortex-assisted liquid phase microextraction of common acaricides in fruit juice followed by HPLC-UV determination

In the present research, several novel and natural hydrophobic deep eutectic solvents (DESs) were prepared using methyltrioctylammonium chloride (MTOAC) as the hydrogen bond acceptor (HBA) and different types of straight chain alcohols as hydrogen bond donors (HBDs). One of the DESs composed of MTOAC and n-butanol was advantageously used to develop a vortex-assisted liquid phase microextraction (VALPME) method combined with high-performance liquid chromatography-ultraviolet detection (HPLC-UV) for the determination of common acaricides in fruit juice samples. Several important parameters influencing extraction efficiency were investigated and optimized, including the type and volume of DES, sample solution pH, effect of salt addition and, extraction and vortex time. Under optimal experimental conditions, the method showed good linearity with the correlation coefficients (R²) of 0.9986–0.9991 in the linear range of 2–300 μg L⁻¹, low limits of detection of 0.5–1 μg L⁻¹ and acceptable extraction recoveries in the range of 85–93%. The proposed method was successfully applied for the extraction and preconcentration of trace acaricides in real fruit juice samples, and the results demonstrated the potential of the synthesized DESs for the extraction and determination of contaminants in aqueous samples.

In this research, several novel hydrophobic deep eutectic solvents (DESs) were prepared using methyltrioctylammonium chloride (MTOAC) as the hydrogen bond acceptor (HBA) and different types of straight chain alcohols as hydrogen bond donors (HBDs).     

FAS/FAS ligand expression and induction of apoptosis in chondrocytes

Objective. To examine the expression of Fas/Fas ligand and the role of this ligand/receptor interaction in the regulation of apoptosis in normal human articular chondrocytes and in osteoarthritis (OA) cartilage. Methods. Normal and OA human knee cartilage and cells isolated from these tissues were tested for Fas expression by flow cytometry. Induction of apoptosis by antibody to Fas was analyzed by DAPI staining and electron microscopy. Results. Treatment of freshly isolated normal human articular chondrocytes with an agonistic Fas antibody induced apoptosis in a subpopulation (-20%) of the cells. Apoptosis induced by anti-Fas was not dependent on nitric oxide (NO), and anti-Fas also did not induce NO production. Analysis of isolated cells demonstrated similar levels of Fas expression on normal and OA chondrocytes (28% and 32%, respectively). In normal articular cartilage, Fas-positive cells were located mainly in the superficial and midzones. In contrast, in fibrillated OA cartilage, surface layers were partially absent and Fas-expressing cells were also detected in the deeper layers. Fas ligand messenger RNA was not detectable in resting or activated normal or OA chondrocytes. Analysis by electron microscopy showed the nuclear and cytoplasmic changes typical of apoptosis in cultures treated with antibody to Fas. Conclusion. A subpopulation of chondrocytes expresses Fas and is susceptible to Fas-induced apoptosis. Fas-mediated chondrocyte apoptosis may contribute to cartilage degradation in arthritis.     

Natal teeth: a potential impediment to nasoalveolar molding in infants with cleft lip and palate

The purpose of this article is to describe two cases of bilateral cleft lip and palate with natal/neonatal teeth. Clinical features, prevalence, possible complications, and treatment modalities are discussed. Two patients with cleft lip and palate and natal/neonatal teeth are described. The first patient was a 4-week-old infant with bilateral cleft lip and palate. On initial inspection an odontogenic vestige was noticed on the right lateral border of the premaxillary segment, bordering the cleft. The second patient was a newborn with a vestige on the right side of the premaxilla. At 20 days, another swelling representing a neonatal tooth on the left side was found. Because the teeth interfered with the fabrication and application of the nasoalveolar molding (NAM) appliance, they were removed from both patients. In the first patient, at 1 week after extraction, the NAM device was placed without difficulty. At 8 months, the infant had adapted well to the NAM device and nursed without problems. The second patient did not follow-up for the placement of the NAM device. In patients with cleft lip and palate with natal/neonatal teeth who require NAM, the tooth must be removed to facilitate the fabrication and placement of the device. Natal/neonatal teeth must be extracted with caution because the tooth buds of neighboring teeth may be damaged and remnants of the dental papillae may be left behind. Although general anesthesia is not always indicated for the removal of these teeth, in cases in which the premaxilla is loose, such as the current cases, general anesthesia is warranted.