Hyperuricemia and incident atrial fibrillation in a normotensive elderly population in Taiwan.

BACKGROUND AND AIM: Atrial fibrillation (AF) is an important cardiovascular disease in the elderly. The association between hyperuricemia and AF is unclear. Therefore, we aimed to investigate the prospective relationship between uric acid and development of AF in a nationally representative cohort of elderly people. METHODS AND RESULTS: A total of 1485 elderly people (age ≥ 65 yrs) from the Elderly Nutrition and Health Survey in Taiwan (1999-2000) were without AF on "electrocardiography" at baseline. Incident AF events (International Classification of Diseases, Ninth Revision, Clinical Modification, ICD-9-CM: 427.31) were identified using data from the National Health Insurance Dataset. Hyperuricemia was defined as levels of uric acid >7.0 mg/dL in men and 6.0 mg/dL in women. A Cox proportional hazards model was used to evaluate the association between hyperuricemia and incident AF. The follow-up period was from 1999 to 2000 to 2008. During the follow-up period (median: 9.16 yrs), 90 AF events occurred (44 in men and 46 in women). Older age, elevated systolic blood pressure, being an ex-smoker, and high uric acid were positively associated with incident AF. Hyperuricemia was positively associated with incident AF in normotensive (age-adjusted hazard ratio (HR): 2.65 and 95% confidence intervals: 1.05-6.69), but not in (1.20:0.74-1.94) hypertensive individuals (systolic blood pressure ≥130 or diastolic blood pressure ≥85 or using hypertensive medicine). A significant association between hyperuricemia and AF (3.78; 1.24-11.59) remained after adjusting for other potential confounders among normotensive older persons. CONCLUSION: Hyperuricemia is associated with the development of AF in elderly people with normal blood pressure.

Enhanced sympathetic outflow and decreased baroreflex sensitivity are associated with intermittent hypoxia-induced systemic hypertension in conscious rats.

Long-term exposure to intermittent hypoxia (IH), such as that occurring in association with sleep apnea, may result in systemic hypertension; however, the time course changes in arterial pressure, autonomic functions, and baroreflex sensitivity are still unclear. We investigated the changes in cardiovascular neural regulations during the development of chronic IH-induced hypertension in rats. Sprague-Dawley rats were exposed to repetitive 1.25-min cycles (30 s of N2+45 s of 21% O2) of IH or room air (RA) for 6 h/day during light phase (10 AM-4 PM) for 30 days. Arterial pressure was measured daily using the telemetry system during RA breathing. The mean arterial pressure (MAP) and interpulse interval (PPI) signals were then used to assess the autonomic functions and spontaneous baroreflex sensitivity by auto- and cross-spectral analysis, respectively. Stable MAP, low-frequency power of MAP (BLF), and low-frequency power (LF)-to-high frequency power (HF) ratio of PPI (LF/HF) were significantly higher in IH-exposed rats, compared with those of RA-exposed rats. Elevation of the MAP, BLF, LF/HF, and minute ventilation started 5 days after IH exposure and lasted until the end of the 30-day observation period. Additionally, IH-exposed rats had significant lower slope of MAP-PPI linear regression (under a successively descending and ascending) and magnitude of MAP-PPI transfer function (at frequency ranges of 0.06-0.6 Hz or 0.6-2.4 Hz) after IH exposure for 17 days. However, RA-exposed rats did not exhibit these changes. The results of this study indicate that chronic IH-induced hypertension is associated with a facilitation of cardiovascular sympathetic outflow and inhibition of baroreflex sensitivity in conscious rats.

Chemotherapy of tuberculosis in mice using single implants of isoniazid and pyrazinamide.

OBJECTIVE: To establish the chemotherapeutic value of a depot drug preparation of isoniazid and pyrazinamide against experimental tuberculosis. DESIGN: To see whether sustained levels of pyrazinamide are available for prolonged periods after a single subcutaneous administration of a biodegradable polylactic-glycolic acid (PLGA) polymer containing the drug, studies were done to ascertain whether a single administration of isoniazid and pyrazinamide in separate PLGA polymers could offer chemotherapeutic protection against a heavy intravenous challenge of susceptible mice with a virulent strain of Mycobacterium tuberculosis similar to that rendered by daily administration of the two drugs for 8 weeks. RESULTS: Even with three times the daily dose of pyrazinamide contained in the single PLGA polymer implant, no abnormally high (burst) levels of the drug were evident after administration, but sustained levels of the drug were seen up to 54 days. The chemotherapeutic activity of the single PLGA polymer implants was similar to that obtained with standard oral treatment with the two drugs given daily for the entire 8 weeks, as judged by mortality and colony forming unit (CFU) counts of tubercle bacilli from lungs and spleen. CONCLUSION: Treatment with single implants of the PLGA polymer containing anti-mycobacterial drugs offers a strong possibility of circumventing the compliance problem.

Small isolated paraspinal arteriovenous fistula.

We report a case of a small, isolated paraspinal arteriovenous fistula (AVF) that arose in an adult without obvious trauma. The fistula, despite its extraspinal location and small size, caused hypertension of the intrathecal venous system and produced symptoms that were similar to those of spinal dural AVF. Detecting such a small lesion is difficult, but contrast-enhanced MR imaging can prove helpful in this regard.

Proton MR spectroscopy in patients with complex partial seizures: single-voxel spectroscopy versus chemical-shift imaging.

BACKGROUND AND PURPOSE: Proton MR spectroscopy has recently been applied to the evaluation of seizures, but few comparisons have been made between different clinical spectroscopic techniques. Our goal was to determine whether there is a significant difference between hippocampal NAA/(Cho+Cr) ratios obtained by single-voxel spectroscopy (SVS) and by chemical-shift imaging (CSI). METHODS: Twelve healthy adults and eight patients with complex partial seizures were studied on a 1.5-T MR scanner using a proton SVS method. Another 12 healthy adults and 10 patients with complex partial seizures were recruited for a proton CSI study, which was performed on a different 1.5-T MR system. The NAA/(Cho+Cr) ratio was calculated from the integral peak areas by curve fitting. The two-tailed t-test was used for statistical analysis. RESULTS: The mean value +/- standard deviation of the hippocampal NAA/(Cho+Cr) ratio in healthy control subjects was 0.63 +/- 0.07 by SVS, with 0.62 +/- 0.15 for the anterior hippocampus and 0.65 +/- 0.11 for the posterior hippocampus by CSI. There was no significant difference between the control group data obtained by SVS and those by CSI, nor was there a regional difference in the CSI NAA/(Cho+Cr) ratio in the hippocampus. Relative to the control group, the patients with seizures had a significant decrease in the NAA/(Cho+Cr) ratio in the abnormal hippocampus: -28% by SVS, and -24% in the anterior hippocampus and -18% in the posterior hippocampus by CSI. Proton SVS and CSI detected hippocampal abnormalities, unilateral or bilateral, in all patients of each group. CONCLUSION: Under similar measurement conditions, proton SVS and CSI provide similar NAA/(Cho+Cr) ratios among healthy control subjects, and they possess comparable ability for detecting hippocampal abnormalities in patients with complex partial seizures.

Magnetic resonance imaging and magnetic resonance spectroscopy in dementias.

This article reviews recent studies of magnetic resonance imaging and magnetic resonance spectroscopy in dementia, including Alzheimer's disease, frontotemporal dementia, dementia with Lewy bodies, idiopathic Parkinson's disease, Huntington's disease, and vascular dementia. Magnetic resonance imaging and magnetic resonance spectroscopy can detect structural alteration and biochemical abnormalities in the brain of demented subjects and may help in the differential diagnosis and early detection of affected individuals, monitoring disease progression, and evaluation of therapeutic effect.

Comparison of process parameters for microencapsulation of plasmid DNA in poly(D,L-lactic-co-glycolic) acid microspheres.

Poly(D,L-lactic-co-glycolic) acid (PLGA) microspheres containing plasmid DNA encoding the firefly luciferase gene were prepared using the water-in-oil-in-water (w/o/w) double emulsion and solvent evaporation method. In this study, we investigated the effects of three process parameters on DNA microencapsulation: (1) emulsification method used to generate the primary emulsion, (2) water/oil ratio during formation of the first emulsion, and (3) surfactant concentration used in the preparation of the second emulsion. The resulting formulations were also analyzed for microsphere size, encapsulation efficiency, and kinetics of DNA release. We found that although each process alteration resulted in encapsulation of biologically active, structurally intact DNA, the surfactant and water/oil ratio significantly affected the size, release kinetics and encapsulation efficiency of plasmid DNA.

Mechanisms of isoniazid release from poly(d,l-lactide-co-glycolide) matrices prepared by dry-mixing and low density polymeric foam methods.

The release mechanisms of a small molecular drug from biodegradable poly(d,l-lactide-co-glycolide) (PLGA) cylindrical matrices were investigated. Isoniazid (INH), one of the most effective drugs against tuberculosis (TB), was selected as the model drug. Controlled-release matrices consisting of the drug and polymer were fabricated by two methods. The first of these, the dry-mixing method, involved the extrusion of a mixture of micronized drug and polymer particles as rods. In the second technique, the low density polymeric foam method, drug particles were enclosed in the cells of porous polymeric foams prior to extrusion. In vitro, the dry-mixed matrices released INH more rapidly than the polymeric foam matrices. The Roseman-Higuchi diffusion model, which had previously been found to be effective in analyzing the release kinetics of INH from the dry-mixed matrices, also fit the kinetics of INH released from matrices prepared from polymeric foams. This indicated that the release was still diffusion-controlled rather than degradation-controlled. The release mechanisms were further investigated, and two diffusion mechanisms, pore diffusion and lattice diffusion, were proposed for the INH controlled-release matrices according to the way in which they were prepared. Matrices prepared by the dry-mixing method appear to segregate drug particles along polymer grain boundaries and thus have a pore diffusion mechanism, while matrices prepared by the foam method entrap drug within the porous structure of foams and thus display a lattice diffusion mechanism. Theoretically, these two diffusion mechanisms can be identified by their activation energies for diffusion. With varying in vitro temperature, the activation energies were calculated from plots of ln (DIT) vs T-1 and in D vs T-1, where D is the diffusivity and T is the in vitro temperature in K. According to the results, we concluded that the INH from the dry-mixed matrices diffused through the drug channels filled with the medium, while the INH from the foam matrices diffused through the polymer lattice.

Antagonistic effect of D-myo-inositol-1,2,6-trisphosphate (PP56) on neuropeptide Y-induced vasoconstriction in the feline dental pulp.

Intra-arterial injection of neuropeptide Y (NPY) (1.3-2.0 micrograms/kg) resulted in decreases of pulpal blood flow by 37.7 +/- 5.7% (mean +/- SEM). The intra-arterial injection of D-myo-inositol-1,2,6-trisphosphate (PP56) (0.3 mg/kg) alone changed pulpal blood flow by 1.0%. The effect of NPY in the presence of PP56 resulted in significantly smaller decreases in pulpal blood flow ranging from 27.2 +/- 5.4 to 16.6 +/- 3.5% from control as compared with NPY alone. In effect, PP56 partially blocked the decreases in pulpal blood flow caused by NPY. The electrical stimulation of the sympathetic nerve alone resulted in decreases in pulpal blood flow of 41.7 +/- 6.2%. The electrical stimulation of the sympathetic nerve following the intra-arterial administration of PP56 decreased pulpal blood flow by 23.1 +/- 6.0% from control, significantly less than the sympathetic nerve stimulation alone. PP56 attenuated the decrease in pulpal blood flow caused by the sympathetic nerve stimulation by 44.4 +/- 11.0%. Similarly, the combination of PP56 and phentolamine followed by electrical stimulation of the sympathetic nerve reduced the decrease in pulpal blood flow caused by the sympathetic nerve stimulation alone by 43.0 +/- 8.6%. These results provide evidence that the non-peptide PP56 is capable of antagonizing vasoconstriction caused by NPY in the feline dental pulp. In addition, they show functional evidence that NPY as well as noradrenaline are released from the sympathetic nerve endings during its stimulation and cause vasoconstriction.

Neuroimaging in intractable complex partial seizures.

We retrospectively analyzed 19 patients with intractable complex partial seizures who underwent temporal lobectomy and compared the usefulness of various imaging techniques in diagnosis and localization. Pathologic findings consistent with mesial temporal sclerosis were found in 12 patients arteriovenous malformations in four, tumors in three, and coexistence of a tumor and mesial temporal sclerosis in one. Electroencephalography and single photon emission computed tomography detected lateralized functional abnormality in two patients when computed tomography (CT) and magnetic resonance imaging (MRI) showed equivocal results. Both CT and MRI showed all arteriovenous malformations and tumors. CT detected only four cases of mesial temporal sclerosis, while MRI showed nine cases. Detection, delineation and diagnosis of lesions responsible for complex partial seizures are essential for good surgical results. Thus, the importance of image studies, especially MRI, should be emphasized in patients with complex partial seizures.

Proton magnetic resonance spectroscopy in patients with complex partial seizures.

We prospectively studied eight patients with complex partial seizures, using single-voxel proton magnetic resonance spectroscopy (MRS). Control data from 12 healthy volunteers were obtained with the same MRS protocol. The ratios between the peak areas of N-acetylaspartate, creatine and phosphocreatine (Cr), and choline-containing compounds (Cho) were analyzed. The results showed statistically significant lower N-acetylaspartate:Cr, N-acetylaspartate:Cho, and N-acetylaspartate: Cho + Cr ratios, and a higher Cho:Cr ratio in the mesial temporal lobes of the patient group than in healthy controls. Because N-acetylaspartate is located in the neurons and Cho and Cr in the glial cells, these observations represent the underlying neuronal loss and reactive astrocytosis in the epileptogenic foci. MRS can detect abnormal metabolic changes in most complex partial seizure patients with normal electroencephalography and magnetic resonance images. MRS can also identify bitemporal abnormalities which are a common feature in patients with complex partial seizures. Proton MRS could not confirm the specific location of seizure foci. Further investigation with quantitative spectral analysis and correlation with surgical outcome is needed to improve the contribution of MRS to the diagnosis and localization of seizure foci.

The resected root surface. The issue of canal isthmuses.

Incomplete debridement of the canal isthmus is responsible for some surgical and nonsurgical endodontic failures. This article reviews the formation of canals isthmus and the new classification system. Recent research findings regarding the incidence of isthmus at different root end levels are included.

Couples' satisfaction with health care service during labor and delivery.

The purpose of this study was to examine consumer satisfaction with health care service during labor and delivery. An exploratory study was conducted by obtaining information from 191 couples who were hospitalized at one medical center in southern Taiwan. A Consumer Satisfaction Questionnaire with three additional open questions developed by the authors and a Social Support Scale modified from the Family APGAR Index were administered. Factor analysis identified the following three factors most often associated with consumers' satisfaction with labor and delivery during hospitalization: (1) the Supply of Equipment, (2) the Participants in the Delivery and (3) the Management of the Ward. Moreover, the level of couples' satisfaction with hospitalization during labor and delivery was significantly correlated with high professional support. Suggestions are also made for future efforts in quality of care and consumer satisfaction.

[Effectiveness of videotape education for mothers of prematurity].

To investigate the effectiveness of an educational videotape on preterm mothers' knowledge, confidence, perceived stress, and social support, mothers who had given birth prematurely were recruited to participate in this study. Sixty-two mothers were randomly assigned to a control or experimental group. During hospitalization, mothers assigned to the experimental group received additional educational videotape which was designed by researchers for this particular study, regarding the knowledge and skills of caring for premature infants. While mothers in the control group received routine educational care. Both groups of mothers filled out the questionnaire including knowledge of prematurity, maternal confidence, perceived stress and perceived social support at three time periods (before discharge, one week after discharge, and one month after discharge). The findings indicated that mothers who received a videotape education reported having higher knowledge and confidence of caring for their preterm babies than mothers who were in the control group. Moreover, mothers in the experimental group perceived lower stress than the control group mothers when their babies were one month old. The scores of perception of stress, parity, and receiving a videotape education are the best predictors to maternal confidence a week after discharge. Further, the mothers' perception of stress, parity, and the perception of social support can predict and explain 47.1% of the variance of the maternal confidence. These results can apply to clinical practice for nursing mothers who have given preterm births. A convenient videotape education can improve mothers' knowledge and confidence of caring for their premature babies at home.

Effect of nitric oxide synthase inhibitor (L-NAME) on substance P-induced vasodilatation in the dental pulp.

AIM: To investigate the vasodilator mechanisms of pulpal vessels, especially the involvement of nitric oxide (NO), during pulpal inflammation. METHODOLOGY: Eleven cats were prepared for intra-arterial administration of test agents through a lingual artery. The pulpal blood flow was measured by laser Doppler flowmetry from ipsilateral mandibular canine teeth. By using the NO synthase (NOS) inhibitor N(G)-nitro L-arginine methyl ester (L-NAME), the effects of L-NAME on various vasodilators, such as Substance P (SP)-, calcitonin-gene related peptide (CGRP)-, and papaverine-induced vasodilatation, were compared in vivo in 11 feline dental pulps. RESULTS: L-NAME pretreatment potentiates SP-induced vasodilatation for a duration of approximately 5 h. The increase of pulpal blood flow ranged from 91.47 to 109.91%, which was significantly different from SP injection alone (48.79%, P < 0.05). Other vasodilators such as CGRP and papaverine did not respond to L-NAME pretreatment. CONCLUSIONS: This study demonstrates that NOS inhibitor L-NAME administration alone has insignificant effects on pulpal blood flow, although L-NAME pretreatment can potentiate SP-induced vasodilatation, probably via increased activity in the enzyme guanylate cyclase. CGRP and papaverine did not respond to L-NAME pretreatment, indicating that they are not mediated via an endothelium-dependent mechanism.

Reproducibility of hippocampal single-Voxel proton MR spectroscopy and chemical shift imaging.

OBJECTIVE: We investigated between- and within-acquisition reproducibility of hippocampal metabolite ratios obtained using automated proton MR spectroscopy. SUBJECTS AND METHODS: We examined 30 healthy adults with a 1.5-T scanner four times on 3 days using single-voxel spectroscopy over the left hippocampus, chemical shift imaging over the left hippocampus, and chemical shift imaging over the bilateral hippocampi. Metabolite ratios were derived from the integral values of three major peaks: N:-acetylaspartate (NAA), choline-containing compounds (Cho), and creatine plus phosphocreatine (Cr). The random-effects model of one-way analysis of variance was used to evaluate the reproducibility in terms of coefficient of variation; the mixed-effects model was used to compare the results of different hippocampal regions and spectroscopic techniques. RESULTS: Most coefficients of variation for the NAA/(Cho+Cr) ratio were less than 20%. All the coefficients of variation for the posterior hippocampus (15-25%) were less than those for the anterior hippocampus (20-44%). The posterior hippocampal NAA/(Cho+Cr) ratio of unilateral chemical shift imaging had the lowest coefficient of variation (<16%). Single-voxel spectroscopy and unilateral chemical shift imaging had similar coefficients of variation for the anterior hippocampal NAA/(Cho+Cr) ratios (17-20%). There was a significant difference in metabolite ratios measured in different hippocampal regions (p<0.01) and in those acquired with different spectroscopic techniques (p<0.001). CONCLUSION: The NAA/(Cho+Cr) ratio is the most reproducible parameter for hippocampal MR spectroscopy on a 1.5-T scanner. Regional variation and technical differences in metabolite ratios must be considered when interpreting proton spectra of the hippocampus.

Lateralization and prognostic value of proton magnetic resonance spectroscopy in patients with intractable temporal lobe epilepsy.

BACKGROUND: The aims of this prospective study were to investigate the stability of hippocampal metabolite ratios obtained by proton magnetic resonance spectroscopy (MRS), to evaluate the ability of MRS to determine the pre-surgical lateralization of seizure focus, and to assess the relationship between MRS results and postoperative outcomes in patients with intractable temporal lobe epilepsy. METHODS: Within- and between-acquisition variations were evaluated in 30 control subjects, using the chemical-shift imaging technique. The most stable metabolite ratio was then applied for pre-surgical evaluation of 14 patients with intractable temporal lobe epilepsy. RESULTS: The ratio between N-acetylaspartate (NAA) and choline-containing compounds (Cho) plus creatine-phosphocreatine (Cr), i.e., NAA/(Cho+Cr), had an overall smaller percentage change between measurements (13%-28%) than did the other ratios: NAA/Cho (18%-37%), NAA/Cr (11%-60%), and Cho/Cr (19%-51%). With a mean follow-up period of 27 months (range, 12-55 months) after an anterior temporal lobectomy, 10 patients were in Engel s class I (71%), 2 were in class II (14%), and 2 were in class III (14%). Lateralization by MRS was consistent with the operation side in 11 (79%) patients, including class I in 8 patients, class II in 1 patient, and class III in 2 patients. Ranges of reduced NAA/(Cho+Cr) values were similar between patients with different post-surgical outcomes: 0.26-0.47 for class I, 0.40-0.45 for class II, and 0.34-0.40 for class III (p=0.651). CONCLUSIONS: Proton MRS may be helpful in pre-surgical lateralization of the seizure focus in patients with intractable temporal lobe epilepsy; however, it cannot provide prognostic information about postoperative seizure control.

Proton chemical shift imaging of the hippocampus in patients with complex partial seizures.

BACKGROUND: Cerebral metabolites can be evaluated non-invasively using in vivo proton magnetic resonance spectroscopy (MRS). Decreased N-acetylaspartate (NAA) and increased choline-containing compounds (Cho) and creatine-phosphocreatine (Cr) have been found in the hippocampus of patients with complex partial seizures (CPS). METHODS: We prospectively studied hippocampal proton MRS of 10 patients with CPS and 12 control subjects by using the chemical shift imaging (CSI) technique. The spectral data were analyzed in terms of the ratio between the integral peak area of NAA and that of (Cho + Cr). RESULTS: Compared with the control group, patients with CPS showed a significantly lower NAA/(Cho + Cr) ratio, both in the anterior and posterior hippocampus (p value = 0.001 and 0.002, respectively). Metabolic abnormalities of the hippocampus were detected using proton CSI in all the patients with normal MRI results (4 patients) and those with normal EEG results (3 patients). Lateralizations using proton CSI were obtained in all the 10 patients in this study, including concordant lateralization in the 6 patients with MRI-detectable abnormalities. CONCLUSION: The hippocampal abnormalities in patients with CPS can be detected early using proton CSI than using MRI or surface EEG. Lateralization of the seizure focus using proton CSI is possible, but further correlation with the surgical outcome in a larger study group is necessary.

Effect of polymer foam morphology and density on kinetics of in vitro controlled release of isoniazid from compressed foam matrices.

The purpose of this study was to compare the effect of polymer foam morphology and density prior to compaction on the kinetics of isoniazid (INH) release from the final high-density extruded matrices. The feasibility of preparing low density foams of several biopolymers, including poly(L-lactide) (PLLA), poly(glycolide) (PGA), poly(DL-lactide-co-glycolide) (PLGA), poly(gamma-benzyl-L-glutamate) (PBLG), and poly(propylene fumarate) (PPF), via a lyophilization technique was investigated. Low-density foams of PLGA, PBLG, and a mixture of PLGA and PPF were successfully fabricated by lyophilization of the frozen polymer solutions either in glacial acetic acid or in benzene. The morphology of these foams depends on the polymer as well as the solvent used in the fabrication process. Thus, PLGA produces a capillary structure when lyophilized from benzene solution and a leaflet structure from glacial acetic acid, but PBLG yields a leaflet structure from benzene. Matrices were prepared by impregnating these foams with aqueous solutions of INH, removing the water by a second lyophilization, and then compressing the low-density INH containing foams by compaction and high-pressure extrusion. The resulting nonporous matrices had densities of approximately 1.30 g/cm3. In vitro kinetics were in accord with the Roseman-Higuchi diffusion model and demonstrate that release rates depend on the initial foam density, while foam structure has little influence on the release kinetics.

Protective immune responses elicited in mice by immunization with formulations of poly(lactide-co-glycolide) microparticles.

Parenteral administration of microparticle encapsulated DNA elicits immune responses to the encoded antigens. Experiments were performed to test whether the addition of certain lipophilic agents to such formulations enhanced the activity of a beta-galactosidase (beta-gal) DNA vaccine. Addition of either taurocholic acid (TA) or monomethoxy polyethylene-glycol-distearoylphosphatidylehanolamine (PEG-DSPE) increased the efficiency of DNA encapsulation. Immunization of mice with encapsulated DNA formulations containing either compound significantly increased the number of antibody positive responders over that achieved with non-lipid containing particles. Moreover, responding animals demonstrated trends towards higher antibody titers and increased T cell responses. Tumor protection against the CT26.CL25 tumor cell line was demonstrated with lipid and non-lipid containing formulations. These results are the first demonstration of protection obtained by parenteral administration of PLG encapsulated DNA vaccines.