Association between body mass index and stroke severity in acute ischaemic stroke with non-valvular atrial fibrillation.

BACKGROUND AND PURPOSE: The objective of this study was to investigate the association between body mass index (BMI) and both initial stroke severity at presentation and functional outcomes after acute ischaemic stroke (AIS) in patients with non-valvular atrial fibrillation (NVAF). METHODS: Patients were categorized on the basis of their BMI into underweight (BMI <18.5, n = 111), normal (18.5 ≤ BMI <25, n = 1036) and overweight to obese (BMI ≥25, n = 472) groups. Initial stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) score and functional outcomes were assessed using the modified Rankin Scale score at discharge. The differences in stroke severity and functional outcomes were compared between groups using robust log-linear regression with a Poisson distribution and binary logistic regression analysis. RESULTS: A total of 1619 AIS patients with NVAF from six hospitals were included. Compared with the NIHSS scores [median 5, interquartile range (IQR) 2-14] of normal-weight patients, the NIHSS scores (median 9, IQR 4-19) of underweight patients were more likely to be higher, whereas those of overweight to obese patients were lower (median 4, IQR 1-12) (P < 0.001). In terms of functional outcomes after stroke, underweight patients had a higher risk of poor functional outcomes (odds ratio 1.78, 95% confidence interval 1.09-2.56, P = 0.01) but overweight to obese patients had no significant difference in functional outcomes compared with normal-weight patients. CONCLUSION: An inverse association was found between BMI and stroke severity in AIS patients with NVAF. This suggests the presence of an obesity paradox for short-term outcomes in patients with NVAF.

Comparative genotyping of Streptococcus mutans by repetitive extragenic palindromic polymerase chain reaction and multilocus sequence typing.

The genetic diversity of Streptococcus mutans has been extensively studied using a variety of genotyping methods. Repetitive extragenic palindromic-polymerase chain reaction (rep-PCR) is a genotyping approach used for screening large numbers of bacterial isolates. This two-part study used multilocus sequence typing (MLST) analysis to evaluate genotypes previously identified as unique using rep-PCR. In part one, an isolate was selected from each of the 22 S. mutans rep-PCR genotype groups representing 8000 clinical isolates. For part two, four additional isolates were selected from the six most commonly occurring genotype groups (GG) for further analysis. Real-time PCR was performed using eight housekeeping S. mutans gene loci and the amplicons were sequenced. Sequence data analysis was performed using CLC DNA Workbench and alleles were compared with the PubMLST database for Oral Streptococcus using the Nakano scheme. Concatenated sequences were evaluated with MEGA using a minimum evolution method with bootstrap. All 22 rep-PCR genotypes were unique by MLST analysis. Within rep-PCR GGs, MLST matched rep-PCR in three groups demonstrating clonality; three groups exhibited more diversity with MLST. The discovery of three clonal groups is unique to this study and suggests that S. mutans genotypes are shared between unrelated subjects. Furthermore, MLST defined 19 new alleles and 26 new sequence types that have been confirmed and registered with PubMLST. Methods for processing were streamlined and a process for using MLST with rep-PCR is suggested. In conclusion, MLST verified that rep-PCR is a reliable and cost-effective method for screening large numbers of S. mutans strains for epidemiological study.

Genetic diversity of plaque mutans streptococci with rep-PCR.

Mutans streptococci (MS) are key organisms associated with the etiology of dental caries. Using probabilities that were tested by oversampling, we designed this study to determine the minimal number of MS isolates from an individual required to evaluate diversity of genotypes. MS isolates were genotyped by repetitive extragenic palindromic-polymerase chain-reaction (rep-PCR). Analysis of 20 isolates from individuals resulted in a mean of 1.6 and 2.4 genotypes in children (N = 12) and adults (N = 10), respectively. In a follow-up study, reducing the number of isolates to 7-10 resulted in a theoretical probability of up to 78% for detecting up to 4 genotypes. A mean of 1.5 genotypes was found in 35 children and 10 adults. These findings provide evidence for the design of studies of MS genotyping that can serve as a model for the analysis of genotypes within individuals.

Asymptomatic kidney stones in long-term survivors of childhood acute lymphoblastic leukemia.

We hypothesized an association between renal calculi and bone mineral density (BMD) deficits, shown in adults, exists in survivors of childhood acute lymphoblastic leukemia (ALL). Thus, we analyzed the associations between quantitative computed tomography (QCT)-determined renal calcifications and clinical parameters (gender, race, age at diagnosis and age at the time of QCT), BMD, treatment exposures and Tanner stage. We investigated the associations between stone formation and nutritional intake, serum and urinary calcium and creatinine levels, and urinary calcium/creatinine ratio. Exact chi(2)-test was used to compare categorical patient characteristics, and the Wilcoxon-Mann-Whitney test to compare continuous measurements. Of 424 participants, 218 (51.4%) were males; 371 (87.5%) were nonblack. Most (n=270; 63.7%) were >or=3.5 years at ALL diagnosis. Mean (s.d.) and median (range) BMD Z-scores of the entire cohort were -0.4 (1.2) and -0.5 (-3.9 to 5.1), respectively. Nineteen participants (10 males; 10 Caucasians) had kidney stones (observed prevalence of 4.5%; 19/424) with a significant negative association between stone formation and body habitus (body mass index, P=0.003). Stone formation was associated with treatment protocol (P=0.009) and treatment group (0.007). Thus, kidney stones in childhood ALL survivors could herald the future deterioration of renal function and development of hypertension. Long-term follow-up imaging may be warranted in these patients to monitor for progressive morbidity.

Dopamine transporter density in the basal ganglia in obsessive-compulsive disorder, measured with [123I]IPT SPECT before and after treatment with serotonin reuptake inhibitors.

It has been suggested that dopamine as well as serotonin are associated with the pathophysiology of obsessive-compulsive disorder (OCD). 5-Hydroxytryptophan inhibits dopamine release in healthy persons as well as in patients with OCD, and serotonin tonic inhibition affects dopamine function in basal ganglia, indicating a close relationship between serotonin and the dopamine system. Using iodine-123-labeled N-(3-iodopropen-2-yl)-2 beta-carbomethoxy-3beta-(4-chlorophenyl) tropane ([(123)I]IPT) single photon emission computed tomography (SPECT), we investigated the dopamine transporter (DAT) density in the basal ganglia of patients with OCD. The test consists of two measurements before and after treatment with serotonin reuptake inhibitors (SRIs). Ten patients with OCD before and after treatment with SRIs were included. We performed brain SPECT 2 h after intravenous administration of [(123)I]IPT using a dual-head SPECT camera (Vertex, ADAC, Calif., USA) and analyzed the SPECT data, reconstructed for the assessment of the specific/nonspecific DAT binding ratio in the basal ganglia. We then examined the correlation between the scores of OCD symptom changes, assessed with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), and DAT binding ratio. Patients with OCD after treatment with SRIs showed a significantly decreased DAT binding ratio in the right basal ganglia compared with baseline. A significant correlation was found between the total scores and compulsion score changes of the Y-BOCS and the changes of the DAT binding ratio of the right basal ganglia. These findings suggest that the dopaminergic neurotransmitter system of the basal ganglia could play an important role in the symptom improvement of OCD patients.

Global detection of molecular changes reveals concurrent alteration of several biological pathways in nonsmall cell lung cancer cells.

To identify the molecular changes that occur in non-small cell lung carcinoma (NSCLC), we compared the gene expression profile of the NCI-H292 (H292) NSCLC cell line with that of normal human tracheobronchial epithelial (NHTBE) cells. The NHTBE cells were grown in a three-dimensional organotypic culture system that permits maintenance of the normal pseudostratified mucociliary phenotype characteristic of bronchial epithelium in vivo. Microarray analysis using the Affymetrix oligonucleotide chip U95Av2 revealed that 1,683 genes showed a >1.5-fold change in expression in the H292 cell line relative to the NHTBE cells. Specifically, 418 genes were downregulated and 1,265 were upregulated in the H292 cells. The expression data for selected genes were validated in several different NSCLC cell lines using quantitative real-time PCR and Western analysis. Further analysis of the differentially expressed genes indicated that WNT responses, apoptosis, cell cycle regulation and cell proliferation were significantly altered in the H292 cells. Functional analysis using fluorescence-activated cell sorting confirmed concurrent changes in the activity of these pathways in the H292 line. These findings show that (1) NSCLC cells display deregulation of the WNT, apoptosis, proliferation and cell cycle pathways, as has been found in many other types of cancer cells, and (2) that organotypically cultured NHTBE cells can be used as a reference to identify genes and pathways that are differentially expressed in tumor cells derived from bronchogenic epithelium.

Post-marketing surveillance study of the safety and efficacy of sildenafil prescribed in primary care to erectile dysfunction patients.

In order to investigate the safety and efficacy of sildenafil prescribed in primary care, a post-marketing surveillance study was undertaken. A total of 651 men with erectile dysfunction (ED) were enrolled from 31 family physicians in Korea from December 1999 to July 2002. Patients were regularly followed up to ascertain the safety and efficacy of sildenafil. Of the 651 patients enrolled, 572 (87.9%) returned for safety evaluation and efficacy assessment. In all, 458 (80.1%) of 572 patients reported improved erectile function with sildenafil. Hypertension, diabetes and low-dose sildenafil were associated with poor efficacy. A total of 71 adverse events were reported among 56 patients (8.6%), with the most frequent being hot flushes (5.6%), followed by headache (2.6%), palpitation (1.0%), anxiety (0.5%) and elevated ALT (0.5%). Only six patients (1.0%) discontinued sildenafil as a direct result of adverse events. These results suggest that sildenafil prescribed by primary care physicians was well tolerated and improved erectile function in patients with ED.

Chiral studies across the spectrum of polymer science.

This Account describes how stereochemical ideas focused on chirality have been directed widely across polymer science allowing experiments that could not be conducted on small molecules and leading to new insights and new kinds of materials. In one approach, a helical polymer was studied, and it was discovered how the chiral information necessary to choose helical sense is greatly amplified. In another approach, the racemization kinetics of atropisomers were used to characterize the restrictions to motion associated with a polyelectrolyte that forms clusters around hydrophobic groups in water and in an entirely different system, the glassy state formed by polymers.

Expression of the second isoform of gonadotrophin-releasing hormone (GnRH-II) in human endometrium throughout the menstrual cycle.

We examined the expression of the protein and mRNA of the newly cloned isoform of human gonadotrophin-releasing hormone (GnRH-II) in the normal human endometrium during the menstrual cycle. Nested RT-PCR and sequence analysis revealed that two spliced variants of GnRH-II mRNA were expressed during the entire menstrual cycle, with the shorter transcript having a 21 nucleotide deletion in the region coding for GnRH-associated peptide. Using immunohistochemistry, we identified immunoreactive GnRH-II in both stromal and glandular epithelial cells during the entire menstrual phase. The immunostaining intensity was stronger during the early and mid-secretory phase compared with the proliferative and late-secretory phase. A large amount of immunoreactive GnRH-II was localized in the apical pole of the glandular lumen. Our results show that the second isoform of GnRH (GnRH-II) is expressed in the human endometrium during the entire menstrual phase. We also suggest that an increased expression of endometrial GnRH-II peptide, noted during the early and mid-secretory phase, may play an important role in human embryo implantation.

HLA-B51 and its allelic types in association with Behçet's disease and recurrent aphthous stomatitis in Korea.

OBJECTIVE: This case-control study was undertaken to evaluate the association of HLA-B51 antigen and its allelic types with Behçet's disease (BD) and with recurrent aphthous stomatitis (RAS), to investigate the degree of this association with diagnostic types and clinical variables of BD. METHODS: The DNA typing of HLA-B51 by nested PCR-SSP was performed in 61 patients with BD, 56 patients with RAS, and in 70 healthy controls. Also, blind quality control study was done to assess the accuracy of nested PCR-SSP in HLA-B51-positive and negative BD patients on the microlymphocytotoxicity. In addition, direct DNA sequencing analysis was carried out in HLA-B51-positive individuals. RESULTS: The outcome of nested PCR-SSP showed 100% concordance with those of the microlymphocytotoxicity. The prevalence of HLA-B51 in patients with BD was 55.7%, 16.1% in patients with RAS, and 15.7% in healthy controls. According to the diagnostic types of BD, all ten patients with complete BD had HLA-B51 antigen, and 47.1% in patients with incomplete BD (p = 0.002). In addition, the prevalence of HLA-B51 was statistically significant in patients with BD who had uveitis (p = 0.003) or erythema nodosum (p = 0.042). Direct DNA sequencing analysis revealed that the major allelic types in BD, RAS, and in healthy control were mostly HLA-B*51011. CONCLUSIONS: Compared to patients with RAS or healthy controls, prevalence of HLA-B51 in the Korean patients with BD was much higher. The BD patients with B51 seemed to be susceptible for manifesting uveitis, erythema nodosum, and the full-blown syndrome as complete BD. Therefore the presence of HLA-B51 antigen in BD patients would be a genetic marker for the severe disease. In addition, there was no difference on the major allelic types of HLA-B51 in BD, RAS, and in healthy control.

Gene polymorphisms of endothelial nitric oxide synthase and angiotensin-converting enzyme in patients with asthma.

BACKGROUND: Nitric oxide, including that produced by endothelial constitutive nitric oxide synthase (ecNOS), may regulate vascular and airway tone in the lungs and may influence various aspects of airway homeostasis. Angiotensin-converting enzyme (ACE) is expressed at high levels in the lungs and plays a role in the metabolism of angiotensin II, bradykinin, and substance P, all of which are potentially involved in the pathogenesis of asthma. An insertion-deletion polymorphism of the ACE gene has been shown to be associated with enzyme activity levels of ACE. To examine the possible involvement of the ecNOS and/or ACE genes as the genetic basis of bronchial asthma, we investigated whether there was any association between bronchial asthma and polymorphisms of the ecNOS and/or ACE genes. METHODS: A total of 310 patients with bronchial asthma and 121 healthy subjects took part in this study. The ecNOS and ACE genotypes were determined in all subjects by polymerase chain reaction. RESULTS: 1) The distribution of one genotype (bb) of ecNOS was significantly higher in the asthma group than in the control population. 2) The ACE genotype distribution was not significantly different between the control and the asthma groups. 3) In asthmatic patients, the ACE and ecNOS genotype distribution did not differ significantly among groups of patients with different severities of asthma. CONCLUSIONS: These results suggest that polymorphisms of the ecNOS gene, but not the ACE gene, may be associated with the development of asthma. However, the severity of asthma may not be influenced by polymorphisms of the ecNOS and ACE genes.

The reliability and acceptability of telemedicine for patients with schizophrenia in Korea.

We conducted a pilot study to evaluate telemedicine for patients with schizophrenia. The telemedicine system was connected over the ordinary telephone network at 33 kbit/s. A computer-based patient record was used to view patient summaries and to allow nursing notes to be entered at the patient's home. Fifteen patients with schizophrenia were assessed over the telemedicine system and 15 patients were assessed face to face, using the Brief Psychiatric Rating Scale (BPRS). Our low-bandwidth telemedicine system appeared to be as reliable as higher-bandwidth ISDN systems. In addition, the patients' acceptance of the telemedicine interview, in terms of comfort, ease of self-expression, quality of interpersonal relationship and usefulness, was good in most cases. The only factors significantly affecting the patients' level of acceptance of their particular type of interview were the assessment type (i.e. whether the patient had had a telemedicine assessment or not) and their BPRS score. Since the system was of low cost and was easy to interface with a notebook computer, it could be used support other home-health nursing services.

Gene polymorphisms of endothelial nitric oxide synthase and angiotensin-converting enzyme in patients with lung cancer.

The objectives of this study were to examine the possible involvement of endothelial nitric oxide synthase (ecNOS) and angiotensin-converting enzyme (ACE) genes in the genetic basis of lung cancer. Two hundred eighteen patients with lung cancer and 121 healthy subjects were included in this study. The ecNOS and ACE genotypes were determined in all subjects by polymerase chain reaction. The distribution of genotypes of ecNOS gene was significantly different in the lung cancer group than in the control population. ACE genotype distribution was not significantly different in the lung cancer group compared with the control group. These results suggest that polymorphisms of the ecNOS gene, but not the ACE gene, may be associated with the development of lung cancer.

Short-term safety and tolerability of antihypertensive agents in Korean patients: an observational study.

PURPOSE: In order to assess the short-term safety and tolerability of newly prescribed antihypertensive monotherapies in Korean patients, a prospective study was carried out. METHODS: A total of 1181 patients were observed from July 1997 to August 1999. At 2, 4, 8 and 12 weeks after initiation of antihypertensive monotherapy, the patients were evaluated for whether treatment was to be continued and the development of any adverse reactions. RESULTS: During the first 12 weeks, the percentage of subjects continuing with their initial angiotensin converting enzyme inhibitors (ACEI) (40.7%) was substantially lower than that of subjects continuing with angiotensin II receptor antagonists (ARA) (66.2%), alpha-blockers (63.0%), calcium channel blockers (CCB) (61.3%), beta-blockers (55.8%), and diuretics (53.5%), respectively (P < 0.01). The following adverse reactions were detected: cough (7.5%), headache (6.1%), dizziness (3.9%), flushing (3.7%) and impotence (2.4%). Cough, headache, and flushing were more frequent in women, and impotence and loss of libido were more frequent in men (P < 0.05). The incidence of cough associated with ACEI (27.9%) was higher than that associated with the other classes of drugs (P < 0.01). CONCLUSIONS: The tolerability of antihypertensive medication was highest in Korean patients treated with ARAs, followed by CCBs, beta-blockers, diuretics, alpha-blockers, and ACEIs. The incidences of adverse reactions were different by sex, age and drug class.

Activation of ErbB2 during wallerian degeneration of sciatic nerve.

We used anti-phosphopeptide-immunodetecting antibodies as immunohistochemical reagents to define the location and activity state of p185(erbB2) during Wallerian degeneration. Nerve damage induces a phosphorylation event at Y1248, a site that couples p185(erbB2) to the Ras-Raf-MAP kinase signal transduction pathway. Phosphorylation of p185(erbB2) occurs within Schwann cells and coincides in time and space with Schwann cell mitotic activity, as measured by bromodeoxyuridine uptake. These visual images of receptor autophosphorylation link activation of p185(erbB2) to the Schwann cell proliferation that accompanies nerve regeneration.

Changes of soluble ICAM-1 levels in serum and bronchoalveolar lavage fluid from patients with atopic bronchial asthma after allergen challenge.

Leukocyte-endothelial cell interaction is essential for leukocyte infiltration into inflammatory sites. Initiation of adhesion is through the up-regulated expression of adhesion molecules in the endothelium or epithelium and the activation of adhesion molecules on leukocytes. To our knowledge, there have been few reports concerning soluble intercellular adhesion molecule-1 (sICAM-1) in patients with atopic bronchial asthma after allergen challenge. If the levels of sICAM-1 vary between bronchial asthma patients and normal controls, this variance would be useful to assess the state of this disease. Therefore, we measured the levels of sICAM-1 in sera from 17 patients with atopic bronchial asthma and normal control subjects. Levels of sICAM-1 in sera from bronchial asthma patients in prechallenge conditions were higher than in normal control subjects. Levels of sICAM-1 in sera from bronchial asthma patients 8 hr after challenge were higher than those in sera obtained during prechallenge periods. sICAM-1 levels in bronchoalveolar lavage (BAL) fluids from bronchial asthma patients 8 hr after challenge were higher than at 30 min after challenge. These results suggest that higher levels of sICAM-1 in sera and BAL fluids reflect the up-regulation of ICAM-1 expression in allergic bronchial asthma and these high levels may contribute to the pathogenesis of atopic bronchial asthma.