Incidence of oral anticoagulant interruption among stroke patients with atrial fibrillation and subsequent stroke.

BACKGROUND AND PURPOSE: We analyzed the incidence and causes of oral anticoagulant (OAC) cessation and subsequent stroke after OAC withdrawal in a cohort of Korean stroke patients with atrial fibrillation. METHODS: The Korean Atrial Fibrillation Evaluation Registry in Ischemic Stroke patients (K-ATTENTION) is a multicenter cohort study, merging stroke registries from 11 tertiary centers in Korea. The number of OAC interruption episodes and the reasons were reviewed from hospital records. Stroke after OAC withdrawal was defined when a patient experienced ischaemic stroke within 31 days after OAC withdrawal. Clinical variables were compared between patients who experienced stroke recurrence during OAC interruption and those who did not experience recurrence. RESULTS: Among 3213 stroke patients with atrial fibrillation, a total of 329 episodes of OAC interruption were detected in 229 patients after index stroke (mean age 72.9 ± 8.3 years, 113 female patients). The most frequent reason for OAC withdrawal was poor compliance [103 episodes (31.3%)] followed by extracranial bleeding [96 episodes (29.2%)]. Stroke after OAC withdrawal was noted in 13 patients. Mean age, vascular risk factor profile and mean CHA2 DS2 -VASc score were not significantly different between patients with and without recurrent stroke. CONCLUSIONS: A considerable number of stroke patients with atrial fibrillation experienced temporary interruption of OAC after index stroke, which was associated with stroke recurrence of 4.0 cases per 100 interruption episodes.

Association between time to treatment and functional outcomes according to the Diffusion-Weighted Imaging Alberta Stroke Program Early Computed Tomography Score in endovascular stroke therapy.

BACKGROUND AND PURPOSE: The rate at which the chance of a good outcome of endovascular stroke therapy (EVT) decays with time when eligible patients are selected by baseline diffusion-weighted magnetic resonance imaging (DWI-MRI) and whether ischaemic core size affects this rate remain to be investigated. METHODS: This study analyses a prospective multicentre registry of stroke patients treated with EVT based on pretreatment DWI-MRI that was categorized into three groups: small [Diffusion-Weighted Imaging Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS)] (8-10), moderate (5-7) and large (<5) cores. The main outcome was a good outcome at 90 days (modified Rankin Scale 0-2). The interaction between onset-to-groin puncture time (OTP) and DWI-ASPECTS categories regarding functional outcomes was investigated. RESULTS: Ultimately, 985 patients (age 69 ± 11 years; male 55%) were analysed. Potential interaction effects between the DWI-ASPECTS categories and OTP on a good outcome at 90 days were observed (Pinteraction  = 0.06). Every 60-min delay in OTP was associated with a 16% reduced likelihood of a good outcome at 90 days amongst patients with large cores, although no associations were observed amongst patients with small to moderate cores. Interestingly, the adjusted rates of a good outcome at 90 days steeply declined between 65 and 213 min of OTP and then remained smooth throughout 24 h of OTP (Pnonlinearity  = 0.15). CONCLUSIONS: Our study showed that the probability of a good outcome after EVT nonlinearly decreased, with a steeper decline at earlier OTP than at later OTP. Discrepant effects of OTP on functional outcomes by baseline DWI-ASPECTS categories were observed. Thus, different strategies for EVT based on time and ischaemic core size are warranted.

Testosterone effects on pain and brain activation patterns.

BACKGROUND: This study investigated whether pain and pain-related unpleasantness ratings were altered by blood testosterone levels. We also investigated whether activation of brain regions that represent pain intensity [primary somatosensory cortex (S1)] and pain-related unpleasantness [perigenual ACC (pACC) and orbitofrontal cortex (OFC)] were affected by blood testosterone levels. METHODS: Twenty-six healthy men were recruited. Blood testosterone levels were measured before fMRI scanning. The participants were classified into two groups (high vs. low testosterone) according to their blood testosterone level (each group n = 13). The middle finger was immersed in a 50°C water bath (50°C, 30 s, five times) to induce identical noxious stimulation in all participants. RESULTS: The low testosterone group showed statistically significantly higher pain (P = 0.047), unpleasantness (P = 0.047), anxiety (P = 0.015), and fear ratings (P = 0.01) than the high testosterone group. Fear rating increased as pain rating rose and as testosterone level decreased (P < 0.001). When participants received noxious stimulation, the pACC and OFC were more highly activated in the low testosterone group compared to the high testosterone group. Activation of S1, a region related to pain intensity, did not differ between both groups. CONCLUSION: Compared to the high testosterone group, the low testosterone group had significant activation in the pACC and OFC, regions that represent pain-related unpleasantness, but not in S1 that represents pain intensity, leading to higher pain ratings. These findings emphasize the importance of considering the effects of testosterone levels when treating patients.

Step-down vs. step-up noxious stimulation: differential effects on pain perception and patterns of brain activation.

BACKGROUND: We hypothesize that pain and brain responses are affected by changes in the presentation sequence of noxious stimuli that are, overall, identical in intensity and duration. METHODS: During functional magnetic resonance imaging (fMRI) scanning, 21 participants experienced three patterns of noxious stimulation: Up-type (step-up noxious stimulation, 15 s), Down-type (step-down noxious stimulation, 15 s), and Down-up-type (decreasing and increasing pattern of noxious stimulation, 15 s). The total intensity and duration of the three noxious stimulation patterns were identical, but the stimulation sequences were different. RESULTS: Pain and unpleasantness ratings in the Down- and Down-up-type noxious stimulations were lower than in the Up-type noxious stimulation. The left prefrontal cortex [(PFC, BA (Brodmann area) 10, (-45, 50, 1)] was more highly activated in the Down- and Down-up-type noxious stimulations than in the Up-type noxious stimulation. The S1, S2, insula, bilateral PFC (BA 46), and midcingulate cortex were more highly activated in the Up-type noxious stimulation than in the Down-type noxious stimulation. PFC BA 10 was located at an inferior level compared to the bilateral PFC BA 46 (Z axis = 1 for BA 10, compared to 22 and 25 for the right and left BA 46, respectively). When cortisol level was increased, the left hippocampal cortex, along with the left parahippocampal cortex, was greatly activated for the Up-type noxious stimulation. CONCLUSION: When pain cannot be avoided in clinical practice, noxious stimuli should be applied to patients in a step-down pattern that delivers the most intense pain first and the least intense pain last.

The effect of diabetic control status on the clinical features of pulmonary tuberculosis.

The aim of this study was to determine whether control status of diabetes mellitus influences clinical and radiographic manifestations and treatment responses in patients with tuberculosis (TB). The medical records of 492 patients who started anti-TB medication between January 2005 and December 2009 were retrospectively reviewed. Diabetes was diagnosed in 124 patients (25.2%). Of these, 74 (59.7%) were uncontrolled (HbA1C≥7.0), 25 (20.2%) were controlled (HbA1C<7.0), and HbA1C levels were not assessed in the remaining 25 (20.2%). There were no differences in clinical symptoms between diabetics and non-diabetics, regardless of diabetes control status. There were also no differences in radiographic findings or AFB results between controlled diabetics and non-diabetics. However, uncontrolled diabetics had more cavitary lesions (p=0.008) and higher positive smear rates (p<0.001) compared with non-diabetics. After adjustment for age, cavities and positive smears before initiation of treatment, uncontrolled diabetes was a significant risk factor for a positive sputum culture at 2 months (odds ratio, 4.316; 95% CI, 1.306-14.267; p=0.017). Uncontrolled diabetics seem to have more cavities, higher positive smear rates and lack of culture conversion after two months of therapy. Therefore, TB patients with uncontrolled diabetes should be carefully managed and treated.

Modulation of pain sensation by stress-related testosterone and cortisol.

Stress increases cortisol and decreases testosterone. It is not known whether pain is affected by stress-related testosterone. Therefore, we investigated whether stress can affect pain perception by decreasing testosterone and increasing cortisol. Pain thresholds, pain and anxiety ratings and salivary testosterone and cortisol levels were measured in 46 healthy men during resting and stressful conditions. Pain was induced by electrical stimulation. Stress was induced by having participants perform a medical test. Stress significantly increased anxiety ratings and salivary cortisol levels, but decreased salivary testosterone levels. Stress also increased pain ratings and decreased pain thresholds. During stress, cortisol levels were negatively correlated with pain thresholds and testosterone levels were positively correlated with pain thresholds. Results indicated that testosterone can decrease and cortisol can increase pain induced by electrical stimulation, suggesting that acute clinical pain may be relieved by controlling stress and managing consequent stress-related testosterone and cortisol.

Spitz naevus is rare in Korea.

BACKGROUND: Spitz naevi have not been widely studied in Asians. AIM: To compare the epidemiology and clinicopathological features of Spitz naevi in Koreans with lesions in western countries. METHODS: In total, 80 Spitz naevi in 77 patients diagnosed over 10 years at 17 university hospitals in Korea were analysed. RESULTS: The relative incidence of Spitz naevus vs. MM was 1 vs. 10.9. In most patients (75%) the Spitz naevi had been present for > 6 months. The size of the lesion was relatively large. Histologically, most of the lesions (54%) were the dermal type and pigmentation was common (49% of lesions). Immunohistochemical study found that all of the 34 lesions were positive for S-100 protein but only 14 (47%) were positive for HMB-45. CONCLUSION: Spitz naevus is rare in Korea. The lesions were more commonly larger, pigmented, and of the dermal type than reported in western countries.

Magnitude of Mycobacterium tuberculosis transmission among household and non-household contacts of TB patients.

The household and non-household contacts of patients with tuberculosis (TB) face varying degrees of risk of infection by Mycobacterium tuberculosis. To quantify new infection and to determine the risk factors associated with new infection among named contacts in San Francisco, CA, USA. We performed a cohort study in patients with culture-positive pulmonary TB. We analyzed patient, contact, environmental and bacterial characteristics. Of the 2422 contacts named by 256 patients, 149 (6.2%) had new infection due to recent transmission from 79 (30.9%) patients. Of the 149 new infections, 87 (58.4%) occurred among household contacts and 62 (41.6%) among non-household contacts. Numerous acid-fast bacilli in sputum (odds ratio [OR] 2.64, 95%CI 1.32-5.25) and contacts being named by more than one patient (OR 2.90, 95%CI 1.23-6.85) were associated with new infection among household contacts. Being older than 50 years (OR 1.93, 95%CI 1.09-3.41) and an Asian/Pacific Islander (OR 3.09, 95%CI 1.50-6.37) were associated with new infection among non-household contacts. Fewer than one third of patients caused new infection to his/her contacts. A substantial proportion of transmission resulting in new infection occurred outside of the household. The risk factors for infection among household and non-household contacts are different and should be considered when prioritizing control interventions. .

Effects of cocaine place conditioning, chronic escalating-dose "binge" pattern cocaine administration and acute withdrawal on orexin/hypocretin and preprodynorphin gene expressions in lateral hypothalamus of Fischer and Sprague-Dawley rats.

Recent evidence suggests an important role for hypothalamic orexins/hypocretins in modulation of drug reward and addiction-like behaviors in rodents. Our recent study has shown that the aversive state of arousal during acute morphine withdrawal is associated with increased orexin gene expression in lateral hypothalamus (LH) of Fischer 344 (F344) inbred rats, with no change in the expression of preprodynorphin (ppDyn), a gene co-expressed with LH orexin. Therefore, we determined whether orexin and ppDyn mRNA levels in LH or medial hypothalamus (including perifornical and dorsomedial areas) of F344 or Sprague-Dawley (SD) outbred rats, are altered following: 1) cocaine (10 mg/kg, i.p.) conditioned place preference (CPP); 2) chronic (14 days) cocaine exposure using both "binge" pattern administration in steady-dose (45 mg/kg/day) and escalating-dose (45-90 mg/kg/day) regimens; and 3) acute (1 day) and chronic (14 days) withdrawal from cocaine with opioid receptor antagonist naloxone treatment (1 mg/kg). We found that orexin mRNA levels were decreased after cocaine place conditioning in the LH of SD rats. A decreased LH orexin mRNA level was also observed after chronic escalating-dose cocaine (but not CPP pattern regimen without conditioning, or steady-dose regimen) in both strains. In F344 rats only, acute withdrawal from chronic escalating-dose cocaine administration resulted in increases in both LH orexin and ppDyn mRNA levels, which were unaltered by naloxone or after chronic withdrawal. Our results suggest that (1) alteration of LH orexin gene expression is region-specific after cocaine place conditioning in SD rats and dose-dependent after chronic exposure in both strains; and (2) increased LH orexin and ppDyn gene expressions in F344 rats may contribute to negative affective states in cocaine withdrawal.

Brain mechanisms of pain relief by transcutaneous electrical nerve stimulation: A functional magnetic resonance imaging study.

BACKGROUND: Although the exact mechanism of TENS pain relief is unknown, it is believed that TENS impulses interrupt nociceptive signals at the dorsal horn of the spinal cord. AIMS: To evaluate the hypotheses that during pain caused by noxious stimuli, brain responses, temporal summation and brain functional connectivity are modulated by TENS, and that mechanisms of pain relief by TENS differ between men and women. METHODS: During fMRI scanning, the same noxious stimuli were delivered to each participant in pain-only and pain+TENS conditions. In the pain-only condition, noxious stimuli were presented without TENS. In the pain+TENS condition, participants received noxious stimuli and TENS concurrently. Participants were initially presented with TENS at an intensity that was just below that causing discomfort. TENS intensity was presented in a step-wise fashion to prevent temporal summation from repetitive noxious stimuli. RESULTS: Pain and unpleasantness ratings were significantly higher in the pain-only than the pain+TENS condition. With non-painful TENS, primary and secondary somatosensory and parietal cortices were activated, and temporal summation from repetitive noxious stimuli was prevented. Periaqueductal gray (PAG) and lateral prefrontal cortex functional connectivity was increased by TENS, and modulated by testosterone and cortisol. Women reported greater pain during TENS than men, and showed greater activation in the temporoparietal junction cortex and increased PAG functional connectivity with the orbitofrontal cortex. CONCLUSION: TENS led to pain reduction, probably due to activation of the descending pain-inhibitory pathway, indicating that this TENS method may be applied in clinical practice.

Reduced sensitivity of the QuantiFERON(®) test in diabetic patients with smear-negative tuberculosis.

SETTING: Immunosuppressive conditions have been associated with low sensitivity of interferon-gamma release assays (IGRAs) and the tuberculin skin test (TST) for the diagnosis of tuberculosis (TB). However, no systematic analysis of patient and bacterial characteristics has been performed before. OBJECTIVE: To determine the sensitivity and the risk factors for false-negative QuantiFERON(®)-TB (QFT) assay and TST in TB patients. DESIGN: We performed a retrospective analysis of data collected in a community-based study of TB in San Francisco, CA, USA. We included 300 TB patients who underwent QFT and TST. RESULTS: The risk factors for false-negative QFT were human immunodeficiency virus infection and the use of QuantiFERON(®)-TB Gold. In patients with sputum smear-negative TB, diabetes mellitus (DM) was associated with false-negative QFT (OR 2.85, 95%CI 1.02-7.97, P = 0.045). TST sensitivity was higher than QFT sensitivity in DM patients (OR 9.46, 95%CI 2.53-35.3). CONCLUSIONS: In San Francisco, QFT sensitivity was lower than that of TST, especially in patients with DM. Stratified analysis by sputum smear results showed that this association was specific to smear-negative TB. In contrast, TST was not affected by the presence of DM.

Candidate cell populations for respiratory chemosensitive fields in the human infant medulla.

The histology and location of human respiratory chemosensitive fields are not known. In contrast, the physiology of respiratory chemosensory areas in the ventral medulla of cats has been studied extensively, and their anatomy has been partially described. Using basic principles of comparative cytoarchitecture and computer-aided reconstructions of serial-sectioned medullae, we describe the histology and three-dimensional distribution of putative respiratory chemosensors in the feline and human infant medulla. We found that ventrolateral neurons of the human nucleus conterminalis are homologous to neurons identified in the feline L chemosensitive field by Trouth and others, and that ventrolaterally situated neurons in the human arcuate nucleus correspond to neurons predominating in the feline S and M fields. In addition, there are foci of thickened marginal glia along the feline ventral medullary surface that colocalize with chemosensitive fields identified by physiologic studies reported by others; we identify similar foci in the infant medulla. Thickened marginal glia are intermixed with neuronal fibers, often adjacent to neurons of the feline chemosensitive fields and their human counterparts, suggesting that they constitute a chemosensory neuropil at the medullary surface. Computer-aided reconstructions provide insight into the three-dimensional topography of putative respiratory chemosensors and their relationships to other brainstem structures in ways not obvious in single or even multiple sections. This delineation of candidate human respiratory chemosensors is a first step toward their postmortem analysis in patients with central ventilatory control disorders where finding histological abnormalities in these sites would support their role in human ventilation.

Specific sequences of fibronectin activate the protein kinase C signal transduction pathway in invasive bladder cancer.

The mechanism of human bladder cancer cell invasion is not clear, but it appears that extracellular matrix components, such as fibronectin, may be involved. To investigate the role of fibronectin in tumor cell invasion and progression, we used an in vitro invasion assay to define the motility stimulating fragment of fibronectin for invasive human bladder cancer T24 cells. Using a modified Boyden chamber assay and purified fragments of fibronectin, we demonstrated that both the 120 kDa chymotrypsin generated fragment of fibronectin (containing the cell attachment RGD motif and additional sequences towards the carboxyl-terminal heparin binding domain), as well as the trypsin generated 60 kDa fragment of fibronectin (containing the carboxyl-terminal heparin binding domain and additional sequences towards the cell attachment RGD motif), were able to stimulate the migration of invasive human bladder cancer T24 cells. Control fragments containing only the amino-terminal gelatin binding region of fibronectin did not stimulate the motility of the human bladder cancer T24 cells. To determine the molecular mechanism in which these fragments may stimulate the migration of the T24 cells, we assayed for intracellular signal transduction pathway protein kinase C (PKC). We demonstrated that both the 120 kDa and the 60 kDa fragments were able to stimulate the activation of protein kinase C. Non-motility stimulating fragments of fibronectin were not able to activate protein kinase C. We conclude that the PKC signal transduction pathway may be involved in matrix mediated motility, and suggest that the inhibition of such pathway(s) may alter the malignant phenotype of human bladder cancer.

The involvement of phospholipase A(2) in ethanol-induced gastric muscle contraction.

To understand the underlying mechanism of ethanol in tonic contraction, the effect of ethanol on phospholipase A(2) and phospholipase C activities and the effects of phospholipase inhibitors on ethanol-induced contraction of cat gastric smooth muscle were tested. Circular muscle strips (2.0 x 0.2 cm) obtained from the fundus of cat stomach were used to measure isometric contraction. Ethanol elicited tonic contraction and activated phospholipase A(2) activity in a dose-dependent manner. Phospholipase A(2) inhibitors, manoalide (0.1--10 microM) and oleyloxyethyl phosphorylcholine (1--10 microM), significantly inhibited ethanol-induced contraction. Furthermore, 342 mM ethanol-induced contraction was significantly inhibited by cyclooxygenase inhibitors, ibuprofen (10--100 microM) and indomethacin (10--100 microM), but not by lipoxygenase inhibitors. On the other hand, phospholipase C inhibitors had no effect on ethanol-induced contraction, indicating that phospholipase C is not involved in ethanol-induced contraction. It is suggested from the above results that ethanol-induced contraction in cat gastric smooth muscle is, in part, mediated by phospholipase A(2) and cyclooxygenase pathways.

Computed tomographic characteristics of chronic subdural hematomas.

Although medical history and physical examination should lead to diagnosis of chronic subdural hematomas, 40% of these patients are likely to be misdiagnosed because many of these symptoms occur in other disease processes, such as transient ischemic attacks, stroke, dementia, and tumors. Computed tomography remains one of the most useful tools in the evaluation of these patients because of its rapidity, cost, availability, and pathologic sensitivity.

The role and results of bone grafting in revision total knee replacement.

Failure in total knee replacement requiring revision surgery is often accompanied by significant bone loss and soft tissue asymmetry. When embarking on these complex reconstructions, careful preoperative planning is necessary to ensure that these deficiencies will be corrected by surgical technique and implant selection. This article discusses various techniques and results of bone grafting in revision total knee arthroplasty.

Ossifying fibroma.

Our experience includes seven cases of ossifying fibroma. The condition also appears in the literature under diagnostic names such as congenital fibrous dysplasia, congenital osteitis fibrosa, congenital fibrous defect of the tibia, and osteofibrous dysplasia of the tibia and fibula. The lesions develop in childhood and are located in the diaphysis of the tibia, or fibula. Of seven patients, we performed wide excision with free vascularized fibular graft in five cases, wide resection of the distal one-third of the fibula in one case, and curettage and bone graft in one case. Two of the patients who had wide excision with free vascularized fibular graft had recurrence. One case of recurrence occurred where incomplete wide excision with free-vascularized fibular graft was performed because the lesion was too close to the distal epiphysis of the tibia. One of the patients who had curettage and bone graft also had recurrence. It was concluded that children who have an ossifying fibroma requiring surgery can safely be treated with wide excision with or without free-vascularized fibular graft.

Clinicohistopathologic comparison of adult type and juvenile type xanthogranulomas in Korea.

Xanthogranuloma (XG) is an uncommon benign disorder characterized by solitary or multiple yellow-red papulonodules on the skin, and occasionally, in other organs. It is predominantly a disease of infancy or early childhood, although adults may rarely be affected. To compare the clinicohistopathological featues of juvenile-type xanthogranulomas UXGs) and adult-type xanthogranulomas (AXGs) (>14 years) in Korea, 30 cases of JXGs and 15 cases of AXGs were compared clinically and histopathologically. Except for the fact AXGs were more often solitary and larger and showed neither other associated systemic diseases nor spontaneous regression, the clinical features such as color, mean number, or site of the lesions in AXGs were not statistically different from JXGs. Histologically, AXCs were not significantly different in amounts of foamy cells, giant cells including Touton cells, and inflammatory cells, although subcutaneous involvement was seen only in the two infant cases. In conclusion, in contrast to AXGs, JXGs need special attention to accompanying systemic diseases and do not need excisional procedures, considering their frequent spontaneous regression.

Trabeculectomy with intraoperative 5-fluorouracil.

BACKGROUND AND OBJECTIVE: To investigate the outcome and complication rates of trabeculectomy following the combined use of intraoperative, topical 5-fluorouracil (5-FU) and low-dose, postoperative subconjunctival 5-FU injections. PATIENTS AND METHODS: Forty-one eyes of 41 patients with advanced, medically uncontrolled glaucoma underwent trabeculectomy with intraoperative episcleral application of 5-FU (50 mg/ml for 5 minutes). A variable number of subconjunctival 5-FU injections were administered postoperatively at the discretion of the operating surgeon. RESULTS: Six-, 12-, and 15-month life-table success rates (5 mm Hg < or = intraocular pressure [IOP < or = 21 mm Hg) were 100%, 97%, and 83%, respectively. Mean postoperative IOP was 12.1 +/- 4.3 mm Hg. An average of 2.2 +/- 1.6 (range 0 to 7) supplemental subconjunctival 5-FU injections were administered postoperatively. Corneal epithelial erosions developed in 7 (17%) of the eyes. Five of 7 patients who underwent subsequent surgical procedures maintained successful control of IOP at an average of 11.0 +/- 4.8 (range 5 to 16) months after the secondary surgery. CONCLUSION: Trabeculectomy with intraoperative 5-FU is effective in controlling IOP while possibly minimizing the need for frequent postoperative injections and the occurrence of corneal epitheliopathy.