Effect of patent foramen ovale closure for prevention on recurrent stroke or transient ischemic attack in selected patients with cryptogenic stroke.

OBJECTIVES: This study was sought to evaluate the effectiveness of patent foramen ovale (PFO) closure in selected patients (PFO shunt grade more than moderate) with cryptogenic stroke (CS). BACKGROUND: Whether closure of PFO is an effective treatment for prevention of CS is still unclear. METHODS: Consecutive 158 patients (mean age: 49.9 years old, closure group: 67 patients, medication group: 91 patients) were enrolled. The primary end point was a composite of recurrent stroke and transient ischemic attack. RESULTS: Baseline characteristics were similar between the two groups, except age which was younger in the closure group (47.7 ± 10.8 vs 51.9 ± 9.9, P = 0.013), and the presence of shunt at rest was more common in the closure group (35.8% vs 10.4%, P = 0.000). Procedural success was 94.0%. Over a mean follow-up of 27.8 months, a total of six primary end point, all of which were strokes, occurred only in the medication group (6.6% vs 0%, P = 0.039). Stroke-free survival rate was significantly higher in the closure group (P = 0.026) CONCLUSIONS: Our study showed that PFO closure may be an effective treatment strategy to prevent recurrent stroke or TIA for patients with CS if it is conducted in selective patients who have PFO shunt more than moderate grade.

fMRI brain activation in patients with insomnia disorder during a working memory task.

PURPOSE: This study used functional magnetic resonance imaging (fMRI) to investigate differences in the functional brain activation of patients with insomnia disorder (n = 21, mean age = 36.6) and of good sleepers (n = 26, mean age = 33.2) without other comorbidities or structural brain abnormalities during a working memory task. METHODS: All participants completed a clinical questionnaire, were subjected to portable polysomnography (PSG), and performed the working memory task during an fMRI scan. The subjects who were suspected of major sleep disorder and comorbid psychiatric disorders except insomnia disorder were excluded. To compare the brain activation on working memory from the insomnia group with those from the good-sleeper group, a two-sample t test was performed. Statistical significance was determined using 3DClustSim with the updated algorithm to obtain a reasonable cluster size and p value for each analysis. RESULTS: We observed higher levels of brain activation in the right lateral inferior frontal cortex and the right superior temporal pole in the insomnia group compared to good sleepers (cluster-based multiple comparison correction, p < 0.001, k = 34 @ α = 0.01). CONCLUSION: Thus, patients with insomnia disorder showed increased brain activation during working memory relative to good sleepers, and this may be indicative of compensatory brain activation to maintain cognitive performance in patients with insomnia disorder without other comorbidities.

Formula for predicting OSA and the Apnea-Hypopnea Index in Koreans with suspected OSA using clinical, anthropometric, and cephalometric variables.

PURPOSE: This study developed formulas to predict obstructive sleep apnea (OSA) and the Apnea-Hypopnea Index (AHI) in Korean patients with suspected OSA using clinical, anthropometric, and cephalometric variables. METHODS: We evaluated relevant variables in 285 subjects with suspected OSA. These included demographic characteristics, sleep-related symptoms, medical history, clinical scales, anthropometric measurements including facial surface measurements, and cephalometric measurements. All participants underwent full-night laboratory polysomnography. The prediction formula for the probability of OSA was created by logistic regression analysis and confirmed by the bootstrap resampling technique. The formula for predicting the AHI was developed using multiple linear regression analysis. RESULTS: The probability of having OSA was as follows: p = 1 / (1 + exponential (exp)-f ), where f = -16.508 + 1.445 × loudness of snoring 4 + 0.485 × loudness of snoring 3 + 0.078 × waist circumference + 0.209 × subnasale-to-stomion distance + 0.183 × thickness of the uvula (UTH) supine + 0.041 × age. The AHI prediction formula was as follows: -112.606 + 3.516 × body mass index + 0.683 × mandibular plane-hyoid supine + 10.915 × loudness of snoring 4 + 6.933 × loudness of snoring 3 + 1.297 × UTH supine + 0.272 × age. CONCLUSION: This is the first study to establish formulas to predict OSA and the AHI in Koreans with suspected OSA using cephalometric and other variables. These results will contribute to prioritizing the order in which patients with suspected OSA are referred for polysomnography.

Comparison of Outcomes after Device Closure with Transseptal Puncture and Standard Technique in Patients with Patent Foramen Ovale and Ischemic Events.

OBJECTIVES: The purpose of this study was to compare the effectiveness of device closure with the transseptal puncture and standard technique in patients with patent foramen ovale (PFO) and ischemic events. METHODS: Eighty-two consecutive patients (men: 60 patients, mean age: 45.2 years) who underwent PFO closure with the Amplatzer PFO Occluder were enrolled. PFO closure with the transseptal puncture was performed in 22 patients (transseptal puncture technique, group I). In the remaining patients (n = 60), PFO closure was performed with the standard technique (group II). The co-primary end points were the incidence of significant residual shunt on follow-up transesophageal echocardiography (TEE) and a composite of death, stroke, transient ischemic attack (TIA), and peripheral embolism. RESULTS: Baseline characteristics were similar between the two groups. On TEE, despite similar grade of interatrial right-to-left shunt, shunt at rest/septal hypermobility was less common in group I than in group II (40.9% vs. 72.9%, P < 0.010). The device was successfully implanted in all patients. On follow-up TEE, significant residual shunt was more common in group I than in group II (28.6% vs. 4.3%, P = 0.021). In addition, composite of death, stroke, TIA, or peripheral embolism was more common in group I than in group II (13.6% vs. 0%, P = 0.017) during the follow-up period (mean 25.4 months). CONCLUSION: Compared to the standard technique, PFO closure with the transseptal puncture technique showed higher incidence of residual shunt and ischemic events. Therefore, this technique might be considered in only highly selected patients as the last option.

Morphine exposure during HIV encephalitis in SCID mice.

HIV encephalitis (HIVE) is often complicated by opiate abuse. Based on human pathological, animal and in vitro studies, opiates are thought to exacerbate HIVE. To test this hypothesis we exposed 10 week old SCID mice with HIVE to morphine and examined histopathological parameters. Mice inoculated intracerebrally with either HIV-infected or uninfected (control mice) human macrophages were immediately implanted subcutaneously with pellets containing saline, morphine or morphine plus naltrexone. They were sacrificed after 10 days. Immunostaining for astrocytes (GFAP), mouse mononuclear phagocytes (CD45) and neuronal dendrites (MAP2) was analyzed by densitometry. HIVE mice exposed to either saline, morphine or morphine plus naltrexone also had brain sections counted for HIV+ human macrophages. Typical HIVE pathology was present, consistent with previously published studies. Surprisingly, there were no effects on astrogliosis, microgliosis and MAP2 decreases in the HIVE, morphine treated group. There was also no effect of morphine exposure on numbers of p24+ human macrophages. These results emphasize the complexities of modeling opiate effects in HIVE and the potential significance of opiate abuse on HIVE in humans.

A case of ossified laryngeal cartilage mimicking a subglottic mass.

A previously healthy 54-year-old man complained of progressive voice changes. A firm subglottic polypoid mass was located at the right posterior site, as seen on fiberoptic laryngoscopy, with a distinctly narrowed subglottic space being seen on neck computed tomography, and there were multiple opacities from the cricoid cartilage to the tracheal rings. Resection was done under general anesthesia. The mass-like elevated lesion showed enchondral ossification of the laryngeal cartilage just beneath the squamous metaplastic surface epithelium. The vocal cord mobility was normal. Compared with the computed tomography and the laryngoscopic examination, the polypoid mass-like elevation corresponded to a ossified vocal process of the right arytenoid cartilage. To date, clinically symptomatic ossification of the laryngeal cartilages has presented with foreign body-like impaction. The present case is a rare case of ossification of the laryngeal cartilage that masqueraded as a subglottic polypoid mass. The ossification of laryngeal cartilage is part of the normal aging process, but a tumor-like mass at the airway related with voice changes, like was seen in the present case, is rare. Albeit rare, clinicians and radiologists should be aware that this heterotopic ossification may mimic a polypoid mass-like presentation as well as the accompanying symptoms.

Identification and morphologic assessment of mesocoelic recess by in vivo human brain imaging with 7.0-T magnetic resonance imaging.

OBJECTIVE: The mesocoelic recess (MCR) is found in the brain of human embryos and fetuses. The mesocoelic recess seems to be functionally related to the subcommissural organ that is one of neurosecretory organs involved in osmoregulation on the basis of data from other species. Subsequently, recent speculation as to the importance of the subcommissural organ in the development of congenital hydrocephalus has been raised. Yet unlike other mammals, MCR is known to be a vestigial structure in the adult human brain. Here, we performed the in vivo imaging identification of this space to investigate functional and clinical correlations. METHODS: We studied adult human brains using a 7.0-T magnetic resonance imaging (MRI). Twenty healthy individuals aged 22 to 30 years were selected, and they were all volunteers. The parasagittal images through the intercommissural line were examined. We determined the type of shape of the MCR; a triangular C shape was classified as type 1, and a trapezoidal concave shape was classified as type 2. RESULTS: In 14 brains, the recesses were radiologically demonstrated just rostral to the tectal plate of the midbrain and covered the ventral aspect of the posterior commissure and pointed the opening into the aqueduct. The average size of the circumference of the MCR measured from the end point of the C-shaped cup was 6.82 mm. CONCLUSIONS: This study on the anatomy of the MCR of adult brains in vivo is the first of its kind, thanks to the availability of 7.0-T MRI because it has been barely discernible even in autopsy specimens as well as in radiology owing to the resolution limit of the currently available imaging system. The current study raises awareness of the MCR, an important but little-known anatomic structure in adult human brain. This visualization of MCR in human in vivo with ultrahigh-field MRI will certainly provide us important clues including the functional information of MCR, a mystery of modern neurological science.

MDCT with coronal reconstruction: clinical benefit in evaluation of suspected acute appendicitis in pediatric patients.

OBJECTIVE: The purpose of this study was to assess the role of the addition of coronal reformatted images to MDCT in the evaluation of suspected acute appendicitis in pediatric patients. CONCLUSION: In pediatric patients with suspected appendicitis, the addition of coronal reformatted scans to axial images in MDCT increases confidence in the diagnosis or exclusion of acute appendicitis.

Highly specific inhibition of C1q globular-head binding to human IgG: a novel approach to control and regulate the classical complement pathway using an engineered single chain antibody variable fragment.

We sought to specifically regulate the binding of human C1q, and thus the activation of the first complement component, via the construction of a single chain antibody variable binding region fragment (scFv) targeting the C1q globular heads. Here we describe details of the construction, expression and evaluation of this scFv, which was derived from a high-affinity hybridoma (Qu) specific for the C1q globular heads. The scFv was comprised of the Qu variable heavy chain domain (VH) linked to the Qu variable light chain domain (VL) and was termed scFv-QuVHVL. When mixed with either purified C1q or with human serum as a source of C1, scFv-QuVHVL bound to C1q and competitively restricted the interaction of C1q or C1 with immobilized IgG or with IgG1 antibody-coated cells, and prevented the activation of native C1 in human serum as determined by analyses of C1-mediated C4 deposition and fluid-phase C4 conversion. However scFv-QuVHVL could be manipulated to become a C1 activator when it was irreversibly immobilized onto microtiter ELISA plates, prior to contact with human serum complement. This functional dichotomy can be a useful tool in selectively elucidating, differentiating, inducing or inhibiting specific roles of human C1q and the classical complement pathway in complement-mediated physiological processes. We project that once fully humanized, fluid-phase scFv-QuVHVL could become a useful therapeutic in limiting inadvertent host tissue damage elicited by the classical complement pathway.

Intraoperative Frozen Cytology of Central Nervous System Neoplasms: An Ancillary Tool for Frozen Diagnosis.

BACKGROUND: Pathologic diagnosis of central nervous system (CNS) neoplasms is made by comparing light microscopic, immunohistochemical, and molecular cytogenetic findings with clinicoradiologic observations. Intraoperative frozen cytology smears can improve the diagnostic accuracy for CNS neoplasms. Here, we evaluate the diagnostic value of cytology in frozen diagnoses of CNS neoplasms. METHODS: Cases were selected from patients undergoing both frozen cytology and frozen sections. Diagnostic accuracy was evaluated. RESULTS: Four hundred and fifty-four cases were included in this retrospective single-center review study covering a span of 10 years. Five discrepant cases (1.1%) were found after excluding 53 deferred cases (31 cases of tentative diagnosis, 22 cases of inadequate frozen sampling). A total of 346 cases of complete concordance and 50 cases of partial concordance were classified as not discordant cases in the present study. Diagnostic accuracy of intraoperative frozen diagnosis was 87.2%, and the accuracy was 98.8% after excluding deferred cases. Discrepancies between frozen and permanent diagnoses (n = 5, 1.1%) were found in cases of nonrepresentative sampling (n = 2) and misinterpretation (n = 3). High concordance was observed more frequently in meningeal tumors (97/98, 99%), metastatic brain tumors (51/52, 98.1%), pituitary adenomas (86/89, 96.6%), schwannomas (45/47, 95.8%), high-grade astrocytic tumors (47/58, 81%), low grade astrocytic tumors (10/13, 76.9%), non-neoplastic lesions (23/36, 63.9%), in decreasing frequency. CONCLUSIONS: Using intraoperative cytology and frozen sections of CNS tumors is a highly accurate diagnostic ancillary method, providing subtyping of CNS neoplasms, especially in frequently encountered entities.

Comparison of Endoscopic Submucosal Dissection and Surgery for Differentiated Type Early Gastric Cancer within the Expanded Criteria.

BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) is a novel alternative treatment for differentiated early gastric cancer (EGC) without lymph node metastasis. We conducted this study to verify the therapeutic usefulness of ESD for treating differentiated EGC compared to that of surgery. METHODS: This is a retrospective cohort study of 382 patients treated with differentiated EGC from March 2006 to May 2010. The propensity score yielded 275 matched patients. They were divided into an ESD group of 175 people and a gastrectomy group of 100 people. The patient demographics, pathologic characteristics, length of hospital stay, complication rate and survival rate were compared. RESULTS: The complication rate was higher for the gastrectomy group than for the ESD group (15.0% vs. 5.1%, p=0.007). The average length of patient hospitalization was longer after gastrectomy than after ESD (8.6 days vs. 2.4 days, p<0.001). There were two cases of mortality in the surgery group within 30 days of procedure. The 5-year survival rates of the two groups did not show a statistically significant difference (92.0% vs. 93.3%, p=0.496). CONCLUSIONS: The long-term survival rates of ESD and gastrectomy were not significantly different. The complication rate was lower for ESD than for gastrectomy, and the length of hospital stay was shorter after ESD than after gastrectomy.

Comparison of Outcomes after Device Closure and Medication Alone in Patients with Patent Foramen Ovale and Cryptogenic Stroke in Korean Population.

PURPOSE: To compare the effectiveness of device closure and medical therapy in prevention of recurrent embolic event in the Korean population with cryptogenic stroke and patent foramen ovale (PFO). MATERIALS AND METHODS: Consecutive 164 patients (men: 126 patients, mean age: 48.1 years, closure group: 72 patients, medical group: 92 patients) were enrolled. The primary end point was a composite of death, stroke, transient ischemic attack (TIA), or peripheral embolism. RESULTS: Baseline characteristics were similar in the two groups, except age, which was higher in the medical group (45.3±9.8 vs. 50.2±6.1, p<0.0001), and risk of paradoxical embolism score, which was higher in the closure group (6.2±1.6 vs. 5.7±1.3, p=0.026). On echocardiography, large right-to-left shunt (81.9% vs. 63.0%, p=0.009) and shunt at rest/septal hypermobility (61.1% vs. 23.9%, p<0.0001) were more common in the closure group. The device was successfully implanted in 71 (98.6%) patients. The primary end point occurred in 2 patients (2 TIA, 2.8%) in the closure group and in 2 (1 death, 1 stroke, 2.2%) in the medical group. Event-free survival rate did not differ between the two groups. CONCLUSION: Compared to medical therapy, device closure of PFO in patients with cryptogenic stroke did not show difference in reduction of recurrent embolic events in the real world's setting. However, considering high risk of echocardiographic findings in the closure group, further investigation of the role of PFO closure in the Asian population is needed.

Retroperitoneal cystic masses: CT, clinical, and pathologic findings and literature review.

Cystic lesions of the retroperitoneum can be classified as either neoplastic or nonneoplastic. Neoplastic lesions include cystic lymphangioma, mucinous cystadenoma, cystic teratoma, cystic mesothelioma, müllerian cyst, epidermoid cyst, tailgut cyst, bronchogenic cyst, cystic change in solid neoplasms, pseudomyxoma retroperitonei, and perianal mucinous carcinoma. Nonneoplastic lesions include pancreatic pseudocyst, nonpancreatic pseudocyst, lymphocele, urinoma, and hematoma. Because the clinical implications of and therapeutic strategies for retroperitoneal cystic masses vary depending on the cause, the ability to noninvasively differentiate between masses is important. Although there is substantial overlap of computed tomographic (CT) findings in various retroperitoneal cysts, some CT features, along with clinical characteristics, may suggest a specific diagnosis. CT may provide important information regarding lesion location, size, and shape; the presence and thickness of a wall; the presence of septa, calcifications, or fat; and involvement of adjacent structures. The most important clinical parameters include patient gender, age, symptoms, and clinical history. Familiarity with the CT and clinical features of various retroperitoneal cystic masses facilitates accurate diagnosis and treatment.

Regression of Colonic Adenomas After Treatment With Sulindac in Familial Adenomatous Polyposis: A Case With a 2-Year Follow-up Without a Prophylactic Colectomy.

Familial adenomatous polyposis (FAP) is an autosomal dominant disorder characterized by hundreds of colorectal adenomatous polyps that progress to colorectal cancer. Management of patients with FAP is with a total colectomy. Chemopreventive strategies have been studied in FAP patients in an effort to delay the development of adenomas in the upper and the lower gastrointestinal tract and to prevent recurrence of adenomas in the retained rectum of patients after prophylactic surgery. Sulindac, a nonsteroidal anti-inflammatory drug, causes regression of colorectal adenomas in the retained rectal segment of FAP patients. However, evidence regarding long-term use of this therapy and its effect on the intact colon has been insufficient. We report a case in which the long-term use of sulindac was effective in reducing the size and the number of colonic polyps in patients with FAP without a prophylactic colectomy and polypectomy; we also present a review of the literature.

Specific inhibition of the classical complement pathway with an engineered single-chain Fv to C1q globular heads decreases complement activation by apoptotic cells.

Apoptotic cells are potent complement activators; and proposed mechanisms include IgM-mediated classical pathway activation, C-reactive protein (CRP)-mediated classical pathway activation, and IgM-mediated lectin pathway activation. While complement activation is beneficial in clearing apoptotic cells, the resulting complement-mediated inflammation may extend damage to the surrounding cells and tissues, as observed in ischemia/reperfusion injury. We previously engineered and characterized a single-chain Fv against C1q globular heads (scFv(QuVHVL)) that blocked C1q binding to immobilized IgG and to IgG-sensitized cells, and thereby inhibited IgG-mediated classical pathway activation [Hwang H.Y., Duvall M.R., Tomlinson S., Boackle R.J., 2008. Highly specific inhibition of C1q globular-head binding to human IgG: a novel approach to control and regulate the classical complement pathway using an engineered single-chain antibody variable fragment. Molecular Immunology 45, 2570-2580]. In the present study, this scFv(QuVHVL) was examined for its ability to restrict complement deposition on apoptotic cells in the presence of fresh normal human serum (NHS). Interestingly, the addition of scFv(QuVHVL) to NHS decreased C1-mediated C4b deposition on apoptotic cells by 60% as compared to appropriate buffer-treated control serum. By inhibiting initiation of the early complement components, the subsequent C3b and membrane attack complex depositions were inhibited by 70%. Apoptotic cells may acquire serum CRP, a known classical complement pathway activator. It was observed that scFv(QuVHVL) blocked C1 binding to CRP and blocked CRP-mediated classical pathway activation using an ELISA format. However, under the experimental conditions used, the addition of exogenous CRP to apoptotic cells did not further increase the levels of C4b, C3b, or MAC deposition significantly, suggesting predominance by other activation mechanisms, such as antibody-C1-mediated complement activation. In summary, the results indicated that C1-mediated classical pathway activation was a highly significant mechanism for complement activation by apoptotic cells. In the future, specific inhibition of classical complement pathway activation by a humanized form of scFv(QuVHVL) may be useful in reducing inadvertent damage to healthy bystander tissue in a variety of acute, complement-mediated inflammatory conditions, including ischemia/reperfusion injury.

MRI of neurosyphilis presenting as mesiotemporal abnormalities: a case report.

The high signal intensities in bilateral mesiotemporal lobes on T2-weighted images are typical findings of herpes encephalitis or paraneoplastic limbic encephalitis. We report a case of neurosyphilis with mesiotemporal involvement on MRI. Positive antibodies in the cerebrospinal fluid confirmed the diagnosis. The results suggest that neurosyphilis should be considered when MRI results indicate mesiotemporal abnormalities.

The effect of dexamethasone on human mucin 1 expression and antibody-dependent complement sensitivity in a prostate cancer cell line in vitro and in vivo.

Dexamethasone has been shown to up-regulate human mucin 1 (MUC1) expression in certain types of cancer cell lines in vitro, suggesting that this gluocorticoid may enhance MUC1-based immunotherapies. Here we investigated the effect of dexamethasone on MUC1 expression in the DU145 human prostate cancer cell line in terms of antibody-mediated complement-dependent cell lysis. Cells treated with 1 x 10-8 m dexamethasone in vitro expressed maximal levels of MUC1 after 6 days, with an approximately 3-fold increase over MUC1 levels on untreated cells. DU145 cells were highly resistant to lysis by anti-MUC1 antibody and complement, and their susceptibility to antibody and complement was unaffected by dexamethasone treatment. However, dexamethasone also induced expression of the complement inhibitor decay accelerating factor (DAF) on DU145 cells. Blocking or overcoming the function of DAF resulted in enhanced complement-dependent lysis of dexamethasone-treated cells with anti-MUC1 antibodies, indicating that the failure of dexamethasone to enhance the complement susceptibility of DU145 cells was caused by the up-regulated expression of DAF. We also investigated MUC1 expression in vivo and found that MUC1 expression was significantly up-regulated on tumour cells isolated from immune-deficient mice that had been injected with dexamethasone. However, in contrast to in vitro data, there was no difference between the levels of DAF expressed on tumour-derived DU145 cells isolated from either phosphate buffered saline (PBS)-treated or dexamethasone-treated mice, and tumour cells isolated from dexamethasone-treated mice were more sensitive to complement-mediated lysis. In the broad context of immunotherapy, the in vivo data support the use of dexamethasone as an adjunct treatment. Up-regulated DAF expression would not be a favourable outcome of dexamethasone treatment in terms of complement-dependent antibody therapy, but the in vivo data caution against extrapolation of in vitro data with regard to the modulation of complement inhibitors reported here and elsewhere.

Differential diagnosis of focal epididymal lesions with gray scale sonographic, color Doppler sonographic, and clinical features.

OBJECTIVE: To determine whether focal epididymal lesions can be differentiated on gray scale sonographic, color Doppler sonographic, and clinical features. METHODS: This was a retrospectiveanalysis of 60 focal epididymal lesions in 57 patients. Focal epididymal lesions were classified into 3 groups: nonspecific epididymitis (n = 43), tuberculous epididymitis (n = 10), and benign epididymal masses (n = 7). The following gray scale sonographic, color Doppler sonographic, and clinical features were analyzed: size, location, echogenicity, and heterogeneity of the lesion; hypoechoic or hyperechoic rim presence; hydrocele presence; degree of blood flow in the lesion; patient's age; duration of symptoms; and scrotal tenderness. RESULTS: Lesions were larger in patients with tuberculous epididymitis than in those with either nonspecific epididymitis (P = .007) or benign epididymal masses (P = .0017). The hypoechoic or hyperechoic rim of the lesion was more common in patients with benign epididymal masses than in those with nonspecific epididymitis (P = .002). The degree of blood flow in the lesion was greater in patients with nonspecific epididymitis than in those with either tuberculous epididymitis (P = .0019) or benign epididymal masses (P < .001). The duration of symptoms was shorter in patients with nonspecific epididymitis than in those with either tuberculous epididymitis (P < .001) or benign epididymal masses (P = .0092). The frequency of scrotal tenderness was higher in patients with nonspecific epididymitis than in those with either tuberculous epididymitis (P < .001) or benign epididymal masses (P < .001). CONCLUSIONS: Gray scale sonographic, color Doppler sonographic, and some clinical features may be helpful for differential diagnosis of focal epididymal lesions.