An autopsy case of progressive multifocal leukoencephalopathy with massive iron deposition in juxtacortical lesions.

Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease caused by JC virus infection of oligodendrocytes. Little has been reported on iron deposits in patients with PML. Herein, we report a case of PML with massive iron deposition in the juxtacortical regions attaching white matter lesions in a 71-year-old woman who developed bilateral visual disturbance and progressive aphasia after 16 months of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone treatment for follicular lymphoma. Magnetic resonance imaging revealed white matter lesions in the left parietal and other lobes with massive iron deposition in the juxtacortical lesions. A PCR test for JC virus was positive, confirming the diagnosis of PML. Despite treatment with mefloquine and mirtazapine, the patient died six months later. At autopsy, demyelination was found dominantly in the left parietal lobe. Moreover, hemosiderin-laden macrophages and reactive astrocytes containing ferritin were abundant in the juxtacortical regions adjacent to the white matter lesions. This is a previously unreported case of PML after lymphoma, in which iron deposition was confirmed both radiologically and pathologically.

A Case of Creutzfeldt-Jakob Disease with Stroke-Like Onset.

Creutzfeldt-Jakob disease (CJD) is a prion disease characterized by rapidly progressive dementia that is often followed by behavioral disturbances, ataxia, myoclonus, and akinetic mutism. The initial symptoms of CJD reportedly vary, but the onset is usually gradual. Here, we report a case of CJD with a sudden, stroke-like onset of right hemiparesis to alert readers that CJD can mimic a stroke during its early stage.

Characteristics of Fecal Incontinence in Male Patients in Japan.

Objectives: Although community studies have shown no difference between the sexes in the prevalence of fecal incontinence (FI), few direct comparisons of disease characteristics between male and female patients have been reported. The aim of this study was to determine whether characteristics of FI differ between male and female patients in Japan. Methods: Included in the study were 408 (149 men, 259 women) patients with FI who visited the Matsushima Hospital Coloproctology Center between October 2016 and September 2017. We retrospectively evaluated data on age, number of bowel movements, Bristol stool form scale, number of FI, incontinence scores, anorectal manometry, comorbidities, and history of anal surgery. Results: Maximum resting pressure and maximum squeeze pressure were found to be within normal range in significantly more male than female patients (34.9% vs. 12.4%, respectively; p < 0.0001). Irritable bowel syndrome (IBS, 20.1% vs. 9.3%; p = 0.003) and a history of anal surgery (29.5% vs. 17.5%; p = 0.02) were more prevalent among male patients than among female patients. Use of mepenzolate as treatment was significantly more common among male patients than among female patients (16.8% vs. 6.6%, respectively; p = 0.005). Responses to the various treatments were good, regardless of sex. Conclusions: FI appears to be more commonly accompanied by normal anal sphincter pressures in male patients than in female patients, and IBS and previous anal surgery appear to be more common among male patients than among female patients. FI appears to be controllable in most patients, regardless of sex.

A Novel Surgical Technique for Anal Fistula Surgery Designed to Preserve the Anal Sphincter Function and Anoderm.

OBJECTIVES: We reviewed surgical outcomes after introducing a novel surgical technique for anal fistula surgery designed to preserve anal sphincter function and the anoderm. METHODS: We studied 200 male patients who underwent a functional preservative operative technique (FPOT group) for anal fistulas and 200 patients who underwent resection of trans-sphincteric anal fistulas (fistulectomy group) between February 2014 and September 2015. We compared complications, such as those affecting anal sphincter function, recurrence, and incontinence. RESULTS: Fistulas recurred in three (1.5%) patients in the FPOT group and two (1%) patients in the fistulectomy group. This difference was not significant. Other complications included gas leakage and other forms of incontinence in 1 (0.5%) and 14 (7%) patients in the FPOT and fistulectomy groups, respectively. Anal function assessment demonstrated that the FPOT was significantly better at preserving function than fistulectomy in all patients. CONCLUSIONS: There were no significant differences between the FPOT and fistulectomy in terms of recurrence or complication rates. Also, because there was no decrease in postoperative anal function, we concluded that the FPOT is an effective preservative surgical technique for treating trans-sphincteric anal fistulas.

Evaluation of Mucopexy-Recto Anal Lifting (MuRAL): A New Method for Treating Hemorrhoids.

OBJECTIVES: Ligation and excision remain the commonly recognized standard surgical modality for treating hemorrhoids. Further, impediments to surgical treatment owing to social factors and the need for minimally invasive procedures and other confounders have resulted in the adoption of the mucopexy-recto anal lifting (MuRAL) method which is associated with favorable outcomes. The objective of this study was to describe the procedure and report the outcomes in patients who underwent MuRAL. METHODS: Between March 2016 and February 2018, 55 patients (26 males and 29 females) underwent MuRAL for hemorrhoids and rectal mucosal prolapse. The duration of the surgical procedure and hospitalization, postoperative complications, and satisfaction were evaluated. RESULTS: The mean age of the male patients (n = 26) was 61.5 ± 4.9 years and that of the female patients (n = 29) was 61.5 ± 3.2 years. The mean duration of surgery was 46 ± 23 minutes for males and 53 ± 28 minutes for females, and the mean observation duration was 317 ± 186 days. Intraoperative hemorrhage was low for males and females. The mean hospitalization period was 3.2 ± 1.5 days for males and 4.3 ± 2.1 days for females. Differences in several postoperative complications were observed between male and female patients. Postoperative satisfaction was rated high by the patients. CONCLUSIONS: Risks of hemorrhage and pain associated with the MuRAL method were low because the procedure does not involve incision or excision. Other than ligation and excision, recurrence is favorable compared with that of other surgical modalities for the treatment of hemorrhoids.

Non-recurrent inferior laryngeal nerve with multiple arterial abnormalities.

Non-recurrent inferior laryngeal nerve (NRILN) is a rare embryologic anomaly that can increase the risk of injury during thyroid surgery. Although the association between the NRILN and an aberrant right subclavian artery has been reported, to date there have been no reports describing cases of NRILN with multiple vascular abnormalities. A 60-year-old man with papillary thyroid carcinoma and a history of right internal carotid artery occlusion by thrombosis was examined with magnetic resonance angiography (MRA). The right NRILN was found during a total thyroidectomy with surrounding lymph node dissection. MRA revealed an aberrant right subclavian artery and aplasia of the bilateral posterior communicating arteries composing the circle of Willis. This is the first clinical report demonstrating NRILN with multiple vascular abnormalities. Patients with NRILN must be examined for vascular anomalies and associated lesions such as aneurysms and thromboembolism.

Pulmonary function is negatively correlated with sputum inflammatory markers and cough clearability in subjects with cystic fibrosis but not those with chronic bronchitis.

BACKGROUND: Polymorphonuclear neutrophil (PMN)-dominated inflammation is prominent in the airways of subjects with cystic fibrosis (CF) and chronic bronchitis (CB). Interleukin (IL)-8, myeloperoxidase (MPO), and DNA are markers of neutrophilic inflammation. We hypothesized that sputum MPO, DNA, and IL-8 concentrations would negatively correlate with pulmonary function and sputum transportability. METHODS: We measured pulmonary function and analyzed sputum IL-8, MPO, and DNA concentrations, as well as the transport properties of sputum samples obtained from 16 subjects with CF and 15 subjects with CB. We also evaluated changes in these measurements in paired sputum samples from these subjects obtained 2 to 12 months apart. RESULTS: IL-8 and MPO concentrations in the sputum of CF subjects was inversely correlated with FEV(1) percent predicted (IL-8: r = -0.40; p = 0.003; MPO: r = -0.38; p = 0.003) and FVC percent predicted (IL-8: r = -0.4; p = 0.02; MPO: r = -0.4; p = 0.02). IL-8 and DNA concentrations were inversely correlated with sputum cough transportability (CTR) [IL-8: r = -0.4; p = 0.02; DNA: r = -0.36; p = 0.048]. Changes in DNA concentration in sputum samples from CF subjects over time were inversely correlated with changes in FEV(1) percent predicted (r = -0.58; p = 0.02), FVC percent predicted (r = -0.74; p = 0.002), and CTR (r = -0.59; p = 0.02). There was no correlation among pulmonary function, sputum properties, and inflammatory markers in the sputum from subjects with CB. CONCLUSIONS: The sputum concentrations of IL-8, MPO, and DNA appear to be closely associated with pulmonary function in subjects with CF but not in subjects with CB.

Vasoactive intestinal peptide stimulates mucus secretion, but nitric oxide has no effect on mucus secretion in the ferret trachea.

Vasoactive intestinal peptide (VIP) and nitric oxide (NO) are neurotransmitters involved in the regulation of bronchial and pulmonary vascular tone. Published studies of the effects of VIP on airway mucus secretion have yielded conflicting results. The purpose of this study was to determine the effect of VIP on mucus secretion in the ferret trachea and if this effect was influenced by NO. We used a sandwich enzyme-linked lectin assay to measure mucin secretion and a turbidimetric assay to measure lysozyme (serous cell) secretion from ferret tracheal segments. VIP (10(-7) M) increased mucin secretion over 2 h. VIP (10(-9) to 10(-5) M) stimulated mucin secretion in a dose-dependent fashion. VIP-induced mucin secretion was partially blocked by a VIP receptor antagonist (a chimeric VIP-pituitary adenylate cyclase-activating peptide analog, VIP receptor antagonist) at a 10-fold excess concentration. At all concentrations tested, neither NG-nitro-L-arginine methyl ester, an inhibitor of NO synthase, nor S-nitroso-N-acetyl-penicillamine, an NO donor, had any significant effect on constitutive or VIP-induced mucus secretion. We conclude that VIP-stimulated mucin and lysozyme secretion was both time dependent and dose dependent and that NO neither stimulates nor inhibits mucus secretion in the ferret trachea.

Hyperosmolar solutions stimulate mucus secretion in the ferret trachea.

STUDY OBJECTIVES: Inhalation of hypertonic saline or mannitol solutions acutely increases mucociliary clearance. Because increased clearance is often coupled with increased mucus secretion, we hypothesized that hyperosmolar agents would stimulate mucus secretion. SETTING AND SUBJECTS: The isolated tracheae of healthy young adult ferrets were studied in a basic research laboratory. MEASUREMENTS AND RESULTS: We demonstrated that there was a dose-dependent increase in mucin secretion by enzyme-linked lectin assay after incubation with 1.69 g/dL (597 mOsm/L), 3.69 g/dL (1,192 mOsm/L), 5.69 g/dL (1,823 mOsm/L), and 10.69 g/dL (3,612 mOsm/L) of saline solution over Krebs-Henseleit solution control (288 mOsm/L) [p < 0.01 for 1.69 g/dL of saline solution and p < 0.0001 for others]. Mannitol solution, 15 g/dL (1,040 mOsm/L), also significantly increased mucin secretion (n = 4, p < 0.005). There was a 47% and 54% increase in secretion of the serous cell product lysozyme after exposure to 3.69 g/dL (1,192 mOsm/L) and 10.69 g/dL (3,612 mOsm/L) saline solutions, respectively (n = 5, p < 0.05). Secretion was only stimulated when the hyperosmolar exposure was on the luminal side of the epithelium. Mucin secretion was induced within minutes of 3.69 g/dL of saline solution exposure, and this increased mucin secretion quickly peaked. The ratio of mucin to lysozyme secretion was approximately 2. This ratio appeared to be independent of the osmotic concentration of the stimulus and therefore of secretory rate. CONCLUSIONS: Mucus secretion is markedly stimulated in response to hyperosmolarity. This may be a protective response. These results also suggest that the therapeutic use of hyperosmolar aerosols should be evaluated with care when used for patients with mucus hypersecretion and impaired mucus clearance.

Enhancement of ordinal CoMFA by ridge logistic partial least squares.

Conventional comparative molecular field analysis (CoMFA) requires at least 3 orders of experimental data, such as IC 50 and K i, to obtain a good model, although practically there are many screening assays where biological activity is measured only by rating scale. To improve three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis, we developed in this study a modified ordinal classification-oriented CoMFA using partial-least-squares generalized linear regression and ridge estimation. The modified Logistic CoMFA was validated using a corticosteroid binding globulin receptor binding data set, a benchmark for 3D-QSAR, and an acetylcholine esterase inhibitor data set. Our results show that modification of Logistic CoMFA enhanced both prediction accuracy and 3D graphical analysis. In addition, the 3D graphical analysis of the modified Logistic CoMFA was much improved. This improvement resulted in more accurate information on the binding mode between proteins and ligands than in the case of conventional CoMFA.

Secretory phospholipases A2 stimulate mucus secretion, induce airway inflammation, and produce secretory hyperresponsiveness to neutrophil elastase in ferret trachea.

Secretory phospholipases A(2) (sPLA(2)) are increased in the bronchoalveolar lavage fluid of patients with asthma and acute respiratory distress syndrome. Intratracheal sPLA(2) instillation induces acute lung injury in the rat and guinea pig. We hypothesized that sPLA(2) would stimulate mucus secretion in vitro and that intratracheal sPLA(2) exposure would induce mucus hypersecretion and airway inflammation in the ferret trachea in vivo. In vitro, porcine pancreatic sPLA(2) at a concentration of 0.5 or 5 U/ml significantly increased mucous glycoconjugate (MG) secretion from the excised ferret trachea. P-bromophenacylbromide (a sPLA(2) inhibitor), quercetin (a lipoxygenase inhibitor), or MK-886 (a 5-lipoxygenase inhibitor), each at 10(-4) M, significantly reduced sPLA(2)-induced MG secretion. sPLA(2)-stimulated MG secretion was decreased in Ca(2+)-free medium. In vivo, ferrets were intubated for 30 min once per day for 3 days using an ETT coated with 20 units of porcine pancreatic sPLA(2) mixed in water-soluble jelly. Constitutive MG secretion increased 1 day after sPLA(2) exposure and returned to control 5 days later. Human neutrophil elastase (HNE) at 10(-8) M increased MG secretion in the sPLA(2)-exposed trachea compared with that in the control trachea, but methacholine at 10(-7) M did not. sPLA(2)-induced secretory hyperresponsiveness continued for at least 5 days after sPLA(2) exposure ended. sPLA(2) increased tracheal inflammation, MG secretion, and secretory hyperresponsiveness to HNE probably through enzymatic action rather than by activation of its receptor.

A preliminary study of the draining lymph node basin in advanced lower rectal cancer using a radioactive tracer.

PURPOSE: This study was designed to examine the draining lymph node basin at highest risk of metastasis in lower rectal cancer using 99 mTc-tin colloid. METHODS: In 43 patients, the area with highest hot nodes density was defined as the draining lymph node basin using a gamma probe. Metastatic states of all removed lymph nodes were examined histologically. RESULTS: A total of 203 hot nodes were identified in 39 patients (91 percent) with a mean of 5.2 nodes. The number of removed lymph nodes was 808 nodes: 670 nodes in the mesorectum, and 138 nodes in the pelvis. In 21 patients, the metastatic states of 119 nodes were investigated histologically. From the distribution of the identified hot nodes, the draining lymph node basins were classified into two patterns: lateral type (n = 17), and mesorectal type (n = 22). Only 20 (17 percent) of 119 positive nodes were identified as hot node. Tumor cells that occupied the lymph node diffusely or massively probably interfered with the exact diagnosis of metastasis. Lymph node metastasis in the pelvis was observed in 5 patients (13 percent). One false negative was of the mesorectal type with diffuse metastases in the para-aortic lymph nodes. The remaining four patients were of the lateral type and all positive lymph nodes, including positive nonhot nodes, were located within the draining lymph node basin. Consequently, in 20 (95.2 percent) of 21 patients with lymph node metastasis, all positive lymph nodes were located within the draining lymph node basin of the tumor. CONCLUSIONS: Two types of the draining lymph node basin of advanced lower rectal cancer were identified using this method. The concordance between lymph node metastases and the draining lymph node basin is good.