Experimental syringohydromyelia induced by adhesive arachnoiditis in the rabbit: changes in the blood-spinal cord barrier, neuroinflammatory foci, and syrinx formation

There are many histological examinations of syringohydromyelia in the literature. However, there has been very little experimental work on blood permeability in the spinal cord vessels and ultrastructural changes. We prepared an animal model of spinal adhesive arachnoiditis by injecting kaolin into the subarachnoid space at the eighth thoracic vertebra of rabbits. The animals were evaluated 4 months later. Of the 30 rabbits given kaolin injection into the cerebrospinal fluid, 23 showed complete circumferential obstruction. In the 7 animals with partial obstruction of the subarachnoid space, intramedullary changes were not observed. However, among the 23 animals showing complete obstruction of the subarachnoid space, dilatation of the central canal (hydromyelia) occurred in 21, and intramedullary syrinx (syringomyelia) was observed in 11. In animals with complete obstruction, fluorescence microscopy revealed intramedullary edema around the central canal, extending to the posterior columns. Electron microscopy of hydromyelia revealed a marked reduction of villi on the ependymal cells, separation of the ependymal cells, and cavitation of the subependymal layer. The dilated perivascular spaces indicate alterations of fluid exchange between the subarachnoid and extracellular spaces. Syringomyelia revealed that nerve fibers and nerve cells were exposed on the surface of the syrinx, and necrotic tissue was removed by macrophages to leave a syrinx. Both pathologies differ in their mechanism of development: hydromyelia is attributed to disturbed reflux of cerebrospinal fluid, while tissue necrosis due to disturbed intramedullary blood flow is considered to be involved in formation of the syrinx in syringomyelia.     

Risk of osteomyelitis of the jaw induced by oral bisphosphonates in patients taking medications for osteoporosis: A hospital-based cohort study in Japan

Oral bisphosphonates (BPs) represent the first line of prevention and treatment for osteoporosis. However, several studies have reported osteonecrosis of the jaw (ONJ), also known as osteomyelitis of the jaw (OMJ), as a side effect of these drugs. Although absolute risk is suggested to be low, information to date on the relative risk or attributable risk has in fact been limited. Here, we estimated risk of oral BPs for OMJ in osteoporosis patients taking oral BPs compared with other osteoporosis drugs. Using an electronic medical records retrieval system and manual confirmation of OMJ, we conducted a retrospective cohort study of patients taking medications for osteoporosis at Kyoto University Hospital between November 2000 and October 2010. To evaluate relative risks of oral BPs for OMJ, logistic regression analysis was performed and odds ratios (ORs) and 95% confidence interval (CIs) were estimated. In addition, sensitivity analyses were performed according to hierarchical diagnosis. A total of 4129 patients (59.6%) were prescribed BPs while 2794 (40.3%) received other osteoporosis drugs. Absolute risk for OMJ was estimated to range from 0.46% to 0.99% (95% CIs: 0.25-0.66 to 0.69-1.2) among patients receiving oral BPs and 0.071% to 0.17% (95% CIs: 0-0.17 to 0.022-0.33) among patients receiving other osteoporosis drugs. The attributable risks of oral BPs for OMJ were estimated to range from 0.38% to 0.81% (95% CIs: 0.38-0.39 to 0.80-0.81). ORs (95% CIs) adjusted for confounding factors were 5.0 (1.9-12.9) to 6.0 (1.3-26.1) for confirmed cases only. In terms of absolute and attributable risks, the risk of oral BPs for OMJ is considered to be less than 1% in patients with osteoporosis. However, oral BPs may increase the risk of OMJ compared with patients treated with other osteoporosis medications and the risk of side effects should be kept in mind.     

Persistent elevation of exhaled nitric oxide and modification of corticosteroid therapy in asthma

BackgroundPersistent airway inflammation, detected by fractional exhaled nitric oxide (FE_NO), is occasionally observed in asthmatic patients, even in those treated with inhaled corticosteroids (ICS). However, improvement in residual airway inflammation and pulmonary function through modification of corticosteroid therapy has not been proven.MethodsThirteen asthmatic patients whose FE_NO levels were over 40 parts per billion (ppb), despite dry-powder ICS therapy, were enrolled. A 3-step change in steroid treatment was undertaken until FE_NO was less than 40 ppb. In the first step, the powder formula was changed to an ultra-fine particle compound as an equipotent ICS dose. In the second step, the ICS dose was doubled. In the third step, oral corticosteroids were added. We measured pulmonary function and FE_NO and alveolar NO concentrations (CAlvNO).ResultsDoubling the ICS dose and changing the ICS formula significantly improved FVC (p<0.001), FEV1 (p<0.05), the slope of the single nitrogen washout curve (dN₂) (p<0.01), FE_NO (p<0.001), and CAlvNO (p<0.05), relative to baseline. The reductions in FE_NO were significantly associated with the improvement in airflow limitation assessed by dN₂ (r=0.73, p=0.007). The remaining FE_NO elevation, even after doubling the ICS dose, did not decrease after oral corticosteroid administration.ConclusionsThese results suggest that modification of ICS therapy can suppress residual FE_NO elevation, and that reduction in FE_NO levels is associated with improvement in airflow limitation. However, steroid-resistance mechanisms may exist in some asthmatic patients with sustained FE_NO elevations.     

Combination therapy of ecabet sodium and cimetidine compared with cimetidine alone for gastric ulcer: prospective randomized multicenter study

BACKGROUND AND AIM: Little is known about the clinical efficacy of co-therapy of ecabet sodium, a mucoprotective agent, and a histamine H2-receptor antagonist. The aim of the present study was to assess its additive benefit in combination with cimetidine for gastric ulcer. METHODS: In this prospective randomized study, after gastric ulcer was confirmed by endoscopy, 200 patients in 47 hospitals received either ecabet sodium 1 g b.i.d and cimetidine 400 mg b.i.d. (EC), or cimetidine 400 mg b.i.d. alone (C) for 8 weeks. Healing was examined by endoscopy at 4 and 8 weeks. RESULTS: Of the intention-to-treat (ITT) population (EC, 103; C, 97), 181 patients comprised the per protocol (PP) analysis (EC, 93; C, 88). At 4 weeks, healing rates were significantly higher in the EC group (60%) than in the C group (36%) ( p < 0.01). At 8 weeks, those by the ITT and PP analyses were 82% (EC) versus 58% (C), and 90% (EC) versus 64% (C), respectively ( p < 0.01 and p < 0.001). Symptom relief rates (EC vs C) at 2, 4 and 8 weeks were 73%versus 47% ( p < 0.01), 89%versus 66% ( p < 0.001), and 97%versus 73% ( p < 0.001), respectively. Significant additive effects of ecabet sodium were observed in patients aged 60 years or older, with solitary and medium to large ulcer, and without smoking or drinking habits. No adverse effects were critical. CONCLUSION: Ecabet sodium significantly augmented gastric ulcer healing and symptom relief by cimetidine, especially in the elderly.     

Psychoses in patients with Parkinson's disease; their frequency, phenomenology, and clinical correlates]

The frequency, phenomenology, and risk factors of hallucinations and delusions were investigated in 64 consecutive inpatients with Parkinson's disease. Fifty patients were admitted to our hospital with symptoms related to Parkinson's disease: psychiatric problems 27 (psychosis 22; anxiety 2; depression 2; mania 1): motor symptoms, 20 (wearing-off 5; akinesia 4; freezing 4; postural instability 4; dyskinesia 2; tremor 2; dystonia 1), and sensory symptoms, 3. Fourteen patients were admitted with other medical problems (pneumonia 4; cerebral infarction 3; bone fracture 3; lumbago 2; seizure 1; cat bite 1). Totally 49 patients had psychiatric problems. Psychosis was present in 43 patients, dementia in 10, depression in 8, mania in 1, anxiety in 10, agitation in 6, stereotypy in 2, and hypersexuality in 2. Of the 43 patients with psychoses, 40 presented with visual hallucinations, 18 with auditory hallucinations, and 23 with delusions. To determine what the clinical correlates with the severity of psychosis were, we divided the patients into 3 groups: the severe group, 22 patients admitted because of psychotic symptoms; the mild group, 21 patients admitted because of problems other than psychosis but presenting psychotic symptoms; and the control group, 21 patients who had no psychotic symptoms. Incidences of auditory hallucinations and delusions were higher in the severe group as compared to the mild group. Patients in the severe group had higher Hoehn-Yahr stages, lower Mini-Mental State Examination scores, decreased H/M ratios of cardiac 123I-MIBG uptake, and lower frequencies of background activity on electroencephalograms. There were no differences in age at admission, age at onset of Parkinson's disease, duration of illness, amounts of levodopa and dopamine agonists received, Hamilton's depression rating scores, and brain MR findings, including atrophy and ischemic changes. Emergence of psychotic symptoms in parkinsonian patients appears to be clearly associated with impaired cognitive function. Therefore, it may be associated with the disease process itself. Terms such as dopaminomimetic or levodopa-induced psychosis may not be appropriate when describing psychosis in Parkinson's disease.     

Evaluation of the alternate blood FLow in esophageal variceal patients by endoscopic color Doppler ultrasonography

Background: Endoscopic color Doppler ultrasonography (ECDUS) is a useful modality for obtaining color ?ow images of esophageal varices. The direction of blood ?ow in passageways is fundamentally hepatofugal ?ow according to ECDUS. The present study is designed to evaluate the alternate direction of color ?ow image of passageways via ECDUS in esophageal variceal patients. Methods: The study involved 125 patients with esophageal varices using ECDUS. The grades of red color (RC) were as follows: RC(+) in 79 cases, RC(+ +) in 35 cases, and RC(+ + +) in 11 cases. We investigated the alternate direction on color ?ow images of the left gastric vein, the palisade vein, and the perforating veins via ECDUS. Results: Color ?ow images of the esophageal varices and the left gastric vein were obtained in all 125 (100%) patients by ECDUS. Color ?ow images of the perforating veins were obtained in 90 (72.0%) of the 125 patients. Vessel images of the palisade veins were detected in 33 (26.4%) of the 125 patients. The alternate direction on color ?ow images was detected in seven (5.6%) of the 125 patients with ECDUS: in three patients, left gastric vein; in three patients, perforating veins; and in one patients, left gastric vein and palisade veins. This phenomenon was observed periodically at regular intervals. The endoscopic ?ndings were RC(+) in all seven patients. Conclusion: The alternate direction of blood ?ow in the passageways was observed in a few cases of RC(+) esophageal varices. We can observe the hemodynamics of esophageal varices non‐invasively and in real time with ECDUS, and clarify the frequencies of the alternate direction of blood ?ow in RC‐positive esophageal variceal patients.     

INTRADUCTAL ULTRASONOGRAPHY OF THE GALLBLADDER IN APPLICATION OF THE ENDOSCOPIC NASO‐GALLBLADDER DRAINAGE

Background: Although endoscopic naso‐gallbladder drainage (ENGBD) for gallbladder disease is useful, the procedure is difficult and investigations involving many cases are lacking. Furthermore, reports on transpapillary intraductal ultrasonography (IDUS) of the gallbladder using a miniature probe are rare. Methods: A total of 150 patients (119 suspected of having gallbladder carcinoma, 24 with acute cholecystitis (AC), and seven with Mirizzi’s syndrome (MS)) were the subject. (i) ENGBD: We attempted to put ENGBD tube into the GB. (ii) IDUS of the gallbladder: Using the previous ENGBD tube, we attempted to insert the miniature probe into the gallbladder and perform transpapillary IDUS of the gallbladder. In five patients, we attempted three‐dimensional intraductal ultrasonography (3D‐IDUS). Results: (i) ENGBD: Overall success rate was 74.7% (112/150); the rate for the patients suspected of having gallbladder carcinoma was 75.6% (90/119), and was 71.0% (22/31) for the AC and MS patients. Inflammation and jaundice improved in 20/22 successful patients with AC and MS. Success rate was higher when cystic duct branching was from the lower and middle parts of the common bile duct than from the upper part, and was higher when branching was upwards than downwards. (ii) IDUS of the gallbladder: Success rate for miniature probe insertion into the gallbladder was 96.4% (54/56). Lesions could be visualized in 50/54 patients (92.6%). Of these, detailed evaluation of the locus could be performed in 41. In five patients attempted 3D‐IDUS, the relationship between the lesion and its location was readily grasped. Conclusion: IDUS of the gallbladder is superior for diagnosing minute images. Improvement on the device will further increase its usefulness.