A case of hypertrophic pachymeningitis, resolved by antimicrobial therapy]

A 65-year-old woman with diabetes mellitus and chronic otitis media developed headache, fever, and hoarseness, all of which did not responded to the oral antibiotics. As stiff neck and lower cranial nerve palsies appeared, bacterial meningitis was suspected. Neurological examination revealed the right hearing disturbance, right recurrent laryngeal nerve palsy, left sternocleidomastoid muscle atrophy and bilateral tongue atrophy. The CSF examination revealed mild pleocytosis and elevated protein, but no bacterial organism was cultured from the CSF. CT scans showed bilateral mastoiditis, and the right mastoid process and a posterior part of the petrous bone were eroded, indicating the exposed bony structures to the posterior fossa. MRI scans demonstrated the thickening of the dura mater of the posterior fossa and the right cerebellar tentorium. This is a rare example of bacterial pachymeningitis of the posterior fossa, the clinical symptoms and MRI findings of which resolved solely by antimicrobial agents without corticosteroid.     

A case of idiopathic bronchiolitis obliterans accompanied with pneumothorax and pulmonary atypical mycobacteriosis]

A 22-year-old man was urgently admitted for pneumothorax. He continued complaining of exertional dyspnea and dry cough after the pneumothorax healed. About three months later, an atypical pulmonary mycobacteriosis by mycobacterium kansasii was identified. Exertional dyspnea increased after chemotherapy was administered, and the patient was readmitted because of difficulty in daily life activities. Chest radiographs and CT scans showed bilateral pulmonary hyperinflation and a narrowed heart shadow. There was also marked combined ventilatory impairment, as identified by a respiratory function test. Furthermore, the histological findings of surgically removed lung tissue revealed accumulation of lymphocytes in the wall of a small bronchus. Idiopathic bronchiolitis obliterans was diagnosed from the clinical course and clinical findings. The patient is now being monitored and is awaiting lung transplantation.     

Purification of fully activated Clostridium botulinum serotype B toxin for treatment of patients with dystonia

Clostridium botulinum serotype B toxins 12S and 16S were separated by using a beta-lactose gel column at pH 6.0; toxin 12S passed through the column, whereas toxin 16S bound to the column and eluted with lactose. The fully activated neurotoxin was obtained by applying the trypsin-treated 16S toxin on the same column at pH 8.0; the neurotoxin passed through the column, whereas remaining nontoxic components bound to the column. The toxicity of this purified fully activated neurotoxin was retained for a long period by addition of albumin in the preparation.     

Galectin-9 as a prognostic factor with antimetastatic potential in breast cancer.

PURPOSE: Galectin-9, a member of the beta-galactoside-binding galectin family, induces aggregation of certain cell types. We assessed the contribution of galectin-9 to the aggregation of breast cancer cells as well as the relation between galectin-9 expression in tumor tissue and distant metastasis in patients with breast cancer. EXPERIMENTAL DESIGN: Subclones of MCF-7 breast cancer cells with high or low levels of galectin-9 expression were established and either cultured on plastic dishes or transplanted into nude mice. The tumors of 84 patients with breast cancer were tested for galectin-9 expression by immunohistochemistry. The patients were followed up for 14 years. RESULTS: MCF-7 subclones with a high level of galectin-9 expression formed tight clusters during proliferation in vitro, whereas a subclone (K10) with the lowest level of galectin-9 expression did not. However, K10 cells stably transfected with a galectin-9 expression vector aggregated in culture and in nude mice. Ectopic expression of galectin-9 also reduced MCF-7 cell adhesion to extracellular matrix proteins. Tumors of 42 of the 84 patients were galectin-9 positive, and those of 19 of the 21 patients with distant metastasis were galectin-9 negative. None of the 13 patients with galectin-9-positive tumors and lymph node metastasis up to level II manifested distant metastasis. The cumulative disease-free survival ratio for galectin-9-positive patients was more favorable than that for the galectin-9-negative group (P < 0.0001). Multivariate analysis revealed that galectin-9 status influenced distant metastasis independently of and to a greater extent than lymph node metastasis. CONCLUSIONS: Galectin-9 is a possible prognostic factor with antimetastatic potential in breast cancer.     

Effects of tissue plasminogen activator on medium-term functional independence: A propensity score-matched analysis

This study revealed the effects of tissue plasminogen activator (tPA) on medium-term functional independence in patients with stroke. We retrospectively examined 240 patients from April 2016 to March 2019 and selected 68 who met our criteria. After adjusting the functional status at the onset by propensity score matching, the functional independence measure (FIM) on admission to and discharge from the convalescent rehabilitation wards was compared between the groups classified by the presence or absence of tPA. Twelve pairs were derived by propensity score matching. Upon admission to the convalescent rehabilitation ward, the median score of the FIM was significantly higher in the tPA group than in the non-tPA group (P = .028). Patients in the tPA group had higher median FIM scores at discharge than those in the non-tPA group (P = .060). The difference in the independence level of activities of daily living (ADL) between the groups with and without tPA may gradually decrease with continuous inpatient rehabilitation. However, the tPA group tended to have high levels of independence in ADL at the time of discharge.     

In Vitro System to Evaluate Oral Absorption of Poorly Water-Soluble Drugs: Simultaneous Analysis on Dissolution and Permeation of Drugs

Purpose. The aim of the present work was to develop a new in vitro system to evaluate oral absorption of poorly water-soluble drugs by utilizing Caco-2 monolayers. Methods. Caco-2 monolayer was mounted between side-by-side chambers, which enabled the simultaneous assay of dissolution and permeation of drugs (dissolution/permeation system; D/P system). Apical and basal sides of the chamber were filled with buffer solutions. Drugs were applied to the apical side as powder, suspension, or solution, and then, the permeated amounts into the basal side were monitored for 2 h. At the same time, dissolved amounts of drugs at the apical side were detected. The amount of drug applied to the D/P system was based on its in vivo clinical dose. Results. Sodium taurocholate (5 mM, apical side) and bovine serum albumin (4.5% w/v, basal side) increased the permeated amount of poorly water-soluble drugs. Both additives were considered to be effective at mimicking in vivo conditions of intestinal drug absorption. From the correlation between the permeated amount of 13 drugs (% dose/2 h) in the D/P system and their percentage dose absorbed in humans in vivo, this system was found to be useful in evaluating oral absorption of poorly water-soluble drugs. Conclusions. With attempts made to mimic the physiologic conditions of the human GI tract, in vivo oral absorption of drugs was quantitatively assessed in the D/P system in vitro. This system is quite useful to predict the oral absorption of poorly water-soluble drugs after administration as solid dosage forms.     

Incidence of second primary cancers among survivors of childhood cancer: A population‐based study,Osaka, Japan, 1975–2015

Second primary cancer (SPC) is one of the most life‐threatening late effects of childhood cancers. We investigated the incidence and survival outcomes of SPC in childhood cancer patients in Japan. Data were obtained from the population‐based Osaka Cancer Registry. Individuals diagnosed with cancer at age 0–14 years during 1975–2014 and survived 2 months or longer were followed through December 2015. The risk of developing SPC was assessed with standardized incidence ratio (SIR), excess absolute risk (EAR, per 100,000 person‐years), and cumulative incidence. Multivariable Poisson regression analysis was carried out to assess relative risks of SPC by treatment method. Survival analysis was undertaken using the Kaplan–Meier method. Of 7229 childhood cancer survivors, 101 (1.4%) developed SPC after a median of 11.6 years. Overall SIR was 5.0, which corresponded with 84.3 EAR. The cumulative incidence was 0.9%, 2.1%, and 3.4% at 10, 20, and 30 years, respectively. Among all SPCs, the type that contributed most to the overall burden was cancers in the central nervous system (EAR = 28.0) followed by digestive system (EAR = 15.1), thyroid (EAR = 8.3), and bones and joints (EAR = 7.8); median latency ranged from 2.0 years (lymphomas) to 26.6 years (skin cancers). Patients treated with radiotherapy alone were at a 2.58‐fold increased risk of developing SPC compared to those who received neither chemotherapy nor radiotherapy. Among patients who developed SPCs, 5‐year and 10‐year survival probabilities after SPC diagnosis were 61.7% and 52.0%, respectively. Risk‐based long‐term follow‐up planning is essential to inform survivorship care and help reduce the burden of SPCs in childhood cancer survivors.