Progressive disseminated histoplasmosis in an immunocompetent patient as an underrecognized imported mycosis in Japan

Histoplasmosis caused by Histoplasma capsulatum is found worldwide. Japan is known to be non-endemic area. Progressive disseminated histoplasmosis (PDH) is a severe form of histoplasmosis. We report a case of PDH in a 54-year-old male who was not immunocompromised. His last travel history to an endemic region was 2 years before onset. He was diagnosed as histoplasmosis by 18S rRNA-PCR from serum and ascites and immunodiffusion test. We treated him with parental liposomal amphotericin B for 2 weeks then changed to oral itraconazole, which was continued for 6 months. Rigorous work up, including HIV status, lymphocyte counts, and adrenal function did not reveal any evidence of immunosuppression of the patient. Our case suggests that PDH can occur in immunocompetent patients as previously described, and must be included in the differential diagnoses if presentation is consistent. In addition, the skills of travel history taking are emphasized.     

Relationship between tumor volume and quantitative values calculated using two-dimensional bone scan images

The bone scan index (BSI) is calculated from a whole-body bone scan image; it shows the tumor burden in bone as a percentage of total skeletal mass. It has been used to determine the prognosis and to assess treatment effects; however, little has been reported on whether the BSI calculated using a two-dimensional image can accurately evaluate the three-dimensional spread in tumor volume. We investigated the relationship between tumor volume and BSI using Monte Carlo simulation (MCS). We simulated a gamma camera and constructed a voxel phantom based on an anthropomorphic phantom computed tomography (CT) image and gamma rays emitted from each part according to technetium-99m-labeled methylene diphosphonate (^99mTc-MDP) uptake (bone 1, soft tissue 0.2, tumor 2–32). We constructed bone scan images from the obtained counts and analyzed them using the BSI calculation software. The BSI increased with increased tumor uptake (two- to 32-fold). However, there was not always a significant difference between change in BSI and tumor uptake of eight times or greater than that of bone. When BSI was calculated with a tumor having an uptake of four-to-eight times higher than that of bone, the BSI was consistent with tumor volume, but decreased to about half the tumor volume when tumors were in the thoracic spine (Th-spine) segment. The BSI can be a good indicator of tumor volume in most segments, even though it is affected by the tumor’s ^99mTc-MDP uptake. Nevertheless, values calculated from the Th-spine should be interpreted carefully.     

Brief Questioning by Nursing Staffs before Endoscopic Examination May Not Always Pick Up Clinical Symptoms of Endoscopic Reflux Esophagitis

The clinical features of patients reflux esophagitis without any symptoms have not been clearly demonstrated. This study evaluated the clinical features of patients with endoscopy-positive reflux esophagitis, who did not complain of symptoms, as detected by brief questioning by nursing staffs. Eight thousand and thirty-one patients not taking medication for gastrointestinal disease, were briefly asked about the presence of heartburn, dysphagia, odynophagia and acid regurgitation by nursing staffs before endoscopy for assessment of esophagitis utilizing the Los Angeles Classification. Endoscopically, 1199 (14.9%) patients were classified as positive for reflux esophagitis. The endoscope positive subjects who complain heartburn were 539/1199 (45.0%).The endoscope positive subjects who do not complain symptoms were 465 in 1199 positive reflux esophagitis (38.8%). We compared endoscopic positive subjects without any complain by brief question by nursing staffs to endoscopic positive subjects with heartburn. Male gender, no obesity, absence of hiatus hernia, and low-grade esophagitis were associated with endoscopy-positive patients who do not complain of symptoms. The results of this study indicated correct detection of clinical symptoms of reflux esophagitis might be not easy with brief questioning by nursing staffs before endoscopic examination.     

Erratum to: Predictors of poor sleep quality in patients with systemic lupus erythematosus

Clinical Rheumatology -     

A randomized placebo-controlled polysomnographic study of eszopiclone in Japanese patients with primary insomnia

ObjectivesTo evaluate the efficacy and dose–response effect of eszopiclone on sleep latency and sleep maintenance in Japanese patients with primary insomnia.MethodsIn this randomized, double-blind, five-way crossover study, 72 patients received placebo, eszopiclone 1 mg, 2 mg, and 3 mg, and zolpidem 10 mg in random order for two consecutive nights with a washout period between treatments. Objective sleep measures from polysomnography (PSG) and subjective patient reports were collected.ResultsAll active treatments produced significant improvement in objective and subjective sleep latency compared with placebo (P < 0.05 for all comparisons); linear dose–response relationships were observed for eszopiclone. PSG-determined wake time after sleep onset (WASO), sleep efficiency, and number of awakenings (NA), and patient-reported measures of WASO, NA, sleep quality, sleep depth, and daytime functioning significantly improved following treatment with eszopiclone 2 mg and 3 mg and zolpidem 10 mg versus placebo (P < 0.05). Eszopiclone at all doses increased total sleep time and stage 2 sleep time (P < 0.001 for both comparisons), but did not alter REM or slow-wave sleep. Eszopiclone was generally well tolerated; the most frequently reported adverse event was mild dysgeusia.ConclusionsIn Japanese patients with primary insomnia, eszopiclone 2 mg and 3 mg significantly improved PSG-determined and patient-reported sleep latency and sleep maintenance relative to placebo.     

COMPLETE DISLOCATION OF THE TRAPEZIUM: Case report

A 24-year-old woman presented with complete, closed dislocation of the trapezium after a skiing accident. Treatment by closed reduction and fixation with a Kirschner wire gave an excellent clinical result with early return to full function. There were no radiological signs of arthrosis or avascular necrosis at 2 years follow-up.     

Ultrastructural changes of the air–blood barrier in mice after intratracheal instillation of lipopolysaccharide and ultrafine carbon black particles

Epidemiological studies have indicated associations between exposure to increased concentrations of ambient ultrafine particles and adverse health effects especially in susceptible individuals. To ellucidate the mechanisms underlying the findings from epidemiological studies, mice pretreated with lipopolysaccharide (LPS) (acute lung injury model) were intratracheally instilled with ultrafine carbon black particles (UFCB), and the air–blood barrier was observed to examine the translocation pathway of UFCB from the lung into the systemic circulation. In addition, lung toxicity induced by the intratracheal instillation of LPS and UFCB was studied with the use of electron microscope. LPS treatment induced acute inflammatory changes with increased number of activated macrophages and neutrophils in the degenerated alveolar walls. UFCB were demonstrated on or in the denuded basement membrane in the air–blood barrier; these findings were associated with edematous changes and fragmentation of the cytoplasms of alveolar epithelial cell type 1, and the damages of alveolar epithelial cell type 1 were frequently observed in the close vicinity of the clumps of UFCB. These findings suggest that translocation of the exposed ultrafine particles may be enhanced in the lung tissues with acute inflammatory changes.     

Classification of extracellularly recorded neurons by their discharge patterns and their correlates with intracellularly identified neuronal types in the frontal cortex of behaving monkeys

Neurons in the cerebral cortex are not homogeneous. However, neuronal types have been ignored in most previous work studying neuronal processes in behaving monkeys. We propose a new method to identify neuronal types in extracellular recording studies of behaving monkeys. We classified neurons as either bursting or non‐bursting, and then classified the bursting neurons into three types: (i) neurons displaying a burst of many spikes (maximum number of spikes within a burst; NSB max ≥ 8) at a high discharge rate (maximum interspike interval; ISI max < 5 ms); (ii) neurons displaying a burst of fewer spikes (NSB max ≤ 5) at a high discharge rate (ISI max < 5 ms); and (iii) neurons displaying a burst of a few spikes (NSB max ≤ 7) at relatively long ISIs (ISI max > 5 ms). We found that the discharge patterns of the four groups corresponded to those of regular spiking (RS), fast spiking (FS), fast rhythmic bursting (FRB) and intrinsic bursting (IB) neurons demonstrated in intracellular recording studies using in vitro slice preparations, respectively. In addition, we examined correlations with the task events for neurons recorded in the frontal eye field and neuronal interactions for pairs of neurons recorded simultaneously from a single electrode. We found that they were substantially different between RS and FS types. These results suggest that neurons in the frontal cortex of behaving monkeys can be classified into four types based on their discharge patterns, and that these four types contribute differentially to cortical operations.     

Establishment of shared antigen reactive cytotoxic T lymphocyte using co-stimulatory molecule introduced autologous cancer cells

Cytotoxic T lymphocytes (CTLs) play an essential role in immunological responses for tumor rejection. In the past decade, many tumor-associated antigens (TAAs) have been identified predominantly in melanomas. Several clinical trials based on such antigenic peptides with or without adjuvants brought about partially favorable results, suggesting that identification of more immunogenic TAAs is needed. We show here the successful establishment of human leukocyte antigen (HLA)-A24-restricted CTL (TcLHK2 line1) from a pleural effusion of lung cancer patient, using B7.1 (CD80) transduced autologous lung cancer cells as an antigen-presenting cell (APC). TcLHK2 line1 recognized autologous lung adenocarcinoma cell line LHK2 in an HLA-A24-restricted fashion. Moreover, this CTL line also recognized allogeneic HLA-A24-positive lung adenocarcinoma cell line, gastric carcinoma cell line and melanoma cell line. These data raise the possibility that co-stimulatory molecule B7.1 (CD80) plays important role to overcome the immunological tolerance. Furthermore, TcLHK2 line1 is a useful tool for the identification of widely expressed shared antigens restricted by HLA-A24. Further analysis of this CTL and autologous cancer cell line will bring about novel TAAs.     

The evolution of Epstein-Barr virus inferred from the conservation and mutation of the virus glycoprotein gp350/220 gene

To study variations of Epstein-Barr virus (EBV), we analyzed the gp350/220 gene for several cell lines and Japanese wild isolates using direct sequencing. The N-terminal region was highly conserved in all EBVs except for Jijoye/P3HR-1 and a few isolates. The variation of the region coincided with EBV types A and B (also referred to as types 1 and 2) and were, respectively, designated as the types a and b. The type A/a was detected in most Japanese cell lines and wild isolates, and was classified as China1 type with latent membrane protein (LMP) 1 gene. The type B/b was detected in only a few wild isolates with the Med and China2 types. The C-terminus had more diversity than the N-terminus and lacked the divergence between types A/a and B/b. The phylogenetic analyses of the gp350/220 and LMP1 genes may suggest a mode of EBV evolution into types A/a and B/b and then to LMP1 subtypes.