First pathological report of a de novo CD5‐positive diffuse large B‐cell lymphoma patient presenting with Guillain–Barré syndrome‐like neuropathy due to neurolymphomatosis

Peripheral neuropathy occurs in approximately 5% of the patients with lymphoma. Two major causes of peripheral neuropathy associated with lymphoma are neurolymphomatosis and paraneoplastic neuropathy such as demyelinating neuropathy. The differential diagnosis between neurolymphomatosis and demyelinating neuropathy is difficult, because electrophysiological findings suggestive of demyelination are frequently observed even in patients with neurolymphomatosis. Here, we report a patient with de novo CD5‐positive diffuse large B‐cell lymphoma (DLBCL) who presented with Guillain–Barré syndrome (GBS)‐like neuropathy. Demyelination due to paraneoplastic neuropathy was clinically suspected. However, autopsy demonstrated that the cause of the neuropathy was neurolymphomatosis. Clinical courses of neurolymphomatosis vary and neurolymphomatosis cases presenting with GBS‐like neuropathy are reported. In addition, DLBCL is the most frequent histological type of malignant lymphoma that develops neurolymphomatosis. Furthermore, “CD5‐positive” DLBCL may tend to develop neurolymphomatosis. If a patient with “CD5‐positive” DLBCL develops peripheral neuropathy, neurolymphomatosis should be considered and imaging studies performed and, if possible, nerve tissue biopsy, regardless of clinical symptoms of the neuropathy. To our knowledge, this is the first report of a patient with de novo CD5‐positive DLBCL with neurolymphomatosis who presented with GBS‐like neuropathy.     

Microbial screening of Cariostat®-inoculated plaque samples from low and high caries risk children

The aim of the present study was to investigate caries activity and it's association with the presence of S. mutans and S. sobrinus. The subjects were 499 children aged 2.5 years old, who participated in dental health examinations held from May 2006 to January 2007 at a health center in Katano City, Osaka, Japan. A dental examination was performed based on caries diagnostic criteria of the Health Policy Bureau, Ministry of Welfare, Japan. Plaque samples were collected using a sterile cotton swab from the maxillary buccocervical surfaces by the same dental hygienist. Two hundred seventy two (54.5%) children who had Cariostat score below 1.5 were determined as low risk and 227 (45.5%) who had a score above 2.0 as high risk. For microbial screening, 100 children were randomly selected from the high and low risk groups. The presence of S. mutans and S. sobrinus were detected using PCR technique. Thirty seven (18.5%) children had S. mutans alone, 20 (10.0%) had S. sobrinus alone, 16 (8.0%) had both S. mutans and S. sobrinus, and 127 (63.5%) had neither S. mutans nor S. sobrinus. Cariogenic bacteria were detected more from high caries risk than low caries risk children. A larger number of S. sobrinus was found in children with high df numbers than low df numbers. In this study, it was shown that S. sobrinus was more closely related with high caries risk activity and high df numbers.     

Comparative effect of lidocaine, bupivacaine and RAC 109 on myocardial conduction and contractility in the rabbit

Nicotine-induced hypothermia is well established, but the nicotinic receptor actions underlying this effect are not clear. Nicotine causes activation and desensitization at a variety of nicotinic receptor subtypes. Sazetidine-A [6-(5(((S)-azetidine-2-yl)methoxy)pyridine-3-yl)hex-5-yn-1-ol] is a novel compound that potently and selectively desensitizes α4β2* nicotinic receptors. The main goal of this study was to investigate the effects of sazetidine-A, on core body temperature (Tc) in mice and rats. Sazetidine-A effects on Tc and the interactions of sazetidine-A with nicotine and selective nicotinic antagonists were investigated to determine the receptor actions underlying nicotine-induced hypothermia. Adult male mice were injected with different dose of nicotine (0.2, 0.4 and 0.8 mg/kg), sazetidine-A (0.3, 1, and 3mg/kg), a mixture of nicotine (0.4 or 0.8 mg/kg) and sazetidine-A (0.3 or 0.6 mg/kg) or saline and Tc was monitored telemetrically. In another set of experiments, the interaction between sazetidine-A and dihydro-β-erythroidine (DHβE), an α4β2* nicotinic receptors antagonist, and methyllycaconitine (MLA), an α7 antagonist, was investigated. Tc of mice was monitored following DHβE (1, 3 and 6 mg/kg), a combination of DHβE (3mg/kg) and sazetidine-A (0.6 mg/kg), MLA (1.5, 3 or 6 mg/kg) or combination of MLA (6 mg/kg) and sazetidine (0.6 mg/kg) or saline. The acute effect of sazetidine-A (1, 3, and 6 mg/kg) on rats Tc was also studied. Acute sazetidine-A caused a pronounced and long-lasting hypothermia in mice; Tc decreased to about 28°C at 100 min and recovered within 230 min. The hypothermic effect of sazetidine in rats was much less in magnitude (about 3°C) and shorter in duration compared with that in mice. Nicotine co-administration with low doses of sazetidine potentiated the magnitude and duration of hypothermia in mice. The α4β2* nicotinic receptors antagonist DHβE significantly prolonged sazetidine-A-induced hypothermia but did not increase its depth. The α7 antagonist MLA caused a modest degree of hypothermia with relatively short duration in mice. MLA failed to counteract the sazetidine-A-induced hypothermia. Overall, our results show that pharmacological modulation of α4β2* nicotinic receptors elicits changes in body temperature that may involve desensitization of these receptors.     

Development of an antigen heterologous enzyme linked immunosorbent assay for measurement of corticosterone in rat serum

Homologous and heterologous combinations of enzyme conjugate and antibody in steroid enzyme immunoassay (EIA) influences unlabeled steroid recognition by antibody that affects sensitivity of the assay. To develop corticosterone enzyme linked immunosorbent assay (ELISA), antibodies were generated against corticosterone-3-carboxymethyloxime-bovine serum albumin (corticosterone-3-CMO-BSA) and corticosterone-21-hemisuccinate-bovine serum albumin (corticosterone-21-HS-BSA). Four horseradish peroxidase (HRP) enzyme conjugates were prepared using two corticosterone derivatives (corticosterone-3-CMO and corticosterone-21-HS) and two cortisol derivatives (Cortisol-3-CMO and Cortisol-21-HS). Eight combinations of homologous and heterologous assays were evaluated. The use of antigen heterologous combination resulted in development of assay. The developed assay is simple, direct, and convenient to use, as it permits the direct addition of the serum sample in to the assay, and it requires only 1.5 hours to complete.     

Spinal Muscular Atrophy: New and Emerging Insights from Model Mice

Spinal muscular atrophy (SMA) is a common and often fatal neurodegenerative disease that primarily afflicts infants and young children. SMA is caused by abnormally low levels of the survival motor neuron (SMN) protein resulting from a combination of recessively inherited mutations in the SMN1 gene and the presence of an almost identical but partially functional copy gene, SMN2. Absence of the uniquely human SMN2 gene in SMA patients has never been reported because the SMN protein is indispensable for cell survival. Modeling SMA in animals therefore poses a challenge. This review describes the different strategies used to overcome this hurdle and model SMA in mice. We highlight new and emerging insights regarding SMA gained by studying the mice and illustrate how the animals serve as important tools to understand and eventually treat the human disease.     

Combined epidural-spinal anesthesia for radical hysterectomy in a patient complicated with bronchiectasis diagnosed on preoperative anesthetic consultation

A radical hysterectomy was performed in a patient complicated with bronchiectasis, under combined spinal-epidural anesthesia. The patient was asymptomatic and preoperatively diagnosed with bronchiectasis on an anesthetic consultation with an anesthesiologist. An epidural catheter was inserted between T12 and L1, and spinal anesthesia was subsequently performed with 0.5% bupivacaine 2.8 ml and fentanyl 10 microg. It was necessary to administer a supplemental epidural dose of 0.375% ropivacaine fifty minutes after the start of the operation. Postoperative epidural analgesia was effective and no perioperative complications were observed.     

Comparing the cochlear spiral modiolar artery in type-1 and type-2 diabetes mellitus:a human temporal bone study

This study examined whether pathological findings were present in cochlear vessels for patients with diabetes mellitus. Twenty-six temporal bones from 13 patients with type 1 diabetes mellitus and 40 temporal bones from 20 patients with type 2 diabetes mellitus were examined. Type 2 diabetic temporal bones were divided into 2 groups according to diabetic management (22 temporal bones with insulin therapy, and 18 with oral hypoglycemic drugs). Age-matched normal control temporal bones were also selected. The vessel wall thickness in the cochlear spiral modiolar artery was measured under a light microscope, and the vessel wall ratio (vessel wall thickness/outer diameter of the vessel x 100) was calculated. The vessel wall thickness and vessel wall ratio in type 1 diabetes mellitus were significantly greater than in normal controls. Type 2 diabetic patients with insulin therapy showed significantly greater vessel wall thickness and vessel wall ratios than controls. In type 2 diabetes mellitus, the vessel wall thickness and vessel wall ratio were greater in patients treated with insulin therapy than in those treated with oral hypoglycemic agents. Type 2 diabetic patients with insulin therapy showed an increased vessel wall thickness and vessel wall ratio compared to patients with type 1 diabetes mellitus. In conclusion, the cochlea in patients with diabetes mellitus shows circulatory disturbance compared to age-matched normal controls.     

Role of salvage cytoreductive surgery in the treatment of patients with recurrent ovarian cancer after platinum-based chemotherapy

OBJECTIVES: The role of cytoreductive surgery, which is well established in the primary treatment for epithelial ovarian cancer, is controversial in recurrent disease. The aim of this study was to assess the clinical benefit of salvage surgical cytoreduction in patients with recurrent ovarian cancer after platinum-based chemotherapy. METHODS: We conducted a retrospective analysis of 46 patients with recurrent epithelial ovarian cancer treated at our department between 1988 and 2003. Twenty-three patients underwent salvage cytoreductive surgery (cytoreductive group), and the other 23 patients were treated without surgery (control group). RESULTS: Patients in cytoreductive group had a median survival of 41.7 months after recurrence, which was significantly longer than control group (18.8 months; P < 0.01). The duration of stay at home and the period oral intake was preserved were significantly longer in the cytoreductive group. In the cytoreductive group, survival was influenced by the residual disease after surgery (residual tumor diameter, <2 cm vs >2 cm; median survival, 50 months vs 35.2 months; P < 0.05). However, the number of recurrent sites (solitary vs multiple) and the lengths of treatment-free intervals after primary treatment (<6 months vs >6 months) showed no significant influence on survival. CONCLUSIONS: The application of cytoreductive surgery might improve the prognosis of patients with recurrent ovarian cancer if the tumor was resectable. Preserved prognoses of platinum-resistant disease with short treatment-free interval demonstrated in this study suggest that the concept of maximum cytoreduction might be introduced in the treatment of recurrent disease in the future.     

Diethyldithiocarbamate induces apoptosis in HHV-8-infected primary effusion lymphoma cells via inhibition of the NF-κB pathway

Primary effusion lymphoma (PEL) is a subtype of B-cell lymphoma caused by human herpes virus 8/Kaposi sarcoma-associated herpes virus (HHV-8/KSHV), which is mostly found in patients with AIDS and has poor prognosis. Nuclear factor (NF)-κB pathway is constitutively activated in HHV-8-infected PEL cells and plays a crucial role in tumorigenesis. Recently, it has been shown that diethyldithiocarbamate (DDTC), an active metabolite of disulfiram, has apoptotic activity in cancer cells. Here, we investigated the effect of DDTC on PEL using a PEL mouse model generated by intraperitoneal injection of BC-3 cells, a PEL cell line. DDTC ameliorated the symptoms of PEL in these mice, such as development of ascites, splenomegaly and increase of body weight, in comparison with PBS-treated controls. Moreover, we determined in vitro that DDTC suppressed the constitutively activated NF-κB pathway in BC-3 cells. Methylthiotetrazole assay revealed that the cell proliferation of various PEL cell lines was significantly suppressed by the treatment of DDTC. DDTC also induced the expression of cleaved caspase-3, an apoptosis marker, whereas the addition of Q-VD-OPh, a pan-caspase inhibitor, inhibited cell apoptosis induced by DDTC treatment. Together, our results indicated that DDTC induces apoptosis via inhibition of the NF-κB signaling pathway in HHV-8-infected PEL cells. This study suggests the potential use of DDTC as a therapeutic approach for PEL.     

An association between Helicobacter pylori and upper respiratory tract disease: Fact or fiction?

Helicobacter pylori(H. pylori) is a major cause of chronic gastritis and gastric ulcers and considerable evidence supports the notion that infection with this bacterium is also associated with gastric malignancy in addition to various other conditions including pulmonary, vascular and autoimmune disorders. Gastric juice infected with H. pylori might play an important role in upper respiratory tract infection. Although direct and/or indirect mechanisms might be involved in the association between H. pylori and upper respiratory tract diseases, the etiological role of H. pylori in upper respiratory tract disorders has not yet been fully elucidated. Although various studies over the past two decades have suggested a relationship between H. pylori and upper respiratory tract diseases, the findings are inconsistent. The present overview describes the outcomes of recent investigations into the impact of H. pylori on upper respiratory tract and adjacent lesions.