Cerebellar posterior superior vermis and cognitive cluster scores in drug-naive patients with first-episode schizophrenia

Previously, we performed an MRI study that revealed smaller volumes of the subregions of the cerebellar vermis in men and women with chronic schizophrenia. An issue that arose from that study was whether similar structural changes in the cerebellum are found in patients with first-episode schizophrenia. In the present study, MRI scans were acquired from 14 drug-naive patients with first-episode schizophrenia and 16 healthy subjects, and used to measure the volumes of their cerebellar subregions. Positive symptom, negative symptom and cognitive cluster scores were attained using the Positive and Negative Syndrome Scale. Patients with first-episode schizophrenia had reduced volumes of the anterior vermis and posterior superior vermis compared with healthy subjects. We confirmed that there was a volume reduction of the cerebellar vermis in drug-naive patients with first-episode schizophrenia. Smaller volumes of the posterior superior vermis were associated with worse cognitive cluster scores in patients with first-episode schizophrenia.     

Study on the colonoscopic features of GVHD enteritis that developed after hematopoietic stem cell transplantation

BACKGROUND/AIMS: Graft-versus-host disease (GVHD) enteritis is a frequent gastrointestinal complication following hematopoietic stem cell transplantation (HSCT). The diagnosis of GVHD enteritis was made if apoptotic bodies in crypt epithelium were observed in a biopsy specimen(s). However, there is no standardized protocol as to what colonoscopic findings to use as a guide, and from which segment of the colon and how many biopsy specimens should be obtained. Our aim was to develop a colonoscopic protocol for detection of GVHD enteritis. METHODOLOGY: This retrospective study included 19 patients who had refractory watery diarrhea beyond day 20 after HSCT and underwent colonoscopic examination. Four to nine colonoscopic biopsy specimens were obtained from various regions of the colon in each patient. Fifteen of the 19 patients were diagnosed with GVHD enteritis. RESULTS: In the 15 patients with GVHD enteritis, colonoscopy revealed non-specific findings such as edema, redness, and erosions. Apoptotic bodies were found in one biopsy specimen in 7 patients, 2 biopsy specimens in 5 patients, and 3 or more biopsy specimens in 3 patients. Apoptotic bodies were found in the distal colon (descending colon or sigmoid colon or rectum) in 8 patients, and in the proximal to transverse colon in the remaining 7 patients. Apoptotic bodies were most frequently detected in colonoscopic biopsy specimens of erosions and aphthous lesions. CONCLUSIONS: When patients who have undergone HSCT develop refractory diarrhea, many biopsy specimens from the entire colon should be obtained on colonoscopic examination for histopathologic detection of GVHD enteritis.     

Mitiglinide, a novel oral hypoglycemic agent, preserves the cardioprotective effect of ischemic preconditioning in isolated perfused rat hearts

Diabetic patients often have manifestation of coronary heart disease. As a consequence, therapeutic strategies for diabetes should pay more attention to hypoglycemic agents which do not have adverse effects on myocardium. Mitiglinide is considered to have little or no impact on the cardioprotective effect of ischemic preconditioning (IP) because of its high selectivity for blocking sulfonylurea receptor1 (SUR1). However, glibenclamide, a nonselective SUR blocker, attenuates this beneficial effect. In the present study, we tested the hypothesis that mitiglinide preserves the protective action of IP evaluated by ischemia/reperfusion ventricular tachyarrhythmia (rVT) in isolated perfused rat hearts. After initial perfusion, the hearts were assigned to one of the following groups: 1) non-IP with control perfusion buffer (non-IP group); 2) IP with control perfusion buffer (IP-C group); 3) IP with perfusion buffer containing glibenclamide (IP-G group); and 4) IP with perfusion buffer containing mitiglinide (IP-M group). The protocol for the non-IP group consisted of 21 minutes of aerobic perfusion before 10 minutes of ischemia. In the other 3 groups (IP groups), there were 3 cycles of 2-minute ischemia followed by 5 minutes of reperfusion before 10 minutes of ischemia. The IP-C group had a significantly shorter rVT duration than the non-IP group (4.4 +/- 1.8 minutes versus 14.3 +/- 2.5 minutes; P < 0.05). rVT duration was the shortest in the IP-M group (3.9 +/- 1.0 minutes), but among the longest in the IP-G group (14.0 +/- 2.6 minutes). In conclusion, mitiglinide preserved the cardioprotective effect of IP, however, glibenclamide abolished this beneficial effect. Therefore, mitiglinide may offer a long-term benefit for myocardial ischemia in diabetic patients.     

Intraperitoneal bleeding due to rupture of the left gastric vein (LGV) in a patient with liver cirrhosis: a case report

Intraperitoneal bleeding from ruptured ectopic varices is a rare and fatal complication in patients with portal hypertension. Although laparotomy with high mortality is performed, it is difficult to detect correct bleeding site and save the patient. This is probably the first case report of rupture from left gastric vein revealed by transjugular intrahepatic portosystemic shunt (TIPS). We propose the use of TIPS for diagnosing and treating intraperitoneal bleeding from ectopic varices.     

rVSV(M Delta 51)-M3 is an effective and safe oncolytic virus for cancer therapy

Oncolytic vesicular stomatitis virus (VSV) is being developed as a novel therapeutic agent for cancer treatment, although it is toxic in animals when administered systemically at high doses. Its safety can be substantively improved by an M Delta 51 deletion in the viral genome, and yet VSV(M Delta 51) induces a much greater, robust cellular inflammatory response in the host than wild-type VSV, which severely attenuates its oncolytic potency. We have reported that the oncolytic potency of wild-type VSV can be enhanced by vector-mediated expression of a heterologous viral gene that suppresses cellular inflammatory responses in the lesions. To develop an effective and safe VSV vector for cancer treatment, we tested the hypothesis that the oncolytic potency of VSV(M Delta 51) can be substantively elevated by vector-mediated expression of M3, a broad-spectrum and high-affinity chemokine-binding protein from murine gammaherpesvirus-68. The recombinant vector rVSV(M Delta 51)-M3 was used to treat rats bearing multifocal lesions (1-10 mm in diameter) of hepatocellular carcinoma (HCC) in their liver by hepatic artery infusion. Treatment led to a significant reduction of neutrophil and natural killer cell accumulation in the lesions, a 2-log elevation of intratumoral viral titer, substantively enhanced tumor necrosis, and prolonged animal survival with a 50% cure rate. Importantly, there were no apparent systemic and organ toxicities in the treated animals. These results indicate that the robust cellular inflammatory responses induced by VSV(M Delta 51) in HCC lesions can be overcome by vector-mediated intratumoral M3 expression, and that rVSV(M Delta 51)-M3 can be developed as an effective and safe oncolytic agent to treat advanced HCC patients in the future.     

Nonrecurrent inferior laryngeal nerve without vascular anomaly as a genuine entity

Inferior laryngeal nerve (ILN), which usually arises from vagus nerve, runs recurrent course and is called recurrent ILN (RILN). Intimate knowledge of normal and anatomic variants of the ILN reduces the risk of nerve injury and vocal cord paralysis in thyroid and parathyroid surgery. The nonrecurrent ILN (NRILN) is a rare nerve anomaly that is associated with a right aberrant subclavian artery. We encountered 2 patients with NRILN during thyroid surgery. Patient 1, a 57-year-old woman, had mediastinal thyroid tumor without vascular anomaly. Patient 2, a 47-year-old woman with a history of esophageal foreign body (fish bone), was suspected to have NRILN with vascular anomaly before surgery, as judged by preoperative enhanced CT. In the patient 1, we verified laryngeal mobility function of the NRILN by nerve stimulation, and confirmed the absence of RILN in usual recurrent course. The findings in the patient 1 indicate that NRILN without subclavian artery anomaly is a genuine entity. In both patients we performed thyroid surgery safely and fast by expectation and identification of NRILN by use of nerve stimulator. In conclusion, we confirm the existence of NRILN without vascular anomaly and show effectiveness of preoperative enhanced CT and valuable use of nerve stimulator for nerve preservation in the patients with NRILN.     

Potency of SMP-601, a novel carbapenem, in hematogenous murine bronchopneumonia caused by methicillin-resistant and vancomycin-intermediate Staphylococcus aureus

We compared the potency of SMP-601, a novel carbapenem, with that of vancomycin in a murine model of hematogenous bronchopneumonia infection caused by methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-intermediate S. aureus (VISA). The MICs of SMP-601 and vancomycin against MRSA were 2 and 1 mug/ml, respectively, while those against VISA were 2 and 8 mug/ml, respectively. Treatment with SMP-601 resulted in a significant decrease in the number of viable bacteria in the MRSA infection model (control, 100 mg/kg vancomycin, and 100 mg/kg SMP-601, 8.42 +/- 0.50, 5.29 +/- 0.71, and 5.50 +/- 0.58 log CFU/lung, respectively,) and in the VISA infection model (control, 100 mg/kg vancomycin, and 100 mg/kg SMP-601, 9.64 +/- 0.63, 8.72 +/- 0.45, 7.42 +/- 0.14 log CFU/lung) (mean +/- standard error of the mean). The survival rate in the VISA infection model treated with SMP-601 (70%) was significantly higher than those in the other two groups (20% for vancomycin and 0% for control; P < 0.05). Histopathological examination revealed that inflammatory changes in the SMP-601-treated group were less marked than in the other two groups. The results of pharmacokinetic-pharmacodynamic analysis supported the results of the bacteriological, histopathological and survival studies. Our results demonstrate the potency of SMP-601 against MRSA and VISA in murine hematogenous pulmonary infection.     

Broncholithiasis managed by surgical resection

Broncholithiasis is frequently associated with hemoptysis and infection. The most common cause of the disease is the presence of calcified material in a bronchus or in a cavity communicating with a bronchus. We present two cases of broncholithiasis treated by surgery. Case 1 involves a 57-year-old woman who presented with cough and bloody sputum. She had suffered from recurrent pneumonia in the left lower lobe caused by broncholithiasis for 2 years. We performed left S6 segmentectomy with bronchoplasty after unsuccessful bronchoscopic removal. Case 2 is a 65-year-old man who had had hilar tuberculous lymphoadenopathy at the age of 20. Recently he had suffered from recurrent bloody sputum and pulmonary suppuration for 3 years. We performed right upper lobectomy because the right B3 was occluded by inflammatory granulation with calcification. Postoperatively, these two patients have been alive and well with no complications. The indications of surgery for broncholithiasis include a difficult bronchoscopic broncholithectomy, massive hemoptysis, and irreversible complications such as chronic pulmonary suppurative disease.     

CARDIOVASCULAR AND SURVIVAL PARADOXES IN DIALYSIS PATIENTS: Kinetic Studies of Atherogenic Lipoproteins in Hemodialysis Patients: Do They Tell Us More about Their Pathology?

Patients with chronic kidney disease have one of the highest risks for atherosclerotic complications. Several large epidemiological studies described an opposite association of total and low density lipoprotein (LDL) cholesterol with cardiovascular complications and total mortality compared to the general population, a circumstance often called "reverse epidemiology." Many factors might contribute to this reversal such as interaction with malnutrition/inflammation, pronounced fluctuations of atherogenic lipoproteins during the course of renal disease, heterogeneity of lipoprotein particles with preponderance of remnant particles, and chemical modification of lipoproteins caused by the uremic environment. A vicious cycle has been suggested in uremia in which the decreased catabolism of atherogenic lipoproteins such as LDL, IDL and Lp(a) leads to their increased plasma residence time and further modification of these lipoproteins by oxidation, carbamylation, and glycation. Using stable isotope techniques, it has been shown recently that the plasma residence time of these particles is more than twice as long in hemodialysis patients as in nonuremic subjects. This reduced catabolism, however, is masked by the decreased production of LDL, resulting in near-normal plasma levels of LDL. The production rate of Lp(a) in hemodialysis patients is similar to that in controls which together with the doubled residence time results in elevated Lp(a) levels. An increased clearance of these altered lipoproteins via the scavenger receptors of macrophages leads to the transformation of macrophages into foam cells in the vascular wall and might contribute to the pronounced risk for cardiovascular complications of these patients. These observations suggest that the real danger of these particles is not reflected by the measured concentrations but by their metabolic qualities.