Ex Vivo Application of Carbon Monoxide in University of Wisconsin Solution to Prevent Intestinal Cold Ischemia/Reperfusion Injury

Carbon monoxide (CO), a byproduct of heme catalysis, was shown to have potent cytoprotective and anti-inflammatory effects. In vivo recipient CO inhalation at low concentrations prevented ischemia/reperfusion (I/R) injury associated with small intestinal transplantation (SITx). This study examined whether ex vivo delivery of CO in University of Wisconsin (UW) solution could ameliorate intestinal I/R injury. Orthotopic syngenic SITx was performed in Lewis rats after 6 h cold preservation in control UW or UW that was bubbled with CO gas (0.1-5%) (CO-UW). Recipient survival with intestinal grafts preserved in 5%, but not 0.1%, CO-UW improved to 86.7% (13/15) from 53% (9/17) with control UW. At 3 h after SITx, grafts stored in 5% CO-UW showed improved intestinal barrier function, less mucosal denudation and reduced inflammatory mediator upregulation compared to those in control UW. Preservation in CO-UW associated with reduced vascular resistance (end preservation), increased graft cyclic guanosine monophosphate levels (1 h), and improved graft blood flow (1 h). Protective effects of CO-UW were reversed by ODQ, an inhibitor of soluble guanylyl cyclase. In vitro culture experiment also showed better preservation of vascular endothelial cells with CO-UW. The study suggests that ex vivo CO delivery into UW solution would be a simple and innovative therapeutic strategy to prevent transplant-induced I/R injury.     

Cibenzoline-induced respiratory muscular paralysis in a hemodialysis patient

A 69-year-old man was admitted to our kidney center with endstage renal failure. We started intermittent peritoneal dialysis immediately because of severe azotemia, hyperkalemia, and metabolic acidosis. Two weeks after admission, he developed uremic pericarditis with frequent ventricular premature contractions and supraventricular premature contractions. The intermittent peritoneal dialysis was then replaced by intensive hemodialysis, and oral administration of 300 mg/d of cibenzoline was started. Four days later, he developed thirst, weakness, and dyspnea due to respiratory muscular paralysis. We initiated respiratory support with a respirator because analysis of his blood gases revealed marked hypercapnia and hypoxia. He also developed hypoglycemia and prolonged PQ and QRS intervals on the electrocardiogram, which we believed were due to cibenzoline intoxication; we discontinued the cibenzoline immediately. All symptoms improved, and he was extubated 5 days later. After 2 months, his pericardial effusion disappeared. He now continues maintenance hemodialysis as an outpatient. We suspect that the cibenzoline induced the respiratory muscular paralysis for 2 reasons: 1) the patient experienced the respiratory muscular paralysis, at the same time he also experienced thirst, weakness, hypoglycemia, and prolonged PQ and QRS intervals on electrocardiogram, and all of these symptoms improved after the discontinuation of cibenzoline, and 2) his plasma concentration of cibenzoline became remarkably elevated, to 20 times above the standard therapeutic level. This patient's clinical course indicates that hemodialysis might be superior to intermittent peritoneal dialysis for treatment of cibenzoline intoxication.     

Clinical evaluation of norfloxacin in gonococcal urethritis

Norfloxacin, a new quinolinecarboxylic acid derivative, was administered to 30 male patients with gonococcal urethritis at a daily dose of 600 mg for 7-21 days. The clinical response was evaluated after administration of 7 days as excellent; Negative culture of N. gonorrhoeae. WBC less than 3/hpf in first voided urine sediment, good; Negative culture, WBC greater than or equal to 3/hpf, and poor; Positive culture. The result was excellent in 14 cases and good in 16 cases. No subjective side effects were observed. The minimum inhibitory concentration (MIC) distribution against the clinically isolated 30 strains of N. gonorrhoeae ranged from 0.0096 micrograms/ml to 0.34 micrograms/ml. Seven of thirty strains were resistant to ABPC. The MIC of these 7 strains ranged from 0.018 micrograms/ml to 0.18 micrograms/ml. Seven cases with ABPC resistant strains had a similar clinical response to other cases. Twelve patients (40%) developed post gonococcal urethritis for 7-14 days after treatment. Clinical observation of this series suggests that a 7 day therapy of Norfloxacin for the patients with gonococcal urethritis is sufficiently effective and that treatment should be changed to other antibacterial agents in the case of post gonococcal urethritis, since continuous administration for more than 7 days of Norfloxacin is not so effective.     

Definition of carcinoma of the gastric cardia

Summary This study concerns the definition of carcinoma of the gastric cardia. The topography of the esophagogastric mucosal junction (mucosal EGJ) was investigated with an endoscope in 182 patients who were free of hiatal hernias, ulcers, and neoplasms in the esophagus and stomach. The relationship between the EGJ and the cardiac gland area was then examined histologically in 56 resected specimens containing intact EGJs and cardia gland areas. Furthermore the cancerous center was determined; the shortest distance between the cancerous center and the EGJ and the amount of esophageal invasion were measured in 102 resected carcinomas located close to the junction; the carcinomas contained the EGJ and were good enough for pathohistological examination. The EGJ was located 0.5–1.0 cm proximal to the His angle (the gastric cardia) in radiological and endoscopic examinations. Histologically the cardiac gland area was found to straddle the EGJ at a range of about 1 cm proximal and 2 cm distal to the junction. Among the upper stomach carcinomas, most of the tumors (87.5%) whose center was located within 2 cm from the EGJ invaded the esophagus. In conclusion, carcinoma of the gastric cardia is defined as a lesion with its center located within 1 cm proximal and 2 cm distal to the EGJ.

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Definition des Kardiacarcinoms

Zusammenfassung Diese Untersuchung befaßt sich mit der Definition von Carcinomen der Kardia. An 182 Patienten, die weder Hiatushernien, Ulcera noch Neoplasien des Oesophagus bzw. des Magens aufwiesen, wurde die Lage des Übergangs von der Oesophagus- zur Magenmucosa (esophagogastric mucosal junction, EGJ) endoskopisch untersucht. Dann wurde die Beziehung zwischen EGJ und dem Drüsengebiet der Kardia histologisch anhand von 56 Resektaten mit intaktem EGJ und Kardiadrüsenzone untersucht. Außerdem wurde an 102 resezierten Carcinomen mit Sitz in der Nähe des gastrooesophagealen Übergangs die kürzeste Ent fernung zwischen Carcinomzentrum und EGJ und das Ausmaß der Oesophagusinfiltration bestimmt; die Proben schlossen den EGJ ein und konnten pathohistologisch beurteilt werden. Bei der radiologischen und endoskopischen Untersuchung fand sind der EGJ 0,5–1,0 cm vom His-Winkel entfernt. Die histologische Untersuchung zeigte, daß die Kardiadrüsenzone sich vom EGJ etwa 1 cm nach proximal und 2 cm nach distal erstreckt. Die meisten Tumoren des oberen Magens (87,5%), deren Zentrum innerhalb von 2 cm vom EGJ entfernt lag, infiltrierten in den Oesophagus. Ein Kardiacarcinom ist demzufolge als Läsion zu definieren, deren Zentrum innerhalb von 1 cm proximal und 2 cm distal des EGJ liegt.

     

Experimental study on the optimal size of the tricuspid valve annular area on annuloplasty

The optimal size of tricuspid valve annular area (TVAA) by annuloplasty for tricuspid regurgitation remains controversial. Recently, we developed a new measuring system which permits to do real-time measurement of tricuspid valve annular area in anesthetized dogs. Using this system, we studied the optimal size of TVAA by annuloplasty. After the right atrial incision, a metal thread which functions as a sense loop of the electromagnetic fields was stitched along the tricuspid valve annulus (visible juncture of the valve leaflets and the cardiac wall). The drive coil assembly was placed perpendicular to the extension of the long axis of the heart and was directed toward the tricuspid valve region. During control conditions, the maximum TVAA appeared at the onset of ventricular systole. The minimum TVAA appeared during the early ventricular diastolic phase which included the ventricular isovolumic relaxation phase. The maximum TVAA varied in five dogs between 2.2 cm2 and 3.1 cm2, the minimum TVAA also varied between 1.8 cm2 and 2.5 cm2: During regular sinus rhythm, a decrease of TVAA during one cardiac cycle ranged between 11.9% and 22.4% of the maximum size. When TVAA was not decreased by annuloplasty to the minimum area which was observed during cardiac cycle in the control state, the cardiac output and the right atrial pressure remained unchanged, because the ventricular filling was not obstructed. On the other hand, when TVAA was decreased smaller than this minimum area, the cardiac output decreased and the right atrial pressure rose.(ABSTRACT TRUNCATED AT 250 WORDS)     

ENDOSCOPIC OBSERVATION OF MUCOSAL SPREAD LESION OF CHOLANGIOCARCINOMA USING PERORAL CHOLANGIOSCOPY WITH NARROW BAND IMAGING

A 69‐year‐old man was admitted to Toho University Omori Medical Center complaining of icterus. Abdominal computed tomography, magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography were suspicious of cholangioma of inferior bile duct. Peroral cholangioscopy using narrow band imaging (NBI) was performed and it was possible to diagnose the mucosal spread lesions of cholangioma. Histological findings reflected the endoscopic findings. Mucosal spread lesions of cholangiocarcinoma were successfully diagnosed using the CHF‐B260 for NBI.     

Long-term results of first-line sequential high-dose carboplatin, etoposide and ifosfamide chemotherapy with peripheral blood stem cell support for patients with advanced testicular germ cell tumor

OBJECTIVE: Standard chemotherapy shows relatively low long-term survival in patients with poor-risk testicular germ cell tumor (GCT). First-line high-dose chemotherapy (HD-CT) may improve the result. High-dose carboplatin, etoposide, ifosfamide chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT) was investigated as first-line chemotherapy in patients with advanced testicular GCT. METHODS: Fifty-five previously untreated testicular GCT patients with Indiana 'advanced disease' criteria received three cycles of bleomycin, etoposide and cisplatin (BEP) followed by one cycle of HD-CT plus PBSCT, if elevated serum tumor markers were observed after three cycles of the BEP regimen. RESULTS: Thirty patients were treated with BEP alone, because the tumor marker(s) declined to normal range. Twenty-five patients received BEP and HD-CT. One patient died of rhabdomyolysis due to HD-CT. Three and six (13% and 25%) out of 24 patients treated with BEP and HD-CT achieved marker-negative and marker-positive partial responses, respectively. The other patients achieved no change. Fifteen (63%) are alive and 14 (58%) are free of disease at a median follow-up time of 54 months. Severe toxicity included treatment-related death (4%). CONCLUSIONS: HD-CT with peripheral stem cell support can be successfully applied in a multicenter setting. HD-CT demonstrated modest anticancer activity for Japanese patients with advanced testicular GCT and was well tolerated. This regimen might be examined for further investigation in randomized trials in first-line chemotherapy for patients with poor-risk testicular GCT.     

Angiotensinogen gene polymorphism as a risk factor for ischemic stroke.

While gene polymorphism for angiotensinogen (AGT) is reported to contribute to the regulation of blood pressure and salt sensitivity, its effect on the risk of ischemic stroke remains controversial. We hypothesized that polymorphism of the AGT gene could be a risk factor for ischemic stroke. Major clinical risk factors and the AGT gene M235T polymorphism were examined in 147 consecutive stroke patients and 133 healthy age-matched controls. All patients were categorized into four stroke types (single lacuna, multiple lacunae, large-artery atherosclerosis and branch atheromatous disease in brainstem) and two vascular groups (large and perforating arterial lesions). The AGT gene M allele significantly increased the risk of single lacuna, multiple lacunae and small arterial lesions, in male patients (p=0.029, 0.031 and 0.026, respectively). Synergistic effects of the AGT gene polymorphism and clinical risks were not observed. In conclusion, AGT M allele may present a risk of lacunar infarctions in Japanese men, independent of hypertension.