Anti-tumor Effect of Chemically Synthesized Sulfolipids Based on Sea Urchin's Natural Sulfonoquinovosylmonoacylglycerols

We recently reported that 3'-sulfonoquinovosyl-1'-monoacylglycerol (designatedA-5) extracted from sea urchin intestine was effective in suppressing the growth of solid tumors. Although the major fatty acid component of A-5 was a saturated C₁₆ acid, there were five other fatty acids, 14:0, 18:0, 14:1, 16:1, and 18:1, which constitute minor components of A-5. Therefore, it remains unclear as to which of these six fatty acid components of A-5 has the anti-tumor effect. In this study, we synthesized sulfolipids each containing only one of these six fatty acids and tested their cytotoxicity against tumor cells and in vivo anti-tumor effects on nude-mice bearing solid tumors of human lung adenocarcinoma cell line A-549. The IC₅₀ values of all products against tumor cells were more than 10^-5 M , suggesting weak cytotoxic activity compared with other chemotherapeutic compounds for cancer. On the other hand, in vivo anti-tumor assay showed that sulfoquinovosyl-monoacylglycerols (SQMG) composed of 14:1 and 18:1 (designated SQMG(14:1) and SQMG(18:1), respectively) were significantly effective in suppressing the growth of solid tumors. Our data suggested that these two SQMGs had a substantial anti-tumor effect in vivo , and they are of interest as candidate drugs for anti-cancer treatment.     

Coronary aneurysms in Kawasaki disease: Follow-up observation by two-dimensional echocardiography

Summary The development and regression of the coronary aneurysms in Kawasaki disease was studied with serial two-dimensional echocardiographic (2D echo) examinations. The diameter of the aneurysms at the proximal portions of the left coronary artery was measured on the 2D echo images in ten patients with Kawasaki disease, in whom left coronary aneurysms were found at the acute stage of the illness, and followed by 2D echo for longer than eight months. It was found that coronary aneurysms usually developed during the second week of the illness, reached maximal size at 3–8 weeks, and regressed gradually thereafter. Small aneurysms disappeared in several months, and those of intermediate size regressed in one to two years. Large aneurysms may remain for many years. Mural thrombi within the aneurysms were detected with 2D echo in three patients. They decreased in echodensity and eventually disappeared echographically.     

Exercise-Induced Ventricular Arrhythmia after Repair of Tetralogy of Fallot

Treadmill exercise electrocardiography (TE) was recorded in 50 patients to evaluate the incidence of exercise-induced ventricular arrhythmias (VAs) in a group of patients who underwent corrective surgery of tetralogy of Fallot (TF) more than four years previously. The results of rhythm evaluation were correlated with cardiac catheterization data as well as clinical information such as the age at surgery and the interval from surgery. Of the 50 patients tested, ventricular premature contraction (VPC) was confirmed in 12 patients (24%) on TE, while five patients (10%) demonstrated VPC on the standard ECG. The interval from surgery was significantly longer in those patients with VA (Group 1) than those without VA (Group 11) on TE (p<0.05). There was no significant difference of the age at corrective surgery between the two groups. In group I, the preoperative hemoglobin level was higher (p<0.05) and the right ventricular ejection fraction was lower (p<0.01). Exercise-induced VAs are closely related to the length of period after surgery and the depressed right ventricular function.     

A clinicopathological study of prognostic factors in esophageal cancer

To evaluate the malignancy of esophageal cancer, we made a statistical clinicopathological study on 66 patients resected with definite operative and histological findings. The cumulative 5-year survival rate was 26.1%. By Cox's proportional hazard model depth and lymph node metastases were the prognostic factors in "Guide Lines for the Clinical and Pathological Studies on Carcinoma of the Esophagus". New histological factors for quantity idea: 1) depth judged by presence of cancer cells before irradiation; 2) intramural spreading characteristics; 3) volume of tumor measuring the infiltrating area of each layer; 4) distribution of metastatic lymph nodes set up by anatomical restriction and surgical risk; 5) number of metastatic lymph nodes. By analyzing the interaction of these 5 factors, the depth was correlated with the volume and the intramural spreading characteristics. The lymph node metastases were correlated significantly with the volume but not with the depth. The depth and the distribution of metastatic lymph nodes influenced prognosis according to Cox's proportional hazard model. Estimated survival rates of these factors were fitted to actual survival rates respectively. Postsurgical survival and adjuvant therapy may be determined by histological factor analysis.     

Hyperthermo-chemotherapy combined with cytoreductive surgery for the treatment of gastric cancer with peritoneal dissemination

Continuous hyperthermic peritoneal perfusion (CHPP) with anticancer agents (mitomycin C and cisplatin) in warm saline was performed in patients with peritoneal dissemination of gastric cancer following resection of the primary lesion. The effect of CHPP was examined by a second-look operation. This study includes 41 cases of gastric cancer with peritoneal dissemination but without liver metastasis treated during the past 6 years. The overall median survival was 14.6 months to 64.2 months from CHPP to death and the 3-year survival rate was 28.5%. Second look surgery revealed a remarkable diminution in the degree of peritoneal dissemination in 7 (50%) of 14 patients with disappearance of ascites after only one course of CHPP in 7 (77.8%) of 9 patients. Long-term 3 year-survival was noted in 4 (9.8%) patients on CHPP. Side effects were renal insufficiency in 2 (5%) patients, leukopenia in 2 (5%) patients, and perforation of the small intestine in 1 (2%) patient. These results suggest the effectiveness of CHPP in the treatment of gastric cancer with peritoneal dissemination.

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Resumen La perfusión hipertérmica continua (PHTC) con agentes anticancerosos (mitocina G y cisplatino) y solutión salina fue realizada en pacientes con cáncer gástrico con diseminación peritoneal después de resección de la lesión primaria, y el efecto de PHTC fue determinado mediante reexploración (operación de second look, OSL). La población de pacientes está constituída por 41 casos de cáncer gástrico con diseminación peritoneal pero sin metástasis hepáticas, tratdos en el curso de los últimos 6 años. La sobrevida media global fue de 437 dias (rango 28 a 1925 días) desde la PHTC hasta la muerte y la tasa de sobrevida a 3 años fue 28.5%. La OSL reveló una notoria disminución de la diseminación peritoneal en 7 (50%) de 14 casos y desaparición de la ascites después de sólo un ciclo de PHTC en 7 de 9 casos con ascitis. Sobrevida de 3 años ocurrió en 4 casos. Los efectos colaterales fueron insuficiencia renal en 2 casos (5%), leucopenia en 2 casos (5%) y perforación del intestino delgado en 1 caso (2%). Los anteriores resultados sugieren que la PHTC es eficaz en el tratamiento del cáncer gástrico con diseminación peritoneal.

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Résumé La perfusion péritonéale continue hyperthermique (PPCH) avec des agents anticancéreux comme le mitomycine C et la cis-platine avec sérum physiologique chauffé a été instaurée lorsqu'une carcinose d'origine gastrique a été trouvée. Les effets de la PCH ont été évalués chez 16 patients lors d'un second-look (SL). Cette étude concerne 41 patients avec carcinose péritonéale sans métastase hépatique observés au cours des 6 dernières années. La survie globale médiane était de 437 jours (extrêmes 28 à 1925 jours): le taux de survie a 3 ans était de 28.5%. Les lésions avaient diminué de façon notable chez 7 (50%) de 14 patients. L'ascite a disparu dans 7 des 9 cas. Une survie à long terme (3 ans) a été notée dans 4 cas. Les effets secondaires ont été une insuffisance rénale dans 2 cas (5%), une leucopénie dans 2 cas (5%) et une perforation de l'intestin grêle dans un cas (2%). Les résultats suggèrent que la PPCH est efficace dans le traitement du cancer gastrique avec dissémination péritonéale.

     

Fetal death following high-dose systemic steroid therapy in a pregnant patient with Vogt-Koyanagi-Harada disease

BACKGROUND: In previous reports, all pregnant women with VKH were successfully treated in the second or third trimester with high-dose systemic corticosterioids without any severe complications. We present a case of fetal death during systemic steroid treatment of a VKH disease patient. RESULTS: A 28-year-old woman in the 30th week of pregnancy was diagnosed with VKH disease. Because of the progression to high bullous retinal detachment in spite of topical corticosteroid therapy, systemic intravenous prednisolone (PSL, 200 mg/day) was begun. On day 18 (PSL, 55 mg/day), sudden intrauterine fetal death occurred. Maternal conditions were normal and there was no apparent abnormality in the umbilical cord, placenta, or fetus; no autopsy was allowed. With gradual tapering of the PSL, the patient's vision was preserved, without recurrence of the VKH disease. CONCLUSIONS: We present a case of fetal death in a 28-year-old pregnant woman being treated with intravenous prednisolone for VKH disease. The cause of the fetal death was not clear. It was reported as an adverse event.     

Single-channel properties of volume-sensitive Cl- channel in ClC-3-deficient cardiomyocytes

It is controversial whether the ClC-3 protein, which is one of the voltage-dependent chloride channel ClC family members, is a candidate for the volume-sensitive outwardly rectifying (VSOR) Cl(-) channel per se or its regulator. Here, for the first time, we examined the single-channel properties of the VSOR Cl(-) channel in ventricular myocytes isolated from ClC-3-deficient mice. The single-channel current induced by cell swelling exhibited Cl(-) selectivity, mild outward rectification, and an intermediate unitary conductance (around 38 pS). A Cl(-) channel blocker, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), reversibly inhibited the outward current. These single-channel properties were identical with those in ClC-3 expressing wild-type ventricular myocytes. These results indicate that the single-channel activity of the VSOR Cl(-) channel is independent of the expression of ClC-3 proteins in mouse ventricular myocytes.     

Hemodynamic changes during off-pump coronary artery bypass anastomosis in patients with coexisting mitral regurgitation: improvement with milrinone

We hypothesized that mitral regurgitation (MR) would be exacerbated, cardiac index (CI) decreased, and mean pulmonary artery pressure (MPAP) increased in patients with coexisting MR during off-pump coronary artery bypass (OPCAB) anastomosis, and that milrinone could ameliorate increases in MR that occur during OPCAB anastomosis. Subjects comprised 140 patients scheduled for elective OPCAB divided into three groups: patients without MR (MR(-) group; n = 57), patients with MR (MR(+) group; n = 41), and patients with MR who received milrinone (M+MR(+) group; n = 42). Patients with grade 1+ or 2+ MR were included, whereas those with grade 3+ or 4+ MR were excluded. Hemodynamic variables were measured after the induction of anesthesia and during anastomosis. IV infusion of milrinone (0.5 microg . kg(-1) . min(-1)) started immediately after the induction of anesthesia in the M+MR(+) group. CI was significantly decreased (P < 0.0001), and MPAP and MR were significantly increased (P < 0.001) during left coronary anastomosis in the MR(+) group compared with the MR(-) group. CI was significantly higher (P < 0.001), and neither MPAP nor MR were increased (P < 0.05) during left coronary artery anastomosis in the M+MR(+) group compared to the MR(+) group. In patients with MR, anastomosis of the left coronary artery branches was associated with decreased CI and increased regurgitation and MPAP. In such patients, treatment with milrinone helps to stabilize hemodynamics during anastomosis.