Effect of immunoglobulin preparations on the aggregation of human erythrocytes

The aggregation of human erythrocytes induced by four kinds of immunoglobulin preparations was examined by a low shear rheoscope. After removing anti-A+ and anti-B+ activities contaminated in all preparations by incubating with erythrocytes of different blood groups, the facilitating effect on the rouleau formation of erythrocytes was compared: (i) The effect of polyethyleneglycol-treated preparation was the same in A+-, B+-, AB+- and O+-erythrocytes. (ii) Sulfonation did not affect the velocity of rouleau formation. (iii) Some of pepsin-treated preparations showed the strongest facilitation for A+-, B+- and AB+-erythrocytes, but the facilitation was much weaker for O+-erythrocytes. The others showed the weak facilitation for all types of erythrocytes (especially O+-erythrocytes). (iv) Plasmin treatment markedly decreased the velocity of rouleau formation of AB+- and O+-erythrocytes, but was not of A+- and B+-erythrocytes.     

Atrioventricular Nodal Physiology After Slow Pathway Ablation

The A V nodal physiology before and 1 week after “slow pathway potential” guided catheter ablation was examined in 32 patients with AV nodal reentrant tachycardia. A mean of 4.9 applications of radiofrequency energy eliminated AV nodal reentrant tachycardia in all patients. There were no significant differences in sinus cycle length (815 ± 159 msec vs 813 ± 162 msec;P = NS) and fast pathway conduction properties before and 1 week after ablation. Slow pathway conduction was completely eliminated in 10 (31%) (group I) of 32 patients after ablation. In the remaining 22 patients residual slow pathway conduction associated with one AV node echo was observed. In 15 patients (47%) (group II), the effective refractory period of the slow pathway showed a change of < 30 msec (265 ± 51 vs 266 ± 51 msec; P = NS), and in 7 patients (22%) (group III), a prolongation of more than 80 msec (247 ± 56 vs 340 ± 42 msec; P = 0.0001) before and 1 week after ablation. Minimal and maximal A₂-H₂ interval over the slow pathway in group II was not significantly changed (Min A₂-H₂:241 ± 37 vs 247 ± 40 msec; P = NS, Max A₂-H₂: 346 ± 79 vs 350 ± 60 msec; P = NS), while a significant prolongation was measured in group III (Min A₂-H₂: 261 ± 53 VS 373 ± 107 msec; P < 0.01. Max A₂-H₂: 359 ± 41 vs 427 ± 63 msec; P < 0.05) before and after ablation. Conclusion: In group II patients there was no evidence shown of impairment of the slow pathway. This suggests that disruption of the link between fast and slow pathways may be responsible for the elimination of AV nodal reentrant tachycardia, besides the elimination or impairment of the slow pathway itself, in “slow pathway potential” guided catheter ablation, and that the slow pathway potential may not necessarily represent activation of the slow pathway itself or of its atrial connection.     

Electrophysiological Features of Atrial Tachycardia Arising from the Atrioventricular Annulus

MATSUOKA, K., et al. : Electrophysiological Features of Atrial Tachycardia Arising from the Atrioven-tricular Annulus. Atrial tachycardia (AT) arises from various sites in the atrium and the mechanisms are nonuniform. McGuire et al. reported that the cells around the atrioventricular annuli resembled nodal cells in their cellular electrophysiology. The purpose of this study was to delineate the electrophysiological features of AT arising from the atrioventricular (AV) annulus (AVAT). The study included five patients with six AVATs that were abolished by the radiofrequency energy delivery. The location of the AV annuli was defined by using the AV ratio of the local electrograms and the amplitude of the ventricular electrograms, in addition to the anatomic findings under fluoroscopic guidance. The tachycardia cycle lengths were  403 ± 117 ms  . An AV ratio of the electrograms at the successful ablation sites was  0.4 ± 0.4  at the tricuspid annulus and  1.5 ± 0.3  at the mitral annulus. Small doses (  mean 3.2 ± 1.8 mg  ) of adenosine triphosphate could terminate all the tachycardia episodes for five of the ATs without the development of AV nodal conduction block. The successful ablation sites were located at the right mid-septum in 1 AT, right posteroseptum in 2 ATs, right posterolateral region in 1 AT, and left anteroseptum in 2 ATs. These findings suggest that the cells with nodal-type action potentials around both annuli might play an important role in the genesis of AVAT.     

Hybrid Therapy of Radiofrequency Catheter Ablation and Percutaneous Transvenous Mitral Commissurotomy in Patients With Atrial Fibrillation and Mitral Stenosis

AF Ablation and PTMC. Background: The rhythm control of atrial fibrillation (AF) associated with mitral stenosis (MS) is often difficult using antiarrhythmic drugs (AADs), even after a percutaneous transvenous mitral commissurotomy (PTMC). Few studies have examined the efficacy and safety of simultaneously performing radiofrequency catheter ablation (RFCA) and a PTMC in patients with MS and AF. Methods: Twenty consecutive patients with drug‐resistant AF and rheumatic MS underwent RFCA combined with a PTMC (n = 10; persistent AF‐8, long‐lasting [>1 year] persistent AF‐2; RFCA group) or transthoracic direct cardioversion (DC) following a PTMC (n = 10; persistent AF‐7, long‐lasting persistent AF‐3; DC group). In all patients, the mitral valve morphology was amenable to a PTMC, and more than 2 AADs had been ineffective in maintaining sinus rhythm (SR). In the RFCA group, a segmental pulmonary vein isolation (PVI) was performed in the initial 5 patients, and an extensive PVI was performed in the remaining 5. Results: During a mean follow‐up period of 4.0 ± 2.7 years, 8 patients (80%) in the RFCA group were maintained in SR, as compared to 1 (10%) in the DC group (hazard ratio, 0.16; 95% confidence interval, 0.03 to 0.75; P = 0.008 by the log‐rank test). The prevalence of the concomitant use of class I and/or class III AADs was comparable between the 2 groups (P = 0.70). No complications occurred during the procedure or follow‐up period in either group. Conclusions: The hybrid therapy using RFCA and a PTMC was safe and feasible, and significantly improved the AF free survival rate compared to DC following a PTMC. (J Cardiovasc Electrophysiol, Vol. 21, pp. 284–289, March 2010)     

Antitumor Activity and Pharmacokinetics of Estra-1,3,5 (10)-Triene-3,17{beta}-Diol, 3-Benzoate, 17-((4-(4-(Bis (2-Chioroethyl)Amino)Phenyl)-1-Oxobutoxy) Acetate) (Bestrabucil) in Human Tumor Xenografts Serially Transplanted into Nude Mice

Bestrabucil (KM2210), the benzoate of an estradiol-chlorambucilconjugate, was used experimental cancer chemotherapy against13 human tumor xenografts serially transplanted into nude mice,and its pharmacokinetics was studied. The tumors were one esophageal,two gastric, six colon, one cholecystic and three breast carcinomas.Two tumor tissue fragments approximately 3x3x3 mm were inoculatedinto BALB/cA nude mice, which were then treated with KM2210at doses of 100, 200 and 300 mg/Kg/day orally starting 24 hrafter the transplantation or when the tumor reached a weightof 100–300 mg. The concentration of KM2210 and its derivativesin the tumor xenografts, normal muscular tissue and blood wereassayed by high performance liquid chroma-tography. Six out of 13 xenografts were found to be sensitive to KM2210.The concentrations of KM2210 and its derivatives in the tumortissues of the sensitive xenografts were five to 10 times higherthan those in blood and muscular tissue, and the antitumor activitycorrelated well with the area under the curve of active metabolitesof KM2210 in the tumor.     

Primary gastrointestinal stromal tumor in the retroperitoneum

Abstract  Gastrointestinal stromal tumor (GIST) is the most frequent non-epithelial neoplasm in the gastrointestinal tract. GIST has received much attention both for its clinical significance and biological nature, while the retroperitoneal condition identical to GIST has been rarely described. Presented herein is a case of GIST arising from the retroperitoneum in a 67-year-old man. The solid tumor measuring 4 cm was uncovered in the retroperitoneum, between the abdominal aorta and inferior vena cava, on computed tomography. The patient underwent surgical excision of the tumor. Histological examination showed proliferating spindle cells in the clearly demarcated tumor; immunoreactivity for Kit and CD34 in tumor cells confirmed the diagnosis of GIST. The histological origin of GIST is suggested to be gastrointestinal pacemaker cells, because they share specific immunoreactivity for CD117/Kit, which is also relevant to pathogenesis of GIST. The present case was a rare primary GIST in the retroperitoneum with typical immunopathological features.     

Long-term effect of α-glucosidase inhibitor on late dumping syndrome

Dumping syndrome commonly occurs after gastrectomy. The late dumping, which is one of the dumping syndromes, is due to postprandial hypoglycaemia caused by an excessive insulin secretion after a sharp rise in plasma glucose. Several treatments, including operation, dietary fibre and somatostatin, have been attempted to relieve dumping symptoms. These treatments take effect through modulation of plasma insulin and glucose levels, but their efficacy is still under consideration. α-Glucosidase inhibitor attenuates the postprandial increase of plasma glucose levels and is widely used for treatment of non-insulin-dependent diabetes mellitus (NIDDM). The acute effect of α-glucosidase inhibitor on late dumping syndrome has been reported by some studies with test meals. The purpose of this study was to evaluate a long-term effect of α-glucosidase inhibitor treatment with ordinary meals in late dumping patients with NIDDM because administration of α-glucosidase inhibitor is only ethically allowed for diabetic patients in Japan. Six late dumping patients with NIDDM were orally administered α-glucosidase inhibitor, acarbose (50 or 100 mg), three times a day before each meal for 1 month. Diurnal changes of plasma glucose, insulin and pancreatic glucagon levels were compared before and after the α-glucosidase inhibitor treatment. All patients had late dumping-related symptoms, such as weakness, palpitation and dizziness before the induction of α-glucosidase inhibitor treatment. Patients suffered from a rapid fall in plasma glucose levels from hyperglycaemia at the same time as dumping symptoms. These late dumping-related symptoms disappeared and a rapid change of plasma glucose and insulin levels were attenuated after the α-glucosidase inhibitor treatment. These data suggest a long-term therapeutic efficacy of α-glucosidase inhibitor for late dumping patients.     

AP-811, a novel ANP-C receptor selective agonist

AP-811 is a derivative of the Phe8-Ile15 region of atrial natriuretic peptide (ANP) and is one of the smallest linear ligands for ANP receptors. The binding and agonist activities of AP-811 have been compared with those of other ANP analogs for the ANP-A and ANP-C receptors. AP–811 binds with a high binding affinity to and is a strong agonist for the ANP-C receptor, indicating that the binding and agonist sites for this receptor are the same or near each other in the ANP sequence. In contrast, AP-811 showed no agonistic effect for the ANP-A receptor, although it could bind to this receptor. Comparing the biological activities of AP-811 with those of other ANP analogs, we propose that the binding and agonist sites for the ANP-A receptor may consist of separate regions of ANP. In conclusion, AP-811 is the smallest C-receptor-selective agonist.     

Microscopic venous invasion in renal cell carcinoma as a predictor of recurrence after radical surgery

BACKGROUND: The objective of the present study was to investigate the significance of microscopic venous invasion (MVI) as a prognostic factor for patients with renal cell carcinoma (RCC) who underwent radical surgery. METHODS: The study included a total of 157 consecutive patients with non-metastatic RCC who underwent radical surgery between January 1986 and December 2002. The median follow-up period was 45 months (range 6-162 months). Microscopic venous invasion was defined by the presence of a cancer cell in blood vessels based on the examination of hematoxylin-eosin stained specimens. Other prognostic variables were assessed by multivariate analysis to determine whether there was a significant impact on cancer-specific and recurrence-free survivals. RESULTS: Microscopic venous invasion was found in 70 patients, and of this number, 17 (24.7%) developed a tumor recurrence and 12 (17.1%) died of cancer progression, while only six (6.9%) of the remaining 87 patients without MVI presented with disease-recurrence and three (3.5%) died of cancer. Among the factors examined, the presence of MVI was significantly associated with age, mode of detection, tumor size, pathological stage and tumor grade; however, only pathological stage was an independent predictor for disease-recurrence, and none of these factors were available to predict cancer-specific survival in multivariate analyses. In 120 patients with pT1 or pT2 disease, MVI was noted in 36 patients. In this subgroup, recurrence-free survival rates in patients with MVI were significantly lower than those in patients without MVI, and MVI was the only independent prognostic predictor for disease-recurrence in a multivariate analysis. CONCLUSION: Microscopic venous invasion is not an independent prognostic factor in patients with non-metastatic RCC who underwent radical surgery; however, it could be the only independent predictor of disease-recurrence after radical surgery for patients with pT1 or pT2 disease.     

Importance of mechanical damage to urinary red blood cells by the glomerular basement membrane

The reasons for morphological changes of urinary red blood cells (RBC) in patients with glomerulonephritis are still controversial. In order to evaluate the importance of mechanical damage by the glomerular basement membrane (GBM), we examined urinary RBC taken from the patients with two different diseases which have characteristic GBM changes. Urinary RBC taken from 20 patients with Alport syndrome and nine with thin GBM disease were examined using a scanning electron microscope. Nineteen out of the 20 patients (95.0%) with Alport syndrome showed ‘glomerular type’, while five of the nine patients (55.6%) with thin GBM disease showed ‘glomerular type’. These results suggest that more complicated GBM abnormalities cause more severe RBC distortion. Therefore, we conclude that mechanical damage by the GBM may be the major factor in dysmorphism of urinary RBC.