A new mutation in the POU3F4 gene in a japanese family with x-linked mixed deafness (DFN3)

Objective: The molecular defect in patients with X-linked mixed deafness showing a perilymphatic gusher at stapedectomy (DFN3) has been attributed to mutations in the POU3F4 gene. This study aimed to clarify an allelic variant of this gene. Study Design: This was a genetic study of a single Japanese family with DFN3. Methods: Products of a polymerase chain reaction (PCR) were subjected to single-strand conformation polymorphism (SSCP) analysis. Direct sequencing of PCR products from patients and carriers showing SSCP variants was performed using the fluorescent dideoxy termination method and a sequencer. Results: Sequencing of the PCR product revealed a 6-base deletion (TTCAAA) at nucleotides 601 to 606, resulting in a two-amino-acid deletion in the POU3F4 protein, (phenylalanine and lysine at amino acid residues 201 and 202). The deletion was adjacent to the site of a nonsense mutation previously described. Conclusion: Microdeletions at a previously undescribed location account for some clinically important POU3F4 mutations. Laryngoscope, 108:1544–1547, 1998     

Analyses of mutation and loss of heterozygosity of coding sequences of the entire transforming growth factor beta type II receptor gene in sporadic human gastric cancer

Mutations in the transforming growth factor beta type II receptor (TGFbetaRII) gene have been detected in several human cancer types exhibiting microsatellite instability. Using intron primers previously reported for examination of the entire coding region of the TGFbetaRII gene, 29 sporadic gastric cancers were screened with non-radioactive single strand conformation polymorphism and subsequent DNA sequencing analysis. Mutations of the TGFbetaRII gene were detected in three out of 29 tumors (10%). Two cases showed deletions in a polyadenine tract in both alleles and was positively associated with replication error. One case had an insertion of GA dinucleotide sequence in one allele. Mutations of the TGFbetaRII gene were restricted to exon 3 and other coding regions were not affected. Loss of heterozygosity was detected by analyzing a polymorphic site in intron 2. Three out of nine (33%) informative cases, which were all of intestinal type and advanced cases, showed loss of heterozygosity but neither TGFbetaRII mutation nor replication error was found in these cases. Immunoreactivity of TGFbetaRII in tumor tissues was reduced to a different extent in the gastric cancer with genetically abnormal transforming growth factor. Although the numbers studied are small, homozygous (A)10 deletion or loss of heterozygosity of TGFbetaRII is involved in tumorigenesis and progression of at least some part of sporadic gastric cancer.      

Entire septal patch technique for postinfarction ventricular septal rupture

Postinfarction ventricular septal rupture is still a surgically challenging situation with high operative mortality. We report a case of ventricular septal rupture in a 75-year-old woman successfully treated with our newly devised technique, in which a pliable large septal path is fixed with transmural sutures placed in posterior left ventricular free wall and anterior ventriculotomy closing sutures, thus covering the septal wall almost entirely. Our method may simplify the operation and reduce the risk of residual leakage.     

Indocyanine green (TCG) clearance as a monitor to evaluate right heart function

Systemic venous return to the heart is disturbed as a result of right heart failure. ICG clearance is known to be influenced by hepatic venous return to the right atrium. Under a hypothesis that right heart function could be evaluated by ICG clearance test, patients with mitral valve disease (Group M, n = 29), aortic valve disease (Group A, n = 16), ischemic heart disease (Group CABG, n = 19) were studied. Preoperative K-ICG (normal range > 0.17) in the Group M was significantly lower than those in the Group A and Group CABG (0.097 +/- 0.037 vs 0.166 +/- 0.032 and 0.171 +/- 0.027, p < 0.05). In the Group M, patients who underwent tricuspid annuloplasty (TAP) had significantly lower K-ICG than the others (0.077 +/- 0.026 vs 0.113 +/- 0.038, p < 0.05). Postoperatively, K-ICG of TAP patients significantly increased (0.092 +/- 0.031, p < 0.05) when compared to their preoperative value. ICG clearance test was useful to quantify the right heart function, especially in the postoperative evaluation.     

Metabolism of 2- and 3-tert-butyl-4-hydroxyanisole (2- and 3-BHA) in the rat. (II): Metabolism in forestomach and covalent binding to tissue macromolecules

The mechanism of action of 2(3)-tert-butyl-4-hydroxyanisole (2-BHA or 3-BHA) on rat forestomach epithelium was studied by examining the metabolites of BHA in the stomach and the covalent binding of BHA to macromolecules in the forestomach epithelium. Male F344 rats 6 weeks old were given a single intragastric injection of 1 g/kg body wt of [tert-14C]-3-BHA (Bu-3-BHA) or [methyl-14C]-3-BHA (Me-3-BHA), and 6 h later BHA metabolites in the forestomach, glandular stomach and stomach contents were examined by thin-layer chromatography. No significant amounts of metabolites were detected in the forestomach or glandular stomach epithelium and almost all the radioactivity in these tissues was extracted with organic solvents. In in vitro experiments also, no significant amounts of metabolites were detected when the 9000 g supernatant of the forestomach or glandular stomach epithelium, or gastric juice was incubated with Bu-3-BHA in the absence or presence of NADPH. In binding studies, rats were given Bu-3-BHA, [tert-14C]-2-BHA (Bu-2-BHA), Me-3-BHA or [methyl-14C] butylated hydroxytoluene (Me-BHT) intragastrically at a dose of 1 g/kg body wt with or without pretreatment with unlabelled 1% 3-BHA or BHT in the diet for 6 days. Six hours after treatment with a labelled compound, the rats were sacrificed and the DNA, RNA and protein of their forestomach, glandular stomach, liver and kidney were isolated. Bu-3-BHA, Bu-2-BHA and Me-3-BHA did not bind covalently to forestomach DNA or RNA, and the amounts of radioactivity of these compounds bound to proteins in the 4 tissues were similar. These findings suggest that BHA acts on the forestomach epithelium directly without metabolic activation, and that its action is not related to its binding to DNA or RNA.     

Effects of tranexamic acid on coagulofibrinolytic markers during the early stage of severe trauma: A propensity score–matched analysis

Tranexamic acid (TXA) reduces the risk of bleeding trauma death without altering the need for blood transfusion. We examined the effects of TXA on coagulation and fibrinolysis dynamics and the volume of transfusion during the early stage of trauma. This subanalysis of a prospective multicenter study of severe trauma included 276 patients divided into propensity score–matched groups with and without TXA administration. The effects of TXA on coagulation and fibrinolysis markers immediately at (time point 0) and 3 hours after (time point 3) arrival at the emergency department were investigated. The transfusion volume was determined at 24 hours after admission. TXA was administered to the patients within 3 hours (median, 64 minutes) after injury. Significant reductions in fibrin/fibrinogen degradation products and D-dimer levels from time points 0 to 3 in the TXA group compared with the non-TXA group were confirmed, with no marked differences noted in the 24-hour transfusion volumes between the 2 groups. Continuously increased levels of soluble fibrin, a marker of thrombin generation, from time points 0 to 3 and high levels of plasminogen activator inhibitor-1, a marker of inhibition of fibrinolysis, at time point 3 were observed in both groups. TXA inhibited fibrin(ogen)olysis during the early stage of severe trauma, although this was not associated with a reduction in the transfusion volume. Other confounders affecting the dynamics of fibrinolysis and transfusion requirement need to be clarified.     

A case of successful management of nonresectable advanced cholangiocellular carcinoma by intermittent hepatic arterial infusion at home

An 82-year-old female was referred to our hospital because a 16 x 8 cm tumor detected in her liver by abdominal ultrasonography (echo, hereafter) and CT. The patient was diagnosed as having highly advanced cholangiocellular carcinoma (CCC) by abdominal angiography. Since excision of the tumor was impossible due to the patient's age, a reservoir was indwelled for intra-arterial injection into the liver. Continuous injection of 1,000 mg 5-FU over 24 hours was performed every 2 weeks using a portable disposable pump 70 times. The tumor has been markedly reduced since the start of chemotherapy, with a reduction rate (PR) of 98% over the 3 years until the present. Since the frequency of administration was low, only twice a month, the patient had few side effects despite her old age, and injections could be performed in the outpatient department. Usually, the prognosis for CCC is poor. However, the patient has maintained a good QOL with the periodic intra-arterial injection of the carcinostatic into the liver, and this treatment has had a strong antitumor effect. This chemotherapy is thus considered useful for CCC which can not be resected.     

Advantages of Using Both Voxel- and Surface-based Morphometry in Cortical Morphology Analysis: A Review of Various Applications

Surface-based morphometry (SBM) is extremely useful for estimating the indices of cortical morphology, such as volume, thickness, area, and gyrification, whereas voxel-based morphometry (VBM) is a typical method of gray matter (GM) volumetry that includes cortex measurement. In cases where SBM is used to estimate cortical morphology, it remains controversial as to whether VBM should be used in addition to estimate GM volume. Therefore, this review has two main goals. First, we summarize the differences between the two methods regarding preprocessing, statistical analysis, and reliability. Second, we review studies that estimate cortical morphological changes using VBM and/or SBM and discuss whether using VBM in conjunction with SBM produces additional values. We found cases in which detection of morphological change in either VBM or SBM was superior, and others that showed equivalent performance between the two methods. Therefore, we concluded that using VBM and SBM together can help researchers and clinicians obtain a better understanding of normal neurobiological processes of the brain. Moreover, the use of both methods may improve the accuracy of the detection of morphological changes when comparing the data of patients and controls.In addition, we introduce two other recent methods as future directions for estimating cortical morphological changes: a multi-modal parcellation method using structural and functional images, and a synthetic segmentation method using multi-contrast images (such as T1- and proton density-weighted images).     

No survival benefit from combined pancreaticosplenectomy and total gastrectomy for gastric cancer

BACKGROUND: It remains unknown whether extended surgery improves the survival rate of patients with gastric cancer. This study was a review of combined pancreaticosplenectomy with total gastrectomy for gastric cancer. METHODS: The clinicopathological details of 190 patients who underwent combined pancreaticosplenectomy with total gastrectomy between 1969 and 1996 were compared retrospectively with those of 206 patients who underwent total gastrectomy with splenectomy alone. RESULTS: There was no statistical difference in the survival rate when pancreaticosplenectomy was added to total gastrectomy. The mortality rate was similar, but the morbidity rate was higher in patients who had pancreaticosplenectomy. Six patients who had direct pancreatic invasion and two thought to have involved lymph nodes along the splenic artery survived for more than 5 years after operation. In the latter group, the metastatic lymph nodes along the splenic artery could have been resected without pancreatectomy. CONCLUSION: Since a combined pancreaticosplenectomy adds no survival advantage to total gastrectomy for gastric cancer, this procedure should no longer be regarded as routine.     

The usefulness of transcatheter arterial embolization for patients with blunt polytrauma showing transient response to fluid resuscitation

BACKGROUND: This study aimed to determine whether nonsurgical management using transcatheter arterial embolization (TAE) is safe for patients with blunt multiple trauma who transiently respond to the initial fluid resuscitation. METHODS: Contrast computed tomography was performed for patients with blunt abdominal injuries, excluding those who did not respond to initial fluid resuscitation. Angiography was performed for patients with injuries showing contrast extravasation or solid organ injury classified, according to the American Association for the Surgery of Trauma, as grade 3 or higher on computed tomography. Transcatheter arterial embolization was performed when angiography showed arterial extravasation. The protocol was abandoned for any patients who became profoundly hypotensive (with systolic blood pressure 60 mm Hg or lower) during computed tomography or angiography. RESULTS: Between January 2000 and December 2002, 269 patients with blunt abdominal injuries underwent TAE immediately after admission. Of these patients, 41 had injuries in at least two regions and underwent TAE for these regions. Among them, 22 patients were hemodynamically stable or showed rapid response to fluid resuscitation. The nonsurgical treatment was successful in all these cases. The remaining 19 patients (Injury Severity Score, 37.3 +/- 8.2), who showed a transient response, were the subjects of this study. Of these patients, 15 underwent TAE for injuries in two regions (13 pelvic fractures, 7 splenic injuries, 6 hepatic injuries, 3 facial bleeding, and 1 renal injury), and 4 patients underwent TAE for injuries in three regions (4 had splenic injuries, 3 hepatic injuries, 2 renal injuries, 2 pelvic fractures, and 1 facial bleeding). For all these patients, TAE was successfully performed. Before TAE, the systolic blood pressure was 79.9 +/- 8.4 mm Hg, and the shock index was 1.45 +/- 0.25 mm Hg. After TAE, the corresponding values were 120.6 +/- 19.3 mm Hg and 0.87 +/- 0.16 mm Hg, respectively (p < 0.001). The rate of fluid administration required after TAE (214.2 +/- 139.3 mL/hour) was significantly less than that required before TAE (1244.2 +/- 347.1 mL/hour; range, 632-1,728 mL/hour) (p < 0.001). The deaths of two patients were classified as nonpreventable on the basis of the Trauma and Injury Severity Score (TRISS), and their respective probabilities of survival were determined to be 0.13 and 0.03. CONCLUSION: Nonsurgical management using TAE can be performed safely even for patients with blunt multiple trauma who are in hemorrhagic hypotension if their hemodynamics are improved by resuscitation with 2 L of fluid.