Effect of cardiac resynchronization therapy in isolated ventricular noncompaction in adults: follow-up of four cases

Background: An isolated ventricular noncompaction (IVNC) is an unclassified cardiomyopathy and, despite the increasing awareness of and interest in this disorder, the role of cardiac resynchronization therapy (CRT) remains obscure. Objective: The purpose of this study was to clarify the long‐term effect of CRT on IVNC in adult patients. Methods: Four cases of IVNC were included in this study. Before the CRT device was implanted, all four patients (54 ± 16‐year‐old, 4 males) presented with symptomatic congestive heart failure. Echocardiography revealed their systolic dysfunction and their left ventricular ejection fraction (LVEF) was 21 ± 8%. There was also mechanical dyssynchrony observed between the LV septum and free wall area. The QRS duration was “narrow” (112 and 120 ms) in two patients. One patient had been resuscitated from ventricular fibrillation (VF) and two had nonsustained ventricular tachycardia (VT). A CRT defibrillator (CRT‐D) was implanted in three patients with VT/VF and a CRT pacemaker (CRT‐P) in a patient without VT/VF. The LV lead was positioned in a lateral branch of the coronary sinus where a thickened noncompacted wall existed. Results: During the follow‐up period (28 ± 23 months), their congestive heart failure had improved in terms of the cardiothoracic ratio on the chest X‐ray, B‐type natriuretic peptide level, LV systolic dimension, and LVEF. No episodes of defibrillation shocks were observed. Conclusion: CRT may improve the prognosis and quality‐of‐life in patients with an IVNC with mechanical dyssynchrony.     

Severity factors of Mamushi (Agkistrodon blomhoffii) bite

The factors determining the severity of a Mamushi ( Agkistrodon blomhoffii ) bite were analyzed based on the findings of our 34 cases and those appearing in the published work. It was not possible to forecast the final severity at the time of the patient's arrival and by the initial blood examination data. The maximal creatinine kinase (CK) values elevated proportionally with the time from the bite, and the relation approximated the equation of y = 300χ, where y represents the maximal CK value and χ indicates the time from the bite to the peak of CK level. In the severe cases which required intensive care, the level of the CK deviated remarkably from this line, and could be grossly distinguished from the non-severe cases. The maximal white blood cell (WBC) count also gradually increased in concordance with the time from the bite, and in addition, the WBC count of most of the severe cases exceeded 20 000/µL. This evidence suggests that the rate of the CK value elevation in relation to the time from the bite can be a useful indicator of the severity of a Mamushi bite, and the WBC count also reflects the severity.     

Myxoid leiomyosarcoma of hte esophagus

A 34-year-old male patient with epigastralgia was found to have an esophageal submucosal tumor based on an endoscopic evaluation 6 years previously. Because an unusual appearance composed of a heterogenous solid area and a cyst area on the endoscopic ultrasonogram and the increased size of the tumor on esophagograms over the past 3 years were suggestive of a malignant character, an operation was thus indicated. The tumor, which measured 3.5 × 2.5 × 2.0 cm in size, was enucleated using videoassisted thoracic surgery and was diagnosed to be a very rare myxoid leiomyosarcoma with a thorough pathologic examination. To our knowledge, this is only the second case of esophageal myxoid leiomyosarcoma reported in the literature. We thus consider this case, which demonstrated an unique appearance on an endoscopic ultrasonogram, to possibly be beneficial to the overall diagnostic analysis of esophageal submucosal tumors.     

Mid-term report on the project "Disaster nursing in a ubiquitous society" in the academic years 2003 and 2004

Aim: This is the mid‐term report of the project titled “Disaster nursing in a ubiquitous society”, funded by the Japanese Government. The purpose of this project is to develop the self‐care abilities of communities and individuals to independently regenerate and recover from the consequences of disasters. Methods: The methods utilized in this project were questionnaires sent by post or placed on websites, and interviews. The participants in our research were people with special needs in the case of a disaster, nursing professionals, ordinary people, and other professionals. Results: During 2003 and 2004, there were activities that progressed according to the original plans, activities that progressed at a faster rate than foreseen in the original plans, and newly expanded research activities that were conducted. New academic knowledge gained from the project activities includes five factors for disaster preparedness, six common issues related to health, care, training, and others, six categories of necessary factors in nursing activities, the clarification of the support needs of care‐providers, and the clarification of specific groups with unique needs including children, pregnant and postpartum women, elderly people, people with chronic conditions, cancer patients, and care‐providers. Conclusions: The growing recognition of our center as a global base of disaster nursing is indicated by the fact that we receive numerous requests from Japan and abroad, that our suggestions influence some governmental policies, and that we take initiatives in promoting the concept of disaster nursing throughout the world. It is necessary to disseminate the results of this project, to develop further knowledge, to clarify future challenges related to disasters, and to contribute to the preparedness of people and communities.     

Postoperative changes in acute phase protein in patients with esophageal cancer]

Thirty-three patients with esophageal cancer were studied to assess the relationship between nutritional state and the acute phase protein responses. Blood samples taken preoperatively and days 1, 4, 7 and 14 after operation were analyzed for C-reactive protein, fibrinogen, alpha 1-antitrypsin, alpha 1-acid glycoprotein and haptoglobin. Significant Spearman's coefficients were found between percent of ideal body weight (IBW) and alpha 1-acid glycoprotein (r = -0.42), between prealbumin and alpha 1-anti-trypsin (r = -0.55), and between retinol-binding protein and alpha 1-antitrypsin (r = -0.51). Postoperatively, the levels of C-reactive protein, fibrinogen, alpha 1-anti-trypsin and alpha 1-acid glycoprotein were significantly lower in the poorly nourished group than in the other groups. The changes of acute phase proteins in the immediate postoperative period were affected by the preoperative nutritional state, and were less marked in the poorly nourished patients. Between two groups of patients in whom lymph node dissection was carried out in 2 or 3 areas, no significant differences were observed in the acute phase protein responses postoperatively. The measurement of acute phase proteins is very important in assessing the body defense capacity of the patient, but it should be noted that the changes may be affected by several factors including malnutrition.     

MAD1 (mitotic arrest deficiency 1) is a candidate for a tumor suppressor gene in human stomach

Mitotic arrest deficiency 1 (MAD1) is a component of the spindle checkpoint factors that monitor fidelity of chromosomal segregation. We previously confirmed that the level of MAD1 protein was decreased in gastric carcinoma compared with non-tumoral mucosa by conducting proteome-based analyses (Nishigaki R, Osaki M, Hiratsuka M, Toda T, Murakami K, Jeang KT, Ito H, Inoue T, Oshimura M, Proteomics 5:3205–3213, 29). In this study, an immunohistochemical analysis was performed to examine MAD1 expression histologically in gastric mucosa and tumor. MAD1 was detected in the supranuclear portion of normal epithelial, intestinal metaplasia, and adenoma cells, but its expression was not restricted to any specific area in carcinoma cells. Lower levels of expression were noted in 16 (47.1%) of 34 adenomas and in 52 (60.5%) of 86 carcinomas, whereas all normal mucosae and intestinal metaplasias were grouped into cases with higher level of expression. Moreover, the expression of MAD1 was significantly lower in advanced carcinomas than early carcinomas and in intestinal than diffuse type, respectively (P < 0.05). Exogenous expression of wild-type MAD1, but not the mutant MAD1, inhibited cell proliferation and resulted in G2/M accumulation in MKN-1, a gastric carcinoma cell line. Taken together, our findings suggest that the MAD1 gene could be a candidate tumor suppressor gene and that down-regulation of MAD1 expression contribute to tumorigenesis in human stomach.     

Tracheal Aspirate as an Alternative Biologic Sample for Pharmacogenomics Testing in Mechanically Ventilated Pediatric Patients

Patients in the pediatric intensive care unit are exposed to multiple medications and are at high risk for adverse drug reactions. Pharmacogenomic (PGx) testing could help decrease their risk of adverse reactions. Although whole blood is preferred for PGx testing, blood volume in this population is often limited. However, for patients on mechanical ventilation, tracheal secretions are abundant, frequently suctioned, and discarded. Thus, the aim of this pilot study was to determine if tracheal aspirates could be used as a source of human genomic DNA for PGx testing. We successfully extracted DNA from tracheal secretions of all 23 patients in the study. The samples were successfully genotyped for 10 clinically actionable single nucleotide variants across 3 cytochrome P450 genes (CYP2D6, CYP2C19, and CYP3A5). Using DNA from whole blood samples in 11 of the patients, we confirmed the accuracy of the genotyping with 100% concordance. Therefore, our results support the use of tracheal aspirates from mechanically ventilated children as an adequate biospecimen for clinical genetic testing.

Children admitted to the pediatric intensive care unit (PICU) receive an average of 10 different medications per day and receive an average cumulative 20 medications during their stay. ¹ Many of these have clinical guidelines for using pharmacogenomic (PGx) testing to guide the drug choice and/or dose, including voriconazole, selective serotonin reuptake inhibitors, tricyclic antidepressants, and codeine. ² , ³ , ⁴ , ⁵ The US Food and Drug Administration (FDA) has placed genetic testing recommendations and black box warnings on over 100 drug labels, including guidelines on gene‐drug pairs. The Clinical Pharmacogenetics Implementation Consortium (CPIC) has published guidelines for 35 medications with plans for writing over 100 more. ⁶ These initiatives are indicative of the importance of PGx to prescribing practices. The use of PGx has not been routinely utilized in the PICU, but as more evidence and guidelines for PGx‐guided dosing emerges, this could play an important role in the safe delivery of medications to patients in the PICU.The preferred biospecimen for PGx testing is whole blood but saliva and buccal swabs have also been validated and used as an alternative source of DNA. ⁷ , ⁸ , ⁹ , ¹⁰ , ¹¹ However, in small patients, blood volumes can be limited and mechanical ventilation or sedation can impair the collection of saliva or buccal swabs. In pediatrics, most current blood sampling guidelines are not evidence based; so, it is generally recommended to use alternatives to blood to ensure patient safety and maximize clinical benefit. ¹² , ¹³ In addition, blood samples cannot be used for genotyping from children that have had stem cell transplants or recent blood transfusions. Therefore, there is a need to identify an alternative source of DNA that can be used for validating biomarkers in clinical trials and conducting clinical PGx testing.Many patients admitted to the PICU are mechanically ventilated. When they are vented, the patient’s respiratory secretions are frequently suctioned and discarded. As this biological sample is plentiful, easily accessible, and collection is noninvasive, we hypothesized that tracheal aspirates from mechanically ventilated patients could be used as a source of DNA for clinical genotyping. Although one might assume that this would work, there could be too little DNA or it could be to degraded to use for genotyping; so, the feasibility needs to be supported by laboratory data. Thus, the aim of this study was to determine if tracheal aspirates from mechanically ventilated pediatric patients can be used as a source of DNA for PGx testing.