A comparison of sudden near maximal exercise test (dash method) and Bruce protocol for pediatric patients

We examined 24 pediatric patients to evaluate the usefulness of sudden near maximal exercise test (dash method), where the subjects began to run at Bruce protocol of the last stage. 1) No considerable differences between two protocols were found in maximal oxygen consumption (V O2max), maximal heart rate (HRmax), maximal systolic blood pressure, and findings of electrocardiography. 2) The sudden maximal exercise test could be completed during a shorter period compared to Bruce protocol. 3) The sudden maximal exercise protocol reached 84% of HRmax and 47% of V O2max at one minute after the onset of the protocol, and produced 96% of HRmax and 89% of V O2max at two minutes after the onset. We considered that sudden maximal exercise protocol was useful to obtain a response similar to Bruce protocol at maximal exercise within a short period. We have to pay attention to the safety of the patients because their cardiopulmonary response to sudden maximal exercise protocol is dramatic.     

Anesthetic management of a patient with perforated necrotic trachea after radical esophageal cancer surgery

We anesthetized a 69-year-old man with perforated necrotic trachea after radical esophageal cancer surgery. We recognized during the reoperation that necrotizing part of the trachea was perforated from the cricoid cartilage to 2cm above the carina. We ventilated the both lungs successfully without leaks by inserting a double-lumen tube into the trachea after tracheostomy. Postoperatively, the carina and the main bronchi were also necrotized and perforated. We ventilated the both lungs without leaks by inserting two single-lumen tubes into the left and right bronchi separately. But, eventually the distal part of the both bronchi was also necrotized and perforated. Finally, the patient died of respiratory failure due to hypoventilation on the 7th day after the re-operation. We should remember this type of emergency complication after radical esophageal cancer surgery.     

Impact of multiple malignancies on surgical outcomes in patients with 1 cm or smaller non-small cell lung cancer

Background

Because most patients with small-sized non-small cell lung cancer (NSCLC) are asymptomatic, their lesions are detected by cancer screenings or routine checkups for other diseases. Incidences of multiple malignancies have been reported to be 27% in patients with stage I–III NSCLC. Some patients have treatment histories for other malignancies, and their small-sized NSCLC was incidentally detected during follow-up. There is no established report regarding the influence of multiple malignancies on small-sized NSCLC prognosis. Therefore, we investigated the correlation between multiple malignancies and surgical outcomes in patients with small-sized NSCLC.

Methods

In total, 44 patients underwent definitive pulmonary resection for NSCLC of 1 cm or smaller between January 2003 and December 2012. Tumor size was measured by macroscopic findings of the resected specimens, and we then retrospectively investigated their clinical courses.

Results

One patient had hemoptysis symptoms, whereas 43 patients were asymptomatic; among them, NSCLC was detected by examinations for other diseases in 31 patients and by cancer screening in 12 patients. In total, 20 patients (45%) had multiple malignancies. The median follow-up period was 68 months. One patient had a recurrence from current NSCLC. No patients died of current NSCLC. The overall 5-year survival rate was 90% for all patients. Patients with multiple malignancies had significantly poorer prognoses compared with those without multiple malignancies (P = 0.016). However, patients with treatment intervals of more than 5 years had prognoses equivalent to those of patients without multiple malignancies (P = 0.829). Only the presence of multiple malignancies was a significantly poor prognostic factor in univariate and multivariate analyses.

Conclusion

NSCLC of 1 cm or smaller showed good prognoses. The presence of multiple malignancies was a significantly poor prognostic factor, and short treatment intervals also correlated with poor prognosis.

     

The Rat Urinary Bladder as a New Target of Heterocyclic Amine Carcinogenicity: Tumor Induction by 3-Amino-l-methyl-5H-pyrido[4,3-β]indole Acetate

In order to examine the carcinogenicity of 3-amino-l-methyl-5 H -pyrido[4,3-β]indole acetate (Trp-P-2), 30 male and 30 female F344 rats were maintained on diet containing 0, 30, or 100 ppm Trp-P-2 for 112 weeks. The overall mean chemical intakes in the 100 ppm and 30 ppm groups were 3.84 and 1.14 mg/kg/day in males, and 4.57 and 1.34 ing/kg/day in females, respectively. Females of the 100 ppm group showed increased mortality in the late period of the study. In the 100 ppm group, significant increases in the incidences of neoplastic lesions were found in the liver, urinary bladder and mammary gland in males, and in the mammary gland, hematopoietic system and clitoral gland in females. Histologically, tumors induced by Trp-P-2 were hepatocellular adenomas, transitional cell tumors (papillomas and carcinomas) of the urinary bladder, fibroadenomas/fibromas of the mammary gland, malignant lymphomas and clitoral gland tumors (adenomas and adenocarcinomas). These results indicate multi-target carcinogenicity of Trp-P-2 in F344 rats and provide evidence that the urinary bladder is also a target for heterocyclic amine action.     

Sudden cardiac death in childhood

To evaluate the mechanism of sudden death in childhood and the physical activity levels at the onset of sudden death, we studied the following items: (1) the incidence and the circumstances surrounding sudden death at school in Kanagawa Prefecture, (2) high risk heart diseases detected among healthy school children by heart disease screening, (3) sudden cardiac death or near miss seen in outpatients with heart disease except congenital heart disease. Among total 15,156,346 school children, sudden death was observed in 97 subjects (M:77, F:20). Annual incidence of sudden death was 6.4 per 10(6). Of the 97 subjects, acute heart failure of unknown etiology was found in 60 (62%), cardiovascular disease in 18 (19%), cerebral vascular accidents in 14 (14%) and heat stroke in 5 (5%). Of the 78 subjects (M:64, F:14) considered as sudden cardiac death, 62 (79%) died during sports activities, and 16 (21%) died at rest. Of the 62 subjects, 29 died during track and field activities and 7 while swimming, both in physical education classes. Eighteen died during athletic club activities and 8 during extracurricular activities. Consequently, 54 subjects (87%) died in the presence of a school teacher. Of the 18 subjects with cardiovascular disease, 9 (hypertrophic cardiomyopathy in 3, myocarditis in 3, Kawasaki disease in 2 and long QT in one) were diagnosed initially by the autopsy study. Latent high risk heart diseases, detected among presumably healthy school children by the heart disease screening program, were the following: hypertrophic cardiomyopathy, long QT syndrome, Kawasaki disease and some arrhythmias (ventricular tachycardia, sick sinus syndrome, A-V block and atrial fibrillation). Follow-up observations of outpatients with heart disease revealed the same results as the heart disease screening program. In order to prevent sudden death at school, the following recommendations should be observed: 1) sports directors should learn "sports medicine in childhood", including primary cardiovascular resuscitation, 2) an accurate heart disease screening program should be operated to detect latent high risk heart diseases, advise on adequate medical treatment, and help ensure an appropriate selection of sports activities, 3) comprehensive autopsy studies should be performed.     

Increased brain serotonin synthesis in migraine.

OBJECTIVE: To measure brain serotonin synthesis with PET using the tracer alpha-[11C]methyl-L-tryptophan in migraine patients. BACKGROUND: Although the cause of migraine remains poorly understood, there is considerable evidence to support a role of the neurotransmitter serotonin in the pathophysiology of migraine. METHODS: We studied 11 women (aged 33+/-7.7 years) with a diagnosis of migraine according to International Headache Society criteria and 8 healthy women (aged 29+/-9.2 years). Five patients were studied before and after chronic treatment with propranolol or nadolol. RESULTS: Serotonin synthesis capacity (K-complex) values in migraine patients were higher than those measured in controls throughout the brain (p = 0.016); mean K-complex for whole brain was 0.0077 + 0.0020 mL/g/min in patients with migraine and 0.0054+/-0.0003 mL/g/min in controls. The regional pattern did not differ between the two groups. However, the K-complex for whole brain in the subgroup of migraine patients with aura (n = 3) did not differ from that of the control group (p = 0.32). In the five patients studied twice (before and after treatment), we found a trend of increased whole-brain K-complex after drug treatment (p = 0.06). CONCLUSIONS: Our findings indicating increased brain serotonin synthesis capacity in migraine patients are consistent with previous reports of systemic alteration of serotonin metabolism in patients without aura. Our results also suggest that the mechanism of action of beta-adrenergic antagonists for migraine prophylaxis may involve regulation of serotonin synthesis.     

Carotid atherosclerosis,cytomegalovirus infection,and cognitive decline in the very old: a community-based prospective cohort study

To investigate various risk factors of cognitive decline in the very old, we studied 494 subjects over 85 years old without diagnosis of dementia at baseline from the Tokyo Oldest Old Survey on Total Health, an ongoing, community-based cohort in Japan. Cognitive function was assessed at baseline and at 3-year follow-up using Mini-Mental State Examination (MMSE). Plasma samples were assayed for levels of cytomegalovirus (CMV) immunoglobulin G (IgG) antibodies, tumor necrosis factor-alpha, interleukin-6, and blood chemistry. Carotid artery plaques were measured using an ultrasonography. In the cross-sectional analyses using Tobit regression, individuals with high carotid artery plaque score (≥5.0) had MMSE scores that were 1.08 points lower compared to those with no plaque (95 % confidence interval (CI) ?1.95 to ?0.20; p?=?0.016), adjusted for age, sex, and education. Individuals with CMV IgG titers in the highest quartile had MMSE scores that were 1.47 points lower compared to individuals in the lowest quartile (95 % CI ?2.44 to ?0.50; p?=?0.003). CMV and carotid atherosclerosis showed evidence of an interaction, where the association between CMV and MMSE was present only in subjects with carotid artery plaque. In the longitudinal analyses using linear regression, carotid atherosclerosis, smoking, low grip strength, and poor activities of daily living (ADL) status were associated with faster cognitive decline, adjusted for age, sex, education, and baseline cognitive function. Our findings suggest that carotid atherosclerosis is consistently associated with low cognitive function in the very old and modifies the association between latent CMV infection and cognition.     

Who is at risk for cardiac events in young patients with long QT syndrome?

The objective of this study was to determine who is at risk for cardiac events among young patients with long QT syndrome (LQTS) with or without a past history of LQTS-related cardiac events. The subjects were young patients with LQTS who had visited one of 36 hospitals from January 1997 to August 2000 in Japan. To predict the risk factors for cardiac events, stepwise regression analyses were performed for a total of 197 cases. There were 7 of 129 cases (5%) without a past history and 32 of the 68 (47%) cases with a past history of LQTS-related cardiac events that experienced new events after diagnosis (p<0.0001). Patients with a family history showed a higher incidence of symptoms both before and after diagnosis than patients with sporadic occurrence. Analyses revealed that noncompliance with medication and a lower age at diagnosis were significant predictors for the group with a past history. A negative predictive value <4 points was 100% in the group without a past history. To prevent future cardiac events, compliance with medication must be improved in those with a past history. A total LQTS score <4 points was useful to predict the absence of cardiac events in the group without a past history.     

TMPRSS11D and TMPRSS13 Activate the SARS-CoV-2 Spike Protein

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) utilizes host proteases, including a plasma membrane-associated transmembrane protease, serine 2 (TMPRSS2) to cleave and activate the virus spike protein to facilitate cellular entry. Although TMPRSS2 is a well-characterized type II transmembrane serine protease (TTSP), the role of other TTSPs on the replication of SARS-CoV-2 remains to be elucidated. Here, we have screened 12 TTSPs using human angiotensin-converting enzyme 2-expressing HEK293T (293T-ACE2) cells and Vero E6 cells and demonstrated that exogenous expression of TMPRSS11D and TMPRSS13 enhanced cellular uptake and subsequent replication of SARS-CoV-2. In addition, SARS-CoV-1 and SARS-CoV-2 share the same TTSPs in the viral entry process. Our study demonstrates the impact of host TTSPs on infection of SARS-CoV-2, which may have implications for cell and tissue tropism, for pathogenicity, and potentially for vaccine development.