Determination of cobalamin and related compounds in foods.

The microbiological assay of total cobalamin (vitamin B12) by Lactobacillus delbrueckii subsp. lactis ATCC7830 is now used worldwide in food analysis because of its high sensitivity, low running cost, and no expensive instruments. It has been recently reported that some foods contain a substantial number of inactive corrinoid compounds, some of which are active in this bacterium. These results indicate that the microbiological method must be replaced with high-performance liquid chromatography or liquid chromatography/electrospray ionization-tandem mass spectrometry as there can specifically determine biologically active cobalamin. Nowadays, powerful tools, such as immunoaffinity columns, purify cobalamin simply and specifically. In this chapter, we summarized the determination methods of cobalamin and related compounds in foods. Various inactive corrinoids found in foods were also characterized.

Simple statistical inference algorithms for task-dependent wellness assessment.

Stress is a key indicator of wellness in human beings and a prime contributor to performance degradation and errors during various human tasks. The overriding purpose of this paper is to propose two algorithms (probabilistic and non-probabilistic) that iteratively track stress states to compute a wellness index in terms of the stress levels. This paper adopts the physiological view-point that high stress is accompanied with large deviations in biometrics such as body temperature, heart rate, etc., and the proposed algorithms iteratively track these fluctuations to compute a personalized wellness index that is correlated to the engagement levels of the tasks performed by the user. In essence, this paper presents a quantitative relationship between temperature, occupational stress, and wellness during different tasks. The simplicity of the statistical inference algorithms make them favorable candidates for implementation on mobile platforms such as smart phones in the future, thereby providing users an inexpensive application for self-wellness monitoring for a healthier lifestyle.

Health-related quality of life does not predict mortality in idiopathic pulmonary fibrosis.

BACKGROUND: Although health-related quality of life (HRQL) has recently been considered to be an important outcome in clinical trials of idiopathic pulmonary fibrosis (IPF), its relationship with survival is unknown. OBJECTIVE: To determine the prognostic significance of HRQL scores in IPF assessed with the SGRQ. DESIGN: Eighty-seven consecutive patients with IPF, who had undergone evaluations and completed the St. George's Respiratory Questionnaire (SGRQ) at diagnosis were included in this study, as is the general practice. Cox proportional hazards analyses were performed to examine the relationship between HRQL scores and survival. RESULTS: The mean observation period was 44.2 +/- 29.6 mo, in the course of which 54 patients (62.0%) died. Univariate analysis revealed that the activity scores in the SGRQ(HR: 1.016, 95% CI: 1.004-1.029, P = 0.01) were significantly predictive of survival, although the symptoms, impacts, and total scores were not significantly related to mortality from all causes. However, multivariate analysis revealed that only the forced vital capacity percent predicted was a significant predictor of survival, and that the activity score in the SGRQwas not significantly related to mortality. CONCLUSIONS: There was no significant relationship between HRQL evaluated with the SGRQ and the subsequent mortality in IPF. The present negative result might suggest that HRQL is measuring an aspect other than one from physiological and functional impairment or disability.

[Resection of a metastatic left ventricular tumor with an aid of thoracoscopy].

A 61-year-old woman who complained of chest pain and cough was admitted to our hospital. She was diagnosed with multiple metastasis of breast or lung cancer, and a cardiac tumor was detected by echocardiography during chemotherapy. The tumor was located on the papillary muscle near the apex, had a smooth surface, and was well mobile. Emergency operation was performed because the tumor was considered to be a cause of cerebral infarction. Under cardiopulmonary bypass, resection of the tumor was performed by trans-mitral-valve approach. By using a thoracoscope, we could share information and obtain the details of the tumor during the operation. Resection using a trans-mitral-valve approach with an aid of thoracoscopy is considered useful.

From mobile phones to personal wellness dashboards.

The paradigm of wellness mobiles will enable health-care professionals to have access to comprehensive real-time patient data at the point of care and anywhere there is cellular network coverage. More importantly, users can continuously and frequently track their health on the go and receive real-time user assistance when needed to alter their lifestyles. Recently, there has been a growing interest in developing proactive wellness products and health-related smartphone applications. However, developing quantifiable measures of wellness for continuous tracking and designing compliant-monitoring systems is quite challenging. This article motivates future research in this emerging field by presenting a ringside view of the recent developments and trends favoring this technology and the challenges facing the next generation of telemedicine.

A simple assessment of dyspnoea as a prognostic indicator in idiopathic pulmonary fibrosis.

The prognosis in idiopathic pulmonary fibrosis (IPF) is poor. No therapy has been shown to prolong survival. The objective of this study was to examine the prognostic significance of dyspnoea in daily living at baseline in IPF using a simple assessment tool. 93 consecutive patients with IPF, who had undergone evaluation at diagnosis, were included. The level of dyspnoea was assessed using the modified Medical Research Council (MRC) scale. The relationship between data at baseline and survival was examined. A univariate Cox proportional-hazard model showed that forced vital capacity % predicted (hazard ratio (HR) 0.965, 95% CI 0.948-0.982; p<0.0001), diffusing capacity of the lung for carbon monoxide % predicted (HR 0.978, 95% CI 0.963-0.993; p = 0.0041), baseline arterial oxygen tension (HR 0.963, 95% CI 0.938-0.989; p = 0.0060) and modified MRC score (HR 2.402, 95% CI 1.495-3.858; p = 0.0003) were significantly predictive of survival. All variables of the 6-min walk test, including walk distance (HR 0.995, 95% CI 0.992-0.998; p = 0.0020), the lowest arterial oxygen saturation measured by pulse oximetry (S(p,O(2))) (HR 0.944, 95% CI 0.918-0.972; p<0.0001) and the Borg scale (HR 1.285, 95% CI 1.091-1.514; p = 0.0027), were also significant. With stepwise, multivariate Cox proportional analysis, the modified MRC score (HR 2.181, 95% CI 1.333-3.568; p = 0.0019) and the lowest S(p,O(2)) during the 6-min walk test (HR 0.952, 95% CI 0.924-0.981; p = 0.0014) were the most significant. Dyspnoea in daily living, assessed with the modified MRC scale at baseline, provides additional prognostic information for patients with IPF.

Observation of reversed-shear Alfvén eigenmodes excited by energetic ions in a helical plasma.

Reversed-shear Alfvén eigenmodes were observed for the first time in a helical plasma having negative q0'' (the curvature of the safety factor q at the zero shear layer). The frequency is swept downward and upward sequentially via the time variation in the maximum of q. The eigenmodes calculated by ideal MHD theory are consistent with the experimental data. The frequency sweeping is mainly determined by the effects of energetic ions and the bulk pressure gradient. Coupling of reversed-shear Alfvén eigenmodes with energetic ion driven geodesic acoustic modes generates a multitude of frequency-sweeping modes.

[Lung cancer detected by fluorodeoxyglucose-positron emission tomography/computed tomography in the course of Mycobacterium avium infection; report of a case].

The patient was 64-year-old male. Chest computed tomography (CT) scan revealed an 18 mm of nodular lesion in the right upper lobe, in which inflammatory lesions due to the Mycobacterium avium infection was preexisted. On fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT scan, value of standard uptake value (SUV) max was 4.0. This finding may be caused by the inflammatory change but the malignancy was more likely with a concomitant finding of elevated serum carcinoembryonic antigen (CEA). Surgical resection by right upper lobectomy was performed. Postoperative pathology confirmed the existence of adenocarcinoma in the lesions of epithelioid granuloma with giant cells. FDG-PET/CT contributed effectively to detect a malignancy in the inflammatory lesions of Mycobacterium avium infection.

Intensive granulocyte and monocyte adsorption versus intravenous prednisolone in patients with severe ulcerative colitis: an unblinded randomised multi-centre controlled study.

BACKGROUND AND AIM: Several uncontrolled studies have reported on the efficacy of adsorptive depletion of peripheral blood granulocytes and monocytes/macrophages (GM) in patients with moderate or severe ulcerative colitis. This study was to compare the efficacy and safety of intensive GMA with intensive intravenous prednisolone in patients with severe ulcerative colitis. METHODS: Seventy patients with clinical activity index 10-23 were randomly assigned to intensive GMA with the Adacolumn, at 2 sessions/week in the first 3 weeks and then 1 session/week for up to 11 sessions (n = 35) or intravenous prednisolone, 40-60 mg/day for 5-10 days (n = 35). No patient received immunomodulators within 8 weeks prior to entry. Clinical response based on intention to treat was assessed at weeks 2, 6 and 12. RESULTS: Four patients in the prednisolone group and two patients in the GMA group discontinued in week 1. At weeks 2, 6 and 12, the remission (clinical activity index < or = 4) rates (%) in the GMA group were 17.1, 54.4, 74.3, respectively. The corresponding values in the prednisolone group were 25.7, 51.4 and 48.6. Further, at week 12, 27 patients (77%) in the GMA group and 5 patients (14%) in the prednisolone group were steroid free (P = 0.0076). In the GMA group, flushing and light-headedness were observed in 5 patients versus typical steroid side effects in 29 patients of the prednisolone group. CONCLUSIONS: In this clinical response to GMA was comparable or better than prednisolone. Further, the response to GMA was slower than to intravenous prednisolone, but was more sustainable than the latter.

Hepatocyte growth factor secreted by cultured adipocytes promotes tube formation of vascular endothelial cells in vitro.

OBJECTIVE: Adipose tissue is closely associated with angiogenesis, but the mechanisms are not fully understood. Some of the adipocyte-derived cytokines are hypothesized to play an important role in angiogenesis. We evaluated tube formation of human umbilical vascular endothelial cells (HUVECs) cultured in type I collagen gel when overlaid with the supernatant of 3T3-L1 cell culture, and expression of tube-forming factor(s) in 3T3-L1 cells with or without pioglitazone. We also studied plasma growth factor levels in patients with type 2 diabetes mellitus treated with pioglitazone. RESULTS AND METHODS: The supernatant of 3T3-L1 cells increased tube formation of HUVECs by 9.03-fold of control. Reverse transcription-polymerase chain reaction showed that hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) mRNA were expressed in 3T3-L1 cells. Western blot analysis also demonstrated HGF and VEGF protein expression. When 3T3-L1 cells were treated with 100 nM small interfering RNAs (siRNAs) for HGF, the HGF mRNA and protein were suppressed. The VEGF mRNA and protein in the cells were also suppressed by siRNA for VEGF. The supernatant of 3T3-L1 cells treated with HGF siRNA suppressed tube formation of HUVECs by 61% compared with the supernatant of cells treated with control siRNA. Addition of VEGF siRNA resulted in no significant changes. The supernatant conditioned with pioglitazone further promoted the tube formation. Pioglitazone enhanced HGF mRNA expression in 3T3-L1 cells. After 12 weeks of pioglitazone treatment, the changes of plasma HGF levels in patients treated with pioglitazone were significantly higher than those in control. CONCLUSION: These results suggest that HGF secreted from 3T3-L1 cells may be the major factor regulating the tube formation, and agents that enhance the differentiation of adipocytes may promote tube formation of HUVECs mediated by HGF secreted by adipocytes.

Penetrance of adrenocortical tumours associated with the germline TP53 R337H mutation.

BACKGROUND: An inherited germline P53 mutation has been identified in cases of childhood adrenocortical carcinoma (ACT), a neoplasm with a high incidence in southern Brazil. The penetrance of ACT in carriers of the point mutation, which encodes an arginine-to-histidine substitution at codon 337 of TP53 (R337H), has not been determined. OBJECTIVE: To investigate the penetrance of childhood ACT in carriers of the R337H TP53 mutation. METHODS: The family histories of 30 kindreds of 41 southern Brazilian children with ACT were obtained. A PCR based assay was used to detect this P53 mutation in a large number of relatives of children with ACT. In all, 927 individuals were tested for the mutation, 232 from the non-carrier and 695 (including the 40 probands) from the carrier parental lines. RESULTS: 40 children with ACT carried the TP53 R337H mutation; the remaining child with ACT was not tested. There was no evidence of Li-Fraumeni syndrome in any of the kindreds; however, seven met the criteria for Li-Fraumeni-like syndrome. The carrier parental line was identified in each kindred. Of the 695 individuals tested in the carrier parental line, 240 (34.5%) were positive for the mutation, while none of the 232 individuals in the other parental line carried the mutation. The penetrance of ACT was 9.9% (95% confidence interval, 8.7% to 11.1%). CONCLUSIONS: The TP53 R337H mutation dramatically increases predisposition to childhood ACT but not to other cancers, and explains the increased frequency of ACT observed in this geographic region.

Factors in maintaining long-term improvements in health-related quality of life after pulmonary rehabilitation for COPD.

The purpose of this study was to reveal predictors for the long-term effects of pulmonary rehabilitation for chronic obstructive pulmonary disease (COPD) patients, in terms of health-related quality of life (HRQoL). We investigated the long-term effects of pulmonary rehabilitation in 53 COPD patients who had completed the outpatient program and could be evaluated continuously for 1 year. We also investigated factors related to long-term maintenance of HRQoL assessed by the St George's Respiratory Questionnaire (SGRQ). In the year following the program, the only items that retained a significant improvement compared with the pre-program levels were respiratory muscle strength and 6-min walking distance. Patients whose total SGRQ score showed improvements that were maintained above the minimal clinically important difference were placed in a maintained-improvements group (n = 18, 34.0%), and the others in a non-maintained group (n = 35, 66.0%). A comparison of the groups revealed that the maintained-improvements group had significantly lower forced vital capacity (FVC), inspiratory capacity (IC), and tidal volume (TV) at rest; higher PaCO(2); greater initial impairments in HRQoL; and more frequent attendance in a maintenance program. In a multiple logistic regression model, only PaCO(2) was identified as predictor for the maintenance of improvement in HRQoL over a long term. In conclusion, higher baseline PaCO(2) is predictor of maintained, long-term improvement in HRQoL after pulmonary rehabilitation. Frequent attendance in a maintenance program is another predictor.

Health-related quality of life in patients with idiopathic pulmonary fibrosis. What is the main contributing factor?

The prognosis of patients with idiopathic pulmonary fibrosis (IPF) is generally considered to be poor. As the disease progresses, patients invariably become severely limited in their activities. Therefore, evaluating the health-related quality of life (HRQoL) in IPF patients is considered to be important. However, there have been few studies of this kind to date. We applied the St. George's Respiratory Questionnaire (SGRQ) to 41 consecutive IPF patients and examined various physiological variables to identify factors that were correlated with the HRQoL. Total lung capacity, transfer factor, arterial partial pressure of oxygen at rest, the lowest oxygen saturation during exercise test, and the baseline dyspnoea index (BDI) score were significantly correlated with the total SGRQ score. A similar tendency was observed in each component. Conversely, peak oxygen uptake, known as one of the important factors that determines HRQoL in chronic obstructive pulmonary disease (COPD), did not correlate with any SGRQ scores. In stepwise multiple regression analysis, the BDI score was selected as the only factor significantly contributing to the total SGRQ score. Dyspnoea was the most important factor determining HRQoL in IPF. The types of other variables that correlated with the HRQoL in IPF patients were different from those in COPD.

Case report: internal and external jugular vein thrombosis with marked accumulation of FDG.

We report an unusual case of idiopathic internal and external jugular vein thrombosis. Positron emission tomography (PET) using (18)F-fluoro-2-deoxy-D-glucose (FDG), which was conducted to assess subclinical malignancy, revealed intense uptake of FDG, corresponding to thrombus within the left internal and external jugular veins. Although FDG-PET is widely used in differentiating between malignant and benign diseases, we should bear in mind that this benign entity can demonstrate high accumulation of FDG.

[A rational approach of limited resection for small peripheral lung adenocarcinoma with curative intent; analyses of multiple primary adenocarcinomas].

Hundred and forty-one small peripheral adenocarcinomas 2 cm or less in diameter were retrospectively studied to determine the rationale of limited resection with curative intent. We used a conventional computed tomography (CT) which used 2.5 mm thick sections to examine only the main tumor during from March 1985 to May 1999 and a spiral CT which produced 2.5 mm thick sections of the entire lung field during from June 1999 to July 2003. The incidence of small peripheral adenocarcinoma significantly increased from 12.6% to 29.1%, suggesting an increase in the rate of detection with spiral CTs. During the spiral CT era, the percentage of females, pathological stage I a tumors, predominant ground-glass opacity (GGO) tumors and limited resection were significantly higher. The incidence of multiple adenocarcinomas 2 cm or less in diameter significantly increased 2.6% to 14.1%. It increases to 21.9% in small adenocarcinomas and 63.6% in predominant GGO type, when minute GGO lesion which have been followed in 5 patients by a watch and wait policy would be bronchioloalveolar carcinoma (BAC). In conclusion, a paradigm shift of the treatment for small peripheral adenocarcinoma should be warrant, because localized BAC as noninvasive cancer is not rare and often found as multiple BACs.

Radiofrequency ablation is useful for selected cases of pelvic recurrence of rectal carcinoma.

BACKGROUND: We evaluated radiofrequency ablation (RFA) as a new local treatment for pelvic recurrence of rectal carcinoma. METHODS: Fourteen lesions in 10 patients were treated by RFA. Four patients with a solitary recurrent tumor were treated curatively, while 10 lesions in the remaining 6 patients with distant metastases were treated palliatively mainly to control pain. RFA was performed under CT guidance and epidural anesthesia. It was carried out by a single insertion for tumors 3 cm or less in diameter or by multiple insertions for tumors greater than 3 cm. Ablation effectiveness was evaluated by magnetic resonance imaging. For palliative cases, severity of pain was assessed using a visual analogue scale. RESULTS: Needle placement and ablation were accomplished in all 14 lesions. Complications following RFA consisted of 2 cases of abscess formation, 2 cases of neuralgia and one case of bleeding. To obtain complete necrosis, the tumor should be under 4 cm in diameter and not involve any major iliac vessels. Three of 4 patients treated curatively met these conditions. Among these 4 patients, only one recurrence was observed after RFA (follow-up, 6-36 months). Five of 6 patients treated palliatively had tumours greater than 4 cm in diameter or involving iliac vessels. In none of the patients did we achieve complete necrosis and satisfactory analgesia. CONCLUSION: Although certain conditions must be met, RFA is a feasible and effective treatment, and it should be considered as one of the treatment options for pelvic recurrence of rectal carcinoma.

Synthesis and antiherpesvirus activities of 5-alkyl-2-thiopyrimidine nucleoside analogues.

Twenty 5-alkyl-2-thiopyrimidine nucleosides were newly synthesized and examined for antiviral activities against herpes simplex virus (HSV), varicella-zoster virus (VZV) and human cytomegalovirus (HCMV). In this study, 2'-deoxy-5-alkyl-2-thiocytidine analogues had lower 50% effective concentration (EC50) values against HSV-1, and 2'-deoxy-5-alkyl-2-thiouridine analogues showed lower EC50 against VZV than their congeners of arabinoside form. Among the compounds examined, 2'-deoxy-5-ethyl and 5-propyl-2-thiocytidine (TN-53 and TN-54) were most potent and selective anti-HSV compounds. Their EC50s were 0.04 and 0.15 microM, and selectivity indexes were more than 7,215 and 1,849, respectively. On the other hand, 2'-deoxy-5-propyl-2-thiouridine (TN-51), 5-bromovinyl-2-thiouracil arabinoside (TN-65) and 5-styryl-2-thiouracil arabinoside (TN-67) were most potent and selective anti-VZV compounds. Their EC50s were 3.1, 3.8 and 2.6 pM for CaQu strain of VZV, respectively, and 2.1 to 3.0 times lower than that of acyclovir. All 2-thiopyrimidine nucleoside analogues did not show antiviral activities against thymidine kinase (TK) negative strains of HSV-1 and VZV. Only three 2-thiocytosine arabinoside compounds showed marginal anti-CMV activities (EC50s were 57-159 pM). All of the five alkyl-2-thio-pyrimidine nucleoside analogues examined were not cytotoxic to human lymphoblastoid cells (RPM18226) and human embryonic fibroblast cells (MRC-5) at 240 microM (100 microg/ml) or more. Regarding the structure-activity relationship of 5-alkyl-2-thiopyrimidine nucleoside analogues, the following remarks will be noted. Elongation of 5-alkyl chain (methyl to ethyl) of 2-thiocytosine in both deoxyribosyl and arabinosyl nucleosides increased anti-HSV-1 activity but not anti-VZV activity. Furthermore, elongation of the same chain (ethyl to propyl) of 2-thiodeoxyuridine increased anti-VZV activity whereas it did not in the case of 2-thiouracil arabinosides.

Mucosal immunoadjuvant activity of the low toxic recombinant Escherichia coli heat-labile enterotoxin produced by Bacillus brevis for the bacterial subunit or component vaccine in pigs and cattle.

A gene encoding the mature Escherichia coli heat-labile enterotoxin (LT) lacking the nick site in the A subunit by deleting tripeptides was introduced in a vector pNH301 and expressed extracellularly as mutant molecule of holotoxin at high levels in Bacilus brevis HPD31-S5 of the host bacterium. The mucosal adjuvant activities of the produced mutant LT (mLT) preparation were studied in pigs and cattle. Intranasal immunization of pigs with the recombinant subunit vaccine of Erysipelothrix rhusiopathiae or the component vaccine of Bordetella bronchiseptica mixed with the mLT resulted in a substantial enhancement of both mucosal and serum-specific antibody levels. The immunized pigs were also protected when challenge-exposed intradermally with a highly virulent E. rhusiopathiae strain or challenge-exposed intranasally with a highly virulent strain of B. bronchiseptica. The mLT intranasally administered with recombinant intimin (an outer membrane adhesin) of E. coli O157:H7 also induced an elevation of IgA-specific antibody in the nasal secretion and saliva of calves as well as an elevation of IgG1-specific antibody level against the intimin in the sera and colostrum of cows. The three kinds tested protein antigens were poorly immunogenic when antigen administered intranasally alone. The mLT intranasally administered at a higher effective dose did not induce local adverse reactions or diarrhea in pigs and cattle. The present study demonstrates that the recombinant mLT produced using the B. brevis expression system might represent promising immunoadjuvants for the potential application of intranasal vaccines directed against infectious diseases in pigs and cattle.

[Analyses of multiple primary lung cancers; recent trend].

We studied multiple primary lung cancers (MPLCs) in 921 patients who had undergone operation for primary lung cancer since March 1979 in Mie University Hospital. There were 14 synchronous and 5 metachronous MPLCs. Combination of synchronous MPLCs were adenocarcinoma (ADC)/ADC in 7, squamous cell carcinoma (SCC)/SCC in 3, and ADC/adenosquamous cell carcinoma, ADC/small cell carcinoma, ADC/large cell carcinoma and multiple AAH in one. The incidence of synchronous MPLCs was 0.7% (6/815 pts) before May 1999 and 7.5% (8/106 pts) after June 1999 when HRCT was introduced for preoperative evaluation and postoperative follow-up. Six cases with multiple bronchioloalveolar carcinomas (BACs) have undergone operation for last 5 years. Most of them were roentgenographically occult and the operative outcome was good in spite of limited resection. In summary, we need new strategy of diagnosis and operative procedure for peripheral small adenocarcinoma, because multiple MPLCs of BAC are not rare.

Cobalamin deficiency results in severe metabolic disorder of serine and threonine in rats.

Dietary cobalamin (vitamin B12; Cbl) deficiency caused significant increases in plasma serine, threonine, glycine, alanine, tyrosine, lysine and histidine levels in rats. In particular, the serine and threonine levels were over five and eight times, respectively, higher in the Cbl-deficient rats than those in the sufficient controls. In addition, some amino acids, including serine and threonine, were excreted into urine at significantly higher levels in the deficient rats. When Cbl was supplemented into the deficient rats for 2 weeks, in coincidence with the disappearance of the urinary excretion of methylmalonic acid (an index of Cbl deficiency), the plasma serine and threonine levels were normalized. These results indicate that Cbl deficiency results in metabolic disorder of certain amino acids, including serine and threonine. The expression level of hepatic serine dehydratase (SDH), which catalyzes the conversion of serine and threonine to pyruvate and 2-oxobutyrate, respectively, was significantly lowered by Cbl deficiency, even though Cbl does not participate directly in the enzyme reaction. The SDH activity in the deficient rats was less than 20% of that in the sufficient controls, and was normalized 2 weeks after the Cbl supplementation. It is thus suggested that the decrease of the SDH expression relates closely with the abnormalities in the plasma and urinary levels of serine and threonine in the Cbl-deficient rats.