Innovative financing for nutrition.

Given the constraints of both overseas development aid and domestic financing for nutrition, innovative financing is critical-yet nutrition lags behind other sectors in catalysing it. Here, we argue that the framing for nutrition must evolve and critical actions must be taken to generate more money for nutrition and more nutrition for money. Food systems hold some of the most powerful opportunities to improve human and planetary health while increasing productivity-and the private sector has a key role to play in this.

PICT1 expression is a poor prognostic factor in non-small cell lung cancer.

PICT1 is a key regulator of the MDM2-TP53 pathway. High mRNA expression levels of PICT1 are associated with poor prognosis in several cancers with wild-type TP53. In this study, we identified the PICT1 protein expression profile in non-small cell lung cancer (NSCLC) with wild-type TP53 in the nucleolus and cytoplasm, and revealed the relationship between PICT1 expression and patient clinicopathological factors. PICT1 expression in the tumor cells of 96 NSCLC patients with wild-type TP53 was evaluated by immunohistochemistry. Forty-three of 96 (44.8%) NSCLC samples were positive for nucleolar PICT1, while 40/96 (41.7%) NSCLC samples were positive for cytoplasmic PICT1. There was no correlation between nucleolar PICT1 expression and clinicopathological factors. However, cytoplasmic PICT1 expression was significantly correlated with sex, smoking history, differentiation, lymphatic invasion and pathological stage. In multivariate analysis, lymphatic invasion was significantly associated with cytoplasmic PICT1 expression (hazard ratio: 5.02, P = 0.026). We scrutinized PICT1 expression in samples of NSCLC with wild-type TP53, and showed a correlation between cytoplasmic PICT1 expression and several clinicopathological factors in these patients. Our results indicate that cytoplasmic PICT1 expression is a poor prognostic factor and is associated with tumor progression via lymphatic invasion in these patients.

Sensitivity and kinase activity of epidermal growth factor receptor (EGFR) exon 19 and others to EGFR-tyrosine kinase inhibitors.

The presence of epidermal growth factor receptor (EGFR) somatic mutations in non-small-cell lung cancer patients is associated with response to treatment with EGFR-tyrosine kinase inhibitors, such as gefitinib and erlotinib. More than 100 mutations in the kinase domain of EGFR have been identified. In particular there are many variations of deletion mutations in exon 19. In this study, using yellow fluorescent protein-tagged fragments of the EGFR intracellular domain, we examined the differences in sensitivity to gefitinib, erlotinib and afatinib between several exon 19 mutants and other common EGFR mutations. We also used serum of patients undergoing treatment with EGFR-tyrosine kinase inhibitors in this system. In addition, we examined the relative kinase activity of these mutants by measuring relative fluorescent intensity after immunofluorescence staining. We found that both sensitivity to EGFR-tyrosine kinase inhibitors and relative kinase activity differed among several EGFR mutations found in the same region of the kinase domain. This study underscores the importance of reporting the clinical outcome of treatment in relation to different EGFR mutations.

Hypoalbuminemia and lymphocytopenia are predictive risk factors for in-hospital mortality in patients with tuberculosis.

OBJECTIVE: The aim of this study was to clarify the association between nutritional state on admission and in-hospital death in tuberculosis (TB) patients, including a high proportion of elderly patients. METHODS: A retrospective cohort study of 246 TB patients was conducted. The serum albumin concentrations and peripheral blood lymphocyte counts were measured on admission, and the primary outcome of interest was in-hospital death. Patient mortality was categorized into two groups: TB death and non-TB death. A multivariate analysis was performed to evaluate the relationship between nutritional state on admission and in-hospital mortality in TB patients. RESULTS: The median [interquartile range] patient age was 79 [69-83] years, and the in-hospital death rate was 20.73% (TB death: 26 patients; non-TB death: 25 patients). The multivariate analysis revealed that the serum albumin concentrations (OR: 0.21, 95% CI: 0.10-0.41; p<0.0001) and peripheral blood total lymphocyte counts (Category 2 [627.2-1,106.7/mm(3)] vs. 1 [<627.2/mm(3)]. OR: 0.28, 95% CI: 0.11-0.73; p=0.009, Category 3 [>1,106.7/mm(3)] vs. 1. OR: 0.24, 95% CI: 0.08-0.76, p=0.015) on admission were significantly associated with all in-hospital deaths in the TB patients. The serum albumin concentrations and peripheral blood total lymphocyte counts were also found to be associated with in-hospital deaths directly caused by TB. CONCLUSION: Hypoalbuminemia and lymphocytopenia on admission are predictive risk factors for in-hospital mortality in TB patients. Nutritional defects should thus receive special attention in order to reduce TB patient mortality, particularly among elderly patients.

Diagnostic value of CEA and CYFRA 21-1 tumor markers in primary lung cancer.

Lung cancer is sometimes difficult to differentiate from benign lung diseases expressing nodular shadow in imaging study. We assessed the diagnostic value of two commonly used tumor markers in distinguishing primary lung cancer from benign lung disease. The serum levels of carcinoembryonic antigen (CEA) and cytokeratin 19 fragments (CYFRA 21-1) were retrospectively analyzed in 655 lung cancer patients and 237 patients with benign lung disease. The standard cut-off levels of 3.2 ng/mL CEA and 3.5 ng/mL CYFRA 21-1 and twice these respective levels (6.4 ng/mL and 7.0 ng/mL) were used. CEA and CYFRA 21-1 levels were elevated in 32% and 11% of benign lung disease patients, respectively. CEA sensitivity and specificity for lung cancer diagnosis was 69% and 68% respectively, while that for CYFRA 21-1 was 43% and 89%, respectively. Thus, the combined value for the specificity of the two tumor markers was greater than either alone. Patients were grouped depending on their hospital status, and prevalence rates were determined. The prevalence rate of lung cancer in admitted patients was 51%, the prevalence rate of lung cancer in outpatients was 12%, and the prevalence rate of lung cancer identified during health check-ups was 0.1%. Positive predictive values (PPVs) were calculated using Bayes' theorem, and varied with the serum tumor marker and prevalence rate: PPVs of CEA [prevalence rate] were 69.2% [51%], 22.7% [12%], and 0.22% [0.1%], while PPVs of CYFRA 21-1 were 80.3% [51%], 34.8% [12%], and 0.39% [0.1%]. However, PPVs for lung cancer diagnosis at a prevalence rate of 51% were 87.3% or higher when the patient exhibited positive CEA and CYFRA 21-1, or CEA or CYFRA 21-1 levels twice the standard cut-off. Our results indicate that CEA and CYFRA 21-1 are reliable serum tumor markers for the diagnosis of lung cancer in addition to CT scans when combined or used individually at twice the standard cut-off level in high prevalence rate groups. The prevalence rate should therefore be taken into account when these serum tumor markers are used as diagnostic tools for lung cancer.

Expression of TrkB and BDNF is associated with poor prognosis in non-small cell lung cancer.

High expression levels of TrkB and BDNF are associated with aggressive malignant behavior in tumor cells and a poor prognosis in patients with various types of cancer. In this study, we aimed to identify the relationship between TrkB and BDNF expression and clinicopathological variables and prognosis in non-small cell lung cancer (NSCLC). We evaluated TrkB and BDNF expression in the tumor cells of 102 NSCLC patients by immunohistochemistry. Out of all clinicopathological factors examined, only vascular invasion was significantly correlated with TrkB (P=0.010) and BDNF (P=0.015) expression. TrkB-positive tumors had significantly worse disease-free survival (P=0.0094) and overall survival (P=0.0019) than TrkB-negative tumors, and TrkB expression was an independent prognostic factor for disease-free survival (HR 3.735, 95% CI 1.560-11.068, P=0.002) and overall survival (HR 4.335, 95% CI 1.534-15.963, P=0.004) in multivariate analysis. Finally, our analysis revealed that co-expression of TrkB and BDNF conferred poorer prognosis compared with overexpression of either protein alone. Our results indicate that expression of TrkB and BDNF is associated with poor prognosis in NSCLC patients.

Relationship between computed tomography findings and nutritional status in elderly patients with pulmonary tuberculosis.

OBJECTIVE: This study was aimed to identify the relationship between radiographic features of elderly pulmonary TB patients and nutritional deficiency. METHODS: Ninety-two patients older than 70 years of age with pulmonary TB were retrospectively enrolled. The influence of nutritional parameters, such as serum albumin concentration and peripheral blood total lymphocyte count on CT findings was examined. CT findings of pulmonary TB patients were classified as those including atypical findings (segmental or lobar consolidation in an unusual location, miliary nodules, and hilar and mediastinal lymphadenopathy) or not. The number of segments involved by TB was also counted. RESULTS: Age- and gender-adjusted analyses for the nutritional parameters and confounders revealed that hypoalbuminemia, lymphocytopenia, and steroid therapy were significantly related to the presence of atypical CT findings. Furthermore, hypoalbuminemia, lymphocytopenia, and the amount of acid-fast bacilli in sputum smears were significantly related to an increased number of involved segments. In multivariate analysis, only hypoalbuminemia was significantly related to the presence of atypical CT findings (OR: 0.335, 95% CI: 0.142-0.794, p = 0.013) and an increased number of involved segments (OR: 0.145, 95% CI: 0.047-0.453, p = 0.0009). Among the CT findings, the tree-in-bud pattern was the most common in all patients (79.3%). However, the presence of the tree-in-bud pattern was not significantly related to any nutritional parameter. CONCLUSION: Elderly TB patients of poor nutritional status, in particular those with hypoalbuminemia, tended to show atypical CT findings and widespread lesions. The tree-in-bud pulmonary pattern could be observed in TB patients in any nutritional state.

[The relationship between the nutritional states of tuberculosis patients at the time of their admission to tuberculosis wards and their treatment results].

OBJECTIVES: To prospectively investigate the relationship between the nutritional states of tuberculosis patients at the time of their admission to tuberculosis wards and their treatment outcomes. PATIENTS AND METHODS: We observed body mass index (BMI), peripheral blood lymphocyte count, serum albumin concentration, and induration size in the PPD skin test of a total of 107 tuberculosis patients after they had been newly admitted to NHO Omuta National Hospital during the period from Aug. 2004 to Jul. 2006. Based on these indices, the patients were divided into four groups according to their nutritional states: severely impaired, moderately impaired, mildly impaired or normal. RESULTS: It was shown that the worse the nutritional state was on admission, the higher the mortality rate from all causes including tuberculosis. There has been no relapse case in patients from this group who have completed tuberculosis treatment despite their poor nutritional states at the start of the treatment. CONCLUSION: This prospective study of the relationship between the nutritional states of tuberculosis patients on admission and their treatment outcomes reproduced the results obtained from a retrospective study that we had previously reported. The assessment method of the nutritional state that was used in our study was proven to be useful for predicting the prognosis of tuberculosis patients.

[Case of angioimmunoblastic T-cell lymphoma with eosinophilia and interstitial shadows].

A 76-year-old woman was admitted because of respiratory failure with bilateral multiple interstitial shadows and mediastinal adenopathy on chest CT images. Blood examination revealed eosinophilia without leukocytosis and elevated C-reactive protein levels. Corticosteroids were administered before diagnosis because of rapid respiratory failure. Although her symptoms and pulmonary lesions disappeared with steroid therapy, they recurred 4 days later. A definitive diagnosis was not obtained until bronchofiberoptic examination. At the time of recurrence 6 months later, angioimmunoblastic T-cell lymphoma (AITL) was diagnosed with axillary lymph node biopsy. AITL is rare, and shows rapid deterioration of respiratory failure with poor prognosis. Lymph node biopsy is necessary to establish a definitive diagnosis.

[Heparin-induced thrombocytopenia and disseminated intravascular coagulation in a patient with drug-induced pneumonia].

An 82-year-old woman was admitted to the hospital with dyspnea and fatigue. She had been given amlodipine, furosemide, candesartan, pravastatin and roxatidine acetate for two months in an other hospital. Chest CT showed patchy consolidations throughout the entire lungs. We suspected drug-induced pneumonia, and treated her with prednisolone under mechanical ventilation. The pulmonary consolidations eventually improved, but on the 15th hospital day the patient developed thrombocytopenia and disseminated intravascular coagulation (DIC). Heparin flushes had been performed since the first hospital day. After these were stopped, her platelet count became normal and the patient recovered from DIC. The clinical course, and the fact that testing for heparin-induced thrombocytopenia (HIT) antibodies was positive, supported the diagnosis of HIT and DIC. We report a rare case of HIT and DIC during treatment for drug-induced pneumonia.

A case of pulmonary epithelioid hemangioendothelioma surviving 10 years without treatment.

A 19-year-old woman was referred to our hospital because of bilateral multiple nodular shadows on the chest radiograph. She complained of no symptoms. The pulmonary lesions were diagnosed pathologically as epithelioid hemangioendothelioma. She has been followed without treatment for more than 10 years. Among all lesions, only two pulmonary nodules enlarged slightly, and it is interesting that one showed significant uptake in a fluorodeoxyglucose positron emission tomography (FDG-PET) scan. The current case suggests the clinical usefulness of an FDG-PET scan in a pulmonary epithelioid hemangioendothelioma (PEH) patient.

Effects of estradiol and the angiotensin II receptor blocker irbesartan on vascular function in postmenopausal women.

OBJECTIVE: Estradiol and angiotensin receptor blockers have prominent effects on the renin-angiotensin-aldosterone system. The purpose of this study was to determine whether irbesartan, an angiotensin receptor blocker, has a greater effect on vascular function when combined with estradiol, compared with irbesartan alone, in hypertensive postmenopausal women. DESIGN: Fifty-one women were studied while off any antihypertensive medications or hormone therapy at baseline and after randomization to one of four treatment arms for 12 weeks: (1) irbesartan and estradiol, (2) irbesartan and placebo, (3) estradiol and placebo, and (4) placebo/placebo. Estradiol and placebo arms served as control groups. Blood pressure, brachial reactivity, aldosterone, insulin, glucose, 24-hour urinary catecholamines, urinary sodium, and creatinine were measured. Fisher's exact test was used for comparison of differences in blood pressure in the treatment arms. Paired t test and analysis of variance were also performed for within- and between-group analysis. RESULTS: A significantly larger number of women in the irbesartan and estradiol group had a decrease of 5 mm Hg or more in both systolic and diastolic blood pressures (P < 0.05) compared with irbesartan alone group. Forearm vascular reactivity was increased significantly compared with baseline (P < 0.05), and there was a significant decrease in the serum aldosterone level after treatment compared with baseline (P < 0.05) in the irbesartan and estradiol combination group. Fasting glucose and insulin, urinary sodium/creatinine ratio, and catecholamines were similar at each time point. CONCLUSIONS: The results suggest that irbesartan and estradiol, when used in combination, may cause a greater lowering of blood pressure in postmenopausal hypertensive women. This effect may be mediated via increased vasodilation and lower aldosterone levels. These results warrant further testing in larger clinical trials.

Effects of conjugated oestrogen and droloxifene on the renin-angiotensin system, blood pressure and renal blood flow in postmenopausal women.

OBJECTIVE: The aim of this study was to evaluate the effect of conjugated equine oestrogen (CEE), and droloxifene, a selective oestrogen receptor modulator (SERM) on individual components of renin-angiotensin-aldosterone (RAAS) and blood pressure (BP) in postmenopausal women. DESIGN AND PATIENTS: Twenty-one normotensive (NT) and 10 hypertensive (HT) postmenopausal women received either CEE (0.625 mg/day) or droloxifene (60 mg/day) for 6 weeks and, after a 4-week washout, were restudied on the alternate medication. MEASUREMENTS: Hormones of the RAAS and supine BP were measured prior to and at the end of each drug treatment in all subjects. In a subgroup of the NT (n = 10), 24 h ambulatory BP was performed and renal blood flow was determined by PAH clearance both basally and in response to 45-min angiotensin II (Ang II) infusion (3 ng/kg/min). RESULTS: CEE significantly increased angiotensinogen, decreased active renin and angiotensin-converting enzyme (ACE), and maintained plasma immunoreactive (ir) angiotensin I (Ang I) levels compared to baseline. With droloxifene, angiotensinogen, active renin and Ang I remained unchanged. Both CEE and droloxifene significantly increased plasma ir-Ang II levels (pmol/l) in NT (baseline: 25.7 +/- 2.5, CEE: 36.6 +/- 3.4, droloxifene: 33.3 +/- 3.1, P < 0.002) and HT women (baseline: 17.9 +/- 2.3, CEE: 27.9 +/- 3.2, droloxifene: 25.9 +/- 4.9, P < 0.005). Renal blood flow was lower on CEE (P = 0.02) compared with baseline. Systemic BP (supine and 24-h ambulatory) was unchanged during both treatments. CONCLUSION: This study demonstrates higher circulating levels of ir-Ang II with CEE and droloxifene.

Assessing the quality of infertility resources on the World Wide Web: tools to guide clients through the maze of fact and fiction.

The Internet has become a major source of health information for women, but information placed on the World Wide Web does not routinely undergo a peer review process before dissemination. In this study, we present an analysis of 197 infertility-related Web sites for quality and accountability, using JAMA's minimal core standards for responsible print. Only 2% of the web sites analyzed met all four recommended standards, and 50.8% failed to report any of the four. Commercial web sites were more likely to fail to meet minimum standards (71.2%) than those with educational (46.8%) or supportive (29.8%) elements. Web sites with educational and informational components were most common (70.6%), followed by commercial sites (52.8%) and sites that offered a forum for infertility support and activism (28.9%). Internet resources available to infertile patients are at best variable. The current state of infertility-related materials on the World Wide Web offers unprecedented opportunities to improve services to a growing number of e-health users. Because of variations in quality of site content, women's health clinicians must assume responsibility for a new role as information monitor. This study provides assessment tools clinicians can apply and share with clients.