Low Phase Angle Is Correlated With Worse General Condition in Patients with Advanced Cancer

Objectives: Phase angle (PA) is a poor prognostic factor in patients with advanced cancer. This study aimed to identify possible correlations between PA and symptoms, quality of life, fluid retention, and laboratory data in cancer patients in palliative care settings.

Methods: Individuals who visited the outpatient clinic or were admitted to the palliative care unit were eligible. Patients with a performance status of 4 and/or those unable to complete questionnaires were excluded. PA was evaluated using a bioanalyzer device. The correlation coefficient between PA and the variables of interest was analyzed.

Results: A total of 102 patients were analyzed. PA was weakly correlated with age (ρ = ?0.22), performance status (ρ = ?0.30), functional well-being (ρ?=?0.20), anorexia/cachexia subscale (ρ?=?0.22), and Functional Assessment of Anorexia/Cachexia Therapy trial outcome index (ρ?=?0.26). PA was also correlated with fluid retention (ρ = ?0.34) and albumin (ρ?=?0.32), C-reactive protein (ρ = ?0.31), and hemoglobin (ρ?=?0.41) levels. Sub-analysis stratified according to sex revealed that males demonstrated the same results; however, female sex demonstrated a correlation between PA and social well-being (ρ = ?0.43).

Conclusions: PA was correlated with physical condition, but not with psychological well-being.     

Use of small-bore silastic drains in general thoracic surgery.

STUDY OBJECTIVE: To evaluate the safety and efficacy of small-bore, silastic drains for patients undergoing general thoracic surgery. PATIENTS AND METHODS: Twenty-five patients who received soft, small-bore, silastic drains were compared with 17 patients who received semi-rigid double lumen (DL) tubes retrospectively. RESULTS: The pain score was significantly lower in patients who received the silastic tubes in video-assisted thoracoscopic surgery (VATS) cases on postoperative days 5 and 6 , after continuous epidural analgesia had finished (P=0.018). No specific morbidity was seen in the patients who received silastic tubes. CONCLUSION: We considered that soft, small-bore silastic drains were just as effective as traditional DL tubes, but caused less pain especially in VATS cases.     

GRO-alpha in Human Serum: Differences Related to Age and Sex

PROBLEM: Human GRO-alpha (GRO-α) is a new member of the chemokine family that is supposed to play an important role in inflammatory and immune reactions. We established a sandwich enzyme-linked immunoassay (ELISA) system with polyclonal antibodies against human GRO-α and investigated the serum level of healthy donors to establish normal ranges for this chemokine in adults. METHODS: GRO-α concentrations were measured cross-sectionally in the sera of 240 healthy adults. The variability of serum GRO-α levels was also measured in normal volunteers, samples from whom were obtained by sequential venipunctures or by a small plastic cannula with a heparin-saline lock, to determine short-term variability. RESULTS: Whereas there was no difference between the concentration of human GRO-α from men (logarithmic mean, 77.6 pg/ml, n = 120) and that from women with normal menstrual cycles (log mean, 71.6 pg/ml, n = 73), the concentration from postmenopausal women (log mean 45.0 pg/ml, n = 31) was lower than that from women with normal menstrual cycles (log mean 71.6 pg/ml, n = 73). However, we could not detect any significant difference between healthy donors' serum levels and those of donors with acute inflammation. Fewer variations were recognized in the case of the sequential venipunctures method than in that of the heparin-saline lock method. CONCLUSION: We found that the GRO-α concentration of postmenopausal women was significantly lower than that of women with normal menstrual cycles. These results suggest the GRO-α serum levels of normal healthy women may have some correlation with sex hormones.     

Structure and mineral content in weight-bearing bones following hindlimb suspension in young rats.

Responses of structure and mineral content in weight-bearing bones to 1-week hindlimb suspension were studied in growing rats. The weight, volume, and length of femur, tibia, and fibula were less in suspended rats than cage controls, although there was no significant difference in the weight/volume ratio. The diameter of mid-shaft, the thickness of cortical bone, and the ratio of cortical bone thickness to femur diameter were significantly less in the suspended rats. The width of marrow space showed no differences, suggesting that the cortical bone was mainly affected. The sum of mineral content and the mineral content per diameter in the cross section of femurs were decreased following suspension, suggesting a change in the internal structure of cortical bone. Data also indicated that the reduction of femur diameter was caused by decreased thickness which is accompanied by the decreased mineral content of the cortical bone. It was suggested that there is a close relationship between the responses of bones and muscles to hindlimb suspension of young rats, although the degree of weight loss was greater in muscles than in bones.     

Spinocerebellar ataxia 27 with a novel nonsense variant (Lys177X) in FGF14

Spinocerebellar ataxia 27 (SCA27) is an autosomal dominant SCA caused by variants in the fibroblast growth factor 14 (FGF14) gene. We examined a Japanese SCA patient whose deceased father also suffered from SCA. The patient was a 63-year-old male. He graduated from junior high school but received no further education. The predominant complaint was slowly progressive dysarthria and gait disturbance, which appeared at age 47. He showed pathological saccadic dysmetria, saccadic intrusions into smooth pursuit eye movements, dysarthria, and limb and truncal ataxia. His gait was wide-based but he did not require a walking stick. Limb muscle strength was intact. Deep tendon reflexes were normal or slightly reduced. Pathological reflexes were absent. He demonstrated mildly impaired vibration sense in the lower limbs. There was no urinary dysfunction. Brain MRI showed cerebellar atrophy without brainstem involvement. We first confirmed the absence of repeat expansion in genes known to be responsible for SCAs 1–3, 6–8, 10, 12, 17, 36 and dentatorubral-pallidoluysian atrophy. By exome analysis, we identified a novel heterozygous variant (NM_004115, c.529A>T; Lys177X) in exon 4 of the FGF14 gene. This variant is expected to generate a truncated FGF14 protein lacking the heparin binding sites, those are likely to modify the activity of FGF14. We confirmed the absence of the variant in 502 healthy Japanese individuals by Sanger sequencing. There is no record of the variant in public databases. We conclude that the novel variation in FGF14 is causative for SCA27 in this patient.     

Sensory scaling of odor based on mathematical studies of rating words

Sensory scales are very important indicators for the evaluation of environmental odors, and of the effect of deodorizers. The purpose of this study is to examine reasonable methods of sensory scaling. For this purpose, the psychological values of rating words for odor intensity, odor hedonics and similarity were measured. The interval distances between categories of each scale were estimated in the method of successive categories as well. Results of this study are as follows. 1) The 6-step odor intensity scale, issued by the Environmental Agency, may be regarded as an ordinal scale, but not as an interval scale. The 9-step hedonics scale may be regarded as an interval scale. 2) Psychological values of rating words are not affected by the size and the number of category steps in the graphic scales applied to the judgements of their values. 3) The number of category steps needs to be determined based on the distribution of the psychological values. The meanings and the order of the rating words have to be clear. 4) In the construction of a numerical scale, the category values should accord nearly as possible with the psychological values of rating words. 5) In results from the method of successive categories applied to the measured values of odor intensity and similarity, interval distances between categories are unequal, and the interval distances are wide on both edges of the scale. In these cases, the values must be converted into "category values of stimuli."     

Spontaneous regression of malignant pleural mesothelioma

We describe the spontaneous regression of a malignant pleural mesothelioma with left pleural effusion, chest pain, and a high fever (38° to 39°C) in a 37-year-old man. The patient was referred to us because multiple nodules were seen on his chest radiograph after he was successfully treated with thoracocentesis and conventional antibiotic therapy for pleural effusion. Our diagnosis was malignant pleural mesothelioma, based on histologic findings in a biopsy specimen obtained during thoracoscopy. Interestingly, the tumors markedly regressed without treatment, and the patient was doing well more than 5 months after the cancer was diagnosed. The spontaneous regression of malignant pleural mesothelioma is rare, and this may represent the first case report.     

Potential role of vacuolar H-adenosine triphosphatase in neointimal formation in cultured human saphenous vein

OBJECTIVE: Vacuolar H(+)-adenosine triphosphatase plays a pivotal role in pH regulation and molecular transport across the vacuolar membranes and is involved in cell proliferation and transformation. In the present study, possible involvement of vacuolar H(+)-adenosine triphosphatase in neointimal formation was investigated in an organ culture model of human saphenous vein. Methods and results: Cultured saphenous vein segments developed neointimal formation and marked thickening of the media within 14 days. Neointimal formation and medial thickening were completely inhibited by 10 nmol/L bafilomycin A(1), a selective inhibitor of vacuolar H(+)-adenosine triphosphatase, although structurally related macrolide antibiotics FK-506 and erythromycin were without an effect. The neointimal cells were positive for alpha-smooth muscle actin and vimentin but negative for desmin, indicative of myofibroblasts. The emergence of myofibroblasts was inhibited, and endothelial cells were preserved in the saphenous vein segments treated with bafilomycin A(1). Uptake of bromodeoxyuridine, a proliferation marker, by myofibroblasts was abrogated in the saphenous vein segments treated with 10 nmol/L bafilomycin A(1). Detection of apoptotic cells by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling concomitant with identification of desmin-expressing smooth muscle cells demonstrated that neointimal myofibroblasts, but not medial smooth muscle cells, that expressed desmin underwent apoptosis by treatment with bafilomycin A(1). CONCLUSIONS: These results suggest that vacuolar H(+)-adenosine triphosphatase may be involved in myofibroblast growth that contributes to neointimal formation and medial thickening in cultured human saphenous vein. Increased sensitivity of myofibroblasts, but not endothelial cells, and differentiated smooth muscle cells to bafilomycin A(1) may have potential therapeutic implications in the treatment for vein graft disease.     

AU-1 from Agavaceae plants causes transient increase in p21/Cip1 expression in renal adenocarcinoma ACHN cells in an miR-34-dependent manner

Here, we show that AU-1, spirostanol saponin isolated from Agavaceae plants, causes a transient increase in cyclin-dependent kinase inhibitor (CDKI) p21/Cip1 through the upregulation of miRNAs, miR-34 and miR-21. AU-1 stimulated p21/Cip1 expression without exerting cytotoxicity against different types of carcinoma cell lines. In renal adenocarcinoma ACHN cells, AU-1 transiently elevated the expression level of p21/Cip1 protein without marked increases in p21/Cip1 mRNA levels. Rapid and transient increases in miR-34 and miR-21, both of which are known to upregulate p21/Cip1, were observed in AU-1-treated cells. Inhibitor for miR-34 and for miR-21 significantly blocked the AU-1-caused increase in p21/Cip1, indicating that elevation of p21/Cip1 protein by AU-1 is dependent on these microRNAs. We further clarified that NAD-dependent deacetylase SIRT1, a direct target of miR-34, is decreased by the treatment with AU-1. Furthermore, we found that SIRT1-knockdown increases p21/Cip1 protein levels in an miR-21-dependent manner. On the other hand, ectopic expression of p21/Cip1 resulted in the lowered expression of miR-34 and miR-21, suggesting that reciprocal regulation exists between p21/Cip1 and these miRNAs. We propose that the following feedback network composed of miR-34/SIRT1/miR-21/p21 is triggered by the treatment with AU-1: in cells treated with AU-1, transient elevation of miR-34 leads to the downregulation of SIRT1, thereby miR-21 is freed from SIRT1-dependent suppression. Then, elevated miR-21 upregulates p21/Cip1 protein, followed by the suppression of miR-34 expression.