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.     

Long-term skeletal stability in the treatment of mandibular prognathism with a physiological positioning strategy

Our aim was to evaluate the long-term skeletal stability of the mandible in 21 patients after orthognathic surgery with physiological positioning. The measurement points SNB, B point (X, Y), Pog (X, Y), and the angle of the ramus were measured on cephalometric photographs to assess skeletal stability preoperatively, immediately after operation, and one and two years postoperatively. In addition, we evaluated the clinical symptoms of disorders of the temporomandibular joint (TMJ). The analysis of the cephalometric photographs showed that SNB, B point X, and Pog X showed no significant differences among the postoperative time points. On the other hand, B point Y and Pog Y showed no significant differences throughout the study period. We compared the angle of the ramus before operation and two years postoperatively, and no significant difference was found. In addition, no cases showed any pathological symptoms of disorders of the TMJ two years postoperatively. The long-term stability after orthognathic surgery with physiological positioning was confirmed, and it seems to be a reliable orthognathic treatment in patients with mandibular prognathism.     

Classification of antipsychotic drugs by gene expression in the frontal cortex of mice.

Antipsychotic drugs are classified as typical and atypical based on extrapyramidal effects. However, since the frontal cortex is one of the most important regions for antipsychotic actions, this study attempted to classify antipsychotic drugs based on gene expression in the frontal cortex. Chlorpromazine and thioridazine were selected as typical antipsychotics, and olanzapine and quetiapine as atypical antipsychotics. Since these drugs have similar chemical structures, the effect of the basic structure on gene expression can be eliminated. Cluster analysis of microarray experiments separated 4-drug-administered mice into chlorpromazine-quetiapine and thioridazine-olanzapine groups. This classification scheme is different from that which is based on criteria currently used to group the typical and atypical drugs and suggests that antipsychotic drugs can be further separated into multiple groups.     

Chemotherapy in the treatment of advanced or recurrent olfactory neuroblastoma

Background: Olfactory neuroblastoma is a rare sino‐nasal tumor arising from the olfactory epithelium and is often characterized by local invasion or metastasis. The role of chemotherapy in the treatment of this tumor is unclear. The purpose of this study was to review our institution’s experience of chemotherapy for advanced or recurrent olfactory neuroblastoma. Methods: Twenty‐one patients with histologically proven olfactory neuroblastoma were treated at our institution between 1992 and 2002. Twelve of these patients received chemotherapy in the setting of unresectable or recurrent disease and were retrospectively reviewed for clinical characteristics, treatment outcome or survival. Results: Eight patients of the 12 patients received cisplatin‐based chemotherapy and the remaining four patients received chemotherapy consisting of docetaxel plus irinotecan (three patients) or cyclophosphamide, doxorubicin, and vincristine (1 patient). A partial response was achieved in five patients, with an overall response rate of 42%, although the chemotherapeutic regimens were heterogeneous. Two partial responses were obtained among the three patients who received docetaxel plus irinotecan. The response rate to chemotherapy was 83% in the younger age group (<40 years), as opposed to 0% in the older age group (≥40 years), and the difference between the two groups was statistically significant (P = 0.02). Conclusion: Our study indicated that olfactory neuroblastoma would be sensitive to chemotherapy, especially with young patients. Docetaxel plus irinotecan has the possibility of showing favorable response, and warrants further investigation.     

Concurrent presence of metabolic syndrome in obstructive sleep apnea syndrome exacerbates the cardiovascular risk: a sleep clinic cohort study.

This cross-sectional study was conducted to examine whether the obstructive sleep apnea syndrome (OSAS) is associated with elevation of the pulse wave velocity (PWV) and increase in the plasma levels of C-reactive protein (CRP), both of which are known markers of cardiovascular risk, and also to determine if the concurrent presence of the metabolic syndrome might exacerbate this elevation in the levels of these cardiovascular risk markers in subjects with OSAS. With these objectives, the PWV and serum CRP were measured in 184 subjects attending a sleep clinic. It was found that the PWV and CRP were higher in the subjects with OSAS (n=94) than in those without OSAS (n=90). Furthermore, among the subjects with OSAS, the PWV and CRP were higher in those with the concurrent presence of the metabolic syndrome (n= 41; PWV=1,562+/-19 cm/s; CRP=1.8+/-0.2 mg/l) than in those without metabolic syndrome (n=53; PWV=1,432+/-21 cm/s; CRP=1.2+/-0.1 mg/l) (p<0.05). A general linear model analysis demonstrated that OSAS and metabolic syndrome were independently associated with elevated PWV and increase of the plasma levels of CRP. OSAS appears to be associated with increased cardiovascular risk, as reflected by both elevated PWV and increase of the plasma CRP. The concurrent presence of metabolic syndrome may exacerbate this increase in cardiovascular risk in subjects with OSAS. Therefore, the concurrent presence of metabolic syndrome may constitute an additive cardiovascular risk factor in subjects with OSAS.     

Steroid pulse therapy impaired endothelial function while increasing plasma high molecule adiponectin concentration in patients with IgA nephropathy.

BACKGROUND: Decreased plasma adiponectin is associated with impaired endothelial function and, thereby, increased risk for cardiovascular events. Glucocorticoid (GC) affects vascular endothelial cells either favourably or harmfully depending upon the dosages and duration. We examined the effect of GC pulse therapy on vascular endothelial function. METHODS: Fourteen young patients with IgA nephropathy were evaluated for flow-mediated vasodilation (FMD), plasma levels of adiponectin both in high molecular weight (HMW adiponectin) form and in single molecular form (total adiponectin), hepatocyte growth factor (HGF), asymmetric dimethylarginine (ADMA), and high-sensitive C-reactive protein, before and after a course of GC pulse therapy. RESULTS: GC pulse therapy significantly decreased FMD (from 7.2 +/- 2.6 to 5.7 +/- 2.5%, P < 0.01). Meanwhile, plasma adiponectin levels were significantly augmented (total adiponectin: from 10.2 +/- 4.0 to 12.1 +/- 6.3 microg/ml, P < 0.05; HMW: from 6.5 +/- 3.2 to 7.7 +/- 3.3 microg/ml, P < 0.05). In parallel, elevated concentrations of serum HGF (from 0.28 +/- 0.12 to 0.63 +/- 0.38 ng/ml, P < 0.01) and plasma ADMA (from 0.45 +/- 0.07 to 0.53 +/- 0.04 nmol/ml, P < 0.05) were observed. CONCLUSIONS: GC pulse therapy impaired endothelial function while increasing plasma adiponectin levels, which may in turn restore the endothelial function in patients with IgA nephropathy.     

CROSSOVER COMPARISON BETWEEN THE DEPRESSOR EFFECTS OF LOW AND HIGH WORK-RATE EXERCISE IN MILD HYPERTENSION

1. The relationship between work-rate and the antihypertensive effect of exercise in hypertensives, and the mechanism of that effect, were investigated by a crossover clinical trial. 2. Ten mild hypertensives were randomly divided into two groups. One group performed low work-rate exercise (LWE) on a cycle ergometer for 10 weeks (blood lactate threshold; ～50% of maximum oxygen consumption [V?_O2max]). After a 10 week interval without exercise training, these subjects were then switched to a high work-rate exercise (HWE) regimen (4 mmol/ L of blood lactate; ～75% of V?_O2max) for another 10 weeks. In the other group, the order of exercise training was reversed. Since two patients withdrew from the protocol during HWE periods, statistical analysis was performed on the data from the remaining eight patients. There were no order effects observed in any of the data from the two groups. 3. During both LWE and HWE, resting blood pressure (BP) fell significantly after the initiation of exercise therapy (P<0.05). Furthermore, the overall effects of 10 weeks of LWE and HWE on BP were not significantly different. 4. The work-rate at the lactate threshold, which reflects physical fitness, had increased significantly by 16 W (P<0.01) after the LWE period and by 11 W (P<0.01) after the HWE. 5. During the LWE period, changes in haemodynamic and humoral variables were not significant, except for a reduction in plasma norepinephrine at week 10 (P<0.05). In the HWE period, changes in haemodynamic and humoral variables were not significant. 6. Based on these findings, LWE is recommended for mild hypertensives because of its safety.     

Prognostic factors in the treatment of hepatocellular carcinoma with transcatheter arterial embolization and arterial infusion.

From January 1986 to December 1988, a prospective trial of transcatheter arterial treatment was carried out for hepatocellular carcinoma (HCC). Two hundred seventy-five patients were included. Okuda's staging system was employed. Patients with Stage I and II HCC were treated by transcatheter arterial embolization (TAE) with a gelatin sponge containing an anti-cancer agent (protocol 1a); a gelatin sponge and iodized oil mixed with an anti-cancer agent (protocol 1b); or iodized oil mixed with an anti-cancer agent (protocol 2). Patients with Stage III HCC were treated with iodized oil with anti-cancer agent (protocol 2). As an exception, patients with an unsuccessful superselective catheterization into the proper hepatic artery by Seldinger technique or obstruction of the main trunk of the portal vein were treated with percutaneous transcatheter arterial infusion into the common hepatic artery regardless of stage (protocol 3). Tumor type and extension, area of tumor involvement, portal vein involvement, method of treatment, and presence of ascites and icterus were found to be the significant factors for an initial response to therapy. Treatment method was the most important factor. Respective survival rates at 1 and 2 years were 70.9% and 55.3% for protocol 1a; 62.3% and 43.8% for protocol 1b; 37.8% and 18.3% for protocol 2; and 16.5% and 0% for protocol 3. Many factors proved to significantly influenced prognosis; however, tumor type had the most important prognostic significance followed by AFP value, ascites, treatment protocol, and area of tumor involvement.     

Observations in simultaneous microencapsulation of 5-fluorouracil and leucovorin for combined pH-dependent release.

5-Fluorouracil (5-FU) in combination with leucovorin (LV) is nowadays the standard treatment in colon cancer and would be a candidate to be delivered orally to the colon. Eudragit P-4135F or Eudragit RS100 were used separately to prepare microspheres by an oil/oil emulsification process trapping 5-FU and LV simultaneously. Scanning electron microscopy permitted a structural analysis, process parameters were analyzed and drug loading and release profiles were recorded. Particle size varied between 123 (RS100) and 146 microm (P-4135F). Generally, higher encapsulation rates were found with RS100 (5-FU, 60.3+/-9.7%; LV, 81.4+/-8.6%) compared to P-4135F (5-FU, 48.3+/-2.0%; LV, 55.4+/-2.7%). Microparticles made from Eudragit RS100 released the incorporated drug combination within 8 h not exhibiting general differences between the kinetics of both drugs. P-4135F was found to maintain the undesired 5-FU release at pH 6.8 lower than 25% within 4 h while at pH 7.4, a nearly immediate release (within 15 min) was observed. Although the release was similar at pH 7.4, at pH 6.8 LV showed a distinct initial drug loss of about 60% and a complete release within 2 h. SEM analyses revealed a substantial presence of LV crystals on the particle surface provoking a distinct burst effect of LV. These observations were concluded to be related to the high lipophilicity of P-4135F provoking a separation between P-4135F and LV during the preparation process.     

Characteristics and course of bone mineral densities among fast bone losers in a rural Japanese community: the Miyama Study

The aim of this study was to clarify and compare the temporal course of bone mineral density (BMD) between fast bone losers and normal residents in Miyama Village, a rural Japanese community. BMD was measured over a 10-year period in a cohort study in Miyama Village, Wakayama Prefecture, Japan, to provide information on rate of bone loss in the mature and elderly population. Subjects (n=400) were selected by sex and age stratum from the full list of residents born in 1910–1949, with 50 men and 50 women in each age decade. Baseline BMD of the lumbar spine and proximal femur was measured using dual energy X-ray absorptiometry in 1990, 1993, 1997 and 2000. In the cohort, 171 men and 189 women completed the follow-up survey performed in 1993. After calculating the rate of bone loss between 1990 and 1993, the greatest tertile from the distribution of bone loss was categorized as fast bone losers, with the remainder considered as normal subjects. Changes in BMD were compared between normal subjects and fast bone losers over the 10-year period. Mean rate of change for BMD at both lumbar spine and femoral neck in fast bone losers recovered to levels similar to those in normal subjects over 7 years of observation. By contrast, BMD at the lumbar spine and femoral neck decreased steeply over the 10-year period in both groups, and mean BMD for fast bone losers was significantly lower than that of normal subjects (P<0.05). These differences were apparent only at the lumbar spine in both men and women, even after adjusting for age. These results indicate that fast bone loss is a transient phenomenon rather than a fixed status, although individuals who have been categorized as fast bone losers at some stage continue to display low BMD in the lumbar spine.