Environmental factors and seasonal influenza onset in Okayama city, Japan: case-crossover study

Seasonal influenza infection is a major challenge in public health. The term "seasonal influenza" refers to the typical increase in the number of influenza patients in the winter season in temperature zones. However, it is not clear how environmental factors within a single flu season affect influenza infection in a human population. Therefore, we evaluated the effects of temperature and humidity in the 2006-7 flu season on the onset of seasonal influenza using a case-crossover study. We targeted patients who attended one pediatric clinic in Okayama city, Japan and who were diagnosed as being infected with the seasonal influenza virus. Using 2 references (time-stratified and symmetric bidirectional design), we estimated the effects of average temperature and relative humidity from the onset day (lag0) to 10 days before (lag10). The total number of subjects was 419, and their onset days ranged from 26 December 2006 to 30 April 2007. While the onset was significantly associated with lower temperature, relative humidity was not related. In particular, temperatures before the 3-day incubation period had higher-magnitude odds ratios. For example, the odds ratio and 95% confidence interval for average temperature at time lag 8 was 1.12 (1.08-1.17) per 1.0℃ decrease. Low environmental temperature significantly increased the risk of seasonal influenza onset within the 2006-7 winter season.     

Haplotype of thrombomodulin gene associated with plasma thrombomodulin level and deep vein thrombosis in the Japanese population

INTRODUCTION: Thrombomodulin (TM) is an essential cofactor in protein C activation by thrombin. Here, we evaluated the contribution of genetic variations in the TM gene to soluble TM (sTM) level and deep vein thrombosis (DVT) in Japanese. PATIENTS AND METHODS: We sequenced the TM putative promoter, exon, and 3'-untranslated region in DVT patients (n=118). Among 17 genetic variations we identified, two missense mutations (R385K, D468Y) and three common single nucleotide polymorphisms (-202G>A, 2487A>T, 2729A>C) were genotyped in a general population of 2247 subjects (1032 men and 1215 women) whose sTM levels were measured. We then compared the frequency of these mutations in DVT patients with that in the age, body mass index-adjusted population-based controls. RESULTS: We identified one neutral mutation (H381) and three missense mutations (R385K; n=2, A455V; n=53 heterozygous, n=14 homozygous, D468Y; n=2) of TM in the DVT patients. Age-adjusted mean values of sTM were lower in C-allele carriers of 2729A>C than in noncarriers in the Japanese general population (women: 16.7+/-0.3 U/ml vs. 17.9+/-0.2 U/ml, p<0.01, men: 19.4+/-0.3 U/ml vs. 20.4+/-0.3 U/ml, p=0.03). Additionally, the CC genotype of this mutation was more common in the male DVT patients than in the male individuals of the general population (odds ratio=2.76, 95% confidence interval=1.14-6.67; p=0.02). This mutation was in linkage disequilibrium (r-square>0.9) with A455V mutation. CONCLUSIONS: TM mutations, especially those with a haplotype consisting of 2729A>C and A455V missense mutation, affect sTM levels, and may be associated with DVT in Japanese.     

A 4-week versus a 3-week schedule of gemcitabine monotherapy for advanced pancreatic cancer: a randomized phase II study to evaluate toxicity and dose intensity

Background

This randomized phase II study compared the efficacy and toxicity between 4-week and 3-week schedules of gemcitabine monotherapy in advanced pancreatic cancer.

Methods

Patients with advanced pancreatic cancer were randomly assigned to either a 4-week schedule (gemcitabine at 1000?mg/m2 as a 30-min infusion weekly for 3 consecutive weeks every 4?weeks) or a 3-week schedule (gemcitabine at 1000?mg/m2 as a 30-min infusion weekly for 2 consecutive weeks every 3?weeks). The primary endpoint was the compliance rate during the first 8?weeks between the two groups.

Results

A total of 90 patients were enrolled. The compliance rate during the first 8?weeks was the same (53.3%). For the 4- and 3-week schedules, the tumor response rates were 14.2 and 17.1% (p?=?0.92), median progression free survival was 112 and 114?days (p?=?0.82), and median overall survival was 206 and 250?days (p?=?0.84), respectively. Grade 3?? neutropenia was the major adverse event in both schedules: 37.7 and 35.5% (p?=?0.82). In contrast, thrombocytopenia (platelet count <70000/mm3) was significantly higher for the 4-week schedule: 26.6 and 4.4% (p?=?0.008). The mean received dose intensity was equal: 588 and 550?mg/m2/week (p?=?0.14).

Conclusions

The 3-week schedule of gemcitabine did not improve the compliance rate during 8?weeks compared with the 4-week schedule, but it attained a comparable efficacy with lower toxicity. Further investigation will be needed to introduce it into daily practice. Clinical trial registration number: UMIN ID 974.     

Impaired binding of thrombin to thrombomodulin is associated with risk of deep vein thrombosis

The complex of thrombin and thrombomodulin (TM) activates protein C, and impaired binding of thrombin to TM may be a risk factor for thrombosis. In this study, we evaluated the reactivity of thrombin to TM by determining the TM-bound thrombin (TMBTh) to total thrombin generation (t-Th) ratio (TMBT ratio). We also examined whether a decreased TMBT ratio is associated with increased risk of thrombosis. TMBTh was measured on TM-coated plates. Thrombin was generated by addition of prothrombin time reagent to plasma. Levels of t-Th and TMBTh were expressed as percentages of the levels in pooled normal plasma. The study included 124 patients with deep vein thrombosis and 150 age- and sex-matched healthy subjects. The TMBT ratio (TMBTh/t-Th) was significantly lower in patients than in control subjects (p < 0.05). Among the 124 patients, 43 (34.7%) showed TMBT ratios below the 5th percentile value of control subjects, and the odds ratio (OR) for development of deep vein thrombosis was 9.4 (95% confidence interval [CI], 4.6-19.1). When patients with a deficiency of natural anticoagulant (antithrombin III, protein C, or protein S) were excluded from analysis, the TMBT ratio in 37 (42.5%) of the remaining 87 patients was below this cutoff point, and the OR (13.1; 95% CI, 6.4-26.9) was increased compared to that in the total patient group. These results suggest that it is possible to evaluate the reactivity of thrombin to TM by determining the TMBT ratio, and this ratio may be a predictor of deep vein thrombosis.     

Effect of simple motor performance on regional dopamine release in the striatum in Parkinson disease patients and healthy subjects: a positron emission tomography study.

To investigate changes in dopamine release in the striatum during motor exercise in human subjects with and without striatal dopamine denervation, eight healthy subjects and eight patients with Parkinson disease (PD) were measured during unilateral foot extension/flexion movement using positron emission tomography with [11C]raclopride. Five subjects in each group were later scanned in the resting condition. Estimation of binding potential (k3/k4) of [11C]raclopride was based on Logan plot method. Significant reductions in [11C]raclopride k3/k4 were found in the dorsal putamen contralateral to the exercise side in the healthy group and ipsilaterally in the PD group. Spearman rank correlation analysis showed that [11C]raclopride k3/k4 correlated inversely with the decrease in performance (velocity and motion range) in the dorsal putamen contralaterally in the healthy group and ipsilaterally in the PD group. These results suggest that simple but laborious motor exercise (motor stimulation) generates significant dopamine release in the dorsal striatum contralateral to the motor execution in humans. Lack of the crossed pattern and ipsilateral increase in dopamine release in the dorsal striatum during the unilateral limb movement may reflect the pathophysiology for hypokinetic and insufficient coordinating movement in PD.     

Inhalation of corticosteroid and β-agonist for persistent cough following pulmonary resection

Background  

Patients undergoing pulmonary resection often suffer from a dry, hacking cough, which is usually refractory to opioid cough suppressors such as codeine. The cough is often painful and impairs the quality of life of the patients. The efficacy of an inhaled corticosteroid plus β2-agonist against the persistent cough after pulmonary resection was evaluated in this study.     

Striatal D2 receptor availability after shunting in idiopathic normal pressure hydrocephalus.

Gait disturbance in idiopathic normal pressure hydrocephalus (iNPH) is reminiscent of parkinsonism. Our recent PET study showed reduction in postsynaptic D(2) receptor binding concomitant with a normality of presynaptic dopamine transporter binding. Here, we investigated the plasticity of D(2) receptor in treating iNPH patients with ventriculoperitoneal (VP) shunting using PET with (11)C-raclopride and discuss the contribution of D(2) receptor to the pathophysiology of iNPH. METHODS: Eight iNPH patients participated in this study. After evaluation of their neuropsychologic abilities, all patients underwent 3-dimensional MRI and quantitative PET measurements twice before and 1 mo after VP shunting. MRI-based morphometric analyses were performed to examine postoperative variations of the ventricles. Estimation of binding potential (BP) for (11)C-raclopride was based on Logan plot analysis. Region-of-interest analysis was used to examine changes in (11)C-raclopride BP in the striatum. A 2-tailed paired t test was used for evaluating changes in PET and MRI parameters between conditions, and correlation analysis was used to investigate clinicopathophysiologic relevance (clinical vs. in vivo findings). RESULTS: Clinical evaluation revealed significant recovery in a 5-m back-and-forth navigation test and an affect test and a mild increase in Mini-Mental State Examination scores after VP shunting. Significant postoperative increases in (11)C-raclopride BP were found in the nucleus accumbens and dorsal putamen, and the increases were significantly associated with emotional (Spearman rank r = 0.66, P < 0.05) and navigational improvement (r = 0.72, P < 0.05), respectively. The (11)C-raclopride BP increase in the striaum as a whole correlated significantly with improvement in general cognitive ability. There was a mild ventricular shrinkage after surgery, albeit there was no correlation of its size with clinical and PET parameters. CONCLUSION: Striatal upregulation of D(2) receptor after VP shunting is associated with amelioration of hypokinetic gait disturbance and anhedonic mentation in iNPH patients, indicating that the effect of VP shunting may reside in noninhibition of functionally suppressed D(2) receptor in the striatum. D(2) receptor responsiveness may indicate a mechanism for iNPH pathophysiology.     

Expansion of the spectral bandwidth by spatial and chemical shift selective saturation in high-speed magnetic resonance spectroscopic imaging

A new spectral bandwidth expansion technique for highspeed magnetic resonance spectroscopic imaging (MRSI) based on an echo-planar technique is presented. This expansion can be achieved by spatial and chemical shift selective saturation without increasing the total measurement time. In addition, displacement along the slice-select direction due to chemical-shift differences between the measured compounds is also suppressed. Experimental results are shown using a phantom consisting of benzene and acetone. High spatial resolution (1 × 1 mm²) and wide spectral bandwidth (1.5–1.8 kHz; the effective spectral bandwidth has been doubled) are obtained without the displacement along the slice-select direction.     

A case of non-curatively resected gastric cancer successfully treated over 3 years with biweekly paclitaxel therapy

We report a case of non-curatively resected gastric cancer successfully treated over 3 years with biweekly administration of paclitaxel. A 69-year-old man underwent non-curative resection with distal gastrectomy for advanced gastric cancer with remarkable lymph node metastasis on June 10, 2002. The metastatic lymph node (No. 8 a, 8 p and 12 a) linked up with the retroperitoneal node, making resection impossible. Postoperatively, he was initially treated with weekly administration of paclitaxel 100 mg/body (68 mg/m(2)) per week. However, due to grade 3 neutropenia in the first course, weekly administration was changed to biweekly administration with dose reduction to 60 mg/body (41 mg/m(2)), resulting in the continuation of paclitaxel therapy. Since then, no grade 3 or more severe adverse reactions have been observed. He has maintained NC for 3 years, and is still being treated on an outpatient basis at present. We believe that, in paclitaxel therapy for advanced gastric cancer, it is important for long-term survival to continue it perseveringly by dose reduction or change of schedule, when major adverse reactions are seen.