Utilization of common inflammatory markers in new, symptomatic, primary care outpatients based on their cost-effectiveness.

Few studies have demonstrated the optimal usage of common inflammatory markers, alone or in combination, based on the cost-effectiveness. We analyzed the yield and cost of C-reactive protein (CRP), white blood cell count (WBC), erythrocyte sedimentation rate (ESR), sialic acid, and protein fractionation in 177 new primary care outpatients with inflammation-related symptoms. A useful result (UR) was assigned if tests contributed to a change in physician's diagnosis or decision-making. Costs of testing were calculated based on either single or simultaneous measurement. Five inflammatory markers generated 147 URs in 123 patients. CRP showed the best contribution to generation of UR, followed by sialic acid, protein fractionation, WBC, and ESR. CRP demonstrated poor correlation with WBC (r = 0.458), while sialic acid strongly correlated with total absolute amount of alpha1 and alpha2 fractions in protein fractionation (r = 0.855) and moderately with ESR (r = 0.651). The combination of CRP and WBC produced the best cost-effectiveness at a cost of Yen 1169 (US dollars 9.6 or Euro 9.7)/additional UR against CRP testing alone. Sialic acid, an automated multichannel analyzer-based test, demonstrated the favorable cost-effectiveness over ESR or protein fractionation when combined with CRP (and WBC). Our results indicate that the optimal usage of these inflammatory markers should involve careful cost-effectiveness considerations.     

LONG‐TERM FOLLOW UP OF PATIENTS WITH SMALL GASTROINTESTINAL STROMAL TUMORS IN THE STOMACH USING ENDOSCOPIC ULTRASONOGRAPHY‐GUIDED FINE‐NEEDLE ASPIRATION BIOPSY

Background: Gastrointestinal stromal tumors (GIST) are one of the most common mesenchymal tumors of the gastrointestinal tract. GIST are defined by positive immunohistochemical staining for KIT or CD34 and thus are generally diagnosed after surgery. Because small GIST are rarely diagnosed before surgery, the clinical course of these small tumors is not clear. The aim of the present study was to follow changes in size and configuration of small GIST that were pathologically confirmed using endoscopic ultrasonography‐guided fine‐needle aspiration biopsy (EUS‐FNAB). Methods: Between July 1997 and December 2003, 16 tumors in 16 patients (10 men and 6 women) with an immunohistochemical diagnosis of GIST were regularly followed in our hospital. The median patient age when EUS‐FNAB was performed was 62 years (range 26–82 years) and the median follow‐up period was 4.9 years (range 0.5–9.6 years). Results: Fourteen tumors showed no remarkable changes in size and shape during follow up compared with the initial diagnosis. Two tumors enlarged: one tumor approximately doubled its diameter in 8 years and the other tumor increased from 1.8 cm at diagnosis to up to 10 cm after only 2 years. Doubling time of the latter tumor was calculated as 3.1 months. Conclusions: We conclude that EUS‐FNAB might be a good modality for final diagnosis of GIST without surgery, and that GIST without rapid growth on follow up can be endoscopically followed.     

IMPROVED BALLOON‐TIPPED TRANS‐ANAL ILEUS TUBE

Background: For management of bowel obstruction due to colorectal cancer, endoscopic trans‐anal decompression technique has been first reported by Lelcuk et al. in 1986 using balloon dilatation technique. Since then, various types of trans‐anal decompression tubes have been clinically used for patients suffering from left side obstructing colorectal cancer as an emergent decompressing device. At present, two types of trans‐anal ileus tube (trans‐anal decompression tube) have been available for clinical use, but they have two main problems that are late colon perforations caused by the tip of the tube and tube obstruction by stool. Methods: Analysis on three late colon perforations experienced with the use of conventional devices drew possible improvements to make a trans‐anal ileus tube less harmful. To overcome the pitfalls inherent to conventional tubes, the author has developed an improved trans‐anal ileus tube with a balloon installed at the very end of the tube (‘balloon‐tipped type’) made of silicone, measuring 1200 or 1700 mm in total length and 22 Fr in outer diameter. It has been used for 12 cases with obstructing colorectal cancer etc. and its outcomes were compared with those obtained by the use of conventional trans‐anal ileus tube. Results: No late perforations have been encountered, but tube obstruction did occur in one of 12 cases. Conclusion: The new trans‐anal ileus tube with a balloon installed at the tip of ileus tube is considered to be safer and especially effective in preventing late colon perforation and tube obstruction.     

Activation of protein kinase C and nicotinamide adenine dinucleotide phosphate oxidase in leukocytes of spontaneously hypertensive rats.

The involvement of oxidative stress in polymorphonuclear leukocytes (PMN) in the pathogenesis of hypertension remains to be elucidated. We analyzed the generation of reactive oxygen species (ROS) by the circulating and peritoneally infiltrating PMN from spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). Flow cytometric analysis revealed that ROS generation by PMN from SHR was higher than that from WKY before (at 6 weeks of age) and after (at 16 weeks of age) the onset of hypertension. In vivo, ROS generation by PMN from SHR, but not that by PMN from WKY, was significantly suppressed by 10-week treatment with 50 mg/kg/day carvedilol, and this treatment did not affect blood pressure. Western blotting analysis revealed that protein kinase C alpha (PKCalpha), but not PKCbetaI or betaII, was activated more strongly in PMN from SHR than in PMN from WKY. Furthermore, expression of p47phox of nicotinamide adenine dinucleotide phosphate oxidase, but not of p67phox, in PMN from SHR was higher than that in PMN from WKY. These results suggest that ROS generation by PMN is principally enhanced in SHR through activation of PKCalpha and p47phox.     

Plasma leptin level and its relationship with body composition in hemodialysis patients

Leptin is a newly found hormone secreted by adipocytes that regulates food intake, thermogenesis, and body fat. We measured plasma leptin levels in 103 patients with chronic renal failure treated by hemodialysis and 167 age- and gender-matched healthy control subjects to examine the impact of renal failure on plasma leptin levels and the influence of leptin on body composition measured by dual-energy X-ray absorptiometry. Hemodialysis patients showed a significant decrease in both body fat mass and lean body mass compared with those of the control subjects. Plasma leptin was significantly elevated in the hemodialysis group over the controls. In both groups, leptin was higher in female than male subjects, and it correlated positively with percent body fat. The subjects were divided into six categories according to percent body fat, and plasma leptin levels were compared between the two groups in the same category. Leptin of hemodialysis patients was significantly higher than that of the control subjects in the percent body fat categories of 30 or greater, whereas there was no statistically significant difference in leptin concentrations in the lower percent body fat categories. This was also true in the comparison in each gender, and leptin levels in female subjects showed a more remarkable difference between the hemodialysis and control groups in obese categories. Multiple regression analysis in all subjects indicated that plasma leptin levels were independently affected by percent body fat, plasma insulin concentration, gender, and renal failure. The positive impact of renal failure on leptin remained significant in the subjects with percent body fat of 30 or greater in the multiple regression model, whereas it was no longer significant in the remaining lean subjects. In multiple regression analysis of factors affecting fat mass index and lean mass index, leptin level was selectively associated with fat mass index, but not with lean mass index, regardless of percent body fat ranges. These results indicate that renal failure is an important factor affecting plasma leptin levels, especially in obese female subjects, and that hyperleptinemia was closely related to fat mass but not to lean body mass in hemodialysis patients.     

Synthesis of antimicrobial agents. 1. Syntheses and antibacterial activities of 7-(azole substituted)quinolones

A series of 6-fluoro- and 6,8-difluoro-7-(azole substituted)-1,4-dihydro-4-oxo-3-quinolinecarboxylic acids were prepared. Structure-activity relationship studies indicated that the antibacterial potency was better when the 6,8-substituents were fluorine atoms and the 7-substituent was either 1-imidazolyl, 20, or 4-methyl-1-imidazolyl, 25. From the results of studies on pharmacokinetic profile and toxicity, 20 and 25 were found to possess excellent antibacterial activities and to show high blood levels after oral administration to mice with low toxicity.     

A case of transient bioprosthetic valve regurgitation and hemolysis devoloping early after surgery using Carpentier-Edwards valve.

The Carpentier-Edwards pericardial bioprosthesis has been markedly improved in the long-term results and valve-related complications including valve dysfunction, compared to the previous generation bioprosthesis. We report a patient in whom transient prosthetic valve regurgitation and hemolysis occurred early after mitral valve replacement using a Carpentier-Edwards pericardial bioprosthesis and were resolved by preservative therapy. The patient was a 77-year-old female diagnosed with severe mitral valve stenosis and insufficiency. She underwent mitral valve replacement with a Carpentier-Edwards pericardial bioprosthesis. Opening and closing of the three leaflets looked good on intraoperative transesophageal echocardiography (TEE). The only prosthetic valve regurgitation was evident at the central region where the leaflets form coaptation, and no abnormal findings were seen. Serum lactate dehydrogenase (LDH) was decreased to 405 U/l after surgery. However, LDH again began to increase on the 3rd day after surgery and it increased to 1,830 U/l on the 14th day after surgery. Hemolytic urine was detected on 10th day after surgery. PVL was not detected, but moderate abnormal regurgitation from the outside of the stent pocket was detected on TEE. Revision of valve replacement was considered, but LDH thereafter to 393 U/l on 41st day after surgery. The TEE was repeated, and only a trace of central jet was detected without abnormal regurgitation, unlike the previous examination. The patient did not develop any complications thereafter and was discharged on 47th day after surgery. LDH was nearly normal at the time of discharge.     

An innovative method to measure skin pigmentation

Background/purpose: It is crucial to establish an accurate method for measuring skin pigmentation in cosmetic science and clinical dermatology. Here, we report a non-invasive precise method for measuring skin melanin content.
Methods: In order to determine the concentrations of melanin and hemoglobin in skin, we used the spectrum resolution (SR) method. In brief, the absorption spectrum of the skin was calculated from the reflection spectrum using a spectrophotometer. The concentrations of melanin and hemoglobin were then determined using a multiple regression analysis, assuming that the absorption spectrum of the skin is expressed as a linear summation of the absorptions of melanin and hemoglobin according to the Lambert–Beer law. The skin changes in the volar forearm, which had been irradiated by ultraviolet rays (UV), were observed daily by the SR method.
Results: A multiple regression analysis with an absorption spectrum of 500–700 nm was performed. The multiple correlation coefficient was 0.993, resulting in a satisfactory precise estimate of the concentrations of melanin. After UV irradiation, the concentration of melanin monitored by the SR method increased until 8 days and decreased gradually afterwards.
Conclusions: The SR method allows the evaluation of the changes of epidermal melanin induced by UV irradiation.     

Prostate Risk Index (PRIX) as a New Method of Risk Classification for Clinically Localized Prostate Cancer

PURPOSE: The aim of this study is (1) to develop a new method of risk classification for clinically localized prostate cancer; (2) to examine it in terms of compatibility with existing data such as nomograms; and (3) to compare it with existing risk-grouping methods. MATERIAL AND METHODS: The new grading system introduced here consists of three factors. The first is a prostate-specific antigen (PSA) of 4.1-10.0 ng/ml (score 0), 10.1-20.0 ng/ml (score 1), and >20.0 ng/ml (score 2). The second is a Gleason score (GS) of 6 (score 0), 7 (score 1), and 8-10 (score 2). The third is T classifications (UICC 2002) of T1c-T2a (score 0), T2b-T2c (score 1), and T3a (score 2). The sum of the three scores was named Prostate Risk Index (PRIX). Then, the compatibility of PRIX with the Partin Table, Kattan Nomogram, and Roach's formula was examined. At the same time, PRIX was compared with D'Amico, the National Comprehensive Cancer Network (NCCN), and Seattle classifications. RESULTS: PRIX 0 corresponded to 1-2% of pathologic lymph node involvement (pLN+) according to the Partin Table; PRIX 1 to 3-4%; PRIX 2 to 7-10%; PRIX 3 to 14-18%; PRIX 4 to 24-29%; PRIX 5 to 32-37%; and PRIX 6 to 42%. PRIX well separated the risks with relatively narrow ranges of probability, while D'Amico, NCCN, and Seattle classifications generally gave wide ranges especially for high-risk groups, both in the Partin Table and Kattan Nomogram. Roach's formula sometimes overestimated the risk compared to the Partin Table. CONCLUSION: PRIX fully corresponded to the Partin Table in terms of pLN+, and corresponded to the other nomograms better than any existing risk-grouping method. PRIX may thus function as a prognostic factor or contribute to patient selection in clinically localized prostate cancer.