The factors affecting glycemic control were examined using HbA_1C as an index in a total of 22 patients with type 2 diabetes mellitus whose ages at onset were less than 18 years old. As a result, the presence or absence of the following cases were considered possible factors for significant exacerbation of glycemic control: diabetic microangiopathy; school phobia or nonworking situation; drug therapy; use of more than two kinds of oral hypoglycemic agents (OHAs) or insulin for the drug therapy cases. No improvement in glycemic control could be achieved even by increasing the number of OHAs for co-administration or by insulin use unless dietary/exercise therapy, a basic therapeutic option, was adequately performed.

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We have reported that percutaneous cardiopulmonary assist systems (PCPS) are effective in treating life-threatening cardiogenic shock that is intractable to treatment with intraaortic balloon pumping (IABP). However, there are few clinical indices that can be used to evaluate the effectiveness of PCPS. End-tidal carbon dioxide (ET-CO₂) content reflects pulmonary blood flow. We monitored ET-CO₂ continuously and determined whether we could use it as a new index to evaluate the effectiveness of PCPS. Seventeen patients with cardiogenic shock were intubated and evaluated by ET-CO₂ monitoring during PCPS. The etiology of shock included acute myocardial infarction (n=10), acute myocarditis (n=2), recent coronary artery bypass graft (n=1), cardiac rupture (n=1), hypertrophic obstructive cardiomyopathy complicated by ventricular fibrillation (n=1), left atrial myxoma (n=1) and artificial valve malfunction (n=1). PCPS was extremely effective in 10 of 17 patients (58.8%), and they recovered from the cardiogenic shock. The remaining 7 patients did not recover from shock, and died during PCPS. Six of ten patients who recovered from shock were successfully weaned from PCPS and 4 patients had good long-term survival. In the cases where PCPS was effective, the ET-CO₂ measured soon after the beginning of PCPS was significantly higher than in the cases in which PCPS was ineffective. Furthermore, the ET-CO₂ content increased gradually with the improvement in hemodynamics. In contrast, ET-CO₂ content remained low if PCPS was not effective. The ET-CO₂ represents a useful predictor of survival or death and is also a good index for weaning in patients treated with PCPS.

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Little is known about the relation between atopic disorders and altitude of residence. The author investigated the prevalence of asthma and atopic dermatitis, and their relationship with altitude of residence. A total of 24,631 children aged four years and under in Gunma Prefecture, Japan, were surveyed. The ATS-DLD questionnaire for asthma was distributed together with an item on atopic dermatitis. Some confounding variables were also asked. The author judged subjects as having asthma when positive answers were given to all 6 items in the ATS/DLD questionnaire. The prevalence of asthma in subjects with atopic dermatitis was higher than in those without (5.1% vs. 1.8%). Logistic regression analyses for asthma and atopic dermatitis were conducted, and male sex, increasing age, family history of target disease, and living at higher altitude commonly and significantly contributed to an increase in the risk of each allergic disorder. For asthma, not being the eldest child, and past or present history of atopic dermatitis were also selected as risk factors. There was an increase in the prevalence of atopic disorders in groups living at a higher altitude was observed in this area.

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To provide new insights into the molecular mechanisms underlying the effect of irradiation on esophageal squamous cell carcinomas (ESCCs), we used a cDNA microarray screening of more than 4,000 genes with known functions to identify genes involved in the early response to ionizing irradiation. Two human ESCC cell lines, one each of well (TE-1) and poorly (TE-2) differentiated phenotypes were screened. Subconfluent cells of each phenotype were treated with single doses of 2.0 Gy or 8.0 Gy irradiations. After a 15 min incubation time-point, the cells were collected and analyzed. Compared with non-irradiated cells, many genes revealed at least 2-fold upregulation or downregulation at both doses in well or poorly differentiated ESCC cells. The common upregulated genes in well and poorly differentiated cell types at both irradiation doses included SCYA5, CYP51, SMARCD2, COX6C, MAPK8, FOS, UBE2M, RPL6, PDGFRL, TRAF2, TNFAIP6, ITGB4, GSTM3, and SP3 and common downregulated genes involved NFIL3, SMARCA2, CAPZA1, MetAP2, CITED2, DAP3, MGAT2, ATRX, CIAO1, and STAT6. Several of these genes were novel and not previously known to be associated with irradiation. Functional annotations of the modulated genes suggested that at the molecular level, irradiation appears to induce a regularizing balance in ESCC cell function. The genes modulated in the early response to irradiation may be useful in our understanding of the molecular basis of radiotherapy and in developing strategies to augment its effect or establish novel less hazardous alternative adjuvant therapies.

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We investigated the ability of angiogenesis in PC9/F9 cells (from a highly metastatic human lung adenocarcinoma cell line) as compared with PC9 cells (from a low metastatic human lung adenocarcinoma cell line). In vivo tumor growth assay using BALB/c nude mice (7 mice/group), showed that the tumor volume of PC9/F9 cells on day 35 (230.7±31.3 mm³) was significantly larger than that of PC9 cells (90.9±24.7 mm³) (p<0.001). However, there was no significant difference between PC9/F9 cells and PC9 cells in an in vitro growth assay. In a dorsal air sac assay (DAS assay) using ICR mice (3 mice/group), PC9/F9 cells (4.7±1.2 vessels) showed stronger neovascurizationin in compared with PC9 cells (0.3±0.4 vessels) (p<0.05). In an enzyme linked immunosorbent assay (ELISA) and Western blotting analysis there were no significant differences between PC9/F9 cells and PC9 cells in the protein expression of vascular endothelial growth factor (VEGF). There was no significant difference between the gene expression levels of PC9/F9 cells and PC9 cells on cDNA array analysis. Matrix metalloproteinase-2 (MMP-2) activity in PC9/F9 cells was remarkably stronger than that of PC9 cells in Gelatin Zymography. From these results, we considered that of the increased metastasis of PC9/F9 cells might be induced by augmented angiogenesis. Furthermore, we speculated that the augmented angiogenesis of the highly metastatic PC9/F9 cell line might be induced by increased MMP-2 activity.

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In 2002, the Centers for Disease Control and Prevention (CDC) published guidelines for surgical handwashing and hand antisepsis on the Internet. According to these guidelines, we revised our surgical handwashing method from scrubbing with brushes to rubbing with antiseptic. The new method consists of scrubbing around the nails with brushes and rubbing the hands and arms with antiseptic from the elbow to the antebrachium. A total of 182 surgeons and operating-room nurses participated in the current study. Bacterial contamination was investigated using the glove-juice method. The new surgical handwashing method is simple, and requires only a short time to perform (2 minutes 50 seconds). The bacterial examination confirmed that rubbing the hands with antiseptic was significantly more effective than scrubbing with brushes. In terms of sterilization or prolonged effects, 4% chlor-hexidine gluconate (CHG) was superior to 7.5% povidone-iodine (PVI) throughout a 3-hour period after hand antisepsis. Although bacterial counts were increased 3 hours after the beginning of surgery, additional hand rubbing with 0.2% chlorhexidine-83% ethanol (Hibisoft^TM) was effective in suppressing the number of bacteria. Hibisoft^TM successfully prolonged sterilization for more than 3 hours. For long surgical procedures, CHG should be used as an antiseptic and gloves should be changed every 3 hours, alcohol-based hand rubbing should also be performed 3 hours after the initial handwashing. This new technique will be included in the OSCE curriculum to ensure its standardization. Moreover, in-depth education regarding central operating-room practices is desired.

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A rare case of carcinoid tumor in the duodenal bulb associated with early gastric carcinoma is reported. An 85-year-old asymptomatic male was admitted to our hospital, referred by his neighboring doctor because of early gastric carcinoma shown by endoscopic examination. X-ray studies of the upper gastrointestinal tract showed irregular lesser curvature of the gastric antrum and a filling defect (&phis;1 cm) at the duodenal bulb. Gastric biopsy revealed the histological findings of Group V. Distal gastrectomy including the duodenal bulb with D2 lymph node dissection was performed. A resected specimens showed superficial depressed type carcinoma at the lesser curvature of the antrum, and an isolated submucosal tumor of 7×7 mm in size at the duodenal bulb. Histological examination disclosed papillary adenocarcinoma in the gastric mucosa and a carcinoid tumor of the duodenal bulb in the submucosal layer without high malignant findings. The patient has been well for 5 years since the surgery. In conclusion, we discussed 46 collected cases of carcinoid tumor of the duodenum associated with gastric carcinoma in Japan. Preoperative diagnosis of carcinoid tumor of the duodenum is very difficult, and thorough examinations are needed for submucosal lesion.

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Hercep Test (DAKO) is an immunohistological screening kit to select cases of advanced breast cancer with indication for treatment with a humanized mouse monoclonal antibody to human epidermal growth factor receptor-2, trasthzumab (Herceptin). We report a case of an 84-year-old female with invasive ductal carcinoma of the right breast, whose neoplastic cells showed a unique staining pattern in Hercep Test. The cells showed an intracytoplasmic fine granular staining pattern, instead of the membranous pattern of typical breast cancer cells. This unique staining pattern suggested some special features of the neoplastic cells. This case was finally diagnosed as invasive ductal carcinoma with focal neuroendocrine differentiation by subsequent imunohistochemical and electron microscopic examinations. The neoplastic cells showed positive reactivity for grimelius stain, chromogranin A, synaptophysin, and neuronspecific enolase, as well as electron-dense neurosecretory granules (up to 150 nm in diameter). This unique staining pattern of the neoplastic cells with Hercep Test is a useful clue to detect breast cancer with neuroendocrine differentiation, which is likely to be missed in routine examination. Clinical and pathologic findings including immunohistochemical and ultrastructural findings of this case are reported, together with a brief review of the literature.

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We report a case of hepatocellular carcinoma with situs inversus totalis treated by hepatectomy. A 70-year-old asymptomatic female with hepatocellular carcinomas in segments 5, 6 and 8 underwent transarterial embolization in the department of medicine. However, hepatocellular carcinoma in segment 8 relapsed, and she was referred to the department of surgery. Laboratory tests revealed elevation of serum PIVKA2 level (4,690 ng/mL). Angiography revealed tumor stain in segment 8, 3 cm in diameter. No aberrant vessels were detected on angiography. The operator stood on the patient's left, and partial hepatectomy could be performed safety after careful examination of the anatomy. Although aberrant vessels are detected in many patients with situs inversus totalis, operations can be performed safely on them with sufficient understanding of the anatomy.

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A 74-year-old woman with advanced carcinoma of the gall bladder underwent anterior and medial segmentectomies, extrahepatic bile duct resection, lymph node dissection, and hepaticojejunostomy with retrograde transhepatic biliary drainage. On the sixteenth postoperative day, bleeding was noted through the biliary drain, but it stopped spontaneously. Two days later, the biliary drain showed bleeding again. Ultrasonography revealed mild dilatation of the intrahepatic bile duct. Cholangiography via the drain disclosed a defect in the jejunal limb. Emergency angiography revealed an aneurysm, 2 cm in diameter, in the posterior branch of the right hepatic artery. Contrast medium demonstrated extravasation into the jejunal limb. The pseudoaneurysm was embolized with coils. No further hemorrhage was noted, and the patient was discharged 30 days after operation.

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A Nobel medical payment system, the Diagnosis Procedure Combination (DPC), was implemented in Nippon Medical School Hospital and 81 other specific-function hospitals in 2003. This payment system depends on the length of hospital stay and diagnosis and medical procedures, and differs from the existing payment system, which depends on a piece rate. The daily payment differs for among almost 2,500 groups of DPC defined by the International Statistical Classification of Diseases and Related Health Problems (ICD-10), and procedures, such as operations (K and J codes of the existing payment system). One of the most important outcomes may be a decrease in lengths of hospital stay, because the range of mean lengths of stay in specific-function hospitals has been officially stated to be 14 to 30 days, and the difference between the longest and shortest mean is almost double. The new medical payment system should stimulate competition among hospitals. In order to decrease the length of stay, we developed clinical pathways for patients undergoing surgery, such as laparoscopic cholecystectomy, gastrectomy, and inguinal hernia operations, as well as clinical protocols for the surgical procedures, such as percutaneous transhepatic cholangiodrainage (PTCD) and percutaneous endoscopic gastrostomy (PEG). Health care is undergoing a challenging transition, and we must improve patient care and clinical practice.

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