Close relationship between strict blood glucose control, including suppression of blood glucose variability, and mortality reduction in acutely ill patients with glucose intolerance investigated by means of a bedside-type artificial pancreas.

The purpose of this study was to elucidate the relationship between strict control of blood glucose (BG) and mortality reduction with the use of an artificial pancreas (AP). Patients were evaluated in the (1) early phase (E phase: mean 3.3 ± 2.6 days after admission, n = 84) and in the (2) late phase (L phase: mean 9.9 ± 3.3 days, n = 88), and were classified into a (1) group with a higher daily mean BG level (BGm) (BGmXa: BGm above Xmg/dl) and a (2) group with a lower BGm (BGmXb: BGm below Xmg/dl). Each group was classified into a (1) subgroup with a higher daily standard deviation of the BG levels (BGsd) and a (2) subgroup with a lower BGsd. In the E phase, the (1) mortality of the BGm200a group was significantly higher than that of the BGm200b group (56 vs. 29%, p < 0.05), and (2) in the BGm200b group, the mortality of the subgroup with a BGsd above 14 mg/dl was significantly higher than that with a BGsd below 14 mg/dl (46 vs. 17%, p < 0.025). In the L phase, the mortality of the BGm175a group was significantly higher than that of the BGm175b group (50 vs. 28%, p < 0.05). In conclusion, (1) a higher BGm and (2) higher BGsd in the E phase were prognostic risk factors. Based on the findings, it was considered that the target for BG control should be set at (1) BGm below 200 mg/dl and BGsd below 14 mg/dl in the E phase, and (2) BGm below 175 mg/dl in the L phase.

Recent progress in mechanical artificial pancreas.

Strict blood glucose (BG) control is proved to improve the outcome in patients with glucose intolerance both in acute and chronic phases, irrespective of whether the patient has diabetes mellitus. However, strict BG control by conventional methods is so complicated that it cannot be performed easily in normal clinical situations. Furthermore, it is sometimes inadequate. Therefore, a clinically applicable, reliable artificial pancreas (AP) has long been sought after for more than 40 years. Considering the present important situations concerning AP, a survey of recent progress in AP is highly desirable. In this review, recent progress in mechanical AP (MAP) and in MAP-related items is presented. MAP is composed of three major components: a BG control algorithm, a drug administration system, and a glucose sensor. Recent progress in development of these components is presented, followed by descriptions of representative MAPs. Although significant progress in the development of MAP has been made, its use in clinical situations is limited or for research purposes at present. The main limiting factor is the slow progress in the development of glucose sensors. However, more widespread clinical application of the MAP will occur in the near future, considering the number of reliable long-life intravenous glucose sensors under development. Another factor is the worldwide recognition of the importance of BG control in acutely ill patients, in whom the period of strict BG control is usually for several days to a few weeks.

Correlation of N-myc downstream-regulated gene 1 expression with clinical outcomes of colorectal cancer patients of different race/ethnicity.

AIM: To evaluate the role of N-myc downstream-regulated gene 1 (NDRG1) expression in prognosis and survival of colorectal cancer patients with different ethnic backgrounds. METHODS: Because NDRG1 is a downstream target of p53 and hypoxia inducible factor-1 alpha (HIF-1 alpha), we examined NDRG1 expression together with p53 and HIF-1 alpha by immunohistochemistry. A total of 157 colorectal cancer specimens including 80 from Japanese patients and 77 from US patients were examined. The correlation between protein expression with clinicopathological features and survival after surgery was analyzed. RESULTS: NDRG1 protein was significantly increased in colorectal tumor compared with normal epithelium in both Japanese and US patient groups. Expression of NDRG1 protein was significantly correlated with lymphatic invasion, venous invasion, depth of invasion, histopathological type, and Dukes' stage in Japanese colorectal cancer patients. NDRG1 expression was correlated to histopathological type, Dukes' stage and HIF-1 alpha expression in US-Caucasian patients but not in US-African American patients. Interestingly, Kaplan-Meier survival analysis demonstrated that NDRG1 expression correlated significantly with poorer survival in US-African American patients but not in other patient groups. However, in p53-positive US cases, NDRG1 positivity correlated significantly with better survival. In addition, NDRG1 expression also correlated significantly with improved survival in US patients with stages III and IV tumors without chemotherapy. In Japanese patients with stages II and III tumors, strong NDRG1 staining in p53-positive tumors correlated significantly with improved survival but negatively in patients without chemotherapy. CONCLUSION: NDRG1 expression was correlated with various clinicopathological features and clinical outcomes in colorectal cancer depending on the race/ethnicity of the patients. NDRG1 may serve as a biological basis for the disparity of clinical outcomes of colorectal cancer patients with different ethnic backgrounds.

Colon carcinoma metastasis to the thyroid gland: report of a case with a review of the literature.

Metastasis of colon cancer to the thyroid gland is very rare and we would like to report a case we have experienced, with a review of the literature. A 66-year-old woman noticed a swelling in the anterior neck area and sought medical attention at our department in August 2003. At age 63, she had undergone surgery for cancer of the ascending colon, but subsequently the cancer metastasized to the liver and she underwent an outer hepatic segmentectomy. Fine-needle aspiration cytology indicated adenocarcinoma with characteristic tall columnar cells, confirming our suspicion that metastasis from the ascending colon cancer had already occurred. Furthermore, lung metastasis was also suspected, because several nodules were found in the lungs. On August 13, resection of the left lobe of the thyroid gland and dissection of the cervical lymph nodes were performed. Histopathology showed metastasis of the ascending colon cancer to the thyroid and lymph nodes.

Pericostal tuberculosis diagnosed by fine needle aspiration biopsy: report of a case with a review of the literature.

We present an 81-year-old woman with pericostal tuberculosis, a rare disease recently, without a past history of pulmonary tuberculosis or tuberculous pleurisy. She developed a subcutaneous nodule on her right chest. She was suspected of skin tuberculosis after the confirmation of acid-fast bacilli in a fine needle aspiration material of the nodule. A tuberculin skin test was strongly positive. The nodule was resected, and preclusive antituberculosis chemotherapy with rifampicin and isoniazid was started. The histological findings included granulomatous changes, central necrosis and Langhans' giant cells. Mycobacterium tuberculosis was identified from a culture of the specimen. About six months after the operation, no erythema, nodule or abscess was observed. We first suspected that she had mammary carcinoma and therefore observed the nodules on the thorax; it is important to differentiate tuberculosis from neoplasms. We also reviewed 22 cases of pericostal tuberculosis in Japan reported in the 15 years from 1976 to 2002.

Telomeric repeat-length alterations in colorectal carcinoma are associated with loss of heterozygosity and point mutation in p53 gene.

The telomere, the terminal region of eukaryotic chromosomes, plays an important role in the stability of DNA replication and in the protection of chromosomal ends. To investigate whether the two-stage mechanism of cellular aging and immortalization in vitro is involved in the carcinogenesis and immortalization of human colorectal carcinomas, we examined for genetic alterations in the telomeres and in the p53, Rb, and K-ras genes. Based on our results, we discuss the effects that these genetic changes might have on mechanisms, such as the mortality stage 1 (M1), that normally prevent immortalization in carcinoma cells. Telomeric repeat-lengths (TRL) were measured by Southern blot analysis, and p53 Rb and K-ras gene variants were detected by PCR based assays. Thirty-six primary colorectal carcinomas were examined. Telomere alterations were found in 19 of 36 (52.8%) cases, while mutations of the p53 gene were observed in 15 of 36 (41.7%) cases and LOH involving p53 observed in 14 of 36 (38.9%) cases. Twelve of 15 (80%) cases with p53 mutations also showed altered TRL, so that p53 mutations were positively associated with TRL alterations (p=0.008). Ten of 14 (71.4%) cases with LOH of p53 also showed alteration in TRL, also revealing a positive association with TRL (p=0.09). The six cases with both p53 mutation and LOH all showed altered TRL. K-ras gene mutations and LOH involving the Rb gene were not associated with alterations in TRL. These results suggest that inactivation of p53 is one of the factors that promotes immortalization and overcomes M1 in colorectal carcinoma.