Comparison of twice-daily injections of biphasic insulin lispro and basal-bolus therapy: glycaemic control and quality-of-life of insulin-naïve type 2 diabetic patients.

OBJECTIVE: The aim of this study was to evaluate twice-daily injections of biphasic insulin lispro vs. basal-bolus (BB) therapy with regard to quality-of-life (QOL) and glycaemic control in insulin-naïve type 2 diabetic patients. METHODS: Twenty-eight patients with type 2 diabetes were randomized to receive either twice-daily 50/50 premixed insulin lispro (Mix50 group) or BB (NPH insulin at bedtime and preprandial insulin lispro) therapy (BB group) for 12 weeks. Glycated haemoglobin (HbA1C), 1,5-anhydroglucitol (1,5-AG), blood plasma glucose level, body mass index (BMI), daily total insulin dosage and insulin therapy-related QOL (ITR-QOL) were studied. RESULTS: ITR-QOL was significantly better in the Mix50 than in the BB group (103.1 +/- 9.8 vs. 90.6 +/- 19.4; p < 0.05). HbA(1c) improved in both groups (from 11.1 +/- 2.1 to 6.9 +/- 1.0% with Mix50 vs. from 11.0 +/- 2.3 to 6.6 +/- 0.8% with BB therapy). CONCLUSION: These results might suggest that twice-daily injections of premixed rapid-acting insulin analogue therapy could achieve good glycaemic control and better QOL compared with BB therapy in insulin-naïve type 2 diabetes.

Tumor angiogenesis and mode of metastasis in patients with colorectal cancer.

Neovascularization promotes tumor growth by facilitating nutrient exchange and by the paracrine effect. To investigate the relationship between tumor angiogenesis and patient outcome in colorectal cancer, 133 primary tumors were immunostained for CD34 antigen. Blood vessels within five microscopic fields at x200 were counted, and the mean was assigned. Mean patient age was 62.9 years, mean follow-up was 56.4 months, and mean vessel count was 112 (range, 23-298). Cox proportional hazards model and multivariate logistic regression analyses showed that the vessel count was the most important prognostic factor and correlated significantly with hematogenous, but not peritoneal or lymph node, metastasis.

Improvement of in vitro chemosensitivity assay for human solid tumors by application of a preculture using collagen matrix.

The use of [3H]thymidine incorporation assay (TIA) to evaluate the drug response of tumor cells has been recognized as a useful chemosensitivity assay for fresh human tumor specimens. However, its low evaluability has been a disadvantage for clinical application. To overcome this drawback, we have applied a preculture stage prior to the TIA. This preculture requires plating the tumor cell suspension onto a collagen matrix for 24 h. In 29 fresh human tumor specimens, a significant increase in both cell viability (P < 0.05) and [3H]thymidine incorporation (P < 0.001) of the cultured cells was observed with preculturing; the composition of cancer cells (epithelial membrane antigen positive) and stromal cells (vimentin positive) did not change. In comparisons between 66 specimens that were precultured and 705 specimens that were not, the evaluability rate increased significantly from 48.5% (342/705) to 75.8% (50/66; P < 0.0001) after preculturing. No significant change in in vitro chemosensitivities was observed. When the clinical responses for cancer chemotherapy were retrospectively compared with the in vitro sensitivities of the corresponding drugs on 16 patients who had measurable lesions, the correlation between the two was satisfactorily strong; the prediction accuracy for sensitivity was 83.3% (5/6), the prediction accuracy for resistance was 95.0% (19/20), and the overall correlation was 92.3% (24/26). These results indicate that TIA with preculturing yields increased rates of evaluability, preserving in vitro drug responses of cultured tumor cells, and has an improved potential to be used for determining clinical chemotherapy.

Tumor angiogenesis and expression of thymidine phosphorylase/platelet derived endothelial cell growth factor in human gastric carcinoma.

To investigate the relationship between tumor angiogenesis and the expression of platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/dThdPase) and between patients' survival and the expression of PD-ECGF/ dThdPase in human gastric carcinoma tissues, we performed immunohistochemical studies with anti-PD-ECGF/dThdPase and anti-CD34 monoclonal antibodies. Out of 154 gastric carcinoma tissue samples, 61 (40%) were evaluated as PD-ECGF/ dThdPase-positive. The expression of PD-ECGF/dThdPase was significantly associated with the intratumoral microvessel counts (P < 0.0001) and the incidence of hematogenous metastasis (P < 0.05). Intratumoral vessel counts were significantly correlated with overall survival of 154 patients (P < 0.000001). Cox proportional hazards model showed that tumor vasculature was an independent and strong prognostic variable. However, the prevalence of the expression of PD-ECGF did not associate the overall survival. We suggest that expression of PD-ECGF/dThdPase plays a role in the promotion of angiogenesis in human gastric carcinomas, without any definite influence on patient's survival.

Density of Helicobacter pylori infection in patients with peptic ulcer perforation.

BACKGROUND: A lack of change in prevalence of severe ulcer complications requiring emergency operation has been reported, despite the common use of histamine-2 (H2)-receptor antagonists and proton pump inhibitors. This may be attributable to use of ulcerogenic drugs or Helicobacter pylori (HP) infection, or both. In this study, HP infection was evaluated semiquantitatively in patients with peptic ulcer who required surgery, and the severity of histologic change was investigated. METHODS: We reviewed a total of 113 consecutive patients (98 men and 15 women) operated on for perforation, hemorrhage, or stenosis of gastroduodenal ulcer between January 1986 and December 1995. Detection of HP was carried out by immunohistochemical staining. We graded the density of HP infection according to the number of individual HP bacteria counted in a highly magnified visual field (x 1,000 of light microscopy). The grade of HP infection was defined as follows: (0) = 0; (1+) = 1-9; (2+) = 10-29; (3+) = 30-99; (4+) > or = 100. The severity of gastritis was evaluated by histologic examination using the criteria of Rauws. RESULTS: Although the number of operations for gastroduodenal ulcer declined significantly, the rate of emergency operation for gastroduodenal ulcer increased from 60% to 90%, with the result that the frequency of operations for perforation or bleeding remained virtually constant and that for stenosis significantly decreased. HP infection was more prevalent in perforated ulcer (92%) than hemorrhagic ulcer (55%) or stenotic ulcer (45%). The grades of HP infection were 3.0 +/- 0.14 (mean +/- SEM) in perforated ulcer, 2.3 +/- 0.34 in hemorrhagic ulcer, and 2.5 +/- 0.22 in stenotic ulcer. Perforated ulcer was associated with significantly more severe HP infection and gastritis changes than hemorrhagic ulcer or stenotic ulcer. CONCLUSIONS: This study indicates that patients with perforated ulcer were infected with HP more severely than those with hemorrhagic ulcer or stenotic ulcer at the time of surgery. A close relationship was observed between the perforated ulcer and the density of HP infection determined semiquantitatively using immunohistochemical stain.

Jejunal pouch to avoid stricture after esophagojejunostomy with circular stapler.

BACKGROUND: Anastomotic stricture is one of the most common problems in esophagojejunostomy using the end-to-end anastomosing (EEA) instrument (Auto Suture Co, Norwalk, CT) after total gastrectomy. To alleviate the stricture, several methods, such as incision to the scar, balloon dilatation, and steroid injection are available. To avoid stricture, the jejunal pouch may allow use of a larger EEA than Roux-en-Y (ReY) reconstruction does. STUDY DESIGN: A total of 45 patients underwent curative total gastrectomy and esophagojejunostomy with jejunal pouch construction (27 patients) or ReY (18 patients), using the EEA. The effects of jejunal pouch construction with a large EEA on avoidance of stricture and benefit to nutritional status were investigated by comparing it with the ReY in terms of postoperative morbidity, postprandial symptoms, and nutritional parameters (serum protein, serum albumin, body weight). RESULTS: EEA28 or larger could be used in 25 patients in the pouch group and 8 patients in the ReY group (p < 0.05). Stricture developed in one patient in the pouch group and in four patients in the ReY group (p < 0.05). Postprandial symptoms were experienced less frequently (p < 0.05) in the pouch group than in the ReY group. When stricture and symptoms were analyzed according to the size of EEA, they occurred more frequently (p < 0.05) in the patients with EEA25 than those with EEA28 or EEA31. No significant differences were evident in nutritional parameters. CONCLUSIONS: The choice of jejunal pouch technique allowed the use of a larger EEA than that of ReY reconstruction, resulting in avoidance of anastomotic stricture and postprandial symptoms, though little benefit in nutritional status was evident to the patients after total gastrectomy.

Two competing mechanisms underlying neon color spreading, visual phantoms and grating induction.

Neon color spreading is closely related to the photopic visual phantom illusion, since these two completion phenomena are characterized by in-phase lightness induction, and the only difference in the stimulus configuration is the difference in the inducer height. This idea was supported by the present study. Neon color spreading showed almost the same function of critical spatial frequency as photopic visual phantoms (Experiment 1), and the critical spatial frequency was constant as the inducer height was changed (Experiment 2). We also examined the relationship between neon color spreading and grating induction (characterized by counterphase lightness induction) in critical spatial frequency (Experiment 3) and in magnitudes of lightness induction (Experiment 4) as a function of the inducer height. The inducer height at which in-phase (neon color spreading) appearance gave way to counterphase (grating) induction was approximately 0.1 deg. These results suggest that neon color spreading shares a common neural mechanism with the photopic visual phantom illusion and that this mechanism is different from, and competes with, the mechanism of grating induction.

In vitro chemosensitivity testing of human tumours by collagen gel droplet culture and image analysis.

It is necessary to develop an in vitro test to overcome the problems often associated with in vitro chemosensitivity tests on individual human tumours. We have developed a collagen gel droplet culture technique that allows for a three-dimensional in vitro growth and drug response assay for human solid tumour cells. Important features of chemosensitivity testing by the collagen gel droplet culture technique include the maintenance of high cloning efficiencies resulting in the need for fewer tumour cells, sufficient suppression of the in vitro proliferation of contaminating non-malignant cells by serum-free medium, and the application of the image analysis system which automatically discriminates between cancer cell colonies and fibroblasts. We described in vitro-in vivo correlations for drug response using 7 human lung cancer xenografts grown in the collagen gel droplet culture and as xenografts in nude mice. Results demonstrated significant correlations with the in vitro drug concentration at 1/10 of the peak plasma concentrations (1/10 Cmax) with the correlation coefficient 0.84 for all four drugs tested. We have cultured 206 tumours thus far obtaining 86% of evaluability for drug response. The drug response data of the fresh lung cancers were similar to not only to data for lung cancer lines but the reported clinical pattern. These results suggested that the collagen gel droplet culture at 1/10 Cmax may have potential in predicting clinical drug responses.

Hepatic undifferentiated (embryonal) sarcoma in an adult: a case report and review of the literature.

Undifferentiated (embryonal) sarcoma of the liver (USL) is a rare malignant tumour with a poor prognosis. The absence of specific symptoms, the rapid tumour growth, the normality of the common tumour markers, and the consequential delay in the diagnosis often result in significant enlargement of the tumour. To our knowledge, there have been only 42 reported cases of USL in adults worldwide during the 40 years since the clinicopathological entity of USL was defined. We report here a 27-year-old male with USL who has been treated successfully with surgical resection and adjuvant chemotherapy using ifosfamide, adriamycin and cisplatin. Although the prognosis of the disease remains generally poor, long-term survival has been achieved recently in patients with a combination of surgery and multi-agent chemotherapy.

[Potential and limitation of scintillation assay (TIA) for clinical chemotherapy].

The clinical significance of the scintillation assay (thymidine incorporation assay) which we developed was summarized as follows; 1)thymidine uptake by tumor cells which can be evaluated in each assay functioned as a significant predictor of prognosis of patients with gastric or colorectal cancer, 2)the tumor cell compartment in this assay system significantly increased more than did those in other culture systems, 3)evaluable rates were increased to more than 80% by introduction of the preculture system with collagen coated flasks, and 4)it can be considered that chemosensitivity testings may benefit for some types of human tumor, but not for all.

Postsurgical sequential methotrexate/5-FU and leucovorin on outpatient basis for advanced colorectal carcinoma.

BACKGROUND/AIMS: The present study compared the effects of sequential methotrexate and 5-fluorouracil followed by leucovorin rescue (MFL), as an adjuvant chemotherapy versus a combination of UFT and mitomycin C (MMC), on patient survival and recurrence after surgery for colorectal carcinoma. METHODOLOGY: Between January 1990 and December 1997, a total of 55 patients with advanced colorectal cancer were treated postsurgically by adjuvant chemotherapy using MFL or UFT-MMC. Surgical treatment was performed according to standardized procedures for radical resection of colorectal cancer. The patients were divided into 2 groups after surgery. The MFL regimen consisted of MTX (100 mg/m2) and 5-FU (600 mg/m2) at hour 24, followed by leucovorin rescue. The UFT-MMC regimen consisted of MMC (12 mg/m2) intraoperatively and MMC (6 mg/m2) every other week after surgery for 2 months, and oral UFT (375 mg/m2/day), a combination of tegafur and uracil in a molar ratio of 1:4, was continued for 3 years or longer depending on the patients tolerance. RESULTS: The overall survival rates after surgery were significantly (P < 0.05) higher in the MFL than the UFT-MMC group. Recurrence rates were significantly lower in the MFL than the UFT-MMC group, especially for liver recurrence. Disease-free survival was significantly (P < 0.05) higher in the MFL than the UFT-MMC group. CONCLUSIONS: These results demonstrated the superiority of MFL therapy for improving postsurgical survival in patients with advanced colorectal cancer, in particular those patients with a high risk of recurrence following potential curative resection.

A case of colon cancer recurrence with P-glycoprotein treated by methotrexate, fluorouracil, and leucovorin.

A 68 year-old female underwent right hemicolectomy for an advanced cecum cancer and had been well without any evidence of recurrence for a year after surgery. Despite post-operative treatment with oral Tegafur (400 mg/m2/day), CEA level increased gradually beginning 15 months after surgery. Sequential chemotherapy with methotrexate (MTX) and 5-Fluorouracil (5-FU), followed by leucovorin rescue (MFL) was started on an outpatient basis, and has been continued every 4 weeks since then. It consisted of MTX (100 mg/m2) and 5-FU (600 mg/m2) started 24 hours after MTX, followed by oral leucovorin (15 mg/body) started 30 hours after MTX 6 times at intervals of 6 hours. CEA level declined initially, but increased slowly for 3 years on MFL, although no evidence of recurrence was detected by imaging studies with computed tomography, ultrasound, and scintigram. Four years after surgery, a tumor recurrence developed in the abdominal wall. The patient underwent resection of the tumor, resulting in a decline of the CEA level. She has been alive and well for 5 years on MFL after the primary surgery. Both the original tumor and recurrent tumor showed immunoreactivity for P-glycoprotein. The present case demonstrates the feasibility of using MFL on an outpatient basis, and its potential to suppress the colon cancer growth with P-glycoprotein expression.

Defensive aspects of burrowing behavior in rats (Rattus Norvegicus): A descriptive and correlational study.

Several burrowing behavioral characteristics of five different, genetically-biased, strains of rats (Rattus norvegicus), with each showing various defensive and open-field behaviors, were investigated to examine the defensive aspects of burrowing behavior. The strains used were the Tsukuba High- and Low-Emotional (THE and TLE), F344/DuCrj (F344), Long Evans (LE), and the Wistar-Imamichi/lar (WI). The THE and LE strains showed significantly shorter burrowing latency, more digging activity, and longer length burrows, with most rats escaping into their burrows at a loud crash sound. On the other hand, the TLE and WI stains displayed significantly longer burrowing latency, less digging activity, and shorter length burrows, with only a few rats escaping. These findings showed the consistency among the burrowing characteristics and a close relationship between burrowing and escape. The F344 strain, on the contrary, showed a shorter burrowing latency and more digging activity than the TLE and WI strains (although similar length burrows), yet few rats escaped. Digging, burying, open-field defecation, and re-emergency latency after escape correlated highly with each other, possibly suggesting their defensive nature. In conclusion, it is possible that burrowing behavior is a species-specific defense reaction (SSDR), yet factors involved in burrowing seem to be complicated, with more extensive studies therefore required.

[Magnetic resonance imaging of a case of bladder leiomyoma].

The complementary use of magnetic resonance imaging (MRI) in the evaluation of bladder-base leiomyoma is reported. The MRI, as compared to computed tomography (CT), gave the characteristics of myoma resembling uterine myoma, submucosal location, the site of origin and relationship to bladder wall. The MRI appearance of homogenous and medium intensity on T1 weighted image, and of low intensity on T2 weighted image, of submucosal solid mass was suggestive of a leiomyoma.

[Clinical significance of P-glycoprotein expression and multidrug resistance assessed by in vitro thymidine incorporation assay in patients with gastric carcinoma].

Drug resistance in chemotherapy is a significant problem in the treatment of gastric carcinomas as well as other malignant tumors. Multidrug resistant cells frequently overexpress the 170 kDa P-glycoprotein (P-gp). Twenty-four fresh tumor specimens of gastric carcinoma were assessed by flow cytometric detection of P-gp using monoclonal antibody C219. Eight patients were P-gp positive. Differentiated gastric carcinomas contained significantly higher concentrations of P-gp positive. Incidence of P-gp positive case was high in advanced stage. Sixteen cases received in vitro chemosensitivity test assessed by thymidine incorporation assay (TIA). Seven of 9 multidrug resistant cases by TIA were P-gp positive, and all of 7 non-multidrug resistance were negative. Expression of P-gp and multidrug resistance were closely correlated (p < 0.01). Also, in 89 patients with operable gastric carcinoma, the relationship between multidrug resistance by TIA and their clinicopathologic features as well as their survival lengths were examined. Thirty-one of 89 specimens from gastric carcinoma patients were multidrug resistant by TIA. Patients with multidrug resistant group had a significantly poorer cumulative survival rate than non-multidrug resistant cases (p < 0.01). The multivariated analyses showed that multidrug resistance analyzed is useful indicator for prognosis (p < 0.1). We suggest that multidrug resistance cases or P-gp-positive cases of gastric carcinoma are highly malignant, and these determinations are clinically useful.

[Behavioral comparisons of rats (Rattus norvegicus) in Runway, open-field, and I-maze].

Behaviors of two strains of rats (F344/DuCrj and Wistar-Imamichi) in three novel situations (Runway, open-field, and I-maze) were compared in order to clarify the characteristics of each situation. Eighty rats were used; 40 were F344/DuCrj and 40 were Wistar-Imamichi. Principal component analysis of each ambulation score abstracted two major components of 'activity' and 'emotionality'. Highly 'active' rats ambulated much in the three situations, whereas highly 'emotional' rats ambulated much in the open-field test and little in the Runway test. These results suggest that there appeared 'escape response' in the open-field test, while 'freezing response' occurred in the same rat in the Runway test. Wistar-Imamichi was more 'active' than F344/DuCrj, whereas the latter was more 'emotional' than the former. This study also confirmed the idea that the rats were frightened in I-maze less than in Runway.

Apparent contraction of edge angles.

The corner effect, the Münsterberg illusion, and the Café Wall illusion are explained by a model postulating that the corner effect is an orientation illusion specific to corner edges and that the perceived orientations of these edges are shifted toward angle contraction. It is also assumed that the effect is greatest when the corner edges show the same or similar edge contrast at the corner. This model yields three new types of illusions: the 'checkered illusion', the 'illusion of shifted gradations', and the 'illusion of striped cords'. Each of them gives many variations making a three-dimensional impression.

Behavioral comparisons of the Tsukuba emotional strains of rats (Rattus norvegicus) in three types of novel situations.

Tsukuba High- and Low-Emotional rats (THE and TLE), Wistar-Imamichi/Iar rats (control group for the Tsukuba Emotional rats), and F344/DuCrj rats were tested in three types of novel situations: the open field, a runway devised as a type of open field with a shelter, and an I-maze devised as a narrow runway with shelters and covers to remove rats' freezing behavior against predatory attack. The TLE was the most active, and the THE the least active in the three tests. While the F344 was inactive in the runway and the I-maze, this strain was as active as the Wistar-Imamichi in the open field. While the THE and F344 defecated frequently, the TLE never defecated.

Three elemental illusions determine the Zöllner illusion.

We have discovered an apparent contraction illusion of acute angles in a special form of the Zöllner figure at the intersecting angles between 36 degrees and 83 degrees (i.e., a reversal of the Zöllner illusion). The necessary condition for this illusion is that inducing lines are long enough and the induced line (test line) is single. When an illusory line is used as the induced line, the magnitude of contraction increases. Short inducing lines give no illusion or a slight expansion of acute angles at the intersecting angle of 45 degrees. We have ascertained that the source of this expansion is the narrow region in the vicinity of the induced line, whereas the source of the contraction is much broader regions. Furthermore, we have discovered another expansion mechanism, which is generated by the symmetrical configuration of the standard Zöllner figure.

Tsukuba high- and low-emotional strains of rats (Rattus norvegicus): an overview.

This report compiles the results of a series of studies on the Tsukuba High- and Low-Emotional strains (THE and TLE) of rats (Rattus norvegicus) established at the University of Tsukuba, Japan. The THE and TLE strains have been selected, respectively, for low and high activity in a runway test. During the course of selection, defecation has increased in the THE strain and decreased in the TLE strain. These strain differences were not affected by maternal influences, early experience, or psychotropic drugs. THE rats were consistently inactive in all novel situations examined, while TLEs were very active. The level of spontaneous activity, however, was similar between the two strains. It was remarkable that THE rats showed more burrowing activity than TLE animals, whereas the latter displayed more aggression than the former. Differences in learning ability, concentration of neural transmitters, and social behavior were examined.