A 6-day subrenal capsule assay for predictive testing of primary esophageal cancers

Subrenal Capsule Assay (SRCA) as a chemosensitivity test was performed on 14 esophageal squamous cell carcinomas in order to select a more effective form of chemotherapy. Of the 14 assays, 12 were evaluable. Mice were treated with anticancer agents (e.g. Cisplatin, Bleomycin, Methotrexate, Vindesine) on days 1 and 3 after transplantation, and on day 6, the sensitivities were determined. Fresh esophageal cancers yielded an evaluable assay rate of 74%. The implant grew progressively for six days in the remaining group of control mice. Histologically, host cell infiltration at the border of the implant was observed from day 3 after transplantation, and cells had degenerated or had been partially replaced by scar tissue by day 6. The results of chemosensitivity tests differed according to the anticancer agent used or from case to case. Clinically, correspondence between the assay results and clinical results was obtained in 5 out of 7 cases. SRCA is a new promising chemosensitivity test which is clinically useful, and the present results indicated the feasibility of its use in developing an effective chemotherapy for esophageal cancer.     

(-)Deprenyl increases activities of superoxide dismutase and catalase in striatum but not in hippocampus: the sex and age-related differences in the optimal dose in the rat.

The dose of (-)deprenyl (2.0 mg/kg/day, sc, for 3 weeks) which significantly increased activities of superoxide dismutase (SOD) and catalase in the striatum of young male rats significantly reduced these activities in young female rats but did not change the SOD activity in old female rats. In order to clarify these effects, different doses of the drug were continuously infused sc for 3 weeks in three groups of rats (young males and young and old females). When a 10-fold smaller dose (0.2 mg/kg/day) was applied in young female rats, activities of both SOD and catalase were significantly increased, while a higher dose of 0.5 mg/kg/day was ineffective and a lower dose of 0.1 mg/kg/day was substantially less effective. In old female rats, doses of both 0.5 and 1.0 mg/kg/day were equally effective in elevating activities of SOD and catalase, while a lower dose of 0.1 mg/kg/day was less effective. The activity of glutathione peroxidase (GSH Px) remained unchanged in all groups, except for a significant decrease in the activity of non-selenium-dependent GSH Px in both young and old female rats given the highest drug dose (2.0 mg/kg/day). Furthermore, activities of all three enzymes remained unchanged in the hippocampus in most groups. The results indicate that (-)deprenyl significantly increases activities of both SOD and catalase in the striatum, but not in hippocampus of rats, and that the optimal dose is very different depending on the sex and age of the animal.     

The effects of intermittent administration of human parathyroid hormone (1–34) on streptozotocin-induced diabetic rats

Intermittent administration of low doses of human parathyroid hormone (h-PTH) has been reported to exhibit an anabolic effect on bone, increasing its mass. We investigated the effects of intermittent administration of h-PTH on bone changes in streptozotocin- (STZ-) induced diabetes mellitus (DM) rats by measuring bone mineral density and bone mineral contents and by bone histomorphometry. Wistar rats, 7–8 months old, were used. Osteoporosis was induced by diabetes mellitus, which was established by an intraperitoneal injection of STZ. Rats were separated into five groups: sham-injected, baseline control, vehicle-only-administered, and low-dose (6.0μg/kg) or high-dose (60.0μg/kg) h-PTH-administered groups. h-PTH or vehicle was injected subcutaneously six times a week for 4 weeks beginning 9 weeks after STZ administration. Bone mineral density and mineral contents were significantly lower in the baseline control and vehicle groups than in the control group. The PTH-administered groups showed higher values compared with both vehicle and baseline control groups. In bone histomorphometry, both bone volume and bone formation in the STZ group were markedly reduced. The h-PTH-administered rats showed increase in both bone volume and bone formation, which are related parameters, but administration of h-PTH did not alter the extent of eroded surface. Our results suggest that intermittent administration of h-PTH is effective in activating bone formation and in preventing further bone loss in osteoporosis developed by STZ-induced DM.     

Effect of meropenem on fecal flora in children]

Meropenem (MEPM, SM-7338), a novel parenteral carbapenem antibiotic, was examined for its effect on intestinal flora in children. Seven children with infectious diseases (3 male and 4 female children of age's ranging from 4 months to 8 years and 9 months weighing from 7.3 to 23.0 kg) were treated with MEPM at doses ranging 10.3 to 40.5 mg/kg 3 or 4 times a day for 6 to 12 days. Before, during and after the treatment, identities and numbers of various bacteria contained in 1 g of feces were determined and fecal beta-lactamase activity and Clostridium difficile D-1 antigen were also assayed. Changes in fecal flora during MEPM treatment was somewhat different depending on cases. Regarding Enterobacteriaceae among aerobes, all of 7 cases exhibited moderate or pronounced reductions in Escherichia coli. Some of the cases exhibited the tendency to increase in Klebsiella oxytoca. Enterobacter cloacae and Citrobacter freundii. E. coli which was reduced during the treatment increased rapidly after the treatment in 5 out of 7 cases, and the initial bacterial counts were restored. Diverse strains were observed within the genus Enterococcus, while the overall bacterial counts of this genus exhibited the tendency to increase during the treatment. As a result, no significant change in total aerobe count was observed in any case except 1 case where Enterococcus count was somewhat reduced. Among anaerobes, major bacteria such as Bacteroides, Bifidobacterium, Eubacterium and Peptococcaceae exhibited tendencies to decrease in some cases during the antibiotic treatment. Two infants and 1 child exhibited significant decreases in total anaerobe counts. In most of the cases, such changes in major anaerobes were transient and bacterial counts recovered to their initial values rapidly after completion of the treatment. In no cases, glucose non-fermentative Gram-negative bacilli or fungus became predominant. Although C. difficile D-1 antigen was observed in 4 cases, its changes had no relationship with characteristics of feces. C. difficile was not detected in any of the cases. MEPM was detected in feces in 4 cases being treatment, in concentrations ranging from 0.35 to 66.0 micrograms/g. Fecal MEPM levels were very low except in 1 case in which beta-lactamase was negative. From these results, effects of MEPM on intestinal flora in children were relatively minor compared to other new beta-lactam drugs. However, a care should be taken to minimize diarrhea and bacterial turnover when a prolonged use of the antibiotic, was practiced because of potential significant effects on intestinal flora.     

False aneurysms after aortic operations.

Between 1980 and August 1991, we encountered 11 non-infected aortic pseudoaneurysms after aortic surgery. The interval between the initial operation and revision varied from 1.8 to 26.8 years (mean 15.2 years). Three were found more than 20 years after operation. Pulling off of and degrading of the silk sutures were considered to be the causes. All patients underwent operative correction without mortality. In thoracic aortic pseudoaneurysm repair, a temporary bypass between the right axillary artery and left external iliac artery was generally adopted. There was no need for heparinization with this technique.     

Surgical exploration for renal cyst: two-case report]

A 59-year-old male was admitted to our clinic for further examination of the calcified renal cyst discovered incidentally on medical workup elsewhere. CT showed a left renal cyst associated with calcification. Ultrasound-guided puncture of the renal cyst was not successful because of thickness of the cystic wall. Renal angiography showed hypervascularity of the cystic wall. Association of renal cell carcinoma could not be ruled out, therefore the exploration was performed. Histological examination revealed benign renal cyst with calcification. A 27-year-old male presented with the chief complaint of left flank pain. Following examinations by US, CT and MRI, a renal cyst associated with renal cell carcinoma was highly suspected. Subsequent exploration revealed cluster of cysts with a yellowish lesion a few mm in diameter. Frozen section revealed no malignancy, and cystic fluid was not hemorrhagic. Therefore as many cystic walls as possible were removed without nephrectomy. Histological examination of the permanent specimen revealed renal cell carcinoma. Renal cyst associated with renal cell carcinoma was regarded as rare clinical entity, but such cases are reported in increasing number in recent years. We report such cases and review the pertinent literature in this paper.     

Gorham massive osteolysis

Gorham syndrome (massive osteolysis) is a very rare tumour-like lesion characterized by progressive osteolysis. The diagnosis must be confirmed by the microscopic finding of intramedullary angioma-like vascular structures. We report a case of a 15-year-old boy with a pathological fracture in his left humerus. Imaging modalities such as magnetic resonance imaging, computed tomography, angiography and bone scintigraphy failed to disclose to tumorous lesion that filled a cavity in the left humerus. After observing the boy's progress for 6 months, a temporary diagnosis of Gorham syndrome was made, and surgical treatment was chosen. After resection of the left humeral head and the proximal one-quarter of the humerus, thorough curettage was performed in the distal humerus and an intramedullary artificial humeral head fixed with adequate success. Pathological examination of the specimen revealed intramedullary haemangioma of the humerus.     

Human scalp hair as evidence of individual dosage history of haloperidol: longer-term follow-up study

The patients reported in our previous paper were followed further, by analyzing hair samples collected monthly for 4 or 5 months, while growing hair continues to reflect the individual dosage history of haloperidol. In patients in whom the drug had been discontinued, the portion of hair that reflected the change of dose continued to move upward. In hair of patients in whom the dosage was decreased by one-half, the portion of change was also shown to move upward. These results indicate the potential usefulness of hair for assessing the individual past dosage history of haloperidol.     

A Comparison of Two Simple Measures to Evaluate the Health Status of Asthmatics: The Asthma Bother Profile and the Airways Questionnaire 20

Simple and concise measures for health status are desirable in clinical practice. The Asthma Bother Profile (ABP), which consists of 23 items, has been developed to assess how much asthma bothers patients. The Airways Questionnaire 20 (AQ20) is a simple instrument which consists of 20 items. The purpose of this study was to investigate how the ABP and AQ20 evaluate the health status of patients with asthma. A total of 166 patients with chronic asthma (age: 48 ± 16 yr, 77 males) completed pulmonary function testing, measurement of airway hyperresponsiveness, dyspnea rating, assessments of their anxiety and depression (HADS; Hospital Anxiety and Depression Scale), and assessments of their health status. The health status was assessed using the ABP, AQ20, the short-form 36 health survey questionnaire (SF-36), the Living With Asthma Questionnaire (LWAQ) and the Asthma Quality of Life Questionnaire (AQLQ). The Japanese version of the ABP included only 15 'bother' items out of the original 23 items due to cultural differences. The scores on the ABP were widely distributed, whereas the scores on the AQ20 were skewed towards the milder end of the scale. The ABP had a strong correlation with the Avoidance and Distress constructs on the LWAQ, and Anxiety and Depression on the HADS (Rs = 0.56 ∼ 0.79), and its strongest correlation with the General Health (Rs = - 0.64) scale among the 8 subscales on the SF-36. The AQ20 had a less significant correlation with the LWAQ, AQLQ, and SF-36 than the ABP. The ABP and AQ20 were short and simple to complete, and both measures could easily be used in clinical practice. The ABP can evaluate patients more specifically with respect to distress and bother than the AQ20.     

Biologic correlates of intratumoral heterogeneity in 18F-FDG distribution with regional expression of glucose transporters and hexokinase-II in experimental tumor.

The biologic mechanisms involved in the intratumoral heterogeneous distribution of 18F-FDG have not been fully investigated. To clarify factors inducing heterogeneous 18F-FDG distribution, we determined the intratumoral distribution of 18F-FDG by autoradiography (ARG) and compared it with the regional expression levels of glucose transporters Glut-1 and Glut-3 and hexokinase-II (HK-II) in a rat model of malignant tumor. METHODS: Rats were inoculated with allogenic hepatoma cells (KDH-8) into the left calf muscle (n = 7). Tumor tissues were excised 1 h after the intravenous injection of 18F-FDG and sectioned to obtain 2 adjacent slices for ARG and histochemical studies. The regions of interest (ROIs) were placed on ARG images to cover mainly the central (CT) and peripheral (PT) regions of viable tumor tissues and necrotic/apoptotic (NA) regions. The radioactivity in each ROI was analyzed quantitatively using a computerized imaging analysis system. The expression levels of Glut-1, Glut-3, and HK-II were determined by immunostaining and semiquantitative evaluation. The hypoxia-inducible factor 1 (HIF-1) was also immunostained. RESULTS: ARG images showed that intratumoral 18F-FDG distribution was heterogeneous. The accumulation of 18F-FDG in the CT region was the highest, which was 1.6 and 2.3 times higher than those in the PT and NA regions, respectively (P < 0.001). The expression levels of Glut-1, Glut-3, and HK-II were markedly higher in the CT region (P < 0.001) compared with those in the PT region. The intratumoral distribution of 18F-FDG significantly correlated with the expression levels of Glut-1, Glut-3, and HK-II (r = 0.923, P < 0.001 for Glut-1; r = 0.829, P < 0.001 for Glut-3; and r = 0.764, P < 0.01 for HK-II). The positive staining of HIF-1 was observed in the CT region. CONCLUSION: These results demonstrate that intratumoral 18F-FDG distribution corresponds well to the expression levels of Glut-1, Glut-3, and HK-II. The elevated expression levels of Glut-1, Glut-3, and HK-II, induced by hypoxia (HIF-1), may be contributing factors to the higher 18F-FDG accumulation in the CT region.