Longitudinal studies of mouse cancer models required large cohorts since autopsy was the only reliable method to evaluate treatment efficacy. This paper reports the use of high-resolution three-dimensional ultrasound micro-imaging to monitor prostate tumor development in genetically engineered mice. Twenty-nine genetically engineered prostate cancer mice, including castrated and uncastrated mice, were imaged by three-dimensional ultrasound. Qualitative comparisons of three-dimensional ultrasound images with histology sections of prostate tumors demonstrate the ability of ultrasound to accurately depict the size and shape of malignant masses in live mice. The correlation coefficient of tumor diameter measurements performed in vivo with three-dimensional ultrasound and at autopsy was 0.997. Prospective tumor detection sensitivity and specificity were 91.7% and 100%. Representative exponential growth curves constructed via longitudinal ultrasound imaging indicated diameter doubling times from 10 to 37 days for four prostate tumors during an initial period of rapid progression. Three-dimensional ultrasound will likely become the micro-imaging modality most readily adopted for mouse pre-clinical trial studies.
The somatotopic organization of the human primary somatosensory (SI) area in the cerebral cortex has been intensively studied for the hand, lip, and tongue, but little is known about the gingiva. Penfield concluded that the gingival SI area was above the tongue area, as shown in his famous homunculus map. However, our recent study suggested that the lingual gingiva area was not so different to the tongue area. To delineate the fine SI somatotopy of the gingiva area, evoked magnetic fields were measured in 6 healthy subjects for the stimulus of the anterior or posterior and upper or lower parts of the lip, buccal and lingual gingiva, and tongue. Source position was estimated by a current dipole model at the first peak of the posterior-oriented current in a total of 12 cerebral hemispheres contralateral to the stimulation side. No significant difference was found between the positions of anterior and posterior or upper and lower parts of each structure. Both buccal and lingual gingiva areas were localized adjacent to the tongue area, but significantly lower than the lip area. We believe that the fine SI somatotopy of the human oral structures should be reconsidered.
Functional electrical stimulation (FES) can improve the gait of stroke patients by stimulating the peroneal nerve in the swing phase of the affected leg, causing dorsiflexion of the foot that allows the toes to clear the ground. A sensor can trigger the electrical stimulation automatically during the stroke gait. We previously used a heel sensor system, which detects the contact pressure of the heel, in FES to correct foot drop gait. However, the heel sensor has disadvantages in cosmetics and durability. Therefore, we have replaced the heel sensor with an acceleration sensor that can detect the swing phase based on the acceleration speed of the affected leg, using a machine learning technique (Neural Network). We have used a signal for heel contact in a gait using the heel sensor before training with the Neural Network. The accuracy of the Neural Network detector was compared with a swing phase detector based on the heel sensor. The Neural Network detector was able to detect similarly the swing phase in the heel sensor. The largest difference in timing of the swing phase was less than 60 milliseconds in normal subjects and 80 milliseconds in stroke patients. We were able to correct foot drop gait using FES with an acceleration sensor and Neural Network detector. The present results indicate that an acceleration sensor positioned on the thigh, which is cosmetically preferable to systems in which the sensor is farther from the entry point of the electrodes, is useful for correction of stroke gait using FES.
Corrosive esophageal burn is a common health problem in the pediatric age group and causes serious esophageal injuries. The medical treatment in acute phase of corrosive esophageal injury is of particular importance for prevention of esophageal stricture. We therefore aimed to investigate the possible beneficial effect of trapidil (triazolopyrimidine), an inhibitor for phosphodiesterase and platelet-derived-growth-factor, during acute phase of esophageal corrosive injury. Wistar albino rats were randomly allocated to untreated, treated, and sham-operated groups (n = 10 for each group). Corrosive esophageal burn was generated with 10% NaOH solution. The rats were left untreated (untreated group) or treated with trapidil as a single dose of 40 mg/kg intraperitoneally after one hour of the injury (treated group). Abdominal esophageal segment was isolated and tied in sham-control group. The studied esophageal segment was removed from each animal after 24 hours. Malondialdehyde (MDA) and nitric oxide (NO) levels were measured in the esophageal tissues. The ulcer depth was graded by histopathologic examination. MDA and NO levels were significantly higher in the untreated group than in the treated group. Namely, trapidil treatment significantly decreased MDA and NO levels in the injured tissues, the levels of which are similar to those in the tissues of control animals. The grades of ulcer depth were significantly improved in the treated group. These results indicate that the reactive oxygen radicals increase in the early phase of corrosive esophagitis and cause tissue damage. We suggest that trapidil treatment may be useful in acute phase of corrosive esophageal injury.
Establishing preadipocyte cell lines from mature adipose tissues could help lead to a better understanding of adipogenesis. We have established a unique preadipocyte cell line, AP-18, derived from the subepidermal layer of ear skin from an adult C3H/HeM mouse. AP-18 cells exhibit fibroblast-like morphology, slow growth, and contact inhibition. The doubling time of AP-18 cells is 50-60 h, which is about 2-fold longer than that of well-known 3T3-L1 cells derived from mouse embryos. A small population of AP-18 cells spontaneously differentiates into adipocytes by 8 days after confluence, as judged by the accumulation of triglyceride droplets. Treatment of confluent AP-18 preadipocytes with adipogenic agents, containing dexamethasone, 3-methyl-1-isobutylxanthine, and insulin, increased triglyceride contents about 5-fold compared to the contents in untreated cells. We also analyzed mRNA expression profiles for key transcription factors involved in adipocyte differentiation, peroxisome proliferator-activated receptor (PPAR)γ and the CCAAT/enhancer binding protein (C/EBP) family, and for differentiation markers, aP2, adipocyte-specific fatty acid-binding protein and adipsin, adipocyte-specific serine protease. AP-18 preadipocytes express mRNAs for C/EBPβ, C/EBPα, PPARγ, and aP2 before differentiation, but not adipsin mRNA. Expression of aP2 mRNA was increased in fully differentiated AP-18 cells. Likewise, expression of adipsin mRNA was increased after induced differentiation of AP-18 cells and reached the highest level in fully differentiated adipocytes. Thus, differentiation of AP-18 cells is associated with the increased expression of aP2 and adipsin mRNAs. The newly established AP-18 cell line provides a useful model for investigating adipocyte differentiation and adipogenesis.
Assessing calcium intake is necessary for epidemiological studies on osteoporosis. This study was aimed at developing a valid food frequency questionnaire (FFQ) to estimate the dietary calcium intake of Japanese people. The FFQ contains 26 items, representing common sources of calcium. The respondents, 74 women aged 15 - 79 years living in Fukui city, whose dietary calcium intake was estimated at 638 ± 306 (S.D.) mg based on a one-day weighted food record kept during the National Nutrition Survey of 1996, were asked to indicate their consumption frequency and usual portion size (large, medium, small) for each food item. Trained dieticians interviewed the subjects to confirm their answers to the FFQs. The mean calcium intake per day according to the FFQ (655 ± 222 mg) did not differ significantly from that according to the one-day food record. The coefficient of correlation between these methods was 0.512, a statistically significant value. The calcium intake from dairy products showed a good correlation, r = 0.717. The coefficient of correlation between the values estimated based on two FFQ filled out three days apart was 0.900, showing good test-retest reliability. Therefore, this FFQ is valid and reliable in estimating dietary calcium intake for epidemiological studies.
There is lack of studies in literature about the long-term effects of hormone replacement therapies and cholesterol levels on mood scores in menopause. In the present study we have investigated whether serum lipid levels affect mood scores in menopause and evaluated the long-term effects of the combined hormone replacement regimens (HRT) on depressive symptoms in postmenopausal women. In this prospective-randomized, placebo-controlled, double-blind study, 286 women in menopause were divided into four groups according to therapeutic regimens they received; 1) Conjugated equine estrogen (CEE) of 0.625 mg plus medroxyprogesterone acetate (MPA) of 2.5 mg (n = 79), 2) CEE (0.625 mg) plus MPA of 5 mg (n = 77), 3) tibolone of 2.5 mg (a selective tissue estrogenic activity regulator) (n = 76), and 4) Calcium (Ca) of 1,000 mg (n = 54). Beck Depression Inventory (BDI), and serum levels of lipoprotein lipids were assessed before and after 12-months of treatment with oral continuous HRT and Ca supplementation. BDI scores in the study groups were not correlated with lipid profiles. We compared two subgroups of patients with initial BDI scores 0-14 (normal mood scores) in order to asses for the possible relation between the lipid profile and mood. Following treatment, first subgroup had increased scores to 15-30 (mildly depressed women, n = 27) and the second subgroup preserved BDI scores of 0-14 (normal mood scores, n = 23). Serum levels of total cholesterol, high-density lipoprotein, low-density lipoprotein and body mass index were found to be similar between these two groups. BDI scores decreased significantly in all HRT groups after 12 months of treatment, compared to Ca group (p < 0.05). We did not observe any correlation between BDI scores and lipid profiles before and following continuous HRT or Ca supplementation. Continuous combined hormone replacement regimens, CEE + MPA and tibolone, have superior long-term effects on mood scores in menopause and should be considered during the decision process for use of HRT due to menopausal symptoms.
Dialysis access surgery is currently one of the most common vascular operations as the dialysis patient population inceases. Although autogenous arteriovenous fistulae stand as the preferred method of access due to excellent patency and lower complication rates, grafts may provide alternative approaches when an autogenous fistula is impractical usually due to depleted veins. We aimed in this study to assess early and midterm outcome with the use of ExpedialTM heterografts (LeMaitre Vascular Ltd., Wrexham, UK) for angioaccess between October 2000 and December 2004. Patients were prospectively followed for pre- and peri-operative course with 1st, 6th and 12th month outpatient controls for patency and complication rates. A total of 34 heterografts were implanted in 30 patients (22 males and 8 females; median age 60.6 years, range 32 - 70). The mean followup for 30 patients were 16.3 ± 6.1 (range 4 - 30) months. 28 grafts (82.4%) were placed in forearm position. Primary and secondary patencies were found as 81% and 94%, respectively (p = 0.15), with the median censored primary and secondary patencies of 27 ± 1.7 months (95% CI, 23.38 to 30.67) and 30.42 ± 1.1 months (95% CI, 28.30 to 32.54), respectively. Only presence of diabetes was found as a significant risk factor in the regression model (p = 0.01). We suggest that the polycarbonate urethane heterografts with acceptable patency/complication rates and shorter maturation times for dialysis access serve an alternative for these patients.
Patients with spine abnormalities, present unique challenges to the health care provider responsible for administrating sedation and anesthesia during surgical and technical procedures. Spinal deformities may cause difficulties with both tracheal intubation and regional anesthesia. This report describes the anesthetic management for two urological operations that were performed in a patient with extremely severe thoracolumbar kyphoscoliosis. After examining the risk factors, spinal block by injecting single dose local anesthetic solution to the intratechal space was chosen to provide anesthesia. It has been suggested that hyperbaric solution, which is of high density compared with cerebrospinal fluid, can safely produce blocks for many operations under spinal anesthesia. In the first procedure, intrathecal injection of 6 mg hyperbaric bupivacaine, a local anesthetic solution (1.2 ml total volume), resulted in inadequate motor and sensory blockade, but the successful motor and sensory blockade at the level of Th10 was achieved in a second attempt with 6.25 mg hypobaric bupivacaine (2 ml). Because of this unexpected effect of local anesthetic solution, in the second operation, the technique was changed to intrathecal injection of 12.5 mg hypobaric bupivacaine (4 ml), and the motor and sensory blockade at Th10 was achieved again. The patient reported satisfactory anesthesia each time, and developed no complications. In conclusion, spinal anesthesia can be successful even in cases of severe thoracolumbar kyphoscoliosis.