Effects of oral UFT combined with or without zoledronic acid on bone metastasis in the 4T1/luc mouse breast cancer

Bone metastasis is one of the major causes of increased morbidity and eventual mortality in breast cancer patients. Therefore, intervention of bone metastases is one of the important targets in the management of breast cancer. In the present study, we examined the effects of the orally administrable chemotherapeutic agent UFT (a combination of tegafur and uracil at a molar ratio of 1:4) on bone metastases using an animal model of the 4T1/luc mouse breast cancer. The 4T1/luc cells developed spontaneous metastases to bone following orthotopic cell inoculation. Oral daily administration of UFT (20 mg/kg/day) significantly reduced the orthotopic tumor burden; however, the lower dose (15 mg/kg/day) did not. In contrast, histologic examination showed that both doses of UFT significantly suppressed bone metastases in a dose-dependent manner. Since clinical studies have demonstrated that bisphosphonates (BPs), specific inhibitors of osteoclastic bone resorption, are beneficial for breast cancer patients with bone metastases, we next examined the effects of UFT combined with the BP zoledronic acid (ZOL) on established bone metastases. The combination of UFT (20 mg/kg/day) with ZOL (250 microg/kg) caused an enhanced reduction of bone metastases compared with UFT alone. In vitro studies showed that 5-fluorouracil (5-FU), an active metabolite of UFT, and ZOL increased apoptosis in 4T1/luc cells and inhibited osteoclast-like cell formation in an additive fashion. Our results suggest that oral UFT is an effective chemotherapeutic agent for advanced breast cancer accompanying bone metastases and that the combination with BP increases its benefits for bone metastases.     

Ultrasound in penile cancer

Ultrasonography clearly visualized the extent of primary tumor and the presence or absence of inguinal node metastases in two patients with penile cancer. These findings enabled us to decide an appropriate level for penile amputation and the indication for lymphadenectomy.     

Some experiments on the allergic reaction among workers in a pharmaceutical factory (author's transl)]

A survey was made on workers handling powdered drugs in a pharmaceutical factory. In this factory, two kinds of anti-inflammatory enzyme (bromelain and trypsin), one anti-inflammatory agent (flufenamic acid), one antispasmodic (flopropion) and two kinds of antibiotics (ampicillin and cephalexin) are mainly produced. Twenty four workers were examined by interviews and checked by Cornell Medical Index, and 18 of them complained of respiratory symptoms. These 18 workers were physically examined by skin scratch tests, pulmonary function tests and serum immunological tests. Among 24 workers, 9 handled powdered drugs (A group), 5 handled the same in the past and had already been transferred to other sections for their symptoms (B group), 3 engaged in the process of capsul-filling (C group) and 7 handled several times occasionally during one year (D group). Their average months spent in handling powdered drugs were, in the case of anti-inflammatory enzyme, A group 53.2, B group 66.2, and in the case of antibiotics, 5 workers in A group 24.0, 2 workers in B group 7.0, 3 workers in C group 25.7. Twenty workers complained of symptoms which were mainly irritation of mucosa including the respiratory system and itching of the skin while they were working, and accelerated nasal discharge, urticaria and asthma after working. Group A and group B were higher than group D in the rate of respiratory complaints in C.M.I. (p less than 0.001). Fourteen workers pointed out anti-inflammatory enzyme as a cause of main symptoms, 7 workers flufenamic acid, 3 workers flopropion, 4 workers antibiotics. Three workers who had past history of asthma or articular rheumatism had been transferred to other sections. Of 18 workers who were physically examined, 11 workers showed positive reactions to skin scratch tests with handling drugs. On 8 workers of them, some kinds of drugs which were pointed out as drugs causing main symptoms reacted positively. Numbers of workers with increased immunoglobin values were, IgE 3, IgM 2, IgA 4, IgM 2. Two workers showed decreased FVC and FEV (1.0 sec.) values in pulmonary function tests. The causes of the occupational allergic reaction in this factory are guessed as follows: 1) control of powdered materials was incomplete in the process of production, 2) various kinds of sensitizing drugs were handled by the same workers.     

Anorexia nervosa with elevated serum TSH

Low or normal serum TSH concentration is common during fasting and in patients with anorexia nervosa. We report here four patients with anorexia nervosa who had elevated serum TSH, low T3 and low free T4 levels when the initial diagnosis was made. Also, an appearance of TSH peak in response to TRH was delayed, but T3 responsiveness to TRH was normal. All patients were clinically euthyroid with negative serum thyroid autoantibodies and without goiter. Following weight gain, basal levels of serum T3, free T4, and TSH, as well as TSH responsiveness to TRH, returned almost to normal. The data indicated that these patients with anorexia nervosa before refeeding had either a latent transient primary hypothyroidism or the low T3 syndrome associated with an inappropriately high secretion of TSH, probably a new condition that is related to their pretreatment nutritional state.     

New technique for superior guiding catheter support during advancement of a balloon in coronary angioplasty: the anchor technique.

To get superior guiding catheter support, we tried a new method called the anchor technique. By inflating a balloon in a nontarget vessel and holding its shaft with backward force while advancing another balloon, the anchor effect for the guiding catheter could be obtained and it appeared to be helpful for a balloon or a stent to cross the target lesion.     

Frequency domain heart rate variability and plasma norepinephrine level in the coronary sinus during handgrip exercise

BACKGROUND: Heart rate (HR) variability has been recognized as an important noninvasive index of autonomic nervous activities. However, the relationship between HR variability and cardiac circulating norepinephrine (NE), especially with respect to coronary ischemia, remains unclear. HYPOTHESIS: This study was undertaken to determine whether HR variability indices can reflect cardiac NE levels during handgrip exercise. METHODS: We simultaneously measured HR variability and cardiac NE overflow rate in 32 patients (30 men, 2 women) during a 6-min isometric handgrip exercise. Among the 32 subjects, 20 (19 men, 1 woman) had coronary artery disease (CAD) and 12 (control group; 11 men, 1 woman) did not. RESULTS: Hemodynamics and cardiac NE overflow rates among subjects at rest were not significantly different between the two groups. In the normal subjects, low-frequency (LF) spectra and LF/HF (high-frequency) ratios were not significantly changed during handgrip exercise, but HF spectra significantly increased from 10.1 +/- 4.5 to 12.2 +/- 7.0 ms (p < 0.05). In the subjects with CAD, LF and LF/HF spectra were significantly (p < 0.05 and 0.01, respectively) increased by handgrip exercise. High-frequency spectra were not significantly changed by handgrip exercise. In the normal subjects, a significant negative relation (r = -0.76, p < 0.01) was obtained between HF change and cardiac NE overflow rate, whereas this relationship was not significant in the subjects with CAD. The correlation between changes of LF/HF and cardiac NE overflow rate was significant in the normal (r = 0.56, p < 0.05) but not in subjects with CAD. CONCLUSION: These results suggest that vagal modulation of HR variability is more prominent in normal coronary artery subjects than in CAD subjects during handgrip exercise. Heart rate variability indices may thus serve as adequate indicators of autonomic nerve activity in subjects with normal coronary arteries but not in those with CAD, probably due to decreased adaptation to physical stress during handgrip exercise.     

Microclimate is an independent risk factor for the development of intraoperatively acquired pressure ulcers in the park‐bench position: A prospective observational study

Preventing pressure ulcers is important in patients undergoing procedures in the park‐bench position. We hypothesized that the microclimate around the skin is a significant risk factor for developing pressure ulcers. This research continuously assessed factors of the microclimate in terms of skin temperature and perspiration as well as the interface pressure in order to determine whether the microclimate is an independent risk factor for the development of park‐bench position‐related pressure ulcers (PBP‐PUs). A prospective observational study was conducted among patients undergoing elective surgery in the park‐bench position at a general hospital in the metropolitan area of Japan between April and November 2014. Factors of the microclimate, including skin temperature and perspiration, in addition to the interface pressure were continuously measured throughout surgery. Twenty‐nine patients were analyzed (mean age 44.4 ± 13.2 years, male 44.8%). Of these 29 patients, seven (24.1%) developed Category I PBP‐PUs. The change in skin temperature from baseline to the end of surgery (2.7 ± 0.3 °C vs. 1.9 ± 0.8 °C) and the average peak pressure (119.1 ± 36.8 mmHg vs. 94.5 ± 23.1 mmHg) were significantly higher in the patients with PBP‐PUs than in those without PBP‐PUs. There were no significant differences in the amount of perspiration between the two groups. A hierarchical logistic regression analysis showed that the change in skin temperature was significantly related to the development of PBP‐PUs (unit = 0.1 °C: odds ratio 1.44, 95% confidential interval 1.09–2.33) when adjusted for the average peak pressure and length of surgery. Our results suggest that a change in skin temperature toward a higher value is an independent risk factor for the development of PBP‐PUs. Proper intraoperative management of skin temperature may therefore be a promising candidate as a preventive method against PBP‐PU development.     

Compressive and diametral tensile strength of glass ionomer cements

The aim of this study was to compare, in different periods of time, the compressive and diametral tensile strength of a traditional high viscous glass ionomer cement: Fuji IX (GC Corporation), with two new Brazilian GIC's: Vitro-Molar (DFL) and Bioglass R (Biodinamica), all indicated for the Atraumatic Restorative Treatment (ART) technique. Fifteen disk specimens (6.0mm diameter x 3.0mm height) for the diametral tensile strength (DTS) test and fifteen cylindrical specimens (6.0mm diameter x 12.0mm height) for the compressive strength (CS) test were made of each GIC. Specimens were stored in deionized water at 37o C and 100% of humidity in a stove until testing. Five specimens of each GIC were submitted to CS and DTS test in each period, namely 1 hour, 24 hours and 7 days. The specimens were tested in a testing machine (Emic) at a crosshead speed of 1.0mm/min for CS and 0.5mm/min for the DTS test until failure occurred. The data were submitted to two-way ANOVA and Tukey tests (alpha=0.05). The mean CS values ranged from 42.03 to 155.47MPa and means DTS from 5.54 to 13.72 MPa, with test periods from 1h to 7 days. The CS and DTS tests showed no statistically significant difference between Fuji IX and Vitro Molar, except for CS test at 1-hour period. Bioglass R had lowest mean value for CS of the cements tested. In DTS test Bioglass R presented no statistically significant differences when compared with all others tested GICs at 1-hour period and Bioglass R presented no difference at 24-hour and 7-day periods when compared to Vitro-Molar. Further studies to investigate other physical properties such as fracture toughness and wear resistance, as well as chemical composition and biocompatibility, are now needed to better understand the properties of these new Brazilian GIC's.