Breast cancer with bone-only metastases. Visceral metastases-free rate in relation to anatomic distribution of bone metastases

The medical records of 82 patients with breast cancer with bone-only metastases were reviewed. According to the distribution of the metastases by bone scan at the time they were first documented, the patients were divided into three groups: Group A (patients who had bone metastases exclusively cranial to the lumbosacral junction), Group B (patients who had bone metastases exclusively caudal to the junction), and Group C (patients who had bone metastases both cranial and caudal to the junction). Group A had a significantly higher visceral metastases-free rate than Groups B or C. Serial bone scans and radiographs of Group A patients revealed that bone lesions cranial to the junction rarely developed into visceral metastases and that bone lesions extending caudal to the junction frequently developed into visceral metastases. These results indicate that the presence of bone metastases caudal to the lumbosacral junction is predictive of visceral metastases.     

Clinical results of conventional fractionation radiotherapy for glottic and supraglottic laryngeal cancers--the usefulness of hyperfractionation for these cancers

Ninety patients with glottic and eighteen patients with supraglottic laryngeal cancer (anyN, M0) were treated by conventional fractionation radiotherapy between July, 1963 and August, 1988. Tumor control and cause specific survival were evaluated according to tumor location (glottic or supraglottic) and tumor size (T1, T2, T3, or T4). As a result, the steepness of dose-response curve for the tumor control in T1-2 glottic and T2 supraglottic tumors was more slanting upwards than that in other laryngeal tumors, and the patients whose tumors were irradiated at larger doses had a tendency to survive longer. These results suggested that T1-2 glottic and T2 supraglottic laryngeal tumors can have a good application for hyperfractionation radiotherapy which is a radiation therapy with multiple fractions per day with a small fraction size and with which tumors can receive larger radiation doses than with conventional fractionation radiotherapy. Five patients with glottic or supraglottic tumors treated by hyperfractionation radiotherapy obtained CR, and now show no recurrence. We are going to investigate the usefulness of hyperfractionation radiotherapy after treating more patients with Twice-A-Day fractionation radiotherapy.     

Serial changes of the myocardium in patients with Duchenne's muscular dystrophy followed by cardiac nuclear imaging. 5 years' observation

In order to evaluate the natural course of Duchenne's cardiomyopathy (DMD), 201T1-SPECT and RI cardioangiography with 99mTc-albumin were performed in 14 patients. They were examined once a year for five years except for 6 patients. Hypo-perfusion were observed in both posterior-inferior and anterior wall at 12 years of age and extended to the lateral wall and septum with aging. The degree of cardiac involvement was different in each case. Systolic parameters (LVEF, 1/3 EF, 1/3 ER-mean) tended to decrease with aging from 15 years of age. Diastolic parameters (%EFV, 1/3 FF, 1/3 FR mean) decreased gradually after 16 years of age. Hypokinetic changes of regional wall motion were observed at 15 years of age and they became severely with aging. Although phase delay appeared visually at 16 years of age, standard deviation of phase angle increased from 15 years of age. Follow up studies by 201T1 myocardial SPECT and gated pool scintigraphy revealed well the progression of cardiac involvement in patients with DMD.     

Mitogenic activity of lipopolysaccharide from Bacteroides intermedius against C3H/HeJ mice spleen cells

Bacteroides intermedius is one of the periodontal disease generative bacteria. Lipopolysaccharide preparation obtained from B. intermedius ATCC 25611 and ATCC 33563 strains was investigated as to Limulus activity observed with Pyrodic (endotoxin specific) reagent, and mitogenic activity in both normal and tolerant mice induced by Escherichia coli. Limulus activities of all LPS's were nearly similar to that of E. coli. LPS's preparation from B. intermedius were found to be strongly mitogenic for C3H/HeN mice spleen cells, whereas no LPS preparations were mitogenic for thymocytes of BALB/c mice. LPS-nonresponsive C3H/HeJ mice spleen cells were found to good mitogenic responses to LPS's from B. intermedius, as well as LPS from B. gingivalis 381 strain. Polymyxin B had remarkable inhibitory effect on the mitogenicity of LPS's from B. intermedius for C3H/HeN and C3H/HeJ mice spleen cells, also that activity of B. gingivalis LPS was inhibited by polymyxin B. The mitogenicity of the LPS from B. intermedius, as measured in C3H/HeJ mice spleen cells, was considerably resistant to the proteolytic effects of proteinase K.     

5-Hydroxytryptamine agonistic action of methysergide and the absence of supersensitivity to 5-HT agonists in spinal flexor reflexes in rats

The intravenous administration of L-5-hydroxytryptophan (5-HTP), 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), p-chloroamphetamine (PCA), LSD and methysergide to acute spinal rats, transected at C1, stimulated the flexor reflexes induced by electrical stimulation applied to the skin of the toe. The enhancement produced by 5-HTP, 5-MeODMT and PCA, was not antagonized by the prior administration of a dose of LSD or methysergide, although the enhancement produced by 5-MeODMT, LSD and methysergide, but not that produced by 5-HTP and PCA, was antagonized by cyproheptadine. In rats treated with 5,6-dihydroxytryptamine (intracisternal administration, 2 weeks previously) supersensitivity was observed to the effects of 5-HTP, a precursor of 5-HT, while subsensitivity was observed for the effects of PCA, a releaser of 5-HT. However, no supersensitivity was observed for the effects of 5-MeODMT, LSD and methysergide. These results suggest that methysergide may have an agonistic action on the 5-HT receptors in spinal cord and that supersensitivity to 5-HTP in rats treated with 5,6-dihydroxytryptamine was due to the lack of uptake of 5-HT into terminals of descending 5-HT fibres or to the change in 5-HT receptors which were not sensitive to 5-MeODMT, LSD, methysergide or cyproheptadine.     

The quality of conduct in Japanese clinical trials: deficiencies found in GCP inspections

The quality of commercially sponsored clinical studies in Japan was examined with reference to deficiencies in the audit reports issued by the Organization for Pharmaceutical Safety and Research (OPSR). The OPSR is responsible for domestic good clinical practice auditing in Japan. Routine audits from 1997 to 2000 for 331 hospitals revealed various types of deficiencies such as errors in case report form (CRF) entries, institutional review board problems, and protocol deviations. The high prevalence of CRF-related deficiencies seemed to stem from peculiarities of the Japanese study environment such as the historical lack of on-site monitoring by the sponsor and the absence of research nurses. Characteristics in usual medical practices such as multiple drug use and loose informed consent also seemed to be associated with prevalence of similar deficiencies in clinical trials.     

Effect of gefarnate on endogenous prostacyclin, prostaglandin E2 and thromboxane in water-immersed rats

The level of endogenous prostacyclin (PGI2), prostaglandin E2 (PGE2) and thromboxane A2 (TXA2) in rat gastric mucosa was determined by radioimmunoassay to examine whether gefarnate, an antiulcer agent, maintained the endogenous prostaglandin (PG) level in rats subjected to water-immersion stress. Seven-hr immersion induced gastric lesions and a marked reduction in PGI2 and PGE2. When gefarnate was injected subcutaneously before stress exposure, the mean ulcer index was reduced and the PGI2 and PGE2 levels were maintained. Our results suggest that the reduction of endogenous PGI2 and PGE2 is a major factor in water-immersion-induced ulcers in rats, and that gefarnate inhibits this ulcer formation by inhibiting a reduction in those PGs induced by water-immersion stress.