Clinical characteristics of pulmonary edema in patients with unstable angina]

To elucidate the clinical characteristics of pulmonary edema in unstable angina, 120 patients with unstable angina who admitted to the hospital within 6 hours after the onset of chest pain were studied. The criteria for the diagnosis of pulmonary edema included interstitial pulmonary edema and diffuse alveolar edema. Pulmonary edema was present in 24 patients. In these patients, the duration of chest pain was relatively longer, and the incidences of diabetes mellitus, emergency coronary revascularization and multiple-vessel coronary artery disease were higher than in those without pulmonary edema. In addition, in-hospital mortality rate in patients with pulmonary edema was higher than in those without it (21 vs 1%, p < 0.001), which is probably due to a large area of myocardial ischemia. For these patients, therefore, early diagnosis and appropriate therapy to save viable segments of the myocardium are mandatory.     

Sex cord-stromal tumors of the ovary

The developmental relationship between granulosa and stromal cells in the fetal ovary was reviewed. The proliferation and expression of basic fibroblast growth factor (bFGF) and luteinizing hormone receptor (LHR) of both the granulosa and theca cells was examined in the adult ovary. Ovarian granulosa cell tumors were then studied under light and electron microscopy and for immunohistochemical expression of bFGF and LHR. In the follicular development of the adult ovary, bFGF expression in the granulosa cells was correlated with theca cell proliferation. In ovarian granulosa cell tumors, estrogen-producing tumors showed a stratified or microfollicular pattern being accompanied by theca cells which had ultrastructural features of steroid-production, and these tumor cells exhibited immunoreactivity for bFGF. In contrast, tumors with no apparent hormone-production showed a solid or gyriform pattern without admixture of theca cells, and were negative for bFGF. LHR was expressed in both types of tumor. Accordingly, bFGF may play an important role in association with the theca cell component in granulosa cell tumors.     

Thinning of ventricular septum in tetralogy of Fallot]

Cross sectional echocardiography was used to evaluate the thickness of the ventricular septum in tetralogy of Fallot (TOF). Forty-six patients with TOF and 20 patients with pseudo-truncus arteriosus underwent echocardiography during a five-year period beginning in 1984. Thicknesses of the right ventricular anterior wall (RVAWT), trabecular septum (IVST) and left ventricular posterior wall (LVPWT) were measured in end diastole on parasternal short axis view at the level of the tips of papillary muscles. The ratios of IVST to RVAWT and IVST to LVPWT were assessed. The ratio of IVST to RVAWT was 1.09 +/- 0.15 in the group aged less than 7 years (less than 7 y.o.) and 0.94 +/- 0.15 in the group aged of 7 years or more (greater than = 7 y.o.). The ratios of IVST to LVPWT were 1.10 +/- 0.14 (less than 7 y.o.) and 0.90 +/- 0.15 (greater than = 7 y.o.), respectively. Both ratios were significantly different (p less than 0.01) in the two age groups, and relative thinning of the septum was demonstrated in the older patients. It is speculated that thinning of the interventricular septum is caused by the lower systolic wall stress of the ventricular septum compared with that of the free walls, which is produced under equal systolic pressure of the two ventricles. It is suggested that this thinning is one of the factors that reduces left ventricular function after repair of TOF.     

Influence of fibroblasts on the invasion and migration of highly or weakly metastatic b16 melanoma cells

We have examined the influence of fibroblasts on the invasive and migratory potential of highly metastatic melanoma B16-BL6 and weakly metastatic B16-FI cells in vitro. Co-culture of B16-BL6 cells with a fibroblast monolayer without cellular contact in a Transwell chamber more effectively induced tumor-cell invasion into Matrigel basement membrane than co-culture of B16-FI cells with a fibroblast monolayer. The activity was closely correlated with the chemotactic migration of tumor cells toward the fibroblast monolayer. We also found that the conditioned medium (CM) from the co-culture of fibroblasts with B16-BL6 cells without cellular contact, i.e., CM (B16-BL6/fibroblast), rather than from co-culture with B16-FI cells, could potentially promote the migration of tumor cells of both types. Tumor cells did not chemotactically migrate to the CM (B16-BL6), CM (B16-FI) or CM (fibroblast). Antibodies against TGF-β1 or FN almost completely abolished the chemotactic migration of B16-BL6 cells to the CM (B16-BL6/fibroblast) or CM (TGF-β1 -treated fibroblast) when these antibodies were c-incubated with fibroblasts and either B16-BL6 or TGF-β1. In contrast, the anti-EGF antibody did not show any inhibitory effects. Analysis of amounts of TGF-β1 or FN in various CM using ELISA plates, and using their specific antibodies, revealed that the concentration of TGF-β1 in the CM (B16-BL6) was slightly higher than in the CM (B16-FI), and the amount of FN in the CM (B16-BL6/fibroblast) was twice as high as in the CM (B16-FI /fibroblast). These results suggest that TGF-β1 released from B16-BL6 cells can stimulate fibroblasts to produce FN; consequently, the tumor cells were able to chemotactically migrate toward the released FN, and the differences in invasive and migratory activities towards fibroblasts in B16-BL6 and B16-FI cells may in part be due to the amounts of TGF-β1 from tumor cells and of FN from TGF-β1 -stimulated fibroblasts.     

A brainstem variant of reversible posterior leukoencephalopathy syndrome (RPLS) presenting with visual disturbance]

A 40-year-old woman noticed blurred vision of the right eye. The optic disc edema of bilateral eyegrounds was noted, and brain MRI showed abnormal signals of the brainstem at a neurosurgical clinic. On her first visit, blood pressure was as remarkably high as 250/130 mmHg. Neurologically, only optic disc edema of bilateral eye-grounds was found. Both T2-weighted MRI and FLAIR showed hyperintense signal areas mainly from the ventral pons to medulla oblongata. These areas were not enhanced with gadolinium. About three weeks after the administration of an antihypertensive agent, brain MRI revealed no abnormal signal. About three months later, the blurred vision disappeared and ophthalmological abnormalities subsided. We diagnosed her with a brainstem variant of RPLS, presenting with visual disturbance caused by hypertensive retinopathy.     

Bicuspid aortic valve stenosis with single coronary artery.

A 56-year-old female with congestive heart failure was transferred to our institution. Aortography demonstrated aortic valve stenosis (AS) with a congenitally bicuspid valve and dilatation of the ascending aorta. Preoperative coronary angiography showed a left single coronary artery. Replacement of the aortic valve and ascending aorta was performed. She had an uneventful postoperative course. We report the case of aortic bicuspid valve stenosis with single coronary artery as an extremely rare congenital cardiac anomaly combination.     

Clinical evaluation of midazolam as an anesthetic for geriatric patients and patients with hepatic dysfunction

This study evaluated the usefulness of midazolam in inducing a anesthetic state in 60 patients who underwent surgery under general anesthesia. The patients were divided into 3 groups; a geriatric group, a hepatic dysfunction group, and a control group (adults without complications). To induce sleep 0.15 mg.kg-1 or 0.2 mg.kg-1 of midazolam was administered intravenously to all three groups. After the administration of midazolam, the mean time for obtaining absence of response to calling name and absence of ciliary reflex were not significantly different in the three groups. The pulse rate and respiratory rate also did not change remarkably. But significant decreases were observed in the systolic blood pressure and tidal volume in all three groups. However, they were not significantly different among the three groups. These results indicate that midazolam is a useful drug for inducing anesthetic state in geriatric patients and patients with hepatic dysfunction.     

Antimetastatic Activity of Polymeric RGDT Peptides Conjugated with Poly(ethylene glycol)

Polymeric peptides containing defined repetitive or cyclic structures of RGDT sequence, (RGDT)_n (n = 1 to 11) and cyclo(RGDT)_n (n=2 to 4), at a dose of 500 μg exhibited an inhibitory effect on experimental lung metastasis upon co-injection with tumor cells and the magnitude of the effect increased in parallel with the increase of degree of repetition of the RGDT sequence. The conjugation of (RGDT)_n (n = 1, 5, 11) with poly(ethylene glycol), PEG as a polymeric carrier led to enhanced inhibition of lung metastasis in proportion to the degree of RGDT sequence repetition and in a dose-dependent manner. Multiple i.v. administrations of PEG-(RGDT)₁₁, at 2-day and 3-day intervals before the excision of primary tumors, effectively inhibited spontaneous lung metastasis by s.c. inoculation of tumors, whereas (RGDT)₁₁ exhibited inhibition of lung metastasis only when given at 2-day intervals. This indicates that the conjugation of PEG with (RGDT)_n allowed the prolongation of administration interval, implying a sustained inhibitory effect on tumor metastasis. In support of this supposition, a decrease in the arrest of radiolabeled tumor cells in the lungs was observed when PEG-(RGDT)₁₁ was co-injected i.v. with tumor cells, or injected i.v. one day before tumor inoculation. In contrast, (RGDT)₁₁ significantly inhibited the tumor cell arrest in the lungs only upon co-injection with tumor cells. We also noted that (RGDT)_n, cyclo(RGDT)_n and PEG-(RGDT)₁₁ inhibited tumor cell invasion into Matrigel in a concentration-dependent manner and in proportion to the degree of RGDT sequence repetition, indicating that the peptide-mediated antimetastatic effect is partly associated with the anti-invasive potential. Thus, the conjugation of anti-cell adhesive and antimetastatic RGDT peptide with PEG might provide a therapeutically promising basis for the prevention of cancer metastasis (“anti adhesion therapy”).