Results of a non-controlled trial of hyperthermia combined with radiation for superficial tumours

Fifty-four patients with 65 superficial malignant lesions were treated by local hyperthermia combined with radiation therapy at the National Cancer Center Hospital, Tokyo. Hyperthermia was delivered with an Aloka Model HMS-020 (2450 MHz) or with a horn-type applicator of BSD-1000 (80-90 MHz). Relatively small tumours, those less than 4 cm in thickness, were treated by using 2450 MHz while 80-90 MHz delivered through the horn-type applicator was used for tumours exceeding 5 cm in thickness. The radiation dose was 4 Gy twice a week or 2 Gy five times a week, the total dose being 40-60 Gy. A total of six to 10 hyperthermia treatments ranging from 40 to 60 min each, with the tumour heated to more than 42.5 degrees C, were given twice a week within 1 h following radiation therapy. Complete response was achieved in 16 of the 30 patients (55 per cent) treated with the 2450 MHz microwave, and partial response in seven others (23 per cent). Tumours treated with the BSD-1000 achieved complete response in 10 out of 33 patients (30 per cent) and partial response in nine others (27 per cent). In five out of nine patients classified as partial responders, however, complete disappearance of tumour cells was noted by post-treatment histological examination. Complete plus partial response rates were thus essentially the same with the Aloka HMS-020 and the BSD-1000, though the rate of complete response was apparently higher with the Aloka unit, probably because it was used on smaller tumours.     

Cardiac tamponade due to intrapericardial rupture of an amebic liver abscess

Pericardial abscess is rare in healthy individuals, especially the amebic type. We report a case of pericardial abscess and cardiac tamponade due to intrapericardial rupture of an amebic liver abscess. A 31-year old Japanese male complained of fever to a local hospital. A liver mass was discovered in his left hepatic lobe by an abdominal echogram. He was referred to the internal department of our hospital and was treated with quinolone antibiotics. Two weeks after medication, he suddenly complained of epigastralgia and severe orthopnea and was admitted. Abdominal computed tomographic scan showed an enlarged liver mass, and massive pericardial effusion suggested cardiac tamponade. He underwent an emergency subxiphoid partial pericardiectomy under local anesthesia. 1,000 ml of light brownish fluid was removed and his condition improved. Although no ameba was cultivated from the pus, the amebic serological test was positive. Metronidazole was administered and the patients was discharged 31 days after surgery.     

Endocrinology: High incidence of embryo transfer cancellations in patients with polycystic ovarian syndrome

This study was aimed at assessing the outcome of in-vitro fertilization(IVF) and embryo transfer in patients with polycystic ovariansyndrome (PCOS). The results of IVF and embryo transfer in PCOSpatients (PCOS group, 78 cycles of 26 patients) were comparedwith those of a control group (423 cycles in 202 patients withoutmale factor; age and ovarian stimulation protocol were matched).Although the pregnancy rate per transfer was not different inthe two groups of patients (25 versus 34%, PCOS versus controlgroup), the PCOS group had a significantly lower pregnancy rateper follicle aspiration (19 versus 31%, P < 0.05). A notableresult was a significantly higher incidence of embryo transfercancellations in the PCOS group (22 versus 8%, P < 0.01),which resulted from unpredictable failure of either oocyte recoveryor fertilization. The incidence of unexplained complete failureof fertilization was significantly higher in the PCOS group(18 versus 5%, P < 0.01). These results may reflect a reducedquality of the oocytes in the PCOS group, and there was a subgroupof PCOS patients who repeatedly produced poor results of treatment.Although the ovarian stimulation regimen best suited to PCOSpatients remains to be determined, special care should be takenduring ovarian stimulation, especially when the PCOS patientshad experienced unexplained failure of oocyte recovery or fertilizationin the previous treatment cycle(s).     

Teratogenic relationship between polydactyly, syndactyly and cleft hand

Several investigators have suggested that polydactyly, syndactyly and cleft hand might have arisen from a common teratogenic mechanism. To confirm this hypothesis, 75 hands with these anomalies were analysed. Advanced cases with central polydactyly or osseous syndactyly in which the fusion area extends as far as the proximal phalanx and metacarpus are identical to typical cleft hand. The author has induced the same deformities using myleran in rat foetuses. The clinical features of these anomalies in rats were the same as those in clinical cases and the critical periods of these anomalies were also the same. The findings suggest that these hand anomalies may appear in human beings when the same teratogenic factor acts on the embryo at the same developmental period and that they should belong to the same teratogenic entity.     

Electron-microscopic and immunohistochemical study of beta-2-microglobulin-related amyloidosis.

beta 2-Microglobulin (beta 2-MG)-related amyloidosis has been reported as a complication in long-term hemodialysis patients. We observed beta 2-MG amyloid deposits in synovial sheaths, bone cysts and gastric mucosa. They showed unique ultrastructural features, that is bundles or nodules consisting of curved or linear amyloid fibrils, associated with various cell reactions. The electron-microscopic histochemical study showed that they strongly stained with periodic acid-silver methenamine stain. A similar phenomenon was noticed in the spicules or bundles of amyloid fibrils in primary and secondary renal amyloidosis. With the cationic reagent toluidine blue 0, proteoglycan-like structures were observed around amyloid bundles and nodules, but not on each fibrils. Based on these results, we postulate that there is a close relationship between ultrastructural features and histochemical characteristics in beta 2-MG amyloid fibrils.     

Growth factors induce actin disruption in cultured human retinal pigment epithelial cells

Exposure of cultured human retinal pigment epithelial cells to platelet-derived growth factor, nerve growth factor or epidermal growth factor resulted in a time- and dose-dependent alteration in the distribution of actin stained by rhodamine-phalloidin. These growth factors (platelet-derived growth factor of 80 ng/ml, nerve growth factor of 10 ng/ml or epidermal growth factor of 10 ng/ml) caused disappearance of actin filaments from the peripheral region of a cell in 1 or 2 h and change of cell configuration to spindle shape in 3 or 4 h. Other growth factors, fibroblast growth factor of 10 ng/ml and insulin of 25 mumol/ml had no effect on actin distribution. The alteration of actin and the change of cellular shape might be associated with stimulation of cell growth and migration of retinal pigment epithelial cells.     

Effects of renin-angiotensin system blockade on macrophage infiltration in patients with hypertensive nephrosclerosis.

The mechanisms of hypertensive nephrosclerosis are not fully understood. In experimental models of the disease, inflammatory reactions such as macrophage infiltration play an important role. In human hypertensive nephrosclerosis, however, there have been few studies examining the role of inflammation histologically. We investigated whether the number of infiltrating macrophages was increased in human hypertensive nephrosclerosis, and evaluated the effects of a blockade of the renin-angiotensin system on clinical and histological findings. We examined macrophage infiltration using immunohistochemistry in renal biopsy specimens obtained from 16 patients with hypertensive nephrosclerosis, 5 patients with IgA nephropathy, 5 patients with membranous nephropathy, and 5 patients with minimal change nephrotic syndrome. The number of infiltrating macrophages in glomeruli was significantly larger in the patients with hypertensive nephrosclerosis than in those with minimal change nephrotic syndrome. The patients with hypertensive nephrosclerosis were divided into groups based on their use of antihypertensive agents at the time of renal biopsy. We investigated the effects of antihypertensive agents on clinical findings, macrophage infiltration, and monocyte chemoattractant protein-1 expression. There was no difference in clinical findings between the hypertensive groups. The numbers of infiltrating macrophages and monocyte chemoattractant protein-1-positive cells in glomeruli were significantly smaller in patients treated with an angiotensin-converting enzyme inhibitor or angiotensin II type 1 receptor blocker, whereas calcium channel blockers had no influence on histological findings. In conclusion, inflammation is involved in the progression of human hypertensive nephrosclerosis and the inflammatory process is inhibited by blocking the renin-angiotensin system.     

Synthetic/secreting and apoptotic phenotypes in renal biopsy tissues from hypertensive nephrosclerosis patients.

The major glomerular abnormalities in hypertensive nephrosclerosis are described as glomerular obsolescence (GO), glomerulosclerosis (GS), and glomerular collapse (GC). However, glomerular cellular changes caused by hypertensive insults have not been well analyzed. Using an immunoenzyme method, we examined eleven biopsy samples from patients with hypertensive nephrosclerosis for two synthetic and secreting phenotypes, a-smooth muscle actin (alpha-SMA) and collagen type III (Col. III), and two apoptotic phenotypes, pro-apoptotic molecule Bax and anti-apoptotic molecule BcI-2. Together with the glomerular and vascular changes and interstitial fibrosis (IF) area, the results were scored quantitatively and semi-quantitatively and compared to the clinical findings, which included systolic blood pressure (SBP), mean arterial pressure (MAP), serum creatinine levels (sCr) and creatinine clearance (Ccr), using univariate and multivariate analyses. As a result, GS was frequently observed in the mild-to-moderate hypertensive group (140 < or = SBP<180 mmHg), whereas GC was positively correlated with SBP. Furthermore, there was a positive correlation of GS with mesangial alpha-SMA and Col. III, suggesting that GS was the reflection of these synthetic and secreting phenotypic changes in mesangial cells. Endothelial Bax was positively correlated with Ccr (p<0.01); in contrast, podocytic Bax was positively correlated with sCr (p<0.05) and showed a tendency to correlate with MAP (p=0.054). In conclusion, these findings support the view that mesangial synthetic and secreting phenotypic changes may be a reflection of cellular activation caused by mild-to-moderate hypertension and that apoptotic phenotypic expression in podocytes, rather than endothelial cells, may be related to the development of a severe form of hypertensive nephrosclerosis.