Biomechanical evaluation of foot pressure and loading force during gait in rheumatoid arthritic patients with and without foot orthosis.

Foot orthoses are commonly used in patients with rheumatoid arthritis (RA) to support the foot and relieve pain, however little is known about the biomechanical effects of in-shoe foot orthoses in reducing or redistributing high pressures and loading forces. The purpose of this study was to compare the foot pressures and loading forces during gait in rheumatoid arthritic patients and healthy subjects, and evaluate the biomechanical effects of the foot orthoses in the RA patients. Twelve female RA patients with foot pain in walking, all Steinbrocker class II, and 8 healthy women without foot pain were matched for age. Foot pressures and loading forces with and without orthoses were measured using the F-Scan program. The pressure distributions and loading forces were standardized by the body weight and compared, and the effects of the foot orthoses were evaluated. The foot orthoses of RA patients provided higher pressure reduction than those of the control group (3.00 +/- 0.38 g/cm2/BW and 3.29 +/- 0.29 g/cm2/BW respectively, p < 0.001). Similar redistribution of plantar pressures and loading forces were found between two groups but the RA patients had a greater change at the stance phase of gait (p < 0.0001). The foot orthosis produces greater pressure and loading force relief and redistribution in RA patients than in normal subjects.

Ovarian endometrioid adenocarcinoma coexistent with benign and borderline endometrioid adenofibroma: a case report.

A well-differentiated endometrioid adenocarcinoma coexistent with benign and borderline-malignant endometrioid adenofibroma was found in the ovary of a 64-year-old woman. She had vaginal bleeding caused by simple hyperplasia of the endometrium due to high levels of sex steroid hormones. A FIGO stage Ia solid ovarian tumor was identified. It was composed of irregularly shaped endometriotic glands with benign and borderline malignant cytologic features embedded in abundant fibromatous stroma. Well-differentiated malignant epithelium was adjacent to these areas, but fibromatous stroma was not predominant. She was treated by surgery and three cycles of chemotherapy. This paper describes this unusual tumor and reviews the literature.

[Combination of irinotecan hydrochloride (CPT-11) and cisplatin as a new regimen for patients with advanced ovarian cancer].

It has been reported that the antitumor effect of CPT-11 is manifested through the inhibition of topoisomerase I by SN-38 which is an active metabolite of CPT-11 produced by intracellular carboxylesterase, and that CPT-11 is effective against recurrent ovarian carcinoma. We investigated the antitumor effect and adverse reactions in the combined therapy with CPT-11 and CDDP in patients with prior chemotherapy for recurrent carcinoma, and in 7 patients without prior chemotherapy, consisting of 4 patients with postoperative adjuvant chemotherapy for clear cell carcinoma and 3 patients with metastatic ovarian carcinoma. CDDP was administered on day 1 and CPT-11 was administered three times on days 1, 8 and 15. The dose of both CDDP and CPT-11 was 50 mg/m2 or 60 mg/m2. Adverse reactions were investigated in all patients and the antitumor effect was assessed in 12 patients with recurrent carcinoma who had measurable lesions. (1) The DLF was neutropenia. The neutrophil count nadiar occurred on day 18 or 19. Grade 3 or 4 adverse reactions were observed in 60% or more of the patients, but they disappeared following short term administration of G-CSF. In patients with recurrent carcinoma given CDDP and CPT-11 at 60 mg/m2, the incidence of grade 3 or 4 adverse reactions and number of occasions on which CPT-11 administration had to be postponed were higher than those in patients given 50 mg/m2. (2) Mild platelet reduction was observed. (3) Grade 3 or 4 diarrhea was observed in 3.2% of patients with recurrent carcinoma and in 7.7% of patients with metastatic ovarian carcinoma. (4) The antitumor effect was evaluated in 12 patients with recurrent carcinoma: CR in 2 patients. PR in 3, NC in 6, and PD in one. The response rate was 41.7%. (5) An antitumor effect was observed in 2 patients with serous carcinoma and in one patient each with mucous carcinoma, clear cell carcinoma and endometrial carcinoma. In conclusion, adverse reactions caused by the combination therapy with CPT-11 and CDDP (CPT-11: 50-60 mg/m2 on days 1, 8 and 15, CDDP: 50-60 mg/m2 on day 1) can be relieved by short term administration of G-CSF and it is suggested that the combination therapy may be effective in treating ovarian carcinoma.

Regulation of 3 beta-hydroxysteroid dehydrogenase expression in human adrenocortical H295R cells.

Previous studies of the effects of angiotensin II (All), alone or in combination with activators of the protein kinase. A signalling pathway, have yielded inconsistent findings on the expression of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD and 17 alpha-hydroxylase cytochrome P450 (P450c17) as well as the corresponding responses on steroid secretory products in human adrenocortical cells. We have used the human adrenocortical carcinoma H295R cell further to evaluate this question, as well as to determine the role of protein kinase C in each of these responses to All. Treatment with All alone resulted in a marked increase in aldosterone secretion and a significant increase in cortisol secretion (1-8-fold). The increased formation of 17-hydroxysteroids was accompanied by an increased level of P450c17 mRNA and activity. Increases in 3 beta-HSD expression were also seen at the level of mRNA and to a lesser extent, at the level of activity. Because of the comparatively low basal 17 alpha-hydroxylase and high basal 3 beta-HSD activities of H295R cells, however, the overall effect of All treatment was actually a rise in the 17 alpha-hydroxylase/3 beta-HSD activity ratio, so resulting in increased formation of 17 alpha-hydroxysteroids such as cortisol. While treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA) reproduced the effect of All on 3 beta-HSD expression, TPA failed to reproduce the effects of All on P450c17 because it caused a marked decrease in P450c17 expression. Thus the stimulatory effect of All on P450c17 expression, unlike that on 3 beta-HSD expression, was not mediated by protein kinase C but, like the action of K, was probably mediated via the Ca2+ signalling pathway. Treatment with forskolin resulted in a dramatic increase in both cortisol and dehydroepiandrosterone (DHEA) secretion together with increases in expression of 3 beta-HSD and P450c17 as measured at the level of mRNA and activity. Consistent with the increase in 17 alpha-hydroxysteroid formation, the effect on P450c17 expression was greater than that on 3 beta-HSD at the level of activity, so a larger 17 alpha-hydroxylase/3 beta-HSD activity ratio was achieved. Cotreatment with forskolin and All, however, resulted in a dose-dependent reduction in cortisol and DHEA secretion concomitant with a marked attenuation of 3 beta-HSD and P450c17 expression. While forskolin-induced expression of 3 beta-HSD was not further increased at the level of mRNA by cotreatment with All, additivity was observed as the level of activity changed. Thus All cotreatment resulted in a marked reduction in the forskolin-induced increase in the 17 alpha-hydroxylase/3 beta-HSD activity ratio, and so 17 alpha-hydroxysteroid synthesis was attenuated. The effect of All cotreatment on changes in forskolin-induced 3 beta-HSD activity was blocked by the All type 1 (AT1) antagonist DuP753 (Losartan), confirming the involvement of the AT1 receptor-linked phospholipase C in activating protein kinase C.

Regulation of 11 beta-hydroxysteroid dehydrogenase type 2 activity and mRNA in human choriocarcinoma cells.

The type 2 isoform of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD2), which catalyzes the conversion of cortisol to hormonally inactive cortisone in man, is principally expressed in the placenta and mineralocorticoid target tissues, kidney and colon. To date, few studies have addressed the regulation of this novel 11 beta-HSD2 isoform. We have characterized the nature and regulation of the 11 beta-HSD activity expressed in a human cytotrophoblastic cell line, the JEG-3 choriocarcinoma cell. The 11 beta-HSD activity in JEG-3 cell homogenates required NAD+ as cofactor with NADP+ ineffective and demonstrated a high affinity for cortisol (apparent Km 31 nM). Incubation of JEG-3 cells with forskolin and dibutyryl cyclic AMP increased 11 beta-HSD2 activity several-fold in a time-dependent manner, while treatment with phorbol ester had little, if any, effect on 11 beta-HSD2 activity. Northern blot analysis of RNA isolated from JEG-3 cells after these treatments demonstrated a marked increase in a 1.9 kb 11 beta-HSD2 mRNA species in cells treated with forskolin for 24 h. We conclude that 11 beta-HSD2 is regulated by activation of the protein kinase A pathway, but not the protein kinase C pathway in human choriocarcinoma cells, and that this regulation occurs at a pretranslational level. JEG-3 cells provide an excellent model for further studies on the regulation of 11 beta-HSD2 gene expression in human trophoblast tissue.

Detection of lymph node metastasis in ovarian carcinoma and uterine corpus carcinoma by preoperative computerized tomography or magnetic resonance imaging.

OBJECTIVE: Preoperative CT or MRI findings were compared with the results of staging the laparotomy to evaluate the accuracy of CT or MRI for detecting pelvic and para-aortic lymph-node metastases. METHODS: In evaluating CTs in 95 ovarian carcinomas, we examined plain and contrast images made in 1- to 1.5-cm-thick slices from the pubis to the xiphoid process. Lymph nodes 1.5 cm or larger were considered to be positive. MRIs of 60 uterine corpus carcinomas utilized T1-weighted contrast, T2-weighted, and short-inversion time inversion-recovery (STIR) images. RESULTS: CT had a sensitivity of 60.9% and a specificity of 93.1%. The positive and negative predictive values were 73.7% and 88.2%, respectively. The diagnostic accuracy of CT for detecting para-aortic lymph-node metastases exceeded that for pelvic node metastases. The results of MRI indicated that the T1-weighted image and STIR image were the most accurate in identifying metastatic nodes. CONCLUSIONS: These results indicate that the most practical approach might be to search for enlarged lymph nodes by CT, and to follow-up with MRI when CT scans are questionable.

Combination treatment with cisplatin and schizophyllan for 7,12-dimethylbenz(a)anthracene-induced rat ovarian adenocarcinoma.

OBJECTIVE: Experimental chemotherapy was conducted to investigate the combined effect of Schizophyllan (SPG) and Cisplatin (CDDP). METHODS: Rats with 7,12-dimethylbenz(a)anthracene (DMBA)-induced ovarian adenocarcinoma received SPG and/or CDDP, were observed for the anti-tumor effect of the drugs and were subjected to immunohistochemical study. RESULTS: 1) Tumor reduction was enhanced by the combined use of SPG and CDDP; 2) The survival rate of rats given SPG alone was significantly higher than that of the control rats, and treatment with SPG combined with CDDP tended to improve the survival rate; 3) Immunohistochemically, an infiltrative increase in cytotoxic T-lymphocytes (CTL) was induced, although the development of helper T-cells and macrophages was immunohistochemically weak at the tumor site. CONCLUSION: The administration of SPG enhanced the anti-tumor effect of CDDP.

Malignant Brenner tumor of the ovary: two cases of unusual histologic features of relapsed tumors.

This study focused on unusual histologic features observed in 2 relapsed Brenner tumors. Case 1: A 67-year-old woman had a malignant Brenner tumor. The tumor relapsed was squamous-cell carcinoma. Case 2: A 51-year-old woman had a proliferating and malignant Brenner tumor with mucinous metaplasia. The relapsed tumor was a well-differentiated mucinous adenocarcinoma. These cases suggest that: (1) the relapsed tumor cells survived chemotherapy; and (2) the relapsed tumor cells transformed.

[Immunohistochemical studies of recessive oncogene p53 and N-myc oncogene expression in 7, 12 dimethylbenz (a) anthracene-induced rat ovarian tumors].

In the present study, the expressions of p53 and N-myc gene were analyzed immunohistochemically in rat ovarian tumors induced by 7,12 dimethylbenz (a) anthracene (DMBA). 1) p53 could be seen in the nucleolei of tumor cells. The positive rates were: adenomas 17%, adenocarcinomas 37%, sarcomas 0%, mixed müllerian tumor 0% and epidermal cysts 100%. Neither the serial-allografted tumor nor DMBA-OC-1 was positive. 2) N-myc could be seen in the cytoplasm and perinuclear cytoplasm of tumor cells. The positive rates were: adenomas 33%, adenocarcinomas 77%, sarcomas 100%, mixed müllerian tumors 100% and epidermal cysts 100%. Both the serial-allografted tumor and DMBA-OC-1 were positive. 3) The positive rates in both p53 and p21 were: adenocarcinoma 20% and epidermal cysts 100%. The positive rates in both N-myc and p21 at the were: adenoma 17%, adenocarcinoma 50%, sarcoma 33%. Both the serial-allografted tumor and DMBA-OC-1 were positive. Only two cases were positive for p53, N-myc and p21. p53 was detected in most of the adenomas. 4) The positive rate for both N-myc and p21 was higher than that for both p53 and p21. This was similar to other reports. The results suggested that p53 plays a role in precancerous tumor as a recessive oncogene. It was supposed that tumors with N-myc gene expression were had malignant growth characteristics.

Intraperitoneal transplantation of ascitic cancer cells from a 7,12-dimethylbenz[a]anthracene (DMBA)-induced ovarian cancer.

Intra-abdominal implantation of 7,12 dimethylbenz[a]anthracene (DMBA)-induced rat ovarian cancer tissue produces intraperitoneal carcinomatosis with a high incidence. The peritoneal carcinoma produces malignant ascites in 62% of the donor rats. The ascites is bloody in appearance and includes an average of 1.2 x 10(6) cancer cells/ml. To observe the transplantability of the ascites, 0.1 ml of a condensed ascites with 4 x 10(6) cancer cells was injected into the abdominal cavity of 118 infant rats that were 2 to 4 days old. In 103 rats (87%), the ascitic cells were successfully transplanted. Twelve rats were sacrificed each week from the 2nd to the 6th week following the inoculation. The omentum was the first site at which the metastastic tumor appeared following the inoculation. Then the tumor disseminated throughout the intraperitoneal cavity and produced bloody ascites by the 3rd week. Eighty-four rats were observed to determine the survival, and it was 34 +/- 10 days. Cytologically the ascites had clusters of tumor cells resembling bunches of grapes. The ultrastructure of the ascitic cells was globular shaped with many microvilli and epithelial attachments. The histology of the developed tumor was that of an adenocarcinoma. Due to morphological similarity with advanced human ovarian cancer and the high reproducibility, this experimental system could be a feasible model for human ovarian cancer, especially the type which produces malignant ascites.

Minimal deviation adenocarcinoma (adenoma malignum) of the uterine cervix associated with mucinous ovarian carcinoma.

A case of minimal deviation adenocarcinoma (MDA: adenoma malignum) of the uterine cervix associated with ovarian mucinous carcinoma is documented. Diagnosis was possible only retrospectively after surgery by histological examinations including immunohistochemistry. Three courses of chemotherapy, consisting of cisplatin, doxorubicin and ifosfamide, could eradicate the residual diseases of ovarian cancer from the peritoneal cavity, but was insufficiently effective against lymph node metastases of the cervical MDA. Subsequently, the disease flared-up retroperitoneally during the sixth course of treatment course, suggesting chemoresistance developed, and further chemotherapy using different regimens were not effective. Therapeutic intractability of MDA as well as the diagnostic difficulty was again emphasized.

An experimental model for advanced ovarian cancer.

Intraperitoneally transplanted tumors implanted and began developing with ascites in about 62% of the female rats within 4 to 6 weeks after transplantation. The tumor used in this study was an adenocarcinoma and which originated from a primary ovarian cancer in rats of the same strain (Wistar). The morphology and biological behavior of the tumor were very similar to the tumor in humans. Moreover, the preliminary results with cisplatin therapy indicate that intraperitoneal cancer corresponding to stage III or IV in the FIGO classification is a promising model for experimental therapeutic studies of common epithelial carcinoma at an advanced stage.

A preliminary study of a combination chemotherapy with ifosfamide, adriamycin and cisplatin for endometrial carcinoma.

Seven patients with uterine endometrial carcinoma received a postoperative combination chemotherapy with ifosfamide (1g/m2) daily for 5 days, and adriamycin (50mg/m2) and cisplatin (50mg/m2) on day 1 (IAP). All except one patient with the disease without myometrial invasion received 5 courses or more of IAP treatment. Of four patients with measurable disease, three achieved complete response (CR) and the other patient obtained partial response (PR), indicating a 100% response rate. In the PR case, the patient had previously been treated by radiation treatment for cervical cancer, and the histology of the tumor was papillary serous adenocarcinoma, a malignant variant of endometrial cancer. Six patients underwent second look operation following the planned IAP treatment courses, and the operation confirmed no pathological evidence of disease in any, although in one disease recurred 7 months after the second laparotomy. Side effects were remarkable, including an 87% incidence of grade 4 leucopenia. However, the patients recovered spontaneously from the hematologic toxicity within 3 weeks of treatment. Other toxic effects including central nervous system toxicity were controllable and acceptable. The results indicated that IAP combination therapy was feasible and promising in the management of patients with endometrial carcinoma.