Stroke Volume estimation using aortic pressure measurements and aortic cross sectional area: Proof of concept.

Accurate Stroke Volume (SV) monitoring is essential for patient with cardiovascular dysfunction patients. However, direct SV measurements are not clinically feasible due to the highly invasive nature of measurement devices. Current devices for indirect monitoring of SV are shown to be inaccurate during sudden hemodynamic changes. This paper presents a novel SV estimation using readily available aortic pressure measurements and aortic cross sectional area, using data from a porcine experiment where medical interventions such as fluid replacement, dobutamine infusions, and recruitment maneuvers induced SV changes in a pig with circulatory shock. Measurement of left ventricular volume, proximal aortic pressure, and descending aortic pressure waveforms were made simultaneously during the experiment. From measured data, proximal aortic pressure was separated into reservoir and excess pressures. Beat-to-beat aortic characteristic impedance values were calculated using both aortic pressure measurements and an estimate of the aortic cross sectional area. SV was estimated using the calculated aortic characteristic impedance and excess component of the proximal aorta. The median difference between directly measured SV and estimated SV was -1.4ml with 95% limit of agreement +/- 6.6ml. This method demonstrates that SV can be accurately captured beat-to-beat during sudden changes in hemodynamic state. This novel SV estimation could enable improved cardiac and circulatory treatment in the critical care environment by titrating treatment to the effect on SV.

Serial histologic observation of endometrial adenocarcinoma treated with high-dose progestin until complete disappearance of carcinomatous foci--review of more than 25 biopsies from five patients.

This study aimed to document chronologic histologic changes of endometrial biopsies from patients with endometrial adenocarcinoma on high-dose progestin therapy. Seven patients with presumptive FIGO stage IA endometrial adenocarcinoma treated with medroxyprogesterone acetate 600 mg/day were investigated retrospectively. Good response was defined as complete disappearance of carcinoma foci within 16 weeks of treatment and poor response as the presence of residual foci at 16 weeks. Two patients were poor responders and were excluded from the study, while five good responders were analyzed. Hematoxylin and eosin (H&E)-stained slides were reviewed and analyzed based on nine histologic features to describe the histology observed commonly in good responders. All the five good responders showed relatively uniform morphologic changes during the high-dose progestin therapy and the common histology was described as follows. The first change was swelling of the neoplastic glandular epithelial cells with pale vacuolated cytoplasm and round to oval nuclei. Mitotic arrest was also observed. Next, the epithelia were disrupted by lymphoplasmocytic infiltration and replaced by low cuboidal epithelium with or without squamous or morular metaplasia. The stromal area increased with predecidual changes. The final morphology was small atrophic glands scattered in predecidual stroma with dilated vessels. Therefore, the morphologic change of the endometrial biopsy observed in earlier stage of treatment might be able to predict good response to high-dose progestin therapy.

Mitotic index and ki-67 nuclear antigen labeling index as predictors of chemotherapy response in uterine cervical carcinoma.

OBJECTIVE: The aim of this study was to determine if the mitotic index (MI) and the Ki-67 nuclear antigen labeling index (Ki67LI) obtained from biopsy specimens could be used as predictors of chemotherapy response in uterine cervical carcinomas. METHODS: Six patients with squamous cell carcinoma who received neoadjuvant chemotherapy before radical surgery were entered into the study. The MI and the Ki67LI were evaluated using hematoxylin and eosin (H&E)-stained and immunostained slides before and after chemotherapy. Tumor size was measured three-dimensionally by magnetic resonance imaging. We compared the values of MI and Ki67LI with changes in tumor size. RESULTS: The cases were classified according to the percentage reduction in tumor mass: one case showed a marked response (98%), four showed a moderate response (53-78%), and one showed a slight response (approximately 0%). In the case with a marked response, the MI values before chemotherapy and 3 and 7 days after chemotherapy were 15, 2, and 0, respectively. The corresponding Ki67LI values were 51, 16, and 0, respectively. In the moderate response cases, the corresponding MI values before and 3 and 7 days after chemotherapy were 3.9-13.6, 0.8-1.6, and 1.6-4.0, respectively. The Ki67LI was 21.8-44.2 before chemotherapy, with two cases increasing and two decreasing at 7 days after chemotherapy. In the case showing a slight response, the MI values before chemotherapy and 3 and 7 days after chemotherapy were 0.5, 0.8, and 1.0, respectively. The Ki67LI was 4.0 before chemotherapy and increased slightly to 6.0 at 7 days after chemotherapy. CONCLUSIONS: In six cases examined, high MI and Ki67LI values before chemotherapy and a marked decrease in MI shortly after chemotherapy appeared to be predictors of good neoadjuvant chemotherapy response in uterine cervical carcinomas.

MRI findings of a case of uterine tumor resembling ovarian sex-cord tumors coexisting with endometrial adenoacanthoma.

A case of uterine tumor resembling ovarian sex-cord tumors is reported. MRI was performed for the staging of the endometrial adenoacanthoma diagnosed by biopsy. A well-defined, slightly hyperintense mass with central hypointensity was noted in the myometrium on T2-weighted images. Pathological diagnosis of the myometrial mass was uterine tumor resembling ovarian sex-cord tumors. The central hypointense area was a leiomyomatous component. Adenoacanthoma was also confirmed. These features of coexisting tumors correlated well with the MRI findings.

Endometrial polyps: a comparison study of patients receiving tamoxifen with two control groups.

Many reports describe an increased frequency and unusual features of endometrial polyps and carcinomas in women treated with tamoxifen (TMX) for breast cancer. Postmenopausal women with endometrial polyps were identified by computer search of pathology files from 1990 to 1996. Medical records were reviewed, and patients were divided into three groups: 28 receiving TMX for breast cancer, 23 receiving hormone replacement therapy (HRT), and 28 untreated controls (UC). Cumulative doses (CDs) of TMX were calculated. Histologic slides of polyps were reviewed blindly and evaluated for size, metaplasias, vascularity, fibrosis, and inflammation. Carcinomas were found in 3 TMX, no HRT, and 1 UC patient. Atypical hyperplasias were found in 1 TMX, 0 HRT, and 1 UC patient. Mean polyp size was larger in the TMX group (2.9 cm) than in the HRT (1.05 cm) and UC (1.35 cm) groups, and stromal fibrosis was more prominent in TMX-related and larger polyps. Mucinous metaplasias were observed more frequently in the patients receiving TMX. No other differences were noted. The two TMX patients in whom low-grade carcinomas developed and the one with atypical hyperplasia had independent risk factors. CDs for these patients were 32.9, 36.5, and 17.6 g, respectively. A high-grade carcinoma developed in a TMX patient without constitutional risk factors at a CD of 94.9 g. On the basis of a literature review and these results, low-grade carcinomas developing after relatively low CDs of TMX may be at least partially attributable to other risk factors. The association between poorly differentiated and nonendometrioid tumors with higher TMX CDs is still speculative, but the current study suggests that they may be related to TMX. A statistically significant increase in the frequency of thyroid replacement use by TMX patients is also noted.

Toward the development of a universal grading system for ovarian epithelial carcinoma. I. Prognostic significance of histopathologic features--problems involved in the architectural grading system.

OBJECTIVE: Because there is no universally accepted grading system for ovarian epithelial carcinoma, we attempted to compare the prognostic utility of the individual components used in some systems--both architectural and cytologic features, as well as mitotic activity and histologic tumor type--to determine which of these components fit best with survival. METHODS: We studied 461 patients with invasive ovarian carcinoma who had uniform treatment, complete clinical data including staging and follow-up, and slides available for review. Each tumor was assigned a histologic subtype, architectural grade (based on whether the predominant pattern was glandular, papillary or solid), nuclear grade, mitotic count, and FIGO grade (based on the system for endometrial carcinoma). These features were compared with each other and with tumor stage and survival. RESULTS: The architectural grade, nuclear grade, and mitotic count were independent variables both in stage I/II and stage III/IV disease. Each of them correlated with survival for most combinations of histologic type and stage. By multivariate analysis, in stage I/II cancer, nuclear grade and architectural grade were significantly correlated with survival, mitotic count showed only a trend, and FIGO grade did not correlate. In stage III/IV disease, nuclear grade, architectural grade 3, and mitotic count were significant, and FIGO grade was not. CONCLUSION: The new architectural grading system proposed worked better than the FIGO system in this study. Furthermore, it could be applied to all histologic subtypes of carcinoma. The nuclear grade and mitotic count were also independent of each other, correlated with survival, and could be utilized for all histologic types. These data support the development of a grading system which combines these architectural, nuclear, and mitotic features and can be applied regardless of the histologic type of carcinoma, modeled after the Nottingham system for grading of breast carcinoma.

Toward the development of a universal grading system for ovarian epithelial carcinoma: testing of a proposed system in a series of 461 patients with uniform treatment and follow-up.

BACKGROUND: Most published series of ovarian carcinoma find a correlation between histologic grade and survival, but the grading system used commonly is not specified, and several different systems exist, some of which use different criteria for different histologic types. However, several studies have shown marked interobserver variability in distinguishing among the histologic types of ovarian carcinoma. The authors attempted to derive a universal grading system for all invasive ovarian carcinomas (IOC), based on the Nottingham system for grading all types of mammary carcinoma. METHODS: The authors studied 461 patients with IOC of different histologic types and clinicopathologic stages who were treated in a uniform manner between 1980 and 1994 with surgery and cisplatin-based chemotherapy. All slides were reviewed and the tumors graded as follows: Architectural pattern (predominant): Glandular = 1, Papillary = 2, and Solid = 3; Nuclear pleomorphism: Slight = 1, Moderate = 2, and Marked = 3; Mitotic activity (mitotic figures per 10 high-power fields [1 HPF = 0.345 mm2]) in most active region: 0-9 = 1, 10-24 = 2, and > or = 25 = 3; Grade 1 = total score (adding three values obtained earlier) 3-5, Grade 2 = 6 or 7, and Grade 3 = 8 or 9. RESULTS: Tumor grade correlated with survival in both early and advanced stage disease and for all major histologic types of IOC except clear cell carcinoma (CCC). Results for CCC approached but did not reach clinical significance. By multivariate analysis, only this tumor grade and performance status were significant in Stage I/II IOC. For Stage III/IV tumors, the new tumor grade also was significant, as were performance status, residual tumor size, response to chemotherapy, and mucinous (unfavorable) or transitional cell (favorable) histologic type. International Federation of Gynecology and Obstetrics grade (based primarily on architectural features) did not correlate significantly with survival except in Stage III/IV serous and Stage I/II mucinous carcinomas. CONCLUSIONS: The new grading system reported is simple, reproducible (among the current study authors), and useful for all histologic types and clinical stages of IOC. Further testing for reproducibility and clinical utility is recommended.

Sebaceous carcinoma of the vulva.

Extraocular sebaceous carcinoma (SC) is a rare tumor usually found on the head and neck. A 78 year old Japanese female who had an asymptomatic vulvar tumor is reported here. The excised specimen showed SC with metastasis to the inguinal lymph nodes. This is the fourth reported case of SC arising from female genitalia, and the second case that apparently arose from the labia minora. Contrary to the previously reported cases, tumor cells in the present case had abundant glycogen. Thus, differential diagnosis of SC from metastatic renal cell carcinoma is difficult morphologically because both of them have glycogen and lipid. Intraepidermal invasion of tumor cells has been reported in SC, but a suspected lesion of this phenomenon in the present case was proved to be histiocytic infiltration by immunohistochemistry using anti-CD 68 antibody.

Plasma adenosine concentration in appropriate- and small-for-gestational-age fetuses.

OBJECTIVE: Our purpose in this study was to investigate the relationship between fetal plasma adenosine concentration and catecholamine concentration, blood gases, and pH in appropriate- and small-for-gestational-age fetuses. STUDY DESIGN: Cordocentesis was performed in 23 appropriate- and 14 small-for-gestational-age fetuses at 30 to 37 weeks' gestation for the measurement of umbilical venous blood plasma adenosine and catecholamine concentrations, blood gases, and pH. RESULTS: In small-for-gestational-age fetuses plasma adenosine concentration was higher, umbilical venous PO2 and pH were lower, and PCO2 was significantly higher than in appropriate-for-gestational-age fetuses. The elevation of plasma adenosine concentration was inversely related to umbilical venous PO2 and pH. CONCLUSION: Some small-for-gestational-age fetuses are exposed to diminished oxygen tension and acidotic blood gas values in utero. We postulate that the accompanying elevation of plasma adenosine may elicit protective adaptation during fetal asphyxia as a stress response.

[Importance of posterior tooth-to-denture base discrepancy in the development of skeletal open-bite malocclusion].

This paper describes the relationship between the development of skeletal open-bite malocclusion and the tooth-to-denture base discrepancy. The cases which have a severe skeletal open-bite malocclusion are presented to evaluate the causing factor of the anterior open-bite. The anterior open-bite was associated with inferiorly positioned maxillary molars caused by the squeezing out effect of the tooth-to-denture base discrepancy, especially those in posterior part of dentition (posterior discrepancy), which provided a less steep maxillary occlusal plane in the denture frame. It was suggested that the posterior discrepancy induced a descending movement of the posterior teeth followed by a change of the occlusal plane and this effect of the posterior discrepancy was important factor in developing anterior open-bite malocclusion.

[An approach to development of skeletal malocclusion with mandibular lateral displacement].

Mandibular lateral displacement (MLD) is a result of temporarily accelerated growth of unilateral condyle. Structure of lower face of typical mandibular lateral displacement malocclusion was analysed by means of modified denture frame analysis. Results of measurement indicated that noteworthy present on difference of maxillary occlusal plane between right and left dentitions. It suggested that the MLD malocclusion result from unilateral elongation of the molars due to posterior discrepancy and functional displacement of mandible associated with the differential condylar growth.

[A case of pulmonary lymphangiomyomatosis induced by pregnancy].

A 35-year-old primigravida was admitted to the Department of obstetrics complaining of dyspnea and left back pain at 21 weeks' gestation. Chest roentgenogram revealed diffuse reticulonodular shadows predominantly in both lower lung fields and arterial hypoxemia was present. Pulmonary function tests showed restrictive impairment and decreased carbon monoxide diffuse capacity. From these results, interstitial pneumonia was suspected and she was first treated with prednisolone. However during her pregnancy, spontaneous pneumothorax occurred. Following spontaneous delivery of healthy infant at 37 weeks, left chylothorax occurred, and pleurodesis was performed with OK432. Thereafter the histological diagnosis of pulmonary lymphangiomyomatosis was made by transbronchial lung biopsy and treatment of prednisolone was stopped. She was treated with tamoxifen. In addition, progesterone-receptor was detected in the pulmonary tissue obtained at open lung biopsy. She was treated with cyclophosphamide in addition to tamoxifen. At present, shortness of breath has decreased slightly in comparison with one year previously, but no improvement has been seen in lung function tests or chest roentgenogram.

[Fetal development and fetal heart function analyzed by M-mode echocardiography].

Real time-directed M-mode echocardiograms were obtained for 215 echographically evaluated AFD fetuses between 24 and 41 weeks of gestation to assess the cardiac function of normally growing human fetuses. The results are as follows. 1. A significant linear correlation exists between gestational weeks and end-diastolic wall thickening of RV, IVS and LV, respectively (RVAWTd, IVSTd and LVPWTd). 2. There is no significant difference among three (RVAWTd, IVSTd and LVPWTd) at any time from 24 to 41 weeks. 3. Percent systolic wall thickening for RV, IVS and LV are 39 +/- 24, 68 +/- 37 and 41 +/- 16(%), respectively. 4. Motion of IVS towards left ventricular free wall during systole, no septal motion or paradoxical movement (systolic septal anterior motion) is seen in 62, 35 and 3% of cases, respectively. 5. Paradoxical movement of IVS is seen in the case in which the RV/LV wall exclusion ratio is extremely low.

[Immunological studies on the patients with Crohn's disease and a new attempt of interferon treatment].

Natural Killer cell activity and lymphocyte subset in peripheral blood were studied in 16 patients with Crohn's disease. The effect of interferon administration was evaluated in 4 patients with Crohn's disease. In the patients with active Crohn's disease, natural killer cell activity was significantly lower in level compared to that in normal controls. Those without increase of natural killer cell activity in non-active stage, had trend of early relapsing. Peripheral lymphocyte subpopulations of OKT4, OKT8, OKIal, OKT4/8 and Leu7 by flow-cytometry showed no significant differences between the patients and the normal controls. Clinical remission was maintained in 2 out of 4 patients for the period from 7 to 21 months after the interferon administration. Benefit of interferon administration was suggested in patients with Crohn's disease.