Adjuvant pelvic irradiation in patients with pathologic T2b carcinoma of the uterine cervix.

Patients with cervical cancer are subject to postoperative adjuvant therapy if the histopathologic examination reveals parametrial involvement. This study evaluated the patterns of failure in patients with pathologic parametrial invasion (pT2b) treated with adjuvant pelvic irradiation. Between April 1985 and March 1997, 45 patients with pT2b cervical cancer were treated with postoperative pelvic irradiation. The median age was 52 years. Preoperative clinical stages were stage Ib in 8 patients, IIa in 4, and IIb in 33. Twenty-three patients had lymph node metastasis. The median total dose of whole pelvic radiation therapy was 50 Gy. Occurrence of pelvic failure or distant metastasis according to the nodal status was examined. None of the 22 patients without lymph node metastasis developed distant metastasis. Among the 23 node-positive patients, 6 developed distant metastasis as an initial failure site. The 5-year overall survival of the entire group was 78%. The actuarial distant metastasis-free rates at 5 years were 73% and 100% for those with and without pelvic lymph node metastasis, respectively (P = 0.016). Results support previous evidence for chemoradiation in patients with pelvic lymph node metastasis. However, it appears that the role of systemic chemotherapy for node-negative pT2b patients is yet to be established.

Indomethacin increases the cytotoxicity of cis-platinum and 5-fluorouracil in the human uterine cervical cancer cell lines SKG-2 and HKUS by increasing the intracellular uptake of the agents.

BACKGROUND: Various approaches have been made to increase the cytotoxicity of cis-platinum (CDDP) and 5-fluorouracil (5FUra), and to reduce their adverse effects. We used two human cancer cell lines of the uterine cervix (SKG-2 and HKUS) and selected indomethacin as a modifying agent to assess its effect on the cytotoxicity of CDDP and 5FUra. METHODS: The effect of indomethacin on the cytotoxicity of CDDP and 5FUra in these tumor cells was evaluated by in-vitro Alamar blue assay, and intracellular uptake of free-CDDP and 5FUra was measured to find out how indomethacin modified the cytotoxicity of CDDP and 5FUra. RESULTS: Indomethacin showed no cytotoxic effect on these tumor cells, but significantly (P < 0.005-0.001) increased the cytotoxicity of both CDDP and 5FUra, compared with single treatment by each agent. The intracellular uptake of both free-CDDP and 5FUra was measured in culture media containing the agents alone (single treatment) or the agents with indomethacin (0.001, 0.01, and 0.1 microgram/ml; combined treatment). The intracellular contents of both free-CDDP (SKG-2, HKUS; P < 0.001) and 5FUra (SKG-2; P < 0.005, HKUS; P < 0.02) were significantly higher in the combined treatment than in the single treatment. CONCLUSION: This study shows that indomethacin increased the cytotoxicity of both CDDP and 5FUra by increasing the intracellular incorporation of free-CDDP and 5FUra, and suggests the effectiveness of indomethacin in reducing the dosage of CDDP and 5FUra or increasing CDDP and 5FUra cytotoxicity when these agents are given without reducing the dose.

Rapid detection of chromosome aneuploidies by prenatal interphase FISH (fluorescence in situ hybridization) and its clinical utility in Japan.

OBJECTIVE: The purpose of this study was to assess the accuracy, informative rate, detection rate, and clinical utility of prenatal interphase fluorescence in situ hybridization (FISH) analysis of amniotic fluid samples from Japanese women. METHODS: Amniotic fluid specimens from 2,639 Japanese women were received for prenatal interphase FISH and chromosome analysis. A questionnaire was designed to evaluate FISH clinical utility by collaboration sites. RESULTS: Based on 2,319 tested samples, the accuracy (100%), informative (94%), and detection (87.6%) rates were all high. The accuracy (100%), informative (90.2%), and detection (90.0%) rates were also remarkable in third-trimester pregnancies. We perceive significant advantages from this test regarding medical management and patient satisfaction. CONCLUSIONS: This novel report shows that in Japan prenatal interphase FISH testing is highly informative and accurate, not only in second-trimester pregnancies but also in third-trimester pregnancies. This test provides advantages to both physicians and patients, provided that its capabilities and limitations are understood.

Postoperative radiation therapy for stage IB-IIB carcinoma of the cervix with poor prognostic factors.

BACKGROUND: To investigate failure pattern and to evaluate the prognostic impact of lymph node metastasis in patients with cervical cancer treated with postoperative adjuvant pelvic irradiation. MATERIALS AND METHODS: Ninety-eight patients with FIGO IB to IIB cervical cancer were treated with radical hysterectomy, bilateral pelvic lymphadenectomy and postoperative radiation therapy. All the patients had at least one of the following pathologic risk factors for pelvic recurrence; 1) positive margins, 2) positive pelvic lymph nodes other than common iliac node, 3) deep stromal invasion more than 50% or parametrial invasion. RESULTS: The 5-year overall survival (OAS) rate for the entire patient group was 82%. Causes of the first failure were pelvic recurrence in 5 cases and distant metastasis in 15 cases. Fifteen of the 47 patients with positive pelvic lymph nodes developed distant metastasis, whereas distant metastasis was noted in only 1 of 51 patients without lymph node metastasis. The 5-year OAS rates for patients with and without pelvic lymph node metastasis were 76% and 89%, respectively (p = 0.018). CONCLUSION: Despite receiving postoperative pelvic irradiation, apparently lower survival was observed for node positive patients.

Ovarian leiomyosarcoma: an autopsy case report.

Primary non-specific sarcoma of the ovary is extremely rare, and only 22 reported cases of pure leiomyosarcoma (LMS) are known to the authors. We present an autopsy case of a primary ovarian leiomyosarcoma in a 73-year-old woman. She had noticed an abdominal mass after difficulty in defecating for several months. The excision of tumor with bilateral salpingo-oophorectomy and hysterectomy was carried out. A diagnosis of pure leiomyosarcoma of the left ovary was made on pathological examination with immunohistochemistry. Adjuvant radio-chemotherapy was not given. At 18 months' follow up, abdomino-pelvic sonography revealed an abdominal tumor and hepatic metastasis. The patient died 3.5 years after the initial surgery. The post-mortem examination revealed a peritoneal recurrent tumor and extensive distant metastases of the liver, lungs, pancreas, gastric mucosa, muscle and skin. The prognosis of the ovarian LMS is poor from the pertinent literature. Several prognostic indicators on histology including mitotic activity, proliferative activity and p53 status of the tumor are discussed.

A case of a primary ovarian leiomyosarcoma.

A primary ovarian leiomyosarcoma is extremely rare. Moreover, there is no established treatment modality other than surgery, and the prognosis is extremely poor. We report a case of a primary ovarian leiomyosarcoma. The patient was a gravida 4, para 2, 73-year-old female. She first presented with chief complaints of constipation and a pelvic mass. A physical examination revealed a solid tumor in the pelvic cavity. Which was about the size of an infant's head and had an irregular shape. The patient was suspected of having a subserosal myoma of the uterus or an ovarian tumor, and she was subjected to a laparotomy. A solid tumor about the size of an infant's head was found in the left uterine adnexa, and an intraoperative rapid pathological diagnosis of an ovarian leiomyosarcoma was made. A total abdominal hysterectomy, a bilateral salpingo-oophorectomy, a pelvic lymphadenectomy, and an omentectomy were then performed. The final pathological diagnosis confirmed a left primary ovarian leiomyosarcoma. After a series of discussions with the patient's family about her therapeutic plan, we decided to let the patient be followed-up without adjuvant therapy. Forty-two months after the surgery, the patient accumulated massive amounts of pleural effusion and ascites, with extensive organ metastasis. She received terminal care and soon died.

High dose rate brachytherapy for carcinoma of the cervix: risk factors for late rectal complications.

PURPOSE: To determine the incidence of late rectal complications in patients treated with high dose rate brachytherapy for FIGO Stage IIB, IIIB carcinoma of the uterine cervix, and to evaluate the treatment factors associated with an increased probability of treatment complications. METHODS AND MATERIALS: Records of 100 patients with FIGO IIB and IIIB cervical carcinoma treated with definitive irradiation using high dose rate intracavitary brachytherapy (HDR-ICR) between 1977 and 1994 were retrospectively reviewed. For each HDR-ICR session, 6-Gy isodose volume was reconstructed retrospectively and the relationship between probability of late rectal complications and several treatment factors, including a specific point dose and parameters representing isodose volume, were examined. Statistical analyses were performed to determine the treatment factors predictive of late rectal complications. RESULTS: Of patients treated for both stages, 33% and 38% had experienced moderate to severe (Grade 2-4) complications at 3 and 5 years, respectively. Mean value of depth (D) of 6-Gy isodose volume in HDR-ICR in patients with and without complication were 51 mm and 46 mm, respectively (p = 0.0070). A significant difference was noted in complication rate between patients with D > 51 mm and D < or = 51 mm (p = 0.0023). Cumulative Point S (2 cm dorsal from the midpoint of the ovoid sources) dose (p = 0.044), and single or total point S dose by HDR-ICR (p = 0.019, each) were significantly higher in patients who developed complication, whereas these factors did not significantly affect the probability of pelvic control. Multivariate analysis revealed that D was the independent predictor for the endpoint of actuarial complication rate (p = 0.047). No significant difference was noted in the product of L, D, and W value (L x D x W) between patients with less than Grade 2 rectal complication and those with Grade 2-4. CONCLUSION: Depth of 6-Gy isodose volume determined three dimensionally (3D) has the predictive value of late rectal complications. This suggests that the shape of the high dose area in HDR-ICR influences the incidence of late rectal complications regardless of its volume.

Labetalol in hypertension during the third trimester of pregnancy: its antihypertensive effect and pharmacokinetic-dynamic analysis.

The hypotensive effect, kinetics, and concentration-response relationship of labetalol, alpha beta- and alpha 1-adrenoceptor blocking drug, were studied in seven women with a moderate-to-severe hypertension (averaged diastolic blood pressure [DBP] of 100 to 120 mm Hg measured during a 1- to 2-day hospitalization period) during the third trimester of pregnancy who received the oral twice-daily doses of 150 to 450 mg. These dosages were individually selected by attaining a therapeutic goal of DBP < or = 100 mm Hg or systolic blood pressure (SBP)/DBP reduction of > 30/15 mm Hg, as compared with the pretreatment value, at any time during the 12-hour dosing interval for a 3- to 5-day dosage escalation period. Labetalol concentrations in plasma were measured by a high-performance liquid chromatography with fluorescence detection, and the plasma drug concentration-response relationship was analyzed by a sigmoidal Emax model. Labetalol decreased significantly (P < 0.05 to 0.01) the pretreatment SBP/DBP (166.3 +/- 5.2/110.3 +/- 3.0 mm Hg, mean +/- SEM) without any recognizable side-effects during the twice-daily dosing period in the mothers. Peaked concentrations occurred at 1 hour postdose in all patients. The elimination half-lives ranged from 4.3 to 6.9 hours, and the apparent oral clearance from 31.9 to 73.3 mL/min/kg. The pharmacodynamic parameters (Emax and EC50) analyzed by the Emax model revealed a 3- to 5-fold interindividual variability. The gestational ages at delivery ranged from 34 to 37 weeks, and the birth weights were < 2000 g in 6 of the 7 neonates. Four neonates developed respiratory distress syndrome after delivery, and one infant died of pulmonary hypoplasia 3 months later. The results indicate that 1) labetalol orally administered in a twice-daily regimen as done in this study is an effective antihypertensive drug in women with hypertension during late pregnancy, and 2) interindividual variability in the kinetic factor (e.g., oral clearance) as well as that in the pharmacodynamic factor (e.g., EC50) appear to be related to the overall variability in the hypotensive responsiveness to the drug. However, whether labetalol and/or hypertension per se would have been related to the fetal outcome remains unanswered from the present study.

Effect of estradiol administration and subsequent nonfeeding on liver estrogen receptor, serum apolipoprotein B-100, and serum triglycerides concentrations in steers.

Estradiol was administered to 3 steers (0.12 mg/kg of body weight/d for 14 consecutive days), followed by 2 days of nonfeeding (starvation). During estradiol administration, liver nuclear estrogen receptor and serum apolipoprotein B-100 (apoB-100), as well as serum triglycerides concentrations were increased, compared with values before administration. Starvation, together with interruption of estradiol administration, resulted in rapid decreases of the receptor, serum apoB-100, and serum triglycerides concentrations, and increase of nonesterified fatty acids concentration. Of the 3 steers, 2 had higher liver triglyceride content, compared with values before treatment. In the control group (3 steers that received vehicle alone, then starved similarly), these concentrations, except for serum nonesterified fatty acids and triglycerides concentrations after starvation, were not changed. In another experiment, serum apoB-100 concentration in dairy cows was significantly (P < 0.05) lower at parturition than values before and after parturition. These results indicate that estradiol may be involved in development of fatty liver in cattle.

Plasma protein binding of disopyramide in pregnant and postpartum women, and in neonates and their mothers.

1. The protein binding of disopyramide was measured in plasma obtained from nonpregnant women, pregnant women in the first, second, and third trimesters, matched pairs of mothers and neonates (cord plasma), and 1 month postpartum women (n = 6 or 8 of each). 2. Plasma samples spiked with 0.2-12.0 micrograms ml-1 of the drug were ultrafiltered and the free fractions were measured with a fluorescent polarization immunoassay. 3. The mean (+/- s.d.) percentages of free drug at a total concentration of 3.0 micrograms ml-1 observed in the third trimester (46 +/- 9%) and neonate (79 +/- 5%) groups were greater (P less than 0.05 or 0.01) than that in the non-pregnant group (34 +/- 7%). In contrast, the corresponding value observed in the postpartum group (23 +/- 8%) was less (P less than 0.05) than that in the non-pregnant group. In addition, there was a significant (P less than 0.01) difference in the mean percentage of free drug at 3.0 micrograms ml-1 in plasma from mothers (43 +/- 9%) and neonates (79 +/- 5%). 4. A multiple regression analysis indicated that alpha 1-acid glycoprotein (r = -0.88, P less than 0.01), rather than albumin (r = -0.008), dominated the binding of disopyramide within the therapeutic range of drug concentration. An analysis of the binding parameters of disopyramide suggested that alterations in binding were attributable to changes in the capacity rather than the affinity of binding.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunohistochemical study of high-grade endometrial stromal sarcoma. An autopsy report in comparison with carcinosarcoma, leiomyosarcoma and normal endometrium.

An autopsy case of high-grade endometrial stromal sarcoma (ESS) is reported. Immunohistochemical study of the ESS was done in comparison with carcinosarcoma (CS), leiomyosarcoma (LMS) and normal endometrium in the uterus in order to trace the origin of ESS, which is a point of some controversy. Co-expression of keratin and vimentin and/or desmin positivity in several elements of CS and LMS, and glandular or stromal tissues in normal endometrium made it difficult immunohistochemically to be certain of the origin of ESS.

Induction of lipid peroxidation in mice by hexavalent chromium and its relation to the toxicity.

Comparative effects of hexavalent (K2Cr2O7:Cr(VI)) and trivalent chromium (Cr(NO3)3:Cr(III)) on the development of lipid peroxidation, and the relationship between the lipid peroxidation and damage to tissues were studied using male ddY strain mice. The animals were administered with either of two chemicals at a dose of 20 mg Cr/kg by a single intraperitoneal injection. The results obtained were as follows: (1) Lipid peroxidation in the liver, as measured by the synthesis of thiobarbituric acid reactive substances (TBARS), showed a significant increase at 24 and 48 hr after Cr(VI) injection, while in the kidney it was observed only at 48 hr. In the mice administered with Cr(III), TBARS formation in the liver went down below the control levels, while no change was observed in the kidney. (2) Chromium contents in the liver and kidney showed a maximum level at 6 hr after injection of Cr(VI) and then those declined to the half of the maximum level at 48 hr, respectively. Chromium contents in the liver and kidney of the mice injected with Cr(III) were lower than those injected with Cr(VI) during the experimental period. (3) Increases of TBARS formation in the liver, chromium content in the liver and kidney, and ornithine carbamyl transferase (OCT) activity indicative of the liver cell damage, and urea nitrogen content in the serum, indicative of the kidney damage, observed at 24 hr after injection of Cr(VI) were inhibited by simultaneous injection of 100 mg/kg of L-ascorbic acid, as antichrome agent, respectively. These observations might suggest a possible causative role of lipid peroxidation in Cr(VI) toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Succinic acidemia: a new syndrome of organic acidemia associated with congenital lactic acidosis and decreased NADH-cytochrome c reductase activity.

Two siblings with succinic acidemia, a hitherto unreported organic acidemia, were investigated. Succinic acidemia, lactic acidosis and respiratory distress were observed in one of the siblings, who died 37 days after birth, and succinic acidemia was also detected in the next sibling at the fetal stage. NADH-cytochrome c reductase activity was significantly low in both cases and NADH-ferricyanide reductase activity was also low in the fetal case, suggesting a complex I deficiency of the electron transport system in the mitochondrial membrane.

Postnatal change of cardiac function in lambs: effects of ganglionic block and afterload.

This study characterizes the maturational change of cardiac function in unanaesthetized lambs from 1 day to 6 months of age. The cardiac function curve, the relationship between left ventricular output (Qco) and left ventricular end diastolic pressure, was studied in lambs of ages 1 day, 2-3 days, 7-8 days, 1 month, 3 months and 6 months. Cardiac output was measured by thermodilution while left ventricular end diastolic pressure was either raised by infusion of 5% glucose, or lowered by haemorrhage. At elevated left ventricular end diastolic pressure, cardiac output tended to reach a plateau of approximately 300 ml/min per kg in lambs less than 1 week of age and 200 ml/min per kg in lambs older than 1 month. Cardiac function was depressed by total ganglionic block in 1-3 days-old lambs, but not in lambs older than 1 week. Heart rate decreased in response to ganglionic block in lambs up to 1 week of age, but it increased in lambs 3-6 months old. Increases in afterload with methoxamine infusion during ganglionic block further depressed cardiac function in all age groups of lambs. The stroke work curve was shifted downward by hexamethonium and returned back to control level by methoxamine. We conclude that newborn cardiac output is near maximum even at 1 month of age. Sympathetic activity and circulating catecholamines help maintain cardiac function in 1-3 days-old lambs. Cardiac function is sensitive to afterload in lambs of all ages studied.

The anterior and the posterior longitudinal ligaments of the lower cervical spine.

The anterior and the posterior longitudinal ligaments (ALL and PLL) of the cervical spine were examined. The ALL and the deep layer of the PLL are continuous, and surround the vertebral body. The superficisl layer of the PLL surrounds the dura mater, nerve roots and the vertebral artery, suggesting that this membrane may serve as a protective membrane for the soft tissues inside the vertebral canal rather than as a conventional ligament.