PCBs, thyroid hormones, and ototoxicity in rats: cross-fostering experiments demonstrate the impact of postnatal lactation exposure.

Previous research has demonstrated the sensitivity of the developing rat to the hypothyroxinemic and ototoxic effects of perinatal exposure to Aroclor 1254 (A1254). We tested the hypothesis that postnatal exposure via lactation is the major cause of the ototoxicity by cross fostering animals at birth. Primiparous rats (22-24/dose) received 0 or 6 mg/kg A1254 (po in corn oil) from gestation day (GD) 6 to postnatal day (PND) 21. On the day of birth, half of the treated litters and half of the control litters were cross-fostered, resulting in the following groups: Ctrl/Ctrl (controls); A1254/A1254 (perinatal exposure); A1254/Ctrl (prenatal exposure only); and Ctrl/A1254 (postnatal exposure only). We assessed offspring at a number of ages for: serum thyroid hormone concentrations, liver and brain concentrations of PCBs, body weight, mortality, age of eye opening, auditory startle amplitudes, and auditory thresholds for 1 kHz and 40 kHz tones. Circulating thyroxine (T(4)) concentrations were sharply reduced at GD 21 in the A1254-exposed group, and on PND 3, 7, 14, and 21 in the A1254/A1254 and the Ctrl/A1254 groups. Smaller decreases in T(4) were observed in the A1254/Ctrl group on PND 3, 7, and 14. PCB concentrations in the liver on PND 21 were sharply elevated in the A1254/A1254 and Ctrl/A1254 groups. Much smaller increases were seen in the A1254/Ctrl group. Age of eye-opening and startle amplitudes were unaffected by treatment. A1254 exposure caused permanent hearing deficits (20 dB increase) at the low frequency (1 kHz) in the A1254/A1254 and Ctrl/A1254 groups. The present findings demonstrated that the critical period for the ototoxicity of developmental A1254 exposure is within the first few postnatal weeks in the rat. This effect is consistent with the greater degree of postnatal hypothyroxinemia resulting from the greater magnitude of exposure that occurs postnatally via lactation.

Aroclor 1242 inhalation and ingestion by Sprague-Dawley rats.

PCBs have been considered to be almost nonvolatile and insoluble in water. However, recent studies have shown the importance of their slight solubility in water and capability to enter the atmosphere and disperse throughout the global environment. This preliminary study was designed to measure uptake and observe any physiological changes in Sprague-Dawley rats. The PCB product Aroclor 1242 is the major pollutant of the Hudson River, NY, and New Bedford Harbor, MA. The rats were exposed for 30 d to 0.9 microg/m3 via inhalation and 0.436 microg/g (ppm) in the food. The inhalation of PCBs gave a greater PCB uptake than ingestion. Both routes of administration caused significant serum thyroid hormone elevations. Histopathologic changes were observed in the urinary bladder, thymus, and the thyroid after both exposure regiments. Rearing and ambulation were significantly decreased in both exposure regiments in an open field behavior test.

Induction of hepatic cytochromes P450 in dogs exposed to a chronic low dose of polychlorinated biphenyls.

Induction of cytochrome P450 isoforms, specifically CYP1A1, and their catalytic activities are potential biomarkers of environmental contamination by polychlorinated biphenyls (PCBs). In this study, dogs were exposed to 25 ppm or 5 ppm Aroclor 1248 (PCB mixture) daily in their diet for 10 or 20 weeks, respectively. Relative to controls, hepatic microsomes from dogs dosed with PCBs had higher levels of CYP1A1 detected in immunoblots and higher levels of EROD activity, but low levels of induction for CYP2B and PROD activity. Concentrations of 96 PCB congeners in serum and liver were evaluated using capillary chromatography. Results showed that all dogs exposed to PCB mixtures had higher levels of PCB in serum and liver. Dogs preferentially sequestered highly chlorinated PCB congeners in liver relative to serum. With these experiments, we demonstrated that EROD activity was a potentially sensitive marker of PCB exposure at 5 and 25 ppm. Furthermore, CYP1A1 and EROD activity were maximally induced in dogs consuming dietary concentrations only 2.5 times the maximal permissible level for human food (FDA). The value of CYP1A1 induction as a biomarker of PCB exposure was tenuous because neither CYP1A1 levels nor EROD activity correlated with total PCB body burden. However, a small subset of congeners were identified in liver that may strongly influence EROD and PROD induction. Finally, two dogs in the 25 ppm dose group were fasted for 48 h. After 24 h of fasting, several new congeners appeared in the serum and remained in the serum for the remainder of the fast. The fast caused a 293% increase in PCB concentration in serum. This increase has strong implications regarding mobilization of toxic PCBs in wildlife during fasting (e.g., migration, hibernation).

Congener-specific distribution of polychlorinated biphenyls in brain regions, blood, liver, and fat of adult rats following repeated exposure to Aroclor 1254.

Our previous in vitro studies with both isolated organelles and primary neuronal cell cultures found that intracellular signal transduction can be perturbed by some noncoplanar PCBs at exposure levels of

Dysgerminoma: the role of conservative surgery.

Twenty-five cases of pure ovarian dysgerminoma treated at UCLA Medical Center between 1958 and 1992 were reviewed retrospectively. Patterns of recurrence and overall survival were analyzed with regard to primary surgery (conservative versus nonconservative), use of adjuvant therapy, and stage of disease. Fourteen patients (56%) underwent conservative surgical therapy defined as preservation of the contralateral ovary, 10 patients (40%) had nonconservative primary surgery, and one patient (4%) had chemotherapy as primary treatment. Three patients (12%) received adjuvant chemotherapy and nine patients (36%) received postoperative radiation therapy. Fifteen patients (60%) had stage I disease, four (16%) stage II, and three each (12%) had stage III and IV disease. Nine patients (36%) experienced recurrence of disease. Seven of these nine patients (78%) had stage I disease and all seven had undergone conservative primary surgery with preservation of the contralateral ovary. Six of the seven had received no adjuvant therapy. Only one of these seven patients experienced recurrence in the preserved ovary. She was found to have a dysgenetic ovary and an XY karyotype. Three patients with recurrent disease had received radiation therapy after primary surgery. Twenty patients (80%) were alive without disease at follow-up, two patients (8%) were alive with disease, and three (12%) had died of disease. There was no statistically significant difference in recurrence rates between those patients treated with conservative surgery and those treated with nonconservative surgery, although the total number of patients with recurrences was greater in the former group. Our data suggest that a conservative surgical approach is the preferred treatment in patients with pure dysgerminoma of the ovary who desire future fertility. Lack of adjuvant chemotherapy or radiation therapy, rather than type of initial surgery, may be associated with a higher risk of recurrence.

What is the role of reassessment laparoscopy in the management of gynecologic cancers in 1995?

One hundred fifty-four patients with a diagnosis of ovarian, primary peritoneal, or fallopian tube carcinoma underwent 181 reassessment procedures to detect persistent or recurrent disease between January 1, 1989 and December 31, 1994 at Cedars-Sinai Medical Center. One hundred four laparoscopic procedures were performed. Eleven of these procedures were converted to laparotomy due to severe adhesions. Therefore, a total of 88 reassessment laparotomies were performed during the study period. Fifty-seven of 93 laparoscopies and 69 of 88 laparotomies were done as second-look procedures. There was no significant difference between the two groups with respect to patient age, tumor histology, degree of primary cytoreduction, and tumor stage or grade. Significant differences were found between laparoscopy and laparotomy groups in the following outcome variables evaluated: estimated blood loss (33.9 ml vs 164.9 ml, P = 0.0001), operative time (81.3 min vs 130.4 min, P = 0.0001), days of hospitalization (0.3 days vs 6.8 days, P = 0.0001), and direct cost/case ($2765 vs $5420, P = 0.0001). Despite obtaining 50% fewer biopsies with laparoscopy than laparotomy, the ability to detect disease was similar between these two groups: 47.3% vs 55.7% for all procedures and 52.6% vs 53.6% in the patients undergoing second-look procedures. Major complications in the laparoscopy group included transverse colon perforation (1), small bowel perforation (2), enterocutaneous fistula (1), and a retroperitoneal hematoma (1). Major complications in the laparotomy group included cystotomy (1), left ureteral injury (1), enterotomy (2), and SBO (4). Laparoscopy, when technically feasible, appears equally as effective as laparotomy in detecting persistent or recurrent malignant disease with less blood loss, less days spent in the hospital, less financial burden, and no increase in patient morbidity.

Pasteurella multocida Bacteremia in a Patient With Ovarian Cancer and Chemotherapy-induced Neutropenia.

BACKGROUND: Pasteurella multocida is a commensal organism found in the saliva and oropharynx of domestic animals. It causes a variety of human infections ranging from cellulitis to bacteremia and sepsis. The severity of infection is somewhat related to the immunocompetency of the infected host. An immunocompromised host is more likely to suffer a disseminated infection as a result of contact with this organism than an immunocompetent host. This case report and review of the literature are presented to further evaluate the types of infections caused by this organism in oncology patients. CASE: A 54-year-old woman with epithelial ovarian cancer and a chemotherapy-induced nadir of her WBC count developed P. multocida bacteremia after she incurred a scratch from her pet cat. She was treated with ceftazidime and then penicillin G with prompt resolution of the bacteremia. CONCLUSION: This paper summarizes an infectious complication that is likely to become more common as chemotherapy-induced neutropenia and pet ownership in the elderly become common coincidences. As such, oncologists and infectious disease physicians should keep this organism in mind when selecting antibiotics to treat the febrile, nadiring cancer patient who has known pet contact.

Mono-ortho- and non-ortho-substituted polychlorinated biphenyls in human milk from Mohawk and control women: effects of maternal factors and previous lactation.

Fifty-four individual human milk samples from 50 mothers (20 Mohawks and 30 controls) were analyzed for four non-ortho- and eight mono-ortho-substituted polychlorinated biphenyls (PCBs). Mean total coplanar PCBs concentrations were 49 ng/g and 55 ng/g lipid for Mohawk and control women, respectively. A statistical evaluation of all analytical data reveals no significant difference of total coplanar PCB level between Mohawk and control women. The level of these contaminants is influenced by the age of the mother, number of breastfed children, and length of nursing period. Older women, primiparae, and cigarette smokers had higher levels of coplanar PCBs. In general, women had higher levels of coplanar PCBs in the first lactation and in the earlier samples of a given lactation, while levels declined both with duration of breast-feeding and with number of children nursed. The contribution of individual non-ortho- and mono-ortho-substituted PCB congeners to the total calculated toxic equivalent values (sigma TEQ) was assessed for the breast milk samples. The levels of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) in human milk of pooled specimens from Los Angeles, California and Binghamton, New York, widely separate cities in the United States (Schecter et al. 1989), were presented for reference purpose. The main contributions to the sigma TEQ were PCB congeners #118 (25.8 pg/g lipid), #126 (25 pg/g lipid), #105 (10.8 pg/g lipid), and #156 (7.4 pg/g lipid). Collectively, these compounds accounted for 70% of the sigma TEQ values.(ABSTRACT TRUNCATED AT 250 WORDS)

Papillary serous cystadenocarcinoma arising in benign glandular inclusion cysts in pelvic and inguinal lymph nodes.

BACKGROUND: Benign glandular inclusion cysts occurring within lymph nodes have been well described in the literature. However, the malignant potential of these glands is unknown. One previous case report described an adenoacanthoma arising within one of these glands. CASE: A 65-year-old woman was previously diagnosed with papillary serous cystadenocarcinoma in the inguinal and pelvic lymph nodes. She had no tumor involving the ovaries or peritoneal surfaces at the time of initial diagnosis. She presented to us 9 years later with a recurrence of this tumor in the obturator fossa and along the vaginal sidewall. Treatment consisted of surgery, radiation, and chemotherapy. CONCLUSION: Although rare, müllerian tumors can occur in the lymph nodes without simultaneous ovarian or peritoneal involvement, and most likely arise de novo within lymph node inclusion cysts.

Epithelial ovarian tumors of borderline malignancy: long-term follow-up.

Thirty-nine patients underwent primary surgery for epithelial ovarian tumors of low malignant potential at the Massachusetts General Hospital between 1970 and 1980. Eighty-five percent of patients were found to have Stage I disease and 15% were found to have Stage III disease. Fifty-four percent of patients had a tumor with serous histology, 39% had a tumor with mucinous histology, and the remainder of patients had tumors with an endometrioid or mixed-cell type. Second malignancies and benign ovarian tumors were frequently found concomitantly with the borderline tumors or in follow-up. Gastrointestinal and endometrial adenocarcinomas were the most common second malignancies and were frequently found associated with a borderline tumor of serous histology. Follow-up was available in all 39 patients (100%). Mean time of follow-up was 11.8 years. Sixty-nine percent of patients are clinically without evidence of disease with a mean follow-up of 14.7 years, 23% died of other causes, 5% died of disease, and 3% died with disease and sepsis. All patients dying with disease did so within 7.3 years of their primary surgery. Seven patients underwent conservative surgery, defined as preservation of some ovarian tissue. Six of 7 patients are clinically free of disease with a mean follow-up of 14.6 years; 1 patient died of other causes. No patients treated conservatively had a recurrence of their disease.

Plasmid-dependent inhibition of growth of bacteriophage T4 ndd mutants.

Mutants of bacteriophage T4 that fail to induce nuclear disruption (ndd mutants) are unable to grow in the wild-type Escherichia coli strain CT447. This inhibition of the growth of ndd mutants occurs only in the presence of a large (ca. 80-megadalton) plasmid resident in CT447 cells.

Separation of neutral lipids of shark liver by "dry-column" chromatography.

"Dry-column" chromatography in mixed solvents has been successfully used to separate gram quantities of neutral lipids from shark liver oil into simpler fractions.