Obstetrical deliveries associated with maternal malignancy in California, 1992 through 1997

OBJECTIVE: This study aims to characterize the rate of occurrence and nature of outcomes associated with obstetrical deliveries in women with malignant neoplasms among 3,168,911 women who delivered in California in 1992 through 1997. DESIGN: The study is a population-based retrospective review of infant birth and death certificates and maternal and neonatal discharge records. Cases of malignant neoplasms associated with obstetrical delivery were attributed to 1 of 3 categories, depending on the earliest documented hospital discharge diagnosis, as follows: "prenatal" if the diagnosis was first documented by hospitalization within 9 months preceding delivery, "at delivery" if the diagnosis was established from the delivery hospitalization, or "postpartum" if the diagnosis was first documented by hospitalization within 12 months after delivery. METHODS: Computer-linked infant birth and death certificates and maternal and neonatal discharge records were used to identify cases and outcomes. Cases of malignant neoplasms were identified by using International Classification of Diseases, Ninth Revision codes (140-208). Noninvasive neoplasms and carcinoma in situ neoplasms were excluded. In analysis of outcomes, the Mantel-Haenszel estimate for adjusted odds ratios was used. RESULTS: Among 3,168,911 obstetrical deliveries over the 6-year span, a total of 2247 cases of primary malignancy were identified. The observed rate of occurrence for primary malignant neoplasms was 0.71 per 1000 live singleton births. Most cases (53.3%) were first documented in the postpartum period as follows: prenatal, 587 cases (0.18 per 1000); at delivery, 462 cases (0.15 per 1000); and postpartum, 1198 cases (0.38 per 1000). The most frequently documented primary malignant neoplasms associated with obstetrical delivery were breast cancer (423 cases, 0.13 per 1000), thyroid cancer (389 cases, 0.12 per 1000), cervical cancer (266 cases, 0.08 per 1000), Hodgkin's disease (172 cases, 0.05 per 1000), and ovarian cancer (123 cases, 0.04 per 1000). Odds ratios for a variety of demographic factors identified maternal age as the most significant risk factor for development of malignant neoplasms (age greater than 40 vs 20-25, odds ratio 5.7, CI 4.6-6.9). Age-adjusted odds ratios for maternal cancer of any type suggested significantly elevated risks for cesarean delivery (odds ratio 1.4, CI 1.3-1.6), blood transfusion (odds ratio 6.2, CI 4.5-8.5), hysterectomy (odds ratio 27.4, CI 20.8-36.1), and maternal postpartum hospital stay greater than 5 days (odds ratio 30.6, CI 27.9-33.6), but not for postpartum maternal death (odds ratio 0.8, CI 0.6-1.0). Odds ratios also suggested significantly elevated risks for premature newborn (odds ratio 2.0, CI 1.8-2.2), very low birth weight (odds ratio 2.9, CI 2.2-3.8), and newborn hospital stay longer than 5 days (odds ratio 2.6, CI 2.4-3.0), but not for neonatal death (odds ratio 1.6, CI 0.8-3.1) or infant death (odds ratio 1.2, CI 0.5-3.3). However, several types of malignant neoplasms did confer significant elevations in risk for neonatal death. Hospital charges for both maternal and neonatal care were significantly elevated in the maternal malignant neoplasm group. CONCLUSION: A lower than expected occurrence rate of obstetrical delivery associated with maternal malignancy was seen when compared with previously published hospital-based reports. Malignant neoplasms associated with obstetrical delivery were most frequently first documented in the postpartum period. Maternal and neonatal morbidity were significantly increased, yet the risk of in-hospital maternal death was not significantly elevated. A significant increase in risk of neonatal death for infants of mothers with cervical cancer was found.     

The alloantibody response in the allogeneically pregnant rat. V. Absence of cell-mediated immunity in high responders

Allogeneically pregnant rats have been examined postpartum to determine whether they are sensitized against paternal class I antigens for cell-mediated immunity. This study was undertaken as this point is ambiguous. Since the response of the female to paternal MHC antigens is genetically controlled it is possible that the inability of some investigations to detect cell-mediated immunity against the paternal strain was due to the use of non-responder strain combinations. Cell-mediated immunity was assayed in a strain combination that is an unambiguous high responder, in which 100% of the females respond to the paternal strain by making alloantibodies. Maternal cell-mediated responses to paternal antigens were measured by the assays of DTH and IL-2 secretion under limiting conditions. We were unable to detect any cell-mediated immunity to paternal class I antigens even though the female produced copious quantities of alloantibody.     

Coxsackievirus-positive cervices in women with febrile illnesses during the third trimester in pregnancy

Coxsackievirus B5 infection was demonstrated in five of seven third-trimester pregnant women with undifferentiated febrile illnesses or aseptic meningitis. Coxsackievirus B5 was recovered from the cervix and throat in four women and from the rectum in three. No obvious illnesses were evident in the babies. These findings suggest that previously unrecognized cervical enterovirus carriage or infection is common in infected pregnant women in the last trimester and that subsequent neonatal infection at delivery may result.     

Signet-ring cell carcinoma of the urinary bladder primary presentation as a Krukenberg tumor

A 34-year-old female presented with a right ovarian Krukenberg tumor, which initially was thought to be a granulosa cell tumor. Eight months later, necropsy revealed a primary signet-ring cell carcinoma (SRCC) of the urinary bladder. When occurring in females, this rare bladder tumor often exhibits ovarian metastases. This case appears to be the first reported example of a signet-ring cell carcinoma of the bladder presenting as a Krukenberg tumor.     

In vivo 31P NMR studies of the hepatic response to L-ethionine in anesthetized rats

Phosphorus-31 surface coil spectroscopy has been used to study the effects of L-ethionine administration on the hepatic metabolism of the anesthetized Sprague-Dawley rat. ATP levels were found to decrease by approximately 30% 3 to 4 hr after administration of 1 mg/g body wt of L-ethionine to the anesthetized rat by gastric gavage. ATP levels returned to control values approximately 8 hr postadministration. The relatively small decrease in ATP level was confirmed by extraction and conventional enzyme assay and is a consequence of the mode of administration of the ethionine. Hepatic inorganic phosphate levels rose concomitantly with the ATP fall. There were no significant changes in either cellular pH or Mg2+ levels as monitored by the 31P shifts of sensitive metabolites. In vivo 31P NMR spectroscopy provides a promising approach to study the effects of hepatotoxicants on cellular ATP, pH, and Mg levels.     

Developmental toxicity of halogenated acetonitriles: drinking water by-products of chlorine disinfection

The developmental toxicity of acetonitrile and 5 halogenated derivatives was examined with an in vivo teratology screen adapted for use in the Long-Evans rat. The screen was extended to an evaluation of growth till postnatal Days 41-42, and weight of several organs at sacrifice. Acetonitrile was without developmental effects even at doses toxic to the dam. Of the halogenated compounds, treatment with trichloroacetonitrile (TCAN) and dichloroacetonitrile (DCAN) resulted in reduced fertility and increased early implantation failure. There was no effect on litter size in females bearing live litters, but pup birth weight was reduced in all litters exposed to halogenated compounds. Perinatal survival of the pups was adversely impacted by DCAN and TCAN. Postnatal growth till Day 4 was reduced by DCAN and bromochloroacetonitrile (BCAN) while growth till Day 42 was consistently affected only by TCAN. Some general observations were made on the usefulness of the criteria used in the screen, and TCAN, the most toxic of the halogenated compounds, was selected for further in-depth evaluation.     

An evaluation of chemical photoreactivity and the relationship to phototoxicity

The existing regulatory guidance for photosafety testing of new drug products states that studies are warranted for those chemicals that both absorb light in the range of 290–700 nm, and that are either applied locally/topically, or “reach” (EMEA)/“significantly partition” (FDA) to the skin or eyes. The initial in vitro study recommended for the assessment of phototoxic potential is the 3T3 Neutral Red Uptake (NRU) Assay. The current study was undertaken to establish superior triggers for the initiation of biological photosafety testing. In this study, photophysical and photochemical parameters for 40 drug or drug-like molecules were studied. Principal Component Analysis (PCA), Partial Least Squares-Discriminant Analysis (PLS-DA), and a fivefold cross-validation PLS algorithm were used to evaluate the relationship between subsets of photophysical and photochemical parameters with the 3T3 NRU PIF/MPE (Photo Irritation Factor/Mean Photo Effect) results. The parameters most indicative of a 3T3 NRU positive PIF or MPE score were the extent of degradation in solution, the quantum yield of formation of singlet oxygen and the relative formation of superoxide anion. The results demonstrate that while absorption of light is critical to the induction of a light-induced process, it is the resultant events that may be used to predict the 3T3 NRU assay result. It is therefore proposed that the trigger for photosafety testing be revised to include a molecular basis for photoreactivity. From this limited investigation, estimated thresholds leading to 3T3 NRU positive results due to photodegradation, formation of singlet oxygen quantum yield or a relative superoxide anion formation value are proposed.     

Some poststimulatory effects on the whole nerve action potential

Short-term poststimulatory effects on the N1 component of the auditory-nerve compound action potential (CAP) were investigated in Mongolian gerbils. Some effects of conditioner level, conditioner frequency and probe level were assessed. In most cases, poststimulatory decrements occurred. The decrements were independent of probe intensity when the conditioner was close in frequency and of equal or less intensity than the probe. At some other conditioner frequencies, decrements decreased as probe intensity increased. Departures from these relationships occurred when a more intense conditioner was applied. In some instances, increases in CAP amplitude were also observed. The roles of single unit responses including spread of cochlear excitation, and possible mechanisms for poststimulatory facilitation are discussed.     

Levocabastine. Evaluation in the histamine and compound 48/80 models of ocular allergy in humans

The efficacy of a new antihistamine, levocabastine, in alleviating the ocular allergic reactions induced by both histamine and 48/80 was evaluated in humans. Levocabastine (0.5%) was instilled in one eye of 30 volunteers, and vehicle in the contralateral eye. After 15 minutes, half of the subjects received histamine (25 mg/ml) and half, 48/80 (7.5 mg/ml). The signs and symptoms of allergy were graded clinically after 30 minutes. Compared with a buffer control, levocabastine significantly alleviated itching (P = 0.01), redness (P = 0.0156), and chemosis (P = 0.005) induced by histamine, and itching (P = 0.032) and redness (P = 0.029) induced by 48/80. The results from these pharmacologic models support the clinical use of levocabastine for the treatment of allergic conjunctivitis.