In three brain regions central to maternal behaviour, neither male nor female Phodopus dwarf hamsters show changes in oestrogen receptor alpha distribution with mating or parenthood.

Oestrogen receptor (ER)alpha immunoreactivity in three brain regions relevant to maternal behaviour (medial preoptic area, bed nucleus of the stria terminalis and medial amygdala) was measured in two species of dwarf hamster that both mate during a postpartum oestrous but differ in expression of paternal behaviour. Male and female Phodopus campbelli and Phodopus sungorus were sampled as sexually naive adults, following mating to satiety, and as new parents. In all brain regions, females expressed higher levels of ER alpha than males. Species did not have an effect on ER alpha distribution except in the medial amygdala, where P. sungorus females had higher expression levels than all other groups. Behavioural status was not associated with altered ER alpha expression. These results were not expected for females and suggest that a primary activational role for oestrogen, acting through ER alpha in these regions, does not generalize to maternal behaviour in Phodopus. In males, these results are consistent with previous manipulations of the ER alpha ligand, oestrogen, and suggest that paternal behaviour in P. campbelli is likely to be regulated by developmental effects of oestrogen on the brain during early life (similar to Microtus ochrogaster), rather than through activation by oestrogen at the time of fatherhood (similar to Peromyscus californicus).

Parental regulation of central patterns of estrogen receptor alpha.

Reduced levels of estrogen receptor alpha (ERalpha) in the medial amygdala (MeA) and bed nucleus of stria terminalis (BST) have been hypothesized to play a significant role in the expression of male behaviors associated with monogamy. Therefore, the regulation of ERalpha could be a critical factor in determining male behavior and the evolution of monogamy. Central expression of ERalpha immunoreactivity was compared in hybrid offspring from crosses between two phenotypically distinct populations of prairie voles (Microtus ochrogaster). Illinois voles (IL) are socially monogamous and display low levels of ERalpha, while Kansas voles (KN) display some characteristics associated with polygyny and have higher levels of ERalpha. In offspring from hybrid crosses, the pattern of ERalpha expression was dependent upon parentage; the two types of hybrid crosses did not produce the same ERalpha pattern in the offspring. In the BST and MeA, hybrid males expressed ERalpha patterns consistent with those of males from their mother's population, while hybrid females had ERalpha patterns typical of females belonging to their father's population. The parental-specific patterns of ERalpha expression are suggestive of genomic imprinting, therefore, the vole ERalpha (Esr1) gene was cloned and sequenced, and examined for allele-specific expression. Results from this study indicate that while maternal factors may play a major role the expression of ERalpha in their male offspring, genomic imprinting is unlikely to be involved, suggesting another mechanism is responsible.

Neonatal manipulation of oxytocin affects expression of estrogen receptor alpha.

In adult females many of the effects of the neuropeptide oxytocin are steroid, and especially estrogen dependent. Here we demonstrate for the first time that neonatal manipulation of oxytocin can affect the expression of estrogen receptor alpha. On the first day of postnatal life male and female prairie voles (Microtus ochrogaster) were randomly assigned to receive one of four treatments; (a) 50 microl i.p. injection of 3 microg oxytocin (approximately 1 microg/g), (b) 0.3 microg of an oxytocin antagonist (approximately 0.1 microg/g), or (c) isotonic saline. A fourth group was handled, but not injected. On postnatal day 8 or 21, brain tissue was collected, fixed and sectioned. Free-floating sections were stained for estrogen receptor alpha using immunocytochemistry, and estrogen receptor alpha immunoreactive neurons were compared by age, treatment, and sex. To compare the temporal expression of estrogen receptor alpha an additional set of brains was collected from untreated males and females on the day of birth. The effects of oxytocin manipulations were age dependent, sexually dimorphic, and site-specific. While there were no significant treatment effects on postnatal day 8, by postnatal day 21 females that received oxytocin showed a significant increase in the number of cells expressing estrogen receptor alpha-immunoreactivity in the ventromedial nucleus of the hypothalamus. Treatment with oxytocin antagonist resulted in a significant decrease in estrogen receptor alpha-immunoreactivity in the medial preoptic area in postnatal day 21 females. While there were no significant effects in males, males treated with oxytocin antagonist trended toward a reduction in estrogen receptor alpha-immunoreactivity in the medial amygdala. The results indicate that oxytocin can have organizational effects on the expression of estrogen receptor alpha, that these effects are sexually dimorphic, and finally that during the preweaning period the development of estrogen receptor alpha is sexually dimorphic.

Neonatal manipulation of oxytocin alters oxytocin levels in the pituitary of adult rats.

The neuropeptide oxytocin (OT) and its OT antagonists (OTA) in infant rats affect their behavior as adults. In this study we attempted to determine whether treating rats on the day of birth (postnatal day 1) with OT or OTA would affect brain OT levels of these rats as adults. Rat pups were injected with OT (3 microg), OTA (0.3 microg) or saline vehicle ip on postnatal day 1. As 60-day-old adults, treated rats were killed, and the OT content in their medial preoptic areas (MPOAs), medial hypothalami (MH) and pituitaries were assayed. In females, treatment with OTA on postnatal day 1 significantly decreased pituitary OT levels as adults. In males, by contrast, treatment with OTA on postnatal day 1 resulted in increased pituitary OT levels when they become adults compared to male rats treated with OT on postnatal day 1. There were no significant effects of neonatal treatment on OT levels in either the MH or MPOA. Day 1 postnatal treatment with OT or OTA had a long-term sexually dimorphic effect on OT levels in the pituitary.

Neonatal manipulations of oxytocin alter expression of oxytocin and vasopressin immunoreactive cells in the paraventricular nucleus of the hypothalamus in a gender-specific manner.

Early postnatal manipulations of oxytocin have long-term behavioral and physiological consequences; the present study examined the hypothesis that oxytocin or its absence influences the subsequent expression of either oxytocin or arginine vasopressin in the CNS. On postnatal day 1 female and male prairie voles (Microtus ochrogaster) received a single i.p. injection of oxytocin (3 microg), oxytocin antagonist (0.3 microg), or 50 microl of isotonic saline or were only handled. On postnatal days 1, 8 and 21, brains were fixed, sectioned and stained for oxytocin or vasopressin immunoreactivity and analyzed as a function of age, treatment and sex. Both oxytocin and vasopressin immunoreactivity were observed on day 1 in the supraoptic and paraventricular nuclei (PVN) of the hypothalamus. Numbers of oxytocin and vasopressin neurons increased with age in both nuclei. Females treated on postnatal day 1 with oxytocin or oxytocin antagonist displayed a significant increase in oxytocin immunoreactivity on day 21 in the PVN. In contrast, males treated with antagonist tended to have decreased vasopressin immunoreactivity in the same region. These results revealed that the effects of neonatal manipulation of oxytocin are age-dependent, site-specific and sexually dimorphic. The long-lasting effects of neonatal exposure to exogenous oxytocin and oxytocin antagonist indicate a role for oxytocin in the development of the CNS during the neonatal period, affecting the development of the oxytocinergic system in females and the vasopressinergic system in males. The developmental effects observed suggest one possible mechanism by which neonatal exposure to oxytocin or neonatal inhibition of endogenous oxytocin produces long-lasting behavioral and physiological alterations and could play a role in the development of male- and female-typical behavior.

Outcome and staging evaluation in malignant germ cell tumors of the ovary in children and adolescents: an intergroup study.

PURPOSE: The aim of this study was to perform an evaluation of outcome and the role of surgical staging components in malignant germ cell tumors (GCT) of the ovary in children and adolescents. METHODS: From 1990 to 1996, 2 intergroup trials for malignant GCT were undertaken by Pediatric Oncology Group (POG) and Children's Cancer Study Group (CCG). Stage I-II patients were treated with surgical resection and 4 cycles of standard dose cisplatin (100 mg/m2/cycle), etoposide, and bleomycin (PEB) chemotherapy. Stage III-IV patients were treated with surgical resection and randomly assigned to chemotherapy with PEB or high-dose cisplatin (200 mg/m2/cycle) with etoposide and bleomycin (HDPEB). Patients unresectable at diagnosis had second-look operation after 4 cycles of chemotherapy if residual tumor was seen on imaging studies. IRB approval of the protocols was obtained at each participating institution. An analysis of outcome data, operative notes, and pathology reports in girls with ovarian primary site was done for this report. RESULTS: There were 131 patients with ovarian primary tumors of 515 entered on these studies. Mean age was 11.9 years (range, 1.4 to 20 years). Six-year survival rate was stage, I 95.1%; stage II, 93.8%; stage III, 98.3%; stage IV, 93.3%. In only 3 of 131 patients were surgical guidelines followed completely. Surgical omissions resulting in protocol noncompliance resulted from failure to biopsy bilateral nodes (97%), no omentectomy (36%), no peritoneal cytology (21%), no contralateral ovary biopsy (59%). More aggressive procedure than recommended by guidelines included total hysterectomy and bilateral salpingo-oophorectomy in 6 patients and retroperitoneal node dissection in 10 patients. Correlation of gross operative findings with pathology results was carried out for ascites, lymph nodes, implants, omentum, and contralateral ovary. CONCLUSIONS: Pediatric ovarian malignant GCT (stages I-IV) have excellent survival with conservative surgical resection and platinum-based chemotherapy. Survival appears to have been unaffected by deviations from surgical guidelines. New surgical guidelines are proposed based on correlation of gross findings, histology, and outcome in these intergroup trials.

The effects of neonatal castration on the subsequent behavioural response to centrally administered arginine vasopressin and the expression of V1a receptors in adult male prairie voles.

Centrally administered arginine vasopressin induces the formation of partner preferences in male prairie voles (Microtus ochrogaster). The expression of many vasopressin-regulated behaviours is testosterone dependent. In this study, we tested the hypothesis that early exposure to gonadal steroids are necessary to establish the typical response of adult male prairie voles to exogenous vasopressin, predicting that adult males which were castrated neonatally would not form partner preferences in response to centrally administered vasopressin. We also examined the effect of neonatal castration on the expression of vasopressin (V1a) receptors. Voles were castrated on the day of birth (NEOCAST), sham-castrated on the day of birth (NEOSHAM) or castrated as adults (ADULTCAST). With the exception of one group of neonatal sham males (NEOSHAM CON), which served as a control for the effects of vasopressin, as adults, all males received a 1- micro l intracerebroventricular injection of vasopressin (100 ng) in artificial cerebrospinal fluid. In addition, 2 weeks before testing, one group of neonatally castrated males received an implant of testosterone propionate (NEOCAST + TP). Between 60 and 90 days of age, an internal cannula was placed in the lateral cerebral ventricle and, 24 h later, males were injected with vasopressin. Subsequently, after an additional 15 min, males were cohabitated with a female 'partner' for 1 h. Immediately following cohabitation, males were placed in a Y-shaped partner preference test apparatus for 3 h, in which the male had access to the 'partner' and a novel female, 'stranger.' Time spent with the partner versus the stranger was compared within and between treatments. The results were found to support our hypothesis as the NEOSHAM and ADULTCAST males formed partner preferences, spending more time with the partner, and they spent significantly more time with their partner than did NEOSHAM CON, NEOCAST or NEOCAST + TP males. Replacement of testosterone in neonatally castrated males did not restore partner preference formation in response to vasopressin in adult males. Finally, neonatal castration did not affect the distribution of V1a receptors.

Malignant retroperitoneal and abdominal germ cell tumors: an intergroup study.

BACKGROUND/PURPOSE: This randomized study examined survival (S) and event-free survival (EFS) rates using high-or standard-dose cisplatin-based combination chemotherapy and surgical resection for this subset of germ cell tumors. METHODS: Twenty-six of 317 patients enrolled on the POG 9049/COG 8882 intergroup study for malignant germ cell tumors had abdomen or retroperitoneum as the primary site. Twenty-five of 26 were eligible for inclusion (n = 25). Patients had biopsy or resection at diagnosis and randomization to chemotherapy including etoposide, bleomycin, and either standard-dose (PEB) or high-dose cisplatin (HDPEB). In patients with initial biopsy, delayed resection was planned. RESULTS: Median age was 26 months. There were 14 girls and 11 boys. There were 3 stage I to II, 5 stage III, and 17 stage IV patients. Surgical management included primary resection in 5, resection after chemotherapy in 13, and biopsy or partial resection in 7 patients. Overall 6-year EFS rate was 82.8% +/- 10.9%, and 6-year survival rate was 87.6% +/- 9.3%. By group, 6-year survival rate was 90.0% +/- 11.6% for PEB and 85.7 +/- 14.5% for HDPEB. Deaths include one from sepsis, one from malignant tumor progression, and one from bulky disease caused by benign components despite response of the malignant elements to chemotherapy. CONCLUSIONS: Malignant germ cell tumors arising in the abdomen and retroperitoneum have an excellent prognosis despite advanced stage in most children. Aggressive resection need not be undertaken at diagnosis, but a concerted attempt at complete surgical removal after chemotherapy is important to distinguish viable tumor from necrotic tumor or benign elements that will not benefit from further chemotherapy.

Ligamentous injuries of the cervical spine in unreliable blunt trauma patients: incidence, evaluation, and outcome.

BACKGROUND: The potential for ligamentous injury of the cervical spine (C-spine) may mandate prolonged neck immobilization via a hard cervical collar in the blunt trauma victim (BTV) with altered sensorium. We investigated the incidence of ligamentous C-spine injuries, and whether applying (post hoc) the practice management guidelines from the Eastern Association for the Surgery of Trauma (three radiograph views plus computed tomographic scan of C1-C2) would have detected the injuries. METHODS: The study was a 3-year retrospective review of BTVs admitted to the state's Primary Adult Resource Center for trauma from 1996 to 1998. Unreliable patients were defined as those with admission Glasgow Coma Scale score < 15. A rigorous algorithm to clear the C-spine was used. Pure ligamentous C-spine injury was defined as a C-spine having abnormal anatomic alignment, dislocation, subluxation, or listhesis, but without fracture. Demographics, diagnostic studies, presence of neurologic deficit, therapy, survival, and disposition were analyzed. RESULTS: There were 14,577 BTVs with 614 (4.2%) patients having C-spine injury. There were 2,605 (18%) unreliable patients, with 143 (5.5%) of these having C-spine injury, 129 (90%) having fracture and 14 (10% of BTVs; 0.5% of unreliable patients) having no fracture. Of the 14 unreliable patients with pure ligamentous C-spine injury, 13 had initial diagnosis by supine cross-table lateral radiograph. The one exception had a normal three-view radiographic series, but atlanto-occipital dislocation was diagnosed by computed tomographic scan. Eight patients had upper level injury (C0-C4) and six were lower (C4-C7). Four patients died within 30 minutes after admission, 4 underwent cervical fusion, and 6 were treated with collar only. Five (50%) of the survivors had no apparent neurologic deficit attributed to the C-spine at admission. Nine patients remained institutionalized after discharge and one was discharged home. CONCLUSION: Ligamentous injuries without fracture of the C-spine are rare. Application of the practice management guidelines developed by the Eastern Association for the Surgery of Trauma for identifying C-spine instability is effective and should facilitate early removal of the cervical collar in unreliable patients.

The effects of peptides on partner preference formation are predicted by habitat in prairie voles.

This study tested the hypothesis that intraspecific variations in mating systems are correlated with differences in the capacity of peripheral arginine vasopressin (AVP) to facilitate partner preferences. It has been hypothesized that differences in environmental conditions, Kansas being more xeric than Illinois, are responsible for some of the intraspecific differences in the mating systems between Kansas (KN) and Illinois (IL) prairie voles. We predicted that prairie voles from KN would be more behaviorally sensitive to peripheral AVP than prairie voles from IL. To test this hypothesis 60- to 120-day-old male and female, lab-reared, prairie voles originating from KN and IL received three subcutaneous injections of AVP or isotonic saline. Animals were then placed with an adult member of the opposite sex, designated a "partner," for a 1-hour period of cohabitation and subsequently tested for preference for the familiar partner versus a comparable stranger. Only KN males treated with AVP displayed a significant preference for the partner. Using the same experimental paradigm we also examined the ability of peripheral oxytocin (OT) to facilitate partner preference in KN prairie voles. OT facilitated partner preference in females, but not males. This finding was consistent with previous results describing the effects of peripheral OT in IL prairie voles. We also examined the hypothesis that the differential response of KN and IL males would be associated with differences in the distribution of AVP (V1a) receptors. However, there was no apparent difference in the distribution of V(1a) receptors between KN and IL males. The results of this study indicate that there is both intraspecific and intersexual variation in the regulation of social behavior in prairie voles. In addition, these findings suggest that the proximate causes of intraspecific variation may be predicted by knowledge of the habitat of origin.

The effect of cisplatin dose and surgical resection in children with malignant germ cell tumors at the sacrococcygeal region: a pediatric intergroup trial (POG 9049/CCG 8882).

PURPOSE: This study was designed to evaluate (1) the efficacy of standard or high-dose cisplatin with etoposide and bleomycin and (2) the role of surgical resection in infants and children with malignant germ cell tumors of the sacrococcygeal region (SCT). METHODS: Seventy-four of 317 children presenting to Pediatric Oncology Group (POG)/Children's Cancer Group (CCG) institutions from 1990 through 1996 with malignant germ cell tumors had malignant SCT. There were 62 girls and 12 boys with a median age of 21 months (range, 3 days to 37 months) and median serum alpha-fetoprotein of 35,500 ng/mL. Twelve had undergone resection of a benign SCT as a newborn. Forty-four (59%) had evidence of metastatic disease at time of diagnosis. Presentation by type (Altman classification) was I, 0; II, 2; III, 30; and IV, 42. The initial procedure was biopsy in 45 and resection in 29. Patients were assigned randomly to receive 4 cycles of chemotherapy with etoposide (E) and bleomycin (B) and either high-dose cisplatin (200 mg/m(2) per cycle; HDP) or standard dose cisplatin (100 mg/m(2) per cycle; P). After completion of chemotherapy, 42 of 45 initially treated with biopsy underwent resection. RESULTS: Overall 4-year survival rate is 90% (SE = 4%) and 4-year event-free survival (EFS) is 84% (SE = 6%). Event-free survival data for subgroups of interest are as follows: 4-yr EFS% (SE) P Values Mets (44) 88 (6).48 No Mets (30) 80 (8) HDP EB (37) 89 (6).21 P EB (37) 78 (7) Initial Resection (29) 90 (7).50 Delayed Resection (42) 83 (7) Complete Resection (49) 90 (5).19 CR/PR Partial Resection (22) 77 (10) Biopsy Only (3) 33 (27).005 (3 way) CONCLUSIONS: (1) The current survival rate of malignant sacrococcygeal tumors is excellent even with metastases. (2) Delayed surgical resection is not associated with an adverse outcome. (3) In this subset the treatment comparison was inconclusive however, followed the trend in the overall study of more than 300 children in which the high-dose cisplatin group had superior EFS (P<.05).

Malignant mediastinal germ cell tumors: an intergroup study.

PURPOSE: This review was conducted to determine clinical characteristics and response to therapy in this rare pediatric neoplasm. METHODS: An intergroup Pediatric Oncology Group (POG) 9049/Children's Cancer Study Group (CCG) 8882 randomized trial was conducted to evaluate response rate and survival with chemotherapy using etoposide, bleomycin, and high or standard dose cisplatin for high-risk malignant germ cell tumors at extragonadal sites. For this review, a secondary analysis of clinical and operative findings in patients with primary site in the mediastinum was carried out. RESULTS: Of the 38 children with malignant mediastinal germ cell tumors (MGCT), 36 had sufficient data to be included in this review. Thirty-four tumors were anterior mediastinal, 2 were intrapericardial. Younger patients had respiratory complaints; older patients had chest pain, precocious puberty, or facial fullness. Yolk sac tumor was the only malignant element in girls. Boys had yolk sac tumor in 7, germinoma in 3, choriocarcinoma in 2, and mixed malignant elements in 15. Benign teratoma elements coexisted in 22 patients. Four patients had biopsy and chemotherapy without tumor resection, and only 1 survived. Fourteen patients had resection at diagnosis followed by chemotherapy with 12 survivors. Eighteen patients had biopsy followed by chemotherapy and postchemotherapy tumor resection with 13 survivors. Tumor size in response to chemotherapy for these 18 patients was stable or increased in 6, and decreased in 12 (mean decrease of 57% in greatest dimension). Overall, 26 of 36 patients survived, with a 4-year patient survival rate of 71%+/-10%, and a 4-year event-free survival rate of 69%+/-10%. Ten patients died: 5 of tumor (all boys > or =15 yr), 2 of sepsis, and 3 of second malignancy. CONCLUSIONS: Malignant MGCT is a complex tumor of varied histology with frequent coexistence of benign elements. Lesions often have incomplete regression with chemotherapy alone. Tumor resection may be undertaken at diagnosis or after attempted shrinkage with chemotherapy. Aggressive attempt at complete tumor resection should be offered to all patients even if bulky tumor persists after induction chemotherapy with expectation of a significant salvage rate. Boys > or =15 years may be a high-risk subgroup for mortality from tumor progression.

Determinants of disability after lower extremity fracture.

BACKGROUND: Factors influencing the progression of physical impairment to patient-perceived disability are not well known. We sought to better understand this relationship in the setting of injury. METHODS: We followed a cohort of 302 patients with lower extremity fractures over a 1-year period. Physical impairment was assessed by range of motion, strength, and pain. Range of motion and strength were assessed together as a proportion of normal function of the extremity (impairment score). Pain was assessed using a Visual Analogue Scale (VAS) pain score. Disability was assessed using the Sickness Impact Profile (SIP), a widely used measure of patient-perceived limitations of everyday activities attributable to illness. The SIP was administered during hospitalization to assess preinjury baseline. Impairment assessment and readministration of the SIP were performed at 12 months after injury. RESULTS: Impairment in leg function (range of motion and strength) was highly correlated (p < 0.001) with overall SIP score at 12 months, but accounted for only 23% of the variance in overall SIP scores. Likewise, VAS pain score was highly correlated (p < 0.001) with overall SIP score at 12 months, but accounted for only 29% of the variance in overall SIP scores. In a multivariate linear regression analysis, variables that were independently associated with overall SIP score included impairment score, VAS pain score, preinjury SIP, poverty status, education status, social support, having hired a lawyer, and involvement with workers' compensation. These variables accounted for 52% of the variance in overall SIP scores at 12 months. CONCLUSION: The degree of physical impairment accounts for only a small amount of the variance in disability from lower extremity fracture. Identifiable patient characteristics including age, socioeconomic status, preinjury health, and social support together with impairment account for over half of the variance in long-term disability. Further research is needed to increase understanding of other factors that influence the progression of impairment to disability, especially those factors that may be amenable to intervention.

Genetic analysis of childhood endodermal sinus tumors by comparative genomic hybridization.

Childhood endodermal sinus tumors (CEST) are a distinct category of germ cell tumors that involve the testis and extragonadal sites of young children. Recurrent deletions of 1p and 6q have been reported by classic cytogenetic analysis of a small number of cases. Comparative genomic hybridization, a technique that screens the entire genome for genetic abnormalities, is applied to additionally define the genetic changes present in CESTs. Sixteen frozen CESTs (10 testicular, 6 extragonadal) obtained from Pediatric Oncology Group-affiliated institutions or from the Cooperative Human Tissue Network were analyzed. The most common changes were gain of 20q (10 tumors), 1q (6 tumors), 11q and 22 (4 tumors each), and loss of 6q (8 tumors with common deleted region of 6q24-qter), 16q (4 tumors), and 1p (4 tumors). Localized regions of gain were identified at 8q24 (2 tumors both showing c-myc amplification by fluorescence in situ hybridization). Gain of 12p, characteristic of adolescent germ cell tumor, was present in one testicular tumor. Comparative genomic hybridization was useful in defining genetic differences between adult and childhood tumors, in determining the common regions deleted on chromosome 6, and in identifying other involved loci to be correlated with clinical parameters in future studies.

Peripheral pulses of oxytocin increase partner preferences in female, but not male, prairie voles.

Centrally administered oxytocin (OT) facilitates social behaviors including the partner preferences that characterize the monogamous social system of prairie voles. In contrast peripherally administered OT generally has been ineffective in influencing central processes including behavior. OT from the posterior pituitary gland is released in pulses into the peripheral circulation. We hypothesized that peripherally administered OT, if delivered in repeated injections mimicking these pulses, would influence behavior. Male and female prairie voles received three subcutaneous injections of OT, a single injection of OT, or isotonic saline. Animals then were placed with an adult member of the opposite sex, designated as a "partner," for a 1-h period of cohabitation, and subsequently tested for preference for the familiar partner versus a comparable stranger. Females treated with pulses of peripheral OT (1, 5, or 20 microg) displayed a significant preference for the partner compared to control females, while females receiving a lower dose of OT (0.1 microg) or a single injection (20 microg) did not. There was also a significant within-group effect as pulsed OT-treated females spent more time with the partner when compared to the stranger, while control females spent equal amounts of time with the partner and stranger. Peripheral pulses of OT were no longer effective in inducing partner preferences when females were pretreated with a selective OT receptor antagonist, administered either peripherally or centrally. In contrast to females, peripheral treatment with OT did not facilitate the formation of partner preferences in males.

Complete surgical excision is effective treatment for children with immature teratomas with or without malignant elements: A Pediatric Oncology Group/Children's Cancer Group Intergroup Study.

PURPOSE: To determine whether the 3-year event-free survival (EFS) of children with completely resected immature teratomas is greater than 85%. PATIENTS AND METHODS: Patients with immature teratomas treated at Pediatric Oncology Group or Children's Cancer Group institutions were eligible. Pathology was centrally reviewed to confirm diagnosis and tumor grading. Follow-up included physical examination, measurement of tumor markers (alpha fetoprotein and human chorionic gonadotropin), and imaging. All patients were monitored for events, defined as tumor recurrence, second malignancy, or death. RESULTS: Seventy-three children (median age, 7.8 years) with extracranial immature teratomas were enrolled on study. Primary tumor sites included ovarian (n = 44), testicular (n = 7), and extragonadal (n = 22). However, on review, 23 patients had foci of yolk sac tumor (n = 21) or primitive neuroectodermal tumor (n = 2), whereas 50 had pure immature teratomas. Twenty-five patients had increased alpha fetoprotein (n = 18), human chorionic gonadotropin (n = 5), or both (n = 2); nine had foci of yolk sac tumor on review. Pathology review identified 23 patients with grade 1, 29 with grade 2, and 21 with grade 3 immature teratomas. With a median follow-up of 35 months, the overall 3-year EFS was 93% (95% confidence interval, 86% to 98%), with 3-year EFS of 97.8%, 100%, and 80% for patients with ovarian, testicular, and extragonadal tumors, respectively. Only four of 23 patients with immature teratoma and malignant foci developed recurrence, suggesting that surgical resection followed by close observation are effective treatment. Overall, five patients had disease recurrence 4 to 7 months from diagnosis, and four (80%) are disease free after platinum-based therapy. The fifth patient has residual tumor after cisplatin, etoposide, and bleomycin treatment requiring further therapy. CONCLUSION: Surgical excision is safe and effective treatment for 80% to 100% of children with immature teratoma.

Prior exposure To oxytocin mimics the effects Of social contact and facilitates sexual behaviour In females.

The purpose of this study was to determine whether pretreatment with oxytocin could mimic the effects of social contact and enhance sexual receptivity in female prairie voles. Female prairie voles require prolonged exposure to males to become sexually active and oxytocin has been shown to play a major role in the establishment of social bonds between males and females. Therefore, we hypothesized that prior exposure to exogenous oxytocin, in the absence of males, would enhance sexual activity in females. Two experiments were conducted to test this hypothesis. Experiment 1 examined the capacity of oxytocin to enhance sexual behaviour in females undergoing natural oestrus. Sexually naive female prairie voles received a daily subcutaneous injection of 20 microg oxytocin or isotonic saline for 5 days before being placed with a sexually experienced male for 48 h. Females treated with oxytocin were significantly more likely to mate during this period than saline-treated females. In experiment 2 the ability of oxytocin to increase subsequent sensitivity of sexually naive females to oestradiol was tested. Females that received oxytocin pretreatment, as in experiment 1, followed by oestradiol displayed a significant increase in sexual receptivity when compared to females treated with saline and oestradiol or oestradiol only. The results supported the hypothesis that prior exposure to oxytocin can mimic the effects of social contact, and can facilitate sexual receptivity by increasing the sensitivity of females to very low doses of oestradiol.

Surgical resection alone is effective treatment for ovarian immature teratoma in children and adolescents: a report of the pediatric oncology group and the children's cancer group.

OBJECTIVE: In both adult women and children the potential for malignant recurrence from ovarian immature teratoma has prompted the standard use of chemotherapy after complete resection of the primary tumor. The efficacy of postoperative chemotherapy in children and adolescents with ovarian immature teratoma, however, has not been established. A pediatric intergroup trial (INT 0106) was designed to determine the need for postoperative chemotherapy in patients with ovarian immature teratoma after management with surgical resection only. STUDY DESIGN: Between 1990 and 1995, 44 patients with completely resected ovarian immature tumor and without postoperative chemotherapy, who were able to undergo assessment, were accrued. Tumor tissue was evaluated by central pathology review to confirm diagnosis and determine tumor grading of immature neural elements. Patients were followed carefully for recurrence of disease with appropriate diagnostic imaging and serum marker studies. RESULTS: Thirty-one patients had pure ovarian immature teratoma with a tumor grade of 1 (n = 17), 2 (n = 12), or 3 (n = 2). Age at diagnosis ranged between 1.5 and 15 years (median, 10). Of the 29 patients studied, the serum alpha-fetoprotein level was elevated in 10 (34%); the median level was 25 ng/ml. Thirteen patients had ovarian immature teratoma plus microscopic foci of yolk sac tumor. Tumor grade was 1, 2, or 3 in 1, 6, and 6 patients, respectively. Age ranged between 6 and 20 years (median, 12). In the 12 patients evaluated for serum alpha-fetoprotein, 10 (83%) had elevated levels; the median level was 262 ng/ml. The 4-year event-free and overall survival for the ovarian immature teratoma group and for the ovarian immature teratoma plus yolk sac tumor group was 97.7% (95% confidence interval, 84.9%-99.7%) and 100%, respectively. The only yolk sac tumor relapse occurred in a child with ovarian immature teratoma and yolk sac tumor who was then treated with chemotherapy and is alive and free of disease 57 months after recurrence. CONCLUSION: The results of this study suggest that surgery alone is curative for most children and adolescents with resected ovarian immature teratoma of any grade, even when elevated levels of serum alpha-fetoprotein or microscopic foci of yolk sac tumor are present. This experience strongly supports avoiding the long-term effects of chemotherapy in most children with ovarian immature teratoma by reserving postoperative therapy for cases with relapse.