Sex Differences and the Impact of Chronic Stress and Recovery on Instrumental Learning.

We have previously shown that 21-day chronic restraint stress impacts instrumental learning, but overall few studies have examined sex differences on the impact of stress on learning. We further examined sex differences in response to extended 42-day chronic stress on instrumental learning, as well as recovery from chronic stress. Rats were tested in aversive training tasks with or without prior appetitive experience, and daily body weight data was collected as an index of stress. Relative to control animals, reduced body weight was maintained from day 22 through day 42 across the stress period for males, but not for females. Stressed males had increased response speed and lower learning efficiency during appetitive acquisition and aversive learning. Males overall showed slower escape shaping times and more shock exposure. In contrast, stressed females showed slower appetitive response speeds and higher appetitive and aversive efficiency but overall reduced avoidance rates during acquisition and maintenance for transfer animals and during maintenance for aversive-only animals. These tasks reveal important nuances on the effect of stress on goal-directed behavior and further highlight sexually divergent effects on appetitive versus aversive motivation. Furthermore, these data underscore that systems are temporally impacted by chronic stress in a sexually divergent pattern.

Oral eplerenone for treatment of chronic central serous chorioretinopathy: a case series.

BACKGROUND AND OBJECTIVE: To evaluate the effect of oral eplerenone on subretinal fluid, visual acuity, and choroidal thickness in patients with chronic central serous chorioretinopathy (CSCR). PATIENTS AND METHODS: Retrospective review of all patients (14 eyes of 14 patients) monitored for a minimum of 3 months with chronic CSCR who were treated with oral eplerenone in a single multi-physician retina practice. Visual acuity, dilated funduscopic examination, and spectral-domain ocular coherence tomography (OCT) with enhanced depth imaging (EDI) were obtained at each visit. Measurement of subfoveal fluid (SFF) height and choroidal thickness were performed. Two-tailed paired t test was used to calculate statistical significance of pre- and post-treatment variables. RESULTS: At 1 month, 10 of 14 eyes had decreased SFF height on OCT and two eyes had complete resolution of SFF. Mean SFF height decreased from 130 µm to 62 µm (P = .05). Mean choroidal thickness decreased from 315 µm to 282 µm (P = .07). Mean visual acuity improved from logMAR 0.41 to 0.40. At 3 months, 13 of 14 (93%) had decreased SFF on OCT, and nine eyes (64%) had complete resolution of SFF. Mean SFF height decreased to 21 µm (P = .004). Mean choroidal thickness decreased to 253 µm (P = .10). Mean visual acuity improved to logMAR 0.28 (P = .02). CONCLUSION: Oral eplerenone may be effective in treating patients with chronic CSCR.

Nicotinic receptor activation in perirhinal cortex and hippocampus enhances object memory in rats.

The perirhinal cortex (PRh) and its cholinergic inputs are implicated in object recognition memory. Conversely, the hippocampus (HPC) may be involved in spatial recognition processes that are not essential to the recognition of objects per se. Systemic nicotine has been shown to facilitate both object and spatial memory. The current study compared the roles of perirhinal and hippocampal nicotinic acetylcholine receptors (nAChRs) in object and spatial recognition memory using spontaneous object recognition (SOR) and object-location (OL) tasks for rats. Systemic pre-sample (acquisition) nicotine administration dose-dependently facilitated SOR and OL performance compared to vehicle conditions in which performance was at chance with a 72-h retention delay between the sample and choice phases. Subsequently, pre-sample intra-PRh infusions of nicotine significantly facilitated SOR; somewhat surprisingly, pre-sample intra-HPC nicotine also enhanced object recognition memory. Further experiments indicated facilitative effects on OL performance caused by pre-sample intra-PRh or intra-HPC nicotine administration. These results not only demonstrate that nAChR activation facilitates performance on object recognition and object-location memory tasks, but suggest that these effects can be produced by nAChR action in either PRh or HPC. Thus, although PRh and HPC are not required for OL or SOR task performance, respectively, nAChR-mediated enhancement of neural function in either of these temporal lobe regions appears capable of promoting stronger memory encoding and/or consolidation in either task. These findings further support the supposed interactive relationship between the HPC and PRh in object information processing and highlight the potential therapeutic value of nicotinic receptor activation in amnesic disorders.

Nerve injury-induced changes in GABA(A) and GABA(B) sub-unit expression in area 3b and cuneate nucleus of adult squirrel monkeys: further evidence of developmental recapitulation.

The primate somatosensory system provides an excellent model system with which to investigate adult neural plasticity. Here, we report immunohistochemical staining data for the GABA(A) α1, GABA(B)R1a, and GABA(B)R1b receptor subunits in somatosensory area 3b, and cuneate nucleus one week after median nerve compression in adult squirrel monkeys. We find a significant decrease in GABA(A) α1 subunit staining across all cortical layers and within both soma and neuropil of the deprived cortical and brainstem regions. The GABA(B) staining showed an opposing shift in deprived regions, with a significant increase in presynaptic GABA(B)R1a staining, and a significant decrease in postsynaptic GABA(B)R1b staining in deprived regions of the cortex and brainstem. These changes in receptor subunit expression generate patterns that are very similar to those reported in the neonate. Furthermore, the similarities between brainstem and cortical expression suggest conserved forms of adult plasticity in these two regions. Taken together these results, along with the results from our previous paper investigating AMPA subunit expression in these same animals, support the hypothesis that deprived neurons enter a previously hidden state of developmental recapitulation that serves to prime the brain for NMDA receptor mediated receptive field reorganization.

The cortical response to sensory deprivation in adult rats is affected by gonadectomy.

The present study investigated the effects of adult-onset sensory deprivation and gonadectomy. Adult male and female rats underwent unilateral transection of the infraorbital nerve. Half of the subjects had been gonadectomized 1 week prior to the nerve injury. We found that the areas of deprived barrels were significantly reduced when compared to barrels in the contralateral control hemisphere, and that this shrinkage was independent of sex and gonadectomy. We also found significant reductions in cytochrome oxidase staining intensity in the deprived barrels. While there were no differences in the magnitude of this effect between males and females, this effect was substantially more pronounced in the gonadectomized subjects. That is, gonadal hormones appeared to play a significant neuroprotective role in the metabolic response of the barrel cortex to deprivation. Thus, either males and females have a common neuroprotective hormonal pathway, or each has a sex-specific hormone pathway that serves an equivalent neuroprotective function.

Long-term results of maximally aggressive trimodality therapy in a high-risk subset of early-stage cervical cancer patients.

OBJECTIVE: To evaluate the long-term survival and treatment-related morbidity associated with treating patients who have early-stage cervical carcinoma metastatic to the paraaortic lymph nodes with radical hysterectomy, pelvic and paraaortic lymphadenectomy, and adjuvant, extended field chemoradiation with cisplatin and 5-fluorouracil (5-FU). STUDY DESIGN: From 1988 to 1997, 14 consecutive patients referred to Radiological Associates of Sacramento following radical hysterectomy and pelvic and paraaortic lymphadenectomy with findings of clinical stage IB or IIA cervical cancer and histologically confirmed lymph node metastasis to the common iliac or paraaortic distributions were treated with adjuvant, extended field chemoradiation utilizing prolonged infusion 5-FU and bolus cisplatin. Retrospective chart review was performed, and survival and morbidity information were analyzed. Recurrence was assessed among patients based on age, race, total number of nodes involved, gross vs. microscopic nodal involvement, squamous vs. nonsquamous tumor histology, time to initiation of adjuvant treatment and time required to complete that treatment. Calculated 5-year survival, mean survival, morbidity type and incidence are reported for the group as a whole. RESULTS: Calculated 5-year survival of patients in this series was 38% by life table analysis. Median survival was 4.4 years; 50% of patients had a recurrence. None of the examined parameters were significant predictors of recurrence. There was 1 treatment-related death and a second case of severe treatment-related morbidity (radiation enteritis requiring colostomy and bilateral ureteral stenosis requiring bilateral nephrostomies). There were 6 cases of minor treatment-related toxicity occurring in 5 of 14 (36%) treated patients. CONCLUSION: In general, survival in the current series of patients was akin to that in clinically similar patients treated with chemoradiation alone. Morbidity among our patients was significant. In the presence of positive paraaortic lymph nodes there were no independent predictors of recurrence among the pathologic or treatment parameters examined.

Malignant thymoma metastatic to the pelvis: a rare case and considerations for management.

BACKGROUND: Thymoma is the most common tumor of the anterior mediastinum. Due to its relative rarity, its inconsistent clinical course and its frequent proximity to vital thoracic structures, management of this generally indolent tumor varies considerably. We present an unusual case of recurrent thymoma metastatic to the pelvis and review treatment experience employing surgical, radiotherapeutic and medical modalities. CASE REPORT: The present case is that of a 46-year-old woman with recurrent thymoma metastatic to a distal pelvic lymph node. Resection of the pelvic recurrence followed many years of local and systemic treatment for her thoracic primary tumor. Her case is unique for its involvement of pelvic anatomy and her clinical course marked by treatment-related congestive heart failure. CONCLUSION: While the indolent clinical course of thyomoma frequently necessitates re-treatment and multi-modality therapy in patients suffering recurrences, treatment selection must take into account potential long-term morbidity and attendant quality of life. When anatomically and technically feasible, resection of recurrent disease should be considered in attempts to avoid potential cumulative and long-term toxicity resultant from radiotherapy and chemotherapy.

Merkel cell carcinoma of the Bartholin's gland.

BACKGROUND: There are a few cases of "small cell neuroendocrine carcinoma" of the Bartholin's gland as well as Merkel cell carcinoma of the vulva reported in the gynecologic oncology literature, most with aggressive clinical behavior. Merkel cells were originally described in the epidermis with neuroendocrine properties. Merkel cell carcinoma is different from the neuroendocrine small cell (oat cell) tumor arising in the lung and other internal organs based on morphology and immunohistochemistry. CASE: A 49-year-old female was diagnosed with a FIGO stage I Merkel cell carcinoma of the Bartholin's gland. The tumor originated from the duct and stained with endocrine markers and cytokeratin 7 and 20. She was treated with radical wide local excision and bilateral inguinal lymph node dissection followed by radiation therapy to the pelvis, perineum, vulva, and inguinal regions. Two years after the diagnosis, she is alive with no evidence of recurrent disease. CONCLUSION: This is a case of Merkel cell carcinoma of the Bartholin's gland discovered in the early stage with a survival of 2 years following diagnosis and treatment with no evidence of disease recurrence.

A retrospective review of 15 years of radical radiotherapy with or without concurrent cisplatin and/or 5-fluorouracil for the treatment of locally advanced cervical cancer.

Radiation therapy is the standard of care treatment for locally advanced cervical cancer in the United States. In 1999 the addition of concomitant chemotherapy to radical radiotherapy became standard. The addition of cisplatin (CDDP) with or without 5-fluorouracil (5-FU) chemotherapy to radiation therapy was based on the near simultaneous reporting of five randomized, controlled clinical trials which all showed an improvement in survival with a magnitude of approximately 35%. The purpose of our study was to test the hypothesis that the addition of chemotherapy improved survival in our patients. We identified 291 patients treated with primary 'intent-to-cure' radiation therapy for locally advanced carcinoma of the cervix between 1985 and 2000. We analyzed patients using a stepwise Cox regression, including as possible predictors: clinical stage, age at diagnosis, use of concurrent chemotherapy with radiation and method of teletherapy delivery. We also examined survival as a function of CRT with a CDDP and/or 5-FU containing regimen using the Kaplan-Meier estimates of overall survival. The use of concurrent CDDP and/or 5-FU chemotherapy with radiation (CRT) was not associated with an increase in disease free survival (p=0.734) or overall survival (p=0.989). In this retrospective study there was no disease free or overall survival benefit from the addition of CDDP and/or 5-FU chemotherapy to radical radiotherapy for the treatment of locally advanced cervical carcinoma, although there was a trend favoring CRT.

Prolonged survival in recurrent endometrial carcinoma to the brain.

BACKGROUND: Recurrence of endometrial cancer in the brain is a rare event generally accompanied by limited life expectancy. We present an unusual case of long-term survival following surgical resection of an intracranial endometrial cancer metastasis. CASE: The present case is a patient with FIGO stage IIB, grade III endometrial cancer which recurred 2 months following completion of primary therapy with an isolated lesion in the brain. Aggressive trimodal therapy was initiated with curative intent and she has remained without clinical or radiographic evidence of disease for more than 30 months following treatment of her recurrence. CONCLUSIONS: Aggressive multi-modal therapy is warranted in the treatment of isolated intracranial recurrences of endometrial cancer in carefully selected patients. With complete surgical resection of disease, the precise nature and role of adjuvant treatment has yet to be clearly defined.