Estradiol and tryptophan depletion interact to modulate cognition in menopausal women.

Despite an abundance of data in animals, there is little research in humans regarding how estrogen and serotonin (5-HT) may interact to influence cognition. Through the use of estrogen treatment (ET) and tryptophan depletion (TRP-D) in a within-subject design involving healthy menopausal women, we have manipulated both estrogen and 5-HT in order to evaluate their individual and joint effects. Although neither manipulation influenced visuospatial learning, a significant interaction suggested that estrogen exerted a protective effect on verbal memory, such that TRP-D impaired performance to a greater extent before the administration of ET. In consonance with this finding, ET was associated with a small, but positive mood effect on the day following active TRP-D. In addition, ET significantly improved letter-cued verbal fluency with and without TRP-D. Finally, time since last menstrual period was significantly associated with verbal memory scores, such that longer length of hypogonadism resulted in decreased verbal memory performance. These data support the interaction of estrogen and 5-HT in nonreproductive behavior in humans as well as highlight the role of ovarian steroids in cognition.     

p53 and skin carcinomas with skull base invasion: a case-control study.

BACKGROUND: Some skin carcinomas may be very aggressive. Increased expression of the protein p53 has been associated with tumor aggressiveness. In this study, p53 expression was evaluated in basal cell carcinomas (BCC) and squamous cell carcinomas (SCC) with skull base invasion, and was compared to tumors with good outcome. STUDY DESIGN AND SETTING: Expression of p53 was immunohistochemically analyzed and it was reported as present or absent in 24 BCC and 11 SCC with skull base invasion. Control group (good outcome) included 23 BCC and 10 SCC. RESULTS: Expression of p53 was noted in 70.83% of BCC with skull base invasion, compared to 43.48% in the control group (P = 0.058). Regarding SCC, p53 positivity was noted in only 9.09% of SCC with skull base invasion, compared to 40.00% in the control group (P = 0.149). CONCLUSIONS: In this study, p53 expression was more common among BCC with skull base invasion, compared to controls with good outcome, and the difference was considered marginally significant. This proportion was reversed in SCC, but the difference was not statistically significant. EBM rating: B-3b.     

Antiemetic care for patients with breast cancer: focus on drug interactions and safety concerns.

PURPOSE: The drug interactions and adverse events that should be considered when individualizing antiemetic therapy for patients undergoing treatment for breast cancer are reviewed. SUMMARY: A variety of antiemetic agents are available, including antihistamines, dopamine-receptor antagonists, serotonin-receptor antagonists, and neurokinin-receptor antagonists. To ensure optimal symptom control for each patient without unnecessarily prolonging treatment, patient- and treatment-specific risk factors must be considered. Neurokinin-receptor antagonists, the newest class of antiemetics, are effective in preventing acute and delayed chemotherapy-induced nausea and vomiting but must be used in combination with a serotonin-receptor antagonist and a corticosteroid. The serotonin-receptor antagonists have become the mainstay of antiemetic therapy, but current guidelines do not distinguish among the different agents in this class. However, there are distinct pharmacologic differences that may affect the potential for drug interactions and, ultimately, patient outcomes and the occurrence of adverse events. Therefore, the potential for drug interactions must be considered when selecting an antiemetic, particularly for patients who are taking multiple concomitant medications. Further, because a number of breast cancer therapies and some antiemetic agents carry cardiovascular warnings or precautions and since breast cancer patients may already be suffering from cardiovascular complications, the possible cardiotoxic effects of the antiemetic or chemotherapy agents or the combinations of these agents should be considered. CONCLUSION: Antiemetic treatment is essential for patients with breast cancer who are undergoing moderately to highly emetogenic cytotoxic treatment. When selecting an antiemetic, clinicians must select an agent that provides optimal protection against nausea and vomiting while avoiding drug-drug interactions and additional adverse events.     

Artifacts due to stimulus correlated motion in functional imaging of the brain

To assess the effect of stimulus correlated motion on the appearance of functional magnetic resonance images, conventional visual and motor protocols were each performed by four normal volunteers and an image co-registration technique was used to retrospectively monitor subject motion. In three studies synthetic data sets were constructed from single baseline images using the positional information obtained from the co-registration procedure. Cumulative difference images were then created from both the synthetic and functional image sets. Stimulus correlated motion was detected in all eight studies and the synthetic cumulative difference images showed striking similarities to the equivalent functional images in each case.     

Relationship between Mandarin speech reception thresholds and pure-tone thresholds in the geriatric population.

BACKGROUND/PURPOSE: In the geriatric population, the reliability of pure-tone threshold (PTT) is sometimes poorer than that in young adults because of various reasons. This study assessed the relationship between Mandarin speech reception thresholds (SRTs) and PTTs in the aged and developed SRT as a measure for corroborating PTT. METHODS: This prospective study enrolled 46 consecutive subjects over 60 years of age. The results of SRT and PTT were collected from one ear randomly selected from each subject. Simple linear and multiple regressions were used to determine the correlation and linear regression coefficients between SRTs and PTTs at various frequencies. RESULTS: In the simple regression analysis, the correlation coefficient was highest at 1000 Hz (r = 0.949) and 500 Hz (r = 0.922), followed by 250 Hz (r = 0.850) and 2000 Hz (r = 0.792). In the multiple regression model with SRT as the dependent variable and PTTs as predictor variables, the resultant multiple correlation coefficient R was 0.967, while R2 was 0.936. In this model, PTTs at the frequencies of 500 Hz and 1000 Hz contributed significantly to the variance in SRTs with p values of 0.029 and < 0.001, respectively. These results demonstrated that the Mandarin SRT is strongly associated with PTTs at the frequencies of 500 Hz and 1000 Hz. CONCLUSION: This study established the agreement between Mandarin SRTs and PTTs in the low tone area of speech frequencies in the geriatric population. In clinical settings, SRT test can be rapidly and easily performed and is relatively inexpensive. It is a vital indicator of the accuracy of PTT measurement.     

Influence of hospital characteristics on operative death and survival of patients after major cancer surgery in Ontario.

BACKGROUND: There is a lack of information from Canadian hospitals on the role of hospital characteristics such as procedure volume and teaching status on the survival of patients who undergo major cancer resection. Therefore, we chose to study these relationships using data from patients treated in Ontario hospitals. METHODS: We used the Ontario Cancer Registry from calendar years 1990-2000 to obtain data on patients who underwent surgery for breast, colon, lung or esophageal cancer or who underwent major liver surgery related to a cancer diagnosis between 1990 and 1995 in order to assess the influence of volume of procedures and teaching status of hospitals on in-hospital death rate and long-term survival. For each disease site and before observing patient outcomes data, volume cut-off points were selected to create volume groups with similar numbers of patients. Teaching hospitals were those directly affiliated with a medical school. Logistic regression and proportional hazards models were used to consider the clustering of data at the hospital level and to assess operative death and long-term survival. We also used 4 measures to gauge the degree of procedure regionalization across the province including (1) the number of hospitals performing a procedure; (2) the percentage of patients treated in teaching hospitals; (3) the percentage of rural patients treated in higher volume procedure hospitals; and (4) median distances travelled by patients to receive care. RESULTS: The number of patients in our cohorts who underwent resection of the breast, colon, lung, esophagus or liver was 14 346, 8398, 2698, 629 and 362, respectively. Surgery in a high-volume versus a low-volume hospital did not have a statistically significant influence on the odds of operative death for patients who underwent colon, liver, lung or esophageal cancer resection. The risk of long-term death was increased in low-volume versus high-volume hospitals for patients who underwent resection of the breast (hazard ratio [HR] 1.2, 95% confidence interval [95% CI] 1.0-1.4, p < 0.05), lung (HR 1.3, 95% CI 1.1-1.6, p < 0.01) and liver (HR 1.7, 95% CI 1.0-2.7, p = 0.04). There were no significant differences in the odds of operative (in-hospital) death or risk of long-term death among patients treated in teaching compared with nonteaching hospitals. There was more regionalization of liver, lung and esophageal operations versus breast and colon operations. CONCLUSIONS: Increased hospital procedure volume correlated with improved longterm survival for patients in Ontario who underwent some, but not all, cancer resections, whereas hospital teaching status had no significant impact on patient outcomes. Across the province, further regionalization of care may help improve the quality of some cancer procedures.     

Spatiotemporal pattern of striatal ERK1/2 phosphorylation in a rat model of L-DOPA-induced dyskinesia and the role of dopamine D1 receptors.

BACKGROUND: We examined the activation pattern of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and its dependence on D1 versus D2 dopamine receptors in hemiparkinsonian rats treated with 3,4-dihydroxyphenyl-L-alanine (L-DOPA). METHODS: 6-Hydroxydopamine-lesioned rats were treated acutely or chronically with L-DOPA in combination with antagonists for D1 or D2 receptors. Development of dyskinesia was monitored in animals receiving chronic drug treatment. Phosphorylation of ERK1/2, mitogen- and stress-activated protein kinase-1 (MSK-1), and the levels of FosB/DeltaFosB expression were examined immunohistochemically. RESULTS: L-DOPA treatment caused phosphorylation of ERK1/2 in the dopamine-denervated striatum after acute and chronic administration. Similar levels were observed in matrix and striosomes, and in enkephalin-positive and dynorphin-positive neurons. The severity of dyskinesia was positively correlated with phospho-ERK1/2 levels. Phosphorylation of ERK1/2 and MSK-1 was dose-dependently blocked by SCH23390, but not by raclopride. SCH23390 also inhibited the development of dyskinesia and the induction of FosB/DeltaFosB. CONCLUSIONS: L-DOPA produces pronounced activation of ERK1/2 signaling in the dopamine-denervated striatum through a D1-receptor-dependent mechanism. This effect is associated with the development of dyskinesia. Phosphorylated ERK1/2 is localized to both dynorphinergic and enkephalinergic striatal neurons, suggesting a general role of ERK1/2 as a plasticity molecule during L-DOPA treatment.     

Treatment of an infected total hip replacement with the PROSTALAC system: Part 1: Infection resolution

INTRODUCTION: Infection after total hip replacement (THR) is a serious medical complication with significant negative ramifications for both the patient and the health care system. The prosthesis of antibiotic-loaded acrylic cement (PROSTALAC) was designed to treat the joint infection while maintaining functional movement in the hip. METHODS: We identified 28 patients treated for infected THR with the PROSTALAC system, by retrospective chart review. Preoperative and intraoperative cultures were taken to identify the causative organism. After PROSTALAC insertion, patients underwent at least 6 weeks of intravenous (IV) antibiotics. Prior to undergoing posttreatment cultures, patients were required to be antibiotic-free for a minimum of 6 weeks, with normal laboratory values. We defined resolution infection as retention of a joint prosthesis for a minimum of 2 years. RESULTS: Infection was identified in 28 patients in either the joint aspirate or intraoperative cultures. Of these patients, 2 failed to clear infection, requiring repeat PROSTALAC insertion. Two additional patients had positive 48-hour cultures post-second stage, treated with additional IV antibiotics. Retention of the post-PROSTALAC prosthesis is 100% at 2 years. CONCLUSION: PROSTALAC has acceptable infection resolution outcomes and appears effective for treating infected THR.