Stress, Coping, and Circadian Disruption Among Women Awaiting Breast Cancer Surgery

Background

Psychological distress and coping related to a breast cancer diagnosis can profoundly affect psychological adjustment, possibly resulting in the disruption of circadian rest/activity and cortisol rhythms, which are prognostic for early mortality in metastatic colorectal and breast cancers, respectively.

Purpose

This study aims to explore the relationships of cancer-specific distress and avoidant coping with rest/activity and cortisol rhythm disruption in the period between diagnosis and breast cancer surgery.

Methods

Fifty-seven presurgical breast cancer patients provided daily self-reports of cancer-specific distress and avoidant coping as well as actigraphic and salivary cortisol data.

Results

Distress and avoidant coping were related to rest/activity rhythm disruption (daytime sedentariness, inconsistent rhythms). Patients with disrupted rest/activity cycles had flattened diurnal cortisol rhythms.

Conclusions

Maladaptive psychological responses to breast cancer diagnosis were associated with disruption of circadian rest/activity rhythms. Given that circadian cycles regulate tumor growth, we need greater understanding of possible psychosocial effects in cancer-related circadian disruption.     

Oxidative stress causes renal dopamine D1 receptor dysfunction and hypertension via mechanisms that involve nuclear factor-kappaB and protein kinase C

Renal dopamine, via activation of D1 receptors, plays a role in maintaining sodium homeostasis and BP. There exists a defect in renal D1 receptor function in hypertension, diabetes, and aging, conditions that are associated with oxidative stress. However, the exact underlying mechanism of the oxidative stress-mediated impaired D1 receptor signaling and hypertension is not known. The effect of oxidative stress on renal D1 receptor function was investigated in healthy animals. Male Sprague-Dawley rats received tap water (vehicle) and 30 mM L-buthionine sulfoximine (BSO), an oxidant, with and without 1 mM tempol for 2 wk. Compared with vehicle, BSO treatment caused oxidative stress and increase in BP, which was accompanied by defective D1 receptor G-protein coupling and loss of natriuretic response to SKF38393. BSO treatment also increased NF-kappaB nuclear translocation, protein kinase C (PKC) activity and expression, G-protein-coupled receptor kinase-2 (GRK-2) membranous translocation, and D1 receptor serine phosphorylation. In BSO-treated rats' supplementation of tempol decreased oxidative stress, normalized BP, and restored D1 receptor G-protein coupling and natriuretic response to SKF38393. Tempol also normalized NF-kappaB translocation, PKC activity and expression, GRK-2 sequestration, and D1 receptor serine phosphorylation. In conclusion, these results show that oxidative stress activates NF-kappaB, causing an increase in PKC activity, which leads to GRK-2 translocation and subsequent D1 receptor hyper-serine phosphorylation and uncoupling. The functional consequence of this phenomenon was the inability of SKF38393 to inhibit Na/K-ATPase activity and promote sodium excretion, which may have contributed to increase in BP. Tempol reduced oxidative stress and thereby restored D1 receptor function and normalized BP.     

Are 3 sentinel nodes sufficient?

HYPOTHESIS: It has recently been proposed that only 3 sentinel lymph nodes (SLNs) are required for an adequate SLN biopsy. Others have advocated removing all nodes that are blue, hot, at the end of a blue lymphatic channel, or palpably suspicious or that have radioactive counts of 10% or greater of the most radioactive SLN. Our objective was to determine the false-negative rate (FNR) associated with limiting SLN biopsy to 3 nodes. DESIGN: Multicenter prospective study. SETTING: Both academic and private practice. PATIENTS: A total of 4131 patients underwent SLN biopsy followed by completion axillary node dissection. MAIN OUTCOME MEASURE: The FNR associated with 3-node SLN biopsy. RESULTS: Of the 4131 patients in this study, an SLN was identified in 3882 (94.0%). The median number of SLNs identified was 2; more than 3 SLNs were removed in 738 patients (17.9%). Of the patients in whom a SLN was identified, 1358 (35.0%) were node positive. The overall FNR in this study was 7.7%. In 89.7% of node-positive patients, a positive SLN was found in the first 3 SLNs removed. If SLN biopsy had been limited to the first 3 nodes, the FNR would be 10.3% (P = .005 compared with removing >3 SLNs). The FNR increased with the strategy of limiting SLN biopsy to fewer SLNs (P<.001). CONCLUSION: Removing only 3 SLNs cannot be recommended, because it is associated with a substantially increased FNR.     

Extramammary Paget's disease of the axilla: an unusual case

Extramammary Paget's disease is a rare lesion, often involving the skin of the genital or perianal regions. Less commonly, it has been reported to affect the skin of the axilla. There are very few other cases of extramammary Paget's disease reported in the literature, and the appropriate use of newer techniques such as magnetic resonance imaging and sentinel lymph node biopsy in this setting is not well-studied. We present a case of extramammary Paget's disease of the axilla, and discuss the known literature regarding this rare disease.     

Thromboembolism in children with lymphoma

PURPOSE: Cancer is a major underlying disease in children with thromboembolism. However, the epidemiology of thrombosis in children with cancer is largely unknown. We undertook the following study to define the epidemiology and to identify the risk factors predisposing children with lymphoma to thrombosis. PATIENTS AND METHODS: We reviewed the medical records of 75 children (<18 years of age) diagnosed with lymphoma from January 1990-December 2004. RESULTS: Nine of 75 patients (12%, 95% CI; 5.6-21.6%) were diagnosed with a total of 16 thrombotic events. Twelve of 16 (75%) events were venous thrombosis; 11 were related to the central venous line. The prevalence of pulmonary embolism was 2.6%. Nine of 51 (17.6%) patients with mediastinal lymphadenopathy developed thrombosis compared to none of 21 patients without mediastinal lymphadenopathy (Z=3.31, p=0.001, 95%CI; 7.2-28.1%). Older children and children with advanced stage disease were at higher, but statistically non-significant risk of thrombosis. There was no effect of gender, lymphoma type, or B-symptoms on the occurrence of thrombosis. Four of 9 patients (44%) experienced recurrent clots and 3 (33.3%) patients had post-thrombotic syndrome. Children with thrombosis had a higher rate of adverse events compared to those without thrombosis (41% vs. 21.2%, p=0.126). CONCLUSION: Thrombosis is a frequent complication in children with lymphoma with over a 40% recurrence rate and significant morbidity. Children with a mediastinal mass were at significantly increased risk of thrombosis. Larger prospective studies are required to confirm these findings and to identify children at an increased risk for the development of thrombosis.     

Synthesis, antiviral, antituberculostic and antibacterial activities of some novel, 4-(4'-substituted phenyl)-6-(4"-hydroxyphenyl)-2-(substituted imino) pyrimidines

A variety of novel 4-[(4'-substituted phenyl)-6-(4"-hydroxyphenyl)-2-substituted imino] pyrimidines were synthesized by reacting 4-(4'-substituted phenyl)-6-(4"-hydroxyphenyl)-2-aminopyrimidines with different substituted aromatic aldehydes, with coumarin and with chloroisatin. The 4-(4'-chlorophenyl)-6-(4"-hydroxyphenyl)-2-aminopyrimidines were synthesized by reacting 3-(4'-substituted phenyl)-1-(4"-hydroxyphenyl)-2-propen-1-ones with guanine hydrochloride. The 3-(4'-substituted phenyl)-1-(4"-hydroxyphenyl)-2-propen-1-ones were synthesized by reacting 4-hydroxyacetophenone with different para substituted aromatic aldehydes. Spectral data (IR, NMR, and mass spectra) confirmed the structures of the synthesized compounds. The synthesized compounds were investigated for their antiviral, antituberculostic and antibacterial activities. The results indicated that the synthesized compounds have mild to potent activities with reference to their appropriate reference standards. However, mechanism related studies could be carried out to predict the structure activity relationship for all the compounds.     

Body mass index influences palpability but not stage of breast cancer at diagnosis

Body mass index (BMI) is associated with breast cancer risk, but its relationship with stage at diagnosis is unclear. BMI was calculated for patients in the North American Fareston and Tamoxifen Adjuvant trial, and was correlated with clinicopathologic factors, including stage at diagnosis. One thousand eight hundred fourteen patients were enrolled in the North American Fareston and Tamoxifen Adjuvant study; height and weight were recorded in 1451 (80%) of them. The median BMI was 27.1 kg/m2 (range, 14.7-60.7). The median patient age was 68 years (range, 42-100); median tumor size was 1.3 cm (range, 0.1-14 cm). One thousand seven hundred ninety-three (99.0%) patients were estrogen receptor positive, and 1519 (84.7%) were progesterone receptor positive. There was no significant relationship between BMI (as a continuous variable) and nodal status (P = 0.469), tumor size (P = 0.497), American Joint Committee on Cancer stage (P = 0.167), grade (P = 0.675), histologic subtype (P = 0.179), or estrogen receptor status (P = 0.962). Patients with palpable tumors, however, had a lower BMI than those with nonpalpable tumors (median 26.4 kg/m2 vs 27.5 kg/m2, P < 0.001). Similar results were found when BMI was classified as a categorical variable (<25 vs 25-29.9 vs > or =30). Increased BMI does not lead to a worse stage at presentation. Obese patients, however, tend to have nonpalpable tumors. Mammography in this population is especially important.     

Efficacy of intravenous magnesium for the management of non-post operative atrial fibrillation with rapid ventricular response: A systematic review and meta-analysis

Background

Intravenous magnesium (IV Mg), a commonly utilized therapeutic agent in the management of atrial fibrillation (AF) with rapid ventricular response, is thought to exert its influence via its effect on cellular automaticity and prolongation of atrial and atrioventricular nodal refractoriness thus reducing ventricular rate. We sought to undertake a systematic review and meta-analysis of the effectiveness of IV Mg versus placebo in addition to standard pharmacotherapy in the rate and rhythm control of AF in the nonpostoperative patient cohort given that randomized control trials (RCTs) have shown conflicting results.

Methods

Randomized controlled trials comparing IV Mg versus placebo in addition to standard of care were identified via electronic database searches. Nine RCTs were returned with a total of 1048 patients. Primary efficacy endpoints were study-defined rate control and rhythm control/reversion to sinus rhythm. The secondary endpoint was patient experienced side effects.

Results

Our analysis found IV Mg in addition to standard care was successful in achieving rate control (odd ratio [OR] 1.87, 95% confidence interval [CI] 1.13−3.11, p = .02) and rhythm control (OR 1.45, 95% CI 1.04−2.03, p = .03). Although not well reported among studies, there was no significant difference between groups regarding the likelihood of experiencing side effects.

Conclusions

IV Mg, in addition to standard-of-care pharmacotherapy, increases the rates of successful rate and rhythm control in nonpostoperative patients with AF with rapid ventricular response and is well tolerated.