Cognitive Effects of Chemotherapy-Induced Menopause in Breast Cancer

This study examined whether chemotherapy-induced menopause affects cognitive functioning in women with early breast cancer. The neuropsychological performance of 121 breast cancer patients (age M?=?49.62, SD?=?8.11, range?=?25.25–67.92) treated with chemotherapy was assessed pre-chemotherapy, as well as 1, 6, and 18 months post-chemotherapy completion. Linear mixed modeling was used to evaluate the data. Type of menopause (pre, chemotherapy-induced, and post menopause) was found to significantly interact with cognitive performance on two cognitive variables. Specifically, chemotherapy-induced menopausal women did not show any significant changes in performance on an abstract reasoning task, while the pre-menopausal and post-menopausal groups significantly improved over time. A significant interaction on a test of finger dexterity and coordination was also found, although inspection of the results indicated that this was due to a significant improvement in the pre-menopausal groups at 6 months post chemotherapy. After chemotherapy most cognitive variables showed improvements over time, although two indicators of verbal memory showed significant declines immediately after chemotherapy, with improvement by 18 months post completion. The current study found little evidence to suggest that chemotherapy-induced menopause broadly affects cognitive functioning after treatment administration. However, longer follow-up assessments are warranted to assess the long-term effects of combined chemotherapy and endocrine treatment.     

Exercise Studies in Patients With Rotary Blood Pumps: Cause,Effects, and Implications for Starling‐Like Control of Changes in Pump Flow

This multicenter study examines in detail the spontaneous increase in pump flow at fixed speed that occurs in exercise. Eight patients implanted with the VentrAssist rotary blood pump were subjected to maximal and submaximal cycle ergometry studies, the latter being completed with patients supine and monitored with right heart catheter and echocardiography. Maximal exercise studies conducted in each patient at three different pump speeds on separate days established initially the magnitude and consistency of increases in pump flow that correlated well with changes in heart rate. However, there was considerable variation, coefficients of variation for mean heart rate and pump flow being 47.9 and 49.3%, respectively. Secondly, these studies indicated that increasing pump flows caused significant improvements in maximal exercise capacity. An increase of 2.1 L/min (35%) in maximum blood flow caused 12 W (16%) further increase in achievable work, 1.26 (9.3%) mL/kg/min in maximal oxygen uptake, and 2.3 (23%) mL/kg/min in anaerobic threshold. Mean increases in lactate were 0.85 mm (24%), but mean B‐type natiuretic peptide fell by 126 mm , (?78%). From submaximal supine exercise studies, multiple linear regression of pump flow on factors thought to underlie the spontaneous increase in pump flow indicated that it was associated with increases in heart rate (P = 0.039), pressure gradient across the left ventricle (P = 0.032), and right atrial pressure (P = 0.003). These changes have implications for the recently reported Starling‐like controller for pump flow based on pump pulsatility values, which emulates the Starling curve relating pump output to left ventricular preload. Unmodified, the controller would not permit the full benefits of this effect to be afforded to patients implanted with rotary blood pumps. A modification to the pump control algorithm is proposed to eliminate this problem     

Influence of HTLV-1 on the clinical, microbiologic and immunologic presentation of tuberculosis

ABSTRACT: BACKGROUND: HTLV-1 is associated with increased susceptibility to Mycobacterium tuberculosis infection and severity of tuberculosis. Although previous studies have shown that HTLV-1 infected individuals have a low frequency of positive tuberculin skin test (TST) and decreasing in lymphoproliferative responses compared to HTLV-1 uninfected persons, these studies were not performed in individuals with history of tuberculosis or evidence of M. tuberculosis infection. Therefore the reasons why HTLV-1 infection increases susceptibility to infection and severity of tuberculosis are not understood.The aim of this study was to evaluate how HTLV-1 may influence the clinical, bacteriologic and immunologic presentation of tuberculosis. METHODS: The study prospectively enrolled and followed 13 new cases of tuberculosis associated with HTLV-1 (cases) and 25 patients with tuberculosis without HTLV-1 infection (controls). Clinical findings, bacterial load in the sputum, x-rays, immunological response and death were compared in the two groups. RESULTS: There were no differences in the demographic, clinical and TST response between the two study groups. IFN-gamma and TNF-alpha production was higher in unstimulated cultures of mononuclear cells of case than in control patients (p < 0.01). While there was no difference in IFN-gamma production in PPD stimulated cultures, TNF-alpha levels were lower in cases than in controls (p = 0.01). There was no difference in the bacterial load among the groups but sputum smear microscopy results became negative faster in cases than in controls. Death only occurred in two co-infected patients. CONCLUSION: While the increased susceptibility for tuberculosis infection in HTLV-1 infected subjects may be related to impairment in TNF-alpha production, the severity of tuberculosis in co-infected patients may be due to the enhancement of the Th1 inflammatory response, rather than in their decreased ability to control bacterial growth.     

Assessment of contrast‐enhanced computed tomography for imaging of cartilage during fracture healing

Assessment of the early stages of fracture healing via X‐rays and computed tomography is limited by the low radio‐opacity of cartilage. We validated a method of contrast‐enhanced computed tomography (CECT) for non‐destructive identification of cartilage within a healing fracture callus. Closed, stabilized fractures in femora of C57BL/6 mice were harvested on post‐operative day 9.5 and imaged ex vivo with micro‐computed tomography (µCT) before and after incubation in a cationic contrast agent that preferentially accumulates in cartilage due to the high concentration of sulfated glycosaminoglycans in the tissue. Co‐registration of the pre‐ and post‐incubation images, followed by image subtraction, enabled two‐ and three‐dimensional delineation of mineralized tissue, soft callus, and cartilage. The areas of cartilage and callus identified with CECT were compared to those identified with the gold‐standard method of histomorphometry. No difference was found between the areas of cartilage measured by the two methods (p = 0.999). Callus area measured by CECT was smaller than, but strongly predictive of (R² = 0.80, p < 0.001), the corresponding histomorphometric measurements. CECT also enabled qualitative identification of mineralized cartilage. These findings indicate that the CECT method provides accurate, quantitative, and non‐destructive visualization of the shape and composition of the fracture callus, even during the early stages of repair when little mineralized tissue is present. The non‐destructive nature of this method would allow subsequent analyses, such as mechanical testing, to be performed on the callus, thus enabling higher‐throughput, comprehensive investigations of bone healing. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 567–573, 2013     

Oscillatory activity during maintenance of spatial and temporal information in working memory

Working memory (WM) processes help keep information in an active state so it can be used to guide future behavior. Although numerous studies have investigated brain activity associated with spatial WM in humans and monkeys, little research has focused on the neural mechanisms of WM for temporal order information, and how processing of temporal and spatial information might differ. Available evidence indicates that similar frontoparietal regions are recruited during temporal and spatial WM, although there are data suggesting that they are distinct processes. The mechanisms that allow for differential maintenance of these two types of information are unclear. One possibility is that neural oscillations may differentially contribute to temporal and spatial WM. In the present study, we used scalp electroencephalography (EEG) to compare patterns of oscillatory activity during maintenance of spatial and temporal information in WM. Time-frequency analysis of EEG data revealed enhanced left frontal theta (5–8 Hz), enhanced posterior alpha (9–12 Hz), and enhanced left posterior beta (14–28 Hz) power during the delay period of correct temporal order trials compared to correct spatial trials. In contrast, gamma (30–50 Hz) power at right lateral frontal sites was increased during the delay period of spatial WM trials, as compared to temporal WM trials. The present results are consistent with the idea that neural oscillatory patterns provide distinct mechanisms for the maintenance of temporal and spatial information in WM. Specifically, theta oscillations are most critical for the maintenance of temporal information in WM. Possible roles of higher frequency oscillations in temporal and spatial memory are also discussed.