Assessment of myocardial hypertrophy by echocardiography in adult patients receiving tacrolimus or cyclosporine therapy for prevention of acute GVHD.

The incidence of myocardial hypertrophy was determined in a comparative study of tacrolimus-based immunosuppression with cyclosporine-based immunosuppression for prevention of acute graft-versus-host disease (GVHD) after unrelated donor bone marrow transplantation. Patients were evaluated for clinical and echocardiographic abnormalities at baseline (prior to pretreatment conditioning and the first dose of study drug) and at 5-8 weeks after transplant when stable levels of oral tacrolimus or cyclosporine had been achieved. Left ventricular geometry and performance were assessed by echocardiography which included 2-D measurements and one Doppler measurement. Derived echocardiographic measurements and left ventricular mass index (LVMI) were also determined. A cut-off of <111 g/m(2) was used for the upper limit of normal for LVMI. Forty-four patients were included in this study (21 tacrolimus and 23 cyclosporine), of which 31 were evaluable for a comparison with both baseline and post-transplant values. There was no significant difference in the changes from baseline for mean left ventricular mass (LVM) or LVM index (LVMI) between treatment groups. Also, within the tacrolimus group there were no significant changes for these variables from baseline to post-transplant evaluations. Within the cyclosporine group there were significant increases from baseline for mean LVM (P = 0.011) and LVMI (P = 0.007). The incidence of myocardial hypertrophy (change of LVMI from <111 g/m(2) baseline to >111 g/m(2) post transplant) was 20% in the tacrolimus group and 56% in the cyclosporine group (P = 0.109). Changes in the LVMI from baseline to post baseline were greater with cyclosporine than with tacrolimus therapy, and there was no evidence that tacrolimus causes myocardial hypertrophy or significant clinical changes in adult bone marrow transplant patients. The increase in LVMI after transplant in the cyclosporine group was greater than in the tacrolimus group but was not associated with any significant clinical events.     

Evidence for the presence of calsequestrin in both peripheral and interior regions of sheep Purkinje fibers

Localization of calsequestrin in sheep Purkinje fibers was determined by indirect immunofluorescence labeling of cryostat sections of sheep myocardium from the intraventricular wall. The results presented show that calsequestrin is present in discrete foci at the peripheral, as well as the interior regions of the cytoplasm. Since Purkinje fibers lack transverse tubules, the presence of calsequestrin at specific foci in the interior regions of the cytoplasm in these cells suggests that calsequestrin is localized in the lumen of peripheral junctional sarcoplasmic reticulum, as well as in the lumen of corbular sarcoplasmic reticulum present in the I band region of the myofibrils. Assuming that the function of calsequestrin is to sequester calcium into the lumen of the sarcoplasmic reticulum, these results imply that two structurally different regions of the sarcoplasmic reticulum function as calcium storage sites in mammalian Purkinje fibers and raises the possibility that calcium storage and/or release from these two sites might be regulated differently.     

No evidence of abnormal metabolic or inflammatory activity in the brains of patients with rheumatoid arthritis: results from a preliminary study using whole-brain magnetic resonance spectroscopic imaging (MRSI)

Clinical Rheumatology - Many individuals with rheumatoid arthritis (RA) report persistent fatigue even after management of peripheral disease activity. This study used whole-brain magnetic...     

Cognitive impairment in three subtypes of multiple sclerosis

Patients with relapsing, primary progressive, and secondary progressive MS were administered the Tower of London and the Stroop Color-Word Interference Test, yielding several measures of executive function and speeded information processing. MS patients' performance was compared with healthy controls and with a clinical control group consisting of patients with rheumatoid arthritis. The MS patients performed the tests more slowly, but did not differ from either group of controls on measures of executive function. Slowing in the speed of information processing was characteristic of MS patients across two basic tasks differing in terms of controlled versus automatic processing and in terms of whether or not rapid responding was an explicit feature of successful performance. Although evident in all subtypes, this slowing was more pronounced in secondary progressive patients and somewhat less pronounced in primary progressive patients. Furthermore, the slowing was unrelated to patients' disability status or level of depression.     

An adult developmental study of the encoding of spatial location.

The present study was designed to test the hypothesis that there is a differential deficit in the ability to encode contextual information with increasing age. Young, middle-aged, and elderly adults were shown target words in various quadrants of a computer screen (contexts) and were told to either (a) remember the words and their locations, (b) remember the words, or (c) tell whether the words referred to something that was alive or not. Following presentation of the words, subjects were given a recognition test for the words and were asked to identify the quadrant in which each word had been presented. If older adults have a contextual encoding deficit, than an interaction between age and instruction condition would be expected in memory for quadrants. Older adults would be expected to perform better relative to younger adults when the locations were target information (intentionally learned) than when they were contextual (not intentionally learned). Since such an interaction was not obtained, the results provide no support for the hypothesis that the elderly have an encoding deficit that is specific to contextual information.     

Model-free reconstruction of three-dimensional myocardial strain from planar tagged MR images

A technique is presented for reconstructing a three-dimensional myocardial strain map from a set of parallel-tagged MR images. Radial strains were reconstructed from in vivo data from an anesthetized dog with values between .05 and .1 with a precision of ± .003 for a tag detection accuracy of .1 mm and a tag spacing of 2.5 mm. The reconstruction spatial resolution was demonstrated by reconstructing a localized displacement abnormality. In the circumferential direction, the abnormality that resulted in 50% displacement attenuation had a full width at half maximum of 5.4 ± .4 mm (mean ± SD). Graphs are presented showing the relationship between the size of an abnormality and the ability of the method to reconstruct that abnormality. The combination of high resolution parallel-tagged MR images and the model-free, coordinate system-free strain reconstruction technique presented in this paper is capable of producing accurate, high resolution strain maps of the myocardium.     

Supervised machine learning for diagnostic classification from large-scale neuroimaging datasets

Brain Imaging and Behavior - There are growing concerns about the generalizability of machine learning classifiers in neuroimaging. In order to evaluate this aspect across relatively large...     

Comparison of the CELLEX™ and UVAR‐XTS™ closed‐system extracorporeal photopheresis devices in the treatment of chronic graft‐versus‐host disease

Extracorporeal Photopheresis (ECP) is a cellular immunotherapy frequently used for steroid‐refractory graft‐versus‐host disease (GVHD). Chronic GVHD (cGVHD), response to ECP is associated with survival benefit. The UVAR‐XTS^TM system and the more recently developed CELLEX^TM device (both Therakos^TM) are the mainstay for ECP‐delivery in the UK and US. No comparison of treatment outcomes has been reported. We retrospectively compared cGVHD response and steroid reduction and withdrawal in patients treated exclusively over 12 months with either the XTS (n = 51) or CELLEX (n = 50). Our hypothesis was that there would be no difference in clinical outcome or steroid changes in the 2 matched cohorts. We also compared infection incidence, infection‐related death (IRD), and treatment time. Significant clinical improvement and regular capacity to reduce or cease steroids was encountered in both cohorts; at 6 months of ECP 70% of cutaneous cGvHD patients had partial or complete responses and 85% of patients receiving steroids pre‐ECP had reduced dosage. In the XTS group we unexpectedly encountered both superior steroid reduction (86% dose at least halved vs. 61% for CELLEX, P = 0.01) and withdrawal (15 vs. 5 CELLEX, P = 0.01) and a trend for superior skin disease response in the CELLEX‐treated cohort at 3 months. No inter‐relationship was evident. Halving or greater reduction of steroid dose by 3 or 6 months was associated with reduced risk of IRD in the XTS cohort as was withdrawal at 6 months for the combined cohorts. By 6 months, XTS‐treated patients had experienced fewer antibiotic‐requiring infections (mean 1.9 vs. 2.8, P = 0.025). Origins for the disparities are unclear and warrant investigation.