Outcomes of low-vision services using optometric and multidisciplinary approaches: a non-randomized comparison

Consecutive patients (n = 215) who were referred to optometric (55%) or multidisciplinary (45%) low-vision services and above 50 years of age were recruited from four hospitals in the Netherlands. They completed two vision-related quality of life questionnaires, the Vision Quality of Life Core Measure (VCM1) and the Low Vision Quality of Life Questionnaire (LVQOL), before their first visit with low-vision services and 1 year later. At follow-up, patients referred to multidisciplinary low-vision services had lower scores on the mobility subscale of the LVQOL than patients referred to optometric low-vision services [5.3 points; 95% confidence interval (CI): 0.2-10.5]. Paired sample t-tests for the two groups of patients taken together show improvement for the VCM1 (3.1 points; 95% CI: 0.6-5.6) and deterioration for the basic aspects of vision (3.5 points; 95% CI: 1.1-5.9) and the mobility (6.6 points; 95% CI: 3.7-9.5) subscales of the LVQOL. In conclusion, people referred to optometric services showed less deterioration in mobility than those referred to multidisciplinary services. No differences were observed for any of the other subscales of the LVQOL and the VCM1. Future research in this field should include randomized controlled designs comparing low-vision services with no treatment or placebo.     

Monophasic action potentials and activation recovery intervals as measures of ventricular action potential duration: experimental evidence to resolve some controversies.

BACKGROUND: Activation recovery intervals (ARIs) and monophasic action potential (MAP) duration are used as measures of action potential duration in beating hearts. However, controversies exist concerning the correct way to record MAPs or calculate ARIs. We have addressed these issues experimentally. OBJECTIVES: To experimentally address the controversies concerning the correct way to record MAPs or calculate ARIs. METHODS: Left ventricular local electrograms were recorded in isolated pig hearts with an exploring electrode grid, with a KCl reference electrode on the left ventricular myocardium, the aortic root, or the left atrium. Local activation was determined from calculated Laplacian electrograms. RESULTS: With the KCl electrode on the aortic root, local electrograms represented local activation. However, with the KCl electrode on the myocardium remote from the exploring electrode, a combined electrogram emerged consisting of local activation recorded from the grid and remote activation recorded from the reference electrode. The remote, inverted monophasic component did not show propagation and did not correlate with the Laplacian complex. When the KCl electrode was placed on the atrium during AV block, remote atrial monophasic components were completely dissociated from local, ventricular deflections. At left ventricular sites with a positive T wave, the Laplacian signal showed that the end of the T wave was caused by remote repolarization. During cooling-induced regional action potential prolongation, the T wave became negative, whereby the positive flank of the T wave remained correlated with repolarization (recorded with a MAP at the same site). CONCLUSIONS: MAPs are recorded from the depolarizing electrode. In both negative and positive T waves, the moment of maximum dV/dt corresponds to local repolarization.     

Glucocorticoids Decrease Hippocampal and Prefrontal Activation during Declarative Memory Retrieval in Young Men

Glucocorticoids (GCs, cortisol in human) are associated with impairments in declarative memory retrieval. Brain regions hypothesized to mediate these effects are the hippocampus and prefrontal cortex (PFC). Our aim was to use fMRI in localizing the effects of GCs during declarative memory retrieval. Therefore, we tested memory retrieval in 21 young healthy males in a randomized placebo-controlled crossover design. Participants encoded word lists containing neutral and emotional words 1 h prior to ingestion of 20 mg hydrocortisone. Memory retrieval was tested using an old/new recognition paradigm in a rapid event-related design. It was found that hydrocortisone decreased brain activity in both the hippocampus and PFC during successful retrieval of neutral words. These observations are consistent with previous animal and human studies suggesting that glucocorticoids modulate both hippocampal and prefrontal brain regions that are crucially involved in memory processing. Electronic Supplementary Material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

MR imaging based strategies in limb salvage surgery for osteosarcoma of the distal femur

Objective. To analyse to what extent MR imaging based decisions were correct in determining the surgical procedure in patients with osteosarcoma of the distal femur. Design. We compared the findings on MR imaging that determined the surgical strategy with the actual surgical findings or histopathological specimen. We assessed to what extent MR images could be used to determine the surgical procedure in patients with osteosarcoma. Patients. Between 1985 and 1992, 34 patients with an osteosarcoma were treated. Two patients had a low-grade osteosarcoma. Thirty-two patients with a high-grade osteosarcoma of the distal femur (17 stage IIB, 15 stage III) were included in this study. Surgical options consisted of either limb salvage surgery or ablative surgery, which included the Van Nes-Borggreve rotationplasty. Limb salvage surgery consisted of extra-articular or transarticular resection, followed by reconstruction. Surgery was planned depending on the local extent of the tumour as depicted on the MR studies, coupled with data from the biopsy, age, patient compliance and histological grade. Follow-up was available in all patients. Nine of 17 patients graded as IIB were alive with an average follow-up of 68 months (range 46–109 months), of whom one has metastases. No local recurrence was encountered. Results. If no tumour involvement on MR imaging was found and this was used as a determining factor, this proved to be correct at subsequent analysis. We found that in eight of 11 cases, when MR images suggested a close relationship between tumour and nerve, an oncologically safe plane could be achieved during surgery. In three, a free plane could not be accomplished, as confirmed at histopathological examination. Hence, when nerve involvement was equivocal on MR imaging we found it valuable to reassess nerve involvement during surgery and reconsider limb salvage surgery. When the decisive factor was the vascular involvement and tumour extension was read as equivocal, it was possible to obtain a oncologically safe plane in six of 13 cases. When comprehensive tumour involvement of any structure was noted pre-operatively, it proved to be correct at histopathological examination, except for one case of assumed vascular involvement that proved to be free. Conclusions. If no tumour involvement of a structure was found on MR imaging and this was used as a determining factor, this proved to be correct. When nerve involvement was equivocal on MR imaging we found it valuable to reassess nerve involvement during surgery and reconsider limb salvage surgery. Extensive tumour involvement of any structure, as shown by MR imaging, could be used correctly as a decisive argument in planning a surgical procedure.     

Xanthogranulomatous pyelonephritis: Comparison of extent using computed tomography and magnetic resonance imaging in one case

In a case of diffuse xanthogranulomatous pyelonephritis, computed tomography (CT) and magnetic resonance (MR) were used. The MR proved to be more precise in the preoperative evaluation of inflammatory extension to the spleen and into the abdominal wall. The CT was more accurate in excluding spread to the colon.     

Does the beneficial effect of HRT on endothelial function depend on lipid changes

OBJECTIVES: To determine whether improvement in endothelial function of the brachial artery observed in women treated with hormone replacement therapy (HRT) may be explained by changes in lipid profile or blood pressure, information was used obtained in a single-centre, randomised, double blind, placebo-controlled trial. METHODS: Hundred-and-five healthy postmenopausal women, aged 50-65 years, were treated with 0.625 mg conjugated equine estrogens (CEE) combined with 2.5 mg medroxyprogesterone acetate (MPA) (CEE+MPA), 2.5 mg tibolone or placebo for 3 months. At baseline and after 3 months, endothelial function was assessed using flow-mediated dilatation (FMD) and nitro glycerine-mediated dilatation (NMD). Furthermore, lipids were measured. Multivariate linear regression analysis was applied to address the research question. RESULTS: Treatment with CEE+MPA resulted in an improvement in FMD of 2.0% (95% CI: -0.1; 4.1). CEE/MPA reduced total cholesterol with 13% (95% CI: -18%; -7%), LDL-cholesterol with 23% (95% CI: -30%; -15%) and lipoprotein(a) (Lp(a)) with 14% (95% CI: -26%; -2%). The magnitude of the relation of CEE/MPA with endothelial function was attenuated to from 2.0 to 1.6% when change in Lp(a) was taken into account. Adjustments for other lipids or blood pressure did not attenuate the association. CONCLUSIONS: The improvement in endothelial function in postmenopausal women treated with CEE+MPA appears to be partially mediated by change in Lp(a), and apparently not by changes in other lipids.     

Functional defects in the fanconi anemia pathway in pancreatic cancer cells

Biallelic BRCA2-mutations can cause Fanconi anemia and are found in approximately 7% of pancreatic cancers. Recently, several sequence changes in FANCC and FANCG were reported in pancreatic cancer. Functional defects in the Fanconi pathway can result in a marked hypersensitivity to interstrand crosslinking agents, such as mitomycin C. The functional implications of mutations in the Fanconi pathway in cancer have not been fully studied yet; these studies are needed to pave the way for clinical trials of treatment with crosslinking agents of Fanconi-defective cancers. The competence of the proximal Fanconi pathway was screened in 21 pancreatic cancer cell lines by an assay of Fancd2 monoubiquitination using a Fancd2 immunoblot. The pancreatic cancer cell lines Hs766T and PL11 were defective in Fancd2 monoubiquitination. In PL11, this defect led to the identification of a large homozygous deletion in FANCC, the first cancer cell line found to be FANCC-null. The Fanconi-defective cell lines Hs766T, PL11, and CAPAN1 were hypersensitive to the crosslinking agent mitomycin C and some to cis-platin, as measured by cell survival assays and G(2)/M cell-cycle arrest. These results support the practical exploration of crosslinking agents for non-Fanconi anemia patients that have tumors defective in the Fanconi pathway.     

Preserved contribution of nitric oxide to baseline vascular tone in deconditioned human skeletal muscle

Deconditioning is a risk factor for cardiovascular disease. Exercise reduces this risk, possibly by improving the vascular endothelial nitric oxide (NO) pathway. The effect of deconditioning on the NO pathway is largely unknown. This study was designed to assess baseline NO availability in the leg vascular bed after extreme, long-term deconditioning (spinal cord-injured individuals, SCI) as well as after moderate, short-term deconditioning (4 weeks of unilateral lower limb suspension, ULLS). For this purpose, seven SCI were compared with seven matched controls. Additionally, seven healthy subjects were studied pre- and post-ULLS. Leg blood flow was measured by venous occlusion plethysmography at baseline and during infusion of 5 incremental dosages of N ^G-monomethyl- l -arginine ( l -NMMA) into the femoral artery. Sodium nitroprusside (SNP) was infused to test vascular responsiveness to NO. Baseline leg vascular resistance tended to be higher in SCI compared with controls (37 ± 4 versus 31 ± 2 arbitrary units (AU), P = 0.06). Deconditioning altered neither the vasoconstrictor response to l -NMMA (increase in resistance in SCI versus controls: 102 ± 33% versus 69 ± 9%; pre- versus post-ULLS: 95 ± 18% versus 119 ± 15%), nor the vascular responsiveness to NO. In conclusion, two human in vivo models of deconditioning show a preserved baseline NO availability in the leg skeletal muscle vascular bed.     

Immune activation modulates hematopoiesis through interactions between CD27 and CD70

The differentiation of hematopoietic stem cells into mature blood cell lineages is tightly regulated. Here we report that CD27, which is expressed on stem and early progenitor cells in bone marrow, can be important in this process. Deletion of CD27 increased the myeloid colony-forming potential of stem and early progenitor cells and enhanced B lymphoid reconstitutive capacity in competitive transplantation experiments. Conversely, stimulation of CD27(+) progenitor cells with CD70, the unique ligand for CD27, inhibited colony-forming potential in vitro and lymphocyte outgrowth in vivo. As CD70 is expressed only on activated immune cells, we suggest that CD27 triggering on early progenitor cells provides a negative feedback signal to leukocyte differentiation during immune activation.