Verbal Working Memory and Atherosclerosis in Patients with Cardiovascular Disease: An fMRI study

BACKGROUND AND PURPOSE: Intimal-medial thickening (IMT) of the carotid wall is an accepted peripheral marker of atherosclerosis. It is associated with increased risk for myocardial infarction and stroke, and lower attention-executive-psychomotor functioning. The purpose of this study was to examine the relationship between IMT and brain activity during a verbal working memory (VWM) task in patients with cardiovascular disease (CVD). METHODS: Thirteen CVD patients underwent functional magnetic resonance imaging (fMRI) during a 2-Back VWM task, and B-mode ultrasound of the carotid arteries. IMT was calculated using an automated algorithm based on a validated edge-detection technique. The relationship between IMT and 2-Back-related brain activity was modeled using partial correlations controlling for age and small vessel disease as measured by white matter signal hyperintensities on MRI (WMH). RESULTS: Higher IMT was associated with lower 2-Back-related signal intensity and in the right middle frontal gyrus, independent of age and WMH. CONCLUSIONS: IMT may be one mechanism contributing to brain dysfunction in CVD. The blood oxygenation level-dependent (BOLD) contrast appears to be highly sensitive to peripheral vascular health as measured by IMT. Future studies should examine the sensitivity and specificity of the BOLD response for predicting cognitive decline in CVD.     

Improved Assessment of Significant Activation in Functional Magnetic Resonance Imaging (fMRI): Use of a Cluster-Size Threshold

The typical functional magnetic resonance (fMRI) study presents a formidable problem of multiple statistical comparisons (i.e, > 10,000 in a 128 x 128 image). To protect against false positives, investigators have typically relied on decreasing the per pixel false positive probability. This approach incurs an inevitable loss of power to detect statistically significant activity. An alternative approach, which relies on the assumption that areas of true neural activity will tend to stimulate signal changes over contiguous pixels, is presented. If one knows the probability distribution of such cluster sizes as a function of per pixel false positive probability, one can use cluster-size thresholds independently to reject false positives. Both Monte Carlo simulations and fMRI studies of human subjects have been used to verify that this approach can improve statistical power by as much as fivefold over techniques that rely solely on adjusting per pixel false positive probabilities.     

Evaluation of a quantitative plasma PCR plate assay for detecting cytomegalovirus infection in marrow transplant recipients.

A plasma PCR test, using a nonradioactive PCR plate assay, was evaluated for detection of human cytomegalovirus reactivation. This assay was compared to Southern blotting and found to perform well. As a noncompetitive method of quantitation, it was similar to a competitive method for detecting the number of genome copies per milliliter of plasma in marrow transplant recipients. This is a technically simplified assay with potential for adaptation to automation.     

The meaning of spirituality: a literature review

This paper presents a literature review in relation to the meaning of spirituality. It is proposed that meeting the spiritual needs of patients is a fundamental part of providing holistic nursing care, but that the assessment and meeting of those needs is impeded by inadequate definitions and conceptual frameworks. It should not be assumed that spirituality is either synonymous, or coterminous, with religion, and it is suggested that to adopt this restrictive view is unhelpful in the provision of individualized care. Reflection on the literature reveals that the self, others and 'God' provide the key elements within a definition of spirituality, and that other emerging themes namely meaning, hope, relatedness/connectedness, beliefs/belief systems and expressions of spirituality, can be articulated in the context of those three key elements. In particular, it is proposed that the nature of 'God' may take many forms and, essentially, is whatever an individual takes to be of highest value in his/her life. It is suggested that the themes emerging from the literature can be utilized as a framework to give practitioners and researchers a direction for future exploration of the concept of spirituality.     

Poorly differentiated ("insular") carcinoma of the thyroid gland: an aggressive subset of differentiated thyroid neoplasms

Four patients with a histologically distinctive thyroid carcinoma--which recently has been referred to as poorly differentiated ("insular") carcinoma--are reported. This study confirms the previous conclusions that patients with this neoplasm often experience an aggressive clinical course, with focal recurrences and distant metastases common, which results in death in the majority of patients. Such aggressive behavior may occur even when the insular component accounts for only a small percentage of an otherwise well-differentiated carcinoma, as seen in one of our patients. After subtotal or total thyroidectomy, three of the four patients have experienced local recurrence (1) and metastases to lung (3), mediastinum (1), and bone (1). All three of these patients died within 2 years of the diagnosis of insular carcinoma. The remaining patient is alive without evidence of disease 1 year after total thyroidectomy. Histologically, this neoplasm is characterized by well-defined nests (insulae) that are composed of relatively small, uniform cells and sometimes associated with small, thyroglobulin-containing follicles. Tumor necrosis is often present. Insular carcinoma may comprise the entire neoplasm (2 patients) or be associated with well-differentiated follicular (1 patient) or papillary (1 patient) carcinoma. The rapid and often fatal course associated with insular carcinoma warrants aggressive treatment at the time of initial diagnosis, including total thyroidectomy and node dissection (if involved), as well as possible iodine-131, external beam irradiation and chemotherapy.     

Genotypes and haplotypes in the IL-1 gene cluster: analysis of two genetically and diagnostically distinct groups of Alzheimer patients

Increased risk of Alzheimer's disease (AD) has been associated with polymorphisms in the IL-1 gene cluster, and in particular with the IL-1alpha-889 T/T genotype. However, this association is still unclear, and needs further investigation. In order to clarify the role of these polymorphisms in the complex pathogenesis of AD we examined genotype and haplotype frequencies of the two C-to-T SNPs at position -889 and -551 in the IL-1alpha and IL-1beta genes, respectively, and of the 86 bp VNTR intron-2 polymorphisms in the IL-1Ra gene. The analysis was performed in two genetically and diagnostically distinct groups of sporadic AD from Italy and the USA. In the Italian group a significant association between the IL-1alpha-889 T/T genotype and AD (OR=3.022, 95% CI: 1.001-9.119) was found, whereas no difference was found in the group from the USA. Results were also compared with previously published studies that analyzed the same IL-1 polymorphisms in AD. In both groups, the analysis of the estimated haplotypes shows that AD patients and controls who carry the IL-1beta-511 C allele, were also more frequently carriers of the IL-1Ra 1 allele (haplotypes -C-1). The total frequency of the two -C-1 haplotypes (C-C-1 plus T-C-1) was about one half of the total frequency of the eight estimated haplotypes. This was confirmed by significant linkage disequilibrium between these two loci in both the Italian and USA groups. In the Italian group a weak association of the T-C-2 haplotype with the disease (OR=1.648, 95% CI: 1.519-1.788) was also found, whereas in the USA group no difference was found. Although ours and other published data on different samples of Caucasian and non-Caucasian AD show a great heterogeneity in the frequencies of the IL-1alpha-889, the IL-1beta-511 and the IL-1Ra VNTR gene polymorphisms, we confirm the role of the IL-1alpha-889 T/T genotype as a risk factor for sporadic AD, and show the presence of an allelic association between IL-1beta C and IL-1Ra 1 alleles in both the Italian and the USA groups, confirmed by the presence of significant levels of linkage disequilibrium between these two loci.     

Susceptibility of bovine macrophages to infectious bovine rhinotracheitis virus infection.

Infectious bovine rhinotracheitis virus replicated in cultured bovine alveolar macrophages (AM). However, yields of infectious virus were low, with maximum titers approximately 100 times that of the residual inoculum. Immunofluorescence and electron microscopic studies indicated that the majority of macrophages produced viral antigen, but after infection at a multiplicity of 0.1, only 4.1% of AM produced infectious centers. Virus-infected AM culture supernatants possessed interfering activity, probably due to interferon. Incubation of fresh AM with these fluids rendered them refractory to infection. Although AM from infectious bovine rhinotracheitis virus-immune and -susceptible donors were equally permissive and their susceptibility was unaltered by incubation with bacterial lipopolysaccharide, bovine mammary macrophages which were elicited with lipopolysaccharide became nonpermissive when further incubated for 48 h with 1 microgram of lipopolysaccharide per ml. Under these conditions, infected mammary macrophages failed to synthesize viral DNA, and there was reduced synthesis of "late" viral polypeptides.     

Antipneumococcal effects of C-reactive protein and monoclonal antibodies to pneumococcal cell wall and capsular antigens.

Antibodies to pneumococcal capsular polysaccharides are well known for their ability to protect against pneumococcal infection. Recent studies indicate that antibodies to cell wall antigens, including pneumococcal surface protein A and the phosphocholine (PC) determinant of teichoic acids as well as human C-reactive protein (which also binds to PC), can protect mice against pneumococcal infection. In the present study we compared the protective effects of these agents as measured by mouse protection, the blood bactericidal assay, and clearance of pneumococci from the blood and peritoneal cavity. Our findings extend previous results indicating that human C-reactive protein and antibodies to noncapsular antigens are generally less protective than anticapsular antibodies. The new results obtained indicate the following: (i) mouse protection studies with intraperitoneal and intravenous infections provide very similar results; (ii) monoclonal immunoglobulin G2a (IgG2a) antibodies to PC, like IgG1, IgG2b, and IgG3 antibodies to PC, are highly protective against pneumococcal infection in mice; (iii) human antibody to PC is able to protect against pneumococcal infection in mice; (iv) antibodies to PspA are effective at mediating blood and peritoneal clearance of pneumococci; (v) complement is required for the in vivo protective effects of both IgG and IgM antibodies to PC; (vi) IgG1, IgG2b, and IgG3 anti-PC antibodies all mediate complement-dependent lysis of PC-conjugated erythrocytes; and (vii) antibodies and human C-reactive proteins that are reactive with capsular antigens but not cell wall antigens are able to mediate significant antibacterial activity in the blood bactericidal assay.     

The vector homology problem in diagnostic nucleic acid hybridization of clinical specimens.

Nucleic acid hybridization techniques using cloned probes are finding application in assays of clinical specimens in research and diagnostic laboratories. The probes that we and others have used are recombinant plasmids composed of viral inserts and bacterial plasmid vectors such as pBR322. We suspected that there was material homologous to pBR322 present in many clinical samples. because hybridization occurred in samples which lacked evidence of virus by other techniques. If the presence of this vector-homologous material was unrecognized, hybridization in the test sample might erroneously be interpreted as indicating the presence of viral sequences. In this paper we demonstrate specific hybridization of labeled pBR322 DNA with DNA from various clinical samples. Evidence is presented that nonspecific probe trapping could not account for this phenomenon. In mixing experiments, it is shown that contamination of clinical samples with bacteria would explain such a result. Approaches tested to circumvent this problem included the use of isolated insert probes, alternate cloning vectors, and cold competitor pBR322 DNA in prehybridization and hybridization mixes. None proved entirely satisfactory. We therefore emphasize that it is essential that all hybridization detection systems use a control probe of the vector alone in order to demonstrate the absence of material with vector homology in the specimen tested.