In Vivo MRI Measurement of Spinal Cord Displacement in the Thoracolumbar Region of Asymptomatic Subjects with Unilateral and Sham Straight Leg Raise Tests.

BACKGROUND: Normal displacement of the conus medullaris with unilateral and bilateral SLR has been quantified and the "principle of linear dependence" has been described. PURPOSE: Explore whether previously recorded movements of conus medullaris with SLRs are i) primarily due to transmission of tensile forces transmitted through the neural tissues during SLR or ii) the result of reciprocal movements between vertebrae and nerves. STUDY DESIGN: Controlled radiologic study. METHODS: Ten asymptomatic volunteers were scanned with a 1.5T magnetic resonance (MR) scanner using T2 weighted spc 3D scanning sequences and a device that permits greater ranges of SLR. Displacement of the conus medullaris during the unilateral and sham SLR was quantified reliably with a randomized procedure. Conus displacement in response to unilateral and sham SLRs was quantified and the results compared. RESULTS: The conus displaced caudally in the spinal canal by 3.54±0.87 mm (mean±SD) with unilateral (p≤.001) and proximally by 0.32±1.6 mm with sham SLR (p≤.542). Pearson correlations were higher than 0.99 for both intra- and inter-observer reliability and the observed power was 1 for unilateral SLRs and 0.054 and 0.149 for left and right sham SLR respectively. CONCLUSIONS: Four relevant points emerge from the presented data: i) reciprocal movements between the spinal cord and the surrounding vertebrae are likely to occur during SLR in asymptomatic subjects, ii) conus medullaris displacement in the vertebral canal with SLR is primarily due to transmission of tensile forces through the neural tissues, iii) when tensile forces are transmitted through the neural system as in the clinical SLR, the magnitude of conus medullaris displacement prevails over the amount of bone adjustment.

Interaction of enterovirus infection and cow's milk-based formula nutrition in type 1 diabetes-associated autoimmunity.

BACKGROUND: Enteral virus infections and early introduction of cow's milk (CM)-based formula are among the suggested triggers of type 1 diabetes (T1D)-associated autoimmunity, although studies on their role have remained contradictory. Here, we aimed to analyse whether interactions between these factors might clarify the controversies. MATERIALS: The study population comprised 107 subjects developing positivity for at least two T1D-associated autoantibodies and 446 control subjects from the Finnish diabetes prediction and prevention cohort. Enterovirus, rotavirus, adenovirus, respiratory syncytial virus and bovine insulin-binding antibodies were analysed from prospective serum samples at 3-24 months of age. Data on infant cow's milk exposure were available for 472 subjects: 251 subjects were exposed to cow's milk before 3 months of age and 221 subjects later in infancy. RESULTS: Signs of an enterovirus infection by 12 months of age were associated with the appearance of autoimmunity among children who were exposed to cow's milk before 3 months of age. Cox regression analysis revealed a combined effect of enterovirus infection and early cow's milk exposure for the development of ICA and any of the biochemically defined autoantibodies (p = 0.001), of IAA (p = 0.002), GADA (p = 0.001) and IA-2A (p = 0.013). CONCLUSIONS: The effect of enterovirus infection on the appearance of T1D-associated autoimmunity seems to be modified by exposure to cow's milk in early infancy suggesting an interaction between these factors. Moreover, these results provide an explanation for the controversial findings obtained when analysing the effect of any single one of these factors on the appearance of T1D-associated autoimmunity.

Rotavirus-specific T cell responses and cytokine mRNA expression in children with diabetes-associated autoantibodies and type 1 diabetes.

Rotavirus infections have been implicated as a possible trigger of type 1 diabetes. We elucidated this connection by comparing peripheral blood T cell responses to rotavirus between children with newly diagnosed type 1 diabetes (n = 43), healthy children with multiple diabetes-associated autoantibodies (n = 36) and control children carrying human leukocyte antigen (HLA)-conferred susceptibility to type 1 diabetes but without autoantibodies (n = 104). Lymphocyte proliferation assays based on stimulation with an antigen were performed using freshly isolated peripheral blood mononuclear cells (PBMC) and IgG and IgA class rotavirus antibodies were measured using plasma samples collected from the children. The expression of interferon (IFN)-gamma, interleukin (IL)-4, IL-10 and transforming growth factor (TGF)-beta in PBMC was studied with real-time polymerase chain reaction (PCR) in a subgroup of 38 children. No differences were observed in the strength or frequency of positive T cell responses to rotavirus between children with overt diabetes, children with multiple autoantibodies and control children. Children with diabetes-associated autoantibodies had, instead, stronger T cell responses to purified coxsackie B4 virus than control children. Rotavirus-stimulated lymphocytes from autoantibody-positive children produced more IL-4 and phytohaemagglutinin (PHA)-stimulated lymphocytes more IL-4 and IFN-gamma than lymphocytes from control children. PHA-stimulated lymphocytes from children with diabetes also produced more IL-4 and purified protein derivative (PPD)-stimulated lymphocytes less TGF-beta than lymphocytes from autoantibody-negative control children. In conclusion, our lymphocyte proliferation studies did not provide evidence supporting an association between rotavirus infections and the development of type 1 diabetes or diabetes-associated autoantibodies in young children.

Rotavirus-specific T-cell responses in young prospectively followed-up children.

Rotavirus is a major cause of gastroenteritis in young children. Antibodies seem to protect against rotavirus infection but cell-mediated immune responses are probably also important for protection. We evaluated the development of T-cell responses to rotavirus in follow-up samples from 20 healthy children with an increased genetic risk for type 1 diabetes. Blood samples from 16 healthy adults were also available for the study. T-cell proliferation was analysed at 3-6 month intervals from the age of 3 months to the age of 4-5 years using the Wa strain of human rotavirus and the NCDV strain of bovine rotavirus as antigens. IgG and IgA antibodies to rotavirus were studied from simultaneously drawn plasma samples with EIA method using NCDV as an antigen. A total of 24 infections were revealed by antibody analysis. Sixteen children showed diagnostic increases in both IgG and IgA antibodies to rotavirus, while 5 children showed increases in IgA antibodies only and 3 in IgG only. Antibody rises were accompanied by T-cell responses to rotavirus (SI > 3) in 9 of the 24 cases. T-cell responses to purified or lysed human rotavirus were stronger after a rise in rotavirus antibodies than the responses before infection (P = 0.017 and 0.027, respectively). There was a correlation between T-cell responses to purified and lysed human rotavirus and NCDV. Strong T-cell responses to rotavirus were transient and the ability to respond usually disappeared in one year, but in all adults T-cell responses to rotavirus were strong implicating that several infections are needed to develop consistent, strong T-cell responsiveness.

Assessing stage of change for physical activity: how congruent are parallel methods?

The single-question self-classification Stages of Change scales (SAS) for two modes of physical activity were compared with parallel staging methods. In Study 1, the participants (N = 50) completed SAS in a questionnaire and were then personally interviewed on their physical activity. In four fifths of the cases, SAS indicated the same stage as the interviewer's judgment. In Study 2, a representative survey sample (N = 600) completed both SAS and, in another questionnaire, a three-question algorithm staging instrument (TSQ) constructed for the same target behaviors. About 50% of all participants were placed in the same stage with both instruments. The compatibility rate rose to 80% when the number of stages was reduced from the original eight to five. However, TSQ also accumulated a higher share of cases in the stages with regular action. In both studies, the most obvious sources for incompatible staging were the regularity and time frame of the targeted behavior. Thus, neither SAS nor TSQ is on its own a sufficiently accurate instrument for use in personalized stage-based interventions. TSQ shows no obvious advantages over SAS. In counseling, SAS seems useful in combination with a personal interview.

Responses of coxsackievirus B4-specific T-cell lines to 2C protein-characterization of epitopes with special reference to the GAD65 homology region.

Coxsackie B viruses (CBV) have been indicated as environmental triggers initiating autoimmune destruction of insulin-producing pancreatic beta-cells, and molecular mimicry might be the mechanism. A prime candidate for inducing cross-reactive immune responses is a homology sequence, PEVKEK, found both in CBV4 2C protein and in GAD65. To characterize the CBV4-specific T-cell epitopes, overlapping peptides covering the 2C protein were synthesized and CBV4-specific T-cell lines were established from healthy and diabetic subjects. The T-cell epitopes were dependent on the HLA-DR genotype of the T-cell donor, but no difference between diabetic and healthy subjects could be detected. Peptide p4, which included the PEVKEK sequence, contained an HLA-DR1-restricted T-cell epitope. Three randomly selected CBV4-specific T-cell lines, which responded to peptide p4, failed to recognize GAD65 protein or GAD65 peptides containing the PEVKEK sequence. We conclude that the CBV4 2C protein is strongly immunogenic for T-cells and PEVKEK is included in a T-cell epitope. However, presentation of this epitope in the context of neutral HLA-DR1 allele does not support its role in pathogenesis of type 1 diabetes.

Cell membrane-associated measles virus components inhibit antigen processing.

Measles virus (MV)-induced immune suppression is an important reason for MV-associated mortality and morbidity. Despite numerous studies, the mechanisms of immune suppression still remain poorly defined. In the present study we analyzed the effect of MV components on the T-cell recognition of specific non-MV antigens. We demonstrated that even inactivated MV could inhibit the presentation of unprocessed protein antigen to specific T cells, whereas MV did not affect the responses of specific T cells to representative synthetic peptide epitopes derived from complex antigens. The inhibition was induced by MV-infected cell membranes. The kinetics of the MV-dependent inhibition suggested an impaired antigen processing in mononuclear cells as addition of MV-infected cell debris 4 h after the beginning of cell cultures no longer inhibited T-cell responsiveness.

Stages of change in two modes of health-enhancing physical activity: methodological aspects and promotional implications.

Measurement scales for stages of change were developed and the stages were assessed in two specific modes of Health-Enhancing Physical Activity (HEPA) in a cross-sectional survey (N = 1516); representative samples were selected from three age groups, i.e. from three phases of adult life. Outdoor Aerobic Exercise (OAE) was used as an example of fitness activity; Everyday Commuting Activity (ECA) was selected to represent lifestyle physical activity. Scales used by the Prochaska team were modified for this study, and the stages of Precontemplation and Preparation were each divided into two new stages. Consistency of the stage measurement was moderate for OAE and good for ECA. As regards content validity, consistent associations were found between stage scores and contextual variables for both behaviors. The results show that, at a given time, a person can be in different stages in different modes of HEPA. Therefore, the behavior of interest must be specified before accurate information on the stages of change in a population can be obtained. The results also indicate the importance of contextual factors in HEPA promotion.

Characterization of T cell epitopes in measles virus nucleoprotein.

T cell epitopes of the measles virus (MV) nucleoprotein were studied by synthesizing overlapping 20 aa peptides over the known sequence of the protein and analysing the proliferation responses of a panel of MV-specific T cell lines and clones against these peptides. T cell lines were established from eleven healthy controls and seven multiple sclerosis patients, all with a history of past MV infection. The epitopes recognized by these lines were concentrated in a few regions of the polypeptide chain. Overlapping peptides containing aa 321-340 and 331-350 were most often recognized. Other epitopes were detected close to the amino-terminal end of the polypeptide chain as each of the peptides 1-20, 21-40, 31-50 and 51-70 contained stimulating moieties. Some responses were also detected towards peptides 151-200 and 221-250, but the carboxy-terminal end of the polypeptide was not recognized by any of the tested T cell lines. The amino acid sequences of the peptides that stimulated the T cell clones and lines, as a rule, contained binding motifs described for HLA-DR alleles found in T cell donors. The regions of protein sequence which did not reveal any T cell epitopes were, instead, relatively free of binding motifs. The results suggest that only a few epitopes of the MV nucleoprotein are important in establishing T cell immunity.

The versatile nature of physical activity--on the psychological, behavioural and contextual characteristics of health-related physical activity.

This paper presents a comprehensive characterisation of physical activity based on psychological, behavioural and contextual aspects. Based on the characterisation it suggests a promotional classification of physical activity into five categories. The categories are: 1, Occupational activity; 2, Lifestyle activity; 3, Recreation activity; 4, Fitness activity; and 5, Sport activity. Examples are given of activities in each category and of the related emotional aspects, outcome expectations, degree of personal choice and health benefits. The importance of the emotional component and the relevance of the outcome expectations are discussed and contextual considerations are presented on the basis of the promotional classification. The implications of the classification for the practice of health-enhancing physical activity promotion are discussed.

Definition of three minimal T helper cell epitopes of rubella virus E1 glycoprotein.

To characterize T cell-recognized epitopes on rubella virus (RV) E1 glycoprotein, IL-2-dependent RV-specific T cell lines were established from 14 rubella-seropositive healthy donors. The responses of these lines were studied by using a panel of 94 partially overlapping synthetic peptides of 15 amino acids (aa) length covering the known nucleotide sequence of RVE1 glycoprotein. Two to seven peptide-defined epitopes were recognized by the T cell lines, but a large interindividual variation was found. T cell reactivity was most often localized to the regions between aa 276 and 290, aa 381 and 395 and aa 410 and 420. Analysis of overlapping, truncated peptides revealed three minimal T helper cell epitopes VIGSQARK, KFVTAALLN and RVIDPAAQ in aa positions 280-287, 385-393 and 412-419, respectively.

The beliefs and values shaping today's health reform debate.

Survey results show that the American public comes to the health care reform debate with ambivalent feelings and a relatively low base of specific knowledge. But Americans also hold a set of core values that will shape their response to various proposals for national change. These include (1) a moral commitment to the uninsured; (2) a desire to achieve personal peace of mind; (3) a lack of self-blame; (4) a limited willingness to sacrifice; (5) reasoned self-interest in what changes are enacted; (6) a distrust of government; and (7) a healthy cynicism about the behavior of our major institutions.

Niacin-induced hepatitis: a potential side effect with low-dose time-release niacin.

Hepatitis developed in five patients who were taking low dosages (3 g/day or less) of time-release niacin. In four of the five patients, clinical symptoms of hepatitis developed after the medication had been taken for a relatively short time (2 days to 7 weeks). This manifestation of hepatotoxicity seems to differ from that previously reported in association with use of crystalline niacin, which occurred with high dosage and prolonged usage of the medication. In view of the recent increased frequency of prescribing niacin for the treatment of hyperlipidemia, physicians should be aware of the potential for hepatotoxicity with even low-dose and short-term use of time-release niacin.

Monitoring drug therapy: an applied approach.

While it has been agreed that drug therapy monitoring in health care institutions is desirable and necessary, the pharmacists who carry out such programs must have a system that fills their special needs. Pharmaceutical Consultant Services, P.A. has developed a manual monitoring system to provide patient profiles for long-term care patients. This instruction guide explains the system and its application; pharmacists may wish to use this system or simply to learn from it.

Assessing the need for pharmacist-conducted drug regimen reviews in skilled nursing and intermediate care facilities.

Federal regulations operating since 1974 require monthly patient drug reviews by pharmacists in skilled nursing facilities (SNFs), but intermediate care facility (ICF) reviews are only required quarterly and can be done by nurses. Based on a few previous reports, the hypothesis of this research was that there is no difference in the need for pharmacist monitoring in SNFs, ICFs, and ICF-mentally retarded (ICF-MR). Stratified by level of care, 353 patients were randomly selected from 24,770 Medicaid recipients in nursing homes throughout Minnesota. Full Medicaid claims profiles were generated for 3 months of service. An interdisciplinary expert panel defined need with explicit criteria for several parallel measures including need for pharmacist monitoring, likelihood of formal chart comment, frequency of monitoring, time per visit, and rationality of therapy. Two judges, experts in drug monitoring, used the criteria to separately score the profiles with significant correlation in the two sets of scores (p < 0.001). Using analysis of variance on the several measures for need, there was no difference between SNFs and ICFs, but ICF-MRs were significantly lower in need scores. It is expected that the explicit monitoring criteria developed in this study will be useful to practitioners in their drug review activities.

Monitoring drug therapy in skilled nursing facility patients.

A discussion of one system designed for monitoring drug therapy in skilled nursing facility (SNF) patients is presented. This system will enable the pharmacist to fulfill the federal requirement for monitoring drug therapy and will provide the opportunity for gathering and analyzing drug usage data in fulfillment of the facility's utilization review requirement. The system described was developed and tested at five SNF's. Follow-up studies at each of the five facilities were then performed for comparison purposes. The data presented describe and analyze the results from both studies for two of the ten drugs studied: digoxin and hydrochlorothiazide. The high rates of nonconformance to the established criteria are discussed and specific insights as to why drug therapy in these patients often seems inappropriate are provided.