The clinical features of the piriformis syndrome: a systematic review

Piriformis syndrome, sciatica caused by compression of the sciatic nerve by the piriformis muscle, has been described for over 70 years; yet, it remains controversial. The literature consists mainly of case series and narrative reviews. The objectives of the study were: first, to make the best use of existing evidence to estimate the frequencies of clinical features in patients reported to have PS; second, to identify future research questions. A systematic review was conducted of any study type that reported extractable data relevant to diagnosis. The search included all studies up to 1 March 2008 in four databases: AMED, CINAHL, Embase and Medline. Screening, data extraction and analysis were all performed independently by two reviewers. A total of 55 studies were included: 51 individual and 3 aggregated data studies, and 1 combined study. The most common features found were: buttock pain, external tenderness over the greater sciatic notch, aggravation of the pain through sitting and augmentation of the pain with manoeuvres that increase piriformis muscle tension. Future research could start with comparing the frequencies of these features in sciatica patients with and without disc herniation or spinal stenosis

The uptake and effect of a mailed multi-modal colon cancer screening intervention: A pilot controlled trial

Abstract Background We sought to determine whether a multi-modal intervention, which included mailing a patient reminder with a colon cancer decision aid to patients and system changes allowing direct access to scheduling screening tests through standing orders, would be an effective and efficient means of promoting colon cancer screening in primary care practice. Methods We conducted a controlled trial comparing the proportion of intervention patients who received colon cancer screening with wait list controls at one practice site. The intervention was a mailed package that included a letter from their primary care physician, a colon cancer screening decision aid, and instructions for obtaining each screening test without an office visit so that patients could access screening tests directly. Major outcomes were screening test completion and cost per additional patient screened. Results In the intervention group, 15% (20/137) were screened versus 4% (4/100) in the control group (difference 11%; (95%; CI 3%;18% p = 0.01). The cost per additional patient screened was estimated to be $94. Conclusion A multi-modal intervention, which included mailing a patient reminder with a colon cancer decision aid to patients and system changes allowing patients direct access to schedule screening tests, increased colon cancer screening test completion in a subset of patients within a single academic practice. Although the uptake of the decision aid was low, the cost was also modest, suggesting that this method could be a viable approach to colon cancer screening

Magnetic resonance imaging indicators of blood-brain barrier and brain water changes in young rats with kaolin-induced hydrocephalus

<p>Abstract</p> <p>Background</p> <p>Hydrocephalus is associated with enlargement of cerebral ventricles. We hypothesized that magnetic resonance (MR) imaging parameters known to be influenced by tissue water content would change in parallel with ventricle size in young rats and that changes in blood-brain barrier (BBB) permeability would be detected.</p> <p>Methods</p> <p>Hydrocephalus was induced by injection of kaolin into the cisterna magna of 4-week-old rats, which were studied 1 or 3 weeks later. MR was used to measure longitudinal and transverse relaxation times (T1 and T2) and apparent diffusion coefficients in several regions. Brain tissue water content was measured by the wet-dry weight method, and tissue density was measured in Percoll gradient columns. BBB permeability was measured by quantitative imaging of changes on T1-weighted images following injection of gadolinium diethylenetriamine penta-acetate (Gd-DTPA) tracer and microscopically by detection of fluorescent dextran conjugates.</p> <p>Results</p> <p>In nonhydrocephalic rats, water content decreased progressively from age 3 to 7 weeks. T1 and T2 and apparent diffusion coefficients did not exhibit parallel changes and there was no evidence of BBB permeability to tracers. The cerebral ventricles enlarged progressively in the weeks following kaolin injection. In hydrocephalic rats, the dorsal cortex was more dense and the white matter less so, indicating that the increased water content was largely confined to white matter. Hydrocephalus was associated with transient elevation of T1 in gray and white matter and persistent elevation of T2 in white matter. Changes in the apparent diffusion coefficients were significant only in white matter. Ventricle size correlated significantly with dorsal water content, T1, T2, and apparent diffusion coefficients. MR imaging showed evidence of Gd-DTPA leakage in periventricular tissue foci but not diffusely. These correlated with microscopic leak of larger dextran tracers.</p> <p>Conclusions</p> <p>MR characteristics cannot be used as direct surrogates for water content in the immature rat model of hydrocephalus, probably because they are also influenced by other changes in tissue composition that occur during brain maturation. There is no evidence for widespread persistent opening of BBB as a consequence of hydrocephalus in young rats. However, increase in focal BBB permeability suggests that periventricular blood vessels may be disrupted.</p

Pathogen Sensing Pathways in Human Embryonic Stem Cell Derived-Endothelial Cells: Role of NOD1 Receptors.

Human embryonic stem cell-derived endothelial cells (hESC-EC), as well as other stem cell derived endothelial cells, have a range of applications in cardiovascular research and disease treatment. Endothelial cells sense Gram-negative bacteria via the pattern recognition receptors (PRR) Toll-like receptor (TLR)-4 and nucleotide-binding oligomerisation domain-containing protein (NOD)-1. These pathways are important in terms of sensing infection, but TLR4 is also associated with vascular inflammation and atherosclerosis. Here, we have compared TLR4 and NOD1 responses in hESC-EC with those of endothelial cells derived from other stem cells and with human umbilical vein endothelial cells (HUVEC). HUVEC, endothelial cells derived from blood progenitors (blood outgrowth endothelial cells; BOEC), and from induced pluripotent stem cells all displayed both a TLR4 and NOD1 response. However, hESC-EC had no TLR4 function, but did have functional NOD1 receptors. In vivo conditioning in nude rats did not confer TLR4 expression in hESC-EC. Despite having no TLR4 function, hESC-EC sensed Gram-negative bacteria, a response that was found to be mediated by NOD1 and the associated RIP2 signalling pathways. Thus, hESC-EC are TLR4 deficient but respond to bacteria via NOD1. This data suggests that hESC-EC may be protected from unwanted TLR4-mediated vascular inflammation, thus offering a potential therapeutic advantage

Clone-specific expression, transcriptional regulation, and action of interleukin-6 in human colon carcinoma cells

<p>Abstract</p> <p>Background</p> <p>Many cancer cells produce interleukin-6 (IL-6), a cytokine that plays a role in growth stimulation, metastasis, and angiogenesis of secondary tumours in a variety of malignancies, including colorectal cancer. Effectiveness of IL-6 in this respect may depend on the quantity of basal and inducible IL-6 expressed as the tumour progresses through stages of malignancy. We therefore have evaluated the effect of <it>IL-6 </it>modulators, i.e. IL-1β, prostaglandin E₂, 17β-estradiol, and 1,25-dihydroxyvitamin D₃, on expression and synthesis of the cytokine at different stages of tumour progression.</p> <p>Methods</p> <p>We utilized cultures of the human colon carcinoma cell clones Caco-2/AQ, COGA-1A and COGA-13, all of which expressed differentiation and proliferation markers typical of distinct stages of tumour progression. IL-6 mRNA and protein levels were assayed by RT-PCR and ELISA, respectively. DNA sequencing was utilized to detect polymorphisms in the <it>IL-6 </it>gene promoter.</p> <p>Results</p> <p><it>IL-6 </it>mRNA and protein concentrations were low in well and moderately differentiated Caco-2/AQ and COGA-1A cells, but were high in poorly differentiated COGA-13 cells. Addition of IL-1β (5 ng/ml) to a COGA-13 culture raised IL-6 production approximately thousandfold via a prostaglandin-independent mechanism. Addition of 17β-estradiol (10^-7M) reduced basal IL-6 production by one-third, but IL-1β-inducible IL-6 was unaffected. Search for polymorphisms in the <it>IL-6 </it>promoter revealed the presence of a single haplotype, i.e., -597A/-572G/-174C, in COGA-13 cells, which is associated with a high degree of transcriptional activity of the <it>IL-6 </it>gene. IL-6 blocked differentiation only in Caco-2/AQ cells and stimulated mitosis through up-regulation of c-<it>myc </it>proto-oncogene expression. These effects were inhibited by 10^-8M 1,25-dihydroxyvitamin D₃.</p> <p>Conclusion</p> <p>In human colon carcinoma cells derived from well and moderately differentiated tumours, IL-6 expression is low and only marginally affected, if at all, by PGE₂, 1,25-dihydroxyvitamin D₃, and 17β-estradiol. However, IL-6 is highly abundant in undifferentiated tumour cells and is effectively stimulated by IL-1β. In case of overexpression of an <it>IL-6 </it>gene variant with extreme sensitivity to IL-1β, massive release of the cytokine from undifferentiated tumour cells may accelerate progression towards malignancy by paracrine action on more differentiated tumour cells with a still functioning proliferative IL-6 signalling pathway.</p

Can Disease Management Target Patients Most Likely to Generate High Costs? The Impact of Comorbidity

CONTEXT: Disease management programs are increasingly used to manage costs of patients with chronic disease. OBJECTIVE: We sought to examine the clinical characteristics and measure the health care expenditures of patients most likely to be targeted by disease management programs. DESIGN: Retrospective analysis of prospectively obtained data. SETTING: A general medicine practice with both faculty and residents at an urban academic medical center. PARTICIPANTS: Five thousand eight hundred sixty-one patients enrolled in the practice for at least 1 year. MAIN OUTCOMES: Annual cost of diseases targeted by disease management. MEASUREMENTS: Patients’ clinical and demographic information were collected from a computer system used to manage patients. Data included diagnostic information, medications, and resource usage over 1 year. We looked at 10 common diseases targeted by disease management programs. RESULTS: Unadjusted annual median costs for chronic diseases ranged between $1,100 and$1,500. Congestive heart failure ($1,500), stroke ($1,500), diabetes ($1,500), and cancer ($1,400) were the most expensive. As comorbidity increased, annual adjusted costs increased exponentially. Those with comorbidity scores of 2 or more accounted for 26% of the population but 50% of the overall costs. CONCLUSIONS: Costs for individual chronic conditions vary within a relatively narrow range. However, the costs for patients with multiple coexisting medical conditions increase rapidly. Reducing health care costs will require focusing on patients with multiple comorbid diseases, not just single diseases. The overwhelming impact of comorbidity on costs raises significant concerns about the potential ability of disease management programs to limit the costs of care

Forward Masking Estimated by Signal Detection Theory Analysis of Neuronal Responses in Primary Auditory Cortex

Psychophysical forward masking is an increase in threshold of detection of a sound (probe) when it is preceded by another sound (masker). This is reminiscent of the reduction in neuronal responses to a sound following prior stimulation. Studies in the auditory nerve and cochlear nucleus using signal detection theory techniques to derive neuronal thresholds showed that in centrally projecting neurons, increases in masked thresholds were significantly smaller than the changes measured psychophysically. Larger threshold shifts have been reported in the inferior colliculus of awake marmoset. The present study investigated the magnitude of forward masking in primary auditory cortical neurons of anaesthetised guinea-pigs. Responses of cortical neurons to unmasked and forward masked tones were measured and probe detection thresholds estimated using signal detection theory methods. Threshold shifts were larger than in the auditory nerve, cochlear nucleus and inferior colliculus. The larger threshold shifts suggest that central, and probably cortical, processes contribute to forward masking. However, although methodological differences make comparisons difficult, the threshold shifts in cortical neurons were, in contrast to subcortical nuclei, actually larger than those observed psychophysically. Masking was largely attributable to a reduction in the responses to the probe, rather than either a persistence of the masker responses or an increase in the variability of probe responses

Association between COX-2 rs 6681231 Genotype and Interleukin-6 in Periodontal Connective Tissue. A Pilot Study

This study was partially undertaken at the UCL Eastman Dental Institute, which received a proportion of funding from the Department of Health’s National Institute of Health Research (NIHR) Biomedical Research Centres funding scheme

C-reactive protein, interleukin-6, and prostate cancer risk in men aged 65 years and older.

Inflammation is believed to play a role in prostate cancer (PCa) etiology, but it is unclear whether inflammatory markers C-reactive protein (CRP) and interleukin-6 (IL-6) associate with PCa risk in older men. Using Cox regression, we assessed the relationship between baseline concentrations of CRP and IL-6 and the subsequent PCa risk in the Cardiovascular Health Study, a population-based cohort study of mostly European American men of ages >64 years (n = 2,234; mean follow-up = 8.7 years; 215 incident PCa cases). We also tested associations between CRP and IL-6 tagSNPs and PCa risk, focusing on SNPs that are known to associate with circulating CRP and/or IL-6. Neither CRP nor IL-6 blood concentrations was associated with PCa risk. The C allele of IL-6 SNP rs1800795 (-174), a known functional variant, was associated with increased risk in a dominant model (HR = 1.44; 95% CI = 1.03-2.01; p = 0.03), but was not statistically significant after accounting for multiple tests (permutation p = 0.21). Our results suggest that circulating CRP and IL-6 do not influence PCa risk. SNPs at the CRP locus are not associated with PCa risk in this cohort, while the association between rs1800795 and PCa risk warrants further investigation