Surgical outcomes for chronic exertional compartment syndrome following improved diagnostic criteria.

INTRODUCTION: Chronic exertional compartment syndrome (CECS) presents with pain during exercise, most commonly within the anterior compartment of the lower limb. A diagnosis is classically made from a typical history and the measurement of intramuscular compartmental pressure (IMCP) testing. Improved, more specific diagnostic criteria for IMCP testing allow clinicians to now be more certain of a diagnosis of CECS. Outcomes following surgical treatment in patients diagnosed using these more robust criteria are unknown. METHODS: All patients undergoing fasciectomy for anterior compartment CECS at a single rehabilitation unit were identified between 2014 and 2017. Wilcoxen signed-rank test was used to compare military fitness grading and paired t-test was used to compare Foot and Ankle Ability Measure, FAAM Sport Specific and Exercise-Induced LimbPain-G outcome measures, presurgery and postsurgery. RESULTS: There was a significant difference in fitness grading between presurgical and postsurgical intervention (Z = -2.68, p < 0.01) with 46 % of patients improving their occupational medical grading. All secondary measures of outcome, looking at clinical symptoms, also improved. CONCLUSION: Almost half of the patients undergoing fasciectomy, following diagnosis using more specific criteria, will have an improvement in occupational medical grading. These outcomes represent the lower end of those reported in civilian populations. This is likely a result of a combination of factors, most notably the different diagnostic criteria followed and the more stringent criteria applied to military occupational grading, compared with civilian practice. Further work is now required to evaluate the impact of differing rehabilitation regimes on postoperative patients identified through this more specific diagnostic testing.

Cheiroarthropathy and tendinopathy in diabetes.

Joint problems commonly occur in people with diabetes. Cheiroarthropathy affects the hands and results in painless limited finger joint extension, appearing to be associated with longer diabetes duration and the presence of microvascular complications. The prevalence of cheiroarthropathy seems to be falling, perhaps as a result of improvements in glycaemic management. Non-enzymatic glycation of collagen results in abnormally crosslinked protein resistant to degradation with subsequent increased build-up of collagen in joints. The management of cheiroarthropathy is predominantly conservative, with occupational and hand therapy at the forefront. Tendinopathy is more common in people with diabetes than those without, and is associated with obesity and insulin resistance. As with cheiroarthropathy, the exact causative mechanism of tendinopathy in diabetes is not known, but may be linked to inflammation, apoptosis and increased vascularity of affected tendons, driven by hyperinsulinaemia. Local fat pads have also been suggested to play a role in the pathogenesis of tendinopathy.

Barefoot plantar pressure measurement in Chronic Exertional Compartment Syndrome.

BACKGROUND: Patients with Chronic Exertional Compartment Syndrome (CECS) have exercise-limiting pain that subsides at rest. Diagnosis is confirmed by intramuscular compartment pressure (IMCP) measurement. Accompanying CECS, subjective changes to gait (foot slap) are frequently reported by patients. This has not previously been investigated. The aim of this study was to investigate differences in barefoot plantar pressure (BFPP) between CECS cases and asymptomatic controls prior to the onset of painful symptoms. METHODS: 40 male military volunteers, 20 with symptoms of CECS and 20 asymptomatic controls were studied. Alternative diagnoses were excluded with rigorous inclusion criteria, magnetic resonance imaging and dynamic IMCP measurement. BFPP was measured during walking and marching. Data were analysed for: Stance Time (ST); foot progression angle (FPA); centre of force; plantarflexion rate after heel strike (IFFC-time); the distribution of pressure under the heel; and, the ratio between inner and outer metatarsal loading. Correlation coefficients of each variable with speed and leg length were calculated followed by ANCOVA or t-test. Receiver operating characteristic (ROC) curves were constructed for IFFC-time. RESULTS: Caseshad shorter ST and IFFC-times than controls. FPA was inversely related to walking speed (WS) in controls only. The area under the ROC curve for IFFC-time ranged from 0.746 (95%CI: 0.636-0.87) to 0.773 (95%CI: 0.671-0.875) representing 'fair predictive validity'. CONCLUSION: Patients with CECS have an increased speed of ankle plantarflexion after heel strike that precedes the onset of painful symptoms likely resulting from a mechanical disadvantage of Tibialis Anterior. These findings provide further insight into the pathophysiology of CECS and support further investigation of this non-invasive diagnostic. The predictive value of IFFC-time in the diagnosis of CECS is comparable to post-exercise IMCP but falls short of dynamic IMCP measured during painful symptoms.

Identifying environmental reservoirs of Clostridium difficile with a scent detection dog: preliminary evaluation.

BACKGROUND AND AIM: Prompted by an article describing a dog trained to detect Clostridium difficile in patients, our institution evaluated a dog's ability to detect C. difficile scent from equipment and surfaces to assist in strategic deployment of adjunctive cleaning measures. METHODS: An expert in drug and explosives scent dog handling trained a canine to identify odours from pure cultures and/or faecal specimens positive for C. difficile. Methods used to assess explosive and drug detection dogs were adapted and included evaluation of (i) odour recognition, using containers positive and negative for the scent of C. difficile, and of (ii) search capability, on a simulation ward with hidden scents. After demonstration that the canine could accurately and reliably detect the scent of C. difficile, formal assessments of all clinical areas began. FINDINGS: Odour recognition (N = 75 containers) had a sensitivity of 100% and specificity of 97%. Search capability was 80% sensitive and 92.9% specific after removal of results from one room where dog and trainer fatigue influenced performance. Both odour recognition and search capability had an overall sensitivity of 92.3% and specificity of 95.4%. The clinical unit sweeps over a period of five months revealed a sensitivity of 100% in alerting on positive quality control hides. These clinical unit sweeps also resulted in 83 alerts during 49 sweep days. CONCLUSION: A dog can be trained to accurately and reliably detect C. difficile odour from environmental sources to guide the best deployment of adjunctive cleaning measures and can be successfully integrated into a quality infection control programme.

Evaluation of two chromogenic media for the isolation and identification of urinary tract pathogens.

Chromogenic media (CM) are available for urine specimens (US) to enable rapid identification of common urinary tract pathogens (UTP). Two CM, chromID™ CPS (CPS4) agar (bioMérieux, St. Laurent, QC) and UriSelect™ 4 (URS4) agar (Bio-Rad, Montreal, QC), were compared to the standard media (SM) for the isolation and identification of UTP. Over a 10-day period, US were inoculated to CPS4, URS4, and SM (BAP and MAC). CM interpretation was done according to the product inserts by one person blinded to the results of SM. SM were read by experienced technologists according to protocol and isolates were identified using BD Phoenix™. The results were grouped into significant (SG), mixed (MG), and no significant growth (NSG). A total of 903 US were studied. SM identified 239 SG, 112 MG, and 552 NSG cultures. The most common pathogens were Escherichia coli (38 %) and Enterococcus spp. (11 %). Comparing CM to SM, the exact agreement was 89.3 and 89.5 % for URS4 and CPS4, respectively. When grouped by clinical significance, agreement with SM was 93.0 and 93.1 % for URS4 and CPS4, respectively. CM were equivalent with respect to processing time. Advantages include decreased need for automated identification of certain species, particularly E. coli. In terms of workflow, CM enables same-day identification for almost 50 % of significant UTP. Overall, both CM compared well to SM and allowed for rapid preliminary identification of many UTP.

Nasal photodisinfection and chlorhexidine wipes decrease surgical site infections: a historical control study and propensity analysis.

BACKGROUND: Pre-operative decolonization therapy (DcTx) using chlorhexidine (CHG) body washes and/or intranasal mupirocin can reduce surgical site infections (SSIs), but compliance is often suboptimal. AIM: To assess the effectiveness of immediate DcTx using a novel approach of intranasal antimicrobial photodisinfection therapy (PDT) combined with CHG body wipes for the reduction of SSIs. METHODS: Between 1(st) September 2011 and 31(st) August 2012, 3068 elective cardiac, orthopaedic, spinal, vascular, thoracic and neurosurgical patients were treated with CHG in the 24h preceding surgery, and received intranasal PDT in the pre-operative area. SSI surveillance methodology remained unchanged from previous years and patients were followed for one year. Results were compared with those for a four-year historical control group of 12,387 patients as well as those for a concurrent control group of 206 untreated patients. FINDINGS: A significant reduction in the SSI rate was observed between treated patients and the historical control group [1.6% vs 2.7%, P = 0.0004, odds ratio (OR) 1.73, 95% confidence interval (CI) 1.2815-2.3453]. This significant reduction was maintained on intent-to-treat analysis (P = 0.021, OR 1.37, 95% CI 1.0476−1.7854) [corrected]. Overall compliance with DcTx was 94%. A 1:4 propensity score analysis of matched treated and untreated patients demonstrated that DcTx reduced the risk of SSIs significantly (P = 0.00026, z = 3.65). CONCLUSION: The combination of CHG wipes and PDT immediately before surgery reduced SSIs, achieved excellent compliance, and was easily integrated into the pre-operative routine.

Complete sequences of a novel blaNDM-1-harbouring plasmid from Providencia rettgeri and an FII-type plasmid from Klebsiella pneumoniae identified in Canada.

OBJECTIVES: Emergence of plasmids harbouring bla(NDM-1) is a major public health concern due to their association with multidrug resistance and their potential mobility. METHODS: PCR was used to detect bla(NDM-1) from clinical isolates of Providencia rettgeri (PR) and Klebsiella pneumoniae (KP). Antimicrobial susceptibilities were determined using Vitek 2. The complete DNA sequence of two bla(NDM-1) plasmids (pPrY2001 and pKp11-42) was obtained using a 454-Genome Sequencer FLX. Contig assembly and gap closures were confirmed by PCR-based sequencing. Comparative analysis was done using BLASTn and BLASTp algorithms. RESULTS: Both clinical isolates were resistant to all ß-lactams, carbapenems, aminoglycosides, ciprofloxacin and trimethoprim/sulfamethoxazole, and susceptible to tigecycline. Plasmid pPrY2001 (113 295 bp) was isolated from PR. It did not show significant homology to any known plasmid backbone and contained a truncated repA and novel repB. Two bla(NDM-1)-harbouring plasmids from Acinetobacter lwoffii (JQ001791 and JQ060896) shared 100% similarity to a 15 kb region that contained bla(NDM-1). pPrY2001 also contained a type II toxin/antitoxin system. pKp11-42 (146 695 bp) was isolated from KP. It contained multiple repA genes. The plasmid backbone had the highest homology to the IncFIIk plasmid type (51% coverage, 100% nucleotide identity). The bla(NDM-1) region was unique in that it was flanked upstream by IS3000 and downstream by a novel transposon designated Tn6229. pKp11-42 also contained a number of mutagenesis and plasmid stability proteins. CONCLUSIONS: pPrY2001 differed from all known plasmids due to its novel backbone and repB. pKp11-42 was similar to IncFIIk plasmids and contained a number of genes that aid in plasmid persistence.

Anatomy and histology of the transverse humeral ligament.

The classic literature describes the transverse humeral ligament (THL) as a distinct anatomic structure with a role in biceps tendon stability; however, recent literature suggests that it is not a distinct anatomic structure. The purpose of this study was to evaluate the gross and microscopic anatomy of the THL, including a specific investigation of the histology of this ligament. Thirty frozen, embalmed cadaveric specimens were dissected to determine the gross anatomy of the THL. Seven specimens were evaluated histologically for the presence of mechanoreceptors and free nerve endings. Two tissue layers were identified in the area described as the THL. In the deep layer, fibers of the subscapularis tendon were found to span the bicipital groove with contributions from the coracohumeral ligament and the supraspinatus tendon. Superficial to this layer was a fibrous fascial covering consisting of distinct bands of tissue. Neurohistology staining revealed the presence of free nerve endings but no mechanoreceptors. This study's findings demonstrate that the THL is a distinct structure continuous with the rotator cuff tendons and the coracohumeral ligament. The finding of free nerve endings in the THL suggests a potential role as a shoulder pain generator.

IFN-γ signaling to astrocytes protects from autoimmune mediated neurological disability.

Demyelination and axonal degeneration are determinants of progressive neurological disability in patients with multiple sclerosis (MS). Cells resident within the central nervous system (CNS) are active participants in development, progression and subsequent control of autoimmune disease; however, their individual contributions are not well understood. Astrocytes, the most abundant CNS cell type, are highly sensitive to environmental cues and are implicated in both detrimental and protective outcomes during autoimmune demyelination. Experimental autoimmune encephalomyelitis (EAE) was induced in transgenic mice expressing signaling defective dominant-negative interferon gamma (IFN-γ) receptors on astrocytes to determine the influence of inflammation on astrocyte activity. Inhibition of IFN-γ signaling to astrocytes did not influence disease incidence, onset, initial progression of symptoms, blood brain barrier (BBB) integrity or the composition of the acute CNS inflammatory response. Nevertheless, increased demyelination at peak acute disease in the absence of IFN-γ signaling to astrocytes correlated with sustained clinical symptoms. Following peak disease, diminished clinical remission, increased mortality and sustained astrocyte activation within the gray matter demonstrate a critical role of IFN-γ signaling to astrocytes in neuroprotection. Diminished disease remission was associated with escalating demyelination, axonal degeneration and sustained inflammation. The CNS infiltrating leukocyte composition was not altered; however, decreased IL-10 and IL-27 correlated with sustained disease. These data indicate that astrocytes play a critical role in limiting CNS autoimmune disease dependent upon a neuroprotective signaling pathway mediated by engagement of IFN-γ receptors.

Carbapenem-resistant Gram-negative bacilli in Canada 2009-10: results from the Canadian Nosocomial Infection Surveillance Program (CNISP).

OBJECTIVES: To investigate the occurrence and molecular mechanisms associated with carbapenemases in carbapenem-resistant Gram-negative isolates from Canadian cases. METHODS: Twenty hospital sites across Canada submitted isolates for a 1 year period starting 1 September 2009. All Enterobacteriaceae with MICs ≥ 2 mg/L and Acinetobacter baumannii and Pseudomonas aeruginosa with MICs ≥ 16 mg/L of carbapenems were submitted to the National Microbiology Laboratory (NML) where carbapenem MICs were confirmed by Etest and isolates were characterized by PCR for carbapenemase genes, antimicrobial susceptibilities, PFGE and plasmid isolation. RESULTS: A total of 444 isolates (298 P. aeruginosa, 134 Enterobacteriaceae and 12 A. baumannii) were submitted to the NML of which 274 (61.7%; 206 P. aeruginosa, 59 Enterobacteriaceae and 9 A. baumannii) met the inclusion criteria as determined by Etest. Carbapenemase genes were identified in 30 isolates: bla(GES-5) (n = 3; P. aeruginosa), bla(KPC-3) (n = 7; Enterobacteriaceae), bla(NDM-1) (n = 2; Enterobacteriaceae), bla(VIM-2) and bla(VIM-4) (n = 8; P. aeruginosa) bla(SME-2) (n = 1; Enterobacteriaceae) and bla(OXA-23) (n = m9; A. baumannii). PFGE identified a cluster in each of Enterobacteriaceae, P. aeruginosa and A. baumannii corresponding to isolates harbouring carbapenemase genes. Three KPC plasmid patterns (IncN and FllA) were identified where indistinguishable plasmid patterns were identified in unrelated clinical isolates. CONCLUSIONS: Carbapenemases were rare at the time of this study. Dissemination of carbapenemases was due to both dominant clones and common plasmid backbones.

Role of differentiation of liver sinusoidal endothelial cells in progression and regression of hepatic fibrosis in rats.

BACKGROUND & AIMS: Capillarization, characterized by loss of differentiation of liver sinusoidal endothelial cells (LSECs), precedes the onset of hepatic fibrosis. We investigated whether restoration of LSEC differentiation would normalize crosstalk with activated hepatic stellate cells (HSC) and thereby promote quiescence of HSC and regression of fibrosis. METHODS: Rat LSECs were cultured with inhibitors and/or agonists and examined by scanning electron microscopy for fenestrae in sieve plates. Cirrhosis was induced in rats using thioacetamide, followed by administration of BAY 60-2770, an activator of soluble guanylate cyclase (sGC). Fibrosis was assessed by Sirius red staining; expression of α-smooth muscle actin was measured by immunoblot analysis. RESULTS: Maintenance of LSEC differentiation requires vascular endothelial growth factor-A stimulation of nitric oxide-dependent signaling (via sGC and cyclic guanosine monophosphate) and nitric oxide-independent signaling. In rats with thioacetamide-induced cirrhosis, BAY 60-2770 accelerated the complete reversal of capillarization (restored differentiation of LSECs) without directly affecting activation of HSCs or fibrosis. Restoration of differentiation to LSECs led to quiescence of HSCs and regression of fibrosis in the absence of further exposure to BAY 60-2770. Activation of sGC with BAY 60-2770 prevented progression of cirrhosis, despite continued administration of thioacetamide. CONCLUSIONS: The state of LSEC differentiation plays a pivotal role in HSC activation and the fibrotic process.

Interferon-gamma release assays are a better tuberculosis screening test for hemodialysis patients: A study and review of the literature.

Diagnosing latent tuberculosis (TB) infection (LTBI) in dialysis patients is complicated by poor response to tuberculin skin testing (TST), but the role of interferon-gamma release assays (IGRAs) in the dialysis population remains uncertain. Seventy-nine patients were recruited to compare conventional diagnosis (CD) with the results of two IGRA tests in a dialysis unit. Combining TST, chest x-ray and screening questionnaire results (ie, CD) identified 24 patients as possible LTBI. IGRA testing identified 22 (QuantiFERON Gold IT, Cellestis, USA) and 23 (T-spot.TB, Oxford Immunotec, United Kingdom) LTBI patients. IGRA and CD correlated moderately (κ=0.59). IGRA results correlated with history of TB, TB contact and birth in an endemic country. TST was not helpful in identifying LTBI patients in this population. The tendency for IGRAs to correlate with risk factors for TB, active TB infection and history of TB argues for their superiority over TST in dialysis patients. There was no superiority of one IGRA test over another.

Le diagnostic d'infection tuberculeuse latente (ITBL) chez les patients sous dialyse est compliqué par le peu de réponse au test cutané à la tuberculine (TCT), mais le rôle du test de libération d'interféron gamma (TLIG) au sein de la population sous dialyse demeure incertain. Les auteurs ont recruté 79 patients pour comparer le diagnostic classique (DC) aux résultats de deux TLIG au sein d'une unité de dialyse. L'association du TCT, de la radiographie pulmonaire et des résultats d'un questionnaire de dépistage (c.-à-d. le DC) a permis de dépister 24 patients comme pouvant être atteints d'une ITBL. Le TLIG a permis de dépister 22 (QuantiFERON Gold IT, Cellestis, États-Unis) et 23 (T-spot.TB, Oxford Immunotec, Royaume-Uni) patients atteints d'une ITBL. Le TLIG et le DC avaient une corrélation modérée (κ=0,59). Les résultats du TLIG étaient corrélés avec les antécédents de tuberculose (TB), les contacts atteints de TB et la naissance dans un pays endémique. Le TCT ne contribuait pas à dépister les patients atteints d'une ITBL au sein de cette population. La tendance des TLIG à être corrélés avec les facteurs de risque de TB, une infection active par la TB et les antécédents de TB laisse supposer leur supériorité par rapport au TCT chez les patients sous dialyse. Aucun type de TLIG n'était supérieur aux autres.

Prevention of hepatic fibrosis in a murine model of metabolic syndrome with nonalcoholic steatohepatitis.

The endocannabinoid pathway plays an important role in the regulation of appetite and body weight, hepatic lipid metabolism, and fibrosis. Blockade of the endocannabinoid receptor CB1 with SR141716 promotes weight loss, reduces hepatocyte fatty acid synthesis, and is antifibrotic. D-4F, an apolipoprotein A-1 mimetic with antioxidant properties, is currently in clinical trials for the treatment of atherosclerosis. C57BL/6J mice were fed a high-fat diet for 7 months, followed by a 2.5-month treatment with either SR141716 or D-4F. SR141716 markedly improved body weight, liver weight, serum transaminases, insulin resistance, hyperglycemia, hypercholesterolemia, hyperleptinemia, and oxidative stress, accompanied by the significant prevention of fibrosis progression. D-4F improved hypercholesterolemia and hyperleptinemia without improvement in body weight, steatohepatitis, insulin resistance, or oxidative stress, and yet, there was significant prevention of fibrosis. D-4F prevented culture-induced activation of stellate cells in vitro. In summary, C57BL/6J mice given a high-fat diet developed features of metabolic syndrome with nonalcoholic steatohepatitis and fibrosis. Both SR141716 and D-4F prevented progression of fibrosis after onset of steatohepatitis, ie, a situation comparable to a common clinical scenario, with D-4F seeming to have a more general antifibrotic effect. Either compound therefore has the potential to be of clinical benefit.

Methicillin-resistant Staphylococcus aureus nasal carriage among injection drug users: six years later.

A survey in 2000 to detect methicillin-resistant Staphylococcus aureus (MRSA) colonization in Vancouver downtown east side injection drug users (IDUs) revealed an MRSA nasal colonization incidence of 7.4%. This is a follow-up study to determine the current prevalence of MRSA colonization and to further characterize the isolates and risk factors for colonization. In this point prevalence study of MRSA nasal carriage among IDUs, nasal swabs were cultured to detect S. aureus. Isolates were studied for their antimicrobial susceptibility patterns and the presence of mecA and Panton-Valentine leukocidin (PVL) genes and by pulsed-field gel electrophoresis (PFGE). S. aureus was isolated from 119 of 301 (39.5%) samples; three (2.5%) participants had both methicillin-sensitive S. aureus (MSSA) and MRSA, resulting in 122 isolates. Of these, 54.1% were MSSA and 45.9% were MRSA, with an overall MRSA rate of 18.6%. USA-300 (CMRSA-10) accounted for 75% of all MRSA isolates; 25% were USA-500 (CMRSA-5). None of the USA-500 isolates were positive for PVL; 41 (97.6%) USA-300 isolates contained PVL. One MSSA isolate, from an individual also carrying USA-300, was positive for PVL. The PFGE pattern of this MSSA isolate was related to that of the MRSA strain. The antibiograms of USA-300 compared to USA-500 isolates showed 100% versus 7.1% susceptibility to trimethoprim-sulfamethoxazole (TMP-SMX) and 54.8% versus 7.1% susceptibility to clindamycin. MRSA nasal colonization in this population has increased significantly within the last 6 years, with USA-300 replacing the previous strain. Most of these strains are PVL positive, and all are susceptible to TMP-SMX.

Review of meningioma histopathology.

The histological appearance of a meningioma is an important predictor of tumor behavior and is frequently a factor in decisions concerning therapy. The relationship between histological features and prognosis is formalized in grading schemes such as those published by the World Health Organization (WHO), most recently in 2007. Although the latest edition is an improvement over previous grading schemes, the WHO scheme still fails to fully address a variety of important issues regarding the relationship between meningioma histological characteristics and behavior. In particular, routine histological examination fails to identify the subset of Grade I tumors that behave aggressively. Because of this, many additional prognostic markers that require immunohistochemical, cytogenetic, or molecular techniques to evaluate are under investigation. Only one, immunohistochemistry for the proliferation marker, Ki 67 (MIB-1), is used routinely and it has only limited utility. It is hoped that an understanding of the genetic changes that underlie tumor progression will improve healthcare professionals' ability to predict the behavior of meningiomas.

Telomerase and markers of cellular proliferation are associated with the progression of cervical intraepithelial neoplasia lesions.

The expression of the catalytic subunit of telomerase protein (human telomerase reverse transcriptase [hTERT]), which is associated with telomerase activity, was evaluated as a potential marker of the high-grade premalignant cervical intraepithelial neoplasia (CIN 2/3) lesions. For comparison, cases of normal cervical squamous mucosa, low-grade CIN1 lesion, and cervical squamous cell carcinoma were included. The hTERT expression was also compared with Ki-67 and topoisomerase II-alpha (TPII-alpha) to determine the proliferative activity of the hTERT-positive dysplastic cells by a quantitative immunohistochemical staining method and was classified as follows: negative, 5% or less; moderate, 6% to 50%; or high, greater than 50% of the positive cells. The hTERT-positive cells were detected in a patchy pattern in the lower parabasal layers and in much of the basal layer in normal squamous mucosa. A similar frequency of Ki-67- or TPII-alpha-positive cells was observed, with the exception of the basal layer cells that were mostly negative. It is worthy to note that the recognizable intact basal layer cells in cases of CIN lesions were also consistently positive for the expression of hTERT, but rarely for Ki-67 or TPII-alpha. The expression of hTERT was detected in a less patchy pattern at a high or moderate percentage of the dysplastic epithelial cells each in 28.5% of cases of CIN1 lesions. A similar frequency, high and moderate percentage combined, of the TPII-alpha-positive dysplastic cell was also observed. In contrast, a high percentage of the hTERT-positive dysplastic cells were detected as diffuse basal or full-length thickness in 87.5% or 95% of cases of CIN2 or CIN3, respectively. A similar frequency of Ki-67 or TPII-alpha expression was observed in the dysplastic cells of CIN3 lesions. The pattern of hTERT-positive malignant cells in squamous cell carcinoma and dysplastic cells in the high-grade CIN lesions, to a greater extent, and dysplastic cells in the low-grade CIN lesion, to a lesser extent, was distinct from that of the normal cervical squamous mucosa. The results suggest that the progressive increase in the hTERT expression, together with the proliferative activity of the dysplastic epithelial cells of the high-grade CIN lesions, represents an early genetic abnormality in cervical pathogenesis.

Liver X receptor activation decreases the severity of experimental autoimmune encephalomyelitis.

Agonists of liver X receptors (LXR), members of the nuclear hormone receptor superfamily, alter secretion of proinflammatory cytokines, suggesting potential antiinflammatory effects. A synthetic LXR agonist inhibited T-cell proliferation and cytokine release in a dose-dependent manner. Treatment of mice during induction of experimental autoimmune encephalomyelitis reduced clinical symptoms, central nervous system cellular inflammation, and major histocompatibility class II expression on microglia, as well as demyelination. In contrast to in vitro analysis, no reductions in peripheral neuroantigen specific T-cell responses were detected in comparing ligand and vehicle treated mice. These data suggest that LXR agonists play an important protective role in the regulation of T-cell-mediated inflammatory disease of the central nervous system.

Investigation of suspected laboratory cross-contamination: interpretation of single smear-negative, positive cultures for Mycobacterium tuberculosis.

Restriction fragment length polymorphism (RFLP) analysis can be used to assess genetic relatedness of Mycobacterium tuberculosis isolates. This study reports a collaborative investigation of false-positive cultures for M. tuberculosis, suspected when the DNA fingerprint from an index case matched an epidemiologically improbable source case. RFLP analysis matched fingerprints in ten of 16 cases of suspected laboratory contamination to four separate smear-positive sources that were processed on the same day in the same laboratory. All single smear-negative, positive cultures processed on the same day as smear-positive specimens should be reviewed on a case-by-case basis to identify possible false-positive cultures.