Relationship between cellular communication network factor 1 (CCN1) and carotid atherosclerosis in patients with rheumatoid arthritis.

BACKGROUND: The cellular communication network factor 1 (CCN1) is one of the matricellular proteins of the CCN family involved in chronic inflammatory disorders like rheumatoid arthritis (RA) and involved in human atherosclerotic lesions. This study was aimed to assess the levels of serum CCN1 in patients with rheumatoid arthritis (RA), evaluating its relation to carotid intima-media thickness (CIMT) and predisposition to subclinical carotid atherosclerosis and its impact on activity of RA disease. MATERIALS AND METHODS: This is a case-control study that included 105 RA patients classified into active and inactive groups according to disease activity score (DAS28) with 50 healthy matched controls. Clinical and laboratory assessments were done including enzyme-linked immunosorbent assay (ELISA) measurement of CCN1 with a bilateral assessment of CIMT using high resolutionultrasonography. Comparison of CCN1 between RA patients and controls, a correlation between CCN1, DAS28, swollen joint count (SJC), tender joint count (TJC), and CIMT were analyzed. RESULTS: There was significant elevation of CCN1 in RA patients compared to controls (235.62±62.5 vs. 73.11±18.2, respectively). The cut off value of CCN1 was 99.25 pg/ml, with an area under the curve (AUC) =0.995, p<0.001, 98 % sensitivity and 95% specificity. CCN1 was inversely correlated with DAS28 and its components in both active and inactive RA patients (r=- 0.92, r=- 0.94, p<0.001). CCN1 was inversely correlated with SJC (r= -0.64, r= - 0.67, p<0.001), TJC (r=- 0.56, r= - 0.63, p<0.001), and with Larsen xray score (r=- 0.68, r= - 0.78, p<0.001) in both active and inactive RA patients, respectively. The CCN1 levels in active RA patients were significantly lower than that in patients with low disease activity. A significant positive correlation between CCN1 levels and CIMT in RA patient groups (r=0.88, r=0.47, p<0.001, respectively) was found. CONCLUSION: Serum CCN1 could be a helpful biomarker in the diagnosis of RA, associated with RA remission. Disruption of serum CCN1 is engaged in the pathogenesis of atherosclerosis in RA patients which could be a clue for a future treatment strategy of atherosclerosis in RA by controlling CCN1 disruption. Regular follow-up of RA patients is recommended for early detection of subclinical atherosclerosis. New research ideas for controlling CCN1 disruption as new aspects of atherosclerosis treatment in RA patients are needed.

A peculiar case of Morel-Lavelle lesion of upper limb.

Morel-Lavallee lesions (MLL) are post-traumatic, closed internal degloving injuries that can result in severe complications if not diagnosed early. It is conventionally seen in cases of the high energy injuries of the pelvis and lower limb. The accumulation of extravasated blood, secondary to fracture and soft tissue damage may cause internal degloving injury, skin necrosis, soft tissue damage and acute osteomyelitis. We report here the clinical and radiological features in a 32-year-old male referred from the emergency department of a tertiary hospital who had sustained high energy motor vehicle accident. On examination, there was a fluctuant, mobile, non-tender subcutaneous mass over the distal arm with suspicion of internal degloving injury. Plain radiographs showed no fractures. Ultrasound showed a fluid collection with the presence of septations and echogenic debris within the collection. Extravasation was noted between subcutaneous tissue layer and fascia at the posterolateral aspect of the arm. Wound debridement under general anaesthesia was carried out. Intraoperative findings reported a significant amount of thick serous fluid with necrotic debris. Unhealthy skin and fat layers were debrided. Underlying muscles were found to be healthy. The results of the intraoperative fluid culture and sensitivity showed no growth. Negative pressure vacuum dressing was carried out. After five cycles of vacuum dressing, the wound showed signs of healing with an improved range of motion of the elbow. Orthopaedic surgeons need to be vigilant of the possibility of MLL in the upper limb as a differential diagnosis in the management of high energy trauma.

Diagnostic delay of pediatric inflammatory bowel disease in Saudi Arabia.

BACKGROUND/AIM: Delay in the diagnosis of inflammatory bowel disease (IBD) is associated with complications. Our aim was to describe the pattern and risk factors associated with delay in the diagnosis of IBD in Saudi children. PATIENTS AND METHODS: This was a multicenter study with a retrospective/prospective design. Data on diagnostic delay in children with Crohn's disease (CD) and ulcerative colitis (UC) were retrieved from physician's notes. Multivariate regression analysis was used to assess the risk factors associated with long delay in diagnosis. RESULTS: There were 240 and 183 Saudi children with CD and UC, respectively. The median delays in diagnosis were 8 and 5 months in CD and UC, respectively, significantly longer in children with CD than UC (P < 0.001). Long diagnostic delays (>75th percentile) were 24 and 8.8 months for CD and UC, respectively. Ileal location was a significant risk factor in CD and the age of onset above 10 years was protective in UC. CONCLUSIONS: Long diagnostic delay in IBD was mainly due to the longer delay in gastroenterologist consultation. Review of the referral system is needed to focus on measures to reduce long delays in diagnosis. The ileal location as a risk factor in CD and age older than 10 years as protective in UC should help recognition and early referral.

Carnitine Supplementation Attenuates Sunitinib-Induced Inhibition of AMP-Activated Protein Kinase Downstream Signals in Cardiac Tissues.

This study has been initiated to investigate whether sunitinib (SUN) alters the expression of key genes engaged in mitochondrial transport and oxidation of long chain fatty acids (LCFA), and if so, whether these alterations should be viewed as a mechanism of SUN-induced cardiotoxicity, and to explore the molecular mechanisms whereby carnitine supplementation could attenuate SUN-induced cardiotoxicity. Adult male Wister albino rats were assigned to one of the four treatment groups: Rats in group 1 received no treatment but free access to tap water for 28 days. Rats in group 2 received L-carnitine (200 mg/kg/day) in drinking water for 28 days. Rats in group 3 received SUN (25 mg/kg/day) in drinking water for 28 days. Rats in group 4 received the same doses of L-carnitine and SUN in drinking water for 28 days. Treatment with SUN significantly increased heart weight, cardiac index, and cardiotoxicity enzymatic indices, as well as severe histopathological changes. Moreover, SUN significantly decreased level of adenosine monophosphate-activated protein kinase (AMPKα2), total carnitine, adenosine triphosphate (ATP) and carnitine palmitoyltransferase I (CPT I) expression and significantly increased acetyl-CoA carboxylase-2 (ACC2) expression and malonyl-CoA level in cardiac tissues. Interestingly, carnitine supplementation resulted in a complete reversal of all the biochemical, gene expression and histopathological changes-induced by SUN to the control values. In conclusion, data from this study suggest that SUN inhibits AMPK downstream signaling with the consequent inhibition of mitochondrial transport of LCFA and energy production in cardiac tissues. Carnitine supplementation attenuates SUN-induced cardiotoxicity.

Mammography equipment performance, image quality and mean glandular dose in Malta.

In this first Maltese national mammography survey, the effectiveness of direct digital (DR) mammography in breast cancer screening has been confirmed. Patient data were made available from three clinics out of the participating nine. A dose survey of mean glandular dose (MGD) calculated for 759 patients examined in the state-owned mammography facilities was performed. An MGD national diagnostic reference level was set at 1.87 mGy for patients with breast compression thicknesses (BCT) between 5.0 and 7.0 cm. This range was selected since patient data were retrieved from three clinics only and the results showed that other international BCT reference levels may be unsuitable for the Maltese population. In fact, the overall average BCT was 5.75 ± 1.4 cm. The survey results have shown that the technical standard of mammographic equipment in the Malta National Breast Screening Programme is on a par with other countries, including its Western European counterparts.

A study to determine the differences between the displayed dose values for two full-field digitalmammography units and values calculated using a range of Monte-Carlo-based techniques:a phantom study.

Modern full-field digital mammography (FFDM) units display the mean glandular dose (MGD) and the entrance or incident air kerma (K) to the breast following each exposure. Information on how these values are calculated is limited and knowing how displayed MGD values compare and correlate to conventional Monte-Carlo-based methods is useful. From measurements done on polymethyl methacrylate (PMMA) phantoms, it has been shown that displayed and calculated MGD values are similar for thin to medium thicknesses and appear to differ with larger PMMA thicknesses. As a result, a multiple linear regression analysis on the data was performed to generate models by which displayed MGD values on the two FFDM units included in the study may be converted to the Monte-Carlo values calculated by conventional methods. These models should be a useful tool for medical physicists requiring MGD data from FFDM units included in this paper and should reduce the survey time spent on dose calculations.

The use of a figure-of-merit (FOM) for optimisation in digital mammography: a literature review.

The use of image quality parameters in digital mammography such as contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR) and detective quantum efficiency (DQE) has been widespread, with the intention of detector evaluation and/or quantitative evaluation of the system performance. These parameters are useful in ensuring adequate system performance when tests are done against international standards or guidelines. Parameters like CNR are relative quantities that lie within a range that is manufacturer and system dependent. The use of a figure-of-merit (FOM) is a relatively new concept as a tool in digital mammography permitting quantitative assessment in terms of image quality and patient dose. This review summarises the available evidence for the use and applicability of an FOM in digital mammography.

Differences in local environment determine the site of physiological angiogenesis in rat skeletal muscle.

The specificity in location of angiogenesis to either glycolytic or oxidative fibre types, or muscle regions, was examined in the tibialis anterior (TA) and extensor digitorum longus (EDL) muscles of rat. Angiogenesis was induced by mechanical means either with (chronic muscle stimulation) or without (muscle stretch by overload) changes in blood flow, treatments which invoked only minor changes in fibre type and fibre size. Proliferation estimated by PCNA labelling of cells co-localised with capillaries was very rare in control muscles, where it occurred mainly in the glycolytic regions, but was increased in both models of angiogenesis. However, when labelled capillaries were scored according to the type of surrounding fibres, only muscle stimulation significantly accentuated proliferation of capillaries surrounded by glycolytic fibres. We conclude that while mechanical stimuli are important for proliferation in glycolytic regions in both models, capillary growth occurs specifically around glycolytic fibres in that region when the angiogenic stimulus includes increased blood flow and/or increased metabolic demand.

Reducing the thrombogenicity of ion-selective electrode membranes through the use of a silicone-modified segmented polyurethane.

The susceptibility of segmented polyurethanes (SPUs) to in vivo oxidative cleavage and hydrolysis constitutes a drawback in the use of these materials in the fabrication of implantable devices. The introduction of poly(dimethylsiloxane) (PDMS) groups into the polymer main chain has been previously reported to enhance the stability of SPUs. Herein, we evaluated the use of BioSpan-S, a silicone-modified SPU, in the design of membranes for cation-selective electrodes. The resulting electrodes exhibited good potentiometric response with all of the tested ionophores (valinomycin, sodium ionophore X, and nonactin). The obtained selectivity coefficients meet the selectivity requirements for the determination of sodium and potassium in blood. Moreover, as reflected by SEM studies, membranes prepared with BioSpan-S showed less adhesion of platelets than membranes prepared with conventional poly(vinyl chloride) (PVC). These results lead to the conclusion that BioSpan-S would be an appropriate candidate for the fabrication of implantable ion-selective electrodes.

Development of a fully integrated analysis system for ions based on ion-selective optodes and centrifugal microfluidics.

A fully integrated, miniaturized analysis system for ions based on a centrifugal microfluidics platform and ion-selective optode membranes is described. The microfluidic architecture is composed of channels, five solution reservoirs, a measuring chamber, and a waste reservoir manufactured onto a disk-shaped substrate of poly(methyl methacrylate). Ion-selective optode membranes, composed of plasticized poly(vinyl chloride) impregnated with an ionophore, a proton chromoionophore, and a lipophilic anionic additive, were cast, with a spin-on device, onto a support layer and then immobilized on the disk. Fluid propulsion is achieved by the centrifugal force that results from spinning the disk, while a system of valves is built onto the disk to control flow. These valves operate based on fluid properties and fluid/substrate interactions and are controlled by the angular frequency of rotation. With this system, we have been able to deliver calibrant solutions, washing buffers, or "test" solutions to the measuring chamber where the optode membrane is located. An analysis system based on a potassium-selective optode has been characterized. Results indicate that optodes immobilized on the platform demonstrate theoretical responses in an absorbance mode of measurement. Samples of unknown concentration can be quantified to within 3% error by fitting the response function for a given optode membrane using an acid (for measuring the signal for a fully protonated chromoionophore), a base (for fully deprotonated chromoionophore), and two standard solutions. Further, the ability to measure ion concentrations by employing one standard solution in conjunction with acid and base and with two standards alone were studied to delineate whether the current architecture could be simplified. Finally, the efficacy of incorporating washing steps into the calibration protocol was investigated.

Flow injection analysis of sulfite ion with a potentiometric titanium phosphate-epoxy based membrane sensor.

A potentiometric sensor based on the use of titanium phosphate (TP) in epoxy matrix membrane is prepared and characterized. The sensor exhibits near-Nernstian response for many anionic species over the concentration range 10(-1)-10(-5) mol l(-1). The origin of response is explained on the basis of the conversion of titanium phosphate cation exchanger into hydrated titanium oxide anion exchanger by the effect of the high pH of the epoxy matrix. The sensitivity and selectivity of the sensor for sulfite ions are optimized by conversion of sulfite into gaseous SO(x) by acidification, and diffusion of the gas through a membrane-based gas dialyzer followed by potentiometric detection of sulfite ions formed within a flowing recipient stream. No interferences are caused by many common anions and acidic gas releasing species except sulfide and nitrite ions. Determination of sulfite ion at levels as low as 10(-4) mol l(-1) or less in the presence of nitrite and sulfide ions is performed by using a modified carrier buffer stream (10(-2) mol l(-1) MES, pH 5.0 containing sulfamic acid) and pretreatment with Pb(2+). Advantages offered by the proposed gas dialyzer/flow injection system with TP-epoxy membrane based sensor over traditional ion exchange based sensors includes long life time (>8 months), excellent stability and reproducibility ( approximately 1 mV), fast response time (<30 s), wide pH working range (pH 5-9), high sample throughput ( approximately 60 samples h(-1)), low detection limit (8x10(-6) mol l(-1)) and high thermal stability (up to 80 degrees C).

Tripodal ionophore with sulfate recognition properties for anion-selective electrodes.

Ionophore topology has a profound effect on the behavior of ion-selective electrodes. This is demonstrated with a new class of ionophores that incorporates aminochromenone moieties linked through urea spacers to different scaffolds that preorganize the ionophore binding cleft into tripodal topologies. Tris(2-aminoethylamine) and cis-1,3,5-tris(aminomethyl)cyclohexane were employed as the scaffolds. The two differ in their rigidity and in the size of ionophore cavity that they create. The electrodes based on the ionophore that incorporates the tris(2-aminoethylamine) scaffold show anti-Hofmeister behavior with an improved selectivity for sulfate. In contrast, the ionophore with the cis-1,3,5-tris(aminomethyl)cyclohexane scaffold exhibits a more Hofmeister-like response.

A selective optical sensor based on [9]mercuracarborand-3, a new type of ionophore with a chloride complexing cavity.

A highly selective optical sensor for chloride, based on the multidentate Lewis acid ionophore [9]mercuracarborand-3, is described herein. This sensor is constructed by embedding the mercuracarborand ionophore, a suitable pH-sensitive lipophilic dye, and lipophilic cationic sites in a plasticized polymeric membrane. The multiple complementary interactions offered by the preorganized complexing cavity of [9]mercuracarborand-3 is shown to control the anion selectivity pattern of the optical film. The film exhibits a significantly enhanced selectivity for chloride over a variety of lipophilic anions such as perchlorate, nitrate, salicylate, and thiocyanate. Furthermore, the optical selectivity coefficients obtained for chloride over other biologically relevant anions are shown to meet the selectivity requirements for the determination of chloride in physiological fluids, unlike previously reported chloride optical sensors. In addition, the optical film responds to chloride reversibly over a wide dynamic range (16 microM-136 mM) with fast response and recovery times.

Chrysosporium parvum keratomycosis.

PURPOSE: To report a case of corneal infection with Chrysosporium parvum, a filamentous fungus usually associated with pulmonary infections. METHODS: A 43-year-old Saudi man had a corneal stromal infiltrate and perforation of his left eye. He was treated with a therapeutic penetrating keratoplasty and topical and systemic antifungal therapy. Corneal scrapings, microbiologic evaluation, and histopathologic examination of the surgical specimen were performed to establish the diagnosis. After the development of recurrent stromal keratitis at the graft-host junction, similar diagnostic and therapeutic maneuvers were performed. RESULTS: Corneal scrapings and histopathologic examination were positive for numerous septate hyphae with endospores, consistent with a diagnosis of filamentous keratomycosis. Microbiologic isolation confirmed the diagnosis of Chrysosporium parvum. Similar diagnostic maneuvers for recurrent keratitis produced identical results. CONCLUSION: To our knowledge, this is the first case of Chrysosporium parvum keratomycosis.

Phototherapeutic keratectomy for macular corneal dystrophy.

PURPOSE: To report a case of early intervention with phototherapeutic keratectomy for treatment of macular corneal dystrophy. METHODS: We report a 21-year-old Saudi male with early macular corneal dystrophy, recurrent erosions, and decreased visual acuity, who underwent phototherapeutic keratectomy in the right eye and penetrating keratoplasty in the left eye with more than 2 years of follow-up. RESULTS: Following phototherapeutic keratectomy, uncorrected visual acuity in the right eye improved from 20/80 to 20/30. Following penetrating keratoplasty in the left eye, uncorrected visual acuity deteriorated from 20/80 to 20/120 due to irregular astigmatism; the eye was not amenable to improvement with spectacle correction, and the patient declined contact lens therapy. In the right eye, there has been no anterior recurrence, although some mid- to deep stromal haze, which is not visually significant, has developed. CONCLUSIONS: Early intervention for symptomatic, anterior macular corneal dystrophy with phototherapeutic keratectomy is relatively safe and preferable to observation or penetrating keratoplasty.

Mercuracarborand "anti-crown ether"-based chloride-sensitive liquid/polymeric membrane electrodes.

Highly sensitive and selective chloride liquid/polymeric membrane electrodes are described that employ [9]-mercuracarborand-3 (MC3), a neutral preorganized macrocyclic Lewis acid, as the anion carrier. MC3-based chloride-sensitive membrane electrodes, doped with different mole percentages of cationic additives (5, 10, and 60 mol % tridodecylmethylammonium chloride) relative to the amount of the carrier, exhibit enhanced potentiometric selectivity for chloride over other anions, including more lipophilic anions such as perchlorate, nitrate, and thiocyanate. In addition, the selectivity coefficients obtained are shown to meet the requirement for clinical applications. The obtained selectivity pattern is shown to correlate very well with 199Hg NMR titrations of MC3 with various anions, performed in organic solvents. Optimized membrane electrodes show a near-Nernstian response toward chloride over a wide concentration range and have micromolar detection limits. MC3-based chloride sensors show a fast response time (in the order of few seconds), as well as short recovery time. The developed mercuracarborand-based sensors do not practically respond to pH changes over the pH range of 2.5-7.0. Response characteristics (e.g., detection limit, linear range, response slope, and selectivity) of the [9]mercuracarborand-3 based chloride sensors remain essentially the same over a period of approximately 2 months, reflecting remarkable stability and well-defined chemistry of the macrocyclic Lewis acid ionophore.

Green fluorescent protein in the design of a living biosensing system for L-arabinose.

Analysis of monosaccharides is typically performed using analytical systems that involve a separation step followed by a detection step. The separation step is usually necessary because of the high degree of structural similarity between different monosaccharides. A novel sensing system for monosaccharides is described here in which living bacteria were designed to detect a model monosaccharide, L-arabinose, without the need for a separation step. In such sensing systems, analytes are detected by employing the selective recognition properties found in certain bacterial proteins. These systems are designed so that a reporter protein is expressed by the bacteria in response to the analyte. The concentration of the analyte can be related to the signal generated by the reporter protein. In the sensing system described here, the green fluorescent protein (GFP) was used as the reporter protein. L-Arabinose concentrations can be determined by monitoring the fluorescence emitted by the bacteria at 509 nm after excitation of GFP at 395 nm. The system can detect L-arabinose at concentrations as low as 5 x 10(-7) M and is selective over D-arabinose, the stereoisomer of the analyte, as well as over a variety of pentose and hexose sugars.

Heparin surface-modified intraocular lenses in patients with inactive uveitis or diabetes.

OBJECTIVE: This study aimed to determine whether heparin surface-modified (HSM) intraocular lenses (IOLs) with a hydrophilic surface would reduce cell adherence and other postoperative changes compared with the conventional polymethylmethacrylate (PMMA) IOLs in patients with either diabetes mellitus or inactive uveitis. DESIGN: The study design was a randomized, double-masked, clinical trial. PARTICIPANTS: Twenty-five patients with bilateral cataracts, 14 with inactive anterior uveitis and 11 with diabetes, with an age range of 11 to 81 years (mean, 52.8 years) participated. INTERVENTION: Bilateral cataract extraction with posterior chamber IOL implantation was measured, each patient receiving an HSM lens in one eye and a PMMA lens in the other. Pharmacia one-piece HSM and PMMA IOLs were used. Postoperative ocular changes were evaluated at regular intervals for 24 months in patients with inactive uveitis and for 6 months in patients with diabetes. Patients and physicians alike were unaware of which eye contained which lens until postoperative results were compiled. Records were kept by a study coordinator. MAIN OUTCOME MEASURES: Comparisons of posterior synechiae, IOL cellular deposits, and posterior capsular fibrosis between PMMA and HSM IOLs were measured. RESULTS: Using the chi-square test, no statistically significant difference was found between the HSM and PMMA IOLs in the number of cellular deposits found on the anterior IOL surface, the number of adhesions between the iris and IOL, or the incidence of capsular opacification. CONCLUSION: The HSM and PMMA IOLs showed similar postoperative results in patients with inactive uveitis or diabetes mellitus.

Endophthalmitis cluster from contaminated donor corneas following penetrating keratoplasty.

OBJECTIVE: To attempt to identify common events or factors in four cases of endophthalmitis that developed after penetrating keratoplasty performed within a 1-week interval. DESIGN: Case series. SETTING: Tertiary care eye hospital in Riyadh, Saudi Arabia. PATIENTS: Four patients in whom endophthalmitis developed after penetrating keratoplasty performed in May 1993. OUTCOME MEASURES: Source of donor tissue, transportation of corneas, handling of corneas at the eye hospital, and causative organism and sensitivity profile. RESULTS: The donor tissue in all four cases originated from the same eye bank. Organisms were cultured from 10 of the 11 donor rims from eye bank A tissue used during the week in question. The causative organisms were Enterococcus faecalis in three patients and Torulopsis glabrata in one patient. In each case the same organism was cultured from the recipient eye and the corresponding donor rim. Two of the four patients had a favourable outcome. CONCLUSIONS: Donor rim culture is essential if the cause of endophthalmitis after penetrating keratoplasty is to be determined. Close communication between eye bank personnel, the microbiology laboratory and the operating surgeon is important as it may influence early detection, choice of treatment and outcome of endophthalmitis after penetrating keratoplasty. Epidemiologic studies from both the source eye bank and the recipient facility are required to fully investigate the cause of a cluster of endophthalmitis cases from contaminated donor tissue following penetrating keratoplasty.