Serum cartilage oligomeric matrix protein (sCOMP) is elevated in patients with knee osteoarthritis: a systematic review and meta-analysis.

OBJECTIVE: To be used in diagnostic studies, it must be demonstrated that biomarkers can differentiate between diseased and non-diseased patients. Therefore, the purpose of this study was to answer the following questions: (1) Is serum cartilage oligomeric matrix protein (sCOMP) elevated in patients with radiographically diagnosed knee osteoarthritis (OA) compared to controls? (2) Are there differences in sCOMP levels when comparing differing radiographic OA severities to controls? METHODS: Systematic review and meta-analysis. DATA SOURCES: A systematic search of CINAHL, PEDro, Medline, and SportsDiscus was completed in March 2010. KEYWORDS: knee, osteoarthritis, sCOMP, radiography. Study inclusion criteria: Studies were written in English, compared healthy adults with knee OA patients, used the Kellgren Lawrence (K/L) classification, measured sCOMP, and reported means and standard deviations for sCOMP. RESULTS: For question 1, seven studies were included resulting in seven comparisons. A moderate overall effect size (ES) indicated sCOMP was consistently elevated in those with radiographically diagnosed knee OA when compared to controls (ES = 0.60, P < 0.001). For question 2, four studies were included resulting in 13 comparisons between radiographic OA severity levels and controls. Strong ESs were calculated for K/L-1 (ES = 1.43, P = 0.28), K/L-3 (ES = 1.05, P = 0.04), and K/L-4 (ES = 1.40, P = 0.003). A moderate ES was calculated for K/L-2 (ES = 0.60, P = 0.01). CONCLUSIONS: These results indicate sCOMP is elevated in patients with knee OA and is sensitive to OA disease progression. Future research studies with a higher level of evidence should be conducted to investigate the use of this biomarker as an indicator for OA development and progression.

Quantitative nuclear and cytoplasmic localization of antisense oligonucleotides by capillary electrophoresis with laser-induced fluorescence detection.

We demonstrate the use of simple extraction procedures to separate nuclear and cytoplasmic material from cell extracts, which have been scrape-loaded with a 2-O-methyl phosphorothioate antisense oligonucleotide. Separation and quantitation of the fluorescein-labeled antisense and the flourescein isothiocyanate (FITC)-dextran (molecular weight 40000) as an internal standard is done using capillary electrophoresis coupled with laser-induced fluorescence detection (CE-LIF). The bulky FITC-dextran is unable to penetrate the nuclear membrane thereby making it a quantitative indicator of any overlap between the nuclear and cytoplasmic materials during separation of the two phases. Using this procedure, the fluorescein-labeled phosphorothioate oligomer was quantitated at 4.1 x 10(-13) and 3.4x 10(-14) mol antisense/microg-total cellular protein in the nuclear and cytoplasmic extracts respectively following scrape-load delivery of the phosphorothioate to a batch of confluent HeLa cells at a concentration of 0.5 microM (5 x 10(-10) total moles of oligomer). Additionally, gene expression was monitored by measurement of the luciferase reporter protein activity. Scrape-load, spontaneous and liposomal delivery were investigated and compared for subcellular distribution of the oligomer and subsequent gene expression.

Quantitation of intracellular concentration of a delivered morpholino oligomer by capillary electrophoresis-laser- induced fluorescence: correlation with upregulation of luciferase gene expression.

Antisense oligonucleotides have shown great promise over the past several years as viable drugs to combat various forms of cancer and viral diseases. However, quantitative detection to monitor cellular association is difficult using conventional methods such as radiolabeling of the oligonucleotide or fluorescence confocal microscopy. In this paper quantitation of intracellular concentration of the morpholino oligonucleotide is investigated using capillary electrophoresis coupled with laser-induced fluorescence detection (CE-LIF). HeLa cells, which produce luciferase as the antisense oligomer enters the cell, were scrape-loaded with varying concentrations of the morpholino antisense. The intracellular antisense concentration measured by CE-LIF was found to correlate with those obtained with the cellular functional assay based on upregulation of luciferase. Intracellular concentrations of the antisense were found to be in the range of 6 to 29 nmol/g total cell protein, depending on the amounts that were scrape-loaded. To our best knowledge, this is the first reported quantitative correlation between delivered antisense concentration in a cell extract and the subsequent antisense upregulation of gene expression.

Should an appendix that looks 'normal' be removed at diagnostic laparoscopy for acute right iliac fossa pain?

OBJECTIVE: To find out whether the removal of the appendix from patients in whom laparoscopy for acute right iliac fossa pain shows no abnormality is justified to avoid the risk of missing acute appendicitis. PATIENTS: The records of patients who, between 1990 and 1997 had emergency laparoscopy for acute right iliac fossa pain were reviewed. Only those in whom laparoscopy had shown no abnormality and had not had the appendix removed were included in the study. METHODS: Outcome was assessed by telephone questionnaire to the patient, the general practitioner, or both. RESULTS: Emergency laparoscopy had been done for 254 patients. No abnormality was detected in 41. Full follow up was available on 34 patients (83%). 21 patients have remained entirely free of symptoms. Of the 13 patients who had recurrent symptoms, 2 subsequently had a histologically normal appendix removed, yet still had symptoms; 2 had a second laparoscopy that showed no abnormality; 5 had ultrasound; and 4 had colonoscopy or a barium enema examination. CONCLUSION: Removal of an appendix that looks 'normal' at emergency laparoscopy for right iliac fossa pain is unjustified.

Preventing the spread of genital warts: using fear appeals to promote self-protective behaviors.

A fear appeal campaign to decrease the spread of genital warts was conducted and evaluated. Theoretically guided by the Extended Parallel Process Model, this field study illustrated why fear appeal campaigns often appear to fail in public health arenas. Five hypotheses, which predicted when and under what conditions fear appeal campaigns would fail or succeed, were tested and supported. The results demonstrated that fear appeals can be powerful persuasive devices if they induce strong perceptions of threat and fear (which motivate action) and if they induce strong perceptions of efficacy with regard to a recommended response (which channels the action in a health protective direction). Recommendations to researchers and public health practitioners are offered.

Predicting risk behaviors: development and validation of a diagnostic scale.

The goal of this study was to develop and validate the Risk Behavior Diagnosis (RBD) Scale for use by health care providers and practitioners interested in promoting healthy behaviors. Theoretically guided by the Extended Parallel Process Model (EPPM; a fear appeal theory), the RBD scale was designed to work in conjunction with an easy-to-use formula to determine which types of health risk messages would be most appropriate for a given individual or audience. Because some health risk messages promote behavior change and others backfire, this type of scale offers guidance to practitioners on how to develop the best persuasive message possible to motivate healthy behaviors. The results of the study demonstrate the RBD scale to have a high degree of content, construct, and predictive validity. Specific examples and practical suggestions are offered to facilitate use of the scale for health practitioners.

Pleurectomy for persistent pain in benign asbestos-related pleural disease.

BACKGROUND: Persistent severe pain is a rare complication of benign asbestos-related pleural disease. METHODS: Four patients are described in whom pain persisted for more than one year (range 18 months to five years) which was incompletely relieved by opioid medication and nerve blocking procedures. All underwent pleurectomy in an attempt to relieve it. RESULTS: At operation the pleura was considerably thickened in all cases. Two of the four patients had successful relief of pain. The other two had a neuralgic component to their pain before surgery which persisted afterwards. One of these patients underwent successful cervical cordotomy. CONCLUSIONS: Pleurectomy may provide relief in patients with constant pleuritic pain due to benign asbestos-related pleural thickening. It seems, however, that patients in whom the pain has a neuralgic component are unlikely to benefit.

Avoidance and management of adverse reactions to antituberculosis drugs.

Potent antibiotics are required to cure tuberculosis and reduce the burden of illness in the community. Minor adverse effects are commonly encountered and can be managed by reassurance and explanation. Significant hypersensitivity reactions require cessation of all antituberculosis drugs. Adverse effects should be treated appropriately. An effective antituberculosis regimen should be reestablished as soon as possible. Desensitisation may be necessary if suitable alternative drugs cannot be used. In the event of drug-induced hepatitis, all hepatotoxic drugs should be ceased until symptoms resolve and liver function tests return to normal. Other significant direct toxic effects should be promptly detected and appropriately treated. A thorough knowledge of potential adverse reactions and pharmacokinetics is essential for any physician using antituberculosis drugs.

Mutations in some Polycomb group genes of Drosophila interfere with regulation of segmentation genes.

Mutations in several Polycomb (Pc) group genes cause maternal-effect or zygotic segmentation defects, suggesting that Pc group genes may regulate the segmentation genes of Drosophila. We show that individuals doubly heterozygous for mutations in polyhomeotic and six other Pc group genes show gap, pair rule, and segment polarity segmentation defects. We examined double heterozygous combinations of Pc group and segmentation mutations for enhancement of adult and embryonic segmentation defects. Posterior sex combs and polyhomeotic interact with Krüppel and enhance embryonic phenotypes of hunchback and knirps, and polyhomeotic enhances even-skipped. Surprisingly, flies carrying duplications of extra sex combs (esc), that were heterozygous for mutations of even-skipped (eve), were extremely subvital. Embryos and surviving adults of this genotype showed strong segmentation defects in even-numbered segments. Antibody studies confirm that expression of eve is suppressed by duplications of esc. However, esc duplications have no effect on other gap or pair rule genes tested. To our knowledge, this is only the second triplo-abnormal phenotype associated with Pc group genes. Duplications of nine other Pc group genes have no detectable effect on eve. Expression of engrailed (en) was abnormal in the central nervous systems of most Pc group mutants. These results support a role for Pc genes in regulation of some segmentation genes, and suggest that esc may act differently from other Pc group genes.

Characterization and purification of Adh distal promoter factor 2, Adf-2, a cell-specific and promoter-specific repressor in Drosophila.

Chromatin footprinting in Drosophila tissue culture cells has detected the binding of a non-histone protein at +8 of the distal Adh RNA start site, on a 10-bp direct repeat motif abutting a nucleosome positioned over the inactive Adh distal promoter. Alternatively the active promoter is bound by a transcription initiation complex. We have characterized and purified a protein Adf-2 that binds specifically to this direct repeat motif 5'TCTCAGTGCA3', present at +8 and -202 of the distal RNA start site. DNase I footprinting, methylation interference, and UV-crosslinking analyses showed that both direct repeats interact in vitro with a nuclear protein of approximately 120 kilodaltons (kDa). We purified Adf-2 through multiple rounds of sequence-specific DNA affinity chromatography. Southwestern analysis showed that the purified 120 KDa polypeptide binds the Adf-2 motif efficiently as a monomer or homomultimer. In vivo titrations of Adf-2 activity with the Adf-2 motif by transient co-transfection competitions in different Drosophila cell lines suggested that Adf-2 is a cell-specific repressor. Adf-2 has been detected ubiquitously in vitro, but is functional in vivo as a sequence-specific DNA binding protein and repressor only in the cells that have the inactive distal promoter. We discuss the possibility that an activation process is required for Adf-2 protein to bind DNA and function in vivo.

Orthopedic surgery and rehabilitation for the prolongation of brace-free ambulation of patients with Duchenne muscular dystrophy.

The purpose of this study was to prospectively evaluate the results of a short comprehensive program involving early lower extremity musculotendinous surgery followed by a definitive course of rehabilitation on contractures and the duration of ambulation for patients with Duchenne muscular dystrophy. Seven patients were treated while ambulating with little difficulty and six were treated just before or after becoming wheelchair-dependent. Predicted post-treatment duration of ambulation was calculated from established clinical criteria. Actual prolongation of brace-free ambulation after treatment was a mean of 0.8 yr greater than predicted for the group as a whole but 0.93 yr for the group treated early by comparison with 0.63 yr for those treated according to the customary approach. The number of falls significantly decreased from 84 +/- 87 to 1 +/- 1 per month postoperatively (P less than 0.05); however, the speed of ambulation over a distance of 10 yards decreased from 10.2 +/- 4 s to 12.1 +/- 7.3 s. Three patients who had tibialis posterior transfers retained antigravity plus dorsiflexor strength and continue to wear normal footwear 2.5, 3.7 and 4.0 yr after loss of ambulation. We conclude that ambulation becomes more stable and brace-free ambulation may be prolonged by a comprehensive program of early orthopedic surgery and rehabilitation. Earlier intervention is also better tolerated.

Estimation of the probability of disturbed breathing during sleep before a sleep study.

We have investigated the ability of a statistical model developed from clinical data and questionnaire responses to predict disturbance of breathing during sleep. Data from 100 consecutive patients referred for sleep study for suspected sleep apnea were used to develop the model using logistic regression analysis. For each subject, the model predicted the probability of having an apnea-hypopnea index (AHI) greater than 15; this probability was compared with the AHI measured from sleep study. A probability cutoff point (= 0.15) was decided on that minimized the number of subjects with false-negative predictions. Four terms--apneas observed by bed partner, hypertension, body mass index, and age--were found to contribute significantly to the model with observed apneas being by far the most predictive term of the four (adjusted odds ratio 19.7). When the model was tested to estimate the probability of an AHI greater than 15 for 105 patients from a second group of consecutive patients referred for sleep study, the model correctly classified 33 of 36 patients with a measured AHI greater than 15 (sensitivity = 92%) and 35 of 69 patients with a measured AHI less than or equal to 15(specificity = 51%). This study shows that analysis of clinical features of patients presenting with suspected sleep apnea may reduce the need for sleep studies by about one-third yet still lead to the identification of the great majority of patients with abnormal breathing during sleep.

Urinary uric acid:creatinine ratio, serum erythropoietin, and blood 2,3-diphosphoglycerate in patients with obstructive sleep apnea.

A noninvasive, inexpensive method of excluding significant sleep-associated hypoxemia would be desirable for patients being investigated and treated for obstructive sleep apnea (OSA). Sixty-eight such patients provided specimens before and after sleep studies for estimation of urinary uric acid:creatinine ratio (UA:Cr), serum erythropoietin (EPO), and blood 2,3-diphosphoglycerate (2,3-DPG). Mean (SD) morning 2,3-DPG was higher in 26 patients with overnight hypoxemia than in 42 normoxemic patients (2.54 [0.46] versus 2.24 [0.44] mmol/L; p = 0.01). Neither overnight change nor absolute values of serum EPO or urinary UA:Cr were significantly different between hypoxemic and normoxemic groups. There was a diurnal variation in serum EPO in normoxemic patients (P.M. EPO = 14.8 [7.1] mU/ml; A.M. EPO = 10.7 [7.1] mU/ml; p less than 0.05) but not in hypoxemic patients. Eighteen hypoxemic patients were restudied after using nasal continuous positive airway pressure (nCPAP) for at least 4 wk. Seven normoxemic patients not using nCPAP were restudied after a similar time. There were no significant differences between pretreatment and posttreatment nights in absolute values or percentage overnight change of blood 2,3-DPG or serum EPO in either group. In the hypoxemic (nCPAP) group, overnight change in urinary UA:Cr was lower on the second night (p = 0.04); there was no significant change in the control group. We conclude that although urinary UA:Cr, serum EPO, and 2,3-DPG may be physiologically related to hypoxemia, none of these measures can be used to predict accurately the presence of moderate nocturnal hypoxemia in patients with OSA or in monitoring the effect of their therapy.