Enoxaparin monotherapy without oral anticoagulation to treat acute symptomatic pulmonary embolism

Conventional anticoagulation for symptomatic pulmonary embolism consists of continuous intravenous unfractionated heparin as a "bridge" to oral anticoagulation. This strategy requires 5 days or more of intravenous heparin while oral vitamin K antagonists gradually achieve a therapeutic effect. Oral vitamin K antagonists require frequent blood testing to optimize dosing, and their interactions with other medications and foods make regulation difficult. Therefore we tested a different approach to therapy: long-term enoxaparin monotherapy. We randomized 60 symptomatic pulmonary embolism patients in a 2:1 ratio to 90 days of enoxaparin as monotherapy without warfarin (N=40) or to intravenous unfractionated heparin as a "bridge" to warfarin, target INR 2.0-3.0 (N=20). Enoxaparin patients received 1 mg/kg twice daily for 14 days during the acute phase followed by randomized assignment during the chronic phase to 1.0 mg/kg vs. 1.5 mg/kg once daily. In an intention-to-treat analysis, 3 of the 40 enoxaparin patients developed recurrent venous thromboembolism compared with 0 of 20 standard therapy patients (p = 0.54). One of the 40 enoxaparin patients had a major hemorrhagic complication compared with 2 of the 20 standard therapy patients (p = 0.26). Median hospital length of stay was shorter with enoxaparin compared to standard therapy (4 vs. 6 days) (p = 0.001). Following our study we can conclude that extended 3-month treatment with enoxaparin as monotherapy for symptomatic, acute pulmonary embolism is feasible and warrants further study in a large clinical trial.     

Homozygous mutations in caveolin-3 cause a severe form of rippling muscle disease

Heterozygous missense mutations in the caveolin-3 gene (CAV3) cause different muscle disorders. Most patients with CAV3 alterations present with rippling muscle disease (RMD) characterized by signs of increased muscle irritability without muscle weakness. In some patients, CAV3 mutations underlie the progressive limb-girdle muscular dystrophy type 1C (LGMD1C). Here, we report two unrelated patients with novel homozygous mutations (L86P and A92T) in CAV3. Both presented with a more severe clinical phenotype than usually seen in RMD. Immunohistochemical and immunoblot analyses of muscle biopsies showed a strong reduction of caveolin-3 in both homozygous RMD patients similar to the findings in heterozygous RMD. Electron microscopy studies showed a nearly complete absence of caveolae in the sarcolemma in all RMD patients analyzed. Additional plasma membrane irregularities (small plasmalemmal discontinuities, subsarcolemmal vacuoles, abnormal papillary projections) were more pronounced in homozygous than in heterozygous RMD patients. A stronger activation of nitric oxide synthase was observed in both homozygous patients compared with heterozygous RMD. Like in LGMD1C, dysferlin immunoreactivity is reduced in RMD but more pronounced in homozygous as compared with heterozygous RMD. Thus, we further extend the phenotypic variability of muscle caveolinopathies by identification of a severe form of RMD associated with homozygous CAV3 mutations.     

Metabolite changes resulting from treatment in children with ADHD: a 1H-MRS study

Previously the authors noted an increase in glutamatergic tone in children with attention deficit hyperactivity disorder compared with age- and gender-matched control subjects. In this study they examine the effect of treatment on metabolite concentrations. Fourteen children with attention deficit hyperactivity disorder were investigated medication free and after treatment, using proton magnetic resonance spectroscopy. In the prefrontal cortex and striatum, metabolite peaks of N-acetyl-aspartate, glutamate/glutamine/gamma-aminobutyric acid, creatine/phosphocreatine, and choline compounds were measured, and ratios of the peaks were calculated and compared before and after treatment. The glutamate/glutamine/gamma-aminobutyric acid-to-creatine/phosphocreatine ratio decreased significantly in the striatum. No other metabolites demonstrated any change in response to medication. These findings suggest that glutamate may be involved in treatment response in attention deficit hyperactivity disorder, especially in the striatum.     

Potential and limitations of fluorescence diagnosis and photodynamic therapy. Part I: Fluorescence diagnosis

Fluorescence diagnostic methods enable tumor visualization via specific excitation of endogenous or exogenous tumor-selective fluorescent markers and subsequent optical measurement of the induced fluorescence signals. In the following review, the reader will be given a clear and extensive understanding of all aspects of these methods relevant for ENT specialists. Apart from a demonstration of the clinical difficulties in the diagnosis of malignant tumors of the upper aerodigestive tract, a historical synopsis of fluorescence diagnosis and an explanation of the biophysical basics, this publication focuses mainly on a detailed discussion of the current status of research and a critical consideration of the commercially available systems for fluorescence diagnosis in ENT oncology. The topic is rounded off by a short account of possible future activities in this field.     

Molecular cloning, sequencing, expression, and site-directed mutagenesis of the 1H-3-hydroxy-4-oxoquinaldine 2,4-dioxygenase gene from Arthrobacter spec. Rü61a

The ring cleaving enzyme 1H-3-hydroxy-4-oxoquinaldine 2,4-dioxygenase (HOD)) of Arthrobacter spec. Rü61a is part of the quinaldine degradation pathway. Carbon monoxide and N-acetyl-anthranilate are the products formed by dioxygenolytic cleavage of two C-C bonds in the substrate's pyridine ring. The gene coding for HOD was cloned and sequenced. An isoelectric point of pH 5.40 and a molecular mass of 31,838 Da was deduced from the sequence. HOD is shown to be remarkably similar to 1H-3-hydroxy-4-oxoquinoline 2,4-dioxygenase (QDO) of Pseudomonas putida 33/1, but not to other dioxygenases described so far. Consensus regions indicative for any chromophoric cofactor or any catalytically relevant metal were not detected. Sequence comparisons and secondary structure predictions revealed HOD as a new member of the alpha/beta hydrolase fold family. Expression in E. coli yielded recombinant catalytically active His-tagged HOD. S101A and D233A, two mutants of HOD, were obtained by site-directed mutagenesis. Since their residual activity is 43.1% and 62.6%, respectively, they probably are of no catalytic relevance although they might play a role in the interaction between enzyme and substrate.     

Detection of squamous cell carcinoma of the oral cavity by imaging 5-aminolevulinic acid-induced protoporphyrin IX fluorescence

OBJECTIVES: Early cancer detection is the best way to improve the prognosis of patients with oral cancer. Therefore this study presents quantitative fluorescence measurements and results in the visualization of cancerous oral mucosa with 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PPIX). METHODS: Time progression and type of porphyrin accumulation were analyzed in neoplastic and surrounding healthy tissue of 58 patients with a suspected cancer of the oral cavity by measuring emission spectra of 5-ALA-induced PPIX fluorescence. Fluorescence images in the red and green spectral range from the tumor tissue were recorded with a charge-coupled device camera. RESULTS: After topical application of 0.4% 5-ALA and incubation for 1 to 2.5 hours, all patients revealed higher intensities of red fluorescence in neoplastic tissue compared with the surrounding normal tissue. Maximum contrast was reached after 1.5 hours of incubation. In 13.8% (n = 8) of the patients, additional findings like dysplasia, carcinoma in situ, primary tumor, secondary carcinomas, and tumor branches were found by means of fluorescence marking in contrast to white light examination. An evaluation of the biopsy specimens resulted in a specificity of 60% and a sensitivity of 99%. CONCLUSIONS: As a fluorescent marker, PPIX could represent a possible new diagnostic tool to detect early malignant and secondary lesions in the oral cavity. In addition, 5-ALA-induced PPIX fluorescence is promising as a useful intraoperative tool for determining adequate surgical margins of resection. Further investigations aim to assess this diagnostic procedure as a sensitive and clinically reliable method for patients with oral cancer.     

Quality of care measures for migraine: a comprehensive review.

Migraine headache is a highly prevalent, chronic, episodic disorder that is associated with high direct and indirect costs. Migraine headache impacts not only patients, but also their employers due to substantial decreases in workplace productivity. Despite the prevalence and clinical and economic burdens of migraine, no national efforts to develop and implement standardized measures of quality of care have been made. The objective of this study was to collect and report on existing quality of care measures for migraine that could be suitable for quality measurement at the health-plan level. Published literature, the Agency for Healthcare Research and Quality's National Quality Measure Clearinghouse, and resources available from quality organizations (eg, the National Committee for Quality Assurance) were examined to identify existing quality indicators that can be used to assess the quality of care delivered to migraine sufferers at the health-plan level. Among the results of the study were the following: Quality of care measures for migraine include patient-reported measures and non-patient reported, diagnosis-related, prevention-related, and treatment-related indicators. Most existing measures have been developed by the Institute for Clinical Systems Improvement or summarized and reported by the RAND Corporation. Few of these measures can be used to assess migraine quality of care at the health-plan level. In conclusion, many measures exist, but they are not intended for use at the health-plan level. Incorporation of valid and reliable quality of care measures may increase the ability of migraine disease management programs to conform to clinical care guidelines. Significant effort is needed to determine what and how to measure quality among health plans to improve the quality of care delivered to individuals with migraine.     

Adolescents with chronic conditions: linkages to adult service systems

Pediatric nurses can assist adolescents with chronic conditions to make the necessary linkages to adult services systems, enabling them to access needed services. Knowledge of the adult services available for adolescents and young adults will enable them to realize their goals for adulthood. This article provides an overview of services available to assist high school students with chronic conditions in making the transition to postsecondary settings.