Variations in corticosteroid/anesthetic injections for painful shoulder conditions: comparisons among orthopaedic surgeons, rheumatologists, and physical medicine and primary-care physicians

<p>Abstract</p> <p>Background</p> <p>Variations in corticosteroid/anesthetic doses for injecting shoulder conditions were examined among orthopaedic surgeons, rheumatologists, and primary-care sports medicine (PCSMs) and physical medicine and rehabilitation (PMRs) physicians to provide data needed for documenting inter-group differences for establishing uniform injection guidelines.</p> <p>Methods</p> <p>264 surveys, sent to these physicians in our tri-state area of the western United States, addressed corticosteroid/anesthetic doses and types used for subacromial impingement, degenerative glenohumeral and acromioclavicular arthritis, biceps tendinitis, and peri-scapular trigger points. They were asked about preferences regarding: 1) fluorinated vs. non-fluorinated corticosteroids, 2) acetate vs. phosphate types, 3) patient age, and 4) adjustments for special considerations including young athletes and diabetics.</p> <p>Results</p> <p>169 (64% response rate, RR) surveys were returned: 105/163 orthopaedic surgeons (64%RR), 44/77 PCSMs/PMRs (57%RR), 20/24 rheumatologists (83%RR). Although corticosteroid doses do not differ significantly between specialties (p > 0.3), anesthetic volumes show broad variations, with surgeons using larger volumes. Although 29% of PCSMs/PMRs, 44% rheumatologists, and 41% surgeons exceed "recommended" doses for the acromioclavicular joint, >98% were within recommendations for the subacromial bursa and glenohumeral joint. Depo-Medrol^®(methylprednisolone acetate) and Kenalog^®(triamcinolone acetonide) are most commonly used. More rheumatologists (80%) were aware that there are acetate and phosphate types of corticosteroids as compared to PCSMs/PMRs (76%) and orthopaedists (60%). However, relatively fewer rheumatologists (25%) than PCSMs/PMRs (32%) or orthopaedists (32%) knew that phosphate types are more soluble. Fluorinated corticosteroids, which can be deleterious to soft tissues, were used with these frequencies for the biceps sheath: 17% rheumatologists, 8% PCSMs/PMRs, 37% orthopaedists. Nearly 85% use the same non-fluorinated corticosteroid for all injections; <10% make adjustments for diabetic patients.</p> <p>Conclusion</p> <p>Variations between specialists in anesthetic doses suggest that surgeons (who use significantly larger volumes) emphasize determining the percentage of pain attributable to the injected region. Alternatively, this might reflect a more profound knowledge that non-surgeons specialists have of the potentially adverse cardiovascular effects of these agents. Variations between these specialists in corticosteroid/anesthetic doses and/or types, and their use in some special situations (e.g., diabetics), bespeak the need for additional investigations aimed at establishing uniform injection guidelines, and for identifying knowledge deficiencies that warrant advanced education.</p

The mechanisms by which polyamines accelerate tumor spread

Increased polyamine concentrations in the blood and urine of cancer patients reflect the enhanced levels of polyamine synthesis in cancer tissues arising from increased activity of enzymes responsible for polyamine synthesis. In addition to their de novo polyamine synthesis, cells can take up polyamines from extracellular sources, such as cancer tissues, food, and intestinal microbiota. Because polyamines are indispensable for cell growth, increased polyamine availability enhances cell growth. However, the malignant potential of cancer is determined by its capability to invade to surrounding tissues and metastasize to distant organs. The mechanisms by which increased polyamine levels enhance the malignant potential of cancer cells and decrease anti-tumor immunity are reviewed. Cancer cells with a greater capability to synthesize polyamines are associated with increased production of proteinases, such as serine proteinase, matrix metalloproteinases, cathepsins, and plasminogen activator, which can degrade surrounding tissues. Although cancer tissues produce vascular growth factors, their deregulated growth induces hypoxia, which in turn enhances polyamine uptake by cancer cells to further augment cell migration and suppress CD44 expression. Increased polyamine uptake by immune cells also results in reduced cytokine production needed for anti-tumor activities and decreases expression of adhesion molecules involved in anti-tumor immunity, such as CD11a and CD56. Immune cells in an environment with increased polyamine levels lose anti-tumor immune functions, such as lymphokine activated killer activities. Recent investigations revealed that increased polyamine availability enhances the capability of cancer cells to invade and metastasize to new tissues while diminishing immune cells' anti-tumor immune functions

Epigenetics of human cutaneous melanoma: setting the stage for new therapeutic strategies

Cutaneous melanoma is a very aggressive neoplasia of melanocytic origin with constantly growing incidence and mortality rates world-wide. Epigenetic modifications (i.e., alterations of genomic DNA methylation patterns, of post-translational modifications of histones, and of microRNA profiles) have been recently identified as playing an important role in melanoma development and progression by affecting key cellular pathways such as cell cycle regulation, cell signalling, differentiation, DNA repair, apoptosis, invasion and immune recognition. In this scenario, pharmacologic inhibition of DNA methyltransferases and/or of histone deacetylases were demonstrated to efficiently restore the expression of aberrantly-silenced genes, thus re-establishing pathway functions. In light of the pleiotropic activities of epigenetic drugs, their use alone or in combination therapies is being strongly suggested, and a particular clinical benefit might be expected from their synergistic activities with chemo-, radio-, and immuno-therapeutic approaches in melanoma patients. On this path, an important improvement would possibly derive from the development of new generation epigenetic drugs characterized by much reduced systemic toxicities, higher bioavailability, and more specific epigenetic effects

Assembly, organization, and function of the COPII coat

A full mechanistic understanding of how secretory cargo proteins are exported from the endoplasmic reticulum for passage through the early secretory pathway is essential for us to comprehend how cells are organized, maintain compartment identity, as well as how they selectively secrete proteins and other macromolecules to the extracellular space. This process depends on the function of a multi-subunit complex, the COPII coat. Here we describe progress towards a full mechanistic understanding of COPII coat function, including the latest findings in this area. Much of our understanding of how COPII functions and is regulated comes from studies of yeast genetics, biochemical reconstitution and single cell microscopy. New developments arising from clinical cases and model organism biology and genetics enable us to gain far greater insight in to the role of membrane traffic in the context of a whole organism as well as during embryogenesis and development. A significant outcome of such a full understanding is to reveal how the machinery and processes of membrane trafficking through the early secretory pathway fail in disease states

Experiência de um ano de modelo de programa de prevenção contínua do melanoma na cidade de Jaú-SP, Brasil One year experience of a model for melanoma continuous prevention in the city of Jaú (São Paulo), Brazil

FUNDAMENTO: A incidência do melanoma aumentou nos últimos anos mais rapidamente do que qualquer outro câncer. Embora represente apenas 4% dos cânceres de pele, é o responsável por 60% das mortes por esta neoplasia. Isto torna o melanoma um problema de saúde pública. OBJETIVOS: O presente estudo propôs o desenvolvimento de um Programa Contínuo de Prevenção do Melanoma, por meio da realização da prevenção primária e do diagnóstico precoce desta neoplasia. MÉTODOS: Foi tomada como piloto uma cidade de aproximadamente 130.000 habitantes. Uma equipe de enfermagem esteve presente por cerca de 30 dias em cada um dos 13 postos de saúde da cidade de Jaú (SP), realizando orientações quanto ao autoexame da pele, fotoproteção e sinais precoces do melanoma. O paciente com lesão suspeita era encaminhado imediatamente ao hospital de referência para dermatoscopia e triagem médica, sendo excisada quando suspeita. RESULTADOS: Foram diagnosticados 4 casos de melanoma em fase inicial e 3 nevos displásicos. Dos entrevistados, 74% trabalham expostos ao sol, variando de meio período ao completo, e mais de 60% nunca fizeram uso de filtro solar. CONCLUSÃO: Este modelo de programa de prevenção é inédito, exclusivo e demonstrou ser eficaz na prevenção e diagnóstico precoce do melanoma em uma cidade de 130.000 habitantes do Estado de São Paulo. Com esclarecimento à população e orientação à equipe de saúde, realiza-se uma rápida triagem e identificam-se lesões suspeitas de melanoma para que, com o diagnóstico em suas fases iniciais, o paciente apresente melhor prognóstico<br>BACKGROUND: Worldwide incidence of melanoma has increased in recent years faster than any other cancer. Although it represents only 4% of skin cancers it is nevertheless responsible for 60% of skin cancer deaths. This makes melanoma a public health problem. OBJECTIVES: The aim of this study was the development of a continuous program for melanoma prevention and early detection. METHODS: A city of around 130,000 inhabitants in the state of São Paulo, Brazil, was chosen for the development of a pilot project covering primary prevention and early diagnosis of melanoma. A nursing team worked for approximately 30 days in each of the 13 health centers in the city of Jaú (SP), providing guidance on self-examination of the skin, photoprotection and recognition of early signs of melanoma. Patients with suspicious lesions were immediately sent to the reference hospital for medical and dermoscopic screening. Excisional biopsies were performed on suspected melanomas. RESULTS: 4 four cases of early stage melanoma and 3 dysplastic nevi were diagnosed. Of the people interviewed, 74% worked either part-time or full-time exposed to sun and over 60% claimed to never use sunscreen. CONCLUSION: This is a new and effective model for melanoma prevention and early diagnosis. In short, the melanoma prevention program is able to quickly identify suspicious lesions, leading to early diagnosis and better chances of surviva