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A 59-year-old male patient with long-standing tophaceous gout (more than 30 years) characterized by polyarticular involvement and recurrent disseminated tophi formation; his past medical history is relevant for poor adherence to urate-lowering medications, as well as persistent use of self-prescribed systemic glucocorticoids. Despite achieving therapeutic goals for serum uric acid levels, new tophi formation with an intradermal location in the form of "miliarial-type gout" was documented. Due to functional limitations, the patient underwent surgical resection of the olecranon bursa. This case illustrates a widespread and recurrent tophi formation associated with long-standing gout and regular and sustained glucocorticoid use, despite an adequate disease control based on serum urate levels and involving an intradermal location of tophi presenting as "miliarial-type" lesions. In addition, the coexistence of urate and cholesterol crystal deposition disease in olecranon gouty bursitis is presented. Finally, a sonographic extended field of view of lesions distributed along the patient's extremities is presented as a novel characterization of this condition.

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Cystic lymphatic malformation (CLM) is a rare and benign entity caused by alterations in the embryological development of lymphatic structures. Its typical location is in the head and neck, although it has also been described at the abdominal level. It may not be evident in the first stages of life and its first manifestation may be a complication such as abdominal distension, hemorrhage, or sepsis, which may put the patient's life at risk. Surgical treatment is increasingly discussed, and less invasive techniques are proposed. OBJECTIVE: To describe an uncommon presentation of CLM, radiographic findings, complications, differential diagnosis, and both invasive and more conservative treatments. CLINICAL CASE: Newborn female infant consulted for fever and irritability, without specific signs on physical examination, with suspicion of sepsis. Ultrasonography showed a complex septate mass with cysts of different sizes encompassing the mesenteric vessels, supravesical location. In its most ante rior aspect, it presented a greater echogenicity that corresponded to the superinfected component. Magnetic resonance imaging identified a multitabulated cystic tumor corresponding to a complica ted mesenteric lymphangioma with signs of infection. Due to its size, which compressed the vena cava and the associated signs of complication, complete resection was decided with good subsequent evolution. CONCLUSION: The treatment of CLM in pediatric age is increasingly individualized and can vary from surgical resection to less invasive approaches that could reduce acute intraoperative or postoperative complications and mortality. In our case, the infection acted as sclerotherapy, mana ging to delimit the CLM and helping to improve the prognosis.

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Li-Fraumeni syndrome is an inherited, autosomal dominant disease. It is categorized as a rare disease caused by mutations of the TP53 gene, which causes increased susceptibility of the patients and their children to many types of cancer. Choroid plexus tumor is rare, which occurs in 0.3 cases per 1,000,000 people, of which 40% turn out to be carcinomas. We present a 12-year-old boy with a history of worsening headaches of more than one month, gait disturbance, projectile vomiting, and right hemiparesis. An intraventricular tumor was identified in the occipital of the left lateral ventricle, which turned out to be a TP53-mutant choroidal plexus carcinoma.

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Cervical cancer is characterized by the cellular transformation caused by Human Papillomavirus (HPV), favoring cell proliferation, migration, invasion, and metastasis. Cervical cancer is conventionally treated with radiation therapy, and chemotherapy focused on the destruction of tumor cells. However, chemoresistance and low selectivity between tumor and non-tumor cells have been reported, causing side effects in patients. Metabolites of natural origin have shown selectivity against tumor cells, suggesting their use for reducing the side effects caused by drugs used in conventional therapy. Among these compounds, several natural coumarins stand out, such as auraptene, scopoletin, osthole, and praeruptorin, of which antiproliferative, anti-migratory, and anti-invasive activity have been reported. Auraptene, scopoletin, osthole, and praeruptorin show a cytotoxic or antiproliferative effect on cervical tumor cells, arresting the cell cycle by inducing the overexpression of negative regulators of the cell cycle, or inducing cell death by increasing the expression of pro-apoptotic proteins and decreasing that of anti-apoptotic proteins. On the other hand, auraptene, scopoletin, and praeruptorin inhibit the capacity for migration, invasion, and metastasis of cervical tumor cells, mainly by inhibiting the expression and activity of matrix metalloproteinase-2 and -9. The PI3K/Akt signal pathway appears to be central to the anti-tumor activity of the coumarins analyzed in this review. In addition, auraptene, osthole, and praeruptorin are useful in sensitizing tumor cells to radiotherapy or chemotherapeutic molecules, such as FOLFOX, cisplatin, or DOX. Coumarins offer an excellent possibility for developing new drugs as complementary medicine with an integrative approach against cervical cancer.

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Rheumatoid Arthritis (RA) is an autoimmune disease with unknown etiology and a global incidence around 1%, a positive family history increases the risk of RA roughly three to five times. Pain is one of the first symptoms to appear in this disease. MicroRNAs (miRNAs) belong to the class of small non-coding RNAs; they regulate multiple cellular processes including embryonic development, cellular proliferation, differentiation and apoptosis among others. A great deal of evidence points to the employment of miRNAs as therapeutic targets and biomarkers for several pathologies. The main objective of this Review is to assess how miRNAs participate in the pathogenesis of RA. Two advanced searches were conducted in databases, one using "micro-RNA" and "rheumatoid arthritis" as key words, and another one with "micro-RNA", "pain" and "nociception". In this Review, we describe how six miRNAs: miR-16-5p, miR-23b-3b, miR-124-3p, miR-146a-5p, miR-155-5p and miR-223-3p, involved in the modulation and transmission of the nociceptive input are unregulated in RA patients. Key molecular pathways involved in nociception, inflammation and autoimmune responses, are regulated by these miRNAs; the NF-κB, TNF-α, interleukins and TLR4. By means of gene repression, the miRNAs here described modulate the nociceptive process as well as the autoimmune response that characterize this disease.

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The two co-authors of the mentioned above article were incorrect. The correct are authors should have been "P. A. Beltrán" instead of "P. A. B. Roa" and "J. F. Diaz-Coto" instead of "L. Diaz Soto".

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INTRODUCTION: Biologics have improved the treatment of rheumatic diseases, resulting in better outcomes. However, their high cost limits access for many patients in both North America and Latin America. Following patent expiration for biologicals, the availability of biosimilars, which typically are less expensive due to lower development costs, provides additional treatment options for patients with rheumatic diseases. The availability of biosimilars in North American and Latin American countries is evolving, with differing regulations and clinical indications. OBJECTIVE: The objective of the study was to present the consensus statement on biosimilars in rheumatology developed by Pan American League of Associations for Rheumatology (PANLAR). METHODS: Using a modified Delphi process approach, the following topics were addressed: regulation, efficacy and safety, extrapolation of indications, interchangeability, automatic substitution, pharmacovigilance, risk management, naming, traceability, registries, economic aspects, and biomimics. Consensus was achieved when there was agreement among 80% or more of the panel members. Three Delphi rounds were conducted to reach consensus. Questionnaires were sent electronically to panel members and comments about each question were solicited. RESULTS: Eight recommendations were formulated regarding regulation, pharmacovigilance, risk management, naming, traceability, registries, economic aspects, and biomimics. CONCLUSION: The recommendations highlighted that, after receiving regulatory approval, pharmacovigilance is a fundamental strategy to ensure safety of all medications. Registries should be employed to monitor use of biosimilars and to identify potential adverse effects. The price of biosimilars should be significantly lower than that of reference products to enhance patient access. Biomimics are not biosimilars and, if they are to be marketed, they must first be evaluated and approved according to established regulatory pathways for novel biopharmaceuticals. KEY POINTS: • Biologics have improved the treatment of rheumatic diseases. • Their high cost limits access for many patients in both North America and Latin America. • Biosimilars typically are less expensive, providing additional treatment options for patients with rheumatic diseases. • PANLAR presents its consensus on biosimilars in rheumatology.

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Alkaptonuria is a rare, hereditary metabolic disorder in which a deficiency in the homogentisate 1,2-dioxygenase enzyme results in an accumulation of homogentisic acid. Deposition of excess homogentisic acid in different intra- and extra-articular structures with high content of connective tissue causes brownish-black pigmentation and weakening, ultimately resulting in tissue degeneration and finally osteoarthritis. Ochronotic arthropathy is considered a rapidly progressive, disabling condition in which weight-bearing joints and the thoracolumbar spine are predominantly affected. Patients often require multiple joint replacements, such as in the case of the patient presented here. At present, there is no definitive cure for ochronosis, and management is predominantly symptomatic.

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Due to the anatomical distribution and function, striated muscle is susceptible to injury especially traumatic requiring imaging methods for diagnosis, the degree of disease and establish the extent possible recovery time. Ultrasonography is a method that has gained an important place in the evaluation of muscle to be safe, affordable, and by allowing static and dynamic assessment of the muscle. The current classification of muscle injuries seen by Ultrasonography has limitations because it does not allow an adequate correlation between the percentage of condition and prognosis.

Debido a la distribución anatómica y función, el músculo estriado es susceptible de sufrir lesiones sobre todo traumáticas que requieren de métodos de imagen para determinar el diagnóstico, el grado de afección y establecer en la medida de lo posible el tiempo de recuperación. La Ultrasonografía es un método que ha ido ganando un lugar preponderante en la evaluación del músculo por ser inocua, de bajo costo, así como por permitir una evaluación estática y dinámica del músculo. La clasificación actual de lesiones musculares vistas por Ultrasonografía tiene limitantes porque no permite fundamentar una adecuada correlación entre el porcentaje de afección y el pronóstico.

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BACKGROUND: Gastric microbiota is a complex ecosystem, composed by diverse microorganisms, where H pylori and Lactobacillus are relevant species. AIM: To study the probiotic properties of Lactobacillus spp isolated from gastric biopsies of subjects bearing or not H pylori. MATERIALS AND METHODS: Gastric biopsies from 197 individuals that consulted for gastrointestinal disorders were cultivated in media specific for H pylori and Lactobacillus spp. Probiotic properties of lactobacilli isolates and histological diagnosis of H pylori colonized patients were performed. RESULTS: Among 197 individuals evaluated, Hpylori was detected in 43%, Lactobacillus spp in 24%, while 8% presented both bacteria simultaneously. Forty one percent of the Lactobacillus spp strains produced hydrogen peroxide, S'3% presented a highly hydrophobic surface and 32% had an inhibitory effect upon Hpylori ATCC 43504, even greater than Lactobacillus LGG or LAL reference strains. The main pathological diagnosis of patients ivas chronic non-atrophic gastritis (73%) followed by intestinal metaplasia (19%). A similar proportion of both conditions were observed in patients colonized by Lactobacillus spp, while not colonized individuals developed preferentially chronic non-atrophic gastritis (p =0.002). CONCLUSIONS: Lactobacillus spp and H pylori were mutually excluded, suggesting a competitive colonization model between probiotic bacteria and pathogens .

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Background: Gastric microbiota is a complex ecosystem, composed by diverse microorganisms, where H pylori and Lactobacillus are relevant species. Aim: To study the probiotic properties of Lactobacillus spp isolated from gastric biopsies of subjects bearing or not H pylori. Materials and Methods: Gastric biopsies from 197 individuals that consulted for gastrointestinal disorders were cultivated in media specific for H pylori and Lactobacillus spp. Probiotic properties of lactobacilli isolates and histological diagnosis of H pylori colonized patients were performed. Results: Among 197 individuals evaluated, Hpylori was detected in 43 percent, Lactobacillus spp in 24 percent, while 8 percent presented both bacteria simultaneously. Forty one percent of the Lactobacillus spp strains produced hydrogen peroxide, S'3 percent presented a highly hydrophobic surface and 32 percent had an inhibitory effect upon Hpylori ATCC 43504, even greater than Lactobacillus LGG or LAL reference strains. The main pathological diagnosis of patients ivas chronic non-atrophic gastritis (73 percent) followed by intestinal metaplasia (19 percent). A similar proportion of both conditions were observed in patients colonized by Lactobacillus spp, while not colonized individuals developed preferentially chronic non-atrophic gastritis (p =0.002). Conclusions: Lactobacillus spp and H pylori were mutually excluded, suggesting a competitive colonization model between probiotic bacteria and pathogens.

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Over the last few years, a growing number of rheumatologists has taken great interest in ultrasonography for its well known advantages and wide spectrum of validated applications in daily rheumatological practice. Most rheumatologists actively performing ultrasonography have had a training experience mainly based on attendance in sonographic courses and/or in radiological or rheumatological units. At present, in Mexico ultrasonography has a still limited diffusion among rheumatologists even if it may play a key role as a first line imaging technique also because of the restricted availability for rheumatic patients for other imaging modalities. This report describes the Mexican experience in education and training on musculoskeletal ultrasound. In 2003, the Mexican School of Musculoskeletal Ultrasound of the Mexican College of Rheumatology (ECOMER) was founded with the intention of joining efforts to launch musculoskeletal ultrasound in Mexico. Essential requirements shared by all the members of ECOMER include: to own an ultrasound machine, to incorporate ultrasonography into clinical daily practice and to keep up-to-date in musculoskeletal ultrasound. The motto of ECOMER is una clara imagen de la reumatologia which means a clear picture of rheumatology. The statute of ECOMER can be read in its web site: www.ecomer.org.mx. This web site also provides a forum for case discussion, consultation and image review.

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Se presenta una propuesta metodológica estructurada con base en los Diagramas de Flujo de Datos (DFD), con la finalidad de evaluar el deterioro agroecológico y ambiental de una región dada, utilizando una metodología multifuncional y participativa, basada en el conocimiento local que poseen las comunidades que habitan en ella. La premisa básica que orienta esta metodología es considerar al ser humano no solo como un productor sino como un receptor de los impactos (efectos) provenientes de su entorno físico, biológico y social, considerando que parte importante de los impactos negativos que recibe son consecuencia de sus propias acciones (causas), situación que condiciona su calidad de vida. La información básica utilizada en esta propuesta metodológica fue extraída de tres proyectos de investigación en la cuenca del río Motatán, en los estados Mérida y Trujillo, Venezuela; específicamente en las subcuencas Alto Motatán, Monaicito, Escuque y La Palma. Esta sistematización de procesos, basada en los instrumentos Matriz Causa-Efecto; Matriz Problema-Solución y en el procedimiento para realizar el Análisis Global del Deterioro Agroecológico y Ambiental, constituye una alternativa para llevar a cabo, en forma rápida, sencilla, a bajo costo y con la participación de las comunidades, este tipo de evaluaciones.

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OBJECTIVE: To evaluate whether the presence of glomerulonephritis is or is not associated with the extent of arterial wall inflammatory cell infiltrate in Takayasu arthritis (TA). METHODS: Retrospective chart and pathology review of large artery and kidney specimens of TA autopsy cases. Kidney specimens were classified, according to their histopathological findings, in those with specific glomerular entities and those with non-specific, ischemic and/or hypertensive, glomerular changes. A control group of autopsy kidney specimens was utilized for comparison. Morphometric analysis was used to assess the extent of the arterial inflammatory infiltrates; results were compared among the different groups with kidney lesions. RESULTS: We included 25 kidney specimens from 25 autopsies. Specific glomerular entities were present in 14 specimens; 10 (40%) were classified as diffuse mesangial proliferative glomerulonephritis (DMPG [Group A]), and 4 (16%) as other associated glomerulopathies (Group B). Non-specific changes were observed in 11 (44%) specimens (Group C). The arterial inflammatory infiltrate proportion was 9.4 % for group A, 1.4% for group B, and 2.7% for group C. Furthermore, a larger proportion of vascular inflammation was confirmed for group A when compared with the other groups (p<0.05). Group A patients were younger than those in groups B and C (p<0.005) and exhibited shorter disease duration. CONCLUSION: The presence of DMPG was associated with a larger extent of vascular inflammatory cell infiltrate, suggesting a relationship between both phenomena.

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OBJECTIVE: To evaluate the efficacy and safety of a concurrent regimen of gemcitabine/cisplatin and radiotherapy in women with locally advanced cervical carcinoma (LACC). METHODS: From April 2001 to June 2002, we enrolled women diagnosed with histologically proven LACC (FIGO stages IIA through IIIB), for treatment with concurrent regimen of chemo-radiotherapy. The treatment consisted of: cisplatin 40 mg/m(2), followed by gemcitabine 125 mg/m(2), once weekly, given about 1 to 2 h before radiotherapy. External beam radiation was delivered 5 days/week to entire pelvic radiation field for a total of 50 Gy in 25 fractions over 5 weeks. After completion of external radiation, patients received brachytherapy with cesium-137 via standard Fletcher-suit applicators delivering 30 Gy to point A. RESULTS: Of the 23 enrolled patients (mean age 47 years), 20 completed the treatment and were evaluable for response and safety. The complete response rate was 90% (18/20), and partial response rate was 10% (2 patients with persistent disease after therapy). Toxicity was moderate: 2 patients required blood transfusions; 5% patients had grade 2 leukopenia or thrombocytopenia; 40% had grade 1-2 nausea-vomiting, and 50% had grade 1 diarrhea. At a median follow-up of 12 months, all patients are alive, and 16/20 (80%) are disease-free. CONCLUSIONS: The gemcitabine/cisplatin combination administered concurrently with radiotherapy is highly active in locally advanced cervical carcinoma. The tolerable toxicity and synergistic activity of this concurrent chemoradiation regimen are consistent with prior reports. Definitive results are awaited from an on-going large, randomized trial comparing this regimen with standard treatment.

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BACKGROUND AND PURPOSE: Despite prominent neurological symptoms reported in Takayasu arteritis (TA), a complete evaluation of the cerebral circulation has not been consistently performed. The purpose of this study is to describe MR angiography (MRA), color Doppler flow imaging, and transcranial Doppler (TCD) findings in the extracranial and intracranial cerebral arteries in TA. METHODS: MRA, color Doppler flow imaging, and TCD were performed in 21 patients with TA. Intima-media thickness was measured in the common carotid artery. The correlation between noninvasive studies and panaorto-arteriography was examined for supraortic vessels. Cerebral angiography findings were compared with the noninvasive methods in 7 patients. Intracranial hemodynamic changes detected by TCD were compared with extracranial circulation lesions assessed by panaorto-arteriography. RESULTS: Noninvasive vascular techniques showed at least 1 abnormality in the extracranial and/or intracranial cerebral arteries in 20 of 21 patients (95%). Both MRA and color Doppler flow imaging showed a substantial correlation in the ability to detect obstructive lesions in supra-aortic vessels compared with panaorto-arteriography. High-resolution ultrasonography displayed common carotid artery wall thickening in 5 vessels that were considered normal by arteriography. In 24% of patients, MRA and TCD showed abnormalities consistent with stenosis of the basal cerebral arteries. In 10 patients with severe extracranial circulation involvement (detected by arteriography), TCD displayed intracranial hemodynamic changes consisting of dampened or blunted waveforms with low pulsatility. CONCLUSIONS: The comprehensive assessment of cerebral circulation in TA patients by noninvasive methods allowed the detection of a high rate of diverse vascular abnormalities in both extracranial and intracranial circulation.

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OBJECTIVE: Hypertrophic osteoarthropathy (HOA) is characterized by the coexistence of digital clubbing and periosteal proliferation of the tubular bones. Localized vascular proliferation associated with platelet/endothelial cell activation are recognized features of this syndrome. Current knowledge suggests that HOA develops from the presence in the systemic circulation of one or more growth factors that are normally inactivated in the lungs. The nature of these purported growth factors has not yet been identified. Vascular endothelial growth factor (VEGF) has several features that may fit in with the pathogenesis of HOA. The objective of our study was to measure serum and plasma levels of VEGF in different groups of patients with HOA. METHODS: We studied 24 patients with HOA; of these, in 12 the HOA was secondary to cyanotic congenital heart disease and in 7 to lung cancer, while 5 represented primary cases. As controls we studied 28 individuals without HOA; of these, 12 were apparently healthy individuals, 7 had cyanosis secondary to chronic obstructive pulmonary disease, and 9 had lung cancer. ELISA was used to measure serum and plasma levels of VEGF. RESULTS: Plasma levels of VEGF were significantly higher in the patients with primary HOA (median 46.2; range 19.4-398.8 pg/ml) and in those with lung cancer-HOA (median 75.5; range 24.6-166.7), compared to healthy controls (median 7.4; range: 0-26.1), p < 0.05. Serum VEGF levels were higher in patients with lung cancer and HOA (median 411.4; range 164.2-959.5 pg/ml) compared with lung cancer patients without HOA (median 74.5; range 13.2-205.4), p < 0.001. CONCLUSIONS: Patients with primary HOA and those with HOA and lung cancer have increased circulating levels of VEGF. This cytokine may play a role in the pathogenesis of HOA.

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