The presence of IFL3/4 rs12979860 C allele influences the in vitro IP-10 production by mononuclear cells from patients with systemic lupus erythematosus.

OBJECTIVE: To explore whether the IFNL3/4 rs12979860 genotype may influence serum levels or production of interferon-inducible protein-10 (IP-10) by peripheral blood mononuclear cells from patients with systemic lupus erythematosus (SLE). METHODS: Sixty-six patients with SLE and 22 healthy blood donors (controls) were included. The IFNL3/4 rs12979860 polymorphism was genotyped by real-time polymerase chain reaction. IP-10 levels in sera supernatants of IFNα stimulated peripheral blood mononuclear cells were measured by enzime-linked immunosorbent assay. RESULTS: Allelic frequencies were CC (29%), CT (52%) and TT (20%) in SLE, and CC (32%), CT (41%) and TT (27%) in healthy controls. Median serum IP-10 levels were higher in SLE patients than in controls (190.8 versus 118.1 pg/ml; p < 0.001), particularly in those with high disease activity (278.5 versus 177.2 pg/ml; p = 0.037). However, serum IP-10 levels were not influenced by IFNL3/4 genotypes. Higher IP-10 production by peripheral blood mononuclear cells was found in both SLE patients (median 519.3 versus 207.6 pg/ml; p = 0.012) and controls (median 454.0 versus 201.7 pg/ml; p = 0.034) carrying the IFNL3/4 C allele compared with carriers of the T allele. CONCLUSIONS: Although IFNL3/4 rs12979860 allele C does not appear to influence serum IP-10 levels in SLE, it plays an important role in the production of IP-10 by peripheral blood mononuclear cells after IFNα stimulation.

[Evidence level and grade of recommendation of the Ponseti method for arthrogryposis-related syndromic talipes equinovarus and Moebius syndrome: a systematic review]. / Nivel de evidencia y grado de recomendación del uso del método de Ponseti en el pie equino varo sindromático por artrogriposis y síndrome de Moebius: una revisión sistemática.

BACKGROUND: Adduct congenital talipes equinovarus (CTE) or clubfoot is a common musculoskeletal malformation affecting between 1 and 4.5 out of every 1000 live births. It is usually associated with arthrogryposis and Moebius syndrome with the latter two being more difficult to treat as they require aggressive surgery to achieve a plantigrade foot. We therefore ask what is the evidence level and grade of recommendation of the Ponseti method to treat syndromic talipes equinovarus resulting from arthrogryposis and Moebius syndrome. METHODS: Systematic review according to the recommendations of the Cochrane group identifying medical subheadings (MeSH) and of the Boolean method to identify the articles that met the selection criteria through the search of primary sources such as OVID, Cochrane, EBSCOhost, Elsevier, Medigraphic. RESULTS: A total of six papers met the selection criteria through the search in the primary sources. Five of them address the treatment of adduct CTE with the Ponseti method in patients with arthrogryposis, and one in patients with Moebius. Evidence levels and grades of recommendation of these papers were: IV-D (3), III-D (1) y II (B). CONCLUSIONS: The Ponseti method is an first-line treatment for arthrogryposis and Moebius syndrome. It is unexpensive, non-invasive and does not require a physician to perform it (however, it does require trained staff). Its use is recommended as it avoids extensive surgeries and medical complications that go beyond the hospitals economic possibilities.

ANTECEDENTES: El pie equino varo aducto congénito (PEVAC) es una malformación musculoesquelética común que afecta de uno a 4.5 de cada 1,000 nacidos vivos; se asocia de manera común a artrogriposis y síndrome de Moebius; éstos son más difíciles de tratar y requieren de tratamientos quirúrgicos agresivos para lograr un pie plantígrado; por lo tanto, ¿cuál es el nivel de evidencia y grado de recomendación del uso del método de Ponseti en el pie equino varo sindromático por artrogriposis y síndrome de Moebius? MÉTODOS: Estudio de diseño de revisión sistemática de acuerdo a las recomendaciones del grupo Cochrane por medio de la identificación de Medical Subject Headings (MeSH) y del método booleano para ubicar artículos que cumplieran con los criterios de selección mediante búsqueda de fuentes primarias como OVID, Cochrane, EBSCOhost, Elsevier, Medigraphic. RESULTADOS: En total, seis artículos cumplieron con los criterios de selección a través de la búsqueda de fuentes primarias: cinco de ellos sobre el tratamiento del PEVAC con método de Ponseti en pacientes con artrogriposis y uno para pacientes con Moebius. Se encontraron artículos con niveles de evidencia y grado de recomendación: IV-D (3), III-D (1) y II (B). CONCLUSIONES: El método de Ponseti es un tratamiento inicial en artrogriposis y síndrome de Moebius; es barato, no invasivo y no requiere de un médico para poderse realizar (pero sí un personal capacitado); se recomienda su uso para evitar cirugías extensas y complicaciones médicas que trascienden al orden económico intrahospitalario.

Guided growth may not be the best option for knee valgus deformity in adolescent patients with Morquio-A.

INTRODUCTION: Valgus deformity in knees is a common concern in Morquio-A patients, preceding premature arthrosis and pain leading to walking disability and loss of ambulatory status. Treatment alternative is the guided growth, but this is sometimes not applied on time. Due to short height reached on these patients, not all will benefit from guided growth surgery. PURPOSE: The purpose of this study is to describe early results of physeal osteotomy for acute valgus correction in adolescent patients and those almost at height peak to achieve alignment. METHODS: We perform the osteotomy in four knees of 10- and 14-year-old patients, fixed with Kirschner wires, and allow early weight bearing. This is compared with one patient who was managed by guided growth. RESULTS: The average acute correction osteotomy was 39 degrees with intermalleolar distance of 350 and 240 mm. At final follow-up, this measure was reduced to 70 and 20 mm, respectively, with clinical valgus of 4° and 2°. For the patient with guided growth, she was operated at 10.2 years old and 36 months in follow-up; preoperative valgus was 28/24° with intermalleolar distance of 140 mm. At the end of follow-up, this distance was increased to 150 mm with clinical valgus of 18/22°. During this follow-up, none of the patients lost ambulatory status. As a part of multi-organic disease progression, none of the three patients completed the 6-min walking test at final follow-up. CONCLUSIONS: This physeal osteotomy is a feasible and optimal option to achieve acute valgus correction on severe deformity when there is not enough remaining growth on adolescent Morquio-A patients, and may help reduce arthritis progression in adjacent joints.

[360 degrees instrumentation for cervical instability due to metastatic bone disease. Case report]. / Manejo con instrumentación 360o de enfermedad ósea metastásica que condiciona inestabilidad en columna cervical. Reporte de un caso clínico.

INTRODUCTION: The spine is the most common site for bone metastases; being the breast, prostate and lung cancer which have most affected. The thoracic spine is involved in 70% of cases, followed by the lumbar and cervical region. MATERIAL AND METHODS: This is a 59 years old female diagnosed with breast adenocarcinoma and metastatic bone disease in cervical spine C2, C3 level and instability of that segment because of a compression fracture of C3 greater than 80% without invasion of the spinal canal, she begins with paresthesias of upper limbs. A 360º instrumentation was performed in two stages. After the surgical procedure the patient were without neck pain and a good neurological status. DISCUSSION: Metastatic bone disease causes significant damage to the spine sometimes create instability proper instrumentation is needed to improve the functional status and prognosis of these lesions.

La columna vertebral es el sitio más frecuente de localización para las metástasis óseas; siendo los tumores de mama, próstata y pulmón los que mayor afectación presentan. La columna torácica es afectada en un 70% de los casos, seguida de la región lumbar y cervical.

Epidermal growth factor receptor expression in gastric tumors and its relationship with the germline polymorphisms - 216 G>T, -191 C>A, (CA) n IVS1, and R521K.

BACKGROUND: Gastric cancer (GC) is the third worldwide leading cause of cancer-related death affecting both sexes. The aberrant expression of epidermal growth factor receptor (EGFR) gene has been detected in many human epithelial malignancies and linked to advanced disease, more aggressive phenotype, and poor prognosis. AIMS: To analyze the relation that the expression of EGFR in gastric tumors holds with pathological characteristics and with the germline polymorphisms -216 G>T, -191 C>A, (CA) n IVS1, and R521K. MATERIALS AND METHODS: We studied 22 biopsies from gastric tumors obtained by endoscopy. EGFR expression was determined by relative quantification real-time polymerase chain reaction with the glyceraldehyde-3-phosphate dehydrogenase reference gene (as for messenger RNA [mRNA]) and by immunohistochemistry (IHC) (as for protein). EGFR germline polymorphisms were analyzed by sequencing, GeneScan, and restriction fragment length polymorphisms. RESULTS: EGFR mRNA expression was increased (>2-fold) in 13.6% of GC cases, decreased (<0.5-fold) in 68.2%, and normal in 18.2%; overexpression was related to well-differentiated gastric tumors, whereas underexpression was linked to moderate or poorly differentiated gastric tumors (P < 0.001). EGFR protein expression was high (IHC 2+ and 3+) in 29.4% of gastric tumors and was normal or low (score 0 to 1+) in 70.6% cases. EGFR expression, in both mRNA and protein, was not related to any EGFR polymorphism (P > 0.05). CONCLUSIONS: Most gastric tumors showed low EGFR expression (mRNA and protein), whereas EGFR overexpression was related to well-differentiated gastric tumors. Furthermore, germinal polymorphisms -216, -191, (CA) n IVS1, and R521K were not related to EGFR expression (mRNA or protein).

EGFR gene polymorphisms -216G>T and -191C>A are risk markers for gastric cancer in Mexican population.

Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein with tyrosine-kinase activity that plays an important role in multiple cellular functions. EGFR overexpression has been observed in several types of tumors and it is significantly associated with disease stage, survival, prognosis, and progression of cancer. The polymorphisms -216G>T, -191C>A, and (CA)n first intervening sequence (IVS1) have been related to EGFR overexpression and have been studied in several types of cancer, but not in gastric cancer (GC). The aim of this study was to determine the association of these 3 polymorphisms and GC. Genomic DNA from 68 GC patients and 102 healthy blood donors were analyzed. Polymorphisms were identified by DNA-sequencing (-216G>T and -191C>A) and GeneScan (CA)n IVS1. The results showed that the distribution of the -216G>T and -191C>A genotypes differed between groups (P < 0.05). The odds ratio for the -216TT genotype was 4.59 (95% confidence interval = 1.55-13.54, P < 0.05) and 10.71 (95% confidence interval = 2.31-49.59, P < 0.05) for the -191AA genotype, both in a recessive model. The genotype and allele distributions of the (CA)n IVS1 repeat was similar in both groups. In conclusion, the -216TT and -191AA genotypes and GA haplotype of the EGFR gene were found to be associated with an increased risk of gastric cancer in a Mexican population.

Ultrastructural aspects of human cystic duct epithelium as a result of cholelithiasis and cholesterolosis.

Although there is a large body of data on the gallbladder and the importance of the cystic duct in surgical procedures, there is insufficient data regarding the morphology of the human cystic duct. In the present study, transmission electron microscopic (TEM) and scanning electron microscopic (SEM) survey of several surgical and autopsy cystic ducts in cholelithiasis and cholesterolosis is reported. In cholelithiasis, similar to gallbladder epithelium, the cystic duct epithelial cells display minor-to-severe alterations of the epithelial surface accompanied by variable erosion of the epithelium. Areas of intact surface epithelium demonstrate microvilli-covered cells coated by a rich glycocalyx and mucous production. In other areas, apical excrescences are associated with mucus hyperproduction and secretory events. Lipoid bodies are also present in many cells and especially in many of the cells' subliminal apical areas. In cholesterolosis, mucous secretory granules appear dilated, fatty deposits are infrequent, and peculiar intracellular cholesterol deposits can be detected in the apical and subapical region of cells and around condensed mitochondria. Following elective cholecystectomies, predominantly in association with cholelithiasis, eroded areas were detected; therefore, it appears that the action of intraluminal calculi may be a principal causative factor in discrete epithelial erosions of the cystic duct. Intraluminal calculi/ debris, along with the alteration of mucus, cell sloughing, and a decreased pool of bile acids and motility may participate in the gallstone nucleation process. The peculiar cholesterol inclusions may also play a role in that nucleating process.

Artificial restoration of voice. I: Experiments in phonatory control of the reinnervated canine larynx.

Coordinated electronic pacing of implanted nerve pedicles into paralyzed laryngeal muscles has allowed selective dynamic control of abduction, adduction, and elongation of the vocal cords. Modifications of the original circuit in a cervical muscle model has added fine tuning to basic "all-or-none" pacing. Rehabilitation of phonation illustrated the sophisticated nature of voice and the need for restoration of fine tuning. Five mongrel dogs received nerve-muscle pedicles into the thyroarytenoideus, cricothyroideus, and posterior cricothyroideus after denervation of one hemilarynx. Following appropriate reinnervation time, pedicles and intact recurrent laryngeal nerves were injected with currents of variable amplitudes and pulse widths to achieve graded vocal fold control while air was blown intratracheally towards the glottic chink. Videoscopic and spectral analyses indicated that artificial phonation could be restored to frequencies measured in the normal state. These experiments suggested that rehabilitation of the impaired voice by servocontrol might eventually be feasible.

Excitation thresholds for nerves reinnervating the paralyzed canine larynx.

Electrical stimulation of paralyzed laryngeal muscles implanted with nerve-muscle pedicles (NMP) has resulted in documented return of motion. No study, however, has yet determined how NMP excitability correlates with that of normal muscle or nerve. In six anesthetized dogs, one hemilarynx was denervated and the paralyzed thyroarytenoid, cricothyroid, and posterior cricoarytenoid muscles were reinnervated via NMPs originating from the ansa hypoglossi nerve. After 4.6 to 5.7 months, an electric stimulator delivering biphasic pulses of variable amplitude and widths was used to test thresholds for contraction in nine stimulatable NMPs, six intact recurrent laryngeal nerves (RLN), and five normal cervical muscles. With one exception (2.1 mA), NMP rheobases varied between 0.0002 and 0.04 mA (mean = 0.020 SD +/- 0.012, n = 6). Two NMPs belonging to animals stimulated for several hours had higher values (0.1 mA). Rheobase varied from 0.01 to 0.09 mA for control RLNs (mean = 0.058 SD +/- 0.025), and from 0.05 to 0.35 mA for muscles (mean = 0.144 SD +/- 0.109). Histologic correspondence with reinnervation was established in implanted muscles by type grouping on ATPase stains. These data suggest that 1) nerve pedicles may offer promise for the eventual construction of implantable low energy consuming laryngeal devices, and 2) the appropriate charge to be injected over time remains to be determined.