miRNAs: una nueva mirada de la enfermedad de Vogt-Koyanagi-Harada / miRNAs: a new look at Vogt-Koyanagi-Harada disease

Vogt-Koyanagi-Harada disease (VKH) is an autoimmune multisystemic syndrome that includes bilateral intraocular inflammation, associated with exudative retinal detachments, and systemic manifestations in the auditory, integumentary, and central nervous systems. The frequency of VKH disease in the world is variable, but in Santiago, Chile, it causes approximately 17% of non-infectious uveitis, an incidence 2 to 3-fold greater than in the USA or European countries. The evidence shows that the pathogenesis of VKH would be caused by cell-mediated autoimmunity directed against melanocytes present in the uveal tissue. CD4+ T lymphocytes (especially hyperactivity of Th17 and Th1 cells), B lymphocytes, cytokines (e.g., TGF-ß, IL-2, IL-6, IL-23 and INF-γ) and chemokines appear to play an important role in the development of VKH. Several lines of evidence support that the pathogenesis of uveitis observed in VKH involves an altered pattern of micro-ribonucleic acids (miRNA) expression, driving the loss of immunological tolerance. In this review, we discuss the evidence related to regulation and altered expression of miRNA associated with Vogt-Koyanagi-Harada and other autoimmune diseases. (AU)

Evaluation of the reproducibility of a protocol for the pharmacokinetic study of breast tumors by dynamic magnetic resonance imaging.

OBJECTIVE: To evaluate the reproducibility of a protocol for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for the pharmacokinetic study of breast tumors. MATERIAL AND METHODS: We carried out this prospective study from October 2009 through December 2009. We studied 12 patients with stage ii-iii invasive breast cancer without prior treatment. Our center's research ethics committee approved the study. The 12 patients underwent on two consecutive days DCE-MRI with a high temporal resolution protocol (21 acquisitions/minute). The data obtained in an ROI traced around the largest diameter of the tumor (ROI 1) and in another ROI traced around the area of the lesion's highest K(trans) intensity (ROI 2) were analyzed separately. We used parametric and nonparametric statistical tests to study the reproducibility and concordance of the principal pharmacokinetic variables (K(trans), Kep, Ve and AUC90). RESULTS: The correlations were very high (r>.80; P<.01) for all the variables for ROI 1 and high (r=.70-.80; P<.01) for all the variables for ROI 2, with the exception of Ve both in ROI 1 (r=.44; P=.07) and in ROI 2 (r=.13; P=.235). There were no statistically significant differences between the two studies in the values obtained for K(trans), Kep and AUC90 (P>.05 for each), but there was a statistically significant difference between the two studies in the values obtained for Ve in ROI 2 (P=.008). CONCLUSIONS: The high temporal resolution protocol for DCE-MRI used at out center is very reproducible for the principal pharmacokinetic constants of breast.

[Using magnetic resonance imaging for staging can change the therapeutic management in patients with breast cancer]. / La estadificación con resonancia magnética puede cambiar el manejo terapéutico en el cáncer de mama.

OBJECTIVE: To compare two series of patients with breast cancer, one staged using preoperative MRI and the other staged using conventional techniques, analyzing the changes to treatment, the number of mastectomies, and the number of reinterventions due to involvement of the margins. MATERIAL AND METHODS: We reviewed 600 patients divided into 300 patients with preoperative MRI (series 1) and 300 without preoperative MRI (series 2). We recorded the following variables: age, menopausal status, tumor size on pathological examination, multiplicity and bilaterality, surgical treatment and type of treatment, the administration of neoadjuvant chemotherapy, and reintervention for involved margins. We used Student's t-test and the chi-square test to compare the variables between the two series. RESULTS: The mean age of patients in the two series was similar (51.5 and 51.8 years, P=0.71). The mean size of the tumor was smaller in series 1 (16.9 mm vs 22.3 mm) (P<.001). More multiple tumors were detected in series 1 (28.7 vs 15.7%) (P<.001). The rate of mastectomies was lower in series 1 (25 vs 48%) (P<.001). Oncoplastic and bilateral surgeries were performed only in series 1. Neoadjuvant chemotherapy was administered more often in series 1 (30.7 vs 9.3%) (P<.001). The difference in the number of reinterventions for involved margins did not reach significance (7.2% in series 1 vs 3.2% in series 2) (P=.095). CONCLUSION: When MRI was used for staging, neoadjuvant chemotherapy and oncoplastic surgery were used more often and the mastectomy rate decreased. Despite the increase in conservative surgery in patients staged with MRI, the number of reinterventions for involved margins did not increase, although there was a trend towards significance.

[Colorectal cancer: 74 patients treated by laparoscopic resection with a mean follow-up of 5 years]. / Cancer colorectal: 74 patients traités par laparoscopie avec un recul moyen de 5 ans.

OBJECTIVE: The aims of this study were to analyse the results and long term outcome in a prospective non randomised trial of 74 patients treated by laparoscopic colo-rectal resection for cancer, and to determine wether survival and recurrence are or are not compromised by an initial laparoscopic approach. PATIENTS AND METHODS: Seventy-four patients with colo-rectal carcinoma were included in a prospective trial and treated by laparoscopic resection. All patients were reviewed at 1, 3, and 6 months interval. A median of 5 years follow up was available. Forty-eight patients (65%) had more than 3 years of follow up. RESULTS: Six conversions (8.1%) were necessary: 2 for tumor invasion of adjacent organs, 2 for limited margin resection in lower rectal tumors, 1 for small bowel injury and 1 for obesity. After surgery, passing flatus occurred at 34.3 +/- 16.7 h and oral intake could be reinstaured at 42.6 +/- 22 h. Mean postoperative stay was 8.2 +/- 3.4 days. No death occurred. The overall morbidity was about 13.5%. The rate of late complications was 5.4%. Two port site metastasis (2.6%) were seen in locally advanced carcinoma. Recurrence rate at 5 years was 0% for Dukes A, 20% for Dukes B, 39.2% for Dukes C. Survival rate at 5 years was 100% for Dukes A, 80% for Dukes B, and 60.7% for Dukes C. These results are similar to those of conventional open surgery. CONCLUSION: Laparoscopic colorectal resection for cancer can be performed safely, with a low morbidity and rare late complications. Long term follow up (5 years) assessment shows similar outcome compared with conventional surgery.

Characterization of a complex translocation [t(4;9;22)(p16;q34;q11)] in chronic myelogenous leukemia by fluorescence in situ hybridization technique.

A patient was referred with a high leukocyte count and diagnosed with chronic myelogenous leukemia (CML). Although practically asymptomatic since the time of diagnosis, he had a variable and inconsistent response to treatment. All of his bone marrow cells had a complex, three-way translocation, involving chromosomes 4, 9 and 22. Translocation of chromosome 4 to chromosome 9 was undetectable by routine cytogenetic techniques; however, by the fluorescence in situ hybridization technique, a three-way translocation was identified, 46,XY,t(4;9;22)(p16;q34;q11). Although, other chromosomes are frequently involved in complex or variant translocations with chromosome 9 and 22, participation of chromosome 4 is a very rare event. So far, two previous cases have been described in the literature with translocations involving chromosome 4p16. We present a third case of CML having similar break points whose clinical presentation is unusual.

New translocations [t(6;15)(p25;q22) and t(6;19)(q16;q13.3)] with t(9;22)(q34;q11) in a Ph-positive chronic myelogenous leukemia.

A case with typical features of chronic myelogenous leukemia (CML) with two complex aberrations in addition to the standard t(9;22) is reported. Cytogenetic evaluation of the patient's bone marrow cells (BMC) showed 46,XX,t(6;19)(q16;p13.3),t(9;22)(q34;q11) in 60% of the mitotic cells and 46,XX,idem, t(6;15)(p25;q22) in the remaining 40% dividing cells. The patient's peripheral blood smear exhibited the usual differential observed in chronic-phase CML and was clinically indistinguishable from patients with the t(9;22) as the only translocation. We performed Southern blotting on BglII-digested DNA with the Trans-Probe (OSI) and in addition to the 4.8-, 2.3-, and 1.1-kilobase (kb) germline fragments, we detected an additional fragment at 7 kb. This probe spans the entire 5.8-kb M-breakpoint cluster region (BCR), and a single breakpoint in this region will appear as either one or two additional fragments. Because only one additional fragment was observed, both cell lines apparently share the same breakpoint in the ABL/BCR gene. Apparently the second aberrant cell line with the additional t(6;15) represents clonal evolution of the original abnormal clone.

Further characterization of the receptors involved in the positive inotropic effect of histamine on rabbit papillary muscle.

The effects of histamine on the force of contraction and calcium-dependent action potentials were studied in rabbit ventricular papillary muscles. The positive inotropic effect of histamine seems to be dependent on stimulation of H1 and H2 receptors. The H1 antagonist chlorpheniramine produced a competitive blockade of the positive inotropic effects of histamine. Cimetidine produced a competitive blockade, which was apparent only after blockade of H1 receptors. Histamine increased the maximum upstroke velocity of slow action potentials. This effect can be entirely accounted for by stimulation of H2 receptors. The phosphodiesterase inhibitor 3-isobutyl-methyl-xanthine potentiated the H2 receptor mediated effects of histamine on the force of contraction and slow action potentials. We conclude that rabbit ventricular muscle possesses both H1 and H2 receptors that mediate the positive inotropic effect of histamine. The H2-mediated effect seems to be causally related to an increase in the calcium slow inward current and is probably linked to an enhanced cellular cyclic adenosine monophosphate content. The mechanism of the H1-mediated positive inotropic effect remains unknown.

Regional versus systemic heparinization.

In 12 mongrel dogs, the comparative effectiveness of systemic versus regional heparinization was studied after injecting 100 units per kilogram of heparin into a systemic vein or regionally into an artery. Activated plasma thromboplastin time was used to monitor the heparin activity, and the coagulability of blood in the general circulation was compared with the coagulability of blood in the excluded circulation distal to the vascular clamps. Both methods of heparinization were found to be equally effective. Heparin injected regionally rapidly achieves a uniform distribution in the excluded, as well as the general, circulation and, as such, cannot be called regional. There was no difference in coagulability of blood in the general circulation compared with the blood in the excluded circulation. Results of this study suggest that regional heparinization is, in fact, systemic heparinization.

Chronic lymphocytic leukemia and lymphosarcoma associated with multiple myeloma: report of three cases.

Three patients had the rare occurrence of multiple myeloma coexisting with chronic lymphocytic leukemia or lymphosarcoma. It is not possible at present to resolve the question as to whether these two diseases represent part of the spectrum of a single B-cell disease or wether multiple myeloma and lymphoproliferative disorders are two separate entities, which may rarely occur by coincidence in the same patient.