Autologous stem cell transplantation for untreated transformed indolent B-cell lymphoma in first remission: an international, multi-centre propensity-score-matched study.

High-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) are used as consolidation in first remission (CR1) in some centres for untreated, transformed indolent B-cell lymphoma (Tr-iNHL) but the evidence base is weak. A total of 319 patients with untreated Tr-iNHL meeting prespecified transplant eligibility criteria [age <75, LVEF ≥45%, no severe lung disease, CR by positron emission tomography or computed tomography ≥3 months after at least standard cyclophosphamide, doxorubicin, vincristine and prednisolone with rituximab (R-CHOP) intensity front-line chemotherapy] were retrospectively identified. Non-diffuse large B-cell lymphoma transformations were excluded. About 283 (89%) patients had follicular lymphoma, 30 (9%) marginal-zone lymphoma and six (2%) other subtypes. Forty-nine patients underwent HDC/ASCT in CR1, and a 1:2 propensity-score-matched cohort of 98 patients based on age, stage and high-grade B-cell lymphoma with MYC, BCL2 and/or BCL6 rearrangements (HGBL-DH) was generated. After a median follow-up of 3·7 (range 0·1-18·3) years, ASCT was associated with significantly superior progression-free survival [hazard ratio (HR) 0·51, 0·27-0·98; P = 0·043] with a trend towards inferior overall survival (OS; HR 2·36;0·87-6·42; P = 0·1) due to more deaths from progressive disease (8% vs. 4%). Forty (41%) patients experienced relapse in the non-ASCT cohort - 15 underwent HDC/ASCT with seven (47%) ongoing complete remission (CR); 10 chimeric antigen receptor-modified T-cell (CAR-T) therapy with 6 (60%) ongoing CR; 3 allogeneic SCT with 2 (67%) ongoing CR. Although ASCT in CR1 improves initial duration of disease control in untreated Tr-iNHL, the impact on OS is less clear with effective salvage therapies in this era of CAR-T.

[Low-risk community-acquired pneumonia: implications of its outcome due to the determining factors for admission not contemplated by the scores]. / Neumonía adquirida en la comunidad de bajo riesgo: Consecuencias evolutivas de los determinantes de internación no contemplados por los scores.

OBJECTIVES: The decision to admit patients with community-acquired pneumonia (CAP) to hospital are based on stratification scales. This classification into risk groups is not perfect. In low-risk community-acquired pneumonia (LR-CAP), physicians often depend on their subjective impressions to decide the need for hospitalisation, which suggests the existence of conditions not considered by the scores. The aim of this article was to describe the determining factors for admission in LR-CAP, and to analyse the relationship between these causes and clinical outcome. MATERIAL AND METHODS: A descriptive, observational, retrospective study, based on the review of medical records during a 2 year-period. It included patients over 18 years, who were hospitalised in a third level hospital in Argentina due to LR-CAP. RESULTS: A total of 80 cases were identified. The causes that led to hospitalisation were: comorbidities not included in the scores, development of pleural effusion and sepsis, lack of response to ambulatory antibiotic treatment, oral intolerance, and social causes. HIV infection was associated with an unfavourable clinical progress during hospital admission (p=.03), as well as the lack of response to outpatient treatment (p=.03) and the development of pleural effusion (p=.03). Social causes were associated with a need for longer intravenous treatment. CONCLUSIONS: HIV infection, social causes, and lack of response to ambulatory treatment were related to unfavourable clinical progress.

Targeting nucleolin for better survival in diffuse large B-cell lymphoma.

Anthracyclines have been a cornerstone in the cure of diffuse large B-cell lymphoma (DLBCL) and other hematological cancers. The ability of anthracyclines to eliminate DLBCL depends on the presence of topoisomerase-II-alpha (TopIIA), a DNA repair enzyme complex. We identified nucleolin as a novel binding partner of TopIIA. Abrogation of nucleolin sensitized DLBCL cells to TopIIA targeting agents (doxorubicin/etoposide). Silencing nucleolin and challenging DLBCL cells with doxorubicin enhanced the phosphorylation of H2AX (γH2AX-marker of DNA damage) and allowed DNA fragmentation. Reconstitution of nucleolin expression in nucleolin-knockdown DLBCL cells prevented TopIIA targeting agent-induced apoptosis. Nucleolin binding to TopIIA was mapped to RNA-binding domain 3 of nucleolin, and this interaction was essential for blocking DNA damage and apoptosis. Nucleolin silencing decreased TopIIA decatenation activity, but enhanced formation of TopIIA-DNA cleavable complexes in the presence of etoposide. Moreover, combining nucleolin inhibitors: aptamer AS1411 or nucant N6L with doxorubicin reduced DLBCL cell survival. These findings are of clinical importance because low nucleolin levels versus high nucleolin levels in DLBCL predicted 90-month estimated survival of 70% versus 12% (P<0.0001) of patients treated with R-CHOP-based therapy.

Patients with classical Hodgkin lymphoma experiencing disease progression after treatment with brentuximab vedotin have poor outcomes.

BACKGROUND: Brentuximab vedotin (BV) is a key therapeutic agent for patients with relapsed/refractory classical Hodgkin lymphoma (cHL). The outcomes of patients experiencing disease progression after BV are poorly described. PATIENTS AND METHODS: We reviewed our institutional database to identify patients with cHL treated with BV who were either refractory to treatment or experienced disease relapse. We collected clinicopathologic features, treatment details at progression and outcome. RESULTS: One hundred patients met inclusion criteria, with a median age of 32 years (range 18-84) at progression after BV. The median number of treatments before BV was 3 (range 0-9); 71 had prior autologous stem cell transplant. The overall response rate (ORR) to BV was 57%, and the median duration of BV therapy was 3 months (range 1-25). After disease progression post-BV, the most common treatment strategies were investigational agents (n = 30), gemcitabine (n = 15) and bendamustine (n = 12). The cumulative ORR to therapy was 33% (complete response 15%). After a median follow-up of 25 months (range 1-74), the median progression-free (PFS) and overall survival (OS) were 3.5 and 25.2 months, respectively. In multivariate analysis, no factors analyzed were predictive of PFS; age at progression >45 years and serum albumin <40 g/l at disease progression were associated with increased risk of death. Among patients who achieved response to therapy, allogeneic stem cell transplantation was associated with a non-significant trend toward superior OS (P = 0.11). CONCLUSIONS: Patients with BV-resistant cHL have poor outcomes. These data serve as a reference for newer agents active in BV-resistant disease.

Factors influencing outcome in advanced stage, low-grade follicular lymphoma treated at MD Anderson Cancer Center in the rituximab era.

BACKGROUND: The optimal initial therapy of follicular lymphoma (FL) remains unclear. The aims of this study were to compare primary treatment strategies and assess the impact of maintenance rituximab and patterns of treatment failure. PATIENTS AND METHODS: We retrospectively analyzed patients with treatment-naive advanced stage, grade 1-2 FL treated at our center from 2004 to 2014. We included 356 patients treated on clinical trials or standard of care with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP, n = 119); R-CHOP with maintenance (R-CHOP + M, n = 65); bendamustine/rituximab (BR, n = 45); BR with maintenance (BR + M, n = 35); R(2) (n = 94). We compared baseline characteristics, progression-free survival (PFS), overall survival (OS) and analyzed prognostic factors using univariate and multivariate analysis adjusted for treatment. RESULTS: After a median follow-up of 4 years (range 0.2-15.0), the 3-year PFS was 60% [95% confidence interval (CI) 51% to 69%] for R-CHOP, 72% (59% to 82%) for R-CHOP + M, 63% (42% to 78%) for BR, 97% (80% to 100%) for BR + M and 87% (78% to 93%) for R(2). Patients treated with R-chemotherapy had more high-risk features than patients treated with R(2) but, by adjusted multivariate analysis, treatment with R(2) [hazard ratio (HR) 0.39 (0.17-0.89), P = 0.02] was associated with a superior PFS. Eastern Cooperative Oncology Group Performance status of one or more predicted inferior OS. Among patients treated with R-chemotherapy, maintenance was associated with the superior PFS [HR 0.38 (95% CI 0.21-0.68)]. By adjusted multivariate analysis, disease progression within 2 years [HR 5.1 (95% CI 1.57-16.83)] and histologic transformation (HT) [HR 11.05 (95% CI 2.84-42.93)] increased risk of death. CONCLUSION: Induction therapy with R(2) may result in disease control which is comparable with R-chemotherapy. Early disease progression and HT are predictive of inferior survival.

Inhalación masiva de amoniaco: reporte de dos casos / Massive ammonia inhalation: report of two cases

Ammonia (NH3) is an irritant and corrosive gas whose inhalation at high concentrations mainly occurs during agricultural and industrial activities, as occupational accidents. The extent and severity of the damage depends on the concentration and time of exposure to the toxic, which can cause skin, eye, respiratory and life-threatening injuries. We present two cases of patients acutely exposed to high concentrations of NH3. Both patients survived to the acute phase of the respiratory injury, but developed chronic lung derangements.

El amoniaco (NH3) es un gas irritante y corrosivo cuya inhalación aguda en altas concentraciones se produce principalmente durante accidentes laborales en el sector agrícola e industrial. La extensión y severidad del daño depende de la concentración y tiempo de exposición al tóxico, el cual puede causar lesiones a nivel cutáneo, ocular, respiratorio y riesgo vital. Presentamos dos casos de pacientes expuestos en forma aguda a NH3 en altas concentraciones. Ambos pacientes sobrevivieron a la fase aguda y evolucionaron con lesiones respiratorias crónicas.

FAS-antisense 1 lncRNA and production of soluble versus membrane Fas in B-cell lymphoma.

Impaired Fas-mediated apoptosis is associated with poor clinical outcomes and cancer chemoresistance. Soluble Fas receptor (sFas), produced by skipping of exon 6, inhibits apoptosis by sequestering Fas ligand. Serum sFas is associated with poor prognosis of non-Hodgkin's lymphomas. We found that the alternative splicing of Fas in lymphomas is tightly regulated by a long-noncoding RNA corresponding to an antisense transcript of Fas (FAS-AS1). Levels of FAS-AS1 correlate inversely with production of sFas, and FAS-AS1 binding to the RBM5 inhibits RBM5-mediated exon 6 skipping. EZH2, often mutated or overexpressed in lymphomas, hyper-methylates the FAS-AS1 promoter and represses the FAS-AS1 expression. EZH2-mediated repression of FAS-AS1 promoter can be released by DZNeP (3-Deazaneplanocin A) or overcome by ectopic expression of FAS-AS1, both of which increase levels of FAS-AS1 and correspondingly decrease expression of sFas. Treatment with Bruton's tyrosine kinase inhibitor or EZH2 knockdown decreases the levels of EZH2, RBM5 and sFas, thereby enhancing Fas-mediated apoptosis. This is the first report showing functional regulation of Fas repression by its antisense RNA. Our results reveal new therapeutic targets in lymphomas and provide a rationale for the use of EZH2 inhibitors or ibrutinib in combination with chemotherapeutic agents that recruit Fas for effective cell killing.

Descripción y seguimiento a largo plazo de 123 pacientes con melanoma y biopsiaselectiva del ganglio centinela / Description and long term follow up of 123 patients with melanoma and sentinel lymph node biopsy

El estudio del ganglio centinela (GC) en el tratamiento del melanoma requiere una estrecha colaboración entre el cirujano plástico, el dermatólogo, el especialista en Medicina Nuclear y el patólogo. Presentamos un estudio retrospectivo sobre un grupo de 123 pacientes con melanoma primario cutáneo en los que se realizó técnica de biopsia selectiva del gangliocentinela (BSGC) entre diciembre de 1999 y diciembre del 2005 en el Hospital Universitario Cruces en Barakaldo (Bizkaia, España) y describimos la evolución a largo plazo y la relación entre los resultados de la BSGC y los eventos clínicos relevantes durante el seguimiento. Fueron extirpados 294 ganglios centinela; en 15 pacientes el patólogo informó de la presencia de micrometástasis en el GC, desarrollando posteriormente metástasis a distancia el 46,6% de esos pacientes frente a un 19% en aquellos con GC negativo (p=0,021). De los 123 pacientes estudiados, 14 fallecieron por melanoma (11´4%):3 en el primer año de seguimiento, 2 en el segundo, 3 en el tercero, 2 en el cuarto y 2 en el quinto año. Nuestra experiencia confirma que la BSGC es una técnica sencilla y útil para el estadiaje del melanoma por mostrar una tendencia hacia la asociación estadística entre la positividad del GC y un peor pronóstico (AU)

The study of sentinel node (SN) in the management of melanoma requires close collaboration among plastic surgeon, dermatologist, specialist in Nuclear Medicine and pathologist. The authors present a retrospective study in a group of123 patients with primary cutaneous melanoma who consented to sentinel node biopsy (SLNB) between December1999 and December 2005 at the University Hospital Cruces (Barakaldo, Bizkaia, Spain). We describe the long-term evolution and the relation between SLNB results and relevant clinical events during follow-up. We removed 294 sentinel nodes; 15 patients had tumour in the centinela node, subsequently developed distant metastasis in 46.6%, compared with 19% in patients with negative SN (p=0.021). Of the 123 patients studied,14 died of melanoma (11´4%): 3 in the first year of follow up, 2 in the second, 3 in the third, 2 in the fourth and2 in fifth year. We corroborate that the SLNB is an easy technique and useful for staging, showing the statistic relationship between positive SN and bad prognostic (AU)

A randomized trial of a single-dose rasburicase versus five-daily doses in patients at risk for tumor lysis syndrome.

BACKGROUND: Tumor lysis syndrome (TLS) is a life-threatening disorder characterized by hyperuricemia and metabolic derangements. The efficacy of rasburicase, administered daily for 5 days, has been well established. However, the optimal duration of therapy is unknown in adults. PATIENTS AND METHODS: We evaluated the efficacy of rasburicase (0.15 mg/kg) administered as single dose followed by as needed dosing (maximum five doses) versus daily dosing for 5 days in adult patients at risk for TLS. RESULTS: Eighty of the 82 patients enrolled received rasburicase; 40 high risk [median uric acid (UA) 8.5 mg/dl; range, 1.5-19.7] and 40 potential risk (UA = 5.6 mg/dl; range, 2.4-7.4). Seventy-nine patients (99%) experienced normalization in their UA within 4 h after the first dose; 84% to an undetectable level (<0.7 mg/dl). Thirty-nine of 40 (98%) patients in the daily-dose arm and 34 of 40 (85%) patients in single-dose arm showed sustained UA response. Six high-risk patients within the single-dose arm required second dose for UA >7.5 mg/dl. Rasburicase was well tolerated; one patient with glucose-6-phosphate dehydrogenase deficiency developed methemoglobinemia and hemolysis. CONCLUSIONS: Rasburicase is highly effective for prevention and management of hyperuricemia in adults at risk for TLS. Single-dose rasburicase was effective in most patients; only a subset of high-risk patients required a second dose.

ABCG2 is a direct transcriptional target of hedgehog signaling and involved in stroma-induced drug tolerance in diffuse large B-cell lymphoma.

Successful treatment of diffuse large B-cell lymphoma (DLBCL) is frequently hindered by the development of resistance to conventional chemotherapy resulting in disease relapse and high mortality. High expression of antiapoptotic and/or drug transporter proteins induced by oncogenic signaling pathways has been implicated in the development of chemoresistance in cancer. Previously, our studies showed that high expression of adenosine triphosphate-binding cassette drug transporter ABCG2 in DLBCL correlated inversely with disease- and failure-free survival. In this study, we have implicated activated hedgehog (Hh) signaling pathway as a key factor behind high ABCG2 expression in DLBCL through direct upregulation of ABCG2 gene transcription. We have identified a single binding site for GLI transcription factors in the ABCG2 promoter and established its functionality using luciferase reporter, site-directed mutagenesis and chromatin-immunoprecipitation assays. Furthermore, in DLBCL tumor samples, significantly high ABCG2 and GLI1 levels were found in DLBCL tumors with lymph node involvement in comparison with DLBCL tumor cells collected from pleural and/or peritoneal effusions. This suggests a role for the stromal microenvironment in maintaining high levels of ABCG2 and GLI1. Accordingly, in vitro co-culture of DLBCL cells with HS-5 stromal cells increased ABCG2 mRNA and protein levels by paracrine activation of Hh signaling. In addition to ABCG2, co-culture of DLBCL cells with HS-5 cells also resulted in increase expression of the antiapoptotic proteins BCL2, BCL-xL and BCL2A1 and in induced chemotolerance to doxorubicin and methotrexate, drugs routinely used for the treatment of DLBCL. Similarly, activation of Hh signaling in DLBCL cell lines with recombinant Shh N-terminal peptide resulted in increased expression of BCL2 and ABCG2 associated with increased chemotolerance. Finally, functional inhibition of ABCG2 drug efflux activity with fumitremorgin C or inhibition of Hh signaling with cyclopamine-KAAD abrogated the stroma-induced chemotolerance suggesting that targeting ABCG2 and Hh signaling may have therapeutic value in overcoming chemoresistance in DLBCL.

Hepatosplenic gamma-delta T-cell lymphoma: clinicopathological features and treatment.

BACKGROUND: Hepatosplenic T-cell lymphoma (HSTCL) is a rare peripheral T-cell lymphoma; treatment with standard anthracycline-containing chemotherapy regimens has been disappointing, and an optimal treatment strategy for this patient population has not yet been determined. METHODS: We identified 15 cases of pathologically confirmed HSTCL in the institution's database. Clinical characteristics and treatment results were reviewed. RESULTS: Complete responses (CRs) were achieved in 7 of 14 patients who received chemotherapy. Achievement of CR was followed by hematopoietic stem-cell transplantation in three patients. Median duration of CR was 8 months (range 2 to 32+ months) with four patients currently alive and in CR at 5, 8, 12, and 32 months, respectively. Median overall survival (OS) was 11 months (range 2 to 36+ months). Patients who achieved a CR had a median OS of 13 months, compared with 7.5 months in patients who did not achieve a CR. Risk factors associated with worse outcome included male gender, failure to achieve a CR, history of immunocompromise, and absence of a T-cell receptor gene rearrangement in the gamma chain. CONCLUSION: A better understanding of the pathophysiology of HSTCL and new therapeutic strategies are needed.

Prospective trial of targeted radioimmunotherapy with Y-90 ibritumomab tiuxetan (Zevalin) for front-line treatment of early-stage extranodal indolent ocular adnexal lymphoma.

BACKGROUND: To determine the efficacy and side-effects of (90)Y ibritumomab tiuxetan (Zevalin) as front-line treatment in patients with early-stage extranodal indolent lymphoma of the ocular adnexa (orbit, conjunctiva, or eyelid). PATIENTS AND METHODS: From August 2004 to November 2007, 12 patients with stages I-E extranodal indolent lymphoma of the ocular adnexa were enrolled in a prospective trial of rituximab followed by (90)Y ibritumomab tiuxetan (Zevalin therapeutic regimen). For each patient, clinical examinations and imaging studies were used to document response to therapy using the The International Working Group response criteria. All patients had (111)In ibritumomab tixuetan imaging to confirm expected biodistribution before (90)Y-Zevalin therapy; in addition, three patients had an optional single photon emission computed tomography-computed tomography scan to estimate the absorbed radiation dose to the orbital and ocular tissues. RESULTS: The study included seven women and five men. The median age was 60 years (range 22-79). Nine patients had mucosa-associated lymphoid tissue lymphoma of conjunctiva or orbit; three patients had grades 1-2 follicular lymphoma of orbit. One patient who had been deemed stage I-E initially was found to have another lesion in her deltoid muscle on positron emission tomography 2 weeks after enrollment. She was kept on trial although her disease was reclassified as stage IV due to this single additional (biopsy-proven) site. Ten patients had a complete response and two partial response (PR) within 3 months of treatment. One patient had a recurrence in the upper eyelid 6 months after an initial PR; he then received 30 Gy of external-beam radiotherapy (EBRT). His disease later progressed again in the orbit and he is currently being considered for other treatments. A second patient who attained a PR has remained stable with no progression 12 months after treatment. With a median follow-up time of 20 months (range 6-44 months), there were no cases of distant (extraorbital) relapse. All 12 patients experienced grade I or II transient pancytopenia during the first 3 months after enrollment in the trial. There were no episodes of grade III or IV myelosuppression. The estimated absorbed radiation dose to the orbital soft tissues was <3 Gy, 10 times lower than that with EBRT. CONCLUSIONS: Rituximab followed by (90)Y ibritumomab tiuxetan is an effective and safe front-line treatment for early-stage extranodal indolent B-cell lymphoma of the ocular adnexa.

The addition of rituximab to CHOP chemotherapy improves overall and failure-free survival for follicular grade 3 lymphoma.

BACKGROUND: The benefit of adding rituximab to anthracycline-based therapy for follicular lymphoma grade 3 has not been studied. PATIENTS AND METHODS: We retrospectively reviewed the records of 45 patients with follicular grade 3 lymphoma who were treated with rituximab and the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) at The University of Texas MD Anderson Cancer Center. Response rate, failure-free survival (FFS), and overall survival (OS) were estimated and a historical comparison to CHOP-only-treated patients was made. RESULTS: The International Prognostic Index (IPI) distribution was 47% low, 36% low intermediate, 13% high intermediate, and 4% high risk. The complete response rate was 96%. Forty-four of 45 patients are still alive. Median follow-up for the alive patients is 3.5 years. The 3-year FFS rate according to the IPI was 80% [95% confidence interval (CI) 64% to 100%] in low, 81% in low intermediate (95% CI 64% to 100%), and 50% (95% CI 25% to 100%) in high-intermediate/high-risk patient group. The addition of rituximab to CHOP improved both 5-year FFS, 71% (95% CI 58% to 87%) compared with 44% (95% CI 36% to 55%) with P value of 0.019, and 5-year OS, 98% (95% CI 93% to 100%) compared with 75% (95% CI 67% to 84%) with P value of 0.0034. CONCLUSION: The addition of rituximab to CHOP provided a high response rate and excellent early survival. Poor-risk patients continue to demonstrate a high rate of failure despite the use of rituximab.

Factores sociodemográficos asociados al antecedente de aborto inducido en cuatro centros de salud de la ciudad de Lima - Perú / Sociodemographic factors associated with background of induced abortion in four health centers in the city of Lima - Peru

Se realizó un estudio descriptivo en 552 mujeres que se habían sometido al aborto inducido. El trabajo se hizo en los centros de salud de Chosica, el Agustino, el centro de Lima y el Hospital Cayetano Heredia durante los años 1999-2003. El objetivo era identificar factores sociodemográficos asociados al aborto inducido en algunos centros de salud de la ciudad de Lima, además de investigar complicaciones médicas según los autores que lo practicaron. La totalidad de mujeres estaban en la edad reproductiva; el 61 por ciento tenía instrucción secundaria completa o superior; el 66 por ciento en unión estable (casadas y convivientes). Habían iniciado su actividad sexual en la adolescencia un 74 por ciento y en esta misma etapa interrumpieron su embarazo un 23 por ciento. Hubieron en total 828 abortos inducidos, 59 por ciento fueron practicados pasado el mes de amenorrea y más de tres meses el 3.26 por ciento. De total de las 552 mujeres un 41 por ciento había interrumpido su primera gestación por medio del aborto inducido. De lo manifestado de este grupo de mujeres, médicos fueron quienes más practicaron esta intervención 84 por ciento, mientras que los empíricos tuvieron mayor proporción de complicaciones 63 por ciento. Las complicaciones se presentaban en mayor proporción mientras mayor fue el tiempo de embarazo y menor el conocimiento médico de quien lo practicó. Razones para tomar la determinación de abortar, fueron la situación económica difícil para las casadas y convivientes, mientras que para las solteras fue el no estar unidad. Una gran mayoría 96 por ciento estaba consciente de que el aborto inducido ponía en peligro su salud, en la misma proporción conocían o habían usado anticonceptivos y sin embargo no tomaron precauciones por descuido 83 por ciento. Sentimientos de culpa poco o nada manifestaron 64 por ciento. Gran proporción manifestó ser creyente a predomino de las católicas 92 por ciento.

It was done a descriptive research in 552 women, who have submitted to an induced abortion. Research was done in Chosica’s Health center, Agustino’s Health center, Lima’s Health center and Cayetano Heredia Hospital since 1999-2003. The propose of this research, was identify sociodemographic factors associated to induce abortion in some Heath Centers around Lima City, also this research was done in order to indicate the medical complications by the same doctors who has done it. All of women were in reproductive age; 61 per cent of them have studied secondary until they finished or in some cases they have continued; 66 per cent of them live together with a partner in a faithful way (married or not married). They have started their sexual activity during adolescence in a 74 per cent, and at this same stage the interrupted their pregnancy in 23 per cent. There were in total 828 cases of induced abortion, 59 per cent of them were done some time later the month of amenorrhea, and 3.25 per cent were done after months. From 552 women as a total, 41 per cent have interrupted their first pregnancy by means of induced abortion. This group of women declares that, doctors were the ones who did this intervention in most of the cases 84 per cent. On the hand, interventions that have been done by empirics result in a high percent of complication 63 per cent. Complications seem to appear in a high rate if the time of pregnancy was long or if the medical knowledge was not enough in them who did this intervention. Some reasons to abort was the hard economy situation for them who live with a partner (married or not married), the single ones considered that beings alone was the reason. A high percent 96 per cent knew that induced abortion included some risks which could be harmful for their health the same percent of women knew or have used contraceptives. Nevertheless they did not take precaution because of oversight 83 per cent. Women felt a bit fault or non fault...

Clasificación y tratamiento de la mama tuberosa / Clasification and treatment of the tuberous breast

La mama tuberosa es una anomalía congénita caracterizada por constricción de la base de la mama, hipoplasi del arénquima mamario, déficit cuténeo, malposición del surco submamario, herniación del tejido mamario en el complejo areola del pezón y exceso de tejido areolar. Los autores presentan cuatro pacientes en las que han practicado distintas maniobras quirúrgicas, usando la clasificación derivada de Meara y col., para su reconstrucción. Emplean las técnicas descritas por los autores Teimourian-Adham y Rees-Aston; mastopexias; implantes mamarios y combinación de ambas. Exponen como conclusiones que para llegar a un tratamiento satisfactorio, éste deberá basarse en los fundamentos de la patología y tipo de deformidad. la expansión de la base de la mama, posición correcta del surco submamario, implante mamario si está indicado, reducción del tejido mamario herniado en la areola y correción del tamaño de las areolas, con la finalidad principal de conseguir simetría mamaria (AU)

Alterations in sperm protein phosphorylation in male infertility.

Protein phosphorylation is involved in sperm capacitation, so the effect of protein phosphatase inhibitors on the capacitation of spermatozoa of males with unexplained infertility was investigated. d-mannose ligand specific receptor expression in fresh, living spermatozoa, capacitated or treated with calyculin A (an inhibitor of protein phosphatases 1 and 2A), was studied in three groups of men: pre-vasectomy (fertile) males, males in couples with male infertility, and males in couples with infertility of unknown aetiology. Flow cytometry showed significant differences between infertile couples with a male factor and fertile couples (P < 0.05), both after capacitation and after treatment with calyculin A. In the group of couples with infertility of unknown aetiology (n = 15), d-mannose receptor expression was diminished in six cases after classical capacitation. However, when the spermatozoa of these six men were treated with calyculin A, five showed an increased specific d-mannose receptor expression. From these results it is suggested that in vitro treatment of spermatozoa with inhibitors of protein phosphatases may be of great value in some cases of unexplained infertility.

Human herpesvirus 8 K1-associated nuclear factor-kappa B-dependent promoter activity: role in Kaposi's sarcoma inflammation?

BACKGROUND: The growing number of human immunodeficiency virus type 1 (HIV-1) infections worldwide and the increasing use of immunosuppressive modalities for organ transplantation have contributed to an epidemic of Kaposi's sarcoma (KS), which has been etiologically linked to human herpesvirus 8 (HHV8) or KS-associated virus. Since the onset of the acquired immunodeficiency syndrome epidemic, inflammation has been recognized as an essential component of KS pathology. HHV8 bears a gene (K1) encoding a transmembrane protein with an immunoreceptor tyrosine-based activation motif. This motif is present in receptors that mediate inflammation. PURPOSE: To dissect the cellular effects of K1 function and the eventual role of K1 in KS, we developed a cell model for studying K1 expression. METHODS: K1 was cloned from BC-3 lymphoma cells. To monitor transcriptional activation, K1 was coexpressed with plasmids containing luciferase under control of various promoters. K1 expression was monitored by indirect immunofluorescence and by combined immunoprecipitation/immunoblot analysis. Inflammatory cytokines were measured by enzyme-linked immunosorbent assay. RESULTS: Cellular transfection of the K1 gene induced reporter expression under control of nuclear factor-kappa B (NF-kappaB), which controls the transcription of numerous proteins involved in inflammation. Treatment of cells with aspirin, an agent that targets this intracellular pathway and blocks cell inflammatory responses, blocked K1-induced NF-kappaB-dependent promoter activity. When a second KS cofactor, i.e., the HIV-1-transactivating gene tat, was coexpressed with K1, we observed an additive effect on NF-kappaB-dependent transcription. K1 transfection stimulated the secretion of cytokines interleukin (IL) 6, granulocyte-macrophage colony-stimulating factor, and IL-12. Cells treated with the conditioned media of K1 transfectants exhibited similar characteristics of K1 transfectants, indicating that a paracrine loop was being activated. CONCLUSION: Thus, K1 may activate cells in which it is expressed, as well as other cells in a paracrine manner. K1 cooperates in signaling with HIV-1 Tat, suggesting that both of the proteins from these viruses converge to reach an enhanced level of inflammation that may underlie progressive KS.

Human Kaposi's sarcoma cell-mediated tumorigenesis in human immunodeficiency type 1 tat-expressing transgenic mice.

BACKGROUND: The human immunodeficiency virus type 1 (HIV-1) transactivator (Tat) protein has been linked to the development and course of Kaposi's sarcoma (KS) associated with acquired immunodeficiency disease syndrome (AIDS-KS). Tat is an 86-101 amino-acid protein encoded by two exons. To evaluate the growth-promoting effects of Tat in AIDS-KS in vivo, we developed transgenic mice expressing the one-exon-encoded 72 amino-acid protein (Tat(72)) and the two-exon-encoded 86 amino-acid protein (Tat(86)). METHODS: Human KS SLK cells were injected subcutaneously into CD4(+) T-cell-depleted male mice, and the tumors that formed after 3-4 weeks were recovered and analyzed for the expression of Tat protein(s), different cytokine messenger RNAs (mRNAs), and matrix metalloproteinases (MMPs). All statistical tests were two-sided. RESULTS: The average tumor weight was maximum in Tat(86) mice ( approximately 600 mg) compared with Tat(72) ( approximately 200 mg) and nontransgenic ( approximately 100 mg) mice (P<.005). Histologic examination of tumors showed spindle-shaped SLK cells with prominent infiltrates of inflammatory cells. All of the tumors from Tat mice expressed abundant Tat mRNA, suggesting that the infiltrating mouse cells actively expressed Tat. A comparison of the growth-promoting cytokines in the tumors from Tat(86)-transgenic and nontransgenic mice showed that the expression of the following cytokines was substantially increased in the tumors of the Tat(86) mice: tumor necrosis factor-alpha, interleukin 6, interleukin 8, granulocyte-macrophage colony-stimulating factor, and basic fibroblast growth factor. Furthermore, these tumors showed abundant expression of a 105-kd MMP activity associated with infiltrates of host leukocytes in the lesions. CONCLUSION: Our in vivo data clearly suggest that extracellular Tat can contribute to the growth and tumorigenesis of human KS cells.

Urinary proteins with pro-apoptotic and antitumor activity.

Analysis of the protein composition of urine has been the subject of much research that has captured the interest of scientific groups over the years. A number of factors have been isolated from urine that possess anti-neoplastic activities as seen both in vitro and in vivo studies. The urine from pregnant women and commercial preparations of crude clinical grade human chorionic gonadotropin contain factors (HAF for hCG associated factor) with anti-Kaposi's sarcoma activity. Also found in urine with activity are eosinophil-derived neurotoxin (EDN), anti-neoplastic urinary protein (ANUP), inhibin, activin A, and angiostatin. The anti-cancer activity of urinary proteins is associated with apoptosis of endothelial cells and of tumor-associated endothelial cells. A better understanding of the biological functions of these various urinary proteins, and of others that remain to be discovered, should provide insights into novel cell regulatory systems operating during pregnancy.