Frecuencia de infección por virus del papiloma humano en pacientes con cáncer del aparato digestivo

Introduction and aim

Cancer is the result of the interaction of genetic and environmental factors. It has recently been related to viral infections, one of which is human papillomavirus. The aim of the present study was to describe the frequency of human papillomavirus infection in patients with digestive system cancers.

Flow cytometric analysis of intestinal intraepithelial lymphocytes in the diagnosis of refractory celiac sprue

The etiology of refractory celiac sprue (RCS) is unclear. In a high proportion of cases, the clonal nature of intestinal intraepithelial lymphocytes (IEL) can be demonstrated and a pathogenetic implication of intestinal IEL has been postulated. The prognosis of this subgroup of RCS is poor, with a high risk to develop an overt lymphoma and uncontrolled malabsorption despite steroid/immunosuppressive therapy. Cases with a relatively indolent clinical course, however, exist and their early diagnosis may be difficult. To gain insight into the pathogenic implication of intestinal IEL in refractory celiac sprue, we have performed an extensive phenotypic and functional characterization of clonal intestinal IEL in a patient with an indolent form of refractory celiac sprue, using multiparametric flow cytometry. The abnormal lymphocyte infiltrate lacked surface membrane expression of CD3/T-cell receptor (TCR) complexes (TCR(-), CD4(-), CD8(-), sCD3(-)), but contained intracellular CD3(epsilon) (CyCD3(+)) and surface CD103(+) and CD7(+). In particular, these cells showed a unique spontaneous ex-vivo cytokine secretion profile with an increased percentage of CD3(-) IEL containing TNF-alpha and IL-10, in the absence of IL-2, IL-4 and IFN-gamma. Altogether our results suggest that flow cytometry immunophenotyping of intestinal IEL, in cases suspected of celiac disease and their complicated forms, could be of great help in the correct diagnosis of RCS and the understanding of the immunopathogenic mechanisms of the disease and their clinical and/or therapeutical implications.     

Repeated thoracentesis: an important risk factor for eosinophilic pleural effusion?

BACKGROUND: Eosinophilic pleural effusion (EPE) is a relatively rare clinical condition. Repeated thoracenteses (RTs) are normally considered a frequent cause of EPE. Yet, to our knowledge, there is no firm evidence (apart from anecdotal case reports) supporting such a statement. OBJECTIVE: To investigate potential relationships between the number, type (with or without pleural biopsy) and time elapsed between RTs and the number of eosinophils present in pleural fluid samples. METHODS: We reviewed retrospectively 273 pleural fluid samples belonging to 120 patients (79 males, 41 females), attended in our institution from 1992 to 2000, whose clinical management had required RTs. Apart from the anthropometric and clinical data of each patient, we included the following variables in the analysis: number of thoracenteses performed in each individual, number of pleural biopsies carried out at each thoracentesis and time between consecutive thoracenteses. We also recorded the total (and differential) leukocyte count, red blood cell count, as well as the main biochemical, microbiological and histological data of both the pleural fluid and peripheral blood samples. RESULTS: We did not observe any significant change in the percentage of eosinophils in relation to the number of thoracenteses performed per patient. This lack of relationship was also observed in the subgroup of patients who required one (or more) pleural biopsies (n = 111) (regardless of the number of biopsies). Our results suggest that RTs are not an important risk factor for the development of EPE, regardless of the time elapsed between two thoracenteses. CONCLUSION: We believe, therefore, that multiple punctures should not longer be considered a prevalent cause of pleural eosinophilia.     

Treatment with plasmapheresis and intravenous immunoglobulin in pregnancies complicated with anti-PP1Pk or anti-K immunization: a report of two patients

BACKGROUND AND OBJECTIVES: In addition to anti-D alloantibody, other antibodies such as anti-K antibody and anti-PP1Pk antibody have been reported to cause severe haemolytic disease of the newborn (HDN). HDN caused by anti-K results not only from destruction of red cells but also from suppression of erythropoiesis. Anti-PP1Pk has been associated with abortion early in pregnancy. We report on two patients, one with anti-PP1Pk and the other with anti-K, who were treated with plasmapheresis and intravenous immunoglobulin (IVIG) during pregnancy in an attempt to reduce the plasma antibody levels. MATERIALS AND METHODS: The patient with anti-PP1Pk had lost all seven previous fetuses in the first trimester and therefore therapy in this patient was started at 8 weeks of gestation. The second patient had been sensitized to the K antigen through blood transfusion and had had two intrauterine fetal deaths at 26 weeks of gestation with signs of hydrops fetalis. Treatment in this patient was started during the 16th week of pregnancy. RESULTS: As a result of therapy, the antibody titre was reduced in both patients. In the first patient a healthy infant was delivered by Caesarean section at 37 weeks of gestation. The second patient gave birth at 36 weeks of gestation. Neither newborn required exchange transfusion. CONCLUSION: In our two patients, plasmapheresis combined with IVIG proved successful in the management of fetomaternal incompatibilities where the mechanism of fetal loss differs from the classical anti-D.     

Elderly age and prior autologous transplantation have a deleterious effect on survival following allogeneic peripheral blood stem cell transplantation with reduced-intensity conditioning: results from the Spanish multicenter prospective trial

Over a 3-year period, 145 patients ineligible for myeloablative conditioning underwent reduced-intensity conditioning (RIC) hematopoietic stem cell transplantation (SCT) from an HLA-identical sibling in a prospective study. The median age was 54 years, 88 patients were male and 61 patients were beyond the early-intermediate phase of their disease. The 100-day probability of developing grade II-IV acute graft-versus-host disease (GVHD) was 34%, and the 1-year probability of developing chronic extensive GVHD was 41%. The 1-year probabilities of transplant-related mortality (TRM), overall (OS) and progression-free survival were 20, 60 and 52%, respectively. Multivariate analyses found a better OS in: (i) patients <60 years; and (ii) recipients of a first SCT; and a higher TRM in: (i) age >60 years, (ii) recipients of a prior autologous SCT, and (iii) an ECOG performance status >1. The 1-year TRM in patients with 0 or 1 and >2 of the above-mentioned adverse prognostic factors were 17 vs 53%, respectively (P<0.001). In summary, our study shows that elderly patients have a higher TRM following an RIC protocol. However, age by itself should not preclude these RIC transplants, since TRM appears to be unacceptably high only in the presence of additional adverse factors.     

Antibiotic prophylaxis with meropenem after allogeneic stem cell transplantation

In the present study, we analyze the efficacy of prophylaxis with meropenem in patients receiving a matched related donor allogeneic transplant. In total, 38 patients were sequentially treated with meropenem starting on the day of the first febrile episode (n=17, group A) vs prophylactic meropenem starting on the first day with <500/mm(3) granulocytes (n=21, group B), and maintained until resolution of fever or after granulocyte count >500/mm(3). Of these, 16 (94%) patients in group A developed fever as compared to 16 (76%) in group B (P=0.02). While only one patient in group A did not require first-line antibiotherapy, there were seven (33%) in group B who did not require it (P=0.01) since fever lasted less than 72 h. In addition, 52% patients in group B did not require second-line antibiotics as compared to 11% among patients in group A (P=0.04). In multivariate analysis prophylaxis with meropenem (HR=2.83, 95% CI (1-8.02); P=0.04) and disease status at transplant (HR for early stage=0.15, 95% CI (0.04-0.62); P=0.04) significantly influenced the development of fever. In conclusion, the current pilot study suggests that the use of prophylaxis with meropenem during the period of neutropenia in patients undergoing allogeneic transplantation favorably affects the morbidity of the procedure by reducing febrile episodes.     

Microscopic colitis. A possible diagnosis in secretory diarrhea

The colitis microscopic was characterized by chronic watery diarrhea accompanied or not of abdominal pain. Present in patients of median age and the diagnosis was realized by means of the microscopic finds of a mucus of colon with an aspect macroscopic normal. They exist 2 types microscopically distinct, the collagenous colitis and the lymphocytic colitis. We referred 2 cases of each one of the types of microscopic colitis, whose manifestation clinic in common was the chronic watery diarrhea.     

Sensitivity of testicular germ cells to toxicant-induced apoptosis in gld mice that express a nonfunctional form of Fas ligand

Germ cell apoptosis in testis is essential for functional spermatogenesis. Recent evidence suggests that the Fas signaling system is critical for the regulation of testicular germ cell apoptosis. To further evaluate the Fas signaling system in testis, we examined the incidence of germ cell apoptosis in gld mice that lack a functional Fas-signaling pathway. gld mice have a small, but significant, increase in testis weight and numbers of spermatid heads per testis compared with wild-type mice. In addition, gld mice have a small increase in the spontaneous incidence of germ cell apoptosis, as indicated by characteristic DNA fragmentation via the terminal deoxynucleotidyl-transferase-mediated deoxy-UTP nick end labeling assay. To test the role of the Fas system in toxicant-induced germ cell apoptosis, mice were exposed to either a Sertoli cell- or germ cell-specific toxicant [mono-(2-ethylhexyl)phthalate (MEHP; 1 g/kg) or 5 Gy radiation, respectively]. These two exposure paradigms induced extensive increases in germ cell apoptosis in wild-type mice. However, exposure of gld mice to MEHP caused only a minimal increase in germ cell apoptosis, whereas they were as sensitive as wild-type mice to radiation exposure. These data indicate that the Fas signaling pathway is 1) involved in regulating the numbers of germ cells in the testis, 2) crucial for the initiation of germ cell apoptosis after MEHP-induced Sertoli cell injury, and 3) differentially active in the cell-specific regulation of germ cell apoptosis that occurs as a consequence of Sertoli cell vs. germ cell injury.     

Does melatonin induce apoptosis in MCF‐7 human breast cancer cells in vitro?

Melatonin inhibits proliferation of the estrogen-responsive MCF-7 human breast cancer cells. The objective of this work was to assess whether melatonin not only regulates MCF-7 cell proliferation but also induces apoptosis. In this experiment we used 1,25-dihydroxycholecalciferol (D3) as a positive control because it inhibits MCF-7 cell proliferation and induces apoptosis. MCF-7 cells were cultured with either I nM melatonin, 100 nM D3 or its diluent to determine their effects on cell proliferation, cell viability, cell-cycle phase distribution, population of apoptotic cells, and expression of p53, p21WAF1, bcl-2, bcl-X(L) and bax proteins. After 24 or 48 hr of incubation, both melatonin and D3-treatment significantly decreased the number of viable cells in relation to the controls, although no differences in cell viability were observed between the treatments. The incidence of apoptosis, measured as the population of cells falling in the sub-G1 region of the DNA histogram, or by the TUNEL reaction, was similar in melatonin-treated and control cells whereas, as expected, apoptosis was higher among cells treated with D3 than in controls. The expression of p53 and p21WAF1 proteins significantly increased after 24 or 48 hr of incubation with either melatonin or D3. No significant changes in bcl-2, bcl-XL and bax mRNAs were detected after treatment with melatonin whereas in D3-treated cells, a significant drop in bcl-XL was observed. These data support the hypothesis that melatonin reduces MCF-7 cell proliferation by modulating cell-cycle length through the control of the p53-p21 pathway, but without clearly inducing apoptosis.