Final results of DIADEM, a phase II study to investigate the efficacy and safety of durvalumab in advanced pretreated malignant pleural mesothelioma.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a cancer with a high mortality rate and few therapeutic options. After platinum-pemetrexed combination, no further promising drug seems to be effective. Immune checkpoint inhibitors may have some activity in pretreated patients and no data are available in this population about durvalumab. MATERIALS AND METHODS: DIADEM was a multicenter, open-label, single-arm, phase II trial aimed at evaluating the efficacy and safety of durvalumab. Patients with locally advanced/metastatic MPM who progressed after platinum-pemetrexed chemotherapy were enrolled to receive durvalumab (1500 mg, intravenously Q4W) for 12 months or until evidence of disease progression or unacceptable toxicity. The primary endpoint was the proportion of patients alive and free from progression at 16 weeks (PFS16wks) calculated from treatment initiation. Secondary endpoints were progression-free survival, overall survival, overall response rate, and safety. RESULTS: Sixty-nine patients with a median age of 69 years (range 44-82 years) were enrolled; 62 patients (89.9%) had epithelioid histotype. As first-line treatment, all patients received platinum derivatives-pemetrexed combination (60.9% with carboplatin and 39.1% with cisplatin). As of March 2021, the median follow-up was 9.2 months (interquartile range 5.2-11.1 months). Six patients (8.7%) completed the 12-month treatment; 60 patients discontinued, of whom 42 for progressive disease, and 4 died. Seventeen patients (28.3%; 95% confidence interval 17.5% to 41.4%) were alive or free from progression at 16 weeks. Eleven patients (18.6%) had a grade 3 or 4 treatment-related adverse event (AE), and one (1.4%) had a grade ≥3 immune-related, treatment-related AE. There was one drug-related death. CONCLUSION: Durvalumab alone in pretreated non-selected MPM did not reach a meaningful clinical activity, showing any new major safety issue signals.

Targeted therapies and immunotherapy in non-small-cell lung cancer.

Non-small-cell lung cancer is still considered a difficult disease to manage because of its aggressiveness and resistance to common therapies. Chemotherapy remains the gold standard in nearly 80% of lung cancers, but clinical outcomes are discouraging, and the impact on median overall survival (OS) barely reaches 12 months. At the end of the last century, the discovery of oncogene-driven tumours completely changed the therapeutic landscape in lung cancers, harbouring specific gene mutations/translocations. Epidermal growth factors receptor (EGFR) common mutations first and anaplastic lymphoma kinase (ALK) translocations later led new insights in lung cancer biology knowledge. The use of specific tyrosine kinases inhibitors overturned the biological behaviour of EGFR mutation positive tumours and became a preclinical model to understand the heterogeneity of lung cancers and the mechanisms of drug resistance. In this review, we summarise the employment of targeted agents against the most representative biomolecular alterations and provide some criticisms of the therapeutic strategies.

The role of Endothelin-1 in obstructive sleep apnea syndrome and pulmonary arterial hypertension: pathogenesis and Endothelin-1 antagonists.

Obstructive Sleep Apnea Syndrome (OSAS) is a recognized risk factor for cardiovascular disorders and in some cases is complicated with Pulmonary Arterial Hypertension (PAH), as the endothelium is affected. Recent studies provide strong evidence for endothelial dysfunction in obstructive sleep apnea. The resultant vasoconstriction, abnormal cell proliferation and hyper-coagulability may lead to the initiation or progression of atherosclerotic cardiovascular and cerebrovascular disorders, which are frequently encountered in OSA patients. While the currently available therapies for OSAS, such as Continuous Positive Airway Pressure therapy (CPAP therapy), improve endothelial dysfunction, they are not well-tolerated by patients. CPAP therapy can reduce nocturnal hypoxemias and decrease noradrenaline circulating levels, but does not affect ET-1 plasma levels. Potent and selective Endothelin-1 receptor antagonists have been developed and have shown promising results in the treatment of cardiovascular diseases such as pulmonary arterial hypertension, acute and chronic heart failure, hypertension, renal failure, and atherosclerosis. However, results are often contrasting and complicated because of the tissue-specific vasoconstrictor actions of Endothelin-B receptors and the fact that endothelin is an autocrine and paracrine factor whose activity is difficult to measure in vivo.

Minisatellite and Hprt mutations in V79 cells irradiated with helium ions and gamma rays.

PURPOSE: To evaluate and compare cytotoxic and mutational effects of graded doses of gamma-rays and 4He++ ions at different LET values (nominally 80 and 123 keV/microm) in V79 cells. MATERIALS AND METHODS: 4He++ ion beams at 80 and 123 keV/microm were supplied by the 7 MV Van de Graaff CN accelerator of the INFN-LNL in the dose range 0.3 2.4 Gy at a dose rate of 1 Gy/min. Gamma-irradiation was performed by the 60Co 'gamma beam' of CNR-FRAE (at the INFN-LNL) in the dose range 0.5 6.0 Gy at a dose rate of 1 Gy/min. After irradiation, the cells were seeded to measure surviving fraction (SF) and mutant frequency (MF) at the Hprt locus on the basis of 6-thioguanine resistance. Alterations at minisatellite sequences (MS) of clones derived from irradiated and unirradiated cells were detected by Southern blot analysis using a multi-locus probe (DNA fingerprinting). RESULTS: Survival data from 4He++ irradiation at two LET values (80 and 123 keV/microm) yielded similar results: alpha = (1.08 +/- 0.04)/Gy and (0.90 +/- 0.03)/Gy, respectively. The best fit for mutant induction at the Hprt locus after 80keV/microm 4He++ was a linear function of the dose in the dose-interval 0-1.5 Gy: alpha= (47.77 +/- 16.01) x 10(-6)/Gy. The best fit for mutant induction after 123 keV/microm 4He++ in the dose-interval 0-1.2 Gv was a linear-quadratic function: alpha=(86.01 +/- 13.80) x 10(-6)/Gy; beta = (42.87 +/- 11.03) x 10(-6)/Gy2. For gamma-irradiation, the best fit of Hprt mutation data gave: alpha = (4.14+2.67)x 10(-6)/Gy: beta = (0.63 +/- 0.86) x 10(-6)/Gy2. The best fitting of MS alteration data with linear-quadratic or linear relationships gave: for gamma-rays, alpha = 0.56 mutants/Gy and beta = 0.52 mutants/Gy2; for 80 keV/microm 4He++, alpha = 3.70 mutants/Gy and beta = 9.00 mutants/Gy2; for 123keV/microm 4He++, alpha = 4.36 mutants/Gy. CONCLUSIONS: The results reported here confirmed the higher cytotoxic and mutagenic effects of helium ions in comparison with gamma-irradiation and the ability of DNA fingerprint analysis to investigate DNA damage induced by different ionizing radiations. The results of the mutagenic effects measured by the two tests are in agreement.

Apoptosis in human sperm: its correlation with semen quality and the presence of leukocytes.

BACKGROUND: Apoptosis plays an important role in regulating spermatogenesis. However, the biological significance of apoptosis in ejaculated sperm is not yet clear. This study set out to investigate how apoptosis correlates with semen quality and the presence of seminal leukocytes. METHODS: Fifty-seven semen samples from the male partners of infertile couples were classified as normal or abnormal according to World Health Organization guidelines. Flow cytometry was used to evaluate sperm populations and seminal leukocytes. Preliminary flow cytometry analysis using 6-carboxyfluoresceindiacetate (6-CFDA), which identifies live cells, and propidium iodide (PI), which stains only dead cells, was performed in order to pinpoint the sperm region accurately. Having thus gated the sperm population, bivariate Annexin V/PI analysis was then carried out in order to measure the percentage of apoptotic and necrotic sperm and the apoptotic index (the ratio between apoptotic:live sperm). Leukocytes were counted by the standard peroxidase test and by flow cytometry using monoclonal antibody (mAb) anti-CD45 or anti-CD53. RESULTS: No significant differences in the apoptotic index and the percentage of live and apoptotic sperm were detected between the subjects with normal and abnormal semen. A significant inverse correlation between sperm concentration and the apoptotic index was observed only in the normal sperm group. There was no correlation between the concentration of leukocytes, detected either by peroxidase or by mAb anti-CD45 or anti-CD53, either with the percentage of apoptotic sperm or with the apoptotic index. In contrast, the ratio between CD45 positive leukocytes and sperm showed a significant correlation with the apoptotic index. A weaker correlation was found when leukocytes were counted by peroxidase, while no correlation was observed using mAb anti-CD53. CONCLUSIONS: Sperm apoptosis did not seem to be correlated with semen quality. In the absence of genito-urinary infection, one of the main functions of seminal leukocytes is probably to provide for the removal of apoptotic sperm.

Minisatellite and HPRT mutations in V79 and human cells irradiated with gamma rays.

The induction of mutations at the Hprt locus and minisatellite sequences was studied in V79 cells, peripheral blood lymphocytes (PBL) and lymphoblastoid cells (CCRF-CEM) exposed to gamma rays. In V79 cells the Hprt mutant frequency increased with dose at least up to 6.0 Gy, whereas the number of HPRT mutant lymphocytes increased up to 3 Gy. Clones derived from single irradiated cells were screened for mutations at minisatellite sequences by DNA fingerprint analysis. In V79 cells, a dose-response curve for minisatellite alterations was obtained up to 4.5 Gy. In contrast, very few mutations at minisatellite sequences (2/137) were detected among clones isolated from PBL of two donors irradiated with 1-4 Gy. Similar results were observed in lymphoblastoid CCRF-CEM cells irradiated with 2-3 Gy (4 mutants/180 clones), suggesting that in human lymphoid cells minisatellite DNA is more stable than in other mammalian and human cell lines.

CD69 expression on alpha-gliadin-specific T cells in coeliac disease.

Coeliac disease (CD) is a T-cell mediated immunological disease of the small intestine which is triggered in susceptible individuals by ingestion of gluten. The pathogenic mechanism of coeliac disease, and the role that alpha-gliadin specific T cells play in mucosal lesions and their involvement in peripheral blood is not yet explained at all. Previous studies have reported proliferative response to alpha-gliadin measured with the classic assay of 3HTdR incorporation. We analysed the activation antigen CD69 on T cells from CD patients and normal individuals following stimulation with alpha-gliadin and different antigens (tetanus toxoid, peptides unrelated to gliadin and PHA). CD69 coexpression with T cell CD3+ and proliferation marker Ki67 was evaluated with time. CD69 coexpression with T cell CD3+, CD4+ and CD8+ was also evaluated. It was found that peripheral blood mononuclear cells (PBMC) of coeliac patients increased their percentage of CD69 positive T cells when stimulated with alpha-gliadin, in comparison with cells from controls. Significant T cell activation was found only in subjects not treated with the gluten free diet; a positive response was found also in two coeliac patients with selective IgA deficiency, anti-endomisium negative, without circulating IgA anti alpha-gliadin or anti-tissue transglutaminase antibodies. The CD69 expression after stimulation was compared with the standard method of 3HTdR incorporation. Our data show that CD69 expression is useful to asses a specific T cell response to alpha-gliadin in coeliac disease. in a very short time. Moreover, the method allows to investigate T cell response at the lymphocyte subsets level, which represents a useful tool in the diagnosis of coeliac disease.

Echinococcus granulosus: intraspecific genetic variation assessed by a DNA repetitive element.

A 186 bp Echinococcus granulosus-specific repetitive element, TREg, was used to assess genetic variation between strains. In G7 genotype (pig strain) it has the characteristics of a satellite DNA element with a copy number of 23000 per haploid genome. Analysis, by sequencing of TREg monomers, showed a great degree of identity within them. In the G1 genotype (common sheep strain) TREg-like repetitive elements were found in an interspersed distribution throughout the genome and in only 120 copies. The sequences of these monomers showed a great degree of variation between them and with TREg of G7 origin. The G6 genotype (camel strain) showed a pattern of distribution and copy number similar to the G7 genotype, and the G2 genotype (Tasmanian sheep strain) similar to the G1 genotype. Isolates from the G5 (cattle strain) and G4 (horse strain) genotypes also showed unique hybridization patterns in Southern blot experiments. The genomic plasticity of E. granulosus, which may have important consequences in the epidemiology and control of cystic hydatid disease is reflected in the results of this work.

Chromosome instability induced in the cell progeny of human T lymphocytes irradiated in G(0) with gamma-rays.

We report the occurrence of chromosome instability in human T lymphocytes irradiated in vitro with gamma-rays and cultured for several generations before analysis. The delayed effects of gamma-radiation have been evaluated by conventional and molecular (chromosome painting) cytogenetics in preparations obtained from long-term bulk cultures or clonal cultures. The results indicate that the cell progeny of gamma irradiated human T lymphocytes can be characterized by a higher rate of chromosome damage, but this effect depends on the individual donor response to ionizing radiation. Evidence has been collected about a differential involvement of chromosomes 7, 9 and 19 in the induced chromosome rearrangements, and this effect is equally visible as an immediate or delayed response of human T lymphocytes to ionizing radiation.

Analysis of mutational effects at the HPRT locus in human G(0) phase lymphocytes irradiated in vitro with gamma rays.

The mutational effects of ionising radiation at the hypoxanthine-guanine phosphoribosyl transferase (HPRT) locus were studied in human peripheral blood G(0) phase lymphocytes irradiated in vitro with gamma rays. The presence of radiation induced mutants was assessed by selecting the HPRT mutants every week on the basis of 6-thioguanine resistance up to 1 month after irradiation. A dose-related increase of 14.25x10(-6) mutants/Gy was measured after an expression time of 7 days. After 2 weeks from culture starting the fraction of clonable cells in irradiated and control cell populations decreased, limiting the measurements of mutant frequency. The mutational spectrum of the HPRT gene was determined by PCR analyses in a total of 99 mutant clones derived from irradiated lymphocytes. The independent origin of mutant clones carrying the same mutation was assessed by analysing the TCR gamma gene rearrangements. The results showed a dose-related increase of deletion mutants up to 3Gy, whereas point mutation frequency increased only up to 2Gy. Two preferentially deleted regions were identified; one involving the HPRT exon 3, and another one the 3'-terminal and the 3'-flanking region of the gene. One complex mutation involving a non-contiguous deletion of exons 2-5 and 7/8 was observed among the mutants isolated after 3Gy irradiation.

Direct in situ PCR allows rapid and sensitive detection of high risk human papillomavirus in cytologic specimens and formalin-fixed paraffin tissues by fluorescent labelling.

We developed a rapid, sensitive and robust high risk human papillomavirus (HR HPV) detection protocol based on direct in situ PCR technology and fluorochrome-modified nucleotides on cytologic specimens (cell smears) and on HPV infected tissues (CIN III). Reproducible results on both cytologic specimens and paraffin-embedded tissues were obtained, providing a powerful tool for clinical investigation on HR HPV infection. Quantitative PCR performed on the same tissue sections adjacent to those used for in situ techniques allowed us to establish the sensitivity of our methods, able to detect rare copies (about 15 in our paraffin-embedded tissues) of HPV.

Echinococcus granulosus: DNA extraction from germinal layers allows strain determination in fertile and nonfertile hydatid cysts.

A method for the isolation of Echinococcus granulosus DNA from germinal layers of hydatid cysts is described. The method includes a hexadecyltrimethylammonium bromide/chloroform extraction and an adsorption to diatomaceous earth suspension. DNA suitable for polymerase chain reaction was obtained and used for parasite strain determination by mitochondrial cytochrome c oxidase I gene sequencing. Fertile and nonfertile cyst isolates from sheep, cattle, pigs, and humans were characterized. Hitherto, no direct parasite strain characterization has been made on nonfertile hydatid cysts, whereas here we report that nonfertile hydatid cysts were produced by sheep strain (G1 genotype) in sheep, cattle, and humans and by pig strain (G7 genotype) in pigs.

Genetic variation and epidemiology of Echinococcus granulosus in Argentina.

Polymerase chain reaction-ribosomal ITS-1 DNA (rDNA) restriction fragment length polymorphism (PCR-RFLP) analysis and sequencing of the mitochondrial cytochrome c oxidase subunit 1 (CO1) and NADH dehydrogenase 1 (ND1) genes were used to characterize 33 Echinococcus granulosus isolates collected from different regions and hosts in Argentina, and to determine which genotypes occurred in humans with cystic hydatid disease. The results of the study demonstrated the presence of at least 4 distinct genotypes; the common sheep strain (G1) in sheep from Chubut Province and in humans from Río Negro Province, the Tasmanian sheep strain (G2) in sheep and 1 human from Tucumán Province, the pig strain (G7) in pigs from Santa Fe Province and the carnel strain (G6) in humans from Río Negro and Buenos Aires Provinces. The finding that pigs harboured the pig strain and the occurrence of the Tasmanian sheep strain has considerable implications for the implementation of hydatid control programmes due to the shorter maturation time of both strains in dogs compared with the common sheep strain. Furthermore, this is the first report of the presence of the G2 and G6 genotypes in humans which may also have important consequences for human health.

Advantages of spinal anesthesia in abdominal gynecologic surgery.

The advantages obtained in vaginal surgery and caesarean section using spinal anesthesia led us to test this anesthesia to verify feasibility, problems and advantages in abdominal surgery. Spinal anesthesia was performed in 60 patients between 21 and 87 years of age. Thirty-seven total abdominal hysterectomies with or without adnexectomy, 5 laparotomic miomectomies, 3 adnexectomies, 5 colposacropexies, 2 hysterectomies with lymphadenectomy, 7 Burch colposuspension with or without hysterectomy and 1 laparoscopy for sterilization were performed. No significant problems during surgery and the postoperative period were observed. Resumption of the different physiologic functions were more rapid, hospital stay shorter and compliance greater than with general anesthesia.

Tissue dose, DNA adducts, oxidative DNA damage and CYP1A-immunopositive proteins in mussels exposed to waterborne benzo[a]pyrene.

A collaborative study was performed on Mediterranean mussels (Mytilus galloprovincialis) exposed to a wide dose-range (0.5-1000 ppb) of benzo[a]pyrene (B[a]P). We selected this model polycyclic aromatic hydrocarbon in order to confirm the formation of a specific DNA adduct, previously detected in gill DNA, and to clarify the in vivo effects of this mutagenic chemical requiring host-metabolism in mussels. B[a]P concentration reached consistently higher values in the digestive gland than in other analyzed tissues of mussels exposed to B[a]P for 2 or 3 days. With the exception of some values at 1000 ppb of B[a]P. DNA adduct levels increased significantly with the dose in gills and digestive gland and ranged from 0.054 to 0.789 adducts per 10(8) nucleotides (mean values per dose-point). Conversely, more complex dose-response relationships were found by detecting in parallel the levels of an oxidative DNA lesion (8-OHdG) and of CYP1A-immunopositive proteins (the latter measured in the digestive gland only). Overall, the formation of DNA adducts, the evidence of oxidative DNA damage, and changes in CYP1A-immunopositive protein levels support the hypothesis that B[a]P can induce DNA damage in mussels through a number of different molecular mechanisms.

Echinococcus granulosus: cloning and characterization of a tandemly repeated DNA element.

A repetitive DNA element from the genome of the cestode Echinococcus granulosus has been cloned and sequenced. The 186-base-pair repeating units are arranged in direct tandem, probably clustered in the parasite genome. The estimated copy number of the repeat is 11,500 and represents between 2 and 3% of the parasite genome. The repetitive sequence is specific for Echinococcus since it does not cross-hybridize with either DNA of other cestode species or pig and dog DNA. The repetitive element is capable of detecting between 250 and 500 pg of E. granulosus DNA by dot blot assay.

Image and flow cytometric analyses of DNA content in human solid tumors. A comparative study.

OBJECTIVE: To compare the sensitivity and potentials of flow and image cytometry in assessing DNA content. STUDY DESIGN: The study was performed on 152 tumors (oral cavity, uterine cervix, bladder, colorectum, breast). Flow cytometry was carried out on cell suspensions from frozen samples, and the results were expressed as the DNA index. Image cytometry was performed on Feulgen-stained sections, and the results were expressed as the rate of cells exceeding 2.5c or 5c. For colorectal and breast cancers, DNA content by image cytometry was also measured on imprints and was expressed as the DNA index or rate of cells exceeding 2.5c and 5c. RESULTS: Among flow cytometric diploid tumors, image cytometric analysis performed on histologic sections showed about 80% diploid tumors from the uterine cervix and breast cancers. The frequency decreased to 36% for oral cavity cancers. Generally satisfactory concordance was observed when flow cytometric aneuploid tumors were analyzed. A highly significant correlation was observed between DNA indices observed by flow and image cytometry on imprints. CONCLUSION: Image cytometry appears more sensitive than flow cytometry in detecting small, aneuploid clones, but its main limitation is the low power in resolving near-diploid cell populations. The results on imprints indicate that image cytometry is a potential alternative approach for small tumor samples.

Detection of micronuclei in gill cells and haemocytes of mussels exposed to benzo[a]pyrene.

Mediterranean mussels were exposed to benzo[a]pyrene for 2 days at doses which had previously caused the formation of specific adducts in gill DNA. Micronuclei and other nuclear abnormalities were detected in gill cells and haemocytes in order to ascertain the induction of cytogenetic damage in two different target cells in parallel. A number of procedural details were examined initially to improve the quality of slides obtained from mussel cells. Adequate cytological preparations were obtained when gill cells and haemocytes were suspended, respectively, in Alsever and sea water with EDTA, cytospun and fixed with absolute methanol. In the exposed mussels, micronuclei significantly increased in both the large gill cells (the main cell type) and the agranular haemocytes. Granular haemocytes, cells present in variable proportions between individual mussels, did not show cytogenetic damage except at the highest B[a]P doses. In the same slides, steady levels of binucleated cells were detected, whereas the incidence of other nuclear abnormalities was significantly higher in the exposed compared with control mussels. Precise knowledge of the replication kinetics of gill cells and haemocytes is still lacking.

[Treatment with tuberculostatic drugs: compliance at a general hospital]. / Terapeutica con tuberculostaticos: cumplimiento en un hospital general.

The purpose of this study was to assess the compliance with tuberculostatic drugs treatment in a public hospital from Córdoba City and to establish the causes of noncompliance. All the patients to which treatment with tuberculostatic drugs was indicated from January 1991 up to December 1994 were included. 45 patients were included: 18 females (40%) and 29 males. Sixteen (35.6%) did not complete the time of treatment indicated. Nine (56.3%) abandoned the treatment 2 months after having initiated it. In the group that did not complete the treatment there was a higher percentage of female patients (62.5%) than in the group that did complete it (27.6%), p = 0.02. There were not statistically significant differences in age, percentages of pulmonar and extrapulmonar tuberculosis and months of treatment indicated between both groups. Thirty-six percent of the patients who abandoned the treatment referred having interrupted it due to their own negligency, knowing the risk of such behavior; 36% suffered side effects and did not come back to hospital; 21% referred having consulted another physician who indicated to interrupt the treatment without performing other tests; and 7% misunderstood the indications. It is concluded that in a general hospital from Córdoba City, the percentage of patients who abandoned tuberculostatic treatment is high. In most cases the cause was related to failures in the conduct of patients, physicians or both.

[Clinical and epidemiologic characteristics of acute diarrhea in adults at a hospital from Cordoba city]. / Caracteristicas clinico-epidemiologicas de la diarrea aguda del adulto en un hospital de la ciudad de Cordoba.

The purpose of this work was to assess the clinical and epidemiologic presentation features of adult acute diarrhea in a general hospital form Córdoba City. All the patients older than 14 years old who assisted to the Hospital Nacional de Clínicas Central Guard for acute diarrhea, during the periods: A (15-12-89 to 15-03-90), B (15-12-93 to 15-03-94) and C (15-12-94 to 15-03-95), were included. 594 patients were studied: 337 female (56.7%) and 257 male, 143 in the period A, 250 in B and 201 in C. The means +/- SD age was 34.6 +/- 13.3 and stool loose per day at admission 7.3 +/- 4.7. Eighty six percent of patients presented liquid consistent stool, 89.6% abdominal pain, 44.7% vomiting and 18.8% bloody stools. The rate of patients who consulted Central Guard referring acute diarrhea increased from period A (2.4%) to B (3.61%); p = 0.002 and decreased form B to C (2.85%); p = 0.01. The mean (+/- SD) days transcurred from the beginning of diarrhea episode till consultation was 3.5 +/- 2.7; 2.7 +/- 2.3 y 2.9 +/- 3.5 in the periods A, B and C respectively, statistically significant difference between A and B, p < 0.01. Thirty six percent, 21.1% and 23.1% of patients presented mucus with their stools in the periods A, B and C (p = 0.01), and high temperature 61.1%, 48.1% and 48.5% respectively (p = 0.04). Twenty seven percent of stools samples cultures became positive in the periods A, 17.6% in B and 11.5% in C, statistically significant difference between A and C; p = 0.008. The results show that in a general hospital from Córdoba City the adult acute diarrhea is a frequent cause of consult. In the last years there were modifications in its clinical an epidemiologic presentation features.