Identifying and optimizing human endometrial gene expression signatures for endometrial dating.

STUDY QUESTION: What are the key considerations for developing an enhanced transcriptomic method for secretory endometrial tissue dating? SUMMARY ANSWER: Multiple gene expression signature combinations can serve as biomarkers for endometrial dating, but their predictive performance is variable and depends on the number and identity of the genes included in the prediction model, the dataset characteristics and the technology employed for measuring gene expression. WHAT IS KNOWN ALREADY: Among the new generation of transcriptomic endometrial dating (TED) tools developed in the last decade, there exists variation in the technology used for measuring gene expression, the gene makeup and the prediction model design. A detailed study, comparing prediction performance across signatures for understanding signature behaviour and discrepancies in gene content between them, is lacking. STUDY DESIGN, SIZE, DURATION: A multicentre prospective study was performed between July 2018 and October 2020 at five different centres from the same group of clinics (Spain). This study recruited 281 patients and finally included in the gene expression analysis 225 Caucasian patients who underwent IVF treatment. After preprocessing and batch effect filtering, gene expression measurements from 217 patients were combined with artificial intelligence algorithms (support vector machine, random forest and k-nearest neighbours) allowing evaluation of different prediction models. In addition, secretory-phase endometrial transcriptomes from gene expression omnibus (GEO) datasets were analysed for 137 women, to study the endometrial dating capacity of genes independently and grouped by signatures. This provided data on the consistency of prediction across different gene expression technologies and datasets. PARTICIPANTS/MATERIALS, SETTING, METHODS: Endometrial biopsies were analysed using a targeted TruSeq (Illumina) custom RNA expression panel called the endometrial dating panel (ED panel). This panel included 301 genes previously considered relevant for endometrial dating as well as new genes selected for their anticipated value in detecting the secretory phase. Final samples (n = 217) were divided into a training set for signature discovery and an independent testing set for evaluation of predictive performance of the new signature. In addition, secretory-phase endometrial transcriptomes from GEO were analysed for 137 women to study endometrial dating capacity of genes independently and grouped by signatures. Predictive performance among these signatures was compared according to signature gene set size. MAIN RESULTS AND THE ROLE OF CHANCE: Testing of the ED panel allowed development of a model based on a new signature of 73 genes, which we termed 'TED' and delivers an enhanced tool for the consistent dating of the secretory phase progression, especially during the mid-secretory endometrium (3-8 days after progesterone (P) administration (P + 3-P + 8) in a hormone replacement therapy cycle). This new model showed the best predictive capacity in an independent test set for staging the endometrial tissue in the secretory phase, especially in the expected window of implantation (average of 114.5 ± 7.2 h of progesterone administered; range in our patient population of 82-172 h). Published sets of genes, in current use for endometrial dating and the new TED genes, were evaluated in parallel in whole-transcriptome datasets and in the ED panel dataset. TED signature performance was consistently excellent for all datasets assessed, frequently outperforming previously published sets of genes with a smaller number of genes for dating the endometrium in the secretory phase. Thus, this optimized set exhibited prediction consistency across datasets. LARGE SCALE DATA: The data used in this study is partially available at GEO database. GEO identifiers GSE4888, GSE29981, GSE58144, GSE98386. LIMITATIONS, REASONS FOR CAUTION: Although dating the endometrial biopsy is crucial for investigating endometrial progression and the receptivity process, further studies are needed to confirm whether or not endometrial dating methods in general are clinically useful and to guide the specific use of TED in the clinical setting. WIDER IMPLICATIONS OF THE FINDINGS: Multiple gene signature combinations provide adequate endometrial dating, but their predictive performance depends on the identity of the genes included, the gene expression platform, the algorithms used and dataset characteristics. TED is a next-generation endometrial assessment tool based on gene expression for accurate endometrial progression dating especially during the mid-secretory. STUDY FUNDING/COMPETING INTEREST(S): Research funded by IVI Foundation (1810-FIVI-066-PD). P.D.-G. visiting scientist fellowship at Oxford University (BEFPI/2010/032) and Josefa Maria Sanchez-Reyes' predoctoral fellowship (ACIF/2018/072) were supported by a program from the Generalitat Valenciana funded by the Spanish government. A.D.-P. is supported by the FPU/15/01398 predoctoral fellowship from the Ministry of Science, Innovation and Universities (Spanish Government). D.W. received support from the NIHR Oxford Biomedical Research Centre. The authors do not have any competing interests to declare.

Differing molecular response of young and advanced maternal age human oocytes to IVM.

STUDY QUESTION: What effect does maternal age have on the human oocyte's molecular response to in vitro oocyte maturation? SUMMARY ANSWER: Although polyadenylated transcript abundance is similar between young and advanced maternal age (AMA) germinal vesicle (GV) oocytes, metaphase II (MII) oocytes exhibit a divergent transcriptome resulting from a differential response to in vitro oocyte maturation. WHAT IS KNOWN ALREADY: Microarray studies considering maternal age or maturation stage have shown that either of these factors will affect oocyte polyadenylated transcript abundance in human oocytes. However, studies considering both human oocyte age and multiple stages simultaneously are limited to a single study that examined transcript levels for two genes by qPCR. Thus, polyadenylated RNA sequencing (RNA-Seq) could provide novel insight into age-associated aberrations in gene expression in GV and MII oocytes. STUDY DESIGN, SIZE, DURATION: The effect of maternal age (longitudinal analysis) on polyadenylated transcript abundance at different stages was analyzed by examining single GV and single in vitro matured MII oocytes derived from five young (YNG; < 30 years; average age 26.8; range 20-29) and five advanced maternal age (AMA; ≥40 years; average age 41.6 years; range 40-43 years) patients. Thus, a total of 10 YNG (5 GV and 5 MII) and 10 AMA (5 GV and 5 MII) oocytes were individually processed for RNA-Seq analysis. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Patients undergoing infertility treatment at the Colorado Center for Reproductive Medicine (Lone Tree, CO, USA) underwent ovarian stimulation with FSH and received hCG for final follicular maturation prior to ultrasound guided oocyte retrieval. Unused GV oocytes obtained at retrieval were donated for transcriptome analysis. Single oocytes were stored (at -80°C in PicoPure RNA Extraction Buffer; Thermo Fisher Scientific, USA) immediately upon verification of immaturity or after undergoing in vitro oocyte maturation (24 h incubation), representing GV and MII samples, respectively. After isolating RNA and generating single oocyte RNA-Seq libraries (SMARTer Ultra Low Input RNA HV kit; Clontech, USA), Illumina sequencing (100 bp paired-end reads on HiSeq 2500) and bioinformatics analysis (CLC Genomics Workbench, DESeq2, weighted gene correlation network analysis (WGCNA), Ingenuity Pathway Analysis) were performed. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 12 770 genes were determined to be expressed in human oocytes (reads per kilobase per million mapped reads (RPKM) > 0.4 in at least three of five replicates for a minimum of one sample type). Differential gene expression analysis between YNG and AMA oocytes (within stage) identified 1 and 255 genes that significantly differed (adjusted P < 0.1 and log2 fold change >1) in polyadenylated transcript abundance for GV and MII oocytes, respectively. These genes included CDK1, NLRP5 and PRDX1, which have been reported to affect oocyte developmental potential. Despite the similarity in transcript abundance between GV oocytes irrespective of age, divergent expression patterns emerged during oocyte maturation. These age-specific differentially expressed genes were enriched (FDR < 0.05) for functions and pathways associated with mitochondria, cell cycle and cytoskeleton. Gene modules generated by WGCNA (based on gene expression) and patient traits related to oocyte quality (e.g. age and blastocyst development) were correlated (P < 0.05) and enriched (FDR < 0.05) for functions and pathways associated with oocyte maturation. LARGE SCALE DATA: Raw data from this study can be accessed through GSE95477. LIMITATIONS, REASONS FOR CAUTION: The human oocytes used in the current study were obtained from patients with varying causes of infertility (e.g. decreased oocyte quality and oocyte quality-independent factors), possibly affecting oocyte gene expression. Oocytes in this study were retrieved at the GV stage following hCG administration and the MII oocytes were derived by IVM of patient oocytes. Although the approach has the benefit of identifying intrinsic differences between samples, it may not be completely representative of in vivo matured oocytes. WIDER IMPLICATIONS OF THE FINDINGS: Transcriptome profiles of YNG and AMA oocytes, particularly at the MII stage, suggest that aberrant transcript abundance may contribute to the age-associated decline in fertility. STUDY FUNDING/COMPETING INTEREST(S): J.M.R. was supported by an Austin Eugene Lyons Fellowship awarded by the University of California, Davis. The Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (awarded to P.J.R.; R01HD070044) and the Fertility Laboratories of Colorado partly supported the research presented in this manuscript.

[Prophylaxis for stress ulcer bleeding in the intensive care unit]. / Profilaxis para sangrado por ulceras de estrés en la unidad de cuidados intensivos.

BACKGROUND: The critically ill patient can develop gastric erosions and, on occasion, stress ulcers with severe gastrointestinal bleeding that can be fatal. AIMS: The purpose of this review was to provide current information on the pathophysiology, risk factors, and prophylaxis of digestive tract bleeding from stress ulcers in the intensive care unit. METHODS: We identified articles through a PubMed search, covering the years 1970 to 2013. The most relevant articles were selected using the search phrases "stress ulcer", "stress ulcer bleeding prophylaxis", and "stress-related mucosal bleeding" in combination with "intensive care unit". RESULTS: The incidence of clinically significant bleeding has decreased dramatically since 1980. The most important risk factors are respiratory failure and coagulopathy. Proton pump inhibitors (PPIs) or H2 receptor antagonists (H2RAs) are used in stress ulcer bleeding prophylaxis. Both drugs have been shown to be superior to placebo in reducing the risk for gastrointestinal bleeding and PPIs are at least as effective as H2RAs. Early enteral feeding has been shown to reduce the risk for stress ulcer bleeding, albeit in retrospective studies. CONCLUSIONS: Admittance to the intensive care unit in itself does not justify prophylaxis. PPIs are at least as effective as H2RAs. We should individualize the treatment of each patient in the intensive care unit, determining risk and evaluating the need to begin prophylaxis.

Patient-reported outcomes in RA patients treated with tofacitinib or bDMARDs in real-life conditions in two Latin American countries.

OBJECTIVE: To describe efficacy, safety, and patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA) with an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) treated with tofacitinib or biological DMARDs (bDMARDs) in real-life conditions. METHODS: A noninterventional study was performed between March 2017 and September 2019 at 13 sites in Colombia and Peru. Outcomes measured at baseline and at the 6-month follow-up were disease activity (RAPID3 [Routine Assessment of Patients Index Data] score), functional status (HAQ-DI [Health Assessment Questionnaire] score), and quality of life (EQ-5D-3L [EuroQol Questionnaire]). The Disease Activity Score-28 (DAS28-ESR) and frequency of adverse events (AEs) were also reported. Unadjusted and adjusted differences from baseline were estimated and expressed as the least squares mean difference (LSMD). RESULTS: Data from 100 patients treated with tofacitinib and 70 patients with bDMARDs were collected. At baseline, the patients' mean age was 53.53 years (SD 13.77), the mean disease duration was 6.31 years (SD 7.01). The change from baseline at month 6 was not statistically significant different in the adjusted LSMD [SD] for tofacitinib vs. bDMARDs for RAPID3 score (-2.55[.30] vs. -2.52[.26]), HAQ-DI score (-.56[.07] vs. -.50[.08]), EQ-5D-3L score (.39[.04] vs. .37[.04]) and DAS28-ESR (-2.37[.22] vs. -2.77[.20]). Patients from both groups presented similar proportions of nonserious and serious AEs. No deaths were reported. CONCLUSION: Changes from baseline were not statistically significantly different between tofacitinib and bDMARDs in terms of RAPID3 scores and secondary outcomes. Patients from both groups presented similar proportions of nonserious and serious AEs. CLINICAL TRIAL NUMBER: NCT03073109.

Cost-utility analysis of ceftazidime-avibactam versus colistin-meropenem in the treatment of infections due to Carbapenem-resistant Klebsiella pneumoniae in Colombia.

BACKGROUND: Ceftazidime-Avibactam (CAZ-AVI) is a new antimicrobial against carbapenem-resistant Klebsiella pneumoniae. The aim of the study is to examine the cost-effectiveness of CAZ-AVI compared to colistin-meropenem (COL+MEM) in Colombia. METHODS: A decision tree model was developed from health-care system perspective assuming a 30-day time horizon. The clinical course was simulated based on treatment response between 48 and 72 hours, and the duration of the treatment was 7-14 days. Cost inputs were extracted from a published Colombian manual tariffs and official databases, expressed in 2019 dollars (USD). RESULTS: In the base case analysis, CAZ-AVI was associated with reduced mortality, length of hospital stay and fewer add-on antibiotics, resulting in an increase of 1.76 QALYs per patient versus COL+MEM and incremental costs associated in CAZ-AVI were $2,521 higher per patient compared to COL+MEM ($755 versus $3,276). The incremental costs were partially increased due to the lower mortality rate observed with CAZ-AVI. The incremental cost-effectiveness ratio was estimated to be $3,317 per QALY. In the probabilistic sensitivity analysis, with a willingness to pay above $2,438, CAZ-AVI has higher probability of being cost-effective. CONCLUSION: CAZ-AVI demonstrates cost-effectiveness as a treatment for Carbapenem-resistant Klepsiella pneumoniae infections by reducing the number of deaths and increasing QALYs. EXPERT COMMENTARY: Previous studies and surveillance programs from Colombia have reported prevalence of pathogens and the antimicrobial susceptibility of infections caused by multidrug-resistant Gram-negative bacteria. The health authorities have to consider and plan adequate surveillance systems in order to predict the resistance type and in choose the optimal antibiotics when infections occur.

The Mexican consensus on the diagnosis, treatment, and prevention of NSAID-induced gastropathy and enteropathy. / Consenso mexicano sobre diagnóstico, prevención y tratamiento de la gastropatía y enteropatía por antiinflamatorios no esteroideos.

More than 30 million persons worldwide take nonsteroidal anti-inflammatory drugs (NSAIDs) on a daily basis, and annual consumption is increasing. In addition to their analgesic and anti-inflammatory properties, NSAIDs also produce well-known gastrointestinal adverse events. There is no consensus in Mexico on the diagnosis, treatment, and prevention of NSAID-induced gastropathy and enteropathy, and so the Asociación Mexicana de Gastroenterología brought together a group of experts to establish useful recommendations for the medical community. Thirty-three recommendations were formulated in the present consensus, highlighting the fact that the risk for NSAID-induced gastrointestinal toxicity varies according to the drug employed and its pharmacokinetics, which should be taken into account at the time of prescription. The risk factors for gastroduodenal complications due to NSAIDs are: a history of peptic ulcer, age above 65 years, high doses of NSAIDs, Helicobacter pylori infection, and the presence of severe comorbidities. The symptoms and gastroduodenal damage induced by NSAIDs vary, ranging from an asymptomatic course to the presentation of iron-deficiency anemia, bleeding, stricture, and perforation. Capsule endoscopy and enteroscopy are direct diagnostic methods in NSAID enteropathy. Regarding prevention, the minimum dose of an NSAID needed to achieve the desired effect, administered for the shortest period of time, is the recommendation. Finally, proton pump inhibitors are the gold standard for the prophylaxis and treatment of gastroduodenal effects, but they are not useful in enteropathy.

[Budd-Chiari syndrome associated with systemic aspergillosis. Case report and literature review.]. / Síndrome de Budd-Chiari asociado a aspergilosis sistémica; informe de un caso y revisión de la literatura.

Budd-Chiari syndrome is a very rare disease related to hepatic vein obstruction. Vascular invasion by fungus is seldom seen and reported. After thorough research of the literature only three cases have been reported. We reported a case of a diabetic patient who showed an acute and aggressive disease, characterized by sepsis, acute hepatic failure and death. Postmortem examination showed disseminated aspergillosis, massive hepatic necrosis, hepatic vein thrombosis and venous occlusion by the fungus.

[Ultrasound-guided puncture of the jugular vein using a posterior approach]. / Punción ecodirigida de la vena yugular interna por abordaje posterior.

BACKGROUND: Ultrasound-guided central venous catheterization provides a direct view of anatomical structures, making it easier to determine the exact puncture site, thereby reducing the associated mechanical complications. PATIENTS AND METHODS: This study included patients scheduled for central venous catheterization. An ultrasound examination was performed on the necks of all patients before the right internal jugular vein was catheterized by a single operator using ultrasound monitoring. RESULTS: We studied 21 men and 14 women; the mean (SD) age of the patients was 53 (17) years. Forty percent were kidney transplant recipients and 57% had had the right internal jugular vein catheterized on other occasions. The carotid artery had accidentally been punctured using the standard catheterization technique in 4 of the patients; the internal jugular vein was then catheterized successfully using ultrasound-guidance, which clearly showed the hematoma caused by the carotid puncture. The right internal jugular vein was successfully catheterized in 34 patients; it was necessary to catheterize the left jugular vein in 1 patient as the ultrasound examination revealed thrombosis of the right vein. A single puncture was performed in all cases and none of the complications associated with venous puncture were observed. CONCLUSION: Ultrasound images allowed us to effectively examine the jugular vein prior to puncture for central venous catheterization. Ultrasound-guided puncture of the vein was satisfactory and free from complications in all cases.

Topical corticosteroids as adjunctive therapy for bacterial keratitis.

BACKGROUND: Bacterial keratitis is a serious ocular infectious disease that can lead to severe visual disability. Risk factors for bacterial corneal infection include contact lens wear, ocular surface disease, corneal trauma and previous ocular or eyelid surgery. Topical antibiotics constitute the mainstay of treatment in cases of bacterial keratitis where as the use of topical corticosteroids remains controversial. Topical corticosteroids are usually used to control inflammation using the smallest amount of the drug. Their use requires optimal timing, concomitant antibiotics and careful follow up. OBJECTIVES: The objective of the review was to assess the clinical effectiveness and adverse effects of corticosteroids as adjunctive therapy for bacterial keratitis. SEARCH STRATEGY: We searched CENTRAL, MEDLINE, EMBASE, and LILACS up to 15 January 2007. We also searched the Science Citation Index to identify additional studies that had cited the included trial, an online database of ongoing trials (www.clinicaltrials.gov), reference lists of included trials, earlier reviews and the American Academy of Ophthalmology guidelines. We also contacted experts to identify any unpublished and ongoing randomized trials. SELECTION CRITERIA: We included randomized controlled trials evaluating adjunctive therapy with topical corticosteroids in people with bacterial keratitis. DATA COLLECTION AND ANALYSIS: Two review authors independently screened all the retrieved articles. Methodological quality of the one included trial was assessed using forms developed using pre-specified criteria by at least two review authors. We planned to extract data on outcomes using forms developed for the purpose. We planned to report risk ratios for dichotomous outcomes and mean differences for continuous outcomes. MAIN RESULTS: A single trial was eligible for inclusion in the review. Participants in the trial were randomized using a random numbers table. Allocation concealment was not attempted. Masking of participants, and care-providers was also not attempted. Outcome assessment was conducted independently by two physicians. Neither was masked to the treatment allocation. The trial reported the healing rate of epithelial defects and improvement in visual acuity. AUTHORS' CONCLUSIONS: There are no good quality randomized trials evaluating the effects of adjunct use of topical corticosteroids in bacterial keratitis. The only randomized trial we identified in the literature suffered from major methodological inadequacies.

A new donor cornea harvesting technique for posterior lamellar keratoplasty.

AIMS: To describe a technique for posterior lamellar keratoplasty donor preparation. METHODS: In an experimental study eight human donor research corneas were mounted onto an artificial anterior chamber and deep stromal pockets dissected. Four corneas were mounted in the standard endothelial side down orientation and dissected using standard instruments (group 1). Another four corneas were mounted endothelial side up and dissected using a flat spatula (group 2). Trephined lamellar graft thickness was assessed by ultrasound pachymetry. The grafts were also analysed using vital staining of the endothelium and standard histological preparation. RESULTS: Achieved posterior graft thickness was 118 (SD 32) microm (group 1) and 92 (23) microm (group 2) (p=0.324). Percentage of devitalised endothelial cells was 0.86% (1.48%) (group 1) and 3.9% (2.9%) (group 2) (p=0.185). The dissections using both harvesting techniques remained in plane and were smooth. CONCLUSIONS: A blunt spatula and endothelium side up orientation on an artificial anterior chamber can be used to create posterior lamellar dissections without compromising endothelial cell number or planarity when compared to standard endothelium side down harvest.

Intracellular spiral inclusions in cerebral cell processes in Creutzfeldt-Jakob disease.

Electron microscopic examination of brain biopsy specimens from two patients with Creutzfeldt-Jakob disease revealed the presence of intracellular membranous spiral inclusions in the processes of cortical cells. These inclusions, 375 nm to 660 nm in length and 50 nm to 88 nm in width, resemble similar structures reported in a patient with the same disease by Bastian and, more recently, in a second patient by Gray et al. These inclusions bear close morphologic resemblance to spiroplasma organisms, a wall-free prokaryote known to cause a "slow-virus"-like disorder in mice.

Process of care performance, patient characteristics, and outcomes in elderly patients hospitalized with community-acquired or nursing home-acquired pneumonia.

STUDY OBJECTIVES: To compare process of care performance, patient characteristics, and outcomes in a contemporary cohort of elderly (> or = 65 years) patients hospitalized with community-acquired pneumonia (CAP) or with nursing home-acquired pneumonia (NHAP). DESIGN: State-wide retrospective cohort study. SETTING: Thirty-four acute-care hospitals in Connecticut. PATIENTS: Elderly Medicare patients hospitalized in 1995-1996 with CAP (1,131) or with NHAP (528). MEASUREMENTS: Antibiotic administration within 8 h of hospital arrival, blood culture collection within 24 h of hospital arrival, oxygenation assessment within 24 h of hospital arrival, demographic and clinical characteristics, in-hospital complications, mortality, and length of stay. RESULTS: Process of care performance rates for patients with CAP and NHAP were equivalent for antibiotic administration within 8 h of hospital arrival (76.8% vs 76.3%, respectively; p = 0.82), blood culture collection within 24 h of hospital arrival (78.1% vs 81.1%, respectively; p = 0.31), and oxygenation assessment within 24 h of hospital arrival (94.7% vs 95. 3%, respectively; p = 0.70). Patients with CAP were younger than those with NHAP (median age, 80 vs 84 years, respectively; p < 0. 001), had less cerebrovascular disease (16.8% vs 34.7%, respectively; p < or = 0.001), and lower mortality risk scores at hospital presentation (median, 100 vs 137, respectively; p < or = 0. 001) than patients with NHAP. The median length of stay was equivalent (7 days), but the in-hospital mortality rate was lower in patients with CAP than in patients with NHAP (8.0% vs 18.6%, respectively; p < or = 0.001). CONCLUSION: Initial hospital processes of care are performed at the same rate in patients hospitalized with CAP or NHAP. However, patients with CAP are younger, are less acutely and chronically ill, and have lower in-hospital mortality rates than patients with NHAP.

Association of pulmonary alveolar lipoproteinosis with mycobacterial infection.

A case of pulmonary alveolar proteinosis associated with tuberculosis of the lung is reported. The patient had fever, cough, and pulmonary cavities. Sputum cultures for Mycobacterium tuberculosis were positive on three occasions. Thirty-three months later, diffuse bilateral lower lobe infiltrates developed. An open lung biopsy revealed filling of the alveoli by a periodic-acid-Schiff-positive amorphous granular material. There is a significant association between this disease and various infectious and fungal agents, but its association with tuberculosis is rare. It has been reported only three times before in the English literature. This appears to be the fourth documented case with this association. A review of the literature with special emphasis on tuberculosis associated with alveolar lipoproteinosis is presented. The electron-microscopic findings are also described.

Retroperitoneal neurofibromatosis and venous anomalies.

A 45-year-old woman had abdominal pain, azotemia, and hypertension. Intravenous pyelography revealed bilateral ureteral compression by extrinsic tumor masses that proved to be neurofibromata by histologic examination. After surgical removal of the tumors, she became normotensive and asymptomatic. In addition, severe medial hypertrophy of veins was seen in the tissue examined. We believe that the latter is most probably related to the neurofibromatosis and is analogous to the hypertrophic arterial changes known to occur in patients with von Recklinghausen's disease.

Impact of milk fish farming in the tropics on potentially pathogenic vibrios.

Ratios of sucrose-negative to sucrose-positive vibrios on TCBS agar (suc-/suc+) indicate the abundance of potential human pathogenic non-cholera vibrios in coastal mariculture environments of the Lingayen Gulf (Philippines. In guts of adult maricultured milkfish (Chanos chanos) of suc- vibrios reached extreme peak values ranging between 2 and 545 million per g wet weight. Suc- vibrios outnumbered suc+ vibrios in anoxic sediments, too, and were rarely predominant in coastal waters or in oxidized sediments. Suc-/suc+ ratios in sediments increased toward the mariculture areas with distance from the open sea at decreasing redox potentials. There is circumstantial evidence that suc- vibrios can be dispersed from mariculture areas to adjacent environments including coral reefs. An immediate human health risk by pathogenic Vibrio species is discounted, since milkfish guts contained mainly members of the Enterovibrio group. A representative isolate of these contained proteolytic and other virulence factors, but no genes encoding toxins characteristic of clinical Vibrio species.

[Delay in diagnosis of HIV infection]. / Retraso diagnóstico de la infección por VIH.

Late presentation of HIV is common. It has been associated with greater risk of AIDS, death, lower immunological response, greater toxicity and a higher probability of transmission. In this study we review the impact of different definitions in terms of mortality and morbidity, associated factors, economic implications, as well as strategies for increasing diagnosis.

Phase II study of orally and rectally administered Tegafur in liver metastases from gastric carcinoma.

Twenty-four eligible and evaluable patients with measurable liver metastases from gastric cancer were treated with oral or rectal Tegafur. Objective responses were seen in 8 of the patients (33.3%), lasting between 1.5 and 15 months. The median survival period was 10 months for the responders and 2.6 months for non-responders. No complete response was observed. The survival of responders was significantly longer than that of non-responders (p less than 0.01). Toxicity was mild and consisted principally of gastrointestinal and hematological side effects. No central nervous system toxicity was seen.