A prospective genome-wide study of prostate cancer metastases reveals association of wnt pathway activation and increased cell cycle proliferation with primary resistance to abiraterone acetate-prednisone.

Background: Genomic aberrations have been identified in metastatic castration-resistant prostate cancer (mCRPC), but molecular predictors of resistance to abiraterone acetate/prednisone (AA/P) treatment are not known. Patients and methods: In a prospective clinical trial, mCRPC patients underwent whole-exome sequencing (n = 82) and RNA sequencing (n = 75) of metastatic biopsies before initiating AA/P with the objective of identifying genomic alterations associated with resistance to AA/P. Primary resistance was determined at 12 weeks of treatment using criteria for progression that included serum prostate-specific antigen measurement, bone and computerized tomography imaging and symptom assessments. Acquired resistance was determined using the end point of time to treatment change (TTTC), defined as time from enrollment until change in treatment from progressive disease. Associations of genomic and transcriptomic alterations with primary resistance were determined using logistic regression, Fisher's exact test, single and multivariate analyses. Cox regression models were utilized for determining association of genomic and transcriptomic alterations with TTTC. Results: At 12 weeks, 32 patients in the cohort had progressed (nonresponders). Median study follow-up was 32.1 months by which time 58 patients had switched treatments due to progression. Median TTTC was 10.1 months (interquartile range: 4.4-24.1). Genes in the Wnt/ß-catenin pathway were more frequently mutated and negative regulators of Wnt/ß-catenin signaling were more frequently deleted or displayed reduced mRNA expression in nonresponders. Additionally, mRNA expression of cell cycle regulatory genes was increased in nonresponders. In multivariate models, increased cell cycle proliferation scores (≥ 50) were associated with shorter TTTC (hazard ratio = 2.11, 95% confidence interval: 1.17-3.80; P = 0.01). Conclusions: Wnt/ß-catenin pathway activation and increased cell cycle progression scores can serve as molecular markers for predicting resistance to AA/P therapy.

Response to pneumococcal polysaccharide vaccine in children with asthma, and children with recurrent respiratory infections, and healthy children.

BACKGROUND: To analyse specific immune response to the 23-valent pneumococcal polysaccharide vaccine by measuring pneumococcal antibodies in children with asthma and with respiratory recurrent infection (RRI) as compared to healthy children. METHODS: The study included 60 children, divided into three groups: 20 with asthma, 20 with RRI, and 20 healthy controls. Post-vaccination specific IgG antibodies against 10 pneumococcal serotypes (S1, S3, S4, S5, S6B, S9V, S14, S18C, S19F, and S23F) contained in the 23-valent pneumococcal polysaccharide vaccine (PPV) were measured. A specific IgG concentration ≥1.3µg/mL was considered a protective response to the vaccine. For statistical analysis, levels of specific IgG antibodies against each of the 10 pneumococcal serotypes were compared across the three groups of children using the x(2) test. RESULTS: All of the children showed antipneumococcal antibody levels >1.3µg/mL for over 70% of the serotypes, considered within the normal range of response. Average IgG antibody levels and percentages of children protected were statistically comparable among the three groups studied. CONCLUSION: The asthmatic children without RRI had pneumococcal antibody levels and percentages of serotype-specific protection to PPV comparable to those of healthy children. Asthmatic children with recurrent infections should be evaluated for specific antibody deficiency (SAD). Because asthma patients are at high risk for invasive pneumococcal infections, it would be worthwhile to explore systematic administration of PPV in children over the age of two years who have not received a pneumococcal conjugate vaccine, considering the positive response to PPV reported here.

Morphine-induced ventilatory failure after spinal cord compression.

We describe a patient who required large doses of parenteral morphine for severe pain secondary to epidural spinal cord compression caused by metastatic cancer. The pain improved suddenly after neurological progression to a complete cord compression. Shortly afterwards, the patient developed acute respiratory depression caused by an apparent relative overdose of morphine. Our hypothesis is that the cord compression relieved the pain by interrupting the nociceptive pathway. The dose of morphine was then physiologically excessive once the neurologic damage was completed and the pain had been relieved. We advise caution in patients receiving high doses of opioids in which a change in disease status or a pain-relieving intervention may produce rapid pain relief.

Use of nebulized bronchodilators in infants under 1 year of age: analysis of four forms of therapy.

The main purpose of this study was to evaluate four different forms of treatment in young infants admitted for acute wheezing (AW). Seventy-nine infants less than one year of age were randomly assigned to one of five groups. Group 1 received nebulized fenoterol plus ipratropium bromide, group 2 fenoterol, group 3 fenoterol plus steroids, and group 4 aminophylline, IV, plus steroids and oral fenoterol; the control group, or group 5, received nebulized normal saline solution. Clinical evaluation was done by means of a scoring system. The effectiveness of treatments was estimated by a score decrease in the first 24 hours, by the percentage of patients whose scores did not decrease during the same period, and by the number of days in the hospital. All infants had significantly decreased scores, except those in the control group; the aminophylline group included a greater percentage of patients who did not abate their scores, and they stayed in the hospital for more days than those in the other groups. The fenoterol group had the shortest hospital stay. All four treatments produced objective clinical improvement in bronchial obstruction. However, the nebulized bronchodilator treatments were more effective than aminophylline IV in decreasing scores on the first day, and they resulted in shorter hospitalization.

[Risk of transmission of cholera by fish products: regional perspective in South America]. / Riesgos de transmisión del cólera por productos pesqueros: perspectiva regional en Sudamérica.

Cholera returned to South America in January 1991, after almost a century of absence. The hygienic status of the countries affected, aggravated by economic and political difficulties, allowed the disease to spread rapidly. In Peru, fishery products were incriminated from the outset, although without conclusive evidence. However, epidemiological and laboratory findings in other countries have confirmed the transmission of the disease by these products. The authors discuss the effects of the recent cholera epidemic on the trade and consumption of fishery products in countries of South America. The actual risk of cholera transmission by food and in particular by the consumption of fishery products is discussed, and a basis for conducting an accurate evaluation of these risks is proposed. Finally, the authors summarise the measures recommended to prevent the transmission of cholera by fishery products.

[Enterobacteriaceae as indicators of the presence of Salmonella and the hygienic conditions of meat and bone meals]. / Enterobacteriaceae como indicadoras de la presencia de Salmonella y de la higiene de harinas de carne y hueso.

The purpose of this study was to establish the relationship between Enterobacteriaceae counts and the presence of Salmonella in meat-and-bone meals. Ninety meat-and-bone meal sample units (9 lots) from five producing plants from the Greater Buenos Aires, Argentina, were analyzed. The presence of Salmonella was detected through pre-enrichment of the samples followed by selective enrichment in two broth cultures and isolations after 24 and 48 hours. For Enterobacteriaceae counts the recovery of sublethally injured cells was carried out for two hours on trypticase soy agar, followed by the addition of selective agar. The overall Enterobacteriaceae count for the 90 sample units was 3.0. Seven (77.7%) of the 9 lots were positive for Salmonella. The correlation coefficient between Enterobacteriaceae counts and Salmonella was 0.81 with a confidence limit (95%) of 0.35-0.95. The results of this study indicate that Enterobacteriaceae counts are not good indicators of the presence of Salmonella in meat-and-bone meals. However, they could be used to assess their hygienic quality.

Promoting safer foods in latin america and the Caribbean.

This article describes the current trends in public health promotion and education in Latin America and the Caribbean. It gives examples of approaches that work and highlights some of the difficulties of concentrating strictly on the use of mass media communication. Various programs and projects for promoting the safe handling of foods are cited from specific countries and subregions in the Americas. Looking back on what has worked and what has failed, the authors recognize that some advancements have been achieved in improving the public's handling and protection of food, particularly in the tourism sector, and yet many challenges lie ahead for improving upon what has already been done.

Survey of the Microbiological Quality of Adult Bovine Rennet Extracts.

Sixty-nine samples of liquid bovine rennet extract from several cheese-making plants were examined for microbiological quality. Wide differences were observed in the microbiological results, as well as in the pH, which ranged from 4.0 to 6.5, reflecting the manufacturing practices and sanitary conditions. The highest level of contamination was always caused by sporulated bacteria, both aerobic and anaerobic. Coliforms, considered to be enteric indicator bacteria were not detected, although halotolerant bacteria were found.

Contaminated weaning food: a major risk factor for diarrhoea and associated malnutrition.

Infections and the malnutrition associated with them are responsible for a significant proportion of the 13 million deaths among infants and children under 5 years of age worldwide each year. After respiratory infections, diarrhoeal diseases are the commonest illnesses and have the greatest negative impact upon the growth of infants and young children. The causes of diarrhoeal diseases have traditionally been ascribed to water supply and sanitation. In attempts to prevent such diseases, efforts by governments and nongovernmental organizations have been focused on and sometimes limited to improving water supply and sanitation as well as promoting and protecting breast-feeding. Based on studies reported in the literature, this review article demonstrates that weaning foods prepared under unhygienic conditions are frequently heavily contaminated with pathogens and thus are a major factor in the cause of diarrhoeal diseases and associated malnutrition. In the light of the evidence presented, it appears that current efforts are not sufficient to prevent diarrhoeal diseases: education of mothers in food safety principles, particularly weaning food, must also receive high priority. Educational programmes based on the hazard-analysis-critical-control-point approach, taking into consideration also sociocultural factors, should be integrated into all national infant feeding or food and nutrition programmes.

PIP: Even though contaminated foods are responsible for up to 70% of diarrheal episodes, efforts to prevent diarrheal diseases often overlook food safety. Food safety is at least as important as breast feeding or providing a safe water supply and sanitation services. In developing countries, weaning foods are often prepared in an unhygienic manner. Thus, the weaning age is an especially dangerous time for infants since they are exposed to infective doses of foodborne pathogens. Infections caused by pathogenic Escherichia coli is probably responsible for as much as 25% of all diarrheal episodes in developing countries. E coli is often linked to weaning foods. Other significant microbial infections causing diarrhea include shigellosis and cholera. Rotavirus most frequently attacks 6-24 month olds and causes 20% of all diarrheal deaths among those under 5 years old. Foodborne infections can have dangerous and longterm effects, especially on nutritional status. In fact, the resistance of infants suffering from nutritional deficiencies is suppressed, leaving them wide open to infectious diseases, particularly those causing diarrhea, which further reduces their ability to fight disease. They then become progressively more malnourished. Food contamination sources include unclean hands, feces, polluted water, flies, pests, domestic animals, unclean utensils and pots, and an unsanitary environment. Cross-contamination during food preparation is also responsible, e.g., contact between raw and cooked foods. Beliefs and practices, ignorance, taboos, poverty, insufficient food, social infrastructure, and shortage of fuel and time often make it more difficult to assure food safety. Food safety could reduce hospital costs since diarrhea is the leading reason for hospitalizations among children. Food safety education for mothers in primary health care and infant feeding programs is the most important intervention in promoting the health and nutritional status of infants and children.

Contaminated food, a hazard for the very young.

Contaminated food is responsible for much diarrhoeal disease in young children, yet the education of mothers and care-givers about the preparation of food under hygienic conditions tends to be neglected.

PIP: Breast milk is no longer sufficient to meet the nutritional requirements of infants aged 4-6 months; thus, during weaning, complimentary foods should be introduced gradually. At this time, infants are at increased risk of getting diarrhea from food-borne pathogens resulting in reduced food intake and loss of nutrients through vomiting and fever. Diminished immunological resistance to infections causes as estimated 13 million fatalities a year among children under 5 years of age as a result of infectious diseases and malnutrition. In developing countries, preparation of weaning foods under unhygienic conditions causes up to 70% of diarrheal cases. Pathogenic strains of Escherichia coli account for up to 25% of diarrhea episodes. The sources of food contamination are night soil, polluted water, files and other pests, domestic animals, dirty utensils and pots, unwashed hands, and dust. Pathogenic bacteria can multiply if the food is prepared several hours before consumption and stored at temperatures favoring the growth of microorganisms and/or production of toxins. Insufficient cooking or reheating can also facilitate bacterial growth. Sociocultural and economic factors contribute to risks, such as short supply of food; maternal ignorance about the link between diarrhea and improper food handling; unsafe water supplies and lack of sanitation with increased risk of food contamination; shortage of fuel for cooking and lack of refrigeration; and insufficient time for food preparation. The World Health Organization Golden Rules for Safe Food Preparation need to be observed. Food should be thoroughly cooked and fed to infants once it is cool enough; food should not be stored where there are no facilities for storage below 10 degrees Celsius or for keeping food at or above 60 degrees Celsius. Mothers should be advised about food safety within the framework of educational programs.

[Current concepts on mucoviscidosis. Report of 2 cases]. / Actualización sobre mucoviscidósis. Presentación de 2 casos.

The main aspects of the genetic cystic fibrosis, are reviewed; they are: incidence, pathophysiology, clinical signs and symptoms, treatment and prognosis. Emphasis is made on the infrequency of the diagnosis in Latin America. The pediatrician's attention is called in order to think in this possible diagnosis in cases of chronic pneumopathy with or without signs of poor intestinal absorption.