Recurrent familial cholestasis disclosed by pregnancy.
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Cholestasis↗
Biomedical subjects
H Reyes
Publications and source records attributed to H Reyes.
A scale without anthropometric measurements can be used to identify low weight-for-age in children less than five years old.
Malnutrition and morbidity have a synergistic association that often leads to death. However, malnutrition in children who die is largely underreported, because anthropometry of the deceased child is rarely known. This study had two purposes: i) to develop a scale that would help determine if a child had low weight-for-age (w/a), in the absence of anthropometric measures; and ii) to select an appropriate cut-off that would give the best sensitivity (Se) and specificity (Sp) of the proposed scale when contrasted with actual w/a measurement. The study was designed as a diagnostic test, and carried out in a rural area in central Mexico. We included 132 children under 5 y old with w/a under -2 Z score and 284 children with marginal or no w/a deficit as a control group. The proposed scale included potential predictive variables from clinical, socioeconomic and family factors. The best logistic regression model to predict low w/a included: birth weight less than 2,800 g, introduction of weaning foods after the sixth month of life, introduction of animal protein after the sixth month of life, low socioeconomic status, low w/a in siblings and more than three morbidity episodes in the previous 6 mon. Selecting a cut-off of 4 for this model to identify children with low w/a showed a Se and Sp of 85 and 95%, respectively. We tested the external validity of the scale in a different locale, and included 877 children under 5 y old from 10 rural communities. In this population, the scale showed Se of 84% and Sp of 81% to identify low w/a. Based on these results, we propose that the scale be included as a means of identifying low w/a in children who have died. We believe that this should be done in verbal autopsies, which, based on our previous research, the Ministry of Health adopted as part of the regular activities to monitor problems in the disease to health-seeking to death process.
Birth Weight↗
[The "impact factor" and the impact of medical journals].
Original articles published in scientific journals are important parameters for committees when they evaluate academic promotions or research grant applications. The analysis usually tries to give each paper a qualitative/quantitative assessment. An article's citation by others is accepted as a fair estimate of the value assigned to its originality and importance. A main determinant of every citation index is the international relevance attained by the journal where the article appeared. The "impact factor" of journals enlisted in the mainstream literature, as defined by the Journal Citation Reports (ISI), is being used by many assessors worldwide. But this index appears to be an unfair unit of measurement for journals that, although included in the main international data bases, are published in non-English languages. Furthermore, some local journals that are not enlisted by the Institute for Scientific Information apply external peer review to select their publications. In contrast, those same journals may have great relevance for their contributing authors and a high impact in their readers. The Editor's proposal is to classify original articles published in biomedical sciences, clinical medicine and public health topics using a three steps scale: a low score to articles published in local journals that use the peer review system, even though they were not enlisted in international data bases; a higher score to articles published in journals included in the mainstream literature, without considering their "impact factors" as differential values; and the highest score to articles published in journals recognized as international leaders in biomedicine, general medicine or in the subspecialties. Therefore, mainstream journals published in non-English languages would not be discriminated from other journals having higher "impact factors" mainly due to their use of the English language.
Bibliometrics↗
[Is the methodology of our original articles essentially inferior to similar papers published in English-speaking journals?].
Randomised controlled trials reported in languages other than English are generally excluded from systematic reviews. This exclusion is often based in the biased opinion that the strictness of methodology and the quality of assessment of the results are essentially inferior to similar articles reported in English. A study published in 1996 in The Lancet compared completeness of reporting, design characteristics, and analytical approaches of 229 randomised controlled trials published in English, French, German, Italian or Spanish, between 1989 and 1994. Eight of those trials had been published in Revista Medica de Chile. No significant differences were found in any single item analysed, between trials published in English and in other languages. The peer review system applied by a journal and the editorial selection of original articles to be published are crucial determinants of the overall quality of its publications. The role of local journals that publish in languages other than English is most important for the communities they are intended to serve and their contribution to disseminating scientific and other important aspects of medicine should be acknowledged and considered by readers, authors and editors in English-speaking countries, especially when these local journals belong to the mainstream literature included in the major international indexing services.
Humans↗
[Biomedical papers written by Chilean authors published in international journals in 1997. A review of MEDLINE].
BACKGROUND: Many Chilean biomedical investigators publish the results of their research in international journals, not easily accessible to fellow physicians of the country. AIM: To assess the amount and quality of papers published by Chilean authors in international journals. DATA SOURCE AND METHODS: Using MEDLINE databases from January to August, 1997, all papers in which Chile appeared in the field "AD" (Address of author) were selected. Papers with a clear relationship to human medicine were identified. RESULTS: During the study period, 390 papers with authors residing in Chile appeared in MEDLINE. Of these, 188 (48%) were published in Chile and the rest was published abroad. Thirty manuscripts had a greater relationship to clinical medicine and the authors of nine of them were invited to submit a translation of their abstract into Spanish to have them reproduced in the present article. CONCLUSIONS: A significant proportion of biomedical research papers originated in Chile is published abroad with the consequent lack of diffusion among non-specialized readers from their own country.
Bibliometrics↗
[Biomedical articles by Chilean authors published in international journals in 1997. A review from MEDLINE].
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Chile↗
Pitfalls of tuberculosis programmes in prisons.
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Attitude to Health↗
Progesterone metabolites and bile acids in serum of patients with intrahepatic cholestasis of pregnancy: effect of ursodeoxycholic acid therapy.
The concentrations in serum of sulfated metabolites of progesterone are known to be elevated in patients with intrahepatic cholestasis of pregnancy (ICP). The profiles of these metabolites and conjugated bile acids were analyzed in serum from 11 patients with ICP before and during administration of ursodeoxycholic acid (UDCA) (8 patients) or placebo (3 patients). The clinical condition of 7 of the patients given UDCA improved markedly, and 1 patient given placebo had a spontaneous remission of the disease. The total concentration of conjugated bile acids in the 11 patients was 25 +/- 6 micromol/L (mean +/- SEM) and decreased to 6.3 +/- 3.5 micromol/L in the 7 patients responding to treatment with UDCA. The level of 7alpha-hydroxy-4-cholesten-3-one was significantly lower (7.2 +/- 2.2 ng/mL) in patients with ICP than in healthy pregnancy (18 +/- 4.6 ng/mL) (P < .05). The concentrations of 5alpha-pregnane-3alpha,20alpha-diol mono- and disulfates decreased by 52% +/- 7.9% and 68% +/- 5.5%, respectively, in the patients responding to treatment. Similar decreases were observed for the mono- and disulfates of 5alpha-pregnane-3alpha,20alpha,21-triol and 5beta-pregnane-3alpha,20alpha-diol. The disulfate of 5alpha-pregnane-3beta,20alpha-diol showed a smaller decrease, while glucuronidated steroids were not affected. The 3alpha-/3beta-hydroxysteroid ratio and di-/monosulfate ratio decreased significantly during UDCA. The magnitudes of the changes of bile acid and steroid concentrations during UDCA were not correlated to each other. The results suggest that UDCA stimulates the biliary excretion of steroids with a 3alpha-sulfoxy group and disulfates. This effect seems to be independent of the effect on bile acid excretion, indicating the use of different transport proteins. The possibility of an effect of UDCA on the formation of the steroid sulfates cannot be excluded.
Bile Acids and Salts↗
The Bellagio Task Force report on transplantation, bodily integrity, and the International Traffic in Organs.
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Animals↗
Ursodeoxycholic acid in the treatment of cholestasis of pregnancy: a randomized, double-blind study controlled with placebo.
BACKGROUND/AIMS: Intense pruritus and the risk of stillbirths and premature deliveries justify the search for an effective pharmacologic treatment of intrahepatic cholestasis of pregnancy. This study was designed to test the efficacy of ursodeoxycholic acid in maternal pruritus, the biochemical abnormalities and the outcome of pregnancy, in patients with intrahepatic cholestasis of pregnancy of early onset. METHODS: Pregnant patients hospitalized in a secondary case-referral center with intense pruritus and abnormal serum levels of bile salts and aminotransferases, detected before week 33 of pregnancy, were randomly assigned to receive ursodeoxycholic acid, 1 g per day orally, or an identical placebo, until delivery, in a double-blind study. A 3-week trial period was chosen to compare drug and placebo effects. The follow-up was extended for 3 months after delivery. RESULTS: Twenty-four patients entered the trial; eight had deliveries before 2 weeks of treatment and one dropped out. The study was then completed in 15 patients: eight received ursodeoxycholic acid and seven placebo. No adverse effects were detected in the mothers or in their babies. After 3 weeks of treatment, patients receiving ursodeoxycholic acid (mean daily dose 16 mg/kg body weight) had a significant improvement in pruritus (p<0.02), in serum bilirubin (0.36+/-0.19 mg/dl (mean+/-SD) versus 0.95+/-0.48 in patients receiving placebo, p<0.01), in aspartate aminotransferase (52+/-42 IU/l vs 98+/-44, p<0.05) and in alanine aminotransferase (54+/-50 IU/l vs 229+/-154, p<0.01); serum total bile salts also tended to be lower in patients receiving ursodeoxycholic acid (26.3+/-33.7 micromol/l vs 55.0+/-44.8, p N.S.). Deliveries occurred at or near term in all mothers who received ursodeoxycholic acid (mean week of pregnancy: 38), while they occurred before week 36 of pregnancy in five patients who received placebo, including one stillbirth. All babies born alive had birth weights adequate for gestational age and they were thriving normally 3 months after delivery. CONCLUSIONS: Ursodeoxycholic acid is effective and safe in patients with intrahepatic cholestasis of pregnancy of early onset, attenuating pruritus and correcting some biochemical abnormalities in the mothers. Relevant aspects of fetal outcome were also improved in patients receiving ursodeoxycholic acid compared to placebo.
Adult↗
Effects of ursodeoxycholic acid on conjugated bile acids and progesterone metabolites in serum and urine of patients with intrahepatic cholestasis of pregnancy.
BACKGROUND/AIMS AND METHODS: The mechanism(s) behind the effects of ursodeoxycholic acid on serum steroid sulphate profiles in patients with intrahepatic cholestasis of pregnancy is not clear. Conjugated progesterone metabolites and bile acids have therefore been analysed in serum and urine of patients with intrahepatic cholestasis of pregnancy before and during treatment with ursodeoxycholic acid using chromatographic and mass spectrometric methods. RESULTS: The concentration of glycine-/taurine-conjugated bile acids decreased from 8.9+/-3 micromol/l (mean+/-SEM) before treatment to 1.8+/-0.6 micromol/l during treatment with ursodeoxycholic acid. The total bile acid excretion in urine decreased from 56+/-14 to 32+/-5.6 micromol/g creatinine. The proportion of cholic acid in serum and urine, and of 1beta-, 2beta- and 6alpha-hydroxylated cholic acids in urine decreased markedly during ursodeoxycholic acid while the percentages of 3alpha,12alpha-dihydroxy-3-oxo-4-cholenoic acid and chenodeoxycholic acid were unchanged. The levels in serum and excretion in urine of sulphated steroids decreased during ursodeoxycholic acid, by 45-49% for disulphates and 33-35% for monosulphates. The ratios of 3alpha- to 3beta-hydroxysteroid disulphates were lowered by ursodeoxycholic acid from 1.1 (mean) to 0.68 in serum, and from 1.2 to 0.70 in urine. The corresponding ratios for monosulphates before and during ursodeoxycholic acid were 6.9 and 4.5, respectively, in serum, and 21 and 5.2, respectively, in urine. The major monosulphates in urine, dominated by 5alpha-pregnane-3alpha, 20alpha-diol, were also conjugated with N-acetylglucosamine. The excretion of these double conjugates decreased from 27+/-8.4 to 15+/-5.3 micromol/g creatinine during ursodeoxycholic acid. In contrast to sulphated steroids, the concentrations of glucuronides were unchanged in serum and their excretion in urine tended to increase during ursodeoxycholic acid. The metabolism of ursodeoxycholic acid was similar to that described in nonpregnant subjects. In addition to metabolites hydroxylated in the 1beta-, 5beta-, 6alpha/beta and 22-positions, a 4-hydroxy-ursodeoxycholic acid was tentatively identified. This occurred predominantly as a double conjugate with glycine/taurine and glucuronic acid, as did other 4-hydroxylated bile acids of probable foetal origin. CONCLUSIONS: The results are compatible with the contention that ursodeoxycholic acid stimulates the biliary excretion of sulphated progesterone metabolites, particularly those with a 3alpha-hydroxy-5alpha(H) configuration and disulphates. The effect(s) appears to be independent of the stimulation of bile acid secretion. An effect of ursodeoxycholic acid on the reductive metabolism of progesterone cannot be excluded.
Bile Acids and Salts↗
Profiles of bile acids and progesterone metabolites in the urine and serum of women with intrahepatic cholestasis of pregnancy.
BACKGROUND/AIMS AND METHODS: The etiology of intrahepatic cholestasis of pregnancy (JCP) is unknown. We have performed comprehensive chromatographic and mass spectrometric analyses of progesterone metabolites and bile acids in serum and urine of six patients in order to characterize changes that might be of importance for the development of the disease. RESULTS: Conjugated bile acids were increased in serum and urine of patients with ICP while the levels of unconjugated bile acids were similar in healthy pregnancies and ICP. Unconjugated and conjugated 7 alpha, 12 alpha-dihydroxy-3-oxo-4-cholenoic acid was excreted in urine both in healthy pregnancies and in ICP, possibly indicating a rate limitation of 3-oxo-delta 4-steroid 5 beta-reductase in pregnancy. The serum levels and urinary excretion of total sulfated progesterone metabolites were increased in ICP while the glucuronides were unchanged or low. Confirming previous results, the fraction of metabolites with 3 alpha-hydroxy-5 alpha(H) configuration was increased. The urinary excretion of 5 alpha-pregnane-3 alpha, 20 alpha-diol 3-sulfate, 20-N-acetylglucosaminide was greatly increased in ICP, as was that of 3 alpha-hydroxy-5 alpha-androstane-17 beta-carboxylic acid, assumed to be a progesterone metabolite. CONCLUSIONS: The combined results of this and previous studies are compatible with a primary change in the reductive metabolism of progesterone in ICP, resulting in increased formation of metabolites with a 3 alpha-hydroxy-5 alpha(H) configuration and a larger fraction of sulfates. There also seems to be a selective defect in the biliary secretion of sulfated metabolites, particularly disulfates.
Bile Acids and Salts↗
Antibiotic noncompliance and waste in upper respiratory infections and acute diarrhea.
A prospective cohort study was conducted to analyze factors associated with antibiotic noncompliance and waste among patients suffering acute respiratory infection (ARI) and acute diarrhea (AD). The study took place in four primary health care clinics in Mexico City, two belonging to the Ministry of Health (MoH) and two to the Mexican Social Security Institute (IMSS). Two hundred twenty-two patients with ARI and 155 with AD were included. Data about study variables and the assessment of compliance were obtained through patient interviews and direct observation. Factors associated with noncompliance were assessed through a multiple logistic regression procedure. Noncompliance was 60% for ARI and 55.5% for AD in both health care systems. Prescription of an antibiotic was justified only in 13.5% of cases. Associated factors were: increased duration of illness (OR 2.95; 95% CI, 1.17-7.41); complexity of the treatment: 3 or more doses per day (OR 2.47; 95% CI, 1.56-3.92), and treatment for more than 7 days (OR 1.94; 95% CI, 1.16-3.26); younger age of patient (OR 1.89; 95% CI, 1.18-3.02); and an inadequate physician-patient relationship (OR 1.87; 95% CI, 1.16-3.02). Antibiotic waste was higher in IMSS (ARI 39.3%, AD 32.6%), than in the MoH (ARI 21.2%, AD 16.4%). Educational strategies to modify physician prescribing practices and strengthen physician-patient relationships might improve compliance and decrease drug waste.
Acute Disease↗
Infant mortality due to acute respiratory infections: the influence of primary care processes.
A population-based case control study was conducted to ascertain whether the process of primary care can be a determinant of infant mortality due to Acute Respiratory Infection (ARI). Cases were 118 infants who died from ARI, individually matched with 118 infants who suffered an ARI episode and recovered. Information was gathered through interviewing mothers. Study variables were assembled into five subsets: children's characteristics; mothers' characteristics; access to medical services; process of primary care, and; sociodemographic variables. An index per subset was built to analyze the independent influence of each on ARI death risk. The index was constructed upon the weighted sum of the adjusted odds ratios (OR) within each subset. Then, the values of each index were collapsed into high/low values with the 50 percentile as a cut-off value. Next, by means of a conditional logistic regression procedure, an explanatory model of ARI mortality was obtained. The final multivariate model included the indexes that showed an independent effect: I) Process of care (OR 9.68, CI 95% 3.59-26.1): inadequate referral, attention provided by more than one physician and being attended by a private physician; II) children's characteristics (OR 7.22, CI 95% 2.35-22.2): perinatal history, lack of breast-feeding and incomplete immunization scheme; III) access to medical services (OR 5.27, CI 95% 2.02-13.7): geographic and economic barriers, lack of confidence in public health services, and; IV) mothers' characteristics (OR 4.03, CI 95% 1.18-13.8), mainly represented by untimely care seeking. We conclude that the management of the disease is a key determinant in which factors relating to the mother and the health services are strongly related. Our study reveals untimely care seeking, difficult access and inadequate disease treatment as important factors which deserve careful attention in the future. We also confirm the importance of biological determinants previously described. A main strategy to reduce infant mortality due to ARI should be to encourage training of primary care physicians, including private practitioners, focused on providing effective case management and emphasizing the education to mothers.
Acute Disease↗
Effect of quality of care on preventable perinatal mortality.
This study assessed and quantified the effect of quality of care on death preventability, independent of social and biological variables. One hundred and eighty-one avoidable perinatal deaths (cases) were compared to 341 non-avoidable ones (controls). Judgement criteria on death preventability were based predominantly on compliance with explicit hospital medical care standards, determined by peer review. The overall perinatal mortality rate was 24.8 per 1000 births and could be reduced by 35% if all avoidable perinatal deaths were prevented. Sixteen per cent of the deaths presented structural and 31.2% process deficiencies; both predominated among avoidable perinatal deaths (35.4% vs 5.3%, p < 0.000; and 79.3% vs 5.9%, p < 0.000, respectively). Structural deficiencies increased the risk of an avoidable perinatal death eleven-fold (95% confidence interval (CI) 4.1, 26.9; p < 0.001) and process deficiencies eighty-eightfold (95% CI 37.2, 204.5, p < 0.001), after controlling for confounders. The strength of the association between quality of care and preventable perinatal mortality was estimated.
Adult↗
Review: intrahepatic cholestasis. A puzzling disorder of pregnancy.
Intrahepatic cholestasis of pregnancy is characterized by skin pruritus and a biochemical cholestasis of mild to moderate severity appearing during pregnancy (mainly in the third trimester) and disappearing after delivery. It recurs in 40-60% of future pregnancies. The intensity of pruritus and the laboratory alterations (increased serum bile salts and transaminases in almost all patients, hyperbilirubinaemia in 20% of patients) fluctuate during one pregnancy and also vary in subsequent affected pregnancies. This disease has no meaningful consequences for the mother; in contrast, it is associated with an increased risk of foetal distress, causing premature deliveries and stillbirths. Cholestasis of pregnancy has been recognized in most countries and ethnic groups but its prevalence is higher in Chile (14% of deliveries in 1975 and approximately 4% in 1995) and in Sweden than in other countries. The cause in unknown. Sex hormones, mainly oestrogens and progesterone, appear to be involved in its pathogenesis. An interplay between a genetic metabolic predisposition and some environmental factor(s) is apparently relevant. Clinical and experimental studies suggest that a marginal selenium deficiency could be a dietary pathogenic factor. Some drugs attenuate pruritus and improve maternal cholestasis, but not the foetal prognosis. Ursodeoxycholic acid (UDCA) administration provides a significant improvement in maternal pruritus and in the biochemical abnormalities, with no adverse effects in the mother or child. Recent clinical and experimental studies show that UDCA administration improves maternal disease and foetal prognosis without any detectable adverse effects.
Cholestasis, Intrahepatic↗
Silicates, silicones and autoimmunity.
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Antibody Formation↗
[A tribute to Germán Schneider, MD, first editor of Revista Médica de Chile].
Germán Schneider was born in 1820 in Magdeburg, Germany, and graduated as M.D. at the University of Bonn. In 1848, caught by the political and intellectual reformist movement in Europe, he was exiled in Paris. As part of a large group of German immigrants, he arrived in Valdivia, Chile, in 1851. Later on he moved to Santiago and in 1871 he was nominated Professor of Clinical Medicine at the University of Chile school of Medicine. An active participant in the academic activities organized by Sociedad Médica de Santiago (a scientific society that evolved into the chilean Society of Internal Medicine) he was the leader of a six-men team who founded Revista Médica de Chile, in 1872. As first Editor of this medical journal, he established the basis for its continuous success and devotion to medical progress and education. Dr. Schneider died in 1884, leaving several distinguished pupils who followed his path, and a medical journal that now stands as one of the oldest in the world.
Chile↗