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Biomedical subjects

J M Lozano

Publications and source records attributed to J M Lozano.

At least 19 recordsLinked to original sources

Influence of nutrition on the effectiveness of superovulation programmes in ewes: effect on oocyte quality and post-fertilization development.

Two experiments were carried out to study the effect of nutrition on embryo development in two periods in superovulated ewes (Expt 1) and on oocyte developmental capacity during the late follicular phase (Expt 2). In Expt 1, a lower superovulation response in terms of animals ovulating (P < 0.05), ovulation rate per ewe ovulating (P = 0.1) and number of good quality embryos per animal treated (P < 0.07) was noted in ewes fed an ad libitum diet compared with ewes offered control (1.5 times the daily maintenance energy requirements, 1.5 x M) or low energy (0.5 x M) diets. Nutrition also modified the morphological and functional quality of the oocytes and embryos recovered. Thus, 92% of day 4 embryos recovered from ewes offered the control diet were classified as good embryos, compared with 70 and 82% of those recovered from ewes offered the ad libitum and low diets, respectively (P < 0.05). Ewes offered the ad libitum diet had a greater percentage of poorly developed embryos compared with ewes offered the control or low diets (P < 0.05). Ewes fed the low diet tended to have more non-fertilized oocytes than ewes offered the control diet (P = 0.09). Diet of recipient ewes to which good quality embryos were transferred on day 4 did not affect embryo quality, when assessed 12 days later (day 16 of pregnancy). However, recipient diet affected prostaglandin F(2alpha) (PGF(2alpha)) production in vitro, and uterine tissue that originated from recipient ewes on the low diet secreted more PGF(2alpha) relative to uterine tissue that originated from recipients on the control diet (P < 0.05). In Expt 2, fewer total (P < 0.05) and good quality (P < 0.01) oocytes and a lower percentage of good quality oocytes (P < 0.01) were obtained from superovulated ewes offered the ad libitum diet compared with ewes offered the low diet. In addition, cleavage rate tended to be higher (51 versus 35%, P = 0.09) in ewes offered the low diet compared with ewes offered the ad libitum diet. In conclusion, changes in diet can affect the quality of the oocyte and embryo in superovulated sheep. A lower superovulation response and a decrease in the quality of oocytes and embryos indicate that ad libitum diets are highly detrimental for superovulatory programmes when compared with low and control diets. In addition, the results from the present study indicate that a low energy diet during early embryo development increased the uterine production in vitro of PGF(2alpha) which could lead to a poor uterine environment thereby compromising the development of the embryo.

Animal Nutritional Physiological Phenomena↗

Ethical challenges in pharmacoepidemiological research in Colombia.

PURPOSE: To illustrate and to discuss some ethical challenges encountered during pharmacoepidemiological research in a developing country (Colombia), as well as the decisions made to solve them. METHODS: The authors in Bogotá describe three recent studies. The first one collected data from clinical records to evaluate the prescriptions patterns in recently graduated physicians. The second used an interrupted time series design, with a set of observations prior and after a combined intervention, to assess whether it improved the quality of intravenous antibiotic prescribing practices in a university-based hospital. The third evaluated pharmacists' advice in childhood acute respiratory infection and acute diarrhea through a community survey, followed by focus groups and in-depth interviews of key informers. RESULTS: The ethical issues raised by these studies include the need for obtaining informed consent from participants (physicians in Study 1 and drug sellers in Study 3), deciding when to intervene in case of gross prescription mistakes detected during the collection of data as part of the time series assessment (Study 2), the use of simulated clients to collect data in the community survey, and the use of study resources to buy, in some cases, useless medications (Study 3). CONCLUSION: Although ethical challenges in pharmacoepidemiology in non-industrialized countries like Colombia may be different from those in developed nations, ethical principles that guide research remain the same. The processes to safeguard these principles in Colombia for virtually all research are also universal in nature, and include the ethical review committee, subject privacy, informed consent, and disclosure of funding sources.

Anti-Bacterial Agents↗

Factors predicting nutritional derangements in patients with obstructive jaundice: multivariate analysis.

Patients with obstructive jaundice (OJ) that requires surgery often have malnutrition associated with increased perioperative morbidity. This study investigated the factors influencing nutritional derangements in these patients. A series of 46 OJ patients were investigated prospectively (28 malignant tumors, 18 benign obstructions). A nutritional risk index of < 83.5 was used to define protein-calorie malnutrition. Liver function, cholecystokinin (CCK), tumor necrosis factor-alpha (TNFalpha), and endotoxin levels were determined. A multivariate analysis was performed, and an obstructive jaundice malnutrition index (OJMI) was obtained. Altogether, 22 (48%) OJ patients had malnutrition (33% with benign obstructions, 57% with malignant disease). Malnourished patients had higher serum bilirubin levels (258 +/- 120 vs. 154 +/- 62 mmol/L; p = 0.005), longer duration of jaundice (16 +/- 9 vs. 9 +/- 5 days; p = 0.03), and higher plasma levels of CCK (4.0 +/- 1.3 vs. 1.7 +/- 1.0 pmol/L; p = 0.005), alanine aminotransferase (ALT) (226 +/- 209 vs. 187 +/- 161 UI/L; p = 0.01), endotoxin (15 +/- 10 vs. 6.5 +/- 7.0 EU/L; p = 0.007), and TNFalpha (69 +/- 82 vs. 23 +/- 15 pg/ml; p = 0.008) than those without malnutrition. However, only serum bilirubin, CCK, ALT, and patient age were predictors for malnutrition by multivariate analysis. Malnutrition might be expected (95% confidence interval) in patients older than 68 years with increased bilirubin (> 290 mmol/L) and ALT (> 210 UI/L) levels that corresponded with an OJMI > 55. It was concluded that nutritional alterations in patients with obstructive jaundice were determined by the intensity of the biliary obstruction correlated with increased plasma CCK levels as well as with liver dysfunction and patient age.

Aged↗

Epidemiology of hypoxaemia in children with acute lower respiratory infection.

OBJECTIVES: To determine the prevalence of hypoxaemia in children aged under 5 years suffering acute lower respiratory infections (ALRI), the risk factors for hypoxaemia in children under 5 years of age with ALRI, and the association of hypoxaemia with an increased risk of dying in children of the same age. DESIGN: Systematic review of the published literature. SETTINGS: Out-patient clinics, emergency departments and hospitalisation wards in 23 health centres from 10 countries. SUBJECTS: Cohort studies reporting the frequency of hypoxaemia in children under 5 years of age with ALRI, and the association between hypoxaemia and the risk of dying. MAIN OUTCOME MEASURES: Prevalence of hypoxaemia measured in children with ARI and relative risks for the association between the severity of illness and the frequency of hypoxaemia, and between hypoxaemia and the risk of dying. RESULTS: Seventeen published studies were found that included 4,021 children under 5 with acute respiratory infections (ARI) and reported the prevalence of hypoxaemia. Out-patient children and those with a clinical diagnosis of upper ARI had a low risk of hypoxaemia (pooled estimate of 6% to 9%). The prevalence increased to 31% and to 43% in patients in emergency departments and in cases with clinical pneumonia, respectively, and it was even higher among hospitalised children (47%) and in those with radiographically confirmed pneumonia (72%). The cumulated data also suggest that hypoxaemia is more frequent in children living at high altitude. Three papers reported an association between hypoxaemia and death, with relative risks varying between 1.4 and 4.6. Papers describing predictors of hypoxaemia have focused on clinical signs for detecting hypoxaemia rather than on identifying risk factors for developing this complication. CONCLUSION: Hypoxaemia is a common and potentially lethal complication of ALRI in children under 5, particularly among those with severe disease and those living at high altitude. Given the observed high prevalence of hypoxaemia and its likely association with increased mortality, efforts should be made to improve the detection of hypoxaemia and to provide oxygen earlier to more children with severe ALRI.

Acute Disease↗

Clinical epidemiological principles in bedside teaching.

Medical education emphasises the transmission of large amounts of short-lived medical information. Strategies must be developed to generate in the students, attitudes towards the independent search for and critical appraisal of evidences. Two complementary strategies are particularly well suited to promote these types of attitudes: clinical epidemiology and evidence-based clinical practice. Clinical epidemiology (CE) has been defined as "the science of making predictions about individual patients by counting clinical events in similar patients, using strong methods for studies of groups of patients to ensure that the predictions are accurate. The purpose of CE is to develop and apply methods of clinical observation that will lead to valid conclusions by avoiding being misled by systematic error and chance". On the other hand, evidence based practice has been defined as "an approach to the practice of medicine in which the clinician is aware not only of the evidences which support clinical practice, but the strength and soundness of such evidences". The paper discusses the usefulness of clinical epidemiology and evidence-based health practice for rational decision making at the bedside, and also as tools for clinical teaching. An example involving evidence-based strategies for the management of a patient with bronchiolitis in the emergency room is discussed.

Child↗

Reading a journal article.

Journal reading is an important continuing educational activity in terms of physician preference, frequency of use amount of time devoted to it and impact in changing practice. Clinicians trying to obtain information from journals face several tasks, including the need to assess both the quality and the applicability of the information found in published articles. This article describes the general principles for reading, critically, scientific papers that report clinical research results, which include establishing the kind of question that the authors were trying to answer, the type of study done, if the research design was appropriate for the question, and if it was conducted correctly. According to several available guidelines, once the reader has a clear idea of the study question it is necessary to assess the methods described by the authors in order to evaluate whether the research strategy used is likely to have errors resulting from bias and chance (random) variation. If the paper methodology seems to be adequate, the reader should proceed to determine the results of the article and their potential clinical impact. Finally, the reader must establish the extent to which the results are helpful in caring for his or her own patients, which means assessing the external validity and other related issues. The use of these strategies will improve the efficiency of readers for incorporating research results to their practice.

Education, Medical, Continuing↗

TNF-alpha dependent production of inducible nitric oxide is involved in PGE(1) protection against acute liver injury.

BACKGROUND: Tumour necrosis factor alpha (TNF-alpha) and nitric oxide modulate damage in several experimental models of liver injury. We have previously shown that protection against D-galactosamine (D-GalN) induced liver injury by prostaglandin E(1) (PGE(1)) was accompanied by an increase in TNF-alpha and nitrite/nitrate in serum. AIMS: The aim of the present study was to evaluate the role of TNF-alpha and nitric oxide during protection by PGE(1) of liver damage induced by D-GalN. METHODS: Liver injury was induced in male Wistar rats by intraperitoneal injection of 1 g/kg of D-GalN. PGE(1) was administered 30 minutes before D-GalN. Inducible nitric oxide synthase (iNOS) was inhibited by methylisothiourea (MT), and TNF-alpha concentration in serum was lowered by administration of anti-TNF-alpha antibodies. Liver injury was evaluated by alanine aminotransferase activity in serum, and histological examination and DNA fragmentation in liver. TNF-alpha and nitrite/nitrate concentrations were determined in serum. Expression of TNF-alpha and iNOS was also assessed in liver sections. RESULTS: PGE(1) decreased liver injury and increased TNF-alpha and nitrite/nitrate concentrations in serum of rats treated with D-GalN. PGE(1) protection was related to enhanced expression of TNF-alpha and iNOS in hepatocytes. Administration of anti-TNF-alpha antibodies or MT blocked the protection by PGE(1) of liver injury induced by D-GalN. CONCLUSIONS: This study suggests that prior administration of PGE(1) to D-GalN treated animals enhanced expression of TNF-alpha and iNOS in hepatocytes, and that this was causally related to protection by PGE(1) against D-GalN induced liver injury.

Alanine Transaminase↗

TNF-alpha but not IL-1alpha is correlated with PGE1-dependent protection against acute D-galactosamine-induced liver injury.

BACKGROUND: Prostaglandin E1 (PGE1) treatment of humans and rodents during acute hepatic failure ameliorates different parameters of hepatic dysfunction. PURPOSE: To investigate whether prevention of acute liver injury induced by D-galactosamine (D-GalN) with preadministration of PGE1 is correlated with a change in the concentration of two proinflammatory cytokines, as tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1alpha, and/or nitrite+nitrate (NOx), as nitric oxide-related end products in serum. RESULTS: D-GalN significantly increased alanine aminotransferase (ALT) and TNF-alpha concentration in serum 5 and 10 mins, respectively, after treatment compared with the control group (P< or =0.05). D-GalN did not change the IL-1alpha concentration at any time during the study. Preadministration of PGE1 to D-GalN-treated rats significantly reduced the ALT content and increased significantly the TNF-alpha concentration in serum 1, 2.5, 5 and 10 mins after D-GalN treatment compared with the D-GalN group (P< or =0.05). Nitric oxide was not involved in either the toxic effect due to D-GalN or the protection observed with PGE1 against D-GalN toxicity. CONCLUSIONS: Acute liver injury induced by D-GalN is correlated with an increased TNF-alpha release. Preadministration of PGE1 to D-GalN-treated rats exerted a priming effect on inflammatory cells to release enhanced levels of TNF-alpha but not IL-1alpha. These findings indicate that stimulation of TNF-alpha release may be involved in the acute D-GalN-induced liver injury and also in PGE1 protection from hepatotoxicity in clinical and experimental studies.

Alanine Transaminase↗

A preliminary report on the effect of dietary energy on prostaglandin F2 alpha production in vitro, interferon-tau synthesis by the conceptus, endometrial progesterone concentration on days 9 and 15 of pregnancy and associated rates of embryo wastage in ewes.

Two groups of ewes were fed to provide 1.70 x (high energy group; n = 15) or 0.56 x (low energy group; n = 15) energy requirements for maintenance of liveweight from 14 d before a synchronized mating in November until slaughter at 9 or 15 d after mating. We investigated the effects on interferon-tau (IFN tau) secretion by the conceptuses, prostaglandin F2 alpha (PG) production in vitro by endometrial tissue, and associated rates of embryo mortality, endometrial progesterone content and progesterone production by luteal tissue. No differences between groups in pregnancy rate were detected on Day 9 between the 2 groups. Proportionately (6/6 vs 2/5), there were more pregnant ewes in the high energy group on Day 15, although this difference did not reach significance (P = 0.06). The proportion of corpora lutea represented by embryos was significantly lower in undernourished ewes (P < 0.05). Secretion in vitro of PG was lower in the 2 pregnant ewes of the low energy group on Day 15, and it was accompanied by higher IFN tau secretion by conceptuses recovered from these ewes. However, the limited number of pregnant ewes recorded on Day 15 prevented any statistical comparison. Neither mean endometrial content of progesterone nor ovarian venous progesterone concentrations and production of progesterone by luteal were affected by nutrition. The provisional results of the present experiment indicate that undernutrition may induce a reduction in the rate of secretion of IFN tau and can therefore increase production of PG from the endometrium. This could initiate luteolysis. The lower pregnancy rates observed in underfed ewes could be mediated through this alteration in the signal of maternal recognition of pregnancy. However, these findings remain to be shown in further experiments including a larger number of animals, as they only represent data from 2 undernourished animals.

Animal Feed↗

Opioidergic and nutritional involvement in the control of luteinizing hormone secretion of postpartum Rasa Aragonesa ewes lambing in the mid-breeding season.

The role of endogenous opioids and nutrition on the inhibition of luteinizing hormone (LH) secretion during the postpartum period was investigated in a Spanish breed of sheep lambing in the mid-late breeding season. Two groups of adult Rasa Aragonesa ewes housed in individual pens and lambing on 30 December were fed during the suckling period to provide maintenance requirements and the production of 1.1 (M; n = 8) or 0.55 (L; n = 8) kg of milk per day. On days 10, 20 and 30 after lambing, the effect of a treatment with the opiate receptor antagonist naloxone (1 mg/kg at four hourly intervals) on LH secretion was assessed in half of the ewes of each group, the remaining females receiving four saline injections. After weaning, animals were fed to provide requirements for maintenance of liveweight. Blood samples were collected twice a week from day 20 postpartum until the end of March, and assayed for progesterone and prolactin. Although underfed ewes showed significantly lower mean plasma concentrations during the control period on day 20 postpartum, nutrition did not seem to modify LH secretion before naloxone or saline injections. Moreover, no differences between nutritional groups in the response to naloxone injections on pattern of LH secretion were found. In fact, naloxone treatment induced an increase of mean LH concentrations on days 10, 20 and 30 postpartum (at least, P < 0.05), of LH pulse frequency on days 20 and 30 (P < 0.05), and of LH pulse amplitude on days 10 and 20 (P < 0.05). Underfed ewes during the postpartum period showed a slower decline in plasma prolactin levels, with significant differences on days 29, 36 and 39 after lambing (P < 0.05). Only 3 M ewes ovulated before the onset of the seasonal anoestrus period. It is concluded that endogenous opioids are involved in the inhibition of LH secretion during the early suckling period of a reduced seasonality breed of sheep without any influence of nutrition on the response to naloxone treatment; however, ewes underfed before weaning failed to reactivate their cyclicity prior to the onset of the seasonal anoestrus.

Animal Nutritional Physiological Phenomena↗

Effect of undernutrition on the distribution of progesterone in the uterus of ewes during the luteal phase of the estrous cycle.

The effect of undernutrition on ovarian and uterine venous progesterone concentrations and endometrial progesterone content on Days 5 and 10 of the estrous cycle were studied. Forty ewes were synchronized using progestagen pessaries. At pessary withdrawal, the ewes were fed diets to provide either 1.5 or 0.5 times the daily maintenance requirement (Group H, n = 20 and Group L, n = 20, respectively). Ewes fed the low nutrition diet (Group L) had higher mean peripheral progesterone concentrations than those fed the high plane diet (Group H; P < 0.05) but lower endometrial progesterone content on Day 5 (P < 0.05). Neither ovarian nor uterine venous levels were affected by nutrition on either Day 5 or 10. Progesterone concentrations in blood samples collected ipsilateral to ovaries bearing a corpus luteum (CL) were higher than in the contralateral samples (P < 0.001). It is concluded that undernutrition can produce a reduction of endometrial content of progesterone the first week after mating. Since no differences in ovarian venous concentrations were observed, it remains to be shown whether this variation is due to other variables, such as the population of endometrial progesterone receptors or other nonhormonal factors.

Animals↗

Reduced amide pseudopeptide analogues of a malaria peptide possess secondary structural elements responsible for induction of functional antibodies which react with native proteins expressed in Plasmodium falciparum erythrocyte stages.

A psi[CH2NH] isoster bond was introduced by replacing one peptide bond at a time within the 1513 malaria peptide KEKMV motif to obtain a set of five pseudopeptides. The motif belongs to a Plasmodium falciparum malarial peptide coded 1513, derived from the MSP-1 protein. This high-binding motif included in the 1513 peptide is involved in the attachment of the malarial parasite to human erythrocytes. The novel malaria 1513 psi[CH2NH] surrogates were analyzed using RP-HPLC and MALDI-TOF mass spectrometry techniques. Nuclear magnetic resonance experiments allowed definition of the five pseudopeptide analogues' secondary structural features. Such structures are present in only a very few molecules in the 1513 parent peptide. A molecular model demonstrating the solution of the three-dimensional structure of the 1 513 peptide Pse-437 analogue was constructed on the basis of 1H-NMR spectral parameters. Monoclonal antibodies were generated to the five 1513 malaria peptide pseudopeptide analogues. These antibodies not only recognize the native MSP-1 (195 kDa) and its 83 kDa and 42 kDa proteolytic processing proteins but also different SPf(66)n malaria vaccine batches containing the native sequence. In addition, the mAbs were able to modify the kinetics of Plasmodium falciparum parasites' intraerythrocytic development and their ability to invade new RBCs. The presented evidence suggests that peptide bond-modified peptides could reproduce a transient state in 1513's native sequence and represent useful candidates in the development of a second generation of effective malarial vaccines.

Amides↗

Effect of PGE1 on TNF-alpha status and hepatic D-galactosamine-induced apoptosis in rats.

Prostaglandin E1 has hepatoprotective properties in several clinical and experimental models of liver dysfunction. Hepatotoxicity induced by D-galactosamine (D-GalN) is a suitable animal model of human acute hepatic failure. The aim of the study was to investigate if prostaglandin E1 (PGE1) protection against hepatic D-GalN-induced apoptosis was related to tumour necrosis factor-alpha (TNF-alpha) content in serum. This cytokine is associated with in vitro apoptosis and general inflammatory disorders. In this study, PGE1 was administered 30 min before D-GalN to rats. In other experiments, several doses of TNF-alpha were administered 15min after PGE1 to D-Ga1N-treated rats. Several parameters related to apoptosis and necrosis were measured by flow cytometry, gel electrophoresis, biochemical analysis, and optical and electron microscopy. Tumour necrosis factor-alpha was quantified by competitive enzyme-linked immunosorbent assay (ELISA). PGE1 by itself did not modify the cell cycle of hepatocytes and liver toxicity, but increased TNF-alpha in serum in comparison with the control group. D-Galactosamine increased the percentage of hepatocytes in apoptosis and in the S phase of the cell cycle, and decreased those in G0/G1. Such an increase of hepatocytes in apoptosis was correlated with a higher number of apoptotic bodies and DNA fragmentation in liver than control samples. Also, D-GalN increased alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase and TNF-alpha in serum compared with the control group. Pre-administration of PGE1 to D-GalN-treated rats reduced all the parameters of apoptosis and necrosis in liver, and increased additionallyTNF-alpha content in serum. In those experiments where low doses of TNF-alpha were administered to PGE1 and D-GalN-treated rats an inverse relationship appeared between TNF-alpha and ALT content in serum. In conclusion, the protective effects of PGE1 on D-GalN-induced apoptosis may be linked to its capacity to modulate cell division and/or its immunomodulatory activity. In this sense, our experimental results suggest that TNF-alpha could be involved in protection or exacerbation of liver damage in relation to the pathophysiological status of the liver.

Alprostadil↗

The effects of RGD (Arg-Gly-Asp) peptides on glaucoma filtration surgery in rabbits.

BACKGROUND AND OBJECTIVE: Integrins are the main mediators of the interaction between fibroblasts and extracellular matrix (ECM) during scar formation. The adhesion motive RGD (Arg-Gly-Asp) is contained in the ECM and is recognized by the integrin receptor. Soluble peptides containing the RGD sequence can compete with -RGD- contained in the ECM for binding to the integrin receptor and thus prevent cell adhesion and scar formation. MATERIALS AND METHODS: The peptides RGD (p602), GRGDSP (p603), GRGDSPCA (p604), and GGRGDSPCA (p605) were used in 25 glaucoma filtering surgeries in rabbits (five eyes per peptide and five with saline). RESULTS: Postoperative subconjunctival injections of peptides were given at days 0, 4, 8, 12, and 16. Bleb size, bleb survival, and signs of toxicity were examined. The GRGDSPCA and GGRGDSPCA showed an increase in bleb formation, size, and survival with no clinical signs of toxicity compared with controls (P < .008). Histopathologic evaluation confirmed inhibitory effects in scar formation with bleb formation, and transmission electron microscopy demonstrated that there was no toxicity to the ciliary body. CONCLUSION: These peptides were effective in controlling scar formation in glaucoma filtering surgery.

Animals↗

Acute lymphoblastic leukemia in children: nonrandomized comparison of conventional vs. intensive chemotherapy at the National Cancer Institute of Colombia.

BACKGROUND: This study aimed to compare the therapeutic efficacy of two treatments for childhood acute lymphoblastic leukemia (ALL), and to evaluate the feasibility of intensive chemotherapy in a developing country. METHODS: The study was conducted at the National Cancer Institute in Bogota, Colombia. Untreated ALL patients under 16 years of age were divided into two groups: a historical control cohort (HC) of 141 patients treated with conventional chemotherapy and an intensive chemotherapy cohort (IC) of 130 patients treated with a modified Berlin-Frankfurt-Münster protocol (m-BFM). Patients were clinically classified into risk categories for relapse, and followed through July 31, 1995. Disease-free survival (DFS) curves were obtained using the Kaplan-Meier method and were compared by the log rank test. RESULTS: Therapy groups had similar clinical baseline characteristics. Nonresponse rate to induction was higher in the HC group (16.3%) than in the IC cohort (7.6%) (P = 0.047), but deaths during induction were more frequent among m-BFM patients (13.8%) than in the HC group (6.4%) (P = 0.064). Bone marrow relapses after complete remission were less common in the IC group than in the HC group (19.4% and 45.9%, respectively; P = 0.0001), but central nervous system relapses showed no difference (12.8% in the HC and 16.3% under IC; P = 0.6). The DFS rates at 10 years were higher for the IC group, regardless of the baseline risk. CONCLUSIONS: IC reduces the frequency of relapses in ALL children in developing countries, when compared to previous therapy. A highly effective therapy such as m-BFM seems to be the most important predictor of outcome in children.

Adolescent↗