Effect of zinc on oropharyngeal mucositis in children with acute leukemia undergoing chemotherapy.

BACKGROUND: Oropharyngeal mucositis (OM) is one of the main side-effects of oncological therapy. There is no treatment to prevent its occurrence, but some zinc-based therapies have been proven to help in decreasing its intensity. The objective of this study was to determine the effect of zinc in OM in children with acute leukemia in the early stages of oncological treatment. MATERIAL AND METHODS: This quasi-experimental study evaluated OM in 2 groups (control group: conventional hospital management, and experimental group: administration of 50 mg of zinc gluconate daily plus conventional hospital management). OM severity was recorded at a two-month follow-up. RESULTS: Forty-nine patients (26 in the control group and 23 in the experimental group) were included. The mean age of the patients was 11.1 ± 2.7 years; 65.3% had a diagnosis of pre-B acute lymphoblastic leukemia. The incidences of OM in the control group and the experimental group were 46.2% and 26.1%, respectively, but the difference was not significant. Based on a negative binomial regression model, females had, on average, 1.5 more days with OM (p = 0.002), and patients assigned to the experimental group had, on average, 2 less days with OM than the control group (p = 0.001). The pain score was higher in the control group (p = 0.0009), as was the mean score on the WHO scale (p = 0.0012). CONCLUSIONS: Zinc facilitated a reduction in the severity and duration of OM; further studies focusing on children are needed to confirm the effects of this trace element.

[Thyroid dysfunction in children with chronic renal failure]. / Alteraciones de la función tiroidea en niños con insuficiencia renal crónica.

OBJECTIVES: To determine the frequency and type of thyroid dysfunction in children with chronic renal failure (CRF) in peritoneal dialysis (PD) or hemodialysis (HD); and to establish the accuracy of the presence of goiter to identify patients with CRF and thyroid dysfunction. PATIENTS AND METHODS: This is a cross-sectional study performed in a tertiary pediatric medical care center. CRF patients younger than 17 years old, with more than three months in PD or HD were included. All patients were assessed regarding their growth and sexual development; thyroid dysfunction was evaluated by serum concentration of thyrotropin (TSH), thyroxine (T4L) and triiodothyronine (T3T). RESULTS: 50 patients were included, 25 were male, and mean age was 12 years old. There were 14 (28%) patients with thyroid dysfunction; nine had subclinical hypothyroidism, three patients had euthyroid sick syndrome and two primary hypothyroidism. Thirteen patients had goiter: seven had thyroid dysfunction and in six patients the thyroid function was normal. The sensitivity of goiter to detect thyroid dysfunction was 50% and the specificity was 83.3%. The two patients with the greatest delay in their growth were hypothyroid. CONCLUSIONS: Given that the high frequency of thyroid dysfunction in children with CRF, these patients need a systematic screening, in order to improve their quality of care.

A pharmaco-economic analysis of second-line treatment with imatinib or sunitinib in patients with advanced gastrointestinal stromal tumours.

Second-line treatments recommended by the National Cancer Center Network to manage advanced-stage gastrointestinal stromal tumours (GIST) were evaluated to determine the cost and cost-effectiveness of each intervention in the Mexican insurance system, the Instituto Mexicano del Seguro Social (IMSS). Treatments examined over a 5-year temporal horizon to estimate long-term costs included 800 mg day(-1) of imatinib mesylate, 50 mg day(-1) of sunitinib malate (administered in a 4 week on/2 week rest schedule), and palliative care. The mean cost (MC), cost-effectiveness, and benefit of each intervention were compared to determine the best GIST treatment from the institutional perspective of the IMSS. As sunitinib was not reimbursed at the time of the study, a Markov model and sensitivity analysis were conducted to predict the MC and likelihood of reimbursement. Patients taking 800 mg day(-1) of imatinib had the highest MC (+/-s.d.) of treatment at $35,225.61 USD (+/-1253.65 USD); while sunitinib incurred a median MC of $17,805.87 USD (+/-694.83 USD); and palliative care had the least MC over treatment duration as the cost was $2071.86 USD (+/-472.88 USD). In comparison to palliative care, sunitinib is cost-effective for 38.9% of patients; however, sunitinib delivered the greatest survival benefit as 5.64 progression-free months (PFM) and 1.4 life-years gained (LYG) were obtained in the economic model. Conversely, patients on imatinib and palliative care saw a lower PFM of 5.28 months and 2.58 months and also fewer LYG (only 1.31 and 1.08 years, respectively). Therefore, economic modeling predicts that reimbursing sunitinib over high dose imatinib in the second-line GIST indication would deliver cost savings to the IMSS and greater survival benefits to patients.

Lipopopeptidephosphoglycan from Entamoeba histolytica activates human macrophages and dendritic cells and reaches their late endosomes.

Lipopopeptidephosphoglycan (LPPG) is a complex macromolecule from the surface of Entamoeba histolytica trophozoites. We analysed the interaction between LPPG and human macrophages and dendritic cells (DCs) and found that LPPG is internalized by these cells and activates them. The internalization process involves intracellular traffic from the cell membrane to late endosomes, as shown by co-localization of LPPG with late endosomes marked with FITC-dextran and LAMP-1. LPPG-activated DCs have increased expression of co-stimulatory molecules CD80, CD86 and CD40 and produce pro-inflammatory cytokines TNF-alpha, IL-8 and IL-12. Taken together, these results show that LPPG activates antigen-presenting cells and reaches intracellular compartments that are involved in antigen presentation.

Triggering receptor expressed on myeloid cells (TREM-1) is regulated post-transcriptionally and its ligand is present in the sera of some septic patients.

Inflammation is necessary for survival, but it is also an important cause of human morbidity and mortality, as exemplified by sepsis. During inflammation, cells of the innate immune system are recruited and activated in response to infection, trauma or injury. These cells are activated through receptors, such as Toll-like receptors (TLRs), which recognize microbial ligands such as lipopolysaccharide (LPS). Triggering receptor expressed on myeloid cells (TREM)-1 amplifies the inflammatory response initiated by TLRs, and its expression on the surface of monocytes increases in the presence of TLR ligands. Here we have shown that in monocytes TREM-1 mRNA levels, measured by reverse transcription-polymerase chain reaction (RT-PCR), remained unchanged and TREM-1 protein levels, measured by flow cytometry, increased, indicating that LPS increases TREM-1 expression by a post-transcriptional mechanism. We also showed that TREM-1/Fc fusion protein decreased the ability of the sera of some patients with sepsis to activate monocytes, indicating that the TREM-1 ligand, whose identity is unknown, may be present in the sera of some of these patients. We describe a mechanism for the regulation of TREM-1 expression on monocytes and the possible presence of its ligand in serum; these findings help to explain the contribution of TREM-1 during systemic inflammation.

Morphometric study of the human fetal heart. I. Arterial segment.

This study measured the dimensions of the great arteries of normal human fetal hearts at an early fetal stage (between 13-20 weeks post-fertilization) in 103 fetuses obtained by necropsy. Different segments of the aorta and the pulmonary artery were dissected and their external diameters measured under stereoscopic magnification. All segments showed linear growth during this period of fetal development. Ranges in median values of external diameters associated with the pulmonary artery were: 2.1-4.2 mm for the valve ring; 2.2-4.2 mm for the main pulmonary trunk; 1.2-2.5 mm for the right pulmonary artery; 0.9-2.18 mm for the left pulmonary artery; and 4.0-8.0 mm for the length of the main pulmonary trunk. Similarly, in the aorta, median diameters were: 2.1-4.2 mm for the ascending aorta; 1.92-3.8 mm for the aortic arch; 1.45-3.0 mm for the aortic isthmus; and 1.75 -3.35 mm for the descending aorta. The diameter of the ductus arteriosus ranged between 1.2-2.45 mm. The growth rates of the pulmonary artery and the aorta were similar. The diameter of the ascending aorta was found to be greater than that of the descending aorta and the right pulmonary artery was wider than the left pulmonary artery. In addition, the magnitude of growth in the various aortic segments was different and the ratios obtained between the aortic isthmus and the ascending and descending aortae, ranged between 0.66-0.93. This study provides important morphometric reference information concerning the dimensions and growth of the great arteries of the fetal heart and has clinical application in pediatric cardiac surgery and echocardiography.

[Frequency and risk factors associated with malnutrition in children with congenital cardiopathy]. / Frecuencia y factores de riesgo asociados a desnutrición de niños con cardiopatía congénita.

OBJECTIVES: To assess the frequency and risk factors of malnutrition among children with congenital heart disease (CHD). MATERIAL AND METHODS: Between August 1997 and May 1998, a cross-sectional survey was conducted among 244 children, at the congenital heart disease ward of the Cardiology Hospital, National Medical Center "Siglo XXI", Mexican Institute of Social Security, in Mexico City. Study subjects were male and female children younger than 17 years, diagnosed with CHD and without any other congenital malformation. Weight/Age (W/A), Height/Age (H/A) and Weight/Height (W/H) were used to measure nutritional status; Z scores greater than -2 was the case definition of malnutrition. Risk factors investigated were age, sex, perinatal history, dietary factors and nutritional supplementation, socioeconomic status, and family composition and functionality. Four CHD groups were studied: acyanotic with and without pulmonary hypertension (APH, AWPH) and, cyanotic with and without pulmonary hypertension (CPH, CWPH). Statistical analysis consisted of the chi-squared, Mann Whitney's U, and Kruskal-Wallis tests. Confounding variables were controlled for with a logistic regression model; odds ratios (OR) and 95% confidence intervals (95%CI) were calculated. RESULTS: APH was the most frequent CHD (62.7%), followed by CWPH (15.6%), AWPH (11.5%), and CPH (10.2%). Malnutrition was identified in 40.9% children with the W/A index, in 24.6% with the H/A index; and in 31.1% with the W/H index. Infants and the CPH group had the worst nutritional status. Risk factors associated with malnutrition were: having a cyanotic CHD (OR 2.54; 95%CI, 0.98-6.58), lack of nutritional supplementation (OR 2.38; 95%CI, 1.06-5.34), and a greater number of family members (OR, 1.42; 95%CI, 0.99-2.05). Older children were more likely to be well-nourished (OR 0.92; 95%CI, 0.89-0.96). CONCLUSIONS: Malnutrition is frequent among children with CHD; it is more common in younger children and in those with cyanotic CHD. Educational programs directed to the families of these children are needed to prevent and decrease the frequency of malnutrition. The English version of this paper is available at: http://www.insp.mx/salud/index.html

Prevalence of serological markers against measles, rubella, varicella, hepatitis B, hepatitis C, and human immunodeficiency virus among medical residents in Mexico.

BACKGROUND: Vaccination programs among health care workers are based on seroprevalence studies, which seldom include medical residents or students. The objective of this study was to determine the seroprevalence of antibodies against measles, rubella, varicella, hepatitis B (HBV), hepatitis C (HCV), and human immunodeficiency virus (HIV) among medical residents. METHODS: This study was designed as a prospective survey. A self-reported questionnaire was used to obtain the information. Serum samples were tested for antibodies by commercial immunoenzymatic assays. Statistical analysis was descriptive; history of exposure was evaluated as a diagnostic test and sensitivity, specificity, and predictive values were calculated according to Bayes theorem. RESULTS: Eighty-nine residents were included, the median age was 27 years, and 58 (65.2%) were female. Seventy-two (79.7%) had been vaccinated against HBV, but vaccination was complete in only 30/72 (41.6%). All were positive for measles and varicella, with the exception of one case for each. The serology for rubella was negative in 12 residents (10 women). Three residents had anti-core against HBV, with negative surface antigen. One positive case for HCV was confirmed by Western blot. All were negative for HIV. A history of prior varicella had a 100% positive predictive value; in contrast, the negative predictive value was quite low (7%). CONCLUSIONS: Negative serology for rubella among women and incomplete vaccination against HBV support the implementation of vaccination programs in medical schools in Mexico.

[Comparative study between bisoprolol and metoprolol, combined with hydrochlorothiazide, as antihypertensive therapy]. / Estudio comparativo entre bisoprolol y metoprolol, asociados a hidroclorotiazida, como terapia antihipertensiva.

The main objective of this research was to compare the efficacy and security of bisoprolol (B), a new cardioselective beta-blocker, that does not have intrinsic sympathomimetic activity, and metoprolol associated to hydrochlorothiazide (HCTZ), in the treatment of patients with mild to moderate hypertension. Sixty-two hypertensive patients (47 females and 15 males) aged 20 to 70 years (mean 52.5 +/- 10.4) were included in a double-blind, placebo controlled and randomized clinical trial. After a two-weeks wash out period and a similar placebo phase, patients were randomly assigned to receive either a once-daily dosing of B (10 mg) with 6.25 mg of HCTZ, or M (100 mg) plus 6.25 mg of HCTZ during four-weeks. If there was no reduction below 90 mmHg at the end of this period, the dosing of either beta-blocker was doubled. After eight weeks of treatment, the mean decreases in systolic/diastolic blood pressures from baseline were 31.8/21.2 and 28.0/20.6 mmHg for B/HCTZ and M/HCTZ, respectively (p < 0.0001). There were no clinically significant changes from baseline in laboratory parameters in either group. Reduction in blood pressure with B/HCTZ is associated with adverse events and metabolic changes similar to those observed with other antihypertensive drugs.

Security and maximal tolerated doses of fluvastatin in pediatric cancer patients.

BACKGROUND: The role of cholesterol in neoplasic cell growth and its inhibition by drugs has recently been studied. Cholesterol biosynthesis inhibitors have been used as adjuvants in the treatment of cancer and possibly as prophylactic in carcinogenesis. OBJECTIVE: The objective of the study was to determine the maximal tolerated doses (MTD) and toxic effects of fluvastatin in pediatric cancer patients. METHODS: This study was carried out in a third level Social Security Hospital in Mexico City. We included pediatric patients from April 1996 to May 1997. All were terminal cancer patients who did not respond to conventional therapies. Fluvastatin was given p.o. at doses of 2 mg/kg/day for 14 days every 4 weeks in three patients. Subsequent cohorts of three patients each had increments of 2 mg/kg/day of the drug until maximal tolerated doses were found. Toxic effects of the drug were evaluated by physical exploration, laboratory assays and a questionnaire given to each patient. RESULTS: Twelve patients were included. Diagnoses included two osteosarcomas, eight central nervous system tumors, one lung tumor, and one Ewing's sarcoma. Ten patients died within 1 to 18 months. Two are alive 22 months after inclusion into the study, both with anaplasic astrocytoma. A total of 27 courses were administered. The MTD was 8 mg/kg/day. Toxic effects were insomnia, nausea, vomiting, abdominal distention and myalgias. Toxicity was dose-dependent. Laboratory assays demonstrated no significant changes during treatment. CONCLUSIONS: Fluvastatin can be safely used at doses of 8 mg/kg/day in pediatric patients with cancer. This dose should be used in additional trials.

[Impact of the Friend of Child and Mother hospital program in a hospital in the Mexican Institute of Social Security]. / Impacto del Programa Hospital Amigo del Niño y de la Madre en un hospital del Instituto Mexicano del Seguro Social.

Breast feeding frequency in our country is between 13 and 80% and it is diminishing. One of the purposes of the Program called Hospital Friend of the Child and the Mother is to favor breast feeding but this has not been evaluated as yet. Frequency of breast feeding among the mothers who received the program, and the ones without it, in the influence area of HGZ 1-A; and the ones factors that could influenced for breast feeding. An analytic transversal study, was carried out, in mothers with a child between 6 and 12 months of age who assisted to the Outpatient consultation at HGZ 1-A and MME 10, 15 and 43, during the study period. The were invited to participate to have an interview, to know the mother's age, civil status, socioeconomical level, schooling and amount of sons. The place where her last delivery took place, was asked for. It was asked if breast feeding took place during the adequate time; the causes for not do it, and other points about breast feeding. The questionnaire in a first phase was prepared in order to be easily understood at the time of its application, and it was carried out by only one person. At the time of interview it was not known if the mother had used breast feeding or not. The amount in the sample was 261 mothers. The statistical analysis was of a descriptive type, for comparison of averages; it was used for comparison of square chi and calculations of reason of momios with IC at 95%. Two hundred and sixty two mothers were interviewed. The interview was done in 211/262, (80.5%) in the UMF and the rest at HGZ. Average age 26 years, 78.6% were married; average schooling, 8 years (74; good socioeconomical level, 70%, home labor. Amount of children was 1 to 6, 48% had only one child; average age of the last child at the time of interview, 11 moths. The resolution of the last pregnancy occurred in 73% of the cases in a IMSS hospital; 15.3% in a private hospital, and the rest in another institution. The program was given, more frequently at the IMSS, than in the rest 232/262; (88%) were breast fed. Average of time of breast feeding, 9 moths. There were no difference of sociodemographic variables in the group with breast feeding, and the one without breast feeding. The common causes (75%) for no breast feeding, were of maternal origin (infections, lack of milk production, work, etc.); the rest mentioned rejection to breast feeding. There was a better knowledge of breast feeding among the mothers who used it. The factors statistically associated to breast feeding were: conjoint lodging; to offer breast during the first hour of life; and have received information about this Program. The Program in the influence area of HGZ 1-A favors breast feeding. The factors for this were: improvement of mother-Child relation and the better knowledge of the advantages of breast feeding.

[Case-control study of an outbreak of S. marcescens in a neonatal intensive care unit]. / Estudio de casos y controles en un brote de S. marcescens en una unidad neonatal de cuidados intensivos.

OBJECTIVE: To analyze an outbreak of Serratia marcescens in a neonatal intensive care unit and identify the risk factors associated to the development of infection. MATERIAL AND METHODS: It was a case-control study from March to July 1995. Factors included were age, sex, intravascular devices, nebulizers, mechanical ventilation, use of total parenteral nutrition (TPN), underlying diseases, surgical interventions, tubes, previous antimicrobial treatment and days of exposure. The associations were explored using the odds ratio. RESULTS: 24 cases and 30 controls were included. In the univariate analysis the significant risk factors (OR,IC) were use of central venous catheter (4.57, 1.01-23.5), days of use of TPN (4.38, 1.03-16.5), days of previous antimicrobial treatment (4.87, 1.60-22) and days of exposure (2.7, 2.65-27.6). In the multivariate analysis the significant risk factors were previous antimicrobial treatment (3.98, 2.36-18.2), days of previous antimicrobial treatment (6.76, 3.02-24.6) and days of use of TPN (4.87, 1.67-15.6). CONCLUSIONS: The significant risk factors in our study were previous antimicrobial treatment, days of antimicrobial and days of use of TPN.

[Neurological and psychological sequelae in children with acute lymphoblastic leukemia who had received radiotherapy and intrathecal methotrexate]. / Secuelas neurológicas y psicológicas que deja la radioterapia o el metotrexate intratecal en niños con leucemia linfoblástica aguda.

UNLABELLED: Our objective was to compare the neurologic and psychological sequelae of children with acute lymphoblastic leukemia (ALL) after three or more years without antineoplasic treatment who underwent cranial irradiation plus intrathecal methotrexate (Group 1) or just intrathecal methotrexate (Group 2). In both groups, a neurologic evaluation, electroencephalogram (EEG) and cranial computed tomography (CCT) were performed. Intellectual quotient and the Bender test were done for the psychological evaluation. Investigators did not know the kind of treatment of each patient. STATISTICS: Fisher's exact test and Mann-Whitney U. There were fourteen patients in group 1 and eight patients in group 2. Intellectual quotient was statistically lower in the first group (median 83.5) than in the second (90.5). Neurologic impairments were found in one patient of each group, alterations of the EEG were found in 6 and 4 in group 1 and 2, respectively, and in the CCT of two patients in group 2 without statistical difference. Children with ALL after cranial irradiation have a greater alteration of intellectual performance than children with intrathecal methotrexate. Neurologic alterations were seen in both groups.

[Evaluation of diagnostic tests for hypocalcemia in critically ill newborns]. / Evaluación de pruebas diagnósticas de hipocalcemia en neonatos gravemente enfermos.

OBJECTIVE: To determine sensitivity (Sn), specificity (Sp), positive and negative predictive values (PPV, NPV) of total and calculated calcium and of QTc and QoTc intervals for the diagnosis of hypocalcemia in critically ill newborns. SETTING: A neonatal intensive care unit. METHODS: We included all newborn less than 28 days of age; we excluded those with calcium treatment, hypomagnesemia or congenital heart disease. Serum levels of total calcium, albumin and ionic calcium were measured as well as the QTc and QoTc intervals. Values for Sn, Sp, PPV and NPV were calculated according to cutoff points of the literature and with those of our receptor operating curves (ROC). Ionic calcium was considered the gold standard (hypocalcemia < 1.10 mmol/L). RESULTS: We included 53 newborns; 21/53 (40%) had hypocalcemia. Clinical features were similar among patients with or without hypocalcemia. For total calcium the Sn was 47%; Sp = 87%; PPV = 71% and NPV = 72%. For calculated calcium there values were: 55, 75, 57 and 73; for QoTc: 47, 81, 61 and 70%; and for QTc: 19, 87, 50 and 62% respectively. With the ROC values the Sn for total calcium and QTc was improved. CONCLUSIONS: Among critical ill newborns, total and calculated calcium were better in identifying patients with hypocalcemia whereas QTc and QoTc were better in those without hypocalcemia.

Empirical antimicrobial therapy in pediatric patients with neutropenia and fever. Risk factors for treatment failure.

BACKGROUND: The use of combinations of antibiotics has been the cornerstone of therapy for febrile patients with cancer and severe neutropenia. Each empirical regimen should be selected according to the epidemiology and susceptibility patterns in each center. We describe here the experience with empirical antimicrobial treatments in pediatric patients with cancer, fever and severe neutropenia, and identify the risk factors associated with treatment failure. METHODS: This is a prospective study including 145 patients with cancer, and 171 episodes of neutropenia and fever. Blood cultures were taken before initiating empirical treatment: a) carbenicillin (400 mg/kg/day) plus amikacin (21 mg/kg/day) (Cb/ak), and b) ceftazidime (100 mg/kg/day), plus amikacin at the same dosage (Cz/ak). RESULTS: The overall response rate was 54.9% and 56.3% for Cb/ak and Cz/ak, respectively. Fifty-seven episodes (33.3%) were microbiologically documented, gram-positive isolated in 38% and gram-negative in 49%. Risk factors associated significantly with treatment failure were acute myelocytic leukemia (AML) (RR 2.59, CI 95% 1.42-4.7, p = 0.003); bacteriological identification (RR = 4.41, CI 95% 2.21-8.8, p < 0.001), and the presence of two or more sites of infection (RR = 2.89, CI 95% 1.03-8.11, p = 0.03). CONCLUSIONS: The rates of response are similar to the combinations used in the hospital (Cb/ak, Cz/ak). The risk factors associated with treatment failure were AML diagnosis, bacteriological identification, and the presence of two or more sites of infection.

[Instrument to measure quality of life based on daily performance in pediatric patients with leukemia]. / Un instrumento para medir la calidad de vida por medio del desempeño diario en pacientes pediátricos con leucemia.

The objective of this study was to determine the validity of a questionnaire to measure daily performance as an evaluation of quality of life in pediatric leukemia patients. A questionnaire of the daily activities of a child according to Lickert's criteria was done. A pilot survey was performed in patients without a chronic or disabling disease in order to assess its validity. The impression of the medical attendance of each pediatric patient with leukemia, of their daily performance, was compared with the results of the instrument. A trained nurse applied the questionnaire to 60 mothers of patients (29 female/31 male) as outpatients during the clinical review. Fifteen questionnaires were applied twice to evaluate its consistency. According to the results, 77% of the patients were in remission. 15% in relapse, and 8% during induction to remission. The mean age of the patients was 9 = 3.6 years, ranging from 2-16 years. One hundred percent of the patients obtained a satisfactory grade greater than 35 points. In conclusion, the questionnaire identified adequately the level of the daily performance in addition to the specific affected areas of the patients with leukemia. Our findings are that their level of performance is satisfactory and is not affected because of the disease or the phase of the treatment.