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Biomedical subjects

J Navarro

Publications and source records attributed to J Navarro.

At least 73 records · Page 4Linked to original sources

Meiotic segregation analysis in a t(4;8) carrier: comparison of FISH methods on sperm chromosome metaphases and interphase sperm nuclei.

Meiotic segregation of a t(4;8)(q28;p23) translocation carrier was determined by two different methods to compare the final results. A total of 352 sperm chromosome complements, obtained after human-hamster in vitro fertilisation, were analysed by whole chromosome painting, and 6590 sperm heads were studied by fluorescence in situ hybridisation (FISH). Frequencies of alternate, adjacent I, adjacent II and 3 : 1 segregations were, for sperm chromosomes, 35.5, 33.2, 19.9 and 11.3% respectively. For sperm head analysis, results were 30.5, 28.5, 20.5 and 19.5% respectively. There were no statistically significant differences between the two methods with respect to the observed frequencies of sperm with balanced and unbalanced chromosome constitutions. Among unbalanced gametes, the methods differed only in the frequency of 3 : 1 segregation (chi(2), P<0.0001). Different factors that could explain this result are discussed. To determine possible interchromosomal effects, multicolour FISH was used on sperm heads. Disomy rates of sex and 18 chromosomes were higher in the translocation carrier than in the control. The differences observed were statistically significant (P<0.0001 for chromosomes X and 18, and P=0.0091 for chromosome Y).

Adult↗

Lansoprazole in children: pharmacokinetics and efficacy in reflux oesophagitis.

BACKGROUND: Data on the proton pump inhibitor lansoprazole in paediatric patients are limited. AIM: To investigate the pharmacokinetics, optimal dosage and efficacy of lansoprazole in paediatric patients. METHODS: A 24-h gastric pH recording and a pharmacokinetic study were performed after 7 days of lansoprazole, 17 mg/m2, in 23 patients with reflux oesophagitis (median age, 3.5 years). Response was defined as pH > 3 for > 65% of the recording. The dosage was doubled in non-responders. Patients with no response on day 14 were excluded. Responders underwent endoscopy after 4 weeks on the response-inducing dosage; abnormal findings led to a repeat endoscopy after four additional weeks. RESULTS: Nine patients responded to 17 mg/m2 and six to 30.3 mg/m2. On day 7, time with pH > 3 was significantly correlated with the area under the plasma concentration-time curve (P=0.003). The area under the plasma concentration-time curve was significantly greater in the nine responders to 17 mg/m2 than in the 14 other patients. Pharmacokinetic parameters were similar in responders and non-responders to the higher dose. After 4 weeks, oesophagitis was healed in 80% of responders. Adverse events occurred in three patients and required treatment discontinuation in one. CONCLUSIONS: Lansoprazole is effective and safe in children. The optimal starting dosage is 30 mg/m2 or 1.4 mg/kg.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Naïve and memory CD4+ T cells and T cell activation markers in HIV-1 infected children on HAART.

The objective of this study was to investigate the relationship between peripheral blood CD4+ T cell subsets and routine viro-immunological markers in vertically HIV-1-infected children undergoing highly active antiretroviral therapy (HAART). CD4+ and CD8+ T cell subsets were examined by three-colour flow cytometry. Plasma viraemia was quantified by a standardized molecular assay. A negative correlation between the %CD4+ T cells and both viral load and the %CD8+ T cells was observed. A strong positive correlation between the %CD4 T cells and naïve, CD38+ and non-activated CD4+ T cell subsets was found, whereas the %CD4 T cells correlated negatively with the numbers of memory, activated and memory-activated CD4+ T cell subsets. Elevated percentages of CD8 T cells were associated with increased memory and CD4+ CD62L-T cell subsets, whereas the naïve and CD4+ HLA-DRCD38+ subsets negatively correlated with the CD8%. Co-expression of CD62L on memory CD4+ cells and high expression of HLA-DR (but not of CD38) were associated with high viral load. No association between viral load and naïve CD4+ T cells was observed. Specific CD4+ T cell subsets may be more informative than routine surrogate markers in defining the evolution of HIV infection and immune reconstitution in children.

ADP-ribosyl Cyclase↗

The effect of repeated controlled ovarian stimulation in donors.

BACKGROUND: The effect of repeated controlled ovarian stimulation in young, healthy women who consented to donate their oocytes was assessed through a retrospective study. METHODS AND RESULTS: Between March 1994 and February 2000, 284 donors consented to at least two controlled ovarian stimulation cycles, with four donors undergoing up to nine cycles. Through an intra-group analysis we studied the oocyte retrieval rate, controlled by the duration and doses of stimulation, as well as the interval between cycles, finding that the number of retrieved oocytes was maintained during repeated controlled ovarian stimulation cycles. The oocyte quality, assessed as fertilization, implantation and pregnancy rates, was similar through five repeated controlled ovarian stimulation cycles. The same result was obtained when the interval in days was analysed as a continuous variable or categorized in <90 and > or =90 days. CONCLUSIONS: The analysis of the data suggests that successive stimulation cycles do not impair ovarian response in terms of quantity and quality of the oocytes obtained in this group of women. Furthermore, the interval between cycles does not influence the result of the stimulations.

Adolescent↗

Intravenous omeprazole in children: pharmacokinetics and effect on 24-hour intragastric pH.

BACKGROUND: Omeprazole is a proton pump inhibitor, acting selectively on the gastric parietal cell H+K+-adenosine triphosphatase. Data on the intravenous route are limited in children and not available in infants. OBJECTIVE: This study was designed to determine the pharmacokinetics and the optimal dosage of intravenous omeprazole in patients younger than 30 months of age. METHODS: Nine children (three girls), aged 4.5 to 27 months, with normal liver and renal functions requiring intravenous omeprazole were studied. After enrollment in the study and randomization, omeprazole was administered once daily, at 8 am, as a 1-hour infusion. Group 1, consisting of the first four patients, received 20 mg/1.73 m2, and group 2, consisting of the following five patients, received 40 mg/1.73 m2. At day 3, a 24-hour intragastric pH and a pharmacokinetic study of omeprazole were performed. Plasma concentrations were measured by high-performance liquid chromatography. RESULTS: Patients in group 2 had a significantly higher median pH (6.99 vs. 3.35; P = 0.01) and percent of monitored time with gastric pH >4 than children given 20 mg/1.73 m2 (90.6% vs. 44.8%; P < 0.01). Four had a pH more than 4 during more than 90% of the time versus none of the patients of group 1. The plasma concentration versus time curves showed rapid elimination of the drug. The median area under the curve of omeprazole was 0.78 microg. mL-1. h-1 (range, 0.55-1.64 microg. mL-1. h-1) and 3.95 microg. mL-1. h-1 (range, 1.9-4.9 microg. mL-1. h-1), respectively, in groups 1 and 2 (P < 0.05). Systemic clearance was not different between the two groups: median values were 0.68 and 0.42 L. kg-1. h-1 (P = 0.22). CONCLUSIONS: In critical situations, intravenous administration of omeprazole may be required in infants. The authors demonstrate that the dose of 20 mg/1.73 m2 is not effective in maintaining 24-hour gastric pH of more than 4 and that a dose of 40 mg/1.73 m2 is required.

Anti-Ulcer Agents↗

Endometrial quality in infertile women with endometriosis.

Several analyses in our infertility (IVF) and oocyte donation programs were carried out to gain clinical knowledge of the factors involved in the etiology of endometriosis-associated infertility. We first compared the IVF outcomes in women with tubal infertility and endometriosis. The results indicated that patients with endometriosis had a poorer IVF outcome in terms of reduced pregnancy rate per cycle, per transfer, and reduced implantation rate per embryo replaced. We then evaluated embryo development in vitro in women with and without endometriosis who underwent IVF and embryo replacement 72 hours after oocyte retrieval. We observed that compared to controls, patients with endometriosis had a significantly reduced number of blastomeres per embryo as well as an increased incidence of arrested embryos in vitro. In subsequent studies we compared fertility parameters in patients receiving donor oocytes. We noted that when donor oocytes came from patients without known endometriosis, embryo development and implantation rates were similar in patients with and without endometriosis. However, when the results of oocyte donation were classified according to the nature of the oocytes donated, patients who received embryos derived from oocytes from women with endometriotic ovaries showed a significantly reduced implantation rate compared to the controls. Taken together, these observations suggest that IVF in patients with endometriosis may be related to alterations within the oocyte, which, in turn, result in embryos of lower quality with a reduced ability to implant.

Endometriosis↗

Factors associated with poor pulmonary function: cross-sectional analysis of data from the ERCF. European Epidemiologic Registry of Cystic Fibrosis.

The European Epidemiologic Registry of Cystic Fibrosis began collecting longitudinal data on European cystic fibrosis patients in 1994. A cross-sectional analysis was performed to identify the factors associated with low values of % predicted forced expiratory volume in one second (FEV1) upon patient enrollment. Data from 7,010 patients aged > or =6 yrs were included. Clinical conditions, microbiological isolates and medications reported at enrollment or within the following 180 days were analysed for age-specific associations. Factors associated with FEV1 that were lower by >10% of pred values were: lower weight for age percentiles, haemoptysis, pneumothorax, pulmonary symptoms at presentation, Pseudomonas aeruginosa, Burkholderia cepacia, oral corticosteroids, nonsteroid anti-inflammatory drugs, dornase alfa, oxygen and assisted ventilation and, in patients >12 yrs old only, use of airway clearance techniques, inhaled bronchodilators, oral nutritional supplements, pancreatic enzymes and insulin or oral hypoglycaemics. Slightly impaired lung function (5-10%) was associated with: diabetes (> or = 18-yrs-old), gastro-oesophageal reflux, allergic bronchopulmonary aspergillosis, asthma-like symptoms, portal hypertension, Aspergillus spp. and Candida spp. Sex, Haemophilus influenzae and Staphylococcus aureus were not associated with impaired pulmonary status. Regular exercise (especially in older patients) and nasal polyposis were associated with slightly better FEV1. The results confirm those of previous studies and suggest selective prescribing in sicker patients.

Adolescent↗

Cystic fibrosis-related diabetes mellitus: clinical impact of prediabetes and effects of insulin therapy.

UNLABELLED: In patients with cystic fibrosis (CF), glucose intolerance preceding diabetes (prediabetes) may have adverse effects on nutritional status and respiratory function, which are reversible after the start of insulin therapy. Respiratory function (forced vital capacity and forced expiratory volume in one second) and body mass index (BMI) were compared retrospectively in a French cohort of 14 patients during the 5 y preceding insulin therapy for diabetes and in 14 age- and sex-matched controls with normal oral glucose tolerance tests. In the diabetic group, all three parameters deviated increasingly from the values in the controls; the differences became statistically different during the 6 mo before insulin therapy. The effect was more important in patients for whom diabetes mellitus was diagnosed on the basis of symptoms of hyperglycaemia than in patients for whom it was diagnosed by systematic screening, but still present in the latter. After insulin was started, respiratory function improved and the BMI returned to normal within 1 y. The annual insulin requirement increased from 0.62 during the first year to 1.25 during the fifth year. Glycosylated haemoglobin (HbAIc) values ranged from 6.6 to 7.8%. Only 2 episodes of severe hypoglycaemia were recorded over 42 patient-years of follow-up. The insulin regimen most often used was two daily injections of a mixture of short- and intermediate-acting insulin (n = 10) given with an insulin pen. CONCLUSION: The clinical status of CF patients who will need insulin therapy deteriorates before the start of insulin. In patients with CF-related diabetes, with or without fasting hyperglycaemia, insulin therapy improves anabolism and provides good glycaemic control with few severe hypoglycaemic episodes.

Adolescent↗

Phosphodiesterase 4 inhibitors prevent cytokine secretion by T lymphocytes by inhibiting nuclear factor-kappaB and nuclear factor of activated T cells activation.

Blockade of phosphodiesterase 4 with rolipram reduced the production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-5, IL-10, and IL-2 but poorly inhibited cell proliferation and interferon-gamma (IFN-gamma) production by activated human T cells. Addition of dibutyryl cAMP mimicked rolipram inhibitions on proliferation, IL-2, TNF-alpha, and IFN-gamma but not on IL-10 or IL-5 production. Moreover, the inhibitory effects of rolipram on proliferation, IFN-gamma, and TNF-alpha but not of IL-10 production can be prevented by a specific protein kinase A inhibitor. Rolipram and pentoxifylline, a nonspecific phosphodiesterase inhibitor, decreased transcription of IL-2 and TNF-alpha promoters in transiently transfected normal T cells. Moreover, they inhibited the activation of nuclear factor-kappaB (NF-kappaB) and nuclear factor of activated T cells (NFAT) and stimulated activator protein-1 (AP-1) and cAMP response element-binding proteins (CREBs). In contrast, dibutyryl cAMP inhibited NF-kappaB but not NFAT activation. Thus, our data indicate that blockade of phosphodiesterase 4 regulates transcription of a particular cytokine through inhibition of NF-kappaB and NFAT, and stimulation of AP-1 and CREB.

3',5'-Cyclic-AMP Phosphodiesterases↗

Increased levels of activated subsets of CD4 T cells add to the prognostic value of low CD4 T cell counts in a cohort of HIV-infected drug users.

OBJECTIVE: To identify subsets of CD4 T lymphocytes that can predict the development of AIDS and to assess whether increased levels of these cellular markers could provide additional independent prognostic information to the CD4 T cell count and plasma HIV-1-RNA levels. DESIGN AND METHODS: In a prospective study, a cohort of 85 HIV-positive intravenous drug users [clinical categories of the CDC classification A (n = 48) and B (n = 37)] were followed for a period of 37+/-13 months. Memory and activated CD4 and CD8 T cells were quantitated by three-colour flow cytometry at baseline and expressed as a percentage of total CD4 and CD8 lymphocytes. Clinical evaluations were performed at 6 month intervals. The relationships between these lymphocyte subsets and progression to AIDS were studied using Kaplan-Meier plots and proportional hazards regression models. RESULTS: After adjustment for the level of CD4 T cells and plasma HIV-1-RNA levels, the elevation in the subset CD4+CD38+DR+ was the marker within the functionally distinct subsets of CD4 T lymphocytes with additional prognostic value in bivariate Cox regression models. In multivariate models, increased percentages of CD4+CD38+DR+ T cells provided the strongest independent prognostic information for progression to AIDS (relative hazard, 1.07; P < 0.0001). CONCLUSION: Our results suggest that high levels of CD4+CD38+HLA-DR+ T cells reflect the increasing degree of CD4 T cell activation during the progression of HIV infection, and could be used together with the CD4 T cell and HIV-RNA levels to evaluate more accurately the progressive cellular immune impairment associated with the risk of progression to AIDS.

Adult↗

Comparison of amplicor, in-house polymerase chain reaction, and conventional culture for the diagnosis of tuberculosis in children.

A total of 251 clinical specimens (235 gastric aspirates and 16 bronchoalveolar lavages) from 88 children were prospectively tested in a blinded manner for the presence of Mycobacterium tuberculosis complex, by use of the Amplicor M. tuberculosis test and by means of in-house polymerase chain reaction (PCR). The results were compared with those obtained by conventional culture and by direct microscopy. All of the children underwent extended follow-up to verify or exclude the clinical diagnosis of tuberculosis. The results of the different tests, when compared to the final clinical diagnosis, were a sensitivity of 60% and a specificity of 96.8% for in-house PCR, 44% and 93.7% respectively for the Amplicor test, 44% and 100% for mycobacterial culture and 12% and 100% for microscopy. Amplicor tests presented false-positive findings in children without tuberculous infection. We conclude that both in-house PCR and the Amplicor test are rapid methods that can be helpful for difficult or urgent diagnosis of tuberculosis in children. However, efforts should be aimed toward improvement of the sensitivity and specificity of an easy-to-use PCR kit.

Child↗

Production of alcohol from raw wheat flour by Amyloglucosidase and Saccharomyces cerevisiae.

Ethanol production, by a simultaneous saccharification and fermentation process from raw wheat flour, has been performed by Saccharomyces cerevisiae and a low level of amyloglucosidase enzyme. The fermentation time was about 60 h after a 6 h pre-saccharification, with an amyloglucosidase (AMG) level of 270 AGU. kg(-1) starch, but only 31 h with a simultaneous saccharification fermentation process (SSF). When an AMG level of 540 AGU. kg(-1) starch was used, the time decreased to 21 h, giving an ethanol concentration of 67 g. l(-1). Sugar composition of the wort after the liquefaction may be responsible of the difference between these two process. Maltose, a fermentable sugar, was produced in high concentration during the liquefaction, allowing a shorter process period, counteracting the effect of the slow starch hydrolysis at 35 degrees C (SSF temperature).

Journal Article↗

[Obesity in the child].

The prevalence of childhood obesity increases dramatically in all industrialized countries. As in adults, it is defined by an increase in fat mass. The United States seem to be facing the most difficult situation. However, rapid changes in the way of life leads to consider that, in a near future, as much as 25% of the children in Europe could be concerned as well. A new epidemiological tool designed by the International Obesity Task Force takes as reference criteria the body mass index and will allow comparisons between countries as well as it will take into account the physiological variations of fat mass during growth. GENETICS AND ENVIRONMENT: A NEW PUZZLE: Inactivity seems to account as much as increased or unbalanced food intakes. While genetics account for a part of the disease at the population level, its role remains unclear in individuals. Most complications occur early in life, in a silent and progressive way. All these aspects do not only open fields of research but also provide new understanding and therapeutic basis for clinicians. PREVENTION: A PUBLIC HEALTH PRIORITY: Prevention has become a priority which should be based on early individual surveillance and Health Policy programs based on "National Recommendations for the diagnosis, prevention and treatment of obesity". All professionals dealing in one way or another with children lifestyle are concerned as well as do the families.

Adolescent↗