Biomedical subjects

C Fernandez

Publications and source records attributed to C Fernandez.

At least 19 recordsLinked to original sources

PubMed2001

Intestinal absorption and metabolism of chlorpheniramine enantiomers in rat.

Chlorpheniramine (CPAM) is a chiral antihistaminic drug commercialized as a racemic mixture. The intestinal absorption and metabolism of CPAM have been investigated in rat using in vivo (oral and IV administration), in situ (intestinal loop model), and in vitro (everted sac model) experiments. Oral and IV administrations of 20 mg/kg of the racemic mixture show that the pharmacokinetics of CPAM are stereoselective, with higher AUCs for the (+)-S-enantiomer compared to its antipode. The monodesmethyl metabolite (DCPM) was quantifiable in blood and its pharmacokinetics are stereoselective after oral but not after IV administration. Experiments using intestinal loops and everted sacs showed that the absorption is not stereoselective and that in vivo stereoselective formation of DCPM is presumably due to stereoselective hepatic metabolism. Moreover, the in vitro and in situ absorption of CPAM are not modified by modulators of P-glycoprotein and cytochromes P450 (cyclosporin A, ketoconazole).

Animals↗

PubMed2001

Characterization of the methylation-sensitive promoter of the imprinted ZAC gene supports its role in transient neonatal diabetes mellitus.

ZAC is a recently isolated zinc finger protein that induces apoptosis and cell cycle arrest. The corresponding gene is imprinted maternally through an unknown mechanism and maps to 6q24-q25, within the minimal interval harboring the gene responsible for transient neonatal diabetes mellitus (TNDM) and a tumor suppressor gene involved in breast cancer. Because of its functional properties, imprinting status, and expression pattern in mammary cell lines and tumors, ZAC is the best candidate so far for both disease conditions. In the present work, we delineated ZAC genomic organization and mapped its transcriptional start site. It is noteworthy that the ZAC promoter localized to the CpG island harboring the methylation imprint associated with TNDM and methylation of this promoter silenced its activity. These data indicate that the methylation mark may have a direct effect on the silencing of the ZAC imprinted allele. Our findings further strengthen the hypothesis that ZAC is the gene responsible for TNDM and suggest a novel mechanism for ZAC inactivation in breast tumors.

Alleles↗

PubMed2001

Comparison of elderly people's technique in using two dry powder inhalers to deliver zanamivir: randomised controlled trial.

OBJECTIVE: To determine whether elderly people can learn to use the inhaler used to deliver zanamivir (Relenza Diskhaler) as effectively as the Turbohaler and to identify which aspects of inhaler technique are most problematic. DESIGN: Randomised, controlled, intervention study. SETTING: Wards for acute elderly care in a large district general hospital. PARTICIPANTS: 73 patients who were unfamiliar with the use of an inhaler, aged 71 to 99 (mean 83) years. MAIN OUTCOME MEASURES: Initial scores and changes in scores 24 hours later using a 10 point scoring system of five aspects of inhaler technique. RESULTS: 38 patients were allocated the Relenza Diskhaler and 35 the Turbohaler. The mean total score was significantly greater in the Turbohaler than Diskhaler groups both initially (8.74 v 7.05) and after 24 hours (8.28 v 5.43). The major difference between inhalers was in loading and priming. After tuition 50% (19 of 38) of patients allocated the Diskhaler were unable to load and prime the device and 65% (24 of 37) were unable to do so 24 hours later. Of those allocated the Turbohaler, two patients were unable to load and prime the device after initial review and one after 24 hours. CONCLUSION: Most elderly people cannot use the inhaler device used to deliver the anti-influenza drug zanamivir. Treatment with this drug is unlikely to be effective in elderly people unless the delivery system is improved.

Administration, Inhalation↗

PubMed2001

Paediatric day-case surgery in a district general hospital: a safe option in a dedicated unit.

Currently, there is a trend towards the centralisation of paediatric surgery in specialist regional units. This study reports the results of 4 years' experience of paediatric day-case surgery in a dedicated unit within a district general hospital. Since its inception in 1993, data have been collected on all individuals undergoing surgery. Between 1993-1997, 804 operations were performed with 80% of procedures being undertaken by a consultant. There were 7 (< 1%) known complications and 7 (< 1%) patients required admission postoperatively. These results compare favourably with those of specialist institutions.

Adolescent↗

PubMed2001

[Criteria of low risk of mortality in children with neutropenia and fever during cancer chemotherapy].

To validate the use of a lower-risk mortality profile in pediatric febrile neutropenia during anticancer therapy and to evaluate the efficacy of a sequential parenteral-oral antibiotic treatment for these children, a prospective study was conducted between May 1997 and December 1999. During this period 247 episodes in 215 patients were included in the present study. Children with neutropenia (ANC < 500/mm3) and fever (> 38 degrees C) due to anticancer therapy were eligible for the study if they presented the following lower-risk conditions: absence of severe co-morbidity factors, good clinical condition, no risk clinical foci, no bacteremia, and responsible parents. They were initially treated with inpatient parenteral short course of ceftriaxone and amikacin followed by ambulatory oral cefixime or ciprofloxacin to complete 7 days. Mean age was 64 (range: 8-200) months. The most common underlying malignant disease was acute lymphoblastic leukemia in 48% (118) of cases and 57% (141) of patients had an indwelling central venous catheter. Clinical evidence of infection was found in 47% (122) of children and the most common site was the upper respiratory tract (81%). Mean period of fever was 1.1 days (r: 1-8) and the duration of neutropenia was 3.9 days (r: 1-9). Sixty-one% (150) of children was discharged with neutropenia. Mean time of hospitalization was 1.5 days. Four clinical failures were detected (1.6%). They all were satisfactorily treated with a secondary treatment and none underwent any major complications or died. The lower-risk profile used was safe and the sequential antibiotic therapy was adequate to manage febrile neutropenia in this subset of children.

Adolescent↗

PubMed2000

Resistance of natural killer T cell-deficient mice to systemic Shwartzman reaction.

The generalized Shwartzman reaction in mice which had been primed and challenged with lipopolysaccharide (LPS) depends on interleukin (IL)-12-induced interferon (IFN)-gamma production at the priming stage. We examined the involvement in the priming mechanism of the unique population of Valpha14 natural killer T (NKT) cells because they promptly produce IFN-gamma after IL-12 stimulation. We report here that LPS- or IL-12-primed NKT cell genetically deficient mice were found to be resistant to LPS-elicited mortality. This outcome can be attributed to the reduction of IFN-gamma production, because injection of recombinant mouse IFN-gamma, but not injection of IL-12, effectively primed the NKT cell-deficient mice. However, priming with high doses of LPS caused mortality of severe combined immunodeficiency, NKT cell-deficient, and CD1-deficient mice, indicating a major contribution of NKT cells to the Shwartzman reaction elicited by low doses of LPS, whereas at higher doses of LPS NK cells play a prominent role. These results suggest that the numerically small NKT cell population of normal mice apparently plays a mandatory role in the priming stage of the generalized Shwartzman reaction.

Animals↗

PubMed2000

Premedication with EMLA cream for ambultory surgery in children.

Objectives: The objective of this study was to confirm the ability of EMLA(R) cream (Eutectic Mixture of Local Anaesthetics, Astra, Sweden) to provide effective dermal analgesia after topical application on the skin of the dorsum of the hand 1 h before venous cannulation for anaesthetic induction. Material and Methods: Prospective, randomized, double blind study. We included 100 children, ASA I-III, distributed into three groups: Group EMLA (E, n=34), Placebo (P, n=33) and Control (C, n=33). Results: The EMLA group of patients (E) refered an evaluation of pain (visual analogical scale (mean=2.34+/-2.41), significantly smaller than the other groups (Placebo=5.54+/-3.40, Control=6.03+/-2.77). Conclusion: EMLA cream, when topically applied 1 h before venous cannulation, provides effective dermal analgesia for venous cannulation. No general or local adverse reactions were observed.

Journal Article↗

PubMed2000

Oral administration of cefixime to lower risk febrile neutropenic children with cancer.

BACKGROUND: Febrile neutropenia is a heterogeneous condition. Recently, several risk factors have been defined, permitting the definition of a lower risk group of patients who may benefit form less aggressive therapy. The use of an oral antibiotic approach was tested in the current trial. METHODS: From May 1997 to March 1998, 154 episodes of lower risk febrile neutropenia in 128 children with a mean age of 62 (range, 8-200) months were enrolled in this randomized, single-institution trial. Inclusion criteria were fever (> 38 degrees C), neutropenia (absolute neutrophil count < 500/mm(3)), lower risk features (i.e., absence of severe comorbidity factors, good clinical condition, negative blood cultures, control of local infection, no fever during the last 24 hours), and compliance of parents. After 3 days of ceftriaxone (100 mg/kg/day administered intravenously [i.v.]) every 12 hours plus amikacin (15 mg/kg/day i.v.) every 24 hours for 3 days, all patients were discharged and randomized to be allocated to 2 treatment arms. Group A (n = 74) received ceftriaxone cefixime (8 mg/kg/day administered orally) every 24 hours for 4 days, whereas Group B (n = 80) was treated with ceftriaxone plus amikacin for 7 days. Failure was defined as the need for second hospitalization during the same episode of neutropenia, or fever during the 7 days after discharge. RESULTS: Most of the patients (49% in Group A and 55% in Group B) had acute leukemia. Fifty-four (72%) children in Group A and 46 (56%) in Group B had fever of unknown origin (P = not significant [NS]). No significant differences were found in the sites of initial infection between the two groups. Overall results were outstanding, with a favorable outcome in 73 of 78 cases (98.6%) in Group A and 78 of 80 cases (97.5%) in Group B (P = NS). Three patients needed a second hospitalization due to failure of the initial therapy: one in Group A and two in Group B. All three did well with secondary treatment. CONCLUSIONS: In lower risk febrile neutropenic children receiving anticancer therapy, the efficacy of oral cefixime, given for 4 days after 72 hours of intravenous ceftriaxone plus amikacin, was similar to that of 7 days of parenteral ceftriaxone plus amikacin. The oral outpatient therapy approach to the treatment of lower risk febrile neutropenia after chemotherapy is safe and may be cost-saving. This strategy might be adopted as standard therapy in the future.

Administration, Oral↗

PubMed2000

The ADP-ribosylating CTA1-DD adjuvant enhances T cell-dependent and independent responses by direct action on B cells involving anti-apoptotic Bcl-2- and germinal center-promoting effects.

We recently developed a novel immunomodulating gene fusion protein, CTA1-DD, that combines the ADP-ribosylating ability of cholera toxin (CT) with a dimer of an Ig-binding fragment, D, of Staphylococcus aureus protein A. The CTA1-DD adjuvant was found to be nontoxic and greatly augmented T cell-dependent responses to soluble protein Ags after systemic as well as mucosal immunizations. Here we show that CTA1-DD does not appear to form immune complexes or bind to soluble Ig following injections, but, rather, it binds directly to B cells of all isotypes, including naive IgD+ cells. No binding was observed to macrophages or dendritic cells. Immunizations in FcepsilonR (common FcRgamma-chain)- and FcgammaRII-deficient mice demonstrated that CTA1-DD exerted unaltered enhancing effects, indicating that FcgammaR-expressing cells are not required for the adjuvant function. Whereas CT failed to augment Ab responses to high m.w. dextran B512 in athymic mice, CTA1-DD was highly efficient, demonstrating that T cell-independent responses were also enhanced by this adjuvant. In normal mice both CT and CTA1-DD, but not the enzymatically inactive CTA1-R7K-DD mutant, were efficient enhancers of T cell-dependent as well as T cell-independent responses, and both promoted germinal center formation following immunizations. Although CT augmented apoptosis in Ag receptor-activated B cells, CTA1-DD strongly counteracted apoptosis by inducing Bcl-2 in a dose-dependent manner, a mechanism that was independent of the CD19 coreceptor. However, in the presence of CD40 stimulation, apoptosis was low and unaffected by CT, suggesting that the adjuvant effect of CT is dependent on the presence of activated CD40 ligand-expressing T cells.

Adjuvants, Immunologic↗

PubMed2000

Stereospecific versus nonstereospecific assessments for the bioequivalence of two formulations of racemic chlorpheniramine.

Chlorpheniramine (chlorphenamine, CPAM) is a racemic antihistaminic H1 drug containing two enantiomers. The aim of this study was to assess the bioequivalence of two formulations (reference and Vietnamese-tested formulation) of racemic chlorpheniramine combined with phenylpropanolamine in an open-labeled, randomized, crossover two-period study, after administration of 8 mg of racemic chlorpheniramine in 12 healthy Vietnamese subjects. First, dissolution of both formulations was tested in vitro according to USP requirements. Then the 12 subjects received both formulations after an overnight fast and a 7-day wash-out period. Plasma samples were collected up to 168 h. Plasma concentrations of total chlorpheniramine and its individual enantiomers were determined with a validated chiral HPLC method and pharmacokinetic parameters were estimated using model-independent analysis. For the reference formulation, Cmax and AUC values were higher for (+)S-chlorpheniramine ((+)S-CPAM) compared to (-)R-chlorpheniramine ((-)R-CPAM) (13.3 vs. 6.8 ng/ml and 409 vs. 222 ng/ml/h, respectively) while Clt/F and Vd/F were lower (9.8 vs. 17.6 l/h and 321 vs. 627 l, respectively). No difference was observed for Tmax, t(1/2), and MRT. Pharmacokinetic parameters were similar for the reference and the Vietnamese-tested formulation. Bioequivalence was assessed by Schuirmann test, as recommended by the current FDA and European Community criteria. Dissolution tests showed that both formulations were equivalent. A nonstereospecific, but not a stereospecific, approach indicated bioequivalence between the formulations.

Adult↗

PubMed2000

Ecotoxicological evaluation of pig slurry.

Swine sewage could be source of nutrients and pollutants. This work estimates the environmental risk in nine samples from different farm treatment systems based on the evaluation of their effects in Daphnia magna acute test, and on the assessment of Cu, Zn and ammonia as main contributors. NH3 and Cu were responsible for LC50 results (1-5% of dilution). Organic compounds were quantified through several extraction methods (SPMDs, SPE and solvent extraction). A more exhaustive extraction was performed in an additional sample, which showed indole and phenol recoveries much higher than the previous ones. This method also includes PCBs (430 ppb) and fatty acids (approximately =150 ppm) quantification.

Ammonia↗

PubMed2000

Intraocular lidocaine in phacoemulsification: an endothelium and blood-aqueous barrier permeability study.

OBJECTIVE: To evaluate the effects of intraocular lidocaine hydrochloride (HCI) on the corneal endothelium and of blood-aqueous barrier (BAB) permeability in ultrasound phacoemulsification. DESIGN: Nonrandomized, comparative trial. PARTICIPANTS: Sixty patients who underwent uneventful, single-surgeon, clear cornea phacoemulsification were studied prospectively. METHODS: Sub-Tenon's anesthesia was administered to 30 patients (group 1), and intraocular lidocaine hydrochloride was administered to an additional 30 patients (group 2). An endothelial study of at least 120 cells per patient, using a noncontact specular microscope and a digital image analysis system, was performed before surgery and 1 month after surgery. Blood-aqueous barrier permeability was evaluated preoperatively and postoperatively (48 hours, 1 week and 1 month) using a laser flare meter. MAIN OUTCOME MEASURES: Endothelial parameters (cell density, hexagonality, and coefficient of variation in cell area) and BAB permeability. RESULTS: No significant differences were found between groups when comparing the postoperative changes produced in endothelial cell density (95% confidence interval [CI], 0.46, 4.7; P = 0.10), hexagonality (95% CI, -2.5, 3.5; P = 0.72), and coefficient of variation in cell area (95% CI, -8.3, 4.6; P = 0.57). A multivariate study detected no significant differences in mean flare values between groups during follow-up (P = 0.40). No clinically significant differences were found between mean preoperative and 1 month postoperative flare values in either group. CONCLUSIONS: The recovery of BAB permeability 1 month after surgery seems to suggest that no additional inflammation was induced by intraocular lidocaine HCI. The fact that no differences in postoperative changes in endothelial parameters were found between groups indicates that no further corneal endothelial damage (other than that caused by surgical manipulation) was incurred. According to our results, intracameral lidocaine HCI appears to be safe for the average phacoemulsification patient in the absence of ocular pathologic conditions.

Aged↗

PubMed2000

Celiac disease and TNF promoter polymorphisms.

The possibility that genetic susceptibility to celiac disease (CD) might be influenced by tumor necrosis factor (TNF) genes polymorphism has repeatedly been put forward. To date, this has only been investigated in case-control studies and results have been contradictory. In order to avoid any possible ethnic mismatching between patients and controls, we have approached this problem studying 71 celiac families, establishing the parental haplotypes and comparing CD versus control haplotypes (the so-called AFBAC or affected family-based controls). We used DNA-based methods to screen for HLA-DRB1, -DQA1, and -DQB1 alleles, TNFalpha promoter polymorphims and TNFa and b microsatellites. The guanine-to-adenine polymorphism at position -308 of the TNFalpha gene promoter region was found associated with CD as the TNF-308A allele appeared significantly increased in frequency in CD haplotypes, and this was shown to be independent of the association between CD and the DRB1*0301,DQA1*0501,DQB1*0201 alleles. Our results indicate that at least another gene, in addition to the known association of CD with HLA class II, has a susceptibility role in this disease. This should be either TNFalpha or another polymorphic gene in the telomeric end of the HLA class III region.

Celiac Disease↗

PubMed2000

LC analysis of benzophenone-3: II application to determination of 'in vitro' and 'in vivo' skin penetration from solvents, coarse and submicron emulsions.

The aim of this study was to determine the skin penetration of benzophenone-3 in vitro and in vivo in order to investigate a possible influence of formulation. Six different vehicles, three solvents and three different emulsion types were evaluated in vitro and in vivo. Each vehicle was applied to the skin model at 2 mg cm(-2). First, histological studies on ear pigskin and human skin were evaluated. In vitro measurements were performed with static diffusion cells using pigskin at 1, 2, 4, and 8-h. In vivo, benzophenone-3 concentration in stratum corneum was evaluated by the stripping method after 30-min application on forearm of volunteers. It was shown that ear pigskin and human skin appear similar and in both experiments significant differences between vehicles were noticed. The six vehicles could be ranked in the same order of benzophenone-3 skin concentration. At 8-h, the highest concentration of benzophenone-3 in skin was obtained with propylene glycol, and O/W submicron emulsion. On the contrary. the two oily solvents. W/O emulsion and O/W coarse emulsion restrain the concentration of this UV-filter in the skin. At each time, permeability in vitro and in vivo were well correlated. Low concentrations were measured in the receptor fluid suggesting that percutaneous absorption of this UV-filter across the skin would be minimal. The in vitro and in vivo skin penetration capacity of benzophenone-3 from six vehicles was confirmed and quantified. A satisfactory relationship between binary in vitro and in vivo was established.

Adult↗

PubMed2000

LC analysis of benzophenone-3 in pigskin and in saline solution: application to determination of in vitro skin penetration.

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Animals↗

PubMed2000

Large-scale mobilization and isolation of CD34+ cells from normal donors.

We describe collection and purification of peripheral blood CD34+ cells from volunteer, normal donors and allogeneic stem cell donors. A total of 98 aphereses were performed on 68 volunteer donors using peripheral venous access. The mean number of nucleated cells collected was 4.6 x 10(10) which included 1.9 x 10(8) CD34+ cells corresponding to 2.7 x 10(6) CD34+ cells/kg. The number of CD34+ cells collected did not differ between males and females but did correlate with the donor's weight and the total number of nucleated cells collected. The Nexell Isolex 300i cell separator was used to isolate CD34+ cells from 30 of the collections. A mean of 0.36% of the total cells was recovered and included 43 +/- 18% of the CD34+ cells. CD34+ cells represented 85 +/- 11% of the recovered cells. The total number of CD34+ cells recovered was not influenced by the number of nucleated cells placed on the Isolex 300i. The percentage of CD34+ cells recovered was not related to the number of CD34+ cells placed on the Isolex 300i. The purity of the final product was influenced by the number of CD34+ cells but not the total number of nucleated cells. An additional 38 CD34+ cell isolations were performed on normal allogeneic stem cell donors with similar results. These observations further support the safety and feasibility of peripheral blood CD34+ cell collection and purification.

Adult↗

PubMed2000

Epidural analgesia-anaesthesia in obstetrics.

Epidural analgesia is the most effective and innocuous technique for obstetrics. Pain relief is its main indication but maternal diseases that might be decompensated by labour and delivery are also accepted indications. Low doses of long-acting local anaesthetics alone or in combination with low doses of fentanyl or sufentanil provide good quality analgesia and are safe for mother and fetus. Test doses in parturients lack sufficient specificity and sensitivity for detecting inadvertent intravascular injection, and subarachnoid migration of the catheter is possible at any time during the procedure. Therefore, every injection must be considered as a test dose and only fractionated injections must be made. Epidural block to T10 is needed for labour and to level T4 for Caesarean section. Maintenance of the block with a continuous infusion, or patient-controlled epidural analgesia with a background continuous infusion, provides more stable analgesia than by intermittent injection. Technical difficulties, dural tap, bloody tap, hypotension and insufficient block are most frequent complications of epidural block in obstetrics. Excessive motor block prolongs the second stage of labour and increases the frequency for instrumental delivery and is therefore considered a complication.

Analgesia, Epidural↗

PubMed2000

Do automated red cell exchanges relieve priapism in patients with sickle cell anemia?

Priapism is a dramatic, painful complication for some men afflicted by sickle cell anemia. Although the natural history remains unclear, many believe replacing the patient's abnormal red blood cells (RBCs) with normal RBCs by apheresis is effective. However, no controlled trials have demonstrated its effectiveness. We exchanged 7 men after medical management failed. All procedures reduced sickle hemoglobin levels to < 30%. Two patients underwent emergency automated red cell exchanges without any detumescence or reduction of pain. The remaining 5 patients were exchanged non-emergently; 4 experienced no detumescence or relief of pain. One adult experienced resolution 8 h postexchange. However, he had a history of "stuttering" priapism. All required decompression procedures. Automated RBC exchanges were not effective in achieving detumescence or reducing pain.

Acute Disease↗