Biomedical subjects
Publications and source records attributed to C Fernandez.
Phosphonate esters react with gamma-alumina under microwave (MW) irradiation; this reaction is a simple preparative method to graft organic pendant groups onto the surface of alumina; the efficiency of the grafting was readily checked by solid-state NMR techniques (31P and 27Al).
To investigate the mechanisms underlying improvement of arterial oxygenation during a protective ventilatory strategy (PVS) in early acute respiratory distress syndrome (ARDS), we studied eight patients during volume-controlled mechanical ventilation, keeping respiratory rate and fraction of inspired oxygen (FI(O(2))) (0.82 +/- 0.20) unchanged: (1) at baseline (tidal volume [VT] 10 to 12 ml x kg(-1); positive end-expiratory pressure [PEEP] 8 to 10 cm H(2)O); (2) during PVS (PEEP 2 cm H(2)O above the low inflexion point (P(FLEX)) and VT of 5 to 7 ml x kg(-1)); and (3) post-PVS, back to baseline conditions. Inert gas measurements were done after 30 min in each ventilatory modality. During PVS, Pa(O(2)) increased significantly from 93 +/- 27 to 166 +/- 77 mm Hg (p < 0.008) and Pa(CO(2)) rose from 39 +/- 7 to 57 +/- 11 mm Hg (p < 0.0002) because of the decrease in minute ventilation (V E) (-3.6 L x min(-1)) (p < 0.005). Both heart rate (HR, +13 min(-1)) (p < 0.002) and cardiac output (Q, +1.2 L x min(-1)) (p < 0.05) increased. Static respiratory system linear compliance increased from 36 +/- 14 to 44 +/- 16 ml. cm H(2)O(-1) (p < 0.0002). PVS provoked recruitment of previously collapsed alveoli and redistribution of pulmonary blood flow from nonventilated alveoli to normal lung. Despite the increase in Q, intrapulmonary shunt fell from 39 +/- 15% to 31 +/- 11% (p < 0.04). We conclude that the decrease in intrapulmonary shunt owing to alveolar recruitment remains the pivotal mechanism to explain improvement of arterial oxygenation during this PVS.
A key question for the understanding of photosynthetic water oxidation is whether the four oxidizing equivalents necessary to oxidize water to dioxygen are accumulated on the four Mn ions of the oxygen-evolving complex (OEC), or whether some ligand-centered oxidations take place before the formation and release of dioxygen during the S(3) --> [S(4)] --> S(0) transition. Progress in instrumentation and flash sample preparation allowed us to apply Mn Kbeta X-ray emission spectroscopy (Kbeta XES) to this problem for the first time. The Kbeta XES results, in combination with Mn X-ray absorption near-edge structure (XANES) and electron paramagnetic resonance (EPR) data obtained from the same set of samples, show that the S(2) --> S(3) transition, in contrast to the S(0) --> S(1) and S(1) --> S(2) transitions, does not involve a Mn-centered oxidation. On the basis of new structural data from the S(3)-state, manganese mu-oxo bridge radical formation is proposed for the S(2) --> S(3) transition, and three possible mechanisms for the O-O bond formation are presented.
The structure of a small-pore framework sodium stannosilicate Na(2)SnSi(3)O(9).2H(2)O (AV-10) has been determined ab initio from powder X-ray diffraction data (XRD). The unit cell is orthorhombic (space group C222(1), Z = 4) with cell dimensions a = 7.9453(5), b = 10.3439(7), c = 11.6252(7) A, V = 955 A(3). The structure of AV-10 is composed of corner sharing SnO(6) octahedra and SiO(4) tetrahedra, forming a three-dimensional framework structure. The SiO(4) tetrahedra form helix chains along [001] interconnected by SnO(6) octahedra. The SnO(6) octahedra are isolated by SiO(4) tetrahedra and, thus, there are no Sn-O-Sn linkages. AV-10 has been characterized by chemical analysis, powder XRD, scanning electron microscopy, (29)Si, (119)Sn, single- and (FAM) triple-quantum (23)Na MAS NMR spectroscopy, thermogravimetry (TGA), and nitrogen adsorption isotherms. The zeolitic water of AV-10 is reversibly lost. The dehydrated material has been studied in situ by powder XRD, TGA, and, in particular, triple-quantum (23)Na MAS NMR.
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).
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.
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.
The combination of large-acceptance high-resolution X-ray optics with bright synchrotron sources permits quantitative analysis of rare events such as X-ray fluorescence from very dilute systems, weak fluorescence transitions or X-ray Raman scattering. Transition-metal Kbeta fluorescence contains information about spin and oxidation state; examples of the characterization of the Mn oxidation states in the oxygen-evolving complex of photosystem II and Mn-consuming spores from the marine bacillus SG- are presented. Weaker features of the Kbeta spectrum resulting from valence-level and 'interatomic' ligand to metal transitions contain detailed information on the ligand- atom type, distance and orientation. Applications of this spectral region to characterize the local structure of model compounds are presented. X-ray Raman scattering (XRS) is an extremely rare event, but also represents a unique technique to obtain bulk-sensitive low-energy (<600 eV) X-ray absorption fine structure (XAFS) spectra using hard (approximately 10 keV) X-rays. A photon is inelastically scattered, losing part of its energy to promote an electron into an unoccupied level. In many cases, the cross section is proportional to that of the corresponding absorption process yielding the same X-ray absorption near-edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) features. XRS finds application for systems that defy XAFS analysis at low energies, e.g. liquids or highly concentrated complex systems, reactive compounds and samples under extreme conditions (pressure, temperature). Recent results are discussed.
B and T lymphocytes develop normally in mice lacking the guanine nucleotide exchange factor Vav-2. However, the immune responses to type II thymus-independent antigen as well as the primary response to thymus-dependent (TD) antigen are defective. Vav-2-deficient mice are also defective in their ability to switch immunoglobulin class, form germinal centers and generate secondary immune responses to TD antigens. Mice lacking both Vav-1 and Vav-2 contain reduced numbers of B lymphocytes and display a maturational block in the development of mature B cells. B cells from Vav-1(-/-)Vav-2(-/-) mice respond poorly to antigen receptor triggering, both in terms of proliferation and calcium release. These studies show the importance of Vav-2 in humoral immune responses and B cell maturation.
The larval stage of the parasite Echinococcus granulosus causes hydatid disease. The hydatid cyst is potentially capable of activating host complement, since it is a large, persistent, carbohydrate-rich structure, coated with host immunoglobulins, and localized in the host's internal organs. Nonetheless, in vitro studies have suggested that the cyst surface, the hydatid cyst wall (HCW), is a poor complement activator. In this study, we assessed the occurrence of in vivo complement activation on the hydatid cyst by measuring the levels of two complement activation products, C3d and complexes bearing a C9 activation neoepitope (TCC/MAC), in extracts from HCW of human origin. Low amounts of C3d and TCC/MAC were found in HCW in comparison with their levels in normal human plasma and activated human sera, suggesting that in vivo complement activation on HCW is efficiently down-regulated. This regulation may contribute to limit host inflammation which has been observed to correlate with parasite degeneration and death.
In 2000-2001 academic year the frequency distribution of hours slept per night was not significantly different from distributions of 1978-79 and 1988-89.
Using data collected from 9,543 university undergraduates, we noted that over three decades, the median hours of sleep reported by these students has decreased by more than one hour.
Over two decades, our data document a substantial linear increase in the percentage of university students who self-reported dissatisfaction with their sleep, i.e., 24% in 1978, 53% in 1988, and 71% in 2000.
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.
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.
OBJECTIVE: histological features of metastasis are not always specific of the origin. The usefulness of cytokeratin 7 and 20 (CK7 and CK20) in cerebral metastases from an adenocarcinoma was studied in a series of 78 patients. RESULTS: metastases from lung adenocarcinoma showed a CK7+/CK20- pattern in 79% of cases, CK7+/CK20+ in 19% and CK7-/CK20- in 2%. When observed, positivity for cytokeratin 20 was generally focal or weak. Breast adenocarcinoma metastases were CK7+/CK20- in 71% of cases and CK7-/CK20- in 29%. Less differentiated tumours were usually negative for both cytokeratins. Metastases by colonic adenocarcinoma were CK7-/CK20+ in 100% of cases. Cytokeratins 7 and 20 are useful to distinguish lung from colonic metastatic carcinoma. In case of double positivity, a more intense CK7 expression is rather suggestive of a lung origin. CONCLUSION: these results might modify paraclinic investigations in search of the primitive tumor.
The atypical teratoid rhabdoid tumor is a rare brain tumor of childhood. We report a congenital case, revealed by peripheral facial palsy. This polymorphous tumor consisted of rhabdoid cells associated with areas of primitive neuroectodermal tumor. The immunoreactivity for the three proteins vimentin, epithelial membrane antigen and smooth-muscle actin was suggestive of rhabdoid tumor. Genetic study showed a homozygous mutation in the tumoral DNA and a constitutional heterozygous mutation, as it was demonstrated in atypical teratoid rhabdoid tumors and in renal and extra-renal rhabdoid tumors.