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Biomedical subjects

J Garcia

Publications and source records attributed to J Garcia.

At least 19 recordsLinked to original sources

Association of insulin-like growth factor-1 receptor polymorphism in dementia.

There is an increasing interest in how oxidative stress can cause cells to go into apoptosis in both normal ageing and in neurodegenerative disorders. Previous research has implicated insulin-like growth factor-1 (IGF-1) as being involved in the pathogenesis in Alzheimer's disease (AD) by protecting the neurons through reducing neuronal susceptibility to oxidative stress. IGF-1 receptor (IGF-1R) polymorphisms alter cerebral and systemic levels of IGF-1 and may alter the function of the receptor. We genotyped the IGF-1R gene by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) to assess whether this gene polymorphism can be linked to dementia. We used leukocyte DNA from 72 patients with AD, 75 patients with vascular dementia (VaD), 14 patients with mixed dementia (AD+VaD), and a control group consisting of 209 individuals without a history of progressive neurological disorders. Analysis of gene frequency for gender revealed a significant difference between female VaD patients and female controls carrying at least one A allele (OR = 1.8, CI 95% 1.1-2.9, p = 0.02), but not for male patients. In addition, we found a strong tendency to a difference between all cases of female dementia patients and controls carrying the A allele (OR = 1.5, CI 95% 0.99-2.2, p = 0.054). Our results suggest that the A allele of IGF-1R may be involved in the pathogenesis of VaD in females.

Aged↗

Laparoscopic intraperitoneal hyperthermic chemotherapy for palliation of debilitating malignant ascites.

AIM: To report the use of laparoscopic Intraperitoneal Hyperthermic Chemotherapy (LIPHC) in the treatment of malignant ascites. METHODS: From September 2001 to December 2003, 14 patients between the age of 56 and 78years were treated. Ascites was from gastric cancer (5 cases), colorectal cancer (3 cases), ovarian cancer (3 cases), breast cancer (2 cases) and peritoneal mesothelioma (1 case). The LIPHC was carried out at 42 degrees C for 90 min with 1.5% dextrose solution as a carrier. Chemotherapy was cisplatin and doxorubicin or mitomycin depending on the type of primary tumor. The drains were left in situ after surgery and removed when perfuse drainage ceased. RESULTS: Ascites was controlled in all the treated cases. A CT scan performed in follow-up showed a small, clinically undetectable, fluid accumulation in the pelvis of one patient. CONCLUSIONS: This method resulted in benefit for those peritoneal carcinomatosis patients with debilitating malignant ascites who were excluded from cytoreductive surgery. Proficiency in laparoscopic staging procedures and experience in the management of carcinomatosis and intraperitoneal hyperthermic chemotherapy (IPHC) are required for the success of the procedure.

Aged↗

A study to validate the method based on DIMOND quality criteria for cardiac angiographic images.

A method based on image quality criteria (QC) for cine-angiography was developed to measure the quality of cine-angiograms (CA). A series of 30 CA for left ventriculography (LV) and left and right coronary angiography (LCA, RCA) have been scored and 172 readings were obtained. Standard deviation of quality scores indicated the reproducibility of the method. Each part of CA was examined separately, giving scores for LV, LCA and RCA and a total score (TS), with clinical (C) and technical (T) criteria defined and examined separately. In 83% of the studies TS was >0.8 and with standard deviation from 0.02 to 0.21. In general, LV had a lower score and greater disagreement compared with RCA and LCA. Disagreement was greater in T, compared with C. In conclusion, these results indicate that QC, translated into a scoring system, yields reproducible data on the quality of cardiac images.

Cineangiography↗

Infectious pancreatic necrosis virus establishes an asymptomatic carrier state in kidney leucocytes of juvenile Atlantic cod, Gadus morhua L.

Juvenile Atlantic cod (10 g) were infected with infectious pancreatic necrosis virus (IPNV) by intraperitoneal injection and cohabitation. Fish showed no signs of disease but IPNV could be re-isolated from kidney tissue for up to 12 weeks. On weeks 2, 5, 8, 10, 11 and 12 following infection, kidney leucocytes were fractionated on Percoll gradients, and cells separated into plastic adherent and non-adherent cell populations after overnight incubation. IPNV was detectable in lysates of both cell populations and in supernatants by culture in CHSE-214 cells. Wells containing 10(5)-10(6) macrophages had an IPNV TCID(50) of about 10(3)/well and in serially diluted macrophages the minimum number of cells required to detect virus ranged from 10(1) to 10(4). These data indicate that about one in 10(4) macrophages were infected and the mean number of virus/infected cell was about 10. Replication of IPNV in the macrophages was low as the titre of the virus in macrophage lysates did not increase between days 1 and 3 of culturing the macrophages, but virus was released into the supernatant over this time.

Animals↗

Ex vivo expansion of umbilical cord blood CD34 cells in a closed system: a multicentric study.

BACKGROUND AND OBJECTIVES: The Dideco 'Pluricell System' is a CE-marked medical device allowing haematopoietic stem cell (HSC) expansion. It comprises a kit of cGMP cytokines and reagents, a closed-cell expansion chamber and a cell-washing set. We tested the system in a multicentric study by expanding CD34(+) cells from eight fresh umbilical cord blood (UCB) samples. MATERIALS AND METHODS: During culture, the mean nucleated cell (NC) count, the mean CD34(+) cell count, fold expansion, viability and apoptosis were measured. Clonogenic assays and immunophenotypical characterization were performed on days 0, 7 and 12. On the expanded cellular product, in three cases cell genotyping, endotoxin level and mycoplasma detection (by polymerase chain reaction) were performed. RESULTS: The mean CD34(+) cell expansion on days 7 and 12 was sevenfold and 12-fold respectively and the mean NC expansion was 69-fold and 180-fold. The mean NC viability on day 12 was 96.9% (94.4-99.1). After 12 days, granulocyte-macrophage colony-forming units (GM-CFU) showed a 20-fold increase: a slight increase in CD34(+) cell apoptosis was observed during culture. In all of three cases neither chromosomal alterations nor mycoplasma contamination was detected. No significant endotoxin levels were detected after expansion. CONCLUSIONS: The device allows the ex vivo expansion of NC and CD34(+) cells in a closed system. The expanded cellular product is a mixture of progenitors (CD34(+) cells) and differentiated (mainly myeloid and megakaryocytic) cells. To reduce cell apoptosis, more frequent cell feeding during culture should be tested.

Antigens, CD34↗

Cytotoxic proteins combined with prodigiosin obtained from Serratia marcescens have both broad and selective cytotoxic activity on tumor cells.

Cytotoxic proteins and prodigiosin obtained from Serratia marcescens strains are known to induce tumor cell death, nevertheless its combination has not been studied. In this paper we evaluate the combined effects of these molecules in a panel of tumor cell lines. The results showed a marked inhibitory effect on the growth of tumor cell lines derived from tumors (i.e., melanoma) which are highly resistant to conventional anticancer drugs, while normal cells were less sensitive than tumor cells. TUNEL (TdT-mediated dUTP nick end labeling) and electrophoresis of HEp-2 cell DNA treated with MG2327 preparation [containing the P50 protein belonging to the serralysins and prodigiosin, from S. marcescens CMIB4202] showed a pattern of DNA fragments typically associated with apoptosis. Interestingly, prodigiosin enhanced by 1.6-fold the cytotoxic effect of P50 when acting in combination on HEp-2 cells. The broad cytotoxic activity of the combination on tumor cells as well as its selectivity open new frontiers in cancer therapy.

Anti-Bacterial Agents↗

Impacts of urbanization on West Nose Creek: a Canadian experience.

The lower reaches of West Nose Creek have been subject to urbanization since the 1970s, leading to channel widening and excessive erosion. This paper discusses what would likely happen if urbanization were allowed to continue in the same manner. Comparisons are presented of the channel width and depth for both the upstream rural and downstream urbanizing reaches. Estimates of the evolution of the creek were generated by linking the dominant discharge to the entire shape and volume of the hydrograph that the creek is subjected to rather than solely considering peak discharges. otential remedial measures and stormwater management philosophies are discussed in relationship to instream flow needs (IFNs) initiatives. IFNs are generally developed by relating the amount of suitable aquatic habitat to the quantity of flow. The emphasis has so far been on IFNs for large river systems. Unfortunately, none of the IFN approaches cover streams that are subject to significant urbanization. In urbanized streams the issue is not as much the impacts due to withdrawals but due to significantly increased runoff rates and volumes generated within the urban areas. Examples are provided how fisheries habitat is impacted by the changed hydrologic regime and changed stream morphology.

Alberta↗

Perfusion MR imaging of an intracranial collision tumor confirmed by image-guided biopsy.

We present a patient with a new intracranial mass lesion that was initially interpreted as a metastasis on conventional anatomic MR imaging. On dynamic, contrast-enhanced, susceptibility-weighted perfusion MR imaging, however, there were regional hemodynamic differences within the lesion. Image-guided open biopsy targeting these regions uncovered a collision tumor between a typical meningioma and a metastatic breast carcinoma. In cases where conventional anatomic MR imaging is ambiguous, physiology-based neuroimaging methods provide complementary physiologic information useful for discriminating between histologically unique tissue types.

Biopsy↗

Young people and healthy eating: a systematic review of research on barriers and facilitators.

A systematic review was conducted to examine the barriers to, and facilitators of, healthy eating among young people (11-16 years). The review focused on the wider determinants of health, examining community- and society-level interventions. Seven outcome evaluations and eight studies of young people's views were included. The effectiveness of the interventions was mixed, with improvements in knowledge and increases in healthy eating but differences according to gender. Barriers to healthy eating included poor school meal provision and ease of access to, relative cheapness of and personal taste preferences for fast food. Facilitators included support from family, wider availability of healthy foods, desire to look after one's appearance and will-power. Friends and teachers were generally not a common source of information. Some of the barriers and facilitators identified by young people had been addressed by soundly evaluated effective interventions, but significant gaps were identified where no evaluated interventions appear to have been published (e.g. better labelling of food products), or where there were no methodologically sound evaluations. Rigorous evaluation is required particularly to assess the effectiveness of increasing the availability of affordable healthy food in the public and private spaces occupied by young people.

Adolescent↗

Pharmacokinetics and synovial fluid concentrations of flurbiprofen enantiomers in horses: chiral inversion.

Flurbirpofen (FBP), a member of the 2-aryl propionate nonsteroidal anti-inflammatory drug class, has potent anti-inflammatory and analgesic properties. The commercial preparation is a racemic mixture of the R(-) and S(+) enantiomers of FBP. In this study, R(-) and S(+) FBP were used to investigate the metabolic chiral inversion. Each enantiomer was administered separately (0.25 mg/kg) and in a racemic mixture (0.5 mg/kg) intravenously to horses. Plasma and synovial concentration of each enantiomer was determined and the disposition of each was analyzed. After intravenous administration of R(-) FBP and S(+) FBP to horses no chiral inversion was detected. After the administration of the FBP racemate and individual enantiomers no differences were observed between pharmacokinetic parameters [t(1/2beta) (h), Cl (L/h.kg), AUC (microg.h/mL), Vss (L/kg) and MRT (h)] for R(-) and S(+) FBF. Synovial fluid concentrations of both FBP enantiomers were lower than plasma concentrations and no stereoselective differences were detected. These data indicate that the disposition of FBF in horses is not enantioselective and demonstrate a difference in the pharmacokinetic behavior of the enantiomers as compared with other 2-aryl-propionic acids, such as carprofen, ketoprofen and vedaprofen in the horse.

Animals↗

Social and ethnic inequalities in the offer and uptake of prenatal screening and diagnosis in the UK: a systematic review.

OBJECTIVE: To review studies addressing the question of whether there are social inequalities in either the offer or the uptake of prenatal testing in the UK. METHOD: Systematic review of studies assessing the offer or uptake of prenatal screening or diagnosis according to social class or ethnic origin. Electronic databases were searched using a strategy developed for a review of inequalities in access to maternity care supplemented with terms specific to prenatal testing. Further papers were identified from reference lists, citation searches and key organizations. RESULTS: From over 600 identified papers, 41 were potentially relevant. Twenty met the inclusion criteria. The studies included covered screening and/or diagnosis for Down's syndrome, neural tube defects, haemoglobin disorders and HIV. Many studies were limited by small numbers or poor reporting of data and analysis. Six studies reported data on prenatal testing according to women's social class or educational level. None found any significant social inequalities in testing. Some studies suggested that women of South Asian origin might be up to 70% less likely to receive prenatal testing for haemoglobin disorders and Down's syndrome than White women. A small number of studies suggested that South Asian women might be less likely to be offered testing. CONCLUSIONS: This review provides some evidence of ethnic inequalities in access to prenatal testing. Further research is required to improve our understanding of why testing may not be offered, the reasons for failure to take up testing when offered, and to identify whether there are other social inequalities in access to prenatal testing.

Down Syndrome↗

[Flexible bronchoscopy in children. Experience at French centers of pediatric pneumology].

INTRODUCTION: Fibreoptic bronchoscopy (FB) is an important diagnostic examination in paediatric pulmonology. In 2002 the Paediatric Pulmonology and Allergy Club undertook a retrospective study to establish the current status of fibreoptic bronchoscopy among its members. METHODS: In 2001 sixty five paediatric pulmonologists carried out an average of 116 examinations (+/- 111) in 35 paediatric centres. FB was performed either in an operating theatre (15 centres), a dedicated bronchoscopy suite (6 centres) or an endoscopy suite shared with gastro-enterologists (7 centres). Other examinations were performed in areas dedicated to, or associated with intensive care. General anaesthesia was routinely used in 18 centres. The others used sedation including an equimolar mixture of oxygen and nitrous oxide in 14 centres. Ten centres performed less than 50 examinations, 12 between 51 and 100, 4 between 101 and 200 and 8 centres more than 200 in the year. Seventy two per cent of the children were less than 6 years old. The washing and disinfection procedures were manual in 20 centres and automatic in 15. RESULTS: Three principal indications were reported: persistent wheezing, suspicion of a foreign body and ventilatory difficulties. Cough, desaturation and fever were the most frequently reported side effects. CONCLUSIONS: This is the first survey in paediatric pulmonology in France. It shows a wide variation in the practice of fibreoptic bronchoscopy in children.

Bronchoscopes↗

Improving services for disadvantaged childbearing women.

BACKGROUND: Tackling health inequalities is high on the political agenda of the Labour government. The government wants to reduce inequalities through policies based on evidence, the health of childbearing women and their babies being priority areas for action. National Service Frameworks (NSFs) are being set up to ensure high quality services for all groups. The External Working Group looking into maternity services for the Children's NSF seeks evidence upon which to plan strategies for all women, while focusing attention on the most disadvantaged. Wide differentials are noted between high- and low-income groups in the outcomes of pregnancy and the health of babies. The worst outcomes appear to be concentrated in small subgroups of disadvantaged women. AIM: To report on a review of studies of interventions improving perinatal outcomes for disadvantaged women, to inform policy and practice around the organization and delivery of statutory services in the UK. METHOD: We searched six relevant databases for reviews, intervention studies, audits and descriptions of services reporting outcomes for disadvantaged groups of women, published between 1990 and 2003. Synthesis was performed around what works and what does not work. Gaps in the evidence base were identified. RESULTS: We found limited evidence of effective and promising interventions for childbearing women from minority ethnic groups, women experiencing domestic violence, women with mental health illness and HIV infected women. Few studies were well-designed or powered to detect effectiveness. There were no studies of interventions for women prisoners, homeless women and travellers. CONCLUSIONS: Searching for intervention studies primarily by participant subgroup has brought in evidence from few well-designed studies on which to plan policy. Combining this approach with searching for intervention studies addressing behaviour like smoking, and needs like social support, may provide further evidence to tackle inequalities in the perinatal period.

Evidence-Based Medicine↗

Perinatal pathology in the context of a clinical trial: attitudes of neonatologists and pathologists.

OBJECTIVE: To describe the attitudes of neonatologists to trial related perinatal postmortem examinations (PMs), in the light of declining perinatal PM rates and poor levels of participation in pathology studies. METHODS: A qualitative study was carried out, using semistructured interviews. Twenty six neonatologists from five UK neonatal units were interviewed; five UK perinatal pathologists also contributed to the study. The professionals involved were all linked to one or both of two neonatal trials. RESULTS: Pathologists expressed concern over the difficulties experienced in UK perinatal pathology and the impact on research of inadequate levels of samples. The interviews with neonatologists reveal discomfort over approaching bereaved parents for PMs, and a widespread concern that parents should not be further distressed or feel under pressure to consent. Although there was support for neonatal trials, the study highlights a view that PMs may be unnecessary if the cause of death seems apparent or when a baby was born prematurely, and a devaluation of PMs among some younger staff. Poor rates of participation in pathology studies may be accounted for by a notable sense of disconnection between trial interventions and pathology studies. CONCLUSIONS: Neonatologists were concerned to protect vulnerable parents and varied in whether they saw this as compatible with inclusion in trial related pathology studies. Dedicated research is needed to document and gain an understanding of the consent process and should examine the usefulness and impact of consent forms. It should assess whether professionals might benefit from training, to help parents to come to their decisions.

Adult↗

Perinatal pathology in the context of a clinical trial: a review of the literature.

Perinatal postmortem rates are declining world wide. In the United Kingdom, perinatal pathology has recently been seriously undermined by controversy. There are important consequences for perinatal trials that include pathology studies. This review looks at the reasons for the decline in perinatal postmortem examinations and the effects on research.

Attitude↗

Perinatal pathology in the context of a clinical trial: attitudes of bereaved parents.

BACKGROUND: Interviews with neonatologists in a related study had revealed a degree of discomfort with approaching bereaved parents for postmortem examinations (PMs) and a widespread concern that parents should not be further distressed or feel under pressure to consent. OBJECTIVE: To report the attitudes of bereaved parents to trial related perinatal PMs, in the light of declining perinatal PM rates and poor levels of participation in pathology studies. METHODS: A qualitative study was carried out, using semistructured interviews. The study involved 11 interviews with 18 bereaved parents from five UK neonatal units. The parents had consented to the enrolment of their baby in one of two neonatal trials. RESULTS: The data provide support for the careful approach described by neonatologists in a related study, but also suggest that it may be possible to approach more parents without undermining their wellbeing. The interviews show the variety of reactions to PMs that one would expect, from parents who were clear that they did not want a PM to others who felt that they needed the information from the examination. Between these extremes were parents who were initially discomforted by the idea but who then made the decision to go ahead. Parents who elected to have a PM did so for their own needs, or to contribute to a trial, or for both reasons. The fact that the subject was raised was generally not seen as inappropriate, and none stated that they felt that they were actually pressured into making their decision. The data also suggest that for some parents the degree of caution and selectivity exercised by the neonatologists may not be entirely appropriate. In two cases, consent for the PM was driven by a sense of making an altruistic contribution to research, and, in another two, altruism was expressed in the context of their own desire for information from a PM. CONCLUSIONS: It is important to determine whether trial related pathology studies are considered by professionals and lay people to be worth while and feasible. If there is support for such studies, the challenge is to develop the means to approach more parents in the most sensitive way.

Adult↗

Analysis of adiabatic coupling between photonic crystal single-line-defect and coupled-resonator optical waveguides.

A detailed analysis of adiabatic coupling between conventional photonic crystal single-line-defect and coupled-resonator optical waveguides is reported. Adiabatic coupling by progressive variation of the radii of the spacing defects between cavities is investigated. Flat transmission spectra with coupling efficiencies greater than 90% are achieved in a broad frequency range with short coupling lengths. Moreover, we find that flat transmission at low frequencies requires longer coupling lengths partly because the requirements imposed for adiabatic transmission in photonic crystals are violated.

Journal Article↗

Carboxy-terminally truncated Dengue 4 virus envelope glycoprotein expressed in Pichia pastoris induced neutralizing antibodies and resistance to Dengue 4 virus challenge in mice.

We have expressed a recombinant Dengue 4 virus envelope glycoprotein (E4rec), truncated at its C-terminus by 53 amino acids, in Pichia pastoris. The presence of E4rec was confirmed by Western-blot using anti-DEN 4 hyper immune mouse ascitic fluid. E4rec migrated during SDS-PAGE as a 64 kDa protein. Treatment with endoglycosidases showed that the E protein was modified by the addition of short mannose chains and the absence of hyperglycosylation. When administered to BALB-C mice, E4rec elicited a DEN 4 neutralizing antibody response haemagglutination inhibition antibodies and specific memory T cell response. Mice immunized were also significantly protected against lethal DEN 4 virus challenge (86.6%, p < 0.001).

Animals↗