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Biomedical subjects

J Garcia

Publications and source records attributed to J Garcia.

At least 55 records · Page 3Linked to original sources

An essential role for the H218/AGR16/Edg-5/LP(B2) sphingosine 1-phosphate receptor in neuronal excitability.

A wealth of indirect data suggest that the H218/AGR16/Edg-5/LP(B2) sphingosine 1-phosphate (S1P) receptor plays important roles in development. In vitro, it activates several forms of development-related signal transduction and regulates cellular proliferation, differentiation and survival. It is expressed during embryogenesis, and mutation of an H218-like gene in zebrafish leads to profound defects in embryonic development. Nevertheless, the in vivo functions served by H218 signalling have not been directly investigated. We report here that mice in which the H218 gene has been disrupted are unexpectedly born with no apparent anatomical or physiological defects. In addition, no abnormalities were observed in general neurological development, peripheral axon growth or brain structure. However, between 3 and 7 weeks of age, H218(-/-) mice have seizures which are spontaneous, sporadic and occasionally lethal. Electroencephalographic abnormalities were identified both during and between the seizures. At a cellular level, whole-cell patch-clamp recordings revealed that the loss of H218 leads to a large increase in the excitability of neocortical pyramidal neurons. Therefore, H218 plays an essential, unanticipated and functionally important role in the proper development and/or mediation of neuronal excitability.

Action Potentials↗

Circadian rhythms and circadian rhythm disorders in children and adolescents.

A clinically applicable review of circadian rhythm physiology is presented, including a detailed examination of the interaction of circadian and homeostatic systems and the maturation of the circadian system from preconception through adolescence. Emphasis is placed on the clinical evaluation gathering information through the history, sleep log, and if necessary, actigraphy and polysomnography. Circadian disorders, including advanced sleep phase syndrome, circadian disorders seen in blind children, delayed sleep phase syndrome, and non-24-hour sleep phase are described. Case descriptions of each are provided. Treatment and interventions for these disorders are described, including the importance of education, light therapy, sleep-wake schedule adjustments, and the occasional use of medications, such as sedative hypnotics and melatonin.

Adolescent↗

Addressing domestic violence through maternity services: policy and practice.

OBJECTIVE: to explore current policies and practices in maternity units that aim to identify, assess and support women experiencing domestic violence. DESIGN AND SETTING: a postal survey, conducted between June and October 1999, of all NHS Trusts in England and Wales that provided maternity services. PARTICIPANTS: Heads of Midwifery or the midwife with expertise or interest in domestic violence in each Trust. MAIN OUTCOME MEASURES: use of written policies and agreed practices for identifying and referring women experiencing domestic violence, such as availability of information, routine questioning of all women and offering women an appointment without their partner. RESULTS: 87% (183) of the 211 NHS Trusts providing maternity care participated in the survey. Twelve per cent of units had written policies for identifying women experiencing domestic violence, and a further 30% had some form of agreed practice. Less than half of maternity units routinely offered women an appointment without their partner, and just over half displayed material about domestic violence in places where women receive maternity care. Only three units had undertaken audit on their domestic violence practices. CONCLUSIONS: there is considerable variability around England and Wales in policies and practices related to domestic violence. It is evident that clear guidelines for identification and referral, training, audit and the integration of domestic violence policies with child protection and other policies are necessary to fully address the issues.

Education, Nursing, Continuing↗

Evaluation of bioadhesive glipizide spheres and compacts from spheres prepared by extruder/marumerizer technique.

The objective of this study was to attempt to deliver glipizide from spheres and compacts containing the natural polymer Carrageenan (Gelcarin, GP 812) and prepared by extruder/marumerizer technique. A second objective was to evaluate the mucoadhesive strength of the bioadhesive spheres onto the mucus membrane of rabbit. The effects of polymer, drug level, and type of spheronizing material were evaluated. All sphere formulations were compacted into tablets using a rotary Manesty B-3B machine equipped with 12/32 flat face tooling. Results show drug release from spheres and compacts decreased as the level of Carrageenan was increased. However as the level of drug was increased drug release also increased. Spheres containing Avicel PH-101 gave higher drug release than spheres of the same composition but prepared with Avicel RC-581. In general, the drug release from tablets was higher than its corresponding spheres and drug release from spheres and tablets containing Carrageenan was higher than control spheres and tablets of the same composition but without Carrageenan. Tablet formulations compacted from spheres containing Avicel RC-581 gave higher release rate constants than tablet formulations of the same composition but prepared with Avicel PH-101. The bioadhesion study showed that mucoadhesion strength between spheres and mucus membrane of the rabbit depends on the levels of polymer, drug, and type of spheronizing material. Developed bioadhesive spheres and tablets increase the solubility of glipizide which may increase its bioavailability and also increased the adherence of the bioadhesive systems to the mucous membrane so that once daily dose can be administered.

Adhesives↗

Training programs for healthcare professionals in domestic violence.

Although women who experience domestic violence seek healthcare services frequently, screening and counseling rates remain low, and healthcare professionals report feeling inadequately trained to care for abused women. The English language literature from 1989 to 1999 was searched to identify and evaluate published assessments of the education of healthcare providers in domestic violence toward women. Major deficiencies in program evaluation were found. They included the use of a historical comparison group, lack of an experimental design, selection of nonstandardized outcomes without clinical performance measures, short-term follow-up, limited documentation of course content and theory, and lack of focus on the impact of programs on abused women. Educational programs generally consisted of a single session of limited duration (1-3 hours). Based on published reports, it appears that few rigorously designed evaluations have been conducted of training programs for healthcare providers in the detection and treatment of women affected by domestic violence.

Curriculum↗

Does poor communication contribute to stillbirths and infant deaths? A review.

BACKGROUND: Assessors from the Confidential Enquiry into Stillbirths and Deaths in Infancy (CESDI) have cited poor communication as a contributory factor in a proportion of such deaths. This review assesses what research evidence exists to support or explain this. METHODS: A structured review was carried out, including all studies of sub-optimal care in stillbirth or infant death and studies of litigation in perinatal care. The following databases were searched: MEDLINE, PsycLIT, The Cochrane Library, BIDS Science and Social Science Citation Indexes, Cinahl and Embase. For included studies, information was extracted on the type of study, the selection criteria and number of cases studied, other methods used and results relevant to the question. RESULTS: One hundred and four studies of potential relevance to the review were identified. Of these, 52 did not meet the inclusion criteria and were excluded. Of the remaining 52 studies, 11 considered communication failure explicitly as a factor in sub-optimal care leading to stillbirth or infant death. In three out of the four studies that presented their findings in terms of numbers of cases, communication failure was noted in between 24 and 29 per cent of cases. There was some consistency across different types of study in the types of communication problems noted. CONCLUSION: Poor communication may contribute to a proportion of stillbirths and infant deaths. However, given the small number of papers that looked explicitly at poor communication as a factor in sub-optimal care and the lack of comparative information on communication in cases that do not end in poor outcome, caution is needed in drawing conclusions based on the findings of these papers.

Communication↗

Pharmacokinetics and residues in milk of oxytetracyclines administered parenterally to dairy goats.

OBJECTIVE: To determine for two commercial preparations of oxytetracycline (OTC) the pharmacokinetic behaviour, the presence of detectable milk residues and the penetration in milk of OTC administered by intravenous (IV) (conventional formulation [CF]) and intramuscular (IM) routes (CF and long-acting [LA] formulations) in goats producing milk. The effects of these formulations on plasma activity values of creatine kinase (CK) and lactate dehydrogenase (LDH) were also determined as indicators of tissue damage. PROCEDURE: Five healthy lactating goats producing 1.5+/-0.5 L/d milk and weighing 56.0+/-4.8 kg were used. Single doses of OTC chlorhydrate (CF) were administered (20 mg OTC/kg) by IV (Trial 1 IV) and IM (Trial 1 IM) routes and OTC dehydrate (LA) by the IM route. The same goats were first given IV CF, then IM CF followed by IM LA with 3 weeks between each treatment. Blood and milk samples were taken. The quantification of OTC was performed by HPLC and the plasma activities of CK and LDH enzymes were determined by spectrophotometry. The presence of OTC residues in milk was determined by a commercial reagent. The plasma pharmacokinetic parameters were calculated using a two-compartment model. RESULTS: Estimates of kinetic variables following IV administration were: Vss= 400.0+/-120.0 mL/kg and CL= 110.0+/-14.0 (mL/h)/kg. The t(fi) for IV= 3.0+/-0.3 h; IM, CF = 10.5+/-2.1 h and IM, LA = 15.1+/-3.1 h. The concentration of OTC in milk at 48 h was: IV= 0.6+/-0.4; IM CF= 1.1+/-0.2 and at 72 h (IM LA)= 0.6+/-0.1 microg/mL and the penetration in milk of OTC was: IV= 70.0+/-18.0; IM CF= 79.0+/-14.0 and IM LA= 66.0+/-6.0%. The areas under the curve of CK and LDH activities in plasma were calculated by the trapezoidal method. Values of CK and LDH IM, LA were greater (P < 0.05) than those observed for IM, CF at 2 and 3 days after administration of the antibiotic. Finally, the bioavailability of OTC CF = 92.0+/-22.0 and LA= 78.0+/-23.0% was suitable for its usage by the IM route in lactating goats. CONCLUSION: Plasma concentration-time values of OTC administered parenterally in production dairy goats showed similar bioavailability for the two pharmaceutical preaprations. The presence of detectable residues in milk indicates that milk should not be used for human consumption for 2 and 3 days after administration of conventional and long-acting formulations, respectively. The increments in CK and LDH activities after the IM administration of LA are consistent with the presence of tissue damage provoked by the pharmaceutical preparations at the injection site.

Animals↗

Thrombopoietin-mediated sustained activation of extracellular signal-regulated kinase in UT7-Mpl cells requires both Ras-Raf-1- and Rap1-B-Raf-dependent pathways.

Thrombopoietin (TPO) regulates growth and differentiation of megakaryocytes. We previously showed that extracellular signal-regulated kinases (ERKs) are required for TPO-mediated full megakaryocytic maturation in both normal progenitors and a megakaryoblastic cell line (UT7) expressing the TPO receptor (Mpl). In these cells, intensity and duration of TPO-induced ERK signal are controlled by several regions of the cytoplasmic domain of Mpl. In this study, we explored the signaling pathways involved in this control. We show that the small GTPases Ras and Rap1 contribute together to TPO-induced ERK activation in UT7-Mpl cells and that they do so by activating different Raf kinases as downstream effectors: a Ras-Raf-1 pathway is required to initiate ERK activation while Rap1 sustains this signal through B-Raf. Indeed, (i) in cells expressing wild-type or mutant Mpl, TPO-induced Ras and Rap1 activation correlates with early and sustained phases of ERK signal, respectively; (ii) interfering mutants of Ras and Rap1 both inhibit ERK kinase activity and ERK-dependent Elk1 transcriptional activation in response to TPO; (iii) the kinetics of activation of Raf-1 and B-Raf by TPO follow those of Ras and Rap1, respectively; (iv) RasV12-mediated Elk1 activation was modulated by the wild type or interfering mutants of Raf-1 but not those of B-Raf; (v) Elk1 activation mediated by a constitutively active mutant of Rap1 (Rap1V12) is potentiated by B-Raf and inhibited by an interfering mutant of this kinase. UT7-Mpl cells represent the second cellular model in which Ras and Rap1 act in concert to modulate the duration of ERK signal in response to a growth factor and thereby the differentiation program. This is also, to our knowledge, the first evidence suggesting that Rap1 may play an active role in megakaryocytic maturation.

Animals↗

[Perspectives of laparoscopy in cardia and gastric surgery].

The authors have made 171 laparoscopic operations in the gastro-esophageal region during the past three and a half years. They have used the achievement of the minimal invasive surgery mainly in the treatment of functional diseases of the gastro-esophageal junction. Besides the hiatal reconstruction and antireflux procedures (142), endoscopic assisted cysto-gastrostomy (7), endoscopic assisted double-lifting gastric wall resection (5), cardiomyotomy (4), Graham suture of perforated duodenal ulcer (4) and enucleation of gastric wall leiomyoma (2) has been performed. There was no postoperative death, the rate of conversion was altogether 4.7% (8/171) while there was no need for reoperation in the early postoperative period.

Adolescent↗

[Laparoscopic adrenalectomy with transperitoneal approach].

UNLABELLED: The feasibility, safety, and results of 52 laparoscopic transperitoneal adrenalectomies were evaluated. METHODS: A total of 52 patients were included in the study based on thorough endocrinological and imaging assessment. 15 patients with Conn syndrome, 3 with Cushing syndrome, 15 with nonfunctioning adenoma, 14 with pheochromocytoma, 2 with adrenocortical cyst, 2 with adrenocortical lipoma and 1 with metastasis were considered eligible for adrenalectomy. Lesion size ranged from 1 to 12 cm (mean 4.53 cm). Concurrent surgical procedures were performed in 6 patients (11%). RESULTS: There was one conversion (during a left adrenalectomy), because of our learning curve. After we changed the technique, there was no more conversion. There were two (3.8%) postoperative complications: postoperative pancreatitis, one of the patients required re-operation (lavage and drainage). There was one wound infection. We had no postoperative mortality. Mean postoperative hospital stay was 6 days (range, 2-27 days). CONCLUSION: Patients with secreting and non-secreting adrenal lesions can be treated safely and effectively by laparoscopic adrenalectomy.

Adolescent↗

Degradation of olive mill wastewater by the combination of Fenton's reagent and ozonation processes with an aerobic biological treatment.

Degradation of olive mill wastewater (OMW) by means of two chemical oxidation processes (Fenton's reagent and ozonation) and their consecutive treatments with aerobic microorganisms have been studied. Fenton's reagent treatment moderately reduces COD and to a greater extent the polyphenolic compounds. Ozonation contributed to low conversion of COD and moderate reduction of polyphenols. The aerobic biological treatments degrade to values higher than 70% and 90% for COD and polyphenolic compounds, respectively. A kinetic study has been carried out in each process, determining the representative kinetic parameters of each model.

Bacteria, Aerobic↗

Preparation of immunoliposomes bearing poly(ethylene glycol)-coupled monoclonal antibody linked via a cleavable disulfide bond for ex vivo applications.

Several methods for the preparation of sterically stabilized immunoliposomes (SIL) have recently been described. This report examines an established method for coupling anti-CD34 My10 mAb to poly(ethylene glycol)-liposomes (PEG-liposomes) containing the anchor pyridyldithiopropionylamino-PEG-phosphatidylethanolamine (PDP-PEG-PE) via a cleavable disulfide bond. Efficient attachment of pyridyldithio-derivatized mAb took place (equivalent to coupling ca. 70% of total input protein) at 2 mol percent of the functionalized PEG-lipid. The My10-SIL bound specifically to CD34+ cells (human leukemic KG-1a and hematopoietic progenitor cells) and the extent of binding was a function of liposomal lipid concentration, the mAb density in the liposome surface and the CD34 cell expression. In mixtures with CD34- cells (CHO or Jurkat), CD34+KG-1a cells were determined by flow cytometry at percentages (1-4%) similar to those reported in clinical samples (such as cord blood, mobilized peripheral blood and bone marrow) using a direct immunostaining with My10-SIL. The disulfide bond was stable in cell culture medium (10% of fetal calf serum) during 8 h and cell-bound SIL can be released from cells by treatment with dithiothreitol as reducing agent under mild conditions (1 h of incubation with 50 mM DTT at 20 degrees C). SIL binding and subsequent dithiothreitol treatment did not influence the cell viability. Our approach should contribute to the development of targetable liposomal vehicles to CD34+ cells for use in ex vivo conditions as sorting of hematopoietic stem cells.

Animals↗

The 7-nitroindole nucleoside as a photochemical precursor of 2'-deoxyribonolactone: access to DNA fragments containing this oxidative abasic lesion.

On the basis of molecular modeling studies, the 7-nitroindole nucleoside 1 was selected as a suitable photochemical precursor for photochemical generation of the C1' deoxyribosyl radical under irradiation, which led to 2'-deoxyribonolactone. The nitro-indole nucleoside derivatives 1a and 1b were prepared and their conformation was determined by X-ray crystallography and NMR spectroscopy. The photoreaction of these nucleosides gave the corresponding deoxyribonolactone derivatives efficiently, with release of 7-nitrosoindole. This reaction was successfully applied to synthesis of oligonucleotides containing the deoxyribonolactone lesion.

Journal Article↗

An association study of bipolar mood disorder (type I) with the 5-HTTLPR serotonin transporter polymorphism in a human population isolate from Colombia.

The short variant of a functional length polymorphism in the promoter region of the serotonin transporter has been associated with several behavioural and psychiatric traits, including bipolar mood disorder. The same short allele has also been implicated as a modifier of the bipolar phenotype. Here we evaluate the etiologic/modifier role of this polymorphism in a case (N=103) / control (N=112) sample for bipolar mood disorder (type I) collected from an isolated South American population. We did not detect an association between bipolar disorder and the 5-HTT promoter polymorphism in this sample. However, an excess of the short allele was seen in younger cases and in cases with psychotic symptoms. When combined with data from the literature, the increased frequency of the short allele in patients with psychotic symptoms was statistically significant.

Age of Onset↗

Patients with chronic obstructive pulmonary disease are at increased risk of death associated with urban particle air pollution: a case-crossover analysis.

The authors assessed the acute association between particulate air pollution and mortality among subjects suffering from chronic obstructive pulmonary disease by using a case-crossover analysis. This design avoided the common concerns about the methods used to assess the acute effects of air pollution. The 1,845 men and the 460 women included were residents of Barcelona, Spain, who were over age 35 years, had died during the period 1990-1995, and had visited emergency rooms because of a chronic obstructive pulmonary disease exacerbation during the period 1985-1989. Particle levels (measured as black smoke at the city monitoring stations) were associated with mortality for all causes (odds ratio (OR) for an increase of 20 microg/m3, the interquartile change, adjusted for temperature, humidity, and influenza = 1.112, 95 percent confidence interval (CI): 1.017, 1.215). The association was stronger for respiratory causes (OR = 1.182, 95 percent CI: 1.025, 1.365), but was not significant for cardiovascular causes (OR = 1.077, 95 percent CI: 0.917, 1.264). Older women, patients admitted to intensive care units, and patients with a higher rate of emergency room visits were at greater risk of dying associated with black smoke. The results reinforced the deleterious role of urban pollution and provided information on factors possibly conferring susceptibility to the acute role of air pollution.

Adult↗

Liver cirrhosis is reverted by urokinase-type plasminogen activator gene therapy.

Liver cirrhosis represents a worldwide health problem and is a major cause of mortality. Cirrhosis is the result of extensive hepatocyte death and fibrosis induced by chronic alcohol abuse and hepatitis B and C viruses. Successful gene therapy approaches to this disease may require both reversal of fibrosis and stimulation of hepatocyte growth. Urokinase-type plasminogen activator (uPA) may serve this function, as it is an initiator of the matrix proteolysis cascade and induces hepatocyte growth factor expression. In a rat cirrhosis model, a single iv administration of a replication-deficient adenoviral vector encoding a nonsecreted form of human uPA resulted in high production of functional uPA protein in the liver. This led to induction of collagenase expression and reversal of fibrosis with concomitant hepatocyte and improved liver function. Thus, uPA gene therapy may be an effective strategy for treating cirrhosis in humans.

Animals↗