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Biomedical subjects

I Garcia

Publications and source records attributed to I Garcia.

At least 37 records · Page 2Linked to original sources
PubMed2002

Temozolomide in second-line treatment after prior nitrosurea-based chemotherapy in glioblastoma multiforme: experience from a Portuguese institution.

Temozolomide is a new cytotoxic alkylating agent that has recently been approved in Portugal for the treatment of recurrent high-grade glioma. From September 1999 to March 2001, 16 patients with recurrent glioblastoma multiforme who had prior nitrosurea-based chemotherapy [procarbazine, carmustine, vincristine (PCV)] were given temozolomide 150-200 mg/m2/day for 5 days every 28-day cycle. The estimated 1-year survival rate was 16% and the median overall survival was 6.5 months. Despite the small sample size, the overall survival achieved with temozolomide was similar to that of other reports. These promising data suggest that randomized trials should be undertaken to assess its use in first-line therapy its inclusion in combined chemotherapy regimes and its effectiveness with concurrent radiotherapy.

Adult↗
PubMed2002

Malnourished elderly people and lipid status.

UNLABELLED: Protein-energy malnutrition is common in the elderly. The relationship between protein-energy malnutrition and lipid status remains uncertain and few studies are available. The aim of this study was to evaluate the lipid status of malnourished elderly subjects recently hospitalized in a geriatric medical care unit. Classical parameters such as total cholesterol, HDL cholesterol, apoproteins A1 et B, vitamins A and E were measured. Particular attention was given to other parameters such as fatty acids. The studied population included 86 elderly subjects. They were divided into two groups, according to serum albumin (alb) and Body Mass Index (BMI). Fifty patients aged 81.5 7.3 years were considered to be well-nourished (WN) with albumin 35 g/l and BMI 21 kg/m2. Thirty six patients aged 84.1 6.6 years were considered to be malnourished (MN) with albumin < 35 g/l and BMI < 21 kg/m2. Our main findings shown significant decrease in all classical lipid parameters : total cholesterol (p< 0.001), HDL cholesterol (p< 0.005), apoproteins A1 (p< 0.001) and B (p< 0.001) in the malnourished group. We found an increase in the rate of v9 fatty acids (p< 0.001 for the oleic acid; p< 0.05 for the eicosatrienoic acid) and also an increase in the triene/tetraene ratio (p< 0.05) as a result of malnutrition. CONCLUSION: Protein-energy malnutrition is accompanied by lipid status alterations.

Aged↗
PubMed2001

Comorbidity and survival of elderly head and neck carcinoma patients.

BACKGROUND: Alcohol and tobacco, the primary etiologic agents for head and neck carcinoma (HNCA), cause other chronic diseases and may contribute to the high prevalence of comorbid conditions and generally poor survival of persons with HNCA. METHODS: The authors explored the prognostic role of comorbidity in persons with HNCA using Health Care Finance Administration Medicare (HCFA) files linked with the appropriate files of the Surveillance, Epidemiology, and End Results (SEER) Program. The Charlson comorbidity index was applied to in-patient data from the HCFA files. The SEER data were used to ascertain survival and identify persons with HNCA diagnosed from 1985 to 1993 (n = 9386). RESULTS: In a proportional hazards regression model adjusted for age and historic stage at diagnosis, race, gender, marital status, socioeconomic status, histologic grade, anatomic site, treatment, and pre-1991 diagnosis, Charlson index scores of 0, 1, and 2+ had estimated relative hazards (RHs) with 95 confidence intervals (CIs) of 1.00, 1.33 (95% CI, 1.21-1.47), and 1.83 (95% CI, 1.64-2.05), respectively (P value for trend < 0.0001). The adjusted RH for a Charlson index score of 1 or more compared with 0, using stratified models, was found to be greater in whites (RH, 1.55; 95% CI, 1.43-1.67) than blacks (RH, 1.24; 95% CI, 0.96-1.60), local (RH, 1.72; 95% CI, 1.50-1.96) versus distant stage (RH, 1.25; 95% CI, 1.00-1.56), and age 65-74 years (RH, 1.53; 95% CI, 1.38-1.69) versus age 85+ years (RH, 1.42; 95% CI, 1.09-1.84). CONCLUSIONS: This study establishes comorbidity as a predictor of survival in an elderly HNCA population and lends support to the inclusion of comorbidity assessment in prognostic staging of patients with HNCA diagnosed after 65 years of age.

Aged↗
PubMed2001

Epithelial cyclooxygenase-2 expression: a model for pathogenesis of colon cancer.

BACKGROUND: Recent studies indicate a close relationship between cyclooxygense-2 (COX-2) expression and the pathogenesis of colorectal cancer, yet little information exists regarding the stimuli and pathways involved in COX-2 expression by the colonic epithelium. We studied the induction of COX-2 in response to such environmental stress as hyperosmolarity and lipopolysaccharide (LPS) in a human colon cell line. We further investigated the transduction cascades mediating COX-2 expression, focusing upon the mitogen-activated protein kinase pathways p38 and extracellular signal-regulated kinase (ERK). MATERIALS AND METHODS: Human colon cancer cells (Caco-2) were stimulated with increasing concentrations of sodium chloride (NaCl) or LPS. Total protein was extracted at different time points and subjected to Western blot analysis with antibodies to human COX-2, COX-1, or phospho-specific antibodies to ERK and p38. RESULTS: LPS failed to induce COX-2 or COX-1 expression. Hyperosmolarity induced COX-2 expression by 2 h, with peak levels occurring at 6-8 h. NaCl at 40 and 100 mM induced a 2-fold and more than 50-fold increase in COX-2 expression, respectively; COX-1 expression was not affected. Hyperosmolarity induced both p38 and ERK activation within 30 min; however, only p38 inhibition attenuated osmotic-induced COX-2 expression; inhibition of ERK activation had no effect. CONCLUSIONS: Increase in osmolarity activates p38 and induces COX-2 expression in the colonic epithelium. The lack of response to LPS is teleologically expected of the colonic epithelium that is in constant contact with the fecal bacteria. This model also predicts that an increase in luminal osmolarity in the colon may induce COX-2 and thereby promote a neoplastic phenotype.

Carcinoma↗
PubMed2001

Quantitation of reduced and total glutathione at the femtomole level by high-performance liquid chromatography with fluorescence detection: application to red blood cells and cultured fibroblasts.

A new rapid and highly sensitive HPLC method with ortho-phthalaldehyde (OPA) pre-column derivatization has been developed for determination of reduced glutathione (GSH) and total glutathione (GSHt) in human red blood cells and cultured fibroblasts. OPA derivatives are separated on a reversed-phase HPLC column with an acetonitrile-sodium acetate gradient system and detected fluorimetrically. An internal standard (glutathione ethyl ester) is added to facilitate quantitation. Total glutathione is determined after reduction of disulfide groups with dithiothreitol; the oxidized glutathione (GSSG) concentration is calculated by subtraction of the GSH level from the GSHt level. The assay shows high sensitivity (50 fmol per injection, the lowest reported), good precision (C.V. <5.0%), an analytical recovery of GSH and GSSG close to 100%, and linearity (r > 0.999). This HPLC technique is very simple and rapid. Its wide applicability and high sensitivity make it a convenient and reliable method for glutathione determination in various biological samples.

Cells, Cultured↗
PubMed2001

Il-4 and IL-13, but not IL-10, protect human synoviocytes from apoptosis.

Interleukin-4, which has been contemplated for the treatment of rheumatoid arthritis and/or osteoarthritis because of its anticatabolic properties, has also been shown to modulate apoptosis. Because inadequate apoptosis is thought to contribute to synovial hyperplasia, we have investigated the ability of IL-4 and other Th2 cytokines to protect human synovial cells from apoptosis. Human synoviocytes or synovial explants were pretreated with IL-4, IL-10, and IL-13 before exposure to NO donor sodium-nitro-prusside (SNP). Apoptosis was evaluated by microscopy, annexin V-FITC, 3-(4,5-dimethylthiazol-2-gl)-5-(3-carboxymethoxylphenyl)-2-(4-sulphophenyl-2H: tetrazolium inner salt (MTS) test, pulse field gel electrophoresis, and a method proposed in this study based on (32)P Klenow end labeling of high m.w. DNA. Pretreatment by IL-4 or IL-13, but not IL-10, protected human synoviocytes from apoptosis induced by SNP. Even at doses as high as 2 mM SNP, up to 86% and 56% protection was achieved, after IL-4 and IL-13 treatment, respectively. Cell survival was dependent on IL concentration. IL-4 and IL-13 also had antiapoptotic effects on SNP-treated human synovial explants. Effects of IL-4 and IL-13 varied in the presence of phosphatidylinositol-3 kinase and protein kinase C inhibitors, implying the involvement of these pathways in antiapoptotic signaling. Antiapoptotic effects were dramatically inhibited by LY294002, and partially by the protein kinase C inhibitor Gö 6976, while insulin-like growth factor increased synoviocyte survival. The possibility that IL-4 and IL-13 may enhance synovial expansion in vivo by their antiapoptotic effects is discussed.

Adjuvants, Immunologic↗
PubMed2001

Differential effects of TNF and LTalpha in the host defense against M. bovis BCG.

Signaling via TNF receptor type 1 (TNFR1) was shown to be crucial in host defense against the intracellular pathogens L. monocytogenes, M. tuberculosis and M. bovis. To investigate the function of TNF and LTalpha in host defense against M. bovis, mice double deficient for TNF and LTalpha (TNF / LTalpha (- / -)), TNF / LTalpha (- / -) mice complemented with a murine LTalpha transgene (TNF(- / -)) and LTalpha (- / -) mice were infected with BCG and the ensuing pathology was investigated. Control mice showed a normal host defense with early clearance of bacteria. The granulomatous reaction in the liver was accompanied by recruitment of activated macrophages characterized by their acid phosphatase positivity and differentiation into epithelioid cells as well as a coordinated expression of proinflammatory transcripts. In contrast, TNF / LTalpha (- / -) mice showed no comparable recruitment of activated macrophages in the liver. Furthermore, these mice showed extensive necrotic pulmonary lesions with massive growth of acid fast bacilli. Reintroduction of LTalpha as a transgene into TNF / LTalpha (- / -) mice prolonged survival but did not restore resistance to BCG. This, at least partially protective role of LTalpha was further supported by data demonstrating that LTalpha -deficient mice as well were susceptible to BCG infection. In contrast to the deleterious effect of TNF / LTalpha deficiency in BCG infection, BCG-infected TNF / LTalpha (- / -) mice were tolerant to LPS-induced shock. These results demonstrate that TNF as well as LTalpha are involved in murine host defense against BCG and that absence of TNF / LTalpha protects BCG-infected mice from LPS mediated shock.

Animals↗
PubMed2001

Incidence and predisposing factors for incisional hernia in patients with liver transplantation.

BACKGROUND: Cirrhotic patients who are transplanted have a high risk of developing incisional hernia (IH). MATERIALS AND METHODS: We have analysed the incidence and treatment of IH in 465 patients with liver transplantation (LT). In order to find predisposing factors, we compared these patients with a similar group of patients with LT without IH. Fifty-four patients (11.6%) developed an IH. Forty-six of these (85%) were males, and in 37% the entire laparotomy incision was involved. Forty patients have been operated on for the hernia, three by primary repair and 37 (92.5%) with a polypropylene mesh. After a follow-up of 42 months, 6 (15%) IHs recurred. Comparing groups, IH patients were older (P<0.05), of male gender (P<0.001), and received more steroids (P<0.01). The IH rate was not related to suture material. CONCLUSIONS: Our rate of IH is perhaps reasonable in these high risk patients. It appears that IH can be reduced if steroids are reduced or avoided. We recommend a large mesh for repair.

Adult↗
PubMed2001

BCR/ABL fusion gene detected on 9q34 by fluorescence in situ hybridization in an acute leukemia with two BCR/ABL positive clones, one Ph-negative and one Ph-positive.

We report cytogenetic, fluorescence in situ hybridization (FISH), and molecular analyses in the first reported case of an acute leukemia with two BCR-positive clones: one cell Ph-positive and all others Ph-negative. A BCR/ABL fusion gene on 9q34 was detected only with a BCR/ABL dual color translocation probe. These FISH interphase signals must be confirmed on a metaphase to avoid an erroneous interpretation. This observation appears to indicate a 2-step mechanism for this aberrant fusion gene localization: first, a classical t(9;22), and then the transfer of the fusion gene formed on chromosome 22 to chromosome 9 by a second translocation between the long arms of the derivative chromosomes 9q+ and 22q-, masking the first chromosome exchange.

Acute Disease↗
PubMed2001

Three cases of typical aplastic anaemia associated with a Philadelphia chromosome.

We report three cases of typical aplastic anaemia (AA) associated with a Philadelphia chromosome. This translocation was detected at the time of diagnosis of AA (one patient) and when overt leukaemia was diagnosed (two patients: one chronic myeloid leukaemia and one acute lymphoblastic leukaemia) after AA therapy and recovery of blood counts. We discuss the literature arguments about considering some cases of AA as preleukaemic disorders and suggest that our cases illustrate the association of AA with a clonal malignant disorder. We conclude that cytogenetic analysis is necessary at diagnosis of AA or after recovery of blood counts.

Adult↗
PubMed2001

A community participatory oral health promotion program in an inner-city Latino community.

OBJECTIVES: This paper reports the planning, implementation, process evaluation, and refinement of an oral health community participatory project in Mount Pleasant, an inner-city Latino neighborhood of Washington, DC. The main goal was to explore the feasibility of implementing such a project. METHODS: The PRECEDE-PROCEED model was used to guide the planning and process evaluation of this project, in conjunction with community organizational methods. A steering committee, which met periodically, was formed to assist in program planning, implementation, and evaluation. The needs assessment of the community identified extensive dental health problems among children and deficiencies in their parents' oral health knowledge, opinions, and practices. In response, culturally appropriate health education and promotion activities were planned and implemented in collaboration with local community organizations, volunteers, and local practitioners. Process evaluation was used to provide feedback into the refinement of the community approach, which included record keeping and an inventory approach to activities completed and resources used. The overall impact and usefulness of this program were assessed informally using an anonymous open-ended questionnaire directed to members of the steering committee, and an outreach survey using a convenience sample at a local Latino health fair. RESULTS: The implementation of such a community participatory approach was feasible and useful for building upon existing local resources and addressing oral health concerns in a community not reached by traditional dental care and health promotion initiatives. Individuals in this community showed a substantial interest in oral health matters and participated in a variety of oral health prevention activities. The community approach adhered to community-based research principles.

Attitude to Health↗
PubMed2000

Inhibition of p-hydroxyphenylpyruvate dioxygenase by the diketonitrile of isoxaflutole: a case of half-site reactivity.

p-Hydroxyphenylpyruvate dioxygenase (HPPD) catalyzes the formation of homogentisate from p-hydroxyphenylpyruvate and molecular oxygen. In plants, this enzyme is the molecular target of new families of very active bleaching herbicides. In the study presented here, we report for the first time on the purification to homogeneity of a plant enzyme, as obtained from recombinant Escherichia coli cells expressing a cDNA encoding carrot HPPD. The purified enzyme allowed us to carry out a detailed characterization of the inhibitory properties of a diketonitile (DKN), the active inhibitor formed from the benzoylisoxazole herbicide isoxaflutole. Inhibition kinetic analyses confirmed that DKN exerts a slow and tight-binding inhibition of HPPD, competitive with respect to the p-hydroxyphenylpyruvate substrate. The stoichiometry of DKN binding to HPPD determined by kinetic analyses or by direct binding of [(14)C]DKN revealed a half-site reactivity of DKN.

4-Hydroxyphenylpyruvate Dioxygenase↗
PubMed2000

Lethal Mycobacterium bovis Bacillus Calmette Guérin infection in nitric oxide synthase 2-deficient mice: cell-mediated immunity requires nitric oxide synthase 2.

The role of nitric oxide (NO) in Mycobacterium bovis Bacillus Calmette Guerin (BCG) infection was investigated using nitric oxide synthase 2 (nos2)-deficient mice, because NO plays a pivotal protective role in M. tuberculosis infection. We demonstrate that nos2-deficient mice were unable to eliminate BCG and succumbed within 8 to 12 weeks to BCG infection (10(6) CFU) with cachexia and pneumonia, whereas all infected wild-type mice survived. The greatest mycobacterial loads were observed in lung and spleen. Nos2-deficient mice developed large granulomas consisting of macrophages and activated T cells and caseous necrotic lesions in spleen. The macrophages in granulomas from nos2-deficient mice had reduced acid phosphatase activities, suggesting that NO is required for macrophage activation. The absence of NOS2 affected the cytokine production of the Th1 type of immune response, except IL-18. Serum amounts of IL-12p40 were increased and IFN-gamma was decreased compared with wild-type mice. The lack of NOS2 resulted in an overproduction of TNF, observed throughout the infection period. Additionally, TNFR1 and TNFR2 shedding was altered compared with wild-type mice. Up-regulation of TNF may be compensatory for the lack of NOS2. The late neutralization of TNF by soluble TNF receptors resulted in heightened disease severity and accelerated death in nos2-deficient mice but had no effect in wild-type mice. In conclusion, the inability of nos2-deficient mice to kill M. bovis BCG resulted in an accumulation of mycobacteria with a dramatic activation of the immune system and overproduction of pro-inflammatory cytokines, which resulted in death.

Animals↗
PubMed2000

Disseminated mycoses in a dog by Paecilomyces sp.

We describe a case of canine mycoses initially diagnosed by clinical signs and enzyme-linked immunosorbent assay anti-fungal test, and later confirmed by the isolation of Paecilomyces sp. during the post-mortem examination. The fungus was isolated from lesions in the kidneys, mitral valve, abdominal aorta and vertebral discs. In this kind of process, it is important to identify the responsible agent early in order to make a study of anti-fungal susceptibility and establish effective treatment.

Animals↗
PubMed2000

Soluble TNF receptors partially protect injured motoneurons in the postnatal CNS.

There is accumulating evidence that cytokines are involved in the functioning of the brain and the spinal cord. However, it has been controversial whether they exert a neurotoxic or a neuroprotective effect. To address this question in vivo, we have examined the survival of injured motoneurons in a line of transgenic mice that overexpress the soluble form of tumour necrosis factor receptor-1 (sTNFR1). In these animals, all of the circulating TNF and lymphotoxin-alpha are neutralized by the continuous expression of the soluble receptor. Following axotomy of the facial nerve in 7-day-old control mice, we observed a loss of approximately 90% of the motoneurons at two weeks survival. In the transgenic mice under the same conditions, the percentage of motoneuron survival was increased two-fold (515 vs. 224) and varied as a function of the level of the circulating receptor. These results indicate that neutralization of endogenous TNF and lymphotoxin-alpha by means of overexpression of the soluble receptor can decrease cell death of injured motoneurons and suggest that these cytokines may play an important role in neuronal degeneration in the CNS following a lesion.

Age Factors↗
PubMed2000

Hypertonic saline solution induces prostacyclin production by increasing cyclooxygenase-2 expression.

BACKGROUND: Previously, we demonstrated that hypertonic saline solution (HTS) and endotoxin (lipopolysaccharide [LPS]) induce prostacyclin (PGI(2)) production in human endothelial cells. Here, we hypothesized that HTS and LPS may induce PGI(2) production by increasing cyclooxygenase (COX) expression. We further examined the activation of p38 and extracellular signal-regulated kinases (ERK) and questioned whether these transduction cascades might mediate COX expression. METHODS: Human umbilical vein endothelial cells were stimulated with varying concentrations of NaCl or LPS. RESULTS: HTS and LPS induced prompt activation of both p38 and ERKs that peaked at 30 minutes. HTS and LPS also induced a dose-related increase in COX-2 with maximal expression within 4 to 6 hours; there was no change in COX-1. This correlated with an increase in supernatant PGI(2) levels, which became statistically significant for NaCl of more than 40 mmol/L and for all LPS doses. The inhibition of p38 with SB202190 abrogated the osmotic and LPS-induced COX-2 expression and PGI(2) production. Inhibition of ERK activation had no effect on COX-2 expression. CONCLUSIONS: Hyperosmolarity and LPS induce, in chronologic order, p38 and ERK activation, COX-2 expression, and PGI(2) production. Because COX is the rate-limiting enzyme in prostaglandin synthesis, it is likely that the increase in PGI(2) production is due to, at least in part, the increased COX-2 expression. The data also suggest that p38 mitogen-activated protein kinase is involved in the signaling cascade for COX-2 expression.

Cell Survival↗
PubMed2000

Primary costochondritis due to Escherichia coli.

We present a case of primary costochondritis by Escherichia coli, in a diabetic woman. The patient suffered a urinary infection by E. coli which may have been the source of haematogenous spread. She received medical and surgical therapy and 5 months later, she was asymptomatic.

Aged↗