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Biomedical subjects

C Martinez

Publications and source records attributed to C Martinez.

At least 73 records · Page 4Linked to original sources
PubMed1999

Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activation polypeptide (PACAP) protect mice from lethal endotoxemia through the inhibition of TNF-alpha and IL-6.

The neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) down-regulate cytokine production. Because human septic shock involves excessive cytokine production, the effect of VIP/PACAP was investigated in a high endotoxemia murine model. Both peptides protect against endotoxin-induced lethality and prevent septic shock-associated histopathological alterations. VIP/PACAP reduce serum and peritoneal TNF-alpha and IL-6, suggesting that the protective effect is exerted by inhibiting the production of endogenous TNF-alpha/IL-6. Consistent with this mechanism, VIP does not protect against septic shock induced by exogenous TNF-alpha. The immunomodulatory role of VIP in vivo is supported by the appearance of high levels of VIP in serum and peritoneal fluid following LPS administration. Thus, the neuropeptides VIP/PACAP protect from the lethal effect of high endotoxemia, presumably by down-regulating TNF-alpha and IL-6 production, and may offer an alternative in the treatment of human septic shock syndrome.

Animals↗
PubMed1999

Regulation of VIP production and secretion by murine lymphocytes.

Vasoactive intestinal peptide (VIP) is a neuropeptide present in the lymphoid microenvironment with a multiplicity of actions. Two sources for VIP have been described in the immune system, the terminals present in central and peripheral lymphoid organs and the immune cells. Although VIP is synthesized by lymphocytes, there is no evidence demonstrating that VIP is released, and which stimuli are able to induce VIP production and secretion. In this study, we demonstrated for the first time, that agents that mediate important immune functions, such as proliferation and antigenic stimulation (Con A, LPS, and anti-TCR antibody), inflammation (LPS, TNFalpha, IL-6 and IL-1beta) or apoptosis (dexamethasone) induce the production and release of VIP to the lymphoid microenvironment. We conclude that VIP is produced and secreted by lymphocytes and propose that during an immune response, the timely release of VIP within the lymphoid organs and peritoneum should influence the differentiation and/or downregulation of the ongoing response.

Animals↗
PubMed1999

HIV/AIDS mental health training for health care providers: an evaluation of three models.

Three models of continuing education--full-day, half-day, and brief workshop--for health providers treating patients with HIV/AIDS were compared on measures of effectiveness with regard to knowledge, attitude, and practice outcomes. Analyses of pre- and postintervention data from two years of training events suggest consistent, modest, program effects in the full-day and half-day approaches, specifically in the area of knowledge enhancement.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Characteristics of a unique visual field defect attributed to vigabatrin.

PURPOSE: Vigabatrin (VGB) therapy is associated with a loss of peripheral vision. The characteristics and prevalence of VGB-attributed visual field loss (V-AVFL) and associated risk factors were evaluated in patients with epilepsy. METHODS: The material comprised the visual fields and case notes of 88 patients with suspected V-AVFL (25 spontaneous reports and 63 cases from an open-label extension trial) and of 42 patients receiving alternative antiepileptic drugs (AEDs) from a cross-sectional study. RESULTS: Forty-two reliable cases of visual field loss could not be assigned to an alternative known cause and were therefore attributed to VGB (13 spontaneous reports and 29 from the open-label study). All cases except one were asymptomatic. Seven cases of field loss were present in the reference cohort of 42 patients; all cases could be attributed to a known aetiology. Thirty-six of the 42 confirmed cases of V-AVFL exhibited a bilateral defect that was most profound nasally, and three, a concentric constriction. The prevalence of V-AVFL was 29% (95% confidence interval, 21-39%). Male gender was associated with a 2.1-fold increased relative risk of V-AVFL (95% confidence interval, 1.20-4.6%). Age, body weight, duration of epilepsy, and daily dose of VGB, and concomitant AEDs did not predict the occurrence of V-AVFL. CONCLUSIONS: The unique visual field defect attributed to VGB is profound in terms of the frequency of occurrence and the location and severity of loss. The asymptomatic nature of the field loss indicates that V-AVFL can be elicited only by visual field examination.

Adult↗
PubMed1999

Effects of pharmacological doses of nandrolone decanoate and progressive resistance training in immunodeficient patients infected with human immunodeficiency virus.

This nonplacebo-controlled, open label, randomized study was conducted to test the hypotheses that pharmacological doses of nandrolone decanoate would increase lean body tissue, muscle mass, and strength in immunodeficient human immunodeficiency virus-infected men, and that these effects would be enhanced with progressive resistance training (PRT). Thirty human immunodeficiency virus-positive men with fewer than 400 CD4 lymphocytes/mm3 were randomly assigned to receive weekly injections of nandrolone alone or in combination with supervised PRT at 80% of the one-repetition maximum three times weekly for 12 weeks. Total body weight increased significantly in both groups (3.2 +/- 2.7 and 4.0 +/- 2.0 kg, respectively; P < 0.001), with increases due primarily to augmentation of lean tissue. Lean body mass determined by dual energy x-ray absorptiometry increased significantly more in the PRT group (3.9 +/- 2.3 vs. 5.2 +/- 5.7 kg, respectively; P = 0.03). Body cell mass by bioelectrical impedance analysis increased significantly (P < 0.001) in both groups (2.6 +/- 1.0 vs. 2.9 +/- 0.8 kg), but to a similar magnitude (P = NS). Significant increases in cross-sectional area by magnetic resonance imaging of total thigh muscles (1538 +/- 767 and 1480 +/- 532 mm2), quadriceps (705 +/- 365 and 717 +/- 288 mm2), and hamstrings (842 +/- 409 and 771 +/- 295 mm2) occurred with both treatment strategies (P < 0.001 for the three muscle areas); these increases were similar in both groups (P = NS). By the one-repetition method, strength increased in both upper and lower body exercises, with gains ranging from 10.3-31% in the nandrolone group and from 14.4-53.0% in the PRT group (P < 0.006 with one exception). Gains in strength were of significantly greater magnitude in the PRT group (P < or = 0.005 for all comparisons), even after correction for lean body mass. Thus, pharmacological doses of nandrolone decanoate yielded significant gains in total weight, lean body mass, body cell mass, muscle size, and strength. The increases in lean body mass and muscular strength were significantly augmented with PRT.

Adult↗
PubMed1999

Inducible binding of cyclic adenosine 3',5'-monophosphate (cAMP)-responsive element binding protein (CREB) to a cAMP-responsive promoter in vivo.

In general, DNA-binding factors that activate gene transcription are thought to do so via reversible interaction with DNA. However, most studies, largely performed in vitro, suggest that the transcriptional activator, cAMP response element-binding protein (CREB), is exceptional in that it is constitutively bound to the promoter, where its phosphorylation leads to the recruitment of CREB-binding protein (CBP) to form a CREB/CBP/promoter complex. We have studied how CREB interacts with DNA in vivo to regulate the cAMP-responsive gene encoding human CRH (hCRH). Protein-DNA complexes were cross-linked in cells expressing the endogenous hCRH gene by exposure to a 10 nsec pulse of high-energy UV-laser light, followed by immunoaffinity purification of CREB-DNA complexes. Binding of CREB to a fragment of the hCRH promoter containing a canonical, functional cAMP response element was absent in untreated cells, but was specifically induced after activation of the protein kinase A pathway with forskolin. These data indicate that, in vivo, CREB, like the majority of other DNA-binding transcriptional activators, undergoes signal-mediated promoter interaction.

Binding Sites↗
PubMed1999

An accelerated schedule for tick-borne encephalitis vaccine: the American Military experience in Bosnia.

Tick-borne encephalitis (TBE) is a viral illness endemic to the Balkan region. United States military forces were deployed to Bosnia in early 1996 as part of Operation Joint Endeavor, a U.S.-led multinational peace-keeping operation. To counteract the TBE threat, an inactivated, parenteral vaccine (FSME-Immun Inject; Immuno AG, Vienna, Austria) was offered to soldiers at high risk on a volunteer basis in an accelerated, 3-dose schedule (0, 7, and 28 days). Passive adverse reaction surveillance was conducted on 3,981 vaccinated personnel. Paired sera from a randomly selected group of 1,913 deployed personnel (954 who received vaccine and 959 who were unvaccinated) were tested for antibodies to TBE by an ELISA. Three-dose recipients demonstrated an 80% seroconversion rate (4-fold or greater increase in anti-TBE titers). By comparison, the TBE infection rate in the unvaccinated cohort was found to be only 0.42% (4 of 959). Only 0.18% of vaccinees reported self-limited symptoms. An accelerated immunization schedule appears to be an acceptable option for military personnel or travelers on short-term notice to TBE-endemic areas.

Adult↗
PubMed1999

[Bypass surgery vs angioplasty for coronary artery disease].

Revascularization techniques such as coronary angioplasty or coronary artery bypass surgery play a growing role in the management of coronary artery disease. Angioplasty is the treatment of choice for single coronary lesions while surgery remains the best approach for the revascularization of multivessel disease. There are some exceptions to this rule, however. Bypass surgery may be recommended for the revascularisation of proximal left anterior descending lesions and, of course, for isolated left main stenosis. On the opposite, coronary angioplasty and stenting is used more frequently in the treatment of multivessel lesions amenable to this technique. Choice of either method of revascularization is pragmatic, based on clinical, anatomical and physiological considerations and organized in the setting of a medicosurgical collaboration.

Angioplasty, Balloon, Coronary↗
PubMed1999

[Massive feto-maternal transfusion. Report of 3 cases with review of the literature].

Massive feto maternal hemorrhage is rare. Early diagnosis is important because massive feto-maternal hemorrhage has a poor prognosis. The clinical manifestations of transplacental hemorrhage are related not only to the size of the hemorrhage but also to the time at which the hemorrhage occurs. In women who are candidates for Rh immune prophylaxis, massive feto maternal hemorrhage may be detected by Kleihauer test and we suggest that 10 micrograms dose of immune globin should be administered for each estimated ml of Rh positive blood given, to prevent an immunization Disappearance of fetal cells by Kleihauer test or appearance residual antibody suggests the adequacy of therapy. Three cases of massive fetomaternal hemorrhage (more than 225 ml) are presented here. Two mothers was Rh negative and they are delivered of rhésus positive children, which necessitated the administration of large volume of anti D. One of the cases shows the possibility of association between choriocarcinoma and positive kleihauer test.

Adult↗
PubMed1998

Interleukin-2 stimulates a late increase in phosphatidic acid production in the absence of phospholipase D activation.

The signal transduction pathways involving phospholipid metabolism during T-cell proliferation remain partly undefined. Herein we show that interleukin-2 caused a late (> 12 h) rise in the intracellular phosphatidic acid content of CTLL-2 cells which was a consequence of the activation of the enzyme diacylglycerol kinase. No activation of phospholipase D was observed at similar times. Incubation of the cells with a recognized diacylglycerol kinase a isoform inhibitor, R59499, prior to interleukin-2 stimulation was able to block cell cycle entry, diacyglycerol kinase activation and phosphatidic acid accumulation. In contrast, when R59499 was added 3 h after interleukin-2, few or no observable effects on the above three parameters were noticed. These results suggest that the early signaling employed by IL-2 involving the alpha isoform of diacylglycerol kinase is sufficient to control the late increase in phosphatidic acid and that phosphatidic acid is a mitogenic agent in T-cells.

3T3 Cells↗
PubMed1998

VIP and PACAP enhance IL-6 release and mRNA levels in resting peritoneal macrophages: in vitro and in vivo studies.

Vasoactive intestinal peptide (VIP), a neuropeptide produced by lymphocytes has been previously reported to modulate cytokine expression in T lymphocytes. In this study, we investigated the effects of VIP and of the structurally related neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP38) on the production of IL-6 in unstimulated murine peritoneal macrophages. Both neuropeptides stimulate rapidly, specifically, and similarly the production of IL-6, exerting their action through two different receptor/signal transduction systems, i.e., primarily through the binding to VIP1/PACAP receptor followed by adenylate cyclase activation, and partially through the activation of protein kinase C following binding to PACAP-R. VIP and PACAP38 regulate the production of IL-6 at a transcriptional level, affecting the de novo synthesis of this cytokine. The stimulatory in vitro effect correlates with the stimulation of IL-6 expression and release in vivo. These studies suggest that VIP/PACAP play a role in immune system homeostasis, participating in the intricate cytokine network and controlling local immune responses. In addition, the understanding of the factors that regulate the expression and release of IL-6 by macrophages is important for the elucidation of the role of IL-6 in health and disease.

Animals↗
PubMed1998

Insulin increases the association of Akt-2 with Glut4-containing vesicles.

Expression of a constitutively active, membrane-associated Akt-1 (PKB alpha) construct in 3T3L1 adipocytes was shown to induce glucose uptake in the absence of insulin by stimulating Glut4 translocation to the plasma membrane (Kohn, A. D., Summers, S. A., Birnbaum, M. J., and Roth, R. A. (1996) J. Biol. Chem. 271, 31372-31378). However, in rat fat cell the vast majority of Akt-1 is cytosolic and shows no re-distribution to the plasma membrane in response to insulin. On the other hand, little work has been done with other Akt family members such as Akt-2 (PKB beta) or Akt-3 (PKB gamma). In this report, an analysis of the subcellular distribution of Akt-2 in rat adipocytes shows that Akt-2 is present in significant amounts in various membrane compartments, as well as in the cytosol, and the former include the light microsomes where Glut4 is present in the basal state. The distribution of Akt-2 in resting adipocytes was found to substantially overlap with that of Glut4 when light microsomes were subfractionated by a sucrose velocity gradient indicating possible co-localization. We confirmed co-localization of Akt-2 and Glut4 in the basal state by immunopurification of Glut4 vesicles, which exhibited a 5.5-fold increase in Akt-2 in response to insulin relative to the amount of Glut4. These results are consistent with the possibility that Akt-2 may be involved in Glut4 vesicle translocation.

Adipocytes↗
PubMed1998

Etiology and prevention of pulmonary complications following beta-mimetic mediated tocolysis.

OBJECTIVES: This study documents biological (haematocrit variations) and therapeutic parameters (salbutamol doses, volumes perfused) in two groups tocolysed with salbutamol, one with and the other without APO in order to define the risk factors linked to APO and to establish a standard protocol of management. STUDY DESIGN: This retrospective study includes data from 68 intravenous salbutamol tocolysis with four resulting APOs, carried out between January 1st, 1993 and December 31st, 1995. RESULTS: There was an excessive level of salbutamol administered over 48 h in the complicated APO-group (122.5+/-52 mg) opposed to the non-APO group (44.9 21 mg) as well as an overload of perfused solute (3.1+/-1.11) versus (1.9+/-1.11). Blood hemodilution was demonstrated in the APO group with a decrease of haematocrit by over 10% between the admission and the control value. No other risk factor was found. CONCLUSION: Tocolysis should be administered at the lowest possible perfusion rate with incremental doses as long as the heart rate stays under 120 beats/min and stopped after 48 h. Administration of maximal 11 of solute perfused/day is recommended. For the patient's follow-up we estimate daily input and output fluid to avoid hydric overload, and a daily control of haematocrit whose variation must be less than 10%.

Acute Disease↗
PubMed1998

Comparative safety evaluation of non-narcotic analgesics.

Both spontaneous reports and single outcome studies may distort the overall safety evaluation of drugs. We identified epidemiologic studies, published from January 1970 to December 1995, that investigated the association of serious adverse effects with aspirin, diclofenac, acetaminophen, and dipyrone to determine and compare the excess mortality associated with short-term drug use. The estimated excess mortality due to community-acquired agranulocytosis, aplastic anemia, anaphylaxis, and serious upper gastrointestinal complications was 185 per 100 million for aspirin, 592 per 100 million for diclofenac, 20 per 100 million for acetaminophen, and 25 per 100 million for dipyrone. The estimates were largely influenced by the excess mortality associated with upper gastrointestinal complications. A relative risk estimate of 300 or more for the association of dipyrone with agranulocytosis would have been necessary for the excess mortality of dipyrone to be comparable to that of aspirin or diclofenac. Based on published epidemiologic evidence used to determine the excess mortality associated with short-term use of these four non-narcotic analgesics, the current regulatory ranking of the drugs appears inappropriate.

Acetaminophen↗
PubMed1998

Tau expression in model adenocarcinomas correlates with docetaxel sensitivity in tumour-bearing mice.

Docetaxel is a new taxoid with clinical activity in breast and lung cancer. Using docetaxel-sensitive and -refractory mammary and pancreatic murine tumours, as well as human-derived neoplasms, we investigated if a determinant of docetaxel sensitivity could be found at the level of its mechanism of action. Because microtubules represent the cellular targets of the drug, we studied their heterogeneity in the tumour models to try to explain the differences in drug sensitivity. Reverse transcription-polymerase chain reaction (RT-PCR) analysis of the expression of microtubular components showed that levels of Mbeta4-tubulin and Tau mRNAs were higher in the murine sensitive neoplasms than in the refractory ones. It was also found that Tau protein levels differed markedly among the tumours. In the human-derived sensitive neoplasm, beta-tubulins and some Tau isoforms were found to be more abundant than in the resistant one. Western blot analysis of MAP2 revealed the presence of several immunoreactive species. Some of these polypeptides were also found in higher amounts in the docetaxel-sensitive tumours. The possible meaning of these correlations is discussed in connection with the regulation of microtubule dynamics.

Adenocarcinoma↗
PubMed1998

Chronic graft-versus-host disease after allogeneic peripheral blood progenitor cell or bone marrow transplantation from matched related donors. A case-control study. Spanish Group of Allo-PBT.

We retrospectively compared the incidence and clinical characteristics of cGVHD in 37 allo-PBT recipients transplanted between July 1994 and October 1996 and 37 historical control allo-BMT recipients in a case-control study. All patients received a first unmanipulated transplant, graft from an HLA-identical sibling donor, with CsA-MTX GVHD prophylaxis and survived more than 100 days after transplant. PBT and BMT groups were well matched for age, grade of acute GVHD, male patients grafted from female donors, and phase of disease. The median CD34+ and CD3+ cell numbers infused in the PBT group were 5.2 x 10(6)/kg and 307 x 10(6)/kg, respectively. The median time to an ANC greater than 0.5 x 10(9)/l was 16 days (range 11-22) after PBT and 22 days (range 14-36) after BMT (P < 0.001). The median time to a platelet count greater than 20 x 10(9)/l was 15 days (range 6-43) after PBT and 28 days (range 12-68) after BMT (P < 0.001). Median follow-up was 12.3 months (range 5.4-30.3) and 58.7 months (range 4-122.3), for patients receiving PBT and BMT, respectively. Seventeen out of 37 (46%) PBT recipients, vs nine out of 37 (24%) BM recipients developed cGVHD. Actuarial probability of cGVHD at 1 year was 59% (95% CI, 39-79) in the PBT group vs 27% (95% CI, 12-42) in the BM group (P = 0.01). Cumulative incidence estimate of cGVHD was 51% and 25%, for patients receiving PBT and BMT respectively (P = 0.03). Clinical characteristics of cGVHD and response to therapy were similar in both groups, except for a higher incidence of de novo cGVHD in the PBT group. Our results suggest that as compared with BMT, PBT may result in an increased incidence of cGVHD.

Adolescent↗