Failure of a patient-controlled analgesia pump in a hyperbaric environment.
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Biomedical subjects
Publications and source records attributed to A Crespo.
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The association between neuroblastic tumours and congenital heart disease is widely confirmed in the literature references. The authors describe a case of a patient with congenital heart disease, high blood pressure, renal artery stenosis and high levels in 24 hours urine metanephrines. A MIBG-I-123 scintigraphy was essential for the diagnosis of neuroblastic tumour.
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The effects of 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine H-7 (a cAMP-dependent protein kinase and protein kinase C inhibitor), n-(2-[methylamino]ethyl)-5-isoquinoline-sulfonamide H-8 (a cAMP- and cGMP-dependent protein kinase inhibitor) and indomethacin (IND, a cyclooxygenase inhibitor) on both the spontaneous metastatic ability of 3LL (Lewis lung carcinoma) tumor cells and anti-tumor host response were studied. The study of tumor progression showed that H-7 and H-8 (2 mg kg(-1) day(-1) , i.p., for 8 days) significantly reduced the mean number of metastases (0.8 +/- 0.2 and 1.0 +/- 0.7, respectively, P < 0.05) with respect to the number of lung metastases (4.2 +/- 2.1) observed in the control group. In turn, the highest tumor-specific cytotoxicity response (50% increase vs. non-treated target cells) was observed when both animal and tumor cells were treated with H-8. This suggests that the protein kinase inhibitors could inhibit tumor progression toward lung metastases formation by blocking the immunosuppressor mechanism triggered by agents that increase intracellular cAMP.
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We report two patients with AIDS and non-Hodgkin lymphoma evolving myocardium. Clinical findings were nonspecific, but rapid progression and cardiac dysfunction developed. An echocardiogram showed restrictive pericarditis in both cases. One of them showed mitral insufficiency because of an infiltrated and trapped posterior mitral valve.
The aim of this study was to establish the usefulness of Tc-99m human polyclonal immunoglobulin (HIG) imaging in a group of patients who were suspected of having inflammatory bowel disease (IBD). The authors performed 30 scans (15 with Tc-99m HMPAO leukocytes and 15 with Tc-99m HIG) on 15 patients with IBD. Ten patients had Crohn's disease and five had ulcerative colitis. The sensitivity of Tc-99m HIG scintigraphy for detecting IBD was 33%, while the sensitivity of Tc-99m HMPAO leukocyte imaging was 100%. The Tc-99m HMPAO leukocyte imaging also detected a larger number of affected segments and provided better image quality of the extent of disease than Tc-99m HIG. On the basis of these results, the authors believe that Tc-99m HIG imaging is not a useful technique in the evaluation of patients with IBD, in the identification of location, or the extension or degree of disease activity.
The effects of acidic fibroblast growth factor (FGF-1) and basic fibroblast growth factor (FGF-2) and a non mitogenic form of FGF1 on myocardial ischemia and reperfusion were assessed. Rats underwent 10 minutes of coronary artery occlusion followed by 24 hours of reperfusion. Creatinine kinase content of the affected myocardium showed that both fibroblast growth factors 1 and 2 effectively protected against ischemia reperfusion injury (p < 0.01), and that the vasoactive but nonmitogenic form of the FGF1 was equally protective (p < 0.01 versus control + vehicle). The results were confirmed by light and electron-microscopy histological studies. Histological evaluations after treatment with the non-mitogenic fibroblast growth factor 1 showed that it did not generate the severe hyperplasia and connective tissue disorganization observed with the native mitogenic proteins. The possibility of using a non-mitogenic form of fibroblast growth factor for cardio-protection circumvents many of the potentially undesirable effects that may derive from systemically introducing broad spectrum acting fibroblast growth factors in vivo. This myocardial protection observed 24 hours after the treatment with fibroblast growth factors, and the efficacy of the non-mitogenic form of the protein, also suggest that the protective effect of fibroblast growth factors may be due to the increased blood flow rather than to angiogenesis.
The efficiency of both anionic and cationic liposomes as vectors for in vivo human alpha1-antitrypsin (AAT) gene transfer was studied in mice with and without an associated partial hepatectomy. The pTG7101 plasmid, containing the full-length human AAT gene, was encapsulated in small liposomes bearing 10% of negatively (phosphatidylserine, PS) or positively (DOTAP) charged lipids. The results indicated that the DNA/lipid ratio was increased in cationic liposomes by inclusion of monosialoganglioside-GM1. The expression of human protein after in vivo gene transfer was quantified in mouse plasma by an ELISA procedure, and revealed that both anionic and cationic liposomes mediated the presence of human protein in mouse plasma for 2-3 weeks. This effect was prolonged (>5 months) when a partial hepatectomy was performed after treatment. In addition, it was observed that the efficacy of liposome-mediated gene transfer was more limited when the plasmid was externally associated to cationic liposomes.
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Adrenal scintigraphy has been shown to be a useful procedure for the characterization of incidentally discovered adrenal tumours. The functional evaluation of these patients is controversial. This paper describes the biochemical and pathological findings in five patients with asymptomatic adrenal masses and unilateral concordant adrenocortical scintigraphic uptake. All the patients were diagnosed as having subclinical Cushing's Syndrome, without clinical or biochemical adrenocortical dysfunction. Scintigraphy is the most sensitive method for detecting an adrenal adenoma in the subclinical setting when the disease is not yet demonstrable by biochemical methods.
B16 melanoma-bearing mice were treated with anti-interleukin 4 antibody, indomethacin or its combination to evaluate the ability of the primary tumor to induce lung metastasis and the antitumor host response. Flow cytometry of tumor cells incubated with sera from tumor-bearing mice showed B16 melanoma to induce a significant antitumor humoral response (39.0 +/- 1.1% positive cells versus 1.8 +/- 0.9% in the control). The treatment of tumor-bearing mice with antimouse anti-interleukin 4 monoclonal antibody plus indomethacin significantly increased (P < .01) the mean value of lung metastasis (from 6.1 +/- 3.0 in the controls to 50.8 +/- 21.8). Also, a significant increase in natural cytotoxicity against tumor cells was observed when both peripheral blood mononuclear cells and splenocytes were used as effector cells. In contrast, an antibody-dependent cellular cytotoxicity decrease was found with effector cells from both normal and tumor-bearing mice. In the former, the antibody-dependent cellular cytotoxicity decrease was 49.4% and 58.4% (P < .05) for peripheral blood mononuclear cells and splenocytes, whereas in the second case the decrease was 40.7% (P < .05) and 29.1% (P < .01), respectively. These results suggest that an efficient antibody-dependent cellular cytotoxicity response might be necessary to secure an effective host antitumor immune response.
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A plasmid (pTG7101) containing the full-length human alpha 1-antitrypsin gene was encapsulated in small liposomes and used for "in vivo" gene transfer to mouse hepatocytes, by i.v. injection (100 ng DNA/mouse and dose). The expression of human protein was evaluated by microspectrophotometry after human alpha 1-antitrypsin immunoperoxidase reaction on liver cryosections and the presence in mouse plasma of de novo synthesized protein was detected by ELISA analysis. Our results indicate that a single dose of encapsulated plasmid induces the expression of human alpha 1-antitrypsin in mouse hepatocytes and a large effect (70%) remains two weeks after treatment. However, no effect was observed when mice were treated with buffer or free plasmid (100 ng/mouse) plus an equivalent lipid dose of empty liposomes. In addition, whereas no additive effect was observed after repetitive treatment-doses, the partial hepatectomy three hours after a single treatment-dose, significantly increased the presence of human alpha 1-antitrypsin in mice plasma.
The human galanin receptor has been characterized pharmacologically from the Bowes melanoma cell line. Using porcine [125I]galanin as the radioligand, a single population of non-interacting high-affinity binding sites (KD = 0.05 +/- 0.01 nM; Bmax = 135 +/- 7 fmol/mg protein) was demonstrated. Human galanin peptide competitively inhibited the specific binding of [125I]galanin (IC50 = 0.35 +/- 0.13 nM) and decreased the forskolin-stimulated cAMP production (EC50 = 0.46 +/- 0.05 nM) with a maximal inhibition of 63 +/- 2% at 10(-7) M. Rat and porcine galanin peptides and the chimeric peptides M15, M35, M32, M40 and C7 also dose-dependently inhibited the forskolin-stimulated cAMP production, while the fragment porcine galanin-(3-29) and [D-Trp2]galanin were found to be inactive. The specific binding of [125I]galanin was decreased in a dose-dependent manner by GTP and the cAMP response was inhibited by the pertussis toxin, suggesting the activation of a G-protein dependent process. The Bowes cell line thus appears to be a relevant tool for the study of human galanin receptor.
Ligand-receptor affinity is classically demonstrated by measuring ligand binding density to a specific site on membrane preparations, and receptor function is studied by measuring calcium flux, cell by cell, using microspectrofluorimetry. In order to study these phenomena in a large cell population, calcium flux was measured in MRC-5 cell line expressing the B2 receptor for bradykinin using an ACAS 570 scanning cytometer. Following incorporation of fluo3/AM, different ligands were studied, singly or in association with bradykinin. This study confirmed that only the B2 receptor is present on the plasma membrane of MRC-5 cells. Bradykinin binding to the B2 receptor was not modified by a B1 agonist (Des-Arg9-bradykinin) or by a B1 antagonist (Des-Arg9-[Leu8]-bradykinin) but was inhibited by a B2 agonist ([Hyp3]-bradykinin) and a B2 antagonist (HOE 140). The source of free calcium was also studied in comparison with ionomycin. The intensity of the calcium peak after binding of bradykinin is independent of the concentration of extracellular calcium. Preincubation with diltiazem or TMB-8 did not modify calcium flux, indicating that transduction of the signal after bradykinin binding in this cell line is independent of voltage-dependent channels and does not require mobilization of intracellular calcium blocked by TMB-8. In conclusion, scanning cytometry can be used to study ligand-receptor binding and to obtain results rapidly from multiple cells. Recording of individual cell variations and kinetics enables identification of active agonists or antagonists and consequently the selection of new compounds.