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Biomedical subjects

A Gonzales

Publications and source records attributed to A Gonzales.

At least 19 recordsLinked to original sources
PubMed2005

CT-angiography for the detection of a lower gastrointestinal bleeding source.

The evaluation of lower gastrointestinal bleeding (LGIB) often involves the collaborative efforts of the gastroenterologist, radiologist, and surgeon. Efforts to localize the acute LGIB have traditionally involved colonoscopy, technetium-labeled red blood cell (RBC) scintigraphy, angiography, or a combination of these modalities. The sensitivity of each method of diagnosis is limited, with the most common cause of a negative study the spontaneous cessation of hemorrhage. Other technical factors include vasospasm, lack of adequate contrast volume or exposure time, a venous bleeding source, and a large surface bleeding area. We report the use of multidetector computed tomography (MDCT), or CT-angiography (CT-A), in the initial evaluation of LGIB, and speculate on the incorporation of this technique into a diagnostic algorithm to treat LGIB. MDCT may offer a very sensitive means to evaluate the source of acute LGIB, while avoiding some of the morbidity and intense resource use of contrast angiography, and may provide unique morphologic information regarding the type of pathology. Screening with the more rapid and available MDCT, followed by either directed therapeutic angiography or surgical management, may represent a reasonable algorithm for the early evaluation and management of acute LGIB in which an active bleeding source is strongly suspected.

Adult↗
PubMed2003

Taenia solium infection in a rural community in the Peruvian Andes.

An epidemiological study was conducted in a highland, rural community in Peru, to determine the seroprevalences of human and porcine infection with Taenia solium and the risk factors associated with human infection. The seroprevalences, determined using an assay based on enzyme-linked-immuno-electrotransfer blots (EITB), were 21% (66/316) in the humans and 65% (32/49) in the pigs. The human subjects aged <30 years were more likely to be positive for anti-T. solium antibodies than the older subjects (P < 0.001). The risk factors associated with human seropositivity were lack of education beyond the elementary level [odds ratio (OR)=2.69; 95% confidence interval (CI)=1.09-6.65] and pig-raising (OR=1.68; CI=0.96-2.92). Curiously, sheep-raising was inversely associated with human T. solium infection (OR=0.50; CI=0.28-0.90). The study site appears to be a new endemic focus for T. solium in the central Peruvian Andes. Although, in earlier studies, the seroprevalence of T. solium infection has generally been found to increase with age, the opposite trend was observed in the present study. The results of follow-up studies should help determine if the relatively high seroprevalence in the young subjects of the present study is the result of a transient antibody response.

Adolescent↗
PubMed2001

Interleukin-2 binds to ganglioside GD(1b).

We have developed a solid matrix immunoassay to determine the binding of interleukin-2 (IL-2) to specific gangliosides. The assay establishes that recombinant human IL-2 binds to ganglioside GD(1b) but not to any other gangliosides (GM(1), GM(2), GM(3), GD(1a), GD(2), GD(3), and GT(1b)). The binding varies with the ratio of GD1b and IL-2. This assay enables distinguishing the nature of the sugar moiety of the ganglioside recognized by IL-2 and establishes the dosimetry of the ganglioside-IL-2 interaction. Since rIL-2 is administered systematically into stage IV melanoma patients, we have examined 45 tumor biopsies for GD(1b) content. The incidence of GD(1b) in tumor biopsies is 51%. We postulate that GD(1b) associated on the tumor or in the circulation of cancer patients may bind to rIL-2 and prevent the availability of rIL-2 to augment antitumor-immune response.

Binding Sites↗
PubMed2000

Gangliosides as targets for immunotherapy for pancreatic adenocarcinoma.

BACKGROUND: Pancreatic adenocarcinoma cells express gangliosides and sialyl Lewis (sLe) antigens. It is not known whether these carbohydrate antigens can be targeted by immunotherapy. The authors measured the expression of GM(2) and sLe antigens on the surface of pancreatic carcinoma cells and the serum levels of total gangliosides, GM(2), and antiganglioside antibodies in patients with pancreatic carcinoma. METHODS: Cell surface GM(2) and sLe antigens were measured by cell suspension enzyme linked immunoadsorbent assay (ELISA) in four pancreatic carcinoma cell lines. Sera from 20 pancreatic carcinoma patients and 20 age- and gender-matched healthy volunteers were analyzed for antiganglioside and anti-sLe immunoglobulin (Ig) M titers by ELISA. Serum levels of total gangliosides and GM(2) also were measured. RESULTS: All cell lines expressed GM(2) and sLe antigens. When compared with age- and gender-matched volunteers, patients had significantly higher serum levels of total gangliosides (25.6 +/- 9.0 mg/dL vs. 15.6 +/- 2.7 mg/dL; P < 0.001), GM(2) (0.278 +/- 0.415 mg/dL vs. 0.013 +/- 0.018 mg/dL; P = 0.02), ELISA units of anti-GM(2) IgM antibody (368 +/- 95 vs. 155 +/- 25; P = 0.04) and anti-GD(1b) IgM antibody (351 +/- 91 vs. 138 +/- 26; P = 0.03), but not anti-sLe(x) IgM (1389 +/- 345 vs. 1081 +/- 224; P = 0.46) or anti-sLe(a) IgM antibody (1097 +/- 253 vs. 1200 +/- 315; P = 0.80). Patients with unresectable tumors had higher serum levels of total gangliosides compared with patients with resectable tumors, and a serum level > 25 mg/dL was found to correlate significantly with poor overall survival (P < 0.02). CONCLUSIONS: Increased serum levels of total gangliosides and GM(2) may reflect shedding or release of gangliosides from the surface of tumor cells. Production of IgM antibody against GM(2) and GD(1b) indicates that these gangliosides are immunogenic antigens that may be potential targets for effective active immunotherapy.

Adenocarcinoma↗
PubMed1998

Heme oxygenase-1-derived carbon monoxide contributes to the suppression of acute hypertensive responses in vivo.

The enzyme heme oxygenase, which exists in inducible (HO-1) and constitutive (HO-2) isoforms, catalyzes the degradation of heme to biliverdin and CO in mammalian tissues. CO has been implicated in the control of vascular tone in a manner similar to that for NO. In the present study, we investigated the contribution of the heme oxygenase/CO pathway to the modulation of acute hypertensive responses in vivo induced by (1) alphaalphaHb, a chemically modified hemoglobin known to scavenge NO, and (2) NG-nitro-L-arginine methyl ester (L-NAME), a competitive NOS inhibitor. Experiments were carried out in conscious rats in which femoral arteries and veins were surgically catheterized 1 or 5 days before treatment with the vasoconstrictor agents. Intravenous infusion of alphaalphaHb (8% solution) or L-NAME (30 micromol/kg) [corrected] produced an acute and significant increase in mean arterial pressure (P<0.05) in rats at 5 days after catheter implantation. In contrast, no change in blood pressure was observed when alphaalphaHb or L-NAME was infused 1 day after the surgical intervention. The suppression of the hypertensive response observed at 1 day after surgery correlated with a significant (P<0.05) HO-1 expression in aorta, heart, and liver as well as increased aortic CO production and cGMP levels. At 1 day after surgery, pretreatment of animals with the heme oxygenase inhibitor zinc protoporphyrin IX (50 micromol/kg IP) markedly decreased aortic CO and cGMP levels and completely restored the vasoconstrictor effects of both alphaalphaHb and L-NAME. These results provide evidence for a crucial role of the heme oxygenase/CO pathway in the regulation of blood pressure under stress conditions in vivo.

Acute Disease↗
PubMed1998

Arterial blood pressure responses to cell-free hemoglobin solutions and the reaction with nitric oxide.

Changes in mean arterial pressure were monitored in rats following 50% isovolemic exchange transfusion with solutions of chemically modified hemoglobins. Blood pressure responses fall into three categories: 1) an immediate and sustained increase, 2) an immediate yet transient increase, or 3) no significant change either during or subsequent to exchange transfusion. The reactivities of these hemoglobins with nitric monoxide (.NO) were measured to test the hypothesis that different blood pressure responses to these solutions result from differences in .NO scavenging reactions. All hemoglobins studied exhibited a value of 30 microM-1 s-1 for both .NO bimolecular association rate constants and the rate constants for .NO-induced oxidation in vitro. Only the .NO dissociation rate constants and, thus, the equilibrium dissociation constants varied. Values of equilibrium dissociation constants ranged from 2 to 14 pM and varied inversely with vasopressor response. Hemoglobin solutions that exhibited either transient or no significant increase in blood pressure showed tighter .NO binding affinities than hemoglobin solutions that exhibited sustained increases. These results suggest that blood pressure increases observed upon exchange transfusion with cell-free hemoglobin solutions can not be the result of .NO scavenging reactions at the heme, but rather must be due to alternative physiologic mechanisms.

Animals↗
PubMed1998

Comparison between short or long exposure to 5-fluorouracil in human gastric and colon cancer cell lines: biochemical mechanism of resistance.

Recent preclinical and clinical data indicate that the main mechanisms of 5-fluorouracil (5-FU) cytotoxicity depend on the mode of administration. To gather further insight into the major causes of acquired 5-FU resistance, drug-sensitive human gastric (M2), colon (HT29) and breast (MCF7) cancer cell lines were repeatedly exposed to a fixed concentration of 5-FU given either for 1 or 24 h. Although equieffective doses (IC50) of 5-FU were used, resistance to a 1 h exposure of 5-FU developed faster in all models than to a 24 h exposure. Cell lines with acquired resistance to a 1 h application of 5-FU were only partly cross-resistant to a 24 h exposure, whereas lines with resistance to protracted application of 5-FU displayed significant cross-resistance to the 1 h schedule. Resistance to methotrexate was only seen in cell lines with acquired resistance to 24 h of 5-FU. All 5-FU-resistant cell lines showed reduced incorporation of 5-FU into cellular RNA. Furthermore, elevations of thymidylate synthase were seen in all cell lines with resistance to 24 h of 5-FU but also in one cell line with resistance to a bolus schedule. No alterations in folylpolyglutamate synthase developed in the resistant cell lines. These data support the concept that the main mechanisms of 5-FU cytotoxicity depend on the mode of application. Incorporation of fluorouridine triphosphate into RNA appears to be the most important mechanism of action for 5-FU bolus schedules, whereas inhibition of thymidylate synthase becomes more important as the infusion time is prolonged. These data could have implications on the interaction of 5-FU given at different schedules with various other cytostatic agents.

Adenocarcinoma↗
PubMed1998

Vascular resistance and the efficacy of red cell substitutes in a rat hemorrhage model.

We have compared polyethylene glycol-modified bovine hemoglobin (PEG-Hb; high O2 affinity, high viscosity, high oncotic pressure) and human hemoglobin cross-linked between the alpha-chains (alpha alpha-Hb; low O2 affinity, low viscosity, low oncotic pressure) with a non-O2-carrying plasma expander (pentastarch, high viscosity and oncotic pressure) after a 50% (by volume) exchange transfusion followed by a severe (60% of blood volume) hemorrhage. Mean arterial pressure and systemic vascular resistance rose significantly in the alpha alpha-Hb but not in the PEG-Hb animals. Two-hour survival was greater in the PEG-Hb animals (93%) than in control (35%), pentastarch (8%), or alpha alpha-Hb (6%) animals. In the PEG-Hb animals, there was no disturbance of acid-base balance, significantly less accumulation of lactic acid, and higher cardiac output than in the other groups. The data suggest that the rise in vascular resistance that follows alpha alpha-Hb exchange transfusion offsets the additional O2 transport provided by the cell-free hemoglobin. When resistance does not rise, as with PEG-Hb, even relatively small amounts of cell-free hemoglobin appear to be a very effective blood replacement.

Animals↗
PubMed1997

Microvascular oxygen delivery and interstitial oxygenation during sodium pentobarbital anesthesia.

BACKGROUND: Anesthesia may represent a considerable bias in experimental medicine, particularly in conditions of stress (such as hemorrhage). Sodium pentobarbital (PB), widely used for cardiovascular investigations, may impair oxygen delivery by hemodynamic and respiratory depression. The critical issue, however, is whether the microcirculation can still maintain tissue oxygenation during anesthesia. To answer this question, the authors studied the effect of PB anesthesia on subcutaneous microvascular oxygen delivery and interstitial oxygenation in Syrian golden hamsters. METHODS: Sodium pentobarbital anesthesia was induced by intravenous injection (30 mg/kg body weight) and maintained by a 15-min infusion (2 mg.kg-1.min-1), with animals breathing spontaneously (PB-S) or ventilated with air (PB-V). Systemic parameters evaluated were mean arterial pressure (MAP), heart rate, cardiac index (CI), arterial oxygen tension (PaO2), arterial carbon dioxide tension (PaCO2), base excess, and pH. Microvascular and interstitial oxygen tension (PO2), vessel diameter, red blood cell velocity (vRBC), and blood flow (Qb) were measured in a dorsal skinfold preparation. Microcirculatory PO2 values were determined by phosphorescence decay. RESULTS: Sodium pentobarbital anesthesia significantly decreased CI, MAP, vRBC, and Qb. During PB infusion, PaO2 values were 56 +/- 12.8 mmHg (PB-S) and 115.9 +/- 14.6 mmHg (PB-V) compared with 69.4 +/- 18.2 mmHg and 61.4 +/- 12.6 mmHg at baseline. However, microvascular PO2 was reduced by 25-55% in both groups, resulting in an interstitial PO2 decrease from 23.9 +/- 5.6 mmHg (control) to 13.1 +/- 9.1 mmHg (PB-S) and 15.2 +/- 7 mmHg (PB-V). Microcirculatory PO2 values were restored 30 min after PB infusion, even though hemodynamic depression and a light anesthetic plane were maintained. CONCLUSIONS: Sodium pentobarbital anesthesia caused impairment of microvascular oxygen delivery and interstitial oxygenation, effects that were not prevented by mechanical ventilation. Although these effects were restricted to deep anesthetic planes, prolonged hemodynamic depression suggests that caution is warranted when using PB as an anesthetic in cardiovascular investigations.

Anesthesia↗
PubMed1997

Blood volume and cardiac index in rats after exchange transfusion with hemoglobin-based oxygen carriers.

We have measured plasma volume and cardiac index in rats after 50% isovolemic exchange transfusion with human hemoglobin cross-linked between the alpha-chains with bis(3,5-dibromosalicyl)fumarate (alpha alpha Hb) and with bovine hemoglobin modified with polyethylene glycol (PEGHb). alpha alpha Hb and PEGHb differ in colloid osmotic pressure (23.4 and 118.0 Torr, respectively), oxygen affinity (oxygen half-saturation pressure of hemoglobin = 30.0 and 10.2 Torr, respectively), viscosity (1.00 and 3.39 cP, respectively), and molecular weight (64,400 and 105,000, respectively). Plasma volume was measured by Evans blue dye dilution modified for interference by plasma hemoglobin. Blood volumes in PEGHb-treated animals were significantly elevated (74.0 +/- 3.5 ml/kg) compared with animals treated with alpha alpha Hb (49.0 +/- 1.2 ml/kg) or Ringer lactate (48.0 +/- 2.0 ml/kg) or with controls (58.2 +/- 1.9 ml/kg). Heart rate reduction after alpha alpha Hb exchange is opposite to that expected with blood volume contraction, suggesting that alpha alpha Hb may have a direct myocardial depressant action. The apparently slow elimination of PEGHb during the 2 h after its injection is a consequence of plasma volume expansion: when absolute hemoglobin (concentration x plasma volume) is compared for PEGHb and alpha alpha Hb, no difference in their elimination rates is found. These studies emphasize the need to understand blood volume regulation when the effects of cell-free hemoglobin on hemodynamic measurements are evaluated.

Animals↗
PubMed1997

Phenytoin and cyclosporine A specifically regulate macrophage phenotype and expression of platelet-derived growth factor and interleukin-1 in vitro and in vivo: possible molecular mechanism of drug-induced gingival hyperplasia.

Phenytoin (pht) is an anticonvulsant drug commonly used for the prevention of seizures. A common side effect of PHT therapy is gingival hyperplasia, occasionally so severe that it requires surgical intervention. Cyclosporine A (CSA) is a drug widely used for the control of rejection phenomena following solid organ and bone marrow transplantation. A frequent side effect of CSA administration is gingival overgrowth. As yet, the molecular mechanisms of drug-induced gingival hyperplasia are unknown although it has been postulated that certain drugs increase fibroblastic activity through alterations in levels of various growth factors and cytokines. The purpose of this study was to: 1) evaluate monocyte/macrophage platelet-derived growth factor (PDGF) and interleukin (IL)-1 beta production in vitro after exposure to CSA; 2) determine the levels of PDGF-B and IL-1 beta gene expression in minimally inflamed gingival tissues of control patients and PHT-treated patients exhibiting gingival overgrowth as well as patients with severe gingival inflammation; and 3) combine characterization of macrophage phenotype with clinical presentation and expression of PDGF-B and IL-1 beta in gingival tissues from the control and PHT-treated patients. For the in vitro studies, commercial ELISA kits were used to measure PDGF-A/PDGF-B and IL-1 beta levels in conditioned media from rat and human monocyte/macrophage cell cultures. CSA caused a significant elevation of PDGF but did not cause any changes in IL-1 beta levels. For the in vivo studies, quantitative competitive reverse transcription polymerase chain reaction (QC-RTPCR) techniques were utilized to measure PDGF-B and IL-1 beta mRNA levels in experimental groups. PHT-treated patients exhibiting gingival overgrowth demonstrated a significant increase in PDGF-B mRNA compared with minimally inflamed controls. Patients with severe gingival inflammation also demonstrated a significant increase in PDGF-B mRNA however, PHT-induced PDGF-B upregulation is approximately 6 times larger than PDGF-B upregulation produced by inflammation alone. PHT-treated patients exhibiting gingival overgrowth demonstrated no significant increase in IL-1 beta mRNA; however, IL-1 beta mRNA levels in the severely inflamed gingival samples demonstrated a significant increase. Additionally, for the clinical samples, macrophage phenotype was characterized immunohistochemically in adjacent sections using specific monoclonal antibodies for inflammatory and reparative/proliferative phenotypes. There were no significant differences in the numbers of either macrophage phenotype in minimally inflamed gingival tissues; however, in the severely inflamed tissue, there was a significant increase in the inflammatory macrophage phenotype and in the hyperplastic gingival tissue, there was a significant increase in the reparative/proliferative macrophage phenotype. The results of this investigation indicate that the clinical presentation of inflamed and hyperplastic gingival tissues is associated with specific macrophages phenotypes which express the pro-inflammatory cytokine IL-1 beta in inflamed tissues or the essential polypeptide growth factor PDGF-B in PHT-induced hyperplastic tissues.

Adult↗
PubMed1996

Techniques in facial identification: computer-aided facial reconstruction using a laser scanner and video superimposition.

A facial image was reconstructed from the skull, part of a complete skeleton found in woodland, of a male person who hanged himself from a tree. In addition, video superimposition was carried out with antemortem photographs of a person suspected of being the victim, and a good match was obtained. In a further case, a cheaper video-transparency superimposition was carried out, with identity later being confirmed on the basis of dental records. The techniques and the problems encountered are discussed. According to our experience, 3D computer reconstruction and video superimposition have a useful role in the process of identification, particularly in the early stages of an investigation and when other more definitive methods may not be available.

Adult↗
PubMed1995

[Nasal carriage of Staphylococcus aureus: prevalence in a hemodialysis center and effect on bacteremia].

We evaluated nasal carriage of Staphylococcus aureus (S. aureus) in 114 hemodialysis patients by performing two nasal swab cultures at a one month interval. The incidence of bacteremia was then followed for one year. Other factors associated with infections in hemodialysis patients, such as diabetes, central venous catheter, and high serum ferritin levels were also evaluated. Nasal carriage of S. aureus was present in 29.8% of patients (34/114). Six S. aureus bacteremia occurred in 6 patients. This represents an annual incidence of 0.058 bacteremia/patient-year. The incidence of bacteremia was higher in patients with S. aureus nasal carriage (0.0945) than in patients without (0.0417), but the difference was not significant. The relative risk (RR) was 2.35. On the contrary, bacteremia were significantly more frequent in patients with diabetes (RR = 11.41; p = 0.004) or in patients with central venous catheter (RR = 14.29; p = 0.002). In conclusion, in our population, diabetes and central venous catheter are more significant risk factors of bacteriemia than S. aureus nasal carriage.

Bacteremia↗
PubMed1994

Diaspirin cross-linked hemoglobin: tissue distribution and long-term excretion after exchange transfusion.

This report describes the tissue distribution and long-term (14-day) excretion of hemoglobin cross-linked between the alpha-chains (alpha alpha Hb) with carbon 14-labeled bis(3,5-dibromosalicyl)fumarate. Fully conscious, chronically cannulated rats (n = 40) were treated with a 50% isovolemic exchange transfusion (ET) with solutions of 14C-labeled alpha alpha Hb (8.0 gm/dl) and were then monitored for as long as 14 days. Thirteen tissue types were analyzed for radioactivity by liquid scintillation counting. The highest concentration of label was found in the kidney and in tissues of the reticuloendothelial system (i.e., spleen, bone marrow, and liver). The 14C-labeled alpha alpha Hb did not appear to cross the blood-brain barrier, because radioactivity in the brain was barely detectable. The dose of 14C-labeled alpha alpha Hb (2.4 gm Hb/kg) produced an initial plasma Hb level of 4.6 gm/dl, with a half-life in the plasma of 5.0 hours. The peak concentration in kidney, spleen, and liver occurred at 24 hours after ET, when at least 92% of the 14C-labeled alpha alpha Hb in plasma had been cleared. At 48 hours, red casts were seen in a tiny number of renal tubules in some rats. By 14 days, up to 64% of the injected radioactivity had been recovered in urine and about 10% was recovered in feces. Most excretion occurred 24 to 48 hours after ET. This study demonstrated that 2 weeks were required for the metabolic degradation and elimination of a large dose of alpha alpha Hb in rats.

Animals↗
PubMed1993

Acute changes in systemic blood pressure and urine output of conscious rats following exchange transfusion with diaspirin-crosslinked hemoglobin solution.

This report describes acute changes in systemic blood pressure and urine output observed after a 50-percent isovolemic exchange transfusion (ET) with diaspirin-crosslinked hemoglobin (alpha alpha Hb). Stroma-free Hb was crosslinked between the alpha chains by using a 14C-labeled diaspirin, bis(3,5-dibromosalicyl)fumarate. Forty conscious, chronically cannulated rats underwent ET with 14C-labeled alpha alpha Hb solution (8.0 g/dL [80 g/L]). This resulted in systemic hypertension for 3 to 4 hours after ET (mean arterial pressure rose from 120 to 145 torr at 1 to 2 hours after ET) and mild bradycardia for 2 to 3 hours (heart rate decreased from 420 to 335 beats/min [bpm] before stabilizing at 360 +/- 10 bpm). This was accompanied by significant diuresis immediately after ET (5- 6-fold increase in urine output, which normalized after 12 hours), and mild hemoglobinuria. The total amount of Hb recovered in the urine was < 5 percent of the injected dose. Reversed-phase high-performance liquid chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis confirmed the presence of crosslinked alpha alpha Hb molecules in the urine. Renal excretion of radioactivity was significantly greater, with 20 percent of total radioactivity being eliminated within 24 hours. The plasma half-life for alpha alpha Hb was 5 hours (administered dose, 2.4 g Hb/kg body weight). Thus, infusion of alpha alpha Hb caused a transient systemic hypertension, and intramolecular crosslinking alone was not enough to exclude completely the filtration of alpha alpha Hb by the kidneys.

Animals↗