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Biomedical subjects

G Gutierrez

Publications and source records attributed to G Gutierrez.

At least 55 records · Page 3Linked to original sources
PubMed1995

Inhibitory effect of Escherichia coli endotoxin on skeletal muscle contractility.

OBJECTIVE: Endotoxemia in rabbits is associated with decreases in oxygen transport, tissue hypoxia, metabolic acidosis, and impaired oxygen extraction. In this study, we tested the hypothesis that endotoxin also inhibits skeletal muscle contractility directly. DESIGN: Randomized animal study. SETTING: Accredited animal research facility. SUBJECTS: New Zealand white rabbits of either sex, weighing 2.55 +/- 0.20 kg. INTERVENTIONS: We compared two groups of rabbits (n = 10 each) undergoing continuous electrical stimulation of the left hindlimb (maximal isometric twitch contraction at 0.25 Hz). One group (septic) was given an intravenous infusion of Escherichia coli endotoxin. The control group was subjected to decreases in cardiac output by inflating a balloon placed in the right ventricle. MEASUREMENTS AND MAIN RESULTS: Endotoxin or balloon inflation resulted in comparable decreases in cardiac output (49% and 53%, respectively). Hindlimb oxygen transport decreased to similar values for both groups (4.9 +/- 0.3 and 4.2 +/- 0.5 mL/min/kg, respectively). Systemic oxygen extraction ratio was greater in the control group (0.72 +/- 0.03) than in the septic group (0.55 +/- 0.04; p < .05). There were no differences in hindlimb oxygen extraction ratio. Decreases in hindlimb forces were greater in the septic group (42 +/- 4%) than in the control group (18 +/- 3%, p < .01). Force frequency curves obtained at the beginning and the end of the experiment showed greater fatigue in the septic group. CONCLUSIONS: The intravenous infusion of Escherichia coli endotoxin produces a direct inhibitory effect on skeletal muscle contractility in rabbits. This phenomenon is independent of decreases in oxygen transport and blood pH. Our data support the notion of a direct cellular effect of endotoxin, or of an associated cytokine, on skeletal muscle contractility. The mechanism responsible for this phenomenon is unknown.

Animals↗
PubMed1994

Effects of dobutamine on oxygen transport and consumption in the adult respiratory distress syndrome.

OBJECTIVE: To determine if oxygen consumption (VO2) in patients with adult respiratory distress syndrome (ARDS) is dependent on, and thus limited by, oxygen transport (TO2) rather than O2 demand. DESIGN: Prospective study. SETTING: Intensive care unit of a tertiary referral center. PATIENTS: 12 patients with ARDS and sepsis syndrome. INTERVENTIONS: Routine intensive care unit monitoring including pulmonary and radial artery catheters. MEASUREMENTS: Dobutamine was used to increase cardiac output, thereby directly varying TO2 under conditions of constant O2 demand. After baseline measurements of TO2 and VO2, dobutamine was infused intravenously at progressively increasing doses of 5, 10, 15 and 20 micrograms/kg/min and measurements of TO2 and VO2 were repeated after 30 min at each dose. RESULTS: Dobutamine increased TO2 in 8 of the 12 patients, by 29% at 5 micrograms/kg/min and by 45% (net) at 10 micrograms/kg/min, but not at higher doses. In these 8 patients dobutamine also increased VO2 by 15% at 5 micrograms/kg/min, but did not further increase VO2 at higher doses. There was no correlation between baseline blood lactate concentration and the response of either TO2 or VO2 to dobutamine. CONCLUSIONS: In some but not all patients with ARDS and sepsis syndrome, short-term infusion of low-dose dobutamine can increase both TO2 and VO2. Achievement of a TO2-independent level of VO2 could not be convincingly demonstrated in any individual patient. The response of TO2 and VO2 to dobutamine could not be predicted from baseline blood lactate concentration. Determination of the impact on patient outcome of a more prolonged infusion of dobutamine requires further study.

Adult↗
PubMed1994

Hydroxymalonate inhibits lactate uptake by the rabbit hindlimb.

Lactate uptake by skeletal muscle occurs under diverse conditions, including hypoxia and electrical stimulation. A possible metabolic fate of lactate in resting muscle is its conversion to pyruvate followed by carboxylation to malate in the cytosolic malic reaction. To test this hypothesis, we measured hindlimb lactate uptake in hypoxic mechanically ventilated rabbits. Rabbits were given intravenous infusions of hydroxymalonate, an inhibitor of the malic reaction (200 mM; n = 7), or normal saline (n = 7) at 1.1 ml/min. Hindlimb lactate uptake/release was calculated as femoral blood flow times the arteriovenous lactate difference. Saline or hydroxymalonate was infused continuously during sequential 30-min periods of normoxia (arterial PO2 approximately 150 Torr), hypoxemia (arterial PO2 approximately 30 Torr), and reoxygenation (arterial PO2 approximately 150 Torr). Hindlimb O2 transport decreased with hypoxemia, but O2 consumption remained unchanged in both groups. During hypoxemia there was net uptake of lactate by the hindlimb of the group given normal saline [4.5 +/- 0.9 (SE) mumol/min]. The hindlimb of the hydroxymalonate group continued to release lactate (-0.5 +/- 1.0 mumol/min). The inhibition of lactate uptake by hydroxymalonate supports the hypothesis that the malic reaction plays a major role in the metabolism of lactate by resting rabbit skeletal muscle.

Animals↗
PubMed1994

Effect of dobutamine on oxygen consumption and gastric mucosal pH in septic patients.

Decreases in gastric mucosal pH (pHi) are associated with splanchnic hypoxia in animals and with increased mortality in patients. In the present study we measured changes in gastric pHi with a tonometer in septic patients after a short-term infusion of dobutamine. These changes were compared with concurrent alterations in systemic O2 consumption (VO2) and arterial lactate. Twenty-one patients admitted sequentially to a medical intensive care unit with sepsis and gastric pHi < 7.32 were prospectively separated into a normal lactate group (< or = 2.2 mM; n = 10) and an elevated lactate group (> 2.2 mM; n = 11). Dobutamine HCl was infused intravenously at 5 micrograms/kg/min for approximately 3 h and then increased to 10 micrograms/kg/min. Measurements were obtained after each increase in the dose of dobutamine. Dobutamine infused at 10 micrograms/kg/min produced increases in O2 transport in both groups (p < 0.05) whereas systemic O2 consumption remained unchanged. These changes were accompanied by decreases in the arterial lactate concentration of the elevated lactate group (p < 0.01). Arterial lactate remained constant in the normal lactate group. Gastric pHi increased in both groups when dobutamine was infused at 5 micrograms/kg/min (p < 0.01), and then again at 10 micrograms/kg/min (p < 0.05). These results imply that regional tissue hypoxia, as characterized by a low gastric pHi, may be present in septic patients with normal arterial lactate concentration. Moreover, a rise in gastric pHi in response to increases in systemic O2 transport may be a better indicator of regional hypoxia in septic patients than related increases in systemic VO2.

Adult↗
PubMed1994

Seroepidemiology of amebiasis in Mexico.

The presence of serum antibodies to Entamoeba histolytica was detected by indirect hemagglutination in a representative sample of the 32 federal entities of the Mexican Republic. This study was designed to include biologic, geographic, social, economic, and educational variables. The total percentage of positive sera was 8.41%. Seroprevalence varied with geographic zones, with the South Central, South Pacific, and Yucatan Peninsula areas showing the highest values (> or = 9%), and the North, Northeast, and Gulf of Mexico areas showing the lowest values (< or = 8.0%). Seroprevalence of anti-E. histolytica antibodies seemed to increase from the northern regions to the southern areas of Mexico. These results indicated that amebiasis is endemic in the Mexican Republic, with areas of high seroprevalence not related to climatic conditions. Exposure to infectious contact with E. histolytica occurred at all ages, with a higher frequency at school age.

Adolescent↗
PubMed1994

Liposomal mitoxantrone for the local treatment of peritoneal carcinomatosis induced by colon cancer cells in mice.

Since liposomes are slowly resorbed from serous cavities, they may constitute a valuable tool for the treatment of peritoneal carcinomatosis. We prepared mitoxantrone (MXN)-liposomes with various lipid compositions and checked their antitumoral activity on a peritoneal carcinomatosis induced by a colon cancer cell injection (1 x 10(5) C51 cells) in BALB/c mice. MXN entrapment in liposomes was rapid and stable due to its high lipophilicity. MXN carried in phosphatidylcholine: cholesterol (2:1; G-liposomes) displayed a reduced toxicity in mice compared to the free drug. When tested at a non-toxic dose (2 mg/kg), MXN entrapped in G-liposomes proved to be as efficient as the free drug. At a higher MXN dose (3 mg/kg), both G-liposomes and phosphatidylcholine:cholesterol:dipalmitoylphosphatidylethanolamine (7:2:1) liposomes, loaded with MXN, significantly increased the life span of mice compared to the free drug and six other liposome formulations. Increase in the MXN therapeutic index, when used in the liposomal form, could then merit further clinical investigations in regard to patients with malignancies confined to serous cavities.

Animals↗
PubMed1993

Goals for the resuscitation of shock.

OBJECTIVE: To remind practitioners of the conventional goals of resuscitation of overt hypotensive or uncompensated shock ("ABC," for airway, breathing, and circulation) and to introduce additional goals, represented by successive letters of the alphabet, to aid clinicians in recognizing the persistence of compensated shock in the splanchnic organs and in achieving more complete resuscitation by eliminating inadequate tissue perfusion in these organs. DATA SOURCES: Review and analysis of current medical literature on shock and organ failure, combined with the author's prior research and expertise in the areas of tissue oxygenation and tonometric monitoring in the critically ill. CONCLUSIONS: In traumatic and septic shock, multiple system organ failure is associated with a persistent state of compensated shock in which hypotension and oliguria are corrected, but in which inadequate perfusion persists in the splanchnic organs and especially in the mucosal lining of the gut. The additional goals recommended include "D" for increasing the delivery of oxygen to levels that meet the metabolic demand by all tissues in the body, especially those tissues within the splanchnic circulation, and "E" for ensuring extraction and utilization of oxygen by the tissues. Future needs for goals that address reperfusion injury, translocation of bacterial toxins, and the release of toxic mediators are also considered.

Animals↗
PubMed1993

Net uptake of lactate by rabbit hindlimb during hypoxia.

Lactate uptake by normoxic tissues is a pH-dependent phenomenon that occurs with increases in arterial lactate concentration. In this study we sought to determine the effect of hypoxia on lactate uptake by the rabbit hindlimb at different arterial blood pH (pHa). Two groups of rabbits were subjected to 20 min of arterial hypoxemia (PaO2 approximately 20 mm Hg). One group was allowed to maintain normal pHa (approximately 7.40 to 7.45; n = 5), whereas the other group was hyperventilated, resulting in hypocarbia and alkalemia (pHa > 7.50; n = 5). Lactate uptake was computed from measurements of femoral blood flow and the arterio-venous lactate difference. We found decreases in hindlimb O2 consumption during hypoxemia from 0.79 +/- 0.08 to 0.33 +/- 0.06 ml/min in the normal pH group (p < 0.01) and from 0.49 +/- 0.06 to 0.24 +/- 0.02 ml/min in the high pH group (p < 0.01). At that time there was net uptake of lactate by the hindlimb of the normal pH group (8.1 +/- 2.0 mumol/min; p < 0.001) and lactate release by the alkalemic group (1.61 +/- 1.0 mumol/min). Furthermore, hindlimb lactate uptake was associated with increased glucose consumption (p < 0.001). We hypothesize that the mechanisms responsible for lactate uptake by resting skeletal muscle during hypoxia may be similar to those that regulate lactate uptake during normoxic exercise.

Animals↗
PubMed1993

Herbimycin A, a pp60c-src tyrosine kinase inhibitor, inhibits osteoclastic bone resorption in vitro and hypercalcemia in vivo.

Since absence of expression of the c-src gene product in mice indicates that the pp60c-src tyrosine kinase is required and essential for osteoclastic bone resorption, we tested the effects of the antibiotic herbimycin A, which is an inhibitor of pp60c-src on osteoclastic bone resorption in vitro and on hypercalcemia in vivo. We examined the effects of herbimycin A on the formation of bone resorbing osteoclasts in mouse long-term marrow cultures, on isolated rodent osteoclasts and on bone resorption in organ cultures of fetal rat long bones stimulated by parathyroid hormone. We found that herbimycin A in concentrations of 1-100 ng/ml inhibited bone resorption in each of these systems. We determined the effects of herbimycin A (100 ng/ml) on src tyrosine kinase activity in mouse marrow cultures and found that it was decreased. Herbimycin A also decreased elevated blood calcium levels that were induced either by repeated subcutaneous injections of recombinant human interleukin-1 alpha or by a human tumor. There was no evidence for toxicity in any of these culture systems or in mice treated with herbimycin A. A different tyrosine kinase inhibitor that does not inhibit pp60c-src was used as a control and caused none of these effects. These data suggest that pp60c-src tyrosine kinase inhibitors may be useful pharmacologic inhibitors of osteoclastic bone resorption and hypercalcemia.

Animals↗
PubMed1993

Differential metabolic and electrical activity in the somatic sensory cortex of juvenile and adult rats.

We have examined relative levels of metabolic and electrical activity across layer IV in the primary somatic sensory cortex (S1) of the rat in relation to regions of differential postnatal cortical growth. Each of several indices used--mitochondrial enzyme histochemistry, microvessel density, Na+/K+ pump activity, action potential frequency, and deoxyglucose uptake--indicate regional variations of metabolic and electrical activity in this part of the brain in both juvenile (1-week-old) and adult (10-12-week-old) animals. At both ages, areas of the somatic sensory map related to special sensors such as whiskers and digital pads showed evidence of the most intense activity. Thus, mitochondrial enzyme staining, blood vessel density, and Na+/K+ ATPase activity were all greatest in the barrels and barrel-like structures within S1, and least in the adjacent interbarrel cortex and the cortex surrounding S1. Multiunit recordings in and around the posteromedial barrel subfield of anesthetized animals also showed that the average ratio of evoked to spontaneous activity was greater in barrels than in the surrounding, metabolically less active cortex. Furthermore, autoradiograms of labeled deoxyglucose accumulation in awake behaving animals indicated systematic differences in neural activity across S1 barrels and barrel-like structures showed more deoxyglucose accumulation than interbarrel, nonbarrel, or peri-S1 cortex. These regional differences in neural activity correspond to regional differences in neocortical growth (Riddle et al., 1992). The correlation of greater electrical activity, increased metabolism, and enhanced cortical growth during postnatal maturation suggests that neural activity foments the elaboration of circuitry in the developing brain.

Action Potentials↗
PubMed1992

Cinchonine, a potent efflux inhibitor to circumvent anthracycline resistance in vivo.

Circumvention of multidrug resistance is a new field of investigation in cancer chemotherapy, and safe and potent multidrug resistance inhibitors are needed for clinical use. We investigated several analogues of quinine for their ability to increase anthracycline uptake in resistant cancer cells. Cinchonine was the most potent inhibitor of anthracycline resistance in vitro, and its activity was little altered by serum proteins. Serum from rats treated with i.v. cinchonine produced greater uptake of doxorubicin in cancer cells (DHD/K12/PROb rat colon cells and K562/ADM human leukemic cells) than did serum from quinine-treated rats (ex vivo assay). Cinchonine was more effective than quinine in reducing tumor mass and increasing the survival of rats inoculated i.p. with DHD/K12/PROb cells and treated i.p. with deoxydoxorubicin. Moreover, the acute toxicity of cinchonine in rats and mice was lower than that of other quinine-related compounds. The lower toxicity and greater potentiation of in vivo anthracycline activity produced by cinchonine are favorable characteristics for its use as an anti-multidrug resistance agent in future clinical trials.

Animals↗
PubMed1992

Gastric intramucosal pH as a therapeutic index of tissue oxygenation in critically ill patients.

Falls in gastric intramucosal pH (pHi) are associated with morbidity and mortality in patients admitted to intensive-care units (ICU). We tested the hypothesis that ICU outcome can be improved by therapy guided by changes in pHi and aimed at improving systemic oxygen availability. We studied 260 patients admitted to ICUs with APACHE II scores of 15-25. After insertion of a gastric tonometer, each patient was randomly assigned to a control or protocol group within the admission pHi category (normal = 7.35 or higher; low = below 7.35). The control groups were treated according to standard ICU practices. The protocol groups received, in addition, treatment to increase systemic oxygen transport or to reduce oxygen demand, whenever the pHi fell below 7.35 or by more than 0.10 units from the previous measurement. The protocol was used, because pHi fell, in 67 (85%) of the protocol group with normal pHi on admission. There were no significant differences between protocol and control groups in demographic characteristics, admission blood gases or haemoglobin concentration, number or type of organ system failures, or the intensity of ICU care. For patients admitted with low pHi, survival was similar in the protocol and control groups (37% vs 36%), whereas for those admitted with normal pHi, survival was significantly greater in the protocol than in the control group (58% vs 42%; p less than 0.01). Therapy guided by pHi measurements improved survival in patients whose pHi on admission to ICU was normal. pHi-guided resuscitation may help improve outcome in such patients by preventing splanchnic organ hypoxia and the development of a systemic oxygen deficit.

Aged↗
PubMed1992

Autism and tuberous sclerosis.

Autism is a behavior disorder with genetic influences indicated from twin and family studies and from the co-occurrence of autism with known genetic disorders. Tuberous sclerosis complex (TSC) is a known genetic disorder with behavioral manifestations including autism. A literature review of these two disorders substantiates a significant association of autism and TSC with 17-58% of TSC subjects manifesting autism and 0.4-3% of autistic subjects having TSC. In initial data collected on 13 TSC probands and 14 autistic probands in our family study of autism and TSC, we identified 7 TSC subjects with autism. The seven TSC autistic probands are similar to non-TSC autistic probands on the Social and Communication domains of the Autism Diagnostic Inventory (ADI) (Le Couteur et al., 1989), but show fewer Repetitive Rituals. There are more male TSC probands with autism than female, despite an equal sex ratio among TSC probands. The TSC probands with autism have significantly more seizures and mental retardation than those without autism; however, the extent and etiology of associations require further study. Our preliminary findings suggest that a fruitful approach for delineating genetic influences in autism may come from further investigation of possible mechanisms underlying the association of autism and TSC.

Autistic Disorder↗