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Biomedical subjects

H Garcia

Publications and source records attributed to H Garcia.

At least 55 records · Page 3Linked to original sources

[Experimental acute necrotico-hemorrhagic pancreatitis in dogs. Treatment by intraductal block].

The aim of this experimental study was to demonstrate that the mortality of calcium chlorine induced acute pancreatitis in the dog was decreased by the intraductal injection of solid substances. Seventy-two dogs were used. In the control group (n = 5) the mortality was 100%. Three different drugs were used for the intraductal injection: Ethibloc (n = 37), Tissucol (n = 10) and silicones (n = 10). The mortality rate has been respectively of 13.5, 10 and 10%. In order to define at which level of the pancreatic duct the obstruction had a maximum efficiency, 10 dogs underwent a distal ligation of the pancreatic duct after induction of the pancreatitis. The mortality rate in this group was 100%. It can be therefore concluded that only the complete obstruction of the pancreatic duct decreases the mortality rate in this experimental model.

Acute Disease↗

Pancreatic duct occlusion in the management of acute necrotizing pancreatitis in a canine model.

Based on results reported by others in using prolamine (Ethibloc; Ethicon Gmb H) to treat patients with chronic pancreatitis, without any observed pancreatic complications, we decided to use pancreatic duct occlusion experimentally in dogs in which we induced acute pancreatitis by the injection of calcium chloride into the pancreatic duct. This injection proved to be 100% lethal in the 5 animals constituting the control group, none of which were treated after the injection. Acute pancreatitis was then induced in 57 animals, also by injection of calcium chloride. These dogs were then treated with one of three substances that share the same physical properties: prolamine; Tissucol (Immuno AG, Vienna), a biologic tissue adhesive; silicone (Xantopren, Bayer Dental D-5090 Leverkusen). Thirty-seven dogs were treated with prolamine, 10 dogs with Tissucol, and 10 with silicone. The mortality rate in the 57 treated animals was 12.2%, compared to the 100% rate in the untreated control group. The mechanical action achieved by blocking the pancreatic duct shows how the evolution of acute pancreatitis at different stages could be modified. This specific treatment limits the pathophysiologic process of acute pancreatitis in dogs. These findings provide us with a promising outlook for the treatment of this severe illness.

Acute Disease↗

Congenital cystic adenomatoid malformation of the lung associated with bile duct hypoplasia.

Congenital cystic adenomatoid malformation (CCAM) is a rare lesion that affects one or two lobes of the lung. Infants are either stillborn or die shortly after birth if therapy is not started immediately. The lesion itself may be solid or cystic, manifesting in an adenomatoid increase in terminal respiratory structures. Clinical, pathological and radiological findings of a child prematurely born are presented. A special feature in this case was hypoplasia of intrahepatic bile ducts, an unusual association with CCAM that has not been previously reported. Pathogenesis and embryological connotations of the two lesions are discussed. The importance of prenatal diagnosis and immediate surgical therapy after birth is stressed.

Abnormalities, Multiple↗

Dose-response relationship between thyroid hormone and growth velocity in cynomolgus monkeys.

To investigate the dose-response relationship between thyroid hormone and linear growth, we studied 10 castrated prepubertal cynomolgus monkeys. Hypothyroidism was induced by administration of methimazole (0.0125% in drinking water) and was confirmed by high serum TSH levels (greater than 40 mU/L) in all animals. Subsequently, each animal received 1, 2, 4, or 8 micrograms/kg.day T4, im, for 9 weeks. The sequence of T4 doses was random, and 6 weeks elapsed between successive T4 doses. Serum T4, T3, TSH, and insulin-like growth factor I (IGF-I) levels and lower leg length were measured every 3 weeks. Methimazole administration decreased thyroid hormone and IGF-I levels and lower leg growth rate. With increasing doses of exogenous T4, serum T4, T3, and IGF-I as well as lower leg growth rate increased significantly. Animals not given T4 had a 65% decrease in lower leg growth rate (P less than 0.01). Animals given 4 and 8 micrograms/kg.day T4 had 56% and 73% increases, respectively, in lower leg growth rate compared to baseline (P less than 0.05 and P less than 0.01, respectively). Lower leg growth rate correlated better with serum T3 (r = 0.50; P less than 0.001) than with serum T4 (r = 0.29; P less than 0.05). Lower leg growth rate also correlated with serum IGF-I levels (r = 0.53; P less than 0.001). Serum IGF-I correlated with serum T3 (r = 0.47; P less than 0.001), but not with serum T4. We conclude that increased serum T4 and T3 levels cause progressive increases in growth velocity and IGF-I levels over a range from moderate hypothyroidism to moderate hyperthyroidism. Growth velocity and IGF-I levels correlated more strongly with the serum T3 than with the serum T4 level.

Animals↗

Clinical validation of a new metabolic monitor suitable for use in critically ill patients.

This report documents the validity of clinical measurements of oxygen consumption (VO2) and carbon dioxide production (VCO2) made with a new metabolic gas monitor (MGM) suitable for use in critically ill patients receiving mechanical ventilatory support. Paired samples of inspired and expired gases were obtained, and exhaled minute volume was measured in 12 patients receiving supplemental oxygen, intermittent mandatory ventilation, and PEEP. Gas volume was measured with a calibrated spirometer and oxygen and CO2 fractions were measured by mass spectrometry. Measured and derived values were compared to those obtained from the MGM connected in series with the ventilator circuit. There were no statistically significant differences between values obtained from the mass spectrometer/spirometer vs. the MGM in exhaled volume (8.60 +/- 3.81 vs. 8.58 +/- 3.72 [SD] L/min), fraction of inspired oxygen (0.451 +/- 0.011 vs. 0.452 +/- 0.010), fraction of expired oxygen (0.413 +/- 0.013 vs. 0.415 +/- 0.012), VO2 (290 +/- 113 vs. 275 +/- 88 ml/min), VCO2 (245 +/- 95 vs. 247 +/- 96 ml/min), or respiratory quotient (0.85 +/- 0.14 vs. 0.88 +/- 0.08). The fraction of expired CO2 measured by the MGM was significantly greater (0.034 +/- 0.006 vs. 0.035 +/- 0.006; p less than .001) than that measured by mass spectrometer/spirometer. Twelve additional patients were studied to compare metabolic measurements made on 45% oxygen with those made at other fraction of inspired oxygen values. There was no significant difference between values measured on 45% oxygen and those measured on 30% to 50% oxygen.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of ketoconazole on rat testicular steroidogenic enzymatic activities.

Ketoconazole (K) is an antifungal imidazole derivative which has been shown to be a potent inhibitor of testosterone (T) biosynthesis in rodents and humans. To study the effect of K on rat testicular steroidogenesis we measured the activities of five testicular microsomal steroidogenic enzymes in K-treated rats and controls. Thirty male adult rats were given either 2 mg K or water every 12 hours by mouth during 5 days. Mean testicular weight was similar in both groups of animals. The K-treated group had a T serum concentration of 83 +/- 14 ng/dL whereas it was 94 +/- 16 ng/dL in the control group (NS). The K-treated animals had decreased activities of the 3 beta-hydroxysteroid dehydrogenase (830 +/- 48 vs 2,245 +/- 109 pmol/mg protein/min, P less than 0.001), 17-hydroxylase (243 +/- 5 vs 676 +/- 17 pmol/mg protein/min, P less than 0.001), 17-ketosteroid reductase (31 +/- 2 vs 169 +/- 7 pmol/mg protein/min, P less than 0.001), and aromatase enzymes (92 +/- 6 vs 123 +/- 7 pmol/mg protein/min, P less than 0.01). The 17,20-desmolase activity was similar in both groups of animals (210 +/- 4 vs 171 +/- 18 pmol/mg protein/min). We conclude that K given orally to rats inhibits the activity of several testicular steroidogenic enzymes.

17-Hydroxysteroid Dehydrogenases↗

Pharmacokinetics and cerebrospinal fluid penetration of moxalactam in children with bacterial meningitis.

The serum pharmacokinetics and CSF penetration of moxalactam were determined in 39 children with bacterial meningitis. The mean serum concentrations 30 minutes after a 37.5 or 50 mg/kg dose were 66.7 and 113 micrograms/ml, respectively. The t 1/2 beta was between 1.8 and 2.0 hours. The mean +/- 1 SD CSF/serum percentage was 18.5 +/- 16.0% (range 2.0 to 61%) for all children on any day of therapy or hour, after the last of three 50 mg/kg doses. Cerebrospinal fluid bactericidal titers were greater than or equal to 1:32 in 13 of 14 CSF specimens. Moxalactam adequately penetrates into the CSF of children with bacterial meningitis after repetitive 50 mg/kg doses.

Blood-Brain Barrier↗

Carcinogenicity test of six nitrosamides and a nitrosocyanamide administered orally to rats.

Six nitrosamides [ethylnitrosourea (ENU), 2-hydroxyethylnitrosourea (HENU), carboxymethylnitrosourea, 1-nitroso-5,6-dihydrouracil (NDHU), 1-nitrosohydantoin, and N-methyl-N-nitrosobenzamide (MNB)] and ethylnitrosocyanamide (ENC) were administered chronically in sodium citrate-buffered drinking water to MRC Wistar rats. ENU induced tumors of the reticuloendothelial system (RES) (50% incidence), mammary glands, and large intestine. NDHU in drinking water produced hepatocellular carcinomas (96% incidence), but NDHU injected ip caused mostly tumors at the injection sites (54% incidence). HENU produced bone tumors (38% incidence) and RES tumors (28% incidence). ENC produced nasal cavity tumors (36% incidence). Papillomas and/or carcinomas of the forestomach, tongue, and pharynx were induced by most of the compounds, with the highest incidence in the forestomach (47% for MNB); these tumors were attributed to local action when the compounds were ingested. Carcinogenicity was not quantitatively correlated with direct mutagenicity for Salmonella typhimurium TA1535.

Administration, Oral↗

The microcirculation in two transplantable melanomas of the hamster. I. In vivo observations in transparent chambers.

Twenty-eight transparent chambers were inserted into the cheek pouches of hamsters and daily serial observations made of the changing vasculature of transplants of 2 varieties (A-Mel-4B32, ZGYP1) of amelanotic melanomas. The tumor A-Mel-4B32 grew at a rate which covered 50% of the viewing area in 3--4 days, while the tumor ZGYP1 covered less than 10% of the viewing area at this time and did not cover 50% of the viewing area until 9.5 days after transplantation. The difference in growth rate was not reflected in any differences in the morphology of the vascular network and distribution of the venous arcades.

Animals↗

The microcirculation in two transplantable melanomas of the hamster. II. Scanning electron microscopy.

Normal and tumor vessels observed in vivo on the hamster cheek pouch membrane in transparent chambers were examined by scanning electron microscopy. Large, thin walled veins were found in the reactive zone around the 2 amelanotic melanomas of the hamster. Sinusoidal vessels and channels contained red cells, which did not possess any vascular wall, were seen in the main substance of the tumors. In this system all the vessels within the central mass of the tumor transplant comprise newly formed vessels. The surfaces of the tumor cells and the lining of the tumor vessels were examined by this technique. The biological history i.e., age of the vessel and location from the growing edge of the tumor, were known. The surface of the tumor cells on cut section differed in appearance from the areolar tissue of the pouch membrane. Scanning electron microscopy of the inner aspect of newly formed tumor vessels permits much greater sampling of the tissue than transmission electron microscopy and further work should reveal aspects of the interaction of the blood with tumor stroma.

Animals↗

Chronic oral administration of 1-nitrosopiperazine at high doses to MRC rats.

1-Nitrosopiperazine was fed to two groups of rats as drinking water solutions containing 400 mg/liter (3.5 millimolar) and 800 mg/liter (7.0 millimolar), respectively. The treatment was 20 ml per rat per day, 5 days per week for life. In both groups many animals died with olfactory tumors (mostly esthesioneuroblastomas), the first at 36 weeks in the higher dose group, the first at 64 weeks in the lower dose group. There was also a small number of liver tumors in both groups. None of these tumors was seen in the untreated controls. The similarity of this tumor distribution to that produced by 1,4-dinitrosopiperazine suggests that the observed carcinogenicity of 1-nitrosopiperazine may be entirely due to its disproportionation in the acidic medium of the rat stomach. Chemical data supporting this interpretation are presented.

Administration, Oral↗