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Biomedical subjects

J H Smith

Publications and source records attributed to J H Smith.

At least 163 records · Page 9Linked to original sources

Management of injuries of the thoracic and abdominal aorta.

Thirty-five patients had surgery for injuries of the aorta at the Los Angeles County-USC Medical Center over a 4 1/2 year period. There were 27 survivors. The principles of management were to operate without delay if there was evidence of continued bleeding after initial fluid replacement as occurred in 11 patients. For the 24 patients who became stable after initial resuscitation, a more deliberate plan of management was used. Blood pressure was carefully monitored and controlled to avoid hypertension. Priorities for associated injuries were established and in several cases, they took treatment precedence over the aortic injury. Delay was sometimes necessary to utilize the more experienced personnel. In no instance did a stabilized patient hemorrhage during the delay. The most common injury seen was a blunt disruption of the proximal descending aorta. The details of the operative technique for this injury have been reported herein, along with a justification for not using either pump bypass or shunt to perfuse the distal aorta during the period of aortic cross-clamping.

Aorta, Abdominal↗

Vectors for the direct selection of cDNA clones corresponding to mammalian cell mRNA of low abundance.

We have constructed two cDNA cloning vectors which (1) carry the intergenic region of phage f1 and (2) permit efficient cloning (by the Okayama-Berg procedure) of full-length copies of mammalian mRNA in either orientation. Infection of cells harboring these vectors with f1 phage results in the encapsidation of single-stranded (ss) plasmid DNA carrying either the sense or the anti-sense sequence of the cDNA inserts. The complementary nature of the cDNA inserts in two such cDNA libraries facilitates preparative hybridization procedures. These vectors have general applicability to any eukaryotic system where changes in the abundance of mRNA transcripts are to be measured and the corresponding cDNA clones isolated.

Cloning, Molecular↗

Obstructive jaundice secondary to pancreatic adenocarcinoma in a seven-year-old male.

Pancreatic carcinoma in childhood is a rare cause of obstructive jaundice. This report deals with such a case in a seven-year-old boy, which was successfully treated with a pancreatoduodenectomy. A brief review of the literature reveals that children will tolerate radical pancreatic resections, including pancreatoduodenectomy, better than adults. The only hope of long-term survival rests with aggressive surgical treatment. Pancreatoduodenectomy in infants and children can be done with a low mortality (9%) and for a mean survival of greater than four years (median two years).

Adenocarcinoma↗

Improvements in the registration and analysis of fetal heart rate records at the bedside.

A microprocessor system is described for on-line analysis of the fetal heart rate detected by conventional Doppler systems. A brief account is given of the instrumentation and program structure. The system has been tested by analysing normal and abnormal antenatal fetal heart rate records. Pulse Doppler with autocorrelation measurement of the fetal pulse interval reduced the signal loss in clinical practice by a factor of 10, to an average of 2.1% in 629 records from uncomplicated pregnancies. Yet it is still necessary to identify signal loss, because it occasionally rises to unacceptable levels in association with fetal movements or hiccups. Medium-term measures of fetal heart rate variation (within 16-0.1 cycles/min) varied with gestational age, but were a better index of fetal well-being than longer-term measures. The application of the system to fetal monitoring is illustrated.

Computers↗

Reversal of postoperative anuria by decompressive celiotomy.

Postoperative oliguria or anuria can rarely be attributed to an increase in intra-abdominal pressure. In this documented case, postoperative anuria responded to reduction in abdominal pressure by celiotomy. Actual abdominal pressure measurements are not available but probably would not be useful. However, hemodynamic measurements that were not consistent with diminished renal blood flow in a middle-aged patient were nevertheless associated with anuria, which responded to release of the abdominal pressure. Because of the association of regional pressure and acute renal decompensation, release of abdominal tension should be considered as a therapeutic option when hemodynamic measurements cannot explain a rapid decline in urine production.

Abdominal Muscles↗

Mechanism of chloroform nephrotoxicity. IV. Phenobarbital potentiation of in vitro chloroform metabolism and toxicity in rabbit kidneys.

Metabolism of chloroform (CHCl3) by a cytochrome P-450-dependent process to a reactive metabolite may be required to elicit hepatic and renal toxicities. Specific inducers or inhibitors of cytochrome P-450 have been employed frequently as tools to demonstrate this relationship between metabolism and toxicity in the liver. The experiments reported herein were designed to identify the relationship between metabolism and toxicity of CHCl3 in the kidney of rabbits, a species in which renal cytochrome P-450 is induced by phenobarbital. Pretreatment with phenobarbital enhanced the toxic response of renal cortical slices to CHCl3 in vitro as indicated by decreased p-aminohippurate and tetraethylammonium accumulation. Phenobarbital pretreatment also potentiated in vitro 14CHCl3 metabolism to 14CO2 and covalently bound radioactivity in rabbit renal cortical slices and microsomes. Addition of L-cysteine significantly reduced covalent binding in renal microsomes from both phenobarbital-treated and control rabbits and was associated with the formation of the radioactive phosgene-cysteine conjugate 2-oxothiazolidine-4-carboxylic acid (OTZ). Formation of OTZ was enhanced in renal microsomes from phenobarbital-pretreated rabbits. Thus, this in vitro model supports the hypothesis that the kidney metabolizes CHCl3 to the nephrotoxic metabolite, phosgene.

Animals↗

The role of the lysine binding sites of human plasminogen in the fibrinogen stimulated rate of active site formation in the streptokinase-plasminogen equimolar complex.

The effect of various concentrations of epsilon-amino caproic acid (EACA) on the rate of active site formation in the human plasminogen moiety of the streptokinase-plasminogen equimolar complex has been studied in the absence and presence of human fibrinogen fragment D1 (FD1). In the absence of FD1, the pseudo first order rate constant (kobs) for active site development in this complex ranges from 8.4-17.9 x 10(-3) sec-1 with Glu1-plasminogen (Glu1-Pg), Lys77-plasminogen (Lys77-Pg), and Val442-plasminogen (Val442-Pg), at levels of EACA from 0-25 mM. In the presence of 2 microM FD1, the kobs for active site formation in the SK . Glu1-Pg complex, of 60.1 x 10(-3) sec-1, was not altered significantly as the EACA level was increased to 25 mM. Similarly, in the SK . Lys77-Pg complex, the kobs for active site formation, of 62.1 x 10(-3) sec-1, was essentially unchanged as the EACA level was increased to 25 mM. Finally, the kobs for active site formation in the SK . Val442-Pg complex, of 113.6 x 10(-3) sec-1, was also unaffected at levels of EACA up to 5 mM, with a slight inhibition at 25 mM EACA. These results show that the stimulation of active site formation in the equimolar Sk . Pg complex by fibrinogen fragment D1 is mediated by sites separate from the lysine binding sites of plasminogen.

Aminocaproic Acid↗

Effect of sex hormone status on chloroform nephrotoxicity and renal mixed function oxidases in mice.

In mice, only males are susceptible to chloroform (CHCl3) nephrotoxicity and the susceptibility appears to be related to renal mixed function oxidase activity. There were sex-related differences of renal cytochrome P-450 and b5 concentrations and of ethoxycoumarin O-deethylase activity in mouse kidneys; in all cases activity was higher in males. Castration of male mice eliminated susceptibility to CHCl3 nephrotoxicity and reduced renal mixed function oxidases to concentrations observed in female mice. Treatment of male and female mice with testosterone increased the susceptibility to CHCl3 nephrotoxicity and increased renal mixed function oxidases to similar activities in both sexes. Previous data have suggested that CHCl3 is metabolized in situ by the kidney, possibly by a mechanism similar to that occurring in the liver. The data from this investigation are consistent with the concept that CHCl3 is metabolized by a cytochrome P-450-dependent mechanism in the kidney.

Animals↗

Mechanism of chloroform nephrotoxicity. III. Renal and hepatic microsomal metabolism of chloroform in mice.

In vitro studies with male ICR mouse renal cortical slices have indicated that chloroform (CHCl3) is metabolized by the kidney to a nephrotoxic intermediate, possibly by a cytochrome P-450-dependent mechanism similar to that occurring in the liver. In this investigation, metabolism of 14CHCl3 by microsomes prepared from renal cortex and liver provided definitive evidence for a role of cytochrome P-450 in the renal metabolism and toxicity of CHCl3. 14CHCl3 was metabolized to 14CO2 and covalently bound radioactivity by male renal cortical microsomes; metabolism required oxygen, a NADPH regenerating system, was dependent on incubation time, microsomal protein concentration, and substrate concentration, and was inhibited by carbon monoxide. Consistent with the absence of CHCl3 nephrotoxicity in female mice, little or no metabolism of 14CHCl3 by female renal cortical microsomes was detected. CHCl3 produced a type I binding spectrum with oxidized male renal cortical and hepatic microsomes. Incubation of glutathione with microsomes and 14CHCl3 increased the amount of aqueous soluble metabolites detected with a concomitant decrease of metabolism to 14CO2 and covalently bound radioactivity, suggesting the formation of a phosgene conjugate as has been described for hepatic CHCl3 metabolism. These data support the hypothesis that renal cytochrome P-450 metabolizes CHCl3 to a nephrotoxic intermediate.

Animals↗

Nephrotoxicity of chloroform: metabolism to phosgene by the mouse kidney.

In this investigation, we have attempted to determine whether chloroform (CHCl3)-induced nephrotoxicity might be due to its metabolism to phosgene (COCl2) in the kidney. We have found that kidney homogenates from DBA/2J male mice in the presence of glutathione metabolize CHCl3 to 2-oxothiazolidine-4-carboxylic acid (OTZ). This product appears to be formed by the initial trapping of COCl2 by two molecules of GSH to form diglutathionyl dithiocarbonate (GSCOSG). Kidney gamma-glutamyl transpeptidase can rapidly metabolize GSCOSG to N-(2-oxothiazolidine-4-carbonyl)-glycine which is then hydrolyzed, possibly by cysteinyl glycinase to OTZ. The finding that deuterium-labeled chloroform (CDCl3) was less nephrotoxic and depleted less renal GSH than did CHCl3 suggests that the metabolism of CHCl3 to COCl2 may also occur in the kidney in vivo and lead to nephrotoxicity.

Animals↗

Fecal weight and composition, serum lipids, and diet among subjects aged 18 to 80 years not seeking health care.

Sixty-two subjects not seeking health care, aged 18 to 80 yr, recorded diet intake, collected feces for 7 days, and gave fasting blood lipids. There was a great variation in stool weight passed (19 to 278 g/24 h). Fecal constituents (bile acids, sterols, fat, electrolytes) correlated strongly with fecal mass. Fecal mass correlated inversely with transit time. There was no relationship between age and fecal weight or transit time. Multiple regression analysis showed that only dietary fiber contributed to stool weight. No single component of fiber appeared to be responsible for this relationship with stool mass. Multiple regression analysis of serum cholesterol showed a relationship only with age and fecal neutral sterols.

Adolescent↗

Promotion of bladder tumours by endoscopic procedures in an animal model.

An experimental study was performed to assess the possible tumour-promoting action of urothelial trauma caused by repeated intravesical diathermy, catheterisation, and the instillation of water, glycine and saline in the rat bladder which had previously been exposed to an initiating dose of the carcinogen N-methyl-N-nitrosourea. An increase in tumours and inflammatory changes was observed, especially in the group treated with water, and the significance of the findings is discussed.

Animals↗

Description of Sarcocystis falcatula stiles, 1893, a parasite of birds and opossums.

Sarcocystis falcatula Stiles, 1893 is re-described. Intermediate hosts of the parasite which was earlier described as Sarcocystis debonei Vogelsang, 1929 are species of passeriform, psittaciform, and columbiform birds. In these birds, muscle zoites are 6.88 X 2.19 (4.8-8.4 X 1.2-3.6) micron and are enclosed in a cyst wall with regular protrusions, 1-5 micron long. The convoluted primary wall has multiple thin areas in the osmiophilic layer. Microtubules originate in the ground substance and extend to the tips of the protrusions. The only known definitive host is the opossum, Didelphis virginiana; rats, cats, a dog, and a ferret could not be infected from muscle cysts. Sporocysts from opossums infected from five different infected avian sources measure 11.2 X 7.4 (9.6-12.0 X 6.0-8.4) micron.

Animals↗

Renal ultrastructural and biochemical injuries induced by aminoglycosides.

Aminoglycoside-induced proteinuria may result from general renal damage or may reflect alterations in specific steps in the renal handling of proteins. To differentiate between the two possibilities, experiments were designed to quantify the effects of nephrotoxic doses of gentamicin, tobramycin and netilmicin in the intact rat, isolated perfused rat kidney (IPK) and kidney slices using the cationic low molecular weight protein lysozyme as a model protein. Each aminoglycoside was administered IP to male Wistar rats (15 or 30 mg/kg/day) for 5 or 7 days. Scanning and transmission electron microscopy indicated that gentamicin and tobramycin induced a decrease in the number and diameter of endothelial fenestrae and degranulation of the myoepithelioid cells of the juxtaglomerular apparatus. Concurrently, gentamicin and tobramycin decrease the glomerular sieving coefficient of lysozyme from 0.8 to 0.6 and 0.5, respectively. Netilmicin did not affect the percentage reabsorption of lysozyme whereas gentamicin and tobramycin induced a 50% decrease in lysozyme reabsorption by the IPK. Gentamicin and tobramycin decreased equally lysozyme degradation by the IPK; this decrease was time- and dose-dependent when evaluated in slices from renal cortex. Perfusion of rat kidneys with gentamicin induced a dose-dependent decrease in reabsorption and catabolism of lysozyme. In conclusion, these studies demonstrate that polycationic aminoglycosides alter ultrastructure and glomerular permeability, tubular reabsorption and intracellular digestion of proteins.

Absorption↗

Chemically induced nephrotoxicity: role of metabolic activation.

Renal xenobiotic metabolism can result in production of electrophiles or free radicals that may covalently bind macromolecules or initiate lipid peroxidation. The mechanisms of renal xenobiotic metabolism may vary in different anatomical regions. Kidney cortex contains a cytochrome P-450 system while medulla contains a prostaglandin endoperoxidase. Recently cysteine conjugated-lyase has been implicated in production of reactive intermediates. Metabolic activation may be amplified by accumulation of xenobiotics within renal cells due to tubular concentrating and/or secretory mechanisms. Additionally, renal xenobiotic detoxicification can occur by conjugation with glucuronide, sulfate or glutathione.

Acetaminophen↗