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Biomedical subjects

C R Smith

Publications and source records attributed to C R Smith.

At least 343 records · Page 19Linked to original sources

Double-blind comparison of cefamandole and penicillin in pneumococcal pneumonia.

We conducted a prospective, randomized, double-blind comparison of intravenous penicillin and cefamandole in the therapy of pneumococcal pneumonia. Patients received either 1 g of cefamandole or 600,000 U of aqueous penicillin G every 6 h. Of the 100 patients entered into the study, 96 had clinical and radiographic evidence of pneumonia. Microbial etiology was determined from the results of sputum and blood cultures and/or sputum Gram stains. Streptococcus pneumoniae was pathogenic in 49 patients, of whom 24 received cefamandole and 25 received penicillin. There was no statistically significant difference in the response or cure rate. Of the 100 patients, 93 were treated for 3 days or more and were evaluated for adverse effects and toxicity. There was no significant difference between cefamandole-treated and pencillin-treated patients in the incidence of colonization, superinfection, phlebitis, thrombocytosis, decrease in hematocrit, or elevated liver function tests. Eosinophilia occurred more frequently in patients treated with penicillin (20 of 42) than in those treated with cefamandole (11 of 42 (chi square, P < 0.05). Only one patient receiving cefamandole developed a positive direct Coombs test. No patient in either group developed meningitis. We conclude that, with the doses and route of administration employed in this study, cefamandole is as effective as penicillin in the therapy of pneumococcal pneumonia without an increased incidence of colonization, superinfection, or adverse effects.

Adult↗

Nephrotoxicity induced by gentamicin and amikacin.

We evaluated 124 patients for nephrotoxicity associated with gentamicin or amikacin therapy. The incidence of definite nephrotoxicity was 10.5% during therapy, with a mean increase in creatinine of 1.0 mg/100 ml (range, 0.5-3.6 mg/100 ml). Nephrotoxicity developed late in therapy (mean, day 10) and the creatinine continued to increase after cessation of therapy for as long as nine days. Age, initial creatinine, total dose and initial "peak" and "valley" levels did not correlate with nephrotoxicity. Nephrotoxicity developed in 8 of 97 patients treated for less than or equal to 11 days and 5 of 19 treated for greater than 11 days (chi square, p less than .01). "Peak" and "valley" levels rose significantly (t-test, p less than .05) during therapy and increased more in those with nephrotoxicity. A "peak" level of amikacin of greater than or equal to 38.5 micrometer/ml or of gentamicin of greater than or equal to 10 micrometer/ml or a rise in the "valley" levels of amikacin above 10 micrometer/ml was also associated with nephrotoxicity (chi square, p less than .025). These data help define the natural history and the host and drug factors that affect the development of gentamicin- and amikacin-induced nephrotoxicity.

Adult↗

Ascorbic acid and cytochrome P-450.

Liver microsomal cytochrome P-450 is significantly reduced in ascorbic acid-deficient guinea pigs and studies are presented on the biochemical basis for this effect. The activities of the key enzymes involved in heme synthesis, delta-aminolevulinic acid (ALA) synthetase. ALA dehydratase and ferrochelatase, were not significantly reduced in livers from ascorbic acid-deficient animals. In addition, there was no significant difference in the amount of "mitochondrial heme" in normal and ascorbic acid-deficient livers. However, ascorbic acid deficiency did affect induction with diethyl-1,4-dihydro-2,4,6-trimethylpyridine-3,5-dicarboxylate; a 6-fold increase in ALA synthetase activity occurred in liver homogenates prepared from normal animals in contrast to no significant increase in homogenates prepared from ascorbic acid-deficient animals. Multiple forms of cytochrome P-450 exist in guinea-pig microsomes as has been demonstrated in microsomes from other species. Separation of 44,000 to 60,000 dalton polypeptides (molecular weight region for the various forms of cytochrome P-450) by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate revealed quantitative differences in the polypeptides from normal and ascorbic acid-deficient microsomes. Ascorbic acid-deficient microsomes consistently demonstrated reductions in three polypeptide bands (molecular weight 44,000, 52,000 and 57,000) and increases in two polypeptide bands (54,000 and 55,000) compared with normal microsomes. Evidence that these polypeptides are cytochrome P-450 was obtained from heme staining with tetramethylbenzidine and from induction studies with phenobarbital and 3-methylcholanthrene. The results indicate that ascorbic acid deficiency does not affect the availability of heme for cytochrome P-450 synthesis and the effect of ascorbic acid may be on the apoprotein moiety of cytochrome P-450.

Animals↗

Controlled comparison of amikacin and gentamicin.

Amikacin or gentamicin was used to treat 174 patients with suspected severe gram-negative infections in a prospective, randomized, double-blind trial. Enteric gram-negative bacilli were pathogenic in 71 cases (39 treated with amikacin, and 32 with gentamicin). Amikacin was effective in 10 to 12 bacteremias, 21 of 24 urinary-tract infections, two of five pneumonias and four of six other serious tissue infections. The toal favorable response rate was 77 per cent for amikacin and 78 per cent for gentamicin. Nephrotoxicity and auditory toxicity could be evaluated in 124 and 67 cases respectively. Definite nephrotoxicity developed in five of 62 (8 per cent) receiving amikacin and seven of 62 (11 per cent) given gentamicin, and possible nephrotoxicity developed in four patients in both groups. Definite ototoxicity developed in four patients in both groups. Definite otoxicity developed in two of 34 (6 per cent) and three of 30 (10 per cent) respectively. These differences were not statistically significant (by chisquare analysis, P greater than 0.05). The results indicate that amikacin is effective against severe gram-negative infections and is not more and not less ototoxic or nephrotoxic than gentamicin.

Adult↗

Electrocardiographic and vectorcardiographic response to right ventricular hypertrophy in the goat.

Basic differences were observed in the elctrocardiographic and vectorcardiogrpahic response to RVH in goats when compared to man and dogs. Instead of RVH inducing a redistribution of major fronts of electrical activity which result in profound QRS complex alterations as in man and dogs, it appears to produce no significant alteration of the QRS complex or major vector orientation in goats. Although slight reorientation of sagittal and horizontal vector forces occurred during development of RVH, no statistically significant changes could be detected.

Animals↗

Synthesis of cephalotaxine esters and correlation of their structures with antitumor activity.

Twenty-two new esters of natural (-)-cephalotaxine with synthetic acids possessing widely divergent structural features have been synthesized. Murinichloroethyl carbonate (27) esters of cephalotaxine are the most active of this group; this activity is less than that of harringtonine and other naturally occurring cephalotaxine esters. Other synthetic esters exhibiting activity are methyl cephalotaxylfumarate (4) and the trichloroethyl carbonate of cephalotaxyl-L-mandelate (21). The specificity of this experimental tumor system apparently requires esters of (-)-cephalotaxine for tumor inhibition because methyl cephalotaxylitaconate (7b) prepared from the synthetic (+) enantiomer of cephalotaxine is inactive.

Alkaloids↗

The syndrome of inappropriate secretion of antidiuretic hormone associated with anaerobic thoracic empyema.

The syndrome of inappropriate secretion of antidiuretic hormone has been associated with many pulmonary diseases, including tuberculosis and bacterial and viral pneumonia: however, it has not been reported with anaerobic infections or empyema in the absence of pneumonia. We report a patient with empyema due to Bacteroides melaninogenicus, Bacteroides oralis, and Peptostreptococcus who developed the syndrome. Eight hours before the start of therapy, his serum sodium concentration was 127 mEq per liter; serum osmolality, 255 mOsm per kg; urine osmolality, 522 mOsm per kg; urinary sodium concentration, 39 mEq per liter. The creatinine clearance and the adrenocorticotropic hormone stimulation test were normal, and there was no evidence of dehydration. No other causes of the syndrome of inappropriate secretion of antidiuretic hormone were apparent. With drainage and antimicrobial drug therapy, the empyema cleared, and the syndrome resolved in 8 days. The patient has been well, without evidence of inappropriate secretion of antidiuretic hormone, for 9 months. Anaerobic infections and/or empyema without pneumonia can be associated with the syndrome of inappropriate secretion of antidiuretic hormone.

Adult↗

Patient education in ambulatory care.

Quality patient education is being demanded both by consumers and by health professionals. Nursing must meet this challenge by updating the attitudes of nurses and by improving their abilities and skills in developing and implementing planned patient education programs. Application to patient education of educational theory and of teaching-learning principles improves the quality and effectiveness of the programs. This can be demonstrated by improved compliance rates, decrease in number of hospital re-admissions, and decreased morbidity. A hospital or agency committee set up to organize and coordinate the various educational programs can help to stimulate development of programs, control quality, and avoid duplication of effort.

Ambulatory Care↗

Concentrations of gentamicin and amikacin in human kidneys.

High kidney concentrations of gentamicin or amikacin, measured by an enzymological assay, were found in 9 of 10 patients who died during therapy with these aminoglycosides. Renal cortical concentrations of gentamicin ranged from 140 to 540 mug/g of tissue, with medullary levels of 128 to 230 mug/g. Concentrations of amikacin ranged from 365 to 1,030 mug/g in the cortex and from 270 to 718 mug/g in the medulla. The only patient with low kidney concentrations was an infant who received a single dose of gentamicin. Tissue levels were high in patients with both normal and abnormal renal function. Our results indicate that gentamicin and amikacin are concentrated in renal cortical and medullary tissue.

Aged↗

Taxus baccata seed oil: a new source of cis-5,cis-9-octadecadienoic acid.

Methyl esters prepared from the seed oil of the conifer Taxus baccata L. were found by gas liquid chromatography to contain 12% of a component which, when isolated by preparative thin layer chromatography and characterized by mass spectrometry, ozonolysis and nuclear magnetic resonance, was identified as cis-5,cis-9-octadecadienoic acid.

Chromatography, Gas↗