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C R Smith

Publications and source records attributed to C R Smith.

439 records · Page 25Linked to original sources
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Role of the carrier solution in cyclosporine pharmacokinetics in the baboon.

Although numerous investigational models have demonstrated the potent immunosuppressive properties of cyclosporine, the effectiveness of any given dosage may vary with the metabolism of the animal, the route of administration, and the carrier solution of the drug. We investigated the pharmacokinetics of intramuscular cyclosporine administration in the baboon using three carriers: polyoxethylated castor oil (Cremophor), a mixture of octanoic and decanoic acids (Miglyol), and olive oil. Cyclosporine prepared in Cremophor, Miglyol, or olive oil was injected intramuscularly into the hindlegs of baboons. Specimens for cyclosporine assay were obtained 2, 4, 6, 12, 18, and 24 hours after single intramuscular injection of 10 mg/kg or 15 mg/kg. In addition, weekly, then monthly, levels were obtained on animals receiving daily intramuscular injections following heterotopic heart xenografts. Attempts at oral administration proved unreliable and were discontinued. Cyclosporine assay was performed on stored serum using the RIA-KIT (Sandoz Pharmaceuticals Corporation, East Hanover, N.J.). Cremophor provides a more bioavailable form of cyclosporine than Miglyol when administered intramuscularly. (Area under curve = 7776 +/- 1437 for Cremophor 15 mg/kg vs 1837 +/- 726 for Miglyol 15 mg/kg; 2579 +/- 694 for Cremophor 10 vs 1123 +/- 393 for Miglyol 10.) Long-term daily intramuscular administration of Cremophor provides a sustained drug serum trough level with wide variability between individual animals (80 to 825 ng/ml). Toxicity was limited to injection site inflammation. There was no biochemical evidence of renal toxicity; however, some animals did demonstrate early histologic changes of cyclosporine effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
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Coronary angiography in smokers undergoing evaluation for lung transplantation: is routine use justified?

Many patients referred for lung transplantation have a history of smoking. For the exclusion of the possibility of asymptomatic coronary artery disease, these patients undergo coronary angiography as part of their preoperative evaluation. The usefulness of this approach remains unknown. We reviewed the records of all smokers referred for lung transplantation who underwent coronary angiography (n = 77). Nine patients (12%) had significant coronary artery disease; six (8%) of these patients had their clinical management altered because of findings on angiography. Eight of nine patients with coronary artery disease (89%) and all of the six patients (100%) whose management was altered had coronary artery disease risk factors other than a history of smoking; therefore, no patient with clinically significant coronary artery disease had history of smoking as the only risk factor. The presence of other coronary artery disease risk factors was significantly associated (p < 0.0001) with the positive findings on angiography. A nonsignificant trend toward older age was found, and a higher proportion of male patients existed in the group with coronary artery disease. Routine angiography for all patients with a history of smoking referred for angiography is unjustified. A subset of patients with high risk identified primarily by the presence of additional coronary artery disease risk factors may benefit from routine angiography.

Coronary Angiography↗
PubMedDate not supplied

Tissue iron storage patterns in fetal hydrops associated with congestive heart failure.

To learn whether fetal congestive heart failure causes a characteristic tissue iron storage pattern, we selected 15 neonatal autopsy cases of hydrops fetalis in which both the clinical and gross autopsy findings suggested intrauterine congestive heart failure. The latter appeared to be due to functional causes in 10 (3 nonhemolytic anemia, 4 cardiac dysrhythmia, 3 dilated cardiomyopathy) and was associated with cardiac malformation in 5. We graded the amount of hepatocellular siderosis, reticuloendothelial siderosis, and renal tubular siderosis in Perls-stained microscopic sections of liver, spleen, and kidney and compared the iron storage pattern with that in 15 normally developed neonatal autopsy controls (4 preterm, 11 term) and a further 7 with hemolytic anemia (5 alpha-thalassemia, 2 parvovirus B19 infection). Liver cell siderosis was absent in the three cases with nonhemolytic anemia. It was increased in 11 of the remaining 12 cases, as in hemolytic anemia controls. Among the five cardiac malformation cases, three had proximal renal tubular siderosis (as in hemolytic anemia controls) attributed to turbulent blood flow through the heart. Among the five, hydrops appeared to be due to prenatal closure of the foramen ovale in one and to prenatal constriction of the ductus arteriosus in another. In one of the five, and despite complex malformation of the heart, hydrops appeared to be due to complete heart block. We concluded that, although clinical information and morphologic assessment of the heart were basic to identifying a cardiac cause of fetal hydrops, histologic assessment of the pattern of iron storage helped confirm the pathologic diagnosis. Analysis of the pathologic findings led to a scheme for categorizing cardiogenic fetal hydrops.

Female↗
PubMedDate not supplied

A 5-year multicenter study on implant-supported single crown restorations.

In this multicenter prospective study, the results achieved with the use of Brånemark implants for single tooth replacement were evaluated. The overall cumulative success rate was 95.9% for implants and 91.1% for crowns. Two of the 99 implants placed had to be removed before the prosthodontic stage of treatment; thus, 97 were restored with CeraOne crowns. Seventy-seven implants were evaluated radiographically at the 1-year follow-up, 57 at 3 years, and 47 at 5 years. Mean marginal bone resorption was well within the limits set by Albrektsson et al in 1986. The status of the soft tissue around crowns and adjacent teeth remained stable over the evaluation period. The gold abutment screw in the CeraOne system seems to have eliminated the problem of loosening abutment screws in single tooth replacements. The results suggest that the Brånemark system can be safely used for tissue-integrated replacement of single teeth.

Adolescent↗