Studies on a ketone reductase in human and rat liver and kidney soluble fraction using warfarin as a substrate.

The enantiomers of warfarin were reduced to warfarin alcohols on incubation with human and rat liver and kidney cytosol. The metabolism was NADPH-dependent with NADH being only one tenth as effective at supporting the reduction. R-warfarin was reduced at a greater rate than S-warfarin by each of the tissues examined. At a concentration of 2·08 mM the rate of S-warfarin reduction ranged from 5 to 50% of the rate occurring with R-warfarin in the same tissue fraction. R-warfarin (1·3 mM) was mainly reduced to warfarin alcohol 1 (RS) (77%) the remainder being warfarin alcohol 2 (RR). S-warfarin formed slightly more warfarin alcohol 2 (SS) (57%) than warfarin alcohol 1 (SR). The apparent K_m values for the reduction of R-warfarin by human and rat liver and kidney cytosol ranged from 0·54 to 1·55 mM. The human liver reductase, even 3·5–8·5 hr after death, was significantly more active (2 times) than the rat liver reductase. Stability studies using rat liver indicated that about half of the reductase activity activity may be lost during the first 6 hr after death. This would suggest that human liver had more than four times the warfarin reductase activity of rat liver.     

Parathyroid adenomas evaluated by Tl-201/Tc-99m pertechnetate subtraction scintigraphy and high-resolution ultrasonography

Thallium-201/technetium-99m pertechnetate subtraction scintigraphy of the parathyroid glands was performed in a prospective study of 33 patients who had undergone bilateral neck exploration for elevated serum calcium and serum parathyroid hormone levels. In 31 cases, the Tl-201/Tc-99m subtraction technique yielded an overall sensitivity of 81%, specificity of 99%, and accuracy of 94% for identifying solitary parathyroid adenomas. Tl-201/Tc-99m subtraction scintigraphy correctly identified 73% of parathyroid adenomas weighing less than 499 mg, 79% of those weighing 500-1,499 mg, and 100% of adenomas weighing more than 1,500 mg. In a subgroup of 24 patients with solitary parathyroid adenomas who underwent both scintigraphy and high-resolution sonography, the sensitivity, specificity, and accuracy of both procedures were similar.     

A prospective evaluation of treatment with Selective Internal Radiation Therapy (SIR-spheres) in patients with unresectable liver metastases from colorectal cancer previously treated with 5-FU based chemotherapy

Background  

To prospectively evaluate the efficacy and safety of selective internal radiation (SIR) spheres in patients with inoperable liver metastases from colorectal cancer who have failed 5FU based chemotherapy.     

Dermatologic Surgical Research and the Institutional Review Board

BACKGROUND: Dermatologic surgical techniques have transformed cosmetic surgery over the last two decades. Many of the advances in cutaneous laser surgery, botulinum toxin injections, tumescent liposuction, and the latest filler agents have been evaluated on willing volunteers as part of organized trials under the auspices of an Institutional Review Board (IRB). OBJECTIVES: To review the developmental history of today's IRB and to provide relevance to cosmetic dermatologic research. RESULTS: Although an IRB must evaluate the "voluntariness" of a proposed research protocol, the risk-benefit ratio, particularly of elective cosmetic dermatologic surgical human studies, is of even greater importance. CONCLUSION: As more dermatologic surgeons become involved in clinical research, an understanding of the function and purpose of the IRB has become increasingly important. Research relating to cosmetic dermatologic procedures raises challenging and perplexing problems for an IRB.     

Pulmonary metastasectomy for pediatric solid tumors

Most pediatric thoracic malignancy is pulmonary disease secondary to solid tumors of childhood. The management of isolated pulmonary metastases in adulthood is well documented. Little has been published to document the long-term outcome of pulmonary metastasectomy in childhood. A retrospective study was undertaken to assess the results of surgery for isolated pulmonary metastases. Twenty children underwent surgery over 12 years (mean follow-up 8 years). Five had Wilms tumor (mean age 51 months), eight had osteogenic sarcoma (mean age 141 months), three had rhabdomyosarcoma (mean age 92 months), two had hepatoblastoma (mean age 30 months) and two had teratoma (mean age 72 months). Four had bilateral synchronous metastases and thoracotomies, and one had bilateral metachronous metastases and thoracotomies. Nineteen children were discharged well within 10 days of surgery. There was one early complication: a death due to pneumonia. Four children subsequently died postoperatively with cranial metastases (mean 29 months postoperatively). The remaining 16 children remain alive and well. As part of the combined therapy, these results would support an aggressive surgical approach to this disease. Preoperative assessment should include contrast enhanced computed tomogram of the head and chest as well as chest X-ray taken immediately preoperatively to exclude metastases. Bilateral synchronous and metachronous thoracotomy is well tolerated in childhood.