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Biomedical subjects

John R Johnson

Publications and source records attributed to John R Johnson.

26 records · Page 2Linked to original sources
PubMed2002

Vertebral osteonecrosis associated with the use of intradiscal electrothermal therapy: a case report.

STUDY DESIGN: This report describes a case of vertebral body osteonecrosis associated with the use of intradiscal electrothermal therapy. OBJECTIVES: To alert clinicians to a previously unreported complication, vertebral body osteonecrosis, after an intradiscal electrothermal therapy procedure. SUMMARY OF BACKGROUND DATA: The intradiscal electrothermal therapy procedure is a new treatment that has been advocated in the management of chronic low back pain of discogenic origin. The intradiscal electrothermal therapy procedure uses a fluoroscopically guided thermal catheter to heat the intervertebral disc. A review of the literature regarding this procedure has not revealed osteonecrosis as a complication. METHODS: The patient's work-up and postoperative course are documented, and all medical records were reviewed retrospectively. RESULTS: The patient's pain had improved only minimally at initial follow-up after L5-S1 combined anterior and posterior spinal fusion, undertaken after intradiscal electrothermal therapy failure. CONCLUSIONS: Intradiscal electrothermal therapy has gained increasing popularity in the treatment of discogenic low back pain, in large part because of its minimally invasive nature and perceived low risk for major complications. Previous reports in the literature have not noted any major complications associated with the proper use of this device. Clinicians should be advised that intradiscal electrothermal therapy can be associated with complications, which in the current case, led to osteonecrosis of the vertebral body.

Adult↗
PubMed2002

The structure of diversity within New World mitochondrial DNA haplogroups: implications for the prehistory of North America.

The mitochondrial DNA haplogroups and hypervariable segment I (HVSI) sequences of 1,612 and 395 Native North Americans, respectively, were analyzed to identify major prehistoric population events in North America. Gene maps and spatial autocorrelation analyses suggest that populations with high frequencies of haplogroups A, B, and X experienced prehistoric population expansions in the North, Southwest, and Great Lakes region, respectively. Haplotype networks showing high levels of reticulation and high frequencies of nodal haplotypes support these results. The haplotype networks suggest the existence of additional founding lineages within haplogroups B and C; however, because of the hypervariability exhibited by the HVSI data set, similar haplotypes exhibited in Asia and America could be due to convergence rather than common ancestry. The hypervariability and reticulation preclude the use of estimates of genetic diversity within haplogroups to argue for the number of migrations to the Americas.

DNA, Mitochondrial↗
PubMed2002

Surgical management of adjacent level degeneration following lumbar spine fusion.

Thirty-eight patients who underwent extension of a prior lumbar fusion for treatment of adjacent level degeneration were retrospectively evaluated. Patient age, pain relief with the initial surgical procedure, and distal level of fusion significantly affected outcome. Overall, this study suggests that adjacent level fusion yields results that are not optimal but provides sigificant clinical improvement for patients with symptomatic adjacent level degeneration.

Adult↗
PubMed2002

Approval summary: letrozole in the treatment of postmenopausal women with advanced breast cancer.

Letrozole (Femara; Novartis Pharmaceuticals Corp., East Hanover, NJ) is a nonsteroidal inhibitor of aromatase enzyme complex. It inhibits the peripheral conversion of circulating androgens to estrogens. In postmenopausal women, letrozole decreases plasma concentrations of estradiol, estrone, and estrone sulfate by 75-95% from baseline with maximal suppression achieved within 2-3 days of treatment initiation. Suppression is dose related, with doses of >or=0.5 mg giving estrone and estrone sulfate values that were often below assay detection limits. At clinically used dosage, letrozole does not impair adrenal synthesis of glucocorticoids or aldosterone. In 1998, letrozole was approved by the United States Food and Drug Administration (FDA) for the treatment of advanced breast cancer in postmenopausal women, with hormone receptor positive or unknown breast cancer, who had failed one prior antiestrogen treatment (i.e., for "second-line" treatment). Approval was based on two randomized trials comparing tumor RRs of patients receiving 0.5 mg of letrozole, 2.5 mg of letrozole, and either megestrol acetate (MA) or aminoglutethimide. In the megestrol trial, 2.5 mg/day letrozole was superior to 0.5 mg of letrozole and MA (RRs 24, 13, and 16%, respectively), whereas in the aminoglutethimide trial, there was no significant difference in 2.5 mg of letrozole and 0.5 mg of letrozole RRs (20 and 17%). There was a trend toward RR superiority of 2.5 mg of letrozole over aminoglutethimide (P = 0.06). Letrozole (2.5 mg) was the dose chosen for comparison with tamoxifen in the first-line setting. In July 2000, a marketing application for first-line letrozole treatment of postmenopausal women with hormone receptor positive or hormone receptor unknown locally advanced or metastatic breast cancer was submitted to the FDA. A single double-blind, double dummy, randomized, and multicenter trial compared 2.5 mg of letrozole to 20 mg of tamoxifen (456 patients/arm). Letrozole was superior to tamoxifen with regard to time to progression (TTP) and objective response rate (RR). The median TTP for letrozole treatment was 9.9 months [95% confidence interval (CI) 9.1-12.2] versus 6.2 months (95% CI 5.8-8.5) for tamoxifen, P = 0.0001, hazard ratio 0.713, (95% CI 0.61-0.84). RR was 32% for letrozole versus 21% for tamoxifen (odds ratio 1.74, 95% CI 1.29-2.34, P = 0.0003). Preliminary survival data (survival data are still blinded) indicate that letrozole is unlikely to be worse than tamoxifen. Both treatments were similarly tolerated. On the basis of these results, the United States FDA approved letrozole tablets, 2.5 mg/day, for first-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor-unknown locally advanced or metastatic breast cancer. The manufacturer made a commitment to provide updated information on survival.

Antineoplastic Agents↗
PubMed2002

Approval summary for imatinib mesylate capsules in the treatment of chronic myelogenous leukemia.

PURPOSE: Chronic myelogenous leukemia (CML) results from the breakpoint cluster region-Abl fusion gene product, a tyrosine kinase involved in cell division and apoptosis. Imatinib, an orally administered inhibitor of the breakpoint cluster region-Abl tyrosine kinase, is capable of blocking proliferation and inducing apoptosis in CML cell lines. In this report, we describe the preclinical profile of imatinib and the data submitted in the New Drug Application that led to its marketing approval. EXPERIMENTAL DESIGN: Chemistry manufacturing and controls, animal toxicology, and biopharmaceutical data are described. Results of Phase I and Phase II clinical studies in patients with CML in blast crisis (CML-BC), in accelerated phase (CML-AP), and in chronic phase disease-resistant or intolerant to IFN-alpha (CML-CP) are summarized. The basis for marketing approval and postmarketing commitments by the pharmaceutical company are discussed. RESULTS: Toxicology studies in the rat, dog, and monkey show the hematological, renal, and hepatobiliary toxicity of imatinib. Pharmacokinetic studies in patients with CML demonstrate 98% imatinib bioavailability. The elimination half-lives of the parent drug and the major active metabolite, CGP74588, from plasma are approximately 18 and 40 h, respectively. Approximately 81% of the drug is eliminated in 7 days, 68% in the feces and 13% in the urine. Cytochrome P-450 3A4 is the main enzyme responsible for imatinib metabolism. Phase I and II clinical studies were conducted. The Phase I study, in 83 CML patients, evaluated oral imatinib doses from 25 to 1000 mg/day. Dose-limiting toxicity was not observed. The three Phase II studies, in CML-CP, CML-AP, and CML-BC, enrolled 1027 patients. CML-CP patients received 400 mg/day imatinib, whereas CML-AP and CML-BC patients generally received 600 mg/day imatinib. Primary study endpoints were cytogenetic response rate (CML-CP) and hematological response rate (CML-AP and CML-BC). The cytogenetic response rate for CML-CP patients was 49%. The hematological response rate of CML-AP and CML-BC patients was 63 and 26%, respectively. The most common imatinib adverse events were nausea, vomiting, myalgia, edema, and diarrhea. Elevated liver enzymes and/or bilirubin were reported in 27 patients (2.6%). CONCLUSIONS: On May 10, 2001, imatinib mesylate (Gleevec, formerly known as STI-571 and Glivec), manufactured and distributed by Novartis Pharmaceuticals, East Hanover, NJ, was approved by the United States Food and Drug Administration for the treatment of CML in three clinical settings: CML-BC, CML-AP, and CML-CP. This report summarizes the Food and Drug Administration's review of the New Drug Application.

Antineoplastic Agents↗
PubMedDate not supplied

Perioperative complications of lumbar instrumentation and fusion in patients with diabetes mellitus.

BACKGROUND CONTEXT: Prior studies have documented an increased complication rate in diabetics treated by lumbar decompression. Despite the assumption that this risk would be exacerbated in larger fusion procedures, a recent study found no such increased risk. PURPOSE: To clarify the perioperative risk for patients with diabetes mellitus undergoing instrumented lumbar fusion as compared with controls. To identify differences, if any exist, between patients with insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes (NIDDM). STUDY DESIGN/SETTING: This is a retrospective case-control study designed to examine the risk of perioperative complications in patients with diabetes mellitus treated by lumbar instrumentation and fusion. This study analyzed 94 diabetic patients and 43 controls treated by posterior lumbar instrumentation and fusion. Outcome was assessed based on the occurrence of perioperative complications. Complications were classified as major or minor. METHODS: Hospital and office records were reviewed for 94 diabetics (51 NIDDM, 43 IDDM) and 43 controls matched for age, sex and procedure with the IDDM group. The groups were compared for demographic characteristics, surgical data, perioperative complications and fusion rate. RESULTS: The NIDDM, IDDM and control groups were equivalent with regard to age, gender, nicotine use, fusion levels, operative time and estimated blood loss. There was a significant difference in complication rate between the NIDDM (53%) and IDDM (56%) groups versus controls (21%). There was a significant increase in complications with multilevel fusion in all groups and with increased operative time in the IDDM group. There was a significantly greater nonunion rate in the NIDDM (22%) and IDDM (26%) groups as compared with controls (5%). CONCLUSIONS: Patients with both IDDM and NIDDM have a significantly increased risk of perioperative complications as compared with controls when treated by lumbar instrumentation and fusion.

Adolescent↗
PubMedDate not supplied

FDA drug approval summary: pemetrexed for injection (Alimta) for the treatment of non-small cell lung cancer.

On August 19, 2004, pemetrexed for injection (Alimta); Eli Lilly and Company, Indianapolis, IN, http://www.lilly.com) received accelerated approval as monotherapy for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who had received prior chemotherapy. Approval was primarily based on a single, controlled, unblinded trial. Five hundred seventy-one protocol-eligible patients were randomized to receive either pemetrexed or docetaxel (Taxotere); Aventis Pharmaceuticals Inc., Bridgewater, NJ, http://www.aventispharmaus.com). The primary efficacy end point was overall survival. The median survival times were 8.3 months in the pemetrexed arm and 7.9 months in the docetaxel arm. Neither superiority nor noninferiority for overall survival could be demonstrated, the latter because a reliable and consistent survival effect of docetaxel could not be estimated and because of significant crossover of pemetrexed-treated patients to docetaxel after tumor progression. Comparable response rates, 9.1% for pemetrexed and 8.8% for docetaxel, times to progressive disease, and progression-free survival times supported the conclusion that an effect of pemetrexed on survival was reasonably likely, however. In addition, pemetrexed was felt to have a more favorable safety profile than docetaxel. Of greatest importance, pemetrexed caused significantly less neutropenia, febrile neutropenia, neutropenic infections, and need for granulocyte/macrophage colony-stimulating factors.

Adult↗