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Biomedical subjects

E Jordan

Publications and source records attributed to E Jordan.

At least 19 recordsLinked to original sources

Pregnancy after cardiac transplantation: principles of nursing care.

The number of cardiac transplants for chronic end-stage disease, congenital heart disease, and primary pulmonary hypertension has increased during the past 20 years. Decreased symptoms, decreased incidence of rejection, and greater tolerance of medical regimens have improved the quality of life for heart transplant recipients. Women of childbearing age who have undergone cardiac transplantation may now consider pregnancy. The principles of nursing care for pregnant women who have undergone heart transplantation are presented in this article. A case report of pregnancy after cardiac transplantation is included.

Adult

Phase I and pharmacokinetic study of recombinant human granulocyte-macrophage colony-stimulating factor given in combination with fluorouracil plus calcium leucovorin in metastatic gastrointestinal adenocarcinoma.

PURPOSE: To determine the toxicities and potential for dose escalation of intravenous (IV) bolus fluorouracil (5-FU) given with 500 mg/m2/d leucovorin (LCV) and granulocyte-macrophage colony-stimulating factor (GM-CSF). PATIENTS AND METHODS: Thirty-seven patients received escalating doses of 5-FU/LCV on days 1 to 5 with subcutaneous GM-CSF either 5 or 10 micrograms/kg/d starting on day 6 or 3 micrograms/kg/d starting on day 1. 5-FU was escalated from 370 mg/m2/d by 15% increments between patient cohorts and within patients according to tolerance. RESULTS: With GM-CSF starting on day 6, dose-limiting toxicity occurred during cycle no. 1 in all three patients entered at 5-FU 490 mg/m2/d. However, individual patients tolerated 5-FU doses up to 644 mg/m2/d. When all cycles were analyzed, grade 3 to 4 mucositis and grade 4 granulocytopenia complicated < or = 15% and < or = 6% of cycles with 5-FU doses < or = 560 mg/m2/d (115 cycles). With GM-CSF starting on day 1, dose-limiting granulocytopenia occurred during cycle no. 1 in five of 10 patients entered at 5-FU 490 mg/m2/d. Although the granulocyte nadirs were significantly lower at each 5-FU dose level with the concurrent GM-CSF schedule (eg, 490 mg/m2/d: median, 879/microL v3,286/microL; two-tailed P [P2] < .001), dose-limiting granulocytopenia complicated < or = 16% of cycles with 5-FU < or = 560 mg/m2/d (99 cycles); > or = grade 3 mucositis occurred in < or = 20% of cycles. Grade 3 to 4 diarrhea was unusual with either GM-CSF schedule. Most patients treated with GM-CSF > or = 5 micrograms/kg/d required dose reductions for constitutional toxicity; 3.0 to 3.8 micrograms/kg/d was better tolerated. Venous thrombosis occurred in 17% of patients (concurrent v sequential GM-CSF, 29% v 5%; P2 = .08). The median delivered 5-FU dose-intensity for GM-CSF starting either on day 6 or on day 1 was 615 and 647 mg/m2/wk (P2 = .41), respectively. Pharmacologic exposure to 5-FU increased with higher doses of 5-FU, and concurrent GM-CSF administration did not affect 5-FU clearance. CONCLUSION: A starting dose of 425 mg/m2/d of 5-FU with LCV on days 1 to 5 could be safely combined with GM-CSF starting either on day 1 or day 6, with further 5-FU dose escalation according to individual tolerance.

Adenocarcinoma

Phase II study of fluorouracil, leucovorin, and interferon alfa-2a in metastatic colorectal carcinoma.

PURPOSE: To test the activity of a regimen of interferon alfa-2a (IFN alpha-2a) 5 x 10(6) U/m2 subcutaneously (SC) days 1 through 7 combined with leucovorin 500 mg/m2/d intravenously (IV) over 30 minutes and fluorouracil (5-FU) 370 mg/m2/d through IV push 1 hour after leucovorin days 2 through 6 in a phase II study. PATIENTS AND METHODS: Forty-six patients with a good performance status (PS) with measurable colorectal cancer and no prior therapy for metastatic disease were entered. Cycles were repeated at 3-week intervals if toxicity had resolved. The 5-FU dose was increased by 15% if toxicity was mild, and decreased by 15% for grade 3 to 4 nonhematologic or grade 4 hematologic toxicity. RESULTS: Three complete responses (CRs) and 21 partial responses (PRs) were seen among 44 assessable patients (54%; 95% confidence interval, 39% to 70%). A moderately strong association was noted between PS and response: PS O (n = 26), two CRs and 15 PRs (65%); PS 1 (n = 13), one CR and six PRs (54%); PS 2 (n = 5), zero CRs and zero PRs (0%; two-tailed P = .026). With a median follow-up duration of 18.8 months, the median time to treatment failure (TTF) and survival were 7.8 months and 16.3 months, respectively. Doses were escalated to 425 mg/m2/d 5-FU in 10 patients, but only four tolerated the higher dose. When expressed as the most severe degree of toxicity experienced by each patient across all cycles, grade 3 to 4 toxicity of the following types was observed; mucositis, 37%; diarrhea, 40%; rash, 7%; fatigue, 14%; granulocytopenia, 13%. Dose-limiting toxicity at 370 mg/m2/d 5-FU eventually occurred in 28 patients (61%). Twelve patients (26%) required an IFN alpha-2a dose reduction for constitutional toxicity. CONCLUSION: This regimen has promising activity in advanced colorectal cancer, particularly in patients with an Eastern Cooperative Oncology Group (ECOG) PS of 0 to 1.

Adult

A bacteriophage RNA polymerase transcribes through a Xenopus 5S RNA gene transcription complex without disrupting it.

Conditions are described for programming with active transcription complexes essentially all the Xenopus 5S RNA genes added to an extract of Xenopus oocyte nuclei. We call this rate enhancement. Transcription by SP6 RNA polymerase of either strand of a Xenopus 5S RNA gene is unimpeded by the presence of a complete transcription complex associated with the internal control region of the gene. Furthermore, the transcription complex remains stably associated with the 5S RNA gene following multiple transits by the prokaryotic polymerase.

Animals

Structure and properties of polysaccharides from Viscum album (L.).

Polysaccharides are possibly involved in the pharmacological effects of Viscum album (mistletoe) extracts, which are used in cancer therapy. Therefore the water-soluble polysaccharides of the fresh plant and the fermented proprietary preparation Iscador were isolated and characterized inter alia by methylation analysis, partial hydrolysis and C-13-NMR spectroscopy. The main polysaccharide of the green parts of Viscum is a highly esterified galacturonan whereas in Viscum 'berries' a complex arabinogalactan is predominant. Both types of these constituents were found in Iscador but with definite changes in molecular weight and structure. An interaction between the arabinogalactan and the galactose-specific lectin (ML I) in Viscum could be demonstrated. In three immunological tests (granulocyte, chemiluminescence, carbon clearance test) the polysaccharides failed to increase phagocytic activity of granulocytes and macrophages.

Carbon

Studies on the standardization of mistletoe preparations.

The newly isolated phenylpropanoids syringin, syringenin-apiosylglucoside, eleutheroside E and the high molecular lectins and viscotoxins were selected for a standardization of mistletoe extracts and drug preparation. The phenylpropanoids found in all alcoholic and aqueous extracts were suitable for an HPLC fingerprint analysis, and for quantitative determination. The lectin content of the drug preparations was determined by single radial immunodiffusion. As shown by the isoelectric focussing method, Iscador and fermented mistletoe extracts contain only the mistletoe lectins ML II/III, whereas the proteins of the ML I complex are missing. For identification and quantitative determination of viscotoxins, an HPLC method was designed.

Chromatography, Affinity

[Detection and quantitative determination of lectins and viscotoxins in mistletoe preparations].

Mistletoe lectins and viscotoxins, which up to now have been isolated only from plant material, were detected and quantitatively determined in the mistletoe preparation Iscador and in a fermented mistletoe extract. Lectins were isolated by affinity chromatography and analyzed by isoelectric focussing. Thus, in Iscador and in the fermented mistletoe extract only the mistletoe lectins ML II/III were found whereas typical proteins of the ML I complex were missing. The lectin content of the preparation and the extract was determined by "single radial immunodiffusion" (SRID). For identification and quantitative determination of viscotoxins, a HPLC method was designed.

Chromatography, Affinity

Intermolecular and intramolecular transposition and transposition immunity in Tn3 and Tn2660.

Intermolecular transposition of Tn2660 into pCR1 was measured at 30 degrees C in recA- and recA+ hosts as between 2.6 and 5.5 X 10(-3), a similar value to that previously found for Tn3. No cointegrate structures were found under conditions where 10(4) transposition events occurred. Immunity to intermolecular transposition of Tn2660, similar to that found for Tn3 was demonstrated by showing that the above transposition frequency was reduced by a factor of between 10(-3) and 10(-4) when a mutant Tn2660 (resulting in the synthesis of a temperature-sensitive beta-lactamase) was present in the recipient plasmid. Intramolecular transposition of Tn3 was found to occur under the same conditions as previously demonstrated for Tn2660 giving rise to similar end products, in which the newly introduced Tn3 is oriented inversely to the resident Tn3 and the DNA sequence between the two transposons has been inverted. Thus, in all respects functional identity of the transposition activities of Tn3 and Tn2660 is shown, thereby identifying characteristics of intramolecular transposition that are not readily accommodated by current models of transposition.

Bacterial Proteins

A quantitative assay for Xenopus 5S RNA gene transcription in vitro.

The in vitro transcription of Xenopus 5S RNA genes and of deletion mutants of these genes has been quantitated by assays that measure the efficiency of transcription and the ability to compete with the transcription of a "wild-type" 5S RNA gene. The difference between the competition strength of one repeating unit of X. borealis somatic 5S DNA and its plasmid vector is fifteenfold. tRNA genes and the adenovirus VA RNA genes are weak competitors of 5S RNA synthesis (and vice versa). Deletion of the 5' flanking region reduces the competition strength of somatic but not oocyte 5S DNA. Except for the influence of the flanking sequence, the regions within the 5S RNA gene that determine competition strength are those that have been shown to interact with a specific transcription factor that is required for accurate initiation of 5S RNA transcription. The major oocyte (Xlo) and trace oocyte (Xlt) 5S RNA genes from X. laevis are transcribed as efficiently as somatic 5S DNAs but compete only one fourth as well. This fourfold difference in the competition strength is due to oocyte-specific base changes within the intragenic control region.

Animals

Multiple myeloma complicating the course of seronegative systemic lupus erythematosus.

A patient with a 20-year history of clinical systemic lupus erythematosus (SLE) who later developed multiple myeloma is described. SLE was diagnosed on the basis of a butterfly rash, photosensitivity, nondeforming arthritis, pleuropericarditis, and alopecia. However, the patient has never had LE cells, antinuclear antibody, or depressed complement. The patient was treated with intermittent courses of corticosteroids over a 20-year period with good results. Multiple myeloma, diagnosed by bone marrow biopsy, has responded favorably to therapy with L-phenylalanine mustard and prednisone.

Adrenal Cortex Hormones

A nuclear extract of Xenopus laevis oocytes that accurately transcribes 5S RNA genes.

Xenopus 5S RNA genes in recombinant form with the plasmid pMB9 are transcribed accurately when added to a supernatant fraction obtained from disrupted nuclei of Xenopus laevis oocytes. After an initial 30 min lag period, the rate of synthesis of 5S RNA is constant for at least an hour and synthesis is still detected after 18 hr. As much as 40% of the total RNA synthesized from the recombinant DNA used in these experiments can be 5S RNA. The coding strand of the 5S RNA genes is transcribed at a rate 10 to 15 times greater than the noncoding strand. Plasmid and spacer DNA, however, are also transcribed. What fraction of total RNA synthesized is 5S RNA is strongly affected by DNA concentration, ionic strength and MgCl2 concentration. Inhibition of transcription by intermediate concentrations of alpha-amanitin demonstrates that RNA polymerase III transcribes at least 90% of all RNA synthesized. Adenovirus 2 DNA is also transcribed in the nuclear supernatant by RNA polymerase III. Approximately 15% of the total RNA synthesized migrates in an acrylamide gel as a band of 5.5S RNA and has been identified as virus-associated RNA1 by its oligonucleotide fingerprint.

Animals