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Biomedical subjects

D Keefe

Publications and source records attributed to D Keefe.

At least 19 recordsLinked to original sources
PubMed2003

Ensembl 2002: accommodating comparative genomics.

The Ensembl (http://www.ensembl.org/) database project provides a bioinformatics framework to organise biology around the sequences of large genomes. It is a comprehensive source of stable automatic annotation of human, mouse and other genome sequences, available as either an interactive web site or as flat files. Ensembl also integrates manually annotated gene structures from external sources where available. As well as being one of the leading sources of genome annotation, Ensembl is an open source software engineering project to develop a portable system able to handle very large genomes and associated requirements. These range from sequence analysis to data storage and visualisation and installations exist around the world in both companies and at academic sites. With both human and mouse genome sequences available and more vertebrate sequences to follow, many of the recent developments in Ensembl have focusing on developing automatic comparative genome analysis and visualisation.

Animals↗
PubMed1999

Multicycle high-dose chemotherapy and filgrastim-mobilized peripheral-blood progenitor cells in women with high-risk stage II or III breast cancer: five-year follow-up.

PURPOSE: To determine the safety and efficacy of multiple cycles of dose-intensive, nonablative chemotherapy in women with poor-prognosis breast cancer. PATIENTS AND METHODS: Women with stage II breast cancer and 10 or more involved nodes or four or more involved nodes and estrogen receptor-negative tumors and women with stage III disease received three cycles of epirubicin 200 mg/m2 and cyclophosphamide 4 g/m2, with progenitor cell and filgrastim support every 28 days (n = 79) or 21 days (n = 20). Patients were reviewed at least twice yearly thereafter. Twenty-six patients had bone marrow and apheresis collections assessed for the presence of micrometastatic tumor cells. RESULTS: Ninety-nine women (median age, 43 years; range, 24 to 60 years) were treated. Ninety-two completed all three cycles of chemotherapy. The major toxicity was severe, reversible myelosuppression that was more prolonged with successive cycles, and this did not differ between patients given treatment every 28 days and those treated every 21 days. Febrile neutropenia occurred in 176 (61%) of 287 cycles. Severe mucositis (grade 3 or 4) occurred in 23% of cycles but tended to be short-lived and was reversible. The cardiac ejection fraction fell by a median of 4% during treatment, and three patients developed evidence of cardiac failure after chemotherapy. Two patients (2%) died of acute toxicity. Three of 26 patients had evidence of circulating micrometastatic tumor cells. The actuarial distant disease-free and overall survival rates at 60-month follow-up were 64% (95% confidence interval [CI], 53% to 75%) and 67% (95% CI, 56% to 78%), respectively. CONCLUSION: Multiple cycles of dose-intensive, nonablative chemotherapy is a feasible and safe approach. Disease control and survival are similar to those in other studies of myeloablative chemotherapy in poor-prognosis breast cancer. The regimen is being evaluated in a randomized trial of the International Breast Cancer Study Group.

Adult↗
PubMed1997

Polarized light microscopy and digital image processing identify a multilaminar structure of the hamster zona pellucida.

The zona pellucida (zona) is a glycoprotein coat that envelopes the oocyte and embryo, binds sperm during fertilization and facilitates transfer of the embryo through the Fallopian tube. Before implantation can occur, the blastocyst must hatch from the zona. Several lines of evidence suggest that the zona is multilaminar. We hypothesized that the multilaminar structure of the zona filaments could be imaged non-destructively with the polarized light microscope. A recent modification of the polarized light microscope (pol-scope), which combines innovations in polarization optics with novel image processing software, allows measurement of birefringence at all points of the image. Hamster metaphase II oocytes were placed on glass coverslips which replaced the bottom of culture dishes, imaged under differential interference contrast (DIC) and pol-scope optics, then digitized and processed to measure birefringence magnitude and orientation. The pol-scope revealed the zona to be divided into outer and inner layers separated by a zone of low retardance. This finding is consistent with filaments in the outer layer oriented tangentially and in the inner layer oriented radially. The multilaminar structure of the mammalian zona suggested by differential lectin binding and by scanning electron microscopy could be imaged non-destructively with the pol-scope. Because the pol-scope provides a non-destructive method to identify macro-molecular organization of the zona, it may prove useful in developmental studies of hatching and to direct resection of the zona.

Animals↗
PubMed1996

Reinventing education.

Explore the source record for details and available documents.

Computer Communication Networks↗
PubMed1994

A phase I trial of intrahepatic verapamil and doxorubicin. Regional therapy to overcome multidrug resistance.

BACKGROUND: Verapamil can modulate multidrug resistance in vitro, but only at levels that are not tolerable when administered systemically. Regional strategies of drug administration may permit the delivery of high concentrations of a drug to specific areas with lower systemic levels. Colorectal cancers typically express the multidrug resistance phenotype. METHODS: A Phase I trial was performed to determine the maximum tolerable dose (MTD) and dose limiting toxicities of verapamil by hepatic artery infusion, together with doxorubicin, to patients with hepatic metastases of colorectal cancer. Fourteen patients with metastatic colorectal cancer received a 14-hour intrahepatic infusion of verapamil. Six hours after the start of the infusion, a fixed dose of doxorubicin (50 mg/m2) was given, also via the hepatic artery, over a 30-minute period. Patients were followed by cardiac telemetry but were not in an intensive care setting, and no invasive monitoring was used. All patients had received prior intrahepatic chemotherapy. RESULTS: The MTD of intrahepatic verapamil on this schedule in this patient population was 1.2 mg/kg/hour. Hypotension was the dose limiting toxicity. No major objective responses were noted in this heavily pretreated patient population. A dose of 1.0 mg/kg/hour is recommended for Phase II trials. CONCLUSIONS: Based on estimations of normal hepatic artery blood flow, the estimated concentration of verapamil delivered to the hepatic tumors at 1.0 mg/kg/hour is 3.6 micrograms/ml (7.3 microM), which is comparable to concentrations at which an in vitro reversal of MDR is seen. This study demonstrates that the systemic toxicities of an MDR reversal agent can be overcome by regional drug delivery, establishing this approach as an important model system for further study of MDR modulation.

Adenocarcinoma↗
PubMed1994

Steroid hormones and Tourette's syndrome: early experience with antiandrogen therapy.

We report here the first use in Tourette's syndrome of the nonsteroidal androgen receptor blocking agent flutamide. One man and one woman underwent open trials of the medication, and a second man participated in a placebo-controlled, double-blind crossover trial. Improvement in tic symptoms ranged from 45 to 60%. The improvement was sustained in the woman during daily flutamide use and in one man during its intermittent use. One man's symptoms became refractory to treatment after 5 weeks of flutamide use, whereas the woman became depressed and had protracted diarrhea during her treatment.

Adult↗
PubMed1993

Intracardiac teratoma 15 years after treatment of a nonseminomatous germ cell tumor.

A patient presented to our center with a 15-year history of medical, surgical and radiation treatment for a nonseminomatous germ cell tumor and contralateral seminoma. He experienced a cerebral infarction, which led to the diagnosis of an intracardiac tumor. The tumor was resected and found to be a mature teratoma. We discuss the diagnosis and management of this unusual metastatic nonseminomatous germ cell cancer.

Adult↗
PubMed1993

Tricuspid valve thromboembolus with recurrent pulmonary embolism--a case report.

The authors describe a fifty-one-year-old man with multiple pulmonary emboli in whom two-dimensional echocardiography clearly showed a large mobile thrombus transiently entrapped in the chordal apparatus of the tricuspid valve, a location rarely noted except in autopsy specimens. Subsequent lung scan and echocardiograms documented clinically silent nonfatal embolization of this large thrombus to the lungs. Whereas most patients with this form of thromboembolic disease come to either surgery or autopsy, this case demonstrates how the combination of echocardiography and lung scanning can be used to differentiate the etiology of some right-heart masses.

Echocardiography↗
PubMed1992

The function of vacuolar beta-1,3-glucanase investigated by antisense transformation. Susceptibility of transgenic Nicotiana sylvestris plants to Cercospora nicotianae infection.

Vacuolar class I beta-1,3-glucanases (EC 3.2.1.39) are believed to be important in the induced defense reaction of plants to fungal infection. We used antisense transformation to test this hypothesis and to identify other possible physiological functions of this enzyme. Nicotiana sylvestris plants were transformed with antisense constructions containing the region from position 27 to 608 of the coding sequence of the basic, vacuolar beta-1,3-glucanase gene GLA of tobacco regulated by cauliflower mosaic virus 35S RNA expression signals. Plants homozygous for this transgene showed a marked, ca. 20-fold reduction in the constitutive expression of class I beta-1,3-glucanase antigen in their leaves. RNA blot analysis indicated that the antisense plants expressed low levels of the sense transcript of the host beta-1,3-glucanase gene and the antisense transcript of the transgene. Immune blot analysis of plant extracts indicated that only expression of the N. sylvestris homologue of class I tobacco beta-1,3-glucanase and not the acidic, class II isoforms of the enzyme was blocked in the antisense plants. Class I isoforms of beta-1,3-glucanase and chitinase were coordinately induced in leaves of untransformed and empty-vector-transformed N. sylvestris plants treated with ethylene or infected with the fungal leaf pathogen Cercospora nicotianae. In antisense plants, chitinase but not beta-1,3-glucanase was induced under these conditions indicating that antisense transformation effectively blocks constitutive as well as induced expression of class I beta-1,3-glucanase. Under greenhouse conditions, antisense plants developed normally and were fertile. The plants did not exhibit increased susceptibility to C. nicotianae infection. These results suggest that expression of the beta-1,3-glucanase isoform blocked by antisense transformation is not necessary for 'housekeeping' functions of N. sylvestris nor defense against the fungal pathogen tested.

Blotting, Northern↗
PubMed1992

Steroid hormones and CNS sexual dimorphisms modulate symptom expression in Tourette's syndrome.

We present our hypothesis that various steroid hormones play an important role in the symptom expression of Gilles de la Tourette's syndrome (TS) and that androgenic hormones, in particular, are likely to exacerbate symptoms of the disorder. We review the clinical evidence supporting our hypothesis. Sex steroids establish brain sexual dimorphisms early in CNS development, and we suggest mechanisms whereby androgenic and other hormonal changes later in human development might act at dimorphic brain regions to influence the natural history of TS. Finally, we discuss the various ways in which neuroendocrine studies might assist in genetic and neurobiologic research programs in TS.

Adolescent↗
PubMed1991

Upper abdominal cancer surgery in the very elderly.

From January 1981 to December 1987, 59 major upper abdominal operations were performed on 57 patients aged 80 to 90 years at Memorial Sloan-Kettering Cancer Center. Procedures for primary adenocarcinoma of the stomach, distal esophagus, pancreas, or hepatobiliary system were performed with curative intent or for palliation in 34 of 59 patients (58%) and bypass with limited or no resection in 13 of 59 patients (22%) patients. Emergency operations were performed in six (10%) patients for gastric bleeding, perforation, or outlet obstruction. Six (10%) patients underwent laparotomy for benign biliary obstruction (1), splenectomy for secondary thrombocytopenia (2), or gastrectomy for sarcoma (2) or lymphoma (1). Hospital mortality was 15% overall and 9% for major resections, 15% for bypass, and 67% for emergency procedures. Major complications occurred in 10 (20%) elective procedures. Mortality was associated with respiratory or cardiac failure while complications most commonly included arrhythmias and wound infection. Mean postoperative hospitalization was 18 days overall and 45 patients (76%) were discharged home. Median survival following major resection was 17.5 months but less than 2 months after bypass procedures. A protocol of pre-operative evaluation, intra-operative hemodynamic monitoring and postoperative intensive care has been formalized for use in elderly or poor-risk patients.

Adenocarcinoma↗
PubMed1991

Oxytocin secretion and human parturition: pulse frequency and duration increase during spontaneous labor in women.

The secretory pattern of oxytocin was determined in blood samples taken at 1-minute intervals for 30 minutes from 32 parturient women. The samples were collected in a manner that minimized degradation by plasma oxytocinase, and a highly specific antibody was used for the radioimmunoassay. The results indicated that oxytocin is secreted in discrete pulses of short duration. The frequency of the pulses was significantly higher during spontaneous labor than before the onset of labor. The mean pulse frequencies per 30 minutes were 1.2 +/- 0.54 before labor, 4.2 +/- 0.45 during the first stage, and 6.7 +/- 0.49 during the second and third stages of labor. The mean pulse durations in these three groups were 1.2 +/- 0.20, 1.9 +/- 0.28, and 2.0 +/- 0.26 minutes, respectively. The amplitude of the pulses was variable with no significant differences between the groups, the majority being around 1.0 microU/ml. The spontaneous pulses were of similar magnitude as those measured in 18 women after intravenous injections of 4 to 16 mU of oxytocin, which doses stimulated uterine contractions. We therefore conclude that the pulses of oxytocin observed at increasing frequency during spontaneous labor are of physiologic significance and provide evidence for the participation of oxytocin in the onset and maintenance of spontaneous labor.

Analysis of Variance↗