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31.
Luigi Camera Seigo Kinuya Kayhan Garmestani Martin W. Brechbiel Chuanchu Wu Lee H. Pai Thomas J. McMurry Otto A. Gansow Ira Pastan Chang H. Paik Jorge A. Carrasquillo 《European journal of nuclear medicine and molecular imaging》1994,21(7):640-646
The biodistribution of indium-111/yttrium-88-labeled B3 monoclonal antibody, a murine IgG1k, was evaluated in non-tumor-bearing mice. B3 was conjugated to either 2-(p-SCN-Bz)-6-methyl-DTPA (1B4M) or 2-(p-SCN-Bz)-1,4,7,10 tetraazacyclododecane tetra-acetic acid (2B-DOTA) and labeled with 111In at 1.4–2.4 mCi/mg and 88Y at 0.1–0.3 mCi/mg. Non-tumor-bearing nude mice were co-injected i.v. with 5–10 Ci/4–10 g of 111In/88Y-labeled B3 conjugates and sacrificed at 6 h and daily up to 168 h post-injection. Mice injected with 111In/88Y (IB4M)-B3 showed a similar biodistribution of the two radiolabels in all tissues except the bones, where significantly higher accretion of 88Y than 111In was observed, with 2.8% ± 0.2% vs 1.3% ± 0.16% ID/g in the femur at 168 h, respectively (P<0.0001). In contrast, mice receiving the 111In/88Y-(DOTA)-B3 conjugate showed significantly higher accumulation of 111In than 88Y in most tissues, including the bones, with 2.0% ± 0.1% vs 1.2% ± 0.09% ID/g in the femur at 168 h, respectively (P<0.0001). Whereas the ratios of the areas underneath the curve (%ID × h/g) in the blood, liver, kidney and bone were 0.96, 1.12, 1.13, and 0.74 for 111In/88Y-(IB4M)-B3 and 0.84, 1.23, 1.56, and 1.31 for 111In/88Y (DOTA)-B3, respectively, ratios 1 were observed between 111In-(IB4M)-B3 and 88Y-(DOTA)-B3. In summary, while neither IB4M nor DOTA was equally stable for 111In and 88Y, the fate of 88Y- (DOTA)-B3 could be closely traced by that of 111 In-(IB4M)-B3. 相似文献
32.
Eliasoph I 《Documenta ophthalmologica. Advances in ophthalmology》1999,98(1):87-94
Emil Gruening was the first chief of ophthalmology at the Mount Sinai Hospital, in New York City. The hospital started in
a couple of brownstone tenement buildings in lower Manhattan. Some eye patients were cared for there and many more after moving
to much larger buildings at 66th Street and Lexington Avenue. Gruening came to the United States from Posen in Prussia and
soon afterwards joined the Union army. From Appomattox he returned to New York for completion of his medical studies. He went
to Europe and studied with such notables as von Graefe and Helmholtz. He did cataract surgery with a Graefe knife, with a
nurse at times holding his beard out of the way. He also did ear, nose, and throat surgery. There is a drawing of him doing
a mastoid operation on a child with Abraham Jacobi, the father of American pediatrics, watching him. While at Mt. Sinai, William
Wilmer participated in the transplant of a rabbit eye into a patient, but went on to achieve greater things in the field.
When Gruening died, Wilmer wrote that next to his own father he respected Gruening more than any man he knew. Emil's son Ernest
became Governor of Alaska and Senator from Alaska. When Gruening retired the Eye service was jointly run by Charles H. May
and Carl Koller, but those are other tales to tell.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
33.
Ira Pastan Lee H. Pai Ulrich Brinkmann David FitzGerald 《Breast cancer research and treatment》1996,38(1):3-9
Summary
Pseudomonas exotoxin has been genetically modified so that it targets cancer cells. This was accomplished by deleting its cell binding domain and replacing it with Fv fragments of antibodies that react with breast, colon, and other cancers. Several recombinant immunotoxins are now in clinical trials.Presented at the symposium "New Approaches in the Therapy of Breast Cancer", Georgetown University Medical Center, Washington DC, October 1994, generously supported by an education grant from Bristol-Myers Squibb. 相似文献
34.
Clinical Guidelines Panel on Erectile Dysfunction: Summary Report on the Treatment of Organic Erectile Dysfunction 总被引:4,自引:0,他引:4
Drogo K. Montague James H. Barada Arnold M. Belker Laurence A. Levine Perry W. Nadig Claus G. Roehrborn Ira D. Sharlip Alan H. Bennett 《The Journal of urology》1996,156(6):2007-2011
Purpose
The American Urological Association convened the Clinical Guidelines Panel on Erectile Dysfunction to analyze the literature regarding available methods for treating organic erectile dysfunction and to make practice recommendations based on the treatment outcomes data.Materials and Methods
The panel searched the MEDLINE data base for all articles from 1979 through 1994 on treatment of organic erectile dysfunction and meta-analyzed outcomes data for oral drug therapy (yohimbine), vacuum constriction devices, vasoactive drug injection therapy, penile prosthesis implantation and venous and arterial surgery.Results
Estimated probabilities of desirable outcomes are relatively high for vacuum constriction devices, vasoactive drug injection therapy and penile prosthesis therapy. However, patients must be aware of potential complications. The outcomes data for yohimbine clearly indicate a therapy with marginal efficacy. For venous and arterial surgery, based on reported outcomes, chances of success do not appear high enough to justify routine use of such surgery.Conclusions
For the standard patient, defined as a man with acquired organic erectile dysfunction and no evidence of hypogonadism or hyperprolactinemia, the panel recommends 3 treatment alternatives: vacuum constriction devices, vasoactive drug injection therapy and penile prosthesis implantation. Based on the data to date, yohimbine does not appear to be effective for organic erectile dysfunction and, thus, it should not be recommended as treatment for the standard patient. Venous surgery and arterial surgery in men with arteriolosclerotic disease are considered investigational and should be performed only in a research setting with long-term followup available. 相似文献35.
Howard Eggers Frederick A. Jakobiec M.D. D.Sc. Ira S. Jones 《Documenta ophthalmologica. Advances in ophthalmology》1976,41(1):43-128
This is a review of primary and secondary tumors of the optic nerve. The emphasis is on optic nerve gliomas and meningiomas.Optic nerve gliomas are slowly growing astrocytic neoplasms of the anterior visual pathways, the majority of which occur within the first two decades of life with equal sex incidence in about 1 of 200,00 patients presenting with eye complaints. The incidence is greater in neurofibromatosis. The typical presentation is visual impairment in a verbal pre-school child with optic canal enlargement and optic atrophy. An intraorbital location of the tumor leads to axial, irreducible, non-pulsatile proptosis. An intracranial location may disturb hypothalamic and pituitary function and produce hydrocephalus. Ocular findings may also include limited motility on a mechanical-restrictive basis, a pupillary relative afferent defect, nystagmus, and variable, non-specific visual field defects. Roentgenographic studies may show concentric unilateral enlargement of the optic canal with preservation of a well corticated margin, a fossa under the anterior clinoid process in continuity with the optic canal (J-shaped sella), and findings of increased intracranial pressure. On pathologic examination the tumor is a smooth, fusiform, intradural enlargement of the optic nerve. Histologically there is proliferation of elongated (pilocytic) astrocytes in reticulated patterns with intervening microcystic spaces containing mucosubstance and surrounding reactive hyperplasia of the arachnoid. Mitoses are not found. The diagnosis is clinical X-ray studies and brain scan should be performed. The differential diagnosis is that of unilateral proptosis in a child and includes acute ethmoiditis, hyperthyroidism, craniostenosis, other neoplasms, Hand-Schuller-Christian disease, and orbital hemorrhage due to trauma. Surgical resection is performed in cases with unilateral optic nerve involvement, the surgical approach being determined by tumor location. Bilateral or chiasmal cases are treated with radiotherapy when progression occurs. Malignant optic nerve gliomas and optic nerve hyperplasia are also discussed.Optic nerve meningiomas arise from the nerve sheath and are to be distinguished from orbital meningiomas arising from ectopic arachnoidal cells or those secondarily involving the orbit by extension from adjacent sites. Up to 80% of orbital meningiomas occur in females, in two age peaks, 25% in the first decade, and the rest in the 5th decade. Meningiomas present with visual loss and may produce proptosis, papilledema and/or optic atrophy, retinal striae, opticociliary shunts, limitation of extra-ocular movements, and lid edema. Signs of von Recklinghausen's disease should be sought. X-rays are the mainstay of diagnosis. Orbital meningiomas are composed of cells in sheets or in whorls with some spindle shaped cells. Calcifications are typical. Usually the dura is penetrated and the orbit invaded. Primary orbital meningiomas are locally infiltrating but do not metastasize. Complete local excision en bloc is recommended. Local recurrences may require reoperation; however, long term survival is excellent.Optic nerve head tumors are mostly benign hamartomatous proliferations of glial, melanocytic, or vascular tissue in the form of the astrocytic hamartomas of tuberous sclerosis, melanocytomas, and angiomatous malformations. There may also be primary or reactive proliferations of the juxtapapillary pigment epithelium. Metastatic lesions of the optic nerve are rare, breast and lung carcinomas accounting for most. The optic nerve may be infiltrated by neopastic cells in the leukemias and lymphomas. The optic nerve may also be involved by inflammatory processes, notably sarcoidosis. Optic nerve medulloepitheliomas are highly malignant and must receive aggressive surgical treatment.From the Edward S. Harkness Eye Institute, Columbia-Presbyterian Medical Center, New York, New York 10032. 相似文献
36.
Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 2. 总被引:16,自引:0,他引:16
Roy S Herbst Giuseppe Giaccone Joan H Schiller Ronald B Natale Vincent Miller Christian Manegold Giorgio Scagliotti Rafael Rosell Ira Oliff James A Reeves Michael K Wolf Annetta D Krebs Steven D Averbuch Judith S Ochs John Grous Abderrahim Fandi David H Johnson 《Journal of clinical oncology》2004,22(5):785-794
PURPOSE: Preclinical studies indicate that gefitinib (Iressa, ZD1839; AstraZeneca, Wilmington, DE), an orally active epidermal growth factor receptor tyrosine kinase inhibitor, may enhance antitumor efficacy of cytotoxics, and combination with paclitaxel and carboplatin had acceptable tolerability in a phase I trial. Gefitinib monotherapy demonstrated unparalleled antitumor activity for a biologic agent, with less toxicity than docetaxel, in phase II trials in refractory, advanced non-small-cell lung cancer (NSCLC). This phase III, randomized, placebo-controlled, double-blind trial evaluated gefitinib plus paclitaxel and carboplatin in chemotherapy-naive patients with advanced NSCLC. PATIENTS AND METHODS: Patients received paclitaxel 225 mg/m(2) and carboplatin area under concentration/time curve of 6 mg/min/mL (day 1 every 3 weeks) plus gefitinib 500 mg/d, gefitinib 250 mg/d, or placebo. After a maximum of six cycles, daily gefitinib or placebo continued until disease progression. End points included overall survival, time to progression (TTP), response rate (RR), and safety evaluation. Results A total of 1,037 patients were recruited. Baseline demographic characteristics were well balanced. There was no difference in overall survival (median, 8.7, 9.8, and 9.9 months for gefitinib 500 mg/d, 250 mg/d, and placebo, respectively; P =.64), TTP, or RR between arms. Expected dose-related diarrhea and skin toxicity were observed in gefitinib-treated patients, with no new significant/unexpected safety findings from combination with chemotherapy. Subset analysis of patients with adenocarcinoma who received > or = 90 days' chemotherapy demonstrated statistically significant prolonged survival, suggesting a gefitinib maintenance effect. CONCLUSION: Gefitinib showed no added benefit in survival, TTP, or RR compared with standard chemotherapy alone. This large, placebo-controlled trial confirmed the favorable gefitinib safety profile observed in phase I and II monotherapy trials. 相似文献
37.
38.
Sufi M Thomas Qing Zeng Michael W Epperly William E Gooding Ira Pastan Qing Cheng Wang Joel Greenberger Jennifer Rubin Grandis 《Clinical cancer research》2004,10(20):7079-7087
PURPOSE: This study was undertaken to determine whether low intratumoral doses of the epidermal growth factor receptor ligand-transforming growth factor alpha (TGF-alpha) fused to Pseudomonas exotoxin (TGF-alpha-PE38)-abrogated head and neck squamous cell carcinoma (HNSCC) tumor growth in vitro and in vivo. EXPERIMENTAL DESIGN: In vitro cytotoxicity assays were carried out to determine the sensitivity of HNSCC cells to TGF-alpha-PE38. TGF-alpha-PE38-treated HNSCC cells were examined by immunoblotting for cleaved poly(ADP-ribose) polymerase to evaluate apoptosis. Nude mice bearing established HNSCC xenografts were treated with several doses of TGF-alpha-PE38 to evaluate the antitumor efficacy in vivo. Tumor sections were stained with terminal deoxynucleotidyl transferase-mediated nick end labeling for apoptosis. To determine the effect of oral administration of TGF-alpha-PE38, gavage injections of TGF-alpha-PE38 were administered, and the esophagus and surrounding soft tissue were then stained for apoptotic cells. RESULTS: HNSCC cell lines examined were sensitive to low doses of TGF-alpha-PE38 (EC(50) in the range of 1.6 to 10 ng/mL). HNSCC cells treated with TGF-alpha-PE38 undergo apoptosis. Antitumor effects were observed using 0.1 and 0.03 microg of TGF-alpha-PE38 administered intratumorally. At these doses, the treatment was well tolerated. Tumors treated with the toxin had a higher number of apoptotic cells compared with the control tumors. No apoptotic cells were observed in the pharyngoesophageal tissues of the mice after gavage administration of the toxin suggesting that the toxin could be orally administered without toxicity. CONCLUSIONS: These results indicate that topical or intratumoral administration of low doses of TGF-alpha-PE38 may demonstrate antitumor effects in HNSCC without associated systemic toxicity. 相似文献
39.
Bergman Ira Ahdab-Barmada Mamdouha Kemp Susan S. Griffin Judith A. Cheung Nai-Kong V. 《Journal of neuro-oncology》1997,34(3):221-231
Leptomeningeal (LM) cancer spread from either a primarybrain tumor or a systemic cancer is rapidlyfatal. Current therapies are ineffective and highly toxicto normal nervous system tissues. A xenograft modelof LM neoplasia in nude rats using adiversity of tumor cell types was established inorder to evaluate new treatment strategies and tostudy the pharmacokinetics and biological effects of treatmentsadministered into the subarachnoid space. Consistent leptomeningeal engraftmentand progressive tumor growth was seen after intrathecalinjection of 9 of 13 tumor cells lines,including 2 melanomas, 2 neuroblastomas, 2 medulloblastomas, 2gliomas, and 1 breast cancer. Clinical signs rangedfrom steady weight loss commencing from the dayafter tumor implantation to absence of any signsfor three weeks until the sudden occurrence ofmajor neurological deficits or death. Pathologic examination showedonly leptomeningeal tumor growth with some cell linesand severe parenchymal invasion with others. CSF cytologyconsistently demonstrated tumor cells in animals with LMdisease. Cranial magnetic resonance (MR) following intravenous (IV)administration of a contrast agent revealed enhancing lesionsone week following melanoma tumor implantation. Reliable ventricularpuncture was demonstrated by radiography following intraventricular (IVent)injection of an iodinated contrast material. IVent instillationof saline, albumin, or antibodies did not provokeclinical toxicity or an inflammatory response. 相似文献
40.
Stimulation of adrenergic activity by desipramine enhances hematopoietic stem and progenitor cell mobilization along with G‐CSF in multiple myeloma: A pilot study 下载免费PDF全文
Aditi Shastri Anjali Budhathoki Stefan K. Barta Noah Kornblum Olga Derman Ramakrishna Battini Radha Raghupathy Amit K. Verma Paul S. Frenette Ira Braunschweig Murali Janakiram 《American journal of hematology》2017,92(10):1047-1051
Hematopoietic stem cell (HSC) release is positively regulated by the sympathetic nervous system through the β3 adrenergic receptor. Preclinical studies have demonstrated that the combination of desipramine and G‐CSF resulted in improved HSC mobilization. Here, we present the results of an open‐label single‐arm pilot study in patients with multiple myeloma undergoing autologous stem cell transplantation (ASCT) to assess the safety and efficacy of desipramine combined with G‐SCF to induce HSC mobilization. The primary endpoint was safety of the combination including engraftment kinetics. The secondary endpoint was the proportion of patients who collected ≥5 × 106 CD34+ cells/kg. Outcomes were compared with historical matched controls during the same time period with multiple myeloma mobilized with G‐CSF. All study patients received desipramine 100 mg daily for 7 days, starting 4 days prior to G‐CSF administration (D‐3) and continued taking it along with G‐CSF for a total of 7 days. Six of ten patients enrolled completed the protocol with minimal side effects. All of them achieved the target collection of 5 × 106 CD34 cells/kg in a median of 1.5 apheresis session with two patients needing additional plerixafor (16%), while 11 out of 13 patients (85%) achieved the target of 5 × 106 CD34 cells/kg in the historical control group in a median of 2 apheresis procedures and seven patients needed plerixafor (54%). The combination of desipramine and G‐CSF is safe and signals improved mobilization over G‐CSF alone, providing a possible alternative means of mobilization that needs further investigation. 相似文献