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91.
Saba R Jabbour E Giles F Cortes J Talpaz M O'Brien S Freireich EJ Garcia-Manero G Kantarjian H Verstovsek S 《Cancer》2005,103(12):2551-2557
BACKGROUND: In 1986, a Phase II trial of recombinant interferon-alpha (IFN-alpha) was initiated as therapy for patients with essential thrombocythemia (ET). METHODS: Patients were treated with subcutaneous IFN-alpha at a dose of 5 x 10(6) units/m(2) daily. In responding patients, the therapy lasted at least 3 years. RESULTS: Twenty-three patients (14 females and 9 males; median age, 41 years; age range, 20-63 years) with a median platelet count of 1350 x 10(9)/L were treated. After a median follow-up of 174 months (14.5 years), 15 of 20 evaluable patients (75%) responded, including 14 patients who achieved a complete hematologic response (CHR) (6 of them with bone marrow remission) and 1 patient who demonstrated a partial response. The median time to response was 6 months (range, 0.5-36 months), and the median response duration was 48 months (range, 5-114 months). Seven patients who achieved a CHR and were taken off therapy after they completed 3 years of maintenance therapy sustained their response for a median of 28 months. No symptoms or signs of thrombosis or hemorrhage were observed in responding patients. Eleven of 14 patients (78%) who achieved a CHR developed a recurrence, and 2 of 5 patients with recurrences who were rechallenged with IFN-alpha achieved a second response. The treatment was tolerated relatively well. CONCLUSIONS: IFN-alpha was safe and effective therapy for patients with ET, and the ability of IFN-alpha to reverse disease pathology and possibly modify the clinical course of patients with ET warrants its investigation in larger, prospective trials. 相似文献
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94.
Hsiung HM Hertel J Zhang XY Smith DP Smiley DL Heiman ML Yang DD Husain S Mayer JP Zhang L Mo H Yan LZ 《Endocrinology》2005,146(12):5257-5266
alphaMSH has generally been accepted as the endogenous ligand for melanocortin 4 receptor (MC4R), which plays a major role in energy homeostasis. Targeting MC4R to develop antiobesity agents, many investigators have performed a structure-activity relationship (SAR) studies based on alphaMSH structure. In this report, we performed a SAR study using human betaMSH (5 - 22) (DEGPYRMEHFRWGSPPKD, peptide 1) as a lead sequence to develop potent and selective agonists for MC4R and MC3R. The SAR study was begun with a truncation of N terminus of betaMSH (5 - 22) together with acetylation of the N terminus and amidation of the C terminus of the peptide. Introduction of a cyclic disulfide constrain and replacement of L-Phe with D-Phe afforded a super potent agonist (peptide 5). Furthermore truncation at the C terminus generated a small and potent MC4R and MC3R agonist (Ac-YRcyclo[CEHdFRWC]amide, peptide 6), which exhibited no MC5R and greatly reduced MC1R activity. Molecular modeling of Ac-YRcyclo[CEHdFRWC]amide (peptide 6) revealed that Arg2 in the peptide formed a salt bridge with Glu4. Subcutaneous or intracerebroventricular administration of peptide 6 in rats showed potent in vivo efficacy as evidenced by its effects in reducing energy balance, increasing fat use, and decreasing weight gain in both acute and chronic rat metabolic studies. Furthermore, the antiobesity effect by peptide 6 was manifested only in wild-type but not MC4R-deficient mice, indicating that antiobesity effects of the peptide were attributed largely through MC4R but not MC3R agonist activity of the peptide. 相似文献
95.
Laryngeal tuberculosis 总被引:1,自引:0,他引:1
Tuberculosis involvement of the larynx is uncommon. However, it is a highly infectious disease and a hazard to both community and hospital staff. It should be considered in the differential diagnosis of patients presenting with chronic hoarseness. Two patients with laryngeal tuberculosis are the objective of the present report. The diagnosis was established by biopsy followed by isolation and identification of Mycobacterium tuberculosis from sputum. 相似文献
96.
97.
Martí R Verschuuren JJ Buchman A Hirano I Tadesse S van Kuilenburg AB van Gennip AH Poorthuis BJ Hirano M 《Annals of neurology》2005,58(4):649-652
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is caused by mutations in the gene encoding thymidine phosphorylase (TP). All MNGIE patients have had severe loss of TP function and prominent plasma accumulations of the TP substrates thymidine (dThd) and deoxyuridine (dUrd). Here, we report for the first time to our knowledge three MNGIE patients with later onset, milder phenotype, and less severe TP dysfunction, compared with typical MNGIE patients. This report demonstrates a direct relationship between the biochemical defects and clinical phenotypes in MNGIE and supports the notion that reduction of dThd and dUrd accumulation or TP replacement could be useful therapy for MNGIE. 相似文献
98.
99.
Agarwal A Ranganathan P Kattal N Pasqualotto F Hallak J Khayal S Mascha E 《Fertility and sterility》2004,81(2):342-348
OBJECTIVE: To examine the outcome of assisted reproduction techniques (ART) using cryopreserved semen from patients with cancer. DESIGN: Prospective. SETTING: Therapeutic semen banking program at a tertiary healthcare center. PATIENT(S): Twenty-nine men with cancer who cryopreserved their sperm before treatment at our facility from 1982 to 2001 and withdrew their samples for assisted reproduction (IUI, IVF, or intracytoplasmic sperm injection [ICSI]). INTERVENTION(S): Sperm bank records were used to identify the patients. Information on fertility potential indices was obtained from medical records and through interviews. Of the 29 patients, 9 had testicular cancer, 12 had Hodgkin's disease, and 8 had other types of cancer. MAIN OUTCOME MEASURE(S): Pregnancy and live births. RESULT(S): A total of 87 ART cycles (42 IUI, 26 IVF, and 19 ICSI) was performed. Of those cycles, 18.3% resulted in pregnancy (7% IUI, 23% IVF, and 37% ICSI), and 75% of the pregnancies resulted in a live birth (100% IUI, 83% IVF, and 57% ICSI). There was no significant difference in the outcomes when the results were stratified by type of ART and malignancy. None of the 11 infants who were born had congenital anomalies. CONCLUSION(S): Our findings emphasize the need for physicians to discuss the issue of semen cryopreservation with all men of reproductive age who have cancer before antineoplastic therapy is started. 相似文献
100.
Definitive diagnosis of mitochondrial neurogastrointestinal encephalomyopathy by biochemical assays 总被引:3,自引:0,他引:3
Martí R Spinazzola A Tadesse S Nishino I Nishigaki Y Hirano M 《Clinical chemistry》2004,50(1):120-124
BACKGROUND: Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is caused by mutations in the gene encoding thymidine phosphorylase (TP). The clinical manifestations of MNGIE are recognizable and homogeneous, but in the early stages, the disease is often misdiagnosed. This study assesses the reliability of biochemical assays to diagnose MNGIE. METHODS: We studied 180 patients with clinical features suggestive of MNGIE, 14 asymptomatic TP mutation carriers, and 20 controls. TP enzyme activity in the buffy coat was determined by a fixed-time method, and the plasma nucleosides thymidine (dThd) and deoxyuridine (dUrd) were assessed by a gradient-elution reversed phase HPLC method. TP was sequenced through standard procedures in patients who met the clinical criteria for MNGIE. RESULTS: Twenty-five of the 180 patients fulfilled the clinical criteria for MNGIE and had homozygous or compound heterozygous TP mutations. All had drastically decreased TP activity [mean (SD), 10 (15) nmol thymine formed. h(-1). (mg protein)(-1) vs 634 (217) nmol thymine formed. h(-1). (mg protein)(-1) for the controls]. Relative to the control mean, TP activities were reduced to 35% in mutation carriers and 65% in MNGIE-like patients. All 25 MNGIE patients had detectable plasma dThd [8.6 (3.4) micromol/L] and dUrd [14.2 (4.4) micromol/L]. Controls, carriers, and MNGIE-like patients showed no detectable plasma dThd and dUrd. CONCLUSIONS: We propose a diagnostic algorithm based on the determination of plasma dThd and dUrd, TP activity in buffy coat, or both to make a definitive diagnosis of MNGIE. Increased concentrations of dThd (>3 micromol/L) and dUrd (>5 micromol/L) in plasma or a decrease in buffy coat TP activity to =8% relative to controls is sufficient to diagnose MNGIE. 相似文献