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Laurence D. Reed 《Public health reports (Washington, D.C. : 1974)》2010,125(4):513-Aug;125(4):513
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C. J. Bowden W. D. Figg N. A. Dawson O. Sartor R. J. Bitton M. S. Weinberger Donna Headlee Eddie Reed C. E. Myers M. R. Cooper 《Cancer chemotherapy and pharmacology》1996,39(1-2):1-8
Introduction: Suramin is a synthetic polysulfonated naphthylurea which has been used for the treatment of African trypanosomiasis and onchocerciasis,
but since the mid-1980s has received attention as a possible antiretroviral and antineoplastic agent. Objective: This clinical trial of suramin was undertaken as a phase I/II study in patients with hormone-refractory prostate cancer,
with the hypothesis that the intensity of therapy with suramin could be increased significantly if measures were undertaken
to maintain the plasma concentrations of the drug under 300 μg/ml. Methods: We report the clinical results of this trial, wherein patients were treated at three different targeted plasma suramin concentrations
(275, 215 and 175 μg/ml) for varying periods of time (2, 4 or 8 weeks), with delivery of the drug by continuous intravenous
infusion. Results: The major toxicity observed in this trial was neurologic, consisting of a motor and sensory peripheral neuropathy that resulted
in both paresis and paralysis of the limbs. Nearly all of this severe (CTEP grade III, IV) neurologic toxicity was observed
in the patients treated at a plasma suramin concentration of 275 μg/ml for 4 or more weeks. A single patient treated at 215 μg/ml
for 8 weeks developed moderate (CTEP grade III) proximal lower extremity weakness, and no patient treated at 175 μg/ml developed
this toxicity. The second most common toxicity observed was infection of the central venous catheter. The overall response
rate for all of the evaluable patients was 17% (13 of 75 patients). In addition, prostate-specific antigen (PSA)-defined responses
were observed in six patients receiving therapy at 175 μg/ml, but these responses were confounded by cessation of therapy
with flutamide during suramin treatment. Conclusions: In summary, although plasma suramin concentrations were maintained below 300 μg/ml, neurologic toxicity nonetheless occurred
with high frequency in patients treated at 275 μg/ml for 4 or more weeks. Therapy at 215 and 175 μg/ml was in general well
tolerated, but central venous catheter-related infection, as well as the inconvenience and expense of continuous infusional
therapy, make this method of drug delivery impractical. Only moderate antitumor activity was observed during this trial, but
it is possible that both continuation of flutamide and flutamide withdrawal during suramin therapy confounded the assessment
of suramin’s activity in hormone-refractory prostate cancer.
Received: 9 June 1995/Accepted: 18 March 1996 相似文献
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The prevalence of Chlamydia trachomatis, Mycoplasma pneumoniae, group A beta-hemolytic streptococcus, and other treatable organisms was studied in children with and without pharyngitis. Children aged 2 to 12 years were evaluated between November 1985 and April 1986 in three family practice offices in the Salt Lake City area. Chlamydia trachomatis was not detected in the pharynx of any of the children studied. Mycoplasma pneumoniae was cultured from 5 percent of the 242 children studied, group A beta-hemolytic streptococcus from 30 percent, non-group A beta-hemolytic streptococcus from 5 percent, Hemophilus influenzae from 4 percent, and Staphylococcus aureus from 14 percent. The symptoms reported were not statistically associated with any organism isolated, and clinical signs of pharyngitis were associated only with the presence of group A beta-hemolytic streptococcus. Based on these results, management of pharyngitis in children should continue to be based on the detection and treatment of group A beta-hemolytic streptococcus. 相似文献
7.
Protein components specifically associated with prespliceosome and spliceosome complexes. 总被引:40,自引:2,他引:38
We have carried out a systematic analysis of the protein composition of highly purified mammalian spliceosomes. We show that > 30 distinct proteins, including 20 previously unidentified components [designated spliceosome-associated proteins (SAPs)], are specifically associated with the spliceosome in a salt-resistant complex. In contrast to these spliceosome-specific proteins, we show that hnRNP proteins are not tightly associated with purified prespliceosome and spliceosome complexes. The splicing factor U2AF65, U1 snRNP-specific proteins, and several SAPs are present in the earliest prespliceosome complex (E). A set of 10 proteins is then added to the first ATP-dependent prespliceosome complex (A), and concomitantly, a significant decrease in the level of U2AF65 is observed. The fully assembled spliceosome is formed by the addition of 12 proteins in a reaction that requires ATP and both the 5' and 3' splice sites. 相似文献
8.
Studies were carried out to investigate the metabolism of senecionine by human liver microsomes and the role of human cytochrome P450IIIA4 in this process. Human liver microsomes metabolized senecionine to two major products, (+/-)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP) and senecionine N-oxide. The rates of product formation (DHP and senecionine N-oxide) varied widely with the microsomal samples tested. There was a 30-fold difference in DHP formation and a 25-fold difference in N-oxidation between the poorest metabolizer and the highest metabolizer of senecionine. The conversion of senecionine to DHP and senecionine N-oxide in human liver microsomes was markedly inhibited by the mechanism-based inactivators of P450IIIA4, gestodene and triacetyloleandomycin. Anti-P450IIIA4 IgG, at a concentration of 1 mg/nmol of P450, was found to inhibit completely the formation of DHP and senecionine N-oxide in human liver microsomes (HL101) having low activity toward senecionine. At 5 mg IgG/nmol P450, anti-P450IIIA4 inhibited 90 and 84% respectively of the formation of DHP and senecionine N-oxide in liver microsomes (HL110) with the highest activity toward senecionine. The formation of DHP or senecionine N-oxide was highly correlated with the amount of P450IIIA4 measured in the microsomes using polyclonal anti-P450IIIA4 IgG. The rate of DHP production also had a strong correlation with the rate of senecionine N-oxide formation (r = 0.999) and with the rate of nifedipine oxidation (r = 0.998). Our present studies provide evidence that P450IIIA4 is the major enzyme catalyzing the bioactivation (DHP formation) and detoxication (senecionine N-oxide formation) of senecionine in human liver. 相似文献
9.
Researchers usually employ orthogonal arrays or D-optimal designs with little or no attribute overlap in stated-choice surveys. The challenge is to balance statistical efficiency and respondent burden to minimize the overall error in the survey responses. This study examined whether simplifying the choice task, by using a design with more overlap, provides advantages over standard minimum-overlap methods. We administered two designs for eliciting HIV test preferences to split samples. Surveys were undertaken at four HIV testing locations in San Francisco, California. Personal characteristics had different effects on willingness to pay for the two treatments, and gains in statistical efficiency in the minimal-overlap version more than compensated for possible imprecision from increased measurement error. 相似文献
10.
JC Sitek† M Loeb‡ JR Ronnevig¶ 《Journal of the European Academy of Dermatology and Venereology》2007,21(7):891-896
BACKGROUND: Since 1997, a number of trials have shown promising results in treating generalized vitiligo with narrowband ultraviolet B (UVB) both in adults and children. However, there is little knowledge concerning the duration and permanency of the treatment-induced repigmentation. OBJECTIVE: Our main objective was to perform a follow-up trial of successfully treated patients receiving narrowband UVB for generalized vitiligo. METHODS: We have investigated to what degree the treatment-induced repigmentation remains stable for up to 2 years post-treatment. We performed an initial open trial including 31 patients with generalized vitiligo. They received narrowband UVB thrice weekly for up to 12 months. Patients experiencing > 75% repigmentation were defined responders and were included in the follow-up trial. Responders were followed every 6 months for up to 2 years after cessation of treatment. We observed the pigmentation status and registered any changes indicating loss of pigmentation and relapse. RESULTS: Eleven of the 31 treated patients were included in the follow-up trial. Six patients had relapse and five patients had stable response 24 months after cessation of treatment. Four out of six relapses were within 6 months post-treatment. CONCLUSION: In our study population of 31 patients with generalized vitiligo, five patients (16%) experienced > 75% stable repigmentation 2 years after cessation of a treatment programme of up to 1 years narrowband UVB therapy. 相似文献