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1.
Najat C Daw Wayne L Furman Clinton F Stewart Lisa C Iacono Mark Krailo Mark L Bernstein Janet E Dancey Rose Anne Speights Susan M Blaney James M Croop Gregory H Reaman Peter C Adamson 《Journal of clinical oncology》2005,23(25):6172-6180
PURPOSE: Epidermal growth factor receptor is expressed in pediatric malignant solid tumors. We conducted a phase I trial of gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, in children with refractory solid tumors. PATIENTS AND METHODS: Gefitinib (150, 300, 400, or 500 mg/m2) was administered orally to cohorts of three to six patients once daily continuously until disease progression or significant toxicity. Pharmacokinetic studies were performed during course one (day 1 through 28). RESULTS: Of the 25 enrolled patients, 19 (median age, 15 years) were fully evaluable for toxicity and received 54 courses. Dose-limiting toxicity was rash in two patients treated with 500 mg/m2 and elevated ALT and AST in one patient treated with 400 mg/m2. The maximum-tolerated dose was 400 mg/m2/d. The most frequent non-dose-limiting toxicities were grade 1 or 2 dry skin, anemia, diarrhea, nausea, and vomiting. One patient with Ewing's sarcoma had a partial response. Disease stabilized for 8 to > or = 60 weeks in two patients with Wilms' tumor and two with brainstem glioma (one exophytic). At 400 mg/m2, the median peak gefitinib plasma concentration was 2.2 microg/mL (range, 1.2 to 3.6 microg/mL) and occurred at a median of 2.3 hours (range, 2.0 to 8.3 hours) after drug administration. The median apparent clearance and median half-life were 14.8 L/h/m2 (range, 3.8 to 24.8 L/h/m2) and 11.7 hours (range, 5.6 to 22.8 hours), respectively. Gefitinib systemic exposures were comparable with those associated with antitumor activity in adults. CONCLUSION: Oral gefitinib is well tolerated in children. Development of the drug in combination with cytotoxic chemotherapy will be pursued. 相似文献
2.
HUGH F. MOLLOY F.A.C.D. ERIC LAMONT-GREGORY M.SC. CHRIS IDZIKOWSKI PH.D. F.B.PS.S. TERENCE J. RYAN D.M. F.R.C.P. 《International journal of dermatology》1993,32(9):668-672
Background. Extensive questioning of patients with a wide variety of skin disorders led to the impression that nocturnal overheating was probably an important factor in the initiation and the perpetuation of many skin disorders. Methods. In order to test the hypothesis, 12 “clean-skinned” subjects (6M/6F) aged 18 to 45 years were monitored electronically every 30 seconds during an 8 hour sleep period (2300 to 0700 hours), sleeping under a standard 10 tog duvet. Results. All the subjects were too hot by 3 to 4°C. All showed changes in their EEG patterns with reduced REM sleep, increased awakenings, and all showed changes in their sleep stage patterns. In addition, they all showed evidence of increased sweating in the “heat-sink” area. Conclusions. The mechanisms where by such changes could be implicated in the precipitation and perpetuation of skin disease are discussed. “Lifestyle” modification as a very effective, noninvasive, therapeutic regime is recommended. Further research along these lines would probably be very valuable and instructive. 相似文献
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Anderson RA; Evans LW; Irvine DS; McIntyre MA; Groome NP; Riley SC 《Human reproduction (Oxford, England)》1998,13(12):3319-3325
Follistatin is a binding protein for the activin and inhibin family of
hormones, regulating their biological activity. In the male reproductive
tract, the interaction of these factors is likely to be involved in the
regulation of the proliferation of several cell types. We have investigated
the presence of follistatin and activin A in seminal plasma using specific
immunoassays and have localized follistatin and activin/inhibin subunits in
the adult human testis, prostate and seminal vesicle to establish their
likely sources. High concentrations of immunoreactive follistatin were
present in seminal plasma in normal men (mean 97.9 ng/ml; 1.43 ng/ml in
peripheral plasma) and were similar in men with oligo/azoospermia and
following vasectomy. Follistatin immunoreactivity was localized to both
Leydig and Sertoli cells of the testis, and to epithelial cells of the
prostate gland and seminal vesicle, which are likely to be the predominant
sources of the hormone in seminal plasma. Activin A was also present in
seminal plasma in normal men but was undetectable following vasectomy, thus
deriving from the testis. Consistent with this finding, the betaA-subunit
was immunolocalized in Sertoli and Leydig cells but was not present in
seminal vesicle or prostate gland. The functional significance of the high
concentrations of follistatin secreted into seminal plasma by the prostate
gland and/or seminal vesicle is uncertain, but they may regulate the
biological activity of testis-derived activin A and inhibin B.
相似文献
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Hanley KA Manlucu LR Gilmore LE Blaney JE Hanson CT Murphy BR Whitehead SS 《Virology》2003,312(1):222-232
An acceptable live-attenuated dengue virus vaccine candidate should have low potential for transmission by mosquitoes. We have identified and characterized a mutation in dengue virus type 4 (DEN4) that decreases the ability of the virus to infect mosquitoes. A panel of 1248 mutagenized virus clones generated previously by chemical mutagenesis was screened for decreased replication in mosquito C6/36 cells but efficient replication in simian Vero cells. One virus met these criteria and contained a single coding mutation: a C-to-U mutation at nucleotide 7129 resulting in a Pro-to-Leu change in amino acid 101 of the nonstructural 4B gene (NS4B P101L). This mutation results in decreased replication in C6/36 cells relative to wild-type DEN4, decreased infectivity for mosquitoes, enhanced replication in Vero and human HuH-7 cells, and enhanced replication in SCID mice implanted with HuH-7 cells (SCID-HuH-7 mice). A recombinant DEN4 virus (rDEN4) bearing this mutation exhibited the same set of phenotypes. Addition of the NS4B P101L mutation to rDEN4 bearing a 30 nucleotide deletion (Delta30) decreased the ability of the double-mutant virus to infect mosquitoes but increased its ability to replicate in SCID-HuH-7 mice. Although the NS4B P101L mutation decreases infectivity of DEN4 for mosquitoes, its ability to enhance replication in SCID-HuH-7 mice suggests that it might not be advantageous to include this specific mutation in an rDEN4 vaccine. The opposing effects of the NS4B P101L mutation in mosquito and vertebrate systems suggest that the NS4B protein is involved in maintaining the balance between efficient replication in the mosquito vector and the human host. 相似文献
8.
Communication between psychiatrists and general practitioners: what style of letters do psychiatrists prefer? 下载免费PDF全文
This study investigated the style of referral letter that psychiatrists would like to receive from general practitioners. Ninety psychiatrists in Edinburgh were asked to answer a brief questionnaire about their preferences and select one of six sample letters presented to them. The most popular letter was one page in length and contained two or three headings. 相似文献
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Y chromosome microdeletions, in azoospermic or near-azoospermic subjects, are located in the AZFc (DAZ) subregion 总被引:9,自引:2,他引:9
Submicroscopic deletions of the Y chromosome and polymorphisms of the
androgen receptor (AR) gene in the X chromosome have been observed in men
with defective spermatogenesis. To further define the subregions/genes in
the Y chromosome causing male infertility and its relationship to
polymorphisms of the AR polyglutamine tract, we screened the genomic DNA of
202 subfertile males and 101 healthy fertile controls of predominantly
Chinese ethnic origin. Y microdeletions were examined with 16
sequence-tagged site (STS) probes, including the RBM and DAZ genes,
spanning the AZFb and AZFc subregions of Yq11, and related to the size of
trinucleotide repeat encoding the AR polyglutamine tract. Y microdeletions
were detected and confirmed in three out of 44 (6.8%) of azoospermic and
three out of 86 (3.5%) severely oligozoospermic patients. No deletions were
detected in any of the patients with sperm counts of >0.5 x 10(6)/ml,
nor in any of the 101 fertile controls. All six affected patients had
almost contiguous Y microdeletions spanning the entire AZFc region
including the DAZ gene. The AZFb region, containing the RBM1 gene, was
intact in five of the six subjects. Y deletions were not found in those
with long AR polyglutamine tracts. Our study, the first in a Chinese
population, suggest a cause and effect relationship between Y
microdeletions in the AZFc region (possibly DAZ), and azoospermia or
near-azoospermia. Y microdeletions and long AR polyglutamine tracts appear
to be independent contributors to male infertility.
相似文献