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Effect of pregnancy on the pharmacokinetics of metformin. 总被引:2,自引:0,他引:2
AIMS: To determine the effects of pregnancy on metformin pharmacokinetics. METHODS: Seven women with Type 2 diabetes mellitus taking metformin throughout pregnancy were studied on two occasions, once at 28-36 weeks gestation and once at least 8 weeks postpartum. Serum metformin concentrations were determined across a dosing interval using high-performance liquid chromatography. The areas under the serum concentration-time curve from 0 to 4 h post-dose (AUC0-4) and 0 to 8 h post-dose (AUC0-8) where possible, were compared in the pregnant and non-pregnant state. RESULTS: Metformin concentrations were lower in pregnancy in six subjects, with a mean (95% CI) AUC0-4 that was 69% (53.6, 84.8) of the postpartum value. The AUC0-4 of one subject was higher in pregnancy at 142% of the postpartum value. Overall, the mean (95% CI) AUC0-4 during pregnancy for all seven subjects was 80% (51.3, 107.8) of the postpartum value (P = 0.053, two-tailed t-test; P = 0.027, one-tailed t-test). CONCLUSION: These results are consistent with our hypothesis that the clearance of metformin increases in pregnancy as a result of enhanced renal elimination. A larger study is required to establish whether metformin dose adjustments are required in late pregnancy to maintain therapeutic effect. 相似文献
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K. Cartwright M. Logan C. McNulty S. Harrison R. George A. Efstratiou M. McEvoy N. Begg 《Epidemiology and infection》1995,115(3):387-397
We describe the first cluster of cases of necrotizing fasciitis (NF) in this century in the United Kingdom (UK). Between 1 January and 30 June 1994 there were six cases (five confirmed, one probable) of Streptococcus pyogenes NF in west Gloucestershire, population 320,000. Two cases died. The first two patients probably acquired their infections during the course of elective surgery performed in the same operating theatre, possibly from a nasopharyngeal carrier amongst the theatre staff. The remaining infections were community-acquired. Of 5 S. pyogenes isolates there were 2 M1 strains, 1 M3, 1 M5 and 1 M non-typeable strain. S. pyogenes NF had not been recorded in west Gloucestershire in the preceding 10 years and the incidence of S. pyogenes bacteraemia in England and Wales had not risen in the past 5 years. The two presumably theatre-acquired infections raised several issues. The need for detailed bacteriological investigation of all cases of post-surgical NF was confirmed. Clusters of S. pyogenes infection following surgery should be managed by closure of the operating theatre until all staff have been screened for carriage. Closure of an operating theatre and screening of staff following a sporadic case is probably not justified because of the infrequency of surgical cross-infection with S. pyogenes. Regular, routine screening of theatre staff is neither practical nor necessary. 相似文献
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Silber SJ; Nagy Z; Devroey P; Tournaye H; Van Steirteghem AC 《Human reproduction (Oxford, England)》1997,12(11):2422-2428
The aim of the study was to determine whether a prior diagnostic testicle
biopsy can predict success or failure of testicular sperm extraction (TESE)
with intracytoplasmic sperm injection (ICSI) in patients with
non-obstructive azoospermia caused by testicular failure, and what is the
minimum threshold of sperm production in the testis which must be surpassed
for spermatozoa to reach the ejaculate. Forty- five patients with
non-obstructive azoospermia caused by testicular failure underwent
diagnostic testicle biopsy prior to a planned future TESE-ICSI procedure.
The diagnostic testicle biopsy was analysed quantitatively, and correlated
with the quantitative findings of spermatogenesis in patients with normal
spermatogenesis, as well as with the results of subsequent attempts at
TESE-ICSI. Men with non- obstructive azoospermia caused by germinal failure
had a mean of 0-6 mature spermatids/seminiferous tubule seen on a
diagnostic testicle biopsy, compared to 17-35 mature spermatids/tubule in
men with normal spermatogenesis and obstructive azoospermia. These findings
were the same for all types of testicular failure whether Sertoli cell
only, maturation arrest, cryptorchidism, or post-chemotherapy azoospermia.
Twenty-two of 26 men with mature spermatids found in the prior testis
biopsy had successful retrieval of spermatozoa for ICSI, 12 of their
partners became pregnant, and are either ongoing or delivered. The study
suggests that 4-6 mature spermatids/tubule must be present in the testis
biopsy for any spermatozoa to reach the ejaculate. More than half of
azoospermic patients with germinal failure have minute foci of
spermatogenesis which are insufficient to produce spermatozoa in the
ejaculate. Prior diagnostic testicle biopsy analysed quantitatively (for
the presence of mature spermatids) can predict subsequent success or
failure with TESE-ICSI. Incomplete testicular failure may involve a sparse
multi-focal distribution of spermatogenesis throughout the entire testicle,
rather than a regional distribution. Therefore, it is possible that massive
testicular sampling from many different regions of the testes may not be
necessary for successful TESE-ICSI.
相似文献
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β-Lactoglobulin was isolated from infant formulae that were ultra high temperature (UHT) -treated, sterilized or spray-dried. The effect of the isolated β-lactoglobulin on SfaII-fimbriae-mediated adhesion of Escherichia coli to human ileostomy glycoproteins was studied in vitro. β-Lactoglobulin isolated from sterilized formulae was found to perform significantly less well than preparations from spray-dried formulae (p = 0:05). Great heterogeneity was observed in the adhesion inhibitory capacity of β-lactoglobulin isolated from UHT-treated formulae. Therefore, no significant difference was observed between UHT-treated and sterilized formulae or spray-dried formulae (p < 0:10). It can be hypothesized that β-lactoglobulin from spray-dried and some UHT-treated infant formulae may affect the colonization of mucous membranes by E. coli strains causing neonatal septicaemia and meningitis. 相似文献
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Publication bias and dissemination of clinical research 总被引:15,自引:0,他引:15
Publication bias is a widely recognized phenomenon that occurs because of the influence of study results on the chances of publication. Usually, studies with positive results are more likely to be published than studies with negative results, which leads to a preponderance of false-positive results in the literature. Empiric studies have demonstrated that the induced bias is large and can have a serious impact on meta-analyses, in which data from several studies are aggregated, as well as on informal reviews. The problem is deeply embedded in current research practice, which encourages demonstration of statistical significance to "prove" theories, and one of its causes is the pressure to publish extensively that is an integral part of the competition for academic promotion. Serious efforts to reduce this problem will involve restructuring the process by which study results are disseminated, changing editorial policies, and altering the style and methods of statistical analysis. 相似文献