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21.
George N Papanikolaou Maria S Baltogianni Despina G Contopoulos-Ioannidis Anna-Bettina Haidich Ioannis A Giannakakis John PA Ioannidis 《BMC medical research methodology》2001,1(1):3
Background
Guidelines published in major medical journals are very influential in determining clinical practice. It would be essential to evaluate whether conflicts of interests are disclosed in these publications. We evaluated the reporting of conflicts of interest and the factors that may affect such disclosure in a sample of 191 guidelines on therapeutic and/or preventive measures published in 6 major clinical journals (Annals of Internal Medicine, BMJ, JAMA, Lancet, New England Journal of Medicine, Pediatrics) in 1979, 1984, 1989, 1994 and 1999.Results
Only 7 guidelines (3.7%) mentioned conflicts of interest and all were published in 1999 (17.5% (7/40) of guidelines published in 1999 alone). Reporting of conflicts of interest differed significantly by journal (p=0.026), availability of disclosure policy by the journal (p=0.043), source of funding (p < 0.001) and number of authors (p=0.004). In the entire database of 191 guidelines, a mere 18 authors disclosed a total of 24 potential conflicts of interest and most pertained to minor issues.Conclusions
Despite some recent improvement, reporting of conflicts of interest in clinical guidelines published in influential journals is largely neglected.22.
Mahadevan Mani S.; Amemiya Chris; Jansen Gert; Sabourin Luc; Baird Stephen; Neville Catherine E.; Wormskamp Nicole; Segers Bart; Batzer Mark; Lamerdin Jane; de Jong Peter; Wieringa Be; Korneluk Robert G. 《Human molecular genetics》1993,2(3):299-304
The mutation causing myotonic dystrophy (DM) has recently beenidentified as an unstable CTG trinucleotide repeat located inthe 3' untranslated region of a gene encoding for a proteinwith putative serine-threonine protein kinase activity. In thisreport we present the genomic sequences of the human and murineDM kinase gene. A comparison of these sequences with each otherand with known cDNA sequences from both species, led us to predicta translation initiation codon, as well as determine the organizationof the DM kinase gene. Several polymorphisms within the humanDM kinase gene have been identified, and PCR assays to detecttwo of these are described. The complete sequence and characterizationof the structure of the DM kinase gene, as well as the identificationof novel polymorphisms within the gene, represent an importantstep in a further understanding of the genetics of myotonicdystrophy and the molecular biology of the gene. 相似文献
23.
Dal Zotto L; Quaderi NA; Elliott R; Lingerfelter PA; Carrel L; Valsecchi V; Montini E; Yen CH; Chapman V; Kalcheva I; Arrigo G; Zuffardi O; Thomas S; Willard HF; Ballabio A; Disteche CM; Rugarli EI 《Human molecular genetics》1998,7(3):489-499
We have recently reported isolation of the gene responsible for X- linked
Opitz G/BBB syndrome, a defect of midline development. MID1 is located on
the distal short arm of the human X chromosome (Xp22. 3) and encodes a
novel member of the B box family of zinc finger proteins. We have now
cloned the murine homolog of MID1 and performed preliminary expression
studies during development. Mid1 expression in undifferentiated cells in
the central nervous, gastrointestinal and urogenital systems suggests that
abnormal cell proliferation may underlie the defect in midline development
characteristic of Opitz syndrome. We have also found that Mid1 is located
within the mouse pseudoautosomal region (PAR) in Mus musculus , while it
seems to be X- specific in Mus spretus. Therefore, Mid1 is likely to be a
recent acquisition of the M. musculus PAR. Genetic and FISH analyses also
demonstrated a high frequency of unequal crossovers in the murine PAR,
creating spontaneous deletion/duplication events involving Mid1. These data
provide evidence for the first time that genetic instability of the PAR may
affect functionally important genes. In addition, we show that MID1 is the
first example of a gene subject to X-inactivation in man while escaping it
in mouse. These data contribute to a better understanding of the molecular
content and evolution of the rodent PAR.
相似文献
24.
A model of corrective gene transfer in X-linked ichthyosis 总被引:5,自引:0,他引:5
Freiberg RA; Choate KA; Deng H; Alperin ES; Shapiro LJ; Khavari PA 《Human molecular genetics》1997,6(6):927-933
Single gene recessive genetic skin disorders offer attractive prototypes
for the development of therapeutic cutaneous gene delivery. We have
utilized X-linked ichthyosis (XLI), characterized by loss of function of
the steroid sulfatase arylsulfatase C (STS), to develop a model of
corrective gene delivery to human skin in vivo. A new retroviral expression
vector was produced and utilized to effect STS gene transfer to primary
keratinocytes from XLI patients. Transduction was associated with
restoration of full-length STS protein expression as well as steroid
sulfatase enzymatic activity in proportion to the number of proviral
integrations in XLI cells. Transduced and uncorrected XLI keratinocytes,
along with normal controls, were then grafted onto immunodeficient mice to
regenerate full thickness human epidermis. Unmodified XLI keratinocytes
regenerated a hyperkeratotic epidermis lacking STS expression with
defective skin barrier function, effectively recapitulating the human
disease in vivo. Transduced XLI keratinocytes from the same patients,
however, regenerated epidermis histologically indistinguishable from that
formed by keratinocytes from patients with normal skin. Transduced XLI
epidermis demonstrated STS expression in vivo by immunostaining as well as
a normalization of histologic appearance at 5 weeks post-grafting. In
addition, transduced XLI epidermis demonstrated a return of barrier
function parameters to normal. These findings demonstrate corrective gene
delivery in human XLI patient skin tissue at both molecular and functional
levels and provide a model of human cutaneous gene therapy.
相似文献
25.
Determination of the parent of origin in nine cases of prenatally detected chromosome aberrations found after intracytoplasmic sperm injection 总被引:1,自引:17,他引:1
Van Opstal D; Los FJ; Ramlakhan S; Van Hemel JO; Van Den Ouweland AM; Brandenburg H; Pieters MH; Verhoeff A; Vermeer MC; Dhont M; In't Veld PA 《Human reproduction (Oxford, England)》1997,12(4):682-686
Prenatal cytogenetic analysis of 71 fetuses conceived by intracytoplasmic
sperm injection (ICSI) resulted in the detection of nine (12.7%) chromosome
aberrations including two cases of 47,XXY, four cases involving a 45,X cell
line and three autosomal trisomies. Molecular analysis of the parental
origin of the deleted or supernumerary chromosome was performed by using
polymorphic microsatellite markers. Six cases involving a sex chromosome
abnormality were found to be of paternal origin while the two trisomic
cases that could be analysed were of maternal origin. Two cases involved
the same infertile couple who had two consecutive ICSI pregnancies
terminated because of a chromosome abnormality. The replaced embryos in
both cases originated from a single batch of ICSI fertilized oocytes of
which part was used to initiate the first pregnancy and part was
cryopreserved and used to initiate the second pregnancy.
相似文献
26.
A longitudinal study of maternal serum inhibin-A, inhibin-B, activin-A, activin-AB, pro-alphaC and follistatin during pregnancy 总被引:6,自引:1,他引:6
Fowler PA; Evans LW; Groome NP; Templeton A; Knight PG 《Human reproduction (Oxford, England)》1998,13(12):3530-3536
Maternal serum concentrations of inhibin-A, inhibin-B, activin-A,
activin-AB, pro-alphaC-related inhibin forms, total follistatin, steroids
and gonadotrophins were measured longitudinally in six normal singleton
pregnancies. Maternal venous blood was collected randomly during a
spontaneous follicular phase prior to donor insemination, at 5, 7, 9, 11,
16, 20, 24, 28, 32 and 36 weeks after the first missed menses and in the
early puerperium. Steroid and gonadotrophin profiles conformed to previous
reports. While at week 5 of gestation inhibin-A, activin-A and follistatin
concentrations were similar to those at the follicular phase, all three
increased progressively (P < 0.001) to maximal concentrations in week
36: approximately 48-fold (3740 +/- 1349 ng inhibin-A/ml), approximately
22-fold (6109 +/- 1443 ng activin-A/ml) and approximately 10-fold (3563 +/-
418 ng follistatin/ml) higher. Pro- alphaC concentrations reached a maximum
in weeks 5 (approximately 5- fold, P < 0.001) and 36 (1027 +/- 174
pg/ml, P < 0.01). Inhibin-B (71 +/- 23 pg/ml prior to pregnancy) was
undetectable (<12 pg/ml) between week 5-16 of gestation but increased
slightly in the third trimester (26 +/- 7 pg/ml in week 36). Activin-AB was
undetectable throughout pregnancy. Post-partum concentrations of inhibin-A
(41 +/- 12 ng/ml), inhibin-B (<12 pg/ml), activin-A (950 +/- 149 pg/ml),
pro-alphaC (128 +/- 22 pg/ml) and follistatin (990 +/- 79 ng/ml) were
substantially lower than at week 36 of gestation. The activin-A:follistatin
ratio increased from 0.5 in week 5 to 1.8 in week 36, suggesting that more
free activin-A is available in the maternal circulation during late
pregnancy.
相似文献
27.
KM Kanal NJ Hangiandreou AM Sykes HE Eklund PA Araoz JA Leon BJ Erickson 《Journal of digital imaging》2002,14(1):30-37
The aims of this work were to measure the accuracy of one continuous speech recognition product and dependence on the speaker's
gender and status as a native or nonnative English speaker, and evaluate the product's potential for routine use in transcribing
radiology reports. IBM MedSpeak/Radiology software, version 1.1 was evaluated by 6 speakers. Two were nonnative English speakers,
and 3 were men. Each speaker dictated a set of 12 reports. The reports included neurologic and body imaging examinations performed
with 6 different modalities. The dictated and original report texts were compared, and error rates for overall, significant,
and subtle significant errors were computed. Error rate dependence on modality, native English speaker status, and gender
were evaluated by performing ttests. The overall error rate was 10.3 +/- 3.3%. No difference in accuracy between men and women
was found; however, significant differences were seen for overall and significant errors when comparing native and nonnative
English speakers (P = .009 and P = .008, respectively). The speech recognition software is approximately 90% accurate, and
while practical implementation issues (rather than accuracy) currently limit routine use of this product throughout a radiology
practice, application in niche areas such as the emergency room currently is being pursued. This methodology provides a convenient
way to compare the initial accuracy of different speech recognition products, and changes in accuracy over time, in a detailed
and sensitive manner. 相似文献
28.
Morphological studies have shown that macrophages and microglia undergo
apoptosis in the central nervous system (CNS) in acute experimental
autoimmune encephalomyelitis (EAE) in the Lewis rat. To assess the relative
levels of macrophage and microglial apoptosis, and the molecular mechanisms
involved in this process, we used three-colour flow cytometry to identify
CD45lowCD11b/c+ microglial cells and CD45highCD11b/c+ macrophages in the
inflammatory cells isolated from the spinal cords of Lewis rats 13 days
after immunization with myelin basic protein (MBP) and complete Freund's
adjuvant. Simultaneously, we analyzed the DNA content of these cell
populations to assess the proportions of cells undergoing apoptosis and in
different stages of the cell cycle or examined their expression of three
apoptosis- regulating proteins, i.e. Fas (CD95), Fas ligand (FasL) and
Bcl-2. Microglia were highly vulnerable to apoptosis and were
over-represented in the apoptotic population. Macrophages were less
susceptible to apoptosis than microglia and underwent mitosis more
frequently than microglia. The different susceptibilities of microglia and
macrophages to apoptosis did not appear to be due to variations in Fas,
FasL or Bcl- 2 expression, as the proportions of microglia and macrophages
expressing these proteins were similar, and were relatively high.
Furthermore, in contrast to T cell apoptosis, apoptosis of
microglia/macrophages did not occur more frequently in cells expressing Fas
or FasL, or less frequently in cells expressing Bcl-2. These results
indicate that the apoptosis of microglia and CNS macrophages in EAE is not
mediated through the Fas pathway, and that Bcl-2 expression does not
protect them from apoptosis. Expression of FasL by macrophages and
microglia may contribute to the pathogenesis and immunoregulation of EAE
through interactions with Fas+ oligodendrocytes and Fas+ T cells. The high
level of microglial apoptosis in EAE indicates that microglial apoptosis
may be an important homeostatic mechanism for controlling the number of
microglia in the CNS following microglial activation and proliferation.
相似文献
29.
The role of size, sequence and haplotype in the stability of FRAXA and FRAXE alleles during transmission 总被引:2,自引:5,他引:2
Murray A; Macpherson JN; Pound MC; Sharrock A; Youings SA; Dennis NR; McKechnie N; Linehan P; Morton NE; Jacobs PA 《Human molecular genetics》1997,6(2):173-184
Factors involved in the stability of trinucleotide repeats during
transmission were studied in 139 families in which a full mutation,
premutation or intermediate allele at either FRAXA or FRAXE was
segregating. The transmission of alleles at FRAXA, FRAXE and four
microsatellite loci were recorded for all individuals. Instability within
the minimal and common ranges (0-40 repeats for FRAXA, 0-30 repeats for
FRAXE) was extremely rare; only one example was observed, an increased in
size at FRAXA from 29 to 39 repeats. Four FRAXA and three FRAXE alleles in
the intermediate range (41-60) repeats for FRAXA, 31-60 for FRAXE) were
unstably transmitted. Instability was more frequent for FRAXA intermediate
alleles that had a tract of pure CGG greater than 37 although instability
only occurred in two of 13 such transmissions: the changes observed were
limited to only one or two repeats. Premutation FRAXA alleles over 100
repeats expanded to a full mutation during female transmission in 100% of
cases, in agreement with other published series. There was no clear
correlation between haplotype and probability of expansion of FRAXA
premutations. Instability at FRAXA or FRAXE was more often observed in
conjunction with a second instability at an independent locus suggesting
genomic instability as a possible mechanism by which at least some FRAXA
and FRAXE mutations arise.
相似文献
30.
J Davies B Srinivasan PA Brennan 《Annals of the Royal College of Surgeons of England》2021,103(1):e42
Lipomas are common benign tumours that can occur in most parts of the body. Lipomas arising from the deep temporal fat pad, found between the two layers of the deep temporal fascia, are rare, however; there has been only one documented case report to our knowledge. We describe a second case arising from the temporal fat pad in a patient treated at our unit, having previously reported the first one, and discuss the relevant anatomy and management. 相似文献