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91.
Histopathological characterisation of effects of the mouse Pax6 missense mutation on eye development
Thaya Ramaesh Steven E. Williams Catriona Paul Kanna Ramaesh John D. West 《Experimental eye research》2009,89(2):263-273
Mutations in PAX6/Pax6 lead to a variety of ocular anomalies in humans and mice. The aim of the study was to characterise the ocular abnormalities caused by the missense Pax6Leca4 mutation and compare them to published observations on Pax6 alleles that are functionally equivalent to Pax6− null alleles (such as Pax6Sey and Pax6Sey-Neu) and human inherited eye diseases. Ocular features of homozygous Pax6Leca4/Leca4 and heterozygous Pax6Leca4/+ embryos at E12.5-E18.5, heterozygous Pax6Leca4/+ young mice at P18 and heterozygous Pax6Leca4/+ adults at 12 weeks were analysed histologically with their wild-type Pax6+/+ littermates. Homozygous Pax6Leca4/Leca4 fetuses died perinatally with no eyes although an optic cup rudiment with pigmented cells developed. Pax6Leca4/+ mice were microphthalmic and a range of other severe ocular phenotypes affected both the anterior and the posterior segments. In contrast to Pax6+/−, the Pax6Leca4/+ eyes had no goblet cells in the corneal epithelium, the iris was not hypoplastic and there was no lens-corneal epithelial plug. However, microphthalmia was more severe, corneal vascularisation occurred earlier (during fetal stages), pigmented cells were present in the vitreous and corneal stroma and the ciliary body was malformed or abnormal. These results show that, although Pax6Leca4/+ lacked some eye abnormalities commonly seen in Pax6Sey/+ and Pax6Sey-Neu/+ eyes, in most respects their eyes were more severely affected. These differences probably reflect both differences between the Pax6Leca4 and the Pax6Sey-Neu mutations and differences in modifier gene expression in different genetic backgrounds. The presence of pigmented cells in the cornea is a novel observation. Some Pax6Leca4/+ ocular abnormalities were similar to those present in human Peters' anomaly and persistent hyperplastic primary vitreous (PHPV) so Pax6Leca4/+ mice provide a useful model for some inherited eye diseases. 相似文献
92.
Steven D. Wexner MD FACS FRCS FRCS Lester Rosen MD Todd H. Baron MD FASGE 《Gastrointestinal endoscopy》2007,65(7):1104-1105
93.
Sumon Nandi Steven Maschke Peter J. Evans Jeffrey N. Lawton 《Hand (New York, N.Y.)》2009,4(4):368-379
Elbow motion is essential for upper extremity function to position the hand in space. Unfortunately, the elbow joint is prone
to stiffness following a multitude of traumatic and atraumatic etiologies. Elbow stiffness can be diagnosed with a complete
history and physical exam, supplemented with appropriate imaging studies. The stiff elbow is challenging to treat, and thus,
its prevention is of paramount importance. When this approach fails, non-operative followed by operative treatment modalities
should be pursued. Upon initial presentation in those who have minimal contractures of 6-month duration or less, static and
dynamic splinting, serial casting, continuous passive motion, occupational/physical therapy, and manipulation are non-operative
treatment modalities that may be attempted. A stiff elbow that is refractory to non-operative management can be treated surgically,
either arthroscopically or open, to eliminate soft tissue or bony blocks to motion. In the future, efforts to prevent and
treat elbow stiffness may target the basic science mechanisms involved. Our purpose was to review the etiologies, classification,
evaluation, prevention, operative, and non-operative treatment of the stiff elbow. 相似文献
94.
Biostatisticians have frequently uncritically accepted the measurements provided by their medical colleagues engaged in clinical research. Such measures often involve considerable loss of information. Particularly, unfortunate is the widespread use of the so‐called ‘responder analysis’, which may involve not only a loss of information through dichotomization, but also extravagant and unjustified causal inference regarding individual treatment effects at the patient level, and, increasingly, the use of the so‐called number needed to treat scale of measurement. Other problems involve inefficient use of baseline measurements, the use of covariates measured after the start of treatment, the interpretation of titrations and composite response measures. Many of these bad practices are becoming enshrined in the regulatory guidance to the pharmaceutical industry. We consider the losses involved in inappropriate measures and suggest that statisticians should pay more attention to this aspect of their work. Copyright © 2009 John Wiley & Sons, Ltd. 相似文献
95.
Steven Z George John D Childs Deydre S Teyhen Samuel S Wu Alison C Wright Jessica L Dugan Michael E Robinson 《BMC musculoskeletal disorders》2007,8(1):92
Background
There are few effective strategies reported for the primary prevention of low back pain (LBP). Core stabilization exercises targeting the deep abdominal and trunk musculature and psychosocial education programs addressing patient beliefs and coping styles represent the current best evidence for secondary prevention of low back pain. However, these programs have not been widely tested to determine if they are effective at preventing the primary onset and/or severity of LBP. The purpose of this cluster randomized clinical trial is to determine if a combined core stabilization exercise and education program is effective in preventing the onset and/or severity of LBP. The effect of the combined program will be compared to three other standard programs. 相似文献96.
回盲部恶性肿瘤的诊治 总被引:1,自引:0,他引:1
目的:分析回盲部恶性肿瘤的诊断和治疗过程,总结经验.以期提高早期确诊率和患者生存率。方法:回顾性分析近5年53例住院治疗的回盲部恶性肿瘤患者的临床资料。结果:53例患者中腺癌、黏液腺癌50例,恶性淋巴瘤3例。首次确诊率为75.5%。误诊或延迟诊断的疾病主要为阑尾炎、阑尾脓肿,胆囊炎、胆石症、下消化道出血、贫血待查等。结论:60岁以上的老年患者为回盲部恶性肿瘤的主要人群,肿瘤类型主要为腺癌。尽管首发症状缺乏特异性,但提高警觉性,详细询问病史,通过大便隐血试验、钡灌肠或气钡双重造影、纤维结肠镜检查仍能有效的提高首次确诊率,积极手术冶疗,可显著改善患者的预后。 相似文献
97.
Gu Su-juan顾素娟Beijing Chaoyang Hospital BeijingWeng Li-ju翁梨驹Be''ijing Municipal Research Department of Family Planning Beijing 《中华医学杂志(英文版)》1987,100(3):219-223
A combination of levonorgestrel 0.15mg and
ethinyl estradiol 0.03mg, an ultra-low dose oral con
traceptive in pellet form, was tried out in 9 Beijing
clinics. A total of l,035 healthy women of reproduc
tive age participated in 9,413 cycles of treatment.
Only one pregnancy was attributed to medication
failure which resulted in a corrected Pearl index of
0.13/100 women-year. The incidence of breakthrough
bleeding and amenorrhea was 0.12% and 0.05% res
pectively. Using the life-table method, the net
cumulative rate of termination due to medical-related
reasons at one year was only 5.93/100 women. The
incidence of side effects was low. The most frequent
complaints were nausea and drowsiness, which re
duced with the increase of treatment cycles. Some
metabolic changes were studied. In comparison
with other OCs used in China, this formula has the
advantages of ultra-low-dose steroids with higher
contraceptive efficacy, better cycle control and
fewer side effects. 相似文献
98.
Synergistic effect of low dose Cyclosporine A and human interleukin 10 overexpression on acute rejection in rat lung allotransplantation 总被引:3,自引:0,他引:3
Jaroslaw Pierog Amiq Gazdhar Uz Stammberger Matthias Gugger Steven Hyde Iacob Mathiesen Tomasz Grodzki Ralph A. Schmid 《European journal of cardio-thoracic surgery》2005,27(6):1030-1035
Objective: Electroporation mediated transfer of plasmid DNA into peripheral muscle results in high transfection efficiency. The aim of this study was to investigate the effect of gene transfer of human IL-10 (hIL-10) into the tibialis anterior muscle (MTA) in combination with low dose Cyclosporine A (CsA) on acute rejection of lung allografts in the rat. Methods: Lung allotransplantation was performed from male BN donor to male Fisher F344 rats. Gene transfer was achieved by intramuscular injection into the MTA of the recipient followed by electroporation (4×20 ms impulses at 200 V/cm) 24 h prior to the transplantation. Group A (n=5) received CsA (2.5 mg/kg bw ip) for 5 days post-transplant and group B (n=5) 2.5 μg of PCIK hIL-10 (plasmid expression vector containing human CMV immediate early gene promoter and enhancer) and a low dose CsA (2.5 mg/kg bw i.p.). Graft function was assessed by blood gas at day 5 after exclusion of the native lung. Animals were sacrificed and blood was drawn to measure serum hIL-10 levels (ELISA) and tissue was sampled for histological grading of rejection. Results: Local expression of hIL-10 was confirmed at the mRNA level by in situ hybridization. All group A control animals showed severe signs of rejection. At day 5 all grafts in group B showed good gas exchange mean PaO2 233±123 mmHg, vs 44±8 mmHg in group A. Histological examination revealed moderate to severe rejection in all animals in group A (IIIB, ISHLT) in contrast to low moderate rejection in group B (II–IIIA). hIL-10 serum levels on day 5 were 14±7 pg/ml in group B vs. 0 in group A. Conclusions: Electroporation mediated hIL-10 overexpression in a peripheral muscle of the recipient in combination with low dose CsA reduces acute rejection in this model of rat lung allotransplantation. 相似文献
99.
Steven Elia Peter Liu Carol Chrusciel Alan Hilgenberg Charrisios Skourtis Demetrios Lappas 《Journal canadien d'anesthésie》1989,36(1):2-8
Global coronary blood flow and metabolism were measured in seven patients on the first postoperative day following coronary
revascularization to test the hypothesis that tracheal extubation produces adverse haemodynamic responses akin to those observed
during tracheal intubation. Regional coronary flow and metabolic measurements were made in five of the seven patients. Extubation
from a continuous positive airway pressure (CPAP) of 5 cm H2O was associated with a statistically significant rise in cardiac index from 3.44 ± 0.23 L · min-1 · m-2 to 3.73 ± 0.15L·min-1 ·m-2 related to an increase in stroke index, without significant changes in heart rate, mean arterial and pulmonary capillary
wedge pressure. Consequently the changes in myocardial oxygen consumption (8.52 ± 0.55 to 8.85 ± 0.93 ml · min-1) and coronary blood flow (172 ± 18 to 179 ± 17 ml·min-1) were less prominent than those reported during intubation, where substantial rises in myocardial oxygen consumption and
coronary flow occurred. Two patients experienced cardiac lactate production but there were no changes in systemic or coronary
haemodynamics, nor were there clinical or electrocardiographic signs of ischaemia. We conclude that extubation does not appear
to be associated with adverse systemic or coronary haemodynamic responses in patients following coronary bypass grafting.
However, the revascularized myocardium may remain vulnerable to anaerobic metabolism in the immediate postoperative period.
Pour savoir si comme ľintubation, ľextubation de la trachée provoque des perturbations hémodynamiques, on a mesuré le métabolisme
et la circulation coronarienne globale chez sept patients, au lendemain ďun pontage aorto-coronarien. On a aussi calculé les
valeurs régionales de ces mêmes variables pour cinq ďentre eux. Ľindex cardiaque de 3.44 ± 0.23 L · min-1 · m-2 sous pression positive en respiration spontanée (CPAP) de 5 cm. H2O s’est élevé à 3.73 ± 0.15 L · min-1 · m-2 post-extubation avec une augmentation significative du volume ďéjection. La fréquence cardiaque et les pressions artérielles
moyennes et capillaires pulmonaires n’ont pas changé. Ainsi ľaugmentation de la consommation ďoxygène du myocarde de 8.52
± 0.55 à 8.85 ± 0.93 ml · min-1 et celle du flot coronarien de 172 ± 18 à 179 ± 17 ml · min-1 ont été moindres que celles, importantes, déjà observées lors de ľintubation. On a noté chez deux patients une production
de lactate par le myocarde, sans changement de ľhémodynamic systémique et coronarienne non plus que de signe clinique ou électrocardiographique
ďischémie. Donc, après un pontage coronarien, ľextubation ne semble pas causer ďeffet néfaste sur les circulations systémique
et coronarienne, toutefois, le myocarde revascularisé peut demeurer sensible au métabolisme anaérobique. 相似文献
100.
David G Hicks Brian J Yoder Sarah Short Shannon Tarr Nichole Prescott Joseph P Crowe Andrea E Dawson G Thomas Budd Steven Sizemore Muzaffer Cicek Toni K Choueiri Raymond R Tubbs Daniel Gaile Norma Nowak Mary Ann Accavitti-Loper Andra R Frost Danny R Welch Graham Casey 《Clinical cancer research》2006,12(22):6702-6708
PURPOSE: This study aims to determine the effect of loss of breast cancer metastasis suppressor 1 (BRMS1) protein expression on disease-free survival in breast cancer patients stratified by estrogen receptor (ER), progesterone receptor (PR), or HER2 status, and to determine whether loss of BRMS1 protein expression correlated with genomic copy number changes. EXPERIMENTAL DESIGN: A tissue microarray immunohistochemical analysis was done on tumors of 238 newly diagnosed breast cancer patients who underwent surgery at the Cleveland Clinic between January 1, 1995 and December 31, 1996, and a comparison was made with 5-year clinical follow-up data. Genomic copy number changes were determined by array-based comparative genomic hybridization in 47 breast cancer cases from this population and compared with BRMS1 staining. RESULTS: BRMS1 protein expression was lost in nearly 25% of cases. Patients with tumors that were PR negative (P=0.006) or HER2 positive (P=0.039) and <50 years old at diagnosis (P=0.02) were more likely to be BRMS1 negative. No overall correlation between BRMS1 staining and disease-free survival was observed. A significant correlation, however, was seen between loss of BRMS1 protein expression and reduced disease-free survival when stratified by either loss of ER (P=0.008) or PR (P=0.029) or HER2 overexpression (P=0.026). Overall, there was poor correlation between BRMS1 protein staining and copy number status. CONCLUSIONS: These data suggest a mechanistic relationship between BRMS1 expression, hormone receptor status, and HER2 growth factor. BRMS1 staining could potentially be used in patient stratification in conjunction with other prognostic markers. Further, mechanisms other than genomic deletion account for loss of BRMS1 gene expression in breast tumors. 相似文献