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61.
Seven eyes of seven patients with visually disabling postkeratoplasty astigmatism underwent arcuate keratotomy to reduce astigmatism. Keratotomy length was prospectively determined by comparing the corneal shape change needed by each patient with shape changes in cadaver eyes induced by arcuate keratotomy. Keratograph ring ovality quantified corneal shape change. Keratotomies were placed in the wound interface using a diamond knife with blade length set to 100% of corneal thickness. Prekeratotomy keratometric astigmatism was 9.27 +/- 2.14 D (mean +/- SD), and at 2.0 to 18.4 months after keratotomy, astigmatism was 2.75 +/- 2.25 D (mean +/- SD). All corneas had decreased keratometric astigmatism and less oval keratoscope rings. Five corneas had 3.00 D or less residual keratometric astigmatism. Change in ring ovality was significantly correlated with keratotomy length and keratometric astigmatism change. The utility of keratoscope ring ovality as a corneal topography metric was demonstrated by systematically investigating the response to arcuate keratotomy. 相似文献
62.
The use of 19F spectroscopy and diffusion-weighted MRI to evaluate differences in gene-dependent enzyme prodrug therapies. 总被引:4,自引:0,他引:4
Daniel A Hamstra Kuei C Lee Joseph M Tychewicz Victor D Schepkin Bradford A Moffat Mark Chen Kenneth J Dornfeld Theodore S Lawrence Thomas L Chenevert Brian D Ross Juri T Gelovani Alnawaz Rehemtulla 《Molecular therapy》2004,10(5):916-928
To evaluate noninvasive measures of gene expression and tumor response in a gene-dependent enzyme prodrug therapy (GDEPT), a bifunctional fusion gene between Saccharomyces cerevisiae cytosine deaminase (CD) and Haemophilus influenzae uracil phosphoribosyltransferase (UPRT) was constructed. CD deaminates 5-fluorocytosine (5FC) to 5-fluorouracil (5FU), and UPRT subsequently converts 5FU to fluorouridine monophosphate, and both of these reactions can be monitored noninvasively in vitro and in vivo using 19F magnetic resonance spectroscopy (MRS). Following transient transfection the CD-UPRT fusion protein exhibited both UPRT and CD enzymatic activities as documented by 19F MRS. In addition, an increase in CD activity and thermal stability was witnessed for the fusion protein compared to native CD. Stable expression of CD-UPRT in 9L glioma cells increased both 5FC and 5FU sensitivity in vitro compared to CD-expressing and wild-type 9L cells. Noninvasive 19F MRS of both CD and UPRT gene function in vivo demonstrated that in animals bearing CD-expressing tumors there was limited conversion of 5FC to 5FU with no measurable accumulation of cytotoxic fluorinated nucleotides (F-nucs). In contrast, CD-UPRT-expressing tumors had increased CD gene activity with a threefold higher intratumoral accumulation of 5FU and significant generation of F-nucs. Finally, CD-UPRT yielded increased efficacy in an orthotopic animal model of high-grade glioma. More importantly, early changes in cellular water mobility, which are felt to reflect cellular death, as measured by diffusion-weighted MRI, were predictive of both durable response and increased animal survival. These results demonstrate the increased efficacy of the CD-UPRT GDEPT compared to CD alone both biochemically and in a preclinical model and validate both 19F MRS and diffusion-weighted MRI as tools to assess gene function and therapeutic efficacy. 相似文献
63.
Victor M. Neira Corey Sawchuk Kenneth S. Bonneville Victor Chu Theodore E. Warkentin 《Journal canadien d'anesthésie》2007,54(6):461-466
PURPOSE: To describe the management of severe acute intracardiac thrombosis in a patient who underwent redo multiple valve replacement and valvular repair. The diagnostic features, associated risk factors, and anesthetic management are reviewed. CLINICAL FEATURES: A 67-yr-old woman undergoing redo mitral and aortic mechanical valve replacement and tricuspid annuloplasty under aprotinin prophylaxis exhibited severe refractory hypotension that began immediately after protamine reversal of intraoperative heparin anticoagulation following separation from cardiopulmonary bypass. Intraoperative transesophageal echocardiography revealed severe thrombosis in the right atrium, right ventricle and pulmonary artery. The patient was managed by immediate reheparinization and return to cardiopulmonary bypass (CPB), surgical thrombectomy, and intraoperative administration of recombinant tissue-plasminogen activator. After removal of the thrombi, and separation from CPB, no further protamine was given. One hundred units of blood products and two surgical re-explorations were required to manage subsequent massive postoperative bleeding. Acute heparin-induced thrombocytopenia (HIT) was ruled out using sensitive assays for HIT antibodies. After 16 days in the intensive care unit and 30 more days in hospital, the patient was subsequently transferred to a chronic care facility and succumbed several weeks later. CONCLUSION: Acute intraoperative thrombosis is a rare and potentially fatal complication of cardiac surgery. Intraoperative transesophageal echocardiography was essential for rapid diagnosis in this case. Multiple interacting prothrombotic factors (e.g., aprotinin use, acquired antithrombin deficiency, long pump time, post-protamine status, transfusion of blood components) were likely contributing factors related to this rare complication. 相似文献
64.
Perry D. Cohen Linda Herman Sheryl Jedlinski Peggy Willocks Paula Wittekind 《Neurotherapeutics》2007,4(3):537-544
A patient-centered paradigm for clinical research and medical care is presented as a solution to the problem of declining
innovation and increasing costs and development time in the pipeline for new therapies. Fundamental differences in values
and motivations among scientists, clinicians, industry sponsor, and patients in neurotherapeutics provide a framework for
analysis of ethical conflicts and the loss of public confidence in medical research. Parkinson advocates’ views on clinical
trial participation, perceived risks and benefits, placebo controls, and sham surgery are presented. These views reflect the
sense of urgency and the unique perspective that comes from living with this progressive, debilitating condition full time.
A patient-centered paradigm that includes authentic voices of patients as collaborators at every stage of development will
help to resolve conflicts, build trust, recruit trial participants, and accelerate new therapies. Key elements are adaptive
clinical trial methods and the development of information technology for the assessment of outcomes and surveillance of safety
over the life cycle of a medical product. Supported by the Parkinson’s Disease Foundation, the Parkinson Pipeline Project
is a grassroots group of Parkinson’s patients whose goal is to represent an authentic voice for patients in the treatment
development process. This group promotes education and communication between members of the Parkinson’s community and active
stakeholders in medical research, industry, and regulatory agencies. Its members are an example of a new breed of knowledgeable
consumers, armed with first-hand access to research findings and reinforced by on-line connections to like-minded peers throughout
the world. 相似文献
65.
Successful immune reconstitution decreases leukemic relapse and improves survival in recipients of unrelated cord blood transplantation. 总被引:3,自引:0,他引:3
Robertson Parkman Geoff Cohen Shelly L Carter Kenneth I Weinberg Bernadette Masinsin Eva Guinan Joanne Kurtzberg John E Wagner Nancy A Kernan 《Biology of blood and marrow transplantation》2006,12(9):919-927
Allogeneic hematopoietic stem cell transplantation (HSCT) is established therapy for selected patients with acute leukemia. After transplantation, antileukemic immune responses are believed to eliminate residual leukemia cells and decrease the likelihood of relapse. However, the clinical effect of successful antigen-specific immune reconstitution after HSCT on the likelihood of leukemic relapse and overall survival is not known. Pediatric recipients of unrelated cord blood transplants who underwent transplantation for acute leukemia were sequentially evaluated for their development of antigen-specific T-lymphocyte immunity to herpes viruses. The clinical effect of a positive antigen-specific response on relapse-free survival was determined. The presence of an antigen-specific response resulted in a relapse-free survival advantage (P = .0001), which was primarily due to a decrease in leukemic relapse (P = .003). Proportional hazards modeling for time to relapse and time to relapse or death defined 3 variables that were strongly associated with a poor outcome: female gender, poor remission status before transplantation, and negative antigen-specific T-lymphocyte proliferation. Notably neither acute nor chronic graft-versus-host disease had any effect on the incidence of leukemic relapse. Successful antigen-specific immune reconstitution after unrelated cord blood transplantation results in decreased leukemic relapse and improved overall survival. 相似文献
66.
Sclerosing stromal cell tumors of the ovary are an uncommon neoplasm that usually does not produce hormonal imbalances. Most patients showing a hormonal effect from this lesion have had menstrual cycle disturbances. Infertility and endometrial hyperplasia have also been described. One other reported case had masculinizing effects. Other authors have documented elevated levels of both estrogenic and androgenic hormones that corrected after surgery. A case of a pregnant 27-year-old Caucasian with hirsutism on her chin and neck and a male suprapubic hair pattern is presented. Elevated androstenedione, dehydroepiandrosterone, and free testosterone levels were present. A 3-cm left ovarian mass was excised and identified as a sclerosing stromal tumor. The histologic features included a pseudolobular pattern with focal areas of sclerosis and a two-cell population of spindled and polygonal cells. Immunohistochemical studies showed a positive vimentin reaction, weakly positive desmin and muscle-specific actin stains, and a negative cytokeratin stain. Following surgery the hormone levels returned to normal and the hirsutism resolved. A normal female infant without evidence of masculinization was delivered from the patient at term. 相似文献
67.
Evaluation of renal transplant dysfunction by duplex Doppler sonography: a prospective study and review of the literature 总被引:5,自引:0,他引:5
R R Perrella A J Duerinckx F N Tessler G M Danovitch A Wilkinson S Gonzalez A H Cohen E G Grant 《American journal of kidney diseases》1990,15(6):544-550
A disconcertingly wide variation exists in the literature as to the accuracy of duplex Doppler sonography in the detection of acute renal transplant rejection. Sensitivities range from 9% to 76%. In an attempt to explain the disparity of results, we undertook a double-blind prospective study of the accuracy of duplex Doppler ultrasound in the detection of acute rejection in renal transplants. We scanned 49 consecutive patients with a total of 65 biopsies; 46 biopsies in 33 consecutive patients were included in our study. In our population, the prevalence of acute rejection was 61% (28/46). Using a resistive index (RI) cutoff of greater than 0.90 based on the main renal artery flow pattern, the sensitivity of our test was 43%, with a 67% specificity. The positive predictive value was 67%. Our results are contrasted and compared with the published data from other groups in a critical survey of the literature. We conclude that duplex Doppler sonography alone is inadequate to evaluate acute rejection in renal transplants. 相似文献
68.
69.
Moshe Stein N. Haim Abraham Kuten Yafa Doron Yehudi T. Ben Arieh Yoram Cohen 《Journal of surgical oncology》1992,51(4):270-273
Thirty-three patients with primary gastrointestinal lymphoma (GIL) followed at Ankara University Medical School have been evaluated. The most frequent locations of the disease are the small intestine (48.4%) and the stomach (39.3%). The intermediate and high grade lymphomas constitute 84.8% of the cases. The mean age of the patients with small intestinal lymphoma is 28.7 years and 47.1 years for those with gastric lymphoma. The patients treated with surgery and chemotherapy (S+CT) have a longer survival than those treated with chemotherapy (CT) alone. In conclusion: 1) Small intestinal lymphoma occurs more frequently than gastric lymphoma in our study. 2) The median age of the Turkish patients with primary GIL is approximately 10 years less than those in the Western countries. 3) The therapeutic results of S+CT are superior to those of CT in the early stages of the disease. 相似文献
70.
Retention properties of a split-shaft threaded post: cut at different apical lengths. 总被引:1,自引:0,他引:1
The retention of the post to the root of an endodontically treated tooth is critical for a successful restoration. Modification of the post length to accommodate a specific clinical situation is common. This study compared the retention of No. 1 and No. 2 Flexi-Post restorations shortened apically from 1 to 5 mm with that reported for full-length control No. 1 and No. 2 Flexi-Post dowels. The experimental material was divided into 10 groups with 10 samples in each group. Retentive values were recorded in pounds with a universal testing machine. Analysis of variance with a Tukey-Student range, multiple-comparison test showed no statistical differences from apical reductions of 1, 2, 3, and 5 mm including the full-length control Flexi-Post No. 1 system. With 4 mm of apical shortening statistically greater retention was recorded. No statistical differences resulted with apical reductions of 1 to 4 mm or with the full-length control Flexi-Post No. 2 system, but 5 mm of apical shortening caused significantly less retention. 相似文献