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31.
32.
Mark C Gillies Anne Mv Brooks Stephanie Young Bill Gillies Judy M Simpson Ivan Goldberg 《Clinical & experimental ophthalmology》1999,27(1):37-44
Purpose: The aim of the present study was to investigate the safety and potential efficacy of subconjunctival interferon-α2b (IFN-α), either alone or in combination with 5-fluorouracil (5-FU), in reducing the risk of failure of glaucoma surgery. Methods: A prospective, masked randomized phase II study was undertaken in which patients received three subconjunctival injections per week for 3–4 weeks postoperatively. Three treatments were compared: (i) IFN-α (1 × 10 6 IU per dose); (ii) 5-FU (5 mg per dose); and (iii) alternating IFN-α and 5-FU (BOTH). The primary outcome measures were: (i) rate of successful control of intra-ocular pressure without further surgery; and (ii) the incidence of side effects. Results: Fifty-seven patients undergoing glaucoma surgery with an increased risk of failure were evaluated, including 23 patients (40%) undergoing trabeculectomy combined with extracapsular cataract extraction as well as other conventional high-risk groups. With 53 patients (93%) completing 2 years follow up, there was no significant difference in success rates among the three groups. Intra-ocular pressure was controlled without further surgery in 79% of patients (95% confidence interval (CI): 61, 97%) receiving IFN-α, in 89% of patients (76, 100%) receiving 5-FU and in 89% of patients (76, 100%) receiving BOTH. Side effects were similar among the three groups. Conclusions: These results are consistent with a beneficial effect of IFN-α2b given either alone or in combination with 5-FU after glaucoma filtering surgery. However, the lack of a clear and substantial benefit over conventional anti-fibrotic therapy does not support the further clinical evaluation of these treatments. 相似文献
33.
Simultaneous in situ hybridisation of native mRNA and immunoglobulin detection by conventional immunofluorescence in paraffin wax embedded sections. 下载免费PDF全文
S. J. Harper J. H. Pringle A. Gillies A. C. Allen L. Layward J. Feehally I. Lauder 《Journal of clinical pathology》1992,45(2):114-119
AIMS: The development of a technique for simultaneous in situ hybridisation for native mRNA and conventional immunofluorescence for cytoplasmic antigens in routine pathology specimens. METHODS: Cocktails of synthetic deoxyoligonucleotides coding for immunoglobulin J chain and kappa light chain were 3' end labelled enzymatically with digoxigenin using terminal deoxynucleotidyl transferase. Native mRNA sequences were "unmasked" using proteolytic digestion with proteinase K and hybrid detection was achieved with an alkaline phosphatase labelled anti-digoxigenin antibody. Alkaline phosphatase was visualised with Fast red/naphthol AS-MX phosphate. Fluorescein isothiocyanate (FITC) conjugated anti-isotype antibodies were used simultaneously at the detection stage to identify the isotype production by individual plasma cells in endoscopic duodenal biopsy specimens. RESULTS: The IgA plasma cells of the lamina propria were identified by immunofluorescence and hybrids were detected in the anticipated plasma cell population by Fast red visualisation. The reaction product was visible in bright field or ultraviolet illumination which allowed FITC and Fast red labels to be visualised together under ultraviolet light at 490 nm. Dual labelled cells were clearly visible. Morphology was well preserved throughout. CONCLUSIONS: This technique permits the demonstration of specific mRNA species in cells expressing immunoglobulin. It combines all the advantages of non-radioactive synthetic oligonucleotide probes and conventional immunofluorescence techniques in routine formol-saline fixed and paraffin wax embedded sections with good retention of morphology. 相似文献
34.
A L Gillies D S Arthur A L Forrest J I Lawson A H Masson A A Spence 《British medical journal》1979,1(6173):1246-1247
Review of 489 "anaesthetic deaths" reported to procurators-fiscal over 10 years disclosed only 30 that were thought to justify such reporting. Most of the remainder occurred in patients so desperately ill at the time of operation that death was expected. Postmortem examinations ordered by the Crown authorities in nearly all cases were probably largely unrewarding and mostly unnecessary. The results suggest that the present regulation on reporting should be revised to focus more attention on the few deaths that occur in patients who have no apparent contraindication to anaesthesia or operation. 相似文献
35.
Neil E Martin Thomas B Brunner Krystina D Kiel Thomas F DeLaney William F Regine Mohammed Mohiuddin Ernest F Rosato Daniel G Haller James P Stevenson Debbie Smith Barnali Pramanik Joel Tepper Wesley K Tanaka Briggs Morrison Paul Deutsch Anjali K Gupta Ruth J Muschel W Gillies McKenna Eric J Bernhard Stephen M Hahn 《Clinical cancer research》2004,10(16):5447-5454
PURPOSE: Preclinical and clinical studies have demonstrated that inhibition of prenylation can radiosensitize cell lines with activation of Ras and produce clinical response in patients with cancer. The aim of this study was to determine the maximally tolerated dose of the dual farnesyltransferase and geranylgeranyltransferase I inhibitor L-778,123 in combination with radiotherapy for patients with locally advanced pancreatic cancer. EXPERIMENTAL DESIGN: L-778,123 was given by continuous intravenous infusion with concomitant radiotherapy to 59.4 Gy in standard fractions. Two L-778,123 dose levels were tested: 280 mg/m2/day over weeks 1, 2, 4, and 5 for dose level 1; and 560 mg/m2/day over weeks 1, 2, 4, 5, and 7 for dose level 2. RESULTS: There were no dose-limiting toxicities observed in the eight patients treated on dose level 1. Two of the four patients on dose level 2 experienced dose-limiting toxicities consisting of grade 3 diarrhea in one case and grade 3 gastrointestinal hemorrhage associated with grade 3 thrombocytopenia and neutropenia in the other case. Other common toxicities were mild neutropenia, dehydration, hyperglycemia, and nausea/vomiting. One patient on dose level 1 showed a partial response of 6 months in duration. Both reversible inhibition of HDJ2 farnesylation and radiosensitization of a study patient-derived cell line were demonstrated in the presence of L-778,123. K-RAS mutations were found in three of the four patients evaluated. CONCLUSIONS: The combination of L-778,123 and radiotherapy at dose level 1 showed acceptable toxicity in patients with locally advanced pancreatic cancer. Radiosensitization of a patient-derived pancreatic cancer cell line was observed. 相似文献
36.
PC NG KW SO TF FOK MC YAM MY WONG W WONG 《Journal of paediatrics and child health》1997,33(4):324-328
Objectives: A prospective study comparing the efficiacy and side-effects of oral sulindac with intravenous indomethacin in clinically stable preterm infants (<1750 g) requiring non-invasive closure of haemodynamically significant patent ductus arteriosus.
Methodology: As maturity and birthweight are the two major determinants of ductal closure, infants were matched as closely as possible for these parameters. An eligible patient was first assigned to the sulindac group and a subsequent patient with similar gestational age (± 1 week) and birthweight (±100 g) to the previously recruited infant would automatically receive indomethacin. A total of eight infants were enrolled in each group.
Results: The ductus arteriosus was successfully closed in all eight infants receiving indomethacin, and in seven of eight infants receiving sulindac. No significant differences were found with regards to the ductal size between the two groups at diagnosis or on each of the consecutive days of treatment ( P >0.25). More renal adverse effects were encountered in the indomethacin group. Significant differences in changes from baseline value for urine output, plasma sodium, urea and creatinine concentrations were noted at 24, 48 and 72 h after commencement of treatment between the two groups ( P <0.05). All the parameters returned to normal or pre-treatment levels 48 h after stopping therapy. Unexpectedly, severe gastrointestinal complications were encountered in the sulindac group.
Conclusions: Sulindac is capable of promoting ductal constriction in clinically stable preterm infants without compromising the renal function. The spectrum of gastrointestinal complications observed in sulindac treated infants were similar to those described for indomethacin. The use of sulindac for ductal closure in the preterm infant should remain experimental. 相似文献
Methodology: As maturity and birthweight are the two major determinants of ductal closure, infants were matched as closely as possible for these parameters. An eligible patient was first assigned to the sulindac group and a subsequent patient with similar gestational age (± 1 week) and birthweight (±100 g) to the previously recruited infant would automatically receive indomethacin. A total of eight infants were enrolled in each group.
Results: The ductus arteriosus was successfully closed in all eight infants receiving indomethacin, and in seven of eight infants receiving sulindac. No significant differences were found with regards to the ductal size between the two groups at diagnosis or on each of the consecutive days of treatment ( P >0.25). More renal adverse effects were encountered in the indomethacin group. Significant differences in changes from baseline value for urine output, plasma sodium, urea and creatinine concentrations were noted at 24, 48 and 72 h after commencement of treatment between the two groups ( P <0.05). All the parameters returned to normal or pre-treatment levels 48 h after stopping therapy. Unexpectedly, severe gastrointestinal complications were encountered in the sulindac group.
Conclusions: Sulindac is capable of promoting ductal constriction in clinically stable preterm infants without compromising the renal function. The spectrum of gastrointestinal complications observed in sulindac treated infants were similar to those described for indomethacin. The use of sulindac for ductal closure in the preterm infant should remain experimental. 相似文献
37.
Aberrant crypt focus promotion and glucose intolerance: correlation in the rat across diets differing in fat, n-3 fatty acids and energy 总被引:1,自引:0,他引:1
Koohestani N; Chia MC; Pham NA; Tran TT; Minkin S; Wolever TM; Bruce WR 《Carcinogenesis》1998,19(9):1679-1684
McKeown-Eyssen (Cancer Epidemiol. Biomarkers Prevent., 3, 687-695, 1994)
and Giovannucci (Cancer Causes Control, 6, 164-179, 1995), noting the
striking similarity in lifestyle risk factors for colorectal cancer and
insulin resistance, proposed that the hyperinsulinemia, glycemia and
hypertriglyceridemia associated with insulin resistance promotes colon
cancer. To compare the effect of diet on colon cancer promotion and insulin
resistance in the F344 rat, we assessed the effect of fat, n-3 fatty acids
and energy in pairwise comparisons on average size of aberrant crypt foci
(ACF) and on glucose intolerance in the same animals in a single
experiment. Diets high in fat and energy increased and diets with increased
n-3 fatty acids and calorie restriction decreased both ACF growth and
glucose intolerance compared with control diets. The measures of promotion
of colon cancer and insulin resistance were strongly correlated (n = 98, r
= 0.67, P < 0.001). In addition, both were highly correlated with daily
energy intake (r = 0.62 and 0.66) and were also correlated with basal
(post-prandial) insulin, glucose and triglycerides (r = 0.31-0.53, P <
0.01). We concluded that ACF growth and glucose intolerance are correlated
for a wide range of diets and that increased circulating energy (glucose
and triglycerides) may lead to both colon cancer promotion and insulin
resistance.
相似文献
38.
Bolontrade MF; Stern MC; Binder RL; Zenklusen JC; Gimenez-Conti IB; Conti CJ 《Carcinogenesis》1998,19(12):2107-2113
In this study we have analyzed the vascular response induced in the two-
stage carcinogenesis model in SENCAR mice. The role of angiogenesis has not
been explored in this model, which is the paradigm of multistage
carcinogenesis and a model for neoplastic lesions derived from exophytic
premalignant lesions (e.g. colon carcinoma, bladder papilloma). We
investigated if angiogenesis is involved in the formation of papillomas and
in the progression from papilloma to carcinoma. To this end we analyzed the
vasculature of normal and hyperplastic skin, focal epidermal hyperplasias
that are precursors of papillomas, papillomas at different stages and
squamous cell carcinomas. We also analyzed the vascularization of
papillomas induced in two strains of mice that differ in their
susceptibility to malignant progression. We show here that angiogenesis is
turned on in the earliest stages of papilloma formation. In late stages,
regardless of state of progression, the predominant response is an increase
in the size of blood vessels. Thus, in the SENCAR mouse model,
representative of exophytic tumors, the angiogenesis switch is a very early
event, probably mechanistically related to the development of the primarily
exophytic lesions. Therefore, the density of blood vessels cannot be used
as a predictor of malignant progression in this model.
相似文献
39.
Christopher J. Twelves Nicola A. Dobbs Helen C. Gillies Christopher A. James Robert D. Rubens Peter G. Harper 《Cancer chemotherapy and pharmacology》1998,42(3):229-234
We studied variability in doxorubicin pharmacokinetics in 24 patients with abnormal liver biochemistry tests. Blood samples
were collected after the first cycle of single-agent doxorubicin given as an i.v. bolus and plasma levels were measured by
high-performance liquid chromatography. The relationship between doxorubicin clearance (dose/AUC) and liver biochemistry tests
(AST, bilirubin, albumin, alkaline phosphatase and indocyanine green clearance) was investigated. Patients with a raised bilirubin
level had reduced doxorubicin clearance, but there was no clear relationship between the extent of this elevation and the
reduction in doxorubicin clearance. Doxorubicin clearance was lower in patients with an isolated increase in AST than in those
with normal liver biochemistry, but this difference was not statistically significant. Nevertheless, there was a significant
correlation between reduced doxorubicin clearance and both raised serum AST levels and low indocyanine green clearance. These
pharmacokinetic data suggest that current dose reductions based solely on the extent to which bilirubin is elevated may not
be optimal.
Received: 20 October 1997 / Accepted: 20 January 1998 相似文献