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
Objectives. To examine relationships between body mass index (BMI) and cardiovascular risk factors in 279 Europeans and 231 Polynesian Pacific Islanders in New Zealand.
Methods. Participants were recruited from Seventh‐Day Adventist church meetings or camps, and were surveyed by self‐administered questionnaire. Blood pressure, weight and height were measured. Fasting blood samples were analysed for lipids, glucose and fructosamine.
Results. Age‐adjusted BMI was higher in Pacific Islanders than in Europeans: 32.8(0.3) versus 25.6(0.3); means(SE); p = 0.0001). In Europeans, BMI was positively associated with systolic and diastolic blood pressures, triglycerides, total cholesterol, LDL cholesterol and fasting blood glucose, and negatively associated with HDL cholesterol. In Pacific Islanders, BMI was associated only with systolic and diastolic blood pressures, and with HDL cholesterol. These associations were stronger in Europeans than in Pacific Islanders.
Conclusions. In this group of Pacific Islanders, the association between BMI and cardiovascular risk factors was weaker than in Europeans. This suggests that either BMI is a poor measure of adiposity in Pacific Islanders, or that adiposity may be less strongly linked to cardiovascular disease in Pacific Islanders. 相似文献
The role of gastric biopsy in the diagnosis of Crohn disease (CD) in the pediatric population has not been well described. We assessed the use of gastric biopsies in the diagnosis of CD using specific histopathologic parameters: granulomata, focal gland injury with neutrophils (glandulitis or glandular abscesses), and/or focal concomitant eosinophilic infiltrates. Multiple (438) consecutive pediatric biopsies with inflammation spanning a 5-year period were identified from archival material in patients ages 2 months to 16 years. A total of 56 CD cases were confirmed using colon biopsies and clinical and radiologic data as the gold standards of diagnosis. Review of hematoxylin and eosin (H&E) slides and Diff-Quik stained slides (negative for Helicobacter pylori) isolated 53 cases which suggested CD on gastric biopsy: 20 cases with granulomata, 14 cases with focal glandulitis and glandular abscesses, and 19 cases of focal glandulitis/glandular abscesses with eosinophilic infiltrates. Seventy-seven percent (43/56) were correctly identified as patients with CD. Twenty-three percent (13/56) of CD cases were not identified primarily because of concurrent H. pylori infection identified on Diff-Quik stain with a superimposed nonspecific diffuse gastritis. The use of Diff-Quik stain to identify H. pylori cases after all other factors are considered was significant (P = 0.0145); a negative stain, combined with the identified histopathologic features indicative of CD, significantly increased the accuracy of CD diagnosis. CD was mimicked by other gastric granulomatous diseases (actinomyces, 1 case; chronic granulomatous disease of childhood, 1 case). Gastric biopsy can be used to identify or support the diagnosis of CD in children in the appropriate clinicopathologic setting. 相似文献
Two family aggregation studies report the occurrence and co-occurrence of oral language impairments (LIs) and reading impairments (RIs). Study 1 examined the occurrence (rate) of LI and RI in children with specific language impairment (SLI probands), a matched control group, and all nuclear family members. Study 2 included a larger sample of SLI probands, as well as their nuclear and extended family members. Probands and their family members who met specific criteria were classified as language and/or reading impaired based on current testing. In Study 1, the rates of LI and RI for nuclear family members (excluding probands) were significantly higher than those for control family members. In the SLI families, affected family members were more likely to have both LI and RI than either impairment alone. In Study 2, 68% of the SLI probands also met the diagnostic classification for RI. The language and RI rates for the other family members, excluding probands, were 25% and 23% respectively, with a high degree of co-occurrence of LI and RI (46%) in affected individuals. Significant sex ratio differences were found across generations in the families of SLI probands. There were more male than female offspring in these families, and more males than females were found to have both LIs and RIs. Results demonstrate that when LIs occur within families of SLI probands, these impairments generally co-occur with RIs. Our data are also consistent with prior findings that males show impairments more often than females. 相似文献
The maternal and developmental toxicities of perfluorooctane sulfonate (PFOS, C8F17SO3-) were evaluated in the rat and mouse. PFOS is an environmentally persistent compound used as a surfactant and occurs as a degradation product of both perfluorooctane sulfonyl fluoride and substituted perfluorooctane sulfonamido components found in many commercial and consumer applications. Pregnant Sprague-Dawley rats were given 1, 2, 3, 5, or 10 mg/kg PFOS daily by gavage from gestational day (GD) 2 to GD 20; CD-1 mice were similarly treated with 1, 5, 10, 15, and 20 mg/kg PFOS from GD 1 to GD 17. Controls received 0.5% Tween-20 vehicle (1 ml/kg for rats and 10 ml/kg for mice). Maternal weight gain, food and water consumption, and serum chemistry were monitored. Rats were euthanized on GD 21 and mice on GD 18. PFOS levels in maternal serum and in maternal and fetal livers were determined. Maternal weight gains in both species were suppressed by PFOS in a dose-dependent manner, likely attributed to reduced food and water intake. Serum PFOS levels increased with dosage, and liver levels were approximately fourfold higher than serum. Serum thyroxine (T4) and triiodothyronine (T3) in the PFOS-treated rat dams were significantly reduced as early as one week after chemical exposure, although no feedback response of thyroid-stimulating hormone (TSH) was observed. A similar pattern of reduction in T4 was also seen in the pregnant mice. Maternal serum triglycerides were significantly reduced, particularly in the high-dose groups, although cholesterol levels were not affected. In the mouse dams, PFOS produced a marked enlargement of the liver at 10 mg/kg and higher dosages. In the rat fetuses, PFOS was detected in the liver but at levels nearly half of those in the maternal counterparts, regardless of administered doses. In both rodent species, PFOS did not alter the numbers of implantations or live fetuses at term, although small deficits in fetal weight were noted in the rat. A host of birth defects, including cleft palate, anasarca, ventricular septal defect, and enlargement of the right atrium, were seen in both rats and mice, primarily in the 10 and 20 mg/kg dosage groups, respectively. Our results demonstrate both maternal and developmental toxicity of PFOS in the rat and mouse. 相似文献
Circulating hormones are associated with mammographic density, an intermediate marker of breast cancer risk. Differences in circulating hormones, including estrone and testosterone, have been observed in premenopausal women based on their capacity to metabolize daidzein, an isoflavone found predominantly in soybeans. Equol and O-desmethylangolensin (O-DMA) are products of intestinal bacterial metabolism of daidzein. There is interindividual variability in the capacity to produce daidzein metabolites; individuals can be equol producers or non-producers and O-DMA producers or non-producers. We tested the hypothesis that daidzein-metabolizing phenotypes are associated with mammographic density. Participants were recruited from among 92 sedentary, postmenopausal women, ages 50 to 75 years, who participated in a 1-year physical activity intervention. Pre-intervention mammographic density was determined using a computer-assisted, gray-scale thresholding technique. Fifty-five of these women consumed supplemental soy protein (>10 mg daidzein/d) for 3 days and collected a first-void urine sample on the fourth day to determine daidzein-metabolizing phenotypes. Equol and O-DMA concentrations were measured using gas chromatography-mass spectrometry. Associations between daidzein-metabolizing phenotypes and percent mammographic density were adjusted for age, maximum adult weight, gravidity, family history of breast cancer, and serum follicle-stimulating hormone and free testosterone concentrations. Mammographic density was 39% lower in equol producers compared with non-producers (P = 0.04). O-DMA producers had mammographic density 69% greater than non-producers (P = 0.05). These results suggest that particular intestinal bacterial profiles are associated with postmenopausal mammographic density, and these associations are not entirely explained by differences in reproductive or anthropometric characteristics or circulating hormones. 相似文献
PURPOSE: Asparaginase therapy is an important component in the treatment of children with acute lymphoblastic leukemia. Polyethylene glycol-conjugated asparaginase (PEG-ASNase) has significant pharmacological advantages over native Escherichia coli asparaginase. We investigated the pharmacokinetics of PEG-ASNase, presence of antibodies to PEG-ASNase, and concentrations of asparagine in serum and cerebrospinal fluid (CSF) in combination chemotherapy for relapsed pediatric acute lymphoblastic leukemia. EXPERIMENTAL DESIGN: Twenty-eight pediatric patients with relapsed medullary (n = 16) and extramedullary (n = 11) acute lymphoblastic leukemia were enrolled at three pediatric institutions and had at least two serum and CSF samples obtained for analysis. Patients received induction therapy (including PEG-ASNase 2500 IU/m2 intramuscularly weekly on days 2, 9, 16, and 23) and intensification therapy (including PEG-ASNase 2500 IU/m2 intramuscularly once on day 7). Serum samples were obtained weekly during induction and intensification. CSF samples were obtained during therapeutic lumbar punctures during induction and intensification. RESULTS: Weekly PEG-ASNase therapy resulted in PEG-ASNase activity of >0.1 IU/ml in 91-100% of patients throughout induction. During intensification, PEG-ASNase on day 7 resulted in PEG-ASNase activity >0.1 IU/ml in 94% and 80% of patients on days 14 and 21, respectively. Serum and CSF asparagine depletion was observed and maintained during induction and intensification in the majority of samples. PEG-ASNase antibody was observed in only 3 patients. CONCLUSIONS: Intensive PEG-ASNase therapy in the treatment of relapsed acute lymphoblastic leukemia reliably results in high-level serum PEG-ASNase activity, and asparagine depletion in serum and CSF is usually achieved. Incorporation of intensive PEG-ASNase in future trials for recurrent acute lymphoblastic leukemia is warranted. 相似文献