Phase II trial of gefitinib in recurrent glioblastoma.

PURPOSE: To evaluate the efficacy and tolerability of gefitinib (ZD1839, Iressa; AstraZeneca, Wilmington, DE), a novel epidermal growth factor receptor tyrosine kinase inhibitor, in patients with recurrent glioblastoma. PATIENTS AND METHODS: This was an open-label, single-center phase II trial. Fifty-seven patients with first recurrence of a glioblastoma who were previously treated with surgical resection, radiation, and usually chemotherapy underwent an open biopsy or resection at evaluation for confirmation of tumor recurrence. Each patient initially received 500 mg of gefitinib orally once daily; dose escalation to 750 mg then 1,000 mg, if a patient received enzyme-inducing antiepileptic drugs or dexamethasone, was allowed within each patient. RESULTS: Although no objective tumor responses were seen among the 53 assessable patients, only 21% of patients (11 of 53 patients) had measurable disease at treatment initiation. Seventeen percent of patients (nine of 53 patients) underwent at least six 4-week cycles, and the 6-month event-free survival (EFS) was 13% (seven of 53 patients). The median EFS time was 8.1 weeks, and the median overall survival (OS) time from treatment initiation was 39.4 weeks. Adverse events were generally mild (grade 1 or 2) and consisted mainly of skin reactions and diarrhea. Drug-related toxicities were more frequent at higher doses. Withdrawal caused by drug-related adverse events occurred in 6% of patients (three of 53 patients). Although the presence of diarrhea positively predicted favorable OS from treatment initiation, epidermal growth factor receptor expression did not correlate with either EFS or OS. CONCLUSION: Gefitinib is well tolerated and has activity in patients with recurrent glioblastoma. Further study of this agent at higher doses is warranted.     

Technetium-99m tetrofosmin SPECT predicts chemotherapy response in small cell lung cancer.

The multidrug resistance gene 1 encoding human P-glycoprotein (Pgp) is thought to play an important role in the multidrug resistance of lung cancer. The purpose of this study was to predict chemotherapy response by technetium-99m tetrofosmin (Tc-99m TF) lung single photon emission computed tomography (SPECT) and compare Pgp expression in patients with untreated small cell lung cancer (SCLC). Forty patients with untreated SCLC received Tc-99m TF lung SPECT prior to chemotherapy. The chemotherapy response was evaluated in the 3rd month after completion of treatment. Immunohistochemical staining of Pgp expression was performed on multiple nonconsecutive sections of biopsy specimens. By quantitative analyses, tumor to background ratios were 1.86 +/- 0.27 and 1.17 +/- 0.26 for patients with a good and poor response, respectively (p < 0.05). All of the 20 patients with a good chemotherapy response also had a positive Tc-99m TF lung SPECT and negative Pgp expression. In contrast, only 4 of the 20 patients with a poor chemotherapy response had a positive Tc-99m TF lung SPECT. Moreover, 10 of the 20 patients with a poor chemotherapy response also had negative Pgp expression (p < 0.05). Therefore, we concluded that Tc-99m TF lung SPECT can accurately predict the chemotherapy response, and Tc-99m TF lung SPECT findings can be partially compatible with Pgp expression in patients with untreated SCLC.     

Growth of asthmatic children is slower during than before treatment with inhaled glucocorticoids

Reports on the influence of inhaled glucocorticoids on growth have been controversial. We studied the growth of prepubertal asthmatic children prior to and during glucocorticoid therapy. We collected retrospectively the notes of 201 asthmatic children aged 1–11 years receiving inhaled beclomethasone dipropionate or budesonide. We calculated their height and height velocity standard deviation scores (HSDS and HVSDS, respectively) before the treatment and up to 5 years during the treatment and compared those with the growth of healthy peers. The dose of the medication was calculated and the severity of asthma was assessed. The asthmatic children grew similarly to their healthy peers before treatment with inhaled glucocorticoids: the mean HSDS was +0.02 and the mean HVSDS +0.01 for boys and -0.16 and +0.13 for girls, respectively. Growth retardation took place soon after the start of the treatment, the most profound decrease in the growth velocity (the change in the mean HVSDS from +0.05 to -0.88) occurring during the first year of treatment. The growth-retarding effect of inhaled glucocorticoids was not dose dependent. In the covariance analysis the increasing severity of asthma had a significant interaction with repeated measurements, showing more growth retardation along with more severe asthma, especially during long-term treatment. Asthma per se does not impair growth, but inhaled glucocorticoids may do so. Careful monitoring of the growth of all asthmatic children receiving inhaled glucocorticoids is necessary because the growth-retarding effect of the medication is not dose dependent. Individual sensitivity might explain the differences seen in the growth patterns of children receiving inhaled glucocorticoids.     

Incident type 2 diabetes mellitus in African American and white adults: the Atherosclerosis Risk in Communities Study

Context  Although the excess prevalence of type 2 diabetes mellitus in African Americans is well established, few studies have compared incident diabetes in African American and white persons. Objectives  To compare risk of incident diabetes in African American vs white adults and to identify explanatory factors for racial disparities. Design  Prospective cohort study using baseline data collected from 1986 to 1989 from the ongoing Atherosclerosis Risk in Communities (ARIC) Study, with 9 years of follow-up. Setting and Participants  A total of 2646 African American and 9461 white adults aged 45 to 64 years without diabetes at baseline, sampled from 4 US communities. Main Outcome Measures  Incident type 2 diabetes, ascertained by self-report of physician diagnosis, use of diabetes medications, or fasting glucose level of at least 7.0 mmol/L (126 mg/dL), compared among white and African American subjects and by presence of potentially modifiable risk factors. Results  Diabetes incidence per 1000 person-years was about 2.4-fold greater in African American women (25.1 [95% confidence interval {CI}, 22.4-28.1] vs 10.4 [95% CI, 9.4-11.4]) and about 1.5-fold greater in men (23.4 [95% CI, 19.9-27.2] vs 15.9 [95% CI, 14.6-17.2]) than in their white counterparts (P<.001). Results from proportional hazards regression models indicated that racial differences in potentially modifiable risk factors, particularly adiposity, accounted for 47.8% of the excess risk in African American women but accounted for little excess risk in African American men. Compared with their white counterparts, African American men and women had higher blood pressures before diabetes onset (diastolic blood pressure difference=5.6 mm Hg in women and 8.4 mm Hg in men; P=.005). Conclusions  Our data indicate that compared with their white counterparts, middle-aged African Americans are at greater risk of developing type 2 diabetes and have higher blood pressure prior to development of diabetes. In women, almost 50% of this excess risk might be related to potentially modifiable factors.      

艾灸足三里治疗顺铂所致迟发性呕吐的临床观察

目的:观察艾灸足三里治疗顺铂所致迟发性呕吐的临床效果.方法:100例患者随机分A、B两组各50例,A组(治疗组):枢星3mg 0.9%NS20ml化疗前30min iv d1-3 艾灸足三里d1-7;B组(对照组):枢星3mg 0.9%NS20ml化疗前30min iv d1～3,观察化疗后7d内呕吐情况.结果:A组控制迟发性呕吐的有效率明显高于B组(P＜0.05).结论:艾灸足三里治疗顺铂所致迟发性呕吐疗效好、经济、方便、安全.     

Postero-medio-anterior approach of the ankle for the pilon fracture

A good view of the operative field is important for better reduction and fixation in surgical treatment of fractures. The exposure of the ankle joint for the pilon fracture is commonly through the anterior approach, or combined with the medical approach. But sometimes it is still difficult to have complete viewing of the articular surface and to apply internal fixation by that approach. In recent years, we developed a "postero-medio-anterior" approach of the ankle joint by one incision. This approach provides an excellent exposure of the anterior, medial and posterior aspects of the ankle joint with a clear view of the articular surface. In our 45 cases of pilon fracture during 1991 to 1995, there was no incisional injury to the neurovascular bundle. Superficial wound edge necrosis was noted in two cases which healed later without further procedure. Therefore, we recommend this approach as a simple and reliable incision for open reduction of pilon fractures.