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.     

Randomised controlled trial of zinc supplementation in malnourished Bangladeshi children with acute diarrhoea

OBJECTIVE: To evaluate the impact of zinc supplementation on the clinical course, stool weight, duration of diarrhoea, changes in serum zinc, and body weight gain of children with acute diarrhoea. DESIGN: Randomised double blind controlled trial. Children were assigned to receive zinc (20 mg elemental zinc per day) containing multivitamins or control group (zinc-free multivitamins) daily in three divided doses for two weeks. SETTING: A diarrhoeal disease hospital in Dhaka, Bangladesh. PATIENTS: 111 children, 3 to 24 months old, below 76% median weight for age of the National Center for Health Statistics standard with acute diarrhoea. Children with severe infection and/or oedema were excluded. MAIN OUTCOME MEASURES: Total diarrhoeal stool output, duration of diarrhoea, rate of weight gain, and changes in serum zinc levels after supplementation. RESULTS: Stool output was 28% less and duration 14% shorter in the zinc supplemented group than placebo (p = 0.06). There were reductions in median total diarrhoeal stool output among zinc supplemented subjects who were shorter (less than 95% height for age), 239 v 326 g/kg (p < 0.04), and who had a lower initial serum zinc (< 14 mmol/l), 279 v 329 g/kg (p < 0.05); a shortening of mean time to recovery occurred (4.7 v 6.2 days, p < 0.04) in those with lower serum zinc. There was an increase in mean serum zinc in the zinc supplemented group (+2.4 v -0.3 mumol/l, p < 0.001) during two weeks of supplementation, and better mean weight gain (120 v 30 g, p < 0.03) at the time of discharge from hospital. CONCLUSIONS: Zinc supplementation is a simple, acceptable, and affordable strategy which should be considered in the management of acute diarrhoea and in prevention of growth faltering in children specially those who are malnourished.     

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.     

Blunt hepatic injury: minimal intervention is the policy of treatment

BACKGROUND: Many publications recommend nonoperative treatment for stable blunt hepatic injury patients. Unstable hemodynamic status is the only indication for surgery. When operation is indicated, controversies exist regarding which operative procedure will be more beneficial to the patients. The purposes of this study are to compare the results of operative and nonoperative management of patients with blunt hepatic injuries and to identify the optimal surgical approach when surgery is indicated. METHODS: Different prospective protocols of treating adult blunt hepatic injuries were conducted. From 1992 to 1993 (group I), urgent surgery would be performed in the presence of hemoperitoneum. The policy shifted to aggressive nonoperative approach between 1996 and 1997 (group II). The patients from each period were divided into three subgroups. Group A included the patients who received nonoperative treatment in either period. Group B consisted of the patients who received surgery in the first period and nonoperative management in the second period. Group C included the patients who were operated on in either group. Comparisons were made between matched groups. RESULTS: Groups IA and IIA patients had minor injuries and could be successfully treated nonoperatively. The results of groups IB and IIB were similar concerning hospital stay, morbidity, and mortality. Transfusion requirements of group IIB patients were significantly higher (2.2 vs. 1.1 units,p = 0.01) than those of group IB. However, 25 (58%) celiotomies of group IB patients were nontherapeutic. When surgery was indicated, group IC patients had significantly higher liver-related mortality (14 of 49 vs. 3 of 55, p = 0.002). Anatomic resection was performed more frequently in that period. CONCLUSION: Nonoperative treatment significantly decreased the rate of nontherapeutic laparotomy but carried the risks of higher transfusion requirements and delaying operation. When surgery was indicated, the policy of minimal intervention positively affected the patients' outcomes. The goal of surgery should be hemorrhage control rather than resection of the injured liver tissues.