Rajesh Sehgal

OBJECT: Endothelial proliferation has been recognized as a marker of high-grade or aggressive glioma. Bevacizumab is a humanized immunoglobulin G1 monoclonal antibody to vascular endothelial growth factor that has been shown to have activity in malignant gliomas when combined with irinotecan. The authors report on a case series of 13 patients with recurrent heavily pretreated malignant glioma that was treated with the combination of bevacizumab and irinotecan. METHODS: Standard therapy with primary resection followed by adjuvant chemotherapy and radiation had failed in all patients. The median number of therapies applied, including initial surgery, was 5 (range 3-7 therapies). Nine patients were started on bevacizumab at a dose of 5 mg/m2 every 2 weeks. Four patients received bevacizumab at a dose of 10 mg/m2; irinotecan was given at a dose of 125 mg/m2 every week for 3 weeks. RESULTS: Of the 13 treated patients, 10 (77%) had a radiologically demonstrated partial response and 3 (23%) had stable disease. Six patients (46%) had a clinical response. The median time to disease progression while on treatment was 24 weeks. The median overall survival was 27 weeks. The disease progressed in 8 patients, despite an initial response. Five patients are still responding to therapy. Six of the 8 patients whose disease progressed have died. Bevacizumab was discontinued in 2 patients because of nonfatal intracranial bleeding. CONCLUSIONS: The combination of bevacizumab and irinotecan is safe and has excellent activity even in this relapsed, heavily pretreated population of patients with high-grade malignant glioma, most of whom would not be candidates for clinical trials.

BACKGROUND: Lantana camara L. (Verbenaceae), a widely growing shrub which is toxic to some animal species, has been used in the traditional medicine for treating many ailments. The purpose of the present study was to evaluate the antimotility effects of Lantana camara leaf constituents in mice intestine. METHODS: Evaluation of antimotility activity was done in intestine of mice treated with Lantana camara leaf powder, Lantana camara methanolic extract (LCME), lantadene A, neostigmine and neostigmine + LCME. Neostigmine was used as a promotility agent. Intestinal motility was assessed by charcoal meal test and gastrointestinal transit rate was expressed as the percentage of the distance traversed by the charcoal divided by the total length of the small intestine. The antidiarrheal effect of LCME was studied against castor oil induced diarrhea model in mice. RESULTS: The intestinal transit with LCME at a dose of 500 mg/kg was 26.46% whereas the higher dose (1 g/kg) completely inhibited the transit of charcoal in normal mice. The % intestinal transit in the neostigmine pretreated groups was 24 and 11 at the same doses respectively. When the plant extracts at 125 and 250 mg/kg doses were administered intraperitonealy, there was significant reduction in fecal output compared with castor oil treated mice. At higher doses (500 and 1000 mg/kg), the fecal output was almost completely stopped. CONCLUSION: The remarkable antimotility effect of Lantana camara methanolic extract against neostigmine as promotility agent points towards an anticholinergic effect due to Lantana camara constituents and attests to its possible utility in secretory and functional diarrheas and other gastrointestinal disorders. This effect was further confirmed by significant inhibition of castor oil induced diarrhea in mice by various doses of LCME.

BACKGROUND: The development of coronary aneurysms as sequelae of Kawasaki disease can result in myocardial ischemia, infarction, and sudden death. Traditionally, these patients have undergone coronary angiography and nuclear stress imaging for risk stratification and follow-up. However, angiography is invasive, and both modalities expose the patient to repeated radiation, which is an important issue in children. The purpose of this study was to determine the feasibility of performing exercise stress echocardiography in children diagnosed with coronary abnormalities secondary to Kawasaki disease. METHODS AND RESULTS: Treadmill exercise stress echocardiographic studies were performed in 28 children ages 6 to 16 years. All had acute Kawasaki disease 1 to 10 years before study, and coronary artery abnormalities were identified during previous echocardiographic imaging. Patients were exercised using a standard Bruce protocol. Transthoracic echocardiographic images, obtained in the parasternal long, short, apical two- and four-chamber views immediately before and after exercise, were digitized for review and analysis. In baseline studies before exercise, wall motion abnormalities were identified in 2 patients; these segments became normal with exercise. Two patients developed new exercise-induced wall motion abnormalities that corresponded to angiographically defined critical stenosis of the left anterior descending coronary artery. No patients had resting or exercise-induced ECG evidence of ischemia. There were no adverse reactions, and 26 of 28 patients had normal exercise tolerance. CONCLUSIONS: Among patients with coronary artery involvement resulting from Kawasaki disease, exercise stress echocardiography is a safe, noninvasive procedure and may identify children with myocardial ischemia that was not detected with ECG stress test alone.

Advances in breast cancer research have led to declining death rates from this disease because of early detection through mammographic screening and improved therapy for breast cancer. The concept that breast cancer, in some cases, can be prevented has been explored over the last three decades. This article, part I of a two-part series, will focus on the epidemiology, the risk factors associated with breast cancer, and the available risk assessment tools, which can help define who should be considered for risk reduction strategies. Part II will focus on discussing risk reduction strategies.

Pregnancy-associated breast cancer (PABC) has been defined as breast cancer diagnosed during pregnancy or within one year of delivery. It is believed that after adjusting for age and stage, the 5-year survival rates are the same in both pregnant and nonpregnant women. We conducted a retrospective case-control study among patients treated at our institution between 1990 and 2005 to compare the 5-year survival outcomes for PABC with women treated for breast cancer who were not pregnant. Overall survival (OS) and disease-free survival (DFS) were estimated by the Kaplan-Meier method, and log rank tests were used to assess the associations between OS, DFS and pregnancy status, HER-2 status, ER/PR status, and family history. The median age was 33 years (range 24-42) for both groups. Twenty-two (55%) patients with PABC were ER/PR receptor positive compared with 20 (50%) for the controls. Ninety percent of patients with PABC received chemotherapy compared with 87.5% in the nonpregnant group. 91.5% of patients with PABC had breast-conserving surgery and 8.5% had mastectomies compared with 86% and 14%, respectively, for the control group. The median OS was 4.9 years in the PABC group compared with 6 years for the controls (p = 0.02). The median DFS was 2.7 years for the PABC group compared with 5.1 years for the controls (p = 0.01). The most common site of relapse was bone for the PABC group (27%) and local recurrence (33%) for the controls. Univariate analysis revealed that OS and DFS were associated with pregnancy status, family history, ER/PR status, and stage. After adjusting for age and stage, PABC patients had higher risk of both death (p = 0.01) and recurrence (p = 0.02) compared with nonpregnant controls. Women with PABC had significantly shorter OS and DFS compared with nonpregnant age and stage-matched controls.