A farnesyltransferase inhibitor increases survival of mice with very advanced stage acute lymphoblastic leukemia/lymphoma caused by P190 Bcr/Abl.

Treatment of chronic myelogenous leukemia with a specific inhibitor of the Bcr/Abl tyrosine kinase, imatinib, has shown great promise. However, acute lymphoblastic leukemias that express Bcr/Abl only transiently respond to imatinib. Therefore, alternative treatments for this type of leukemia are urgently needed. Here, we examined the activity of the farnesyltransferase inhibitor SCH66336 as a single chemotherapeutic agent in a nude mouse model representative of very advanced stage Bcr/Abl P190-positive lymphoblastic leukemia/lymphoma. Our results show that oral administration of the inhibitor was able to significantly increase the survival of these mice compared to controls treated with vehicle (P<0.005), and caused marked regression of the tumor burden in the treated mice. Upon prolonged treatment, lymphomas re-emerged and a subset of cells from two of such lymphomas tested was able to survive in the presence of increased concentrations of SCH66336. The same cells, however, remained sensitive towards imatinib. A combination of the two drugs, preceded by a therapy to reduce the initial tumor burden, could be very effective in the treatment of Ph-positive ALL. We conclude that SCH66336, on its own, is remarkably effective in eradicating large numbers of lymphoblastic lymphoma cells and causing visible reduction in tumor size, with minimal toxicity.     

Myxoma of maxilla

A case of Myxoma involving left Maxilla, presenting as swelling of left side of face and Oral cavity with bilateral nasal obstruction is reported.     

Toxic cardiogenic shock in a patient receiving weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin

A 54-year-old man was treated with weekly 24-h infusion of high-dose 5-fluorouracil (2600 mg/m2) and leucovorin (100 mg/m2) for metastatic colon cancer. At first, he tolerated the treatment well and no significant toxicity was identified. After a total of eight courses of treatment, a stable disease was observed, but mild shortness of breath was found on occasion. The patient had no previous history of cardiac disease and the heart performance assessed by left ventricular ejection fraction before treatment was normal. Unfortunately, acute pulmonary edema with lethal cardiogenic shock occurred during the ninth course of treatment, in spite of intensive medical treatment. The chest X-ray showed extreme cardiomegaly. Repeated assessment of his heart function by echocardiogram and ventricular ejection fraction revealed a very poor cardiac performance. Toxic cardiogenic shock during weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin is extremely rare. To the best of our knowledge, no case has been reported in the English literature. We report a case and the relevant literature about the incidence, clinical picture and possible pathophysiology on 5-fluorouracil-related cardioxicity is reviewed.      

Three Year Health Outcomes Among Older Women at Risk of Elder Abuse: Women's Health Australia

BACKGROUND: Older women are at increasing risk of various forms of familial violence, yet detection is poor and very little is known of the long-term health effects of this psychosocial problem. The effectiveness of the 'Vulnerability to Abuse' Screening Scale (VASS) in predicting three year health outcomes was investigated among women enrolled in the Australian Longitudinal Study on Women's Health, now known as Women's Health Australia. METHODS: The sample comprised a cohort of 10,421 women aged 73-78 who completed the 1996 and 1999 postal surveys (attrition rate 19.5%). The Time 2 sample had a small bias towards lower risk for elder abuse at Time 1 and better health on SF-36 and self-rated health. The VASS is a 12-item self-report measure with 4 factors: vulnerability, coercion, dependence and dejection. RESULTS: Overall, physical health (PCS) declined while mental health (MCS) increased over the three year period. Decline in physical health was predicted by only the dejection factor, but not by factors which seem to more directly measure abuse. The predictive validity of the VASS for three year mental health outcomes was given partial support. Three of the four VASS factors (dejection, vulnerability, and coercion) predicted decline in mental health at the univariate level, however, after adjusting for confounders, only one VASS factor (dejection) independently predicted decline in mental health. CONCLUSIONS: While the VASS shows some promise as a marker of health risk in older women, only the dejection factor proved consistently predictive of declining health status. Further research is needed to determine longer term predictive validity of the scale and to gain a clearer picture of how abusive experiences impact on older women's health.     

Predictors of all‐cause mortality among patients hospitalized with influenza,respiratory syncytial virus,or SARS‐CoV‐2

BackgroundShared and divergent predictors of clinical severity across respiratory viruses may support clinical and community responses in the context of a novel respiratory pathogen.MethodsWe conducted a retrospective cohort study to identify predictors of 30‐day all‐cause mortality following hospitalization with influenza (N = 45,749; 2010‐09 to 2019‐05), respiratory syncytial virus (RSV; N = 24 345; 2010‐09 to 2019‐04), or severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2; N = 8988; 2020‐03 to 2020‐12; pre‐vaccine) using population‐based health administrative data from Ontario, Canada. Multivariable modified Poisson regression was used to assess associations between potential predictors and mortality. We compared the direction, magnitude, and confidence intervals of risk ratios to identify shared and divergent predictors of mortality.ResultsA total of 3186 (7.0%), 697 (2.9%), and 1880 (20.9%) patients died within 30 days of hospital admission with influenza, RSV, and SARS‐CoV‐2, respectively. Shared predictors of increased mortality included older age, male sex, residence in a long‐term care home, and chronic kidney disease. Positive associations between age and mortality were largest for patients with SARS‐CoV‐2. Few comorbidities were associated with mortality among patients with SARS‐CoV‐2 as compared with those with influenza or RSV.ConclusionsOur findings may help identify patients at greatest risk of illness secondary to a respiratory virus, anticipate hospital resource needs, and prioritize local prevention and therapeutic strategies to communities with higher prevalence of risk factors.