Phase II trial of 10 deaza-aminopterin in patients with bladder cancer

Summary Deaza-aminopterin is a folate analog which is transported more rapidly than methotrexate into cells and appears to be more active than methotrexate against human and animal tumor in vitro. Fifteen patients with advanced urothelial tract cancer were given deaza-aminopterin 30–37.5 mg/m² IV QW. In responding patients drug was given QOW after 4–6 consecutive doses. Doses were escalated or de-escalated by 7.5 mg/m² depending on toxicity. Twelve patients had received prior chemotherapy which included methotrexate in nine. Three patients achieved a partial remission lasting 1, 3, and 3 months respectively: all responders had previously failed methotrexate after an initial response to a methotrexate containing regimen. None of the six patients who were methotrexate naive responded to deaza-aminopterin; 3 subsequently received methotrexate without response. Mild mucositis was universal and in 5 was severe. Six patients had an increase in liver transaminases probably secondary to anti-folate hepatotoxicity. Other toxicities included diarrhea, nausea, skin rash and fever. Further studies are needed to define the precise efficacy of deaza-aminopterin in patients with urothelial tract cancers.     

Patients with Fabry disease on dialysis in the United States.

BACKGROUND.: Fabry disease results from an X-linked deficiency of lysosomal alpha-galactosidase A and is a rare cause of end-stage renal disease. Little is known about the characteristics of patients with Fabry disease that initiate dialysis in the United States, although data from Europe suggests these individuals have a poor survival. METHODS.: Using the United States Renal Disease System database, we first studied in detail 42 Fabry patients who initiated dialysis between April 1995 (following the introduction of the new detailed HCFA 2728 form) and July 1998. To examine crude survival in a larger cohort, 95 Fabry patients were studied who initiated dialysis between 1985 and 1993, similar to the European Registry. Diabetic and non-diabetic controls matched by age, gender, race, year of dialysis initiation, and initial dialysis modality were examined for comparison. RESULTS.: During the years 1995 to 1998, the mean age of Fabry patients that initiated dialysis was 42 years, 83% were Caucasian, and 10% were African American. Despite the X-linked inheritance of Fabry disease, 12% of Fabry patients on dialysis were female. At initiation of dialysis mean serum albumin and creatinine were significantly higher and mean body mass index was significantly lower among Fabry patients, but mean glomerular filtration rate was similar to controls. Fabry patients tended to have a lower three-year survival compared to non-diabetic controls, but the results were not significantly different. In a larger cohort of Fabry patients who initiated dialysis between 1985 and 1993, the three-year survival of Fabry patients was significantly lower than non-diabetic controls: 63% (95% CI, 50 to 75%) versus 74% (95% CI, 67 to 80%; P=0.03). CONCLUSION.: End-stage renal disease is associated with significant morbidity and mortality among patients with Fabry disease. Recent evidence that progression of Fabry disease may be attenuated by enzyme replacement therapy necessitates increased awareness of Fabry disease and its comorbidities.     

BUILDING THE FOUNDATION OF EXCELLENCE IN HEART FAILURE NURSING

This column contains the presidential address presented during the Third Annual Meeting of the American Association of Heart Failure Nurses on June 28, 2007, in San Diego, California, titled "Building the Foundation of Excellence in Heart Failure Nursing."     

Second‐degree atrioventricular block (Mobitz Type I) in an adolescent with anorexia nervosa: Intrinsic or acquired conduction abnormality

Anorexia nervosa (AN) can cause both functional and structural cardiac complications, including a variety of different conduction abnormalities. This is the first case report of symptomatic diurnal second‐degree atrioventricular (AV) block (Mobitz Type I) in an adolescent with AN. We present a 12‐year‐old girl with AN, restrictor sub‐type who reported cardiac symptoms during weight gain, at the time of the initial diagnosis of AV block. Second‐degree AV block (Mobitz Type I) is discussed as a possible complication of the AN, as well as being an intrinsic conduction system disease. © 2009 by Wiley Periodicals, Inc. Int J Eat Disord 2009     

DNA damage from polycyclic aromatic hydrocarbons measured by benzo[a]pyrene-DNA adducts in mothers and newborns from Northern Manhattan, the World Trade Center Area, Poland, and China.

Polycyclic aromatic hydrocarbons (PAH), of which benzo[a]pyrene is a representative member, are combustion-related environmental pollutants and include known carcinogens. Laboratory animal studies indicate that the dose of PAHs to the fetus is on the order of a 10th that to the mother and that there is heightened susceptibility to PAH-induced carcinogenesis during the fetal and infancy periods. Carcinogen-DNA adducts, a measure of procarcinogenic genetic damage, are considered a biomarker of increased cancer risk. Here we compare the levels of benzo[a]pyrene-DNA adducts as a proxy for PAH-DNA damage measured in maternal blood and newborn cord blood obtained at delivery in four different populations of mothers (total of 867) and newborns (total of 822), representing a 30-fold range of exposure to ambient PAHs. The populations include residents in Northern Manhattan, participants in a study of the effects of the World Trade Center disaster, residents in Krakow, Poland, and residents in Tongliang, China. Mean adduct concentrations in both maternal and cord blood and the proportion of samples with detectable adducts, increased across the populations [Northern Manhattan < World Trade Center (WTC) < Krakow < Tongliang], consistent with the trend in estimated ambient exposure to PAHs (P < 0.001). For mothers, the means in the respective populations were Northern Manhattan (0.21 adducts per 10(8) nucleotides), WTC (0.23 adducts per 10(8) nucleotides), Krakow (0.28 adducts per 10(8) nucleotides), Tongliang (0.31 adducts per 10(8) nucleotides); the corresponding means in the newborns were Northern Manhattan (0.23), WTC (0.24), Krakow (0.29), Tongliang (0.31). The percentage of mothers with detectable levels of adducts in the respective populations were Northern Manhattan (36.8%), WTC (57.5%), Krakow (72.9%), Tongliang (73.4%); the corresponding percentages among the newborns were Northern Manhattan (42.4%), WTC (60.6%), Krakow (71.1%), Tongliang (79.5%). Despite the estimated 10-fold lower PAH dose to the fetus based on laboratory animal experiments, the adduct levels in the newborns were similar to or higher than in the mothers. This study suggests that the fetus may be 10-fold more susceptible to DNA damage than the mother and that in utero exposure to polycyclic aromatic hydrocarbons may disproportionately increase carcinogenic risk. The data support preventive policies to limit PAH exposure to pregnant women and children.