"Concentration x time" methotrexate via a subcutaneous reservoir: a less toxic regimen for intraventricular chemotherapy of central nervous system neoplasms

Neurotoxicity associated with intrathecal methotrexate therapy has been shown to correlate with elevated concentrations of the drug in the cerebrospinal fluid as well as with the total cumulative dosage. In our study 19 patients with meningeal leukemia were randomized to receive courses of intraventricular methotrexate via an Ommaya reservoir consisting of either single injections of 12 mg/sq m/dose or a low-dose "concentration x time" (C x T) schedule of 1 mg every 12 hr for 3 days. There were no significant differences between the two treatment groups in the rate of remission induction, the number of relapses, or the durations of remission. The mean (+/- 1 SD) cumulative methotrexate dose was 66 +/- 41 mg/sq m in the C x T group and 173 +/- 64 mg/sq m in the 12 mg/sq m/dose group (p less than 0.005). Neurologic toxicity occurred in one of the eight patients in the C x T group and in seven of ten patients in the 12 mg/sq m/dose group (p less than 0.05). These observations suggest that the C x T dosage schedule is less neurotoxic and equally effective in the treatment of central nervous system leukemia.     

Higher premenarcheal bone mass in elite gymnasts is maintained into young adulthood after long‐term retirement from sport: A 14‐year follow‐up

Sports that impact‐load the skeleton during childhood and adolescence increase determinants of bone strength such as bone mineral content and density; however, it is unclear if this benefit is maintained after retirement from the sport. The purpose of this study was to assess whether the previously reported higher bone mass in a group of premenarcheal gymnasts was still apparent 10 years after the cessation of participation and withdrawal of the gymnastics loading stimulus. In 1995, 30 gymnasts 8 to 15 years of age were measured and compared with 30 age‐matched nongymnasts. Twenty‐five former gymnasts and 22 nongymnasts were measured again 14 years later (2009 to 2010). Gymnasts had been retired from gymnastics training and competition for an average of 10 years. Total body (TB), lumbar spine (LS), and femoral neck (FN) bone mineral content (BMC) was assessed at both measurement occasions by dual‐energy X‐ray absorptiometry (DXA). Multivariate analysis of covariance (MANCOVA) was used to compare former gymnasts' and nongymnasts' BMC while controlling for differences in body size and maturation (covariates: age, height, weight, and years from menarche [1995] or age at menarche [2009 to 2010]). Premenarcheal gymnasts (measured in 1995) had significantly greater size‐adjusted TB, LS, and FN BMC (p < 0.05) (15%, 17%, and 12%, respectively) than nongymnasts. Ten years after retirement, gymnasts had maintained similar size‐adjusted TB, LS, and FN BMC differences (p < 0.05) (13%, 19%, and 13%, respectively) when compared with nongymnasts. Bone mass benefits in premenarcheal gymnasts were still apparent even after long‐term (10 years) removal of the gymnastics loading stimulus. © 2012 American Society for Bone and Mineral Research     

Former premenarcheal gymnasts exhibit site‐specific skeletal benefits in adulthood after long‐term retirement

Young female gymnasts have greater bone strength compared to controls; although possibly due to selection into gymnastics, it is thought that their loading activity during growth increases their bone mass, influencing both bone geometry and architecture. If such bone mass and geometric adaptations are maintained, this may potentially decrease the risk of osteoporosis and risk of fracture later in life. However, there is limited evidence of the persisting benefit of gymnastic exercise during growth on adult bone geometric parameters. Therefore, the purpose of this study was to determine whether adult bone geometry, volumetric density, and estimated strength were greater in retired gymnasts compared to controls, 10 years after retirement from the sport. Bone geometric and densitometric parameters, measured by peripheral quantitative computed tomography (pQCT) at the radius and tibia, were compared between 25 retired female gymnasts and 22 controls, age range 22 to 30 years, by multivariate analysis of covariance (covariates: age, height, and muscle cross‐sectional area). Retired gymnasts had significantly greater adjusted total and trabecular area (16%), total and trabecular bone mineral content (BMC) (18% and 22%, respectively), and estimated strength (21%) at the distal radius (p < 0.05) than controls. Adjusted total and cortical area and BMC, medullary area, and estimated strength were also significantly greater (13% to 46%) in retired gymnasts at the 30% and 65% radial shaft sites (p < 0.05). At the distal tibia, retired gymnasts had 12% to 13% greater total and trabecular BMC and volumetric bone mineral density as well as 21% greater estimated strength; total and cortical BMC and estimated strength were also greater at the tibial shaft (8%, 11%, and 10%, respectively) (p < 0.05). Former female gymnasts have significantly better geometric and densitometric properties, as well as estimated strength, at the radius and tibia 10 years after retirement from gymnastics compared to females who did not participate in gymnastics in childhood and adolescence. © 2012 American Society for Bone and Mineral Research.     

Neurotoxicity, anticoagulant activity and evidence of rhabdomyolysis in patients bitten by death adders (Acanthophis sp.) in southern Papua New Guinea

Thirty-two patients with enzyme-immunoassay-proven death adder (Acanthophis sp.) bites were studied in Port Moresby, Papua New Guinea. Eighteen were envenomed; local signs were rare and none had incoagulable blood, but all except one had signs of neurotoxicity. Five (27.7%) envenomed patients required intubation and ventilation. One patient developed renal failure, previously undescribed following death adder bites. Laboratory investigations showed mild prolongation of prothrombin and partial thromboplastin times in some patients. In vitro studies showed that the venom contains anticoagulant activity, but does not cause fibrinogenolysis. In contrast to taipan envenoming, neurotoxicity did not progress after antivenom administration, and there was reversal of neurotoxicity, evident within 6 h, in three severely envenomed patients treated less than 12 h after the bite. One patient treated with antivenom and anticholinesterases had the most dramatic response to treatment; the optimum management of bites by this species may include prompt treatment with both antivenom and anticholinesterases in addition to effective first aid.      

Informed consent for blood transfusion: a regional hospital survey

Ninety-two hospitals in a three-state mid-Atlantic region were surveyed to determine their policy toward obtaining written informed consent for transfusion and to examine the content of written consent documents and the process by which consent is obtained. Of 81 hospitals responding, 50 (62%) required written informed consent. Hospitals with fewer than 200 beds were more likely to require written informed consent. The attending physicians had responsibility for obtaining consent in 28 (57%) of 49 institutions, most often on the day or evening before surgery. Twenty-seven of 48 forms mentioned complications: hepatitis in 80 percent, human immunodeficiency virus infection in 46 percent, nonhemolytic reactions in 32 percent, and hemolysis in 25 percent. Alternatives to allogeneic transfusion were mentioned infrequently; eight hospital forms listed autologous transfusion options and only two mentioned designated donation. The reading level required to comprehend 34 consent forms submitted was grade 14.6, which has been attained by only 23 percent of the adult United States population. Although the majority of respondent institutions require written informed consent, those forms, per se, do not document that the fundamental tenets of informed choice have been applied to the decision to transfuse blood.     

Pathology of steatohepatitis

Pathologists have long been involved in clinical diagnosis and investigative studies of various forms of liver disease, including alcoholic liver disease. The concept that progressive fatty liver disease may result from causes other than alcohol toxicity can be noted in the literature. However, acceptance of this as a bona fide form of liver disease has been credited to an in-depth study published in 1980 of patients gathered from cases in the files of the pathology department of the Mayo Clinic in whom liver biopsies showed histological similarities to alcoholic steatohepatitis, but for whom clinical evidence of alcohol use was absent. Subsequent studies of the natural history and pathogenesis of non-alcoholic steatohepatitis have relied on detailed histopathological correlations. This chapter will elucidate the constellation of microscopic findings, the issues of concern for pathological evaluation and the knowledge to date of their significance in various forms of fatty liver disease.