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.     

Telephone dissatisfaction in pediatric practice: Denver and Baltimore

A survey of pediatricians in private practice in the Denver and Baltimore metropolitan areas was conducted to assess pediatricians' satisfaction with the telephone in their practices. The response rates were 84% (89/106) in Denver and 72% (90/125) in Baltimore. In both cities, 42% of the physicians were dissatisfied with their telephone systems. Dissatisfied physicians were less likely to provide a morning telephone hour (P less than .02), less likely to delegate calls to office staff (P less than .01), more likely to believe that they lacked sufficient time to handle daytime calls (P less than .0001), and more likely to be in group rather than solo practice (P less than .05). Younger age of the respondent approached, but did not reach, statistical significance in its association with dissatisfaction.     

Practical value of a new serum digitoxin assay

The purpose of this study was to evaluate a new fluorescence polarization immunoassay, TDx, for digitoxin by comparing the results of this assay with those of a radioimmunoassay (RIA). Thirty-three serum samples were obtained from 15 patients during, and for 4 weeks after, a 4-week course of digitoxin therapy. Each sample was separated by centrifugation, coded, and frozen until analysis. At the time of analysis, each sample was divided and analyzed simultaneously by TDx and RIA. Nine samples yielded results less than 2 ng/ml (limit of assay sensitivity) by one or both methods and were excluded from further data analysis. Linear regression analysis of the results of the remaining 24 paired samples (x = TDx, y = RIA) revealed a strong correlation coefficient of r2 = 0.95, slope = 0.95, and a y intercept of -0.99 (y = -0.99 + 0.95x). Additionally, the TDx results were lower than the RIA values in only five of 33 paired samples; and these occurred in four patients who had a significantly lower mean estimated creatinine clearance than that of the other 11 patients (39.0 +/- 9.1 ml/min/1.73 m2 vs. 63.3 +/- 11.8 ml/min/1.73 m2, p less than 0.01). The TDx system is a comparable alternative to the RIA method, but differences in specificity and sensitivity may exist and should be evaluated more thoroughly.     

Defecation dynamics and behavior profiles in encopretic children

The social competence and behavioral profiles of 38 encopretic children were evaluated, and the social competence and behavioral ratings were correlated with physiologic abnormalities found during anorectal manometric and EMG evaluation and with treatment outcome. When defecation was studied, 66% of encopretic children were not able to defecate rectal balloons and 63% were not able to relax the external anal sphincter during defecation attempts. Total social competence and behavior problem scores were not different for boys able and unable to defecate balloons. Total social competence scores were significantly lower in girls unable to defecate balloons than in those able to (P less than .006), whereas behavior problem scores were similar in girls able to and unable to defecate. We found that persistence of encopresis at 6-month and 12-month follow-up was not related to the social competence (P greater than .2) or behavioral scores (P greater than .2) but was significantly related to the inability to defecate (P less than .01) and to the inability to relax the external sphincter during defecation attempts (P less than .03).     

Ultrastructural observations of organelle accumulation in the equine recurrent laryngeal nerve

Summary The left recurrent laryngeal nerves from five horses with sub-clinical neuropathy were examined by light and electron microscopy in a study designed to examine accumulation of axonal organelles at paranodal and internodal locations. Transverse sections of the nerve showed scattered fibres with split myelin sheaths and axonal accumulation of organelles. On longitudinal sections these collections were seen to result from an axonal outpouching in which dense lamellar bodies and mitochondria had accumulated. These paranodal collections, which could be found on both sides of the node, were often associated with infoldings of the terminal loops of myelin and with occasional paranodal demyelination. The fact that many of the organelles in the outpouches were lysosomal in nature was confirmed by their positive staining for cathepsin D activity. Longitudinal sections demonstrated a number of axons which were swollen over a long distance and which contained focal accumulations of similar organelles. In places, however, there was a clear separation between these organelles and the cytoskeletal proteins. In each case these swollen axons were surrounded by Schwann cell nuclei and their processes, forming well-ordered onion bulbs. The possibility that these two types of changes, i.e. the paranodal accumulations and the axonal swellings could result from a disturbance in axonal transport in this distal axonopathy is discussed.     

Partial deletion of short arm of chromosome 8

46, XY, del(8) (p21-pter) aberration was found in a 5 year old boy with moderate craniofacial dysmorphia, mental and somatic retardation. The cytogenetic and clinical features of the patient were compared to 11 cases found in the literature. Partial 8p monosomy does not produce a unique phenotypic alteration. Postnatal growth deficiency, craniofacial dysmorphia and mental retardation are the main and common characteristics of many structural autosomal aberrations. The importance of cytogenetic analysis in such cases is stressed.     

Effect of heat or chemical treatment on leptospiral antigens.

The use of bacterins is one of the primary methods in the control of leptospirosis in domestic animals, especially cattle, swine, and dogs. Bacterins have been made using chemically treated or heat-inactivated organisms. Many of the initial studies indicated that the bacterins gave complete protection, whereas later reports found that some inactivation methods resulted in bacterins that protect against death but not against kidney infection and renal shedding. This raised the possibility that some of the antigens had been altered. To investigate this possibility, we heat or chemically treated Leptospira interrogans serovar icterohaemorrhagiae CF-1, L. interrogans serovar canicola Moulton, L. interrogans serovar grippotyphosa SC4397, L. interrogans serovar hardjo Hardjoprajitno, and L. interrogans serovar pomona MLS. Temperatures used to determine alterations in antigens were 50, 56, 80, 100, and 121 degrees C. The chemicals used were formaldehyde, phenol, and thimerosal. Analysis was done using Laemmli gels and Western blots. We found that heating at 50 or 56 degrees C had the smallest effect on antigens, whereas heating at 80 or 100 degrees C caused the appearance of high-molecular-weight bands on Western blots. Heating at 121 degrees C caused almost all the bands to disappear, in both the stained gel and the Western blot. Both phenol and Formalin treatment altered proteins, whereas thimerosal treatment appeared to have little effect compared with heating at 50 degrees C.