A high-pressure liquid chromatographic method for bromide measurement is used to determine extracellular water volume in humans. The method uses 5 microL serum ultrafiltrate and has a sensitivity of 7.5 pmol. Because of the extreme sensitivity of this method, relatively small quantities of Br can be administered and small amounts of blood are needed for the analysis. By this method, the mean corrected Br space in 82 healthy adults representing a wide range of body weights was 0.218 +/- .034 L/kg (mean +/- 1 SD) with a range of 0.153-0.295 L/kg, which is consistent with reported values. There was a significant, inverse relationship between corrected Br space per kilogram and obesity as measured by body mass index. The corrected Br space in six children aged 3-36 mo was 0.335-0.394 L/kg, which is also consistent with reported values in children of this age. This method for Br measurement can easily and readily be applied for the determination of extracellular water volume.
The hematological status of 81 infants with Down syndrome was reviewed retrospectively. Twenty babies had no hematological evaluation, 33 had a normal hematological status, and 28 had at least one abnormality, either of hematocrit, white cell count, or platelet count. Among these were 18 babies with increased hematocrit, one with decreased hematocrit, four with decreased platelet count, one with increased white cell count, three with increased hematocrit and decreased platelet count, and one with increased platelet count and increased white cell count. Some of these babies were evaluated for neoplasia or sepsis; however, in all the abnormal blood findings disappeared by 3 weeks without evidence of malignancy or infection. We conclude that hematological abnormalities with a benign natural history are common in Down syndrome infants.
The acetylator phenotype of 26 bladder cancer patients and 26 controls was determined by the sulfamethazine method to evaluate whether patients with the slow acetylator phenotype have a greater susceptibility for bladder cancer. This hypothesis has been suggested by experimental animal and human epidemiological observations. Of the 26 bladder cancer patients 12 (46 per cent) had the slow acetylator phenotype compared to 18 of 26 controls (69 per cent). Within the bladder cancer group there was no striking excess of the slow acetylator phenotype when subgrouped by occupational and smoking history. Our results show no significant association between the slow acetylator phenotype and human bladder cancer.
DNA slit-scan flow cytometry was used to analyze 150 bladder irrigation specimens from 83 patients. Specimens were categorized into groups based on cystoscopy, histology, and cytopathology. Cells were stained for DNA with propidium iodide using a whole cell protocol. Nonspecific fluorescence in the cytoplasm of some urothelial cells together with differential DNA staining of cell types in certain specimens was noted. DNA frequency distributions were analyzed using a semi-automated technique. Data were gated using slit-scan morphological features to remove cellular debris, multiple nuclei, and cells exhibiting nonspecific cytoplasmic fluorescence. Specimens were classified abnormal if they were aneuploid or had a hyperdiploid fraction (HDF) greater than 8%. The sensitivity to abnormality was 89% for grade 3 transitional cell carcinoma (TCC), 70% for grade 2 TCC, and 67% for grade 1 TCC. Specificity was 61%. Specimen data were then reprocessedusing slit-scan morphological features to enrich for urothelial cells. The urothelial cells were identified by the ratio of nuclear diameter to cell diameter. This method was found to be in good agreement with immunofluorescent labeling of urothelial cells using the urothelium-selective T16 monoclonal antibody. The sensitivity to abnormality remained 89% for grade 3 TCC and 70% for grade 2 TCC, but fell to 52% for grade 1 TCC. Specificity for the urothelial cell enriched data increased to 77%. Reprocessing of data to enrich for urothelial elements resulted in 16 fewer specimens with an aneuploid DNA distribution and 2 fewer specimens with increased HDF. These data illustrate the necessity for recognition of urothelial cells in the flow analysis of unfixed bladder irrigation specimens stained with propidium iodide using a whole cell technique. Differential staining of blood and urothelial cells can mimic aneuploidy or contribute to an increased hyperdiploid fraction. These may result in the specimen being classified as abnormal if they are not recognized as such.
The influence of phenytoin on theophylline elimination was studied in six healthy, nonsmoking subjects who were not taking any other drugs. Subjects were given an intravenous infusion of theophylline (aminophylline), 5 mg/kg, and several blood specimens were drawn over the following 24 hr for theophylline concentration determination. Subjects then began a 2-wk course on oral phenytoin, 300 mg/day, and on day 15 were again challenged with theophylline. For each subject theophylline clearance (ClT) was greater when taking phenytoin (range 31% to 65%). Mean ClT of the six subjects was 45% greater when taking phenytoin than when not taking phenytoin. In one subject, 24-hr urine collections were obtained in the untreated and treated state for analysis of theophylline metabolites. These results showed a general increase in excretion for each of the three major theophylline metabolites in the phenytoin pretreated state compared to the control state. Results indicate that phenytoin increases theophylline elimination. Patients taking phenytoin may require larger theophylline doses than recommended to achieve therapeutic blood theophylline concentrations.
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