Biomedical subjects
Publications and source records attributed to D Buss.
We describe a case of T-cell acute lymphoblastic lymphoma/leukemia with trisomy 5 as the sole cytogenetic anomaly. This is only the second such case reported in acute lymphoblastic leukemia (ALL). A review of this rare abnormality and the associated clinical features is presented.
Radiation and pagetic osteogenic sarcomas should be distinguished from classical osteogenic sarcoma. Both occur in older patients with significantly greater comorbidity. Roentgenographically, radiation osteogenic sarcoma is typically sclerotic, whereas pagetic osteogenic sarcoma is lytic and associated with pathologic fracture. Radical resections give the best result, local control, and survival. Chemotherapy has not proven effective to date. Improvements in tumor imaging and more intensive chemotherapy regimens may permit limb-sparing surgery. Overall results remain poor, with approximately 15% five-year survival in each condition.
Characterization of breast cancer cells by histology, flow cytometry, and steroid receptors was performed on 197 Stage II breast node positive cancer patients given adjuvant chemotherapy, plus tamoxifen for patients with positive hormone receptors. Histologic and steroid receptor assays were performed using standard techniques; flow cytometric analysis was performed from paraffin-embedded blocks obtained from the primary tumor. Quality control studies on reproducibility, tissue heterogeneity, and analysis procedures have been included. Of the 197 patients studied, aneuploidy was found in 102 (52%); the median %S value was 8% with a range of 0.4% to 38%. Our results demonstrated that number of positive nodes, receptor status, and grade were of prognostic value. Cell cycle kinetic data were not of independent prognostic value in this series. However, ploidy could differentiate in prognosis in the receptor-negative subgroup. Patients with receptor-negative tumors had a significantly better overall survival if the tumor was diploid in nature. Cell kinetics was not significantly prognostic for either receptor subgroup, although patients with higher %S tended to have better relapse-free and overall survival. This is in disagreement with other studies and may demonstrate that treatment has confounded our results and diminished the ability of flow cytometry data to help predict outcome.
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The purpose of this technical report is to determine the reproducibility of flow cytometry data for ploidy and cell cycle kinetics using paraffin-embedded blocks of breast cancer tissue. One block from each of 39 tumors was studied in this report with each block having multiple sections analyzed independently. All of these sections gave ploidy analyses, while only 34 gave cell kinetic values. The standard deviation for the DNA index value in the multiple analysis study was less than 0.1 in all but three cases. The cell kinetic values gave larger variability, and the actual values were dependent on the method of analysis. Comparison of the variability for each method of analysis could not predict which procedure was superior. These results would indicate that ploidy is a reproducible value, while cell kinetic parameters should only be used as an indicator of proliferative activity that has been normalized to the mean or median of a large set of observations processed and analyzed by the same procedure.
Total plasma and mixed stimulated saliva theophylline concentrations (by high performance liquid chromatography) and free plasma theophylline concentrations (by equilibrium dialysis) were measured in simultaneously collected samples from 32 outpatients receiving chronic oral theophylline treatment, who had received the drug at least two hours before sampling. There was a close relationship between saliva and total plasma theophylline concentration and between total saliva and free plasma concentration. The mean saliva to total plasma drug concentration ratio was 0.69 (SE 0.09) and the mean difference between paired saliva and free plasma concentration was 0.65 (0.17) microgram/ml. It is concluded that stimulated mixed saliva provides a simple, non-invasive method of assessing total (and free) plasma theophylline concentrations during chronic oral treatment. The therapeutic range for saliva, corresponding to the generally accepted total plasma concentration range (10-20 micrograms/ml), is approximately 7-14 micrograms/ml.
It has been suggested that the variability in clinical response between individuals at any given total plasma theophylline concentration may be related to interpatient variability in theophylline plasma protein binding. We therefore measured the plasma protein binding of theophylline in plasma from 39 outpatients with chronic airflow obstruction who were receiving long term oral theophylline treatment. The protein binding was measured at 37 degrees C and pH 7.4 by equilibrium dialysis. Total plasma theophylline concentration was measured by high performance liquid chromatography and the free concentration calculated by multiplying total concentration by the free (unbound) fraction. The total plasma theophylline concentration varied from 0.7 to 22.0 micrograms/ml, mean 10.6 (SD 5.3) micrograms/ml (3.9-121 mumol/l, mean 58.3 (29.2) mumol/l). The free fraction of theophylline varied only from 0.58 to 0.69 (mean 0.626 (0.024] microgram/ml and was not related to the total concentration (r = -0.236, n = 39, p greater than 0.05). There was a very close relationship between free and total plasma concentrations (r = 0.996, n = 39, p less than 0.001). It is concluded that there is little variability in plasma protein binding of theophylline in patients with chronic airflow obstruction. Other factors appear to be responsible for variability between individuals in the response to a given total plasma theophylline concentration.
1 The plasma protein binding of theophylline was determined after addition of [14C]-theophylline (15 micrograms/ml) to plasma from 24 healthy drug-free volunteers and equilibrium dialysis for 2 h at 37 degrees C. 2 The percentage of drug unbound was 60.0% +/- 2.2% (s.d.) with very little variation between individuals. The binding ratio of theophylline was not significantly related to the plasma albumin or alpha 1-acid glycoprotein (AAG) concentrations but was significantly, although weakly, negatively related to the logarithm of the non-esterified fatty acid concentration (NEFA) (r = 0.443, P less than 0.05). 3 Intravenous administration of heparin (1000 units) caused a significant rise in plasma NEFA concentration and in the percentage of drug unbound in plasma after equilibrium dialysis. 4 In human serum albumin solutions, the binding ratio of theophylline was significantly related to the albumin concentration and at the albumin concentration seen in the 24 normal subjects, the percentage of drug unbound was almost identical. Addition of AAG in physiological concentrations did not enhance theophylline binding but oleic acid, and to a lesser extent palmitic acid, reduced binding significantly. 5 The percentage of theophylline unbound in plasma varied markedly with pH so that at pH7 the percentage unbound was 52% greater than at pH 8. There was no evidence of concentration dependence of binding up to 140 micrograms/ml theophylline. 6 Theophylline appears to bind almost exclusively to albumin and its plasma protein binding varies little in healthy subjects, showing no concentration-dependence over the therapeutic range of concentrations. The binding is affected by pH and by NEFA concentration, however, and these factors may be of greater importance in disease states. Caution should be employed in the use of heparin in studies of plasma protein binding of theophylline.
UNLABELLED: In order to determine the effect of subfracture loads on articular cartilage, we impacted twelve adult canine patellofemoral joints utilizing a drop-tower with two different force-levels. The joints were examined with light and electron microscopy at two, four, and six weeks after impaction. In ten additional animals a single knee was impacted and they were analyzed biochemically at similar time-periods, using the contralateral joint as a control. In all impacted specimens changes were observed in the zone of calcified cartilage, represented by an increase in cellular clones, vascular invasion, and proteoglycan content of the matrix. Ultrastructural evaluation of the superficial and deep radial zones of the articular cartilage revealed loss of the cellular processes and territorial matrices of chondrocytes in both layers. Ruthenium-red staining of impacted samples revealed a 40 per cent decrease in proteoglycan associated with collagen fibers in the extraterritorial matrix. An increase in collagen-fiber width was observed in the four and six-week groups. The earliest changes in articular cartilage included activation of the zone of calcified cartilage as well as ultrastructural alterations in the superficial and radial zones. Biochemical analysis revealed an increase in water content and hexuronic acid at two weeks. These changes occurred at a subfracture level in the absence of surface disruption. CLINICAL RELEVANCE: These animal experiments indicate that adult articular cartilage may show significant alterations in its histological, biochemical, and ultrastructural characteristics without disruption of the articular surface. This model of articular cartilage "contusion" may represent a corollary to the joint damage that is observed following direct blunt trauma transmitted across articular surfaces without radiographic evidence of fracture. The possibility that this form of injury may be the precursor of chondromalacic changes in patellar or femoral cartilage merits further study.
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Circadian rhythms of body temperatures, pulse rate, and respiration rate were measured in 11 subjects every 4 h during certain periods on two submarine patrols. Data on systolic and diastolic blood pressure were also obtained on five crew members during the first period. All the subjects of the first patrol were on an 18-h watch schedule (6 h on, 12 h off). During the second patrol, three subjects were on an 18-h watch schedule and three were on a 24-h watch schedule. Cosinor analysis for positive (P less than 0.05) detection of rhythm demonstrated that all subjects on the 18-h watch schedule developed 18-h cycles of body temperature, pulse rate, respiration rate, and systolic and diastolic blood pressure, which were then superimposed on the persisting 24-h cycles of the same function. The three subjects on a 24-h watch schedule did not show the 18-h cycles. Moreover, additional 12-, 36-, and 48-h cycles (harmonics and subharmonics of 24-h cycles) were found in all subjects on both patrols, attesting to the disintegration of circadian cycles under these conditions. Average sleep time tended to decrease toward the end of the patrol.
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