Biomedical subjects
Publications and source records attributed to A E Anderson.
Blind-ending ureteral duplication is a rare anomaly. The authors report on a 5-year-old girl who presented with an asymptomatic abdominal mass in which computerized axial tomography was used to make the diagnosis. The embryology of this anomaly is reviewed.
Studies were undertaken to compare tetanus toxin-induced electrographic and behavioral seizure activity in immature and adult rats. Multifocal epileptiform activity was induced by unilateral hippocampal injection of tetanus toxin in 10-day-old immature and in 90-120-day-old adult rats. Bilateral cortical surface electrodes and, in some animals, hippocampal depth electrodes were placed and serial video EEG was recorded for 2 h during the week following tetanus toxin injection. Tetanus toxin-induced interictal spike frequency was significantly higher and seizure duration was significantly longer in immature compared to adult rats. Immature rats tended to have more frequent seizures compared with adults, but the difference was not statistically significant. Ictal behaviors were different for the two groups with immature rats commonly demonstrating wild running seizures which were not seen in adult rats. These findings suggest that there are age-dependent differences in electrographic and behavioral seizure expression in the tetanus toxin seizure model and that the epileptic syndrome in immature rats is more severe.
Very low birth weight (n = 154) and term infants (n = 119) had neurologic and developmental assessment at 6 and 12 months of age. Preterm infants with severe neonatal complications were considered to be at high risk, and those with milder complications were considered to be at low risk, for neurodevelopmental abnormality. Compared to term infants, high- and low-risk infants had abnormalities at 6 months in total neurologic score, cranial nerves, motor tone, motor coordination, and reflexes (P < .001). At 12 months, all groups had improved. However, high-risk infants had persistent abnormalities in the same subcategories (P < .001), whereas low-risk infants differed from term infants only in motor tone (P < .001). Bayley developmental scores were different for all groups at 6 months (P < .001), but at 12 months only high-risk infants differed from term infants (P < .01). These results demonstrate improvement in neurologic and developmental scores over time in very low birth weight infants. The degree of neurodevelopmental abnormality and improvement over time is related to severity of neonatal complications in preterm infants.
An in vivo model for the study of human transitional cell carcinoma (TCC) in the urinary tract is desirable. Orthotopic xenografts are useful in order to approximate better the behavior of human tumor cells in situ. Prior models have been described in the urinary bladder of the nude mouse and rat. We have developed the first model of implantation of human TCC in the upper urinary tract of an experimental animal. The kidneys of homozygous nude rats 4 weeks of age were inoculated with 1-5 x 10(6) cells of the RT4 well-differentiated papillary human TCC line through bilateral flank incisions, with transparenchymal injection of tumor cells into either the collecting system (renal pelvis) or the parenchyma. The overall implantation rate was 92% (54/59 kidneys). However, implantation into the collecting system occurred in only 45% (18/45) of the group. Ligation of the ureter prior to inoculation to produce urine stasis improved the mucosal implantation rate. Despite suspect urine cytology findings in the renal pelvis injection group, no distal seeding of the urinary tract was seen. Intraparenchymal tumor growth was less differentiated and had a higher fraction of mitotic cells than mucosal tumors. Vascular and lymphatic invasion were commonly seen; however, distant metastasis was not observed. This model will prove useful in determining the role of seeding in recurrent disease and in developing less invasive modalities for the treatment of upper tract TCC.
PURPOSE: An in vivo tumor model for the study of human urothelial carcinoma is desirable. Orthotopic xenografts are useful in order to better approximate human tumor cell behavior in situ. A prior model has been described in the nude mouse. However, its small bladder size limits both histologic characterization and the application of intravesical therapeutics. In the absence of preirradiation, orthotopic xenografts of human transitional cell carcinoma in the nude rat has not been previously reported. MATERIALS AND METHODS: Nude rats 2 to 4 weeks of age were inoculated with 1-5 x 10(6) cells of RT4 (well differentiated papillary human bladder tumor cell line). Inoculation was performed via open cystotomy. Techniques of mucosal injury including acid treatment and cautery were explored in an effort to optimize tumor implantation and growth. Animals were sacrificed at varying intervals and histologic assessment was performed. RESULTS: The overall rate of tumor implantation and growth was 93.4% (57 of 61). Tumors reliably grew within the muscularis and mucosal growth was seen as well. Intramuscular tumor growth was less differentiated and had a higher fraction of mitotic cells than mucosal tumor. Tumor growth was consistently seen as early as 2 weeks after inoculation which facilitates experimental trials. Distant metastasis was not observed. Mucosal injury did not increase the rate of tumor implantation. CONCLUSION: This model is highly reproducible and will prove useful in the further study of bladder cancer progression as well as in the development of therapeutic modalities for both superficial and muscle invasive bladder carcinoma.
Dissemination of coccidioidomycosis is rare. The skin, musculoskeletal system, and central nervous system have been described as the most common sites of extrapulmonary disease. We present a case of an asymptomatic patient in whom the diagnosis of coccidioidomycosis was made on a lymph node biopsy. The biopsy was performed because of an abnormal mammogram and physical findings suggestive of malignancy.
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Bladder tumors respond to cisplatin-based chemotherapy in 68% of cases, but only 30% will have a durable response. Recent studies have suggested that ras point mutations may produce cisplatin drug resistance in cell lines. To determine the role of ras point mutations in human tumors resistant to cisplatin, we evaluated ten tumors exposed to cisplatin and eight untreated bladder tumors for ras point mutations. Using polymerase chain reaction DNA amplification and allele-specific oligo-hybridization, we found that only one of the ten treated tumors and none of the untreated tumors harbored a ras point mutation. We conclude that ras point mutations occur infrequently in untreated bladder tumors and do not appear to correlate with cisplatin drug resistance in vivo.
The preceding paragraphs describe several uses of specific antibodies to IL-1. Standard radioimmunoassays and ELISA procedures were developed with demonstrated utility in studies attempting to quantitate the cytokine in cell culture fluids. In part, antibody-based assays circumvent the problems associated with bioassays. Bioassays are difficult to perform, often lack specificity due to the presence of competing cytokines and are insensitive when used with complex biological fluids due to non-specific protein binding and the presence of IL-1 antagonists. Thus, bioassays have not been broadly applicable with specimens in a clinical setting. In contrast, monoclonal antibodies and polyclonal antisera have provided a means of identifying functionally important regions of the IL-1 molecule, monitoring the post-translational processing of IL-1 which may include biologically inactive moieties, and developing new assays as illustrated by cell blot procedures.
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Until recently, cytogenetic detection of the Philadelphia chromosome (Ph) was the only reliable test to diagnose chronic myelogenous leukemia (CML) and detect minimal disease or early relapse following treatment. However, the recently developed ability to detect the Ph chromosome as a rearrangement in the bcr gene of chromosome 22 permits identification of the leukemic clone comprising as little as 5% of the cell population. We present results of simultaneous cytogenetic and DNA rearrangement studies in 28 CML patients considered for or treated with bone marrow transplantation. Our results show that the molecular method is significantly more sensitive than the cytogenetic method in the detection of minimal disease Ph-positive clones.
In an endeavor to delineate an alveolar configuration that would reasonably mirror the natural state, polygonal shapes of normal alveoli were tabulated in histological sections from inflation-fixed specimens of 16 men aged 16-48 years. The resulting alveolar population varied from three- to ten-sided polygons with a preponderance of tetragons, pentagons, and hexagons. These observations were compared with the possible combinations of polygonal sections through various polyhedral models proposed by other workers and the five classical regular polyhedrons. The potential types of sections through the regular dodecahedron, i.e., a twelve-sided shape with faces consisting of pentagons, seemed to fit best with present findings, and this is suggested as an idealized configuration that might be useful in various geometric determinations, e.g., estimates of alveolar surface area and volume.
We evaluated the clinical and metabolic effects of a new triphasic regimen developed in the continuing attempt to reduce the dose of estrogen and progestogen in oral contraceptives. A combination of ethinyl estradiol (EE) and levonorgestrel (LNg) was used (six tablets with 30 micrograms EE + 50 micrograms LNg, five tablets with 40 micrograms EE + 75 micrograms LNg, and 10 tablets with 30 micrograms EE + 125 micrograms LNg), also known as Triphasil (Wyeth). In a private practice, 409 subjects participated in 7,286 treatment cycles. Three pregnancies occurred, all due to subject failure. Menstrual regulation was excellent and the incidence of side effects extremely low. Withdrawals from the study for possibly drug-related medical reasons totaled 9.0% through 56 cycles of treatment. Metabolic changes also were evaluated in 14 of these women over a 6-month period. The only statistically significant increase in carbohydrate values occurred at 6 months. The mean glucose level at 30 minutes of the oral glucose tolerance test was above the baseline mean value, but serum insulin levels showed no statistically significant deviation. Lipid values presented are total lipids, total cholesterol, triglycerides, alpha-, beta-, and pre-beta-lipoproteins, and high density and low density lipoprotein cholesterol. There was no statistically significant difference between the mean values at baseline and those during treatment for any lipid variable. These results indicate that this triphasic oral contraceptive has a high degree of efficacy, a low incidence of side effects, excellent cycle control, and high subject compliance, and would seem to indicate a minimal influence on the metabolism of lipids and carbohydrates in the small number of subjects studied.
Radial keratotomy surgery was first performed in the United States in 1978. Although all the questions regarding surgical flattening of the cornea have not been answered, a great deal of what happens is understood. Currently, eight factors are noted either pre- or intraoperatively which appear to have a correlation with the outcome of the surgery. These factors along with a discussion of available surgical procedures and the most common intra- and postoperative complications, both normal and abnormal, are discussed.
A 66-year-old man developed fever, chills, myalgias, three erythematous skin lesions, and transient left eyelid lag. Because of persistent fever, he was hospitalized 4 weeks after the onset of disease; a peripheral blood smear showed Babesia microti in 3% of his erythrocytes. Eighteen hours later, he died unexpectedly. Autopsy showed pancarditis with a diffuse lymphoplasmacytic infiltrate, and spirochetes were found in the myocardium. Antibody titers to both the Lyme disease spirochete Borrelia burgdorferi and Babesia microti were elevated. The finding of spirochetes in the myocardium and the elevated antibody titers to Borrelia burgdorferi suggest that the patient died from cardiac involvement of Lyme disease.
To elucidate interrelations of airway inflammation and emphysema, bronchi from subjects with severe panlobular and centrilobular disease and normal lungs were compared. This disclosed an intense infiltration with chronic inflammatory cells, mucous gland hypertrophy, and thickening of bronchi, primarily in association with emphysema having a panlobular configuration. These changes complement a generalized thickening and inflammation of nonrespiratory bronchioles previously observed in these cases. We conclude that the panlobular pattern may be a close function of inflammatory thickening of the conductive airways to respective lungs and lung parts, but centrilobular emphysema is not reliant on these changes. The precursory defect for the centrilobular lesion instead has been shown to be a more peripherally oriented respiratory bronchiolitis around the centers of lobules.
Histological measurements in cases of severe paniobular and centrilobular emphysema and in normal lungs disclosed a generalized thickening of the walls of small airways in the panlobular group. With mathematical models, this was depicted as a potential basis for airway closure at higher than normal lung volumes and trapping of air. Lungs with mixtures of panlobular and centrilobular emphysema predominate in the general population, and the obstructive component of airways in this setting is likely a net result of multiple lesions. These may be common in varying degrees to both varieties of disease but especially characteristic of one form. Bronchiolar thickening is one such general process. Present findings suggest that this is prone to be linked to emphysema with a panlobular pattern.
1 During chronic treatment of hypertensive patients observed mean steady-state plasma labetalol levels in ten patients were consistently and significantly higher than predicted from initial acute pharmacokinetic analysis. 2 Mean steady-state levels varied from 36 to 183 ng/ml on a chronic dose of 200 mg twice daily. 3 Patients with lower steady-state levels on a fixed dose of labetalol usually required higher maintenance doses to control blood pressure.