Biomedical subjects
Publications and source records attributed to R A Schmidt.
The case history is presented of a patient with a tracheal schwannoma who remains free of disease five and a half years after laser resection. This illustrates the potential of this approach in the management of tracheal schwannoma.
Preoperative evaluation of voiding patterns and detailed urodynamic evaluation before radical retropubic prostatectomy was carried out in an attempt to identify patients at higher risk of developing urinary incontinence postoperatively. Ninety-two men, mean age 64 years (range 54-72), who completed 1 year of follow-up after radical retropubic prostatectomy for clinically localized adenocarcinoma of the prostate were included in the study. According to the preoperative urodynamic findings, patients were divided into two main groups: group 1 (n = 64) patients with normal urodynamic findings, and group 2 (n = 28) patients with abnormal urodynamic findings. The latter group was further subdivided according to the abnormality: detrusor instability (n = 12), weak sphincter mechanism (n = 9), and detrusor and sphincter instability (n = 7). The degree and incidence of urinary incontinence were evaluated in both groups at the 1-year follow-up visit. There was a substantial difference in the incidence of urinary incontinence between the two main groups with only 2 patients with incontinence in group 1 (3%) versus 11 patients in group 2 (39%). In addition, the incidence of incontinence in group 2 differed depending on the type of abnormality: the lower incidence occurred in patients with detrusor instability (17%) and the higher incidence in patients with both detrusor and sphincter instability (71%). Identification of sphincteric and bladder dysfunction preoperatively may indicate a high risk of urinary incontinence after radical prostatectomy.
OBJECTIVE: Recent reports have described severe precocious pulmonary emphysema in persons who inject methylphenidate (crushed Ritalin tablets) i.v. We retrospectively evaluated the plain radiographic and CT features in 21 such patients. MATERIALS AND METHODS: The chest radiographs, available CT scans, and clinical and pathologic data were reviewed in 21 cases of i.v. Ritalin use. The patients were from 35 to 54 years old. Twelve patients were men, and nine were women. Emphysema was graded on the basis of findings on chest radiographs, by consensus, on a four-point scale as absent, mild, moderate, or severe. CT scans were available for three patients, including one imaged after a single lung transplantation. Autopsy results were available for four patients. Fixed inflated lung specimens and corresponding high-resolution CT scans were available in three cases. RESULTS: Radiographs showed pulmonary emphysema in all cases. The distribution of disease was basilar and symmetric. Small apical bullae were suggested in only one case. Basilar emphysema was rated as mild in four patients, moderate in three patients, and severe in 14 patients. In 11 patients who had serial chest radiographs, the basilar emphysema was noted to progress over a 2- to 7-year period. No evidence of progressive massive fibrosis was seen in any patient. CT scans confirmed emphysema, most severe at the lung bases. CONCLUSION: The plain radiographic and CT findings in patients who inject Ritalin are similar to those found in patients with alpha 1-antitrypsin deficiency and different from the findings seen in other types of i.v. drug use. The finding of basilar pulmonary emphysema should alert the radiologist to the possibility of i.v. injection of Ritalin.
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Transgenic mice carrying the SV40 early region fused to the Drosophila hsp70 promoter developed smooth muscle and bone neoplasms. The smooth muscle tumors appeared in aged mice and were preferentially located on the muzzle or eyelids. Multiple neoplasms were often present and each appeared to be an independent proliferation. In contrast, the bone tumors typically developed in the petrous ridge and had all the features of osteogenic sarcomas, displaying distant metastasis and invasion of the brain. Cells in both types of tumors exhibited nuclear expression of SV40 T antigen. Mice homozygous for the transgene had a shorter latency for appearance of smooth muscle tumors and developed osteosarcomas more frequently than hemizygous mice. This model system implicates the cellular T antigen-binding proteins, such as Rb and p53, in the pathogenesis of bone and soft tissue neoplasms in mice.
BACKGROUND: Preoperative chemotherapy has been advocated for the treatment of soft tissue sarcomas, yet there is little information about how these tumors respond pathologically to therapy or whether tumor response can be predicted from a pretreatment biopsy. METHODS: Biopsy was done of 25 intermediate- or high-grade soft tissue sarcomas before they were treated with three cycles of doxorubicin and cisplatin and resected. The authors compared the pathologic features of the treated tumors with clinical and radiologic evidence of response to identify the pathologic features that best reflected chemotherapeutic effect. They analyzed the pretreatment biopsy specimens by light microscopic study and flow cytometry to identify parameters that predict short-term response to chemotherapy. RESULTS: In the treated tumors, the clearest indicator of early chemotherapeutic effect was the percentage of the resected mass composed of viable neoplasm. Eleven of 25 resection specimens contained less than 15% viable neoplasm (patients with pathologic response); 9 of these had 5% or less. Flow cytometric estimates of the proliferative rate in the initial biopsy specimen predicted early chemotherapeutic effect; 7 of 10 tumors with S-phase fractions (SPF) greater than 6% responded pathologically, whereas only 3 of 12 tumors with lower SPF responded (P = 0.041). Initial tumor grade, cell type, percent tumor necrosis, mitotic rate, cellularity, and ploidy did not predict chemotherapy response. CONCLUSION: These results indicate that soft tissue sarcomas often respond dramatically to chemotherapy, that the amount of residual viable sarcoma is an indicator of short-term effect, and that flow cytometric estimates of cell proliferation predict early response to chemotherapy.
We introduce a rat model that allows simultaneous or independent recording of bladder and sphincteric activity. Via a polyethylene tube inserted into the bladder dome, bladder pressure is measured in response to constant intravesical saline perfusion. The electrical activity of the intra-abdominal urethra (a well-defined striated muscular tube which, in the rat, constitutes the external urethral sphincter) is recorded simultaneously with an electromyography needle electrode. Thus, precise statements can be made about detrusor/sphincter interrelationships. Changes in urodynamic parameters with the anesthetics urethane, methoxyflurane (Metofane), and thiobutabarbital sodium (Inactin) were investigated. High-frequency oscillations in intraluminal bladder pressure could be demonstrated during micturition cycles only in rats anesthetized with urethane or Metofane. As this high-frequency activity is generated by the striated muscle of the intra-abdominal urethra, the external sphincter of the rat is the force behind urine expulsion. The anesthetic Inactin combined with a low intravesical perfusion rate attenuated spontaneous bladder and sphincteric activity and abolished micturition cycles. This rat model can provide accurate and reproducible measurements of urodynamic changes in response to electrical stimulation of the pelvic and pudendal nerves and pharmacologic stimulation with neuropeptides at the lumbosacral spinal cord level. We recommend using this model with urethane or Metofane for physiologic studies of micturition and with Inactin for meticulous neuropharmacologic and electrostimulatory evaluation of urodynamic parameters.
The effect of pelvic plexus denervation on biochemical, morphologic and functional characteristics of the rat prostate was assessed in 11 adult Sprague-Dawley rats. Unilateral denervation was performed by removing the right pelvic ganglion from the surface of the prostate; the contralateral lobe was similarly dissected, but not denervated, to serve as a control. After 15 to 18 days, the prostate was excised and specimens from both sides were used for morphologic (light and electron microscopy) and biochemical studies (sodium-dodecylsulfate-polyacrylamide gel electrophoresis). With light microscopy, histologic features of the denervated prostate showed an overall decrease in cell height and a reduction of the clear apical area of the supranuclear region. At an ultrastructural level, denervated prostatic epithelial cells showed a slight, but significant, reduction in the number of secretory granules, a decrease in the height of the supranuclear region, and fewer and less abundantly dilated apical cisternae of endoplasmic reticulum. These changes indicate a modification of the secretory activity and reflect a change in epithelial metabolism, which was further supported by the results of SDS gel electrophoresis: the denervated prostate tissue showed an increase in the expression of 108 kDa and 80 kDa protein bands and a decrease in the expression of the 45 kDa protein band. This modification in the protein content is probably temporal and would undergo further evolution with time. The finding that denervation of the prostate causes significant morphologic and functional changes of the glandular epithelium strongly suggests that prostate function is not subject solely to the regulatory influence of the hormonal milieu. It is also dependent on the anatomical and, quite possibly functional, integrity of the nervous system.
In 4 male and 5 female cadavers we undertook a detailed anatomical dissection of the caudal segment of the spinal cord with special emphasis on the conus medullaris, length of the spinal segment and pattern of nerve bridging between adjacent sacral roots. We found an unexpectedly high incidence of intradural bridging--some of simple formation and others more complex. These interconnections were more frequent between dorsal than ventral roots but never joined dorsal to ventral roots or vice versa. Ventral S5 was missing in some cases and we found no coccygeal roots. The dural sac was seen to extend to the S1 to S2 intervertebral disk or the lower margin of S2, permitting a limited sacral laminectomy to expose the intradural sacral roots in their entirety. Towards the end of the dural sac the ventral and dorsal roots were joined by an extremely thin epineurium, and each root was composed of several lightly fused rootlets that could be separated under magnification but that combined to constitute the root nerve bundle. Our study suggests that the sacral spinal cord is neither symmetrical nor metameric. It exhibits more numerous interconnections and variations than the rest of the spinal roots, which is consistent with the greater incidence of congenital malformations affecting this segment and the varying responses found with neurostimulation.
The minimal invasiveness of laparoscopy prompted us to investigate its use for placement of electrodes for stimulation of the hypogastric nerve and the vas deferens. In an acute canine model, pressure changes in the vas deferens secondary to electrostimulation were recorded. The laparoscopic approach included four ports. Monopolar cuff electrodes were placed around the hypogastric nerve and the vas deferens, and the leads of both were pulled through the abdominal wall. After multiple percutaneous stimulations (20 mAmp., 20 Hz. and 200 microsecond pulse width), the abdomen was opened through a midline incision to check the position of the electrodes. Electrostimulation was repeated with the abdomen open. Electrostimulation of both the hypogastric nerve and vas deferens resulted in marked pressure rises in the vas. These increases were similar in response to both surface and percutaneous stimulation. We thus believe that laparoscopic implantation of electrodes followed by percutaneous preliminary stimulation of the superior hypogastric plexus or the vas deferens may be a viable future approach to anejaculation.
The purpose of the study was to examine the effects of a reduced feedback frequency on the learning of generalized motor programs and movement parameterization. Subjects practiced three movement patterns with the same relative timing and the same relative amplitude, but with varied movement time (Experiment 1) or varied movement amplitude (Experiment 2). KR was given either on 100% or 63% of the trials, with learning being assessed by retention and transfer tests. In both experiments, reduced KR frequency enhanced GMP learning but generally degraded parameter learning. These data provide converging evidence for the dissociation of the program and parameterization processes postulated in GMP theory.
RATIONALE AND OBJECTIVES: Identification of regions as possible masses on digitized screen film mammograms is an important initial step in the computerized detection of breast carcinomas. Possible masses may be initially extracted using criteria based on optical densities, geometric patterns, and asymmetries between corresponding locations in right and left mammograms. In this study, the usefulness of information arising from mammographic asymmetries for the identification of mass lesions is investigated. METHODS: Two techniques are investigated--a nonlinear bilateral-subtraction technique based on image pairs and a local gray-level thresholding technique based on single images. Detection performances obtained with the two techniques in combination with various feature-analysis techniques are evaluated using 154 pairs of mammograms and compared using free-response receiver operating characteristic (FROC) analysis. RESULTS: The nonlinear bilateral-subtraction technique performed better than the local gray-level thresholding technique. CONCLUSION: The incorporation of asymmetric information appears to be useful for computerized identification of possible masses on mammograms.
Computer-aided diagnosis (CAD) involves a computerized analysis of radiographs that is used as a "second opinion" by the radiologist. The approach presented incorporates computer vision and artificial intelligence techniques and includes schemes for the analysis of lung nodules, interstitial infiltrates, and cardiomegaly seen on chest radiographs; masses and clustered microcalcifications on mammograms; and stenoses and blood flow on angiograms. The demonstration of various CAD schemes in chest radiography and mammography on a six-monitor workstation simulates one possible clinical implementation of CAD in radiology. Whether soft- or hard-copy display media are used, the radiologist can refer to the CAD results and still use the original radiograph for the final diagnosis. Although initial impressions of this simulated "intelligent" workstation are encouraging, CAD is still in a preliminary stage of development. Various methods for effectively and efficiently integrating CAD into a clinical radiology department are being investigated.
The authors investigated the potential utility of artificial neural networks as a decision-making aid to radiologists in the analysis of mammographic data. Three-layer, feed-forward neural networks with a back-propagation algorithm were trained for the interpretation of mammograms on the basis of features extracted from mammograms by experienced radiologists. A network that used 43 image features performed well in distinguishing between benign and malignant lesions, yielding a value of 0.95 for the area under the receiver operating characteristic curve for textbook cases in a test with the round-robin method. With clinical cases, the performance of a neural network in merging 14 radiologist-extracted features of lesions to distinguish between benign and malignant lesions was found to be higher than the average performance of attending and resident radiologists alone (without the aid of a neural network). The authors conclude that such networks may provide a potentially useful tool in the mammographic decision-making task of distinguishing between benign and malignant lesions.
Transforming growth factor-alpha (TGF-alpha), a member of the epidermal growth factor (EGF) family, is a potent mitogen for several cell types. To investigate the possible role of TGF-alpha in the development of midgestation human fetal lung, we studied its distribution with immunohistochemistry and determined levels of steady-state TGF-alpha mRNA by Northern analysis of cellular RNA isolates from lung. Lung was obtained from fetuses at 10 to 22 wk of gestation (n = 14) and immunostained for TGF-alpha. TGF-alpha was localized in epithelial cells at all gestational ages examined. Immunostaining was particularly prominent in bronchiolar epithelial cells. TGF-alpha immunoreactivity was also associated with arterial smooth muscle cells, as well as with nerves. Occasional chondrocytes were also associated with TGF-alpha immunoreactivity. Total cellular RNA was isolated from lung tissue obtained from additional fetuses at gestational ages 10 to 24 wk (n = 22). TGF-alpha mRNA was present in RNA extracts of all fetal lungs studied. We conclude that TGF-alpha is probably produced in human fetal lung during mid-gestation. The prominent immunostaining of bronchiolar epithelial cells for TGF-alpha is consistent with its playing a role in distal airway formation.
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Surgical resection currently offers the best chance for cure of non-small cell lung cancer but its efficacy is limited by subsequent tumor recurrence. Even the most favorable cancers (T1N0 tumors) recur 20% to 30% of the time within 5 years and there is currently no way to anticipate precisely which tumors will recur. To test whether DNA flow cytometric study might be useful in this regard, the authors performed a retrospective case-control study of 102 tumors (51 recurrent cases and 51 controls) from a prospective registry of patients with completely resected, meticulously staged T1N0 non-small cell carcinomas. Unbiased relative hazard ratios of recurrence were estimated for ploidy and proliferative rate, as well as for tumor histologic type and clinical variables. Ploidy abnormalities were slightly more common among cases (67%) than controls (57%) but this difference was not statistically significant. Estimation of proliferative rates was possible for 85 tumors but there was no significant difference between cases and controls and proliferative rates were not prognostic of recurrence. In multivariate analyses, the observed predictive value for each of the flow cytometric parameters was modest at best and smaller than that seen for tumor histologic type. These results suggest that flow cytometric analysis has limited value in guiding management of patients with early stage non-small cell carcinoma.
Pulmonary cavitation and pneumothorax may complicate severe cases of Pneumocystis carinii pneumonia. Both complications likely result from tissue necrosis, although how such injury occurs is unknown. To investigate mechanisms of tissue destruction in P carinii pneumonia, histochemical, immunocytochemical, and electron microscopic studies were conducted in pulmonary wedge resections or autopsy specimens from patients with the acquired immunodeficiency syndrome (n = 7) or leukemia (n = 2). Tissue invasion, defined as Pneumocystis organisms in the interstitial compartment, was present in eight of nine cases. Organisms were found in alveolar septa (eight cases), pleura (six cases), and vessel walls (two cases). All cases with tissue invasion exhibited regional necrosis as well as extensive invasion of apparently viable parenchyma. Pulmonary cavitation occurred in seven of eight cases with tissue invasion, and six of these patients developed pneumothoraces. Despite extensive tissue invasion and necrosis there was little host inflammatory or stromal response. Ultrastructurally, both the tissue-invasive and intra-alveolar organisms were predominantly of the trophozoite form; they were present in much greater numbers than suggested by routine silver stains (which detect only cysts). Immunocytochemical techniques, which detect both trophozoite and cyst forms, were much more sensitive than silver stains. These results indicate that extensive tissue invasion by P carinii can occur in severe P carinii pneumonia. We hypothesize that such invasion is an important step in the development of pulmonary necrosis, cavitation, and pneumothorax.