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Biomedical subjects

W H Warren

Publications and source records attributed to W H Warren.

At least 55 records · Page 3Linked to original sources

The role of central and peripheral vision in perceiving the direction of self-motion.

Three experiments were performed to examine the role that central and peripheral vision play in the perception of the direction of translational self-motion, or heading, from optical flow. When the focus of radial outflow was in central vision, heading accuracy was slightly higher with central circular displays (10 degrees-25 degrees diameter) than with peripheral annular displays (40 degrees diameter), indicating that central vision is somewhat more sensitive to this information. Performance dropped rapidly as the eccentricity of the focus of outflow increased, indicating that the periphery does not accurately extract radial flow patterns. Together with recent research on vection and postural adjustments, these results contradict the peripheral dominance hypothesis that peripheral vision is specialized for perception of self-motion. We propose a functional sensitivity hypothesis--that self-motion is perceived on the basis of optical information rather than the retinal locus of stimulation, but that central and peripheral vision are differentially sensitive to the information characteristic of each retinal region.

Adult↗

Flow cytometric DNA content analysis in neuroendocrine carcinoma of the lung. Correlation with survival and histologic subtype.

The DNA content of 53 primary and locally metastatic pulmonary neuroendocrine carcinomas was retrospectively determined by flow cytometric analysis of nuclei released from paraffin-embedded tissues and compared with histologic subtypes and clinical survival. Forty-one percent (9 of 22) of tumors classified as well-differentiated neuroendocrine carcinoma (WDNC) were aneuploid. In contrast, 85% (17 of 20) of small cell neuroendocrine carcinoma (SCNC), and 73% (8 of 11) of intermediate cell neuroendocrine carcinoma (ICNC) were aneuploid. DNA content was not a significant independent predictor of patient survival within each histologic subtype (P greater than 0.05 for all subtypes). Yet, when all cases were examined as a single group, diploid cases showed better clinical survival than cases with DNA aneuploidy (P less than 0.02). However, the survival advantage for diploid DNA content did not quite achieve statistical significance when only cases of limited stage disease were analyzed (0.10 greater than P greater than 0.05). Histologic subtype was also a prognostic indicator, with WDNC cases showing a significantly longer survival than either SCNC (P less than 0.05) or ICNC (P less than 0.02), for those cases with limited-stage disease. These results indicate information on clinical staging and the histologic subtype are important parameters to compare with DNA content analysis in determining independent prognostic factors in neuroendocrine or small cell carcinoma of the lung.

Adult↗

On the sufficiency of the velocity field for perception of heading.

All models of self-motion from optical flow assume the instantaneous velocity field as input. We tested this assumption for human observers using random-dot displays that simulated translational and circular paths of movement by manipulating the lifetime and displacement of individual dots. For translational movement, observers were equally accurate in judging direction of heading from a "velocity field" with a two-frame dot life and a "direction field" in which the magnitudes of displacement were randomized while the radial pattern of directions was preserved, but at chance with a "speed field" in which the directions were randomized, preserving only magnitude. Accuracy declined with increasing noise in vector directions, but remained below 2.6 degrees with a 90 degrees noise envelope. Thus, the visual system uses the radial morphology of vector directions to determine translational heading and can tolerate large amounts of noise in this pattern. For circular movement, observers were equally accurate with a 2-frame "velocity field", 3-frame "acceleration" displays, and 2-frame and 3-frame "direction fields", consistent with the use of the pattern of vector directions to locate the center of rotation. The results indicate that successive independent velocity fields are sufficient for perception of translational and circular heading.

Humans↗

Bronchopleural fistula after stapled closure of bronchus.

The incidence of bronchopleural fistula after stapling among 2,243 pulmonary resections at the Rush-Presbyterian-St. Luke's Medical Center has been reviewed. There were 35 fistulas in 1,773 stapled and in 470 sutured bronchi (segmentectomy, 2; lobectomy, 1; bilobectomy, 9; and pneumonectomy, 23). We have found that the stapler is expedient and simple to use, and that it produces a hermetic and uniform closure. The stapler is contraindicated when the bronchus is thickened, inflamed, or of insufficient length. The overall incidence of bronchopleural fistula was 1.6%. Approximately two thirds of the patients with bronchopleural fistula had preoperative radiation therapy or chemotherapy or both.

Bronchial Fistula↗

Perception of circular heading from optical flow.

Observers viewed random-dot optical flow displays that simulated self-motion on a circular path and judged whether they would pass to the right or left of a target at 16 m. Two dots in two frames are theoretically sufficient to specify circular heading if the orientation of the rotation axis is known. Heading accuracies were better than 1.5 degrees with a ground surface, wall surface, and 3D cloud of dots, and were constant over densities down to 2 dots, consistent with the theory. However, there was an inverse relation between the radius of the observer's path and constant heading error, such that at small radii observers reported heading 3 degrees to the outside of the actual path with the ground and to the inside with the wall and cloud. This may be an artifact of a small display screen.

Adult↗

Neuroendocrine differentiation and prognosis of extrahepatic biliary tract carcinomas.

From 1980 to 1987, 35 patients underwent exploratory surgery for carcinomas of the extrahepatic biliary tract (EBT). Samples from 28 of these tumors (15 gallbladder, 13 bile duct) were assessed by immunohistochemical analysis for exocrine and/or neuroendocrine differentiation. Seven patients were excluded from the study because of insufficient available specimen or loss to follow-up. Paraffin sections were immunostained for neuroendocrine differentiation markers: neuron-specific enolase (NSE), chromogranin-A, synaptophysin, serotonin, somatostatin, substance-P, and glucagon. Additional sections were also stained with monoclonal antibody A-80 that recognizes a glycoprotein related to exocrine differentiation. The tumors were reclassified on the basis of immunophenotyping data: (I) pure exocrine carcinoma (n = 8); (II) predominantly exocrine carcinoma with occasional neuroendocrine cells (n = 9); (III) mixed exocrine-neuroendocrine carcinoma (n = 4); (IV) pure neuroendocrine (n = 2); and (V) predominantly neuroendocrine with occasional exocrine cells (n = 5). Survival time among the two pure neuroendocrine (group IV) and five predominantly neuroendocrine carcinomas (group V) was significantly less than the survival time of patients from the other groups (2.6 +/- 2.2 months vs 13.5 +/- 12.3 months; p = 0.015). No difference was noted between groups in extent of disease, treatment rendered, or location of tumor (bile duct vs gallbladder). This study indicates that (1) the incidence of neuroendocrine differentiation in cancers of the EBT is higher than generally recognized, (2) carcinomas of the EBT may be phenotypically reclassified on the basis of immunohistochemical analysis, and (3) the presence of pure or predominant neuroendocrine differentiation in carcinomas of the EBT is associated with shorter survival time than carcinomas with pure or predominant exocrine differentiation (or mixed exocrine and neuroendocrine factors).

Biliary Tract Neoplasms↗

Reevaluation of pulmonary neoplasms resected as small cell carcinomas. Significance of distinguishing between well-differentiated and small cell neuroendocrine carcinomas.

The clinicopathologic features of 50 cases of surgically resected small cell carcinoma were reevaluated (doubly blinded). Two pulmonary carcinomas were excluded because neuroendocrine features could not be demonstrated; two additional cases also were excluded because the tumors grossly invaded the chest wall and their pulmonary origin was not substantiated. Thirty-four tumors were confirmed to be small cell neuroendocrine carcinoma (SCNC). Only seven of 11 (64%) patients with T1N0,T2N0 tumors survived more than 1 year; one of 11 (9%) patients survived more than 2 years. In 12 cases, the diagnosis was changed to well-differentiated neuroendocrine carcinoma (WDNC). Of these, nine of nine (100%) patients with T1N0,T2N0 tumors survived more than 1 year; six of eight (75%) patients survived more than 2 years. These observations strongly indicate that a significant number of long-term survivors with the diagnosis of small cell carcinoma may, in fact, have a distinctly less aggressive type of pulmonary neuroendocrine carcinoma. It was concluded that the distinction between small cell and well-differentiated types of neuroendocrine carcinomas has significant prognostic and therapeutic implications.

Adult↗

Immunohistochemical analysis of pulmonary and pleural neoplasms with monoclonal antibodies B72.3 and CSLEX-1.

Sequential paraffin sections of 222 epithelial lung tumors comprising all common histologic types, and 31 pleural mesotheliomas of all variants were immunostained with monoclonal antibodies (Mabs) B72.3 and CSLEX-1. Reactivity with Mabs B72.3 and CSLEX-1 respectively was noted in 7/57 and 4/57 squamous carcinomas, in 44/70 and 60/70 adenocarcinomas, 9/16 and 11/16 bronchioloalveolar carcinomas, 8/25 and 14/25 large cell undifferentiated carcinomas, 3/3 and 3/3 adenosquamous carcinomas, 0/11 and 0/11 carcinoids, 0/10 and 2/10 well differentiated neuroendocrine (NE) carcinomas, 4/13 and 5/13 intermediate cell NE carcinomas, 0/17 and 0/17 small cell NE carcinomas, and 0/31 and 1/31 mesotheliomas. In most instances, both Mabs stained the same tumors; however, reactivity with CSLEX-1 was more intense and extensive, and involved more cases. Therefore, regardless of conventional histologic type, staining with Mabs B72.3 and CSLEX-1 defines 4 subsets of lung tumors: one expressing both antigens, two expressing one but not the other, and one expressing neither. The possible biological and/or clinical significance of these subsets remains undetermined. When correlated with conventional histologic tumor types, our findings indicate: 1). both of these Mabs recognize most but not all adenocarcinomas and bronchioloalveolar carcinomas, and since CSLEX-1 stained more cases than B72.3, it may be argued that the former is a broader exocrine phenotype marker than the latter; 2). both of these Mabs select exocrine subsets of large cell undifferentiated carcinomas; 3). both of these Mabs stain exocrine cell subpopulations in well differentiated and intermediate cell NE carcinomas but not in carcinoids or small cell NE carcinomas, and 4). except for rare cases, neither B72.3 nor CSLEX-1 reacts with mesotheliomas regardless of variant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

Superior vena caval reconstruction using autologous pericardium.

Tumor involvement of the superior vena cava can occur either by direct extension of the primary tumor or by invasion of superior mediastinal lymph nodes. Removal of a portion of the caval wall may be required to allow adequate margins of resection. The technique described involves placement of an intraluminal shunt and resection of the involved caval wall with reconstruction using autologous pericardium.

Adult↗

Surgical management of pulmonary metastatic leiomyosarcoma with gross endobronchial extension.

Metastatic leiomyosarcoma occasionally is seen with gross endobronchial extension without invasion of the bronchial wall. These patients have major airway obstruction and partial or total atelectasis of the lung. Precise bronchoscopic assessment coupled with intraoperative bronchotomy allows the surgeon to determine the origin of the tumor and to save uninvolved pulmonary parenchyma. Our experience with 4 such patients illustrates the possibility of saving lung tissue despite total bronchial obstruction.

Adult↗

Malignant cells of epithelial phenotype limited to thoracic lymph nodes.

Asymptomatic thoracic lymphadenopathy was incidentally discovered in three patients with no definitive diagnoses. Enlarged lymph nodes, removed at thoracotomy, had irregularly distributed, pleomorphic, malignant-appearing cells. Mitoses were frequent. Electron microscopy showed tonofilament bundles and desmosomes. By immunocytochemistry, these cells uniformly expressed desmoplakin and cytokeratins 8 and 18 and various patterns of coexpression with other cytokeratins. One patient had lymphadenectomy, segmental lung resection and radiotherapy; the second had lymphadenectomy and later a lymphadenectomy with pneumonectomy; and the third had lymphadenectomy and radiotherapy. Neoplastic cells were detected exclusively within thoracic lymph nodes. The patients are well 111, 39 and 13 months after initial presentation. The clinical course and the patterns of intranodal distribution and marker expression of the neoplastic cells are unusual and distinct from most carcinomas metastatic to lymph nodes and reminiscent of "lymphoepithelioma-like carcinomas" described in the thymus and other sites. While the malignant cells may reflect metastases from as yet occult primaries or malignantly transformed ectopic epithelial nests, these tumours may arise by transformation from the cytokeratin-positive "extrafollicular reticulum cells" indigenous to lymphoid organs.

Adult↗

Eye movements and optical flow.

Translation of an observer through a static environment generates a pattern of optical flow that specifies the direction of self-motion, but the retinal flow pattern is confounded by pursuit eye movements. How does the visual system decompose the translational and rotational components of flow to determine heading? It is shown that observers can perceive their direction of self-motion during stationary fixations and pursuit eye movements and with displays that simulate the optical effects of eye movements. Results indicate that the visual system can perform the decomposition with both continuous and discontinuous fields on the basis of flow-field information alone but requires a three-dimensional environmental structure to do so. The findings are inconsistent with general computational models and theories based on the maximum of divergence, oculomotor signals, or multiple fixations but are consistent with the theory of reliance on differential motion produced by environmental variation in depth.

Eye Movements↗

Long-term follow-up of classical bronchial carcinoid tumors. Clinicopathologic observations.

Twenty-seven cases of classical bronchial carcinoid were followed up for at least 10 years after curative resection. Surgery was conservative in 15 cases. True lymph-node metastases were identified at operation in two cases. Distant metastases were confirmed in two patients after 5 and 10 years, respectively. One died of unrelated cause 10 years, and the other is alive 19 years, postoperatively. Radiotherapy relieved bone pain in both cases, and chemotherapy halted disease progression in one of them. In immunostaining the original histologic material, all carcinoids expressed neuron-specific enolase, and most expressed chromogranin A, synaptophysin and serotonin. Demonstration of ACTH and related opiopeptides did not portend a more aggressive course or identify cases with nodal metastases. Despite their low malignant potential, long-term follow-up of bronchial carcinoids is warranted. Even in the rare cases of distant metastases, long-term survival seems to be the rule. The occasional presence of nodal metastases and/or demonstration of ACTH and other opiopeptides, while more frequent in neuroendocrine carcinomas, are not inconsistent with bronchial carcinoids and seemingly do not alter their overall favorable prognosis.

Adolescent↗

Immunohistochemical analysis of normal and mutated ras oncogene p21 expression in human pulmonary and pleural neoplasms.

In this study we examined 214 cases of primary human pulmonary neoplasms for the expression of a mutated form of the ras oncogene p21 product, recognized by the monoclonal antibody (MCA) DWP. Adjacent serial sections from these same cases had previously been used to demonstrate the frequency of ras p21 expression using the broadly reactive anti-ras p21 MCA RAP-5. Confirmation of the increased expression of p21 was accomplished using MCA Y13-259. The use of adjacent tissue sections from these cases allows the direct comparison of the expression of the mutated and non-mutated forms of ras p21. If reactivity with DWP would prove to be significantly more restrictive than that of the "pan" ras MCAs, RAP-5 and Y13-259, it would lend support to the possibility that DWP (and similar MCAs which detect other specific mutations) could be used to define subsets of these neoplasms based on their specific ras p21 phenotype. Since one would anticipate that the valine/cysteine substitution at position 12 of the ras p21 would occur at only low frequencies in human tumors, our results with DWP are consistent with this hypothesis. As previously reported, RAP-5 reacted with a high proportion of lung tumors (100/214 or 47%). In this report, we demonstrate the selective expression of the mutation recognized by the MCA DWP in only 5% of these same tumors (13/214), and that the expression of this mutated form is not restricted to any of the conventional histological subclasses of pulmonary neoplasms.

Antibodies, Monoclonal↗

Preoperative chemotherapy and irradiation for stage III non-small cell lung cancer.

Surgical therapy for stage III non-small cell lung cancer (NSCLC) has not resulted in substantial long-term survival. Neoadjuvant treatment programs that could down-stage the tumor and achieve increased long-term survival would be of obvious benefit. We have used preoperative simultaneous chemotherapy and irradiation in 85 patients with clinical stage III non-small cell lung cancer considered candidates for surgical resection. One group of 56 patients was treated with cisplatin, 5-fluorouracil, and simultaneous irradiation for five days every other week for a total of four cycles. After treatment, 39 patients underwent resection, and the operative mortality was 2 (5%) of 39. A second trial was undertaken in which etoposide (VP-16) was added because of its synergism with cisplatin. In this group, 29 patients were considered to have potentially resectable disease, and 23 underwent thoracotomy with 1 operative death (4%). Of the total of 62 patients having thoracotomy, 60 underwent resection (97%). Complications were major, and there were four bronchopleural fistulas. For the 85 patients eligible for surgical intervention in these two groups of patients, the Kaplan-Meier median survival estimate is 40% at 3 years. The median survival of the 62 patients having thoracotomy is 36.6 months. Combination preoperative chemotherapy and irradiation is feasible with acceptable toxicity and operative mortality in patients with clinical stage III non-small cell lung cancer. Prospective randomized studies are suggested for further evaluation of this treatment program.

Carcinoma, Non-Small-Cell Lung↗

Age differences in perceiving the direction of self-motion from optical flow.

Patterns of optical flow produced at the eye of a moving observer are important for the guidance of locomotion. This study examined age-related changes in the ability to perceive one's direction of self-motion, or heading, from optical flow, using computer displays that simulate translational or curvilinear movement parallel to a random-dot ground surface. We found small but significant decrements in performance with age, such that the mean heading threshold rises from 1.1 degrees in younger observers to 1.9 degrees in older observers for translation, and from 1.4 degrees to 2.9 degrees for curvilinear movement, under comparable dot density and speed conditions. The absence of an age by dot density interaction indicates that there is no age-related shift in strategy, but rather a general decline in the ability to detect and localize global optical flow patterns. The decrement appears to be due to higher level losses in the visual system rather than ocular or low-level sensory losses. The results may have implications for the control of high-speed locomotion and falls in older adults.

Adolescent↗

Expression of a new mucin-type glycoprotein in select epithelial dysplasias and neoplasms detected immunocytochemically with Mab A-80.

We studied by immunocytochemistry 573 tissue and 106 cytologic samples of human tumors, non-neoplastic proliferative lesions and normal tissues with the monoclonal antibody (Mab) A-80 that recognizes a mucinous glycoprotein from the colon carcinoma cell line LS-174T. The spectrum of benign and malignant breast lesions was studied as were epithelial tumors of the colon, stomach, pancreas, lung, salivary glands, thyroid, prostate, kidney, endometrium, skin and mesothelium; non-epithelial tumors included lymphomas, melanomas, gliomas, meningiomas, and sarcomas of soft tissue and bone. With a single exception, breast carcinomas regardless of histologic type were reactive while few fibroadenomas stained weakly and focally. In fibrocystic disease, the presence and intensity of the reactivity paralleled the severity of the epithelial proliferation, e.g. staining was strong in foci of severe or atypical hyperplasia, borderline lesions and carcinomas in situ; apocrine metaplasia stained often but less strongly. Barrett's mucosa, colonic polyps and most gastric and colonic carcinomas stained regardless of glandular features while small cell neuroendocrine carcinomas did not. Adenocarcinomas of the pancreas and lung, and a subset of large cell lung carcinomas reacted whereas neuroendocrine carcinomas of those sites did not. Carcinomas of endometrium, ovary and prostate reacted variably whereas thyroid and renal carcinomas and mesotheliomas were either negative or weakly reactive despite the presence of glands. Lymphomas, skin adnexal tumors, nevi, schwannomas, melanomas, gliomas and sarcomas generally did not react but occasional A-80-positive cells were seen in rare sarcomas and meningiomas. Immunostaining patterns in cytologic specimens were similar to the aforementioned. We conclude that Mab A-80 is an excellent marker for breast carcinomas, and for certain proliferative forms of fibrocystic disease that may precede or be associated with carcinomatous transformation. In colonic, pulmonary and gastric carcinomas, staining with Mab A-80 revealed exocrine features regardless of the absence of glands whereas in renal and thyroid carcinomas and in mesotheliomas staining was focal and weak or absent irrespective of glandular features. We suggest that Mab A-80 is a very promising immunolabel for select exocrine carcinomas, and for some of the dysplasias that may precede their development; its ease of application on tissue sections and cytologic specimens should broaden its usefulness.

Antibodies, Monoclonal↗