Biomedical subjects

W H Warren

Publications and source records attributed to W H Warren.

At least 73 records · Page 4Linked to original sources

PubMed1989

Surgical treatment of primary lung cancer and solitary intracranial metastasis.

From 1976 through 1986, 12 patients underwent 14 thoracotomies (two patients had a second thoracotomy for recurrence) and 16 craniotomies (two patients had three craniotomies for recurrence) for carcinoma of the lung and solitary intracranial metastasis. Age ranged from 40 to 65 years. Adjuvant therapy (chemotherapy and thoracic irradiation) was employed in three patients prior to thoracotomy and in four patients following thoracotomy. Whole-brain irradiation was used in four patients after craniotomy. Improvement in neurologic symptoms following craniotomy was noted in 15 of 16 instances. There were no operative mortalities. Overall survival from the time of initial diagnosis ranged from 13 to 63 months. Survival following initial craniotomy ranged from 12 to 56 months. Eight patients are currently alive and well with no disabling neurological symptoms. These results support an aggressive approach to the resection of solitary brain metastasis from bronchogenic carcinoma, both for palliation and prolongation of survival.

Adenocarcinoma↗

PubMed1989

Neuroendocrine neoplasms of the lung. A clinicopathologic update.

One hundred forty-six cases of pulmonary neuroendocrine tumors are assessed according to the classification of Gould and associates and are evaluated for their clinical presentation and subsequent clinical course. Bronchial carcinoids are characteristically found to be central tumors often occurring in comparatively young patients; surgical resection with minimal but clear margins is usually curative. The long-term prognosis is excellent in the majority of patients, although rarely regional nodal and distant metastases develop. Well-differentiated neuroendocrine carcinomas are most frequently peripheral tumors. In stage I and II disease, surgical resection alone is curative and patients with locally advanced tumors may have a prolonged disease-free interval. The overall prognosis is less favorable than that of bronchial carcinoids but considerably better than that of small cell neuroendocrine carcinomas, with which they are still at times confused. Intermediate-sized cell neuroendocrine carcinomas are often wrongly categorized as large cell undifferentiated carcinoma. They have a distinctly aggressive clinical course comparable with that of small cell neuroendocrine carcinoma and should be treated similarly. Small cell neuroendocrine carcinomas are aggressive, rapidly disseminating neoplasms. Even in clinical stage I tumors, patients must be considered to have disseminated metastases. The role of surgical therapy in these two latter tumor types is adjuvant to aggressive systemic chemotherapy.

Adult↗

PubMed1988

Well differentiated and small cell neuroendocrine carcinomas of the lung. Two related but distinct clinicopathologic entities.

Twenty-two resected pulmonary well differentiated neuroendocrine carcinomas (WDNC) were re-evaluated histologically as were 28 resected intermediate-small cell neuroendocrine carcinomas (IC-SCNC). WDNC were distinguishable from IC-SCNC by their consistently recognizable organoid architecture, and by the absence or limited extent of necrosis. Furthermore, WDNC could be subclassified into 3 subsets based upon the degrees of pleomorphism, local and vascular invasion, and stromal fibrosis, the mitotic count, and the extent of tumor necrosis. Whereas all those parameters were important in discriminating between WDNC and IC-SCNC, the quality of the organoid architecture, and the extent and pattern of necrosis emerged as the most significant. WDNC with the more aggressive histologic features (subset III) had, as a group, a distinctly worse clinical course that those displaying blander features (subsets I and II). Nevertheless, even subset III of WDNC had, as a group, a longer survival than similarly treated Stages I and II IC-SCNC. We conclude that the histologic spectrum of WDNC is broader than generally recognized. Moreover, 3 subsets of WDNC are definable based on conventional histologic criteria provided sufficient, well preserved samples are examined. Even the most aggressive subset of WDNC can be thus histologically discriminated from IC-SCNC, and, given comparable stages, has a better prognosis than the latter.

Adult↗

PubMed1988

Immunohistochemical evaluation of neuroendocrine cells and neoplasms of the lung.

The dispersed neuroendocrine (NE) system is represented in the bronchopulmonary tract by submucosal nerves and ganglion cells and, in the mucosal lining by solitary NE cells and neuroepithalial bodies (NEB's). The latter two components variably express pan-NE markers including NSE, chromogranin (s) and, notably, synaptophysin. The expression of serotonin, bombesin, calcitonin and leu-enkephalin has been well established; additional eutopic materials include somatostatin and calcitonin gene-related peptide. Solitary NE cells and NEB's are epithelial structures as defined by their consistent cytokeratin expression. Hyperplasia and dysplasia of NE cells may be found in association with various forms of chronic injury; they have been noted in chronic bronchiectasis and in the vicinity of neoplasms of various types. Hyperplastic and dysplastic pulmonary NE cells frequently express ectopic materials particularly ACTH. NE neoplasms of the bronchopulmonary tract comprice a spectrum that includes a) carcinoids, b) well differentiated NE carcinomas, c) intermediate cell NE carcinomas and d) small cell NE carcinomas. The precise pathologic criteria defining these entities are discussed in detail as are their clinical implications. The entire spectrum of lung NE neoplasms express NE markers demonstrable by immunocytochemistry; these include pan-NE markers, serotonin and numerous neuropeptides. The expression of multiple hormonal materials is frequent. Within any given tumor, some variation in expression may be noted in different sites and in different periods of the "normal" or therapeutically modified lifespan of the tumor. The entire spectrum of lung NE neoplasms is epithelial for they express cytokeratin polypeptides and desmoplakin; subsets of the tumors coexpress cytokeratins and neurofilament proteins. Also, subsets of these NE neoplasms may be immunostained with monoclonal antibodies to antigens related to exocrine phenotype suggesting focal amphicrine features.

Carcinoid Tumor↗

PubMed1988

Immunohistochemical identification of exocrine and neuroendocrine subsets of large cell lung carcinomas.

Formalin fixed, paraffin embedded sections of 52 cases of pulmonary large cell undifferentiated carcinoma (LCUC) as defined in the current WHO classification were studied immunohistochemically to assess features of exocrine and neuroendocrine (NE) differentiation. Monoclonal antibody 44-3A6 was applied to detect a membrane association protein related to exocrine differentiation. A panel of ten neuroendocrine markers including antibodies to synaptophysin, chromogranin A, serotonin, and seven neuropeptides was used to assess NE differentiation. The broad spectrum anticytokeratin antibody PKK1 was used to confirm the epithelial differentiation of these tumors. Exocrine differentiation was detected in 40/52 (77%) of surgically resected LCUC, despite the absence of recognizable glands by light microscopy. Eighteen of 52 (35%) LCUC exhibited NE differentiation; synaptophysin was the most frequently detected NE marker. Cytokeratin immunostaining with PKK1 was demonstrated in 41/52 (79%) cases. Subsets of LCUC were defined based on their expression of exocrine or NE phenotypic markers. Accordingly, 28/52 (54%) LCUC displayed an exocrine phenotype, 6/52 (12%) a NE phenotype, 12/52 (23%) had combined exocrine and NE phenotypes, and 6/52 (12%) exhibited neither phenotype. In this surgical series, there were no significant differences in stage at presentation for the four subsets. Interestingly, two year survival appeared decreased in patients with tumors displaying the "pure" NE phenotype.

Biomarkers, Tumor↗

PubMed1988

Perception of translational heading from optical flow.

Radial patterns of optical flow produced by observer translation could be used to perceive the direction of self-movement during locomotion, and a number of formal analyses of such patterns have recently appeared. However, there is comparatively little empirical research on the perception of heading from optical flow, and what data there are indicate surprisingly poor performance, with heading errors on the order of 5 degrees-10 degrees. We examined heading judgments during translation parallel, perpendicular, and at oblique angles to a random-dot plane, varying observer speed and dot density. Using a discrimination task, we found that heading accuracy improved by an order of magnitude, with 75%-correct thresholds of 0.66 degrees in the highest speed and density condition and 1.2 degrees generally. Performance remained high with displays of 63-10 dots, but it dropped significantly with only 2 dots; there was no consistent speed effect and no effect of angle of approach to the surface. The results are inconsistent with theories based on the local focus of outflow, local motion parallax, multiple fixations, differential motion parallax, and the local maximum of divergence. But they are consistent with Gibson's (1950) original global radial outflow hypothesis for perception of heading during translation.

Eye Movements↗

PubMed1988

Neuroendocrine carcinomas of the colon and rectum: a clinicopathologic evaluation.

Neuroendocrine carcinomas were diagnosed in 13 of 683 patients who had colon cancers removed from January 1980 to June 1987 for an incidence of 1.9%. The patients were 28 to 89 years of age (median, 72 years). There were seven male and six female patients. The treatment was as follows: right hemicolectomy, 5; transverse colectomy, 1; left hemicolectomy, 1; low anterior resection, 2; abdominal-perineal resection, 1; and in 3 patients with rectal tumors, biopsy examination only was performed. Microscopic stages were as follows: Dukes' stage B, 1; stage C, 6; stage D, 5; and stage indeterminate, 1. By light microscopy, the tumors showed solid clusters or ribbons of round to fusiform, small to intermediate-sized cells with variably abundant mitoses. Eight tumors had foci of glandular and/or squamous differentiation. By immunohistochemistry, all tumors showed one or more neuroendocrine markers, including neuron-specific enolase, chromogranin, synaptophysin, serotonin, and various neuropeptides. By electron microscopy, single membrane-bound neurosecretory granules were noted. The sites of metastases included regional nodes, 8; liver, 5; bone, 1. Four patients were treated with a combination of chemotherapy and radiation therapy. These tumors were, as a group, aggressive, with eight patients dead within 12 months of diagnosis. Median survival was 7 months, with three patients alive at 2, 38, and 68 months, respectively. Specifically, small- and intermediate-cell neuroendocrine carcinomas of the colon and rectum behaved very aggressively and displayed numerous structural and functional similarities with their bronchopulmonary counterparts.

Adult↗

PubMed1987

Immunohistochemical demonstration of lacto-N-fucopentose III in lung carcinomas with monoclonal antibody 624A12.

Bronchopulmonary carcinomas were analyzed immunohistochemically using monoclonal antibody 624A12. The antibody was raised against a human "small cell carcinoma" cell line NCI-H69. It recognizes a particular sugar sequence in lacto-N-fucopentose III, which is preserved in formalin fixed and paraffin embedded tissue. Various bronchopulmonary carcinomas revealed characteristic patterns of immunoreactivity. Forty nine/50 adenocarcinomas were immunoreactive either diffusely or focally. The immunostaining was usually limited to the cell membranes with occasional intracytoplasmic immunostaining in large cells. The only negative case had been irradiated before surgical resection. Twenty seven/38 squamous cells carcinomas did not immunostain while the remaining 11 displayed focal immunoreactivity in areas of "loose cellular apposition" associated with necrosis and, rarely, in squamous pearls. All of six adenosquamous carcinomas showed immunoreactivity focally. Eleven/30 large cell carcinomas and 10/11 bronchiolo-alveolar carcinomas were either diffusely or focally immunoreactive. Seven/26 intermediate cell neuroendocrine carcinomas were focally immunoreactive while none of 33 typical small cell neuroendocrine carcinomas, 21 carcinoids, and 10 well differentiated neuroendocrine carcinomas was immunoreactive. An adenoid cystic carcinoma was diffusely immunoreactive, and a mucoepidermoid carcinoma was focally immunoreactive. We conclude that various bronchopulmonary neoplasms have characteristic patterns of distribution of this antigen, and that monoclonal antibody 624A12 may be useful for the differential diagnose among bronchopulmonary carcinomas, and their differential diagnosis from pleural mesotheliomas.

Adenocarcinoma↗

PubMed1987

Visual guidance of walking through apertures: body-scaled information for affordances.

A necessary condition for visually guided action is that an organism perceive what actions are afforded by a given environmental situation. Warren (1984) proposed that an affordance such as the climbability of a stairway is determined by the fit between properties of the environment and the organism and can be characterized by optimal points, where action is most comfortable or efficient, and critical points, where a phase transition to a new action occurs. Perceiving an affordance, then, implies perceiving the relation between the environment and the observer's own action system. The present study is an extension of this analysis to the visual guidance of walking through apertures. We videotaped large and small subjects walking through apertures of different widths to determine empirically the critical aperture-to-shoulder-width ratio (A/S) marking the transition from frontal walking to body rotation. These results were compared with perceptual judgments of "passability" under static and moving viewing conditions. Finally, we tested the hypothesis that such judgments are based on intrinsic or body-scaled information specifying aperture width as a ratio of the observer's eyeheight. We conclude (a) that the critical point in free walking occurs at A/S = 1.30, (b) that static monocular information is sufficient for judging passability, and (c) that the perception of passability under such conditions is based on body-scaled eyeheight information.

Body Height↗

PubMed1987

The way the ball bounces: visual and auditory perception of elasticity and control of the bounce pass.

Human observers may perceive not only spatial and temporal dimensions of the environment, but also dynamic physical properties that are useful for the control of behavior. A study is presented in which visual and auditory perception of elasticity in bouncing objects, which was specified by kinematic (spatiotemporal) patterns of object motion, were examined. In experiment 1, observers could perceive the elasticity of a bouncing ball and were able to regulate the impulse applied to the ball in a bounce pass. In experiments 2 and 3, it was demonstrated that visual perception of elasticity was based on relative height information, when it was available, and on the duration of a single period under other conditions. Observers did not make effective use of velocity information. In experiment 4, visual and auditory period information were compared and equivalent performance in both modalities was found. The results are interpreted as support for the view that dynamic properties of environmental events are perceived by means of kinematic information.

Adult↗

PubMed1986

Visual control of step length during running over irregular terrain.

Running over uneven ground requires visually regulating step length to secure proper footing. To examine how this is achieved, we studied subjects running on a treadmill on a series of irregularly spaced targets. The movements of their lower limbs and coccyx relative to the targets were monitored opto-electronically by a Selspot system. The results indicated that step length was adjusted to strike the targets primarily by varying the vertical component of impulse applied to the ground during the stance phase. In contrast, horizontal impulse was not varied significantly, and changing the reach forward of the foot on landing contributed little to variation in step length. Changing the vertical impulse simply altered the step time proportionately. Thus the data are consistent with a time-based model in which vertical impulse is modulated by the optic variable delta tau (Lee, 1976) specifying the time gap that has to be bridged by the runner between two targets.

Coccyx↗

PubMed1986

Malignant mesotheliomas. Improved differential diagnosis from lung adenocarcinomas using monoclonal antibodies 44-3A6 and 624A12.

Forty-three malignant pleural mesotheliomas and 10 known metastatic pulmonary adenocarcinomas to the pleura were studied by immunohistochemistry using monoclonal antibodies 44-3A6 and 624A12. Monoclonal antibodies 44-3A6 and 624A12 were raised against human pulmonary carcinoma cell lines; they recognize a membrane-associated protein of 40,000 mol wt and a specific sugar sequence of lacto-N-fucopentose III, respectively. Samples were also studied with a broad-spectrum antikeratin antibody and a polyclonal antibody to carcinoembryonic antigen (CEA). These investigations were performed on formalin-fixed and paraffin-embedded tissues. The mesotheliomas comprised only grossly evident, pleurectomized, or pneumonectomized cases; they included 22 epithelial, 15 biphasic, and 6 spindle cell types. Electron-microscopic study was also done on 9 cases. None of the mesotheliomas was immunoreactive to 624A12, while 9/10 metastatic pulmonary adenocarcinomas were convincingly immunoreactive. Monoclonal antibody 44-3A6 immunostained all of the metastatic adenocarcinomas strongly, whereas only 10/43 mesotheliomas were focally and weakly immunoreactive. The latter included 5 epithelial and 4 biophasic mesotheliomas and 1 spindle cell mesotheliomas; the immunoreaction was confined to scattered single cells, and the staining pattern was readily discernible from that of adenocarcinomas. Forty of 43 mesotheliomas were strongly immunoreactive with the broad-spectrum anti-keratin antibody, whereas 8/10 metastatic pulmonary adenocarcinomas showed focal and rather weak staining. Seven of 10 metastatic adenocarcinomas were immunoreactive to anti-CEA antibody, while only 15/43 mesotheliomas displayed weak immunoreactivity. It is concluded that monoclonal antibodies 44-3A6 and 624A12 are excellent phenotypic markers of metastatic pulmonary adenocarcinomas to the pleura and thus are useful for the differential diagnosis of pleural mesotheliomas. Given conventionally fixed and processed tissues, it appears that the combined use of these monoclonal antibodies may be more effective for that differential diagnosis than anti-CEA and anti-keratin antibodies.

Adenocarcinoma↗

PubMed1985

Bombesin in human neuroendocrine (NE) neoplasms.

Bombesin is a 14 amino acid peptide isolated from amphibian skin which was found to have stimulatory effects upon gastric and pancreatic secretions, release of gastrointestinal hormones, gallbladder contraction and bronchoconstriction. It is present in amphibian gastric endocrine cells, avian proventriculus endocrine cells and avian brain. In mammals it is present mainly in nerve cells and fibers. The only mammalian endocrine cell shown to date to have bombesin is the P-cell in fetal lung. Bombesin is also found in mammalian brain, with its highest concentration in the hypothalamus. We examined several groups of human neuroendocrine neoplasms for the presence of bombesin by immunohistochemistry. Our findings indicate that bombesin is present 68% of bronchial carcinoids, 65% of pulmonary neuroendocrine carcinomas, 62% of neuroendocrine carcinomas of the skin, 5-10% of pheochromocytomas and extraadrenal paragangliomas and 35% of gastrointestinal carcinoids and neuroendocrine carcinomas. Parallel studies in a wide variety of non neuroendocrine neoplasms failed to reveal the presence of bombesin. We conclude that bombesin is a highly specific marker of neuroendocrine differentiation and thus a valuable tumor marker. Furthermore, its specificity compares favorably with another neuroendocrine marker, neuron specific enolase, an enzyme thought to be present only in neural tissues and neuroendocrine cells but recently found in non neural human tissues and non neuroendocrine neoplasms.

Bombesin↗

PubMed1985

Pulmonary resection in patients after pneumonectomy.

In 15 patients with a previous pneumonectomy (eight on the right and seven on the left), a new "lesion" developed in the remaining lung. Fourteen had the pneumonectomy for carcinoma (13 men and 1 woman), and 1 woman had a pneumonectomy for blastomycosis. At the second operation (4 months to 16 years after the pneumonectomy), limited resection of a primary or metastatic malignancy was done. The excision ranged from lobectomy to multiple wedges. One patient died on the sixth postoperative day, presumably a cardiac death. Eight patients died 2 to 33 months postoperatively. Six patients are now living: 3 have no evidence of disease (18, 35, and 70 months), and 3 have recurrent disease (26, 41, and 73 months). There is evidence that pulmonary resection after pneumonectomy is feasible with a low operative mortality and that resection of these "secondary" tumors can result in prolonged, worthwhile survival.

Adult↗

PubMed1985

Paragangliomas of the head and neck: ultrastructural and immunohistochemical analysis.

Eighteen head and neck paragangliomas were studied by light microscopy and light microscopic immunohistochemistry by the peroxidase technique for the presence of NSE (neuron-specific enolase), serotonin, and a battery of neuropeptides. Seven of these tumors were also studied by electron microscopy. All 18 cases demonstrated immunostaining for NSE; 10 of the 11 carotid body tumors had immunostaining for multiple hormones. Considering all 18 cases, the most frequently demonstrated hormonal substances were in order: serotonin, leu-enkephalin, gastrin, substance P, vasoactive intestinal polypeptide (VIP), somatostatin, bombesin, calcitonin, and alpha MSH. In several tumors, adjacent-step sections stained for different hormonal substances strongly suggested reactivity for more than one hormone in given tumor cells. By electron microscopy, all 7 cases studied displayed considerable heterogeneity of the neurosecretory granules with respect to size, shape, and electron density. This demonstrated that branchiomeric paragangliomas are capable of producing a spectrum of neuropeptides in addition to their known amine content. The presence of immunoreactive serotonin in most of these neoplasms was confirmed. In addition to these findings, neurofibrils within the substance of carotid body paragangliomas demonstrated immunoreactivity for somatostatin and a gastrinlike neuropeptide. The significance of the neuropeptides in these neoplasms and their possible presence and role in normal and hyperplastic paraganglia remain to be defined.

Carotid Body Tumor↗

PubMed1985

Neuroendocrine neoplasms of the bronchopulmonary tract. A classification of the spectrum of carcinoid to small cell carcinoma and intervening variants.

Eighty-one primary pulmonary neuroendocrine neoplasms were assessed by the classification of Gould and associates. The neuroendocrine features of these tumors were studied by a combination of conventional light microscopy, electron microscopy, and immunohistochemical staining for hormonal substances and neuron-specific enolase. In each case, clinical follow-up was obtained to test the prognostic value of this new pathological classification. This study indicated that bronchial carcinoids are very low-grade neuroendocrine neoplasms that are locally invasive and only occasionally metastasize late in their course. Well-differentiated neuroendocrine carcinomas are relatively low-grade carcinomas that either present with or subsequently develop nodal or distant metastases in 73% of patients. Intermediate cell neuroendocrine carcinomas are highly aggressive tumors often mistakenly called "large cell undifferentiated carcinoma." Their clinical course is comparable to that of small cell neuroendocrine carcinomas, which has a mean survival of 9 months. The different clinical courses of these tumors demonstrate the predictive value of the proposed classification. It appears particularly valuable to identify well-differentiated neuroendocrine carcinoma as a low-grade carcinoma, distinct from true bronchial carcinoids. This classification may resolve some discrepancies regarding the therapy for and prognosis of "carcinoids" and their presumed variants.

Biopsy↗

PubMed1984

Perceiving affordances: visual guidance of stair climbing.

How do animals visually guide their activities in a cluttered environment? Gibson (1979) proposed that they perceive what environmental objects offer or afford for action. An analysis of affordances in terms of the dynamics of an animal-environment system is presented. Critical points, corresponding to phase transitions in behavior, and optimal points, corresponding to stable, preferred regions of minimum energy expenditure, emerge from variation in the animal-environment fit. It is hypothesized that these points are constants across physically similar systems and that they provide a natural basis for perceptual categories and preferences. In three experiments these hypotheses are examined for the activity of human stair climbing, by varying riser height with respect to leg length. The perceptual category boundary between "climbable" and "unclimbable" stairs is predicted by a biomechanical model, and visually preferred riser height is predicted from measurements of minimum energy expenditure during climbing. It is concluded that perception for the control of action reflects the underlying dynamics of the animal-environment system.

Adult↗

PubMed1984

Auditory perception of breaking and bouncing events: a case study in ecological acoustics.

The mechanical events of bouncing and breaking are acoustically specified by single versus multiple damped quasi-periodic pulse patterns, with an initial noise burst in the case of breaking. Subjects show high accuracy in categorizing natural tokens of bouncing and breaking glass as well as tokens constructed by adjusting only the temporal patterns of components, leaving their spectral properties constant. Differences in average spectral frequency are, therefore, not necessary for perceiving this contrast, though differences in spectral consistency over successive pulses may be important. Initial noise corresponding to glass rupture appears unnecessary to categorize breaking and bouncing. The data indicate that higher order temporal properties of the acoustic signal provide information for the auditory perception of these events.

Adult↗