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Biomedical subjects

W H Warren

Publications and source records attributed to W H Warren.

At least 19 recordsLinked to original sources
PubMed2001

Coupling of posture and gait: mode locking and parametric excitation.

We investigate the temporal coordination of human gait and posture and infer the nature of their coupling. Participants viewed a sinusoidally oscillating visual display which induced medial-lateral postural sway during treadmill walking, while display frequency was varied (0.075-1.025 Hz). First, postural responses exhibited the usual low-pass characteristic but with an additional resonance peak near the preferred stride frequency, although shifted downward by 0.12 Hz; this provides evidence of a coupling from gait to posture. Second, the step cycle adapted to mode lock with the visual driver and postural sway, as well as displaying instances of intermittency (slipping in and out of phase) and quasiperiodicity (phase wandering); this provides evidence of a coupling from posture to gait. We observed a spectrum of integer mode locks, including a large 1:1 trapping region about the stride frequency and superharmonic entrainment (stride frequency > driver frequency) at lower driver frequencies. A coupled-oscillator model that incorporates a novel parametric coupling from posture to the gait "stiffness" term reproduces these features of the data, including the resonance peak shift. Biological coordination patterns may thus emerge naturally as properties of a system of appropriately coupled oscillators.

Adult↗
PubMed2001

Optic flow is used to control human walking.

How is human locomotion visually controlled? Fifty years ago, it was proposed that we steer to a goal using optic flow, the pattern of motion at the eye that specifies the direction of locomotion. However, we might also simply walk in the perceived direction of a goal. These two hypotheses normally predict the same behavior, but we tested them in an immersive virtual environment by displacing the optic flow from the direction of walking, violating the laws of optics. We found that people walked in the visual direction of a lone target, but increasingly relied on optic flow as it was added to the display. The visual control law for steering toward a goal is a linear combination of these two variables weighted by the magnitude of flow, thereby allowing humans to have robust locomotor control under varying environmental conditions.

Models, Biological↗
PubMed2000

Cytokine biosynthesis by tumor-infiltrating T lymphocytes from human non-small-cell lung carcinoma.

PURPOSE: The purpose of this work was to assess the capacity of tumor-infiltrating leukocytes (TIL) from human non-small-cell lung carcinoma (NSCLC) specimens to synthesize type-1 and type-2 cytokines. METHODS: TIL were isolated from tumors following digestion with collagenase/DNase and further enriched by ficoll-hypaque gradient centrifugation. Membrane phenotypes and intracellular cytokine protein expression of TIL were assessed by flow cytometry. RESULTS: The majority of TIL expressed the CD3 antigen with a CD4:CD8 ratio of approximately 2:1. Other leukocytes such as macrophages (CD14), B lymphocytes (CD20), and natural killer (NK) cells (CD56) were also found to infiltrate the tumors, but in significantly lower numbers. Owing to the limited recovery of non-CD3(+) leukocytes, our analysis of cytokine biosynthesis has focused on T lymphocytes. In the absence of activation, a small percentage of CD3(+) TIL synthesized cytokines ( <4%). Following activation with anti-CD3+interleukin-2 (IL-2), CD3(+) TIL synthesized predominantly a type-1 cytokine profile; however, the type-2 cytokines, IL-6 and IL-10, were also detected in a small percentage of infiltrating cells. Following activation with phorbol 12-myristate 13-acetate + ionomycin, CD3(+) TIL also expressed more type-1 than type-2 cytokines and in significantly greater numbers of cells. The CD3(+)CD8(+) component of the TIL synthesized only type-1 cytokines, whereas the CD3(+)CD4(+) component synthesized both type-1 and type-2 cytokines. CONCLUSION: These results show that the majority of the TIL isolated from NSCLC specimens are T lymphocytes with the capacity to synthesize type-1 cytokines.

Adenocarcinoma↗
PubMed2000

Perception of heading during rotation: sufficiency of dense motion parallax and reference objects.

How do observers perceive the path of self-motion during rotation? Previous research suggests that extra-retinal information about eye movements is necessary at high rotation rates (2-5 degrees /s), but those experiments used sparse random-dot displays. With dense texture-mapped displays, we find the path can be perceived from retinal flow alone at high simulated rotation rates if (a) dense motion parallax and (b) at least one reference object are available. We propose that the visual system determines instantaneous heading from the first-order motion parallax field, and recovers the path of self-motion by updating heading over time with respect to reference objects in the scene.

Cues↗
PubMed2000

Malignancies involving the pericardium.

Malignancies rarely arise from the pericardium. Mesothelioma, the most common of these, is usually unresectable and almost always incurable. Malignancies may secondarily involve the pericardium by direct extension. Carcinoma of the lung and malignant thymoma with limited direct invasion of the pericardium both can undergo complete and potentially curative resections, but adjuvant therapy is usually indicated. More frequently, malignancies involve the pericardium by a process of retrograde lymphangitic spread or hematogenous dissemination. These patients present with a symptomatic pericardial effusion and occasionally pericardial tamponade. Subxiphoid pericardiostomy and drainage is a safe procedure that provides effective and durable symptomatic relief in these terminally ill patients. More aggressive open procedures should be reserved for loculated or recurrent pericardial effusions.

Antimetabolites, Antineoplastic↗
PubMed2000

Palliation of dysphagia.

This article discusses the diagnosis and interventional options apart from surgical resection for carcinoma of the esophagus. Other topics discussed are methods of inserting plastic and self-expanding metal stents in conjunction with their complications, and neodymium:yttrium-aluminum-garnet photodynamic therapy, cryoablation, and BICAP (bipolar cautery probe) options. Clinical scenarios illustrate the pros and cons of these approaches.

Deglutition Disorders↗
PubMed2000

Epithelial tumors of the lung.

Our knowledge and understanding of bronchopulmonary tract tumors have grown considerably; modern pathology enables the phenotyping of many tumors with increasingly improving techniques and tools and, arguably, improving criteria. By the same token, at least some of the new data may not be readily grafted onto traditional classification schemes. Some traditional designations will be dropped and replaced. And, although it has been overenthusiastically argued that molecular classifications may be attained, that ideal might not be truly an improvement. For classifications to be useful, they should be relatively simple, easily reproducible, and clinically significant. Still, modern marker pathology has revealed new vistas for the evaluation, diagnosis, and therapy of at least some tumors. These developments merit optimism but also caution from clinicians and pathologists.

Adenocarcinoma↗
PubMed1999

Pericardial effusion: subxiphoid pericardiostomy versus percutaneous catheter drainage.

BACKGROUND: Optimal management of cardiac tamponade resulting from pericardial effusion remains controversial. METHODS: Cardiac tamponade in 117 patients was treated with either subxiphoid pericardiostomy (n = 94) or percutaneous catheter drainage (n = 23). Percutaneous catheter drainage was used for patients with hemodynamic instability that precluded subxiphoid pericardiostomy. Effusions were malignant in 75 (64%) of 117 patients and benign in 42 (36%) of 117. RESULTS: Subxiphoid pericardiostomy had no operative deaths and a complication rate of 1.1% (1 of 94). In contrast, percutaneous drainage had significantly (p < 0.05) higher mortality and complication rates of 4% (1 of 23) and 17% (4 of 23), respectively. Patients with an underlying malignancy had a median survival of 2.2 months, with a 1-year actuarial survival rate of 13.8%. In comparison, patients with benign disease had a median survival of 42.8 months and a 1-, 2-, and 4-year actuarial survival rate of 79%, 73%, and 49%, respectively (p < 0.05). Effusions recurred in 1 (1.1%) of 94 patients after subxiphoid pericardiostomy compared with 7 (30.4%) of 23 patients with percutaneous drainage (p < 0.0001). CONCLUSIONS: Benign and malignant pericardial tamponade can be safely and effectively managed with subxiphoid pericardiostomy. Percutaneous catheter drainage should be reserved for patients with hemodynamic instability.

Cardiac Tamponade↗
PubMed1999

The role of central and peripheral vision in postural control during walking.

Three hypotheses have been proposed for the roles of central and peripheral vision in the perception and control of self-motion: (1) peripheral dominance, (2) retinal invariance, and (3) differential sensitivity to radial flow. We investigated postural responses to optic flow patterns presented at different retinal eccentricities during walking in two experiments. Oscillating displays of radial flow (0 degree driver direction), lamellar flow (90 degrees), and intermediate flow (30 degrees, 45 degrees) patterns were presented at retinal eccentricities of 0 degree, 30 degrees, 45 degrees, 60 degrees, or 90 degrees to participants walking on a treadmill, while compensatory body sway was measured. In general, postural responses were directionally specific, of comparable amplitude, and strongly coupled to the display for all flow patterns at all retinal eccentricities. One intermediate flow pattern (45 degrees) yielded a bias in sway direction that was consistent with triangulation errors in locating the focus of expansion from visible flow vectors. The results demonstrate functionally specific postural responses of both central and peripheral vision, contrary to the peripheral dominance and differential sensitivity hypotheses, but consistent with retinal invariance. This finding emphasizes the importance of optic flow structure for postural control regardless of the retinal locus of stimulation.

Adult↗
PubMed1998

Integrin laminin receptor profile of pulmonary squamous cell and adenocarcinomas.

The differential expression of laminin receptors has been shown to modulate the invasive capability of malignant cells. We have investigated the reactivity of human pulmonary squamous carcinomas (SSC, n = 20) and adenocarcinomas (ADC, n = 20) with monoclonal antibodies to the cytoplasmic and extracellular domains of the integrin subunits alpha3 and alpha6. Integrins containing these subunits are laminin receptors. Monoclonal antibodies to beta1 and beta4 subunits, the beta1C splice variant of beta1, as well as to Ki-67, were also used. Reverse transcription polymerase chain reaction (PCR) single-strand conformational polymorphism analysis was done to detect possible mutations in the cytodomains. All carcinomas expressed alpha3 extensively; alpha3 expression predominated (40 of 40) over alpha6 (25 of 40). In all alpha6-positive carcinomas, alpha6A was expressed, whereas alpha6B was weakly expressed only in some of them. No mutations of the intracytoplasmic domain A of alpha3 and of the A or B intracytoplasmic domains of alpha6 were shown. Notably, in normal bronchial epithelium, alpha6 colocalized with beta4, whereas in the tumors, alpha6A frequently overlapped with beta1 in a circumferential pattern; alpha6beta1 coexpression was also shown by coprecipitation experiments. Strong and extensive beta4 reactions were invariably polarized at the cell/stroma interface in SCC and ADC. An inverse correlation was found between the expression of beta1C and Ki-67. The prevalence of alpha6A in pulmonary SCC and ADC is in contrast with previous results in colonic ADC in which alpha6B prevails, and alpha6 predominates over alpha3. The absence of mutations of the cytodomains suggests that the integrin subunits of these carcinomas are potentially active. Predominance of alpha3 over alpha6 and of alpha6A over alpha6B may contribute to explain the aggressive and metastatic behavior of lung carcinomas.

Adenocarcinoma↗
PubMed1998

Lung volume reduction surgery: an analysis of hospital costs.

OBJECTIVE: Lung volume reduction surgery (LVRS) represents a potential breakthrough in the management of advanced emphysema, although questions remain about clinical and economic implications of widespread application of LVRS. In this report, we describe hospital costs, excluding physicians' fees, for LVRS. DESIGN: Hospital charges were obtained from billing records and converted to costs by applying multiple cost-to-charge ratios. SETTING: A large, urban academic medical center. PATIENTS: Fifty-two consecutive patients who received bilateral LVRS through a median sternotomy between April 1995 and August 1996. RESULTS: Median hospital stay was 10 days (mean= 14.8+/-12.8 days; range=3 to 48 days), including 2 days (mean=6+/-9.2 days; range=1 to 35 days) in the ICU. One hospital death occurred. Hospital costs per case ranged from $11,712 to $121,829, with mean costs of $30,976 and median costs of $19,771. Costs were related significantly to duration of ICU stay and length of hospitalization. Patients who accrued the highest costs were significantly older than the remainder of the sample (69.3 years vs 62.4 years). CONCLUSIONS: Hospital costs of LVRS vary significantly but are related directly to hospital stay. Identification of factors associated with prolonged stays can be used in assessing benefits and risks of LVRS against utilization of health-care dollars.

Academic Medical Centers↗
PubMed1997

Immunolocalization of integrins in the normal lung and in pulmonary carcinomas.

Cryosections of normal adult lung (n = 7) and pulmonary epithelial tumors, including squamous (n = 8), adeno (n = 8), bronchioloalveolar (n = 5), and large cell (n = 4) carcinomas (SCC, ACC, BAC, LCC), carcinoids (Cd, n = 7), and neuroendocrine carcinomas (NEC) of variable grades (n = 14) were immunostained by the avidin-biotin peroxidase (ABC) method with monoclonal antibodies to the alpha1-6 and alpha(v) and the beta1-4 integrin subunits. Normal adult alveolar septae showed variably intense immunoreactivity for alpha1,3,6 and beta1, whereas reactions for alpha5 and alpha(v) were weaker and uneven; the remaining integrin subunits were not detected. Bronchial and bronchiolar epithelium showed variably intense staining for alpha2.3,6,v and beta1,4. Reactions were often, though not invariably, basally polarized. SCC, ADC, and LCC showed variably intense reactions for alpha2.3,6,v and beta1,4. BAC were strongly and uniformly stained for alpha1.3 and beta1. In Cd, alpha1,2,3,v and beta1 reactions were noted, whereas in NEC, weak alpha1,3 and beta1 staining was detected with only traces of alpha6 and alpha(v). We conclude that alveolar epithelial cells do not express the hemidesmosome-associated, laminin-binding integrin alpha6beta4 of the bronchial epithelium but rather the alpha1beta1 and alpha3beta1, collagen IV, and laminin receptors, respectively. SCC, ADC, and sampled LCC express an integrin repertory qualitatively similar to that of the bronchial epithelium. Distinct from the latter, the integrin repertory of BAC parallels that of the alveolar epithelium by its strong expression of the multipotential alpha1beta1 and alpha3beta1 integrins. NEC tumors do not display the laminin receptors alpha6beta4 and alpha6beta1 shown by SCC and ADC but express instead alpha1beta1, a collagen IV-laminin receptor rarely found in epithelial neoplasms except for BAC. In NEC tumors, integrins, especially alpha2, decrease with dedifferentiation. Notably distinct from epithelial mesotheliomas, the major fibronectin-binding integrin alpha5beta1 was not found in any type of lung carcinoma.

Adenocarcinoma↗
PubMed1997

Pleural mesotheliomas have an integrin profile distinct from visceral carcinomas.

Cryosections of epithelial, sarcomatoid, and biphasic malignant mesotheliomas (EMM, n = 11; SMM, n = 5; BMM, n = 6) of the pleura were immunostained with monoclonal antibodies to integrin subunits alpha 1-6 and v, and beta 1-4. Localization patterns were compared with those known to occur in pulmonary and other adenocarcinomas (PADC, ADC). EMM and the epithelial component of BMM (ecBMM) expressed alpha 1,3,5,6, and v and beta 1 and 4. SMM and the sarcomatoid elements of BMM (scBMM) reacted variably for alpha 1,3,5,6 and v, and beta1. Reactions for alpha3, found in all tumors, were strongest in EMM, ecBMM, and PADC. Our findings indicate that EMM and ecBMM parallel PADC and most ADC in their expression of alpha6 beta4, underscoring that this laminin integrin receptor is intimately associated with these neoplastic epithelial phenotypes. Also, our observations on alpha3 beta1 suggest that this cell-cell adhesion-mediating integrin is related to the epithelial phenotype. Notably, all malignant mesotheliomas (MM), including those with distinct glandular structures, expressed the alpha5 beta1 fibronectin receptor, thus paralleling most sarcomas and differing from PADC and most other ADC. We conclude that irrespective of architectural and cytologic variants, transformed mesothelial cells possess an integrin repertory that differs significantly from that of most ADC, including those of the lung. These findings set mesothelium apart from epithelia and may prove helpful as adjunct tools for the differential diagnosis between EMM and AD.

Adenocarcinoma↗