Search PubMed⌕ Search

Biomedical subjects

T E King

Publications and source records attributed to T E King.

At least 19 recordsLinked to original sources
PubMed1996

Impact of shock on pain reactivity: II. Evidence for enhanced pain.

Shocked rats (Rattus norvegicus) often exhibit longer tail withdrawal latencies to radiant heat, which suggests that exposure to shock reduces pain. But at the same time, rats appear hyperreactive to shock, suggesting than pain is enhanced. Experiment 1 replicated these findings and showed that when tail movement was monitored, shocked rats were less responsive to heat and hyperreactive to shock even when the same behavioral criteria were used. When latency to vocalize was measured, shocked rats appeared hyperreactive to both test stimuli (Experiments 2 and 3). Prior exposure to shock also enhanced the acquisition of conditioned fear in a different context (Experiment 4) and the speed with which rats learned a response to avoid a thermal stimulus (Experiment 5). The results suggest that exposure to shock enhances pain.

Animals↗
PubMed1996

Pulmonary histiocytosis X: pulmonary function and exercise pathophysiology.

Pulmonary histiocytosis X (PHX) is a diffuse, smoking-related lung disease characterized pathologically by bronchocentric inflammation, cyst formation, and widespread vascular abnormalities and physiologically by exercise limitation. The major mechanism underlying exercise impairment in this disease has not been previously defined. Spirometry, lung volumes, lung mechanics, and exercise physiology were performed on 23 patients with PHX. Two subgroups were identified on the basis of elastic recoil: 12 subjects had an elevated coefficient of elastic recoil with 11 demonstrating a predominant pattern of restriction, and 10 subjects had normal elastic recoil and relatively normal lung function. Exercise performance was severely limited in both subgroups (workload 53 +/- 3%). Abnormalities of ventilatory function and gas exchange were present but did not appear to be exercise-limiting in the majority of subjects. Indices reflecting pulmonary vascular function (DLCO, baseline VD/VT, exercise VD/VT) were abnormal. Strong correlations between overall exercise performance (% predicted VO2max) and indices of vascular involvement were present: DLCO (r = 0.68, p = 0.0004), baseline VD/VT (-0.65, 0.001), exercise VD/VT (-0.67, 0.0004). Similar correlations were found when exercise performance was measured by maximal workload achieved. We conclude that (1) subjects with PHX present with either normal or predominantly restrictive pulmonary physiology and that (2) exercise impairment is common and appears to reflect pulmonary vascular dysfunction.

Adult↗
PubMed1996

Lymphangioleiomyomatosis: the pathophysiology of diminished exercise capacity.

Dyspnea with exertion is nearly always present in patients with pulmonary lymphangioleiomyomatosis, but the mechanisms underlying exercise impairment have not been well defined. Spirometry, lung volumes, lung mechanics, and exercise physiology were performed on a cohort of 16 patients. We determined the relative contribution of airflow limitation, gas exchange abnormalities, and pulmonary vascular abnormalities to the exercise performance achieved. The patients had normal TLC and Vtg, but RV was elevated in 88% of the subjects. A moderate to severe obstructive pattern was present in 69% of the subjects, and the DLCO was reduced, often markedly, in 81% of the subjects. Exercise performance was limited (work load, 68% +/- 6) with abnormalities of ventilatory function and gas exchange present. Strong correlations between overall exercise performance (percent predicted VO2max and maximal work load achieved) and indices of airflow and vascular involvement were present. Poor exercise performance was due primarily to ventilatory limitation. The etiology of this ventilatory limitation appears twofold. First, subjects had a reduced ventilatory ceiling because of airflow limitation. Second, subjects demonstrated an excessive ventilatory response as a result of increased dead-space ventilation thought to be due to disease-associated cystic changes and associated pulmonary vascular dysfunction or destruction.

Adult↗
PubMed1996

Quantitative CT predicts the severity of physiologic dysfunction in patients with lymphangioleiomyomatosis.

PURPOSE: To assess quantitative high-resolution CT (quantitative CT) as a diagnostic and prognostic tool in pulmonary lymphangioleiomyomatosis. METHODS: Spirometry, lung volumes, diffusing capacity, exercise physiology, and expiratory high-resolution CT (HRCT) examinations were performed on a cohort of ten patients with the diagnosis of lymphangioleiomyomatosis (LAM) referred to a tertiary care center. HRCT examinations were also done on ten normal control subjects. A thresholding technique was used to quantitatively assess the amount of abnormal cystic parenchyma present on each of the two images obtained for each subject with LAM and for each normal control subject. This numeric index of cystic parenchyma, the quantitative CT index, was then examined (1) as a diagnostic measure to distinguish the subjects with LAM from the normal control subjects and (2) as a prognostic measure to assess disease severity in the subjects with LAM. Linear regression of the quantitative CT index against physiologic indexes of pulmonary function and exercise performance was analyzed to determine the relationship between this radiologic assessment of disease severity and functional impairment. RESULTS: The quantitative CT index was significantly greater for the LAM patients, 37.2 +/- 6.9 (SEM), compared with the control group, 0.8 +/- 0.2 (p = 0.0001). Linear regression analysis demonstrated significant linear correlation between the quantitative CT index and measures of airflow (FEV1, r = -0.90, p = 0.0005), air trapping (residual volume, r = 0.70, p = 0.02), diffusing capacity (diffusing capacity for carbon monoxide, r = -0.76, p = 0.01), gas exchange (alveolar to arterial oxygen gradient) at rest, r = 0.69, p = 0.007, and at maximum exercise, r = 0.79, p = 0.007) and exercise performance (maximum workload, r = -0.84, p = 0.002), and oxygen utilization (oxygen utilization at maximum exercise, r = -0.76, p = 0.01). CONCLUSION: Quantitative CT techniques can distinguish subjects with LAM from normal controls. Further, the quantitative CT index correlates well with physiologic measurements of airflow, lung volumes, diffusing capacity, and exercise performance and, thus, may provide a useful measure of disease severity.

Adult↗
PubMed1995

Comparison of propofol and methohexitone in anaesthesia for ECT: effect on seizure duration and outcome.

The effect of the induction agents propofol and methohexitone on seizure duration and clinical outcome was assessed in a prospective, randomised, double blind study in 32 depressed patients receiving electroconvulsive therapy (ECT). Assessments comprised Hamilton rating scales pre-ECT, weekly during the course, and at one month follow-up. Patients showed a significant improvement in depression as measured by the Hamilton rating scale across the course of the ECT treatment. This improvement was not significantly different in the propofol and methohexitone groups. Nor was the amount of improvement related to either the total duration of seizure experienced by the patient during the ECT series or the use of tricyclic antidepressants by some patients.

Adult↗
PubMed1995

Recovery after electroconvulsive therapy: comparison of propofol with methohexitone anaesthesia.

We have studied prospectively 39 patients receiving a course of electroconvulsive therapy (ECT) for major depressive disorder; they were allocated randomly to receive either propofol or methohexitone for anaesthesia. Recovery after the third ECT treatment was assessed by finger tap and digit symbol substitution tests at 15, 30, 45, 60 and 90 min after induction. Seizure duration (median (interquartile range)) was shorter with propofol (24 (10) s) than methohexitone (29 (17) s) (P = 0.08). There was no significant difference in psychometric recovery for drug type, duration of the seizure or initial severity of depression. These results suggest that the more rapid recovery rates noted with propofol in other procedures are not evident after electrically induced seizures.

Adult↗
PubMed1995

Human alveolar macrophages produce predominantly the 35-kD pro-forms of interleukin-1 alpha and interleukin-1 beta when stimulated with lipopolysaccharide.

Alveolar macrophages (AM) play a key role in local immunoregulation. The objective of these studies was to compare the production of the pro- and mature forms of both interleukin-1 alpha (IL-1 alpha) and interleukin-1 beta (IL-1 beta) by AM from nine nonsmoking control subjects, six asymptomatic smokers, and nine patients with interstitial lung disease (ILD). IL-1 alpha and IL-1 beta steady-state mRNA levels in AM cultured over 20 h were determined using specific cDNA probes. IL-1 alpha, 35-kD pro-IL-1 beta, and 17-kD mature IL-1 beta protein levels in cell lysates and supernatants were determined by individual specific ELISAs. Before culture, the isolated AM contained no IL-1 alpha or IL-1 beta mRNA. AM from nonsmoking control subjects and asymptomatic smokers produced comparable levels of IL-1 alpha protein, 5.01 +/- 1.02 ng/ml and 4.54 +/- 1.07 ng/ml, respectively, only after stimulation with lipopolysaccharide (LPS) and not with granulocyte-macrophage colony-stimulating factor (GM-CSF). The majority of the IL-1 alpha was present in the cell lysates as 35-kD pro-IL-1 alpha, as determined by Western blot analysis. AM from patients with ILD produced higher levels of LPS-induced cell-associated IL-1 alpha protein (9.78 +/- 1.80 ng/ml, p = 0.031). LPS-induced IL-1 beta production by AM from nonsmoking control subjects (5.22 +/- 1.89 ng/ml) and asymptomatic smokers (4.39 +/- 0.66 ng/ml) was equivalent to total IL-1 alpha protein production.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Surfactant protein A predicts survival in idiopathic pulmonary fibrosis.

The purpose of this study was to determine if the measurement of surfactant protein A (SP-A) in bronchoalveolar lavage (BAL) fluid predicts survival in patients with idiopathic pulmonary fibrosis (IPF). We performed BAL on 44 patients with IPF and 33 healthy volunteers. SP-A and total phospholipid (PL) were measured in the surfactant pelleted by centrifugation and expressed as a ratio to account for differences in the alveolar surface area sampled. The mean SP-A/PL was lower in patients with IPF than in healthy volunteers (31.8 +/- 2.8 versus 63.9 +/- 6.4 micrograms/mumol, p = 0.006) and in patients who died within 2 yr than in those who survived (23.4 +/- 2.6 versus 37.5 +/- 4.2 micrograms/mumol, p = 0.015). Using Cox's proportional hazard model, we found that SP-A/PL modeled continuously was associated with survival time (p = 0.002). The 5-yr survival of patients with SP-A/PL above the median level for all patients with IPF (29.7 micrograms/mumol) was more than twice that of patients below the median (68 versus 30%, p = 0.007). SP-A/PL improved upon prediction of survival modeled by most routine physiologic variables with the exception of percent predicted TLC or the multifarious clinical-radiographic-physiologic score (CRP). Cellular analysis of lavage did not predict survival in this cohort of patients. We conclude that SP-A/PL is a biochemical marker in lavage that predicts survival in patients with IPF.

Adult↗
PubMed1995

Immunohistochemical identification and characterization of smooth muscle-like cells in idiopathic pulmonary fibrosis.

The interstitium of the fibrotic lung possesses a contractile capability that is unusual for nonmuscle tissue. An abundance of actin filament-laden cells have been demonstrated in animal and human studies of fibrotic lung tissue and have frequently been termed myofibroblasts. The origin and significance of these cells remain unclear. Proliferation of cells with the capability to contract and thereby generate force within the parenchyma is potentially a significant contribution to the increased lung elastic recoil of advanced pulmonary fibrosis. In the present study, we immunohistochemically examined these intermediate phenotypes of filament-laden cells with a focus on those expressing smooth muscle-associated isoforms of actin. The monoclonal antibody HHF35 was used to study the presence and distribution of cells expressing alpha and gamma smooth muscle actin in idiopathic pulmonary fibrosis (IPF). Adjacent sections of tissue from open lung biopsies of eight patients with IPF were stained with a pentachrome stain and with multiple antibodies (HHF35, polyclonal anti-actin, anti-vimentin, anti-keratin, anti-procollagen I, and anti-von Willebrand Factor VIII) to identify specific cell types. In addition, anti-laminin antibody was used to stain basement membrane. Many tightly packed, HHF35-reactive cells were found to be architecturally dissociated from airways and blood vessels in all eight patients with IPF. Some HHF35-reactive bundles were composed of loosely associated cells, and single smooth muscle cell types (SMC) were distributed in the fibrotic interstitium. Interestingly, some of the SMC were distinctly negative for anti-laminin and stained atypically with pentachrome. Moreover, some single SMC were found to be anti-procollagen type I reactive with double staining technique.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMed1995

How common are renal angiomyolipomas in patients with pulmonary lymphangiomyomatosis?

Pulmonary lymphangiomyomatosis has been associated with renal angiomyolipoma in case reports, but the prevalence of this association has not been well documented. The objective of this study was to determine the frequency of renal angiomyolipoma in a series of subjects with pulmonary lymphangiomyomatosis. Eighteen consecutive patients with pulmonary lymphangiomyomatosis were seen at a single institution between 1989 and 1994. Of these, one patient was excluded because she did not have an abdominal computed tomographic (CT) scan. We found eight out of 17 (47%) patients with pulmonary lymphangiomyomatosis to have renal angiomyolipomas. These were found either at surgery or on abdominal CT scanning. Thus, renal angiomyolipomas occur commonly in association with pulmonary lymphangiomyomatosis. Consequently, the early detection of renal angiomyolipoma by abdominal CT may be important, because lesions with dimensions larger than 4 cm may present an increased risk for complications related to tumor growth or hemorrhage. Serial follow-up by ultrasonography or CT scanning is important in identifying and monitoring high-risk patients. Prophylactic treatment (partial or total nephrectomy) may be considered for patients with tumors that show significant growth or other complications, such as hemorrhage.

Adult↗
PubMed1995

Correlation of structure and function in idiopathic pulmonary fibrosis.

The early stage of idiopathic pulmonary fibrosis (IPF) is thought to involve a smaller number of alveoli and to be characterized predominantly by cellularity and minimal fibrosis, whereas advanced disease involves a large number of alveoli and is characterized predominantly by fibrosis with minimal cellularity. In addition, correlative studies have indicated that prognosis and response to therapy is determined in part by the extent of fibrosis and cellularity. This study was undertaken to determine whether pulmonary function assessment would help distinguish between the cellular and fibrotic phases of this disorder, as determined by a semiquantitative pathology scoring system that comprised four factor scores: fibrosis, cellularity, granulation/connective tissue, and desquamation. Ninety-six untreated patients with biopsy-confirmed IPF (27 never smokers, 32 current smokers, and 37 ex-smokers) were evaluated. In the group as a whole, there was no significant relationship between the fibrosis or the connective/granulation tissue factor scores and any of the physiologic parameters. The DLCO correlated with the "desquamation" and the total pathology scores, whereas the TLC and FVC correlated with the cellularity factor score. In the current smokers, the coefficient of elastic retraction, DLCO/VA, and FEV1/FVC ratio were significantly lower than in never smokers and ex-smokers, and TLC and FVC were higher than in never smokers. Also, the mean cellularity and granulation/connective tissue factor scores were significantly lower, and the desquamation factor score was significantly higher than those in never smokers and ex-smokers. Both age and smoking status were significant for the cellularity factor score, whereas for the connective/granulation tissue factor score, age was not significant but smoking status was.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Can CT distinguish hypersensitivity pneumonitis from idiopathic pulmonary fibrosis?

OBJECTIVE: The clinical management of patients with idiopathic pulmonary fibrosis differs markedly from that of patients with hypersensitivity pneumonitis. However, the two diseases often cannot be differentiated on clinical grounds. The purpose of this study was to establish whether CT can be used to make the distinction. MATERIALS AND METHODS: Thirty-six patients with idiopathic pulmonary fibrosis and 27 patients with hypersensitivity pneumonitis were studied. All diagnoses were confirmed or supported by open lung biopsy. Three of the patients with idiopathic pulmonary fibrosis had desquamative interstitial pneumonia, and the remainder had usual interstitial pneumonia. In 19 of the 27 patients with hypersensitivity pneumonitis, the disease was chronic (symptoms lasting more than 1 year), while eight had acute or subacute symptoms. Two radiologists, who had not previously seen any of the cases and were blinded to the diagnosis, reviewed the CT images by consensus. The extent and distribution of CT features (including ground-glass attenuation, honeycombing, and micronodules) were recorded. In each case, a CT diagnosis was made, and the level of diagnostic confidence was recorded. RESULTS: A CT diagnosis was made with a high level of confidence in 39 (62%) of 63 patients. In these patients, the CT diagnosis was correct in 35 cases (90%): 23 of 26 patients with a CT diagnosis of idiopathic pulmonary fibrosis and 12 of 13 patients with a CT diagnosis of hypersensitivity pneumonitis. In the three patients with desquamative interstitial pneumonia, the CT diagnoses were probable hypersensitivity pneumonitis in two cases and definite hypersensitivity pneumonitis in one case. Of the 19 patients with chronic hypersensitivity pneumonitis, only seven had a definite diagnosis of hypersensitivity pneumonitis based on CT findings; three had a definite diagnosis of idiopathic pulmonary fibrosis. The patients with idiopathic pulmonary fibrosis and usual interstitial pneumonia were more likely to have honeycombing and peripheral or lower lung zone predominance of disease, and less likely to have micronodules, than were patients with chronic hypersensitivity pneumonitis. The patients with idiopathic pulmonary fibrosis and desquamative interstitial pneumonia had widespread ground-glass opacity indistinguishable from some cases of acute or subacute hypersensitivity pneumonitis. CONCLUSION: Our results show that CT can be used to distinguish idiopathic pulmonary fibrosis from hypersensitivity pneumonitis in most but not all cases. Desquamative interstitial pneumonia cannot reliably be distinguished from acute or subacute hypersensitivity pneumonitis. Chronic hypersensitivity pneumonitis may have findings identical to those of usual interstitial pneumonia. Lung biopsy should still be considered the gold standard for diagnosis of interstitial lung disease.

Alveolitis, Extrinsic Allergic↗
PubMed1994

TCR expression of activated T cell clones in the lungs of patients with pulmonary sarcoidosis.

Sarcoidosis is a systemic granulomatous disease of unknown etiology in which CD4+ T cells seem to be critically involved. In the lungs of patients with pulmonary disease, CD4+ T cells accumulate in large numbers, and a subset of these cells is activated. By using both quantitative PCR and anti-V beta mAbs, we analyzed the TCR repertoire of total and activated bronchoalveolar lavage T cells, the latter subset being defined by the ability to proliferate in short-term culture supplemented with IL-2. Overall, there was little difference when TCR V beta expression of freshly isolated lung and peripheral blood cells was compared in individual patients. Some individuals did demonstrate a modest increase in a few V beta-expressing subsets. However, after 1 to 2 wk of in vitro growth in IL-2-supplemented media, bronchoalveolar lavage cells from most patients, but not from any healthy individuals, demonstrated a selective expansion of particular V beta-expressing subsets. Interestingly, different V beta-bearing subsets were expanded in different patients. Junctional region sequencing indicated that the proliferating T cells in culture were strikingly oligoclonal and were derived from T cell clones already selectively expanded in vivo. These results provide evidence for a disease process that involves recognition of local Ag(s) by specific subsets of CD4+ T cells. Analysis of the Ag specificity of these IL-2-expanded populations is likely to provide insight into the pathogenesis of this disease.

Adult↗
PubMed1994

Rapidly progressive bronchiolitis obliterans with organizing pneumonia.

Bronchiolitis obliterans with organizing pneumonia (BOOP) is a distinct clinical pathologic syndrome. Most patients experience a good response to therapy, and death from progressive BOOP is uncommon. This report describes the clinical features, etiologic factors, pathologic findings, and outcome of 10 patients with rapidly progressive BOOP that was characterized by severe respiratory failure. The major clinical manifestations were dyspnea, cough, fever, crackles on chest examination, and hypoxemia at rest. Underlying conditions or exposures included connective-tissue disease, exposure to birds, and chronic nitrofurantoin therapy. All patients had the characteristic histopathologic findings of BOOP. However, at autopsy in six patients, the predominant histologic pattern was that of alveolar septal inflammation and fibrotic honeycombing. Seven patients died and three patients survived but had persistent pulmonary dysfunction despite aggressive care. In two patients BOOP has progressed, with severe chronic respiratory decompensation. Thus, there is a subset of patients with BOOP who present with a fulminant course leading to death or chronic severe fibrosis and marked impairment of lung function. In addition, the histologic picture of BOOP may be a manifestation of early lung injury that can resolve or progress rapidly to alveolar septal inflammation, end-stage fibrosis, and honeycombing.

Adult↗
PubMed1994

Compartmentalized immune response reflects clinical severity of beryllium disease.

Although beryllium disease has been associated with a bronchoalveolar lavage (BAL) lymphocytosis and T cell-mediated immune response, we do not know if either the BAL cellular profile or the compartmentalized pulmonary response to the antigen reflect the severity of the disease. We studied 110 subjects divided into three groups of subjects: beryllium disease patients (n = 55), beryllium-sensitized patients without disease (n = 8), and control subjects (n = 47). Evaluation included completion of a respiratory symptom questionnaire, clinical examination, chest radiograph, spirometry, body plethysmographic lung volumes, and diffusing capacity (DLCO). In the patient groups, we performed maximal exercise testing with an indwelling arterial line. In addition, we examined BAL and performed blood and BAL beryllium lymphocyte transformation tests (BeLT) as measures of the beryllium-specific T cell-mediated response in these two compartments. In beryllium disease patients we correlated the BAL cellular constituents with clinical parameters indicative of disease severity. Beryllium disease patients exhibited elevated numbers of white cells and lymphocytes in BAL compared with both other groups; however, this lymphocytic alveolitis was significantly obscured in smokers. The BAL cellular constituents correlated with BAL BeLT but not with the blood BeLT. BAL cellular constituents also correlated with the radiographic profusion of small opacities, FEV1/FVC, DLCO, maximal achievable work load, VO2max, and measures of gas exchange at rest and at maximum exercise. We conclude that the lymphocyte-predominant pulmonary inflammatory response in beryllium disease is related to the magnitude of the localized response to antigen and that BAL cellularity, differential cell count, and BeLT reflect beryllium disease clinical severity.(ABSTRACT TRUNCATED AT 250 WORDS)

Berylliosis↗
PubMed1994

Cryptogenic organizing pneumonia: increased expression of interleukin-8 and fibronectin genes by alveolar macrophages.

Cryptogenic organizing pneumonia (COP) is a fibrotic process that primarily involves the alveolar spaces, alveolar ducts, and small conducting airways. The pathogenesis is not understood. Recent histopathologic studies have shown that during the cellular phase of COP, fibronectin deposits are present in the lung. Moreover, a neutrophil alveolitis is frequently seen in COP. Little is known about the involvement of alveolar macrophages in the pathogenesis of COP. However, alveolar macrophages are the principal resident cells in the airways, and they are thought to play a central role in the fibrotic process by virtue of their ability to express and release cytokines such as interleukin-8 (IL-8; a neutrophil chemotactic factor) and fibronectin (FN; a fibrogenic matrix-associated protein). We have quantified the spontaneous gene expression of IL-8 and FN by alveolar macrophages from five nonsmoking individuals with COP and compared them with 10 normal, healthy volunteers (five smokers, five nonsmokers). Expression of IL-8 and FN was measured by a quantitative assay employing reverse transcription of mRNA and the polymerase chain reaction. beta-actin mRNA expression was quantified as an internal standard, and the expression of FN and IL-8 transcripts was calculated as a ratio with beta-actin. The mean +/- SEM of the IL-8/beta-actin ratio in alveolar macrophages from patients with COP was 0.45 +/- 0.07, which was significantly higher than the level from either normal smokers (0.19 +/- 0.02, P = 0.008) or normal nonsmokers (0.16 +/- 0.01, P = 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗