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C C Hsia

Publications and source records attributed to C C Hsia.

At least 19 recordsLinked to original sources
PubMed1999

Cardiopulmonary limitations to exercise in restrictive lung disease.

Cardiopulmonary limitations to exercise in restrictive lung disease. Med. Sci. Sports Exerc., Vol. 31, No. 1 (Suppl.), pp. S28-S32, 1999. Restrictive lung disease encompasses a large and diverse group of disorders characterized by a diminished lung volume. These disorders exhibit common pathophysiologic features including abnormal gas exchange caused by loss of functioning alveolar-capillary unit, abnormal respiratory muscle energetics caused by altered mechanical ventilatory function, and secondary hemodynamic and cardiac dysfunction. Impaired gas exchange is the most prominent exercise abnormality in interstitial lung disease and eventually develops in other causes of lung restriction as well. Measurements of diffusing capacity (DLCO) and alveolar-arterial oxygen tension gradient during exercise are more sensitive detectors of disease than measurements at rest. Excessive dead space ventilation is common in pulmonary parenchymal, pleural, and thoracic diseases, leading to a higher minute ventilation and ventilatory work during exercise. The associated increase in the metabolic energy requirement of respiratory muscles may exceed 50% of available total body oxygen delivery and result in insufficient energy delivery to nonrespiratory muscles that sustain locomotion. Pulmonary arterial hypertension develops secondarily to an increased pulmonary vascular resistance. In addition, diastolic filling of the ventricles during exercise may be restricted by pulmonary fibrosis or anatomical restriction of the pleura and thorax, contributing to secondary cardiac dysfunction. Examples of heart-lung interaction are illustrated by the patient after unilateral pneumonectomy. These pathophysiologic changes help explain why functional disability in these patients is often out proportion to the impairment in lung function.

Animals↗
PubMed1999

Vascularization of small hepatocellular carcinomas: correlation with differentiation.

BACKGROUND: Hepatocellular carcinoma (HCC) is generally considered a hypervascular tumor when visualized by angiography. However, small HCCs are not always found to be hypervascular. METHODS: To evaluate this, 50 HCCs < or =3 cm in diameter were studied. The 50 tumors consisted of 16 well-differentiated HCCs, 25 moderately differentiated HCCs, and 9 that were each a mixture of well- and moderately differentiated HCC. RESULTS: The mean number of portal tracts in the well-differentiated HCCs was 34% of the number in the surrounding nontumorous liver, and few intratumoral arterioles were seen. In contrast, the mean number of portal tracts in the moderately differentiated HCCs was 0.6% of the number in the surrounding nontumorous liver, and abundant intratumoral arterioles were seen. For HCCs that contained both well-differentiated and moderately differentiated tumor, the distribution of portal tracts and intratumoral arterioles in each portion was similar to that seen in well-differentiated or moderately differentiated HCC alone, respectively. HCCs that were larger than 1.5 cm in diameter had fewer portal tracts and more intratumoral arterioles than HCCs whose diameters were < or =1.5 cm. CONCLUSIONS: As small HCCs increase in size and become increasingly dedifferentiated, the number of portal tracts apparently decreases and intratumoral arterioles develop. These findings may reflect changes in the hemodynamics as the HCC develops.

Actins↗
PubMed1999

Compensatory alveolar growth normalizes gas-exchange function in immature dogs after pneumonectomy.

To determine the extent and sources of adaptive response in gas-exchange to major lung resection during somatic maturation, immature male foxhounds underwent right pneumonectomy (R-Pnx, n = 5) or right thoracotomy without pneumonectomy (Sham, n = 6) at 2 mo of age. One year after surgery, exercise capacity and pulmonary gas-exchange were determined during treadmill exercise. Lung diffusing capacity (DL) and cardiac output were measured by a rebreathing technique. In animals after R-Pnx, maximal O2 uptake, lung volume, arterial blood gases, and DL during exercise were completely normal. Postmortem morphometric analysis 18 mo after R-Pnx (n = 3) showed a vigorous compensatory increase in alveolar septal tissue volume involving all cellular compartments of the septum compared with the control lung; as a result, alveolar-capillary surface areas and DL estimated by morphometry were restored to normal. In both groups, estimates of DL by the morphometric method agreed closely with estimates obtained by the physiological method during peak exercise. These data show that extensive lung resection in immature dogs stimulates a vigorous compensatory growth of alveolar tissue in excess of maturational lung growth, resulting in complete normalization of aerobic capacity and gas-exchange function at maturity.

Animals↗
PubMed1999

Red cell distribution and the recruitment of pulmonary diffusing capacity.

The distribution of red blood cells in alveolar capillaries is typically nonuniform, as shown by intravital microscopy and in alveolar tissue fixed in situ. To determine the effects of red cell distribution on pulmonary diffusive gas transport, we computed the uptake of CO across a two-dimensional geometric capillary model containing a variable number of red blood cells. Red blood cells are spaced uniformly, randomly, or clustered without overlap within the capillary. Total CO diffusing capacity (DLCO) and membrane diffusing capacity (DmCO) are calculated by a finite-element method. Results show that distribution of red blood cells at a fixed hematocrit greatly affects capillary CO uptake. At any given average capillary red cell density, the uniform distribution of red blood cells yields the highest DmCO and DLCO, whereas the clustered distribution yields the lowest values. Random nonuniform distribution of red blood cells within a single capillary segment reduces diffusive CO uptake by up to 30%. Nonuniform distribution of red blood cells among separate capillary segments can reduce diffusive CO uptake by >50%. This analysis demonstrates that pulmonary microvascular recruitment for gas exchange does not depend solely on the number of patent capillaries or the hematocrit; simple redistribution of red blood cells within capillaries can potentially account for 50% of the observed physiological recruitment of DLCO from rest to exercise.

Capillaries↗
PubMed1999

Postpneumonectomy alveolar growth does not normalize hemodynamic and mechanical function.

Immature foxhounds underwent 55% lung resection by right pneumonectomy (n = 5) or thoracotomy without pneumonectomy (Sham, n = 6) at 2 mo of age. Cardiopulmonary function was measured during treadmill exercise on reaching maturity 1 yr later. In pneumonectomized animals compared with Sham animals, maximal oxygen uptake, ventilatory response, and cardiac output during exercise were normal. Arterial and mixed venous blood gases and arteriovenous oxygen extraction during exercise were also normal. Mean pulmonary arterial pressure and resistance were elevated at a given cardiac output. Dynamic ventilatory power requirement was also significantly elevated at a given minute ventilation. These long-term hemodynamic and mechanical abnormalities are in direct contrast to the normal pulmonary gas exchange during exercise in these same pneumonectomized animals reported elsewhere (S. Takeda, C. C. W. Hsia, E. Wagner, M. Ramanathan, A. S. Estrera, and E. R. Weibel. J. Appl. Physiol. 86: 1301-1310, 1999). Functional compensation was superior in animals pneumonectomized as puppies than as adults. These data indicate a limited structural response of conducting airways and extra-alveolar pulmonary blood vessels to pneumonectomy and suggest the development of other sources of adaptation such as those involving the heart and respiratory muscles.

Airway Resistance↗
PubMed1998

Work of breathing in anesthetized patients: laryngeal mask airway versus tracheal tube.

STUDY OBJECTIVE: To compare the work of breathing associated with the laryngeal mask airway (LMA) and tracheal tube (TT) in spontaneously breathing anesthetized patients. DESIGN: Randomized, prospective, controlled trial. SETTING: University teaching hospital. SUBJECTS: 20 ASA physical status I and II patients scheduled for elective peripheral surgery with general anesthesia. INTERVENTIONS AND MEASUREMENTS: A standardized anesthetic protocol was utilized, and patients were allowed to breathe spontaneously through a circle absorption system. Patients were randomly assigned to receive either LMA (n = 10) or TT (n = 10) for airway management. Work of breathing was determined after the patients' ventilatory status had been allowed to stabilize for 15 minutes and before the onset of the surgical stimulus. Airflow and esophageal pressures were measured using a pneumotachograph and an esophageal balloon, respectively, and the values were subsequently integrated to determine work of breathing. MAIN RESULTS: The two groups were similar with respect to demographic characteristics and the end-tidal concentrations of carbon dioxide and isoflurane. Work of breathing per minute through the LMA (1.4+/-0.3 J/min) was significantly lower than that through the TT (1.9+/-0.4 J/min). CONCLUSION: In healthy, anesthetized, spontaneously breathing patients, work of breathing is significantly lower through the LMA than the TT.

Adult↗
PubMed1998

Fixed maximal stroke index in patients after pneumonectomy.

Patients who have undergone pneumonectomy (PNX) show limited exercise capacity, partly attributable to an impaired stroke index (SI). To determine whether this limitation is due to deconditioning, we assessed exercise performance and cardiopulmonary function in seven patients after PNX (age: 59 +/- 2 yr, mean +/- SEM) and eight normal, healthy nonsmokers (52 +/- 3 yr) before and after an ergometer exercise training program for 30 min per day, 5 d per week, for 8 wk at 65% of measured maximal O2 uptake. Lung volume, diffusing capacity of carbon dioxide (DL(CO)) and cardiac index (CI) were determined during steady-state exercise by a rebreathing method. Exercise endurance was measured at 80% of maximal power. As compared with normal subjects, patients who had had PNX showed diminished maximal oxygen uptake (VO2max), as well as diminished lung volumes, ventilatory capacities, and maximal cardiac and stroke indexes. After training, VO2max, endurance, and peripheral O2 extraction improved in both groups. However, maximal cardiac and stroke indexes increased only in normal subjects and not in patients. We conclude that an irreversibly fixed maximal SI is a major source of exercise limitation after PNX, probably because of pulmonary arterial hypertension and/or mechanical distortion of the cardiac fossa. Ventilatory impairment after PNX did not prevent a training-induced increase in VO2max. Exercise training confers significant functional benefit on postpneumonectomy patients by enhancing peripheral O2 extraction.

Adult↗
PubMed1998

p53 overexpression in small hepatocellular carcinomas containing two different histologic grades.

There is evidence to suggest that a focus of less-differentiated hepatocellular carcinoma (HCC) may arise within a pre-existing well-differentiated HCC, eventually replacing it. In the present study, the p53 tumor suppressor gene was analyzed by immunohistochemistry in 31 hepato-cellular carcinomas (HCCs) containing two or more regions in the same nodule with different histologic grades. p53 was overexpressed in the nucleus in 13 of 31 HCCs (42%), in seven of which p53 overexpression was seen only in the less-differentiated area of the tumor. This suggests that overexpression of presumed mutant p53 may have contributed to dedifferentiation during the development of HCC.

Adult↗
PubMed1997

Deletion mutants of the hepatitis B virus X gene in human hepatocellular carcinoma.

Two patients with hepatocellular carcinoma (HCC) were identified who had substantial deletions within the hepatitis B virus (HBV) X gene from HCC tissues. In one patient, the deletion was found at nt. 382-389 (codons 128-130) of the X gene, followed by two nucleotide substitutions, a frame shift, and formation of a new stop codon. In the second patients, the deletion was found at nt. 389-396 (codons 130-132) of the X gene, followed by one nucleotide substitution, a frame shift, and formation of a new stop codon. The resulting X proteins in both cases would be truncated at the 3' end and would be 20 amino acids shorter than the full length X protein. These patients had been identified during a study of 25 HCC patients from Qidong, China in whom a 228-base region of the X gene was sequenced. No deletions were found within this X gene sequence in HCC tissues from the other 23 patients or in the 20 adjacent noncancerous liver samples available from these patients. However, the fact that these deletions encompassed codons 130 and 131, two adjacent codons where point mutations were found in 21 of the remaining 23 patients, suggests that this region may play an important role in hepatocarcinogenesis.

Adult↗
PubMed1997

Binding of wild-type p53 by topoisomerase II and overexpression of topoisomerase II in human hepatocellular carcinoma.

In order to study the mechanisms by which p53 function is regulated, human wild-type p53 cDNA was cloned into a vaccinia virus vector and the expressed p53 protein was used to investigate binding of the p53 by cellular proteins from a cDNA expression library from human liver. One protein that bound wild-type p53 had > 99% homology with DNA topoisomerase IIb. p53 protein was coimmunoprecipitated from topoisomerase II-rich cell lysates (but not from topoisomerase II-deficient cell lysates) by an antibody to topoisomerase IIa and IIb. This binding was shown to occur without a dsDNA intermediary. Hepatocellular carcinomas (HCCs) and adjacent nontumorous liver tissues from ten patients were studied to determine the level of expression of topoisomerase II and p53. Overexpressed topoisomerase II proteins were detected by western blot in six of ten HCCs (60%), including several in which presumed wild-type p53 was detected by immunohistochemistry. No topoisomerase II expression was detectable in the ten nontumorous liver tissues from the same patients or in a sample of normal human liver.

Antibodies, Monoclonal↗
PubMed1997

Glycemic control and cardiopulmonary function in patients with insulin-dependent diabetes mellitus.

BACKGROUND: We studied cardiopulmonary function during exercise in young subjects with long-standing insulin-dependent diabetes mellitus (IDDM) who have no clinical cardiopulmonary disease to determine the relationships of aerobic capacity, gas exchange, ventilatory power requirement, and cardiac output to chronic glycemic control. METHODS: Eighteen subjects with IDDM and 14 normal control subjects were studied. Nine diabetic subjects received twice daily insulin injections and had chronically elevated levels of glycosylated hemoglobin (hyperglycemic group); 9 other diabetic subjects received insulin via continuous infusion pumps and maintained chronic near-normal levels of glycosylated hemoglobin (normoglycemic group). At the end of at least 7 years of regular follow-up, aerobic capacity was determined by cycle ergometry. Lung volume, diffusing capacity, and cardiac output during exercise were measured by a rebreathing technique. Ventilatory power was measured by the esophageal balloon technique. RESULTS: Maximal work load and oxygen uptake were markedly impaired in chronically hyperglycemic diabetic patients associated with significant restrictions of lung volume, lung diffusing capacity, and stroke index during exercise. Membrane diffusing capacity was significantly reduced at a given cardiac index. The normoglycemic patients consistently showed less impairment than the hyperglycemic patients. CONCLUSION: Physiologically significant cardiopulmonary dysfunction develops in asymptomatic patients with long-standing IDDM. Chronic maintenance of near-normoglycemia is associated with improved cardiopulmonary function.

Adult↗
PubMed1997

In vivo assessment of changes in air and tissue volumes after pneumonectomy.

We examined the progression and topographical distribution of postpneumonectomy volume changes in immature foxhounds undergoing right pneumonectomy (R-Pnx, n = 5) or sham pneumonectomy (Sham, n = 6) at 2 mo of age and subsequently raised to maturity. Volumes of lung air (Vair) and tissue (Vti) were estimated by computerized tomography (CT) scan at 7, 22, and 52 wk after surgery at a transpulmonary pressure of 20 cmH2O. Estimates of Vti by CT scan included both septal tissue as well as nonseptal tissue (small- and medium-sized airways and blood vessels); these were compared with estimates of septal Vti by an acetylene rebreathing (Rb) method. We found significant correlations between these techniques (Vair(CT) = 0.83 Vair(Rb) + 275, R = 0.97; Vti(CT) = 1.62 Vti(Rb) - 30, R = 0.81). Extravascular septal Vti returned to normal 7 wk after R-Pnx and remained normal up to maturity. Nonseptal Vti remained significantly below normal. The greatest increase in Vti occurred in the midlung region just cephalad and caudal to the heart. After an early period of accelerated tissue growth after R-Pnx, the rate of septal tissue growth matched that of somatic growth, whereas nonseptal tissue growth lagged behind. Compensatory growth of the remaining left lung was not associated with selective alterations in thoracic development.

Acetylene↗
PubMed1997

Red cell distortion and conceptual basis of diffusing capacity estimates: finite element analysis.

To understand the effects of dynamic shape distortion of red blood cells (RBCs) as it develops under high-flow conditions on the standard physiological and morphometric methods of estimating pulmonary diffusing capacity, we computed the uptake of CO across a two-dimensional geometric capillary model containing a variable number of equally spaced RBCs. RBCs are circular or parachute shaped, with the same perimeter length. Total CO diffusing capacity (DLCO) and membrane diffusing capacity (DMCO) were calculated by a finite element method. DLCO calculated at two levels of alveolar PO2 were used to estimate DMCO by the Roughton-Forster (RF) technique. The same capillary model was subjected to morphometric analysis by the random linear intercept method to obtain morphometric estimates of DMCO. Results show that shape distortion of RBCs significantly reduces capillary diffusive gas uptake. Shape distortion exaggerates the conceptual errors inherent in the RF technique (J. Appl. Physiol. 79: 1039-1047, 1995); errors are exaggerated at a high capillary hematocrit. Shape distortion also introduces additional error in morphometric estimates of DMCO caused by a biased sampling distribution of random linear intercepts; errors are exaggerated at a low capillary hematocrit.

Algorithms↗
PubMed1996

Role of hematocrit in the recruitment of pulmonary diffusing capacity: comparison of human and dog.

In dogs, maximal O2 uptake (VO2max) per kilogram of body weight is two- to threefold that in humans; the difference cannot be explained solely by differences in structural features between species. We compared the functional recruitment of pulmonary diffusing capacity (DLCO) during exercise in dogs with that in humans to determine whether pulmonary gas exchange is matched to VO2max or the size of the lungs and to define the potential role of exercise-induced polycythemia in producing the superior aerobic capacity of the dogs. We compared the relationships of DLCO, membrane diffusing capacity (DMCO), and pulmonary capillary blood volume (Vc) with respect to pulmonary blood flow (Qc) by a rebreathing method during steady-state exercise in adult male human subjects and in conditioned adult male foxhounds. The slopes and intercepts of the relationships of DLCO and DMCO to Qc are significantly greater in dogs than in humans; the slopes of the relationship of Vc to Qc are similar. In dogs diffusive pulmonary gas transport is matched to the higher VO2max. The enhanced recruitment of DLCO and DMCO in dogs during exercise could potentially be explained entirely by the exercise-induced polycythemia, which is seen in dogs but not in humans.

Adult↗
PubMed1996

A modified rebreathing technique using an infrared gas analyzer.

To lower the cost and improve accessibility of the rebreathing technique for measuring cardiopulmonary function during exercise, we implemented a fast-response infrared (IR) gas-analyzer system to simultaneously measure lung diffusing capacity, cardiac output lung tissue volume, and lung volume by a rebreathing technique in five healthy subjects at rest and during steady-state exercise. Interferences by water vapor and CO2 on the analyzer were determined and corrected for. During rebreathing, a gas mixture of 0.4% C2H2-0.3% CH4-9% He-30% O2, and either 0.3% C18O or 0.3% C16O in a balance of N2 was simultaneously sampled by both a mass spectrometer and the IR analyzer, permitting paired comparisons. Measurements obtained by the two devices were not significantly different. We conclude that this modified rebreathing technique using the IR analyzer is accurate for the measurement of cardiopulmonary function at rest and during exercise.

Adult↗
PubMed1996

Temporal course of gas exchange and mechanical compensation after right pneumonectomy in immature dogs.

To determine the temporal progression and magnitude of functional compensation in immature dogs raised to maturity after extensive lung resection, we performed right pneumonectomy (R-Pnx) or right thoracotomy without pneumonectomy (Sham) in matched foxhounds at 2 mo of age. At 4, 8, 20, 40, and 60 wk after surgery, static transpulmonary pressure-lung volume relationships were determined. Lung diffusing capacity, membrane diffusing capacity, pulmonary capillary blood volume, pulmonary blood flow, septal lung tissue volume, and lung volumes were measured simultaneously by a rebreathing technique. During maturation, total lung capacity, lung volume at a given distending pressure, and compliance were lower in the R-Pnx group than in the Sham group (P < 0.05). Pulmonary viscous resistance at maturity was elevated after R-Pnx. There were no significant differences in total lung diffusing capacity, membrane diffusing capacity, pulmonary capillary blood volume, pulmonary blood flow, and septal lung tissue volume between groups. Compensation of alveolar-capillary gas exchange was complete by 4-8 wk after R-Pnx, but compensation of mechanical properties remained incomplete throughout maturation. Relative magnitude of compensation after R-Pnx was greater in immature dogs than in adult dogs studied previously by similar techniques.

Airway Resistance↗