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Biomedical subjects

M Ramanathan

Publications and source records attributed to M Ramanathan.

At least 73 records · Page 4Linked to original sources

Cardiopulmonary adaptations to pneumonectomy in dogs. IV. Membrane diffusing capacity and capillary blood volume.

Lung diffusing capacity for carbon monoxide (DLco) and its components, membrane diffusing capacity (Dmco) and capillary blood volume (Vc), as well as pulmonary blood flow (Qc), were measured at rest at several lung volumes and during treadmill exercise by a rebreathing technique in four adult dogs after right pneumonectomy (R-PNX) and in six matched control dogs (Sham) 6-12 mo after surgery. In both groups, lung inflation at rest was associated with a small increase in DLco and Dmco but not in Vc. After R-PNX, total DLco was lower by 30% at peak exercise compared with control values. When compared with DLco in a normal left lung, DLco in the remaining lung continued to increase along the normal relationship with respect to Qc up to a cardiac output equivalent to 34 l/min through both lungs of the Sham dog. There was no evidence of an upper limit of DLco being reached. The augmentation of DLco from rest to exercise was associated with corresponding increases in Dmco and Vc; after R-PNX, both Dmco and Vc continued to increase with respect to Qc along similar relationships as in control dogs without reaching an upper limit, suggesting a much larger alveolar-capillary reserve for gas exchange by diffusion than previously recognized. At higher levels of blood flow through the remaining lung, DLco was greater in adult dogs after R-PNX than after left pneumonectomy (Carlin et al. J. Appl. Physiol. 70: 135-142, 1991), suggesting that additional sources of compensation, e.g., lung growth, exist after removal of > 50% of lung.

Animals↗

Idiopathic oedema: a lesson in differential diagnosis.

This paper outlines our approach to the diagnosis of Idiopathic Oedema. The patient presented illustrates some of the pertinent clinical and laboratory pointers one has to take into consideration before labelling a person as suffering from idiopathic oedema. The discussion also includes a brief review of the literature on the patho-physiology and management of this benign disorder.

Adult↗

Identification and partial characterization of a group of weakly beta-hemolytic intestinal spirochetes of swine distinct from Serpulina innocens isolate B256.

Comparative analyses of a group of 16 weakly beta-hemolytic spirochetes isolated from feces and mucosal scrapings of intestines of swine in the midwestern United States, and eastern Canada revealed the existence of a phenotypically and genotypically related group of 7 isolates. Although isolates in this group differed from all known reference isolates of intestinal spirochetes of swine, partial similarity was detected with S. joneseae isolate 16, a newly identified weakly beta-hemolytic intestinal spirochete of human beings. In addition to producing weak beta-hemolysis on blood agar plates, S. innocens isolates B256 and 4/71, S. joneseae isolate 16, and the 16 field isolates lacked the characteristic ring phenomenon described for Serpulina hyodysenteriae, an enteropathogenic spirochete of swine. All but one of the field isolates of weakly beta-hemolytic intestinal spirochetes gave negative results for indole production. The same isolates yielded variable results for alpha-galactosidase production. By transmission electron microscopic examination of negatively-stained cross-sections of spirochetes, the isolates segregated into groups containing either 4 to 7 or 9 to 16 profiles of axial filaments per cell cross-section. Analyses of genomic DNA of selected isolates using whole-genome cross-hybridization revealed a single genetic type consisting of 7 field isolates of weakly beta-hemolytic intestinal spirochetes. The 7 field isolates were distinct from the reference isolates S. innocens isolates B256 and 4/71, S. hyodysenteriae isolates B78 and B204, and Treponema succinifaciens isolate 6091 based on the number of axial filaments per cell cross-section and lack of cross-hybridization signal. S. joneseae isolate 16, had the same number of axial filaments per cell cross-section and produced a weak hybridization signal with a representative isolate of the 7 weakly beta-hemolytic field isolates from swine. This report suggests the existence of a widely distributed group of closely related weakly beta-hemolytic intestinal spirochetes of swine with genotypic characteristics distinct from S. innocens isolate B256.

Animals↗

Predictions of effect for intracellular antisense oligodeoxyribonucleotides from a kinetic model.

We have analyzed the implications of a simple two-compartment mathematical model (Hargrove and Schmidt, 1989) to anticipate the limits of antisense oligodeoxyribonucleotide action within single cells. The steady-state equations are derived for four special cases representing the following mechanisms: (i) ribosome blockage, (ii) mRNA cleavage by RNase H, (iii) concurrent ribosome exclusion and RNase H action, and (iv) decreased delivery of mature mRNA to the cytoplasm due to transcriptional blockage, interference with nucleocytoplasmic transport, or splicing. Dose-response relationships have been derived for these mechanisms under ideal conditions. Our results indicate that frequently translated mRNAs producing stable proteins are the most attractive antisense targets because these protein levels are sensitive to the changes in the mRNA levels that can be effected using antisense oligodeoxyribonucleotides. The nonsteady-state solutions show that both mRNA and protein half-life can determine the kinetics of antisense oligonucleotide action. A rapid onset of effect will be observed when the mRNA is rapidly degraded and slowly translated and when the translated protein is rapidly degraded. When the protein is slowly degraded, the kinetics of effect are limited by protein half-life. When the translational rate constant is large compared to the absolute difference between the mRNA and protein degradation rate constants, the kinetics of antisense action are determined by both degradation rate constants but are limited by the slower of the two degradative processes. We also show that the steady-state and nonsteady-state solutions may be used to design experiments that discriminate among mechanisms of antisense action.

Algorithms↗

Cardiopulmonary adaptations to pneumonectomy in dogs. II. VA/Q relationships and microvascular recruitment.

Ventilation-perfusion relationships, diffusing capacity for O2, and hemodynamic response were measured at rest and during exercise while five adult dogs breathed air and 15% O2 2 mo (Pnx-A, n = 2) or 12 mo (Pnx-B, n = 3) after right pneumonectomy (removal of 58% of lung tissue). Results were compared with those in five sham-operated controls. The multiple inert gas elimination technique was employed. Maximal O2 uptake was reduced by 50% in Pnx-A and by 15% in Pnx-B. Ventilation-perfusion matching was impaired in Pnx-A but not in Pnx-B. The increase in O2 diffusing capacity during exercise was significantly restricted in Pnx-A but was partially restored in Pnx-B. Mean pulmonary arterial pressure at a given blood flow through the remaining lung was normal in Pnx-A but lower than normal in Pnx-B compared with control values for a single lung. Stroke volume and cardiac output were lower in both Pnx-A and Pnx-B than in controls at a given exercise level. All functional abnormalities were more severe at 2 mo than at 12 mo postpneumonectomy. Gas phase diffusion resistance was present in both Pnx-A and Pnx-B but not in controls. We conclude that physiological compensation postpneumonectomy is progressive. Inability to recruit pulmonary vascular bed with incremental perfusion pressure or flow appears to be the major pathophysiological process that limits early functional capacity after right pneumonectomy.

Animals↗

Respiratory muscle limitation in patients after pneumonectomy.

Exercise capacity is significantly impaired in postpneumonectomy patients who have relatively normal remaining lungs. Our objectives are to determine (1) the nature and extent of mechanical ventilatory abnormalities and oxygen cost of breathing in such patients, and (2) the efficacy of a selective respiratory muscle training program in improving ventilatory and exercise performance. A group of eight postpneumonectomy and eight normal subjects (mean ages 59 and 50 yr, respectively) were studied during steady-state exercise and resting voluntary hyperventilation. Ventilation, work of breathing, cardiac output, and oxygen costs of breathing were determined. Four postpneumonectomy and five normal subjects were studied before and after a respiratory muscle training program. In patients after pneumonectomy compared with normal control subjects, maximal oxygen uptake (VO2) was 56% lower (p < 0.001). Work of breathing was significantly higher at a given ventilation. Mechanical efficiency of ventilation was lower by 44% (p < 0.05). Near maximal VO2, 48% of any additional increment of total-body VO2 was required to sustain the associated increment in ventilatory work, compared with 28% in normal subjects (p < 0.05), suggesting that competition between respiratory and nonrespiratory muscles for oxygen delivery is a significant factor limiting exercise after pneumonectomy. After respiratory muscle training, maximal respiratory pressures improved but maximal sustained ventilation and maximal VO2 did not improve significantly, suggesting that selective respiratory muscle training is of limited utility in postpneumonectomy patients.

Analysis of Variance↗

Haemophagocytosis in typhoid fever.

This report deals with a young man who developed features of haemophogocytosis during the course of typhoid fever. The pertinent clinical and laboratory features of typhoid-associated haemophagocytosis are discussed. The need for blood component replacement therapy in addition to specific anti-microbials to treat haemophagocytosis complicating typhoid fever is stressed.

Adult↗

Respiratory muscle blood flow in exercising dogs after pneumonectomy.

In three foxhounds after left pneumonectomy, the relationships of ventilatory work and respiratory muscle (RM) blood flow to ventilation (VE) during steady-state exercise were examined. VE was measured using a specially constructed respiratory mask and a pneumotach; work of breathing was measured by the esophageal balloon technique. Blood flow to RM was measured by the radionuclide-labeled microsphere technique. Lung compliance after pneumonectomy was 55% of that before pneumonectomy; compliance of the thorax was unchanged. O2 uptake (VO2) of RM comprised only 5% of total body VO2 at exercise. At rest, inspiratory muscles received 62% and expiratory muscles 38% of the total O2 delivered to the RM (QO2RM). During exercise, inspiratory muscles received 59% and expiratory muscles 41% of total QO2RM. Blood flow per gram of muscle to the costal diaphragm was significantly higher than that to the crural diaphragm. The diaphragm, parasternals, and posterior cricoarytenoids were the most important inspiratory muscles, and internal intercostals and external obliques were the most important expiratory muscles for exercise. Up to a VE of 120 l/min through one lung, QO2RM constituted only a small fraction of total body VO2 during exercise and maximal vasodilation in the diaphragm was never approached.

Animals↗

Recruitment of diffusing capacity with exercise in patients after pneumonectomy.

Patients after pneumonectomy are severely limited upon exercise, but impairments in gas exchange are generally mild. One potential explanation of this observation is the existence of functional reserves of diffusing capacity (DLCO), which may be recruited during exercise, predominantly by increasing pulmonary blood flow (Qc). After pneumonectomy, DLCO reserves are recruited even at rest. To investigate if the pattern of recruitment of DLCO is altered and if reserves of DLCO are exhausted during exercise after pneumonectomy, DLCO, lung volume, and cardiac output were measured by the rebreathing method at rest and at multiple levels of steady-state exercise in eight subjects after pneumonectomy and in eight age- and sex-matched nonsmoking normal subjects. In patients after pneumonectomy, the slopes of increase in DLCO [ml.(min.mm Hg)-1.m-2] with respect to QC [ml.min-1.m-2] were normal (0.91 +/- 0.09 x 10(-3) in the pneumonectomy group, 1.16 +/- 0.12 x 10(-3) in the control group, mean +/- SE, p less than 0.05). Thus, the pattern of DLCO recruitment was not significantly affected by pneumonectomy. The ratio of DLCO/Qc fell more rapidly during exercise in patients after pneumonectomy, but the lowest value of the ratio achieved was relatively normal in all except one patient. Declines in arterial O2 saturation at exercise were mild and insufficient to explain the exercise limitation except in the patient whose DLCO/Qc fell below normal. There was no evidence that an upper limit of recruitment was approached. We conclude that the normal ability to recruit DLCO during exercise after pneumonectomy constitutes an important compensatory feature that prevents significant arterial O2 desaturation. In most patients, exercise is limited by a reduced maximal stroke index before reserves of diffusing capacity are exhausted.

Adult↗

Estimation of diffusion limitation after pneumonectomy from carbon monoxide diffusing capacity.

In three foxhounds, diffusing capacity for carbon monoxide (DLCO) was reduced by 25-30% after left pneumonectomy. Based on previous morphometric data in animals and physiologic data in humans, this reduction should not result in any impairment in gas exchange. However, experimental evidence indicates that diffusion limitation develops during exercise after pneumonectomy. Our objective is to determine whether this diffusion limitation to gas exchange can be predicted from physiologic measurements of DLCO. DLCO measured by the rebreathing technique was translated into diffusing capacity for O2 (DLO2) using an average conversion factor for canids obtained morphometrically (Weibel et al., Respir. Physiol. 54: 173-188, 1983). Arterial O2 saturation (SaO2) at various intensities of steady state exercise was calculated from DLO2 and measured values of O2 consumption, alveolar PO2, hemoglobin and arterial pH, and compared to observed SaO2. After pneumonectomy, SaO2 declined progressively with increasing exercise load. In all dogs, the observed pattern of arterial O2 saturation could be predicted from DLCO measured at similar work loads. The relationship between predicted (Pr) and observed (Ob) SaO2 is: SaO2(Pr) = 22.73 + 0.77SaO2(Ob), r = 0.92. The slope is significantly less than 1.0 (P less than 0.005), indicating that other factors must also contribute to arterial desaturation. We conclude that physiologic measurement of DLCO is a meaningful indicator of diffusion limitation to gas exchange. In the foxhound, a modest reduction in DLCO significantly impairs O2 transport during exercise; but other gas exchange abnormalities, e.g. ventilation perfusion inhomogeneity, must also develop.

Animals↗

Recruitment of lung diffusing capacity with exercise before and after pneumonectomy in dogs.

Although the left lung constitutes 42% of the total by weight and volume in dogs, carbon monoxide diffusing capacity (DL) after left pneumonectomy in adults falls less than 30% at rest, indicating a significant increase of DL in the remaining lung. DL normally increases during exercise, presumably by recruitment of alveolar capillaries and surface area as lung volume (Vs) and pulmonary blood flow (Qc) increase. We asked whether the increase of DL in the remaining lung after pneumonectomy in adult dogs could be explained by this kind of passive recruitment by the increased volume and Qc in the remaining lung. We measured the relationship between DL and Qc with a rebreathing technique at increasing treadmill loads in adult foxhounds, before and 6 mo after left pneumonectomy, and the relationship between DL and Vs by the same technique under anesthesia as Vs was expanded. DL was reduced by 29.1% at rest and 26.5% with heavy exercise after left pneumonectomy, indicating either recruitment or new growth in the right lung. With the assumption that the right lung normally receives 58% of the Qc and contains 58% of the DL, DL of the right lung increased with Qc in accordance with the following relationships before and after left pneumonectomy: right lung DL (before pneumonectomy) = 6.44 + 2.40(Qc) (r = 0.963) and right lung DL (after pneumonectomy) = 7.51 + 1.75(Qc) (r = 0.958). Only approximately 7% of the increase in DL from rest to peak exercise could be attributed to the increase in Vs during exercise before pneumonectomy and approximately 15% after pneumonectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of pneumonectomy on the remaining lung in dogs.

To determine the magnitude of functional compensation after pneumonectomy and whether compensation is related to maturity of the animal at the time of resection, we performed left pneumonectomy in either adult or 10-wk-old beagles. Studies were performed in adults 7-9 mo after surgery and in puppies 18-23 mo after surgery when the dogs reached full maturity. Results were compared with those in age- and sex-matched unoperated controls. Measurements included pressure-volume relationships, pulmonary hemodynamics, rebreathing studies of lung volume, diffusing capacity and its components, lung tissue volume, and pulmonary blood flow. Computerized-tomographic scans were performed in the puppy groups to determine changes in thoracic shape and size. Morphometric analysis of the lungs was performed under light microscopy. There was partial compensation for loss of one lung by functional improvement in the remaining lung. Compensation was greater in those pneumonectomized as puppies than as adults. Volume of the remaining lung was larger than predicted for a given transpulmonary pressure in both groups. Diffusing capacity, pulmonary capillary blood volume, and lung tissue volume were larger than expected for the normal right lung. After pneumonectomy, compliance of the rib cage was greater in puppies than in adults. Weight of the costal diaphragm was reduced in pneumonectomized puppies. Pulmonary hypertension at rest did not develop, and pulmonary vascular reactivity to hypoxia was unchanged after pneumonectomy in both groups. Significant correlations were obtained between physiological and morphometric measurements.

Age Factors↗

Regional deformation of the canine diaphragm.

To follow regional deformation of the diaphragm in dogs, radiopaque markers were implanted under surgical anesthesia into different anatomic regions of the muscle in triangular arrays (approximately 1 cm to a side). After recovery from surgery, changes in area and shape of the triangles were followed with biplane cinefluorography during quiet breathing and during inspiratory efforts against an occluded airway (Mueller maneuvers). From changes in shape of the triangles during contraction, area changes were decomposed into a major direction and magnitude of shortening (Eg1) and a minor length change (Eg2) perpendicular to Eg1, both expressed as a fraction of initial length at end expiration. With the use of these techniques, systematic differences in regional area change were observed in different parts of the diaphragm during inspiratory efforts at different lung volumes. Regional area always decreased during contraction in the crural and midcostal zones of apposition to the rib cage. Area decreased less and often increased during inspiratory efforts in the costal dome near the central tendon and in the costal region near its rib cage insertion. Differences in regional area change were not due to differences in the Eg1 in different parts of the diaphragm but were a consequence of differences in widening of the muscle along Eg2 perpendicular to the direction of Eg1. As lung volume was passively increased above functional residual capacity, regional area decreased in all parts of the diaphragm except in the costal regions near rib cage insertion, where area increased.

Animals↗

Unusual hepatic manifestations in typhoid fever.

This paper deals with two patients with typhoid fever in whom hepatic manifestations were the dominant and presenting features of the illness. The ability of typhoid hepatitis to simulate other common infectious diseases in this region is highlighted. It is recommended that typhoid hepatitis should be included in the differential diagnosis of patients presenting with fever and jaundice particularly in the tropics.

Adult↗

Haemophagocytosis in dengue haemorrhagic fever: a case report.

Virus associated haemophagocytic syndrome (VAHS), a distinct clinico-pathologic entity, is characterised by systemic proliferation of non-neoplastic histotiocytes showing haemophagocytosis resulting in blood cytopaenia. It has been described in relation to several viruses earlier. Here we describe a young girl who developed this reactive process during the course of dengue haemorrhagic fever (DHF).

Adult↗

Nonmenstrual toxic shock syndrome--a case report.

We present a young lady who satisfied the criteria for the diagnosis of toxic-shock syndrome (TSS). The differential diagnoses of TSS in the local setting are outlined. The pertinent clinical features of TSS and its increasing association with nonmenstruating females are highlighted.

Adult↗

Hemodynamic changes after pneumonectomy in the exercising foxhound.

Pulmonary arterial pressure is higher during exercise after pneumonectomy than before. Several factors may contribute to the elevation, e.g., loss of vascular bed, overinflation of the remaining lung, and active pulmonary vasoconstriction. We measured hemodynamic changes during graded exercise in conditioned foxhounds and compared pulmonary pressure-flow relationships before and after left pneumonectomy. Pulmonary arterial pressure-flow relationship in the remaining lung is not altered by pneumonectomy, suggesting that the increase in pulmonary vascular resistance post-pneumonectomy is largely the passive consequence of increased pulmonary blood flow to the remaining lung. The potential for chronic hyperinflation of the remaining lung to increase pulmonary resistance after pneumonectomy may have been counterbalanced by a concomitant reduction in lung elastic recoil. Unexpectedly, both mean systemic blood pressure and hematocrit were higher with respect to cardiac output after pneumonectomy. Cardiac output and stroke volume at any given work load were lower after pneumonectomy than before, and heart rate response was unaltered. This pattern of responses suggests that increases in left and right ventricular afterload may have contributed to the reduction in cardiac output.

Animals↗