Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cough response following inhalation challenge with the sensory nerve irritant resiniferatoxin was compared with that of capsaicin and citric acid in guinea-pig and man. Capsaicin and citric acid gave comparable dose-response curves in the two species. The mean (+/- SEM) concentration producing five coughs in man was 141.3 (1.3) mM (n = 10) for citric acid and 2.8 (1.3) microM (n = 10) for capsaicin. Those for the guinea-pig were 74.1 (1.2) mM (n = 10) for citric acid and 6.0 (2.4) microM (n = 10) for capsaicin. Resiniferatoxin was active at a lower concentration than either citric acid or capsaicin and maximal tolerable cough response was achieved at concentrations of 3 microM (n = 5) in guinea-pig and 300 nM (n = 1) in man. The cough response to resiniferatoxin was greatly prolonged in both guinea-pig and man. Resiniferatoxin, like capsaicin, caused respiratory distress in the guinea-pig which is linked to bronchoconstriction. Resiniferatoxin probably causes cough by stimulation of capsaicin sensitive neurones.
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PMID:A comparative study of the effects of citric acid, capsaicin and resiniferatoxin on the cough challenge in guinea-pig and man. 821 71

The hypotensive effect, kinetics, and concentration-response relationship of labetalol, alpha beta- and alpha 1-adrenoceptor blocking drug, were studied in seven women with a moderate-to-severe hypertension (averaged diastolic blood pressure [DBP] of 100 to 120 mm Hg measured during a 1- to 2-day hospitalization period) during the third trimester of pregnancy who received the oral twice-daily doses of 150 to 450 mg. These dosages were individually selected by attaining a therapeutic goal of DBP < or = 100 mm Hg or systolic blood pressure (SBP)/DBP reduction of > 30/15 mm Hg, as compared with the pretreatment value, at any time during the 12-hour dosing interval for a 3- to 5-day dosage escalation period. Labetalol concentrations in plasma were measured by a high-performance liquid chromatography with fluorescence detection, and the plasma drug concentration-response relationship was analyzed by a sigmoidal Emax model. Labetalol decreased significantly (P < 0.05 to 0.01) the pretreatment SBP/DBP (166.3 +/- 5.2/110.3 +/- 3.0 mm Hg, mean +/- SEM) without any recognizable side-effects during the twice-daily dosing period in the mothers. Peaked concentrations occurred at 1 hour postdose in all patients. The elimination half-lives ranged from 4.3 to 6.9 hours, and the apparent oral clearance from 31.9 to 73.3 mL/min/kg. The pharmacodynamic parameters (Emax and EC50) analyzed by the Emax model revealed a 3- to 5-fold interindividual variability. The gestational ages at delivery ranged from 34 to 37 weeks, and the birth weights were < 2000 g in 6 of the 7 neonates. Four neonates developed respiratory distress syndrome after delivery, and one infant died of pulmonary hypoplasia 3 months later. The results indicate that 1) labetalol orally administered in a twice-daily regimen as done in this study is an effective antihypertensive drug in women with hypertension during late pregnancy, and 2) interindividual variability in the kinetic factor (e.g., oral clearance) as well as that in the pharmacodynamic factor (e.g., EC50) appear to be related to the overall variability in the hypotensive responsiveness to the drug. However, whether labetalol and/or hypertension per se would have been related to the fetal outcome remains unanswered from the present study.
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PMID:Labetalol in hypertension during the third trimester of pregnancy: its antihypertensive effect and pharmacokinetic-dynamic analysis. 822 70

In older children and adults, physiologic instability associated with severe illness causes increased cellular oxygen consumption (VO2), increased serum lactate and cortisol levels, and more negative nitrogen balance. To determine the metabolic response of preterm infants to severity of respiratory illness, we analyzed VO2, nitrogen balance, urinary 3-methyl-histidine and norepinephrine concentrations, and serum levels of lactate and cortisol as a function of ventilatory index (VI). Twelve 2-day-old premature infants who were appropriate in size for gestational age (mean +/- SEM birth weight: 1460 +/- 251 gm) and who required mechanical ventilation for respiratory distress syndrome had VO2 and carbon dioxide production measured by indirect calorimetry and blood and urine samples obtained concurrently. All infants received amino acids, 1.0 gm/kg per day, and a mean energy intake of 27 +/- 3 kcal/kg per day, provided as a parenteral dextrose solution. The resting energy expenditure exceeded energy intake in all infants. The VO2 value ranged from 5.5 to 9.2 ml/kg per minute and was directly correlated with VI (r = 0.79; p = 0.002). Nitrogen balance ranged from -160 to 53 mg/kg per day (mean: -33 +/- 21 mg/kg per day) but was not dependent on VI (r = 0.04) or VO2 (r = 0.01). The serum lactate level correlated directly with VI (r = 0.82; p = 0.002) and VO2 (r = 0.60; p = 0.05), but cortisol and urinary norepinephrine levels did not. We conclude that preterm infants with respiratory distress syndrome have increased VO2 rates and serum lactate concentrations directly related to the degree of respiratory illness. They are generally in a state of mildly negative nitrogen balance, the degree of which is not related to severity of illness. Although these infants may require increased energy delivery during illness, they do not appear to require excessive amounts of amino acids.
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PMID:Metabolic response of preterm infants to variable degrees of respiratory illness. 830 40

To study the potential role of endothelin-1, a potent endothelium-derived vasoconstrictor peptide, in the pathophysiology of persistent pulmonary hypertension of the newborn (PPHN), we measured arterial concentrations of immunoreactive endothelin-1 (irET-1) in 24 neonates with PPHN. Secondary diagnoses included meconium aspiration syndrome (13 patients), sepsis (2), congenital diaphragmatic hernia (1), asphyxia (1), pulmonary hemorrhage (1), aspiration of blood (1), and respiratory distress syndrome (1). Compared with irET-1 levels in umbilical cord blood in normal infants (15.1 +/- 4.1 pg/ml; mean +/- SEM) and in newborn infants with hyaline membrane disease who were supported by mechanical ventilation (11.8 +/- 1.2 pg/ml), infants with PPHN had markedly elevated circulating irET-1 levels (27.6 +/- 3.6 pg/ml; p < 0.01 vs cord blood, hyaline membrane disease). Infants with severe PPHN requiring extracorporeal membrane oxygenation (ECMO) therapy had higher irET-1 levels than infants with milder disease (31.0 +/- 4.7 for ECMO-treated infants vs 21.2 +/- 2.0 for non-ECMO-treated infants; p < 0.05). In patients treated without ECMO, irET-1 progressively decreased during the following 3 to 5 days, paralleling clinical improvement. In contrast, irET-1 concentrations remained elevated in infants with severe PPHN during ECMO therapy. We conclude that circulating irET-1 levels are elevated in newborn infants with PPHN, are positively correlated with disease severity, and decline with resolution of disease in patients who do not require ECMO therapy. Whether endothelin-1 contributes directly to the pathophysiology of PPHN or is simply a marker of disease activity remains speculative.
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PMID:Elevated immunoreactive endothelin-1 levels in newborn infants with persistent pulmonary hypertension. 815 68

The pulmonary outcome for preterm infants 1 year after synthetic surfactant replacement for respiratory distress syndrome was assessed by examining their pulmonary status and the results of pulmonary function tests. A total of 47 infants were followed: 13 infants mean +/- SD: birth weight, 1960 +/- 616 gm; gestation, 32 +/- 1.1 weeks) had been assigned to the placebo group and 34 (birth weight = 1890 +/- 530 gm; gestation = 32 +/- 2.5 weeks) to surfactant treatment. The infants were examined at 3 to 6 months of age (n = 45) and at 9 to 12 months of age (n = 36). There were no significant differences between the two groups in predisposing clinical conditions that would lead to chronic lung disease. The infants had similar patterns of growth, respiratory-related illness, and need for theophylline therapy, diuretic therapy, or both. None had hypoxemia by pulse oximetry. Mean (+/- SEM) values for pulmonary mechanics and energetics in surfactant-treated infants were significantly (p < 0.01) lower for total pulmonary resistance in late infancy (57.7 +/- 11.7 vs 35.3 +/- 4.6 cm H2O/L per second). Lower values (mean +/- SEM) of resistive work of breathing were also measured in the surfactant-treated group (60.7 +/- 12.0 vs 38.2 +/- 3.6 gm-cm/kg per breath). The dynamic pulmonary compliance values were in the low-normal range for both groups, and the mean (+/- SEM) peak-to-peak esophageal pressure values were elevated (11.47 +/- 2.26 cm H2O in the placebo group; 9.24 +/- 0.69 cm H2O in the surfactant group). Forced expiratory flow measurements in late infancy demonstrated significant (p < 0.01) improvement in expiratory reserves and reduced evidence of airflow obstruction in the surfactant-treated infants (peak flow (mean +/- SEM): 287.1 +/- 69 vs 396.9 +/- 27 ml/sec; forced expiratory flow (mean +/- SEM) at functional residual capacity: 56.3 +/- 7.5 vs 83.4 +/- 19.5 ml/sec). No significant differences in pulmonary functions were noted in early infancy. These data suggest that surfactant replacement for respiratory distress syndrome may be associated with beneficial long-term effects on the resistive airflow properties of larger preterm infants.
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PMID:Long-term pulmonary consequences of respiratory distress syndrome in preterm infants treated with exogenous surfactant. 844 Nov 4

Intraalveolar fibrin deposition is a typical finding in acute lung injury and is not necessarily harmful. However, persistence of intraalveolar fibrin deposit may lead to hyaline membrane formation and subsequent alveolar fibrosis, a histologic hallmark of late stages of acute respiratory distress syndrome (ARDS). Thus, timing of the intraalveolar clotting disorder seems to be critical. To explore the time course of factors contributing to fibrin deposition and resolution, we sequentially analyzed procoagulant activity and fibrin degradation (by D dimer) in bronchoalveolar lavage (BAL) fluid of patients developing ARDS and those at risk for, but finally not developing, the syndrome. A total of 36 bronchoalveolar lavages were performed in 11 patients developing ARDS and 15 lavages in 10 patients at risk for but not developing this syndrome. All patients were admitted to the intensive care unit for the treatment of sepsis, trauma, or shock. In early phases of ARDS, the procoagulant activity (PCA) in BAL was significantly higher than in the patients at risk, 320 +/- 83 U (mean +/- SEM) versus 50 +/- 25 U, p < 0.05. A similar difference was noted in subacute stages (280 +/- 91 versus 46 +/- 16 U, p < 0.05). In early ARDS we observed higher levels of D dimer in BAL than in patients at risk: 1,841 +/- 827 versus 293 +/- 134 ng/ml, p < 0.05. Similarly, values of D dimer in the subacute phase were 2,776 +/- 836 versus 237 +/- 125 ng/ml, p < 0.05. In ARDS as well as in the at-risk group, D dimer in BAL fluid showed good correlation with the polymorphonuclear leukocyte count and with protein content of BAL. There was no correlation between plasma and BAL levels of D dimer. We conclude that in ARDS both the procoagulant pathway and the fibrin degradation are markedly activated compared with these in patients at risk but finally not developing this syndrome. These findings expand our understanding of intraalveolar coagulation abnormalities by providing evidence of increased fibrin breakdown in this syndrome.
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PMID:Time course of procoagulant activity and D dimer in bronchoalveolar fluid of patients at risk for or with acute respiratory distress syndrome. 854 11

The present study was undertaken to determine if a synthetic peptide, KLLLLKLLLLKLLLLKLLLLK (KL4), in which K = lysine and L = leucine, in an aqueous dispersion of phospholipids (DPPC and POPG), would expand pulmonary alveoli and improve gas exchange in premature human infants with respiratory distress syndrome (RDS). The KL4 peptide was synthesized to resemble the amino acid pattern of surfactant protein B (SP-B). Forty-seven infants with RDS were treated within 4 h of birth with the KL4-peptide/phospholipid mixture, called KL4-Surfactant. The average arterial-to-alveolar oxygen tension ratios (a/A O2) of 39 patients included in efficacy analyses rose from pretreatment values of 0.14 +/- 0.02 (mean +/- SEM) to 0.40 +/- 0.04 (normal value > or = 0.40) by 12 h of age. Mean airway pressures and oxygenation index values fell concomitantly, and expansion of the lungs was observed on radiographs. The median duration of mechanical ventilation was 5.0 d. Of the 39 included infants, 29 required only a single dose. Radiographic data indicate that those patients requiring a second instillation of KL4-Surfactant but not showing a sustained rise in a/A O2 ratios did, in fact, exhibit expansion of alveoli in the lung. There were no RDS-related deaths; the incidence of complications was no higher than found in other comparable published studies. The data demonstrate that the synthetic peptide, KL4, which mimics the hydrophobic and hydrophilic pattern of SP-B, when formulated in an aqueous dispersion with the phospholipids DPPC and POPG, creates a strong and durable surfactant activity as judged by expansion of pulmonary alveoli and improvement of gas exchange in infants with RDS.
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PMID:The efficacy and safety of KL4-surfactant in preterm infants with respiratory distress syndrome. 854 50

Eighteen preterm infants severely ill with respiratory distress syndrome who required assisted ventilaton were given modified natural surfactant (Survanta) endotracheally. They had a mean +/- SEM gestational age of 31.2 +/- 0.4 weeks (range 28-34) and a mean +/- SEM birthweight of 1562 +/- 71 g (range 1160-2010). Average time of initial surfactant administration was 15 +/- 1.7 hour (range 5-24). No significant side effects were found during surfactant instillation. Post surfactant, the air entry was improved, oxygenation and arterial/alveolar gradients increased, and the levels of inspired oxygen could be reduced. Some of the radiological abnormalities were resolved. In 13 infants, patent ductus arteriosus became clinically evident, seven of whom received Indomethacin. There were 4 cases of pulmonary air leak, 5 cases of pulmonary hemorrhage and 8 cases of bronchopulmonary dysplasia. Four infants expired, two were due to severe asphyxia/shock and two died of unrelated causes. Among the 14 survivors who came for follow-up, two cases of retinopathy of prematurity had gradually regressed, one had cerebral palsy and delayed development. Surfactant rescue therapy is a supplemental beneficial treatment for severe respiratory distress syndrome while newborn intensive care concept is necessary for efficient diagnosis and treatment of RDS.
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PMID:Surfactant treatment in the neonate with severe respiratory distress syndrome. 870 7

Changes in color Doppler imaging measurements of renal artery blood flow velocity have been reported previously during fetal life and during the first week postnatally in term and preterm infants. This study reports longitudinal, developmental changes in renal artery and aortic blood flow velocities occurring postnatally, from birth to day 1 of life, at 1 week, and at 2 to 3 weeks of age in 14 premature babies (mean gestation, 30 +/- 4 (SD) weeks; birth weight, 1.45 +/- 0.57 kg), and identified by means of color Doppler imaging and pulsed Doppler spectral analysis. Results indicate that a significant increase in renal artery systolic blood flow velocity occurs within the first week of life (from 40 +/- 3 (SEM) cm/sec at birth or on day 1, to 53 +/- 3 cm/sec on day 7, to 51 +/- 4 cm/sec on day 14 to 21; repeated-measures analysis of variance, p = 0.004), concurrently with a significant increase in abdominal aortic blood flow velocities, both systolic (from 40 +/- 4 at birth or on day 1, to 70 +/- 8 on day 7, to 76 +/- 8 cm/sec on day 14 to 21; p <0.001) and diastolic (from 4 +/- 2 at birth or on day 1, to 11 +/- 2 on day 7, to 11 +/- 2 cm/sec on day 14 to 21; p = 0.00 1). Systemic blood pressure did not increase concomitantly during the some period. Neither the presence of respiratory distress syndrome or patent ductus arteriosus nor treatment with indomethacin altered developmental increases in observed renal artery blood flow velocities. The presence of an umbilical artery catheter in the high thoracic position in five infants, however, created turbulence at the level of the renal arteries, significantly increasing renal artery systolic flow velocity from 32 +/- 4 to 44 +/- 5 cm/sec (p = 0.009) and increasing renal resistive index from 0.90 +/- 0.03 to 0.96 +/- 0.04 (p = 0.046). These results suggest that renal artery blood flow velocity increases during the first postnatal week in preterm infants and is likely related to increases in aortic blood flow velocity and reduction in renal vascular resistance.
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PMID:Developmental changes in renal artery blood flow velocity during the first three weeks of life in preterm neonates. 904 51

Studies were conducted to assess the efficacy and safety of a synthetic peptide-containing surfactant in the treatment of respiratory distress syndrome (RDS) in preterm (approximately 80% of normal gestation) infant rhesus monkeys. Surfactant was prepared consisting of the phospholipids dipalmitoylphosphatidyl choline and palmitoyl-oleoyl phosphatidyl glycerol and a synthetic peptide modeled after surfactant protein B (SP-B), "KL4-Surfactant" contained a peptide having the sequence KLLLLKLLLLKLLLLKLLLLK, where "K" is lysine and "L" is leucine. The peptide was selected because it mimics the repeating stretches of hydrophobic residues with intermittent basic hydrophilic residues seen in SP-B. KL4-Surfactant was shown to have biophysical activity assessed as the ability to lower surface tension at an air-liquid interface in a pulsating bubble surfactometer. Thirty premature rhesus monkeys were treated shortly after birth with one dose of KL4-Surfactant. The arterial to alveolar oxygen partial pressure ratio (a/A) was found to rise from a pretreatment level of 0.11 +/- 0.01 (mean +/- SEM), indicative of severe RDS, to 0.40 +/- 0.02 at 12-13 h post-treatment. The improvement in oxygenation persisted throughout the study period, with a mean a/A at 22-23 h of 0.45 +/- 0.07. Chest radiographs and gross and microscopic examination of the lungs all confirmed the reversal of the atelectasis seen before treatment. Animals treated with a dose of 200 mg/kg showed a faster, more consistent, and greater response than did a group treated with an average dose of 127 mg/kg. There was no evidence of toxicity after treatment with the higher dose as demonstrated by physiologic, hematologic, biochemical, and pathologic data. The importance of the peptide in the synthetic surfactant was apparent from the results obtained with a control group of nine premature monkeys treated with a non-peptide-containing surfactant; the a/A of this group was 0.15 +/- 0.03 at nine hours of age as compared with a value of 0.38 +/- 0.02 for 30 comparable animals receiving KL4-Surfactant.
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PMID:Efficacy of synthetic peptide-containing surfactant in the treatment of respiratory distress syndrome in preterm infant rhesus monkeys. 884 50


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