Growth and colony-stimulating factors mediate eosinophil fibroblast interactions in chronic airway inflammation.
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Cell Line↗
Biomedical subjects
H Kirpalani
Publications and source records attributed to H Kirpalani.
Cytokine expression by neutrophils and macrophages in vivo: endotoxin induces tumor necrosis factor-alpha, macrophage inflammatory protein-2, interleukin-1 beta, and interleukin-6 but not RANTES or transforming growth factor-beta 1 mRNA expression in acute lung inflammation.
Using a rat model of acute lung inflammation induced by intratracheal instillation of lipopolysaccharide (LPS), we investigated the kinetics of mRNA expression and the potential cellular sources of tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-2 (MIP-2), interleukin (IL)-1 beta, IL-6, RANTES, and transforming growth factor-beta 1 (TGF-beta 1). By Northern blot analysis, TNF-alpha and MIP-2 mRNAs in total lung tissue increased markedly by 30 min and peaked by 1 h after LPS exposure, whereas expression of IL-1 beta and IL-6 was not detected until 1 h and peaked within 6 h. In contrast, neither RANTES nor TGF-beta 1 mRNA was induced by LPS throughout 72 h, although a basal expression was detected in both saline- and LPS-treated lung tissues. At 1 h after LPS, the bronchoalveolar lavage (BAL) fluid contained about 98% alveolar macrophages (AM), whereas by 6 or 12 h, 88% of BAL cells were polymorphonuclear neutrophils (PMN). Upon extraction of total RNA after separation of AM from PMN in BAL, Northern analysis showed that at 1 h, AM expressed pronounced signals for TNF-alpha, MIP-2, IL-1 beta, and IL-6. At 6 and 12 h, however, while cytokine transcripts decreased in AM, PMN exhibited strong signals for these cytokines. A low basal noninducible signal for TGF-beta 1 but not RANTES was detected in both AM and PMN. Finally, by in situ hybridization techniques, PMN in the lung tissue, particularly those located in the vicinity of the bronchiole and vasculature, were demonstrated to localize MIP-2 mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)
Acute Disease↗
Measurement of functional residual capacity by sulfur hexafluoride in small-volume lungs during spontaneous breathing and mechanical ventilation.
We modified a sulfur hexafluoride (SF6) washout technique to allow functional residual capacity (FRC) determinations in small-volume lungs both during spontaneous breathing and controlled mechanical ventilation. This method facilitates measurements in subjects who attempt spontaneous breaths between ventilator-generated breaths. We wished to confirm the accuracy and precision of the measurements and the method's sensitivity to change. The method uses a pneumotach together with a fast, mainstream infrared SF6 sensor mounted between the endotracheal tube and the ventilator circuit. A low flow of pure SF6 is delivered into the constant gas flow of the ventilator circuit to wash in tracer gas at a concentration of less than 2%. The flow signal and the instantaneous SF6 concentration is processed on-line by a computer. The calibration of the SF6 sensor's nonlinear signal and the ability of the flow sensor to reflect flow values precisely near zero flow had a major impact on the accuracy of the FRC estimate. This accuracy was tested by comparing measured FRC values with a dummy lung's true FRC that was varied from 7 to 70 mL. The comparison differed by 0.7 +/- 3.2% (mean +/- SD; range, -5.1 to 7.8%). As a measure of reproducibility (precision) across 20 FRC determinations in five adult rabbits, the average coefficient of variation was 1.7% (range, 0.57 to 4.33%) during continuous positive airway pressure and 1.98% (range, 0.35 to 3.81%) during controlled mechanical ventilation. The method proved sensitive to changes in FRC related to changes in airway pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Resistive and elastic unloading to assist spontaneous breathing does not change functional residual capacity.
Resistive and/or elastic unloading (a negative ventilator impedance, otherwise termed proportional assist ventilation) may be a useful means to assist spontaneous breathing. This only applies if the ventilator accurately provides pressure changes at the airway opening (P(ao)) proportional to the instantaneous flow and/or volume signal of spontaneous breathing and no significant phase lag. We designed such an infant ventilator, which controls the P(ao) by a negative feedback loop, and superimposes a second positive feedback circuit to generate unloading. To test this mode and the ventilator's accuracy in performing the synchronized pressure changes, we examined the functional residual capacity (FRC). We hypothesized that unloading by itself would not alter FRC because P(ao) should return to a preset baseline at end-expiration, and furthermore, that FRC could be actively altered by changing the baseline. Five anesthetized, tracheotomized, spontaneously breathing rabbits [respiratory system compliance 22.4 +/- 4.6 mL/kPa (mean +/- SEM)] were exposed to end-expiratory P(ao) levels of 0, 0.2, 0.4, and 0.6 kPa. At each of these levels a period of regular continuous positive airway pressure (CPAP) was alternated with a period of unloading (-40 mL/kPa ventilator compliance combined with -3 kPa/L/s ventilator resistance). FRC measured by a sulfur hexafluoride washout technique was virtually identical on CPAP and during unloading at equal end-expiratory P(ao) (difference, 1.41% +/- 0.95%), but FRC increased upon elevation of the end-expiratory P(ao) by 29.4 +/- 3.6 mL/kPa on CPAP and 30.2 +/- 3.2 at unloading (difference NS). We conclude that FRC is not destabilized by unloading, but that during unloading, as during CPAP, it depends on the end-expiratory P(ao).
Animals↗
A randomized, controlled trial of platelet transfusions in thrombocytopenic premature infants.
A multicenter prospective, randomized controlled trial was conducted to determine whether early use of platelet concentrates would reduce the incidence or extension of intracranial hemorrhage or both in sick preterm infants with thrombocytopenia. The effects on bleeding as reflected by the amount of blood product support administered and a shortened bleeding time were assessed as secondary outcomes. Premature infants with a platelet count < 150 x 10(9)/L within the first 72 hours of life were randomly assigned to receive either conventional therapy or conventional therapy plus platelet concentrates (10 ml/kg). The platelet count was maintained < 150 x 10(9)/L until day 7 of life by one to three platelet transfusions. In 22 (28%) of the 78 treated infants and 19 (26%) of the 74 control infants, either a new intracranial hemorrhage developed or an already-present one became more extensive (p = 0.73). Similar numbers of infants had each grade of intracranial hemorrhage on both initial and follow-up ultrasonography. Similar numbers of infants received fresh frozen plasma and packed red blood cells, but treated infants received less of both. The bleeding time was prolonged in the treated group before the infusion of platelet concentrates but subsequently shortened (mean difference, 79.0; 95% confidence interval, 73.1 to 84.9). Subanalysis of the control group showed that infants with platelet counts < 60 x 10(9)/L (n = 21) on at least one occasion received more fresh frozen plasma and packed red blood cells than did those with platelet counts > 60 x 10(9)/L.(ABSTRACT TRUNCATED AT 250 WORDS)
Blood Component Transfusion↗
Spinal cord injury at birth: diagnostic and prognostic data in twenty-two patients.
OBJECTIVES: To establish criteria, evident soon after birth, that predict long-term outcome of neonates with spinal cord injury (SCI) at birth. DESIGN: Retrospective case-series. SETTING: Five Canadian regional neonatal tertiary care centers. PATIENTS: Consecutive samples of patients referred to five centers for a total of 22 subjects, in whom SCI was diagnosed during life. Sites of lesions were above the fourth cervical vertebrae (n = 14), at the fourth cervical to the fourth thoracic vertebrae (n = 6), and at the thoracolumbar region (n = 2). MEASUREMENTS AND MAIN RESULTS: All 14 patients with upper cervical SCI had cephalic presentations, whereas all 6 patients with cervicothoracic SCI had breech presentations (p < 0.0001). The site and extent of lesion were best diagnosed by clinico-imaging correlations. Ultrasonography appeared to be the most useful imaging study. In patients with upper cervical SCI who had no coexistent central nervous system abnormality associated with early death, long-term outcome in survivors (dependency on mechanical ventilation and on aids for upper limb activity and for ambulation) was best predicted by age when breathing was first observed and by rate of recovery of limb motor function in the first 3 months. The presence of breathing movements on day 1 (n = 2) was associated with mild disability. The absence of breathing movements on day 1 and little or no recovery of motor function in the first 3 months was associated with permanent total dependency on mechanical ventilation and severe quadriplegia (n = 5). Apnea on day 1 and intermediate recovery rates in the first 3 months was associated with variable long-term prognoses (n = 3).
Birth Injuries↗
Polymorphonuclear leukocytes as a significant source of tumor necrosis factor-alpha in endotoxin-challenged lung tissue.
The kinetic expression and potential cellular source of tumor necrosis factor-alpha (TNF-alpha) in lipopolysaccharide-(LPS) induced acute lung inflammation was investigated using a rat model by Northern blot analysis, in situ hybridization and immunohistochemistry. LPS induced a polymorphonuclear leukocyte infiltrate in the lung that peaked between 6 and 24 hours. TNF-alpha messenger (m)RNA was strongly induced by LPS in whole lung tissues shown by Northern analysis. Both alveolar macrophages and polymorphonuclear leukocytes (PMNs), purified from bronchoalveolar lavage fluids of LPS-treated rats, were shown to express TNF-alpha mRNA by Northern analysis. However, PMNs displayed several times more TNF-alpha mRNA, relative to actin mRNA, than alveolar macrophages at 6 and 12 hours. By in situ hybridization, most of the cells positive for TNF-alpha mRNA at 6 and 12 hours seemed to be PMNs located within the tissue near bronchioles or vessels. By immunohistochemistry, TNF-alpha protein was localized mainly to alveolar macrophages at early times (1 to 3 hours) after LPS challenge, and thereafter, PMNs seemed to be the predominant source of TNF-alpha protein as more than 90% of total intraalveolar positive cells at 6 and 12 hours were PMN. Thus, our data provide the first in vivo evidence that PMNs can serve as a significant source of TNF-alpha at sites of acute inflammation.
Animals↗
Birthweight, early passive respiratory system mechanics, and ventilator requirements as predictors of outcome in premature infants with respiratory failure.
Early respiratory mechanics have been reported to predict outcome in newborns with respiratory failure. However, it remains unknown whether measurements of pulmonary function add significantly to the predictive value of more readily available variables The present study was designed to answer this question. Passive respiratory system mechanics were measured by an airway occlusion technique in 104 ventilator-dependent premature infants between 6 and 48 hours of life and corrected for infant size. A ventilation index [FiO2 x mean airway pressure (MAP)] was calculated at the time of pulmonary function testing. Poor outcome was defined as death from respiratory failure or need for supplemental oxygen at 28 days. Stepwise logistic function regression examined whether ventilation index and respiratory mechanics added predictive power over and above birthweight. Five infants died, and 45 patients required supplemental oxygen at 28 days. Birthweight was a strong predictor and would have entered the logistic model first in any case. Ventilation index added significantly to the predictive model (P = 0.038). Respiratory system conductance (P = 0.15) and compliance (P = 0.93) entered on the third and last step, respectively. We conclude that in premature infants with respiratory failure, birthweight is a strong predictor of outcome. Early ventilator requirements but not respiratory system mechanics, add significantly to this predictive model.
Birth Weight↗
Informational needs of parents of sick neonates.
Sixty-one parents of 43 neonates in a neonatal intensive care unit were interviewed within 3 days of their first conference with the neonatologist to assess their needs for medical information. The conference with the physician and the interview with the investigator were audiotaped. Information given by the physician and information recalled by the parents was categorized and rated by the investigator. The physicians gave very detailed information about diagnosis in 77% of cases whereas 39% of the parents recalled diagnostic information in great detail. Respective percentages for prognosis were 16 and 33; for current management (eg, investigation, therapy), 28 and 66; and for cause of illness, 16 and 18. The statistical significance of the differences between the very detailed information int he physician-parent conferences and in the parent-investigator interviews was, by category, less than .002, less than .041, less than .004, and not significant, respectively. Information in the respective categories was described as "most helpful" by 20%, 67%, 90%, and 8% of parents. All but one of the parents stated that they wanted the whole truth. Physician uncertainty in providing information was significantly associated with severity of illness. It is concluded that while parents wanted information in all categories, they paid most attention to that relating to management. Physician-parent discordances with respect to information about management, diagnosis, and prognosis suggest directions for future investigation of the optimal content of information for parents in this context.
Adult↗
The Medical reform Group has a purpose.
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Delivery of Health Care↗
End-tidal carbon dioxide measurements in critically ill neonates: a comparison of side-stream and mainstream capnometers.
To determine whether end-tidal PCO2 (PETCO2) measurements obtained with two infrared capnometers accurately approximates the arterial PCO2 (PaCO2) in critically ill neonates, simultaneous measurements of PETCO2 were obtained from the distal and proximal ends of the tracheal tube with a sidestream capnometer (Puritan Bennett/Datex--BP/D) and from the proximal end with a mainstream capnometer (Hewlett-Packard-HP) in 20 intubated neonates. Distal sidestream PETCO2 and mainstream PETCO2 correlated with the PaCO2 (r2 = 0.66 and 0.61, respectively) within the range of 26-57 mmHg PaCO2. However, proximal PETCO2 with the sidestream capnometer correlated very poorly (r2 = 0.09) with PaCO2. The slope of the least square regression line for the distal sidestream capnometer, 0.67, was significantly less than that for the mainstream capnometer, 0.78 but both were significantly greater than that for the proximal sidestream capnometer, 0.39 (P less than 0.05). The slope of the regression for the proximal sidestream capnometer did not differ significantly from horizontal. Insertion of the mainstream sensor for the HP capnometer significantly increased the transcutaneous CO2 when compared with preinsertion values. We conclude that both distal sidestream and mainstream capnometry provide accurate estimates of the PaCO2 in critically ill neonates.
Carbon Dioxide↗
Measuring on-line compliance in ventilated infants using hot wire anemometry.
We investigated the validity of using tidal volume (VT) as measured by the neonatal volume monitor (NVM) to derive respiratory compliance. The NVM is a noninvasive device that measures VT by hot wire anemometry. The quotient of VT and the inflation pressure amplitude from the mechanical ventilator provided a measure of respiratory compliance. This was validated against the single breath occlusion technique in 15 infants (birth weight 0.9 to 4.4 kg). To ensure fully passive expiration, only paralyzed or sedated patients were studied. Only 12 of the 15 infants were analyzed because of limitations in the single breath technique. In three infants the flow-volume curves obtained were alinear, indicating inhomogeneity. In the 12 infants with acceptable single breath data, agreement between the two methods was excellent. Using the expired volume, r2 was .99. We conclude that the NVM can be used to obtain valid estimates of respiratory compliance on-line in intubated infants.
Airway Resistance↗
Respiratory response and pharmacokinetics of intravenous salbutamol in infants with bronchopulmonary dysplasia.
The effects of iv salbutamol on respiratory mechanics were studied in six infants with bronchopulmonary dysplasia. Salbutamol was infused at a dose of 30 micrograms/kg over 30 min in five infants; a sixth infant received 66.7 micrograms/kg over 4 min. Salbutamol caused improvement in total respiratory system compliance and in airflow resistance. There was no correlation between salbutamol serum concentration and pulmonary function. Elimination half-time appears to be dictated in these infants more by the distribution volume (Vd) than by clearance (Cl). The area under concentration-time curve of salbutamol correlated inversely to the change in heart rate (HR). There was a significant positive correlation between Vd and percent HR change. These data provide evidence that preterm infants have measurable activity of bronchiolar beta 2 receptor responsive to salbutamol.
Airway Resistance↗
Widened subarachnoid space in pre-discharge cranial ultrasound: evidence of cerebral atrophy in immature infants?
The authors examined the incidence of widened subarachnoid spaces (SAS) among 75 infants with birthweights less than or equal to 1250g, and their significance in developmental outcome. Nine of 30 infants with gestations less than or equal to 27 weeks had widened SAS in their pre-discharge ultrasound scans. Three of the nine, including two with periventricular leukomalacia (PVL), had late-onset ventricular enlargement, unrelated to intraventricular haemorrhage (IVH): all three were developmentally impaired. The other six infants without ventricular enlargement developed normally, including one with IVH. Five of the remaining 21 infants with gestations less than or equal to 27 weeks and without widened SAS were developmentally impaired. Widened SAS was not associated with a significantly increased risk of developmental impairment; ventricular enlargement and PVL were the only significant factors. The authors conclude that an isolated finding of widened SAS is not predictive of impairment in immature infants.
Atrophy↗
Case 6. Perinatal hemochromatosis.
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Female↗
Searching MEDLINE for randomized clinical trials involving care of the newborn.
Randomized clinical trials make up only a small fraction of published articles concerning care of the newborn infant and an even smaller fraction of articles about all human subjects. The busy pediatrician who wants to keep abreast of the medical literature requires strategies to detect such relevant studies promptly and reliably. Computer searching of MEDLINE is an attractive, potentially powerful but not sufficiently validated means of achieving this goal. Therefore, the sensitivity, specificity, and positive predictive value of two MEDLINE search strategies designed to detect randomized clinical trials for prevention and treatment of newborn diseases among all original articles about human subjects appearing in ten pediatric and general medical journals during 1985 were determined. The yield of both MEDLINE searches was compared to that of a manual search. Fifty-three randomized clinical trials of newborn care were identified by hand search among 233 articles concerning care of the newborn and 2,988 original articles about human subjects. The sensitivities of the MEDLINE searches were 53% and 34%, respectively, and the positive predictive values were 82% and 69%, respectively. Specificity of both computer searches was virtually 100%. Twenty-one randomized clinical trials were not identified by either MEDLINE search strategy, 17 of them for failure of the indexer to assign any methodologic terms at all or failure to assign sufficiently stringent methodologic terms. Consequently, sensitivities were higher, 77% and 68% respectively, when no methodologic terms were used during repeat searches. However, positive predictive values decreased concomitantly to 20% or less.(ABSTRACT TRUNCATED AT 250 WORDS)
Clinical Trials as Topic↗
Strengths and limitations of the Apgar score: a critical appraisal.
The Apgar score is widely used for several purposes: to discriminate between infants who require resuscitation at birth and those who do not; to predict outcome; and to evaluate change in the condition of the newly born over the first minutes of life. Using published evidence of its clinical reliability and validity, this article explores whether the Apgar score serves all three measurement purposes equally well. Methodologic guidelines for assessing health indices are applied to examine the structure of the Apgar score as well as its function where performance data are lacking or inadequate. Despite the advent of modern technology, the Apgar score remains the best tool for the identification of newly born infants in need for cardiopulmonary resuscitation. For predicting later death or handicap, the Apgar score is insensitive but fairly specific. The ability of the Apgar score to measure change over time has not been studied systematically; however, available data suggest that serial Apgar ratings in infants with early low scores detect clinically important recovery of lack thereof.
Apgar Score↗