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Biomedical subjects

R H Clark

Publications and source records attributed to R H Clark.

At least 19 recordsLinked to original sources
PubMed1996

A randomized, double-blind, placebo-controlled, controlled antigen delivery study of the onset of action of aerosolized triamcinolone acetonide nasal spray in subjects with ragweed-induced allergic rhinitis.

BACKGROUND: Clinically apparent relief of nasal symptoms of allergic rhinitis is generally recognized to occur within 3 days to 1 week when intranasal corticosteroids are used. OBJECTIVE: A study was designed to evaluate the onset of action of triamcinolone acetonide (TA) in patients with ragweed-induced allergic rhinitis with an environmental exposure unit (EEU). METHODS: Eighty-five adults with ragweed-induced allergic rhinitis were primed with ragweed allergen in the EEU. Symptoms were recorded during a baseline exposure in the EEU, and subjects were randomized with a 5:1 ratio to receive either TA 400 micrograms (n = 71) or its propellant (n = 14). Subjects received study medication for 7 days under supervision in the morning and returned to the EEU in the evening for ragweed allergen challenge and symptom assessment. Clinically apparent onset of action was defined as a 25% decrease in symptom scores from baseline. RESULTS: A mean reduction in nasal congestion from baseline of greater than 25% (onset of action) was observed in the TA group, but not in the placebo group, by 10 hours. This was also observed for itching of the nose or palate and a combined measure of symptoms. In addition, the proportion of subjects with less nasal congestion after 1 day of treatment was greater in the TA group (41%) than in the placebo group (7%) (p less than 0.05). CONCLUSION: The unexpected early relief of symptoms observed in the TA group and, to a lesser extent in the placebo group, has important clinical implications in the treatment of allergic rhinitis.

Administration, Intranasal↗
PubMed1996

Efficacy of immunotherapy to ragweed antigen tested by controlled antigen exposure.

BACKGROUND: Immunotherapy is a recognized component in the management of allergic rhinitis. Its efficacy has been evaluated in a number of clinical field trials. These methods of evaluation are limited by control of antigen exposure. OBJECTIVE: A study was designed to evaluate the efficacy of immunotherapy in ragweed-induced rhinoconjunctivitis using an environmental exposure unit. METHODS: Forty-three subjects were grouped into (1) immunotherapy group: ragweed-allergic subjects on maintenance ragweed immunotherapy for at least 2 years (N = 16), (2) positive control group: ragweed-allergic subjects who had never received immunotherapy (n = 16), and (3) negative control group: ragweed-nonallergic subjects (N = 11). Ragweed specific skin tests and ragweed IgE levels were obtained prior to exposure. The study was done in a room where levels of 2,500 to 3,000 grains m3 of ragweed were maintained over three hours. Symptoms were recorded every 15 minutes. RESULTS: Nasal symptoms in the immunotherapy group were significantly less than in the positive control group after 45 minutes (P = .025). Significant differences were not observed for ocular symptoms. Combined nasal and ocular scores were 50% less in the immunotherapy group than in the positive control group by 75 minutes (P = .039). Ragweed-specific skin tests and IgE were significantly less in the immunotherapy group than in the positive control group. Rhinoconjunctivitis symptoms in the negative control group were absent throughout. CONCLUSIONS: Controlled ragweed pollen exposure in this setting demonstrated that ragweed immunotherapy significantly reduced symptoms of ragweed-allergic rhinitis but had no significant effect on ocular symptoms. This system presents opportunities for additional studies on immunotherapy for allergic respiratory conditions.

Adolescent↗
PubMed1996

Glutathione supplements protect preterm rabbits from oxidative lung injury.

The main objective of this study was to determine if glutathione (GSH) supplementation attenuated hyperoxic lung injury. Preterm (29 days) rabbits were delivered and exposed for 24 h to 1) room air, 2) room air and GSH, 3) 95% oxygen and GSH. GSH supplements (1 mM) were delivered in the nutritional support of 10% dextrose and saline through a peritoneal catheter. Animals assigned to oxygen had decreased lung volumes at 35 cmH2O, decreased lung compliance, increased edema, decreased cell viability, and decreased lung tissue and lavage-reduced/oxidized GSH levels, compared with control animals. Despite exposure to hyperoxia, animals supplemented with GSH were not different from room air controls with respect to lung mechanics, edema, cell viability, or tissue and lavage GSH. These studies suggest that GSH supplementation maintains normal lavage and lung tissue GSH levels in preterm animals exposed to hyperoxia and attenuates the changes in lung mechanics associated with oxygen-induced lung injury.

Animals↗
PubMed1996

Outcome of respiratory failure: a case-control study.

Despite the availability of ECMO (extracorporeal membrane oxygenation) services for nearly a decade, the criteria for the institution of ECMO for pediatric respiratory failure are still not clearly defined. Therefore, a chart review was performed on children who were mechanically ventilated more than 48 hours in 1989-1990 in order to evaluate possible predictors of death from pediatric respiratory failure. Twenty-three children died as a consequence of respiratory failure. Nonsurvivors in both years were compared with the 78 survivors in 1990, and potential predictors were subjected to multivariate analysis. After 4 days of mechanical ventilation, an alveolar-arterial oxygen gradient (AaDO2) greater than 400 torr (53.3 kPa) was a weak predictor of death due to respiratory failure, and yet an AaDO2 less than 400 torr (53.3 kPa) was a stronger predictor of survivability. Combination of variables did not yield a better predictor than any single variable. Early prediction of mortality from respiratory failure in this population was not found.

Acute Disease↗
PubMed1996

The safe introduction of new technologies into neonatal medicine.

In neonatal medicine, there is a technologic revolution in progress. During the past 10 years, we witnessed the introduction and improvement of monitoring equipment, the development of new modes of assisted ventilation, and the proliferation of extracorporeal membrane oxygenation. This article reviews how we might improve the process of the safe introduction of new technologies into neonatal medicine.

Animals↗
PubMed1995

Preferential use of venovenous extracorporeal membrane oxygenation for congenital diaphragmatic hernia.

Acute respiratory failure (ARF) secondary to congenital diaphragmatic hernia (CDH), unresponsive to maximal medical management, has traditionally been treated with venoarterial (VA) extracorporeal membrane oxygenation (ECMO). Venovenous (VV) ECMO offers several benefits over VA ECMO including preserved pulmonary blood flow, preservation of the carotid artery, and pulsatile flow. However, use of the VV modality has not been widespread because of concerns of the cardiac instability during bypass, and because only one double-lumen (DL) catheter size is available in the United States. The authors hypothesize that VV ECMO is a safe and effective treatment for CDH, symptomatic at birth, and report a single institution experience of preferential VV use for CDH. Over an 18-month period, 14 patients with CDH were placed on ECMO after maximal medical management failed, including high-frequency ventilation and nitric oxide in some cases. Ability to place the 14 Fr DL catheter was the sole criteria for VA or VV selection. Nine patients were successfully placed on VV and 5 on VA; no VV patient required conversion to VA. The two groups of patients were similar with respect to degree of illness, birth weight, EGA, time on and age at start of ECMO. Overall survival for this series was 64%: 66% in the VV group and 60% in the VA group. Two patients in the VV group were found to have congenital heart disease incompatible with life, were withdrawn from therapy and allowed to die, and are listed as treatment failures. The authors conclude that CDH patients receive adequate oxygenation and show hemodynamic stability on VV ECMO.(ABSTRACT TRUNCATED AT 250 WORDS)

Extracorporeal Membrane Oxygenation↗
PubMed1995

Prediction of mortality in neonates with congenital diaphragmatic hernia treated with extracorporeal membrane oxygenation.

OBJECTIVE: To determine if data collected by the Extracorporeal Life Support Organization Registry could be used to identify neonates with congenital diaphragmatic hernia who had a > 90% mortality rate, despite the use of extracorporeal membrane oxygenation (ECMO) support. DESIGN: We retrospectively reviewed data reported to the Extracorporeal Life Support Organization Registry on neonates with congenital diaphragmatic hernia. PATIENTS: Data regarding 1,089 neonates with congenital diaphragmatic hernia reported to the Extracorporeal Life Support Organization Registry between 1980 and 1992 formed the basis of this study. All of the neonates studied had been treated with ECMO. This patient population includes neonates with right- and left-sided diaphragmatic hernia. This registry does not include neonates with congenital diaphragmatic hernia who were not treated with ECMO. MEASUREMENTS AND MAIN RESULTS: Of 1,089 neonates with congenital diaphragmatic hernia, 679 (62%) survived. There were no differences between the two groups in gender or in the year they were treated. Survival rate did not significantly increase over the years between 1980 and 1992. When compared with survivors, nonsurvivors were more immature (38 +/- 2 vs. 39 +/- 2 wks; p = .01), had lower birth weights (3.0 +/- 0.5 vs. 3.21 +/- 0.53 kg; p = .001), were more often prenatally diagnosed (42% vs. 32%; p = .03), were cannulated at a younger age (31 +/- 54 vs. 40 +/- 50 hrs; p = .01), and had more severe respiratory compromise (higher peak pressures and PaCO2, lower PaO2 values). Multivariate analysis showed that arterial pH and PaO2 just before ECMO, and birth weight, had the highest discriminant coefficients. By using these variables in a discriminant function (D[fx] = 0.68 x pH + 0.62 x birth weight + 0.29 x PaO2; using standardized coefficients and variables), we could identify neonates who died with a sensitivity of 62%, a specificity of 63%, a positive-predictive value of 50%, and a negative-predictive value of 74%. No single variable or combination of variables yielded better results. CONCLUSIONS: Although a number of factors identify neonates with diaphragmatic hernia as being at higher risk of dying despite ECMO support, data currently collected by the neonatal Extracorporeal Life Support Organization Registry do not allow clinicians to effectively discriminate nonsurvivors from survivors.

Analysis of Variance↗
PubMed1995

Venovenous extracorporeal membrane oxygenation affects renal function.

OBJECTIVE: We evaluated the effect of venovenous extracorporeal membrane oxygenation (ECMO) on renal function and fluid balance in neonates with severe respiratory failure. DESIGN: We retrospectively reviewed the charts of 30 consecutive patients who met criteria for treatment with ECMO. Twelve were managed without ECMO (comparison group) and 18 were treated with venovenous ECMO (treatment group). SETTING: The study was conducted in a single level III neonatal intensive care unit in a regional children's hospital accepting medical and surgical neonatal transfers. Our hospital does not have an inborn service. PATIENTS: Neonates were included if their gestational age was more than 34 weeks, they weighed more than 2 kg, and their respiratory failure was severe enough to warrant consideration of ECMO as a mode of support. All the neonates in this study were treated with high-frequency ventilation before being considered for ECMO; none were treated with nitric oxide. Criteria used to determine whether a neonate was a candidate for ECMO included: (1) alveolar-arterial oxygen difference greater than 60 kPa (610 torr) for 8 hours; (2) alveolar-arterial oxygen difference greater than 59 kPa (605 torr) and a peak airway pressure greater than 3.7 kPa (38 cm H2O) for 4 hours; (3) oxygenation index greater than 40 on three of five postductal blood gases obtained at least 30 minutes apart and unstable patient condition; or (4) refractory, severe respiratory failure with sudden decompensation (partial pressure of arterial oxygen 3.4 kPa or lower, 35 torr) despite maximal medical management for 2 hours. We did not include patients with congenital diaphragmatic hernia. MAIN RESULTS: There were no differences between the groups in gestational age, birth weight, age at admission, gender, or diagnoses. Over the course of the 108 hours reviewed for each case, neonates treated with ECMO had higher positive fluid balance (P < .001), lower urine flow rates (P < .01), and higher blood urea nitrogen (P < .01) and creatinine (P < .01) levels than neonates managed without ECMO. There were no differences in mean blood pressure, protein intake, serum albumin, or use of diuretic therapy that might explain the differences between the groups. CONCLUSION: We conclude that venovenous ECMO is associated with transient impairment in renal function and marked fluid retention.

Blood Pressure↗
PubMed1995

Predictors of failure of high-frequency oscillatory ventilation in term infants with severe respiratory failure.

OBJECTIVE: To identify clinical factors in term neonates with severe respiratory failure that predict which neonates are unlikely to respond to high-frequency oscillatory ventilation (HFOV). DESIGN: This was a retrospective review of patient charts and medical records. PATIENTS: We studied 190 newborns treated with HFOV between July 1985 and December 1992. All patients were at least 35 weeks' estimated gestational age and had severe respiratory failure, defined as arterial to alveolar oxygen ratio (a/A ratio) of less than 0.2 or the need for peak inspiratory pressure greater than 35 cm H2O on conventional ventilation. RESULTS: Of the 190 patients, 111 (58%) responded to HFOV (HFOV responders), and 79 (42%) were placed on extracorporeal membrane oxygenation (ECMO) after HFOV failed to improve gas exchange (nonresponders). The two groups were similar in gender and birth weight. Factors associated with failure of HFOV to produce a sustained improvement in gas exchange were a diagnosis of congenital diaphragmatic hernia and more severe respiratory compromise as assessed by admission blood gas. Stepwise logistic regression analysis showed that a diagnosis of congenital diaphragmatic hernia/lung hypoplasia (CDH/LH) and the a/A ratio at initiation of and after 6 hours of HFOV were the only significant independent predictors of the need for ECMO. Among all the patients, the presence of CDH/LH or an initial a/A ratio of 0.05 or lower yielded a sensitivity of 74% and specificity of 77% in correctly identifying neonates in whom HFOV failed to produce a sustained improvement in oxygenation. When neonates with CDH/LH were excluded from analysis, the most significant predictor of failure of HFOV was the a/A ratio after 6 hours of HFOV. In neonates without CHD/LH, a 6-hour a/A ratio of 0.08 or lower discriminated responders from nonresponders (ie, treatment with ECMO) with a sensitivity of 77% and specificity of 92%. CONCLUSIONS: In our patients, the presence of CDH/LH, severe respiratory failure (a/A ratio 0.05 or lower) at initiation of HFOV, and lack of improvement in oxygenation (a/A ratio 0.08 or lower after 6 hours of HFOV) were associated with failure of HFOV and treatment with ECMO. This information should help other centers to identify neonates who are at the greatest risk for requiring ECMO support and thus allow prompt transfer to an ECMO center.

Acute Disease↗
PubMed1994

Prospective, randomized comparison of high-frequency oscillation and conventional ventilation in candidates for extracorporeal membrane oxygenation.

OBJECTIVE: To compare the safety and efficacy of high-frequency oscillation (HFO) with conventional ventilation in the treatment of neonates with respiratory failure. DESIGN: We conducted a multicenter, prospective, randomized trial. Patients were stratified according to pulmonary diagnosis and then were randomly selected for conventional ventilation or HFO. A balanced crossover design offered patients who met criteria of treatment failure a trial of the alternative mode of ventilation. SETTING: Four tertiary, level 3 neonatal intensive care units accepting regional referrals for extracorporeal membrane oxygenation. PATIENTS: Neonates were eligible for enrollment if their gestational age was > 34 weeks, their birth weight was > or = 2 kg, they were < 14 days of age, they required fractional inspired oxygen > 0.50 and a mean airway pressure > 0.98 kPa (10 cm H2O) to support adequate oxygenation, and they required a peak inspiratory pressure > 2.9 kPa (30 cm H2O) and a rate > 40 breaths per minute to support adequate ventilation. Exclusion criteria were lethal congenital anomalies, profound shock, need for cardiopulmonary resuscitation, and failure to obtain consent. MAIN RESULTS: Of 79 patients studied, 40 were assigned to conventional ventilation and 39 to HFO. Neonates randomly assigned to HFO required higher peak pressure (3.8 +/- 0.5 vs 3.3 +/- 0.8 kPa, 39 +/- 5 vs 34 +/- 8 cm H2O; p = 0.004) and more often met extracorporeal membrane oxygenation criteria (67% vs 40%; p = 0.03) at study entry than did those given conventional ventilation. Twenty-four patients (60%) assigned to conventional ventilation met treatment failure criteria compared with 17 (44%) of those assigned to HFO (not significant). Of the 24 patients in whom conventional ventilation failed, 15 (63%) responded to HFO; 4 (23%) of the 17 in whom HFO failed responded to conventional ventilation (p = 0.03). There were no differences between the two groups with respect to outcome, need for extracorporeal membrane oxygenation, or complications. CONCLUSIONS: We conclude that HFO is a safe and effective rescue technique in the treatment of neonates with respiratory failure in whom conventional ventilation fails.

Extracorporeal Membrane Oxygenation↗
PubMed1993

Efficacy of venovenous extracorporeal membrane oxygenation for neonates with respiratory and circulatory compromise.

We report a 12-month experience at Egleston Children's Hospital in Atlanta, Ga., with a protocol under which venovenous extracorporeal membrane oxygenation (ECMO) was used instead of venoarterial ECMO. Fifty-five newborn infants were referred for ECMO, four of whom had disqualifying conditions (all four died). Thirty-one infants were supported without recourse to ECMO, one of whom died. Of the 20 remaining patients, three were placed on a venoarterial ECMO regimen because of our early uncertainty about the efficacy of venovenous ECMO or because of technical constraints. All other patients (n = 17), including three with congenital diaphragmatic hernia, were supported with venovenous perfusion. No patient begun on a venovenous ECMO regimen required conversion to venoarterial bypass. Before ECMO, venovenous patients required an average dopamine dose of 16 micrograms/kg per minute and an average dobutamine dose of 6 micrograms/kg per minute. Of 15 patients studied before ECMO, three had significantly impaired contractility, and all had evidence of pulmonary hypertension on an echocardiogram. Mean blood pressure did not change while heart rate fell from 172 to 146 beats/min during the first 2 hours of ECMO and vasoactive drug doses were reduced. Of the 17 venovenous ECMO patients, 15 (88%) survived. We conclude that neonatal patients with severe hypoxia and substantial circulatory compromise can be effectively supported by venovenous ECMO in most cases.

Blood Circulation↗
PubMed1993

Effects of venovenous extracorporeal membrane oxygenation on cardiac performance as determined by echocardiographic measurements.

We evaluated the effects of venovenous extracorporeal membrane oxygenation (ECMO) on cardiac performance by echocardiographic measurements in 15 infants. Heart rate and blood pressure were also recorded. Echocardiographic measurements included aortic and pulmonary peak blood flow velocities, pulmonary time to peak velocity, left ventricular shortening fraction, velocity of circumferential fiber shortening corrected for heart rate, and peak systolic wall stress before, during, and after venovenous ECMO. Pre-ECMO echocardiograms showed borderline or normal indexes of cardiac function. After initiation of venovenous ECMO, all infants had normalization and no infant had deterioration of cardiac performance. The inotropic agents dopamine and dobutamine were decreased from average doses of 12 and 3.6 micrograms/kg per minute, respectively, to 3.7 and 1.3 micrograms/kg per minute, respectively, within 8.8 hours of the institution of venovenous ECMO. During this time the mean arterial pressure remained stable, and the heart rate decreased (169 +/- 21 vs 136 +/- 15 beats/min; p < 0.001). During the course of ECMO there were no changes in left ventricular shortening fraction, velocity of circumferential fiber shortening corrected for heart rate, or aortic peak blood flow velocities. Pulmonary artery peak blood flow velocity (69 +/- 22 vs 92 +/- 28 cm/sec; p = 0.04) and pulmonary time to peak velocity improved (47 +/- 11 vs 65 +/- 16 msec; p = 0.026). We conclude that venovenous ECMO does not have deleterious effects on cardiac performance.

Echocardiography↗
PubMed1993

Extracorporeal membrane oxygenation service at Egleston: two years' experience.

Extracorporeal membrane oxygenation (ECMO) is a perfusion support procedure that has been used to treat more than 7,000 patients with life threatening cardiac and/or respiratory failure. After 6 months of training and preparation, an ECMO service was opened on January 2, 1991, in Egleston Children's Hospital at Emory University. During the first 2 years, 96 neonatal, 31 pediatric, and 8 cardiac patients have been referred for possible ECMO. Of these 135 patients, 21 had disqualifying conditions. Sixty-four were considered candidates for ECMO but were able to be supported using less invasive therapies; only one of these died. Fifty patients were treated with ECMO of whom 39 survived (78%). Survival rates for neonatal, pediatric, and cardiac cases as separate groups as well as for each diagnostic category within these groups compare favorably with those reported by the international ELSO Registry. Notable in this series is the fact that 26/35 neonatal patients and 7/10 pediatric patients were successfully supported using venovenous (VV) rather than venoarterial (VA) perfusion, with the major indication for venoarterial ECMO being inability to introduce the 14F venovenous catheter into the patient's internal jugular vein. No patient initially managed with VV ECMO required conversion to VA. It is anticipated that avoidance of carotid ligation along with other innovations, such as the impending commercial availability of heparin-coated ECMO circuits, will make ECMO a highly attractive and appropriate therapy for an increasing number of high risk neonatal and pediatric patients in our state and region.

Adolescent↗
PubMed1993

Effect of maternal race on outcome of preterm infants in the military.

Previous studies suggest that low birth weight black infants have less morbidity and birth-weight-specific mortality during the perinatal period than low birth weight white infants. We studied the effect of maternal race on outcome in preterm infants born at a military hospital that offers free access to obstetric and neonatal care. Between January 1, 1986, and December 31, 1991, data were prospectively collected on all 667 infants delivered at Wilford Hall USAF Medical Center with an estimated gestational age of less than 35 weeks. Three hundred ninety-two white infants and 165 black infants were included in the data analysis. The mean (+/- SD) birth weight was 1701 +/- 65 g for white infants and 1462 +/- 66 g for black infants. The mean estimated gestational age was 31.0 +/- 3.2 weeks for white infants and 29.9 +/- 3.8 weeks for black infants. Preeclampsia was more frequent in black mothers than in white mothers for the entire study population (21% vs 14%), but the birth weight differential between races remained after correction for preeclampsia. There were no significant differences between races in stillbirths, gender, maternal age, maternal transfer status, number of prenatal visits, or percentages of mothers with small-for-gestational-age infants, multiple-gestation infants, prolonged rupture of membranes, or initial prenatal visit during the first trimester. Intraventricular hemorrhage was more frequent in white infants at 27 through 29 weeks estimated gestational age (50% vs 13%). There were no significant differences between the two groups in survival or in the occurrence of severe intraventricular hemorrhage or bronchopulmonary dysplasia.(ABSTRACT TRUNCATED AT 250 WORDS)

Birth Weight↗
PubMed1992

Rescue ventilation with high frequency oscillation in premature baboons with hyaline membrane disease.

We tested the hypothesis that high-frequency oscillatory ventilation can be efficacious in hyaline membrane disease (HMD) even after lung injury is established. We compared high frequency oscillatory ventilation (HFOV) rescue (n = 8; 15 Hz; I:E = 1:2) after 8 hours of positive pressure ventilation (PPV) with positive end-expiratory pressure, to continued PPV (control, n = 7) in premature baboons with HMD over a 24 hour period. Ventilator settings and physiologic parameters were recorded hourly. At necropsy (24 hours), lung status pressure-volume curves, alveolar phospholipids (PL), platelet activating factor-like activity (PAF), and lung water were determined. Roentgenographic and morphologic differences in lung inflation were quantified by standard techniques. No intergroup differences were found in heart rate, blood pressures, ventilator settings, FiO2, blood gases, or chest radiographs during the first 8 hours. Both groups had progressive physiologic disease. At 8 hours, HFOV-rescue animals, in contrast to controls, had immediate significant time-related improvements in Pa/AO2 (at the same Paw) and in oxygenation index (Pa/AO2/Paw) lasting for 16 hours. No significant intergroup differences in lung/body weight, lung water, lung mechanics, PL, PAF, or frequency of moderate to severe roentgenographic changes existed at 24 hours. Although all animals had morphologic evidence of HMD, saccular aeration was more uniform and airway dilatation less evident in HFOV rescue (P less than 0.0001). Based on the improved gas exchange, we conclude that HFOV rescue was efficacious in the "late' treatment of HMD, presumably because of the more uniform saccular aeration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗