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Biomedical subjects

R H Clark

Publications and source records attributed to R H Clark.

At least 37 records · Page 2Linked to original sources
PubMed1999

Early prediction of neonatal chronic lung disease: a comparison of three scoring methods.

A variety of postnatal therapies have been and will be evaluated for prevention or treatment of neonatal chronic lung disease (CLD). A simple method for early selection of the highest risk infants would optimize intervention trials. Our study compared a clinical scoring system for predicting neonatal CLD (defined at 36 weeks postconceptional age) with previous regression models developed by Sinkin et al. (Sinkin model) [Pediatrics 1990;86:728-736] and Ryan et al. (Ryan model) [Eur J Pediatr 1996;668-671] in two distinct populations. A respiratory failure score (RFS) was prospectively developed for infants at <32 weeks of gestation admitted to the Wilford Hall Medical Center from January 1990-December 1992. Logistic regression modeling identified three independent predictors of CLD: gestation, birth weight, and RFS. Applying a modified RFS score (to include gestation and birth weight), the RFS, Sinkin, and Ryan models were compared among high-risk infants admitted to Wilford Hall from January 1993-December 1995, and to Crawford Long Hospital (Atlanta, GA) from January 1993-December 1994. Predictive values, sensitivity, specificity, and receiver operating characteristic (ROC) curves were determined for the primary outcome variable: CLD at 36 weeks of corrected gestation. Of 248 infants at <32 weeks admitted to Wilford Hall, 220 survived >7 days. Thirty of 31 (97%) infants diagnosed with CLD were <29 weeks or < or =1,000 g at birth. Despite important demographic and treatment differences between the study populations, similar ROC curves were found for each scoring method when individually evaluated among the three study groups. The RFS method at 72 h demonstrated the greatest area under the ROC curve for prediction of neonatal CLD in the groups as a whole. Application of the RFS method for early prediction of neonatal CLD at age 72 h should improve patient selection for early prevention trials.

Chronic Disease↗
PubMed1999

Protein electrostatic surface distribution can determine whether calcium oxalate crystal growth is promoted or inhibited.

Acidic proteins found in mineralized tissues act as nature's crystal engineers, where they play a key role in promoting or inhibiting the growth of minerals such as hydroxyapatite and calcium oxalate. Despite their importance in such fundamental physiological processes as bone and tooth formation, however, there is remarkably little known of the protein structure-function relationships that govern crystal recognition. We have taken a model system approach to elucidate some of the relationships between protein surface chemistry and secondary crystal growth of biological minerals. We show here that the distribution of electrostatic surface charge on our model protein, Protein G, determined whether the secondary growth of calcium oxalate, the principal mineral phase of kidney stones, was promoted or inhibited when the proteins were preadsorbed at low and equivalent surface coverages of <10%. The native Protein G, which contains 10 surface carboxylates, increased the rate of calcium oxalate growth from aqueous solution under constant composition conditions up to 97%, whereas a site-directed mutant with six of the surface charges removed inhibited the growth rate by 60%. The adsorption isotherms of both proteins were determined and suggested that the differences in electrostatic surface properties also lead to differences in protein orientation on the crystal surface. These results demonstrate that differences in electrostatic surface potential of proteins can directly determine whether secondary calcium oxalate growth is promoted or inhibited, and a model is proposed that suggests the distribution of carboxylate residues determines the interrelated binding orientation and exposed surface chemistry of the adsorbed Protein G.

Amino Acid Sequence↗
PubMed1999

Support of gas exchange in the delivery room and beyond: how do we avoid hurting the baby we seek to save?

With the availability of more sophisticated techniques for evaluating the premature neonate comes a parallel responsibility to carefully asses the process of resuscitation and assisted ventilation. The most fragile patients whom delivery room personnel are called to assist are the very low-birthweight preterm neonates. Their lung volumes are small, their chest walls are compliant, and their cerebral blood flow is low compared with term neonates. In this setting, everything that is done to the neonate must be performed with extreme caution and great care. This article discusses the causes of iatrogenic injury and suggests how such injury might be avoided.

Cerebrovascular Circulation↗
PubMed1998

A peptide that inhibits hydroxyapatite growth is in an extended conformation on the crystal surface.

Proteins play an important role in the biological mechanisms controlling hard tissue development, but the details of molecular recognition at inorganic crystal interfaces remain poorly characterized. We have applied a recently developed homonuclear dipolar recoupling solid-state NMR technique, dipolar recoupling with a windowless sequence (DRAWS), to directly probe the conformation of an acidic peptide adsorbed to hydroxyapatite (HAP) crystals. The phosphorylated hexapeptide, DpSpSEEK (N6, where pS denotes phosphorylated serine), was derived from the N terminus of the salivary protein statherin. Constant-composition kinetic characterization demonstrated that, like the native statherin, this peptide inhibits the growth of HAP seed crystals when preadsorbed to the crystal surface. The DRAWS technique was used to measure the internuclear distance between two 13C labels at the carbonyl positions of the adjacent phosphoserine residues. Dipolar dephasing measured at short mixing times yielded a mean separation distance of 3.2 +/- 0.1 A. Data obtained by using longer mixing times suggest a broad distribution of conformations about this average distance. Using a more complex model with discrete alpha-helical and extended conformations did not yield a better fit to the data and was not consistent with chemical shift analysis. These results suggest that the peptide is predominantly in an extended conformation rather than an alpha-helical state on the HAP surface. Solid-state NMR approaches can thus be used to determine directly the conformation of biologically relevant peptides on HAP surfaces. A better understanding of peptide and protein conformation on biomineral surfaces may provide design principles useful for the modification of orthopedic and dental implants with coatings and biological growth factors that are designed to enhance biocompatibility with surrounding tissue.

Amino Acid Sequence↗
PubMed1998

Current surgical management of congenital diaphragmatic hernia: a report from the Congenital Diaphragmatic Hernia Study Group.

BACKGROUND: Repair of congenital diaphragmatic hernia (CDH) has changed from an emergent procedure to a delayed procedure in the last decade. Many other aspects of management have also evolved since the first successful repair. However, most reports are from single institutions. The lack of a large multicenter database has hampered progress in the management of congenital diaphragmatic hernia (CDH) and makes determination of the current standard difficult. METHODS: The CDH study group was formed in 1995 to collect data from multiple institutions in North America, Europe, and Australia. Participating centers completed a registry form on all live-born infants with CDH during 1995 and 1996. Demographic information, data about surgical management, and outcome were collected for all patients. RESULTS: Sixty-two centers participated, with 461 patients entered. Overall survival was 280 of 442 patients (63%) where survival was recorded. The defect was left-sided in 78%, right-sided in 21%, and bilateral in 1%. A subcostal approach was used in 91% of patients, with pleural drainage used in 76%. A patch of some kind was used in just over half (51%) of the patients, with polytetrafluoroethylene being the most commonly used material (81%) in those patients with a patch. The mean surgical time was 102 minutes, with an average blood loss of 14 mL (range, 0 to 500 mL). The overwhelming majority of patients underwent repair between 6:00 AM and 6:00 PM (289 of 329, 88%). Nineteen percent of patients had surgical repair on extracorporeal membrane oxygenation (ECMO) at a mean time of 170 hours into the ECMO course (range, 10 to 593 hours). The mean age at surgery in patients not treated with ECMO was 73 hours (range, 1 to 445 hours). CONCLUSIONS: The multicenter nature of this report makes it a snapshot of current management. The data would indicate that prosthetic patching of the defect has become common, that after-hours repair is infrequent, and that delayed surgical repair has become the preferred approach in many centers. Furthermore, the mean survival rate of 63% indicates that despite decades of individual effort, the CDH problem is far from solved. This highlights the need for a centralized database and cooperative multicenter studies in the future.

Chi-Square Distribution↗
PubMed1998

Controversies in high-frequency ventilation.

Clinical care of newborns with respiratory failure is constantly changing and improving. Thus, optimizing health care is a commitment to constant, but careful change. This article addresses five current controversies about high-frequency ventilation and provides a discussion on each debated question.

Extracorporeal Membrane Oxygenation↗
PubMed1997

Onset of action and efficacy of terfenadine, astemizole, cetirizine, and loratadine for the relief of symptoms of allergic rhinitis.

BACKGROUND: Terfenadine, astemizole, cetirizine, and loratadine are compared in their abilities to produce relief of symptoms of allergic rhinitis. OBJECTIVE: The aim of this study was to compare the onset of action and efficacy of the study medications. METHODS: 111 ragweed-sensitive subjects were primed with pollen in the Environmental Exposure Unit. Study entry required adequate symptoms over a 3 hour exposure to 5000 +/- 300 grains/m3 of ragweed pollen. On the test day, subjects were given a single dose of either terfenadine 60 mg (22), astemizole 10 mg (22), cetirizine 10 mg (23), loratadine 10 mg (22), or placebo (22) when sufficiently symptomatic after a 60-minute exposure. Allergen levels were maintained and symptoms recorded every 30 minutes. RESULTS: Proportions of subjects with clinically important relief were cetirizine, 69.6%; terfenadine, 54.5%; loratadine, 50.0%; astemizole, 40.9%; and placebo, 31.8% but differences weren't significant between treatment groups (P = .119). Survival curves for times to onset of clinically important relief for the four treatment groups were not different (P = .119). Subjects realizing definitive relief were cetirizine, 65.2%; terfenadine, 45.5%; loratadine, 31.8%; placebo, 27.3%; and astemizole, 22.7% (P = .023). Survival analysis of onset time for definitive relief found significant differences (P = .010). The ranking was cetirizine --> terfenadine --> loratadine --> astemizole (quickest to slowest). Global evaluation based on subject willingness to take the medication again yielded percentages: cetirizine, 82.6%; terfenadine, 66.7%; astemizole, 63.6%; loratadine, 40.9%; and placebo, 36.4% (P = .036). CONCLUSION: Cetirizine and terfenadine continuously ranked higher in terms of onset of action and efficacy, while loratadine and astemizole ranked lower. Significance was detected in definitive relief and relative efficacy.

Adolescent↗
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↗
PubMed1996

The Provo multicenter early high-frequency oscillatory ventilation trial: improved pulmonary and clinical outcome in respiratory distress syndrome.

OBJECTIVE: To compare the hospital course and clinical outcome of preterm infants with respiratory distress syndrome treated with surfactant and managed with high-frequency oscillatory ventilation (HFOV) or conventional mechanical ventilation (CV) as their primary mode of ventilator support. DESIGN: A prospective randomized clinical trial. SETTING: Three community-based level III neonatal intensive care units. SUBJECTS: A total of 125 neonates who were 35 weeks or less estimated gestation requiring intubation and assisted ventilation for respiratory distress syndrome with arterial to alveolar oxygen ratio less than .50. INTERVENTIONS: Patients were randomized to continue CV (61 patients) or be changed to HFOV (64 patients) after exogenous surfactant administration (100 mg/kg). HFOV was used in a strategy to promote lung recruitment and maintain lung volume. Protocol respiratory care guidelines were followed; otherwise routine care was provided by each neonatal intensive care unit. MEASUREMENTS AND MAIN RESULTS: No differences were noted in demographic features between the two study groups. The study population birth weight was 1.51 +/- .47 kg (mean +/- SD), gestational age was 30.9 +/- 2.5 weeks, and study entry age was 2 to 3 hours. Patients randomized to HFOV demonstrated the following significant findings compared with CV-treated patients: vasopressor support was less intensive; surfactant redosing was not as frequent; oxygenation improved more rapidly and remained higher during the first 7 days; fewer infants required prolonged supplemental oxygen or ventilator support; treatment failure was reduced; more patients survived without chronic lung disease at 30 days; need for continuous supplemental oxygen at discharge was less; frequency of necrotizing enterocolitis illness was lower; there were fewer abnormal hearing tests; and hospital costs were decreased. No differences were seen between the two study groups in the frequency or severity of patent ductus arteriosus, air leak, retinopathy of prematurity, or intraventricular hemorrhage. Length of hospital stay and survival to discharge were similar for HFOV- and CV-treated infants. CONCLUSIONS: When used early with a lung recruitment strategy, HFOV after surfactant replacement resulted in clinical outcomes consistent with a reduction in both acute and chronic lung injury. Benefit was evident for preterm infants both less than or equal to 1 kg and more than 1 kg. In addition, early HFOV treatment may have had a more global effect on patient health throughout the hospitalization, resulting in reduced morbidity and decreased health care cost.

Equipment Failure↗
PubMed1996

Intraventricular hemorrhage and high-frequency ventilation: a meta-analysis of prospective clinical trials.

OBJECTIVE: The association between high-frequency ventilation (HFV) and intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL) has been debated. PURPOSE: To determine if premature neonates treated with HFV are at greater risk for developing IVH and/or PVL than neonates treated with conventional ventilation, we completed a meta-analysis of all prospective randomized control trials comparing HFV and conventional ventilation in the management of respiratory distress syndrome. METHODS: The meta-analysis included nine studies comparing HFV and conventional ventilation in the management of preterm neonates. To summarize the data, we calculated the difference in absolute risk for IVH and PVL between neonates treated with HFV and those treated with standard ventilation. These differences were combined to determine an overall difference in the absolute risk and its confidence interval. We examined the effect of estimated gestational age, birth weight, surfactant, and age at study entry on the results. Because one trial (HIFI study) was much larger than the other studies, it dominated the analysis, so we evaluated the data with and without including data from the HIFI trial. RESULTS: The occurrences of IVH and PVL ranged from 14% to 47% and 5% to 16%, respectively. This variation may be explained by the difference in the populations of neonates treated. The meta-analysis showed that use of HFV was associated with an increased risk of PVL (odds ratio = 1.7 with a confidence interval of 1.06 to 2.74), but not IVH or severe (> or = grade 3) IVH. When the results of the HIFI study were excluded, there were no differences between HFV and conventional ventilation in the occurrence of IVH or PVL. CONCLUSIONS: The association between HFV and adverse neurologic outcomes is primarily influenced by the results of the HIFI trial. Meta-analysis of more recent studies does not confirm the findings of the HIFI trial and suggests that HFV is not associated with increased occurrence of IVH or PVL.

Cerebral Hemorrhage↗