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Biomedical subjects

R M Ward

Publications and source records attributed to R M Ward.

At least 19 recordsLinked to original sources
PubMed2006

Basic and translational research in neonatal pharmacology.

Pharmacologic study is needed in the extremely immature newborns who currently survive. Study is needed of both the drug treatment previously established in more mature neonates and of novel drug therapy. Carefully controlled studies are needed to identify accurately both beneficial and harmful drug therapy and the mechanisms of that toxicity. Careful pharmacologic study of drug disposition and its mechanisms might lead to dosing paradigms or patient selection that minimize toxicity and maximize efficacy. In vivo, translational models of neonatal diseases are limited, but can be used to identify novel treatments and study mechanisms of established, successful therapy. Findings from such studies can generate hypotheses for study in humans leading to a continuing scientific interchange from bedside to bench to bedside. Similarly, clinical observations can generate hypotheses for study in translational models where more invasive analyses are possible. Specific areas of drug treatment should focus on neonatal disorders with long-term, adverse outcomes, such as chronic lung disease, that is amenable to translational study with animal models. National data show a progressive decrease in the clinician-scientist pool entering biomedical research. The future of neonatal pharmacology studies requires an increase in training programs for the physician-scientist whose clinical education in neonatology can be complemented by rigorous basic-science training. Success as a clinician-scientist will require collaboration with full-time basic scientists who can continue studies during periods of clinical work and provide critical study methodology to the overall study design. Such a work environment must be supported by academic institutions and may require more flexibility in the promotion and tenure schedule and process, such as the nature of what it rewards. To complement this, the NIH could modify its grant reporting process to identify co-investigators in studies who may provide unique input to the study concepts and design, such as clinical correlations or clinical investigations.

Animals↗
PubMed2003

Viscosity of rice flour: a rheological and biological study.

Rice breeders frequently use rapid visco analysis (RVA) as in index of rice quality. Potentially, viscosity curves could also be used to predict the sensory properties of a sample of rice or the processing properties of rice when used as an ingredient. The aim of this study is to determine the contribution of the main components of rice flour-starch and protein polymers and lipids-to the viscosity curve, accounting for biological and rheological contributions, and interactions with water. By deconstructing the rice flour, resistance to shear is generally the primary factor that affects rheological processes in the RVA, often masking the physical processes of cooking. Thus, higher concentrations of water reveal more about the true biological and physical processes of the transition from a powder to paste. Proteins contribute to peak height, offset thixotropy, and contribute to the final viscosity. Starch-lipid complexes can mask differences in the molecular structures of amylose and amylopectin, and removing lipids alters the structure of the paste significantly, which consequently alters viscosity curves.

Amylose↗
PubMed2001

Albuterol delivery in a neonatal ventilated lung model: Nebulization versus chlorofluorocarbon- and hydrofluoroalkane-pressurized metered dose inhalers.

The aim of this study was to compare albuterol delivery in a neonatal ventilated lung model, using three delivery methods: 1) jet nebulizer; 2) chlorofluorocarbon-pressurized metered dose inhaler (CFC-MDI) actuated into an ACE(R) spacer; and 3) hydrofluoroalkane-pressurized MDI (HFA-MDI) actuated into an ACE(R) spacer. The bench model consisted of a mechanically ventilated infant test lung with ventilator settings to simulate a very low birth weight neonate with moderate lung disease. Albuterol solution (0.5%) was nebulized at the humidifier and temperature port, 125 cm and 30 cm from the Y-piece, respectively. Albuterol metered dose inhalers (MDIs) were actuated into an ACE(R) spacer that was tested in two positions: 1) inline between the endotracheal (ET) tube and the Y-piece; and 2) attached to the ET tube and administered by manual ventilation. Albuterol was collected on a filter at the distal end of the ET tube and was quantitatively analyzed by high performance liquid chromatography. Albuterol delivery by CFC-MDI (position 1, 4.8 +/- 1.0%, vs. position 2, 3.8 +/- 1.6%, P > 0.05) and HFA-MDI (position 1, 5.7 +/- 1.6%, vs. position 2, 5.5 +/- 2.4%, P > 0.05) were significantly greater than delivery by nebulization at 30 cm (0.16 +/- 0.07%) and 125 cm (0.15 +/- 0.03%) from the Y-piece (P < 0.001). A single actuation of albuterol MDI delivered the equivalent of nebulizing 2.5-3.7 mg of albuterol solution. We conclude that albuterol administered by MDI and ACE(R) spacer resulted in more efficient delivery than by nebulization in this mechanically ventilated neonatal lung model. There was no significant difference in drug delivery between CFC-MDI and HFA-MDI; nor did the placement of the spacer significantly affect drug delivery.

Administration, Inhalation↗
PubMed2001

Difficulties in the study of adverse fetal and neonatal effects of drug therapy during pregnancy.

This article reviews the difficulties in studying adverse effects of drugs during pregnancy on the fetus and newborn. A study design should strive for prospective recording of drug intake during pregnancy, comparison to appropriate control groups adjusted for inherited traits, and single drug exposures for evaluation of specific syndromic causation, such as the Fetal Hydantoin Syndrome. Animal models are best used in mechanistic study of adverse drug effects on the fetus rather than for screening for adverse effects. Careful conclusions about causation of drug-induced adverse effects are needed to avoid false associations while providing appropriate safeguards to the fetus and newborn.

Abnormalities, Drug-Induced↗
PubMed1999

Ten guiding principles for teaching children and adolescents about medicines. US Pharmacopeia.

In 1996, an open conference sponsored by the US Pharmacopeia (USP) and attended by more than 100 health care professionals established the need and rationale for teaching children and adolescents about medicines. After the conference, a public, iterative, consensus-development process including participation by 35 health-professional organizations was undertaken. This process resulted in a USP position statement, "Ten Guiding Principles for Teaching Children and Adolescents About Medicines," which supports the right of children and adolescents to receive developmentally appropriate information and direct communications about medicines that are consistent with their health status, capabilities, and culture. The position statement is intended to stimulate activities that will help children become active participants in the process of appropriate use of medicines and prepare them for the day they begin to use medicines independently.

Adolescent↗
PubMed1999

Cisapride: a survey of the frequency of use and adverse events in premature newborns.

OBJECTIVE: This survey estimated the frequency of use and adverse events associated with cisapride treatment of premature newborns in intensive care units. It was initiated in response to a warning issued in Canada cautioning against cisapride treatment of premature infants of <36 weeks' gestation and <3 months of age. METHODOLOGY: Surveys were mailed to 105 neonatology training program directors to obtain the total number of neonatal intensive care unit (NICU) admissions, the number of admissions of infants of <36 weeks' gestation, the number of years that cisapride had been used, the estimated percent/number of premature patients treated with cisapride per year, and the frequency and nature of arrhythmias or other adverse events associated with cisapride treatment. Of 105 programs, 46 responded to a single mailing of the first survey. A second survey mailed to the 45 respondents to the first survey sought to determine the indications, diagnostic tests, and dosages used with cisapride treatment of premature newborns. Of the 45 programs, 26 responded to the second survey. RESULTS: More than 58 000 premature newborns of <36 weeks' gestation were admitted to the NICUs we surveyed, and approximately 19% were treated with cisapride. No deaths attributable to cisapride were reported among >11 000 preterm newborns treated. Three nonfatal arrhythmias were reported; two associated with 10-fold dosing errors and one with co-treatment with erythromycin, a macrolide antibiotic that reduces the metabolism of cisapride. Diarrhea was reported in 12 patients, and reversible liver enzyme changes were noted in one patient. Typically, cisapride treatment was started in dosages of 0.1 to 0.2 mg/kg/dose, repeated every 6 to 8 hours. Treatment usually was begun empirically, without a preceding study to document gastroesophageal reflux. The most frequent indications for cisapride treatment were choking or gagging, with associated apnea, bradycardia, and desaturation. Approximately 50% of patients had discontinued cisapride treatment before discharge. Eighty-four percent of clinicians judged cisapride to be effective for the problems being treated. CONCLUSIONS: Cisapride treatment of premature infants of <36 weeks' gestation and <3 months of age in NICUs appears to be widespread in the United States. Complications and adverse events were seen when cisapride was administered in excessive dosages or in combination with a drug that inhibits its metabolism and leads to increased serum concentrations. Severe toxicities such as arrhythmias were reported with a frequency of <1/11 000 NICU admissions. However, in a retrospective survey, episodes of toxicity, including mortality, attributable to cisapride may not have been recognized or reported.

Cisapride↗
PubMed1998

Visual search for a tilted target: tests of spatial uncertainty models.

We report that spatial cueing of a parafoveal target in the presence of distractors enhances orientational acuity for that target. When no distractors were present, orientation thresholds were in the range 1-4 degrees. For long exposure times, distractors increased threshold by the amount predicted from a winner-takes-all spatial uncertainty model. For short (100-msec) exposures followed by a random dot mask, the rise in threshold with distractors was considerably greater than that predicted from spatial uncertainty. For brief exposures the effect of distractors was greater when the target and distractors were spatially crowded rather than widely spaced. Adding a tilt to the distractors in the opposite direction to the target increased thresholds still further. Cueing the target with a spatial pointer decreased the effect of distractors, even when they were crowded. We suggest that when attention cannot be appropriately focused, discrimination is carried out by a relatively coarse texture analyser, which averages over several elements, and that focused attention permits the analysis of the target over a smaller area of space.

Attention↗
PubMed1998

Genetic studies into inherited and sporadic hemolytic uremic syndrome.

Hemolytic uremic syndrome (HUS) in adults carries a high morbidity and mortality, and its cause remains unknown despite many theories. Although familial HUS is rare, it affords a unique opportunity to elucidate underlying mechanisms that may have relevance to acquired HUS. We have undertaken a genetic linkage study based on a candidate gene approach. A common area bounded by the markers D1S212 and D1S306, a distance of 26 cM located at 1q32 segregated with the disease (Z max 3.94). We demonstrate that the gene for factor H lies within the region. Subsequent mutation analysis of the factor H gene has revealed two mutations in patients with HUS. In an individual with the sporadic/relapsing form of the disease we have found a mutation comprising a deletion, subsequent frame shift and premature stop codon leading to half normal levels of serum factor H. In one of the three families there is a point mutation in exon 20 causing an arginine to glycine change, which is likely to alter structure and hence function of the factor H protein. Factor H is a major plasma protein that plays a critical regulatory role in the alternative pathway of complement activation. In light of these findings and previous reports of HUS in patients with factor H deficiency, we postulate that abnormalities of factor H may be involved in the etiology of HUS.

Adult↗
PubMed1998

Congenital malformations presenting during the neonatal period.

Discharge of the newborn within 24 to 48 hours after birth makes it more difficult to detect some congenital malformations and increases the need for careful examination and review of the history of the pregnancy, delivery, and nursery course. Progressive physiologic changes after birth, especially in the cardiovascular system, precede the development of signs indicative of disease for certain congenital malformations. Discharge before these changes occur may delay their detection because the newborn is not being monitored by medical or nursing caregivers. The AAP Committee on the Fetus and Newborn has published guidelines for criteria for safe discharge and follow-up evaluation to help create a safe situation for such early discharges. Some specific observations at birth may lead to earlier diagnosis. Careful attention to subtle differences between the initial and follow-up examination, such as a changing cardiac murmur or quality of pulses or abdominal fullness, may provide clues to the diagnosis of congenital malformations. Coordinated suck and swallow with successful feeding and passage of stool and urine within 24 hours after birth should occur before discharge. Reports of feeding difficulties should be reviewed. Although a thorough examination is facilitated by a sleeping infant, documentation of a normal pitched cry helps in the evaluation of the upper airway. Parents should be counseled about signs of illness that warrant medical attention, and early follow-up is needed to detect problems early enough to intervene effectively. In addition, although passage of a feeding tube through each nare and to the stomach with aspiration and measurement of gastric volume is not a routine procedure in the well, term newborn, this may be a useful early diagnostic tool in infants with signs or a maternal or nursery history suggestive of nasal or GI obstruction.

Cardiovascular Abnormalities↗
PubMed1996

Acute response to inhaled nitric oxide in newborns with respiratory failure and pulmonary hypertension.

OBJECTIVE: Systemic oxygenation is improved by inhaled nitric oxide therapy in some newborns with respiratory failure and pulmonary hypertension. Our results with inhaled nitric oxide were reviewed to determine factors associated with an acute improvement in systemic oxygenation. METHODS: Newborns with oxygenation indices of 25 to 40 were prospectively randomized to receive conventional therapy with or without 20 ppm inhaled nitric oxide. All newborns with oxygenation indices greater than 40 were treated with inhaled nitric oxide. Hemodynamic, blood gas, and Doppler ultrasound measurements were performed before and after 30 to 60 minutes of observation or therapy. The severity of lung disease was classified by the chest radiograph as: (1) normal or focal disease; (2) moderate diffuse disease-diffuse lung disease with well-defined heart borders; or (3) severe diffuse disease-diffuse lung opacification with indistinct heart borders. RESULTS: Heart rate, blood pressure, and ductal diameters did not change. Blood gases and ductal shunting acutely improved only in patients treated with inhaled nitric oxide. Patients with normal lung fields or focal disease had the greatest degree of improvement in systemic oxygenation. Changes in oxygenation were not influenced by gestational age, baseline blood gases, the proportion of right-to-left ductal shunting, prior treatment with a surfactant, or the use of conventional or high-frequency jet ventilation. Collectively, blood gases and ductal shunting did not improve with inhaled nitric oxide in patients with lung hypoplasia or severe diffuse lung disease. Sustained improvement in oxygenation occurred in 87% of patients with oxygenation indices greater than 40 in whom oxygenation indices less than 40 acutely developed after exposure to nitric oxide, whereas 90% of patients in whom oxygenation indices less than 40 did not acutely develop were treated with extracorporeal membrane oxygenation or ultimately died. CONCLUSIONS: Inhaled nitric oxide acutely improves systemic oxygenation in many newborns with respiratory failure and pulmonary hypertension. The diagnosis and chest radiograph are helpful in identifying patients who will have favorable acute responses to therapy. In patients with severe hypoxemia, the need for invasive support with extracorporeal membrane oxygenation may be determined by an acute trial of inhaled nitric oxide.

Acute Disease↗
PubMed1994

Motion displacement thresholds for compound stimuli predicted by the displacement of centroids.

Minimum displacement thresholds were measured using a compound motion stimulus, in which a single bar split into oppositely moving components, having different luminances and absolute displacements. The results fit a simple model in which observers detect the movement of the centroid of the combined luminance pattern of the two components. This was so even when the two components were separated by more than the static spatial resolution limit of 30 sec arc.

Humans↗
PubMed1994

Pharmacologic enhancement of fetal lung maturation.

During the 22 years since the first clinical reports of prenatal corticosteroid treatment to enhance fetal lung maturation, this treatment has been studied in thousands of preterm newborns. These studies demonstrated that prenatal steroid treatment reduces RDS among premature newborns at 26 to 33 weeks gestation. The potent fluorinated steroids, betamethasone and dexamethasone, are more effective in accelerating lung maturation than are the less potent corticosteroids, cortisol, cortisone, and prednisone. No immediate or long-term adverse effects have been demonstrated for the newborn or fetus. With PROM, mothers may have an increased risk of endometritis without a clear increase in overall frequency of infection, at the same time steroids significantly decrease the frequency of RDS in the newborns. During these 22 years of evaluation and application of prenatal steroid treatment to reduce RDS, the survival of the very low birth weight (< 1501 g) newborn has increased dramatically. Major morbidities, however, impact significantly on the quality of life for these survivors with birth weights as low as 500 g and gestations as short as 22 to 23 weeks. Prenatal steroid treatment reduces the frequency of PDA, intraventricular hemorrhage, NEC, and bronchopulmonary dysplasia. These are the most important and frequent morbidities that reduce the quality of life for the very low birth weight survivor. Without clearly demonstrable and major adverse effects for the mother or child from corticosteroid treatment, the cost/benefit ratio strongly and clearly favors treatment when preterm delivery is anticipated. Hopefully, obstetricians will use corticosteroids more often in the management of preterm labor because this treatment may markedly improve the quality of survival for many premature newborns.

Animals↗
PubMed1993

Drug therapy of the fetus.

The fetus has become an intended object of drug therapy administered through the mother with the successful prevention of hyaline membrane disease with glucocorticoids. Maternal drug treatment has now been undertaken for a variety of fetal problems, including arrhythmias, congestive heart failure, infections, and inborn errors of adrenal metabolism. Interestingly, this planned maternal drug exposure during pregnancy coincided with increasing concerns during the last two decades about inadvertent transplacental exposure of the fetus to licit and illicit drugs. Efforts to direct drug therapy to the fetus have pointed out important gaps in knowledge of the pharmacology of the maternal-placental-fetal-unit (MPFU), whereas other observations illustrated recognized principles of the pharmacology of the MPFU. Many of these principles fit the basic framework of pharmacokinetics: absorption, distribution, metabolism and excretion. Rapid changes in maternal-placental physiology and fetal development during gestation, however, lead to dramatic variations in these processes throughout pregnancy.

Arrhythmias, Cardiac↗
PubMed1993

Neonatal glucose determinations obtained from an umbilical artery catheter: evaluation for accuracy using an in vitro model.

Accuracy of glucose values is crucial in the management of the critically ill neonate. Sampling for these values may be obtained from an umbilical artery catheter (UAC), but dextrose solutions infused through these catheters may contaminate samples obtained for glucose determination. An in vitro study was conducted to evaluate the effect of blood withdrawal amount and normal saline irrigation on the accuracy of glucose measurements obtained from a UAC. Methods included randomization of blood withdrawal amounts and irrigation with normal saline solution prior to obtaining the blood for glucose measurement. Two hundred and eighty glucose samples were obtained. Results revealed a significant difference between measured and baseline glucose values for all withdrawal amounts and varying flush volumes. This inability to approximate the baseline glucose values could mean that a UAC sample may not reflect the neonate's actual glucose value.

Blood Glucose↗