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Biomedical subjects

D K Stevenson

Publications and source records attributed to D K Stevenson.

At least 145 records · Page 8Linked to original sources
PubMed1993

Are children born small for gestational age at increased risk of short stature?

OBJECTIVE: To assess the height outcome of newborns born small for gestational age. DESIGN: A historical prospective study. SETTING: A cohort of 1758 newborns born at a single university hospital maternity ward and subsequently examined at the military draft medical board at age 17 years. PARTICIPANTS: Newborns whose weight at birth was below the third percentile were defined as small for gestational age. Their body measurements at age 17 years were compared with those of their peers who were appropriate for gestational age. MEASUREMENTS/MAIN RESULTS: The adjusted mean +/- SEM height for boys born small for gestational age vs peers born appropriate for gestational age was 169.9 +/- 1.5 vs 175.4 +/- 0.8 cm (P < .0001); and for girls, 159.4 +/- 1.3 vs 163.1 +/- 0.8 cm (P < .0005). In addition, the risk for height attainment below the 10th percentile was significantly increased for newborns born small for gestational age. The adjusted odds ratio was 4.13 for boys (95% confidence interval, 1.66 to 10.25; P < .0006) and 3.32 for girls (95% confidence interval, 1.38 to 8.05; P < .0005). CONCLUSION: Infants born small for gestational age may be at increased risk for short stature in late adolescence.

Adolescent↗
PubMed1993

Inhibition of heme oxygenase after oral vs intraperitoneal administration of chromium porphyrins.

The effects of chromium porphyrins on suckling rat heme oxygenase activity were compared following oral vs intraperitoneal dosing. Chromium protoporphyrin (CrPP), chromium mesoporphyrin (CrMP), or chromium deuteroporphyrin 2,4 bis glycol (CrBG) were administered at 40 mumol/kg to 2-week old suckling rats either orally or intraperitoneally. Six hours after intraperitoneal dosing, CrPP and CrMP had significantly reduced hepatic and splenic heme oxygenase activity by more than 55%. CrBG effectively reduced hepatic heme oxygenase activity by 42%. More importantly, only CrMP was an effective inhibitor of hepatic heme oxygenase activity 6 hr after oral administration. In the first reported comparison of chromium porphyrin efficacy in vivo, our data suggest that chromium porphyrins, and particularly CrMP, may be effective in chemopreventive strategies for the treatment of neonatal jaundice.

Administration, Oral↗
PubMed1993

Role of lipid peroxidation in metalloporphyrin-mediated phototoxic reactions in neonatal rats.

Our group previously demonstrated dose-dependent mortality in neonatal rats treated with tin protoporphyrin and light. We hypothesize that lipid peroxidation may be responsible for the toxic effects of photosensitizing metalloporphyrins. Neonatal rat blood samples with or without metalloporphyrins (40 mM) were exposed to cool white light (20 microW/cm2/nm) for 30 min at 37 degrees C. In the in vivo model, neonatal rat pups were given injections of 40 mumol of either tin protoporphyrin (4 mM), zinc protoporphyrin/kg body weight, or saline and placed over cool white light. The control animals were similarly treated but kept in the dark. After 3 h, the animals were killed, and their tissues were analyzed for malondialdehyde, conjugated dienes, and disappearance of polyunsaturated fatty acids as indices of lipid peroxidation. In all cases, the known photosensitizer tin protoporphyrin was associated with increased conjugated dienes in the liver and disappearance of polyunsaturated fatty acids and increased malondialdehyde in the liver and brain when animals were exposed to light. Zinc protoporphyrin was not associated with increased lipid peroxidation in the light except in the case of blood in vitro where malondialdehyde levels increased. We conclude that lipid peroxidation plays a role in metalloporphyrin-mediated phototoxicity in neonatal rat tissues.

Animals↗
PubMed1993

Selection of metalloporphyrin heme oxygenase inhibitors based on potency and photoreactivity.

The heme oxygenase inhibitor, tin protoporphyrin, is being studied for the prevention of neonatal jaundice. This potential drug, however, is also a photosensitizer that could cause serious and unknown side effects when administered to newborns. Therefore, we have developed in vitro and in vivo procedures for the screening and further characterization of potentially safe heme oxygenase inhibitors. The ideal inhibitor: 1) contains a biocompatible metal, 2) is not degraded in tissues, 3) is a highly potent inhibitor of heme oxygenase, and 4) does not participate in photochemical reactions. Proto- and mesoporphyrin derivatives with the tin, zinc, manganese, chromium, nickel, and magnesium were screened in vitro for suitability. Chromium protoporphyrin and mesoporphyrin were further studied in vitro and in vivo and were found to meet the ideal criteria. Chromium mesoporphyrin appeared to be the most potent in vitro inhibitor of adult Wistar rat tissue heme oxygenase. Four mumol of chromium protoporphyrin or chromium mesoporphyrin/kg body weight, administered intraperitoneally to adult male Wistar rats given a heme load through intraperitoneal administration of 30 mumol heme/kg body weight, caused significant suppression of hemolysis-induced increase in carbon monoxide production to 72 and 44% of control, respectively, 5.5 h after treatment. At t = 6 h, the tissue heme oxygenase activity, measured in vitro, was significantly reduced to 33 and < 5% in liver and to 22 and < 5% in spleen after the administration of chromium protoporphyrin and mesoporphyrin, respectively, but was not reduced in brain. The results show that there exist effective metalloporphyrin heme oxygenase inhibitors without photosensitizing properties.

Animals↗
PubMed1993

Targeting zinc protoporphyrin liposomes to the spleen using reticuloendothelial blockade with blank liposomes.

Metalloporphyrin inhibitors of heme oxygenase have been studied for use in the prevention of hyperbilirubinemia of the neonate. One report has suggested that incorporation of these drugs into liposomes can increase their localization to the spleen, dramatically reducing heme oxygenase activity in that important heme-degrading organ. We sought to further increase porphyrin delivery to the spleen by using reticuloendothelial blockade with blank liposomes 2 h before injection of 0.3 microns extruded zinc protoporphyrin liposomes (L-ZnPP). Control adult rats without hemolysis had splenic heme oxygenase activity of 1.07 +/- 0.09 nmol carbon monoxide (CO)/h/mg protein. Rats treated with L-ZnPP alone had splenic heme oxygenase activity of 0.53 +/- 0.16 nmol CO/h/mg protein 6 h after L-ZnPP dosing. However, rats treated with 1000 mumol of blank liposomes per kg to saturate the reticuloendothelial system 2 h before L-ZnPP administration had splenic heme oxygenase activity of 0.25 +/- 0.16 nmol CO/h/mg protein at t = 6 h, which is significantly less than that of the L-ZnPP alone group (p < 0.05). In adult rats treated with heat-damaged red blood cells (RBC) to simulate hemolysis, treatment with 10 mumol of aqueous ZnPP per kg or 10 mumol of untargeted L-ZnPP per kg did not produce a difference from control in total body bilirubin production as estimated by CO excretion. However, RBC-treated rats given 1000 mumol of blank liposomes per kg 2 h before L-ZnPP administration produced significantly less CO than control, aqueous ZnPP-treated, and untargeted L-ZnPP-treated rats from 8 to 12 h after RBC treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Is the association between birthweight and height attainment independent of the confounding effect of ethnic and socioeconomic factors?

The association between birthweight and body height attainment at 17 years of age was investigated by studying a sample of 30,083 subjects born in Jerusalem between 1964 and 1971. Birthweights obtained from the computerized records of the Jerusalem Perinatal Study were matched with demographic and medical examination results available from the military draft boards. Linear regression models for standing height by birthweight were fitted for the data in order to adjust for the possible confounding effect of ethnic origin, socioeconomic status (as determined by parental education level), birth order and maternal age. Separate models were constructed for each sex. A significant (P < 0.0001) linear increase in standing height by birthweight of 3.33 cm/1,000 g was observed for the males (mean +/- SE height 174.5 +/- 0.1 cm) and 2.85 cm/1,000 g for the females (mean +/- SE height 163.5 +/- 0.1 cm). This positive linear association between body height at 17 years of age and birthweight was also demonstrated after stratification according to various categories of social class and ethnic origin. Adult body height was thus found to be strongly related to birthweight in both sexes, regardless of ethnic and socioeconomic influences.

Adolescent↗
PubMed1993

Measurement of carboxyhemoglobin and total hemoglobin by five specialized spectrophotometers (CO-oximeters) in comparison with reference methods.

We measured total hemoglobin (CtHb) and carboxyhemoglobin (COHb) in 100 patients' blood samples by using five specialized spectrophotometers (CO-oximeters)--IL 482 CO-Oximeter, Corning 2500 CO-oximeter, Radiometer OSM 3 Hemoximeter, Corning 270 CO-oximeter, and the AVL 912 CO-Oxylite--and compared the results with those obtained with the manual cyanmethemoglobin method and a gas-chromatographic (GC) method, respectively. For the CtHb measurements, the differences between the cyanmethemoglobin method and the CO-oximeters were not clinically important for any model. For the blood COHb measurements, the direction of the bias relative to GC was dependent on COHb concentration. In general, the CO-oximeters underestimated COHb concentration for COHb > 2.5% of total hemoglobin but overestimated COHb concentration for COHb < or = 2.5%. We conclude that all five CO-oximeters compared favorably with the reference methods for CtHb and for high concentrations of COHb. However, the inaccuracy of CO-oximeters for low-concentration (< or = 2.5%) COHb measurements may make these instruments unsuitable for some applications.

Carboxyhemoglobin↗
PubMed1993

Prediction of the development of low birth weight preterm infants by a new neonatal medical index.

A new neonatal medical index (NMI) was used to predict the mental and motor development of low birth weight, preterm infants up to 3-years-old. The NMI is a summary score of only a few clinically salient items that are readily available on brief chart review. The sample consisted of 512 of 608 infants randomly assigned to the control group of the eight-site Infant Health and Development Program and on whom the complete set of developmental outcome measures was available. The developmental tests administered were the Bayley Scales at 12 and 24 months and the Stanford-Binet at 3 years. The findings indicated the NMI was predictive of later cognitive and motor development, and in infants born weighing less than 1500 g, the effects of neonatal medical complications continued to adversely influence these children's development to at least 3 years of age. In the heavier babies the developmental effects of sociodemographic factors predominated by 24 months and beyond.

Child Development↗
PubMed1992

Delayed compliance increase in infants with respiratory distress syndrome following synthetic surfactant.

Recent research has demonstrated that Exosurf (EXSF), a newly synthesized artificial surfactant, increases survival when administered endotracheally to premature infants with RDS. This study examines the effects of EXSF on static respiratory system compliance (Crs). Thirty-four patients received two doses of EXSF in this rescue protocol. Crs (mL/cmH2O/kg) did not significantly change within the first 4 hours after either dose. However, Crs values did increase significantly (paired Student's t-test, P = 0.005) when data collected after the second dose (0.36 +/- 0.13 mL/cmH2O/kg) were compared to first week follow-up data (0.51 +/- 0.21 mL/cmH2O/kg). Crs data collected between 2 and 4 weeks after treatments were again not significantly different from non-concurrent control data collected at 3-4 weeks of life. The measurement of Crs in infants receiving EXSF may have been affected by an increase in lung inflation, which could mask an increase in Crs. We speculate that improved lung inflation may occur with less barotrauma in the first week of life due to surfactant replacement treatment and may in part explain the improved Crs seen at 1 week of age. Many investigators using different surfactants, dosing schedules, and pulmonary function methodologies to evaluate lung mechanics have reported that the improvement in compliance after surfactant treatment usually follows the clinical improvement in gas exchange. Additional studies are needed to explain the mechanism of early improvement following surfactant replacement in infants with RDS.

Drug Combinations↗
PubMed1992

Maturation of jejunoileal gradients in rat intestine: the role of intraluminal nutrients.

Jejunoileal gradients of intestinal function are thought to be established during the third week of life in the rat when postnatal intestinal maturation occurs. In order to investigate the normal development of jejunoileal gradients and whether either the absence of intraluminal nutrients or the form in which they are provided affected the development of jejunoileal gradients, gradients for mucosal DNA, protein, lactase and sucrase were studied in suckling rats undergoing normal weaning and compared to gradients in rats receiving no intraluminal nutrients or rats receiving nutrients in elemental form. In suckling animals, preexisting jejunoileal gradients for DNA and protein persisted through the weaning period, gradients for lactase formed by rapid decline of ileal function and sucrase gradients formed by rapid increase in jejunal activities. Intraluminal nutrients in elemental form resulted in the formation of jejunoileal gradients similar to those in intestines of normally weaned rats. The lack of intraluminal nutrients resulted in no qualitative differences in the expression of jejunoileal gradients for sucrase, but provision of elemental nutrients resulted in increased jejunoileal differences for this enzyme. The lack of intraluminal nutrients resulted in no gradients for DNA, less pronounced jejunoileal differences for protein and delayed maturational decline of ileal lactase which prevented development of jejunoileal gradients for the enzyme. These studies indicate that the formation of jejunoileal gradients in the maturing rat intestine for the parameters investigated require intraluminal nutrients regardless of the form in which they are provided for their normal expression.

Aging↗
PubMed1992

Noninvasive methods for estimating in vivo oxygenation.

Clinical signs of hypoxia and hyperoxia are nonspecific and unreliable, yet both are potentially injurious. Noninvasive methods of oxygen assessment fill the gap between clinical observation and invasive tests, helping physicians deliver sufficient oxygen with minimum toxicity. Potential sites for oxygen measurement vary between the blood and the mitochondria; each method measures at a different site and detects different types of hypoxia and hyperoxia. Thus, values obtained by two different methods are not equivalent, giving each method unique strengths and weaknesses. We review two clinical methods (pulse oximetry and transcutaneous oximetry), as well as four experimental methods (near-infrared spectrophotometry, magnetic resonance spectroscopy, magnetic resonance saturation imaging, and time-of-flight absorbance spectrophotometry). The principles of each method and the clinical situations in which each succeeds or fails are discussed. A fundamental understanding of each method can help in deciding which methods, if any, are appropriate for a given patient and how best to correct observed oxygenation problems once they are discovered.

Blood Gas Monitoring, Transcutaneous↗