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Biomedical subjects

D Berry

Publications and source records attributed to D Berry.

At least 73 records · Page 4Linked to original sources

A comparison of two regimens for high-risk acute lymphocytic leukemia in childhood. A Pediatric Oncology Group Study.

Four hundred thirty patients with high-risk acute lymphoid leukemia were entered on the acute leukemia in childhood protocol (AlinC 12) of the Pediatric Division of the Southwest Oncology Group (now the Pediatric Oncology Group) between 1976 and 1979. This study was a prospective randomized comparison of two regimens that had as their primary differences: (1) an intensification period with Cytoxan (cyclophosphamide) and asparaginase after induction; (2) a period of intravenous methotrexate before initiating maintenance; and (3) in the regimen that had those two additions, triple-drug chemoprophylaxis of the central nervous system (CNS) using methotrexate, hydrocortisone, and cytosine arabinoside as compared to cranial irradiation and intrathecal methotrexate. All patients received vincristine and prednisone induction, 6-mercaptopurine and methotrexate maintenance, and vincristine and prednisone pulse intensification. There was no significant difference in the rate of bone marrow relapse. However, overall disease-free survival favored the arm with intensification and chemoprophylaxis because of a lesser incidence of extramedullary relapse. Thus, for treatment 1 versus treatment 3 the two-sided P values were for overall disease-free survival 0.16; bone marrow relapses 0.13; all CNS relapses 0.04; and all extramedullary disease relapses 0.013. It is concluded that intensification as delivered in this protocol protects against testicular relapse and that chemoprophylaxis is adequate prophylaxis against isolated CNS relapse.

Adolescent↗

Lung perfusion and aerosol distributions in preterm ventilated lambs.

The relative distributions of ventilation as measured by 99Tc-sulfur colloid aerosol deposition and pulmonary perfusion (measured with radiolabeled microspheres) were determined in 12 preterm lambs that were delivered at 138 days gestational age and ventilated for 4 hrs. To verify that unventilated lung segments in these lambs would have decreased perfusion, a balloon catheter was placed in a major bronchus either at birth or after 2 hrs of ventilation. This catheter prevented ventilation of 24.5 +/- 3.2% of the lung tissue. After 4 hrs of ventilation, the lambs were sacrificed and the lungs were divided into about 60 1-g pieces. Apart from the occluded, atelectatic segments, the lungs were visually well aerated with only 5.3 +/- 1.8% of the nonobstructed lungs being spontaneously atelectatic. There was a 66.5 +/- 0.07% decrease in blood flow to the area of lung made atelectatic by the balloon. The blood flow also was decreased to lung regions assessed to be spontaneously atelectatic. No 99Tc-sulfur colloid was recovered from balloon-occluded lung regions, and less 99Tc-sulfur colloid was found in the spontaneously atelectatic areas than in aerated lung regions. There were significant correlations (P less than 0.001) between pulmonary blood flow and aerosol recovery in each of the 12 animals. Premature lambs had a wide variability in ventilation and perfusion, but the relative ventilation to perfusion ratio was regulated to minimize the intrapulmonary shunt.

Aerosols↗

Sleep quality and pulmonary function in the healthy elderly.

Loss of sleep causes deterioration of pulmonary function and ventilatory responsiveness in normal humans and in patients with chronic obstructive pulmonary disease. To evaluate the effects of variations in sleep quality on breathing, we studied 48 healthy elderly volunteers (mean age, 70 years). Electroencephalographically derived indices of sleep quality were correlated with spirometric performance, MIP, MEP, and waking SaO2. We found significant correlations between several indices of sleep quality and the spirometric measurements in the group as a whole, and striking correlations between sleep quality and PFTs in those with sleep efficiency less than or equal to 70 percent. We conclude that sleep disturbance may be related to poor performance on PFTs. These results suggest that spirometry should be performed on well-rested patients. The results also point to sleep quality as a potentially important variable in the management of patients with pulmonary disease.

Aged↗

Sleep apnea: prevalence of risk factors in a general population.

People with snoring, excessive daytime somnolence, and nocturnal breath cessation are very likely to have sleep apnea, particularly if they are obese or hypertensive. We collected epidemiologic data to determine the frequency of these findings in an unselected adult population. Respondents in a random digit dialing telephone survey included 685 people (356 women and 329 men, with a mean age of 50 years). Snoring was reported by 37%, gasping by 8%, excessive daytime somnolence by 36%, and hypertension by 28%; all symptoms were more prevalent in respondents older than 50 years. Snoring and gasping were more common in men than in women. Six persons (1%) had all four risk factors, plus a body mass index of one standard deviation above the mean. Eleven respondents (2%) had all four risk factors, but lower weight. We conclude that all risk factors for sleep apnea are more prevalent in persons over the age of 50 years, and that the incidence of sleep apnea in the general population may be 1%.

Age Factors↗

Stimulation of transcription in vitro by binding sites for nuclear factor I.

Nuclear factor I (NFI) is a site-specific DNA binding protein required for the replication of adenovirus DNA in vitro and in vivo. We have examined the effect of natural and synthetic binding sites for NFI (FIB sites) on RNA synthesis in HeLa whole cell extracts. The natural binding site used is the 26bp FIB-2 site previously isolated from the human genome. When present upstream of the TATA box of the adenovirus major late promoter, the FIB-2 site stimulates RNA synthesis 3 to 5-fold. This stimulation occurs with either orientation of the FIB-2 site. A point mutation in FIB-2 that decreases NFI binding at least 100-fold reduces, but does not completely abolish, the stimulation of transcription. A number of synthetic binding sites for NFI were tested for the ability to increase RNA synthesis. The strongest binding sites stimulated transcription the most, while the weakest sites had the least effect. These studies strongly suggest a role for NFI and cellular FIB sites in the control of RNA synthesis.

Binding Sites↗

Pulmonary effects of acute prenatal asphyxia in ventilated premature lambs.

The effect of profound repetitive prenatal asphyxial insults on the cardiopulmonary function of premature ventilated lambs was studied. Twenty-nine fetal lambs (approximately 138 days gestational age) were exteriorized. In 16 of these lambs, the umbilical cord was occluded for 4 min then released for 10 min. This asphyxial episode was repeated until the arterial pH was approximately 7.00, and the mean arterial blood pressure was less than 40 mmHg and falling. The 13 control lambs were simply exteriorized with the umbilical circulation intact. The lambs were then ventilated for 3-4 h. There were no differences between the control vs. asphyxiated lambs in pulmonary compliances (0.57 and 0.58 ml.cmH2O-1.kg-1) wet-to-dry weight ratios (8.18 and 7.55), cardiac outputs (177.8 and 141.8 ml.kg-1.min-1), surfactant-saturated phosphatidylcholine pool sizes, or atrial and/or ductal shunts. Asphyxia did not interfere with the redirection of blood away from atelectatic lung segments created by bronchial obstruction with balloon catheters. Also, although the bidirectional flux of protein into and out of the airways of these preterm lambs was large relative to term lambs, there was no effect of asphyxia on this protein leak. In this animal model, prenatal asphyxia did not impact negatively on the severity of the respiratory failure.

Animals↗

The disposition of feprazone and its hydroxylated metabolite in human volunteers.

1. 14C-Feprazone administered as a single oral dose (17 mg/subject) to each of 3 human volunteers on the 6th day of repeated dosage with unlabelled feprazone (200 mg/subject, twice daily) was excreted slowly, with only 19-38% of the dose excreted in the urine in 8 days, with a further 27-49% of the dose in the faeces. 2. 14C-Feprazone had a half-life of 30-33 h, similar to that after single dosage of unlabelled feprazone (22-33 h). The half-life for total 14C was not significantly different from that for unchanged feprazone, indicating that no metabolite with a very long half-life was formed. 3. Only feprazone and 4'-hydroxyfeprazone were detected in the plasma of subjects dosed orally with feprazone, the metabolite being characterized by mass spectrometry. The time of peak plasma concentration of feprazone was 4-5 h after dosage, and of 4'-hydroxyfeprazone was approx. 25 h. The urine contained feprazone plus its C-glucuronide, and 4'-hydroxyfeprazone plus its conjugate (glucuronide), in the ratio of approx. 5:1. 4. When 4'-hydroxyfeprazone was administered as a single oral dose to a human volunteer the plasma elimination half-life of the metabolite was 18 h, but after administration of feprazone the half-life of 4'-hydroxyfeprazone was 45 +/- 29 h (10 subjects), indicating the slow hydroxylation of feprazone and the slow excretion of 4'-hydroxyfeprazone. The clearance of feprazone was 5.2 and of 4'-hydroxyfeprazone was 5.5 ml/kg/h. 5. These studies have shown that even though enterohepatic recirculation of the drug in man is indicated, the plasma half-life of feprazone is unchanged on repeated dosage, and accumulation of the drug at a daily dosage of 2 x 200 mg, does not occur.

Carbon Radioisotopes↗

Development and validation of a particle-enhanced turbidimetric immunoassay for C-reactive protein.

The development of a particle-enhanced turbidimetric immunoassay for C-reactive protein is described. The method demonstrates excellent precision, with the calibration curve remaining stable for at least 16 weeks. The method compares well with established techniques and there is no interference from a variety of autoantibodies, endogenous serum constituents or commonly used drugs.

Autoantibodies↗

Induction of a cationic shift in IgG anti-DNA autoantibodies. Role of T helper cells with classical and novel phenotypes in three murine models of lupus nephritis.

We investigated the underlying mechanisms of systemic autoimmune disease in MRL-+/+, (NZB X NZW)F1, and (NZB X SWR)F1 mice, since these strains develop glomerulonephritis without the superimposition of any secondary lupus-accelerating genes. All three strains manifested a common immunoregulatory defect specific for the production of pathogenic anti-DNA autoantibodies that are of IgG class and cationic in charge. At or just before the age they began to develop lupus nephritis, spleen cells of the mice contained a subpopulation of Th cells that selectively induced their B cells in vitro to produce highly cationic IgG autoantibodies to both single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA). By contrast, T cells from younger preautoimmune mice were incapable of providing this help. Moreover, only B cells of the older lupus mice could be induced to secrete cationic anti-DNA antibodies of IgG class. B cells of young lupus mice could not produce the cationic autoantibodies even with the help of T cells from the older mice, nor upon stimulation with mitogens. In the older lupus mice we found two sets of Th cells that spontaneously induced the cationic shift in autoantibodies; one set belonged to the classical Th category with L3T4+,Lyt-2- phenotype, whereas the other surprisingly belonged to a double-negative (L3T4-,Lyt-2-), Lyt-1+ subpopulation. The latter set of unusual Th cells were unexpected in these lupus mice since they lacked the lpr (lympho-proliferation) gene. Thus three apparently different murine models of systemic lupus erythematosus possess a common underlying mechanism specific for the spontaneous production of pathogenic anti-DNA autoantibodies.

Animals↗

Serotype-converting bacteriophage D3 of Pseudomonas aeruginosa: vegetative and prophage restriction maps.

D3 is a temperate serotype-converting bacteriophage of Pseudomonas aeruginosa. A restriction map, based upon BamHI, PstI, PvuI, HindIII and SmaI sites, indicates that the phage genome is 56.4 kb long, and that it possesses cohesive ends. The prophage map suggests a unique insertion site in the strain AK1380 genome. Phage DNA integration occurs upon the circularization of D3 genome with the integration point approximately equidistant from the two ends.

Bacteriophages↗

Effect of growth temperature on the lipids, outer membrane proteins, and lipopolysaccharides of Pseudomonas aeruginosa PAO.

Growth of Pseudomonas aeruginosa PAO1 at 15 to 45 degrees C in tryptic soy broth resulted in changes in the lipids, lipopolysaccharides (LPSs), and outer membrane proteins of the cells. Cells grown at 15 degrees C contained, relative to those cultivated at 45 degrees C, increased levels of the phospholipid fatty acids hexadecenoate and octadecenoate and reduced levels of the corresponding saturated fatty acids. Furthermore, the lipid A fatty acids also showed thermoadaptation with decreases in dodecanoic and hexadecanoic acids and increases in the level of 3-hydroxydecanoate and 2-hydroxdodecanoate as the growth temperature decreased. In addition, LPS extracted from cells cultivated at the lower temperatures contained a higher content of long-chain S-form molecules than that isolated from cells grown at higher temperatures. On the other hand, the percentage of LPS cores substituted with side-chain material decreased from 37.6 mol% at 45 degrees C to 19.3 mol% at 15 degrees C. The outer membrane protein profiles indicated that at low growth temperatures there was an increase in a polypeptide with an apparent molecular weight of 43,000 and decreases in the content of 21,000 (protein H1)- and 27,500-molecular-weight proteins.

Adaptation, Physiological↗

Effects of distention of the preterm fetal lamb lung on lung function with ventilation.

Constant distending pressure when applied to the immature fetal lamb lung was reported to improve compliance and prevent the subsequent development of the respiratory distress syndrome after delivery. These experiments were designed to repeat those observations and identify the mechanism(s) responsible for the effects of constant distending pressure on subsequent lung function. The compliance of the lungs of exteriorized fetal lambs at 130 to 133 days gestational age increased 2.5-fold after 1 h of 15 cm of distending pressure. However, subsequent ventilation of the lambs exposed to distending pressure and control lambs resulted in comparable sequential compliance and blood gas and pH measurements. Severity of lung disease as reflected by the peak inspiratory pressure needed to normalize Pco2 values decreased as surfactant-saturated phosphatidylcholine pool sizes increased (r values greater than 0.90) and minimum surface tensions of alveolar washes decreased, but the distention procedure did not change these relationships. Distention of the fetal lung did result in an apparent increase in pulmonary blood flow in the fetus and an increased leak of labeled albumin from the vascular space to the lung interstitium and airways during the 1-h period of ventilation after delivery. However, the leak of protein into the lungs exposed to the distending pressures was not increased during the period of exteriorization and distention, suggesting that distention sensitized the preterm lung to leak protein with subsequent mechanical ventilation. The leak of labeled albumin out of the airways was not changed by distention, and total lung water was not changed.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗

Corticosteroids and surfactant change lung function and protein leaks in the lungs of ventilated premature rabbits.

Fetal rabbits were treated with corticosteroids by maternal administration for 48 h before delivery at 27 d gestational age. The treated and control rabbits were placed on ventilator-plethysmographs so that ventilation could be adjusted by regulation of tidal volumes to 10-13 ml/kg body wt. [125I]albumin was mixed with fetal lung fluid at birth, alternate rabbits from each litter were treated with Surfactant-TA, and [131I]albumin was injected intravascularly. The movement of the labeled albumins into and out of the alveolar wash and lung tissue was measured after 30 min of ventilation. Corticosteroid treatment (total dose, 0.2 mg/kg betamethasone) significantly decreased the protein leak across the endothelium (P less than 0.001) but increased the protein leak across the epithelium (P less than 0.001). Surfactant treatment decreased both the endothelial and epithelial leaks, and the combination of surfactant and corticosteroid treatments decreased endothelial leaks to 29% of control values and increased compliance more than either treatment alone. The 48-h corticosteroid treatment did not increase alveolar surfactant pool sizes. Corticosteroids significantly changed lung protein leaks independently of surfactant, and improved the response of the preterm lung to surfactant treatments.

Adrenal Cortex Hormones↗

Comparison of four surfactants: in vitro surface properties and responses of preterm lambs to treatment at birth.

Natural sheep surfactant, rabbit surfactant, human surfactant, and surfactant TA were compared for in vitro surface properties and for responses of preterm lambs to treatment. Equivalent amounts of sheep, rabbit, and human surfactants were needed to lower the surface tension to less than 10 dynes/cm, whereas four times less surfactant TA similarly lowered the surface tension. Surface-spreading rates were similar for the surfactants. The surface adsorption of the batch of human surfactant tested was much slower than was adsorption of the other surfactants. Ventilation was significantly improved in all surfactant-treated lambs relative to the control lambs, indicating the general efficacy of the surfactant treatments. Overall, surfactant TA had the best in vitro characteristics, yet the preterm lambs treated at birth with surfactant TA had lower PO2 values and higher ventilatory requirements than did the sheep surfactant-treated lambs. The in vivo responses to rabbit surfactant were intermediate between the responses to sheep surfactant and to surfactant TA. Human surfactant resulted in the least effective clinical response. More of the phosphatidylcholine associated with human surfactant and surfactant TA was lost from the alveoli and lung tissue after four hours of ventilation than was lost from sheep or rabbit surfactant-treated lambs. More intravascular radiolabeled albumin leaked into the alveoli of the surfactant TA-treated lambs than sheep or rabbit surfactant-treated lambs. The four surfactants also had different sensitivities to the effects on minimum surface tensions of the soluble proteins present in alveolar washes. The study demonstrates that the range of clinical responses was not predictable based on the in vitro surface properties that we measured.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Pharmacodynamics and side effects of flecainide acetate.

We compared side effects with flecainide trough levels and ECG intervals among 43 patients who received flecainide for up to 34 months. Flecainide plasma levels were higher when associated with cardiovascular side effects (mean 1063 ng/ml; range 296 to 2050 ng/ml) than when no side effects occurred (mean 609 ng/ml; range 89 to 1508 ng/ml; P less than 0.001). The PR interval (P less than 0.001), QRS interval (P less than 0.001), and the rate-corrected QT interval (P less than 0.001) were greater at the time of cardiovascular side effects, but the rate-corrected JT interval was not. The therapeutic-toxic window for flecainide plasma level was 381 ng/ml (at least 50% probability of efficacy) to 710 ng/ml (less than 10% probability of cardiovascular side effects). The risk of cardiovascular side effects increases at higher plasma levels of flecainide and is associated with greater increases in the PR and QRS intervals from baseline than are routinely observed during flecainide dosing.

Aged↗

Thymus deficiency in an infant with a chromosome t(18;22)(q12.2;p11.2)pat rearrangement.

The finding of an unbalanced t(18;22)pat chromosome rearrangement in a boy with multiple anomalies including apparent absence of the thymus is described. The observation is of interest because of the reported association of chromosome 22 rearrangements with the DiGeorge sequence. In contrast to previous reports of this association, the deletion involving chromosome 22 is confined to the short arm.

Abnormalities, Multiple↗