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Biomedical subjects

S Powell

Publications and source records attributed to S Powell.

At least 37 records · Page 2Linked to original sources

Nitrous oxide (laughing gas) is an NMDA antagonist, neuroprotectant and neurotoxin.

Extensive research has failed to clarify the mechanism of action of nitrous oxide (N2O, laughing gas), a widely used inhalational anesthetic and drug of abuse. Other general anesthetics are thought to act by one of two mechanisms-blockade of NMDA glutamate receptors or enhancement of GABAergic inhibition. Here we show that N2O, at anesthetically-relevant concentrations, inhibits both ionic currents and excitotoxic neurodegeneration mediated through NMDA receptors and, like other NMDA antagonists, produces neurotoxic side effects which can be prevented by drugs that enhance GABAergic inhibition. The favorable safety record of N2O may be explained by the low concentrations typically used and by the fact that it is usually used in combination with GABAergic anesthetics that counteract its neurotoxic potential.

Animals↗

Users evaluate LupusLine, a telephone peer counseling service.

OBJECTIVE: To assess the impact of LupusLine during its pilot phase of operation by determining patterns of utilization and user satisfaction. LupusLine is a peer counseling service designed to provide ongoing emotional support from home to home by telephone appointment. METHODS: One hundred fifty-three respondents were surveyed, using a 72-item structured questionnaire administered over the telephone by interviewers separately trained and hired specifically for this purpose. The questionnaire was pilot tested on 10 volunteers with systemic lupus erythematosus (SLE), and a panel of related health professionals reviewed the questionnaire for face validity. RESULTS: Most users were women (94.5%) who had SLE themselves (87.5%) and who called the service because of recent changes in their physical functioning and reported feelings of depression and anxiety about their illness. Forty-one percent of respondents made 6 or more calls to their assigned peer counselor. Respondents reported high levels of satisfaction across 5 highly correlated measures, with 92% of callers reporting at least moderate satisfaction with the service. Over 60% of respondents who reported a change in 6 "feeling" categories attributed this change to using LupusLine. Fewer users reported a change in 4 specific behaviors since using the service, but more respondents attributed changes, when they occurred, to LupusLine. CONCLUSIONS: Based on these initial findings, we believe that telephone networks similar to the LupusLine model may be able to offer substantial benefit to people coping with the complex, ongoing psychosocial challenges of SLE. Further, the at-home accessibility and low cost of such volunteer-based interventions may play an ever more needed role in the present health care environment.

Adult↗

Imitation of pretend play acts by children with autism and Down syndrome.

Although there has recently been considerable research interest in the difficulties that children with autism have engaging in pretend play, little attention has been paid to the ability of these children to imitate pretend play acts. Furthermore, suggestions that children with Down syndrome have relatively advanced abilities in pretend play have not been accompanied by an examination of their capacity to imitate pretend play. Three groups of children: autistic, Down syndrome, and normally developing were studied for their capacity to imitate single pretend acts and a series of pretend acts that formed scripts. While the children with autism were surprisingly better than the other two groups on the single-scheme task, they demonstrated specific difficulties on the multischeme task. Results are discussed in relation to current theories of autism and the notion of imitation.

Adolescent↗

Effect of diuretics on urinary oxalate, calcium, and sodium excretion in very low birth weight infants.

OBJECTIVE: To study the effect of diuretic drugs on urinary oxalate excretion in premature infants, and to examine the relationship between urinary calcium and sodium excretion in premature infants. METHODOLOGY: We measured urinary oxalate, calcium, and sodium excretion in 32 premature infants at approximately 34 weeks gestational age. Seven infants were receiving furosemide, 5 infants were receiving thiazide, 8 infants were receiving furosemide plus thiazide, and 12 infants who were not receiving diuretics served as controls. RESULTS: Urinary oxalate to creatinine ratios in infants receiving furosemide (0.48 +/- .26), thiazide (0.54 +/- .20), furosemide plus thiazide (0.44 +/- .19), and control infants (0.51 +/- .43) were similar by analysis of variance (ANOVA). Data expressed as oxalate concentration gave similar results. Urinary calcium to creatinine ratios in infants receiving furosemide (0.81 +/- .30), thiazide (0.54 +/- .25), furosemide plus thiazide (0.75 +/- .49), and control infants (0.37 +/- .25) were similar by ANOVA. The urinary calcium concentration in infants receiving furosemide plus thiazide (0.085 +/- 0.042 mg/mL) was different from control infants (0.044 +/- .023) by ANOVA and Student-Newman-Keuls test. Urinary calcium to creatinine ratio was correlated with sodium to creatinine ratio (r = .751). CONCLUSION: Urinary oxalate excretion in premature infants is not affected by diuretic drugs. Urinary sodium and calcium excretion are closely linked in sodium supplemented premature infants receiving diuretics. The calciuric effect of furosemide is not decreased by the addition of thiazide in premature infants receiving sodium supplements.

Analysis of Variance↗

Effects of choosing academic assignments on a student with attention deficit hyperactivity disorder.

The effects of choosing academic assignments on the undesirable behaviors manifested by a second-grade student with attention deficit hyperactivity disorder were analyzed. This study extended Dunlap et al.'s (1994) research on choice making as a form of antecedent control. A reversal design showed that undesirable behaviors decreased when the student was given a choice of academic assignments.

Attention↗

Ruptured bacterial intracranial aneurysm in pregnancy. A case report.

BACKGROUND: Rupture of a documented infectious cerebral aneurysm is a rare complication of infectious endocarditis, with a high morbidity and mortality rate. The only previously reported case was associated with maternal and neonatal mortality. No known report exists of a ruptured bacterial intracranial aneurysm complicating an ongoing pregnancy with maternal or fetal survival. CASE: A 38-year-old, white woman, gravida 9, para 4, at 18 weeks' gestation, developed infectious endocarditis with peripheral and cerebral emboli secondary to intravenous drug abuse, causing renal failure and cortical strokes. She required hemodialysis and also suffered a subarachnoid hemorrhage due to rupture of cerebral bacterial aneurysms. A team approach to her care was necessary. At 28 weeks' gestation she delivered by cesarean section for abruptio placentae. Both the mother and neonate recovered. CONCLUSION: Rupture of mycotic aneurysms can be catastrophic and is often managed surgically. The patient described here was severely affected, and though indicated, surgical intervention was not possible. An aggressive team approach provided a good maternal and fetal outcome.

Adult↗

Global regulatory considerations for unified assay specifications.

When developing a biotechnology product for global registration, there are several aspects to evaluate in an effort to unify specifications. These include differences between the United States, Europe and Japan, and Rest-of-World (ROW) countries with regard to the respective regulatory guidelines and pharmacopoeias in force, the state-of-the-art of product testing analytical methods, and the interval between submitting a registration dossier to different countries. In terms of regulatory guidelines, one country may have a monograph or required specifications for particular tests, for example the potency that a product has to meet before clinical trials can be initiated. For pharmacopoeias, different assay methods are required for sterility, general safety, and pyrogen testing, so that one may have to test a specific lot of a product at two or three different times to evaluate the same parameter, because of specific testing differences required for each country's pharmacopoeia. In addition, the state of analytical methods is always evolving and better analytical techniques become available. Sometimes, from starting with one set of tests, and based on the time in development, new tests may be added to the existing list of release specifications, because new analytical techniques have become available. Examining the global registration approval process for Betaseron, (interferon beta-1b) illustrates when specifications were able to be unified and when they were not.

Animals↗

Evidence for altered cell-mediated immunity in postmastectomy lymphoedema.

Patients with chronic lymphoedema are prone to develop chronic infections and various tumours in the lymphoedematous limb, suggesting that regional immune surveillance is impaired. To test the hypothesis that cutaneous cell-mediated immunity is impaired, 35 women with postmastectomy lymphoedema were investigated using dinitrochlorobenzene to test the afferent and efferent loops of the allergic contact immune response. The results support the role of lymphatics as an important component of the immune response to allergens by the demonstration of impairment of both the afferent and efferent loops of the allergic contact dermatitis reaction, and confirm that there is suppression of immune competence in a lymphoedematous limb.

Adult↗

Equivalence of fast flush and square wave testing of blood pressure monitoring systems.

BACKGROUND: The accurate recording of intraarterial pressure depends upon an appropriate dynamic response of the monitoring system. Generation of a square wave (SW) at the catheter tip is the engineering and in vitro laboratory gold standard. Fast flush (FF) testing is the clinical test of choice. Results from these two test methods have been assumed equal but have not been empirically confirmed. METHODS: We studied three different 5.1 cm catheter sizes (16 G, 18 G, 20 G Becton Dickinson, Sandy, UT) attached to three different lengths of arterial pressure tubing (36 in, 91.4 cm; 72 in, 182.9 cm; 108 in, 274.3 cm). An arterial recording system was assembled in the standard fashion by attaching a catheter to arterial pressure tubing, which was attached to a transducer (TXX-R, Ohmeda, formerly Viggo-Spectramed, Oxnard, CA) whose signal was recorded by a strip chart recorder (Gould 2400, Rolling Meadows, IL). The system was attached to a pressurized saline flush. The catheter tip was inserted into one port of a pressure generator. With the other port of the pressure generator open to atmosphere, FF tests were performed by activating the flush device of the transducer. Subsequent step response signals from the FF tests were then recorded from which natural frequency (fn) and damping coefficient (zeta) were calculated. Next, square waves were generated by closing the port that was open to atmosphere and attaching a signal generator to a pressure generator. Square waves so generated were recorded as described above and natural frequency and damping coefficients calculated. These procedures were repeated after 0.05 cc of air was introduced in the transducer and repeated again in a system containing a damping device (R.O.S.E., Resonant OverShoot Eliminator, Viggo-Spectramed, Oxnard, CA). RESULTS: There was no significant difference between fn and zeta as calculated from the step response generated from the FF test versus fn and zeta as calculated from the square wave (SW) test in systems without air. However, in systems containing air, fn by FF testing was always less than fn by SW testing for all catheter sizes and extension tubing lengths (p < 0.05). Damping was also always greater by FF testing than by SW testing in systems with air for all catheter sizes and extension tubing lengths (p < 0.05). The R.O.S.E device created marked qualitative differences, although exact fn and zeta could not be quantified. CONCLUSIONS: For the characterization of dynamic response of invasive blood pressure monitoring systems, the FF test and SW test yield identical results. However, under certain conditions-air, R.O.S.E device-dynamic response as measured by FF testing was not equivalent to dynamic response as measured by the gold standard-the SW test. Specifically, small amounts of air in fluid-filled invasive blood pressure monitoring systems cause a slightly worse dynamic response as measured by FF testing versus the laboratory gold standard-the SW test.

Blood Pressure Monitors↗

Selected pediatric viral infections.

Viral infections of the central nervous system in infants and children are uncommon but potentially serious illnesses. Common causes have included the enteroviruses (particularly polioviruses and coxsackieviruses), herpes viruses (type 1 and type 2 herpes simplex, varicella, and cytomegalovirus), arboviruses, rubella, mumps, measles (including subacute sclerosing panencephalitis), and human immunodeficiency virus. Several of these viruses, such as cytomegalovirus, herpes simplex, and vertically transmitted human immunodeficiency virus, may cause congenital infections. Others are acquired later in childhood. In recent years, immunization programs have significantly reduced the occurrence of some of these diseases. A brief survey of the clinical and pathological manifestations of these illnesses will be discussed along with current incidence data.

Central Nervous System Infections↗

Mitochondrial deoxyribonucleic acid deletions in oocytes and reproductive aging in women.

OBJECTIVE: To determine whether oocytes from women harbor deletions in mitochondrial DNA (mtDNA) and whether deleted mtDNA is more common in oocytes from older women than oocytes from younger women. DESIGN: A polymerase chain reaction (PCR)-based strategy, which depends on deletions approximating otherwise widely separated primers to demonstrate mtDNA deletions in individual oocytes, was used. SETTING: Yale In Vitro Fertilization Clinic and Laboratory at Yale University School of Medicine. MAIN OUTCOME MEASURES: Primers flanked a region of the mitochondrial genome in which long direct repeated sequence predispose to deletions. The primers identified the 0.5-kb "common" deletion. Deleted mtDNA was represented by a 0.5-kb band when primers separated by 5 kb were used. Control reactions used primers that amplify mtDNA outside the deletion hotspot. Positive controls included brain and/or muscle from aged individuals, and negative controls included fetal tissue and DNA-free blanks. Nested primers confirmed the specificity of the deleted product. RESULTS: Unfertilized oocytes, muscle, and brain tissue contained PCR products consistent with deleted mtDNA. Fetal tissue lacked the mtDNA deletion product. Deleted mtDNA was detected in single oocytes. Oocytes from older women were more likely to contain deleted mtDNA than oocytes from younger women. CONCLUSION: Deleted mtDNA in unfertilized oocytes may serve as a marker of oocyte senescence.

Adult↗

6-Methyluracil excretion in 2-methylacetoacetyl-CoA thiolase deficiency and in two children with an unexplained recurrent ketoacidaemia.

6-Methyluracil (6MU) has been identified in urine collected during acute illness in two children with beta-ketothiolase deficiency (approximately 1 mmol/L) and in two children with recurrent infection-related ketoacidaemia of unknown aetiology (levels of 6.3 and 7.1 mmol/mmol creatinine). Significant amounts of 6MU were not detected in children with fasting ketosis in whom a metabolic disorder was excluded (normal levels less than 25 mumol/mmol creatinine). We propose that the production of 6MU may be related to the accumulation of acetoacetyl-CoA and thus be a marker for disorders where this occurs.

Acetyl-CoA C-Acetyltransferase↗

Metabolic disease and sudden, unexpected death in infancy.

The prevalence of metabolic disease in infants dying suddenly and unexpectedly is controversial. Most studies have centered on major pediatric institutes with appropriate facilities to study inherited metabolic disease. No studies have been reported from nonacademic centers. We have prospectively studied urine and blood organic and fatty acids from 58 consecutive infant deaths over a 1-year period in nonteaching hospital medical examiners' offices in the state of Illinois for evidence of metabolic disease. One infant was found to have medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, homozygous for the common A985G mutation. One had probable non-A985G MCAD deficiency based on the identification of cis-4-decenoic acid in blood and one had ethylmalonic-adipic aciduria. Thus, we found evidence that inherited metabolic defects are related to unexpected infant death in this population. These disorders are present in a significant minority of infants who probably would have been given the diagnosis of sudden infant death syndrome if they had not undergone metabolic evaluation. We recommend that all infants who have died suddenly and unexpectedly be regarded as high-risk candidates for metabolic disease and that all such deaths be appropriately investigated as part of the routine autopsy procedure.

Acyl-CoA Dehydrogenase↗

Isolation and characterization of neurokinin A receptor cDNAs from guinea-pig lung and rabbit pulmonary artery.

cDNA clones for NK-2 receptors (NK-2R) were isolated from guinea-pig lung (GPl) and rabbit pulmonary artery (Rpa) using a polymerase chain reaction based methodology. The GPl NK-2R consists of 402 amino acids and encodes a protein with a relative molecular mass of 45,097. The Rpa NK-2R consists of 384 amino acids and encodes a protein with a relative molecular mass of 43,169. The GPl and Rpa NK-2Rs share significant amino acid sequence homology amongst themselves (90.1%), as well as with human, bovine, hamster and rat NK-2 receptors. The two receptors were stably transfected into mouse erythroleukemia cells, high-speed membranes were prepared from induced cells and their pharmacological properties examined utilizing [3H]-NKA in a receptor-binding assay. [3H]NKA bound to both NK-2Rs with high affinity (KD = 2-7 nM) and saturable (Bmax = 633-9000 fmol/mg protein) manner which was inhibited by GTP analogs. Competition experiments with agonists demonstrated identical order of potency in both NK-2Rs; NKA > [Nle10]NKA(4-10) > [beta-Ala8]NKA(4-10) > > Substance P > > > Senktide. Similarly, an identical profile for both receptors was observed with selective NK-2 antagonists: SR48,968 > MEN10,376 > > R396. The rank order of antagonist affinity is consistent with that in cloned human NK-2R and the observations of NK-2 receptor pharmacology in native human, guinea pig and rabbit tissues.

Amino Acid Sequence↗

Tiglylglycine excreted in urine in disorders of isoleucine metabolism and the respiratory chain measured by stable isotope dilution GC-MS.

Tiglyglycine (TG), an intermediate product of the catabolism of isoleucine, is increased in the urine of patients with beta-ketothiolase deficiency or with disorders of propionate metabolism. It is also implicated as a useful diagnostic marker in disorders of the respiratory chain. We present a method for the synthesis of TG and tiglyl[13C, 15N]glycine and the development of a stable isotope dilution mass spectrometric assay for TG. We compare data from controls with that from subjects with beta-ketothiolase deficiency and propionyl-CoA carboxylase deficiency, and with six patients with enzyme-confirmed disorders of the respiratory chain. TG was increased in the urine from all of the patient groups. The increased TG excretion did not persist in one patient with a respiratory chain defect, which suggests that, in some patients, multiple sample analysis may be necessary to identify a respiratory chain defect. This is the first urinary compound to be implicated as a potential marker of disorders of the respiratory chain.

Acetyl-CoA C-Acyltransferase↗

The risk of repeating low birth weight and the role of prenatal care.

OBJECTIVE: To estimate the influence of adequacy of prenatal care and other known risk factors on the risk of repeating low birth weight (LBW) (less than 2500 g). METHODS: This was a retrospective cohort study of women having two births in Washington state during 1984-1990, as recorded using linked birth certificate records. Logistic regression was used to control for maternal age, marital status, smoking, miscarriage, inter-pregnancy interval, and prenatal care. RESULTS: Compared to the reference group of women with normal-weight first births (at least 2500 g), women with LBW first births, either preterm or small for gestational age (SGA), were significantly more likely to have an LBW second birth. The estimated relative risk of repeating LBW in general was 7.0 (95% confidence interval 4.8-10.1). Smoking during the second pregnancy was a significant effect modifier. The risk estimates were not significantly affected by any of the other variables entered into the models, including adequate prenatal care. CONCLUSIONS: Prior delivery of a preterm or SGA LBW infant was the strongest predictor of LBW delivery in a subsequent pregnancy. Adequate prenatal care during the second pregnancy did not provide statistically significant protection against the risk of repeat LBW. The tendency for women to have repeat LBW deliveries despite adequate prenatal care indicates a need for a better understanding of the underlying pathophysiology of preterm and SGA delivery.

Adult↗