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Biomedical subjects

B J Clark

Publications and source records attributed to B J Clark.

At least 127 records · Page 7Linked to original sources
PubMed1991

X-linked dilated cardiomyopathy with neutropenia, growth retardation, and 3-methylglutaconic aciduria.

Seven boys with an apparently X-linked syndrome of dilated cardiomyopathy, growth retardation, neutropenia, and persistently elevated urinary levels of 3-methylglutaconate, 3-methylglutarate, and 2-ethylhydracrylate were studied. The natural history of the disorder was characterized by severe or lethal cardiac disease and recurrent infections during infancy and early childhood but relative improvement in later childhood. The initial presentation of the syndrome varied from congenital dilated cardiomyopathy to infantile congestive heart failure to isolated neutropenia without clinical evidence of heart disease. The excretion of 3-methylglutaconate and 3-methylglutarate appeared to be independent of the metabolism of leucine, the presumed precursor of these organic acids in humans. Although the cause of the organic aciduria remains obscure, the constellation of biochemical and clinical abnormalities forms a distinct syndrome that may be a relatively common cause of dilated cardiomyopathy or neutropenia in boys during infancy and childhood.

Adult↗
PubMed1991

Common complaints with cardiac implications in children.

Chest pain, palpitations, and dizziness are not infrequent complaints in the office of a primary care physician. Historical events and physical findings can lead to a more accurate determination of cardiac causes of these symptoms. Electrocardiogram and chest radiographs are two additional tests most often helpful in determining cardiac causes of symptoms.

Arrhythmias, Cardiac↗
PubMed1991

Diode array detection and simultaneous quantitation of the coeluting atenolol-related synthetic route impurities, PPA-Diol.

The diode array multichannel detector is used to acquire spectral information at specified intervals in the elution profile of atenolol and its related impurities for post-chromatographic data analysis. The applicability of a number of peak homogeneity testing methods, including spectral normalization, absorbance ratio, chromatographic derivatives, and spectral suppression (SS), are assessed for suitability in simultaneous determinations of the coeluting atenolol-related synthetic impurities, PPA-Diol. Spectral suppression displays a superior performance in comparison to all the other techniques in that both qualitative and quantitative information are acquired on the system.

Acetamides↗
PubMed1991

Management of inborn errors of metabolism during pregnancy.

An increasing number of women with inherited metabolic disorders survive, conceive and have children. In order to safeguard the health of the mother and the developing embryo, fetus, and newborn during pregnancy, delivery, and the neonatal period it is necessary to be aware of the range of metabolic disorders, the risks to mothers and children, and appropriate management strategies. The roles of the Paediatrician, Obstetrician and Dietitian in the management of Maternal Hyperphenylalaninaemia and phenylketonuria are reviewed.

Birth Weight↗
PubMed1991

Biochemical adaptations to training: implications for resisting muscle fatigue.

Skeletal muscle activity is invariably associated with a decline in force-generating capacity (fatigue). The build-up of metabolic by-products such as intracellular H+ and inorganic phosphate (Pi) has been shown to be one of the potential mechanisms of muscle fatigue. The use of phosphorus magnetic resonance spectroscopy is a repeatable and useful tool to study the effect of pH and Pi on force development. When maximal exercise is preceded by submaximal exercise to reduce the starting muscle pH and increase Pi, the degree of muscle fatigue correlates more strongly with H2PO4- than pH or Pi alone. However, other studies in humans have found that H2PO4- does not always correlate well with fatigue. The use of ramp exercise protocols allow repeatable and sensitive measurement of changes in muscle metabolism in response to endurance training. Chronic electrical stimulation in dogs and endurance training in humans results in reduced pH and Pi changes at the same exercise intensities. This means that the effect of pH and Pi in depressing force development is reduced, which could partially explain the increased fatigue resistance seen following endurance training.

Exercise↗
PubMed1991

Skeletal muscle bioenergetics during frequency-dependent fatigue.

The bioenergetic correlates of skeletal muscle fatigue were assessed in vivo with phosphorus-31 nuclear magnetic resonance (31P-NMR) spectroscopy. After surgical construction of latissimus dorsi muscle ventricles, seven beagles underwent 31P-NMR spectroscopy during 12-min exercise protocols at 25- and 85-Hz stimulation frequencies and during both isovolumetric and dynamic contractions. Exercise at 85 Hz was associated with significantly greater fatigue than exercise at 25 Hz. At both frequencies, the onset of exercise was associated with a marked increase in inorganic phosphate (Pi) and a decrease in phosphocreatine (PCr). As the muscle fatigued at 85 Hz but not at 25 Hz, the phosphorus spectra returned to near baseline with a decrease in Pi and increase in PCr. For a given amount of force generated, the Pi-to-PCr ratio was higher for dynamic contractions than for isovolumetric contractions. This study indicates that high-frequency fatigue is unlikely to result from the direct effects of high-energy phosphate metabolism and that contractions producing external work consume more metabolic energy than equally forceful isometric contractions.

Animals↗
PubMed1991

Global cerebral ischemia in piglets under conditions of mild and deep hypothermia.

BACKGROUND AND PURPOSE: To investigate the effects of hypothermia on the rate of change and degree of recovery of brain adenosine triphosphate and phosphocreatine concentrations and intracellular pH, we have developed a model that allows phosphorus nuclear magnetic resonance spectroscopy of the intact piglet brain during circulatory arrest. METHODS: Three groups of piglets were studied. Three control animals underwent cardiopulmonary bypass at normothermia for 1 hour; five group 1 animals underwent bypass at a brain temperature of 15 degrees C, followed by a period of circulatory arrest such that adenosine triphosphate was absent for 21 minutes, followed by 1 hour of reperfusion; and five group 2 animals underwent bypass at a brain temperature of 37 degrees C, followed by a period of circulatory arrest such that adenosine triphosphate was absent for 21 minutes, followed by reperfusion for 1 hour. RESULTS: Control animals showed no significant metabolic effects of bypass. Group 1 animals showed a slower decay of the adenosine triphosphate and phosphocreatine concentrations than group 2 animals, consistent with a lower metabolic rate, and had a higher pH at the onset of ischemia. Recovery of the adenosine triphosphate concentration was significantly better in group 1 animals (95%) than in group 2 animals (30%) (p less than 0.02), and recovery of the phosphocreatine concentration was also better in group 1 animals (93%) than in group 2 animals (32%) (p less than 0.02). Intracellular pH recovered in group 1 animals, but not in group 2 animals. Regional biochemical assays of metabolites performed in the group 2 piglets and in five pilot piglets exposed to deep hypothermia generally confirmed the spectroscopic findings but demonstrated considerable regional variation, specially in the group 2 piglets' brains. CONCLUSIONS: We conclude that hypothermia exerts a protective effect on the piglet brain during global ischemia even after the adenosine triphosphate pool has been completely depleted.

Adenosine Diphosphate↗
PubMed1991

The role of vasopressin and atrial natriuretic factor in postoperative fluid retention after the Fontan procedure.

The Fontan procedure results in right atrial distention and is complicated by fluid retention. Since systemic fluid balance may be hormonally mediated in part and related to right atrium size, we measured plasma atrial natriuretic factor and plasma arginine vasopressin levels in 19 patients undergoing the Fontan procedure and in 12 control patients undergoing other types of heart operations. Preoperative plasma atrial natriuretic factor levels were higher in patients undergoing the Fontan procedure than in control patients (95 +/- 16 pg/ml preoperatively versus 50 +/- 8 pg/ml; p less than 0.05) and increased in patients undergoing the Fontan procedure to 330 +/- 48 pg/ml by postoperative day 2 (p less than 0.05) but not in control patients. Increased plasma atrial natriuretic factor levels could enhance capillary transudation, but elevated plasma atrial natriuretic factor levels should also enhance diuresis and prevent fluid retention. Vasopressin levels, however, were also increased in patients undergoing the Fontan procedure (from 9 +/- 2 pg/ml preoperatively to 144 +/- 37 pg/ml at end of operation) and were higher and remained elevated longer than in control patients undergoing heart operations (37 +/- 7, 20 +/- 4, 16 +/- 6 pg/ml on postoperative days 1, 2, and 3 to 10 for the Fontan group compared with 15 +/- 4, 4 +/- 1, 4 +/- 2 pg/ml for control patients). Vasopressin levels were highest in the Fontan group with the most severe fluid retention and effusions (for example, 51 +/- 10 pg/ml versus 23 +/- 4 pg/ml, on postoperative day 1). Increased vasopressin and atrial natriuretic factor could act synergistically to result in the development of effusions after the Fontan procedure when atrial natriuretic factor-induced capillary transudation is combined with vasopressin-induced antidiuresis.

Atrial Natriuretic Factor↗
PubMed1991

Effects of potassium cardioplegia on high-energy phosphate kinetics during circulatory arrest with deep hypothermia in the newborn piglet heart.

The protective effects of hypothermia and potassium-solution cardioplegia on high-energy phosphate levels and intracellular pH were evaluated in the newborn piglet heart by means of in vivo phosphorus nuclear magnetic resonance spectroscopy. All animals underwent cardiopulmonary bypass, cooling to 20 degrees C, 120 minutes of circulatory arrest, rewarming with cardiopulmonary bypass, and 1 hour off extracorporeal support with continuous hemodynamic and nuclear magnetic resonance spectroscopic evaluation. Group I (n = 5) was cooled to 20 degrees C; group II (n = 4) was given a single dose of 20 degrees C cardioplegic solution; group III (n = 7) was given a single dose of 4 degrees C cardioplegic solution; and group IV (n = 4) received 4 degrees C cardioplegic solution every 30 minutes. At end ischemia, adenosine triphosphate, expressed as a percent of control value, was lowest in group I 54% +/- 6.5% but only slightly greater in group II 66% +/- 7.0%. Use of 4 degrees C cardioplegic solution in groups III and IV resulted in a significant decrease in myocardial temperature, 9.9 degrees C versus 17 degrees to 20 degrees C, and significantly higher levels of adenosine triphosphate at end ischemia; with group III levels at 72% +/- 6.0% and group IV levels at 73% +/- 6.0%. Recovery of adenosine triphosphate with reperfusion was not related to the level of adenosine triphosphate at end ischemia and was best in groups I and II, with a recovery level of 95% +/- 4.0%. In group IV, no recovery of adenosine triphosphate occurred with reperfusion, resulting in a significantly lower level of adenosine triphosphate, 74% +/- 6.0%, than in groups I and II. Recovery of ventricular function was good for all groups but was best in hearts receiving a single dose of 4 degrees C cardioplegic solution. In this model, multiple doses of cardioplegic solution were not associated with either improved adenosine triphosphate retention during arrest or improved ventricular function after reperfusion, and in fact resulted in a significantly lower level of adenosine triphosphate with reperfusion. The complete recovery of adenosine triphosphate in groups I and II, despite a nearly 50% adenosine triphosphate loss during ischemia, may result from a decrease in the catabolism of the metabolites of adenosine triphosphate consumption in the newborn heart.

Adenosine Triphosphate↗
PubMed1990

Construction and expression of human/bovine P45017 alpha chimeric proteins: evidence for distinct tertiary structures in the same P450 from two different species.

In the human and bovine adrenal cortex, 17 alpha-hydroxylase (P45017 alpha) catalyzes reactions involved in the production of C21-glucocorticoids (17 alpha-hydroxylation) and C19-androgens (17,20-lyase). The bovine and human forms of P45017 alpha share 71% primary sequence identity. Using naturally occurring restriction sites common to cDNAs encoding both human and bovine P45017 alpha, we have constructed bovine/human (bovine amino terminus and human carboxy terminus) and human/bovine (human amino terminus and bovine carboxy terminus) cDNAs that have been expressed in COS 1 cells, and the enzymatic properties of the resultant chimeric proteins have been examined. The three bovine/human chimeras studied have 17 alpha-hydroxylase activities intermediate between those of the wild-type bovine and wild-type human enzymes, although the 17,20-lyase activity of these chimeras is significantly lower than that of either of the wild-type enzymes. Surprisingly, the opposite chimeras (those containing a human amino-terminal sequene and a bovine carboxy-terminal sequence) are all virtually inactive, even though they appear to be expressed at normal levels. These results indicate that the folding of P45017 alpha initiated by the bovine amino terminus can accommodate human P45017 alpha sequences of various lengths to produce a relatively normal 17 alpha-hydroxylase having decreased 17,20-lyase activity. On the other hand, folding initiated by the human P45017 alpha amino terminus does not easily accommodate bovine carboxy-terminal sequences to produce a functional enzyme. Presumably this difference arises from the fact that the tertiary structures of the bovine and human forms of P45017 alpha are sufficiently different so that interchanging sequences will not lead to functional enzymes in a predictable fashion.

Amino Acid Sequence↗
PubMed1990

Posterior axial corneal malformation and uveoretinal angiodysgenesis--a neurocristopathy?

This clinicopathological report describes an unusual combination of axial corneal malformation and angiodysgenesis in the uvea, retina and optic nerve in three eyes. In each specimen there was hypocellularity in the posterior axial stroma, with corresponding loss of the corneal endothelium. The vascular malformation consisted of numerous telangiectatic endothelium-lined tubes with inconspicuous or absent media. One globe was obtained from a stillborn fetus (36 weeks) in which renal agenesis and a sireniform malformation (mermaid fetus) occurred in conjunction with a Fallot's tetralogy, pulmonary hypoplasia and atresia of the trachea and duodenum. Eyes with almost identical malformations were obtained from a 39-week female neonate who died after 5 h as a consequence of renal agenesis and pulmonary hypoplasia. This combination of ocular tissue malformations can be explained by embryological studies, which have shown that the corneal stroma and endothelium and the ocular periendothelial vascular tissues are derived from the neural crest.

Abnormalities, Multiple↗
PubMed1990

Oculokinetic perimetry for the assessment of visual fields.

The visual fields of 13 children aged 7 to 16 (mean 10.7 years) were assessed by oculokinetic perimetry (OKP), a technique where the field of vision is tested at reading distance using a simple chart, and the results compared with conventional Goldmann perimetry. Cooperation with testing was greater for OKP than Goldmann perimetry and in some cases OKP was better correlated with clinical findings. The advantages of visual field assessment by OKP for children are the close proximity of observer and child, the absence of the requirement for prolonged fixation, and the inexpensiveness and portability of the testing equipment. The disadvantages are movements of the head, with variability in the distance from the target, and the limitation to the central 25 degrees of the visual field.

Adolescent↗
PubMed1990

Chest pain in children. Follow-up of patients previously reported.

During a 1-year period, 407 children with chest pain were seen in the Emergency Department of Children's Hospital of Philadelphia. Analysis of the clinical data of these children was reported previously. The authors successfully followed 149 of these children for 6 months or more, and 51 for 2 years or more. These patients returned for an average of 3.4 visits during the follow-up period. Thirty-four percent of the initial diagnoses were altered. Usually, during the follow-up period, the authors concluded that chest pain resulted from nonorganic causes. A new organic etiology was uncovered in only 12 of 149 cases. Only 1 child was found to have a heart abnormality (mitral valve prolapse), and 3 were found to have asthma. Chest pain did not resolve during the follow-up period in 43 percent of those followed. Children with chest pain should have follow-up care because of the persistence of symptoms, but serious disease is unlikely to be found over time.

Adolescent↗
PubMed1990

Variation in the response of chick embryos to incision of the roof plate of the neural tube at different developmental stages.

The effects of microsurgical reopening of the neural tube were examined in chick embryos of Stages 12-18. The roof plate of the thoracic neural tube was incised for a length equivalent to 7 somites. The site of incision was studied histologically and by SEM and TEM at intervals up to 48 hours. 48 hours after operation, persistent neural tube defects were more frequent and longer in embryos of more advanced stages at operation. Exposure of embryos to Streptomyces hyaluronidase, which inhibits neurulation in normal embryos, has no effect on the healing of the incised neural tube in the young embryos. Healing of the lesion in younger embryos appeared to occur in two stages: initially, by repair of the surface ectoderm, by a cephalo-caudal zipper-like mechanism, followed by a reconstitution of the roof plate by migration of neurectodermal cells on the deep surface of the ectoderm. Neural tubes of older embryos splay open more widely on incision of the roof plate, apparently making healing mechanically more difficult. This wider splaying may be related to the decline of forces which maintain occlusion of the neural canal in younger embryos.

Animals↗
PubMed1989

Dental pit and fissure sealants: implications for school health personnel.

While tooth decay among schoolchildren has declined in recent years, 95% of all schoolchildren still experience tooth decay. School-based fluoride rinse programs have made a significant contribution to the decrease in tooth decay. Pit and fissure sealants, one other preventive dentistry measure, also fight tooth decay. A pit and fissure sealant placed on the chewing surfaces of permanent molars acts as a barrier and protects caries-prone areas of the teeth. For sealants to be effective, it is important that school health educators, nurses, and administrators have the dental health knowledge necessary to make informed decisions about school-based dental sealant programs. Examples of successful programs are discussed.

Attitude of Health Personnel↗