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Biomedical subjects

S Brennan

Publications and source records attributed to S Brennan.

At least 55 records · Page 3Linked to original sources

Traumatic rupture of an aortic ulcerative atherosclerotic plaque producing aortic dissection: a complication of interscapular back blows used to dislodge objects from the esophagus.

Penetrating atherosclerotic ulcer of the aorta is a rare entity which usually occurs in the descending thoracic aorta. Herein, we report an unusual case of penetrating aortic ulcer which ruptured into the mediastinum. Interscapular back blows were performed on our patient in an attempt to dislodge an aspirin which she thought was lodged in her esophagus. Unlike previously reported cases of this entity, the penetrating aortic ulcer in our patient was located in the distal thoracic ascending aorta. Diagnosis of penetrating aortic ulcer can be made by utilizing aortography, contiguous dynamic contrast-enhanced computed tomography or magnetic resonance imaging. Treatment consists of adjunctive medical therapy until surgery can be performed.

Aged↗

Developmental regulation of a serum response element binding activity in amphibian embryos.

As part of our studies of transcriptional control during early development in vertebrates, we have examined embryos of the amphibian Xenopus laevis for the presence of sequence-specific DNA-binding proteins, using gel electrophoresis mobility-shift assays. Our analysis has focused on sequence elements in the cytoskeletal actin gene, whose embryonic transcription is initially activated at the gastrula stage, approximately 16 hours after fertilization. We detect activities capable of specific binding to two known transcriptional regulatory elements, the serum response element and the GC-box, located in the 5'-flanking region of the cytoskeletal actin gene. Binding activity specific for a region downstream of the transcriptional startsite is also detected, in a region which may be involved in controlling developmental activation of this gene. Serum response element-binding activity, as well as the downstream binding activity, is enriched in extracts from gastrula and neurula stage embryos, compared to egg extracts, suggesting that increased levels of one or both of these activities might play a role in developmentally timed transcriptional activation of the cytoskeletal actin gene in the embryo.

Actins↗

Pharmacokinetic and pharmacodynamic study of midazolam in children during esophagogastroduodenoscopy.

We undertook a prospective study to evaluate the relationship between the onset and degree of sedation and the midazolam plasma concentration in children between 6 and 18 years of age during esophagogastroduodenoscopy. Thirteen boys and seven girls (median age 13.5 years) were studied. Midazolam was injected intravenously for 5 minutes, and the dose was titrated to sedation or a maximum dose of 0.1 mg/kg was given. Plasma midazolam concentration was determined just before and at 5, 10, 15, 30, 45, and 60 minutes after the start of midazolam injection. The patient's level of sedation was evaluated by an assistant at each blood sampling time. Clearance, volume of distribution, and terminal elimination (beta) half-life were estimated from a biexponential fit of the serial plasma midazolam concentrations. Mean beta half-life of midazolam was 47 +/- 26 minutes and mean clearance was 10.0 +/- 5.0 ml/min per kilogram of body weight. Maximum level of sedation occurred at 5 minutes after initiation of the injection and corresponded to a mean peak midazolam serum concentration of 229 +/- 39 micrograms/L. Thereafter, a decline of mean sedation scores paralleled the decrease in midazolam concentration. Mean oxygen saturation remained greater than 94% during the study. We conclude that children metabolize and excrete midazolam more rapidly than adults do and that sedation adequate for endoscopy is safely achieved in the majority of children with a midazolam dose of 0.05 to 0.1 mg/kg and a mean peak midazolam concentration greater than 200 microgram/L.

Adolescent↗

Effect of pH on citrate reabsorption in the proximal convoluted tubule.

Urinary citrate is an important endogenous inhibitor of calcium nephrolithiasis. Systemic acidosis increases renal citrate reabsorption (decreases urinary excretion) and hence is associated with nephrolithiasis; systemic alkali administration increases citrate excretion. We studied the mechanism by which acidosis and alkalosis alter citrate reabsorption in the proximal convoluted tubule, the predominant nephron segment reabsorbing citrate. Tubules were perfused in vitro and citrate reabsorption was measured by use of luminal [14C]citrate. Changes in solution pH were accomplished by changes in bicarbonate concentration with constant PCO2. Decreasing peritubular pH acutely from 7.4 to 7.2 caused an increase in citrate reabsorption. However, the change seen with an acid peritubular pH was abolished by additional buffering of the luminal solution. Increasing peritubular pH from 7.4 to 7.6 resulted in a fall in citrate reabsorption that was not significantly greater than a time-dependent fall in citrate reabsorption in this preparation. The effect of luminal pH on proximal citrate reabsorption was also examined directly. Decreasing perfusate (luminal) pH from 7.4 to 7.2 with constant peritubular pH increased citrate reabsorption. Increasing perfusate pH to 7.6 decreased citrate reabsorption insignificantly (0.1 less than P less than 0.2). These data suggest that luminal pH in the proximal tubule is an important determinant of alterations in citrate reabsorption with acid-base disorders. The effect of luminal pH on citrate reabsorption is probably due to a change in concentration of the transported ionic species, citrate2-.

Acetazolamide↗

Methods for study of the effects of diuretics.

We live in an imperfect world, and no single technique of renal investigation has demonstrated a superiority in all aspects of diuretic research. We have tried to present a balanced view of the advantages and disadvantages of several of the most common techniques used to study diuretics. Because of space limitations, we have been unable to touch on important studies of diuretic effects on extrarenal tissues or even the effects of diuretics on nontransporting renal preparations (eg, metabolism in renal slices). There is still a time and a place for nearly all the techniques summarized here in the study of diuretics and their impact on renal physiology. It is our hope that this brief introduction into renal methodology will allow the discerning reader of studies of diuretics to decide for himself whether the tools chosen by the investigator were appropriate to answer the questions posed, and if not, how the questions may be more properly addressed. It is important to remember that data are neither right nor wrong; the results exist and cannot be otherwise. However, our interpretation of the data may be wrong, and the most important aspect of any experiment is not the technique but the thought behind it.

Animals↗

Amino acid sequence of atrial natriuretic peptides in human coronary sinus plasma.

Two atrial natriuretic peptides were purified from pooled human coronary sinus plasma by Sep-Pak extraction, immunoaffinity chromatography and reverse phase HPLC. The amino acid sequences of the two peptides were homologous with 99-126 human atrial natriuretic peptide (hANP) and 106-126 hANP, the latter being most probably linked to 99-105 ANP by the disulphide bond. The molar ratio of the peptides in plasma, as assessed by radioimmunoassay was 10:3.

Amino Acid Sequence↗

Hematopoietic cell transplantation in murine globoid cell leukodystrophy (the twitcher mouse): effects on levels of galactosylceramidase, psychosine, and galactocerebrosides.

Hematopoietic cell transplantation (HCT) prolongs survival in the twitcher mouse, an authentic animal model of human globoid cell leukodystrophy (Krabbe disease; galactosylceramidase deficiency), but the effects of HCT on levels of galactosylceramidase, psychosine, and cerebrosides in the tissues of twitcher mice have not been previously studied. Galactosylceramidase was less than 8% of control activity in tissues of untreated twitcher mice but reached normal values in brain and spleen and 20-30% of control in kidney of 100-day-old twitchers that received HCT at age 10 days. Using a recently developed method for the simultaneous determination of psychosine and cerebrosides, we measured the tissue levels of these lipids in the above animals. The levels of psychosine in brain, sciatic nerve, and kidney of untreated twitcher mice were 44, 200, and 12 times control values, respectively, in 30-day-old animals and 69, 500, and 14 times control levels in 40-day-old mice. On the other hand, levels of cerebroside were approximately 35% of control values in sciatic nerve, remained about the same in the brain, and were elevated 10-fold in the kidney of twitcher mice. After HCT, psychosine levels in the brains of 30-day-old twitchers were lowered to 30-35% of values in untreated twitchers, and the levels remained in that range during the post-HCT period. Similarly, brain cerebroside levels remained low in HCT-treated twitcher mice. Although psychosine levels in sciatic nerves of HCT-treated twitcher mice increased more slowly than in the nerves of untreated twitchers, the levels in 100-day-old HCT-treated twitcher mice had reached the same high values as those seen in untreated 40-day-old twitchers. It is not known whether the extremely high levels of psychosine in sciatic nerves ultimately contribute to the death of twitcher mice after HCT.

Aging↗