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Biomedical subjects

S Golden

Publications and source records attributed to S Golden.

At least 19 recordsLinked to original sources

Combination propofol-ketamine anaesthesia in sick neonates.

Two critically ill, opioid-tolerant neonates were anaesthetized using pancuronium and a mixture of propofol (PROP) and ketamine (KET). Three mg of KET were added per ml (10 mg) of PROP in a single syringe and infused at a rate of 100-150 microg x kg(-1) x min(-1) of the PROP component (30-45 microg x kg(-1) x min(-1) KET). Total doses of 12-15 and 3.6-4.5 mg x kg(-1) of PROP and KET, respectively, were administered. Both patients remained haemodynamically stable throughout their surgical procedures. PROP-KET is a rational and effective combination for intravenous anaesthesia in critically ill neonates who are likely to be opioid-tolerant when an anaesthesia vaporizer is not readily available.

Anesthesia, Intravenous↗

Effect of topical nasal azelastine on the symptoms of rhinitis, sleep, and daytime somnolence in perennial allergic rhinitis.

BACKGROUND: Recent data suggested that daytime somnolence in patients with allergic rhinitis was secondary to disrupted sleep caused by nasal congestion. Medications, which decreased congestion, would be expected to improve sleep and daytime somnolence. Previously, we demonstrated that nasal steroids improved all three symptoms. The effect of topical nasal antihistamines on these symptoms has yet to be studied. OBJECTIVE: The objective of this 8-week, double-blind, placebo-controlled study was to determine whether topical nasal azelastine was effective at decreasing congestion, daytime somnolence, and improving sleep. METHODS: We recruited 24 subjects with perennial allergic rhinitis and randomized them in a double-blinded, crossover fashion, to receive placebo or azelastine two sprays BID, using Balaam's design. Questionnaires, daily diary, and Epworth Sleepiness Scale were used as tools. The last 2 weeks of each 4-week treatment period were summarized, scored, and compared by PROC MIXED in SAS. RESULTS: The analysis of the Rhinitis Severity Score showed significant improvement only of rhinorrhea in the azelastine group (P = .03). The symptom severity of nasal congestion and daytime somnolence was not significantly different between placebo and azelastine. Subjects considered azelastine effective at improving their sleep (P = .04), but daytime somnolence (P = .06) and congestion (P = .09) were not statistically improved. CONCLUSION: Azelastine is effective in reducing rhinorrhea and improving sleep quality. We were unable to demonstrate that azelastine can significantly reduce the severity of congestion or daytime somnolence.

Administration, Topical↗

Interval-force relation is unaffected by the presence of cardiomyopathy or coronary artery disease in patients with atrial fibrillation.

BACKGROUND: We tested the hypothesis that cycle length-dependent cardiac contractility in atrial fibrillation is primarily governed by the negative interval-force relation in patients with normal and depressed systolic function. METHODS AND RESULTS: We performed two-dimensional guided M-mode echocardiography in 41 patients (mean age, 69 +/- 4 years; range, 48 to 92 years; 19 men, 11 women). Twelve patients had objective evidence of left ventricular systolic dysfunction (CMP; mean ejection fraction, 37% +/- 7%) in the absence of coronary artery disease (CAD), 13 patients had documented CAD (mean ejection fraction, 43% +/- 6%), and 16 patients had normal resting left ventricular systolic function (mean ejection fraction, 58% +/- 7%). Simultaneous beat-to-beat blood pressure, end-systolic and end-diastolic dimension, circumferential velocity of fiber shortening (Vcf), and end-systolic wall stress (ESWS) were calculated for all patients. All three groups showed a significant linear relation between beat-to-beat Vcf and Vcf corrected for afterload (represented as the Vcf/ESWS ratio) and preceding cycle length. There was, however, no significant difference in the relation between either of these variables and cycle length among the three groups. There was also no difference in the rate of change in either Vcf or Vcf corrected for afterload (Vcf/ESWS ratio) from beat-to-beat among the three groups. Control patients with normal systolic function showed greater Vcf at any given cycle length compared with patients with CMP or CAD. CONCLUSION: Our data show that, for each beat in atrial fibrillation, Vcf and Vcf/ESWS ratio are decreased after shorter cycle lengths and increased after long cycles, but there is no significant attenuation of this effect in patients with systolic dysfunction with or without coronary disease compared with controls. Thus, the negative interval-force relation, the predominant determinant of beat-to-beat variation in contractility in atrial fibrillation, is preserved in patients with CAD or reduced left ventricular systolic function.

Aged↗

The molecular basis of Boston-type craniosynostosis: the Pro148-->His mutation in the N-terminal arm of the MSX2 homeodomain stabilizes DNA binding without altering nucleotide sequence preferences.

Craniosynostosis, Boston type is an autosomal dominant disorder that results in the premature fusion of calvarial bones and ensuing abnormalities in skull shape. We showed previously that this disorder is tightly linked to the Msx2 homeobox gene on the long arm of chromosome 5, and that affected individuals bear a mutated copy of Msx2. In addition, transgenic mice in which either mutant or wild-type mouse Msx2 is overexpressed in the developing skull also exhibit craniosynostosis. That both mutant and wild-type Msx2 elicit craniosynostosis in transgenic mice and that the Boston type mutation is dominant led us to hypothesize that the mutation might enhance the normal function of Msx2. The mutation is located in position 7 of the N-terminal arm of the homeodomain, a region implicated in both target sequence recognition and protein-protein interactions. Here we test the hypothesis that the Pro148-->His mutation alters the DNA binding properties of Msx2. Using gel shift and binding site selection analyses, we show that the mutation enhances the affinity of Msx2 for a set of known Msx2 target sequences but has little or no effect on the site specificity of Msx2 binding. The enhancement of Msx2 binding is due largely if not entirely to an increased stability of the mutant Msx2-DNA complex. These data provide a molecular-level explanation of how the Pro148-->His mutation enhances Msx2 function and thus leads to the dominant craniosynostosis phenotype.

Animals↗

Can phage defence maintain colicin plasmids in Escherichia coli?

We examined the role of plasmid-based phage defence in maintaining plasmids, using colicin plasmids in Escherichia coli as a model system. Experimental data indicated that the possession of a colicin plasmid can confer limited protection against bacteriophages. A continuous culture model, using these experimental values, indicated that the observed limited protection alone could selectively maintain colicin plasmids, without requiring a competitive advantage due to colicinogeny. Phage defence might explain the current maintenance of colicin plasmids, given the naturally occurring high levels of resistance to colicins. This model also suggests that many plasmids might be maintained in natural populations, in part, by phage resistance, including 'cryptic' plasmids for which no phenotype is known.

Bacteriocin Plasmids↗

Follow-up study of owner attitudes toward home care of paraplegic dogs.

A questionnaire was mailed to 30 owners of paraplegic dogs who had been caring for their dogs at home for 3 to 72 months. It was designed to collect information on demographic variables, duration of ownership and paralysis, age of the pet, pet/owner relationship, owner expectations and perceptions of the pet's quality of life, problems the pet experienced, effect that maintaining a paralyzed pet had on the owners' quality of life, and whether use of a cart was beneficial. Significant correlation was found between prior expectations that the pet would lead a high-quality life and perception that the pet, in fact, had a high quality of life during paralysis (r2 = 0.61, P = 0.01). Owners who had anticipated that extra work would be necessary to care for their paraplegic dog had a more positive attitude toward home care (r2 = 0.55, P = 0.03). Overall, owners involved in the study were satisfied with all aspects of maintaining paraplegic dogs at home. Our findings support the feasibility of dedicated owners successfully maintaining small (average body weight, 9 kg) paraplegic dogs at home for extended periods.

Age Factors↗

Active hepatic glycogen synthesis from gluconeogenic precursors despite high tissue levels of fructose 2,6-bisphosphate.

When fasted rats ate regular lab chow there was a lag time of about 2 h before the concentration of fructose 2,6-bisphosphate (Fru-2,6-P2) in liver began to rise from its low basal level. By contrast, in animals refed on a sucrose-based diet hepatic [Fru-2,6-P2] increased 20-fold (to a value of approximately 12 nmol/g wet weight) during the first hour. These responses correlated with differences in the ability of the two diets to increase the circulating [insulin]/[glucagon] ratio and thus to elevate the ratio of 6-phosphofructo-2-kinase to fructose-2, 6-bisphosphatase. Liver glycogen was deposited briskly in both groups of rats. To assess its mechanism of synthesis (directly from glucose versus indirectly via the gluconeogenic pathway), animals eating the chow or sucrose diets received intravenous infusions of [14C]bicarbonate, [1-14C] fructose, and 3H2O. After isolation, the glycogen was subjected to positional isotopic analysis of its glucose residues. The results established that regardless of the diet the bulk of liver glycogen was gluconeogenic in origin. The fact that with sucrose feeding carbon flow through hepatic fructose-1,6-bisphosphatase remained active despite high levels of Fru-2,6-P2 (a potent inhibitor of this enzyme in vitro) presents a metabolic paradox. Conceivably, the suppressive effect of Fru-2, 6-P2 on hepatic fructose-1,6-bisphosphatase is overridden in vivo by some unknown factor or factors generated in response to sucrose feeding. Alternatively, metabolic zonation in liver might result in the coexistence of hepatocytes rich in Fru-2,6-P2 (high glycolytic, low gluconeogenic, low glycogenic capacitites) with cells depleted of Fru-2,6-P2 (low glycolytic, high gluconeogenic, high glycogenic capacities).

Animals↗

Primary intrascrotal nontesticular schwannoma.

A supratesticular intrascrotal mass clinically mimicking a spermatocele was found to be a scrotal neoplasm histologically identified as a schwannoma. We herein present the first case of intrascrotal schwannoma to our knowledge.

Diagnosis, Differential↗

Lactate metabolism in the perfused rat hindlimb.

A preparation of isolated rat hindleg was perfused with a medium consisting of bicarbonate buffer containing Ficoll and fluorocarbon, containing glucose and/or lactate. The leg was electrically prestimulated to deplete partially muscle glycogen. The glucose was labelled uniformly with 14C and with 3H in positions 2, 5 or 6, and lactate uniformly with 14C and with 3H in positions 2 or 3. Glucose carbon was predominantly recovered in glycogen, and to a lesser extent in lactate. The 3H/14C ration in glycogen from [5-3H,U-14C]- and [6-3H,U-14C]-glucose was the same as in glucose. Nearly all the utilized 3H from [2-3H]glucose was recovered as water. Insulin increased glucose uptake and glycogen synthesis 3-fold. When the muscle was perfused with a medium containing 10 mM-glucose and 2 mM-lactate, there was little change in lactate concentration. 14C from lactate was incorporated into glycogen. There was a marked exponential decrease in lactate specific radioactivity, much greater with [3H]- than with [14C]-lactate. The 'apparent turnover' of [U-14C]lactate was 0.28 mumol/min per g of muscle, and those of [2-3H]- and [3-3H]-lactate were both about 0.7 mumol/min per g. With 10 mM-lactate as sole substrate, there was a net uptake of lactate, at a rate of about 0.15 mumol/min per g, and the apparent turnover of [U-14C]lactate was 0.3 mumol/min per g. The apparent turnover of [3H]lactate was 3-5 times greater. When glycogen synthesis was low (no prestimulation, no insulin), the incorporation of lactate carbon into glycogen exceeded that from glucose, but at high rates of glycogen deposition the incorporation of lactate carbon was much less than that of glucose. Lactate incorporation into glycogen was similar in fast-twitch white and fast-twitch red muscle, but was very low in slow-twitch red fibres. We find that (a) pyruvate in muscle is incorporated into glycogen without randomization of carbon, and synthesis is not inhibited by mercaptopicolinate or cycloserine; (b) there is extensive lactate turnover in the absence of net lactate uptake, and there is a large dilution of 14C-labelled lactate from endogenous supply; (c) there is extensive detritiation of [2-3H]- and [3-3H]-lactate in excess of 14C utilization.

Animals↗

Mitochondrial-reticular cytostructure in liver cells.

This study examines the structural relationship of mitochondria and the endoplasmic reticulum in liver. Livers of rat and Japanese quail were homogenized and fractionated in media of 0.25 M-sucrose, either 5mM or 50 mM in sodium Hepes [4-(2-hydroxyethyl)-1-piperazine-ethanesulphonic acid], pH 7.4 (2.2 mM or 22 mM in Na respectively), designated here as low- and high-salt media. Three particulate fractions were prepared by sequential centrifugation. A nuclear pellet sedimenting at 300 g was obtained as described by Shore & Tata [(1977) J. Cell Biol. 72, 714-725], and from the resulting supernatant thereof a low-speed pellet (1100-1500 g) and a high-speed pellet (8000-10 000 g) were prepared. In the low-salt medium the yields of mitochondrial matrix enzymes (citrate synthase, glutamate dehydrogenase, ornithine carbamoyltransferase) and their specific activities in the low-speed pellet were over twice those in the high-speed pellet. In the high-salt medium the yield of matrix enzymes was 4-5 times, and the specific activities were up to 3 times, higher in the low-speed pellet than in the high-speed pellet. Oxygen uptake and respiratory control ratio were also much higher in the low-speed pellets in both media. Some 50-65% of the microsomal marker enzyme glucose 6-phosphatase was in the supernatant from the high-speed pellet, and the rest sedimented with the mitochondria. Repeated washing with the high-salt medium removes only a limited amount of reticulum. Washing with salt-free sucrose removes most of the reticulum, but a fraction remains strongly bound to mitochondria. Homogenates from quail and rat liver were fractioned isopycnically on Percoll gradients in either 0.25 M-sucrose or 0.25 M-sucrose/50 mM-sodium Hepes. Up to five particulate bands were separated and assayed. Mitochondria were present in two to three bands and were associated with endoplasmic reticulum. As seen in the phase-contrast microscope the mitochondria prepared in the low-salt medium consist of separate organelles. In the high-salt medium the mitochondria appear as chains of from three to ten organelles not touching each other. On addition of univalent ions at concentrations above 20 mM, the mitochondria aggregate into chains, and at higher ionic strength larger multidimensional aggregates are formed. The dispersion and aggregation of mitochondria are reversible. Negatively stained electron micrographs reveal a branched mitochondrial structure, with mitochondria held together by strands of reticulum.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗