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Biomedical subjects

K J Brown

Publications and source records attributed to K J Brown.

At least 37 records · Page 2Linked to original sources
PubMed1995

In-hospital cost of percutaneous coronary revascularization. Critical determinants and implications.

BACKGROUND: Hospital charges associated with percutaneous transluminal coronary revascularization (PTCR) in the United States exceeded $6 billion in 1994 and are likely to be constrained in some manner in the near future. Despite this high cost to the public, little is known about the major determinants and sources of variability of PTCR. METHODS AND RESULTS: From a consecutive series of 1258 procedures with attempted PTCR at a single tertiary referral center, we analyzed 65 clinical, angiographic, physician, and outcome variables as potential correlates of total (hospital and physician) cost. Direct and indirect costs, both hospital and physician, were determined on the basis of resource utilization using "top-down" methodology and were available for 1237 procedures (1086 patients) (98.3%). Mean (+/- SD) patient age was 62 +/- 11 years, 76% were male, 3% had acute myocardial infarction, 71% had unstable angina, 58% had multivessel disease, left ventricular ejection fraction was 54 +/- 12%, 26% had use of at least one nonballoon revascularization device, and median length of stay was 4.4 days. Procedural success was obtained in 89%, and major complications (death, bypass surgery, or Q-wave myocardial infarction) occurred in 3.8%. The median cost was $9176, but it was asymmetrically distributed, and the interquartile and total ranges were wide ($7333 to $13,845 and $3422 to $193,474, respectively). Analyses of independent correlates of cost and loge(cost) were performed using multivariate linear regression in training and test populations. Modeling found 15 independent preprocedural correlates of loge(cost) (R2 = .37) and 23 overall correlates (R2 = .65), excluding length of stay per se. Additional of length of stay to the model increased the explanatory power of the model to R2 = .82. Preprocedural variables most predictive of loge(cost) included presentation with acute myocardial infarction, decision delay (> 48 hours between admission and diagnostic angiography and/or > 24 hours between angiography and intervention), weekend delay, use of intra-aortic balloon counterpulsation, intention to stent, creatinine > or = 2.0 mg%, and lesion complexity (modified American College of Cardiology/American Heart Association score) (all P < .001). In the model that included postprocedural variables as well, length of stay, noncardiac death, urgent bypass surgery, use of the Rotablator, Q-wave myocardial infarction, rise in creatinine > or = 1.0%, and blood product transfusion were all strong independent correlates of loge(cost) (P < .001). CONCLUSIONS: The range of total hospital costs associated with percutaneous intervention is extraordinarily wide. Baseline patient characteristics account for nearly half of the explained variance, but procedural complications and system delays account for much of the remainder. Quantification of the determinants of cost may promote more economically efficient care in the future.

Aged↗
PubMed1995

Acidic and basic fibroblast growth factor bind with differing affinity to the same heparan sulfate proteoglycan on BALB/c 3T3 cells: implications for potentiation of growth factor action by heparin.

Heparan sulfate proteoglycans on the cell surface act as low affinity binding sites for acidic and basic fibroblast growth factor (FGF) [Moscatelli (1987): J Cell Physiol 131:123-130] and play an important role in the interaction of FGF with the FGF receptor (FGFR). In this study, several aspects of the interaction of FGFs with cell surface heparan sulfate proteoglycans were examined. Reciprocal cross blocking studies demonstrated that acidic FGF (aFGF) and basic FGF (bFGF) bind to identical or closely associated heparan sulfate motifs on BALB/c 3T3 cell surface heparan sulfate proteoglycans. However, the binding affinity of the two growth factors for these heparan sulfate proteoglycans differs considerably, competition binding data indicating that aFGF has a 4.7-fold lower affinity than bFGF for 3T3 heparan sulfate proteoglycan. Subsequent studies of dissociation kinetics demonstrated that bFGF dissociates from the FGFR at least 10-fold slower than aFGF, whereas, following removal of cell surface heparan sulfate proteoglycans by heparinase treatment, the dissociation rate of both FGFs is similar and rapid. These results support the concept that cell surface heparan sulfate proteoglycans stabilize the interaction of FGF with FGFR, possibly by the formation of a ternary complex.

3T3 Cells↗
PubMed1995

Evidence that carboxyl-reduced heparin fails to potentiate acidic fibroblast growth factor activity due to an inability to interact with cell surface heparin receptors.

Recently we reported that carboxyl-reduced heparin (CR-heparin), despite binding acidic fibroblast growth factor (aFGF) as effectively as native heparin, was much less potent at augmenting aFGF-induced mitogenesis. This paper describes experiments which examined this phenomenon in more detail in the hope that it would shed light on the mechanism by which heparin potentiates aFGF activity. Initial studies confirmed that heparin, with 60% of its carboxyl groups reduced, although binding aFGF with the same affinity as native heparin (Kd 35 +/- 5 nM), was a poor potentiator of aFGF-induced mitogenic activity. Proteolysis protection experiments also revealed that CR-heparin was as effective as native heparin at protecting aFGF from proteolytic degradation. In contrast, CR-heparin was considerably less effective than native heparin at enhancing the binding of aFGF to the fibroblast growth factor receptor (FGFR) on 3T3 cells. Furthermore, CR-heparin only bound to a subset (approximately 1/3) of heparin receptors on 3T3 cells. Based on these data, it is proposed that CR-heparin is less efficient than heparin at facilitating the formation of a quaternary complex among aFGF, the FGFR, and cell surface heparin receptors.

3T3 Cells↗
PubMed1995

Effects of housing on male and female rats: crowding stresses male but calm females.

Housing conditions affect behavioral and biological responses of animals. Effects of same-sex grouped, crowded, or individually housed conditions on plasma corticosterone levels of male and female Wistar rats were examined in two experiments. Experiment 1 examined the effects of individual vs. crowded housing conditions on corticosterone, a biochemical index of stress, in seven male and seven female rats. Experiment 2 extended the findings of Experiment 1 by separately manipulating spatial and population aspects of housing with 50 male and 50 female rats. Male rats had higher corticosterone levels under crowded conditions. In contrast, female rats had higher levels when individually housed. Spatial crowding was the key variable for males, whereas the number of other animals was more important for females. These results indicate that investigators must consider housing conditions as an intervening variable that is likely to differentially affect behaviors of male and female rats.

Analysis of Variance↗
PubMed1995

Strain and age differences in acoustic startle responses and effects of nicotine in rats.

Two experiments examined the effects of age, genetic strain, and nicotine on acoustic startle response (ASR) amplitude and prepulse inhibition (PPI) in rats. ASR amplitude measures reactivity to external stimulation, and PPI is used as an index of sensory gating related to attention. Both ASR amplitude and PPI have been previously reported to be increased by nicotine in adult rats. Experiment 1 examined effects of chronically administered nicotine and saline on ASR and PPI in Wistar, Long-Evans, and Sprague-Dawley rats (40 days of age). Experiment 2 examined the effects of chronically administered nicotine and saline in Sprague-Dawley rats of two age groups: 40 and 70 days of age at the beginning of the study. ASR amplitude differed significantly across strains with the values for Wistar > Sprague-Dawley > Long-Evans, and there were no differences in percent of PPI among the three strains. In addition, results of Experiment 2 indicated that older rats had significantly greater ASR amplitudes and PPI than younger rats. Consistent with previous reports, nicotine increased ASR and PPI in the older rats; however, there were no significant differences in the younger rats. Therefore, age and genetic strain are important variables in the analysis of nicotine's effects on startle behaviors in rats.

Aging↗
PubMed1994

Histidine-rich glycoprotein and platelet factor 4 mask heparan sulfate proteoglycans recognized by acidic and basic fibroblast growth factor.

Recent studies have shown that fibroblast growth factors (FGFs) need to interact with cell-surface heparan sulfate proteoglycans (HSPGs) in order to bind to and activate FGF receptors. In this paper, three major heparin-binding proteins, histidine-rich glycoprotein (HRG) and antithrombin III (ATIII), which are constitutively present at high concentrations in plasma, and platelet factor 4 (PF4), which is released locally at high concentrations by degranulating platelets, were tested for their ability to act as modulators of FGF activity by competing with the FGFs for cell-surface HSPGs. HRGs from both chicken and human, and human PF4, were demonstrated to compete with each other and with acidic FGF (aFGF) and basic FGF (bFGF) for binding to BALB/c 3T3 cell-surface HSPGs, whereas ATIII did not compete. Thus, HRG, PF4, aFGF, and bFGF all interact with the same HS chains on the 3T3 cell surface, either binding to the same or binding to adjacent saccharide sequences on the chains. In terms of their relative binding affinity for cell-surface HSPGs, the hierarchy was shown to be PF4 > or = bFGF > aFGF = cHRG > hHRG. HRG was also shown to significantly inhibit both FGF-stimulated and endogenous 3T3 cell DNA synthesis. HRG also binds to extracellular matrices (ECM), originating from bovine corneal endothelial cells, in a heparin-inhibitable manner. Indeed, both HRG and PF4, at physiological concentrations, were shown to effectively inhibit the binding of 125I-aFGF and 125I-bFGF to ECM. In addition, HRG was able to displace biologically active bFGF from the ECM. On the basis of these findings, it is proposed that HRG and PF4 may act as positive regulators of FGF activity by displacing FGF from the ECM or basement membrane and making FGF available to responsive cells. Alternatively, they could act as negative regulators by masking HSPGs on responsive cells and preventing FGF receptor activation.

3T3 Cells↗
PubMed1993

Spermatic cord torsion: loss of spermatogenesis despite return of blood flow.

Previous work in animal models has recapitulated and refined the clinical observation that longer periods of testicular torsion are associated within increased damage to the testis. Minimum times of damage-inducing torsion have not been established, however, nor has it been established to what degree blood flow returns to the testis on examination several hours or days after the torsion repair. Adult male rats were subjected to 0.5-h or 1.0-h 720 degrees torsion and examined for effects on testis weight, histology, and daily sperm production (DSP). None of the parameters examined were affected by 0.5-h, but all were affected by 1.0-h torsion. In a subsequent experiment, adult rats were subjected to unilateral, 1-h, 720 degrees torsion, and bilateral testicular blood flow as measured by radiolabeled microsphere distribution was determined during torsion and 4 h, 24 h, 2 days, 7 days, 15 days, and 30 days after repair of torsion. Ipsilateral testicular blood flow was reduced 94% during torsion. Blood flow was not significantly different from control or contralateral values by 4 or 24 h after repair of torsion. In spite of this return of blood flow, testis weights were significantly reduced by half by 7 days after torsion repair and spermatogenesis was clearly disrupted upon histological examination 30 days after torsion repair. Increasing the time of torsion to 2 or 4 h did not inhibit return of blood flow to the testis as measured 48 h after torsion repair. Unless the testis is infarcted, testicular blood flow in the rat model returns to normal after torsion repair.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Molecular cloning and nucleotide sequence determination of the Bacillus stearothermophilus NCA 1503 superoxide dismutase gene and its overexpression in Escherichia coli.

The gene (sod) encoding Bacillus stearothermophilus Mn-superoxide dismutase (MnSOD) has been cloned in Escherichia coli and its entire nucleotide sequence determined. With the exception of the post-translationally cleaved N-terminal methionine residue, the predicted amino acid sequence exhibits complete identity to the previously determined amino acid sequence. The recombinant MnSOD was shown to be functionally active in E. coli both in vitro and in vivo, and was expressed to 49% of the soluble cell protein by coupling its transcription to the E. coli trp promoter. The sequenced region of DNA was also found to encompass a second open reading frame. The putative encoded polypeptide exhibited no significant primary sequence homology to any currently characterised protein.

Amino Acid Sequence↗
PubMed1990

Depression and anxiety among chronically ill heart patients: age differences in risk and predictors.

Anxiety and depression for 399 survivors of a 1,102-member heart disease cohort were assessed 8 to 9 years post-hospitalization. Approximately one-third reported symptoms of emotional distress and one-fourth were on anti-anxiety drugs. Predictors of anxiety and depression were analyzed through logistic regression. Subjects age 65 and over were less likely than younger patients to report anxiety or depression and also reported less heart-associated disability, the strongest predictor of distress for both age groups. Other significant predictors included a previous history of distress, low income, female sex, and beta blocker use.

Age Factors↗
PubMed1986

Cohort study of Silastic obstetric vacuum cup deliveries: II. Unsuccessful vacuum extraction.

In a cohort analysis of Silastic vacuum extractor deliveries, 65% were completed with the vacuum extractor alone, 24% with outlet forceps, 3% with midforceps, and 7% with cesarean section (vacuum extractor-cesarean). Control groups were formed by using the next sequential forceps delivery, spontaneous vaginal delivery, and every second cesarean section after a trial of labor. The infants were examined using a neurobehavioral scale, an encephalopathy assessment, cranial ultrasound, and indirect ophthalmoscopy. In the combined vacuum extractor and forceps delivery subgroup (vacuum extractor-forceps), all but 3% were converted from a high mid-forceps delivery to outlet forceps by the initial vacuum extractor procedure, thus eliminating many difficult midforceps deliveries. The study yielded no significant difference in maternal morbidity between vacuum extractor-forceps and forceps delivery, no difference in vaginal trauma for vacuum extractor-cesarean versus vacuum extractor delivery, and no greater hospital stay, infection rate, or need for transfusion for either vacuum extractor-forceps versus forceps delivery or vacuum extractor-cesarean versus cesarean delivery. Neonatal morbidity did not differ between successful and unsuccessful trial of vacuum extractor, except for an increased frequency of retinal hemorrhage. The frequency of scalp trauma, including cephalohematoma, did not differ between vacuum extractor-forceps and forceps delivery, or between vacuum extractor-cesarean and vacuum extractor delivery. For vacuum extractor-forceps versus forceps delivery and vacuum extractor-cesarean versus cesarean section, there were no significant differences in neurobehavioral or encephalopathy scores, or in the frequency of neonatal jaundice, facial palsy, anemia, fractures, or mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

Cesarean Section↗
PubMed1984

Nucleotide specificity for reactivation of organelle movements in permeabilized axons.

In a permeabilized axon model, exogenous ATP can reactivate intraaxonal saltatory organelle movements (microscopically visible manifestations of fast axonal transport). We have studied the dependence of the reactivated movements on the ATP concentration and have also examined the nucleotide specificity of the reactivation. Organelle transport was visualized in isolated lobster giant motor axons using Nomarski optics and video microscopy. The axons were permeabilized with saponin, and movement was reactivated with ATP or other nucleotides. Some slight movement was seen with ATP concentrations as low as 10 microM. The velocity and frequency of the reactivated transport increased with increasing ATP concentrations up to about 5 mM. Movement was also reactivated by deoxyadenosine triphosphate, but not by AMP-PNP (a nonhydrolyzable ATP analogue), ADP, or AMP. Although other nucleotides (CTP, GTP, UTP, ITP) could reactivate transport, movement equivalent to that produced by 0.1 mM ATP was only seen with tenfold or greater concentrations of the other nucleotides. This pattern of specificity is consistent with the hypothesis that a dynein-like ATPase, rather than a myosin, is involved in fast axonal transport.

Adenosine Triphosphate↗
PubMed1983

Selective inhibition of retrograde axonal transport by erythro-9-[3-(2-hydroxynonyl)]adenine.

Retrograde transport of microscopically visible organelles in isolated lobster axons was selectively inhibited by erythro-9-[3-(2-hydroxynonyl)]adenine (EHNA), with little or no effect on anterograde transport. The retrograde velocity was reduced both in living axons and in permeabilized axons in which movement was reactivated with exogenous ATP. This is the first report of an agent that selectively inhibits axonal transport in one direction.

Adenine↗
PubMed1983

Fast axonal transport in permeabilized lobster giant axons is inhibited by vanadate.

We have developed a method for permeabilizing axons and reactivating the fast transport of microscopically visible organelles. Saltatory movements of organelles in motor axons isolated from lobster walking legs were observed using Nomarski optics and time-lapse video microscopy. In the center of the axon most of the particles and mitochondria moved in the retrograde direction, but immediately below the axolemma the majority moved in the anterograde direction. When axons were permeabilized with 0.02% saponin in an adenosine 5'-triphosphate (ATP)-free "internal" medium, all organelle movement ceased. Saltatory movements resembling those in intact axons immediately reappeared upon the addition of MgATP. Very slight movement could be detected with ATP concentrations as low as 10 microM, and movement appeared to be maximal with 1 to 5 mM ATP. Vanadate, which does not affect axonal transport in intact axons, inhibited the reactivated organelle movements in permeabilized axons. Movement was rapidly and reversibly inhibited by 50 to 100 microM sodium orthovanadate. The effects of vanadate, including the time course of inhibition, its reversibility, and its concentration dependence, are consistent with the hypothesis that a dyneinlike like molecule may play a role in the mechanism of fast axonal transport.

Adenosine Triphosphate↗
PubMed1981

Extended wear soft contact lenses in the correction of aphakia.

This paper reports the study over a 2-year period of forty patients with uniocular aphakia fitted with spherical extended wear hydrophilic lenses: Sauflon 85 per cent and Duragel 72 per cent. The patients' ages ranged from 17 to 87 years (mean 52). They were unable to handle a daily wear soft lens or tolerate a hard lens. The success rate was 85 per cent.

Adolescent↗
PubMed1980

The assay on a defined medium of the effects of beta-2-thienylalanine on the growth of anaerobic bacterial isolates from phenylketonuric patients.

Faecal samples were taken from three diet-managed phenylketonuric children to determine effects of beta-2-thienylalanine (beta-2-t) on indigenous bacteria. From sample swabs, 127 anaerobes were identified and tested for beta-2-t inhibition on a phenylalanine (Phe)-free medium, Anaerobe Inhibition Test (AIT) agar. Of the isolates, 77.9% grew sufficiently to assay reactions on at least 25% of AIT plates. Using Phe-containing Columbia agar, 86.5% of the strains could be assayed. None of 28 Bacteroides cultures was inhibited by beta-2-t on AIT. Of the genera, Bifidobacterium, Eubacterium, Lactobacillus, Peptostreptococcus, and Propionibacterium, no isolates which would grow on AIT were inhibited. At least one isolate of each of the genera Peptococcus, Fusobacterium, and Clostridium was inhibited. Of 127 total isolates, only nine were inhibited by beta-2-t on AIT, and inhibition was abolished on Columbia agar. Thirty-nine "aerobes" were isolated from the same patients. Strains of the genera tested reacted similarly to previously tested strains from non-PKU sources. Also, anaerobically isolated Excherichia coli were inhibited, while Streptococcus faecalis cultures were not, confirming results on aerobically-isolated non-PKU cultures of the same species. These studies, the first dealing with beta-2-t and anaerobic bacteria, suggest that little change in intestinal bacterial populations might be expected during in vivo beta-2-t treatment.

Agar↗
PubMed1980

Comparison of liquid and agar-solidified defined media regarding the physiological mechanism by which beta-2-thienylalanine inhibits growth of Escherichia, Shigella, and Salmonella cultures.

Growth comparisons were made, using Shigella, Escherichia, and Salmonella cultures, in liquid and agar-solidified defined media containing beta-2-thienylalanine (beta-2-t). The comparisons were performed to determine the nature of growth inhibition by beta-2-t under different physical growth conditions. In a plate assay, with increasing beta-2-t mixed into the agar, inhibition of Escherichia and Shigella increased. However, Salmonella cultures were not inhibited even at the highest beta-2-t concentrations used. With beta-2-t added to liquid cultures, however, dose-response growth relationships were exhibited by all three genera. The differences occurring in beta-2-t inhibition between liquid and plate assay conditions were not due to composition of culture plates, time of challenge of cultures with beta-2-t, availability of oxygen and associated differences in ratios of volume of media to available surface area, selection of mutants in the plate assay, or to extractable substances from the agar. However, when beta-2-t diffusion into the liquid medium was delayed by using agar plug diffusion cultures, a physiological mechanism was demonstrable which largely protected Salmonella cultures, but not Escherichia and Shigella cultures, from growth inhibition.

Agar↗