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Biomedical subjects

S McLaughlin

Publications and source records attributed to S McLaughlin.

At least 91 records · Page 5Linked to original sources
PubMed1990

Cost-effective screening by nursing staff for urinary tract infection in the spinal cord injured patient.

Screening tests for urinary tract infections (UTI) are used in the clinical laboratory setting. This study evaluated the efficacy of screening by nursing staff on the inpatient unit, instead of the clinical laboratory, in the spinal cord-injured population. Fifty-three consecutive traumatically spinal cord-injured patients had weekly urine collection, except when infected or on antibiotics. Each urine sample was tested by a nitrite and leukocyte esterase (LE) dipstick (Chemstrip LN by Bio-Dynamics) and by routine clinical laboratory culture. A total of 169 tests were completed. The correlation coefficients of the LE and the nitrite tests with the culture were 0.604 (P less than 0.001) and 0.663 (P less than 0.001), respectively. The correlation of the combined tests was 0.837 (P less than 0.001). The sensitivity, specificity and positive and negative predictive values of nitrite-LE testing by nursing staff were calculated and compared favorably with published performances of clinical laboratory staff. When measured against the culture, the combined nitrite and LE test had a sensitivity of 79%, specificity of 99% and positive and negative predictive values of 96% and 95%, respectively. The use of a protocol where laboratory culture is performed only when the dipstick test is positive, would reduce the number of cultures by 83%. After extra costs of the additional screen are added, the use of dipstick screening methods by nursing staff can reduce the cost of weekly urine screening by 73%, with a false negative rate of only 4.4%. The expense and complexity of screening for UTI is reduced, response time is minimized and laboratory cultures will have a higher probability of useful clinical information.

Adolescent↗
PubMed1990

Developmental rearrangement of cyanobacterial nif genes: nucleotide sequence, open reading frames, and cytochrome P-450 homology of the Anabaena sp. strain PCC 7120 nifD element.

An 11-kbp DNA element of unknown function interrupts the nifD gene in vegetative cells of Anabaena sp. strain PCC 7120. In developing heterocysts the nifD element excises from the chromosome via site-specific recombination between short repeat sequences that flank the element. The nucleotide sequence of the nifH-proximal half of the element was determined to elucidate the genetic potential of the element. Four open reading frames with the same relative orientation as the nifD element-encoded xisA gene were identified in the sequenced region. Each of the open reading frames was preceded by a reasonable ribosome-binding site and had biased codon utilization preferences consistent with low levels of expression. Open reading frame 3 was highly homologous with three cytochrome P-450 omega-hydroxylase proteins and showed regional homology to functionally significant domains common to the cytochrome P-450 superfamily. The sequence encoding open reading frame 2 was the most highly conserved portion of the sequenced region based on heterologous hybridization experiments with three genera of heterocystous cyanobacteria.

Amino Acid Sequence↗
PubMed1990

Effect on gastric and duodenal mucosal prostaglandins of repeated intake of therapeutic doses of naproxen and etodolac in rheumatoid arthritis.

The synthesis of gastric and duodenal mucosal prostaglandin E2, prostaglandin I2, and thromboxane B2 during a 60 minute incubation of biopsy specimens, the degree of endoscopic and histological damage, and the anti-inflammatory response were all studied after a four week, double blind study of therapeutic doses of two non-steroidal anti-inflammatory drugs, naproxen and etodolac, received by 27 patients with active rheumatoid arthritis (13 receiving naproxen, 14 etodolac). Prostaglandin values after treatment did not differ from the baseline levels when all the patients were analysed as one group. Subgroup analysis showed that naproxen suppressed gastric prostaglandin E2 from a median of 29 to 9 ng/mg protein, duodenal prostaglandin E2 from 34 to 11 ng/mg, and duodenal prostaglandin I2 from 62 to 15 ng/mg protein. No overall suppression occurred with etodolac. Also, on the second assessment patients receiving naproxen had lower gastric and duodenal prostaglandin E2 and prostaglandin I2, but higher values of duodenal thromboxane B2, than patients receiving etodolac. Both drugs had comparable anti-arthritic activity and caused microscopic gastritis in similar proportions of patients. No correlation was detected between prostaglandin values and the mucosal damage which developed in seven patients receiving naproxen (54%) and three receiving etodolac (21%). These findings indicate that, unlike naproxen, etodolac does not seem to affect gastric or duodenal prostaglandin synthesis; other mechanisms of injury need to be considered.

Adolescent↗
PubMed1990

Methodology of ECG interpretation in the Glasgow program.

This paper describes the methods currently used in Glasgow Royal Infirmary for computer analysis of electrocardiograms. The software is designed to analyse from 3 to 15 simultaneously recorded leads, with facilities for analysis of rhythm and serial changes. Options for Minnesota Code (with serial comparison) and XYZ lead interpretation are available.

Diagnosis, Computer-Assisted↗
PubMed1989

Binding of neomycin to phosphatidylinositol 4,5-bisphosphate (PIP2).

Schacht (Schacht, J. (1976) J. Neurochem. 27, 1119-1124) demonstrated that neomycin, an aminoglycoside antibiotic, binds with high affinity to phosphatidylinositol 4,5-bisphosphate (PIP2). We investigated the binding of neomycin to PIP2 by making electrophoretic mobility measurements with multilamellar bilayer vesicles and surface potential measurements with monolayers. The bilayers and monolayers were formed from mixtures of PIP2 and egg phosphatidylcholine (PC) in 0.1 M KCl at pH 7. Neomycin does not bind to PC; 10(-3) M neomycin affects neither the zeta potential of PC vesicles nor the surface potential of PC monolayers. In contrast, 10(-6) M neomycin reduces the magnitude of the zeta potential of PC/PIP2 vesicles (5, 9, and 17 mol% PIP2) and the surface potential of monolayers (17 mol% PIP2) to less than 50% of their initial values. The electrophoretic mobility results indicate that neomycin forms an electroneutral complex with PIP2; high concentrations (greater than 10(-4) M) of neomycin reduce the zeta potential of the PC/PIP2 vesicles to zero. We could describe our data with the Gouy-Chapman-Stern theory assuming the intrinsic association constant of the 1:1 neomycin-PIP2 complex is 10(5) M-1. Neomycin is widely used in cell biology to interfere with the generation of second messengers; we discuss the relevance of our results to these studies. Specifically, 10(-6) M neomycin binds greater than 50% of the PIP2 in a bilayer or monolayer but 10(-5)-10(-3) M neomycin is required to affect the turnover of PIP2 in permeabilized platelets, mast cells, and sea urchin eggs. This result is consistent with a hypothesis that most of the PIP2 in the inner leaflet of these plasma membranes is not accessible to neomycin because it is associated with proteins.

Electrophoresis↗
PubMed1989

Normal limits of the high-fidelity pediatric ECG. Preliminary observations.

A study of more than 1,780 neonates, infants, and children was carried out, using a digital electrocardiograph with a sampling rate of 500 per second, to revise the normal limits of the pediatric ECG. The 12-lead ECG was used with V4R replacing V3. All leads were recorded simultaneously off-line in digital form on magnetic tape and were subsequently analyzed using well-established computing techniques. The results showed that the upper 98 percentile limit of normal amplitudes could be up to 46% higher than previously published limits. Differences in some mean values were very much higher, though these are of less clinical significance. In addition, QRS durations were found to be wider than previously published data. Sex-related differences could be demonstrated in both amplitude and duration measurements, particularly in the early adolescent years. This study confirms that to record pediatric ECGs with high fidelity, it is necessary to use equipment that converts the ECG from analog to digital form at a rate of 500 samples/sec. Significant errors in amplitude and duration measurements may be expected if a much lower sampling rate is utilized.

Adolescent↗
PubMed1989

Evaluation of the efficacy and comparative effects on gastric and duodenal mucosa of etodolac and naproxen in patients with rheumatoid arthritis using endoscopy.

The therapeutic efficacy and upper gastrointestinal side effects of a twice daily dose of 300 mg etodolac and 500 mg naproxen were compared in 30 hospital out-patients with active rheumatoid arthritis. Drugs were taken for 4 weeks in a double-blind, randomized, parallel group, single centre study. Rheumatological, endoscopic and laboratory assessments were performed at the start and on completion of the study. Mucosal lesions developed in only three (20%) patients of the etodolac group and they all had low endoscopy scores, compared to eight (53%) patients of the naproxen group with significantly worse endoscopy scores (p less than 0.05). Lesions were asymptomatic in all but one patient (on naproxen), and the gastric antrum was the commonest region involved. Of the 11 patients who developed endoscopic abnormalities in both groups, seven (64%) were moderate to heavy smokers. Etodolac had a similar antiarthritic effect to naproxen, but it appears to be better tolerated by the upper gastrointestinal mucosa as shown by endoscopy.

Adult↗
PubMed1988

Adsorption of cations to phosphatidylinositol 4,5-bisphosphate.

We investigated the binding of physiologically and pharmacologically relevant ions to the phosphoinositides by making 31P NMR, electrophoretic mobility, surface potential, and calcium activity measurements. We studied the binding of protons to phosphatidylinositol 4,5-bisphosphate (PIP2) by measuring the effect of pH on the chemical shifts of the 31P NMR signals from the two monoester phosphate groups of PIP2. We studied the binding of potassium, calcium, magnesium, spermine, and gentamicin ions to the phosphoinositides by measuring the effect of these cations on the electrophoretic mobility of multilamellar vesicles formed from mixtures of phosphatidylcholine (PC) and either phosphatidylinositol, phosphatidylinositol 4-phosphate, or PIP2; the adsorption of these cations depends on the surface potential of the membrane and can be described qualitatively by combining the Gouy-Chapman theory with Langmuir adsorption isotherms. Monovalent anionic phospholipids, such as phosphatidylserine and phosphatidylinositol, produce a negative electrostatic potential at the cytoplasmic surface of plasma membranes of erythrocytes, platelets, and other cells. When the electrostatic potential at the surface of a PC/PIP2 bilayer membrane is -30 mV and the aqueous phase contains 0.1 M KCl at pH 7.0, PIP2 binds about one hydrogen and one potassium ion and has a net charge of about -3. Our mobility, surface potential, and electrode measurements suggest that a negligible fraction of the PIP2 molecules in a cell bind calcium ions, but a significant fraction may bind magnesium and spermine ions.

Adsorption↗
PubMed1988

Fluorescent probes of electrostatic potential 1 nm from the membrane surface.

We measured the electrostatic potential 1 nm from the surface of charged phospholipid bilayer membranes to test the predictions of the Gouy-Chapman theory. Fluorescent probes (anthraniloyl, 5-(dimethylamino)naphthalene-1-sulfonyl, Lucifer yellow) were attached covalently to the sialic acid residue of the ganglioside galactosyl-N-acetylgalactosaminyl(N-acetylneuraminyl)galactosylglucosylc eramide (GM1). These fluorescent gangliosides were incorporated into neutral [phosphatidylcholine (PC)] or charged [phosphatidylserine (PS)] phospholipid bilayers, and the fluorescence was quenched with the cations thallium and 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (tempamine). We calculated the electrostatic potential at the chromophore from the quenching ratio using the Boltzmann relation: the average potential was -30 mV for PS bilayers in 0.1 M NaNO3. We assume the chromophore is 1 nm from the surface because X-ray diffraction measurements demonstrate that the sialic acid residue of GM1 is 1 nm from the surface of a PC/GM1 bilayer [McDaniel, R. V., & McIntosh, T. J. (1986) Biophys. J. 49, 94-96]. We also used thallium and tempamine to quench the fluorescence of chromophores located at the surface of the PS membranes; in 0.1 M NaNO3 the average surface potential was -80 mV, which agrees with other measurements. The Gouy-Chapman theory predicts that the potential 1 nm from a membrane with a surface potential of -80 mV is -24 mV; this prediction agrees qualitatively with the experimental results obtained with fluorescent gangliosides.

Electrochemistry↗
PubMed1988

Surgical treatment of the incontinent female patient with myelomeningocele.

Surgical therapy was required for 42 incontinent female patients with myelomeningocele who had urodynamically documented high pressure bladders. Conservative treatment consisting of cholinolytic and alpha-adrenergic agents, and intermittent self-catheterization had failed. The surgical approach consisted of perivesical denervation (for hyperreflexia), Burch bladder neck suspension, enlargement cystoplasty and ureteral reimplantation when required. Among 33 patients (79 per cent) there was no incontinence on intermittent self-catheterization and 6 (14 per cent) had improvement with rare urgency or stress incontinence. In 3 patients (7 per cent) sphincteric incompetence required a transvaginal sling procedure.

Adolescent↗
PubMed1988

Fascial sling to correct male neurogenic sphincter incompetence: the McGuire/Raz approach.

We report the surgical approach used in 4 male myelomeningocele patients suffering from severe urinary incontinence owing to poor bladder compliance and sphincter incompetence. While bladder compliance was corrected by enlargement cystoplasty the sphincteric incompetence was treated by an autologous fascial sling around the bladder neck with excellent results. We consider this operation as an alternative to the artificial urinary sphincter in cases of male neurogenic sphincter incontinence.

Adolescent↗
PubMed1988

Cations that alter surface potentials of lipid bilayers increase the calcium requirement for exocytosis in sea urchin eggs.

1. We examined the effects of cations that bind to phospholipid bilayers on the calcium requirement for exocytosis in vitro. 2. Tetracaine and trifluoperazine, two monovalent cations that bind hydrophobically to lipid bilayers, decreased the zeta-potential of lipid vesicles with a phospholipid composition similar to sea urchin plasma membranes; the decrease in the magnitude of the negative zeta-potential was consistent with the Gouy-Chapman-Stern theory. 3. Trifluoperazine and tetracaine also increased the concentration of calcium required to produce half-maximal exocytosis (Ca50) in isolated fragments of plasma membranes from sea urchin eggs. 4. The effects of trifluoperazine and tetracaine on the Ca50 of egg fragments can be explained quantitatively from the zeta-potential data obtained with phospholipid vesicles if we assume the calcium binding sites responsible for triggering exocytosis lie within a Debye length (less than 1 nm) of the surface of the plasma membranes, such that the concentration of calcium at the sites is affected by the surface potential of the membrane. 5. The divalent cation magnesium, which binds specifically to the phosphate group of lipids, affected Ca50 in a manner that can also be explained quantitatively from its effects on the zeta-potential of phospholipid vesicles. 6. The polyvalent cation neomycin, which adsorbs to the lipid phosphatidylinositol 4,5-bisphosphate with high affinity, also binds co-operatively to phosphatidylinositol; its effect on Ca50 can be explained quantitatively from its effects on the zeta-potential of vesicles containing the latter lipid. 7. A decrease in the ionic strength increases the magnitude of the surface potential of membranes; the effect of ionic strength on Ca50 can be explained qualitatively from its effect on the zeta-potential of phospholipid vesicles. 8. All our results are consistent with the hypothesis that calcium binding sites lie within a Debye length of the plasma membrane; they also indicate that drugs with specific, high-affinity sites may affect exocytosis by a non-specific mechanism.

Action Potentials↗
PubMed1987

The role of fixed and mobile buffers in the kinetics of proton movement.

We derive a simple expression for the effective diffusion coefficient of protons in Fick's second law, Deff, when both spatially fixed, HF, and mobile, HM, buffers are present. These buffers are present at moderately high concentrations ([Ftot], [Mtot] greater than 1 mM) in most biological systems. We consider only the case where the protonation reactions remain at equilibrium during the diffusion process. When the pH is to the alkaline side of the pK values of the fixed and mobile buffers ([H+] less than KF, KM), the effective diffusion coefficient of protons in Ficks second law is: (Formula: see text) where DH is the diffusion coefficient of the protons free in the aqueous phase and DHM is the diffusion coefficient of the mobile buffer. The equation illustrates three features of diffusion in a buffered system. Firstly, the effective diffusion coefficient of protons is always lower than the diffusion coefficient of free protons. Secondly, increasing the concentration of fixed buffers always decreases Deff. Thirdly, increasing the concentration of mobile buffer can increase Deff when fixed buffers are present.

Biological Transport↗
PubMed1987

How do protons cross the membrane-solution interface? Kinetic studies on bilayer membranes exposed to the protonophore S-13 (5-chloro-3-tert-butyl-2'-chloro-4' nitrosalicylanilide).

A simple carrier model describes adequately the transport of protons across lipid bilayer membranes by the weak acid S-13. We determined the adsorption coefficients of the anionic, A-, and neutral, HA, forms of the weak acid and the rate constants for the movement of A- and HA across the membrane by equilibrium dialysis, electrophoretic mobility, membrane potential, membrane conductance, and spectrophotometric measurements. These measurements agree with the results of voltage clamp and charge pulse kinetic experiments. We considered three mechanisms by which protons can cross the membrane-solution interface. An anion adsorbed to the interface can be protonated by a H+ ion in the aqueous phase (protolysis), a buffer molecule in the aqueous phase or water molecules (hydrolysis). We demonstrated that the first reaction cannot provide the required flux of protons: the rate at which H+ must combine with the adsorbed anions is greater than the rate at which diffusion-limited reactions occur in the bulk aqueous phase. We also ruled out the possibility that the buffer is the main source of protons: the rate at which buffers must combine with the adsorbed anions is greater than the diffusion-limited rate when we reduced the concentration of polyanionic buffer adjacent to the membrane-solution interface by using membranes with a negative surface charge. A simple analysis demonstrates that a hydrolysis reaction can account for the kinetic data. Experiments at acid pH demonstrate that the transfer of H+ from the membrane to the aqueous phase is limited by the rate at which OH- combines with adsorbed HA and that the diffusion coefficient of OH- in the water adjacent to the bilayer has a value characteristic of bulk water. Our experimental results demonstrate that protons are capable of moving rapidly across the membrane-solution interface, which argues against some mechanisms of local chemiosmosis.

Kinetics↗
PubMed1986

An experimental test of the discreteness-of-charge effect in positive and negative lipid bilayers.

The electrostatic properties of charged bilayers and the bilayer component of biological membranes are often described theoretically by assuming the charge is smeared uniformly over the surface. This is one of the fundamental assumptions in the Gouy-Chapman-Stern (GCS) theory. However, the average distance between the charged phospholipids in a typical biological membrane is 2-3 nm, which is 2-3 times the Debye length in a 0.1 M salt solution. Existing discreteness-of-charge theories predict significant deviations from the GCS theory for the adsorption of ions to such membranes. We considered the predictions of the simplest discreteness-of-charge theory [Nelson, A. P., & McQuarrie, D. A. (1975) J. Theor. Biol. 55, 13-27], in which the charges are assumed to be fixed in a square lattice and the potential is described by the linearized Poisson-Boltzmann relation. This theory predicts deviations that are larger for counterions than for co-ions and much larger for divalent than for monovalent counterions. We tested these predictions by measuring the adsorption of a fluorescent monovalent anion and a paramagnetic divalent cation to both positive and negative membranes, which we demonstrated experimentally had the same average surface potential. All our experimental results with probes, including those obtained on membranes in the gel rather than in the liquid-crystalline state, agreed with the predictions of the GCS theory rather than with the discreteness-of-charge theory. A simple calculation indicates that the agreement between the experimental results and the predictions of the GCS theory could be due to the finite size of the lipids.

Dimyristoylphosphatidylcholine↗
PubMed1986

Electrokinetic and electrostatic properties of bilayers containing gangliosides GM1, GD1a, or GT1. Comparison with a nonlinear theory.

We formed vesicles from mixtures of egg phosphatidylcholine (PC) and the gangliosides GM1, GD1a, or GT1 to model the electrokinetic properties of biological membranes. The electrophoretic mobilities of the vesicles are similar in NaCl, CsCl, and TMACl solutions, suggesting that monovalent cations do not bind significantly to these gangliosides. If we assume the sialic acid groups on the gangliosides are located some distance from the surface of the vesicle and the sugar moieties exert hydrodynamic drag, we can describe the mobility data in 1, 10, and 100 mM monovalent salt solutions with a combination of the Navier-Stokes and nonlinear Poisson-Boltzmann equations. The values we assume for the thickness of the ganglioside head group and the location of the charge affect the theoretical predictions markedly, but the Stokes radius of each sugar and the location of the hydrodynamic shear plane do not. We obtain a reasonable fit to the mobility data by assuming that all ganglioside head groups project 2.5 nm from the bilayer and all fixed charges are in a plane 1 nm from the bilayer surface. We tested the latter assumption by estimating the surface potentials of PC/ganglioside bilayers using four techniques: we made 31P nuclear magnetic resonance, fluorescence, electron spin resonance, and conductance measurements. The results are qualitatively consistent with our assumption.

Egg Yolk↗