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Biomedical subjects

G Johnson

Publications and source records attributed to G Johnson.

At least 37 records · Page 2Linked to original sources
PubMed2001

Targeting acute ischemic stroke with a calcium-sensitive opener of maxi-K potassium channels.

During ischemic stroke, neurons at risk are exposed to pathologically high levels of intracellular calcium (Ca++), initiating a fatal biochemical cascade. To protect these neurons, we have developed openers of large-conductance, Ca++-activated (maxi-K or BK) potassium channels, thereby augmenting an endogenous mechanism for regulating Ca++ entry and membrane potential. The novel fluoro-oxindoles BMS-204352 and racemic compound 1 are potent, effective and uniquely Ca++-sensitive openers of maxi-K channels. In rat models of permanent large-vessel stroke, BMS-204352 provided significant levels of cortical neuroprotection when administered two hours after the onset of occlusion, but had no effects on blood pressure or cerebral blood flow. This novel approach may restrict Ca++ entry in neurons at risk while having minimal side effects.

Animals↗
PubMed2001

Understanding the community perspectives of trachoma: The Gambia as a case study.

Trachoma has justifiably attracted an incredibly large amount of research interest and literature over the last several decades. Perhaps, the area which is least explored is the social aspect of the disease. Most of the major constraints to trachoma control on the global scale appear to be concerned with this aspect of the disease. Recently, a study was conducted in The Gambia with the aim of highlighting the socio-cultural determinants of trachoma. We applied qualitative methods of Focus Group Discussion and Semi-structured interview to explore the local people's concepts of the disease among two traditional ethnic groups, the Jolas and the Manjagos, in five rural communities. Our results show that there appears to be a poor understanding of the chronic nature of the active inflammatory phase of trachoma among the local people. But more importantly, there is a lack of mental connection between this childhood infection and blindness resulting from trichiasis in adults. This probably explains why it is difficult for the people in these communities to see the need for prolonged use of antibiotic eye ointment as required in the treatment of active inflammatory trachoma. Moreover, the local concepts about the cause(s) of the disease tend to compel the people to seek the traditional herbal remedies first, though there is adequate knowledge and experience among them that modern methods of treatment may produce cure, as in the case of corrective lid surgery for trichiasis. This ambivalent attitude of the people to health services appear to be a universal phenomenon in many local communities in Africa, and perhaps hinges on the local people's perspective of the disease, which varies from place to place. We conclude that for any intervention strategy to achieve the set goals of eliminating trachoma in spite of these constraints, community support and participation is essential, and in order to achieve this, the health care provider needs to have a better understanding of the community perspectives of the disease.

Adult↗
PubMed2001

The effect of instrumental and vocal music on adherence to a physical rehabilitation exercise program with persons who are elderly.

This study compared live, instrumental music, vocal music, and no music on the repetition frequencies for 14 prescribed physical therapy rehabilitation exercises. Male (N = 4) and female (N = 15) residents of care centers for older adults served as subjects. They ranged in age from 65 to 90 years (M= 84.3), and were either referred to physical therapy or were already involved in a physical therapy exercise pro-gram. All subjects (N = 19) participated in 6 treatment sessions under 3 conditions: Two sessions with live instrumental music, two with live vocal music, and two with no music. In all music sessions, familiar and recognizable songs were paired with specific exercises. Each exercise in all conditions had the same duration, and a metronome established consistent tempos. Each session was videotaped for later review and data collection. Analyses of variance were calculated for treatment effects and mean differences among the three conditions which yielded significant treatment effects and treatment differences among conditions for 6 of the 14 exercises. Unsolicited comments from subjects indicated preference for music over no music conditions while exercising. Further study is required to establish the relationship between music enhanced exercises and adherence to exercise regimens in populations of older adults.

Aged↗
PubMed2001

Effects of rapacuronium on respiratory function during general anesthesia: a comparison with cis-atracurium.

BACKGROUND: With its introduction for widespread clinical use, there has been an increase in reports of bronchospasm related to the administration of rapacuronium. As it is commonly used for rapid sequence intubation, it has been suggested that these effects may be related to an inadequate depth of anesthesia. The current study examines the airway effects of rapacuronium in tracheally intubated, anesthetized adults. METHODS: Endotracheal intubation was accomplished without the use of neuromuscular blocking agents. Dynamic compliance, tidal volume, peak inspiratory flow rate, peak expiratory flow rate, and peak inflating pressure were measured after administration of either rapacuronium (1.5 mg/kg) or cis-atracurium (0.2 mg/kg) to 20 adult patients (10 received rapacuronium and 10 received cis-atracurium) anesthetized with propofol-remifentanil. RESULTS: Statistically significant increases in peak inflating pressure (22 +/- 6 to 28 +/- 9 cm H2O, P = 0.0012) and decreases in dynamic compliance (108 +/- 43 to 77 +/- 41 ml/cm H2O, P = 0.0001), peak inspiratory flow rate (0.43 +/- 0.11 to 0.39 +/- 0.09 l/s, P = 0.0062), peak expiratory flow rate (0.67 +/- 0.10 to 0.59 +/- 0.09 l/s, P = 0.0015), and tidal volume (744 +/- 152 to 647 +/- 135 ml, P = 0.0293) occurred after administration of rapacuronium. No changes were seen after administration of cis-atracurium. CONCLUSION: These data demonstrate that rapacuronium, but not cis-atracurium, has significant airway effects in intubated, mechanically ventilated adults.

Adult↗
PubMed2001

Paediatric prehospital care: postal survey of paramedic training managers.

BACKGROUND: The process of prehospital care continues to develop in the UK. AIMS: To evaluate the availability of important paediatric resuscitation equipment in emergency ambulances and the extent of paramedic training in paediatric emergency medicine. METHODS: Postal survey of paramedic training managers. RESULTS: Completed questionnaires were returned by 41 (93%) training managers. No trust provided all of the equipment listed. Facemasks and self inflating bags (of appropriate sizes for all children) are provided by 32% and 42% of trusts respectively. Less than one third carry paediatric oximeter probes. Of the respondents, 16 (39%) trusts provide less than eight hours training in paediatric emergency medicine and five (12%) offer no training at all. Ongoing education varies from none to regular yearly updates. CONCLUSIONS: Paramedics seem ill prepared to deal with paediatric emergencies. Important deficiencies in the provision of equipment and training are noted. The results of this survey provide information against which improvements can be measured.

Allied Health Personnel↗
PubMed2001

An analysis of calls referred to the emergency 999 service by NHS Direct.

INTRODUCTION: NHS Direct was launched in West Yorkshire in April 1999. A 999 ambulance can be dispatched to the patient as a result of a call to NHS Direct. The aim of this study is to compare cases that had been referred by NHS Direct via the 999 service, with those who had dialled 999 themselves. METHODS: The study was carried out in three accident and emergency (A&E) departments in West Yorkshire, between 1 April 1999 and 21 August 1999. NHS Direct generated 999 calls were identified. The comparison group was selected at random from a list of all other 999 cases attending the three departments. The study involved retrieving basic demographic data, as well as duration of symptoms before dialling 999, triage category on arrival in A&E and disposal of patient. Ethical approval and statistical advice were obtained. RESULTS: 91 NHS Direct generated 999 calls were identified. Of the comparison group (260 cases), 28 were excluded from the study. There were no differences in the triage categories assigned to the two groups on arrival in A&E. There were notable differences in presenting complaint between the two groups and in particular, trauma was less common among the NHS Direct patients (6.6%) compared with those who had self dialled (37.5%). Patients who had first called NHS Direct were younger (p=0.033) and had endured their symptoms for longer (p<0.001); they were less likely to be admitted, and if discharged, were less likely to have follow up arranged (p=0.014). CONCLUSIONS: Both groups received similar triage categories suggesting that severity of illness is equally well assessed by self as by NHS Direct. There are large differences in case mix between the two groups studied and these almost certainly explain the differences in outcome.

Diagnosis-Related Groups↗
PubMed2001

MR renography with low-dose gadopentetate dimeglumine: feasibility.

PURPOSE: To develop a low-dose magnetic resonance (MR) renographic method performed with and without an angiotensin converting enzyme (ACE) inhibitor and in conjunction with gadolinium-enhanced MR angiography in patients with suspected renovascular disease. MATERIALS AND METHODS: Thirty-two patients underwent MR renography (turbo fast low-angle shot sequence: repetition time, 5 msec; echo time, 2.3 msec; flip angle, 15 degrees; one coronal image acquired every 2 seconds for 4 minutes) following intravenous injection of 2 mL of gadopentetate dimeglumine, which was repeated following intravenous injection of an ACE inhibitor. Contrast material-enhanced MR angiography was also performed. On the basis of renographic findings, renal cortex and renal medulla enhancement curves and normalized enhancement ratios were analyzed. RESULTS: The cortex and medulla showed an early transient period of enhancement within 20 seconds (vascular phase). During 1-2 minutes, a second, gradual increase in medullary enhancement, reflecting transit of filtered contrast material, was observed that was significantly greater in patients with a serum creatinine level less than 2 mg/dL (177 micromol/L) than in those with a level of 2 mg/dL or greater (P < .01). After injection of the ACE inhibitor, patients with elevated creatinine levels showed low renal medullary enhancement regardless of the presence of renal artery stenosis (RAS). However, in patients with creatinine less than 2 mg/dL, medullary enhancement ratios after injection of the ACE inhibitor were consistently lower in patients with RAS of 50% or greater than in those without stenosis (P = .02 to .08). CONCLUSION: Low-dose MR renography can be performed in the clinical setting before and after injection of an ACE inhibitor, and its potential use for evaluating decreased renal function as a consequence of RAS is promising.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

The 14-3-3 cerebrospinal fluid immunoassay lacks utility in the diagnosis of clinical scrapie.

This study determined whether the immunoassay for cerebrospinal fluid 14-3-3 protein concentration was sensitive and specific in the diagnosis of naturally occurring clinical scrapie in sheep. Cerebrospinal fluid was collected from 9 sheep with the confirmed diagnosis of scrapie. Additionally, cerebrospinal fluid was collected from 13 clinically normal sheep, which originated from a closely monitored flock with no history of scrapie. Sensitivity and specificity were calculated using standard epidemiological methods. Cerebrospinal fluid immunoassay results did not differ significantly between positive and negative sheep. Test sensitivity varied from 0.55 to 0.66, depending on the choice of test endpoint. Test specificity varied from 0.30 to 0.77, depending on the choice of test endpoint. The 14-3-3 cerebrospinal fluid immunoassay appears to have no value in the diagnosis of clinical scrapie in sheep.

14-3-3 Proteins↗
PubMed2001

The Columbia University single-ion microbeam.

A single-ion microbeam facility has been constructed at the Columbia University Radiological Research Accelerator Facility. The system was designed to deliver defined numbers of helium or hydrogen ions produced by a van de Graaff accelerator, covering a range of LET from 30 to 220 keV/microm, into an area smaller than the nuclei of human cells growing in culture on thin plastic films. The beam is collimated by a pair of laser-drilled apertures that form the beam-line exit. An integrated computer control program locates the cells and positions them for irradiation. We present details of the microbeam facility including descriptions of the collimators, hardware, control program, and the various protocols available. Various contributions to targeting and positioning precision are discussed along with our plans for future developments. Beam time for outside users is often available (see www.raraf.org).

Equipment Design↗
PubMed2001

Real-time interactive duplex MR measurements: application in neurovascular imaging.

OBJECTIVE: Real-time interactive duplex MR imaging is a new phase-contrast MR imaging technique that enables the quantification and display of flow velocities in real time without the need for cardiac gating. We investigated the feasibility and reliability of the technique to assess hemodynamic information both in vitro and in vivo in the carotid arteries and in the venous sinuses. SUBJECTS AND METHODS: Real-time interactive duplex MR measurements (TR/TE, 53/27; flip angle, 90 degrees; encoding velocity, 100 or 150 cm/sec) were performed in vitro with a steady-flow phantom and in 10 healthy volunteers in whom common and internal carotid artery velocities were measured. In eight volunteers, velocity measurements were also performed in the superior sagittal sinus during both normal breathing and hyperventilation. Time-velocity plots were analyzed qualitatively and quantitatively and compared with findings from conventional segmented k-space phase-contrast MR imaging and Doppler sonography. RESULTS: Velocity determinations for real-time duplex MR and conventional phase-contrast MR imaging showed an in vitro correlation of 0.99 and an in vivo correlation of 0.83 (carotid arteries) and 0.76 (venous sinus). Velocity measurements in the carotid arteries with real-time MR imaging were significantly lower than those obtained with conventional phase-contrast MR (averaged, 7.8%; p = 0.003) or sonography (23.7%, p < 0.001), likely because of volume averaging. Small but significant velocity changes occurring in the venous sinus during hyperventilation were reliably identified with both MR techniques. CONCLUSION: Real-time interactive duplex MR imaging can be effectively applied in neurovascular imaging to obtain hemodynamic information.

Adult↗
PubMed2001

BMS-229724 is a tight-binding inhibitor of cytosolic phospholipase A2 that acts at the lipid/water interface and possesses anti-inflammatory activity in skin inflammation models.

Cytosolic phospholipase A2 (cPLA2) catalyzes the selective release of arachidonic acid from the sn-2 position of phospholipids and is believed to play a key cellular role in the generation of arachidonic acid. BMS-229724 (4-[4-[2-[2-[bis(4-chlorophenyl)methoxy]ethyl-sulfonyl]ethoxy]phenyl]-1,1,1-trifluoro-2-butanone) was found to be a selective inhibitor of cPLA2 (IC50 = 2.8 microM) in that it did not inhibit secreted phospholipase A2 in vitro, nor phospholipase C and phospholipase D in cells. The compound was active in inhibiting arachidonate and eicosanoid production in U937 cells, neutrophils, platelets, monocytes, and mast cells. With a synthetic covesicle substrate system, the dose-dependent inhibition could be defined by kinetic equations describing competitive inhibition at the lipid/water interface. The apparent equilibrium dissociation constant for the inhibitor bound to the enzyme at the interface (K(I)*(app)) was determined to be 1. 10(-5) mol% versus an apparent dissociation constant for the arachidonate-containing phospholipid of 0.35 mol%. The unit of concentration in the interface is mole fraction (or mol%), which is related to the surface concentration of substrate, rather than bulk concentration that has units of molarity. Thus, BMS-229724 represents a novel inhibitor of cPLA2, which partitions into the phospholipid bilayer and competes with phospholipid substrate for the active site. This potent inhibition of the enzyme translated into anti-inflammatory activity when applied topically (5%, w/v) to a phorbol ester-induced chronic inflammation model in mouse ears, inhibiting edema and neutrophil infiltration, as well as prostaglandin and leukotriene levels in the skin. In hairless guinea pigs, BMS-229724 was active orally (10 mg/kg) in a UVB-induced skin erythema model in hairless guinea pigs.

Administration, Oral↗
PubMed2000

Method of immobilization of carboxymethyl-dextran affects resistance to tissue and cell colonization.

Coatings from carboxymethylated dextrans (CMDs) were fabricated, analyzed by XPS, and investigated for their ability to inhibit corneal epithelial tissue outgrowth and bovine corneal epithelial cell attachment and growth. CMDs with differing degrees of carboxymethyl substitution and various molecular weights were synthesized by the solution reaction of dextrans with bromoacetic acid under different reactant ratios. The CMD compounds thus obtained were attached onto aminated surfaces produced in two ways: by the plasma deposition of a coating from n-heptylamine vapour, and by the plasma deposition of an acetaldehyde coating onto whose surface aldehyde groups the polyamine compounds polylysine, polyethyleneimine and polyallylamine were immobilized to provide platforms for CMD immobilization. XPS spectra showed that the latter route produced thicker coatings than the former approach. CMD molecules attached directly onto the plasma-fabricated amine surface supported some tissue migration; the extent of carboxymethyl substitution and the molecular weight of the CMDs had little influence. For CMDs immobilized via polyamine spacers, on the other hand, tissue outgrowth was completely inhibited, and again there were no discernible effects from the extent of carboxymethyl substitution and the molecular weight of the CMDs. In assays involving cell attachment and growth, analogous observations were found. Thus, the mode of immobilization of these polysaccharide coatings is the dominant factor in their anti-fouling performance, suggesting that optimization of the architecture of polysaccharide coatings may be an important factor for maximizing their cell-repellent abilities.

Journal Article↗
PubMed2000

Peptoid-containing collagen mimetics with cell binding activity.

Collagen mimetic peptides containing the peptoid residue Nleu (Goodman Bhumralkar, Jefferson, Kwak, Locardi. Biopolymers 1998;47:127-142) were tested for interactions with epithelial cells and fibroblasts. Molecules containing the sequence Gly-Pro-Nleu with a minimum of nine repeats showed cell binding activity. The activity of these molecules appeared to be conformationally sensitive, with the triple-helical form being preferred. When immobilized on a surface, the (Gly-Pro-Nleu)(10)-Gly-Pro-NH(2) sequence stimulated the attachment and growth of corneal epithelial cells and fibroblasts and the migration of epithelial tissue. The peptide sequence KDGEA inhibited cell attachment to the (Gly-Pro-Nleu)(10)-Gly-Pro-NH(2) sequence, suggesting that cell binding to this collagen mimetic involves the alpha2beta1 heterodimer integrin receptor. Interestingly, peptides containing the sequence (GlyNleu-Pro-)(10)-NH(2) did not have cell binding activity. The discovery that triple-helical peptides containing the Gly-Pro-Nleu sequences interact with cells opens up new opportunities in the design of collagen mimetic biomaterials.

Amino Acid Sequence↗
PubMed2000

Combination nucleoside analog reverse transcriptase inhibitor(s) plus nevirapine, nelfinavir, or ritonavir in stable antiretroviral therapy-experienced HIV-infected children: week 24 results of a randomized controlled trial--PACTG 377. Pediatric AIDS Clinical Trials Group 377 Study Team.

One hundred eighty-one antiretroviral-experienced, protease inhibitor-naive, clinically stable HIV-infected children between 4 months and 17 years of age were randomly assigned to receive one of four combination regimens to evaluate the change in plasma HIV RNA, safety, and tolerance when changing antiretroviral therapy to a protease inhibitor-containing combination regimen. All four regimens contained stavudine; in addition children received nevirapine plus ritonavir, lamivudine plus nelfinavir, nevirapine plus nelfinavir, or lamivudine plus nevirapine plus nelfinavir. Twelve additional children chose to receive stavudine plus lamivudine plus nelfinavir, with nelfinavir given bid, rather than tid as for the main regimens. Overall, 51% (89/176; 95% CI 43-58%) of the children on the randomized portion of the study had an HIV RNA response (< or =400 copies/ml) on at least two of the three HIV RNA determinations taken at Weeks 8, 12, and 16. At Week 24 the proportion of children with an HIV RNA response still on initial therapy was 47% (83/176; 95% CI 40-55%) and ranged from 41 to 61% for the four randomized treatment arms. Rash was frequently seen (27%) on the treatment arms containing nevirapine. At Week 24 64% (7/11, 95% CI 31-89%) of the children on the bid nelfinavir combination regimen were still on initial therapy with an HIV RNA response as compared with 46% (23/50; 95% CI 32-61%) on the corresponding tid nelfinavir combination regimen. A change in antiretroviral therapy to a protease inhibitor-containing regimen was associated with a virological response rate of approximately 50% for this patient population.

Anti-HIV Agents↗
PubMed2000

Clusters and fluctuations at mean-field critical points and spinodals

We show that the structure of the fluctuations close to spinodals and mean-field critical points is qualitatively different from the structure close to non-mean-field critical points. This difference has important implications for many areas including the formation of glasses in supercooled liquids. In particular, the divergence of the measured static structure function in near-mean-field systems close to the glass transition is suppressed relative to the mean-field prediction in systems for which a spatial symmetry is broken.

Journal Article↗