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Biomedical subjects

M Johnson

Publications and source records attributed to M Johnson.

At least 325 records · Page 18Linked to original sources
PubMed1997

Women with HIV disease attending a London clinic.

OBJECTIVE: To examine ethnic, relationship, health, and mental health factors for a cohort of women with HIV infection attending an inner London clinic. DESIGN AND METHODS: Structured schedules were utilised to analyse ethnic group, family, and reproduction issues, mental and physical health for 100 women drawn consecutively from attenders at an inner London HIV clinic RESULTS: 51% of the women were non-ethnic minority groups and 49% were from ethnic groups. HIV testing was often as a result of symptoms or partner illness. One in five had disclosed their status to one person only or no one. Ethnic minority women were more likely to restrict disclosure. Forty seven per cent of the women had 100 children with more children reported in ethnic minority families; 28% of the children had been tested for HIV and five were confirmed HIV positive; 9% of children were born after HIV diagnosis. Nineteen women reported one or more termination of pregnancy, the majority before HIV diagnosis. Three quarters had a partner of whom 56 knew the partner's status. Women with HIV positive partners were more likely to have children. Women kept in ignorance of partner status were more likely to be ethnic minority women. Thirty two per cent had an AIDS diagnosis, diagnosed mostly in the UK. Medical and counselling service uptake was high. Gynaecological problems were common (49% had one or more problem) and 34% had at least one hospital admission. A wide range of counselling issues were recorded, with variations over time. Suicidal issues were relevant for 13% of women (69% ideation, 31% attempts). Significant life events were noted for many women with allied coping demands. CONCLUSIONS: There are a wide range of issues for women with HIV and systematic differences between ethnic and non-ethnic women and those with or without children.

AIDS Serodiagnosis↗
PubMed1997

Effect of salmeterol on Pseudomonas aeruginosa infection of respiratory mucosa.

We have studied the effect of salmeterol on both P. aeruginosa interactions with the mucosa of nasal turbinate organ cultures and on pyocyanin-induced (20 microg/ml) and elastase-induced (100 microg/ml) damage to nasal epithelial cells. Organ cultures were exposed to salmeterol either by preincubation with 4 x 10(-7) M salmeterol for 30 min or by pipetting 20 microl of 4 x 10(-7) M salmeterol onto the organ culture surface immediately prior to bacterial inoculation. Infected organ cultures (8 h) had significantly (p < or = 0.01) increased epithelial damage, and P. aeruginosa was predominantly associated with damaged epithelium and mucus. Salmeterol significantly (p < or = 0.02) reduced epithelial damage caused by infection and the total number of adherent bacteria (p < or = 0.05), but bacterial distribution on the mucosa was unchanged. Nasal epithelial cells incubated with pyocyanin (20 microg/ml) or elastase (100 microg/ml) for 3 h had significantly (p < or = 0.05) increased cytoplasmic blebbing and mitochondrial damage versus control values. Elastase also significantly (p < or = 0.05) increased cell projection and reduced the level of ciliation. Cells preincubated with salmeterol (2 x 10(-7) M) showed a significant reduction in some features of cell damage caused by both toxins, which was inhibited by the beta2-adrenoceptor antagonist propranolol. Our results indicate that salmeterol reduces P. aeruginosa-induced damage to both organ culture and nasal epithelium.

Adrenergic beta-Agonists↗
PubMed1997

Outcomes for home and community nursing in integrated delivery systems.

In these tumultuous times in health care, nursing providers are under pressure to capture data that demonstrate the effectiveness of nursing interventions on client health. At the University of Iowa, researchers are attempting to develop a client outcome classification system that uses a standardized language across different health care settings to capture this vital information.

Centers for Medicare and Medicaid Services, U.S.↗
PubMed1997

Effects of continuous venovenous hemofiltration on cardiopulmonary function in a porcine model of endotoxin-induced shock.

OBJECTIVE: To determine whether continuous venovenous hemofiltration, proposed to remove inflammatory mediators from circulation, would resolve cardiopulmonary derangements in a model of established endotoxic shock. ANIMALS: 16 clinically normal pigs. PROCEDURE: Endotoxin was infused, IV, into anesthetized pigs for a total of 50 minutes. Thirty minutes after termination of the infusion period, extracorporeal circulation was initiated through a 50-kd diafilter, or past the filter without ultrafiltrate formation. Cardiac and respiratory variables were monitored for a period of 4 hours. RESULTS: Infusion of lipopolysaccharide resulted in a severe hypodynamic circulatory state, with significant decreases in mean arterial pressure and cardiac output concurrent with a significant increase in pulmonary arterial pressure. Hemofiltration was not associated with any correction of lipopolysaccharide-induced cardiopulmonary derangements. CONCLUSIONS: Continuous venovenous hemofiltration, as used in this acute experiment, did not improve cardiopulmonary dysfunction during endotoxic shock. CLINICAL RELEVANCE: Continuous venovenous hemofiltration needs further investigation before it can be recommended as a clinically effective treatment.

Animals↗
PubMed1997

Domestic violence among family practice patients in midsized and rural communities.

BACKGROUND: This study was designed to determine the prevalence and character of domestic violence among female patients at three family practice clinics (FPCs) in communities of varying sizes. METHODS: Structured interviews with 127 consecutive, consenting women were conducted in three FPCs in midwestern communities with populations of 85,000, 8000, and 3000. The main outcome measures included patient self-reports of emotional, social, physical, and sexual violence, and reasons for their clinic visit. RESULTS: Women at the clinics in the smaller communities were significantly older, reflecting their communities' demographics. Fewer women in the larger community than in the rural settings reported currently having a violent partner (12% vs 25%, P = .01). In the total sample, 46% reported violence from a previous or current partner. Emotional and social abuse were associated with moderate violence (eg, slapping and pushing), severe violence (eg, punching and kicking), and use of weapons. Sexually abused women were emotionally abused and often physically battered. Forty-six percent of currently battered women reported abuse at least once a week, and most (81%) visited their respective clinics for episodic care. CONCLUSIONS: Domestic violence is a prevalent health problem in all family practice settings. The finding that women in the larger community were less likely to be in a current battering relationship may reflect the effectiveness of local intervention programs. Because battered women present primarily for episodic care, physicians should routinely screen for battery, provide education about violence, assess the danger, review safety plans, and refer women appropriately.

Ambulatory Care Facilities↗
PubMed1997

Factors affecting the pores of the inner wall endothelium of Schlemm's canal.

PURPOSE: A linear relationship between the density of pores in the inner wall of Schlemm's canal and aqueous outflow facility has been reported previously in a study in which investigators examined only eyes fixed at constant pressure, so that fixative flow rates differed from eye to eye. Because pores may form as a function of flow rate, the purpose in the current study was to verify the previous findings, using constant flow perfusions. METHODS: Outflow facility was measured in enucleated human eyes. Eyes were fixed under either constant flow or constant pressure conditions, microdissected to expose the inner wall of Schlemm's canal, and prepared for scanning electron microscopy. The density and diameter of pores in the inner wall were measured. RESULTS: Statistical analysis showed no correlation between outflow facility and either the density or the diameter of pores. Pore density decreased significantly during the hours after death. Examining only eyes for which experimentation was started within 20 hours of death, we found that pore density increased significantly with the volume of fixative that had been perfused through the outflow pathway. CONCLUSIONS: The correlation found by Allingham et al between outflow facility and pore density in the inner wall endothelium was not confirmed. However, the relationship between pore density and volume of fixative perfused is consistent with and may be responsible for the finding in the previous study. Because fixation conditions can influence the apparent pore density in the inner wall endothelium significantly, the conclusion reached previously, that pores contribute only 10% of the aqueous outflow resistance, may require reevaluation.

Adolescent↗
PubMed1997

Fish vaccine antigens produced or delivered by recombinant DNA technologies.

Current efforts to develop vaccines, particularly for aquacultured species, have turned largely to biotechnology because it provides the means to inexpensively produce sufficient quantities of the immunoprotective antigen. These efforts have resulted in several prototype vaccines for fish and the publication of a large number of articles on the subject. However, there are only a few recombinant DNA-based vaccines for aquaculture in the licensing pipeline. Continued funding of research on recombinant DNA vaccines comes from the recognition by industry and government funding agencies that this research can lead to an increased understanding of the mechanisms in protective immunity. This is especially important for fish and shellfish species since our knowledge of the immune mechanisms in these animals is pitifully meagre. This presentation discusses the relative merits of the different recombinant DNA technologies that have been used to produce viral vaccines for fish and the promising approaches that are under consideration to increase the efficacy of these vaccines. There are many approaches to antigen production by recombinant DNA techniques including: (i) the preparation of purified antigenic proteins produced from the cloned viral genes in a variety of vector/host expression systems, (ii) chemical synthesis or the use of fusion vectors to produce peptides corresponding to known epitopes, (iii) defined attenuations, i.e. specific genetic alterations, of live virus vaccines, (iv) the use of live bacterial or viral vectors to deliver resistance genes or viral antigens, (v) anti-idiotype antibodies, and (vi) DNA vaccines where purified plasmid DNA expressing the pathogen gene under a eucaryotic promoter is injected. All of these technologies have been used more or less successfully in the development of vaccines for aquacultured species. However, the requirements for safety, effectiveness, ease of application and low cost/dose restrict their commercial development for aquaculture. The ideal viral vaccine for aquaculture must be effective in preventing death, be inexpensive to produce and license, provide immunity of long duration, and be easily administered. In addition, these vaccines must not only provide protection against the lethal effects of virus infection but prevent the formation of virus persistence. This is especially true for infectious haematopoietic necrosis virus (IHNV) which has been shown to persist in survivors in the presence of high antibody levels. Since resolution of virus persistence is thought to be correlate with cell-mediated immunity, vaccines designed to augment the cell-mediated immunity must be developed for fish. Approaches that are being considered include the use of cytokines in combination with subunit vaccines and the use of specific MHC-I inducer adjuvants with the vaccine. The "tailoring" of vaccine immunogenicity using different combinations of antigen and adjuvant will be presented.

Animals↗
PubMed1997

The effect of rolipram, a type IV phosphodiesterase inhibitor, on Pseudomonas aeruginosa infection of respiratory mucosa.

We have investigated the effect of rolipram, a type IV phosphodiesterase inhibitor, on Pseudomonas aeruginosa infection of the respiratory mucosa of an organ culture model and on the reduction in intracellular cAMP levels seen in human nasal epithelial cells incubated with P. aeruginosa culture filtrate. We have compared rolipram with salmeterol, a long-acting beta-2 agonist, and have also studied the effect of the two agents together. Infected organ cultures had significantly (P < or = .05) increased epithelial damage. Rolipram significantly (P < or = .05) reduced P. aeruginosa-induced epithelial damage and reduced the total number of bacteria adhering to the respiratory mucosa (P < or = .04) in a concentration-dependent manner, although neither rolipram nor salmeterol affected P. aeruginosa growth in broth cultures. Rolipram reduced P. aeruginosa-induced mucosal damage more than salmeterol (P < or = .03). The effect of the two agents was neither additive nor synergistic. Rolipram, salmeterol and both agents together significantly (P < or = .01) increased intracellular cAMP levels in epithelial cells treated with P. aeruginosa culture filtrate. Rolipram alone increased cAMP more than salmeterol or both agents together (P < or = .01), probably because of an interaction between the two agents. These results suggest that agents that elevate intracellular cAMP protect the epithelium during bacterial infection. Rolipram is more effective than salmeterol in preventing P. aeruginosa-induced epithelial damage.

Bacterial Adhesion↗
PubMed1997

Pre-eruptive coronal radiolucency in a mandibular premolar: a case report and literature review.

This report describes a coronal radiolucency in an unerupted mandibular premolar. This anomaly, which most frequently involves the mandibular second molars, has been variously attributed to dental caries, dentine hypoplasia, inclusions of uncalcified enamel matrix, and resorption. The present instance was considered to be due to external resorption. Because these lesions may enlarge rapidly, frequent radiographic monitoring of an affected tooth is recommended. Early restorative treatment has been shown to be successful even in affected teeth with small pulp exposures.

Adolescent↗
PubMed1997

Interendothelial junctions in normal human Schlemm's canal respond to changes in pressure.

PURPOSE: To determine if changes in the structure and complexity of junctions between endothelial cells lining Schlemm's canal (SC) occur in normal human eyes with changes in perfusion pressure. METHODS: Twelve normal human eyes were either perfusion-fixed (at 15 or 45 mm Hg) or immersion-fixed (0 mm Hg) in modified Karnovsky's fluid. 'Outflow facility was measured continually during the perfusion fixation. The intercellular junctions of the endothelial cells of SC were ultrastructurally examined in thin sections, including serial sections and freeze-fracture replicas. Morphometric data on the number of junctional strands per total length of tight junction were documented and categorized by the number of strands (one, two, or three or more). The length of endothelial cell overlap was measured on thin sections. RESULTS: In freeze-fracture replicas, perfusion-fixed eyes demonstrated less complex junctions. At 15 mm Hg, 18.06% of the total junctional length was represented by three or more strands; at 45 mm Hg, this percentage decreased to 8.59%. In immersion-fixed eyes, 24.17% of the total junctional length was represented by three or more strands. These differences were statistically significant (P < 0.0012). In sections, the amount of endothelial cell overlap, and thus the length of paracellular pathway, was reduced in perfusion-fixed versus immersion-fixed eyes (P < 0.02). Extensive serial sectioning demonstrated that giant vacuoles were formed, either by individual endothelial cells or by two or more adjacent endothelial cells. CONCLUSIONS: When compared with specimens fixed at zero pressure, overlap between endothelial cells of SC is reduced significantly when this cell layer is under conditions of flow similar to those encountered in vivo. The tight junctions between cells of the inner wall of SC become less complex with increasing pressure. Our data suggest that the paracellular pathway into SC in the normal eye is sensitive to modulation within a range of physiologically relevant pressures.

Aged↗
PubMed1996

Evaluation of dose calculation algorithm of the peacock system for multileaf intensity modulation collimator.

PURPOSE: To evaluate the dose calculation algorithm used in the inverse treatment planning computer system for the intensity modulation multileaf collimator. METHODS AND MATERIALS: The inverse treatment-planning computer system calculates the intensities of multiple pencil beams to achieve an optimal distribution and modulates the beam intensity through the special multileaf collimator. The system's dose calculation algorithm made the two basic assumptions: (a) The tissue-maximum ratios (TMRs) of a single pencil beam have the same values as TMRs for raylines through each pencil beam that are determined from percentage depth dose isodose curves along the long axis of the 2 x 20 cm2 field with all leaves open; and (b) the relative output factors (ROF) of each pencil beam also have the same values as the rayline TMR at d(max) of the 2 x 20 cm2 field. To verify these two assumptions, a special multileaf collimator was installed to our linear accelerator which produces 4 MV x-rays. The TMRs and ROFs for the single leaves 1 through 10 were measured using an ion chamber and TLD dosimeter in either a water or a polystyrene phantom. The values of rayline TMRs were calculated from the measured crossplane isodose curves of the 2 x 20 cm2 field. Comparisons were made between these two sets of data. RESULTS: Based on our measurements, we found that the ROFs of a pencil beam obtained from the rayline TMRs at d(max) are as much as 7.6% greater than that of single pencil beams. The ROF of the 1 x 1 cm2 pencil beam is 4 and 6.5% less than that of a cluster of four neighboring pencil beams forming a 2 x 2 cm2, and a 2 x 20 cm2 field respectively. However, the rayline TMRs are generally larger than the TMRs of a single pencil beam. At a depth of 8 cm, the average depth in the middle of intracranial space, the rayline TMRs of the pencil beams of leaves 1 and 10 are 5.4 and 9% higher than a single pencil beam TMR at the same depth, respectively. Also interesting is to note that the TMRs of each of the single pencil beams were found to be equal. CONCLUSIONS: In our article, evaluations and comparisons of TMRs and ROFs were made for two extreme conditions. The measured values of TMRs and ROFs of a single beam have been shown to be significantly different from those used in the calculations. Because both the TMR and ROF are influenced by the scattering radiation in the same direction, the deviations for these two factors would be expected to be magnified. Thus, for the two extreme situations we have investigated, dose deviations would be on the order of 15%. In real patient treatment; of course, these deviations may be somewhat less, but still significant. Our results, however, show that further investigations are warranted.

Algorithms↗
PubMed1996

Sustained activation of a G protein-coupled receptor via "anchored" agonist binding. Molecular localization of the salmeterol exosite within the 2-adrenergic receptor.

An inherent therapeutic limitation of many G protein-coupled receptor agonists is a short duration of action due to rapid dissociation from receptors. Salmeterol is a modified beta-adrenergic receptor (betaAR) agonist that has a long duration of action at the beta2AR (but not the beta1AR) both in vitro and in vivo and that is persistent despite extensive washout of the agonist. It has been proposed that salmeterol binds not only to the active site of the beta2AR (localized to receptor transmembrane spanning domains (TMDs) 3 and 5) but also to another site (termed the "exosite") that anchors it to the receptor and provides for repetitive active-site binding events. To identify the location of this exosite, we used site-directed mutagenesis to replace beta2AR amino acids 149-173 (within TMD4) with beta1AR sequence. The resulting constructs were then expressed in COS-7 cells for radioligand binding studies. Using this approach, when this domain was replaced with the analogous beta1AR sequence, the ability of salmeterol to persist at the receptor under washout conditions was reduced by 67%. The results from more selective mutants (S-(149-166), S-(164-173), and S-(149-158)) indicated that a limited 10-amino acid region (beta2AR residues 149-158), localized at the interface of the cytoplasm and the transmembrane domain, contains a critical determinant for exosite binding. Whereas CHW cells stably expressing wild-type beta2AR displayed persistent salmeterol-promoted cAMP accumulation despite agonist washout, substitution of beta2AR residues 149-158 with beta1AR sequence resulted in a 56% attenuation of salmeterol-promoted cAMP accumulation under identical washout conditions. A reverse chimera was also studied, which consisted of a substitution of beta2AR residues 152-156 into the beta1AR. This substitution was found to confer exosite binding to the beta1AR. None of these mutations decreased the affinity of salmeterol for the receptor at the active site as assessed in competition binding studies. Anchored binding to this motif thus represents a novel mechanism by which agonists like salmeterol can repetitively activate receptors. Conceivably, with other G protein-coupled receptors that have similar motifs, anchored ligands can be designed to provide for long durations of action by this mechanism.

Adrenergic beta-Agonists↗
PubMed1996

Safety and efficacy of lamivudine-zidovudine combination therapy in antiretroviral-naive patients. A randomized controlled comparison with zidovudine monotherapy. Lamivudine European HIV Working Group.

OBJECTIVE: To compare safety and efficacy of lamivudine-zidovudine combination therapy with zidovudine monotherapy in treating human immunodeficiency virus type 1 (HIV-1)-infected, antiretroviral therapy-naive patients. DESIGN: Double-blind, randomized, multicenter, comparative trial of 129 patients throughout 24 weeks followed by 24 weeks of open-label lamivudine in combination with zidovudine. SETTING: Outpatients from 14 hospitals in Belgium, France, Germany, Spain, and the United Kingdom were enrolled within 6 months. PATIENTS: HIV-1-positive, antiretroviral-naive ( < or = 4 weeks prior zidovudine use) patients aged atleast 18 years with CD4+ cell counts between 0.10 x 10(9)/L and 0.40 x 10(9)/L (100-400/microL). INTERVENTION: Patients received either 300 mg of lamivudine every 12 hours in combination with 200 mg of zidovudine every 8 hours for 24 weeks or zidovudine monotherapy for 24 weeks. All patients were then allowed to receive zidovudine in combination with open-label lamivudine (300 mg every 12 hours). MAIN OUTCOME MEASURES: Efficacy was assessed by changes in CD4+ cell counts beta 2-microglobulin, neopterin, HIV-1 immune-complex dissociated (ICD) p24 antigenemia, and HIV-1 viral load. Safety was assessed by incidence of adverse clinical events and defined laboratory-measured toxic effects. RESULTS: Combination therapy showed superior treatment effects compared with monotherapy during the first 24 weeks as documented by changes in CD4+ cell counts (increase of 0.08 x 10(9)/L vs 0.02 x 10(9)/L; P < .001), ICDp24 (-88% vs -49%; P = .04), cellular viremia (-1.27 vs -0.20 log10 median tissue-culture infected dose [TCID50] per 10(6) peripheral blood mononuclear cells; P = .001), and viral load measured by HIV-1 RNA polymerase chain reaction using a Roche method (-1.33 vs -0.57 log10 copies/mL; P = .001) or an immune-capture method (-0.6 vs -0.14log10 copies/mL; P = .008). Observed changes were sustained to 48 weeks for patients continuing to receive combination therapy. Patients switching to receive combination therapy at week 24 showed improvements in CD4+ cell count and viral load to week 48. Mutation results suggested that mutations associated with zidovudine resistance may have developed more slowly over the first 24 weeks in patients receiving combination therapy. In contrast, mutations associated with lamivudine resistance appeared to develop rapidly, despite sustained antiviral treatment effect. However, the number of patients evaluated for genotypic changes was small, and confirmation of these results is needed in larger studies. No statistically significant differences in incidence or severity of clinically manifested or laboratory-measured toxic effects were noted between treatment groups. CONCLUSIONS: The combination of lamivudine and zidovudine results in a potent and sustained antiviral effect in antiretroviral-naive patients that is superior to that observed with zidovudine monotherapy.

Adult↗
PubMed1996

Latent inhibition effects reflected in event-related brain potentials in healthy controls and schizophrenics.

The present study examined the effects of pre-exposure of an irrelevant stimulus on reaction time and the contingent negative variation (CNV) in healthy controls and schizophrenic patients. In Phase I, subjects were either pre-exposed (PE) or not pre-exposed (NPE) to repeated presentations of an auditory probe stimulus (white noise), while engaged in counting auditory nonsense syllables. In Phase II, all subjects were required to produce a rapid motor response to a visual imperative stimulus that was preceded by the previously irrelevant auditory stimulus. During Phase II in controls, for PE as compared to NPE subjects, the build-up of CNV across trials was delayed. In schizophrenics, for both PE and NPE subjects, there was no pre-exposure effect on the CNV component. These findings indicate that ERPs may be useful in explicating the normal latent inhibition effect (poor associative learning to a stimulus after it has been passively pre-exposed) and its disruption in schizophrenia.

Adult↗