Search PubMed⌕ Search

Biomedical subjects

J Marshall

Publications and source records attributed to J Marshall.

At least 127 records · Page 7Linked to original sources
PubMed1999

In vitro protein adsorption to 2 intraocular lens materials.

PURPOSE: To study in vitro protein adsorption to poly(methyl methacrylate) (PMMA) and foldable AcrySof intraocular lenses (IOLs). SETTING: Department of Ophthalmology, United Medical and Dental Schools of Guy's and St. Thomas' Hospitals, London, United Kingdom. METHODS: Poly(methyl methacrylate) (Alcon Surgical, model MC60BM) and AcrySof (Alcon Surgical, model MA60BM) IOLs were incubated in physiological concentrations of radiolabeled albumin or fibronectin at 37 degrees C for periods between 5 minutes and 1 week. The IOLs were removed and rinsed in buffered saline, and the amount of adsorbed protein was calculated by measuring the radioactivity with scintillation spectrometry. RESULTS: The adsorption of both proteins occurred rapidly over the first 2 hours; the rate of adsorption was concentration dependent. Quantitative differences were found: PMMA lenses bound significantly greater quantities of albumin. Initial fibronectin adsorption to both materials was similar, but increased adsorption to AcrySof IOLs was found at days 1 and 7. CONCLUSIONS: The differences in protein absorption to PMMA and AcrySof IOLs in vitro may contribute to the differences in the biological response to these IOLs, including the lower rates of posterior capsule opacification associated with acrylic lenses.

Acrylic Resins↗
PubMed1999

A study to determine the pharmacokinetics and inflammatory fluid penetration of gatifloxacin following a single oral dose.

A single 400 mg oral dose of gatifloxacin was given to each of nine healthy male volunteers and the concentrations of the drug in plasma, cantharidine-induced inflammatory fluid and urine were measured over the following 24 h. The mean peak concentration in plasma of 4. 1 mg/L was attained at a mean time of 1.8 h post dose. The mean peak concentration in inflammatory fluid was 3.6 mg/L and was attained at a mean time of 4.2 h post dose. The mean plasma elimination half-life of gatifloxacin was 6.8 h and that in inflammatory fluid was 7.2 h. The mean penetration into the inflammatory fluid was 117%. Recovery of drug from urine during the first 24 h post dose was 65% of that administered. Our data suggest that gatifloxacin dosed at 400 mg od should be adequate to treat systemic infections caused by most bacterial species.

Administration, Oral↗
PubMed1999

Corneal surface temperature change as the mode of stimulation of the non-contact corneal aesthesiometer.

PURPOSE: The non-contact corneal aesthesiometer (NCCA) assesses corneal sensitivity by using a controlled pulse of air, directed at the corneal surface. The purpose of this paper was to investigate whether corneal surface temperature change was a component in the mode of stimulation. METHODS: Thermocouple experiment: A simple model corneal surface was developed that was composed of a moistened circle of filter paper placed on a thermocouple and mounted on a glass slide. The temperature change produced by different stimulus pressures was measured for five different ambient temperatures. Thermal camera experiment: Using a thermal camera, the corneal surface temperature change was measured in nine young, healthy subjects after exposure to different stimulus air pulses. Pulse duration was set at 0.9 s but was varied in pressure from 0.5 to 3.5 millibars. RESULTS: Thermocouple experiment: An immediate drop in temperature was detected by the thermocouple as soon as the air flow was incident on the filter paper. A greater temperature change was produced by increasing the pressure of the incident air flow. A relationship was found and a calibration curve plotted. Thermal camera experiment: For each subject, a drop in surface temperature was detected at each stimulus pressure. Furthermore, as the stimulus pressure increased, the induced reduction in temperature also increased. A relationship was found and a calibration curve plotted. CONCLUSION: The NCCA air-pulse stimulus was capable of producing a localized temperature change on the corneal surface. The principal mode of corneal nerve stimulation, by the NCCA air pulse, was the rate of temperature change of the corneal surface.

Air↗
PubMed1999

Risk factors for clinically important upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group.

OBJECTIVE: To evaluate the incidence and risk factors for clinically important upper gastrointestinal bleeding in critically ill patients requiring mechanical ventilation. DESIGN: In duplicate, blinded adjudicators determined the presence of clinically important gastrointestinal bleeding using a priori criteria, evaluating relevant clinical, laboratory, and diagnostic data. Cox proportional hazards regression analyses were used to examine baseline and time-dependent risk factors for bleeding. SETTING: Sixteen university-affiliated intensive care units (ICUs) in Canada. PATIENTS: A total of 1,077 critically ill ICU patients ventilated for at least 48 hrs. INTERVENTIONS: Patients were randomized to stress ulcer prophylaxis with intravenous ranitidine or nasogastric sucralfate; otherwise, management was at the discretion of the ICU team. MEASUREMENTS AND MAIN RESULTS: Demographic data included patient characteristics, Acute Physiology and Chronic Health Evaluation II score, and multiple organ dysfunction (MOD) score. Each day in the ICU, physiologic measurements including MOD score, feeding, and other treatment variables were recorded. The significant risk factors for upper gastrointestinal bleeding in the univariable analyses were low platelet count, maximum serum creatinine, maximum MOD score, maximum pulmonary component of the MOD score, maximum hepatic component of the MOD score, maximum renal component of the MOD score, enteral nutrition, and stress ulcer prophylaxis with ranitidine. The only independent predictors of bleeding in the multivariable analysis were maximum serum creatinine (relative risk = 1.16 [95% confidence interval = 1.02-1.32]), enteral nutrition (relative risk = 0.30 [95% confidence interval = 0.13-0.67]), and ranitidine administration (relative risk = 0.39 [95% confidence interval = 0.17-0.83]). CONCLUSIONS: In critically ill ventilated patients, renal failure was independently associated with an increased risk of clinically important gastrointestinal bleeding, whereas enteral nutrition and stress ulcer prophylaxis with ranitidine conferred significantly lower bleeding rates.

APACHE↗
PubMed1999

Novel endogenous type D retroviral particles expressed at high levels in a SCID mouse thymic lymphoma.

A xenograft model of the human disease Langerhans cell histiocytosis (LCH) was investigated with severe combined immunodeficiency (SCID) mice. Transplantation of human LCH biopsy material into SCID mice resulted in the generation of mouse tumors resembling lymphomas. A thymoma cell line (ThyE1M6) was generated from one of these mice and found to display significant levels of Mg2+-dependent reverse transcriptase activity. Electron microscopy revealed particles with type D retroviral morphology budding from ThyE1M6 cells at a high frequency, whereas control cultures were negative. Reverse transcription-PCR of virion RNA with degenerate primers for conserved regions of various mouse, human, and primate retroviruses amplified novel sequences related to primate type D retroviruses, murine intracisternal A particles, Jaagsiekte sheep retrovirus, and murine long interspersed nuclear elements but not other retroviral classes. We demonstrate that these sequences represent a novel group of endogenous retroviruses expressed at low levels in mice but expressed at high levels in the ThyE1M6 cell line. Furthermore, we propose that the activation of endogenous retroviral elements may be associated with a high incidence of thymomas in SCID mice.

Acid Anhydride Hydrolases↗
PubMed1999

Variation in red cell transfusion practice in the intensive care unit: a multicentre cohort study.

OBJECTIVES: To determine the degree of interinstitutional transfusion practice variation and reasons why red cells are administered in critically ill patients. STUDY DESIGN: Multicentre cohort study combined with a cross-sectional survey of physicians requesting red cell transfusions for patients in the cohort. STUDY POPULATION: The cohort included 5298 consecutive patients admitted to six tertiary level intensive care units in addition to administering a survey to 223 physicians requesting red cell transfusions in these units. MEASUREMENTS: Haemoglobin concentrations were collected, along with the number and reasons for red cell transfusions plus demographic, diagnostic, disease severity (APACHE II score), intensive care unit (ICU) mortality and lengths of stay in the ICU. RESULTS: Twenty five per cent of the critically ill patients in the cohort study received red cell transfusions. The overall number of transfusions per patient-day in the ICU averaged 0.95 +/- 1.39 and ranged from 0.82 +/- 1.69 to 1.08 +/- 1.27 between institutions (P < 0.001). Independent predictors of transfusion thresholds (pre-transfusion haemoglobin concentrations) included patient age, admission APACHE II score and the institution (P < 0.0001). A very significant institution effect (P < 0.0001) persisted even after multivariate adjustments for age, APACHE II score and within four diagnostic categories (cardiovascular disease, respiratory failure, major surgery and trauma) (P < 0.0001). The evaluation of transfusion practice using the bedside survey documented that 35% (202 of 576) of pre-transfusion haemoglobin concentrations were in the range of 95-105 g/l and 80% of the orders were for two packed cell units. The most frequent reasons for administering red cells were acute bleeding (35%) and the augmentation of O2 delivery (25%). CONCLUSIONS: There is significant institutional variation in critical care transfusion practice, many intensivists adhering to a 100g/l threshold, and opting to administer multiple units despite published guidelines to the contrary. There is a need for prospective studies to define optimal practice in the critically ill.

Journal Article↗
PubMed1999

The clinical utility of invasive diagnostic techniques in the setting of ventilator-associated pneumonia. Canadian Critical Care Trials Group.

OBJECTIVE: To evaluate the clinical utility of bronchoscopy with protected brush catheter (PBC) and BAL for patients with ventilator-associated pneumonia (VAP). DESIGN: Prospective cohort study. SETTING: Ten tertiary care ICUs in Canada. PATIENTS: Ninety-two mechanically ventilated patients with a clinical suspicion of VAP who underwent bronchoscopy were compared with 49 patients with a clinical suspicion of pneumonia who did not. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: We compared antibiotic use, duration of mechanical ventilation, ICU stay, and mortality. In addition, for patients who received bronchoscopy, we administered a questionnaire (before and after bronchoscopy) to evaluate the effect of PBC or BAL on (1) physician perception of the probability of VAP, (2) physician confidence in the diagnosis of VAP, and (3) changes to antibiotic management. After bronchoscopy results became available, from the physician's perspective, the diagnosis of VAP was deemed much less likely (p < 0.001), confidence in the diagnosis increased (p = 0.03), and level of comfort with the management plan increased (p = 0.02). Following the results of invasive diagnostic tests, in the group that underwent bronchoscopy, patients were receiving fewer antibiotics (31/92 vs 9/49, p = 0.05) and more patients had treatment with all their antibiotics discontinued (18/92 vs 3/49, p = 0.04) compared with the group that did not undergo bronchoscopy. Duration of mechanical ventilation and ICU stay were similar between the two groups, but mortality was lower in the group that underwent bronchoscopy with PBC or BAL (18.5% vs 34.7%, p = 0.03). CONCLUSIONS: Invasive diagnostic testing may increase physician confidence in the diagnosis and management of VAP and allows for greater ability to limit or discontinue antibiotic treatment. Whether performing PBC or BAL affects clinically important outcomes requires further study.

Anti-Bacterial Agents↗
PubMed1999

The pathogenesis of edema in diabetic maculopathy.

Diabetic maculopathy is characterized by the accumulation of extracellular fluid in Henle's layer and the inner nuclear layer of the retina. The localization of the edema is likely to be due, in part, to the relative barrier properties of the inner and outer plexiform layers. The origin of the extracellular fluid is from the intravascular compartment. Although changes to retinal blood flow may partly explain the extravasation of fluid, the most important mechanism is breakdown of the blood retinal barriers. Both the inner blood retinal barrier formed by the retinal capillary endothelial cell tight junctions and the outer barrier formed by the retinal pigment epithelial cell tight junctions can be affected. The mechanism of breakdown of the blood retinal barriers is likely to be changes to the tight junction proteins including occludin and ZO-1. The biochemical messenger inducing these changes may be vascular endothelial growth factor. The origin of this or other cofactors may be the retinal glial cells. The underlying biochemical stimulus to the production of vascular endothelial growth factor is chronic hyperglycaemia, but it is uncertain by what pathway this is effected.

Animals↗
PubMed1999

The interpretation of optical coherence tomography images of the retina.

PURPOSE: To determine the relationship between optical coherence tomography (OCT) images of the retina and retinal substructure in vitro and in vivo. METHODS: In vitro, OCT images of human and bovine retina were acquired after sequential excimer laser ablation of the inner retinal layers. Measurements of bands in the OCT images were compared with measurements of retinal layers on histology of the ablated specimens. In vivo, OCT images were acquired of retinal lesions in which there was a displacement of pigmented retinal pigment epithelial (RPE) cells: retinitis pigmentosa and laser photocoagulation (eight eyes each). RESULTS: The mean thickness of human inner OCT bands (131 microm; 95% confidence interval [CI], 122-140 microm) was 7.3 times that of the retinal nerve fiber layer (RNFL). This band persisted despite ablation greater than 140 microm. The inner aspect of the outer OCT band corresponded to the apical RPE, but the mean thickness of this band in human tissue (55 microm; 95% CI, 48-62 microm) was 2.6 times the thickness of the RPE-choriocapillaris complex. OCT measurement of total retinal thickness was accurate (coefficient of variance, 0.05) and precise (coefficient of correlation with light microscopy, 0.98). Hyperpigmented lesions gave rise to high signal, attenuating deeper signal; hypopigmented lesions had the opposite effect on deeper signal. CONCLUSIONS: The inner band is not RNFL specific, partly consisting of a surface-related signal. The location, not thickness, of the outer band corresponds to RPE melanin. Given the additional effect of polarization settings, precise OCT measurement of specific retinal layers is currently precluded.

Adult↗
PubMed1999

Age-dependent variation in metalloproteinase activity of isolated human Bruch's membrane and choroid.

PURPOSE: To characterize and determine the effect of aging on the matrix metalloproteinase (MMP) component of the extracellular matrix-remodeling mechanism of isolated human Bruch's-choroid. METHODS: Immunohistochemical techniques and western blot analysis were used to detect and localize various members of the MMP family of proteolytic enzymes in the Bruch's-choroid complex. Gelatin substrate zymography was used to detect and quantify the levels of MMP-2 and -9 in homogenates of Bruch's-choroid from both macular and peripheral regions of the human fundus. Aging alterations in these enzymes were quantified by densitometric analysis of photographic negatives of the zymography gels. RESULTS: Intact preparations of Bruch's-choroid showed the presence of inactive forms of two gelatinases (MMP-2, 65 kDa, and MMP-9, 92 kDa), interstitial collagenase (MMP-1, 52 kDa) and stromelysin (MMP-3, 57 kDa). MMP-1 and -3 were localized primarily to Bruch's membrane. MMP-9 was distributed evenly in Bruch's membrane with some patchy presence in the choroidal mass. Distribution of MMP-2 was similar to that of MMP-9, but the staining in Bruch's was much fainter. On gelatin zymography, an active form of MMP-2 (58-kDa species) was frequently observed in peripheral samples but only occasionally in macular regions. The levels of MMP-2 and -9 increased with aging in both the macular and the peripheral regions of the fundus (P < 0.05). MMP-2 levels were lower in macular regions than in the periphery but no such variation was observed with MMP-9. Both these inactive gelatinases could be activated in vitro. CONCLUSIONS: A matrix-degrading mechanism essential for extracellular remodeling was shown to be present in Bruch's membrane. In macular regions, increasing levels of inactive forms of metalloproteinase and scarcity of active forms of MMP-2 suggests possible involvement of impaired extracellular degradation in both aging and macular degeneration.

Adolescent↗
PubMed1998

Efficiency of cationic lipid-mediated transfection of polarized and differentiated airway epithelial cells in vitro and in vivo.

Systematic analysis of a large number of different cationic lipids has led to the identification of novel structures (GL-67) and formulations of cationic lipid:plasmid DNA (pDNA) complexes that facilitate high levels of gene expression in lungs of mice. However, despite significant improvement in gene transfer activity, we show here that the efficiency of GL-67-mediated gene transduction of intact airway epithelia is still relatively low. Administration of GL-67:pCF1-CFTR (encoding the cystic fibrosis transmembrane conductance regulator) complexes into the nasal epithelium of cystic fibrosis (CF) transgenic mice resulted only in marginal correction of the ion transport defects. Measurements of nasal potential differences (PD) showed no correction of the sodium (Na+) transport defect, and only partial restitution of the chloride (Cl-) transport defect was achieved in a small proportion of the animals after perfusion of the nasal epithelium with the complexes. Furthermore, in contrast to results obtained following instillation of GL-67:pDNA complexes into the lungs of mice, perfusion of GL-67:pDNA into the nasal epithelium resulted only in a moderate enhancement of gene transduction activity relative to that attained with naked pDNA alone. To determine the basis for this low efficiency of transfection, a series of studies was conducted to identify some of the barriers governing cationic lipid-mediated gene transfer to the airway epithelium. We show here that the transfection activity of GL-67 was affected by the polarization, differentiation, and proliferative state of the cells. Diminished transfection activity was observed with nonmitotic, highly polarized and differentiated airway epithelial cells. This observed reduction in gene expression with nonmitotic cells was determined to be due in part to inefficient nuclear translocation of the pDNA from the cytoplasm. Together these data indicate that much improvement in the ability of cationic lipids to transfect polarized and differentiated airway epithelial cells is a necessary prerequisite for effective cationic lipid-mediated gene therapy of airway diseases such as CF.

Animals↗
PubMed1998

The reported training and experience of editors in chief of specialist clinical medical journals.

CONTEXT: The majority of the peer-reviewed clinical literature is edited by editors whose training in editorial matters may be limited or nonexistent. We suspect that editors are selected for their clinical or academic rather than editorial ability. OBJECTIVE: To test the hypothesis that editors of medical specialist clinical journals were recruited from active clinicians rather than those with evident ability or training as editors. DESIGN, SETTING, AND SUBJECTS: Anonymous mail survey to editors of the 262 peer-reviewed clinical journals that had received at least 1000 citations in the 1994 Science Citation Index. MAIN OUTCOME MEASURES: Training and editorial practices of editors. RESULTS: Replies were received from 191 editors (73%): in 1994 the journals they edited had 6060 (27300/1000 [maximum/minimum]) citations, 234 (740/31) source items, and an impact factor of 2.10 (18.3/0.2); nonresponders' journals had similar characteristics. Of the responding editors, 181 (95%) were part-time, 132 (69%) treated patients, and 164 (86%) were recruited by one of the following methods: election by a scientific society (49 [30%]), nomination by the previous editor (41 [25%]), or response to an advertisement (29 [18%]). There was no strong association between method of recruitment or formal editorial training and the status of the journal. Only 9% of editors in the United States send at least half of the papers to reviewers outside their own country, compared with 41% of editors in the United Kingdom and 73% in other countries, and 69% do not feel bound to follow the advice they receive concerning acceptance of papers. CONCLUSIONS: Clinical journals are usually edited by practicing clinicians who are self-taught part-time editors, but willing to accept further training. They usually consult 2 reviewers, but exercise independent judgment on the acceptability of papers.

Peer Review↗
PubMed1998

Potentiation of gene transfer to the mouse lung by complexes of adenovirus vector and polycations improves therapeutic potential.

Recombinant adenovirus (Ad) vectors are being considered for in vivo delivery of various therapeutic genes. One limiting factor in the development of Ad-based gene therapy is the low efficiency of gene transfer to target tissues such as vascular endothelium, smooth muscle, and airway epithelium. Complexing Ad vector with various polycations has been shown to enhance transduction of cell lines otherwise resistant to Ad infection in vitro. On the basis of this observation, the activity of Ad/polycation complexes was tested in vivo in the mouse lung. The results indicated that several polycations were capable of enhancing transduction of mouse respiratory epithelium, leading to a 1-2 log increase in levels of transgene expression. Poly-L-lysine (PLL) and DEAE-dextran were examined further and were found to increase Ad-mediated gene transfer without any additional toxicity as assessed histologically or through the measurement of inflammatory cytokines in bronchoalveolar lavages. The two polycations also failed to affect the humoral response against Ad vector and were themselves nonimmunogenic under conditions leading to enhanced gene transfer. Moreover, the ability to use reduced doses of vector complexed with polycations resulted in lower levels of Ad-specific antibodies and, thereby, improved readministration of vector. These results suggest that complexing Ad vectors with polycations has the potential to improve the therapeutic index by increasing transgene expression while reducing unwanted responses associated with high doses of vector.

Adenoviridae↗
PubMed1998

Verb retrieval and sentence production in aphasia.

This paper presents a subject with a selective verb retrieval deficit. Nouns were produced more successfully than verbs in spontaneous speech, picture naming and when naming to definition. The word class effect was not observed in comprehension tasks, reading aloud or writing. This indicated that it was due to a specific problem in accessing verbs' phonological representations from semantics. The second part of the paper explores the implications of the verb deficit for sentence production. Analyses of narrative speech revealed a typically agrammatic profile, with minimal verb argument structure and few function words and inflections. Two investigations suggested that the sentence deficit was at least partly contingent upon the verb deficit. In the first, the subject was asked to produce a sentence with the aid of a provided noun or verb. The noun cues were not effective in eliciting sentences, whereas verb cues were. The second investigation explored the effects of therapy aiming to improve verb retrieval. This therapy resulted in better verb retrieval and improved sentence production with those verbs. These findings suggest that an inability to access verbs' phonological representations can severely impair sentence formulation. Implications for models of sentence production are considered.

Aphasia, Broca↗
PubMed1998

Why does monitoring fail in jargon aphasia? comprehension, judgment, and therapy evidence.

Many people with jargon aphasia seem unaware of their speech disorder. The first section of this paper reports data from four subjects which indicate that self-monitoring can fail even when subjects' input skills are apparently adequate to detect their errors. Explanations for this dissociation have attributed monitoring failure to a deficit in auditory feedback, or to a resource limitation which prevents concurrent speaking and monitoring. Section 2 reports a series of naming and judging experiments with one of the subjects which rule out these explanations. These show that the subject can detect his neologisms when he is repeating, but not when he is naming. These results suggest that his monitoring difficulties arise when he is accessing phonology from semantics. Section 3 presents a study which supports this inference, since it shows that semantically focused intervention yields improvements in self-monitoring. It is concluded (1) that monitoring failure can arise from deficits within the production process which preclude comparison of actual with intended output, and (2) that this deficit is best explained within a connectionist model in which monitoring is performed by feedback mechanisms in the word production process.

Aged↗
PubMed1998

A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group.

BACKGROUND: Critically ill patients who require mechanical ventilation are at increased risk for gastrointestinal bleeding from stress ulcers. There are conflicting data on the effect of histamine H2-receptor antagonists and the cytoprotective agent sucralfate on rates of gastrointestinal bleeding, ventilator-associated pneumonia, and mortality. METHODS: In a multicenter, randomized, blinded, placebo-controlled trial, we compared sucralfate with the H2-receptor antagonist ranitidine for the prevention of upper gastrointestinal bleeding in 1200 patients who required mechanical ventilation. Patients received either nasogastric sucralfate suspension (1 g every six hours) and an intravenous placebo or intravenous ranitidine (50 mg every eight hours) and a nasogastric placebo. RESULTS: The patients in the two groups had similar base-line characteristics. Clinically important gastrointestinal bleeding developed in 10 of 596 (1.7 percent) of the patients receiving ranitidine, as compared with 23 of 604 (3.8 percent) of those receiving sucralfate (relative risk, 0.44; 95 percent confidence interval, 0.21 to 0.92; P=0.02). In the ranitidine group, 114 of 596 patients (19.1 percent) had ventilator-associated pneumonia, as compared with 98 of 604 (16.2 percent) in the sucralfate group (relative risk, 1.18; 95 percent confidence interval, 0.92 to 1.51; P=0.19). There was no significant difference between the groups in mortality in the intensive care unit (ICU) (23.5 percent in the ranitidine group and 22.9 percent in the sucralfate group) or the duration of the stay in the ICU (median, nine days in both groups). CONCLUSIONS: Among critically ill patients requiring mechanical ventilation, those receiving ranitidine had a significantly lower rate of clinically important gastrointestinal bleeding than those treated with sucralfate. There were no significant differences in the rates of ventilator-associated pneumonia, the duration of the stay in the ICU, or mortality.

Aged↗