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Biomedical subjects

J Marshall

Publications and source records attributed to J Marshall.

At least 73 records · Page 4Linked to original sources

Eclipse retinopathy.

PURPOSE: Solar retinopathy is a well-recognised clinical entity of macular damage caused by viewing the sun, induced by a photochemical process. The term 'eclipse retinopathy' is frequently employed when the condition is sustained as a result of viewing a solar eclipse. Considerable public excitement had been raised in anticipation of the full solar eclipse on 11 August 1999. Whilst experience has shown that visual morbidity is likely to be temporary, current evidence is anecdotal and restricted to isolated case reports and series. This study was conducted to establish the true visual morbidity associated with a solar eclipse, and whether it was temporary or permanent. METHODS: A 3 month active case ascertainment study was carried out from July to September 1999 to record cases presenting to ophthalmologists with visual symptoms arising from solar viewing. Further information about the cases was sought using a short questionnaire. A follow-up questionnaire requesting outcome data at 6 months was also employed. RESULTS: There were 70 reported cases of visual loss. The average age was 29.5 +/- 12.9 years. Half the cases presented to an ophthalmologist within 2 days of the eclipse. An abnormal macular appearance was reported in 84% of patients at presentation. There have been no reported cases of continued visual loss or symptoms at 6 months. CONCLUSIONS: This is the largest nationwide study of the visual effects of a solar eclipse ever undertaken. There were no recorded cases of permanent visual loss, which corroborates the previous evidence that visual morbidity is likely to be temporary. It would appear probable that public health education was most effective in reducing visual morbidity and hence keeping the consequent burden on the NHS to a minimum.

Adolescent↗

The minimum stimulus energy required to produce a cooling sensation in the human cornea.

PURPOSE: To estimate the minimum stimulus energy required to stimulate the corneal nerves, using a thermally cooling stimulus. METHODS: The localised temperature change produced in the pre-corneal tear film by the air-pulse stimulus of the Non-Contact Corneal Aesthesiometer (NCCA) was analysed using a thermal imaging camera. Assuming that the cornea behaves as a near perfect black-body, the threshold for energy loss was calculated by combining Stefan-Boltzmann's law and Kirchoff's law for imperfections in black-body radiation, taking into account the likely thermal conductivity of the human cornea. RESULTS: The average normal subject has a threshold for detecting a cooling effect when the local corneal tear film surface temperature drops from a mean of 33.2-32.9 degrees C (i.e. 0.3 degrees C), over a 1 mm diameter circular area (0.785 mm2), and a stimulus time duration of 0.9 s. This gives rise to a sensation threshold for perceiving a loss of heat energy of 7.0 ergs, or 7.0 x 10(-7) joules. CONCLUSION: The cornea possesses stimulus specific receptors, which have an exquisite sensitivity to a rapid, thermally cooling stimulus.

Cold Temperature↗

Antegrade continence enemas in the treatment of slow-transit constipation.

BACKGROUND/PURPOSE: Children with anorectal dysfunction can now be treated by antegrade continence enema (ACE), as described Malone et al. Those with idiopathic constipation, however, are not thought to be suitable for this treatment. Over 150 children attend the authors' department with proven slow transit constipation (mostly proven on nuclear transit/X-ray study), and the authors reviewed the outcome in the 40 of these who have had the ACE procedure. Families completed a questionnaire and attended interview with an independent assessor. METHODS: Of the 40 patients, 32 patients were assessed. Follow-up ranged from 3 to 54 months (median, 18 months) and age ranged from 5 to 17 years (median age, 10 years). Three of 32 stomas were no longer in use. Frequency of soiling was reduced significantly in 20 patients, and a further 6 patients were clean (P <.01). Abdominal pains were relieved significantly (P <.05), and appetite and mood improved. RESULTS: Stomal complications were frequent, (stenosis in 16 of 29, mucus leak in 20 of 29, fecal leak 3 of 29, catheter-related pain in 20 of 29). Slow evacuation (12 of 29) and pain with enema (17 of 20) also were common. CONCLUSION: Malone appendicostomy does improve the well being of patients with slow transit constipation, but the advantages are less dramatic than in children with normal motility.

Adolescent↗

[Topical Mitomycin C for the prophylaxis of recurrent haze after excimer laser photorefractive keratectomy (PRK) - a pilotstudy of 5 patients].

PURPOSE: Corneal haze is a severe complication after excimer laser PRK and may lead to a compromised visual performance and regression. Currently, corticosteroids are topically applied to inhibit the appearance of haze. However, this therapy is not always successful in preventing haze. Various animal studies have shown that topical applied mitomycin C reduces keratocyte activity and collagen synthesis and subsequently haze. MATERIAL AND METHODS: We have treated 5 patients (5 eyes) with severe haze and regression after PRK. In all eyes we have mechanically debrided the haze and 0.02 % mitomycin C was applied to the area of previous ablation for 1 minute. In 2 eyes we have only performed the debridement, whereas in 3 eyes we also have performed a re-PRK after the laser ablation the mitomycin was applied. The postop follow-up was 9 months. RESULTS: In all eyes the surgery and the postop time was without any complications. The haze could be removed in all eyes completely and in the entire postop period recurrent haze was not more than trace. Regression could be eliminated in the three eyes with a re-PRK, whereas the 2 eyes without re-PRK still remained myop. We could not observe any mitomycin C associated complications on the conjunctiva or cornea. CONCLUSION: Topical applied mitomycin C seems to be a promising therapy to prevent recurrent haze after a second PRK procedure. As mitomycin C can be associated with a variety of serious complications, it should only be used in patients with high risk of haze.

Adult↗

Implementation of a 4-y, high-fiber, high-fruit-and-vegetable, low-fat dietary intervention: results of dietary changes in the Polyp Prevention Trial.

BACKGROUND: The Polyp Prevention Trial (PPT) was a multicenter randomized clinical trial designed to determine the effects of a high-fiber (4.30 g/MJ), high-fruit-and-vegetable (0.84 servings/MJ), low-fat (20% of energy from fat) diet on the recurrence of adenomatous polyps in the large bowel. OBJECTIVE: Our goal was to determine whether the PPT intervention plan could effect change in 3 dietary goals and to examine the intervention's effect on the intake of other food groups and nutrients. DESIGN: Participants with large-bowel adenomatous polyps diagnosed in the past 6 mo were randomly assigned to either the intervention (n = 1037) or the control (n = 1042) group and remained in the trial for 4 y. Three dietary assessment instruments were used to measure dietary change: food-frequency questionnaires (in 100% of the sample), 4-d food records (in a 20% random cohort), and 24-h dietary recalls (in a 10% random sample). RESULTS: Intervention participants made and sustained significant changes in all PPT goals as measured by the dietary assessment instruments; the control participants' intakes remained essentially the same throughout the trial. The absolute differences between the intervention and control groups over the 4-y period were 9.7% of energy from fat (95% CI: 9.0%, 10.3%), 1.65 g dietary fiber/MJ (95% CI: 1.53, 1.74), and 0.27 servings of fruit and vegetables/MJ (95% CI: 0.25, 0.29). Intervention participants also reported significant changes in the intake of other nutrients and food groups. The intervention group also had significantly higher serum carotenoid concentrations and lower body weights than did the control group. CONCLUSION: Motivated, free-living individuals, given appropriate support, can make and sustain major dietary changes over a 4-y period.

Adenomatous Polyps↗

The effect of long-term, daily contact lens wear on corneal sensitivity.

PURPOSE: To assess the effect of long-term, daily-wear soft contact lenses and rigid gas permeable (RGP) contact lenses on corneal sensitivity using a noninvasive, air-pulse stimulus. METHODS: The central and peripheral (temporal, medial, inferior) corneal sensation thresholds of 40 non-lens wearers, 40 soft lens wearers, and 40 RGP lens wearers were assessed using the Non-Contact Corneal Aesthesiometer (NCCA). The individuals who wore contact lenses were grouped according to the number of years of lens wear (10 years or less, 11-20 years, and 21 years or more). RESULTS: Although a significant reduction in corneal sensitivity was found between the contact lens wearers and non-lens wearers (p = 0.000), no difference was found between the two lens-type subgroups (p = 0.939). This pattern of significance was repeated at each of the peripheral test locations. No relationship between corneal sensitivity and years of lens wear was found centrally (r2 = 0.004) or at any of the peripheral test locations. No significant difference was found between the central corneal sensation thresholds for the different subgroups of lens wear duration (p = 0.469) or for any of the peripheral test locations. CONCLUSIONS: Both soft and RGP lens wear produce a similar type of corneal sensitivity loss, although the mechanism for this loss is different for the two lens types. The extent of sensitivity loss is not related to the duration of lens wear and appears to plateau after the first few months of wear. No topographical variation in sensitivity loss was found with lens type or with the duration of lens wear.

Adult↗

Is a low transfusion threshold safe in critically ill patients with cardiovascular diseases?

OBJECTIVE: To compare a restrictive red blood cell transfusion strategy with a more liberal strategy in volume-resuscitated critically ill patients with cardiovascular disease. SETTING: Twenty-two academic and three community critical care units across Canada. STUDY DESIGN: Randomized controlled clinical trial. STUDY POPULATION: Three hundred fifty-seven critically ill patients with cardiovascular diseases from the Transfusion Requirements in Critical Care trial who had a hemoglobin concentration of <90 g/L within 72 hrs of admission to the intensive care unit. INTERVENTIONS: Patients were randomized to a restrictive strategy to receive allogeneic red blood cell transfusions at a hemoglobin concentration of 70 g/L (and maintained between 70 and 90 g/L) or a liberal strategy to receive red blood cells at 100 g/L (and maintained between 100 and 120 g/L). RESULTS: Baseline characteristics in the restrictive (n = 160) and the liberal group (n = 197) were comparable, except for the use of cardiac and anesthetic drugs (p <.02). Average hemoglobin concentrations (85 +/- 6.2 vs. 103 +/- 6.7 g/L; p <.01) and red blood cell units transfused (2.4 +/- 4.1 vs. 5.2 +/- 5.0 red blood cell units; p <.01) were significantly lower in the restrictive compared with the liberal group. Overall, all mortality rates were similar in both study groups, including 30-day (23% vs. 23%; p = 1.00), 60-day, hospital, and intensive care unit rates. Changes in multiple organ dysfunction from baseline scores were significantly less in the restrictive transfusion group overall (0.2 +/- 4.2 vs. 1.3 +/- 4.4; p =.02). In the 257 patients with severe ischemic heart disease, there were no statistically significant differences in all survival measures, but this is the only subgroup where the restrictive group had lower but nonsignificant absolute survival rates compared with the patients in the liberal group. CONCLUSION: A restrictive red blood cell transfusion strategy generally appears to be safe in most critically ill patients with cardiovascular disease, with the possible exception of patients with acute myocardial infarcts and unstable angina.

APACHE↗

Clinical applications of wall-stress analysis in the pediatric intensive care unit.

OBJECTIVE: To determine whether serial, noninvasive assessment of afterload, contractility, and Doppler-derived cardiac output reliably detects variations in cardiac function in unstable pediatric patients. DESIGN: Prospective, blinded clinical trial. SETTING: The pediatric intensive care unit at Massachusetts General Hospital. PATIENTS: Fourteen critically ill pediatric patients. INTERVENTIONS: Pediatric patients meeting criteria for hemodynamic instability underwent serial echocardiograms every 6 hrs until they met exit criteria, generating 75 studies. MEASUREMENTS AND MAIN RESULTS: Shortening fraction, cardiac index (CI), end-systolic wall stress (ESWS), and corrected velocity of circumferential shortening (Vcfc) were measured in each patient. Data points were plotted as a stress-velocity relationship, compared with published normal values, then correlated with changes in vital signs and pharmacologic interventions. Fourteen of 16 patients who were enrolled completed the study. A strong negative correlation between ESWS and Vcfc was confirmed (p < .001). As an internal measure of validity, Vcfc had a strong positive correlation with CI measurements (p = .012). An increase in dopamine infusion was associated with a fall in ESWS (p = .02), an increase in Vcfc (p = .03), and an increase in the CI as measured by Doppler (p = .035). The infusion of dopamine above renal perfusion levels moved patients from zones of normal or compensated contractility for afterload on a modified stress-velocity relationship to a zone of high contractility for afterload. Urine output was the only clinical index of cardiac function that had a significant correlation with the echocardiographic indices. Hemodynamically unstable patients followed similar patterns of deterioration and recovery on the modified stress-velocity graph. All surviving patients returned to a normal or compensated zone. CONCLUSIONS: Wall-stress analysis of cardiac function is easily and safely performed on mechanically ventilated pediatric patients with the production of consistently high-quality data. For internal validity, Vcfc and CI measurements were correlated and were strongly positive. Wall-stress indices reliably detected patient deterioration, recovery, and response to changes in dopamine infusion. Patients who failed to return to areas of normal or compensated levels of contractility and afterload did poorly in this study. Noninvasive measures of afterload and contractility appear useful for monitoring cardiac function of critically ill children in an intensive care setting.

Adolescent↗

New strategies for clinical trials in patients with sepsis and septic shock.

OBJECTIVE: The difficulty in identifying new treatment modalities that significantly reduce the mortality and morbidity rates associated with sepsis has highlighted the need to reevaluate the approach to clinical trial design. The United Kingdom Medical Research Council convened an International Working Party to address these issues. DATA SOURCES: The subject areas that were to be the focus of discussion were identified by the co-chairs, and group leaders were nominated. Preconference reading material was circulated to group members. STUDY SELECTION AND DATA EXTRACTION: Small-group discussion fed into an iterative process of feedback from plenary sessions, followed by the formulation of recommendations. Finally, each working group prepared a summary of its recommendations and these are reported herein. DATA SYNTHESIS: There were five key recommendations. First, investigators should no longer rely solely on the American College of Chest Physicians/Society of Critical Care Medicine definitions of sepsis or sepsis syndrome as the basis of trial entry. Entry criteria should be based on three principles: a) All patients should have infection; b) there should be evidence of a pathologic process that represents a biologically plausible target for the proposed intervention, for example, an abnormal circulating level of a biological marker pertinent to the study drug; and c) patients should fall into an appropriate category of severity (usually severe sepsis). Second, investigators should use a scoring system for organ dysfunctions that has been validated and that can be incorporated into all sepsis studies; agreement on the use of a single system would simplify comparisons between studies. Third, the primary outcome measure generally should be mortality rates, but under appropriate circumstances major morbidities could be considered as primary end points. Regardless of choice of the duration to primary end point, patients should be followed for > or =90 days. Fourth, sample size needs to be based on a realistic assessment of achievable effect size based on knowledge of the at-risk population. Fifth, subgroups should be few in number and should be defined a priori on the basis of variables present before randomization. CONCLUSIONS: Important changes in several aspects of trial design may improve the quality of clinical studies in sepsis and maximize the chance of identifying effective therapeutic agents.

Clinical Trials as Topic↗

Multiple organ dysfunction: baseline and serial component scores.

OBJECTIVE: The multiple organ dysfunction score (MODS) describes and quantifies organ-specific physiology. The objective of this study was to examine the relation between six components of MODS (cardiovascular, respiratory, renal, central nervous system, hepatic, and hematologic) measured at admission to the intensive care unit (ICU) and during the ICU stay, with time to death in the ICU. DESIGN: Prospective observational cohort study. SETTING: Sixteen Canadian ICUs. PATIENTS: A total of 1,200 patients were mechanically ventilated for >48 hrs. MEASUREMENTS AND MAIN RESULTS: The six organ systems comprising MODS were measured at ICU admission (baseline scores) and daily thereafter. The change in organ dysfunction each day (serial scores) were calculated as daily component scores minus the corresponding baseline component scores. In Cox regression analyses, the independent explanatory variables were the MODS components measured at baseline and serially, and the dependent variable was the time from admission to ICU mortality. When each organ system was analyzed individually, both the baseline and serial MODS for the cardiovascular, respiratory, renal, central nervous system, and hematologic components were significantly associated with ICU mortality. After adjusting for the serial hepatic score, the baseline hepatic score was unrelated to mortality. After adjusting for all baseline and serial MODS components in aggregate, four organ systems were significantly associated with ICU mortality: cardiovascular (baseline relative risk [RR], 1.5; serial RR, 1.4); respiratory (baseline RR, 1.4; serial RR, 1.4); renal (baseline RR, 1.3; serial RR, 1.5); and central nervous system (baseline RR, 1.6; serial RR, 1.7). We found that the relative risk of mortality related to organ dysfunction varied significantly over time and among organ systems. Baseline respiratory function was not associated with mortality until the second ICU week (week 1: RR, 1.1 [0.9-1.4]; week 2 onward: RR, 1.9 [1.5-2.4]); the same was true for the change in respiratory function as measured by the serial respiratory score (week 1: RR, 1.2 [1.0-1.5]; week 2 onward: RR, 1.7 [1.4-2.1]). The serial hepatic score was not associated with mortality until the fourth ICU week (weeks 1-3: RR, 0.9 [0.7-1.1]; week 4 onward: RR, 1.4 [1.0-2.0]). CONCLUSIONS: Organ dysfunction scores describe physiology at ICU admission and during ICU stay. Although patterns vary by system, daily MODS component scores provide additional prognostic value over baseline MODS.

APACHE↗

Are the Twelve Steps more acceptable to drug users than to drinkers? A comparison of experiences of and attitudes to Alcoholics Anonymous (AA) and Narcotics Anonymous (NA) among 200 substance misusers attending inpatient detoxification.

The present study is a cross-sectional interview-based investigation comparing experiences of and attitudes towards Alcoholics Anonymous (AA) and Narcotics Anonymous (NA) in a sample of 200 patients attending inpatient substance misuse detoxification services. Two hundred consecutive admissions were recruited; 100 each from one drug and one alcohol in-patient treatment service in which attendance at AA/NA was a voluntary adjunct to a generic treatment programme. Although there were no differences in the history of AA/NA attendance, the drug users (who were on average younger) reported significantly more positive attitudes towards AA/NA, more willingness to attend during their in-patient treatment and greater intention to attend following completion of their detoxification. In particular, despite no differences in spiritual/religious orientation, the drug users reported more positive views of the Twelve Steps. As AA/NA remain popular and accessible forms of substance misuse support, it is critical that we develop a clearer understanding of their impact and of the scope for their integration with generic forms of substance misuse treatment.

Adult↗

Do blood transfusions improve outcomes related to mechanical ventilation?

BACKGROUND: Correcting the decrease in oxygen delivery from anemia using allogeneic RBC transfusions has been hypothesized to help with increased oxygen demands during weaning from mechanical ventilation. However, it is also possible that transfusions hinder the process because RBCs may not be able to adequately increase oxygen delivery. In this study, we determined whether a liberal RBC transfusion strategy improved outcomes related to mechanical ventilation. METHODS: Seven hundred thirteen patients receiving mechanical ventilation, representing a subgroup of patients from a larger trial, were randomized to either a restrictive transfusion strategy, receiving allogeneic RBC transfusions at a hemoglobin concentration of 7.0 g/dL (and maintained between 7.0 g/dL and to 9.0 g/dL), or to a liberal transfusion strategy, receiving RBCs at 10.0 g/dL (and maintained between 10.0 g/dL and 12.0 g/dL). The larger trial was designed to evaluate transfusion practice rather than weaning per se. RESULTS: Baseline characteristics in the restrictive-strategy group (n = 357) and the liberal-strategy group (n = 356) were comparable. The average durations of mechanical ventilation were 8.3 +/- 8.1 days and 8.3 +/- 8.1 days (95% confidence interval [CI] around difference, - 0.79 to 1.68; p = 0.48), while ventilator-free days were 17.5 +/- 10.9 days and 16.1 +/- 11.4 days (95% CI around difference, - 3.07 to 0.21; p = 0.09) in the restrictive-strategy group vs the liberal-strategy group, respectively. Eighty-two percent of the patients in the restrictive-strategy group were considered successfully weaned and extubated for at least 24 h, compared to 78% for the liberal-strategy group (p = 0.19). The relative risk (RR) of extubation success in the restrictive-strategy group compared to the liberal-strategy group, adjusted for the confounding effects of age, APACHE (acute physiology and chronic health evaluation) II score, and comorbid illness, was 1.07 (95% CI, 0.96 to 1.26; p = 0.43). The adjusted RR of extubation success associated with restrictive transfusion in the 219 patients who received mechanical ventilation for > 7 days was 1.1 (95% CI, 0.84 to 1.45; p = 0.47). CONCLUSION: In this study, there was no evidence that a liberal RBC transfusion strategy decreased the duration of mechanical ventilation in a heterogeneous population of critically ill patients.

APACHE↗

Parallel processing and image analysis in the eyes of mantis shrimps.

The compound eyes of mantis shrimps, a group of tropical marine crustaceans, incorporate principles of serial and parallel processing of visual information that may be applicable to artificial imaging systems. Their eyes include numerous specializations for analysis of the spectral and polarizational properties of light, and include more photoreceptor classes for analysis of ultraviolet light, color, and polarization than occur in any other known visual system. This is possible because receptors in different regions of the eye are anatomically diverse and incorporate unusual structural features, such as spectral filters, not seen in other compound eyes. Unlike eyes of most other animals, eyes of mantis shrimps must move to acquire some types of visual information and to integrate color and polarization with spatial vision. Information leaving the retina appears to be processed into numerous parallel data streams leading into the central nervous system, greatly reducing the analytical requirements at higher levels. Many of these unusual features of mantis shrimp vision may inspire new sensor designs for machine vision.

Animals↗

The UK education of overseas students in speech and language therapy.

Informal evidence suggests that many overseas speech and language therapists (SLTs) either do not return to their home country on qualification or do not work as SLTs in the public sector. Many factors may contribute to this situation. However, concern that it may result in part from a poor match between UK SLT education and the demands of the role in other countries, led the Royal College of Speech and Language Therapists (RCSLT) to fund a study of overseas SLT students' experiences of UK qualifying courses. The study involved questionnaires and interviews with current students and those qualifying since May 1994. The focus of this paper is the respondents' experiences of studying and working in the UK, their views of the advantages and disadvantages of working in their home countries and the UK and supportive strategies that UK universities and other agencies might adopt. Implications of the findings are discussed.

Consumer Behavior↗

Expression of growth factors in Dictyostelium discoideum.

Growth factors and their binding proteins are important proteins regulating mammalian cell proliferation and differentiation so there is considerable interest in producing them as recombinant proteins, especially in hosts that do not already produce a complex mixture of growth factors. Many growth factors require post-translational modifications making them unsuitable for production in Escherichia coli or other prokaryotes. Since several expression vector systems have been recently developed for foreign protein production in the cellular slime mould, Dictyostelium discoideum, we attempted to use two of these systems to express human insulin-like growth factor binding protein 6 (hIGFBP6) and bovine beta-cellulin (bBTC) as secreted proteins. Although both proteins were successfully produced in stably transformed amoebae, no secretion was detected in spite of several attempts to facilitate this occurring.

Amino Acid Sequence↗

Activation of MLK2-mediated signaling cascades by polyglutamine-expanded huntingtin.

We previously reported that expression of polyglutamine-expanded huntingtin induces apoptosis via c-Jun amino-terminal kinase (JNK) activation in HN33 cells (Liu, Y. F. (1998) J. Biol. Chem. 273, 28873-28822). Extending this study, we now demonstrate a role of mixed-lineage kinase 2 (MLK2), a JNK activator, in polyglutamine-expanded huntingtin-mediated neuronal toxicity. We find that normal huntingtin interacts with MLK2, whereas the polyglutamine expansion interferes with this interaction. Similar to the expression of polyglutamine-expanded huntingtin, expression of MLK2 also induces JNK activation and apoptosis in HN33 cells. Co-expression of dominant negative MLK2 significantly attenuates neuronal apoptosis induced by the mutated huntingtin. Furthermore, over-expression of the N terminus of normal huntingtin partially rescues the neuronal toxicity induced by MLK2. Our results suggest that activation of MLK2-mediated signaling cascades may be partially involved in neuronal death induced by polyglutamine-expanded huntingtin.

Animals↗