Treatment of aqueous misdirection by trans-scleral diode laser photocoagulation.
Explore the source record for details and available documents.
Aged↗
Biomedical subjects
J Morgan
Publications and source records attributed to J Morgan.
A capillary whole blood method for measuring the INR.
This study describes a method of measuring the INR on native whole blood capillary samples using Innovin recombinant thromboplastin. Modification of the reagent was necessary to compensate for the nonoptimal level of calcium in the sample/reagent mixture. Ninety-five percent of results obtained by the capillary blood method were no more than 0.42 INR higher or 0.38 INR lower than the venous blood method. The effect of changes in haematocrit was minimal. Significant differences in results were found between the Innovin and Thrombotest capillary blood methods. Provided the reagent was properly stored, there was no reagent drift and satisfactory results were obtained on samples supplied by UKNEQAS (coagulation) from previous trials. The method described is a convenient, simple and accurate method of measuring the INR using native capillary whole blood and Innovin recombinant thromboplastin.
Blood Coagulation Tests↗
An investigation into diet treatment for adults with previously untreated phenylketonuria and severe intellectual disability.
There is evidence in the literature which suggests that adults with previously untreated phenylketonuria (PKU) benefit from a low phenylalanine diet. A prospective study providing a phenylalanine-restricted diet to five subjects with severe intellectual disability arising from untreated PKU is reported. Physical, social and behavioural measures were used to monitor the effects of the diet Four out of the five subjects derived considerable benefit. It is concluded that the restricted diet is worth trying in most individuals with previously untreated PKU, and that possible benefits are in the areas of concentration, alertness, mood, irritability and adaptive behaviour.
Adult↗
Comparative mortality of hemodialysis and peritoneal dialysis in Canada.
BACKGROUND: Comparisons of mortality rates in patients on hemodialysis versus those on peritoneal dialysis have been inconsistent. We hypothesized that comorbidity has an important effect on differential survival in these two groups of patients. METHODS: Eight hundred twenty-two consecutive patients at 11 Canadian institutions with irreversible renal failure had an extensive assessment of comorbid illness collected prospectively, immediately prior to starting dialysis therapy. The cohort was assembled between March 1993 and November 1994; vital status was ascertained as of January 1, 1998. RESULTS: The mean follow-up was 24 months. Thirty-four percent of patients at baseline, 50% at three months, and 51% at six months used peritoneal dialysis. Values for a previously validated comorbidity score were higher for patients on hemodialysis at baseline (4.0 vs. 3.1, P < 0.001), three months (3.7 vs. 3.2, P = 0.001), and six months (3.6 vs. 3.2, P = 0.005). The overall mortality was 41%. The unadjusted peritoneal dialysis/hemodialysis mortality hazard ratios were 0.65 (95% CI, 0. 51 to 0.83, P = 0.0005), 0.84 (95% CI, 0.66 to 1.06, P = NS), and 0. 83 (95% CI, 0.64 to 1.08, P = NS) based on the modality of dialysis in use at baseline, three months, and six months, respectively. When adjusted for age, sex, diabetes, cardiac failure, myocardial infarction, peripheral vascular disease, malignancy, and acuity of renal failure, the corresponding hazard ratios were 0.79 (95% CI, 0. 62 to 1.01, P = NS), 1.00 (95% CI, 0.78 to 1.28, P = NS), and 0.95 (95% CI, 0.73 to 1.24, P = NS). Adjustment for a previously validated comorbidity score resulted in hazard ratios of 0.74 (95% CI, 0.58 to 0.94, P = 0.01), 0.94 (95% CI, 0.74 to 1.19, P = NS), and 0.88 (95% CI, 0.68 to 1.13, P = NS) at baseline, three months, and six months. There was no survival advantage for either modality in any of the major subgroups defined by age, sex, or diabetic status. CONCLUSIONS: The apparent survival advantage of peritoneal dialysis in Canada is due to lower comorbidity and a lower burden of acute onset end-stage renal disease at the inception of dialysis therapy. Hemodialysis and peritoneal dialysis, as practiced in Canada in the 1990s, are associated with similar overall survival rates.
Canada↗
Comparative hospitalization of hemodialysis and peritoneal dialysis patients in Canada.
BACKGROUND: Most comparisons of hemodialysis (HD) and peritoneal dialysis (PD) have used mortality as an outcome. Relatively few studies have directly compared the hospitalization rates, an outcome of perhaps equal importance, of patients using these different dialysis modalities. METHODS: Eight hundred twenty-two consecutive patients at 11 Canadian institutions with irreversible renal failure had an extensive assessment of comorbid illness and initial mode of dialysis collected prospectively immediately prior to starting dialysis therapy. The cohort was assembled between March 1993 and November 1994. The mean follow-up was 24 months. Admission data were used to compare hospitalization rates in HD and PD. RESULTS: Thirty-four percent of patients at baseline and 50% at three months used PD. Twenty-five percent of HD and 32% of PD patients switched dialysis modality at least once after their first treatment (P = NS). Nine percent of HD patients and 30% of PD patients switched modality after three months (P < 0. 001). Total comorbidity was higher in HD patients at baseline (P < 0. 001) and at three months (P = 0.001). The overall hospitalization rate was 40.2 days per 1000 patient days after baseline and 38.0 days per 1000 patient days after three months. When an adjustment was made for baseline comorbid conditions, patients on PD had a lower rate of hospitalization in intention-to-treat analysis according to the type of dialysis in use at baseline (RR 0.85, 95% CI, 0.82 to 0.87, P < 0.001), but a higher rate according to the type of dialysis in use three months after study entry (RR 1.31, 95% CI, 1.27 to 1.34, P < 0.001). In analyses based on the amount of time actually spent on each treatment modality, PD was associated with a higher rate of hospitalization when analyzed according to the type of dialysis in use at baseline (RR 1.10, 95% CI, 1.07 to 1.13, P < 0.001) and according to the type of dialysis in use three months after study entry (RR 1.26, 95% CI, 1.23 to 1.30, P < 0.001). CONCLUSIONS: Conclusions regarding comparative hospitalization rates are heavily dependent on the analytic starting point and on whether intention-to-treat or treatment-received analyses are used. When early treatment switches are accounted for, HD is associated with a lower rate of hospitalization than PD, but the effect is modest.
Canada↗
Effect of hemoglobin levels in hemodialysis patients with asymptomatic cardiomyopathy.
BACKGROUND: Hemoglobin levels below 10 g/dL lead to left ventricular (LV) hypertrophy, LV dilation, a lower quality of life, higher cardiac morbidity, and a higher mortality rate in end-stage renal disease. The benefits and risks of normalizing hemoglobin levels in hemodialysis patients without symptomatic cardiac disease are unknown. METHODS: One hundred forty-six hemodialysis patients with either concentric LV hypertrophy or LV dilation were randomly assigned to receive doses of epoetin alpha designed to achieve hemoglobin levels of 10 or 13.5 g/dL. The study duration was 48 weeks. The primary outcomes were the change in LV mass index in those with concentric LV hypertrophy and the change in cavity volume index in those with LV dilation. RESULTS: In patients with concentric LV hypertrophy, the changes in LV mass index were similar in the normal and low target hemoglobin groups. The changes in cavity volume index were similar in both targets in the LV dilation group. Treatment-received analysis of the concentric LV hypertrophy group showed no correlation between the change in mass index and a correlation between the change in LV volume index and mean hemoglobin level achieved (8 mL/m2 per 1 g/dL hemoglobin decrement, P = 0.009). Mean hemoglobin levels and the changes in LV mass and cavity volume index were not correlated in patients with LV dilation. Normalization of hemoglobin led to improvements in fatigue (P = 0.009), depression (P = 0.02), and relationships (P = 0.004). CONCLUSIONS: Normalization of hemoglobin does not lead to regression of established concentric LV hypertrophy or LV dilation. It may, however, prevent the development of LV dilation, and it leads to improved quality of life.
Adult↗
Bone marrow micrometastases and gastrointestinal cancer detection and significance.
Accurate staging of cancer is important, as the presence or absence of systemic spread determines treatment. The sensitivity of current imaging and biochemical techniques is suboptimal for the detection of minimal residual disease and latent metastases. This results in understaging and potential undertreatment. To improve detection of disseminated epithelial malignancy, immunohistochemical and molecular methods have been employed that search for epithelial cell-specific proteins in nonepithelial tissue. Bone marrow is mesenchymal tissue (that does not normally express epithelial cell components) and represents an accessible window for detection of micrometastatic carcinoma cells. Detection methods for epithelial cell components (cytokeratins, epithelial membrane antigen, carcinoembryonic antigen) include immunohistochemistry, flow cytometry, reverse transcriptase polymerase chain reaction (rt-PCR), and enzyme linked immunoassay (ELISA). Micrometastatic cells in bone marrow are viable, capable of proliferation, resistant to immune attack, and insensitive to s-phase chemotherapeutic agents. Patients with carcinomas of the lung, breast, prostate, or gastrointestinal tract and in whom bone marrow micrometastases are detected have a foreshortened interval to recurrence and impaired survival. Detection of micrometastases deserves serious consideration in treatment protocols, and standardization of methods is now required.
Bone Marrow Neoplasms↗
Comparison of photodynamic targets in a carcinoma cell line and its mitochondrial DNA-deficient derivative.
The relative contribution, to cell death, of photodynamic damage to respiratory proteins (known targets of photodynamic therapy with many photosensitizers) and other cellular sites was examined. The models were a human ovarian carcinoma cell line 2008, and its mitochondrial DNA-deficient derivative ET3, which lacks several key respiratory protein subunits. Phototoxicity was compared in the two cell lines with photosensitizers that localized to different cellular compartments. Photosensitizers included Victoria Blue BO (VBBO; mitochondria); Photofrin with a short incubation, (plasma membrane) or a long incubation (intracellular membranes including mitochondria); and Nile Blue A (NBA; lysosomes). Photosensitizer content and localization did not differ between the 2008 and ET3 cells. For sensitizers without a primary mitochondrial localization (NBA and Photofrin with a short incubation), there was no significant difference between 2008 and ET3 toxicity. Consistent with a mitochondrial localization of VBBO and independence from respiratory-chain damage, ET3 cells were less susceptible than 2008 to both dark- and light-activated VBBO-mediated damage. Statistical analysis of the data demonstrated minimal photobleaching of VBBO and a significant difference between the phototoxicity curves of ET3 and 2008. For Photofrin with a long incubation, dark- and phototoxicity effects were similar for both cell lines. Inhibition of respiratory enzymes is thus only a minor component of Photofrin-mediated (long incubation) phototoxicity in these cell lines and is overwhelmed by more significant damage elsewhere, whereas it is a major but not the exclusive element of death mediated by VBBO.
DNA, Mitochondrial↗
Triage: a retrospective evaluation.
Explore the source record for details and available documents.
Emergency Nursing↗
Cerebral oxygenation at high altitude and the response to carbon dioxide, hyperventilation and oxygen. The Birmingham Medical Research Expeditionary Society.
Cerebral oxygenation is likely to be of critical importance in determining function at high altitude. The present study has used the technique of near-IR spectroscopy to monitor changes in cerebral regional oxygenation in response to inhaled carbon dioxide, hyperventilation and supplementary oxygen on ascent to 4680 m over 3 days. At sea level, inhaled CO(2) resulted in a significant rise in cerebral regional oxygenation [from mean 69.6% (S.D. 2.4% to 71. 1+/-2.3%; means+/-S.D.; P<0.001). At 4680 m, CO(2) increased regional cerebral oxygenation (63.8+/-2.5% to 65.9+/-2.2%; P<0.001) and also increased peripheral oxygen saturation (75.1+/-6.1% to 83. 6+/-4.0%; P<0.001). Voluntary hyperventilation resulted in improved peripheral oxygen saturation at 2770 m, 3650 m and 4680 m, whereas cerebral regional oxygenation was reduced at sea level and at 2770 m, unchanged at 3650 m and increased at 4680 m. Supplementary oxygen (6 1itres/min) at 4680 m resulted in greater improvements in peripheral oxygen saturation (76.7+/-7.9% to 98.1+/-1.5%; P<0.001) and cerebral regional oxygenation (64.6+/-3.3% to 70.6+/-2.9%; P<0. 001) than were found with CO(2) or hyperventilation. We conclude that attempts to increase CO(2) inhalation or ventilation at high altitude are likely to be beneficial for cerebral oxygenation in the short term.
Adult↗
Thrombolysis in the air. Air-ambulance paramedics flying to remote communities treat patients before hospitalization.
PROBLEM ADDRESSED: First Nations* communities in the North have a high prevalence of coronary artery disease and type 2 diabetes and face an increasing incidence of myocardial infarction (MI). Many conditions delay timely administration of thrombolysis, including long times between when patients first experience symptoms and when they present to community nursing stations, delays in air transfers to treating hospitals, uncertainty about when planes are available, and poor flying conditions. OBJECTIVE OF PROGRAM: To develop a program for administration of thrombolysis on the way to hospital by air ambulance paramedics flying to remote communities to provide more rapid thrombolytic therapy to northern patients experiencing acute MIs. COMPONENTS OF PROGRAM: Critical care flight paramedics fly to northern communities from Sioux Lookout, Ont; assess patients; communicate with base hospital physicians; review an exclusion criteria checklist; and administer thrombolytics according to the Sioux Lookout District Health Centre/Base Hospital Policy and Procedure Manual. Patients are then flown to hospitals in Sioux Lookout; Winnipeg, Man; or Thunder Bay, Ont. CONCLUSION: This thrombolysis program is being pilot tested, and further evaluation and development is anticipated.
Adult↗
Premillennial and postmillennial coding.
Explore the source record for details and available documents.
Abstracting and Indexing↗
The impact of a structured programme of asthma care in general practice.
The impact of a new GP programme of asthma care was examined using: a) a retrospective pre- and post-casenote survey of 400 asthma patients, comparing patients in practices using the health board programme (HBP) and other programmes (OP); and b) a patient satisfaction questionnaire, completed by 532 people on asthma clinic lists in HBP and OP practices. Outcomes assessed were health service use, perceived change in symptoms and asthma self-management. The casenote survey indicated improved health service use by patients in HBP practices, with fewer patient-initiated (p < 0.05), emergency (p < 0.05) and other chest-related attendances (p < 0.01) and increased clinic attendance (p < 0.05) post intervention. OP practices also showed reduced patient-initiated (p < 0.01) and increased asthma clinic use (p < 0.01). Increased use of management plans (p < 0.01) and peak flow diaries (p < 0.01) was noted post intervention for HBP practices. Responders to the questionnaire survey perceived that clinic attendance improved asthma symptoms, including severity and control, sleep disturbance and early morning wheeze. People in HBP practices were more likely than those in OP practices to possess a peak flow meter, a diary and a personal management plan (all p < 0.01 or above) but were not more likely to use a peak flow diary. Notwithstanding methodological difficulties in the selection of practices, both studies showed trends towards improvement in health service use and asthma self-management. The HBP was associated with greater improvement in self-management processes and outcomes, and greater patient satisfaction with asthma care.
Adolescent↗
Reversal of metabolic block in glycolysis by enzyme replacement in triosephosphate isomerase-deficient cells.
Inherited deficiency of the housekeeping enzyme triosephosphate isomerase (TPI) is the most severe clinical disorder of glycolysis. Homozygotes manifest congenital hemolytic anemia and progressive neuromuscular impairment, which in most cases pursues an inexorable course with fatal outcome in early childhood. No effective therapy is available. Hitherto specific enzyme replacement has not been attempted in disorders of glycolysis. Primary skeletal muscle myoblasts and Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines generated from homozygous TPI-deficient patients were cultured in the presence of exogenous enzyme or cocultured with human K562 erythroleukemia cells as an exogenous source of TPI. Uptake of active enzyme by TPI-deficient cells resulted in reversal of intracellular substrate accumulation, with a reduction in dihydroxyacetone phosphate (DHAP) concentration to levels seen in TPI-competent cells. Evidence of successful metabolic correction of TPI deficiency in vitro establishes the feasibility of enzyme replacement therapy, and has important implications for the potential role of allogeneic bone marrow transplantation and gene therapy as a means of sustained delivery of functional enzyme in vivo.
Adolescent↗
Indications for cholesterol-lowering medication: comparison of risk-assessment methods.
BACKGROUND: Recommendations for the prescription of lipid-lowering drugs emphasise the importance of an assessment of absolute coronary heart disease (CHD) risk based on all risk factors, rather than simply the serum cholesterol concentration. If, however, the methods recommended for risk assessment are inaccurate, recommended prescribing will not occur. We compared several sets of guidelines for such treatment in a series of patients referred to a lipid clinic, to assess the difference in degree of risk of CHD at which lipid-lowering medication is recommended by each set of guidelines. METHODS: For a series of 570 patients (50% men) without pre-existing clinical evidence of atherosclerosis referred to a lipid clinic, we compared the algorithms, charts, and tables used by the US National Cholesterol Education Program (NCEP), the joint guidelines of the European Society of Cardiology, the European Atherosclerosis Society, and the European Society of Hypertension, and the report of the UK Standing Medical Advisory Committee with the Framingham risk equation programmed into a computer. FINDINGS: In 386 patients for whom the NCEP and UK guidelines could be compared, 62% of the men and 72% of the women met NCEP criteria for lipid-lowering medication, whereas only 9% of the men and less than 1% of the women met the UK criteria. The Framingham equation estimated a CHD risk of more than 3% per year in 22% of the men and 7% of the women, which shows that the UK tables underestimated CHD risk. European guidelines could be applied to only 261 patients, and were reasonably accurate in assessment of a CHD risk of 2% per year. INTERPRETATION: Guidelines for the use of statin treatment in patients with CHD differ in their assessment of CHD risk. The method of risk assessment recommended in future guidelines for CHD prevention should be critically tested in relevant groups of patients.
Algorithms↗
Control of porcine proliferative enteropathy by oral administration of chlortetracycline.
Explore the source record for details and available documents.
Administration, Oral↗
Nitric oxide mediates excitotoxic and anoxic damage in rat retinal ganglion cells cocultured with astroglia.
BACKGROUND: Nitric oxide has been implicated in the process of retinal ganglion cell death in glaucoma. OBJECTIVE: To investigate the role of nitric oxide in mediating retinal ganglion cell death in a culture system that models glial-neuronal interactions at the level of the optic nerve head. METHODS: Dissociated retinal ganglion cells from neonatal rats were plated on monolayers of astroglia and identified by retrograde labeling with the fluorescent marker 1.1-dioctadecyl-,3,3,3,tetramethylindocarbocyanineperchlorate. Two days after dissociation, cocultures of retinal ganglion cells and glia were treated with graded concentrations of the nitric oxide synthase inhibitor N-nitro-L-arginine (NNA), and exposed to either anoxia for 1 to 24 hours or excitatory amino acids for 6 hours. Surviving retinal ganglion cells were counted with fluorescence microscopy and expressed as a percentage of retinal ganglion cells surviving in control cultures. RESULTS: Cell survival after anoxia increased in a dose-dependent fashion with exposure to NNA. Mean +/- SD survival rate of retinal ganglion cells after 6 hours of anoxia was 57%+/-10% with NNA treatment compared with 31%+/-3% without treatment (P<.01). When treated with excitatory amino acids, cell survival was 31%+/-6% after administration of N-methyl D-aspartate, 500 micromol/L, and 27%+/-8% after administration of sodium glutamate, 500 micromol/L. Survival was increased in cultures with exposure to NNA, 100 micromol/L, to 53%+/-11% and 69%+/-11%, respectively (P<.01). CONCLUSION: In this coculture of retinal ganglion cells and astroglia, reduction of the glial source of nitric oxide through nitric oxide synthase inhibition provided partial but significant protection against the lethal effects of anoxia and excitatory amino acids on retinal ganglion cells. CLINICAL RELEVANCE: Neuroprotective agents may play a role in patients with glaucoma who have progressive visual field loss, despite satisfactory control of intraocular pressure. Inhibition of nitric oxide synthase at the level of the optic nerve head may contribute to a clinically significant level of neuroprotection.
Animals↗
Pharmacokinetics and tolerability of formoterol in healthy volunteers after a single high dose of Foradil dry powder inhalation via Aerolizer.
OBJECTIVE: The pharmacokinetics of the long-acting beta2-agonist formoterol fumarate, which is a racemate of the (S,S)- and (R,R)-enantiomers were evaluated in 12 healthy (eight male, four female) volunteers after a single inhaled high dose of 120 microg of formoterol fumarate. The tolerability and safety were also assessed. METHODS: Each volunteer inhaled the single 120-microg dose through the Aerolizer device within 2-5 min, using ten 12-microg dry powder capsules for inhalation. Formoterol, i.e., the sum of both enantiomers, was determined in plasma over 24 h, whereas the separate enantiomers were determined in urine over 48 h. Incidence, seriousness and severity of adverse experiences, electrocardiogram (ECG), including the corrected QT interval (QTc) calculation, systolic blood pressure, heart rate, and plasma potassium levels were recorded. RESULTS: In nine of the 12 volunteers, the peak plasma concentration of formoterol was observed already at 5 min after inhalation. The absorption kinetics were complex, as depicted by multiple peaks or shoulders within 0.5-6 h after inhalation. Mean with (SD; n = 12) of maximum concentration (Cmax) and area under the curve (AUC) of formoterol in plasma were 266 (108) pmol x l(-1) and 1330 (398) pmol x l(-1), respectively. The moderate inter-individual variability in systemic exposure of formoterol reflects the homogeneous pharmacokinetics of the drug. A predominant slow elimination of formoterol from plasma with a mean half-life (t1/2) of 10 h was demonstrated. Assuming linear kinetics in plasma suggested by urinary data, the steady-state trough plasma levels of formoterol for a b.i.d. dosing regimen are predicted to amount to 20% of Cmax. In urine, mean with (SD; n = 10) of the amount excreted over 48 h was 3.61 (0.89)% of dose for the pharmacologically active (R,R)-enantiomer and 4.80 (1.33)% of dose for the (S,S)-enantiomer. The terminal half-lives calculated from the excretion rate-time curves, i.e., 13.9 h and 12.3 h for the (R,R)- and (S,S)-enantiomer, respectively, confirm the slow elimination of formoterol from plasma. The dose inhaled was 10 times the most frequently recommended dose (12 microg) and 5 times the highest recommended dose (24 microg). Ten of 12 subjects experienced mild and transient nervousness. Pulse readings demonstrated the maximum mean increase of 25.8 beats x min(-1) at 6 h. The mean maximum QTc increase was 25 msec at 6 h. Pulse and QTc values returned to baseline or close to baseline values at 24 h or before. Potassium levels in plasma decreased in eight out of 12 subjects; the lowest mean value was 3.53 mmol x l(-1) at 2 h post-dose. The lowest individual potassium measurement was 2.95 mmol x l(-1) between 15 min and 6 h. By 8 h post-dose all values had returned to within the normal ranges. CONCLUSIONS: The extremely fast appearance of formoterol in plasma shows the predominance of airways absorption shortly after inhalation. Due to a terminal elimination half-life of about 10 h, sustained systemic concentrations of formoterol are predicted for a twice daily treatment regimen without noteworthy accumulation. The excreted amounts in percent of dose of the enantiomers in urine and the enantiomer ratio are similar to data reported previously after lower doses and suggest linear kinetics for doses between 12 microg and 120 microg of formoterol fumarate. The expected side effects on heart rate, QTc interval, and plasma potassium were small and had no clinical consequences in spite of the very high dose of 120 microg (5 to 10 times the recommended therapeutic dose of Foradil). It should be noted that the impact of high doses may be greater in patients. Nevertheless these findings provide reassurance on the safety margin of formoterol after accidental and intentional overdosing.
Administration, Inhalation↗