Several studies have shown salmeterol to be more potent than salbutamol for systemic effects.
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Adrenergic beta-Agonists↗
Biomedical subjects
J Bennett
Publications and source records attributed to J Bennett.
Effect of long-term treatment with salmeterol on asthma control: a double blind, randomised crossover study.
OBJECTIVES: To determine the effect of adding salmeterol 50 micrograms twice daily for six months to current treatment in subjects with asthma who control their inhaled corticosteroid dose according to a management plan. DESIGN: A double blind, randomised crossover study. SETTING: Nottingham. SUBJECTS: 101 subjects with mild or moderate asthma taking at least 200 micrograms twice daily of beclomethasone dipropionate or budesonide. INTERVENTIONS: Salmeterol 50 micrograms twice daily and placebo for six months each, with a one month washout. Subjects adjusted inhaled steroid dose according to guidelines. MAIN OUTCOME MEASURE: Reduction in inhaled steroid use, exacerbations of asthma, and use of oral steroids. RESULTS: Data were available for 87 subjects. When compared with placebo salmeterol treatment was associated with a 17% reduction in inhaled steroid use (95% confidence interval 12% to 22%) with no significant difference in the number of subjects who had an exacerbation (placebo 25%, salmeterol 16%) or use of oral steroids. For secondary end points salmeterol treatment was associated with higher morning and evening peak expiratory flow and forced expiratory volume in one second; a reduction in symptoms, bronchodilator use and airway responsiveness to methacholine; and no effect on serum potassium concentration, 24 hour heart rate, or the final forced expiratory volume in one second achieved during a salbutamol dose-response study. CONCLUSIONS: In subjects who adjusted their inhaled steroid treatment according to guidelines the addition of salmeterol 50 micrograms twice daily was associated with a reduction in inhaled steroid use and improved lung function and symptom control.
Administration, Inhalation↗
International scoring system for evaluating prognosis in myelodysplastic syndromes.
Despite multiple disparate prognostic risk analysis systems for evaluating clinical outcome for patients with myelodysplastic syndrome (MDS), imprecision persists with such analyses. To attempt to improve on these systems, an International MDS Risk Analysis Workshop combined cytogenetic, morphological, and clinical data from seven large previously reported risk-based studies that had generated prognostic systems. A global analysis was performed on these patients, and critical prognostic variables were re-evaluated to generate a consensus prognostic system, particularly using a more refined bone marrow (BM) cytogenetic classification. Univariate analysis indicated that the major variables having an impact on disease outcome for evolution to acute myeloid leukemia were cytogenetic abnormalities, percentage of BM myeloblasts, and number of cytopenias; for survival, in addition to the above, variables also included age and gender. Cytogenetic subgroups of outcome were as follows: "good" outcomes were normal, -Y alone, del(5q) alone, del(20q) alone; "poor" outcomes were complex (ie, > or = 3 abnormalities) or chromosome 7 anomalies; and "intermediate" outcomes were other abnormalities. Multivariate analysis combined these cytogenetic subgroups with percentage of BM blasts and number of cytopenias to generate a prognostic model. Weighting these variables by their statistical power separated patients into distinctive subgroups of risk for 25% of patients to undergo evolution to acute myeloid leukemia, with: low (31% of patients), 9.4 years; intermediate-1 (INT-1; 39%), 3.3 years; INT-2 (22%), 1.1 years; and high (8%), 0.2 year. These features also separated patients into similar distinctive risk groups for median survival: low, 5.7 years; INT-1, 3.5 years; INT-2, 1.2 years; and high, 0.4 year. Stratification for age further improved analysis of survival. Compared with prior risk-based classifications, this International Prognostic Scoring System provides an improved method for evaluating prognosis in MDS. This classification system should prove useful for more precise design and analysis of therapeutic trials in this disease.
Acute Disease↗
A carboxy-terminal truncation of 99 amino acids resulting from a novel mutation (Arg555-->stop) in the CHM gene leads to choroideremia.
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Adolescent↗
S-HAM induction chemotherapy with or without GM-CSF in patients with high-risk myelodysplastic syndromes.
Thirty-one adult patients with high-risk myelodysplastic syndromes (MDS) were enrolled in a prospective randomized double-blind placebo-controlled trial evaluating the efficacy of sequential high-dose Ara C/mitoxantrone chemotherapy with or without GM-CSF. GM-CSF or placebo was given subcutaneously once daily at a dose of 250 micrograms/m2 starting 48 h prior to chemotherapy and continued until neutrophil recovery. This design allowed us to investigate the role of GM-CSF as a priming factor for the leukemic clone, as well as its effect on the recovery of normal hematopoiesis. Twenty-eight patients are currently evaluable for response. The patients reached a complete remission (36%), eight patients had persistent MDS (29%), and ten patients died within 6 weeks after the onset of treatment (early death). Infectious complications during cytopenia were the major cause of death (8/10). Median time to complete hematologic recovery (neutrophils > 500/microliter and platelets 20,000/microliter) and time to neutrophil recovery above 1500/microliter was 29 and 35 days, respectively. Median remission duration was 190 days (6.4 months). Analysis of prognostic subgroups showed a low CR rate (25%) and a high early-death rate (44%) in patients > 55 years of age, suggesting that the intensified treatment approach should be limited to younger patients. No data concerning the influence of GM-CSF on response to chemotherapy or duration of neutropenia are presently available.
Adult↗
Measles vaccination of Thai infants by intranasal and subcutaneous routes: possible interference from respiratory infections.
Reactogenicity and seroresponses were studied after standard doses of Edmonston-Zagreb measles vaccine were given intranasally (i.n.) and subcutaneously (s.c.) to 6-month-old Thai children. Few children given i.n. vaccine (2/31), but most (13/21) given s.c. vaccine, seroconverted. All but 1 of 51 children were seropositive after receiving vaccine s.c. at 9 months-of-age. Upper respiratory infection (URI) outbreaks with onsets in the week following vaccination occurred after each vaccination session and were equally common in all groups. URIs following i.n. vaccination at 6 months may have adversely affected response to i.n. vaccine, while URIs after s.c. vaccination at 9 months adversely affected final geometric mean antibody titers. I.n. measles vaccination does not appear to be an acceptable route for routine vaccination.
Administration, Intranasal↗
Capnography and ventilatory assessment during ambulatory dentoalveolar surgery.
PURPOSE: The purpose of this study was to determine whether capnography is a more sensitive monitor than auscultation of breath sounds in detecting ventilatory changes consistent with hypoventilation, obstruction, or apnea and in detecting ventilatory changes that can be associated with oxygen desaturation. PATIENTS AND METHODS: Fifty-five patients received intravenous agents and supplemental oxygen to achieve a state of deep sedation or general anesthesia for removal of impacted third molars. The surgeon/anesthetist monitored respiratory status using a pretracheal stethoscope and direct observation. A blinded observer with no access to the patient or anesthetist monitored respiratory status using capnography. A second observer monitored all respiratory parameters to allow for correlation between clinical and electronic monitors. RESULTS: Ventilatory status was continuously represented by capnogaphy. The Pearson correlation coefficient showed a positive correlation between increased end-tidal CO2 (PETCO2) and decreased oxygen saturation that became stronger with greater positive changes in PETCO2. An additive relationship was found between PETCO2 and respiratory rate (RR), with increased PETCO2 and decreased RR contributing to decreased oxygen saturation. CONCLUSION: Patients with nasal ventilatory exchange maintain this exchange throughout the anesthesia so that sampling of nasal PETCO2 is an effective way to monitor ventilatory status. Respiratory depression or obstructive ventilatory changes detected by capnography showed a high sensitivity and low positive predictive value in detecting oxygen desaturation. The current technology does not show a clinically satisfactory correlation between PETCO2 and oxygen saturation. However, a combined increase in PETCO2 and decrease in RR suggested a trend of decreasing oxygen saturation.
Adolescent↗
Critically ill children: the case for short-term care in general intensive care units.
This paper contests the claim that all children should be nursed in paediatric intensive care units (PICUs). Although there is an undoubted need for prolonged care to be undertaken within PICUs, they are a scarce resource and many children's critical illness is of short duration. Following a discussion on the negative aspects of transferring a critically ill child this paper then establishes how a general intensive care unit (GICU) can maintain-awareness and standards which make it a safe environment for children with a short-term critical illness, as well as contribute towards future management and practice.
Child↗
The ABCs of AMD.
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ATP-Binding Cassette Transporters↗
Spectrum of mutations in the RPGR gene that are identified in 20% of families with X-linked retinitis pigmentosa.
The RPGR (retinitis pigmentosa GTPase regulator) gene for RP3, the most frequent genetic subtype of X-linked retinitis pigmentosa (XLRP), has been shown to be mutated in 10%-15% of European XLRP patients. We have examined the RPGR gene for mutations in a cohort of 80 affected males from apparently unrelated XLRP families, by direct sequencing of the PCR-amplified products from the genomic DNA. Fifteen different putative disease-causing mutations were identified in 17 of the 80 families; these include four nonsense mutations, one missense mutation, six microdeletions, and four intronic-sequence substitutions resulting in splice defects. Most of the mutations were detected in the conserved N-terminal region of the RPGR protein, containing tandem repeats homologous to those present in the RCC-1 protein (a guanine nucleotide-exchange factor for Ran-GTPase). Our results indicate that mutations either in as yet uncharacterized sequences of the RPGR gene or in another gene located in its vicinity may be a more frequent cause of XLRP. The reported studies will be beneficial in establishing genotype-phenotype correlations and should lead to further investigations seeking to understand the mechanism of disease pathogenesis.
Carrier Proteins↗
Evaluation of Doppler ultrasonography and dynamic contrast-enhanced CT in acute and chronic renal obstruction.
The development of a reliable, minimally invasive method of distinguishing physiologically significant renal obstruction from dilation without obstruction would have important clinical implications. As it is well known that renal blood flow decreases over time in the presence of obstruction, we investigated the ability of color flow Doppler ultrasonography and dynamic contrast-enhanced CT scanning to detect changes in blood flow in unilaterally obstructed porcine kidneys. In the initial phase of this study, the effect of acute unilateral obstruction were studied in nine pigs. The resistive index (RI) was measured with Doppler ultrasonography, and renal blood flow was quantitated with dynamic CT using tracer kinetic principles and deconvolution. The RI measurements were unable to distinguish between the obstructed kidneys and their controls. Dynamic CT scanning demonstrated a greater fall in blood flow in the obstructed kidney, and this change was significantly different from baseline. The same findings were supported by radiolabelled microsphere blood-flow measurement. In the chronic portion of the study, after surgical creation of a partial ureteric obstruction, the kidneys were studied by both techniques at 1, 2, and 3 weeks. Again, RI was unable to demonstrate any difference between obstructed and unobstructed kidneys, while CT showed a progressive fall in blood flow in each successive week that was statistically significant. Dynamic contrast-enhanced CT scanning is a promising diagnostic tool that might be used to distinguish a functionally significant renal obstruction from nonobstructive dilation. Further clinical studies to validate this technique are warranted.
Acute Disease↗
Protective effects of topical antimicrobials against neonatal tetanus.
BACKGROUND: Case-control studies previously conducted in Pakistan suggested that topical antimicrobials might provide protection against neonatal tetanus (NNT) when applied to the umbilical cord wound during the first several days of life. The present case-control study, the largest such study yet reported, was undertaken in Punjab Province, Pakistan and afforded further opportunities to evaluate such effects. METHODS: A population-based, matched, case-control study was undertaken to assess topical antimicrobials and other factors related to NNT risk in rural parts of Punjab Province. RESULTS: Continuous use of antimicrobial agents (antibiotics and antiseptics) at delivery and during the first few days after delivery was highly protective in univariate testing (matched odds ratio 0.2 [95% confidence interval: 0.11-0.64], P = 0.003), and remained significantly protective when other delivery and cord care practices were controlled. In contrast, applying nothing to the wound was risky compared with antimicrobial exposures. Hand washing and delivery by a trained birth attendant appeared protective. Application of animal dung or ash to the umbilical wound was hazardous. Similarly, predelivery cutaneous or intravaginal exposure of mothers to ghee (clarified butter) and delivery on a surface prepared with dried cow dung were risky, with significant interaction noted between them. Mortality and NNT were far more likely among previous births to mothers of cases. CONCLUSIONS: Topical antimicrobials offer a new, effective and inexpensive means to prevent NNT, and could usefully complement maternal immunization with tetanus toxoid in controlling the disease. Special prevention efforts should be directed towards mothers of NNT cases.
Administration, Topical↗
Gabapentin for treatment of bipolar and schizoaffective disorders.
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Acetates↗
Improving clinical processes: one dialysis facility's experiences.
Northeast Louisiana Dialysis Center implemented continuous quality improvement (CQI) to improve the quality of care delivered to end stage renal disease (ESRD) patients treated by hemodialysis in their facility. The unit chose to address normalization of calcium and phosphorus and parathyroid hormone (PTH), anemia, nutrition, adequacy of dialysis and dialyzer reuse as well as performance benchmarks by the Health Care Financing Administration (HCFA) core indicators. This article presents the results obtained and the methodology used in this improvement effort. The article also presents nine principles the authors believe necessary for a successful CQI program.
Algorithms↗
The moral challenge of children at risk: protective policies and pediatrics. A report of the Children's Services, Inc. Task Force of Greater Cleveland.
Social workers and pediatricians are among the professionals who share a society-wide concern with current public policies regarding the placement of children at extreme risk. A healthcare professional may successfully treat a child, only to learn later that this same child was the victim of a tragic incident of domestic violence after returning home. Such events are not uncommon, create considerable frustration for pediatricians, and demand an integrated interprofessional and interdisciplinary response. This report emerged from 6 months of task force dialogue with leaders of children's services programs, healthcare professionals, clergy, ethicists, and other community leaders in one major urban environment. It indicates innovative directions in children's protective services with regard to family preservation, foster care, residential care, and adoption. The latter two options could be used much more creatively than is the case currently. The report also asserts that far too few resources are being directed to this problem area.
Adoption↗
Cell-mediated immune response and stability of intraocular transgene expression after adenovirus-mediated delivery.
PURPOSE: To evaluate the role of cell-mediated immunity in the stability of ocular adenovirus-mediated transgene expression. METHODS: Adenovirus (4 x 10(6) pfu) containing lacZ (Ad.CMVlacZ) was injected intravitreally or subretinally into one or both eyes of immunocompetent (+/+) and immunocompromised (nu/nu) CD-1 mice. Control eyes received injections of saline. Additional +/+ mice received subretinal injections of Ad.CMVlacZ with coadministration of 200 microg of human immunoglobulin (Ig) G or CTLA4Ig by intraperitoneal, intravitreal, or subretinal injection. The mice were killed at various times after injection, and their eyes were examined histologically and immunohistochemically. RESULTS: LacZ expression was extended from 1 week to more than 5 weeks in the corneal endothelium, iris, and trabecular meshwork of nu/nu mice compared with time of expression in +/+ mice when adenovirus was administered intravitreally. In contrast, subretinal injection resulted in only a minimal increase in transgene stability in nu/nu mice compared with that in +/+ mice. Neither systemic nor intraocular administration of IgG or CTLA4Ig affected the stability of lacZ expression in the retina or retinal pigment epithelium after subretinal injection in +/+ mice. Immunoglobulin G and CTLA4Ig enhanced the stability of transgene expression in the trabecular meshwork. CONCLUSIONS: A T-cell-mediated immune response appears to play a role in the loss of adenovirus-mediated lacZ expression after intravitreal but not after subretinal injection. This result implies that the subretinal space is an immune-privileged site and a favorable site for gene transfer.
Abatacept↗
Real-time, noninvasive in vivo assessment of adeno-associated virus-mediated retinal transduction.
PURPOSE: To evaluate the efficiency, cell specificity, stability, and toxicity of recombinant adeno-associated virus (rAAV)-mediated retinal transduction in vivo in the adult immunocompetent mouse. To assess the usefulness of green fluorescent protein (GFP) for real-time, noninvasive monitoring of retinal transgene expression in vivo. METHODS: Assessment of ocular GFP expression was performed in cohorts of mice for 11 weeks after subretinal injection of a recombinant adeno-associated virus carrying the complementary DNA (cDNA) for GFP. Examinations were performed in vivo by direct observation of fluorescence by ophthalmoscopy, using excitation-barrier filters. Histologic analyses of retinal tissue were used to identify transduced cells and to assess inflammation. RESULTS: Retinal GFP expression can be monitored in vivo using real-time, noninvasive imaging. Recombinant AAV efficiently transduces a variety of cells of the neural retina and of the retinal pigment epithelium (RPE). Transgene expression was not observed until 1 week after infection. The number of GFP-expressing cells increased over 3 weeks, and expressing photoreceptors and RPE, cells persisted at least through 11 weeks (the termination of the experiment). There was no clinical or histologic evidence of inflammatory response. CONCLUSIONS: Retinal gene transfer mediated by rAAV is stable and efficient and is associated with no clinically or histologically detectable toxicity or immune reaction. Green fluorescent protein allows noninvasive assessment of the extent and location of retinal transgene expression as a function of time and promises to be useful alone and as a tag for other transgenes delivered experimentally or therapeutically to the retina.
Animals↗
Humoral response after administration of E1-deleted adenoviruses: immune privilege of the subretinal space.
An important limitation of E1-deleted recombinant adenoviruses in gene therapy is the immune response that they engender and that rapidly destroys transduced cells. Transduced cells of the outer retina appear to be an exception. To determine whether differences in immune sequestration of the outer retina contribute to the increased stability of transgene expression in this tissue, we examined the systemic humoral response to an E1-deleted adenovirus injected into the subretinal space. Subretinal injection of Ad.CMVlacZ in mature immunocompetent mice resulted in minimal circulating antibody production. In contrast, subcutaneous administration of equivalent doses of Ad.CMVlacZ resulted in high-titer antibody production against adenoviral proteins. Circulating antibodies in systemically immunized animals had minimal effect on retinal transgene expression patterns measured 2 weeks after subretinal injection of Ad.CMVlacZ. Histologic examination showed minimal retinal toxicity attributable to subretinal adenovirus in naive or immunized mice, although 3/18 (14%) of eyes from the latter set contained a localized granulomatous infiltrate at the ocular injection site. The data demonstrate that the subretinal space is an immune-privileged site regarding humoral immunity. Further, short-term transduction efficiency is not affected by the presence of anti-adenoviral antibodies. The retina may be a favorable environment for replication-defective virus-mediated genetic therapy.
Adenovirus E1 Proteins↗