Continuing and preventive care unit.
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Curriculum↗
Biomedical subjects
K Blake
Publications and source records attributed to K Blake.
The role of CNS glucagon-like peptide-1 (7-36) amide receptors in mediating the visceral illness effects of lithium chloride.
Peripheral administration of large doses of lithium chloride (LiCl) to rats causes a spectrum of effects that are consistent with visceral illness. LiCl reduces food intake, decreases salt ingestion after sodium depletion, induces pica, and produces robust conditioned taste aversions. Because some of the effects of peripheral LiCl are mimicked by centrally administered glucagon-like peptide-1 (7-36) amide (GLP-1), we hypothesized that this peptide is involved in the neural pathways by which LiCl causes visceral illness. To test this hypothesis, we pretreated rats with a selective and potent GLP-1 receptor antagonist given directly into the third ventricle via an indwelling cannula before administration of peripheral LiCl. The GLP-1 receptor antagonist completely blocked the effect of LiCl to reduce food intake, induce pica, and produce a conditioned taste aversion. The same dose of GLP-1 receptor antagonist did not reverse the LiCl-induced reduction in NaCl intake. The data indicate a role for GLP-1 receptors in the CNS pathway that mediates some of the effects of visceral illness.
Angiotensins↗
Learning adolescent psychosocial interviewing using simulated patients.
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Adolescent↗
The role of the route of administration of poly-chlorinated biphenyls (PCBs) on the reproductive and vital organs of adult female rats.
Studies have shown that high doses of Polychlorinated biphenyls (PCBs) given by conventional methods (orally or injections) have adverse effects on the reproductive and vital organs of adult female rats. However, there has not been documentation as to the effects of PCBs on adult female rats by means of a sustained delivery system. The specific objectives of this study were: (1) to investigate the effects of sustained delivery (TCPL ceramics) of PCB versus conventional mode of administration (injection) on the reproductive and vital organs of the adult female rat, (2) to evaluate the role that PCB that might have on the estrus events of adult female rats upon the exposure by sustained delivery (TCPL ceramics) and conventional mode (injection), and (3) to histopathologically evaluate the effect that PCB might have on the ovarian and accessory organs upon the sustained delivery for 21 days. A total of 10 adult female rats (BW 270-300 gm) were randomly divided into three groups. Group 1 (n = 3) served as the control, group 2 (n = 4) was injected intramuscularly every other day with Aroclor 1254 (0.1 cc), and each rat in-group 3 (n = 3) was implanted with TCPL capsules (5 mg of 2,3,3',4,5-Pentachlorobiphenyl). Aseptic surgical techniques were performed throughout the experiment. Blood (1 cc) was collected biweekly for biochemical analysis, and body weights were recorded as well. Pap smears were taken daily at approximately the same time for 25 days, and two slides were made for each pap taken (1 pap stain, 1 Diff Quik). At the end of 21 days post-implantation, all control and experimental animals were sacrificed following standard lab procedures (overdose of Halothane). The reproductive and vital organs were collected, weighed, fixed, embedded, sectioned, and stained (H&E) for histological evaluations. Data obtained from this investigation suggest the following: (1) TCPL devices were able to deliver PCB at sustained levels for 21 days, (2) regardless of the route of PCB administration no significant change was observed in total body weight compared to the controls, (3) conventional administration of PCB resulted in a remarkable changes in the fallopian tubes compared to control and sustained delivery implanted animals, (4) there were no obvious change was observed in the phases of estrus cycles upon the exposure of PCB, and (4) histopathological evaluation of spleen, kidneys, heart, adrenals, ovaries, uterus, and cervix tissues exposed to PCB did not reveal any significant changes compared to the intact group.
Adrenal Glands↗
Exhaled nitric oxide measurements in childhood asthma: techniques and interpretation.
In this review, we outline the role of nitric oxide in airway inflammation in children with asthma. We also discuss the various methods reported for measuring exhaled nitric oxide and provide some insight as to the pros and cons and pitfalls of these techniques. Guidelines for measurements of exhaled nitric oxide based on our experience are provided, as well as suggestions for the use of this technique as a new "airway inflammation test."
Asthma↗
Prevention of exercise-induced bronchospasm in pediatric asthma patients: a comparison of salmeterol powder with albuterol.
BACKGROUND: Exercise-induced bronchospasm (EIB) is a common problem in children with asthma. Pretreatment with the beta2 (beta 2)-adrenoreceptor agonist albuterol is effective for preventing EIB, but is recognized as providing only short-term (2 to 3 hour) protection. OBJECTIVE: To evaluate the 12-hour efficacy and safety of single doses of 25 micrograms and 50 micrograms of salmeterol powder administered via Diskus inhaler versus albuterol aerosol via pressurized metered-dose inhaler and placebo in preventing EIB in asthmatic children. METHODS: A randomized, double-blind, placebo-controlled, double-dummy, single-dose, four-way crossover study was conducted in pediatric patients (4 to 11 years of age) demonstrating EIB and mild-to-moderate asthma. Serial forced expiratory volume in 1 second (FEV1) was measured before and after standard treadmill exercise at hour 1, hour 6, and hour 12 after administration of 25 micrograms or 50 micrograms salmeterol powder, 180 micrograms albuterol aerosol, or placebo. Adverse events were recorded. RESULTS: After completion of the hour 1 exercise challenge, mean minimum % predicted FEV1 was significantly higher following albuterol (91.3%) than for placebo (75.3%) and for both dosages of salmeterol (86.9% and 85.8% for salmeterol 25 micrograms and 50 micrograms, respectively; P < or = .026). After completion of both the hour 6 and hour 12 exercise challenges, the 50-microgram salmeterol treatment produced a significantly higher mean minimum percent of predicted FEV1 (90.6% and 87.3% predicted, respectively) than the mean minimum percent of predicted FEV1 for placebo or albuterol (73.8% to 78.4% of predicted; P < or = .041). At hour 6, the 25-microgram salmeterol treatment was not significantly different from albuterol or placebo. At hour 12, the 25-microgram salmeterol treatment mean minimum percent of predicted was significantly higher than albuterol (87.9% versus 73.8% of predicted; P = .006) and there was also a trend toward significance over placebo (76.9% predicted; P = .056). At all exercise periods, no statistically significant differences in spirometry values were observed between the two salmeterol treatment groups. Safety profiles were similar among treatments, including placebo. No drug-related adverse events or withdrawals due to adverse events occurred. Changes in laboratory values, vital signs, 12-lead ECGs, and physical examinations were unremarkable. CONCLUSIONS: A single 50-microgram dose of salmeterol powder provided effective and safe protection against EIB for at least 12 hours in asthmatic children and provided a significantly more prolonged effect than albuterol aerosol (180 micrograms).
Administration, Inhalation↗
Adolescent girls as simulators of medical illness.
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Adolescent↗
Recruiting and following adolescent standardized patients.
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Adolescent↗
Montelukast dose selection in 6- to 14-year-olds: comparison of single-dose pharmacokinetics in children and adults.
Montelukast, an oral leukotriene-receptor antagonist, has demonstrated efficacy and tolerability for the treatment of chronic asthma in adults. A once-daily 10 mg dose (film-coated tablet) was selected as the optimal adult dose based on dose-ranging studies. Asthma is a similar disease and is treated with the same medications in children and adults. These observations suggested that a dose of montelukast in children providing overall drug exposure (i.e., montelukast plasma concentrations) similar to that of the 10 mg film-coated tablet dose in adults would be efficacious, well tolerated, and obviate the need for separate dose-ranging studies in children. Therefore, the dose of montelukast for 6- to 14-year-old children was selected by identifying the chewable tablet dose of montelukast yielding a single-dose area under the plasma concentration-time curve (AUC) comparable to that achieved with the adult 10 mg film-coated tablet dose. Based on this approach, which included dose normalization of data from several pediatric pharmacokinetic studies, a 5 mg chewable tablet dose of montelukast was selected for use in clinical efficacy studies in 6- to 14-year-old children with asthma.
Acetates↗
The clinical course of asymptomatic mesenteric arterial stenosis.
PURPOSE: The incidence of subsequent symptomatic mesenteric vascular disease is unknown for patients who have asymptomatic mesenteric arterial stenosis. The purpose of this study was to determine the risk of developing acute and chronic mesenteric ischemia in patients identified by lateral aortography to have significant mesenteric artery stenosis. METHODS: From 1989 through 1995, 980 consecutive aortograms with anteroposterior and lateral projections were reviewed within 1 week of arteriography to identify patients who had significant mesenteric stenosis but no symptoms of mesenteric ischemia. Eighty-two patients were found to have 50% stenosis of at least one mesenteric artery and were monitored by interview to determine if symptoms of acute or chronic mesenteric ischemia developed. RESULTS: Ten patients were lost to follow-up, and 12 patients were withdrawn from the study because of mild mesenteric arterial disease (1% to 49% stenosis) in combination with more significant disease of other vessels. Follow-up was 1 to 6 years. The overall mortality rate was 40%, and mesenteric ischemia developed in four patients. Each of these four patients had significant (>50%) stenosis or occlusion of the celiac artery, superior mesenteric artery, and inferior mesenteric artery. Eighty-six percent of the 15 patients with significant three-vessel arterial disease had mesenteric ischemia, had other vague abdominal symptoms, or died. CONCLUSIONS: Patients with significant three-vessel mesenteric arterial stenosis should be considered for prophylactic mesenteric arterial reconstruction. Mesenteric arterial reconstruction should be routine when these patients undergo aortic reconstruction for aneurysmal or occlusive disease.
Acute Disease↗
Differences in muscle contractile characteristics among bodybuilders, endurance trainers and control subjects.
The purpose of this investigation was to compare the myosin heavy chain (MHC) isoform expression of the triceps brachii muscle and isoinertial, isometric and isokinetic strength indices in competitive bodybuilders (CB, n = 5), recreational resistance trainers (RT, n = 5), endurance-trained rowers (ER, n = 5) and control (C, n = 5) subjects. Muscle tissue samples were analysed for MHC isoform content using 6% sodium dodecyl sulphate-polyacrylamide gel electrophoresis. The CB possessed significantly smaller (P < 0.05) percentage of MHC type IIb proteins [12.92 (SD 7.08)%] than RT [30.08 (SD 6.58)%] ER [31.20 (SD 2.74)%] and C [38.22 (SD 2.95)%] groups (i.e. CB < RT approximately ER < C). While the content of MHC type IIa isoforms did not differ significantly between the two resistance-trained groups [CB = 55.76 (SD 5.38)%; RT = 45.72 (SD 7.8)%], CB presented significantly more type IIa MHC isoforms than ER [42.84 (SD 2.98)%] and C [34.72 (SD 1.57)%] subjects (i.e. CB approximately RT > ER approximately C). The MHC type I protein content did not differ significantly among RT [24.20 (SD 4.89)%] ER [25.38 (SD 1.67)%] and C [27.06 (SD 1.81)%] groups. The CB [31.32 (SD 2.67)%] presented significantly more type I MHC isoforms only in comparison with RT. However, when changes in the percentage of MHC type I isoforms were converted to effect sizes (ES), it appeared that low statistical power rather than the absence of an effect accounted for the nonsignificant differences between CB and other groups (i.e. CB > RT approximately ER approximately C). Significant differences existed in isoinertial strength among the trained athletes (i.e. CB > RT > ER approximately C), while isometric and isokinetic strength were not significantly different among any of the trained groups. However, the ES transformation of data demonstrated that large differences existed between resistance-trained groups and ER for isometric and isokinetic strength (i.e. CB approximately RT > ER approximately C). A statistically significant negative correlation (P < 0.001) was found between MHC type IIb isoforms and isoinertial strength index (r = -0.68). The MHC type IIa proteins were positively related to all the strength measures considered (r = 0.51 0.61; P < 0.001). These data demonstrated different patterns of MHC isoform expression among the different groups of athletes and it is suggested that these differences on occasion may affect the expression of strength.
Adult↗
Changes in the myosin heavy chain isoform profile of the triceps brachii muscle following 12 weeks of resistance training.
The purpose of this investigation was to determine whether 12 weeks of resistance training, which increased arm girth (5%) and forearm extensor strength (39%), also altered the myosin heavy chain (MHC) characteristics of the triceps brachii muscle. Fifteen healthy, active men volunteered to participate under experimental (n = 11) or control (n = 4) conditions. The experimental group completed four sets of eight to 12 repetitions for each exercise (i.e. triceps pushdown, close grip bench press, triceps kickbacks and biceps curl) with loads of between 70-75% of one repetition maximum (1RM) three times a week. The inter-set and inter-exercise recovery period was only 90 s. Skeletal muscle tissue was removed from the triceps brachii muscle prior to (W0) and following 4 (W4), 8 (W8) and 12 (W12) weeks of the investigation. Samples were analysed for MHC isoform content using 6% sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). MHC isoform composition in the control group did not change significantly. However, the percentage of MHC type IIb isoform decreased significantly from W0 to W4 and again from W4 to W12 [W0: 39.7 (9.2); W12: 29.2 (8.2%)] in the experimental condition. The increments in MHC type IIa [W0: 34.0 (9.9); W12: 41.5 (10.4)] and type I [W0: 26.3 (7.9); W12: 29.3 (9.6)] isoforms were not significant for the experimental group. However, the effect size (ES) transformation of changes in types IIa MHC content was moderate (ES = 0.75). Changes in MHC isoform content were not significantly correlated with changes in 1RM strength for the triceps pushdown exercise. These data indicated that resistance training rapidly, and in an ongoing manner, changed the contractile protein profile of trained skeletal muscle. However, changes in MHC isoform composition in the first 12 weeks of training were not implicated in the development of 1RM triceps pushdown strength.
Adult↗
Unit profile: St George Hospital cardiac intensive care (NSW).
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Coronary Care Units↗
Evidence that normal fetal growth can be noncontinuous.
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Adult↗
Future of the State Veterinary Service.
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Government Agencies↗
Allelic losses on chromosome band 11q13 in aldosterone-producing adrenal tumors.
We examined loss of heterozygosity (LOH) in 14 aldosterone-producing adrenal tumors, with six linearly ordered restriction fragment length polymorphism (RFLP) markers that map within a 12-cM region containing the MEN1 locus on 11q13. Among 11 tumors that were informative for at least one marker, five showed LOH at one or more loci, and two distinct regions of deletion were identified. The proximal region overlapped with the location of the MEN1 locus previously predicted by linkage analyses in MEN1 families and the commonly deleted region in hyperparathyroid tumors. This suggests that one of the genes associated with development of aldosterone-producing adrenal tumors may coincide with the MEN1 locus, and that a second gene, distal to the MEN1 locus, may also play a role in the development of this type of tumor.
Adrenal Gland Neoplasms↗
Theophylline attenuation of airway responses to allergen: comparison with cromolyn metered-dose inhaler.
BACKGROUND: The purpose of this study was to compare the protection afforded by individualized doses of theophylline and a cromolyn metered-dose inhaler (MDI) during allergen challenge. METHODS: The study design was randomized, double-blind, and crossover. Responses to inhaled allergen were measured in 16 subjects with allergic asthma (age range, 18 to 35 years) after 7 days of treatment with either placebo, once daily slow-release theophylline producing a mean +/- SD serum concentration of 16 +/- 5 micrograms/ml during the late phase, or 2 mg of cromolyn administered by MDI four times daily. Forced expiratory volume in 1 second was measured at frequent intervals, and airway responsiveness to histamine was measured before and 3 hours after allergen challenge. RESULTS: The mean +/- SD maximum decrease in forced expiratory volume in 1 second during the late phase was 30% +/- 14% during placebo treatment, 16% +/- 13% during theophylline treatment, and 13% +/- 14% during cromolyn treatment (placebo vs theophylline and cromolyn, p = 0.0001; theophylline vs cromolyn, p = 0.1). The geometric mean fold increase in airway responsiveness was 3.0 +/- 1.7 during placebo treatment, 1.7 +/- 1.7 during theophylline treatment, and 1.5 +/- 1.6 during cromolyn treatment (placebo vs theophylline and cromolyn, p = 0.0001; theophylline vs cromolyn, p = 0.1). CONCLUSIONS: Theophylline, when administered once daily as a slow-release formulation, was as effective as cromolyn, administered four times daily through an MDI, in attenuating airway responses to inhaled allergen. The protection afforded by both treatments, however, was modest when compared with the results of similar studies with inhaled corticosteroids or other cromolyn formulations that deliver more drug to the lungs than the MDI available in the United States.
Adolescent↗
The effect of nedocromil sodium on childhood asthma during the viral season.
Viral-induced symptomatic respiratory infections (SRI) frequently cause exacerbations of asthma in children. This study investigated the protective effects of 0.5% nedocromil sodium nebulizer solution given three times a day in preventing asthma exacerbations associated with SRI. Ninety-three mild-moderate asthmatic children (6 to 12 yr of age) received either 0.5% nedocromil sodium or placebo for 24 wk during the viral season. The nedocromil sodium group was symptom-free 58% of the days, and the placebo-treated patients were symptom-free 45% of the days (p = 0.027). During Weeks 1-12, significant differences favored nedocromil sodium for asthma summary score (means: nedocromil sodium = 0.61, placebo = 0.92; p = 0.026), and daytime asthma (nedocromil sodium = 0.78, placebo = 1.22; p = 0.03). Significant differences were noted during monthly intervals for cough (Weeks 1-4: nedocromil sodium = 0.61, placebo = 0.92, p = 0.027) and peak expiratory flow rate (PEFR) (nedocromil sodium 262, placebo = 254 L/min, p = 0.041 Weeks 9-12). Patients in the active treatment group reduced their need for rescue inhaled beta 2-agonist by 10%, whereas patients treated with placebo demonstrated a 24% increase. There was a strong correlation between asthma symptoms and SRI symptoms (r = 0.47; p < 0.001). During SRIs, patients in the nedocromil sodium group demonstrated more rapid resolution of asthma symptoms immediately following infection (p = 0.033 summary score, p = 0.039 sleep difficulty). No serious adverse events were noted. Nedocromil sodium did not prevent the infection or exacerbation of asthma symptoms during SRI.(ABSTRACT TRUNCATED AT 250 WORDS)
Anti-Asthmatic Agents↗