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Biomedical subjects

A Allen

Publications and source records attributed to A Allen.

At least 55 records · Page 3Linked to original sources

School preparation for the asthmatic student.

Questionnaires given to school nurses were used to collect data regarding emergency asthma equipment and plans. Sixty-three percent reported <10 asthmatic visits per month, 25% reported 10-50, and 12% reported >50. Only 20% of school nurses reported that 75%-100% of asthmatic students had an emergency plan, and 24% did not know if asthmatic students had a plan. Only half of the nurses had input into the plan. Equipment varied: 16% had oxygen, 45% had peak flow meters, 0% had MDIs, and 20% had nebulizers available. Many asthmatic students lack emergency plans, and many school nurses are not involved in the plans.

Asthma↗

Rosiglitazone does not alter the pharmacokinetics of metformin.

Rosiglitazone is a potent oral antidiabetic agent of the thiazolidinedione class that works through activation of the peroxisome proliferator-activated nuclear receptor. It improves insulin sensitivity in peripheral tissues and effectively lowers blood glucose in patients with type 2 diabetes. Metformin is a dimethyl-biguanide, also used in type 2 diabetes, that lowers fasting blood glucose primarily by decreasing hepatic glucose output. Rosiglitazone and metformin reduce plasma glucose concentrations via different mechanisms and thus could potentially be used in combination to optimize glycemic control. This study evaluated the effects of the coadministration of these two agents on the pharmacokinetics of both rosiglitazone and metformin. Sixteen male volunteers (22-55 years old) received oral metformin (500 mg every 12 hours), rosiglitazone (2 mg every 12 hours), or the combination each for 4 days. Plasma collected on day 4 of each regimen was assayed for rosiglitazone and metformin concentrations. Oral doses of rosiglitazone and metformin were safe and well tolerated when administered alone or in combination. There were no clinically significant episodes of hypoglycemia or increased blood lactic acid levels following treatment with any regimen. Coadministration of rosiglitazone and metformin had no significant effects on the steady-state pharmacokinetics (AUC(0-12 h), Cmax, tmax, or t1/2) of either drug. The authors conclude that rosiglitazone can be safely administered with metformin and, due to the different mechanisms of action of these agents, may offer a therapeutic advantage in patients with type 2 diabetes mellitus.

Acidosis, Lactic↗

Randomized secondary prevention trial of azithromycin in patients with coronary artery disease and serological evidence for Chlamydia pneumoniae infection: The Azithromycin in Coronary Artery Disease: Elimination of Myocardial Infection with Chlamydia (ACADEMIC) study.

BACKGROUND: Chlamydia pneumoniae commonly causes respiratory infection, is vasotropic, causes atherosclerosis in animal models, and has been found in human atheromas. Whether it plays a causal role in clinical coronary artery disease (CAD) and is amenable to antibiotic therapy is uncertain. METHODS AND RESULTS: CAD patients (n=302) who had a seropositive reaction to C pneumoniae (IgG titers >/=1:16) were randomized to receive placebo or azithromycin, 500 mg/d for 3 days, then 500 mg/wk for 3 months. Circulating markers of inflammation (C-reactive protein [CRP], interleukin [IL]-1, IL-6, and tumor necrosis factor [TNF]-alpha), C pneumoniae antibody titers, and cardiovascular events were assessed at 3 and 6 months. Treatment groups were balanced, with age averaging 64 (SD=10) years; 89% of the patients were male. Azithromycin reduced a global rank sum score of the 4 inflammatory markers at 6 (but not 3) months (P=0. 011) as well as the mean global rank sum change score: 531 (SD=201) for active drug and 587 (SD=190) for placebo (P=0.027). Specifically, change-score ranks were significantly lower for CRP (P=0.011) and IL-6 (P=0.043). Antibody titers were unchanged, and number of clinical cardiovascular events at 6 months did not differ by therapy (9 for active drug, 7 for placebo). Azithromycin decreased infections requiring antibiotics (1 versus 12 at 3 months, P=0.002) but caused more mild, primarily gastrointestinal, adverse effects (36 versus 17, P=0.003). CONCLUSIONS: In CAD patients positive for C pneumoniae antibodies, global tests of 4 markers of inflammation improved at 6 months with azithromycin. However, unlike another smaller study, no differences in antibody titers and clinical events were observed. Longer-term and larger studies of antichlamydial therapy are indicated.

Anti-Bacterial Agents↗

Clomipramine vs desipramine crossover trial in body dysmorphic disorder: selective efficacy of a serotonin reuptake inhibitor in imagined ugliness.

BACKGROUND: Body dysmorphic disorder (preoccupation with an imagined or slight defect in appearance) is a common and disabling disorder associated with high rates of delusional symptoms and suicide attempts. Although preliminary studies suggest that serotonin reuptake inhibitors may be effective for body dysmorphic disorder, to date no controlled treatment studies have been published. METHODS: Forty patients were enrolled and 29 were randomized into a 16-week, double-blind, crossover-design study of clomipramine, a potent serotonin reuptake inhibitor, and active control desipramine, a selective norepinephrine reuptake inhibitor. Outcome measures included specific ratings of body dysmorphic disorder severity, delusionality, and functional impairment. RESULTS: Clomipramine was superior to desipramine in the acute treatment of body dysmorphic disorder symptoms as measured by assessment of patients' obsessive preoccupation with perceived body defects, repetitive behaviors in response to this preoccupation, and global ratings of symptom severity. Treatment efficacy was independent of the presence or severity of comorbid diagnoses of obsessive-compulsive disorder, depression, or social phobia. Likewise, clomipramine was equally effective regardless of whether the patients had insight or held their dysmorphic misperception with delusional intensity. Clomipramine was also superior to desipramine in improving functional disability. CONCLUSIONS: Clomipramine is more effective than desipramine in the treatment of body dysmorphic disorder and is effective even among those patients who are delusional.

Adrenergic Uptake Inhibitors↗

Systemic exposure to rosiglitazone is unaltered by food.

OBJECTIVE: To evaluate the effect of food on the bioavailability and pharmacokinetics of the insulin sensitizer rosiglitazone. METHODS: In a randomized, open-label, period-balanced, single-dose, crossover study, rosiglitazone 2 mg was administered to 12 healthy male volunteers either in the fasting state or following a standard high-fat breakfast. The primary end points of the study were AUC(0-inf) and Cmax. RESULTS: Single oral doses of rosiglitazone were safe and well tolerated. Overall exposure to rosiglitazone was unaffected by food. The geometric mean ratio of AUC(0-inf) in the fed:fasted regimens was 0.94 (95% CI: 0.82, 1.06); t1/2 was unaffected. Absorption of rosiglitazone in the fed state was more gradual and sustained than in the fasted state. Cmax was reduced by approximately 20% (point estimate 0.80; 95% CI 0.65 to 0.97) and tmax was modestly delayed in the fed state. CONCLUSION: These data support dosing guidelines that will permit the administration of rosiglitazone without regard to meals for treatment of type 2 diabetes mellitus.

Adolescent↗

Development of a personal monitoring method for nitrogen dioxide and sulfur dioxide with Sep-Pak C18 cartridge sampling and ion chromatographic determination.

Personal monitoring methods for the determination of hourly integrated concentrations of NO2 and SO2 in ambient air have been developed. Triethanolamine (TEA)-impregnated C18 Sep-Pak cartridges were used to collect NO2 and SO2 simultaneously. After sampling, NO2 and SO2 as their nitrite, nitrate, sulfite and sulfate analogues were stripped from the cartridges with a solution of 5% methanol in distilled, deionized water (DDW) and then determined by ion chromatography. Laboratory tests were conducted to evaluate the sampling rate, collection and recovery efficiencies, breakthrough volumes, absorption capacity, interference and sample stability on the cartridge during storage. NO2 and SO2 detection limits of 0.3 and 0.4 ppb respectively for 1 h samples were obtained. Recoveries for both NO2 and SO2 exceeded 85%.

Air Pollutants↗

Pigeon fanciers' lung: identification of disease-associated carbohydrate epitopes on pigeon intestinal mucin.

Pigeon intestinal mucin, a complex high molecular weight glycoprotein, is a key antigen in the development of pigeon fanciers' lung (PFL). We have studied the specificity of antibodies to mucin in patients with PFL and asymptomatic antibody-positive individuals. Extensive papain digestion, which removes the non-glycosylated regions of the mucin leaving the heavily glycosylated 'bottle brush' regions, resulted in a 600-fold decrease in IgG3 antibody titres with little effect on IgG1 and IgG2 titres. This suggests that IgG1 and IgG2 are directed against the region rich in O-linked sugar chains whilst the majority of the IgG3 is directed against epitopes which are proteinase-sensitive. Lectin mapping of the carbohydrates present on pigeon intestinal mucin demonstrated high levels of exposed N-acetyl neuraminic acid, N-acetyl galactosamine and N-acetyl glucosamine, with lower levels of fucose and some galactose. Sera from pigeon fanciers inhibited binding of lectins specific for N-acetyl neuraminic acid, N-acetyl galactosamine, internal N-acetyl glucosamine and fucose. Sera from people with PFL, compared with sera from asymptomatic antibody-positive fanciers, had significantly higher titres of antibody that inhibited binding of four lectins specific for N-acetyl galactosamine and one fucose-specific lectin, suggesting that these sugars may play a dominant role in disease-associated epitopes. The results suggest that different IgG subclasses recognize different epitopes on mucin and that the epitopes recognized by the major subclasses are present on the O-linked oligosaccharides. Further, the carbohydrate-specific anti-mucin antibodies produced by PFL patients may differ in their specificity from those found in asymptomatic individuals.

Animals↗

VCAM-1 contributes to rapid eosinophil accumulation induced by the chemoattractants PAF and LTB4: evidence for basal expression of functional VCAM-1 in rat skin.

The aim of the present study was to investigate the role of the adhesion pathway alpha4 integrins/vascular cell adhesion molecule type 1 (VCAM-1) in rapid eosinophil accumulation induced by the chemoattractants PAF and LTB4. For this purpose we have used an in vivo model of local 111In-eosinophil accumulation to quantify eosinophil accumulation induced by intradermal administration of platelet-activating factor (PAF) and leukotriene B4 (LTB4) in rats. Initial experiments carried out over 4 hr demonstrated that intravenous administration of an anti-VCAM-1 monoclonal antibody (mAb; 5F10) or an anti-alpha4 integrin mAb (TA2) caused a significant reduction in PAF- or LTB4-induced 111In-labelled eosinophil accumulation. Time-course experiments demonstrated that the anti-VCAM-1 mAb was effective at suppressing early phases of the 111In-labelled eosinophil accumulation induced by PAF and LTB4 (e.g. within the first 60 min). In contrast, 111In-labelled eosinophil accumulation induced by these chemoattractants was unaffected by the local administration of the transcriptional inhibitor actinomycin D, suggesting a role for basally expressed VCAM-1. Indeed, basal expression of VCAM-1 in rat skin sites was demonstrated by the localization of intravenously administered radiolabelled mAb. The localization of the radiolabelled antibody was not altered in skin sites injected with PAF or LTB4. Finally, the inhibitory effects seen with the anti-VCAM-1 mAb were enhanced when the antibody was co-injected into rats with an anti-intercellular adhesion molecule-1 (ICAM-1) mAb (1A29). The combination of these two mAb also caused a significant inhibition of PAF-induced oedema, as quantified by the local accumulation of 125I-labelled human serum albumin. The results indicate a role for alpha4 integrins/VCAM-1 and ICAM-1, in PAF- and LTB4-induced eosinophil accumulation in vivo and suggest that basally expressed VCAM-1 may have a functional role in rapid accumulation of eosinophils induced by chemoattractants.

Animals↗

Changes in the registration of stillbirths < 500 g in Canada, 1985-95. Fetal-Infant Mortality Study Group of the Canadian Perinatal Surveillance System.

We assessed recent temporal trends in the registration of stillbirths in Canada, with particular regard to stillbirths < 500 g. Data from the Statistics Canada live birth and stillbirth databases for the period 1985-95 were used for the study. The primary analysis was restricted to data from 10 of the 12 provinces and territories of Canada. Data from Newfoundland were excluded because birthweight distributions were not available prior to 1990, and data from Ontario were excluded because of concerns about data quality. The proportion of stillbirths < 500 g increased by 47% [95% confidence interval (CI) 32, 63%], from 12.7% of stillbirths with known birthweight in 1985-7 to 18.7% in 1993-5. Similarly, the rate of stillbirths < 500 g increased by 36% [95% CI 21, 53%], from 7.2 to 9.8 per 10,000 total births from 1985-7 to 1993-5. Similar increases in stillbirth rates were not observed in other low birthweight categories. Live births < 500 g increased 53% [95% CI 33, 77%], from 4.6 to 7.0 per 10,000 live births. Some provinces and territories had low rates of stillbirths < 500 g and no increasing trend, whereas other provinces showed higher rates and increases over time. These regional differences were consistent with differences in stillbirth definitions across the provinces and territories of Canada. Spatio-temporal comparisons of crude stillbirth rates are likely to be compromised unless differences and changes in birth registration practices are addressed.

Canada↗

Adherent surface mucus gel restricts diffusion of macromolecules in rat duodenum in vivo.

The aim of this study was to investigate the permeability of the adherent mucus gel layer in rat duodenum in vivo to macromolecules applied in the lumen. Rats were anesthetized with thiobarbiturate, and the duodenum was perfused with isotonic NaCl solution containing large-molecular-size secretagogues. Effects on mucosal HCO(-)(3) secretion and blood-to-lumen (51)chromium-labeled EDTA clearance were used as indexes that compounds had migrated across the mucus layer. Exposure to a low concentration of papain (10 U/100 ml) for 30 min removed the mucus layer without damage to the epithelium and induced or markedly enhanced HCO(-)(3) secretory responses to cholera toxin (molecular mass of 85 kDa) or glucagon (3.5 kDa). Water extracts from a VacA cytotoxin (89 kDa) producing Helicobacter pylori strain, but not from a toxin-negative isogenic mutant, caused a small increase in HCO(-)(3) secretion but only after the mucus layer had been removed by papain. The duodenal surface mucus gel thus significantly restricts migration of macromolecules to the duodenal surface. Release of bacterial toxins at the cell-mucus interface may enhance or be a prerequisite for their effects on the gastrointestinal mucosa.

Animals↗

An analysis of the suitability of home health visits for telemedicine.

To determine what percentage of traditional home health nursing visits could be done by telemedicine, we carried out a retrospective review of nursing charts (clinical records). Data of two types were recorded. The objective data, which were abstracted from the records, included demographic information, patient assessments, teaching activities and interventions. The subjective data were the opinions of four observers as to whether the visit could have been done using currently available telemedicine technology. Records were sampled randomly for patients who had received home nursing care from three home health agencies in rural and urban areas during the winter and summer of 1996. A 54-item coding instrument was applied to 906 different charted home nursing visits. For 412 (46%) of these, the on-site nursing could reasonably have been replaced by telenursing. Significant factors determining the possible use of telenursing included primary diagnosis, number of interventions and patient age. Among the 10 most common primary diagnoses, the most amenable to telenursing care were chronic airway obstruction and joint disorders; the least amenable were coagulation disorders and anaemia. Telenursing visits could substitute for a substantial fraction of on-site home nursing visits. This has important implications in terms of reducing the cost of home nursing care.

Feasibility Studies↗

Methamphetamine overdose: experience with six cases.

We describe experience with 6 cases of methamphetamine overdose. Because of its low cost, easy availability and longer duration of action compared to cocaine, methamphetamine has become the drug of choice in various communities. Marked change in mental status was observed in all of our patients. One patient had a myocardial infarction that responded well to thrombolytic therapy. Clinicians should be familiar with the medical effects and treatment of acute methamphetamine toxicity.

Adult↗

Determinants of preterm birth rates in Canada from 1981 through 1983 and from 1992 through 1994.

BACKGROUND: The rates of preterm birth have increased in many countries, including Canada, over the past 20 years. However, the factors underlying the increase are poorly understood. METHODS: We used data from the Statistics Canada live-birth and stillbirth data bases to determine the effects of changes in the frequency of multiple births, registration of births occurring very early in gestation, patterns of obstetrical intervention, and use of ultrasonographic dating of gestational age on the rates of preterm birth in Canada from 1981 through 1983 and from 1992 through 1994. All births in 9 of the 12 provinces and territories of Canada were included. Logistic-regression analysis and Poisson regression analysis were used to estimate changes between the two three-year periods, after adjustment for the above-mentioned determinants of the likelihood of preterm births. RESULTS: Preterm births increased from 6.3 percent of live births in 1981 through 1983 to 6.8 percent in 1992 through 1994, a relative increase of 9 percent (95 percent confidence interval, 7 to 10 percent). Among singleton births, preterm births increased by 5 percent (95 percent confidence interval, 3 to 6 percent). Multiple births increased from 1.9 percent to 2.1 percent of all live births; the rates of preterm birth among live births resulting from multiple gestations increased by 25 percent (95 percent confidence interval, 21 to 28 percent). Adjustment for the determinants of the likelihood of preterm birth reduced the increase in the rate of preterm birth to 3 percent among all live births and 1 percent among singleton births. CONCLUSIONS: The recent increase in preterm births in Canada is largely attributable to changes in the frequency of multiple births, obstetrical intervention, and the use of ultrasound-based estimates of gestational age.

Birth Rate↗

The MUC2 gene product: a human intestinal mucin.

The MUC2 gene product is the first human secretory mucin protein core to be fully sequenced. Like the other eight human MUC genes identified to date, MUC2 is characterised by tandem and irregular repeat sequences rich in threonine and serine, the potential sites of attachment of the oligosaccharide chains. The MUC2 gene product is more than 5100 amino acids in its commonest allelic form and accounts for one fifth by weight of the mucin glycoprotein molecule (80% oligosaccharide side chains). The MUC2 product is polymerised end to end through disulphide bridges to form large secreted polymeric gel-forming mucins (Mr approximately 10(7)). The primary function of the MUC2 gene product is to provide a protective barrier between the epithelial surfaces and the gut lumen. There is decreased expression of MUC2 in colonic cancer and defective polymerisation of secreted mucin in ulcerative colitis. Elucidation of the MUC2 and other mucin gene sequences has opened the way for a full structural characterisation and an improved understanding of the structure and function of these complex mucus gel secretions.

Amino Acid Sequence↗