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Biomedical subjects

A Allen

Publications and source records attributed to A Allen.

At least 73 records · Page 4Linked to original sources

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↗

IgG subclass responses to pigeon intestinal mucin are related to development of pigeon fanciers' lung.

BACKGROUND: Pigeon fanciers' lung (PFL) is a form of extrinsic allergic alveolitis. Affected individuals produce antibodies to various pigeon antigens, and the resulting immune complexes are thought to initiate the disease. However, high antibody titres also occur in some asymptomatic individuals. Previously attention has focused on protein antigens, but we have recently identified pigeon intestinal mucin as a novel antigen in PFL. OBJECTIVE: To determine the relationship between IgG subclass antibodies to pigeon intestinal mucin and the development of pigeon fanciers' lung. METHODS: Sera were collected from 250 pigeon fanciers, who also completed a clinical questionnaire. Sera were screened for precipitating antibodies to pigeon serum and droppings. Individuals with symptoms and precipitating antibodies were considered to have classical PFL. Serum IgG and IgG subclass antibodies to pigeon intestinal mucin and pigeon serum proteins were investigated by quantitative enzyme-linked immunosorbent assay (ELISA). RESULTS: Very high titres of IgG antibodies against pigeon mucin were found in all precipitin-positive individuals. A strong positive correlation was seen between titres of antibodies to mucin and to serum proteins, but this was not due to crossreactivity. No significant differences in IgG titres to either mucin or pigeon serum proteins were found between individuals with PFL and asymptomatic precipitin positive fanciers. IgG1 and IgG2 were the major subclasses of anti-mucin, with lower titres of IgG3. Patients with PFL had significantly higher titres of IgG1 to mucin than asymptomatic, precipitin-positive individuals. In contrast, no significant differences were seen between PFL and asymptomatic precipitin-positive sera with respect to the subclass titres against pigeon serum proteins. CONCLUSION: The high titres of anti-mucin IgG in sera of all individuals with PFL, together with the finding that high IgG1 titres to mucin are associated with the development of disease confirm pigeon intestinal mucin as an important antigen in PFL.

Adult↗

Pigeon fanciers' lung: effects of smoking on serum and salivary antibody responses to pigeon antigens.

A reduced prevalence of pigeon fanciers' lung has been reported in pigeon breeders who smoke cigarettes. Serum and salivary antibodies to pigeon intestinal mucin and pigeon serum proteins were investigated in 227 pigeon fanciers, subdivided according to smoking habit and clinical status. Smokers had a lower incidence of precipitating antibodies to pigeon antigens and lower titres of serum IgG and IgA antibodies to mucin and to pigeon serum proteins in ELISA compared with non-smokers and ex-smokers. In contrast, IgG antibody titres to tetanus toxoid were similar in smoking and non-smoking groups. In contrast to serum antibodies, salivary IgA antibody titres to pigeon antigens were similar in smokers and non- or ex-smokers. Approximately one third of the smokers reported symptoms consistent with pigeon fanciers' lung but did not have precipitating antibodies. Only some individuals with precipitating antibodies had disease symptoms, and IgG antibody titres in these individuals were not significantly higher than in many asymptomatic individuals. Salivary IgA titres against pigeon mucin were significantly higher in asymptomatic individuals, consistent with a protective role for these antibodies. The results confirm that smoking is associated with a decreased serum antibody response to inhaled pigeon antigens, affecting IgG1, IgG2 and IgA responses, but this impairment does not extend to salivary IgA or to antibody responses to a parenterally administered protein antigen. The fact that responses to pigeon serum proteins and to pigeon intestinal mucin were similarly affected suggests that cigarette smoking depresses both T-independent and T-dependent responses to inhaled antigens.

Animals↗

Helicobacter pylori in vivo causes structural changes in the adherent gastric mucus layer but barrier thickness is not compromised.

BACKGROUND: It has been proposed that a pathogenic effect of Helicobacter pylori is a weakening of the protective mucus barrier; however, this remains controversial. AIMS: To clarify the effects of H pylori infection on the mucus gel barrier in vivo. METHODS: Mucus gel polymeric structure and the thickness of the adherent mucus barrier were measured in endoscopic biopsy samples in subjects with and without H pylori infection. RESULTS: There was a significant 18% reduction in the proportion of polymeric gel forming mucin in the adherent mucus layer in H pylori positive compared with negative subjects. There was no change in the adherent mucus thickness between H pylori positive and negative subjects without gastric atrophy (mean (SD): 104 (26) micron, 106 (30) micron, respectively). There was however a significant reduction in mucus thickness in those H pylori positive subjects with underlying gastric atrophy (84 (13) micron, p=0.03) compared with those without atrophy. CONCLUSIONS: A partial breakdown in gel forming structure of the gastric mucus barrier does occur in H pylori infection per se but this is insufficient to cause a collapse of the mucus barrier.

Aged↗

Pigeon fanciers' lung: the mucin antigen is present in pigeon droppings and pigeon bloom.

BACKGROUND: Pigeon intestinal mucin has been implicated as an important antigen pigeon fanciers' lung. This study investigated whether mucin is detectable in pigeon droppings and bloom, the likely antigenic sources in disease. METHODS: Soluble extracts of a number of materials found in a pigeon loft were prepared and specific IgG subclass antibodies to these antigens were measured in 14 antibody-positive pigeon fanciers. Cross-reactivity between these materials and purified pigeon intestinal mucin was investigated by inhibition of anti-mucin ELISA. Mucin was purified from the soluble extracts of these crude antigen mixtures by CsCl density gradient centrifugation. RESULTS: The patterns of IgG subclass responses to purified pigeon intestinal mucin and to the four materials collected from the pigeon loft were similar. Subclass differences between symptomatic and asymptomatic individuals, demonstrable against purified mucin, were similarly seen against pigeon droppings and pigeon bloom. Both pigeon droppings and pigeon bloom were capable of inhibiting IgG binding to purified pigeon mucin, and mucin inhibited substantially the binding of IgG to these materials. Glycoprotein with a density similar to that described for pigeon intestinal mucin was purified from each source. CONCLUSION: Pigeon intestinal mucin is present in a variety of materials found in the environment of the pigeon loft in a form capable of reacting with anti-mucin antibodies in the sera of exposed individuals. Reduction in exposure to these materials may decrease the likelihood of developing pigeon fanciers' lung and minimise reactions in sensitised individuals.

Animals↗

A joint US-UK study of home telenursing.

Nursing notes for patients nursed at home in the USA and the UK were reviewed using an abstraction instrument developed and tested in the US. More than 1700 episodes of patient care at home were reviewed: 906 in the US and 839 in the UK. Preliminary data suggest that in the US approximately 45% of home nursing visits could be done via telemedicine, while the figure is lower in the UK, less than 15%. Pilot trials of an analogue video-telephone in Kansas City and Belfast suggest that even relatively low-quality compressed video may be useful for home nursing. Clearly, there are differences between the two countries which merit further study, but there is evidence to suggest that telemedicine may have a role in the delivery of home health care.

Aged↗

A cost measurement study for a tele-oncology practice.

The costs of providing oncology services in three different ways were measured. Services were provided to a peripheral hospital by: conventional clinics, in which the oncologist worked at the hospital concerned; outreach clinics, in which an oncologist was flown in periodically from a central hospital; telemedicine clinics, in which the oncologist at the central hospital practised via a video-link. During a one-year study period, 2400 patients were seen in conventional clinics, 81 in outreach clinics and 103 in telemedicine clinics. At these workloads the average costs per patient were $149, $897 and $812, respectively. However, the average costs cannot be compared directly without further information about the shape of the unit cost curves.

Cost-Benefit Analysis↗

The potential for telemedicine in home nursing.

We assessed the proportion of home nursing visits that could be replaced by home telenursing in the UK. A retrospective review of nursing notes in the UK was undertaken using an abstraction instrument developed and tested in the US. A total of 1951 episodes of patient care at home were reviewed: 1450 from Liverpool and 501 from Belfast. A total of 1626 (83%) of the episodes involved 'hands-on' interventions. In Belfast two observers estimated that 14% of home nursing visits could be done via telemedicine while in Liverpool two more observers gave an estimate of 16%. Inter-rater agreement was high (kappa = 0.93 for the Belfast observers and 0.79 for the Liverpool observers). Pilot trials of an analogue video-phone in Belfast suggested that even relatively low-quality compressed video might be useful for home nursing. These findings suggest that telemedicine may have a significant role in the delivery of home health care in the UK.

Adult↗