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Biomedical subjects

A C Allen

Publications and source records attributed to A C Allen.

At least 19 recordsLinked to original sources
PubMed2006

Predictors of respiratory depression at birth in the term infant.

OBJECTIVE: To evaluate predictive factors for respiratory depression at birth in infants >/=37 weeks. DESIGN: A population-based cohort study of respiratory depression at birth at term and post-term. SETTING: Nova Scotia, Canada. POPULATION: All 126 604 nonanomalous, singleton deliveries >/=37 weeks in cephalic presentation from 1988-2002. METHODS: An analysis of maternal, antenatal, intrapartum, and neonatal factors associated with respiratory depression at birth >/=37 weeks. MAIN OUTCOME MEASURES: A composite outcome of delay in initiating and maintaining respiration after birth, 5-minute Apgar score </= 3, or neonatal seizures due to hypoxic-ischaemic encephalopathy. RESULTS: The rate of respiratory depression at birth with delay in respiration was 5.2/1000, with Apgar </= 3 1.0/1000 live births, and with neonatal seizures 0.7/1000. A composite of any of the three respiratory depressions at birth criteria showed comparable low rates with spontaneous delivery (4.4/1000) and elective caesarean (4.8/1000). Compared with elective caesarean delivery, vacuum (13.2/1000, relative risk [RR] 3.97, P < 0.001), forceps (8.8/1000, RR 1.84, P= 0.003), failed vacuum (13.3/1000, RR 2.76, P= 0.005), failed forceps (33.3/1000, RR 6.93, P < 0.001), and caesarean in labour (17.0/1000, RR 3.54, P < 0.001) had significantly higher rates of the composite outcome. CONCLUSION: Overall, the rate of respiratory depression at birth in the term infant was low and the serious manifestation of seizures was less than 1 in 1000. There was a significant relationship between operative delivery in labour and respiratory depression at birth.

Asphyxia Neonatorum↗
PubMed2005

Haloacetic acids in drinking water and risk for stillbirth.

BACKGROUND: Trihalomethanes (THMs) occurring in public drinking water sources have been investigated in several epidemiological studies of fetal death and results support a modest association. Other classes of disinfection by-products found in drinking water have not been investigated. AIMS: To investigate the effects of haloacetic acid (HAA) compounds in drinking water on stillbirth risk. METHODS: A population based case-control study was conducted in Nova Scotia and Eastern Ontario, Canada. Estimates of daily exposure to total and specific HAAs were based on household water samples and questionnaire information on water consumption at home and work. RESULTS: The analysis included 112 stillbirth cases and 398 live birth controls. In analysis without adjustment for total THM exposure, a relative risk greater than 2 was observed for an intermediate exposure category for total HAA and dichloroacetic acid measures. After adjustment for total THM exposure, the risk estimates for intermediate exposure categories were diminished, the relative risk associated with the highest category was in the direction of a protective effect, and all confidence intervals included the null value. CONCLUSIONS: No association was observed between HAA exposures and stillbirth risk after controlling for THM exposures.

Acetates↗
PubMed2002

Expression of T cell receptor variable region families by bone marrow gammadelta T cells in patients with IgA nephropathy.

IgA nephropathy (IgAN) is characterized by mesangial deposition of polymeric IgA (pIgA). Abnormalities of the IgA system include reduced mucosal and increased bone marrow (BM) pIgA production. Gammadelta T cells are regulators of mucosal IgA production and oral tolerance. We have described previously a deficiency of gammadelta T cells expressing Vgamma3 and Vdelta3 from the duodenal mucosa in IgAN. Since pIgA production is displaced to the BM, we have now studied BM gammadelta T cells in IgAN. Peripheral blood and BM aspirates were obtained from 14 patients with IgAN and 15 controls. Expression of TCR gamma and delta V region families was analysed by semiquantitative RT-PCR, and CDR3 spectratyping of Vgamma1-4 and Vdelta3 genes was performed. We found no difference between IgAN and controls in the V region usage of blood gammadelta T cells. However, in the BM of patients with IgAN, there was significantly reduced expression of the V region families Vgamma3 and Vdelta3, with the decrease in Vdelta3 being particularly striking. CDR3 spectratyping showed no abnormalities in blood or BM samples. Vgamma3 and Vdelta3 are underexpressed in the duodenum and the BM in IgAN. The combination of imbalanced mucosal and systemic pIgA production with deficient expression of gammadelta T cells using Vgamma3 and Vdelta3 in both sites may imply a role for these gammadelta T cells in the normal regulation of IgA immune responses, and in the complex immunopathogenesis of IgAN.

Adult↗
PubMed2001

Implausible birth weight for gestational age.

Various rules have been proposed to identify and exclude live births with implausible values of birth weight for gestational age from large perinatal data sets. The authors carried out a preliminary evaluation of common rules by examining the frequency and nature of rule-based exclusions among live births in Canada (excluding Ontario) between 1992 and 1994. There were 625 (0.09%), 133 (0.02%), 170 (0.02%), and 2,858 (0.40%) live births identified for exclusion by a median birth weight for gestational age +/-4 standard deviations (SD) rule, a +/-5 SD rule, a rule based on expert clinical opinion, and a modification of Tukey's rule, respectively. The birth weight and gestational age distribution of the exclusions depended on the particular rule used; for example, 12.1% and 0.3% of live births of > or =4,500 g were excluded under Tukey's rule and the rule based on expert opinion, respectively. Infant mortality rates among those excluded were 8-13 times higher than among all live births. Current rules for identifying implausible birth weight for gestational age tend to flag live births at high risk for infant death. Such rules may erroneously attenuate temporal trends in important perinatal outcomes.

Algorithms↗
PubMed2001

Causes and consequences of recent increases in preterm birth among twins.

OBJECTIVE: To examine the causes and consequences of the recent increase in preterm birth among twins. METHODS: We studied all twin births among residents of the province of Nova Scotia, Canada, between 1988 and 1997. Rates of preterm birth, preterm labor induction, preterm cesarean, small-for-gestational age (SGA), respiratory distress syndrome (RDS), stillbirth, perinatal mortality, and infant mortality were compared between past and more recent years. Changes in perinatal mortality were examined using logistic regression to adjust for the effects of other determinants. RESULTS: The study included 2516 twin births (73 stillbirths and 2443 live births). The rate of preterm birth increased from 42.3% in 1988-1992 to 48.2% of twin live births in 1993-1997 (14% increase, P =.04). Twin live births born after preterm labor induction increased from 3.5% in 1988-1989 to 8.6% in 1996-1997 (P for trend =.007). Of live births between 34 and 36 weeks' gestation, the proportion born SGA decreased from 17.5% in 1988-1992 to 9.2% in 1993-1997 (P =.005). Over the same period, rates of prophylactic maternal steroid therapy increased substantially and rates of RDS declined. Perinatal mortality rates among pregnancies reaching 34 weeks decreased from 12.9 per 1000 total births in 1988-1992 to 4.2 per 1000 total births in 1993-1997 (P =.05). CONCLUSION: Increases in preterm labor induction appear to be responsible for the recent increase in preterm birth among twins. These changes have been accompanied by decreases in perinatal morbidity and mortality among twin pregnancies that reach 34 weeks' gestation.

Adult↗
PubMed2001

Mesangial IgA1 in IgA nephropathy exhibits aberrant O-glycosylation: observations in three patients.

BACKGROUND: In IgA nephropathy (IgAN), circulating IgA1 molecules display an abnormal pattern of O-glycosylation. This abnormality may potentially contribute to mesangial IgA1 deposition, but this is unproven because the O-glycosylation of mesangial IgA1 has not been analyzed. METHODS: IgA1 was eluted from glomeruli isolated from the kidneys of three IgAN patients obtained after nephrectomy or at postmortem. Serum from these patients, other patients with IgAN, and controls was subjected to the same treatment as the glomerular eluates. The O-glycosylation of eluted and serum IgA1 was measured by lectin binding using an enzyme-linked immunosorbent assay-based system. RESULTS: In all three cases, the lectin binding of IgA1 eluted from the glomeruli of IgAN patients was markedly higher than that of the serum IgA1 of the same individual, and also all but one of a series of serum IgA1 samples from other patients and controls. CONCLUSIONS: The higher lectin binding of glomerular compared with serum IgA1 suggests that O-glycosylated IgA1 molecules abnormally and selectively deposit in the kidney. These results provide the first evidence that mesangial IgA1 is abnormally O-glycosylated, and support a direct role for abnormal IgA1 O-glycosylation in the mechanism of mesangial IgA deposition in IgAN.

Adult↗
PubMed2001

Haptic perception of the horizontal by blind and low-vision individuals.

We examined haptic perception of the horizontal in visually impaired people. Blind people (late blind and congenitally blind), persons with very low vision, and blindfolded sighted individuals felt raised-line drawings of jars at four angles. They had to demonstrate their understanding that water remains horizontal, despite jar tilt, by selecting the correct raised-line drawing given four choices. Low-vision subjects, with near perfect scores, performed significantly better than the other groups of subjects. While the late-blind and blindfolded sighted subjects performed slightly better than the congenitally blind participants, the difference between the late-blind and congenitally blind groups was nonsignificant. The performance of the congenitally blind subjects indicates that visual experience is not necessary for the development of an understanding that water level stays horizontal, given container tilt.

Adult↗
PubMed2001

Changes in stillbirth and infant mortality associated with increases in preterm birth among twins.

OBJECTIVE: To examine whether the recent substantial increase in preterm birth among twins has been associated with changes in fetal and infant mortality. DESIGN: Cohort study based on information in the linked live birth, stillbirth, and mortality databases of Statistics Canada. SETTING: Ten of 12 provinces and territories in Canada. PARTICIPANTS: All twin live births and stillbirths between 1985 and 1996, along with information on deaths during infancy (1985-1997). MAIN OUTCOME MEASURE: Fetal and infant mortality rates. RESULTS: The rate of preterm birth among twin live births increased significantly by 17% (95% confidence interval: 14%-20%) from 42.5% between 1985 and 1987 to 49.6% between 1994 and 1996. Overall, stillbirth rates among twins declined from 22.4 per 1000 total births in 1985 to 1987 to 18.8 per 1000 total births in 1994 to 1996. Among twin fetuses >/=34 weeks' gestation, stillbirth rates decreased from 9.5 per 1000 in 1985 to 1987 to 5.4 per 1000 fetuses at risk in 1994 to 1996. Infant mortality rates among twin live births declined substantially in all categories of gestational age above 24 weeks except for live births at 32 to 33 and 34 to 36 weeks' gestation. CONCLUSIONS: The recent increase in preterm birth among twins was associated with a substantial reduction in stillbirth rates at and near term gestation. Infant mortality rates declined concurrently, although the absence of a significant decrease in infant mortality among twin live births at 32 to 33 and 34 to 36 weeks' gestational age needs additional scrutiny.

Canada↗
PubMed2000

Gestational age- and birthweight-specific declines in infant mortality in Canada, 1985-94. Fetal and Infant Health Study Group of the Canadian Perinatal Surveillance System.

We studied infant mortality rates in Canada within specific gestational age and birthweight categories after using probabilistic techniques to link information in Statistics Canada's live births data base (1985-94) with that in the death data base (1985-95). Gestational age- and birthweight-specific mortality rates in 1992-94 were contrasted with those in 1985-87 with changes expressed in terms of relative risks with 95% confidence intervals [CI]. Statistically significant reductions in infant mortality were observed beginning at 24-25 weeks of gestation and extended across the gestational age range to post-term births. Crude infant mortality rates, infant mortality rates among those > or = 500 g and among those > or = 1000 g decreased by 22%, 25% and 26%, respectively, from 1985-87 to 1992-94. The magnitude of the reductions in infant mortality rates ranged from 14% [95% CI 7, 21%] at 24-25 weeks of gestation to 40% [95% CI 31, 47%] at 28-31 weeks. Almost all reductions in gestational age- and birthweight-specific infant mortality between 1985-87 and 1992-94 were due to approximately equal reductions in neonatal and post-neonatal mortality. Live births > or = 42 weeks of gestation did not follow this rule; post-neonatal mortality rates among such live births decreased significantly by 51% [95% CI 26, 68%], although neonatal mortality rates showed no significant change. The mortality reductions observed across the gestational age and birthweight range are probably a consequence of specific clinical interventions complementing improvements in fetal growth. Temporal changes in the outcome of post-term pregnancies need to be carefully examined, especially in relation to recent changes in the obstetric management of such pregnancies.

Adult↗
PubMed2000

Identification of a novel Fcalpha receptor expressed by human mesangial cells.

BACKGROUND: IgA nephropathy (IgAN) is characterized by mesangial deposits of polymeric IgA (pIgA). The pathological consequences of IgA deposition are believed to center on direct interaction between IgA and the glomerular mesangial cell (MC). We have characterized a novel mesangial receptor that recognizes the Fc portion of IgA. METHODS: Five primary MC cultures were evaluated for IgA binding by flow cytometry, and specificity of binding was determined by competitive inhibition. Relative affinities of the receptor for all IgA isoforms were also determined, and binding of pIgA1 was compared to monomer. The identified Fc receptor was then compared with CD89, hitherto the only other Fcalpha receptor reported. CD89 protein and mRNA expression were detected by conventional and intracellular flow cytometry, sequencing of reverse transcription-polymerase chain reaction (RT-PCR) products, and Northern blotting. RESULTS: All MCs constitutively expressed a receptor that bound IgA in an Fcalpha-dependent fashion. The receptor recognized secretory and serum IgA1 and IgA2 equally, but pIgA bound with much greater affinity than monomer. At no time were we able to detect CD89 synthesis, although three novel CD89-related mRNA transcripts were identified by RT-PCR. CONCLUSIONS: We have clearly demonstrated that MCs consistently express an FcalphaR distinct from the myeloid FcalphaR CD89. This novel receptor binds pIgA with high affinity and may therefore mediate the mesangial injury that follows IgA deposition in IgAN. While immunogenically distinct, the mesangial Fcalpha receptor may share some molecular homology with CD89, as mRNA transcripts with partial identity to CD89 were found in all five MC cultures.

Antigens, CD↗
PubMed2000

IgA myeloma presenting as Henoch-Schönlein purpura with nephritis.

IgA nephropathy (IgAN) and Henoch-Schönlein purpura (HSP) are both characterized by IgA-mediated tissue injury, including mesangial proliferative glomerulonephritis. Abnormalities of IgA1 glycosylation are described in IgA nephropathy and HSP nephritis. IgA-antineutrophil cytoplasmic antibodies (ANCA) have been inconsistently described in the serum of patients with HSP. In IgA myeloma, the paraprotein-mediated renal lesion is typically cast nephropathy; IgAN or HSP have only rarely been reported in myeloma even when an IgA paraprotein is circulating in large concentrations. We report the case of a 50-year-old man with IgA myeloma who presented with HSP including nephritis and rapidly progressive renal failure. His IgA1 had altered O-glycosylation in the pattern seen in IgAN and also contained an IgA-ANCA. This case adds further weight to the evidence that IgA1 O-glycosylation abnormalities predispose to mesangial IgA deposition and also that IgA-ANCA may have a pathogenic role in the development of HSP.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2000

Relation between stillbirth and specific chlorination by-products in public water supplies.

During water treatment, chlorine reacts with naturally occurring organic matter in surface water to produce a number of by-products. Of the by-products formed, trihalomethanes (THMs) are among the highest in concentration. We conducted a retrospective cohort study to evaluate the relationship between the level of total THM and specific THMs in public water supplies and risk for stillbirth. The cohort was assembled from a population-based perinatal database in the Canadian province of Nova Scotia and consisted of almost 50,000 singleton deliveries between 1988 and 1995. Individual exposures were assigned by linking mother's residence at the time of delivery to the levels of specific THMs monitored in public water supplies. Analysis was conducted for all stillbirths and for cause-of-death categories based on the physiologic process responsible for the fetal death. Total THMs and the specific THMs were each associated with increased stillbirth risk. The strongest association was observed for bromodichloromethane exposure, where risk doubled for those exposed to a level of [greater and equal to] 20 microg/L compared to those exposed to a level < 5 microg/L (relative risk = 1. 98, 95% confidence interval, 1.23-3.49). Relative risk estimates associated with THM exposures were larger for asphyxia-related deaths than for unexplained deaths or for stillbirths overall. These findings suggest a need to consider specific chlorination by-products in relation to stillbirth risk, in particular bromodichloromethane and other by-product correlates. The finding of a stronger effect for asphyxia deaths requires confirmation and research into possible mechanisms.

Adult↗
PubMed2000

The Matthew effect: infant mortality in Canada and internationally.

OBJECTIVE: To examine whether the magnitude of improvement in the health status of a population over time is dependent on the previous health status of that population. DESIGN AND SETTING: A study of infant mortality rates in Canada's 12 provinces and territories between the periods 1961-1965 and 1991-1995, and of infant mortality rates in 133 countries between 1960 and 1995. MAIN OUTCOME MEASURES: Spearman's rank correlations, relative risks, and risk differences to measure the relationship between infant mortality in the 1960s and changes in infant mortality between the 1960s and 1990s. RESULTS: In Canada, regional rankings based on infant mortality rates in 1961-1965 were strongly correlated (inversely) with rankings based on the percent change in infant mortality between 1961-1965 and 1991-1995 (correlation coefficient = -.85). In contrast, internationally, rankings based on infant mortality rates in 133 countries in 1960 were positively correlated with percent change between 1960 and 1995 (correlation coefficient =.56). Regional differences in infant mortality rates, measured using relative risks, declined in Canada (highest relative risk: 4.2, compared with Ontario in the 1960s; highest relative risk: 2.2, compared with Ontario in the 1990s) but increased globally (highest relative risk: 5.0, compared with industrialized countries in 1960; highest relative risk: 15.1, compared with industrialized countries in 1995). CONCLUSIONS: Canadian regions with higher infant mortality rates in 1961-1965 achieved larger improvements compared with regions with initially lower infant mortality rates. The pattern observed within Canada is unlike the pattern observed internationally.

Canada↗
PubMed2000

An assessment of the validity of a computer system for probabilistic record linkage of birth and infant death records in Canada. The Fetal and Infant Health Study Group.

Studies on the validity of probabilistic record linkage are sparse. We performed a probabilistic linkage to link the 1984-1994 birth records (obtained from the Canadian Birth Data Base) with 1984-1995 infant death records (from the Canadian Mortality Data Base) in Canada. We extracted the linked birth-death records for Nova Scotia and Alberta (from January 1990 to December 1991) obtained from Statistics Canada's vital registration data and compared them with corresponding records from provincial data (primarily hospital records). The results showed that over 99% of infant deaths (153/155) in the Nova Scotia provincial data were successfully located in the linked Statistics Canada file; the corresponding figure for Alberta neonatal deaths was also 99% (365/367). The distributions of gestational age and birth weight in matched cases demonstrated high agreement between the two data sources. We conclude that the computer system for probabilistic linkage developed by Statistics Canada using the available personal identifying variables in the Canadian Birth Data Base and the Canadian Mortality Data Base is valid.

Alberta↗
PubMed1999

Exaggerated systemic antibody response to mucosal Helicobacter pylori infection in IgA nephropathy.

Numerous studies in the literature report aberrant immune responsiveness in immunoglobulin A (IgA) nephropathy. However, all these studies investigate immune responses invoked by an artificially engineered antigen challenge. For the first time in IgA nephropathy, we report the systemic humoral responses generated as part of an active mucosal immune response against a common environmental pathogen, Helicobacter pylori (Hp). We studied 22 patients with IgA nephropathy and 9 controls without renal disease who were shown to be infected with Hp, using a 13C-urea breath test. Hp antigen-specific enzyme-linked immunosorbent assays were established to measure the anti-Hp IgA, IgG, and IgA and IgG subclass antibody levels. In addition, anti-Hp responses in the monomeric and polymeric (pIgA) fractions of serum IgA were measured after separation by gel filtration high-performance liquid chromatography. IgA nephropathy was associated with both a greater rate of IgA anti-Hp seropositivity (P < 0.05) and a more pronounced IgA anti-Hp antibody response (P < 0.01). In almost all cases, IgA anti-Hp was IgA1, and more than 90% was polymeric. There was no difference in the frequency of IgG anti-Hp seropositivity, but patients produced a much greater IgG anti-Hp response (P < 0.01). In addition, the IgG subclass responses were markedly different, with IgG1 predominant in controls and IgG2 and IgG3 the major subclasses produced in IgA nephropathy. We have shown an exaggerated systemic antibody response to mucosal infection caused by Hp in patients with IgA nephropathy, predominantly consisting of pIgA1, IgG2, and IgG3. This suggests that in IgA nephropathy, not only is pIgA1 production poorly controlled, but regulation of IgG isotype switching in response to mucosal pathogens is also deranged.

Adolescent↗
PubMed1999

Analysis of IgA1 O-glycans in IgA nephropathy by fluorophore-assisted carbohydrate electrophoresis.

Abnormal O-glycosylation of IgA1 may contribute to pathogenic mechanisms in IgA nephropathy (IgAN). Observations of altered lectin binding to IgA1 in IgAN suggest that the O-glycan chains may be undergalactosylated, but precise structural definition of the defect has proved technically difficult, and it remains unconfirmed. This is the first study using fluorophore-assisted carbohydrate electrophoresis (FACE) to analyze IgA1 O-glycans in IgAN and controls. IgA1 was purified from serum, and the intact O-glycans were released by hydrazinolysis at 60 degrees C. After re-N-acetylation, the glycans were fluorophore-labeled and separated by polyacrylamide gel electrophoresis. Sequential exoglycosidase digestions of IgA1 allowed identification of the different O-glycan bands on FACE gels, and their relative frequencies in IgA1 samples were measured by ultraviolet densitometry. Lectin binding of the IgA1 samples was also measured. In some patients with IgAN, FACE analysis demonstrated a significant increase in the percentage of IgA1 O-glycan chains consisting of single N-acetyl galactosamine (GalNAc) units rather than the more usual galactosylated and sialylated forms. This finding was confirmed using both desialylated IgA1 and enzymatically released O-glycans. Good correlation was also found between O-glycan agalactosylation on FACE analysis and IgA1 lectin binding in IgAN, supporting the value of lectins as tools for detection of this abnormality. This is the first study in which all of the predicted O-glycan forms of IgA1 have been analyzed simultaneously, and demonstrates that in IgAN, the IgA1 Oglycan chains are truncated, with increased terminal GalNAc. This abnormality has the potential to significantly affect IgA1 behavior and handling with pathogenic consequences in IgAN.

Adult↗
PubMed1999

Pathogenesis of IgA nephropathy.

IgA nephropathy (IgAN) is initiated by glomerular deposition of polymeric IgA1(pIgA1). In IgAN pIgA production is reduced in the mucosal immune system, perhaps mediated by a mucosal gamma delta T cell defect, and mucosal IgA responses to immunisation are impaired. But pIgA1 production by the marrow is increased. Human pIgA1 has an O-glycosylated hinge region unique to circulating immunoglobulins and there is reduction of galactosyl residues in the hinge of serum IgA1 in IgAN and Henoch-Schönlein nephritis. This reduced galactosylation may be due to a functional defect in plasma cell beta 1,3-galactosyltransferase. Altered hinge region glycosylation may alter IgA1 structure, modifying interactions with matrix proteins, IgA receptors and complement, and therefore influence mesangial deposition and subsequent injury through mechanisms other than classical antigen-antibody reactions. IgA clearance through the hepatic asialoglycoprotein receptor or Fc alpha receptors on circulating white cells may also be impaired. The unique features of human IgA1 have prevented development of satisfactory animal models for the early stages of IgAN. It is likely that events after pIgA1 deposition which result in glomerular inflammation and scarring are not specific to IgAN but generic to many forms of glomerulonephritis.

Animals↗