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Biomedical subjects

A Allen

Publications and source records attributed to A Allen.

At least 37 records · Page 2Linked to original sources
PubMed2001

Alveolar metabolism of natural vs. synthetic surfactants in preterm newborn rabbits.

We compared the recoveries of four surfactant preparations: two natural [term fetal rabbit surfactant (FRS) and adult rabbit surfactant (ARS)] and two commercially available preparations [apoprotein-based Survanta (S) and synthetic Exosurf (E)] from 27-day gestation rabbit pups treated at birth and ventilated up to 120 min. At 5, 60, and 120 min, we measured the recovery of the heavy-aggregate, metabolically active form (H) and the light-aggregate, nonsurface active metabolic breakdown form (L) of alveolar surfactant and determined the phospholipid content and composition of the intracellularly stored lamellar body (LB) pool. Pups treated with FRS had <15% loss of H by 2 h. ARS-treated pups had a >50% loss of H by 1 h, and E- and S-treated pups had approximately 50% loss by 5 min, with a slower rate of continuing loss of up to 80% by 2 h. The major losses of H phospholipid were not explained by the L-form recovery. LB phospholipid significantly increased only in the E-treated pups and only at 2 h. FRS provides a biologically active form (H) of surfactant that appeared to remain in the airway for a significantly longer time than the other surfactant preparations. The unique properties of FRS merit further study.

Animals↗
PubMed2001

A new and improved population-based Canadian reference for birth weight for gestational age.

BACKGROUND: Existing fetal growth references all suffer from 1 or more major methodologic problems, including errors in reported gestational age, biologically implausible birth weight for gestational age, insufficient sample sizes at low gestational age, single-hospital or other non-population-based samples, and inadequate statistical modeling techniques. METHODS: We used the newly developed Canadian national linked file of singleton births and infant deaths for births between 1994 and 1996, for which gestational age is largely based on early ultrasound estimates. Assuming a normal distribution for birth weight at each gestational age, we used the expectation-maximization algorithm to exclude infants with gestational ages that were more consistent with 40-week births than with the observed gestational age. Distributions of birth weight at the corrected gestational ages were then statistically smoothed. RESULTS: The resulting male and female curves provide smooth and biologically plausible means, standard deviations, and percentile cutoffs for defining small- and large-for-gestational-age births. Large-for-gestational age cutoffs (90th percentile) at low gestational ages are considerably lower than those of existing references, whereas small-for-gestational-age cutoffs (10th percentile) postterm are higher. For example, compared with the current World Health Organization reference from California (Williams et al, 1982) and a recently proposed US national reference (Alexander et al, 1996), the 90th percentiles for singleton males at 30 weeks are 1837 versus 2159 and 2710 g. The corresponding 10th percentiles at 42 weeks are 3233 versus 3086 and 2998 g. CONCLUSIONS: This new sex-specific, population-based reference should improve clinical assessment of growth in individual newborns, population-based surveillance of geographic and temporal trends in birth weight for gestational age, and evaluation of clinical or public health interventions to enhance fetal growth. fetal growth, birth weight, gestational age, preterm birth, postterm birth.

Algorithms↗
PubMed2001

A preliminary double-blind, placebo-controlled trial of divalproex sodium in borderline personality disorder.

BACKGROUND: Borderline personality disorder is characterized by affective instability, impulsivity, and aggression and is associated with considerable morbidity and mortality. Since anticonvulsant agents may be helpful in such symptomatology, we compared divalproex sodium with placebo in patients with borderline personality disorder. METHOD: A 10-week, parallel, double-blind design was conducted. Sixteen outpatients meeting Structured Clinical Interview for DSM-IV Axis II Personality Disorders criteria for borderline personality disorder were randomly assigned to receive placebo (N = 4) or divalproex sodium (N = 12). Change was assessed in global symptom severity (Clinical Global Impressions-Improvement Scale [CGI-I]) and functioning (Global Assessment Scale [GAS]) as well as in specific core symptoms (depression, aggression, irritability, and suicidality). RESULTS: There was significant improvement from baseline in both global measures (CGI-I and GAS) following divalproex sodium treatment. A high dropout rate precluded finding significant differences between the treatment groups in the intent-to-treat analyses, although all results were in the predicted direction. CONCLUSION: Treatment with divalproex sodium may be more effective than placebo for global symptomatology, level of functioning, aggression, and depression. Controlled trials with larger sample sizes are warranted to confirm these preliminary results.

Adolescent↗
PubMed2001

Short report: codon 125 polymorphism of CD31 and susceptibility to malaria.

Platelet-endothelial cell adhesion molecule 1 (PECAM-1/CD31) has been identified as an endothelial cell receptor of Plasmodium falciparum-infected erythrocytes. The significance of adhesion of infected erythrocytes to this receptor in malaria infection has not been determined. We have therefore studied the association of the functional mutation CTG-->GTG (Leu-->Val) in codon 125 of the Cd31 gene with severe disease in 2 case-control studies of malaria in Madang Hospital, Papua New Guinea, and in Kilifi District Hospital, Kenya. We analyzed data from 442 cases and controls from Papua New Guinea and data from 396 cases and controls from Kenya. The codon 125 polymorphism was not associated with severe malaria in either study. We conclude that the presence of CTG-->GTG (Leu-->Val) substitution in codon 125 in CD31 is not associated with protection from severe malaria, and we suggest that selective forces other than malaria may maintain this high-frequency polymorphism.

Case-Control Studies↗
PubMed2001

Recent trends in fetal and infant outcomes following post-term pregnancies.

All births and infant deaths in 1985 87 and 1992 94 in Canada, except in Ontario and Newfoundland, were analyzed to assess the potential impact of the recent increased use of elective labour induction for post-term pregnancies. Probabilistic linkage was carried out of infant death records (Canadian Mortality Database) and respective birth registrations (Canadian Birth Database) for the periods 1985 87 and 1992 94. The combined fetal and infant mortality declined by 20 30% between 1985 87 and 1992 94 at each gestational week beginning at 37 weeks, with no increased reduction among post-term pregnancies. Asphyxia-related fetal and infant deaths, the most likely cause of death being preventable by labour induction for post-term pregnancies, did not decrease among post-term pregnancies. In contrary, a substantial decrease of asphyxia-related deaths was observed at 37 and 38 weeks over the same periods of time. Because fetal and infant deaths are rare events and because the number of pregnancies passing 42 weeks of gestation decreased dramatically during 1992 94, statistically unstable results may be inevitable in the comparison of mortality in this group of pregnancies.

Canada↗
PubMed2001

Significant absorption of topical tacrolimus in 3 patients with Netherton syndrome.

BACKGROUND: Tacrolimus is a macrolide immunosuppressant approved in oral and intravenous formulations for primary immunosuppression in liver and kidney transplantation. Topical 0.1% tacrolimus ointment has recently been shown to be effective in atopic dermatitis for children as young as 2 years of age, with minimal systemic absorption. We describe 3 patients treated with topical 0.1% tacrolimus who developed significant systemic absorption. OBSERVATION: Three patients previously diagnosed as having Netherton syndrome were treated at different centers with 0.1% tacrolimus ointment twice daily. Two patients showed dramatic improvement. All patients were found to have tacrolimus blood levels within or above the established therapeutic trough range for oral tacrolimus in organ transplant recipients. None of these patients developed signs or symptoms of toxic effects of tacrolimus. CONCLUSIONS: Patients with Netherton syndrome have a skin barrier dysfunction that puts them at risk for increased percutaneous absorption. The Food and Drug Administration recently approved 0.1% tacrolimus ointment for the treatment of atopic dermatitis. Children with Netherton syndrome may be misdiagnosed as having atopic dermatitis. These children are at risk for marked systemic absorption and associated toxic effects. If topical tacrolimus is used in this setting, monitoring of serum tacrolimus levels is essential.

Administration, Cutaneous↗
PubMed2000

Randomized secondary prevention trial of azithromycin in patients with coronary artery disease: primary clinical results of the ACADEMIC study.

BACKGROUND: Chlamydia pneumoniae is associated with coronary artery disease (CAD), although its causal role is uncertain. A small preliminary study reported a >50% reduction in ischemic events by azithromycin, an antibiotic effective against C pneumoniae, in seropositive CAD patients. We tested this prospectively in a larger, randomized, double-blind study. METHODS AND RESULTS: CAD patients (n=302) seropositive to C pneumoniae (IgG titers >/=1:16) were randomized to placebo or azithromycin 500 mg/d for 3 days and then 500 mg/wk for 3 months. The primary clinical end point included cardiovascular death, resuscitated cardiac arrest, nonfatal myocardial infarction (MI), stroke, unstable angina, and unplanned coronary revascularization at 2 years. Treatment groups were balanced, and azithromycin was generally well tolerated. During the trial, 47 first primary events occurred (cardiovascular death, 9; resuscitated cardiac arrest, 1; MI, 11; stroke, 3; unstable angina, 4; and unplanned coronary revascularization, 19), with 22 events in the azithromycin group and 25 in the placebo group. There was no significant difference in the 1 primary end point between the 2 groups (hazard ratio for azithromycin, 0.89; 95% CI, 0.51 to 1.61; P:=0.74). Events included 9 versus 7 occurring within 6 months and 13 versus 18 between 6 and 24 months in the azithromycin and placebo groups, respectively. CONCLUSIONS: This study suggests that antibiotic therapy with azithromycin is not associated with marked early reductions (>/=50%) in ischemic events as suggested by an initial published report. However, a clinically worthwhile benefit (ie, 20% to 30%) is still possible, although it may be delayed. Larger (several thousand patient), longer-term (>/=3 to 5 years) antibiotic studies are therefore indicated.

Adult↗
PubMed2000

Increased growth hormone response to sumatriptan challenge in adult autistic disorders.

Serotonergic (5-HT) abnormalities have been documented in autism. To assess sensitivity of the 5-HT1d receptor, growth hormone response to the 5-HT1d receptor agonist sumatriptan was studied in adult autistic patients and matched normal controls. In this study, 11 adult patients with autism or Asperger's disorder were compared with nine matched controls. All subjects were randomized to single dose sumatriptan (6 mg SQ) and placebo challenges, separated by a 1-week interval, and growth hormone was measured before and during the challenges. The results showed a highly significant diagnosisxdrugxtime interaction on repeated measure analysis covaried for baseline. This suggests that autistic patients had significantly greater growth hormone response to sumatriptan than normal controls, independent of placebo effects. Therefore, abnormalities in 5-HT regulation in autism may be related to increased sensitivity of the 5-HT1d inhibitory receptor in autism.

Adolescent↗
PubMed2000

IgG subclass responses to pigeon intestinal mucin in pigeon Fanciers' lung

Pigeon fanciers' lung (PFL) is a form of extrinsic allergic alveolitis caused by exposure to avian antigens. Although the mechanisms involved in the pathogenesis of PFL are unclear it has been suggested that immune complexes formed on the alveolar epithelial surface of the lung initiate the symptoms of the acute stages of discase. Pigeon intestinal mucin has been implicated as an important antigen in the pathogenesis of PFL, and affected fanciers have very high antibody titres against this antigen. In this study we investigated the IgG and IgG subclass responses to both intact and papain digested mucin in 250 pigeon fanciers classified according to the presence of absence of precipitating antibodies and clinical status. Sera were screened by quantitative ELISA for IgG and IgG subclass activity to these antigens. There was no significant difference in the median IgG titre to pigeon mucin in individuals with PFL and asymptomatic antibody positive individuals. IgG1 and IgG2 were the major antibody subclasses against pigeon intestinal mucin with lower titres of IgG3 and negligible IgG4. Patients with PFL had significantly higher titres of anti-mucin IgG1 than asymptomatic antibody positive individuals (p = 0.0019) whilst there was no significant differences in IgG2, IgG3 and IgG4 titres between these two groups. Papain digestion of mucin resulted in a 600 fold decrease in IgG3 titres whilst IgG1 and IgG2 titres were essentially unaffected as compared to undigested mucin. This suggests that both IgG1 and IgG2 are directed against the O-linked oligosaccharides in the papain resistant regions of mucin whilst the majority of IgG3 is directed against papain sensitive protein epitopes (or possibly N-Iinked sugars in the sparsely glycosylated regions). - The difference between symptomatic and asymptomatic sera in the IgG subclass profiles to pigeon intestinal mucin together with the very high titres of anti-mucin antibody in all individuals with PFL confirm pigeon mucin as a major antigen in disease. Differences in antibody subclass profiles are likely to affect the composition and properties of the immune complexes, with consequences for the developmcnt of disease.

Journal Article↗
PubMed2000

An investigation of imidazole and oxazole syntheses using aryl-substituted TosMIC reagents.

This article describes efficient and mild protocols for preparing polysubstituted imidazoles in a single pot from aryl-substituted tosylmethyl isocyanide (TosMIC) reagents and imines generated in situ. Traditional imine-forming reactions employing virtually any aldehyde and amine followed by addition of the TosMIC reagent delivers 1,4,5-trisubstituted imidazoles with predictable regiochemistry. Employing chiral amines and aldehydes, particularly those derived from alpha-amino acids, affords imidazoles with asymmetric centers appended to N-1 or C-5 with excellent retention of chiral purity. 1,4-Disubstituted imidazoles are also readily prepared by a simple variant of the above procedure. Selecting glyoxylic acid as the aldehyde component of this procedure leads to intermediates such as 48, which readily undergo decarboxylation and elimination of the tosyl moiety to deliver 1,4-disubstituted imidazoles in high yields. Alternatively, using NH(4)OH as the amine component in conjunction with a variety of aldehydes delivers 4, 5-disubstituted imidazoles in moderate to good yields in a single pot while avoiding the need for protecting groups. Finally, the facile preparation of mono- and disubstituted oxazoles from these TosMIC reagents and aldehydes is described.

Aldehydes↗
PubMed2000

Domiciliary occupational therapy for patients with stroke discharged from hospital: randomised controlled trial.

OBJECTIVE: To establish if a brief programme of domiciliary occupational therapy could improve the recovery of patients with stroke discharged from hospital. DESIGN: Single blind randomised controlled trial. SETTING: Two hospital sites within a UK teaching hospital. SUBJECTS: 138 patients with stroke with a definite plan for discharge home from hospital. INTERVENTION: Six week domiciliary occupational therapy or routine follow up. MAIN OUTCOME MEASURES: Nottingham extended activities of daily living score and "global outcome" (deterioration according to the Barthel activities of daily living index, or death). RESULTS: By eight weeks the mean Nottingham extended activities of daily living score in the intervention group was 4.8 points (95% confidence interval -0.5 to 10.0, P=0.08) greater than that of the control group. Overall, 16 (24%) intervention patients had a poor global outcome compared with 30 (42%) control patients (odds ratio 0.43, 0.21 to 0.89, P=0.02). These patterns persisted at six months but were not statistically significant. Patients in the intervention group were more likely to report satisfaction with a range of aspects of services. CONCLUSION: The functional outcome and satisfaction of patients with stroke can be improved by a brief occupational therapy programme carried out in the patient's home immediately after discharge. Major benefits may not, however, be sustained.

Activities of Daily Living↗
PubMed2000

Patterns of infant mortality caused by major congenital anomalies.

BACKGROUND: We assessed the impact of recent advances in perinatal care on infant mortality due to congenital anomaly. METHODS: Analysis of trends in congenital anomaly-attributed infant mortality, using the 1981-1995 Statistics Canada's birth and death records, with a total of 2,878,826 live births, 21,883 infant deaths, and 6, 908 infant deaths due to congenital anomalies. RESULTS: Infant mortality due to major congenital anomaly decreased from 3.11 per 1, 000 live births in 1981 to 1.89 per 1,000 live births in 1995. Cause-specific infant mortality rates for anencephaly, spina bifida, other central nervous system anomalies, cardiovascular system anomalies, respiratory system anomalies, digestive system anomalies, certain musculoskeleton anomalies, urinary system anomalies, chromosomal anomalies, and multiple congenital anomalies were 0.20, 0.23, 0.27, 1.04, 0.24, 0.08, 0.22, 0.16, 0.22, and 0.13 per 1,000 live births, respectively, in 1981-1983, whereas corresponding rates were 0.07, 0.07, 0.18, 0.73, 0.25, 0.03, 0.12, 0.12, 0.26, and 0.06 per 1,000 live births, respectively, in 1993-1995. CONCLUSIONS: Recent Canadian data show that infant deaths caused by major congenital anomalies have decreased significantly, but reductions varied substantially according to specific forms of anomalies.

Canada↗
PubMed2000

Body dysmorphic disorder.

The understanding of BDD and its treatment has expanded significantly in the past decade as controlled research has followed the leads from case reports and clinical experience. BDD is recognized as a severe, disabling disorder that is more common that had been assumed. Although BDD is still difficult to treat, success has been demonstrated for SRIs and CBT. Much remains to be discovered. To date, little is known about the causes and pathophysiology of BDD. Research that would illuminate these also would increase understanding of its relationship to other disorders, such as OCD, depression, and social phobia, and open up possibilities for prevention and new approaches to treatment. Investigations in brain imaging and genetics are underway. Research in pharmacotherapy and CBT, individually and combined, is needed to refine, extend, and optimize treatment.

Cognitive Behavioral Therapy↗
PubMed2000

Pharmacotherapy for obsessive-compulsive disorder.

SSRIs and the tricyclic antidepressant clomipramine are the first-line therapies for patients with OCD, with the side-effect profile of SSRIs being more favorable than that of clomipramine. As many as 40% to 60% of patients with OCD may not respond to adequate trials of SRIs. Not all patients tolerate SSRIs, and delays in full therapeutic responses often occur. Thus, other pharmacologic approaches to treating patients with OCD have been investigated. Augmentation and monotherapy have been explored with serotonergic enhancers, dopamine and 5-HT antagonists, enhancers of second-messenger systems, and GABAergic agents with varying efficacy.

Antidepressive Agents, Tricyclic↗
PubMed2000

The relationship between repetitive behaviors and growth hormone response to sumatriptan challenge in adult autistic disorder.

Autism is heterogeneous with respect to clinical symptoms and etiology. To sort out this heterogeneity in autism, we investigated whether specific neurobiological markers vary in parallel to core symptomatology. Specifically, we assessed growth hormone response to the 5-HT 1d agonist, sumatriptan, and linked this measure of serotonergic function to the severity of repetitive behaviors in adult autistic patients. Eleven adult patients with autism or Asperger's disorder were randomized to single dose sumatriptan (6 mg SQ) and placebo challenges, separated by a one-week interval. In adult autistic disorders, severity of repetitive behaviors at baseline, as measured by YBOCS-compulsion score, significantly positively correlated with both peak delta growth hormone response and area under the curve growth hormone response to sumatriptan. Thus, the severity of a specific behavioral dimension in autism (repetitive behaviors) parallels the sensitivity of the 5-HT 1d receptor, as manifest by sumatriptan elicited GH response.

Adolescent↗