Biomedical subjects

W Craig

Publications and source records attributed to W Craig.

At least 19 recordsLinked to original sources

PubMed2006

Oral versus intravenous rehydration for treating dehydration due to gastroenteritis in children.

BACKGROUND: Dehydration associated with gastroenteritis is a serious complication. Oral rehydration is an effective and inexpensive treatment, but some physicians prefer intravenous methods. OBJECTIVES: To compare oral with intravenous therapy for treating dehydration due to acute gastroenteritis in children. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (March 2006), CENTRAL (The Cochrane Library 2006, Issue 1), MEDLINE (1966 to March 2006), EMBASE (1974 to March 2006), LILACS (1982 to March 2006), and reference lists. We also contacted researchers, pharmaceutical companies, and relevant organizations. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing intravenous rehydration therapy (IVT) with oral rehydration therapy (ORT) in children up to 18 years of age with acute gastroenteritis. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed quality using the Jadad score. We expressed dichotomous data as a risk difference (RD) and number needed to treat (NNT), and continuous data as a weighted mean difference (WMD). We used meta-regression for subgroup analyses. MAIN RESULTS: Seventeen trials (1811 participants), of poor to moderate quality, were included. There were more treatment failures with ORT (RD 4%, 95% confidence interval (CI) 1 to 7, random-effects model; 1811 participants, 18 trials; NNT = 25). Six deaths occurred in the IVT group and two in the ORT groups (4 trials). There were no significant differences in weight gain (369 participants, 6 trials), hyponatremia (248 participants, 2 trials) or hypernatremia (1062 participants, 10 trials), duration of diarrhea (960 participants, 8 trials), or total fluid intake at six hours (985 participants, 8 trials) and 24 hours (835 participants, 7 trials). Shorter hospital stays were reported for the ORT group (WMD -1.20 days, 95% CI -2.38 to -0.02 days; 526 participants, 6 trials). Phlebitis occurred more often in the IVT group (NNT 50, 95% CI 25 to 100) and paralytic ileus more often in the ORT group (NNT 33, 95% CI 20 to 100, fixed-effect model), but there was no significant difference between ORT using the low osmolarity solutions recommended by the World Health Organization and IVT (729 participants, 6 trials). AUTHORS' CONCLUSIONS: Although no clinically important differences between ORT and IVT, the ORT group did have a higher risk of paralytic ileus, and the IVT group was exposed to risks of intravenous therapy. For every 25 children (95% CI 14 to 100) treated with ORT one would fail and require IVT.

Administration, Oral↗

PubMed2006

Associations between risk behavior and injury and the protective roles of social environments: an analysis of 7235 Canadian school children.

OBJECTIVE: The social etiology of adolescent injury remains poorly understood. The Population Health Framework suggests that the etiology of adolescent injury involves interactions between individual risk factors and the natures of adolescent environments. The purpose of this study was to apply this framework to examination of relationships between adolescent risk taking and injury, and the potential modifying effects of supportive home and school environments. METHODS: The analysis was conducted in a representative sample of 7235 males and females (10-16 years old) from Canada. Results were based on records from the 2001/02 World Health Organization Health Behaviour in School-Aged Children Survey. Individual items and factor analytically derived scales were used to describe and then model injury outcomes, risk behaviors, perceived home, and school climates, and the relationships between these variables in a theory driven etiological analysis. RESULTS: Adolescents with supportive home and school environments experienced lower relative odds of engagement in risk taking behavior and lower relative odds of injury. Gradients were observed between the extent of adolescent risk taking and the occurrence of injury. Interactions were not observed between risk taking behavior, perceived support in home and school climates, and injury. CONCLUSIONS: Risk taking is common among adolescents and plays a role in the etiology of injury. Supportive social climates clearly protect adolescents from engaging in these behaviors, and also the occurrence of some forms of injury. However, once an adolescent chooses to engage in risk taking behaviour, a supportive environment may not protect them from injury.

Adolescent↗

PubMed2005

Direct gene transfer in potato: a comparison of particle bombardment of leaf explants and PEG-mediated transformation of protoplasts.

Direct gene transfer methods in potato would facilitate the transfer of multiple genes and the manipulation of metabolic pathways in this species. In this study, up to 1.8 transformation events per shot (=0.5 per bombarded leaf) and 67.2 events per million protoplasts treated were obtained with particle bombardment and PEG-mediated direct DNA uptake, respectively. Limited disassociation of both HPT and GUS genes appeared to occur during the process of integration in only 19% of transformants. A large number of transformed potato plants with transgene expression at levels comparable to Agrobacterium-mediated transformation was obtained. High levels of GUS expression were only obtained in lines derived from PEG treatment. No correlation between the number of gene insertions and gene expression levels was found, suggesting that multiple insertions may have little or no effect on transgene expression.

Biolistics↗

PubMed2005

Patient motivations surrounding participation in phase I and phase II clinical trials of cancer chemotherapy.

Successful advances in the treatment of advanced malignant diseases rely on recruitment of patients into clinical trials of novel agents. However, there is a genuine concern for the welfare of individual patients. The aim of this study was to examine motives of patients entering early clinical trials of novel cancer therapies. Questionnaire survey with both open- and close-ended questions. The patients were surveyed after they had given informed consent and before or during the first cycle of treatment. In all, 38 phase I/II trial patients participated and completed the survey. Obtaining possible health benefit was listed by 89% as being a 'very important' factor in their decision to participate, with only 17% giving reasons of helping future cancer patients and treatment. Other items cited as a 'very important' motivating factor were 'trust in the doctor' (66%), 'being treated by the latest treatment available' (66%), 'better standard of care and closer follow-up' (61%), and 'closer monitoring of patients in trials' (58%). Only 47% patients indicated that someone had explained to them about any 'reasonable' alternatives to the trial. In total, 71% strongly agreed that 'surviving for as long time as possible was the most important thing (for them)'. Nearly all (97%) indicated that they knew the purpose of the trial and had enough time to consider participation in the trial (100%). In this survey, most patients entering phase I and II clinical trials felt they understood the purpose of the research and had given truly informed consent. Despite this, most patients participated in the hope of therapeutic benefit, although this is known to be a rare outcome in this patient subset. Trialists should be aware, and take account of the expectations that participants place in trial drugs.

Adult↗

PubMed2003

Hereditary haemochromatosis and hepatocellular carcinoma in males: a strategy for estimating the potential for primary prevention.

OBJECTIVES: Homozygosity for the C282Y mutation of the HFE gene is the main cause of iron overload in hereditary haemochromatosis. This study calculated the number of hepatocellular carcinoma cases among a cohort of white males that could be attributed to C282Y homozygosity. A better understanding of the extent of potentially preventable mortality arising from this cancer might help with decision making about the feasibility of population screening. METHODS: We combined information from published life tables, age-specific cancer rates and DNA studies of archived liver biopsy specimens to calculate the number of cases of hepatocellular carcinoma that might occur during the lifetime of a cohort of 1,000,000 men, including a subgroup of 5000 C282Y homozygotes. RESULTS: Hepatocellular carcinoma was estimated to occur in 2673 men in the cohort (1:374); 267 of these cases were in the subgroup of 5000 C282Y homozygotes (1:17). If these 267 cases were prevented, the remaining lifetime risk among all males would be 1:416. The relative risk for this cancer in C282Y homozygotes is 23. CONCLUSIONS: There continues to be uncertainty about the efficacy of screening for haemochromatosis. Hepatocellular carcinoma is the most readily quantifiable serious health problem attributable to this source. Further confirmatory DNA (C282Y) studies would be helpful in larger, unbiased sets of archived biopsy specimens, as a way to confirm the present estimate. Any strategy designed to prevent attributable liver cancer is likely to prevent other serious problems from haemochromatasis as well.

Adult↗

PubMed2001

Photoacoustic point source.

We investigate the photoacoustic effect generated by heat deposition at a point in space in an inviscid fluid. Delta-function and long Gaussian optical pulses are used as sources in the wave equation for the displacement potential to determine the fluid motion. The linear sound-generation mechanism gives bipolar photoacoustic waves, whereas the nonlinear mechanism produces asymmetric tripolar waves. The salient features of the photoacoustic point source are that rapid heat deposition and nonlinear thermal expansion dominate the production of ultrasound.

Journal Article↗

PubMed2001

The interpersonal context of romantic autonomy in adolescence.

This study explored the interpersonal context of romantic autonomy in mid adolescence by examining within-relationship links with romantic intimacy and affiliation, links across relationships with mothers and friends, and individual differences due to age and gender. Two hundred and thirty adolescents in grades 9, 10 and 11 with a current romantic partner, completed self-report questionnaires assessing their relationships. The results indicated that romantic autonomy was positively linked to romantic intimacy and affiliation, although this link differed according to the duration of the romantic relationship. The results also indicated that romantic autonomy was higher among girls than boys. Finally, romantic autonomy was uniquely linked to intimacy and autonomy in both maternal and friend relationships. Overall, this study highlights the interconnection of intimacy and autonomy in romantic relationships and the interconnections across relationships.

Adolescent↗

PubMed2001

Managing chronic hepatitis C acquired through intravenous drug use.

We retrospectively reviewed the provision and uptake of hospital services for 253 current and ex-intravenous drug users with hepatitis C virus (HCV). Overall, 237 attended at least one clinic (mean age 32 years, 70% male, 43% on maintenance methadone); 81% had evidence of active viral replication and 137 agreed to a liver biopsy to assess disease severity. Of these 137, 24% had mild chronic hepatitis with a low risk of progression to cirrhosis, but 9% had cirrhosis (mean age 40 years, mean time since initial intravenous drug use 15.8 years). Only 50 of the 100 patients in whom antiviral therapy was indicated, commenced treatment; 18 (36%) have had a sustained virological response. The natural history or response to treatment of chronic HCV in those who acquire it through intravenous drug use is not different to that previously reported for post-transfusion HCV. However, a substantial proportion default from follow-up or decline further intervention. As intravenous drug use is now the main risk factor for acquisition of HCV, these data have implications for future delivery of care aimed at limiting the morbidity of chronic HCV, and limiting the spread of hepatitis C virus infection amongst intravenous drug users.

Adolescent↗

PubMed2001

HLA and interleukin 1 gene polymorphisms in primary biliary cirrhosis: associations with disease progression and disease susceptibility.

BACKGROUND AND AIMS: Twin and family studies suggest that there is a genetic component to primary biliary cirrhosis (PBC) but the genetic associations which have been described are weak with marked variations between centres. PBC is heterogeneous and genetic associations with disease progression may be obscured when the PBC population is analysed only as a whole and not subdivided. METHODS: We have investigated two candidate gene loci in 164 well characterised patients, 88 (54%) of whom had advanced disease. RESULTS: There was an increased frequency of the HLA DRB1*0801-DQA1*0401-DQB1*0402 haplotype in patients who had progressed to late stage disease (23% v 2% of controls; p=0000044; odds ratio (OR) 15.5, 95% confidence interval (CI) 3.52-68.4) but not in those with early stage disease (4% v 2%). Patients had a higher frequency of the IL-1B*1,1 genotype and lower frequencies of the IL-1B*1,2 and *2,2 genotypes (p=0.00078; OR 2.37, 95% CI 1.38-4.06), and higher frequency of the IL-1RN*1,1 genotype and lower frequency of the IL-1RN*1,2 genotype (p=0.0011; OR 2.28, 95% CI 1.34-3.89). The difference in the IL-1B*1,1 genotype distribution was most marked in patients with early stage disease (77% v 43% of controls; p=0.000003; OR 4.8, 95% CI 2.31-10) but the IL-1RN genotype distribution was similar in patients with early and late stage disease. CONCLUSIONS: These data indicate a complex relationship between immunoregulatory genes and PBC. While the IL-1 genes are markers of both disease susceptibility and progression, HLA genes appear to be principally associated with disease progression.

Case-Control Studies↗

PubMed2000

Bacteriologic efficacies of oral azithromycin and oral cefaclor in treatment of acute otitis media in infants and young children.

A prospective, open-label, randomized study was conducted in order to determine the bacteriologic efficacies of cefaclor and azithromycin in acute otitis media (AOM). Tympanocentesis was performed on entry into the study and 3 to 4 days after initiation of treatment. Bacteriologic failure after 3 to 4 days of treatment with both drugs occurred in a high proportion of culture-positive patients, especially in those in whom AOM was caused by Haemophilus influenzae (16 of 33 [53%] of those treated with azithromycin and 13 of 34 [52%] of those treated with cefaclor). Although a clear correlation of the persistence of the pathogen with increased MICs of the respective drugs could be demonstrated for Streptococcus pneumoniae, no such correlation was found for H. influenzae. It is proposed that susceptibility breakpoints for H. influenzae should be considerably lower than the current ones for both cefaclor and azithromycin for AOM caused by H. influenzae.

Acute Disease↗

PubMed2000

Dating experiences of bullies in early adolescence.

In this study, 196 young adolescents who reported that they bullied their peers were identified out of a sample of 1,758 students in Grades 5 through 8. After selecting from the total sample a group of nonbullying youth who were matched on gender, school, and grade, a comparison was made of the groups' dating experiences, quality of friend and boyfriend or girlfriend relationships, and acts of physical and social aggression. The results indicated that bullies started dating earlier and engaged in more advanced dyadic dating than comparison adolescents. Bullies were highly relationship oriented, yet their views of their friends and boyfriends or girlfriends were less positive and less equitable than the comparison adolescents. Finally, bullies were more likely to report physical and social aggression with their boyfriends or girlfriends. Although the bullies reported more advanced pubertal development, this factor did not fully account for their dating precocity and negative romantic relationships. The results confirmed our hypotheses that adolescents whose peer relationships are characterized by bullying are at risk in their development of healthy romantic relationships.

Adolescent↗

PubMed1999

Peer involvement in bullying: insights and challenges for intervention.

The purpose of this research was to examine the peer processes that occur during bullying episodes on the school playground. These processes were examined from a social learning perspective, allowing us to consider the effects of various types of reinforcement among bullies, victims, and peers. Fifty-three segments of video tape were examined. Each segment contained a peer group (two or more peers) that viewed bullying on the school playground. Peers were coded for actively joining or passively reinforcing the bully, and for actively intervening on behalf of the victim. On average, four peers viewed the schoolyard bullying, with a range from two to 14 peers. Averaged across all episodes, peers spent 54% of their time reinforcing bullies by passively watching, 21% of their time actively modelling bullies, and 25% of their time intervening on behalf of victims. Older boys (grades 4-6) were more likely to actively join with the bully than were younger boys (grades 1-3) and older girls. Both younger and older girls were more likely to intervene on behalf of victims than were older boys. The results were interpreted as confirming peers' central roles in the processes that unfold during playground bullying episodes. We discuss the results in terms of the challenges posed to peer-led interventions. Peers' anti-bullying initiatives must be reinforced by simultaneous whole-school interventions.

Aggression↗

PubMed1998

Predictors of outcome in drug treatment of adolescent inpatients.

Little is known about for whom treatment is most effective and how to match adolescent clients to substance-abuse treatment. 280 adolescents treated in a multifaceted program participated. Of these, 128 did not complete treatment prior to termination of the 2-mo. inpatient phase. They were significantly different from clients who completed treatment measures of alienation, social maladaptation, aggression, and lower occupational status of the father. Of those who completed inpatient treatment and remained in the study at 1-mo. postdischarge (n = 69) two groups were formed, those who improved and those who either remained the same or worsened in terms of substance abuse. For those who improved factors which differentiated them were identification with middle-class values, tendency to be older, initial difficulty identifying emotions, and depressive symptoms at intake. Clients who did not change or worsened were distinguished by more social anxiety, depressive symptoms, and troubling thoughts at intake. These results suggest that individual characteristics may identify cases who are more likely to benefit from treatment.

Adolescent↗

PubMed1998

Sex steroids, the insulin-like growth factor regulatory system, and aging: implications for the management of older postmenopausal women.

Aging is associated with profound changes in the growth hormone/insulin-like growth factor (IGF) regulatory system. These include reductions in growth hormone, IGF-I, IGFBP3, and IGFBP-5 and an increase in IGFBP-4. These changes, coupled with rather marked declines in sex steroid production from both the ovary and adrenals may combine to have very deleterious effects on several organ systems in the postmenopausal woman. In particular, the prevalence of two very common diseases, osteoporosis and coronary artery disease, increase dramatically after the cessation of gonadal steroid production. The complex interrelationship between the IGF regulatory system and estrogens/androgens in the postmenopausal period may provide important clues as to the pathophysiology of both these disorders. In this paper, we begin to define the role of IGF-I (and its constituent IGF binding proteins) in skeletal and vascular tissue. Recent experimental data show the effects of estrogen on circulating and tissue IGFs in older individuals. Finally, estrogen replacement therapy affects the IGF regulatory system in postmenopausal women. Although conclusions from early studies remain somewhat preliminary, it is likely that the IGF regulatory system will be a prime target for future studies into the pathogenesis of several age and sex hormone related degenerative disorders.

Aged↗

PubMed1995

Further characterization of the plasma lipoprotein(a) distribution.

The plasma lipoprotein (a) [Lp(a)] distribution in caucasians is heavily skewed to the right, with evidence of bimodality. As there is a well-described inverse relationship between apolipoprotein(a) [apo(a)] size and Lp(a) concentration, it is likely that the presence of multiple apo(a) isoforms of differing frequency has a significant impact on the final distribution of Lp(a) concentrations. We have previously described an immunoblot method for examining the relationship between apolipoprotein(a) [apo(a)] size and lipoprotein(a) [Lp(a)] mass among samples heterozygous for apo(a) size, thus eliminating confounding by null or undetected apo(a) isoforms. In the present study, this method has been applied to examine the plasma Lp(a) distribution, independent of the effects of apo(a) isoform size and frequency. Seventy subjects heterozygous for apo(a) size were studied. To take into account the inverse relationship (P < 0.001) between apo(a) isoform size and Lp(a) concentration, Lp(a) data associated with each apo(a) isoform were normalized as multiples of the median Lp(a) concentration for that isoform. These apo(a) isoform-independent Lp(a) data demonstrated a strikingly multimodal distribution, with five major peaks. The relative frequencies of Lp(a) peaks 1-5 were 17.1%, 15.0%, 35.7%, 23.6%, and 8.6%, and associated median Lp(a) concentrations were 1.0, 6.2, 15.0, 21.8, and 39.6 mg/dL, respectively. Multivariate analysis demonstrated that apo(a) isoform size accounted for 23% and isoform-independent Lp(a) peaks for 59.5% of the variation in Lp(a) concentration. Further investigation of the characteristics of the apo(a) isoform-independent Lp(a) distribution is warranted.

Adult↗

PubMed1994

CD45 isoform expression on human haemopoietic cells at different stages of development.

Alternate splicing and glycosylation produce multiple CD45 isoforms which are selectively expressed on the surface of cells of the haemopoietic system. The expression of CD45RA, CD45RB and CD45RO on CD34+ and CD34- haemopoietic cells from umbilical cord blood, bone marrow and fetal liver were studied by flow cytometry. CD34+ subpopulations defined by CD45 isoform expression were sorted from bone marrow and tested in long-term culture assays. By combining results of functional studies with phenotypic data and previously published information, the following pattern of CD45 isoform expression on early haemopoietic cells was established. The most primitive CD34+ cells are CD45RO+ CD45RB+ and express low or undetectable levels of CD45RA. Upon erythroid differentiation, CD34+ cells remain CD45RO+ CD45RB+, whereas commitment into the myeloid and lymphoid lineages coincides with down-regulation of CD45RO and up-regulation of CD45RA. As a result, the majority of CD34+ cells can be divided into two mutually exclusive populations of cells which express either CD45RO or CD45RA. This notion was confirmed in this study by three-colour immunofluorescence. The alternative expression of various CD45 isoforms on functionally distinct haemopoietic cells suggests an important role for these molecules in the proliferation and differentiation of haemopoietic cells.

Alternative Splicing↗

PubMed1993

Expression of Thy-1 on human hematopoietic progenitor cells.

Expression of Thy-1 on hematopoietic cells from human fetal liver (FL), cord blood (CB), and bone marrow (BM) was studied with a novel anti-Thy-1 antibody, 5E10. Specificity of 5E10 for human Thy-1 was demonstrated by immunoprecipitation of a 25-35-kD molecule, and the sequence of a cDNA that was cloned by immunoselection of COS cells transfected with a cDNA library derived from a 5E10+ cell line. Two- and three-color immunofluorescence staining experiments revealed that the Thy-1 expression is restricted to, an average, 1-4% of FL, CB, and BM cells, and binding to these cell types is essentially restricted to a very small subset of lymphoid cells and approximately 25% of CD34+ cells. Thy-1+ CD34+ cells were further characterized as CD38lo/CD45RO+/CD45RA-/CD71lo/c-kit(lo) and rhodamine 123dull. When CD34+ cells were sorted on the basis of Thy-1 expression, the majority of clonogenic cells were recovered in the CD34+Thy-1- fraction, whereas the majority of cells capable of producing myeloid colonies after 5-8 wk of long-term culture (long-term culture initiating cells) were recovered in the Thy-1+CD34+ fraction. In addition to CD34+ cells, Thy-1 was found to be expressed on a variable, very small number (< 1%) of CD34- mononuclear cells in BM, CB, and peripheral blood that were further characterized as CD3+ CD4+ lymphocytes. The restricted expression of Thy-1 on primitive hematopoietic cells is in agreement with a previous report (Baum et al., 1992. Proc. Natl. Acad. Sci. USA. 89:2804) in which Thy-1 expression was used to enrich for primitive hematopoietic cells from fetal tissue. Compared with those previous studies, we found Thy-1 expression on a larger proportion of CD34+ cells (25% in our study vs. 5% in Baum et al.) and furthermore performed studies on Thy-1 expression on CD34+ cells from CB, FL, and BM in relation to markers that are known to be differentially expressed on hematopoietic cells. Taken together our results indicate that Thy-1-specific antibody 5E10 is an attractive tool for further studies on the biology and purification of human stem cells.

Adult↗

PubMed1993

Risk assessment in immunotoxicology. II. Relationships between immune and host resistance tests.

We have reported on the design and content of a screening battery using a "tier" approach for detecting potential immunotoxic compounds in mice (Luster et al., Fundam. Appl. Toxicol., 10, 2-19, 1988). The data base generated from these studies, which consists of over 50 selected compounds, has been collected and analyzed in an attempt to improve future testing strategies and provide information to aid in developing future quantitative risk assessment for immunotoxicity. In a recent study it was shown that as few as two or three immune parameters were needed to predict immunotoxicants in mice (Luster et al., Fundam. Appl. Toxicol., 18, 200-210, 1992). In particular, enumeration of lymphocyte populations and quantitation of the T-dependent antibody response were particularly beneficial. Furthermore, commonly employed apical measures (e.g., leukocyte counts, lymphoid organ weights) were fairly insensitive. The present analyses focus on the use of this data base to develop statistical models that examine the qualitative and quantitative relationship(s) between the immune function and host resistance tests. The conclusion derived from these analyses are: (1) A good correlation exists between changes in the immune tests and altered host resistance in that there were no instances where host resistance was altered without affecting an immune test(s). However, in some instances immune changes occurred without corresponding changes in host resistance. (2) No single immune test could be identified which was fully predictive for altered host resistance, although most assays were relatively good indicators (i.e., > 70%). Several others, such as proliferative response to lipopolysaccharide and leukocyte counts, were found to be relatively poor indicators for host resistance changes. (3) The ability to resist infectious agent challenge is dependent upon the degrees of immunosuppression and the quantity of infectious agent administered. (4) Logistic and standard regression modeling using one extensive chemical data set from the immunosuppressive agent, cyclophosphamide, indicated that most immune function-host resistance relationships followed linear rather than linear-quadratic (threshold-like) models. For most of the relationships this could not be confirmed using a large chemical data set and, thus, a more mechanistically based approach for modeling will need to be developed. (5) Using this limited data set, methods were developed for modeling the precise quantitative relationships between changes in selected immune tests and host resistance tests.

Animals↗