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Biomedical subjects

B Law

Publications and source records attributed to B Law.

At least 37 records · Page 2Linked to original sources
PubMed1999

A combined vaccine against hepatitis A and B in children and adolescents.

BACKGROUND: Pediatric monocomponent formulations of vaccines against hepatitis A and B have been proved to be safe and immunogenic in children. OBJECTIVES: To investigate the safety and immunogenicity of a combined hepatitis A/B vaccine in children 1 to 15 years of age. METHODS: Three doses of a combined vaccine containing 360 enzyme-linked immunosorbent assay units of hepatitis A antigen and 10 microg of hepatitis B surface antigen were administered in a 0-, 1-, 6-month schedule to three groups of children: a group of 1- to 6-year-olds (n = 60); and two groups of 6- to 15-year-olds (both n = 60). RESULTS: Reactogenicity, assessed using diary cards, was not affected by the age of the subjects or the vaccine lot and was similar to that described with the monocomponent vaccines. Local and systemic reactions were mostly mild or moderate and resolved spontaneously. One month after the second dose 100 and 98.8% of all three groups had seroconverted against hepatitis A virus and hepatitis B virus, respectively. After the third dose all subjects were seropositive for both components, with geometric mean titers for anti-hepatitis A virus of 6518 to 8907 mIU/ml and for anti-hepatitis B surface antibody of 7255 to 11732 mIU/ml in the three groups. CONCLUSION: The combined pediatric hepatitis A/B vaccine formulation was well-tolerated and highly immunogenic in children 1 to 15 years old.

Adolescent↗
PubMed1999

A case-control study of Yersinia enterocolitica infections in Auckland.

OBJECTIVE: To identify major risk factors for Yersinia enterocolitica (YE) and identify measures to reduce YE infections. METHODS: A prospective case control study, group age matched, using 186 cases of YE identified by community pathology laboratories and 379 randomly selected controls. Conducted between April 1995 and June 1996 in Auckland, New Zealand. Face-to-face interviews used a standardised questionnaire examining exposures to factors potentially associated with YE infections including untreated water, unreticulated sewerage, consumption of selected foods, selected food handling practices and socio-demographic factors. Multivariate logistic regression was used to calculate adjusted odds ratios for the potential risk factors. Population attributable risk (PAR) was calculated for significant exposures. RESULTS: Having more than two people living in the home was more common among cases than controls (OR = 2.2). Town supply water (OR = 0.2), reticulated sewerage (OR = 0.34) and looking after a young child (OR = 0.51) were significantly less common. Of the meats, only pork (OR = 1.34) had a higher consumption rate, while bacon (OR = 0.75) and smallgoods (OR = 0.73) were consumed less frequently by cases than controls. Eating food from a sandwich bar was more frequent among cases (OR = 1.18). Fruit and vegetable consumption was marginally less (OR = 0.98). The population attributable risk of these factors was 0.89, implying that 89% of YE would be eliminated if adverse exposures were removed. CONCLUSIONS: The risk of YE illness is increased by contact with untreated water, unreticulated sewerage and consumption of pork. Investigation of non-town water supply, informal sewerage systems and methods of preparation and consumption of pork are recommended to determine how YE enters the human food chain.

Adolescent↗
PubMed1999

Cost of chickenpox in Canada: part I. Cost of uncomplicated cases.

OBJECTIVE: The purpose of this study was to assess the direct medical costs and productivity losses associated with uncomplicated chickenpox (no hospitalization) in Canada. METHODS: A total of 179 otherwise healthy 1- to 9-year-old children with active chickenpox were recruited from schools, day care centers, and physician offices in 5 provinces. Direct medical (physician contacts, medication, and diagnostic tests) and nonmedical (personal expenses including child care) resources expended during the illness were determined by caregiver interview. Productivity losses attributable to the disease were determined by assessing caregiver time lost from work and daily activities. Unit costs for all resources were obtained from sources in 2 provinces, and per-patient treatment costs were determined from the patient, Ministry of Health, and societal perspectives. RESULTS: From a societal perspective, the per-case cost for children from 1 to 4 years of age and from 5 to 9 years of age was $370.2 and $236.5, respectively. Direct medical costs accounted for 10% of the total costs in both groups. The largest cost driver in patient care was caregiver productivity losses, which amounted to $316.5 in the younger age group and to $182.7 in the older age group. Based on an estimated yearly incidence of 344 656 cases of uncomplicated chickenpox in Canada, the total annual societal burden of the disease can be estimated at $109.2 million, with a cost to the Ministry of Health of $11.2 million. CONCLUSION: Chickenpox is one of the last common childhood diseases prevalent in Canada, and the uncomplicated disease, despite its rather benign course, imparts a large annual economic burden.

Canada↗
PubMed1999

Cost of chickenpox in Canada: part II. Cost of complicated cases and total economic impact. The Immunization Monitoring Program-Active (IMPACT).

OBJECTIVE: Primarily, to determine the direct medical costs and productivity losses associated with complicated chickenpox (hospitalized cases) and, secondarily, to quantify the overall economic burden of chickenpox in Canada. METHODS: Direct medical resource consumption patterns were determined by chart review of 160 otherwise healthy children and 40 children with leukemia hospitalized for chickenpox. Children were selected from the database of the Immunization Monitoring Program Active (IMPACT), a network of 11 tertiary-care hospitals in Canada that collected information at the time of hospitalization from January 1991 to March 1996. An additional 26 healthy children hospitalized were recruited prospectively by IMPACT. Productivity losses (time lost from work and daily activities) were assessed by caregiver interviews. Treatment costs were determined from the patient, Ministry of Health, and societal perspectives. RESULTS: The average societal per case cost for complicated chickenpox in healthy children was $7060 and $8398, respectively, from the retrospective and prospective assessments. For children with leukemia, the direct medical cost was estimated at $7228. These costs were combined with a cost established previously for uncomplicated chickenpox. The estimated yearly overall economic impact of chickenpox in Canada was $122.4 million, with $24.0 million attributable to Ministry of Health costs, assuming an estimated yearly incidence of 346 527 cases and a 0.54% rate of hospitalization for healthy children. CONCLUSIONS: Direct medical costs are the major cost driver in the care of complicated chickenpox. However, in the context of the overall economic burden of the disease, uncomplicated chickenpox is the major cost driver, contributing 89% to the total cost.

Canada↗
PubMed1999

Treatment with farnesyl-protein transferase inhibitor induces regression of mammary tumors in transforming growth factor (TGF) alpha and TGF alpha/neu transgenic mice by inhibition of mitogenic activity and induction of apoptosis.

Mouse mammary tumor virus-transforming growth factor alpha (MMTV-TGF alpha) and MMTV-TGF alpha/neu transgenic mice develop mammary tumors after a long latency and therefore provide useful model systems for breast cancer with its recognized activation of receptor tyrosine kinase signaling. We used these mice to study the antitumor effect of L-744,832 (FTI), a potent and selective inhibitor of farnesyl-protein transferase, and hence of Ras function. A total of 55 mice were assigned randomly to treatment with FTI or vehicle, and one-half of the mice were crossed over after initial treatment to the opposite group. L-744,832 induced reversible regression of mammary tumors that was paralleled by a decrease in serum levels of TGF alpha secreted by the tumor cells. There was no difference in response to treatment with FTI between MMTV-TGF alpha mice, in which tumorigenesis was accelerated by multiparity or the chemical carcinogen 7,12-dimethylbenzanthracene, and MMTV-TGF alpha/neu mice. The tumor histological type had no impact on FTI sensitivity. For mechanistic analyses, tumor excision biopsies were obtained from 12 mice before and after treatment with L-744,832. In these samples, tumor regression was paralleled biochemically by inhibition of mitogen-activated protein kinase activity and biologically by an increase in G1-phase and decrease in S-phase fractions, as well as induction of apoptosis. These results suggest that the potential clinical use of FTI could be expanded to include cancers harboring activated receptor tyrosine kinases as well as those containing activated Ras.

Alkyl and Aryl Transferases↗
PubMed1998

The application of strong cation exchange high-performance liquid chromatography to drug analysis.

The application of strong cation exchange (SCX) HPLC to the analysis of drugs in plasma, tissue and rodent feed is presented. This approach is shown to give useful separations allowing the separation of physiochemically diverse compounds in a simple isocratic system. The SCX columns are not as robust as standard reversed-phase materials and to ensure maximum column lifetimes the use of a guard column is recommended.

Animal Feed↗
PubMed1998

An approach to the evaluation and comparison of reversed-phase high-performance liquid chromatography stationary phases.

An approach to the evaluation and comparison of reversed-phase high-performance liquid chromatography stationary phases with particular emphasis on data analysis and presentation is described. Assessment is based on the peak efficiency, asymmetry (USP tailing factor) and relative retention properties shown by 24 basic compounds having a wide range of structural and physico-chemical properties. A novel approach to data normalisation and presentation is described. This overcomes the problems associated with the quality of the column packing process, as well as differences in stationary phase selectivity which in conjunction with extra column band broadening effects can make comparisons meaningless.

Buffers↗
PubMed1998

The determinants of fat intake in a multi-ethnic New Zealand population. Fletcher Challenge--University of Auckland Heart and Health Study Management Committee.

BACKGROUND: The New Zealand diet is high in total and saturated fat and this is likely to be contributing to the increasing prevalence of obesity and relatively high rates of coronary heart disease in New Zealand. The identification of subgroups with a high-fat intake will enable nutrition-related public health strategies to be better targeted. METHODS: Subjects from two surveys were included in the study: 7574 employees from a large multinational workforce survey and 2447 people aged 35-84 years selected from a stratified random sample of the electoral roll in central Auckland. Fat and saturated fat intake were assessed by short questionnaire which gave a dietary fat habits (DFH) score and supplemented by a six-item food frequency questionnaire. RESULTS: The DFH scores were higher in males than in females at all ages, and there was an inverse relationship with age which was stronger for males. Age-adjusted scores showed significantly higher DFH scores for Maori than for Europeans. Lower socioeconomic status was associated with higher DFH scores in males. Current smoking and heavy drinking (in males) were associated with significantly higher DFH scores after controlling for socioeconomic status. The results of the limited food frequency questionnaire supported the trends in DFH scores. CONCLUSIONS: The subgroups with high total and saturated fat intakes which should be a priority for public health action are young and middle-aged males, Maori and lower socioeconomic status males. The clustering of high-fat intake with smoking and heavy drinking should be considered when developing preventative strategies.

Adult↗
PubMed1997

A practical guide for the diagnosis and treatment of pediatric pneumonia.

OBJECTIVE: To develop guidelines for the diagnosis and management of community-acquired pediatric pneumonia. OPTIONS: Clinical assessment, radiography, laboratory testing, and empirical antimicrobial therapy. OUTCOMES: Increased awareness of age-related causes, improved accuracy of clinical diagnosis, better utilization of diagnostic testing and the rational use of empirical antimicrobial therapy resulting in more rapid diagnosis, initiation of appropriate therapy and decreased morbidity and mortality. EVIDENCE: A MEDLINE search for relevant articles published from 1996 to September 1996 using the MeSH terms "pediatric," "pneumonia," "respiratory tract infection," "pneumonitis," "etiology," "diagnosis," "therapy," "antibiotics," "resistance," "radiology," "microbiology" and "biochemistry." VALUES: A hierarchical evaluation of the strength of evidence modified from the methods of the Canadian Task Force on the Periodic Health Examination was used. When application of the hierarchy was not feasible or appropriate, different evaluation criteria were used. BENEFITS, HARMS AND COSTS: Increased awareness of the causes of pneumonia, accurate diagnosis and prompt treatment should reduce costs associated with unnecessary investigations and complications due to inappropriate treatment. RECOMMENDATIONS: Age is the best predictor of the cause of pediatric pneumonia, viral pneumonia being most common during the first 2 years of life. The absence of a symptom cluster of respiratory distress, tachypnea, crackles and decreased breath sounds accurately excludes the presence of pneumonia (level II evidence). Bacterial cultures of samples from the nasopharynx and throat have no predictive value; however, Gram staining and culture of sputum from older children and adolescents are useful (level III evidence). Oral antimicrobial therapy will provide adequate coverage for most mild to moderate forms of pneumonia in children (level III evidence). Parenteral therapy is typically reserved for neonates and patients with severe pneumonia admitted to hospital (level III evidence). VALIDATION: These recommendations are based on consensus of Canadian experts in infectious diseases and microbiology. They are the only guidelines to address antimicrobial treatment from an age-related, etiologic perspective. SPONSOR: The development of these guidelines and the technical support and assistance of Core Health Inc. in preparing this manuscript were funded through an unrestricted educational grant from Abbott Laboratories Canada. The sponsoring company was not involved in determining the membership of the consensus group or the content of the guidelines.

Adolescent↗
PubMed1997

The development and evaluation of a diluter-ultraviolet spectrophotometric analysis system for the determination of drugs in solutions and suspensions.

An automated system has been developed and validated for the analysis of liquid formulations (solution and suspension). The system comprises a multi-place magnetic stirrer, a diluter and a diode array UV spectrophotometer. The system can handle a wide range of drug formulation concentrations (> 200 mg ml-1) and gives excellent precision and accuracy with no detectable carryover. The analysis acceptance parameters are user-definable and the analysis process, including interpretation and reporting of the data, is fully automated.

Chemistry, Pharmaceutical↗
PubMed1996

The development and performance of a radioimmunoassay for the analysis of ZM 213,689, the major metabolite of meropenem--a carbapenem antibiotic--in plasma and urine.

The development of a radioimmunoassay for the analysis of ZM 213,689, the major metabolite of meropenem found in the plasma and urine of rat, dog and humans, is described. The assay is rapid in order to minimise the effect of degradation of meropenem to ZM 213,689 in biological samples and has a working range of 0.08-3.5 mg l-1 (RSD < or = 15%). The antibody was specific for ZM 213,689 with cross-reactivity to meropenem of only 0.4%. The synthesis of the immunogen and radiotracer involved a novel approach due to the multifunctional nature of ZM 213,689.

Animals↗
PubMed1996

Surveillance of vaccine-related adverse events in the first year of life: a Manitoba cohort study.

This study used data from the population database through which the province of Manitoba, Canada, administers its universal health insurance plan. Enrollment, hospitalization, and immunization files from children born in the 1987-1989 period were linked using the unique identification number assigned to each population member. Analysis of these linked data successfully identified serious potential adverse events in the first year of life and the timing of events around immunization. Not only is population-based active surveillance for immunization-related events feasible, but the techniques described, applied to years of data accumulated through surveillance, offer powerful research tools. Baseline population incidences of adverse events were calculated, temporal relationships between events and immunization assessed, and incidences for events showing true temporal associations determined. Eventual goals are the quantification of vaccine-related risk and the gathering of evidence concerning casual associations. The approach could be used readily by several other Canadian provinces and by health maintenance organizations in the United States.

Cohort Studies↗
PubMed1996

Study of booster doses of two Haemophilus influenzae type b conjugate vaccines including their interchangeability.

A prospective, two center study of 319 children was undertaken to assess responses to booster immunization in healthy 18-month-olds who completed primary immunization 12 months earlier with Haemophilus influenzae type b (Hib) conjugate vaccine (either HbOC or PRP-T). Interchangeability of these products as boosters was also assessed, using combination products containing diphtheria, pertussis and tetanus components. The study was randomized and evaluator blinded. Sera obtained prior to booster vaccination and 4 weeks later were tested for anti-PRP using an IgG-specific enzyme immunoassay. Pre-immunization anti-PRP levels were low: unmeasurable levels (< 0.06 microgram ml-1) were present in 47% of those primed with HbOC and 35% of those primed with PRP-T (P < 0.05). Most children responded strongly to booster vaccination. Interchanging the products had no detrimental effect. Children who lacked measurable antibody prior to re-vaccination had significantly weaker responses 4 weeks afterward. Earlier Hib booster vaccination should be considered in Canada to avoid low anti-PRP trough levels. Extended follow-up of antibody levels and vaccine protective efficacy is also advisable given the observed heterogeneity of responses to booster vaccination.

Antibodies↗
PubMed1995

The dimeric and catalytic subunit forms of protein phosphatase 2A from rat brain are stimulated by C2-ceramide.

Protein phosphatase 2A (PP-2A) is a heterotrimeric enzyme consisting of a catalytic (C) subunit and A and B regulatory subunits. PP-2A is activated by ceramide in vitro suggesting that PP-2A may be a target of this putative second messenger in vivo (Dobrowsky, R. T., Kamibayashi, C., Mumby, M. C., and Hannun, Y. A. (1993) J. Biol. Chem. 268, 15523-15530). In this study, sensitivity to ceramide was only observed when the B subunit was present, suggesting that the B subunit was required for ceramide activation. Here we show that dimeric PP-2A, produced from trimeric PP-2A by heparin-agarose-induced dissociation of the B subunit and isolated by preparative native electrophoresis, is activated by ceramide. The catalytic subunit of PP-2A, produced from trimeric PP-2A by freezing and thawing in the presence of 0.2 M beta-mercaptoethanol and isolated by gel filtration, is also activated by ceramide. The trimeric and catalytic subunit forms of PP-2A exhibit a similar dose dependence of activation by ceramide, and are stimulated to a similar extent at ceramide concentrations yielding maximal activation. These findings indicate that neither the A nor the B subunit is required for ceramide stimulation of PP-2A. Together, these results demonstrate that the catalytic subunit contains a ceramide binding site and suggest that efforts to understand the mechanism of activation of PP-2A by ceramide should be focused on this subunit. The discovery that the catalytic subunit contains a ceramide binding site raises the possibility that other members of this serine/threonine phosphatase gene family may contain lipid binding sites and be regulated by ceramide or other lipid second messengers.

Animals↗
PubMed1995

Identification of soluble protein phosphatases that dephosphorylate voltage-sensitive sodium channels in rat brain.

Rat brain sodium channels are phosphorylated at multiple serine residues by cAMP-dependent protein kinase. We have identified soluble rat brain phosphatases that dephosphorylate purified sodium channels. Five separable forms of sodium channel phosphatase activity were observed. Three forms (two, approximately 234 kDa and one, 192 kDa) are identical or related to phosphatase 2A, since they were 85-100% inhibited by 10 nM okadaic acid and contained a 36-kDa polypeptide recognized by a monoclonal antibody directed against the catalytic subunit of phosphatase 2A. Immunoblots performed using antibodies specific for isoforms of the B subunit of phosphatase 2A indicate that the two major peaks of phosphatase 2A-like activity, A1 and B1, are enriched in either B' or B alpha. The remaining two activities (approximately 100 kDa each) probably represent calcineurin. Each was relatively insensitive to okadaic acid, was active only in the presence of CaCl2 and calmodulin, and contained a 19-kDa polypeptide recognized by a monoclonal antibody raised against the B subunit of calcinerurin. Treatment of synaptosomes with okadaic acid to inhibit phosphatase 2A or cyclosporin A to inhibit calcineurin increased apparent phosphorylation of sodium channels at cAMP-dependent phosphorylation sites, as assayed by back phosphorylation. These results indicate that phosphatase 2A and calcineurin dephosphorylate sodium channels in brain, and thus may counteract the effect of cAMP-dependent phosphorylation on sodium channel activity.

Animals↗