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Biomedical subjects

D Fraser

Publications and source records attributed to D Fraser.

At least 37 records · Page 2Linked to original sources
PubMed2000

Cloning and functional expression of a first inducible avian cytochrome P450 of the CYP3A subfamily (CYP3A37).

CYP3As represent a family of cytochromes P450 involved in the metabolism of both endogenous and exogenous natural and synthetic compounds. Well described in mammals, none have yet been cloned and characterized in avian species. In this paper, we report the cloning and analysis of an avian CYP3A (CYP3A37). Using an RNA differential display approach, an 80-bp phenobarbital-inducible cDNA fragment was amplified from chicken embryo liver. Based on its homology with mammalian CYP3As, this fragment was used to clone a full-length cDNA consisting of 1638 bp encoding a putative protein of 509 amino acids. The sequence shares between 57.4 and 62% identity at the amino acid level with CYP3As of other species. This cDNA was designated CYP3A37 according to the current cytochrome P450 nomenclature. When expressed in COS1 cells, the CYP3A37 cDNA produced a protein of congruent with55 kDa, which was recognized by polyclonal anti-rat CYP3A1 antiserum. In a bacterial expression system, the CYP3A37 cDNA produced a protein capable of steroid 6beta-hydroxylation. At a substrate concentration of 100 microM, progesterone, testosterone, and androstenedione were found to be 6beta-hydroxylated at a rate of 15.4, 11.7, 12.2 nmol/min/nmol P450, respectively. Used as control, the human CYP3A4 gave similar hydroxylation rates. Finally, in both chicken embryo liver and chicken hepatoma cells (LMH), CYP3A37 mRNA was increased after treatment with typical CYP3A inducers, such as metyrapone, phenobarbital, dexamethasone, and pregnenolone 16alpha-carbonitrile, but not rifampicin. CYP2H1, a well-characterized inducible chicken cytochrome P450, also was induced by the same compounds, suggesting similar regulation of CYP3 and CYP2 genes in this species.

Amino Acid Sequence↗
PubMed2000

Posttraumatic stress disorder and short-term outcome in early methadone treatment.

The aim of this study was to determine treatment adherence relative to frequency of violence and posttraumatic stress disorders (PTSD) among new methadone patients. Ninety-six opiate-abusing patients were evaluated for childhood physical and sexual abuse (CPSA), adulthood exposures to violence (ADVIOL), PTSD, and treatment adherence. Overall, 43% of the subjects dropped out of treatment within 3 months of intake. Occurrence of trauma or PTSD did not predict drop-out rates. A 2 (Gender) x 2 (PTSD) analysis of covariance (ANCOVA) with severity of other drug use on admission as a covariate, however, revealed a main effect for PTSD, F(4, 71) = 7. 69, p < or =.01, such that those patients with current PTSD revealed significantly more ongoing drug use at 3 months (M = 24.3, SD = 20. 9) than those without (M = 8.9, SD = 11.8). Examination of ongoing cocaine use using a 2 (Gender) x 2 (PTSD) ANCOVA also revealed a main effect for PTSD, F(4, 17) = 8.24, p < or = .005, such that those patients with current PTSD revealed significantly more ongoing cocaine use at 3 months postadmission (M = 51.6, SD = 37.6) than those without (M = 24.3, SD = 20.9). For both genders, CPSA and ADVIOL were associated with higher rates of PTSD, which in turn predicted poorer treatment adherence as measured by ongoing co-occurring drug abuse 3 months postadmission. Results underscore the need for routine assessment and targeted treatment of trauma in methadone patients.

Adult↗
PubMed2000

An exploration into the role of the teacher/lecturer in practice: findings from a case study in adult nursing.

Against a background of increasing concern over the widening theory practice gap and research evidence of problems in providing quality practice education, the English National Board (ENB) commissioned an 18 month study into the role of the teacher/lecturer in practice. This article, after providing a brief overview of the background, literature and methods, outlines the results from the Adult Case Study stage of the research. Documents, individual and focus group interviews of lecturers (n = 76), practitioners (n = 46) and students (n = 131) in five schools of nursing and midwifery provided data for analysis. A role labeled as 'link lecturer' was the most common approach acknowledged by all respondent groups. Despite overt commitment to the practice role by schools of nursing and midwifery, findings indicate that lecturers are unprepared, unsupported and unmonitored. Students and practitioners had very variable experiences and expressed a strong need for a better-organized approach which would provide them with consistent and sustained support in the practice setting. Overall the study highlighted a lack of strategic management of the practice role by university schools of nursing and midwifery. Convergence of findings from midwifery and the other branches of nursing provides strong research evidence for recommendations for more active management of the practice curriculum to be implemented as part of any future proposed reforms for nurse education in the UK.

Adult↗
PubMed2000

Giardia lamblia carriage in Israeli Bedouin infants: risk factors and consequences.

Giardiasis is a common protozoan infection, with varying clinical manifestations. We investigated the associations between Giardia lamblia carriage and environmental, family, illness, and growth characteristics. Bedouin infants (n=234) were followed from birth to age 18-23 months. At monthly home visits, stool samples were obtained, history of illness was determined, and an environmental assessment was done. The comparisons presented are between 4 groups defined by length of carriage of G. lamblia. Study children had a mean+/-SD of 4.1+/-2.9 diarrhea episodes. No illness, environmental, or family characteristics were associated with length of carriage. Significant differences were found in weight-for-age and weight-for-height z scores between the never-positive-for-G. lamblia group and all other carriage groups combined. Faltering growth was shown to be subsequent to G. lamblia infection rather than preceding it. Our findings confirm that G. lamblia carriage is not associated with diarrhea. However, the effect on growth deserves further investigation.

Adolescent↗
PubMed2000

Serological analysis of a cryptosporidiosis epidemic.

BACKGROUND: A cryptosporidiosis epidemic occurred among residents and visitors to Collingwood, Ontario, during March 1996. Fifty-five per cent of 36 confirmed cases were Collingwood visitors and 57% of Collingwood resident cases were under 10 years of age. The low level of reported diarrhoeal illness among adult Collingwood residents caused government officials and physicians to question whether an epidemic had occurred in Collingwood. METHODS: To better evaluate the extent of the epidemic, anonymous surplus sera from 89 adult Collingwood residents, collected for routine tests prior to, during and after the epidemic, and from 80 adult Toronto residents were tested using a Western blot assay for IgG antibody response to two Cryptosporidium antigen groups (15/17-kDa and 27-kDa). RESULTS: For sera collected from 1 January 1996 to 17 June 1996, a higher fraction of Collingwood residents had a detectable serological response (P < 0.002) and the mean intensity of serological responses was higher for Collingwood than Toronto residents (P < 0.001). The mean intensity of serological responses for Collingwood residents was higher in specimens drawn during the 8 weeks following the initial case reports compared to those drawn before or after this period (15/17-kDa, P < 0.02; 27-kDa, P < 0.10). CONCLUSIONS: These elevated serological responses indicate that Cryptosporidium infections among Collingwood residents likely occurred more commonly than illness reports suggested, consistent with a community-wide cryptosporidiosis epidemic. Similar studies should be considered in future suspected cryptosporidiosis epidemic investigations.

Adult↗
PubMed2000

An unexpected and serious complication of treatment with the atypical antipsychotic drug clozapine.

A 49-year-old man developed acute renal failure due to interstitial nephritis during treatment with the drug clozapine. Referral and diagnosis were delayed through a failure to consider complications of treatment other than neuroleptic malignant syndrome. Although this association has not previously been reported in the literature, we include details of a further 7 cases of acute renal failure in association with clozapine therapy reported to the Committee On Safety Of Medicines in the UK.

Acute Kidney Injury↗
PubMed2000

Technology transfer in France: the main players.

A new era of French innovation beckons. This profile of the private and public organizations involved in the technology-transfer process in France highlights a new thrust in innovation activity that is supported by recent legal and political changes.

Capital Financing↗
PubMed2000

Negev nutritional studies: nutritional deficiencies in young and elderly populations.

The importance of nutrition to public health and preventive medicine is evident. Undernutrition is a main nutritional risk factor in the elderly and has been established as a cause of excess morbidity and mortality in different segments of the older population. In the infant population, inadequate nutrition is one of the causes of iron-deficiency anemia, which is associated with impaired physical and cognitive development and lowered immunity. The aim of this paper was to estimate the nutritional pattern and micronutrient deficiencies in elderly and young populations in the Negev. In southern Israel, 351 subjects over 64 years old reported mean dietary intake that was lower than that in younger persons and was independent of the presence of chronic diseases. Current data from southern Israel on healthy Jewish children revealed anemia prevalence of 15% in the second year of life. Data from recent prospective study on Bedouin children showed that anemia affected one quarter of children at age one year. Thus, infants in this area are at high risk for iron deficiency. The findings require the attention of public health authorities and food manufacturers, and should result in a range of activities including publicity and educational programs, fortification of foods, and supplementation programs in high risk-groups.

Age Factors↗
PubMed1999

The use of capillary high performance liquid chromatography with electrospray mass spectrometry for the analysis of small volume blood samples from serially bled mice to determine the pharmacokinetics of early discovery compounds.

The methodology described demonstrates, for the first time, the feasibility of performing pharmacokinetic studies in the serially bled mouse model to support the early development of discovery compounds. Sample analysis, using capillary high performance liquid chromatography combined with tandem mass spectrometry, has facilitated the achievement of this milestone and has successfully been applied to determine pharmacokinetic information following both intravenous and oral administration of a single discovery compound. The methodologies described demonstrate potential for a reduction in the amount of new chemical entity required to undertake pharmacokinetic studies. Typically, such studies are performed in larger rodents with a significantly increased body mass (ten times in the case of the rat) and therefore it follows that to undertake the same experiment in the mouse would require ten times less compound to effect an equivalent dose. Conventionally, pharmacokinetic studies to obtain both intravenous and oral information, e.g. clearance and half-life, and the resultant bioavailability have been performed using two parallel groups of rodents, collecting blood by exsanguination, separating off the plasma and analysing this using conventional liquid chromatography/tandem mass spectrometry. The use of capillary high performance liquid chromatography (HPLC) has facilitated the analysis of small volume blood samples by increasing the effective sensitivity of the analytical method. Consequently, we have established a protocol for serially bleeding mice thus reducing the number of animals and so further reducing the amount of compound required for such experiments. This paper reports data obtained from collected and processed blood volumes of <20 microL with the subsequent injection of only 1 microL of precipitated extract onto a capillary column.

Administration, Oral↗
PubMed1999

Effectiveness of a nationwide infant immunization program against Haemophilus influenzae b. The Israeli Pediatric Bacteremia and Meningitis Group.

An ongoing nationwide prospective surveillance program for invasive H. influenzae b (Hib) disease in Israel enabled us to study the effectiveness of a national infant Hib immunization program, which included all infants born since January 1994. The vaccine used was Hib polysaccharide conjugated to outer membrane protein complex of Neisseria meningitidis b (PRP-OMPC). For the cohort born during the 3 years since January 1994, the vaccine effectiveness was 94.9% for all invasive Hib diseases and 96.6% for meningitis. The efficacy in fully immunized subjects was 98.7 and 99.5%, respectively. A herd immunity effect could be observed, since a reduction in cases also occurred among infants too young to be immunized. No increase in invasive cases caused by S. pneumoniae and N. meningitidis was observed during the study period. This is the first report outside North America and Western Europe that demonstrates a nationwide extensive reduction of invasive Hib disease within a short time of the introduction of Hib conjugate vaccines to the infant immunization program.

Bacterial Outer Membrane Proteins↗
PubMed1999

Maternal knowledge and environmental factors associated with risk of diarrhea in Israeli Bedouin children.

Diarrhea is still a major cause of morbidity and mortality among children in developing countries. As it is due to multiple causative agents including viruses, bacteria and parasites, biological interventions are not currently available to markedly reduce incidence and severity. We examined maternal knowledge and reported behavior during diarrheal episodes, as well as environmental factors to determine their association with diarrhea. The children and mothers were from a Bedouin township in southern Israel, which has developed preventive and curative health care facilities. The Bedouin population in Israel is in transition from a nomadic to a settled life style. While almost all mothers exhibited good knowledge regarding food storage and prevention of diarrhea episodes in the children, the rate of illness in the children remained relatively high (two episodes per child year of observation). In a multivariate analysis, cessation of breastfeeding during diarrhea, child sleeping with siblings and lack knowledge about risk factors, were the major risk factors for illness with odds ratios (OR): 4.6, p = 0.02, 5.6, p = 0.03 and 1.7, p = 0.06, respectively. These data indicate that even in this population with free access to preventive medical care, greater efforts should be made to educate mothers regarding risk factor for diarrheal disease identification and the benefits of maintaining breastfeeding during diarrhea episodes.

Arabs↗
PubMed1999

Marked differences in pneumococcal carriage and resistance patterns between day care centers located within a small area.

Carriage rates of Streptococcus pneumoniae and their antibiotic resistance, capsular types, and genetic patterns were studied among 264 children aged 12-35 months attending 8 day care centers located within a 2.5-mile radius in the same city. Nasopharyngeal cultures were obtained within a 2-month interval from all 264 children. Significant differences in each of the studied characteristics were found between day care centers, and each day care center had a unique pattern of the carried pneumococci. Our findings show that day care centers are independent microenvironments and emphasize their role in the transmission and augmentation of antibiotic-resistant S. pneumoniae in the community.

Carrier State↗
PubMed1999

Evaluation of screening for hepatitis B surface antigen during pregnancy in a population with a high prevalence of hepatitis B surface antigen-positive/hepatitis B e antigen-negative carriers.

BACKGROUND: Universal hepatitis B vaccination in infancy was implemented in Israel in 1992. The program consists of active vaccination at birth and at 1 and 6 months of age, without hepatitis B surface antigen (HBsAg) screening during pregnancy. Infants of HBsAg carrier mothers do not receive specific hepatitis B immunoglobulin in addition to vaccine at birth. The recently arrived Jewish immigrants from Ethiopia are the group with the highest rate of HBsAg carriage (approximately 10%) in Israel. AIM: The objective of this study was to evaluate whether the present policy is effective against perinatal HBV transmission from mothers of Ethiopian origin to their infants. METHODS: The study group included 411 Israeli born children, offspring of mothers of Ethiopian origin. All infants were fully vaccinated starting at birth. Sera were collected from the children at the age of 9 to 36 months and from their mothers. Tests for HBsAg, antibodies to HBsAg (anti-HBs) and antibodies to hepatitis B core antigen (anti-HBc) were performed. RESULTS: Eighty-nine percent of the children had detectable anti-HBs, including 82.2% with protective anti-HBs concentrations (> or =10 mIU/ ml). Although 24 mothers (6.2%) were HBsAg carriers, none of the children was HBsAg-positive. Seven of 394 infants (1.7%) tested positive for anti-HBc. This test became negative in 5 of 6 who were followed for 12 months. The percentage of infants with protective anti-HBs concentrations decreased significantly from 91.4% at 9 to 12 months to 70.1% at 31 to 36 months of age. The mother's infection status was not associated with the infant's response to vaccine. Calculation based on the above data suggests that screening for HBsAg in pregnancy in that group is not cost-effective. CONCLUSIONS: Our results suggest that the Israeli vaccination program against HBV infection is effective, even in a high risk population, and additional measures are not cost-effective.

Carrier State↗
PubMed1999

An insider's guide to knowledge transfer. From Academia to industry.

Higher education institutions (HEIs) can improve the quality of their research through working with industry. Industry can develop more profitable products as a result of working with HEIs. This article explores the process of forming a rewarding partnership and lists the dos and don'ts for academic and commercial people seeking to form a partnership with the "other side."

Education↗