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Biomedical subjects

A Johnson

Publications and source records attributed to A Johnson.

At least 73 records · Page 4Linked to original sources
PubMed2001

"Folate before pregnancy": the impact on women and health professionals of a population-based health promotion campaign in South Australia.

OBJECTIVES: To evaluate a South Australian campaign to promote and implement knowledge that taking adequate folate/folic acid in the periconceptional period can reduce the risk of having a baby with a neural tube defect. DESIGN AND SETTING: The campaign, conducted in October 1994--August 1995, targeted women of reproductive age and health professionals. Evaluation was by computer-assisted telephone interviews undertaken by random dialling throughout the State before and after the campaign, and by self-administered questionnaires to health professionals and women in the postnatal period. PARTICIPANTS: Women of reproductive age and four groups of health professionals. MAIN OUTCOME MEASURES: Knowledge about folate, folate-rich foods and the periconceptional period; participation of health professionals in advising women about folate; use of periconceptional folic acid supplements; sales of folic acid tablets; and prevalence of neural tube defects. RESULTS: Significant increases in knowledge about folate followed the campaign. Health professionals and women in the postnatal period had higher initial levels of knowledge about folate, which also increased significantly. The proportions of women taking periconceptional folic acid supplements, and of health professionals advising women planning a pregnancy about folate, also increased significantly, and folic acid tablet sales doubled. Total prevalence of neural tube defects declined between 1966 and 1999 from a baseline of 2.0 per 1,000 births to 1.1 per 1,000 births (Poisson regression, P= 0.03; average decline of 1.0% per year). CONCLUSIONS: A short educational campaign with a limited budget ($40,000) can promote folate successfully, but alternative strategies such as food fortification are likely to be needed to achieve adequate periconceptional folate intake for a very high proportion of women.

Adolescent↗
PubMed2001

Theiler's virus-infected L-selectin-deficient mice have decreased infiltration of CD8(+) T lymphocytes in central nervous system but clear the virus.

Mice with targeted deletion of L-selectin gene (L-sel(-/-)) were used to investigate the role of adhesion molecule in immunologic responses following virus infection in the central nervous system (CNS). L-Sel(-/-) mice from a resistant H-2(b) genetic background and parental wild-type H-2(b) (C57BL/6) mice were infected with Theiler's murine encephalomyelitis virus (TMEV) intracerebrally and the kinetics of virus replication and infiltration of immune cells in the CNS determined. The levels of infectious TMEV, as measured by plaque assay at 3, 7, 14, and 28 days after infection were between 4 and 6 log(10) PFU of virus per gram of CNS tissues at days 3 and 7 post-infection, and then decreased to undetectable levels by day 14 after infection in both strains of mice. The L-sel(-/-) mice had decreased numbers of CD8(+) T lymphocytes (17.72%+/-2.4) infiltrating into the CNS at 7 days post-infection when compared to wild-type mice (31.02%+/-7.5). In addition, the L-sel(-/-) mice had significantly lower levels of TMEV-specific serum IgG resulting in lower virus neutralizing activity of the serum when compared to wild-type mice. However, the L-sel(-/-) mice had 2.5-fold increase in B lymphocytes in the CNS (8.29%+/-1.1) when compared to wild-type mice (3.2%+/-0.4). Taken together, these data indicate that L-selectin plays a role in recruitment of B and CD8(+) T lymphocytes into the CNS following virus infection, which, however, did not affect the ability of the mice to clear TMEV infection.

Animals↗
PubMed2001

UK collaborative randomised trial of neonatal extracorporeal membrane oxygenation: follow-up to age 4 years.

Extracorporeal membrane oxygenation (ECMO) is a supportive intensive-care technique used for babies with acute respiratory failure. We examined morbidity at age 4 years in surviving children recruited to the UK Collaborative ECMO Trial, and provide long-term data on ECMO support compared with contemporary conventional care. The neonatal ECMO policy resulted in improved survival and a favourable outcome. We therefore advocate the safety and efficacy of this intervention.

Acute Disease↗
PubMed2001

Analysis and occurrence of polybrominated diphenyl ethers in Washington state freshwater fish.

A method is described for analyzing polybrominated diphenyl ethers (PBDEs) in fish tissue using gas chromatography with atomic emission detection (GC/AED) and quantitation by compound independent calibration (CIC). The method has the advantage of an element-selective response, including selectivity between bromine and chlorine. An analysis of fish tissue samples from selected locations in Washington State showed total PBDE concentrations ranged from 1.4 microg/kg (wet weight) in rainbow trout from a remote spring-fed stream to 1,250 microg/kg in mountain whitefish from the urbanized Spokane River. Tetra and penta isomers were the major compounds present. There appear to be substantial between-species differences in the ability of fish to metabolize PBDEs.

Animals↗
PubMed2001

Magnetic resonance imaging-guided core needle biopsy and needle localized excision of occult breast lesions.

BACKGROUND: Breast magnetic resonance imaging (MRI) has been reported to be twice as sensitive and three times more specific in detecting breast cancer. We report a series of MRI-guided stereotactic breast biopsies (SCNBB) and needle localized breast biopsies (NLBB) to evaluate MRI as a localization tool. METHODS: Forty-one breast lesions were identified in 39 patients who subsequently had SCNBB or NLBB. Suspicious areas of enhancement were stereotactically biopsied with 16-G core biopsy needles or localized with 22-G wires for excision under laser guidance. RESULTS: Forty-one breast lesions were identified from 1,292 breast MRIs. SCNBB identified three malignancies and two areas of atypia. Two additional cancers were found after NLBB. In patients having NLBB alone, five cancers and two areas of atypia were identified. CONCLUSIONS: In this initial series, breast MRI-guided SCNBB and NLBB were valuable tools in the management of patients with suspicious abnormalities seen only on MRI.

Adult↗
PubMed2001

Antigen, allele, and haplotype frequencies report of the ASHI minority antigens workshops: part 1, African-Americans.

HLA typing was performed on 977 African Americans residing throughout most of the United States. Class I and class II antigens and class II alleles were defined for all individuals and class I alleles were determined for a subset of individuals. The occurrence of 854 of the individuals in family groups permitted direct counting of allele and haplotype frequencies. The data were analyzed for antigen, allele, and haplotype frequencies; recombination frequencies; segregation distortion; distribution of haplotype frequencies; linkage disequilibria; and geographic distribution of DR antigens. Tables of the antigen, allele, the most common two and three point haplotypes, and 88 extended haplotypes that include class I and class II alleles are presented. Notable findings include a lower than expected frequency of recombination between the B and DR loci (theta= 0.0013), lower than expected frequency of inheritance (44.5% vs 54.5%) of the DRB1*1503; DQB1*0602 haplotype, lower than anticipated linkage disequilibrium values for DR; DQ haplotypes, and a skewed geographic distribution of DR antigens.

Alleles↗
PubMed2001

Prognostic importance of the soluble plasminogen activator receptor, suPAR, in plasma from rectal cancer patients.

Colorectal cancer is one of the most common tumour types with approximately one third of the tumours located within the rectum. Rectal cancer differs somewhat from colon cancer, e.g. regarding the method of operation and the use of preoperative radiotherapy due to a tendency for local tumour recurrence. Proteolytic enzymes have been identified as key molecules in tumour invasion and metastasis, and factors within the urokinase-plasminogen activation (uPA) system have been associated with prognosis in several tumour types, including colorectal cancer. Recently, methods have been developed to analyse the soluble fraction of the plasminogen activator receptor (suPAR) in blood samples. An association between elevated suPAR levels and poor prognosis has recently been demonstrated in colorectal cancer. We have measured suPAR levels in pretreatment plasma samples from 173 rectal cancer patients in order to confirm its prognostic strength in this clinical entity. suPAR levels were determined in ethylenediamine tetraacetic acid (EDTA) plasma by a kinetic enzyme-linked immunosorbent assay (ELISA) and analysed with respect to sex, age, Dukes' stage, tumour differentiation grade and survival. In a univariate analysis, continuous suPAR plasma levels were associated with survival (P<0.001) with shorter survival among patients with high suPAR values. Patients with suPAR values within the upper quartile had significantly shorter survival (hazard ratio (HR) 2.2, 95% confidence interval (CI) 1.3-43.7, P=0.002). In a multivariate Cox analysis, increasing suPAR values predicted shorter survival independent from Dukes' stage and tumour differentiation grade with an adjusted HR of 2.2 per ng/ml suPAR (95% CI 1.2-4.0, P=0.01). This study thus confirms that measurement of suPAR in preoperative plasma samples gives independent prognostic information in rectal cancer patients, higher values being associated with shorter survival.

Adult↗
PubMed2001

An outline of consumer participation in health.

Awareness about the importance of consumers' participating in decision making in health is being increasingly advocated as a way of improving the safety and quality of health care. This article briefly describes some of the key international and national health directions and research that support a more active role for consumers in decision making in health. In addition, it proposes four key dimensions of consumer participation as a framework to describe the scope for consumers to participate in decision-making in individual care processes, health services and the broader health system. Finally, a new Commonwealth Government funded initiative, the National Resource Centre for Consumer Participation in Health, is described which aims to increase the access of service providers and consumer organisations to information about the various methods and models of consumer feedback and participation and provide support to enhance their application of the methods and models to practice.

Australia↗
PubMed2001

A quantitative assay of telomerase activity.

PURPOSE: Telomerase is a ribonucleoprotein that extends telomeres at the ends of chromosome. Increased telomerase activity is associated with cellular immortality. The currently available assay for telomerase, i.e., telomeric repeat amplification protocol (TRAP), consists of 2 steps: (a) telomerase-mediated extension of an oligonucleotide primer by the enzyme-containing extracts of cells and tissues, and (b) amplification of the telomerase-extended primer products by polymerase chain reaction (PCR) and detection of the PCR products. It is generally accepted that the current TRAP assay lacks quantitative precision. The present study was to develop a quantitative telomerase assay with greater precision and sensitivity. METHODS: This new method used the primer extension method as in TRAP, plus the following modifications: (a) used a lysis buffer that yielded complete lysis of nuclei; (b) removal of PCR inhibitors by phenol/chloroform extraction after primer extension; and (c) used primers for the internal standard that were designed to reduce their competition with the telomerase products for PCR. RESULTS: The modified method showed a good correlation (r2 = 0.99, P < 0.001) between telomerase amount (expressed as total protein in cell lysate) and its activity (expressed as telomerase products). Compared to the conventional TRAP, the new method (a) was more sensitive (average of 5.5-fold in cultured cancer cells and >5.9-fold in patient tumors), (b) had a lower inter- and intra-day variability (>3fold), and (c) showed a 2 to 4-fold broader range of linearity in the standard curve. The higher assay sensitivity further enabled the use of a nonradioactive method, i.e., ethidium bromide staining of DNA, to detect the TRAP products, as opposed to the use of radioactive nucleotide and the more labor-intensive autoradiography mandated by the conventional TRAP. CONCLUSION: We report here a quantitative assay for telomerase activity in cultured human cancer cells and patient tumors.

Biological Assay↗
PubMed2001

Does breast cancer grade worsen with time? Evidence from breast screening.

It has been suggested that alteration of the distribution of histological grades, that has been found in screening programmes, is evidence for progression in histological grade with increasing size. A predictive model, that was based upon estimated growth data from an unselected series of 98 new primary breast cancers, is used to estimate the proportions of tumors that would be diagnosed according to limiting screen diagnostic and clinical diagnostic sizes after particular screening intervals; windows of opportunity are created. The results show that the limitations imposed by time and size criteria alter the distribution of growth rates of tumours that may appear in the windows. Small screen diagnostic sizes and short screening intervals allow only the most rapidly growing tumours to reach large sizes. This produces an apparent association of grade 3 tumours with large size. Interval cancers are also likely to be more rapidly growing while the more slowly growing tumours will be diagnosed at the subsequent screen to produce a spurious association of slowly growing grade 1 tumours with small size. We conclude that the evidence from screening does not support the thesis of progression of histological grade with the ageing of the tumour, since the changes that have been observed are predictable from a simple model based upon patterns of tumour growth rates and the relationships between growth rate and histology.

Breast Neoplasms↗
PubMed2001

Adenotonsillectomy in children: a comparison of morphine and fentanyl for peri-operative analgesia.

This study compared the effectiveness and side-effects of intra-operative fentanyl with fentanyl and morphine for elective adenotonsillectomy in a double-blind study, in 60 children randomly allocated to receive either intravenous fentanyl 1 microg x kg(-1) intra-operatively or intramuscular morphine 100 microg x kg(-1) at induction. All children received a standard anaesthetic induction with intravenous fentanyl 1 microg x kg(-1) and propofol 4-5 mg x kg(-1) and maintenance with oxygen, nitrous oxide and isoflurane. Pain scores, emetic episodes and supplemental morphine requirements were recorded for 24 h postoperatively. The overall incidence of postoperative vomiting was high in both groups: 70% in the fentanyl group and 78% in the morphine group. The incidence of postoperative vomiting was lower in the fentanyl group (p < 0.03) in the first 4 h, but similar by 24 h. Children who received morphine at any time in the first 24 h had more median (range) episodes of vomiting [2 (0-7)] than children receiving fentanyl only [l (0-3); p < 0.03]. Administration of rescue anti-emetics, pain scores in recovery and pain scores over the next 24 h were similar between the two groups.

Adenoidectomy↗
PubMed2001

Cerebral palsy, low birthweight and socio-economic deprivation: inequalities in a major cause of childhood disability.

There is currently little and conflicting evidence concerning the existence of socio-economic inequalities in cerebral palsy prevalence, or the extent to which this is influenced by socio-economic inequalities in low birthweight, a strong risk factor for cerebral palsy. The study is based on 753 children registered with cerebral palsy, resident in the former Oxford Regional Health Authority area and born in the years 1984-90. Two population definitions were used: 1. Children with cerebral palsy resident at birth in the area, with resident births as denominator, 2. Children with cerebral palsy resident at age 5 in the area, with children of ages 1-7 resident in the area in the 1991 census as denominator. Children with cerebral palsy and all births/children were classified according to the Carstairs area deprivation index (grouped into quintiles) of their ward of residence. The prevalence among residents at birth varied from 2.08 per 1000 births in the most affluent quintile to 3.33 in the most deprived quintile (trend P < 0.001). Although there was a tendency for children to move to more affluent areas during early childhood, the socio-economic gradient was similar at age 5. A greater proportion of births in the more deprived quintiles were of low or very low birthweight, the proportion rising from 5.6% in the most affluent quintile to 8.2% in the most deprived. Within the normal birthweight category there was a trend for higher prevalence of cerebral palsy in more deprived quintiles, from 1.29 per 1000 in the most affluent quintile to 2.42 in the most deprived quintile (trend P < 0.001). Within the low birthweight and very low birthweight groups, separately or combined, there was no evidence of any relationship between cerebral palsy prevalence and deprivation. We estimate that up to 17% of cerebral palsy cases might be "preventable" in terms of the reduction to be expected if the whole population had the rate of cerebral palsy of the most affluent quintile. Although the strong socio-economic gradient for cerebral palsy was restricted to the normal birthweight category, we estimate that two-thirds of the excess cases in the population associated with greater socio-economic deprivation were normal birthweight cases, and one-third were low birthweight cases owing to the greater prevalence of low birthweight in more deprived populations. The pattern of socio-economic inequalities should be further explored in other regions, and should be taken into account in aetiological research, and in the effective delivery and evaluation of services.

Cerebral Palsy↗
PubMed2001

Renal cortical cholesterol accumulation is an integral component of the systemic stress response.

BACKGROUND: Direct tubular injury (such as ischemia or myohemoglobinuria) increases renal cortical cholesterol content. This study explored whether systemic forms of stress (such as heat shock or sepsis) can trigger renal cholesterol accumulation, and if so, whether increased 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGCR) expression might be involved. METHODS: Male CD-1 mice were subjected to glycerol-induced myohemoglobinuria (MH), systemic heat shock (HS), or E. coli sepsis. Free cholesterol (FC), cholesteryl esters (CE), and HMGCR (Western blot) levels were assessed 18 hours later. Statin effects on renal cholesterol levels and on the severity of MH-acute renal failure (ARF) were also determined. RESULTS: Sepsis and HS each induced dramatic FC and CE increments, comparable to those observed with myohemoglobinuria, and without inducing acute tubular necrosis (ATN). Part of the cholesterol increments was localized within plasma membrane (detergent resistant) microdomains (for example, rafts/caveolae). HS and MH each increased renal HMGCR, as well as HS protein (HSP-72) expression. Oxidant stress (Fe) imposed on cultured proximal tubule (HK-2) cells also enhanced HMGCR content. Conversely, sepsis did not raise renal HMGCR or HSP-72 levels. Statin therapy decreased the severity of MH-ARF and renal cholesterol content. However, this appeared to arise from a statin-mediated decrease in glycerol-induced extrarenal tissue damage (myolysis/LDH release). CONCLUSIONS: Cholesterol appears to be a renal 'acute phase reactant' with tissue levels increasing with either systemic stress (such as, heat shock, sepsis), or direct tissue damage (such as ATN). Increased HMGCR expression can contribute to this result. Mechanisms other than HMGCR induction also can mediate stress-induced cholesterol increments (for example, in the case of sepsis), and statins can mitigate MH-ARF. However, systemic anti-inflammatory effects, rather than a primary renal action, appear more likely to be involved.

Acute Kidney Injury↗
PubMed2001

Cholesterol ester accumulation: an immediate consequence of acute in vivo ischemic renal injury.

BACKGROUND: Cholesterol is a major constituent of plasma membranes, and recent evidence indicates that it is up-regulated during the maintenance phase of acute renal failure (ARF). However, cholesterol's fate and that of the cholesterol ester (CE) cycle [shuttling between free cholesterol (FC) and CEs] during the induction phase of ARF have not been well defined. The present studies sought to provide initial insights into these issues. METHODS: FC and CE were measured in mouse renal cortex after in vivo ischemia (15 and 45 minutes)/reperfusion (0 to 120 minutes) and glycerol-induced myoglobinuria (1 to 2 hours). FC/CE were also measured in (1) cultured human proximal tubule (HK-2) cells three hours after ATP depletion and in (2) isolated mouse proximal tubule segments (PTSs) subjected to plasma membrane damage (with cholesterol oxidase, sphingomyelinase, phospholipase A2, or cytoskeletal disruption with cytochalasin B). The impact of cholesterol synthesis inhibition (with mevastatin) and FC traffic blockade (with progesterone) on injury-evoked FC/CE changes was also assessed. RESULTS: In vivo ischemia caused approximately threefold to fourfold CE elevations, but not FC elevations, that persisted for at least two hours of reperfusion. Conversely, myoglobinuria had no effect. Isolated CE increments were observed in ATP-depleted HK-2 cells. Neither mevastatin nor progesterone blocked this CE accumulation. Plasma membrane injury induced with sphingomyelinase or cholesterol oxidase, but not with phospholipase A(2) or cytochalasin B, increased tubule CE content. High CE levels, induced with cholesterol oxidase, partially blocked hypoxic PTS attack. CONCLUSIONS: In vivo ischemia/reperfusion acutely increases renal cortical CE, but not FC, content, indicating perturbed CE/FC cycling. The available data suggest that this could stem from specific types of plasma membrane damage, which then increase FC flux via aberrant pathways to the endoplasmic reticulum, where CE formation occurs. That CE levels are known to inversely correlate with both renal and nonrenal cell injury suggests the potential relevance of these observations to the induction phase of ischemic ARF.

Acute Disease↗