Clinical chemistry of common apolipoprotein E isoforms

Apolipoprotein E plays a central role in clearance of lipoprotein remnants by serving as a ligand for low-density lipoprotein and apolipoprotein E receptors. Three common alleles (apolipoprotein E(2), E(3) and E(4)) give rise to six phenotypes. Apolipoprotein E(3) is the ancestral form. Common apolipoprotein E isoforms derive from nucleotide substitutions in codons 112 and 158. Resulting cysteine-arginine substitutions cause differences in: affinities for low-density lipoprotein and apolipoprotein E receptors, low-density lipoprotein receptor activities, distribution of apolipoprotein E among lipoproteins, low-density lipoprotein formation rate, and cholesterol absorption. Accompanying changes in triglycerides, cholesterol and low-density lipoprotein may promote atherosclerosis development. Over 90% of patients with familial dysbetalipoproteinaemia have apolipoprotein E(2)/E(2). Apolipoprotein E(4) may promote atherosclerosis by its low-density lipoprotein raising effect. Establishment of apolipoprotein E isoforms may be important for patients with diabetes mellitus and several non-atherosclerotic diseases. Apolipoprotein E phenotyping exploits differences in isoelectric points. Isoelectric focusing uses gels that contain pH 4-7 ampholytes and urea. Serum is directly applied, or prepurified by delipidation, lipoprotein precipitation or dialysation. Isoelectric focusing is followed by immunofixation/protein staining. Another approach is electro- or diffusion blotting, followed by protein staining or immunological detection with anti-apolipoprotein E antibodies and an enzyme-conjugated second antibody. Apolipoprotein E genotyping demonstrates underlying point mutations. Analyses of polymerase chain reaction products are done by allele-specific oligonucleotide probes, restriction fragment length polymorphism, single-stranded conformational polymorphism, the primer-guided nucleotide incorporation assay, or denaturating gradient gel electrophoresis. Detection with primers that either or not initiate amplification is performed with the amplification refractory mutation system. Disparities between phenotyping and genotyping may derive from isoelectric focusing methods that do not adequately separate apolipoprotein E posttranslational variants, storage artifacts or faint isoelectric focusing bands.     

Clinical oncology nurses' perceptions of research

Within the realm of oncology nursing, research has been an integral part in its development as a specialty practice. Yet despite the growing volume of published nursing research studies, little is known about how nurses working in oncology care settings perceive research. Therefore, the purposes of this study were to examine clinical oncology nurses' perceptions of research and to determine factors influencing their perceptions. Two hundred and eighty-three registered nurses providing cancer care to patients in 40 health care agencies across northern Ontario participated in the survey. Data were collected using a questionnaire developed by Alcock and colleagues (1990) which addressed nurses' perceived value of research, their role, interest and experience in research as well as the research climate of the agency. The findings showed that respondents valued nursing research and perceived a research role for staff nurses. However, the respondents did not perceive strong administrative or collegial support for nurses' involvement in research activities. In addition, the study results indicated that the clinical oncology nurses' perceptions of research were influenced by educational preparation.     

Effect of acute increases in filtered HCO3- on renal hydrogen transporters: II. H(+)-ATPase

Adaptive increases in renal bicarbonate reabsorption occur in response to acute increases in filtered bicarbonate (FLHCO3). In a previous study, we showed that an increase in FLHCO3 induced by plasma volume expansion increased the Vmax for Na+/H+ exchange activity in renal cortical brush border membrane vesicles (BBMV), providing a potential mechanism for the adaptive increase in HCO3- reabsorption. The present studies were undertaken to determine whether the increase in FLHCO3 induced by plasma expansion also stimulates the other major H+ transporter in cortical BBMV, the H(+)-ATPase. H(+)-ATPase activity was assessed in BBMV obtained from hydropenic and plasma expanded Munich-Wistar rats, using a NADH-linked ATPase assay. H(+)-ATPase activity was measured as the ouabain and oligomycin-insensitive, bafilomycin A1-sensitive component of total ATPase activity. Acute plasma expansion doubled single nephron FLHCO3, and this change was associated with a 64% increase in the Vmax for H(+)-ATPase activity, with no change in apparent Km. The Vmax for H(+)-ATPase activity correlated directly with whole kidney GFR and FLHCO3 (r = 0.68 and 0.72, respectively), and with single nephron GFR and FLHCO3 (r = 0.76 and 0.80, respectively). Thus, the mechanism for the adaptive increase in proximal tubular HCO3- reabsorption that occurs in response to acute increases in FLHCO3 appears to be related to increased activity of both H(+)-ATPase and Na+/H+ exchange in the apical membrane of the proximal tubule epithelium.     

Interleukin-2 enhancement of cytotoxicity by humanized monoclonal antibody M195 (anti-CD33) in myelogenous leukemia

The mass childhood immunization programme has traditionally been viewed as a safe and effective preventative measure by health promoters, primary health care professionals and governments. This consensus has meant that immunization has rarely been viewed as ethically problematic. A number of recent changes in the context of the delivery of health care, particularly the emphasis on consumerism and the effect of the marketization of services, makes timely an examination of ethical, social and political issues. This article examines four main grounds for problematizing the mass childhood immunization programme. These are: clinical research evidence about the safety and efficacy of vaccines; the masking of wider social and political determinants of ill health; the contradictory strictures about collective and individual rights in relation to immunization; and the uniqueness of childhood immunization as a physical intrusion into a healthy body. The implications of these ethical issues are discussed in relation to informed consent and the need for a 'greenfield' review that includes the views of dissenting parents, lawyers and moral philosophers, as well as health professionals.     

The effects of lead exposure on learning in a multiple repeated acquisition and performance schedule

This study sought to determine the selectivity of Pb-induced changes in learning, as distinct from non-specific or performance effects, and to explore the nature of the underlying error patterns contributing to any learning deficits. To accomplish this, rats were chronically exposed to 0, 50, or 250 ppm Pb acetate in drinking water from weaning and trained on a multiple repeated acquisition (RA) and performance (P) schedule beginning at 55 days of age. The RA component required the rat to learn a new 3-member sequence of responses during each experimental session (Center Right Left, RLC, CLR, RCL, and LRC), while the correct sequence of responses for the P component was constant across sessions (LCR). Significant decrements in accuracy on the RA component but not on the P component were found in Pb-exposed groups compared to control, effects that could not be attributed to differential rates of responding. Analyses of error patterns revealed that the effects of Pb exposure on RA accuracy levels derived from two sources. The first consisted of a perseveration of P-like sequence responding (LCR) even during the RA component. Secondly, Pb exposure increased perseverative responding on a single lever, even though the schedule itself never directly reinforced such repetitive responding. The increase in frequency of these two types of perseverative behavior was incompatible with acquisition of non P-like sequences during the RA component. Adding a 5 sec tone to the light stimuli signalling the transition between RA and P components of the multiple schedule failed to attenuate these effects of Pb, suggesting that deficits in stimulus control were not the sole behavioral mechanism of these impairments. Examination of individual data revealed the presence of both 'learners' and 'non-learners' in each group, with the prevalence of the latter being suggestively higher in Pb-exposed groups than in controls. These findings may be relevant to the classroom setting, where periods requiring learning may frequently be interspersed with periods of performance of learned skills.     

Vesicoureteral reflux and ureteropelvic junction obstruction: association, treatment options and outcome

PURPOSE: We investigated the association, treatment options and outcomes of patients with ureteropelvic junction obstruction and concomitant vesicoureteral reflux. MATERIALS AND METHODS: We analyzed 6,790 consecutive pediatric urology records at our university. Treatment options included observation, and primary pyeloplasty, ureteroneocystostomy and nephroureterectomy. Hydronephrosis, reflux and obstruction were judged as resolved, improved, unchanged or worse. RESULTS: A total of 1,140 patients had vesicoureteral reflux, 224 had ureteropelvic junction obstruction and 41 had both conditions (39 ipsilateral and 6 contralateral kidneys). There was no increased risk of obstruction in patients with reflux when all grades of reflux were grouped (odds ratio 1.26, confidence interval 0.91 to 1.71). In contrast, subgroup analysis of patients with high grade reflux demonstrated a 5-fold increased risk of obstruction (odds ratio 5.0, confidence interval 2.4 to 10.8). One patient was lost to followup. Observation of 6 kidneys led to resolution of reflux in 3 (50%), resolution of obstruction in 3 (50%) and resolution or improvement of hydronephrosis in 4 (67%). Primary pyeloplasty was done on 29 kidneys with 10 (35%) requiring subsequent ureteroneocystostomy. At latest followup hydronephrosis resolved or improved in 24 patients (83%), vesicoureteral reflux resolved or improved in 19 (66%) and ureteropelvic junction obstruction resolved in all. Primary ureteroneocystostomy was performed on 5 kidneys, all of which required subsequent pyeloplasty. Hydronephrosis resolved in 3 patients (60%), and reflux and obstruction resolved in all. Two patients treated with primary nephroureterectomy, and 1 who underwent concomitant pyeloplasty and ureteroneocystostomy have had no subsequent urological problems. One patient awaits primary pyeloplasty. CONCLUSIONS: High grade vesicoureteral reflux is associated with ureteropelvic junction obstruction. No association with low or intermediate grade reflux was demonstrated. While some patients may be monitored expectantly, in our series pyeloplasty or nephrectomy was required in 81% and ureteroneocystostomy was required in 36%. In no case did primary ureteroneocystostomy protect against the subsequent need for pyeloplasty.