Search PubMed⌕ Search

Biomedical subjects

J Powell

Publications and source records attributed to J Powell.

At least 145 records · Page 8Linked to original sources
PubMed1996

Induction of human factor VIII inhibitors in rats 2: Fine mapping of rat anti-human rFVIII antibodies.

Inhibiting antibodies in patients with hemophilia A pose a significant therapeutic dilemma in the treatment of bleeding episodes. The genetic factors which predispose hemophiliacs to inhibitors and the optimal method for inhibitor suppression remain obscure. Hence, an animal model of the human FVIII inhibitor response is of potential value. Sprague-Dawley rats immunized with human recombinant FVIII (rFVIII) subsequently developed abnormal coagulation parameters coincident with the development of an immune response to the human protein. The epitopes for the resultant rat anti-rFVIII antibodies were mapped using a random fragment expression library constructed from the FVIII cDNA. Antigenic regions located within the A1, First and Second Acidic and B domains were mapped. Rat immunoglobulins reactive with the individual epitopes were immunoaffinity purified and assayed for inhibitory activity. Several of the epitopes mapped using the rat antibodies were similar to regions previously shown to be antigenic for human inhibitors. By contrast, no epitopes were mapped to the A2 domain with the techniques used. This may be due to the possible presence of conformational epitopes in this area which cannot undergo fragmentation and still retain antigenicity or the presence of relatively low concentrations of antibodies to this region. The rat model shares some similarity with both the auto- and alloimmune human response to FVIII and therefore may be a valuable model for studies on the induction and suppression of the inhibitor response.

Animals↗
PubMed1995

Evidence for a genetic association between alleles of monoamine oxidase A gene and bipolar affective disorder.

We present evidence of a genetic association between bipolar disorder and alleles at 3 monoamine oxidase A (MAOA) markers, but not with alleles of a monoamine oxidase B (MAOB) polymorphism. The 3 MAOA markers, including one associated with low MAOA activity, show strong allelic association with each other but surprisingly not with MAOB. Our results are significant only for females, though the number of males in our sample is too small to draw any definite conclusions. Our data is consistent with recent reports of reduced MAOA activity in patients with abnormal behavioral phenotypes. The strength of the association is weak, but significant, which suggests that alleles at the MAOA locus contribute to susceptibility to bipolar disorder rather than being a major determinant.

Alleles↗
PubMed1995

Suppression of tumor growth in vivo by local and systemic 90K level increase.

Expression levels of the immunostimulatory 90K antigen in mammary carcinoma, glioblastoma, and other tumor-derived cell lines inversely correlate with their tumorigenicity in athymic mice. Engineered enhancement of 90K expression results in significant (> 80%) tumor growth inhibition, not by direct action on the tumor cell, but by stimulation of the residual cell-mediated immune defense of the nude mouse. Enhanced 90K level effects are both localized and systemic and involve induction of ICAM-1 and VCAM-1 in the tumor endothelium. The findings presented suggest a role for 90K as a molecular alarm signal for the body's cellular defense against pathogens, which in a subset of tumors is suppressed to allow cancer progression.

Animals↗
PubMed1995

Cyclin/proliferation cell nuclear antigen immunohistochemistry does not improve the prognostic power of Dukes' or Jass' classifications for colorectal cancer.

Immunohistochemistry of cyclin/proliferation cell nuclear antigen (PCNA) is an attractive alternative to tumour cell proliferation activity determined by flow cytometry which has been shown to be independently predictive of survival in patients with colorectal carcinoma and to enhance Dukes' classification. Dukes' and Jass' histopathological classifications were determined in 91 patients who had undergone curative resection for cancer of the colon (n = 51) or rectum (n = 40) and followed up for a minimum of 10 years. PCNA immunohistochemistry was possible in 79 tumours. Univariate analysis revealed that Jass' (P < 0.0001) and Dukes' classifications (P < 0.0002) were powerful predictors of survival but that the PCNA index had little prognostic power (P = 0.4). Multivariate analysis of both classifications showed similar predictive power and the PCNA index improved the prediction of survival when used with either classification for patients with colon cancer (chi 2 = 5.3, 1 d.f., P = 0.02 for each combination). The PCNA index, however, was not predictive for rectal cancer. Patients with the lowest PCNA index had the worst prognosis.

Adenocarcinoma↗
PubMed1995

Effects of method of internal fixation of symphyseal disruptions on stability of the pelvic ring.

This study tested different methods of internal fixation of a symphyseal disruption, in comparison with the mechanics of the intact pelvis. Unembalmed cadaveric pelves were tested in simulated bilateral stance in a servohydraulic materials-testing machine. Motion of the superior and inferior pubic symphysis, and at two levels of the posterior sacroiliac complex, was measured using high resolution displacement transducers. The fixations tested were (1) double plating (4.5 mm reconstruction plates), (2) wire loops around two 6.5 mm, fully threaded cancellous screws, and (3) an absorbable suture material (polydioxanone). Each pelvis was first tested intact, recording displacements in response to a cyclic axial load up to a maximum of 500 N applied through the proximal sacrum. The pubic symphysis was then sectioned and the sacrum fractured to produce an unstable pelvis (Tile C-type). Recordings were then repeated, following fixation of the sacral fracture with lag screws and sequential fixation of the symphysis with each of the test methods. The results from eight pelves revealed that internally fixed symphyseal motion was generally greater than intact, regardless of fixation method. The superior symphysis was usually compressed, while there was distraction inferiorly. Wiring resulted in significantly less symphyseal motion than the other methods (P < 0.02), provided four loops were used, reducing the separation inferiorly. There was no significant difference in sacral fracture motion between the three methods. The results indicate that in osteoporotic bone, as used in this study, symphyseal wiring is best able to oppose the tensile loads in the inferior symphysis that are associated with bilateral stance loading. These biomechanical findings must be interpreted within the broader context of surgical management of these complex injuries.

Aged↗
PubMed1995

Epidemiology of high grade prostatic intraepithelial neoplasia.

The prevalence of high grade prostatic intraepithelial neoplasia (HGPIN), the age at which this lesion starts and the potential racial or ethnic differences in its distribution are poorly documented. HGPIN is becoming increasingly implicated as a premalignant lesion for clinically significant prostatic carcinoma (PCa) with mounting evidence linking it to carcinoma according to morphologic immunohistochemical and recent genomic studies. We describe our experience with the age and race distribution of HGPIN resulting from two study populations of African-American (AA) and Caucasian (C) males. The first component of this report describes an autopsy study aimed at determining the prevalence of latent PCa and HGPIN in AA and C men 20 years of age or older; 370 (218 AA and 152 C) consecutive step-sectioned, totally embedded prostate glands were microscopically evaluated and mapped for HGPIN and PCa. HGPIN was first identified in the third decade and increased steadily with age. Latent PCa increased steadily with age with no significant difference in the prevalence between AA and C males in any age group (3rd to 8th decades). HGPIN, on the other hand, was more prevalent in AA men with 18, 31, 69, 78 and 86% in their 4th, 5th, 6th, 7th and 8th decades harboring the lesion. The corresponding figures for C men were 14, 21, 38, 50 and 63% respectively. When HGPIN was quantitated as focal and extensive according to the degree of glandular involvement, extensive HGPIN appeared earlier in AA males under 60 years of age compared to C males cohort. The difference in age distribution appeared to follow a chronological pattern, with HGPIN in AA preceding that of C males by approximately a decade. The second component of this report describes a surgical series of 345 consecutive radical prostatectomies from patients (155 AA and 190 C) with clinically localized PCa, which were thoroughly evaluated microscopically by two urologic pathologists. Similar to the findings in the autopsy study, extensive HGPIN was more prevalent in AA men 60 years of age or younger (57% vs. 33%). In both races, the mean percentage of the gland involved by HGPIN decreased with advancing age in contrast to the mean tumor volume that increased with patient age. These findings indicating a different prevalence of HGPIN in the two racial groups may help explain the higher incidence of prostatic cancer in African-Americans.

Adenocarcinoma↗
PubMed1995

Conditioned responses to drug-related stimuli: is context crucial?

Research into the elicitation of conditioned responses (CRs) by drug-related stimuli in drug and alcohol addicts has produced apparently conflicting results in relation both to the form of the CR (drug-like or drug-opposite) and to its importance in influencing relapse rates after detoxification. Most studies looking at cue-elicited responses directly have taken place with recently detoxified addicts in a laboratory setting. The present study examined cue-elicited reactions in eight currently dependent opiate users (receiving prescribed physeptone) during their drug preparation rituals. Seven were seen in their own homes and one in hospital. Subjects rated their mood and physical state before getting out the drug and paraphernalia, during preparation to inject, and after injection. By contrast with the withdrawal-like reactions, which are the most common finding in laboratory exposure studies where drugs are not subsequently accessible for use, these subjects showed a significant reduction in subjectively rated withdrawal symptoms during the pre-injection drug preparation ritual. The results are discussed in relation to the impact of the context of exposure in influencing subjective expectancies, with perception of drug availability seen as a critical part of the conditioned stimulus complex.

Adult↗
PubMed1995

Autism, mental retardation, multiple exostoses and short stature in a female with 46,X,t(X;8)(p22.13;q22.1).

A young adult female with multiple exostoses, short stature, autism, mental retardation and 46,X,t(X;8)(p22.13;q22.1) is described. Although the clinical features and translocation breakpoints raise the possibility of a number of specific conditions, the constellation of problems is not consistent with any previously reported genetic syndrome. It is argued that her clinical disorder is likely due to the chromosomal abnormality and that further detailed molecular genetic investigation may shed light on the genetic basis to various components of her phenotype including the autism.

Abnormalities, Multiple↗
PubMed1995

Genetic association between alleles of pancreatic phospholipase A2 gene and bipolar affective disorder.

Chromosome 12q is a region of interest for the genetics of bipolar affective disorder because of reports of apparent cosegregation between this disorder and Darier's disease in a small number of families. Findings from a recent linkage study suggest that this chromosomal region may contain a susceptibility gene for bipolar affective disorder. We have found evidence of an allelic association between bipolar disorder and a marker at the pancreatic phospholipase A2 gene (PLA2A) in this region (p < or = 0.01). These results are consistent with the linkage study, and warrant additional investigations.

Alleles↗
PubMed1995

Selection of a hospital based director of pastoral care: process and stakeholders.

Details the steps which were taken in the process of hiring a Director of Pastoral Care for a 274-bed acute care regional referral center in southern Alberta, Canada. Stresses the importance of anchoring the hiring process steps within a relevant context. Offers recommendations for hospitals and clergy faced with a similar project.

Alberta↗
PubMed1995

The influence of vascular pressure and different primes on the fluid balance of, and oxygen supply to, the patient during CABG.

Detrimental changes of blood and erythrocyte rheology, and fluid exchange between the vascular and interstitial spaces, which influence the rate that oxygen is supplied to the patient, occur during cardiac bypass surgery. Venous flow is subject to a pulsatile and uncertain variation, because the vena cava is more than 30 mmHg below atmospheric pressure. This occurs because the patient is about 1 m above the air-blood surface of the bypass reservoir. Before any reliable study of fluid exchange can be undertaken this effect must be controlled. It was then established that optimum oxygen exchange occurs when equilibration of the plasma oncotic pressure and the capillary hydrostatic pressure is achieved without alteration of the interstitial fluid volume. At the lower arterial blood pressures used during bypass, it is necessary to reduce the plasma oncotic pressure by using an appropriate volume of crystalloid prime.

Coronary Artery Bypass↗
PubMed1995

Using a softer approach. Techniques for interviewing older people.

1. There is an increasing population of older people, many of whom need health and social care. 2. It is important to obtain their viewpoints in order to provide services that meet their needs. 3. Consideration must be given to the way their views are obtained. 4. The information must be fed back to service providers.

Aged↗
PubMed1994

Drug and alcohol referrals: are elderly substance abuse diagnoses and referrals being missed?

OBJECTIVE: To examine the diagnosis of problem substance use in hospital inpatients aged 65 years and over and their referral to drug and alcohol services by medical staff. DESIGN: Questionnaire to registrars or house officers caring for patients 65 years of age and over with problem substance use. SETTING: 3 hospitals in New South Wales, Australia. SUBJECTS: Medical staff caring for 263 inpatients. RESULTS: Medical staff did not recognise substance misuse in older hospital patients and did not seem to be aware of current recommendations of the National Health and Medical Research Council recommendations for safe use of alcohol and benzodiazepines. Three out of 88 problem users of benzodiazepines, 29 out of 76 smokers, and 33 out of 99 problem drinkers were identified by medical staff. Of those identified with problems, 2 benzodiazepine users, 6 smokers, and 19 drinkers were considered for referral to drug and alcohol services. CONCLUSIONS: Greater awareness of recommendations for dealing with problem use of benzodiazepines and alcohol needs to be promoted among medical staff, along with an increased emphasis in medical education on substance use as a potentially important problem for older people. Drug and alcohol services also need to promote a broader role, particularly in regard to early intervention in a hospital setting for older patients.

Aged↗