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Biomedical subjects

J Powell

Publications and source records attributed to J Powell.

At least 127 records · Page 7Linked to original sources

DNA by mail: an inexpensive and noninvasive method for collecting DNA samples from widely dispersed populations.

As specific genes are identified that are associated with behavior, it becomes increasingly important for behavioral geneticists to be able to incorporate these genes in their research. Rather than using blood, DNA can be extracted from cheek swabs, which makes it possible to obtain DNA inexpensively by mail from large, widely dispersed individuals. The purpose of this paper is to recommend this technique to the behavioral genetics community and to present results of our use of this technique to obtain DNA by mail for 114 2-year-olds and 116 adults.

Adult↗

Processing of amyloid precursor protein in human primary neuron and astrocyte cultures.

Increased production of amyloid beta peptide (A beta) is highly suspected to play a major role in Alzheimer's disease (AD) pathogenesis. Because A beta deposits in AD senile plaques appear uniquely in the brain and are fairly restricted to humans, we assessed amyloid precursor protein (APP) metabolism in primary cultures of the cell types associated with AD senile plaques: neurons, astrocytes, and microglia. We find that neurons secrete 40% of newly synthesized APP, whereas glia secrete only 10%. Neuronal and astrocytic APP processing generates five C-terminal fragments similar to those observed in human adult brain, of which the most amyloidogenic higher-molecular-weight fragments are more abundant. The level of amyloidogenic 4-kDa A beta exceeds that of nonamyloidogenic 3-kDa A beta in both neurons and astrocytes. In contrast, microglia make more of the smallest C-terminal fragment and no detectable A beta. We conclude that human neurons and astrocytes generate higher levels of amyloidogenic fragments than microglia and favor amyloidogenic processing compared with previously studied culture systems. Therefore, we propose that the higher amyloidogenic processing of APP in neurons and astrocytes, combined with the extended lifespan of individuals, likely promotes AD pathology in aging humans.

Amyloid beta-Protein Precursor↗

Longitudinal study of prognostic factors in established periodontitis patients.

Numerous indicators for disease progression have been described in the last decade. The purpose of this study was to examine, longitudinally, a large battery of clinical, microbiological, and immunological indicators, to try to determine whether the presence of one or a combination of these parameters at baseline, would correlate positively with increased attachment and or bone loss (true prognostic factors). Following initial screening, 79 patients with established periodontitis were monitored longitudinally for one year. Whole mouth clinical measurements, plaque gingival and calculus indices, together with pocket depth and attachment level measurements, were repeated every three months. Full mouth radiographic survey, performed at baseline and 12 months, served to determine changes in crestal bone height using an image enhancement technique. Subgingival plaque samples were taken at baseline and every 3 months. Immunofluorescence assays were performed for the a battery of target microorganisms. Serum and GCF samples for IgG subclasses analysis were obtained at each visit and assayed using ELISA techniques. Likewise blood, samples were also drawn at each visit for a quantitative analysis of serum cotinine level. The overall mean attachment loss (AL) and bone loss (BL) were almost identical (0.159 mm and 0.164 mm, respectively). Individual patients variation was large (-0.733 to +1.004 mm). An overall 6.89% of sites were active; individual patients' means ranged from 0-28.9%. Mean pocket depth (PD) showed minimal change over the study period (-0.033 mm) thus suggesting that most if not all the AL was accompained by concomitant gingival recession. Smokers exhibited greater AL and radiographic BL compared to non-smokers. Likewise, patients' cotinine level showed direct correlation with outcomes of progressive periodontal breakdown. Past severity of periodontal involvement, as reflected in the patients baseline PD, AL and crestal bone height, showed good correlation with longitudinal changes in the periodontium. This correlation was higher for crestal BL as the outcome variable, while somewhat smaller for change in AL as the outcome variable. Bacteroides forsythus (Bf.), Prevotella intermedia (Pi.) and Porphyromonas gingivalis (Pg.) were frequently found in these patients. The presence of these microorganisms at baseline was associated with further disease progression. Subjects with mean baseline pocket depth equal or greater than 3.2 mm were at greater risk for future bone loss 1 year later (O.R. 2.97; C.I. 1.02-8.70). Smokers were at significantly greater risk for further attachment loss when compared to non-smokers (O.R. 5.41; C.I. 1.50-19.5). Subjects that harbored B. forsythus at baseline, were at seven times greater risk for increased pocket depth (O.R. 7.84; C.I.1.74-35.3). In conclusion, past periodontal destruction, smoking habits, Bf., Pg., & Pi. are prognostic factors for further periodontal breakdown. When designing clinical trials, or when evaluating epidemiological data, it is most important to balance for these factors. Also, treatment strategies should attempt to eliminate or modify these factors.

Adult↗

A common polymorphism in the methylenetetrahydrofolate reductase gene, homocysteine, and ischemic cerebrovascular disease.

BACKGROUND AND PURPOSE: A common polymorphism (T/t) in the gene encoding the methylenetetrahydrofolate reductase (MTHFR) enzyme has been associated with elevated serum homocysteine, itself a risk factor for stroke. Some studies have reported an association with ischemic heart disease, but no published studies have examined its relationship with stroke. METHODS: We determined the TT genotype frequency and T allele frequency in 345 patients with ischemic cerebrovascular disease (CVD) and 161 control subjects. In a subgroup we also determined serum homocysteine and folate concentrations. RESULTS: In the patient group there was a significant relationship between TT genotype and homocysteine concentration after we controlled for other risk factors. Controlling for serum folate weakened this relationship, and folate itself was independently related to serum homocysteine. There was no difference between patients and control subjects in either TT genotype frequency (10.7% versus 13.7%; P = .34) or T allele frequency (0.68 versus 0.67; P = .67). There was no association when analysis was limited to individuals deficient in folate (serum folate < 25th centile) or to younger individuals (< 65 years). There was no association between TT genotype and any stroke subtype or with degree of carotid stenosis. CONCLUSIONS: In patients with CVD we confirmed a relationship between the MTHFR genotype and serum homocysteine concentration and an interaction with serum folate concentration. We found no association between CVD and genotype. However, the interaction with serum folate suggests that the genotype could still be a risk factor in populations with a low folic acid intake.

Aged↗

Type of hospital setting and treatment outcome with heroin addicts. Results from a randomised trial.

BACKGROUND: General psychiatrists have recently been encouraged to provide treatment to heroin addicts, including in-patient detoxification. No comparison has previously been made of specialist versus general psychiatric in-patient care. METHOD: During a randomised study of cue exposure, 186 opiate addicts were also randomised to either specialist in-patient (DDU; n = 115) or general psychiatric (GEN; n = 71) wards in the same hospital. RESULTS: From pre-treatment (post-randomisation) onwards, patient outcomes differed across the two in-patient settings. Of the original randomised sample, significantly more DDU than GEN subjects accepted their randomisation (100 v. 77%), were subsequently admitted (60 v. 42%), and completed in-patient detoxification (45 v. 18%). Of patients admitted, more DDU than GEN patients completed detoxification (75 v. 43%). During seven-month follow-up, of those 43 patients who reached the end of treatment, significantly more ex-DDU than ex-GEN subjects were opiate-free. CONCLUSIONS: From pre-treatment onwards, significant differences in process and outcome were found after allocation to treatment on either DDU or GEN. Further randomised studies are required to replicate and explain these findings.

Adult↗

The influence of smoking on reward responsiveness and cognitive functions: a natural experiment.

AIMS: To investigate the effects of (a) nicotine abstinence and (b) cigarette smoking after abstinence, on reward responsiveness and cognitive functions which are putatively dependent on activity in the dopaminergic system implicated in smoking. DESIGN: During Ramadhan, Muslim smokers elected to abstain from smoking either for the whole month (RAMQUIT) or during daylight hours (DAYQUIT). These groups, and non-smokers (NOSMOKE), were assessed on two occasions 6 hours apart (TEST1 and TEST2). DAYQUIT participants had abstained for 6 hours at TEST1 and smoked a single cigarette immediately prior to TEST2. RAMQUIT participants had abstained for at least 10 days prior to TEST1 and remained abstinent at TEST2. NOSMOKE and RAMQUIT participants are a small snack prior to TEST2 to control for non-specific consummatory effects. SETTING: TEST1 was conducted at the mosque and TEST2 in participants' homes. PARTICIPANTS: All were male; mean age was 26.7 years. Modal cigarette consumption prior to Ramadhan by both the 13 DAYQUIT and the 11 RAMQUIT smokers was 21-30 per day. DAYQUIT subjects rated themselves as more dependent. MEASUREMENTS: The Card Arranging Reward Responsivity Objective Test (CARROT), testing behavioural responsiveness to small financial incentive; digit span, measuring attention; verbal fluency, indexing frontal lobe function; and the two-choice guessing test (2CGT; at TEST1 only), measuring response stereotypy. FINDINGS: At TEST1, compared with non-smokers, both smoking groups showed greater stereotypy (2CG) and lower reward responsiveness (CARROT). DAYQUIT participants improved on all measures after smoking a single cigarette. No marked changes were seen in the other groups. CONCLUSION: These data suggest that (i) abstaining smokers have impaired dopaminergic function and (ii) nicotine consumption may boost their dopaminergic activity.

Adult↗

Effects of a beta-human chorionic gonadotropin subunit immunogen administered in aqueous solution with a novel nonionic block copolymer adjuvant in patients with advanced cancer.

The clinical and immunological effects of a vaccine consisting of CTP37, a synthetic peptide corresponding to the COOH-terminal peptide (CTP) of beta-human chorionic gonadotropin (beta-hCG) conjugated to diphtheria toxoid, combined with CRL 1005, a novel synthetic nonionic block copolymer adjuvant, were examined. Twenty-one patients with metastatic, nontrophoblastic cancers received up to four immunizations by i.m. injection of a fixed dose of CTP37 and escalating doses of CRL 1005. Doses of CRL 1005 adjuvant as high as 75 mg were administered with 1 mg of CTP37 without evidence of significant local or systemic toxicity. Immunizations resulted in the production of IgG antibody to beta-hCG. CRL 1005 doses of 3-25 mg appeared to be optimal for antibody induction. Immunizations also resulted in increases in the cellular response of peripheral blood mononuclear cells (PBMCs) to the unconjugated CTP, hCG, and diphtheria toxoid. Responding PBMCs specifically secreted the TH1-associated cytokines IFN-gamma and interleukin (IL)-2 as well as the TH2-associated IL-5 and IL-10. Increased expression of IFN gamma and IL-5 mRNAs by PBMCs 4 h after immunization was also observed. CRL 1005 administered with CTP37 in aqueous solution is well tolerated. The CTP37-CRL 1005 subunit vaccine has the capacity to stimulate potentially beneficial humoral and cellular immune responses in patients with advanced cancer.

Adjuvants, Immunologic↗

Association between a PS-1 intronic polymorphism and late onset Alzheimer's disease.

Previous work suggests an association between allele 1 and the 1-1 genotype of an intronic polymorphism in the presenilin-1 (PS-1) gene and late onset Alzheimer's disease. We found an excess of the 1-1 genotype in our late onset clinical sample (p = 0.006, one-tailed) but not in our postmortem confirmed sample, which instead exhibited an excess of allele 1 (p = 0.02, one-tailed). No interaction between PS-1 and ApoE genotype was detected and the findings remained significant when the effects of ApoE were taken into account (p = 0.03, one-tailed). These results suggest that the PS-1 polymorphism, or a locus in linkage disequilibrium with it, acts as a risk factor for late onset AD.

Age of Onset↗

Paediatric meningeal tumours.

We review our experience of meningeal tumours in patients under 16 years who were treated between 1957 and 1993. These were 16 with meningiomas (median age 12 years) and 5 with poorly differentiated malignant meningeal tumours (median age 3 years). The incidence of meningeal tumours in this period was 1.62% of all CNS tumours. There were 19 supratentorial tumours (5 intraventricular), 1 tentorial and 1 cervical. Surgical excision was complete in 12 patients and incomplete in 6; in 2 patients a biopsy only was undertaken. The remaining patient had radiological diagnosis only. All 5 patients in the group with malignant poorly differentiated tumours died (median survival 5 months), confirming the aggressive nature of these lesions. Of the 16 patients with meningiomas, 4 died during followup but 11 of the 12 meningioma patients remaining alive had complete resections. There is a strong tendency for paediatric meningeal tumours to have a supratentorial origin and intraventricular location. The female preponderance found in adults is not evident in children. Incomplete surgical excision or focal neurological deficit at presentation was associated with poor outcome.

Adolescent↗

Long-term follow-up of women with borderline ovarian tumors.

OBJECTIVE: To examine the long-term survival of patients with borderline ovarian carcinomas. METHOD: A population-based retrospective analysis of patients registered with West Midlands Regional Cancer Registry. The files of all patients registered with ovarian carcinoma during the triennium 1985-1987 were examined and those with borderline ovarian carcinomas identified. RESULTS: During the period, 1654 patients were registered, of whom 1344 had histologically confirmed ovarian carcinoma. From these 54 (4%) patients had borderline tumors--all Stage I or II. Follow-up ranged from 5 to 10 years, with only 2 patients identified where death was due to recurrent ovarian malignancy. CONCLUSIONS: Epidemiological studies avoid the bias associated with hospital-based series, and enable a crude evaluation of practice standards. From this series certain areas were identified where management could be improved. Thus the information gleaned can be utilized to address such issues, and comparative studies performed in the future to assess the impact of any changes made. The series confirms the excellent prognosis associated with early stage borderline ovarian carcinomas.

Adolescent↗

The strength of iliosacral lag screws and transiliac bars in the fixation of vertically unstable pelvic injuries with sacral fractures.

This study compares the relative strengths of iliosacral lag screws and transiliac bars in the fixation of vertically unstable pelvic injuries with sacral fractures. A vertical sacral fracture was artificially induced by vertical loading in eight pelvises from cadavers, which were then fixed with two 6.5 mm iliosacral lag screws or two 6.4 mm transiliac bars. The pelvises were then loaded again to failure. The mean strength of iliosacral lag screw fixation was 819 newtons and for transiliac bars it was 1066 newtons, but the study was too small for the difference to be judged as statistically significant. Various advantages and disadvantages of each method of fixation are discussed.

Bone Plates↗

Unilateral laterothoracic exanthem. A clinicopathologic study of forty-eight patients.

BACKGROUND: Four years ago, we began seeing young children with an unusual, predominantly unilateral, morbilliform and eczematous, self-limited cutaneous eruption. It appeared to correspond to unilateral laterothoracic exanthem (ULE) reported from France and to an eruption described as "a new papular erythema of childhood" in the United States. OBJECTIVE: We conducted a prospective study of ULE to define its clinical evolution, pathology, and therapy. In addition, we performed epidemiologic and microbiologic investigations in an attempt to determine the cause of ULE. METHOD: We studied 48 children with ULE. In some patients, blood, urine, stool, as well as skin biopsy specimens were analyzed. RESULTS: ULE is a morbilliform, eczematous eruption that often begins close to the axilla and spreads to become bilateral, although it usually retains a unilateral predominance. Patients' mean age at onset is 24.3 months, with a female predominance (2:1) and mean duration of 5 weeks, followed by spontaneous resolution that may or may not be improved with topical corticosteroids. It is characterized by a unique eccrine lymphocytic infiltration. Although signs of infection were reported by most patients, no one infectious agent was identified. No significant epidemiologic factor was found. CONCLUSION: ULE, in young children, is a self-limited morbilliform and scarlatiniform eruption that may represent a specific skin reaction to one or more infectious agents.

Administration, Topical↗

The influence of age on the surgical management of carcinoma of the stomach.

The medical records of 31,808 patients with gastric cancer registered with the West-Midlands Cancer Registry between 1957-1981 were reviewed to determine the influence of age on presentation, stage assessment, management, survival and mortality rates. When analysed by stage, and excluding post-operative deaths, survival was similar in all age groups. This study confirms stage of disease to be the single most important prognostic factor. The inverse relationship between laparotomy and age implies inadequate assessment of stage in the elderly. The poor prognosis in unresected cases suggests that increased precise staging by laparotomy or laparoscopy will have minimal adverse effects. On the other hand this may result in increased resections and survival.

Age Factors↗

The effects of reboxetine and amitriptyline, with and without alcohol on cognitive function and psychomotor performance.

Reboxetine is a novel antidepressant that has been shown to be effective in the treatment of major depressive disorders. The present experiment was designed to assess whether it affects the cognitive and psychomotor skills necessary for optimum function in everyday life. Ten healthy male volunteers received reboxetine 0.5 mg, 1 mg or 4 mg, amitriptyline 25 mg, or matched placebo with and without alcohol (0.6 mg kg-1) in a double-blind 10-way crossover study. A psychometric test battery was administered at baseline and at 1, 2.25, 3.5, 6 and 9 h post-dose. The results showed that reboxetine had little or no effect on performance at any dose, compared with placebo. Amitriptyline, however, with and without alcohol, lowered critical flicker fusion threshold compared with placebo and/or reboxetine at all test points (e.g. at 3.5 h: 28.51 vs 30.33 Hz; P < 0.05); increased reaction time (e.g. 619 vs 540 ms; P < 0.05); increased tracking error (e.g. 16.34 vs 8.54 RMS units; P < 0.05); and slowed short-term memory scanning (e.g. 742 vs 590 ms; P < 0.05). It is concluded that reboxetine at doses of 4 mg and below is free from disruptive effects on cognitive function and psychomotor performance, and that it does not act synergistically with alcohol, in contrast to amitriptyline.

Adolescent↗

Double-blind, randomized trial of cessation of smoking after audiotape suggestion during anaesthesia.

We studied the use of intraoperative tape suggestion to improve the rate of cessation of smoking in 363 smokers who wanted to stop smoking. They were allocated randomly to hear a taped message encouraging them to stop smoking or to a blank tape, played during general anaesthesia. Overall 56 patients (15.4%, 95% confidence interval (CI) 11.7-19.1%) had claimed to have stopped smoking at 2 months and 29 patients (8.0%, 95% CI 5.9-10.1%) were confirmed to have stopped smoking at 6 months. There was no significant difference between the groups at either 2 or 6 months (risk ratios 1.06 and 1.09, respectively, P = 0.78). A preoperative:postoperative ratio of a visual analogue scale measuring the patient's motivation to stop smoking was not significantly different (control group 1.13 vs message group 1.10, P = 0.55). This study does not support the hypothesis that intraoperative tape suggestion can change smoking behaviour.

Adolescent↗

Comparison of the diagnostic and prognostic value of biological markers in neuroblastoma. Proposal for a common methodology of analysis. SENSE group.

BACKGROUND: The prognosis of pediatric neuroblastoma depends both on clinical presentation and on certain cellular and molecular characteristics. Screening programs have been initiated in infants of less than one year of age, based on the hypothesis that neuroblastoma progresses from early to late clinical stages through a classical multistep process linked to an accumulation of molecular abnormalities. However, recent analyses suggest that most cases discovered by screening are low stage tumors considered as dysembryogenetic residues devoid from major abnormalities and that high-grade tumors with molecular abnormalities are unrelated diseases. AIM OF THE REVIEW: To confirm one or the other hypothesis, and eventually identify biological factors possibly responsible for the initiation and progression of the disease, it is of utmost importance that all investigators agree on biological criteria for analysis when neuroblastoma tissue is available in screened and unscreened populations. This paper reviews the biological tools available for prognosis in neuroblastoma, the priority for analysis of biological markers according to both methodological reliability and feasibility, and the conditions of tissue storage for further analysis of these biological markers. CONCLUSION: The standardized biological evaluation of neuroblastoma will allow to collect sufficient data for multivariate analysis; such analysis is now fundamental if one wants to clearly define the respective impacts of biological abnormalities on neuroblastoma progression.

Biomarkers, Tumor↗