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Biomedical subjects

A Young

Publications and source records attributed to A Young.

At least 55 records · Page 3Linked to original sources

The significance of the source of zinc and its anti-VSC effect.

UNLABELLED: The anti-VSC (volatile sulphur compounds) effect of zinc is known to be associated with free zinc ions. OBJECTIVE: To examine whether zinc salts with low stability constants were more suitable as sources of zinc in zinc lozenges than zinc salts with high stability constants. The former provide free zinc ions upon dissolution in water, whereas the latter provide few such ions. DESIGN AND PARTICIPANTS: Identical lozenges were produced which contained either zinc acetate, zinc gluconate (low stability constants), zinc citrate or amino-acid chelated zinc (extremely high stability constants). All the lozenges contained 0.1 per cent of zinc. A test panel of 10 volunteers used the different lozenges randomly. VSC were measured by GC. RESULTS AND CONCLUSION: The lozenge with the highest stability constant was as effective as those with very low stability constants. The anti-VSC effect was thus not related to this constant. These findings may be explained by the possibility that alternative ligands with stronger affinity for zinc than the original ligands in the lozenges may be present in the oral cavity. An in vitro experiment indicated that the sulphide ion (S2-) may be such a ligand.

Adult↗

Modelling the costs and effects of leflunomide in rheumatoid arthritis.

This study investigated the cost-effectiveness of leflunomide (LEF) compared to methotrexate (MTX) and sulfasalazine (SSZ) in the United Kingdom. A Markov model was constructed using health states defined by Health Assessment Questionnaire score. The model is based on a cohort of patients with recently diagnosed definite RA who were followed for up to 15 years at nine rheumatology clinics in the UK. The treatment effect was calculated based on clinical trials comparing LEF to MTX (one international and one United States trial) and to SSZ (one international trial). Transitions between health states for the first 2 years of treatment were calculated from the clinical trials, while the extrapolation beyond the trial was based on the Early Rheumatoid Arthritis Study cohort, using an ordered probit model. This makes it possible to predict transitions for patients with similar characteristics (age, time since disease onset) as in the trials. Separate analyses were performed for each trial, and all analyses covered a 10-year timeframe. Using the US trial, LEF had slightly lower costs and better effects (44,017 and 4.307 pounds QALYs, compared to 44,988 and 4.158 pounds QALYs for MTX), while for the international trial this was reversed (34,070 and 4.487 pounds QALYs for MTX compared to 36,351 and 4.372 pounds QALYs for LEF). Compared to SSZ, the cost of using LEF was slightly lower, with an increase in QALYs (35,855 and 3.896 pounds QALYs compared to 36,731 and 3.721 pounds QALYs for SSZ). The two trials comparing LEF to MTX gave differing results. One possible reason for this is that MTX patients in the US trial were given folic acid, whereas in the international trial folate supplementation was not mandated. This may have reduced the effectiveness of MTX. In the UK it is standard practice to use folic acid with MTX, and therefore the results from the US trial may be more relevant for the UK. Compared to SSZ, the use of LEF appears to be cost-effective in the UK.

Journal Article↗

Perceived proficiency in endoscopic techniques among senior obstetrics and gynecology residents.

STUDY OBJECTIVES: To assess current training methods in laparoscopic surgery employed in United States obstetrics and gynecology residency programs, level of proficiency in various minimally invasive surgery procedures amongst senior obstetrics and gynecology residents, and ways in which training in minimally invasive surgery can be improved. DESIGN: Survey (Canadian Task Force classification III). SETTING: Accredited obstetrics and gynecology programs in the United States. SUBJECTS: All fourth-year residents in accredited obstetrics and gynecology programs in the United States. INTERVENTION: Residents received a survey regarding their perceived proficiency performing various laparoscopic procedures and the type of training they received in these techniques. MEASUREMENTS AND MAIN RESULTS: Responses were received from 133 programs (52.4%) and 295 residents (26.8%). Of these, 67% of residents thought emphasis on laparoscopic surgery training should be increased or greatly increased; 87% thought laparoscopic skills were important for building a successful practice. Formal teaching methods were clearly associated with improved perception of proficiency, and those with higher perception of proficiency expected to perform more laparoscopic procedures after graduation. Residents lacked perceived competency in most advanced laparoscopic procedures. CONCLUSION: Residents seem to benefit significantly from a formal curriculum in minimally invasive surgery, but they do not feel competent performing some advanced procedures on graduation. In our opinion, more emphasis should be placed on training in laparoscopic surgery in United States obstetrics and gynecology programs.

Curriculum↗

Which patients stop working because of rheumatoid arthritis? Results of five years' follow up in 732 patients from the Early RA Study (ERAS).

OBJECTIVES: To assess the occurrence and prognostic factors for the ability to maintain paid work in patients with rheumatoid arthritis (RA). SETTING: Inception cohort of patients with RA recruited from rheumatology departments in nine NHS Hospital Trusts in England. PATIENTS: All consecutive patients with RA of less than two years' duration, before any second line (disease modifying) drug treatment, and followed up for five years. METHODS: Clinical, laboratory, and radiological assessments, and all treatments were recorded prospectively using a standardised format at presentation and yearly. OUTCOME MEASURES: Changes in, and loss of paid work by five years' follow up. RESULTS: 732 patients completed the five year follow up. 353/721 (49%) were gainfully employed at the onset of RA, 211 (60%) were still working at five years, 104 (29%) stopped because of the disease, and 31 (9%) retired for reasons other than RA. Work disability at five years was more likely in manual workers (odds ratio (OR) 2.3, 95% confidence interval (CI) 1.4 to 3.8) and worse baseline Health Assessment Questionnaire (HAQ>1.5, OR 2.26, 95% CI 1.38 to 3.7). In combination with other baseline variables (erythrocyte sedimentation rate, sex, age of onset, and radiological erosions), employment outcome was predicted in 78% using multivariate analysis. CONCLUSIONS: Nearly half of the patients with RA were in paid employment at onset, work disability was an adverse outcome for a third of these patients by five years, and manual work and high baseline HAQ were important predictors for this. These details are likely to be useful to clinicians, health professionals, and patients in order to plan medical, orthopaedic, and remedial treatments in early RA. Future disease modifying treatments could be compared with this cohort of patients who were treated with conventional second line drugs.

Adult↗

Why we should not seek individual informed consent for participation in health services research.

Ethics committees now require that individuals give informed consent to much health services research, in the same way as for clinical research. This is misguided. Existing ethical guidelines do not help us decide how to seek consent in these cases, and have allowed managerial experimentation to remain largely unchecked. Inappropriate requirements for individual consent can institutionalise health inequalities and reduce access to services for vulnerable groups. This undermines the fundamental purpose of the National Health Service (NHS), and ignores our rights and duties as its members, explored here. Alternative forms of community consent should be actively pursued.

Decision Making, Organizational↗

Relativistic effects and two-body currents in (H)((-->)e(')p)n using out-of-plane detection.

Measurements of the (2)H((-->)e,e(')p)n reaction were performed with the out-of-plane magnetic spectrometers (OOPS) at the MIT-Bates Linear Accelerator. The longitudinal-transverse, f(LT) and f(')(LT), and the transverse-transverse, f(TT), interference responses at a missing momentum of 210 MeV/c were simultaneously extracted in the dip region at Q2 = 0.15 (GeV/c)(2). In comparison to models of deuteron electrodisintegration, the data clearly reveal strong effects of relativity and final-state interactions and the importance of two-body meson-exchange currents and isobar configurations. We demonstrate that such effects can be disentangled by extracting these responses using the novel out-of-plane technique.

Journal Article↗

Screening for diabetes in general practice: cross sectional population study.

OBJECTIVE: To assess the policy proposed by the American Diabetes Association of universal screening in general practice of all patients aged over 45 years for diabetes. DESIGN: Cross sectional population study. SETTING: Local general practice in the United Kingdom. PARTICIPANTS: All patients aged over 45 not known to have diabetes. MAIN OUTCOME MEASURES: Prevalence of diabetes in the screened population, cardiovascular risk profile of patients diagnosed as having diabetes after screening. RESULTS: Of 2481 patients aged over 45 and not known to have diabetes, 876 attended for screening. There were no significant demographic differences between the screened and unscreened patients. Prevalence of diabetes in patients with age as a sole risk factor was 0.2% (95% confidence interval 0% to 1.4%). Prevalence of diabetes in patients with age and one or more other risk factors (hypertension, obesity, or a family history of diabetes) was 2.8% (1.6% to 4.7%). Four hours a week for a year would be needed to screen all people over 45 in the practice's population; about half this time would be needed to screen patients with risk factors other than age. More than 80% of patients newly diagnosed as having diabetes had a 10 year risk of coronary heart disease >15%, 73% (45% to 92%) were hypertensive, and 73% (45% to 92%) had a cholesterol concentration >5 mmol/l. CONCLUSIONS: Screening for diabetes in general practice by measuring fasting blood glucose is feasible but has a very low yield in patients whose sole risk factor for diabetes is age over 45. Screening in a low risk population would best be targeted at patients with multiple risk factors.

Aged↗

Search for quadrupole strength in the electroexcitation of the delta+(1232).

High-precision 1H(e,e'p)pi(0) measurements at Q2 = 0.126 (GeV/c)2 are reported, which allow the determination of quadrupole amplitudes in the gamma*N-->Delta transition; they simultaneously test the reliability of electroproduction models. The derived quadrupole-to-dipole ( I = 3/2) amplitude ratios, R(SM) = (-6.5+/-0.2(stat+sys)+/-2.5(mod))% and R(EM) = (-2.1+/-0.2(stat+sys)+/-2.0(mod))%, are dominated by model error. Previous R(SM) and R(EM) results should be reconsidered after the model uncertainties associated with the method of their extraction are taken into account.

Journal Article↗

VN training scheme.

Explore the source record for details and available documents.

Animal Technicians↗

Cell adhesion molecule expression in the cervix and myometrium during pregnancy and parturition.

OBJECTIVE: To determine the expression and localization of cell adhesion molecules intercellular adhesion molecule-1 (ICAM-1), E-selectin, platelet-endothelial cell adhesion molecule (PECAM), and vascular cell adhesion molecule (VCAM) in the cervix and myometrium during pregnancy and labor. METHODS: Biopsies of myometrium and cervix were obtained from non-pregnant women and from pregnant women before and after onset of spontaneous labor at term. Cell adhesion molecule mRNA expression was quantified using Northern blotting and cell adhesion molecule protein was localized using immunohistochemistry. RESULTS: ICAM-1 mRNA was upregulated in the cervix (10-fold increase, P <.01) and myometrium (10.5-fold increase, P <.01) during labor. ICAM-1 was localized in the vascular endothelium and in leukocytes in the cervix and myometrium from all three groups of women. VCAM mRNA was upregulated in the cervix (2.5-fold increase, P <.01) during pregnancy and there was no further change during labor. VCAM localized weakly to the vascular endothelium in cervical and myometrial biopsies from pregnant and non-pregnant women. PECAM mRNA was significantly upregulated in myometrium during pregnancy (ninefold increase, P <.01) and did not change with the onset of labor. PECAM localized to the vascular endothelium in all cervical and myometrial biopsies and was identified on leukocytes. There were no significant changes in E-selectin mRNA expression in either tissue with pregnancy or parturition. CONCLUSION: Cell adhesion molecule expression changes in human cervix and myometrium during pregnancy and parturition. At least part of these changes are attributable to expression by leukocytes infiltrating these tissues.

Adult↗

Gastrin-releasing peptide: a potential growth factor expressed in human neuroblastoma tumors(1).

PURPOSE:Gastrin-releasing peptide (GRP) is a 27-amino acid neuropeptide that has been identified in the cytoplasm of many neuroendocrine tumors. Gastrin releasing peptide has been labeled as an autocrine growth factor in small cell lung carcinomas. Recent work has also shown this to be true in the growth of neuroblastoma cells in vitro. The purpose of this study was to demonstrate GRP and its receptor (GRP-R) in resected human neuroblastomas and to correlate the presence or absence with other known predictors of poor prognosis.To demonstrate the presence of GRP and GRP-R mRNA, total RNA was extracted from human neuroblastoma cells. A reverse transcription-polymerase chain reaction (RT-PCR) was then performed using specific primers. The products of the RT-PCR were then confirmed to be GRP and GRP-R cDNA by Southern blot analysis. The RT-PCR products were then sequenced, and these sequences were compared with the know sequences of GRP and GRP-R DNA.N = 19. GRP and GRP-R mRNA were present in all neuroblastoma specimens. Although no correlation with other known predictors of poor prognosis existed, transcripts of four different sizes (400, 450, 500, and 950 bp) were seen in the GRP-R transcripts. The sequences of the 950 bp-sized transcript reverse transcription PCR products were identical to the known GRP-R.We conclude that gastrin releasing peptide and gastrin releasing peptide receptor mRNA are present in all human neuroblastomas. Although qualitatively it appears to lack prognostic significance, its ubiquitous nature in the tumor suggests it may be a useful target on which to base future treatment modalities.

Journal Article↗

Our traumatic neurosis and its brain.

During the nineteenth century, physicians either discovered or invented a variety of clinical autobiography called "traumatic memory." Freud produced two versions of this memory, the final version in the 1920s. A revolutionary nosology (DSM-III), adopted in 1980, promised to extirpate Freud and the concept of neurosis from American psychiatry. However, it made a tacit exception for Freud's concept of traumatic neurosis, renaming it "postraumatic stress disorder." The following decades have been a period of intense clinical and scientific interest in this disorder. An influential research program has investigated traumatic neurosis and its brain through variations in cortisol excretion. I describe the history of this program, and examine its distinctive knowledge product. its running narrative of its achievements. The narrative's structure is analyzed and found to resemble a crossword puzzle constructed from heterogenous kinds of inference, recalling The Interpretation of Dreams. My conclusion is that, far from extirpating Freud's neurosis, biological research has secured a place for it in today's post-Freudian psychiatry.

Brain↗

Design guidelines for accommodating amputees in the workplace.

Rehabilitation experts have been addressing the problem of accommodating disabled workers in the workplace for many years. When these disabled workers return to work, accomplishing the tasks they performed prior to their disability can present a serious challenge. Meeting this challenge successfully requires that employers provide accommodations at the workplace so that the disabled workers can continue to contribute efficiently to the operation of the enterprise. Disabilities that are caused by amputations are quite critical. The severity of the injury in terms of loss of a limb and the costs associated with accommodations make this type of disability extremely significant. This paper deals with accommodating "permanent partial" and "permanent total disabilities" due to amputations. The paper is divided into two main parts. The first part focuses on the causes of amputations, types, and difficulties that an amputee faces in the work environment. In this part, an understanding of the amputee physiology has been developed. The second part of the paper addresses the various measures that employers may take in accommodating the amputees at the workplace. Design guidelines are provided to make the workplace suitable for the amputees.

Amputation, Surgical↗

Effects of metal salts on the oral production of volatile sulfur-containing compounds (VSC).

BACKGROUND/AIM: Halitosis, mainly caused by bacteria located on the posterior dorsum of the tongue and in periodontal pockets, is due to formation of volatile sulfur compounds (VSC). The hypothesis to be tested was that the affinity of a metal for sulfur determines its anti-VSC activity. METHOD: Clinical tests were carried out on 12 subjects who rinsed with cysteine to induce halitosis (baseline) before rinsing with 7.34 mM ZnCl2, SnF2 and CuCl2. Mouth air VSC analyses were repeated following cysteine rinses at 1 h, 2 h and 3 h using a gas chromatograph. In vitro experiments tested toxic metals Hg2+, Pb2+ and Cd2+. 10-microl aliquots of metal salts were added to 1-ml aliquots of human whole saliva from 30 subjects. Samples were incubated overnight at 37oC and saliva headspace was analyzed for VSC in a gas chromatograph. CLINICAL RESULTS: Cu2+>Sn2+>Zn2+ (supports hypothesis). Zn2+ had significantly less anti-VSC effect compared with Cu2+ and Sn2+ at 1, 2 and 3 h. In vitro results indicated that Hg2+, Cu2+ and Cd2+ had close to 100% anti-VSC effect, and that Pb2+ was less effective and Cd2+ more effective than expected in inhibiting VSC. CONCLUSIONS: Apart from Hg2+ and Cu2+, the metals had a significantly greater effect on H2S than on CH3SH. Cu2+ and Hg2+ have well-known antibacterial activity and may presumably also operate by this mechanism.

Adult↗

Long-term RNase P-mediated inhibition of HIV-1 replication and pathogenesis.

Advances in genetic analysis and a greater understanding of human immunodeficiency virus (HIV) molecular pathogenesis have identified critical viral targets for gene interference strategies. RNase P molecules have been proposed as a novel approach for gene targeting based upon their potent catalytic activity, as well as versatile external guide sequence (EGS) which can be modified to specifically recognize almost any target mRNA. We designed a truncated EGS to specifically recognize the highly conserved U5 region of HIV-1 mRNA and mediate subsequent cleavage of hybridized mRNA by the RNase P enzyme component. The active U5-EGS (560), as well as a disabled U5 EGS (560D) control, were cloned into plasmids containing proviral constructs and transfected into a CD4(+) T cell line that was thereafter infected with HIV-1 MN. CD4(+) T cells treated with the active U5 EGS (560) were observed to maintain CD4(+) expression and did not produce HIV p24 gag antigen, form syncytia or undergo apoptosis up to 30 days after infection. Identical cells expressing the inactivated form of the U5 RNase P EGS completely down-regulated CD4 expression, produced elevated levels of HIV-1, formed large syncytia and underwent apoptosis similar to untreated cells. HIV-1 replication and related cytopathology can be effectively inhibited in CD4(+) T cells expressing a protective U5 EGS (560).

Annexin A5↗

Insulinotropic actions of exendin-4 and glucagon-like peptide-1 in vivo and in vitro.

This study compares in vitro effects of exendin-4 and glucagon-like peptide (GLP)-1 on basal and glucose-stimulated insulin release from isolated rat islets and in vivo insulinotropic actions of exendin-4 and GLP-1 after an intravenous glucose challenge in rats. In static incubation of isolated islets, changing ambient glucose concentration from 3 mmol/L to 10 mmol/L stimulated insulin secretion 9.8 +/- 1.3-fold. The addition of exendin-4 or GLP-1 (1 nmol/L to 1 micromol/L) increased glucose-stimulated insulin secretion up to 5.8 +/- 1.6-fold and 3.3 +/- 1.0-fold, respectively, over basal rates (defined as no hormones added, 3 mmol/L glucose) and 19.6 +/- 2.3-fold and 15.0 +/- 3.1-fold at 10 mmol/L glucose. In dynamically perfused isolated islets exposed to 7.5 mmol/L glucose, insulin secretion increased 6.4 +/- 1.5-fold, and exendin-4 (20 nmol/L) or GLP-1 (20 nmol/L) increased this similarly by up to 13.5 +/- 2.8 and 12.7 +/- 3.9-fold,respectively. Anesthetized rats administered 5.7 mmol/kg intravenous glucose increased plasma insulin concentration 3.0-fold. Infusion of exendin-4 or GLP-1 increased this to a maximum of 7.6-fold and 5.3-fold, respectively. As with isolated islet studies, in vivo dose responses and concentration responses with exendin-4 and GLP-1 were bell-shaped. When insulinotropic effects were mapped onto the steady-state plasma concentrations associated with these infusion rates, both peptides exhibited bell-shaped concentration responses with peak insulinotropic effects occurring with plasma peptide concentrations of approximately 1 nmol/L in this model. In summary, exendin-4 and GLP-1 exhibited similar insulinotropic potencies (median effective dose [ED(50)]) when assessed on a concentration basis in in vitro and in vivo models, while exendin-4 exhibited greater efficacy (maximum response).

Animals↗

Comorbidity of psychiatric and substance use disorders in late adolescence: a cluster analytic approach.

Cluster analysis was used to identify subgroups of youths with past-year substance and/or psychiatric disorders (N = 110, mean age 19.0 years). Data for this study came from a community-based, prospective longitudinal investigation of speech/language (S/L) impaired children and matched controls who participated in extensive diagnostic and psychosocial assessments at entry into the study at 5 years of age and again at follow-up. Clustering variables were based on five DSM diagnostic categories assessed at age 19with the University of Michigan Composite International Diagnostic Interview. Using Ward's method, the five binary variables were entered into a hierarchical cluster analysis. An iterative clustering method (K-means) was then used to refine the Ward solution. Finally, a series of analyses of variance (ANOVAs) were run to analyze group differences between clusters on measures of Global Assessment of Functioning (GAF), criminal involvement, anxiety and depressive symptomatology, and frequency of drug use and heavy drinking. The analysis yielded eight replicable cluster groups, which were labeled as follows: (a) anxious (20.9%); (b) anxious drinkers (5.5%); (c) depressed (16.4%); (d) depressed drug abusers (10%); (e) antisocial (16.4%); (f) antisocial drinkers (10%); (g) drug abusers (8.2%); (h) problem drinkers (12.7%). These groups were differentiated by external criteria, thus supporting the validity of our cluster solution. Cluster membership was associated with a history of S/L impairment: A large proportion of the depressed drug abusers and the antisocial cluster group had S/L impairment that was identified at age 5. Clarification of the developmental progress of the youths in these cluster groups can inform our approach to early intervention and treatment.

Adolescent↗