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Biomedical subjects

A Collier

Publications and source records attributed to A Collier.

At least 19 recordsLinked to original sources
PubMed2006

Cochrane Skin Group systematic reviews are more methodologically rigorous than other systematic reviews in dermatology.

BACKGROUND: The Cochrane collaboration aims to produce high-quality systematic reviews. It is not known whether the methods used in producing Cochrane Skin Group (CSG) reviews result in higher quality reviews than other systematic reviews in dermatology. OBJECTIVES: To determine how the methodological quality of dermatological CSG reviews published in The Cochrane Library and in peer-reviewed journals compare with non-Cochrane systematic reviews. METHODS: Two blinded investigators independently assessed review quality using the 10-item Oxman and Guyatt scale. RESULTS: Thirty-eight systematic reviews (17 Cochrane reviews published in The Cochrane Library, 11 Cochrane reviews published in peer-reviewed journals and 10 non-Cochrane reviews published in peer-reviewed journals) were examined. The Cochrane Library reviews included quality of life (11/17 vs. 1/10, P = 0.014) and adverse outcomes (14/17 vs. 2/10, P = 0.003) more often than non-Cochrane reviews published in peer-reviewed journals. Cochrane reviews published in both peer-reviewed journals and The Cochrane Library were more likely to include comprehensive search strategies (11/11 and 17/17 vs. 6/10, P-values = 0.04 and 0.01), take steps to minimize selection bias (11/11 and 16/17 vs. 3/10, P-values = 0.003 and 0.001) and appropriately assess the validity of all included trials (10/11 and 16/17 vs. 4/10, P-values = 0.04 and 0.007) than non-Cochrane reviews. Overall, Cochrane reviews published both in peer-reviewed journals and in The Cochrane Library were assigned higher quality scores by reviewers than non-Cochrane reviews (median = 6.0 and 6.5 vs. 4.5, P-values = 0.01 and 0.002). CONCLUSIONS: The Cochrane Library systematic review methodology leads to higher quality reviews on dermatological topics.

Dermatology↗
PubMed2005

Psychological functioning in African American women at an increased risk of hereditary breast and ovarian cancer.

Despite attention to psychological issues during genetic counselling and testing for hereditary breast and ovarian cancer risk, limited information is available on cancer-specific distress among African American women being targeted for participation in counselling and testing. Therefore, the purpose of this study is to examine cancer-specific distress in African American women at an increased risk of hereditary breast and ovarian cancer and to identify factors having significant associations with distress in this population. Respondents were 141 African American women identified for participation in genetic counselling and testing for BRCA1/2 mutations. Overall, respondents reported moderate levels of cancer-specific distress. Younger age (coefficient=6.0, p=0.001), being unemployed (coefficient=-5.0, p=0.01), and having a personal history of cancer (coefficient=5.0, p=0.02) had significant associations with intrusion. Younger age was also associated significantly with greater avoidance (r=6.0, p=0.02). These results suggest that African American women aged 50 and younger, those who are unemployed and women with a personal history of breast or ovarian cancer may be the most vulnerable to experiencing elevated levels of distress during genetic counselling and testing. Greater attention to psychological issues, including concerns about cancer and cancer risks, may be needed during genetic counselling and testing for BRCA1/2 mutations with these women.

Adult↗
PubMed2001

Hydroxyurea does not enhance the anti-HIV activity of low-dose tenofovir disoproxil fumarate.

Tenofovir disoproxil fumarate (DF) is an adenosine analogue with significant activity against HIV-1. Hydroxyurea decreases the intracellular concentrations of deoxyadenosine triphosphate, the active metabolite of adenosine. We therefore tested the hypothesis that hydroxyurea could enhance the anti-HIV activity of low-dose tenofovir in vivo. Eight patients received tenofovir DF, 75 mg, plus hydroxyurea, 500 mg bid, for 28 days. Changes in plasma HIV RNA levels were compared with a previously studied cohort of patients treated with tenofovir DF, 75 mg once daily ( n = 8), or tenofovir placebo ( n = 12). The median change in HIV RNA levels after 28 days of continuous treatment was -0.01 log(10) copies/ml for tenofovir placebo, -0.33 log(10) copies/ml for tenofovir 75 mg once daily, and -0.22 log(10) copies RNA/ml for tenofovir plus hydroxyurea. The difference between placebo and tenofovir-treated groups was significant ( p <.05); however, the difference between the tenofovir and tenofovir plus hydroxyurea groups was not significant ( p =.90). We conclude that hydroxyurea does not significantly enhance the antiviral activity of low-dose tenofovir.

Adenine↗
PubMed2001

Phase i/ii trial of the pharmacokinetics, safety, and antiretroviral activity of tenofovir disoproxil fumarate in human immunodeficiency virus-infected adults.

Tenofovir DF is an antiviral nucleotide with activity against human immunodeficiency virus type 1 (HIV-1). The pharmacokinetics, safety, and activity of oral tenofovir DF in HIV-1-infected adults were evaluated in a randomized, double-blind, placebo-controlled, escalating-dose study of four doses (75, 150, 300, and 600 mg given once daily). Subjects received a single dose of tenofovir DF or a placebo, followed by a 7-day washout period. Thereafter, subjects received their assigned study drug once daily for 28 days. Pharmacokinetic parameters were dose proportional and demonstrated no change with repeated dosing. Reductions in plasma HIV-1 RNA were dose related at tenofovir DF doses of 75 to 300 mg, but there was no increase in virus suppression between the 300- and 600-mg dose cohorts, despite dose-proportional increases in drug exposure. Grade III or IV adverse events were limited to laboratory abnormalities, including elevated creatine phosphokinase and liver function tests, which resolved with or without drug discontinuation and without sequelae. No patients developed detectable sequence changes in the reverse transcriptase gene.

Adenine↗
PubMed2000

Intervening to reduce weight gain in pregnancy and gestational diabetes mellitus in Cree communities: an evaluation.

BACKGROUND: A high prevalence of gestational diabetes mellitus and type 2 diabetes has been observed among the Cree of James Bay, Quebec. To address this problem, a diet and activity intervention during pregnancy, which was based on social learning theory, was initiated in 4 Cree communities. METHODS: A prospective intervention compared dietary, weight and glycemic indicators for 107 control subjects and for 112 women who received the intervention during the course of their pregnancy. A control period in 4 communities (July 1995-March 1996) was followed by an intervention period (April 1996-January 1997) when subjects were offered regular, individual diet counselling, physical activity sessions and other activities related to nutrition. RESULTS: The intervention and control groups did not differ at baseline regarding their mean age (24.3 years [SD 6.29] v. 23.8 years [SD 5.86]), mean prepregnancy weight (81.0 kg [SD 19.46] v. 78.9 kg [SD 17.54]) and mean gestational age at recruitment (17.1 weeks [SD 7.06] v. 18.5 weeks [SD 6.92]). The intervention did not result in differences in diet measured at 24-30 weeks' gestation, rate of weight gain over the second half of pregnancy (0.53 kg per week [SD 0.32] v. 0.53 kg per week [SD 0.27]) or plasma glucose level (50 g oral glucose screen) between 24 and 30 weeks (7.21 mmol/L [SD 2.09] v. 7.43 mmol/L [SD 2.10]). Mean birth weights were similar (3741 g [SD 523] v. 3686 g [SD 686]), as was maternal weight at 6 weeks post partum (88.1 kg [SD 16.8] v. 86.4 kg [SD 19.0]). The only changes in dietary intake were a reduction in caffeine (pregnancy) and an increase in folate (post partum). INTERPRETATION: This intervention had only a minor impact on diet; finding ways of encouraging appropriate body weight and activity levels remains a challenge.

Adult↗
PubMed2000

Two double-blinded, randomized, comparative trials of 4 human immunodeficiency virus type 1 (HIV-1) envelope vaccines in HIV-1-infected individuals across a spectrum of disease severity: AIDS Clinical Trials Groups 209 and 214.

The potential role of human immunodeficiency virus type 1 (HIV-1)-specific immune responses in controlling viral replication in vivo has stimulated interest in enhancing virus-specific immunity by vaccinating infected individuals with HIV-1 or its components. These studies were undertaken to define patient populations most likely to respond to vaccination, with the induction of novel HIV-1-specific cellular immune responses, and to compare the safety and immunogenicity of several candidate recombinant HIV-1 envelope vaccines and adjuvants. New lymphoproliferative responses (LPRs) developed in <30% of vaccine recipients. LPRs were elicited primarily in study participants with a CD4 cell count >350 cells/mm(3) and were usually strain restricted. Responders tended to be more likely than nonresponders to have an undetectable level of HIV-1 RNA at baseline (P=.067). Induction of new cellular immune responses by HIV-1 envelope vaccines is a function of the immunologic stage of disease and baseline plasma HIV-1 RNA level and exhibits considerable vaccine strain specificity.

AIDS Vaccines↗
PubMed2000

A potential RNA drug target in the hepatitis C virus internal ribosomal entry site.

Subdomain IlId from the hepatitis C virus (HCV) internal ribosome entry site (IRES) has been shown to be essential for cap-independent translation. We have conducted a structural study of a 27-nt fragment, identical in sequence to IlId, to explore the structural features of this subdomain. The proposed secondary structure of IlId is comprised of two 3 bp helical regions separated by an internal loop and closed at one end by a 6-nt terminal loop. NMR and molecular modeling were used interactively to formulate a validated model of the three-dimensional structure of IlId. We found that this fragment contains several noncanonical structural motifs and non-Watson-Crick base pairs, some of which are common to other RNAs. In particular, a motif characteristic of the rRNA alpha-sarcin/ricin loop was located in the internal loop. The terminal loop, 5'-UUGGGU, was found to fold to form a trinucleotide loop closed by a trans-wobble U.G base pair. The sixth nucleotide was bulged out to allow stacking of this U.G pair on the adjacent helical region. In vivo mutational analysis in the context of the full IRES confirmed the importance of each structural motif within IIId for IRES function. These findings may provide clues as to host cellular proteins that play a role in IRES-directed translation and, in particular, the mechanism through which host ribosomes are sequestered for viral function.

Base Pairing↗
PubMed2000

Spinal epidural abscess in a young child.

This is a case report of a spinal epidural abscess, caused by Staphylococcus aureus, in a 3-year-old girl. The child presented with fever and hip pain, but without any neurologic deficit. After normal plain films and a normal bone scan were obtained, the diagnosis was made via magnetic resonance imaging (MRI). The neurosurgery and pediatric infectious disease teams evaluated the patient, and the decision was made to forego surgical drainage and to treat medically with appropriate intravenous and then oral antibiotics. Several months later, the child was doing well without any signs of neurologic sequelae. Because of the rarity of this disease in children, the treatment guidelines are controversial. Many suggest that a spinal epidural abscess must be drained surgically. Our experience adds to the literature a case of a child successfully treated with antibiotics alone. We believe that this success is related to the fact that the child was diagnosed by MRI early in the course of the disease and that she never displayed any neurologic deficits.

Anti-Bacterial Agents↗
PubMed1999

Teaching and assessing ethics and law in the dental curriculum.

The General Dental Council's recommendations on dental education places a new emphasis on the importance of ethics and law in the dental curriculum, stating that students should have an awareness of moral and ethical responsibilities involved in the provision of care to individual patients and to populations. The duties of care to protect a patient's life and health at all times, to respect their autonomy to make informed choices about what happens to them, and to do this fairly and without prejudice, are widely accepted as the fundamental ethical principles governing all health care. The specifics of these duties of care are detailed in Maintaining Standards: guidance to dentists on professional and personal conduct, published by the GDC.

Adult↗
PubMed1999

Cellular immunity and target cell susceptibility in persons with repeated HIV-1 exposure.

We prospectively studied 37 HIV-1 uninfected persons engaging in repeated high risk sexual activity with an HIV-1 infected partner, as well as 18 of their infected partners. Only one subject (3%) demonstrated the homozygous 32-bp deletion delta32delta32 of the HIV-1 co-receptor CCR5. CD4+ cells from all high risk subjects except the delta32delta32 CCR5 homozygote were susceptible in vitro to both CCR5-dependent and CXCR4-dependent HIV-1 strains. Median HIV-1 plasma RNA levels of the infected partners were not significantly different from levels of matched infected controls. Thirteen subjects demonstrated HIV-1 specific CTL at one or more visits, and these activities were more commonly observed in persons with the wild type CCR5 genotype. These results indicate that cellular immunity rather than inheritance of the delta32 CCR5 mutation accounts more often for persistently HIV-1-resistant cases.

Adult↗
PubMed1999

Protection against human immunodeficiency virus type 1 infection in persons with repeated exposure: evidence for T cell immunity in the absence of inherited CCR5 coreceptor defects.

It has been hypothesized that protection against human immunodeficiency virus (HIV)-1 infection may result from either acquired host immunity, inheritance of a dysfunctional CCR5 HIV-1 coreceptor, or a low or attenuated virus inoculum. Thirty-seven HIV-1-uninfected persons engaging in repeated high-risk sexual activity with an HIV-1-infected partner were prospectively studied to determine the contribution of these factors in protecting against HIV-1 transmission. More than one-third (13/36) demonstrated HIV-1-specific cytotoxicity, and this activity significantly correlated with the wild type CCR5 genotype (P=.03). Only 1 subject (3%) demonstrated the homozygous CCR5 32-bp deletion (Delta32/Delta32). Median plasma HIV-1 RNA levels from 18 HIV-1-infected sex partners were not statistically different from those of matched infected control patients. These results indicate that inheritance of the Delta32 CCR5 mutation does not account for the majority of persistently HIV-1-resistant cases, and the presence of cellular immunity in these persons suggests either undetected infection or protective immunity.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Use of collaborative audit to assist local implementation of the SIGN guideline for prevention of visual impairment in diabetes.

OBJECTIVES: To use audit to inform the local implementation of a national clinical guideline for the prevention of visual impairment in diabetes. DESIGN: Computer and patient record search in hospital and general practice to determine levels of morbidity and follow-up. Questionnaire to each practice to determine models and techniques of eye screening. SETTING: Ayrshire and Arran Health Board area, Scotland. SUBJECTS: All known diabetic patients. MAIN MEASURES: Proportion of diabetic patients who have had diabetic eye review and monitoring of risk factors within one year. Proportion of diabetic patients who have risk factors recorded within target level. Proportion of eye screening centres with recommended mechanisms in place. RESULTS: Both district general hospitals, and 59 of the 63 general practices, in the area took part in the audit. A total of 6,217 diabetic patients were included; the prevalence of diabetes in this population was 1.65%. Twenty-seven per cent were insulin treated. Seventy-two per cent of diabetics who were not registered blind had a record of having had fundoscopy performed through dilated pupils within one year. Sixty-nine per cent of those who were not registered blind had had corrected visual acuity measured within one year. Eighty-five per cent of diabetics had HbA1C recorded within one year and of these 65% had a level of 8% or less. Eighty-eight per cent had a blood pressure recording within twelve months and 52% of recorded pressures were 140/90 mmHg or less. Smoking status was recorded for 89% of patients and 75% of patients with a record were non-smokers. Representatives of 57 practices returned a completed questionnaire. All these practices had a Snellen chart, but only 83% had near vision testing equipment and only 54% had a pinhole occluder. CONCLUSIONS: An area wide collaborative audit provided local data to inform the process of guideline implementation and baseline data from which to evaluate this process. Wide stakeholder involvement increased interest, motivation and support for the process. The audit highlighted specific areas for change and provided the local stimulus for change.

Cooperative Behavior↗
PubMed1997

The safety and efficacy of adefovir dipivoxil, a novel anti-human immunodeficiency virus (HIV) therapy, in HIV-infected adults: a randomized, double-blind, placebo-controlled trial.

Adefovir dipivoxil is a novel nucleotide analogue with several promising in vitro anti-human immunodeficiency virus (HIV) characteristics. To evaluate the safety and efficacy of adefovir dipivoxil monotherapy, a randomized, double-blind, placebo-controlled study was initiated involving 72 subjects with moderately advanced HIV disease. Subjects were randomly assigned in a 2:1 ratio to receive adefovir dipivoxil or placebo as a once-daily oral dose for 6 weeks, followed by 6 weeks of open-label adefovir dipivoxil. Two dose levels were studied (125 mg and 250 mg). Adefovir dipivoxil was determined to be safe and well-tolerated when administered for 12 weeks. At week 6, changes in absolute CD4 T cell levels and HIV-1 RNA levels were significantly greater with adefovir dipivoxil than with placebo. These effects were sustained through 12 weeks of treatment. As determined by standard RNA sequencing techniques, only 1 of the 24 subjects who received adefovir dipivoxil (125 mg/day) developed any genotypic change from baseline.

Adenine↗
PubMed1996

Phase 1 study of combination therapy with L-697,661 and zidovudine. The ACTG 184 Protocol Team.

We performed a pilot study that examined the clinical and pharmacokinetic interactions between zidovudine (ZDV) and a pyridinone derivative, L-697-661. The results indicate that the drugs were well tolerated, with no important pharmacokinetic interactions, when administered concomitantly for as long as 8 weeks. Although the number of study participants was small, we noted rapid emergence of resistance to L-697,661 among ZDV-naive study subjects who were administered L-697,661 as monotherapy but did not observe isolates of human immunodeficiency virus type 1 (HIV-1) resistant to L-697,661 among those who were administered concomitant ZDV. These results suggest a potential interaction between development of resistance to L-697,661 and ZDV. Although the clinical development of L-697,661 has been halted, our results support the need for further studies to test whether specific interactions among antiretroviral agents administered in combination and the molecular target can delay the emergence of isolates that exhibit resistance to all drugs in the regimen.

Adult↗