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Biomedical subjects

A Carr

Publications and source records attributed to A Carr.

At least 73 records · Page 4Linked to original sources
PubMed2000

Characterization of three nef-defective human immunodeficiency virus type 1 strains associated with long-term nonprogression. Australian Long-Term Nonprogressor Study Group.

Long-term survivors (LTS) of human immunodeficiency virus type 1 (HIV-1) infection provide an opportunity to investigate both viral and host factors that influence the rate of disease progression. We have identified three HIV-1-infected individuals in Australia who have been infected for over 11 years with viruses that contain deletions in the nef and nef-long terminal repeat (nef/LTR) overlap regions. These viruses differ from each other and from other nef-defective strains of HIV-1 previously identified in Australia. One individual, LTS 3, is infected with a virus containing a nef gene with a deletion of 29 bp from the nef/LTR overlap region, resulting in a truncated Nef open reading frame. In addition to the Nef defect, only viruses containing truncated Vif open reading frames of 37 or 69 amino acids could be detected in peripheral blood mononuclear cells isolated from this patient. LTS 3 had a viral load of less than 20 copies of RNA/ml of plasma. The other two long-term survivors, LTS 9 and LTS 11, had loads of less than 200 copies of RNA/ml of plasma and are infected with viruses with larger deletions in both the nef alone and nef/LTR overlap regions. These viruses contain wild-type vif, vpu, and vpr accessory genes. All three strains of virus had envelope sequences characteristic of macrophagetropic viruses. These findings further indicate the reduced pathogenic potential of nef-defective viruses.

Amino Acid Sequence↗
PubMed2000

Rosiglitazone does not alter the pharmacokinetics of metformin.

Rosiglitazone is a potent oral antidiabetic agent of the thiazolidinedione class that works through activation of the peroxisome proliferator-activated nuclear receptor. It improves insulin sensitivity in peripheral tissues and effectively lowers blood glucose in patients with type 2 diabetes. Metformin is a dimethyl-biguanide, also used in type 2 diabetes, that lowers fasting blood glucose primarily by decreasing hepatic glucose output. Rosiglitazone and metformin reduce plasma glucose concentrations via different mechanisms and thus could potentially be used in combination to optimize glycemic control. This study evaluated the effects of the coadministration of these two agents on the pharmacokinetics of both rosiglitazone and metformin. Sixteen male volunteers (22-55 years old) received oral metformin (500 mg every 12 hours), rosiglitazone (2 mg every 12 hours), or the combination each for 4 days. Plasma collected on day 4 of each regimen was assayed for rosiglitazone and metformin concentrations. Oral doses of rosiglitazone and metformin were safe and well tolerated when administered alone or in combination. There were no clinically significant episodes of hypoglycemia or increased blood lactic acid levels following treatment with any regimen. Coadministration of rosiglitazone and metformin had no significant effects on the steady-state pharmacokinetics (AUC(0-12 h), Cmax, tmax, or t1/2) of either drug. The authors conclude that rosiglitazone can be safely administered with metformin and, due to the different mechanisms of action of these agents, may offer a therapeutic advantage in patients with type 2 diabetes mellitus.

Acidosis, Lactic↗
PubMed2000

Urban public attitudes to the treatment of psychological problems and depression in general practice.

A previous national study of public attitudes to depression indicated that only 17% spontaneously mentioned their general practitioner as someone who could help with depression, in contrast to 79% of respondents being willing to consult their G.P. in a similar U.K. survey. The present study undertook to examine the public perception of an urban sample to the treatment of depression in general practice and the factors associated with expressed unwillingness to consult. A random sample from the electoral register was drawn and 54 (89%) of 61 subjects selected were interviewed. While 85% of respondents were satisfied with their general practice care, only 24% to 52%, depending on the context and wording of the question, said that they would seek help from their general practitioner for depression. Factors associated with an expressed reluctance to consult were being male, dissatisfied with general practitioner care and believing that general practitioners were not qualified to treat depression.

Adolescent↗
PubMed1999

Impact of early HIV-1 RNA and T-lymphocyte dynamics during primary HIV-1 infection on the subsequent course of HIV-1 RNA levels and CD4+ T-lymphocyte counts in the first year of HIV-1 infection. Sydney Primary HIV Infection Study Group.

Plasma HIV-1 RNA and CD4+ T-cell counts after HIV-1 seroconversion are important independent markers that predict the clinical course of HIV-1 infection. The prognostic significance of these parameters during primary HIV-1 infection, however, remains largely unknown. In a cohort of 53 male study subjects (age, 33 +/- 7 years), who consecutively presented with primary HIV-1 infection, we analyzed the relationship between early plasma HIV-1 RNA, CD4+ and CD8+ T-cell counts, beta2-microglobulin, and p24-antigen levels determined in the first 3 months and subsequent plasma HIV-1 RNA levels and CD4+ T-cell counts 6 to 12 months after onset of primary symptoms. Peak, nadir, and median HIV-1 RNA levels in the first 30 days were already significantly associated with HIV-1 RNA levels at 6 to 12 months (p = .02, p < .0001, and p = .01, respectively). Similarly, early nadir and median CD4+ T-lymphocyte counts in the first 30 days showed a significant relationship with CD4+ T-cell counts at 6 to 12 months (p = .009 and p = .0008, respectively). Study subjects with an early decline of CD4+ counts to <500 cells/microl had an eightfold higher risk that CD4+ counts were <500 cells/microl at 1 year. Of all evaluated virologic parameters, only nadir HIV-1 RNA at 76 days predicted CD4+ counts at 6 to 12 months (p = .006). Early HIV-1 RNA levels and CD4+ counts are already associated with the time course of those parameters 6 to 12 months after onset of symptoms. Nadir viral load was the strongest predictor of HIV-1 RNA levels as well as of CD4+ counts at 6 to 12 months. An early decline of CD4+ T lymphocytes may be a useful clinical prognostic marker for rapid disease progression.

Adult↗
PubMed1999

Enhancement of the immune response to poorly immunogenic gangliosides after incorporation into very small size proteoliposomes (VSSP).

Certain gangliosides are tumor-associated antigens that constitute potential targets for cancer immunotherapy. A major drawback in the design of ganglioside-based cancer vaccines, however, is the poor immunogenicity of these glycolipids. Here we report the immunological and physicochemical properties of very small size proteoliposomes (VSSP) obtained by using anionic detergents to incorporate gangliosides into the outer membrane protein complex (OMPC) of N. meningitidis. VSSP of three different gangliosides, GM3, NGcGM3 and GD3, were tested. These gangliosides differ in level of expression in normal tissues and in immunogenicity in different animal species. We show that the immunization with VSSP in an oil adjuvant consistently induced both IgM and IgG anti-ganglioside antibodies. In the mouse, the anti-ganglioside IgG fraction was not restricted to the typical T-independent isotype IgG3. Unexpectedly, significant levels of the T-dependent IgG1, IgG2a and particularly IgG2b were also found. VSSP-mediated enhancement of the immunogenicity was not restricted to the relatively immunogenic ganglioside GD3, satisfactory immune responses against highly tolerated GM3 and NGcGM3 were also obtained. Similar results were achieved in chickens and monkeys. No reactogenicity was observed even when self-gangliosides were used for immunization. VSSP overcame natural tolerance to gangliosides in an adjuvant dependent fashion.

Adjuvants, Immunologic↗
PubMed1999

Diagnosis, prediction, and natural course of HIV-1 protease-inhibitor-associated lipodystrophy, hyperlipidaemia, and diabetes mellitus: a cohort study.

BACKGROUND: The prevalence and severity of lipodystrophy syndrome with long-term therapy for HIV-1 infection that includes a protease inhibitor is unknown. We studied the natural course of the syndrome to develop diagnostic criteria and identifying markers that predict its severity. METHODS: We assessed 113 patients who were receiving HIV-1 protease inhibitors (mean 21 months) and 45 HIV-1-infected patients (28 with follow-up) never treated with a protease inhibitor. Lipodystrophy was assessed by questionnaire (including patients' rating of severity), physical examination, and dual-energy x-ray absorptiometry. Body composition and fasting lipid and glycaemic variables were compared with data obtained 8 months previously. Oral glucose tolerance was investigated. FINDINGS: There was 98% concordance between patients' reports of the presence or absence of lipodystrophy (reported by 83% of protease-inhibitor recipients and 4% of treatment-naïve patients; p=0.0001) and physical examination. Patients' ratings of lipodystrophy were significantly associated with declining total body fat (p=0.02). Lower body fat was independently associated with longer duration of protease-inhibitor therapy and lower bodyweight before therapy, and more severe lipodystrophy was associated with higher previous (p < 0.03) and current (p < or = 0.01) triglyceride and C-peptide concentrations, and less peripheral and greater central fat (p=0.005 and 0.09, respectively). Body fat declined a mean 1.2 kg over 8 months in protease-inhibitor recipients (p=0.05). The prevalence of hyperlipidaemia remained stable over time (74% of treated patients vs 28% of naïve patients; p=0.0001). Impaired glucose tolerance occurred in 16% of protease-inhibitor recipients and diabetes mellitus in 7%; in all but three patients these abnormalities were detected on 2 h post-glucose load values. INTERPRETATION: Diagnosis and rating severity of lipodystrophy is aided by the combination of physical examination, patient's rating, and measurement of body fat, fasting triglycerides, and C-peptide. Weight before therapy, fasting triglyceride, and C-peptide concentrations early in therapy, and therapy duration seem to predict lipodystrophy severity. Lipodystrophy was common and progressive after almost 2 years of protease inhibitor therapy, but was not usually severe. Hyperlipidaemia and impaired glucose tolerance were also common.

Adult↗
PubMed1999

Comprehensive classification of symptoms and signs reported among 218 patients with acute HIV-1 infection.

Acute HIV-1 illness presents a wide range of clinical manifestations. We assessed a classification and data reduction of clinical features among 218 patients with acute HIV-1 infection enrolled in four prospective seroincidence studies. Factor analysis allows the definition of eight factors based on groups of symptoms and signs: gastrointestinal transit disturbances, weight loss/abdominal pain, lymphadenopathy, myalgia/arthralgia, neurologic features, constitutional and mucocutaneous features, oral candidiasis, and anorexia/pharyngitis. These groups reflected the main target systems involved at the time of acute HIV-1 disease. Grouping of symptoms and signs based on groups of patients is potentially more informative than observations made on individual patients. It might facilitate diagnosis, suggest pathogenic mechanisms and reduce the number of variables for characterizing acute HIV-1 illness.

Acute Disease↗
PubMed1999

A comparison of in vivo and in vitro DNA-binding specificities suggests a new model for homeoprotein DNA binding in Drosophila embryos.

Little is known about the range of DNA sequences bound by transcription factors in vivo. Using a sensitive UV cross-linking technique, we show that three classes of homeoprotein bind at significant levels to the majority of genes in Drosophila embryos. The three classes bind with specificities different from each other; however, their levels of binding on any single DNA fragment differ by no more than 5- to 10-fold. On actively transcribed genes, there is a good correlation between the in vivo DNA-binding specificity of each class and its in vitro DNA-binding specificity. In contrast, no such correlation is seen on inactive or weakly transcribed genes. These genes are bound poorly in vivo, even though they contain many high affinity homeoprotein-binding sites. Based on these results, we suggest how the in vivo pattern of homeoprotein DNA binding is determined.

Animals↗
PubMed1999

The use of human immunodeficiency virus postexposure prophylaxis after successful artificial insemination.

A case is reported of a woman who was exposed to human immunodeficiency virus through self-insemination. She was artificially inseminated with fresh semen obtained from a gay man in whom HIV seroconversion was taking place. Postexposure prophylaxis with antiretrovirals was initiated 10 days later, and despite successful conception, HIV infection was not established. A healthy male infant was subsequently delivered with no obvious toxicity related to medication.

Adult↗
PubMed1999

Wine-induced asthma: a placebo-controlled assessment of its pathogenesis.

BACKGROUND: The sulfite family of food additives has been implicated in the pathogenesis of wine-induced asthma. However, the evidence supporting this is weak, and because wines have many hundreds of components, nonsulfite-associated mechanisms may also play a role. OBJECTIVES: The aim of the study was to assess the potential sensitivity of persons with asthma to nonsulfite components in wine by using low-sulfite wine challenges. METHODS: Sixteen adults with a strong history of wine-induced asthma were challenged with both low-sulfite red and white wines and wine-placebo drinks. Challenges were performed double blind, using a Latin square design, with lung function being assessed before the challenge and at 5, 10, 15, 30, and 60 minutes after the challenge. Subsequently, single-blind challenges with high-sulfite white wine were also completed in 10 individuals whose lack of reactivity to low-sulfite white wine suggested possible reactivity to sulfite additives. RESULTS: The mean FEV1; forced expiratory flow, mid-expiratory phase; and peak expiratory flow of subjects to low-sulfite red and white wines and red and white placebo wines were not significantly different. Furthermore, with a predetermined criterion of a fall in FEV1 of more than 15% representing a positive challenge, only one individual exhibited a positive reaction in the presence of a negative response to placebo. Only 2 of the 10 test individuals who were challenged with a high-sulfite wine demonstrated a marked and rapid fall in FEV1. Reactivity to low-sulfite wines appears to occur only in a small number of individuals who report sensitivity to wines, suggesting that the sulfite additives may be the major cause of wine-induced asthmatic reactions. However, direct challenge with high-sulfite wine revealed only 2 clear reactions in this asthma cohort. CONCLUSION: Wine-induced asthma appears to be a complex phenomenon and may involve several mechanisms that are codependent.

Adult↗
PubMed1999

Evaluation of the effectiveness of the stay safe primary prevention programme for child sexual abuse.

OBJECTIVE: This child abuse prevention study aimed to evaluate the effectiveness of the Stay Safe Programme in training unscreened 7 and 10 year old children in personal safety skills. Subsidiary aims were to evaluate the program's impact on children's self-esteem and parents' and teachers' knowledge and attitudes of relevance to child abuse and protection. METHOD: Changes in safety knowledge and skills and self-esteem of 339 children who participated in the Stay Safe Programme were compared with those of 388 waiting list controls. Children in the training group were also followed up at 3 months. In addition, the knowledge and attitudes of parents and teachers of children who completed the program were evaluated before and after the program and 5 month follow-up data were collected from teachers only. RESULTS: Compared with waiting-list controls, trained children showed significant improvements in safety knowledge and skills and these gains were maintained at follow-up. The greatest gains were made by 7 year olds. Children who participated in the program also showed significant improvements in self-esteem which were maintained at 3 months follow-up but only the 7 year olds in the training group made significantly larger gains in self-esteem than their control group counterparts. Children with a higher socioeconomic status benefited more from the program than less privileged children. Both parents and teachers showed significant improvements in knowledge and attitudes concerning protection over the course of the program and for teachers, these gains were maintained at follow-up. CONCLUSION: The findings suggest that the Stay Safe Programme was effective in training children in safety skills and so may usefully be used as a primary prevention intervention for child abuse.

Child↗
PubMed1999

Helping children to the other side of silence: a study of the impact of the stay safe programme on Irish children's disclosures of sexual victimization.

OBJECTIVE: This study aimed to evaluate the effectiveness of a school based safety skills program--The Stay Safe Programme--in facilitating the disclosure of sexual abuse among sexually victimized children and adolescents in Dublin. METHOD: A Cohort of 145 children who had participated in the Stay Safe Programme prior to their referral to a sexual abuse assessment unit were compared with a cohort of 443 children who had not participated in the prevention program on a range of disclosure related variables abstracted from case notes. RESULTS: More Stay Safe participants, particularly female adolescents, made disclosures of suspected sexual abuse than non-participants. A higher rate of initial disclosure to teachers was made by Stay Safe participants and more teachers in schools participating in the Stay Safe Programme initiated referrals for evaluation of suspected child sexual abuse. Following assessment a higher rate of confirmed abuse occurred among Stay Safe participants and for these confirmed cases more Stay Safe participants made purposeful disclosures and in significantly more cases referral was due to the child telling someone about the abuse. These differences in disclosure between program participants and non-participants were unrelated to demographic factors or characteristics of the abuse. CONCLUSIONS: The Stay Safe Programme was an effective secondary prevention intervention deserving widespread implementation.

Adolescent↗
PubMed1999

Unawareness of illness and its relationship with depression and self-deception in schizophrenia.

Both poor insight and depressive symptomatology are common features of schizophrenia that may be independent of positive and negative symptoms. Forty-six patients with DSM-III-R schizophrenia were evaluated for level of insight (schedule for unawareness of mental disorder), depression (Calgary depression scale for schizophrenia, Beck depression inventory), and self-deception or denial (balanced inventory of desirable responding). Patients with a greater unawareness of their illness had relatively less depressive symptomatology and relatively greater self-deception. This relationship was particularly strong for unawareness of the social consequences of having a mental disorder. These results suggest that the presence of depressive symptomatology in schizophrenia is related to the level of insight, and contingent at least in part on the absence of self-deception as a denial defense.

Adult↗