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Biomedical subjects

A Carr

Publications and source records attributed to A Carr.

At least 109 records · Page 6Linked to original sources
PubMed1998

Duplication of ATR inhibits MyoD, induces aneuploidy and eliminates radiation-induced G1 arrest.

Chromosome 3q alterations occur frequently in many types of tumours. In a genetic screen for loci present in rhabdomyosarcomas, we identified an isochromosome 3q [i(3q)], which inhibits muscle differentiation when transferred into myoblasts. The i(3q) inhibits MyoD function, resulting in a non-differentiating phenotype. Furthermore, the i(3q) induces a 'cut' phenotype, abnormal centrosome amplification, aneuploidy and loss of G1 arrest following gamma-irradiation. Testing candidate genes within this region reveals that forced expression of ataxia-telangiectasia and rad3-related (ATR) results in a phenocopy of the i(3q). Thus, genetic alteration of ATR leads to loss of differentiation as well as cell-cycle abnormalities.

Aneuploidy↗
PubMed1998

Effects of IL-2 therapy in asymptomatic HIV-infected individuals on proliferative responses to mitogens, recall antigens and HIV-related antigens.

The effects of IL-2 therapy on lymphoproliferative responses to mitogens, recall antigens and HIV epitopes were studied in asymptomatic HIV-infected patients enrolled in a phase II study of intermittent continuous intravenous (Ci.v.) IL-2 and subcutaneous infusions of polyethylene glycol-modified (PEG) IL-2. Sixteen consecutive patients randomized to receive Ci.v. IL-2 (n = 5), PEG IL-2 (n = 7) or anti-viral therapy alone (n = 4) were studied. All patients were vaccinated with tetanus toxoid (TT) before receiving therapy. Proliferative responses to phytohaemagglutinin (PHA), soluble anti-CD3, TT, streptokinase/streptodornase (SK/SD) and 11 previously described HIV-specific T-helper epitopes from gag and env were studied at weeks 0, 16, 30 and 48. Median CD4+ lymphocyte increases of 272 and 255CD4+ cells/microl were observed in the Ci.v. IL-2 and PEG IL-2 groups at week 48, while decreasing by 104 cells/microl in the anti-retroviral therapy alone group. At each time point proliferative responses to PHA, anti-CD3, TT and SK/SD were not different between treatment arms. Similarly, no differences in responses to HIV epitopes were found between the groups and no new responses to HIV epitopes were detected. IL-2 therapy results in a significant increase in peripheral blood CD4+ lymphocyte count, but this increase is not associated with quantifiable improvements in lymphoproliferative responses to mitogens, recall or HIV antigens.

Adult↗
PubMed1998

A meta-analysis of nausea and vomiting following maintenance of anaesthesia with propofol or inhalational agents.

A number of prospective randomized comparator studies have suggested that there is a reduction in post-operative nausea and vomiting following maintenance of anaesthesia with propofol compared with inhalational agents. We analysed these studies in more detail by examining the effects of induction agent, choice of inhalation agent, presence/absence of nitrous oxide, age of patient or use of opiate on the incidence of emesis. A search of the Zeneca database MEDLEY was undertaken and prospective randomized comparator studies identified. These were examined individually and independently by two of the authors and log-odds ratios, calculated from the incidence data of each individual trial, were determined and combined using a fixed-effects meta-analysis approach. Patients who received maintenance of anaesthesia with propofol had a significantly lower incidence of post-operative nausea and vomiting in comparison with inhalational agents regardless of induction agent, choice of inhalation agent, presence/absence of nitrous oxide, age of patient or use of opiate.

Adult↗
PubMed1998

Patterns of viral dynamics during primary human immunodeficiency virus type 1 infection. The Sydney Primary HIV Infection Study Group.

This study used curve-fitting techniques to detail the dynamics of human immunodeficiency virus (HIV)-1 and its relationship to circulating T lymphocyte changes in a cohort of 41 male patients (mean age 36+/-7 years) infected with HIV-1. The following characteristics of viral kinetics were obtained: virus load peak, 6. 35+/-0.71 log10 RNA copies/mL at 12.2+/-7.1 days; virus load drop from peak, 2.02+/-0.93 log10 copies/mL; viral decay rate from peak, 0.071+/-0.042 log10 RNA copies/mL/day; and steady state virus load, 4.57+/-0.68 log10 copies/mL at 135+/-81 days. Analysis of individual virus load curves revealed highly variable viral kinetics. Although these could be grouped into three distinct patterns, virus load and CD4 lymphocyte counts were similar in all patterns at 12 months, but the interval from infection to achievement of steady state virus load varied significantly.

Adult↗
PubMed1998

Outpatient continuous intravenous interleukin-2 or subcutaneous, polyethylene glycol-modified interleukin-2 in human immunodeficiency virus-infected patients: a randomized, controlled, multicenter study. Australian IL-2 Study Group.

The safety and activity of outpatient-based continuous intravenous interleukin-2 (CIV IL-2) or a slow-release, polyethylene glycol (PEG)-modified IL-2 were studied in human immunodeficiency virus (HIV)-infected persons with CD4 cell counts between 200 and 500/mm3. One hundred fifteen patients were randomized to antiretroviral therapy plus cyclical CIV IL-2 (n = 27), subcutaneous PEG IL-2 (n = 58), or no IL-2 (n = 30). Toxicity withdrawal rates were low (4% for CIV IL-2 and 7% for PEG IL-2). There were median CD4 cell count increases of 359 and 44 cells/mm3 and a decline of 46 cells/mm3 in the 3 groups, respectively, over 1 year (P < .0001 for each intergroup comparison). CD4 cell count increases were greatest in those with lower HIV RNA load. Delayed-type hypersensitivity scores increased and HLA-DR expression on CD8 cells decreased significantly with IL-2 therapy. HIV RNA levels were unaffected. IL-2 therapy may expand the existing immune repertoire but not immediately reconstitute lost immune function.

Adult↗
PubMed1998

Severity and prognosis of acute human immunodeficiency virus type 1 illness: a dose-response relationship.

This study examined the relationship between the severity of acute human immunodeficiency virus type 1 (HIV-1) illness and disease progression and death. The population included 218 patients with acute HIV-1 illness and 41 asymptomatic patients who underwent HIV-1 seroconversion; the patients were followed up prospectively. We analyzed progression to Centers for Disease Control and Prevention clinical categories B and C (AIDS-defining conditions) and death according to an additive clinical score (CS) based on six predictive clinical features at the time of acute HIV-1 infection. Compared with patients with a CS of 0 (asymptomatic patients), those with a CS of 3-4 and 5-6 had faster progression to category B disease (adjusted hazard ratio [HR], 1.39; 95% confidence interval [CI], 1.01-1.92; and HR, 1.80; 95% CI, 1.34-2.40; respectively); those with a CS of 5-6 had faster progression to category C disease (HR, 1.37; 95% CI, 1.01-1.89) and death (HR, 2.05; 95% CI, 1.27-3.32). Thus, the number of symptoms and signs at the time of acute HIV-1 illness affects disease progression and survival, even in symptomatic patients who have undergone seroconversion.

Acute Disease↗
PubMed1998

Questionnaire on the perceptions of patients about total knee replacement.

We have developed a 12-item questionnaire for patients having a total knee replacement (TKR). We made a prospective study of 117 patients before operation and at follow-up six months later, asking them to complete the new questionnaire and the form SF36. Some also filled in the Stanford Health Assessment Questionnaire (HAQ). An orthopaedic surgeon completed the American Knee Society (AKS) clinical score. The single score derived from the new questionnaire had high internal consistency, and its reproducibility, examined by test-retest reliability, was found to be satisfactory. Its validity was established by obtaining significant correlations in the expected direction with the AKS scores and the relevant parts of the SF36 and HAQ. Sensitivity to change was assessed by analysing the differences between the preoperative scores and those at follow-up. We also compared change in scores with the patients' retrospective judgement of change in their condition. The effect size for the new questionnaire compared favourably with those for the relevant parts of the SF36. The change scores for the new knee questionnaire were significantly greater (p < 0.0001) for patients who reported the most improvement in their condition. The new questionnaire provides a measure of outcome for TKR that is short, practical, reliable, valid and sensitive to clinically important changes over time.

Aged↗
PubMed1997

Safety and immunogenicity of UBI HIV-1MN octameric V3 peptide vaccine administered by subcutaneous injection.

Twenty-four HIV-seronegative men, at high risk of HIV infection, were recruited into a phase I/II safety and immunogenicity trial of a prototype HIV vaccine. The immunogen was a synthetic, monovalent, octameric HIV-1MN V3 peptide in an aluminum hydroxide (alum) adjuvant. The vaccine had been evaluated previously using a standard 0-, 1-, 6-month intramuscular schedule and was found to stimulate neutralizing antibody in 60-90% of volunteers. Participants were randomized to receive either 500 micrograms (n = 10; high dose) or 100 micrograms (n = 10; low dose) of immunogen or placebo (alum alone; n = 4) at 0, 1, and 6 months by subcutaneous injection. Responses to the immunogen were evaluated by enzyme-linked immunosorbent assay (ELISA)-detectable antibody and by proliferative responses. Safety was monitored by both clinical assessment and regular review with a clinical psychologist. No serious adverse experiences were observed following administration of the assigned medication. One individual (placebo) seroconverted while on study, following exposure to HIV. After the vaccination course only four individuals (three high dose and one low dose) had ELISA-detectable antibody against the immunogen. In the evaluable samples, from 19 volunteers, only 7 vaccine recipients (3 high dose and 4 low dose) had demonstrable lymphoproliferative responses to preparations of the immunogen. Subcutaneous administration of its candidate vaccine was safe but did not result in uniform or robust immunological responses.

AIDS Vaccines↗
PubMed1997

High-dose nevirapine in previously untreated human immunodeficiency virus type 1-infected persons does not result in sustained suppression of viral replication.

High-dose nevirapine treatment has been reported to confer sustained antiretroviral effects, despite a rapid development of resistance. The use of this strategy was evaluated in 20 previously untreated human immunodeficiency virus type 1 (HIV-1) p24 antigenemic persons with CD4 cell counts between 100 and 500/mm3. Treatment consisted of 400 mg of nevirapine, after a 2-week lead-in dose of 200 mg. Rash was the most frequently reported adverse event, occurring in 25%. While sustained declines in p24 antigen levels were observed in the majority, serum HIV-1 RNA load and CD4 cell counts returned to baseline values within 12 weeks in virtually all subjects. The resistance-conferring tyrosine-to-cysteine substitution at reverse transcriptase position 181 was detected after 4 weeks in most subjects. These observations suggest that plasma drug levels attained with high-dose nevirapine were not sufficient to inhibit nevirapine-resistant virus, although they were approximately 2-fold higher than reported IC50 values of resistant virus.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Acute human immunodeficiency virus type 1 disease as a mononucleosis-like illness: is the diagnosis too restrictive?

The purpose of this study was to describe the frequency and duration of clinical features at the time of acute human immunodeficiency virus type 1 (HIV-1) disease in 218 patients with documented symptomatic primary HIV-1 infection. The mean duration of acute HIV-1 disease was 25.1 days (median, 20.0 days) and did not differ by gender, age, and risk factor. The frequency and mean duration of clinical features occurring in >50% of patients were as follows: fever, 77.1% and 16.9 days; lethargy, 65.6% and 23.7 days; cutaneous rash, 56.4% and 15 days; myalgia, 54.6% and 17.7 days; and headache, 50.9% and 25.8 days. Only 15.6% of patients presented with a typical mononucleosis-like illness (MLI) defined as fever, pharyngitis or sore throat, and cervical adenopathy, and 10% had no features of an MLI. A meningitis-like syndrome occurred in 20 patients (9.2%). Acute HIV-1 disease is more diverse than previously reported, and the absence of fever or other MLI features does not rule out acute HIV-1 disease.

Acute Disease↗
PubMed1997

Increased frequency of CCR-5 delta 32 heterozygotes among long-term non-progressors with HIV-1 infection. The Australian Long-Term Non-Progressor Study Group.

BACKGROUND: The beta-chemokine receptor CCR-5 is used as a coreceptor by macrophage-tropic strains of HIV-1 to gain entry into CD4+ cells. OBJECTIVE: To determine the effect of a common 32 base-pair deletion mutation in the CCR-5 gene (CCR-5 delta 32) on progression of HIV infection to AIDS, and to assess the level of heterozygosity for this mutation in a well-defined group of long-term non-progressors (LTNP). PARTICIPANTS: Sixty-four HIV-1-infected LTNP (CD4+ T lymphocyte count > 500 x 10(6)/l after 8 years) were compared with 95 individuals infected within a similar period (1983-1986) but who had rapidly progressed to AIDS and death, and with a further 120 HIV-positive individuals with CD4+ counts < 500 x 10(6)/l. METHODS: The presence of the CCR-5 delta 32 mutation was assessed using polymerase chain reaction with primers spanning the 32 base-pair deletion. CD4+ and CD8+ counts, plasma HIV-1 RNA, p24 antigen and beta 2-microglobulin levels in LTNP carrying the CCR-5 delta 32 mutation were compared with LTNP lacking the mutation. RESULTS: A marked increase in the frequency of CCR-5 delta 32 heterozygosity was found among LTNP (35.9%) compared with rapid progressors (12.6%; P = 0.0005) and patients selected on the basis of a CD4+ T-cell count < 500 x 10(6)/l (12.5%; P = 0.0004). LTNP heterozygous for CCR-5 delta 32 had a significantly higher CD8+ T-cell count than those without the mutation (1218 versus 972 x 10(6)/l; P = 0.044). No significant correlation was observed between heterozygosity and CD4 count, viral load, p24 antigen or beta 2-microglobulin within the LTNP group. CONCLUSIONS: This study provides the strongest evidence to date for the importance of a single copy of the CCR-5 delta 32 mutation in long-term non-progression of HIV infection, which may involve, in part, CD8+ T lymphocytes.

Disease Progression↗
PubMed1997

Positive practice in family therapy.

Positive practice, a brief integrative approach to consultation with families, is described in this paper. A clear distinction is made between the stages of planning, assessment, therapy, and disengagement. Guidelines for progression from one stage to the next are provided. Frameworks for deciding who to invite to preliminary sessions and methods for planning and organizing lines of inquiry are incorporated into this approach to practice. A three-column model is used to construct formulations. The model allows therapists and clients to map information about the pattern of interaction around the presenting problem, beliefs that constrain family members from altering their roles in these problem-maintaining patterns, and factors that have predisposed family members to hold these beliefs. Positive practice offers methods for evolving new behavioral patterns and belief systems within sessions and for arranging homework tasks for clients between sessions. It also incorporates methods for dealing with resistance, for managing therapeutic crises, for convening individual sessions and broader network meetings, for disengaging from the consultation process, and for recontracting for further episodes of therapy. This evolving approach to practice draws on ideas from many traditions within the family therapy field and takes account of recent research relevant to the practice of family therapy.

Adult↗
PubMed1997

Simulation of resistance forces acting on surgical needles.

High precision in the manual control of needles and biopsy probes in medical treatment requires high skill and dexterity levels. In anaesthesia, force sensation is an important feedback mechanism, and the practitioner needs to refresh or develop skills to improve on the interpretation of needle progress towards the target site. This paper describes an experimental tactile force simulator for uniaxial needle action for which the force resisting progress of the needle is derived from measured data. As an example, the approach taken to develop the simulation of the insertion of epidural needles is described. Adaptation to other procedures would be possible by adopting new reference models based on appropriate measured force data.

Animals↗