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Biomedical subjects

N McCarthy

Publications and source records attributed to N McCarthy.

At least 19 recordsLinked to original sources
PubMed2006

Passive sexual transmission of human immunodeficiency virus type 1 variants and adaptation in new hosts.

Human immunodeficiency virus type 1 (HIV-1) genetic diversity is a major obstacle for the design of a successful vaccine. Certain viral polymorphisms encode human leukocyte antigen (HLA)-associated immune escape, potentially overcoming limited vaccine protection. Although transmission of immune escape variants has been reported, the overall extent to which this phenomenon occurs in populations and the degree to which it contributes to HIV-1 viral evolution are unknown. Selection on the HIV-1 env gene at transmission favors neutralization-sensitive variants, but it is not known to what degree selection acts on the internal HIV-1 proteins to restrict or enhance the transmission of immune escape variants. Studies have suggested that HLA class I may determine susceptibility to HIV-1 infection, but a definitive role for HLA at transmission remains unproven. Comparing populations of acute seroconverters and chronically infected patients, we found no evidence of selection acting to restrict transmission of HIV-1 variants. We found that statistical associations previously reported in chronic infection between viral polymorphisms and HLA class I alleles are not present in acute infection, suggesting that the majority of viral polymorphisms in these patients are the result of transmission rather than de novo adaptation. Using four episodes of HIV-1 transmission in which the donors and recipients were both sampled very close to the time of infection we found that, despite a transmission bottleneck, genetic variants of HIV-1 infection are transmitted in a frequency-dependent manner. As HIV-1 infections are seeded by unique donor-adapted viral variants, each episode is a highly individual antigenic challenge. Host-specific, idiosyncratic HIV-1 antigenic diversity will seriously tax the efficacy of immunization based on consensus sequences.

AIDS Vaccines↗
PubMed2004

Immunogenicity and safety of a low-dose diphtheria, tetanus and acellular pertussis combination vaccine with either inactivated or oral polio vaccine as a pre-school booster in UK children.

This open, randomised controlled trial studied the immunogenicity and reactogenicity of two combined low-dose diphtheria, tetanus and acellular pertussis vaccines (Td5aP-IPV, REPEVAX, Aventis Pasteur MSD; and Td5aP, COVAXIS, Aventis Pasteur MSD + OPV, GlaxoSmithKline) in comparison with a standard dose diphtheria pre-school booster vaccine (DT2aP-IPV, TETRAVAC, Aventis Pasteur MSD) in a population of 3.5-5-year-old children administered concomitantly with measles, mumps and rubella vaccine (M-M-R II, Aventis Pasteur MSD). A linked sub-study aimed to evaluate the immunogenicity and reactogenicity of Td5aP-IPV in a population of younger children, aged 3-3.5 years. This study demonstrated non-inferiority of seroprotection rates for diphtheria and tetanus for the study vaccines and comparable immunogenicity for pertussis and polio components of the vaccines. Reactogenicity was similar for all three vaccines. The study vaccines containing low-dose diphtheria antigen (Td5aP-IPV and Td5aP + OPV) are immunogenic and have acceptable reactogenicity for use as a pre-school booster vaccine administered concomitantly with MMR.

Antitoxins↗
PubMed2003

Association of the metabolic syndrome with both vigorous and moderate physical activity.

BACKGROUND: Cross-sectional relationships between moderate and vigorous physical activity and the metabolic syndrome (MS) were examined in the Whitehall II study of civil servants (age 45-68 years). We assessed cardiovascular fitness and body mass index (BMI) as possible mediators of the observed association. METHODS: Measures of 2-hour glucose, systolic blood pressure, fasting triglycerides, waist-hip ratio, and high density lipoprotein (HDL) cholesterol were obtained in 5153 white European participants. Participants in the most adverse sex-specific quintile for three or more of these risk factors were classified as having MS. Self-reported leisure-time physical activity was categorized into separate moderate and vigorous activity classes. BMI and resting heart rate (HR) were used to estimate body fatness and cardiovascular fitness respectively. RESULTS: The odds ratios (95% CI) for having the metabolic syndrome in the top categories of vigorous and moderate activity were 0.52 (95% CI: 0.40, 0.67) and 0.78 (95% CI: 0.63, 0.96) respectively, adjusted for age, sex, smoking, alcohol intake, socioeconomic status, and other activity. Adjustment for BMI and resting HR substantially attenuated both of the above associations. CONCLUSIONS: Moderate and vigorous physical leisure-time activity are each associated with reduced risk of being classified with MS independently of age, smoking, and high alcohol intake. Both vigorous and moderate activities may be beneficial to the MS cluster of risk factors among middle-aged populations. Reduced BMI and increased cardiovascular fitness may be important mediators of this association for both intensities of activity.

Aged↗
PubMed2002

Vascular endothelial growth factor gene therapy in ischaemic rat skin flaps.

Gene therapy with the complementary DNA (cDNA) of the angiogenic cytokine vascular endothelial growth factor (VEGF) has emerged as a promising strategy in the treatment of myocardial and lower-limb ischaemia. The objective of this study was to determine whether these principles could be applied to a recognised model of skin-flap ischaemia. Plasmid vectors including the cDNA of green fluorescent protein (GFP) and one of three VEGF isoforms (A165, B167 or B186) were constructed, and their base sequences confirmed. GFP expression was used as a marker of successful in vitro transfection of human endothelial cells with each plasmid. The plasmids were then administered subcutaneously to rat abdominal skin flaps surgically rendered ischaemic, and the percentage of viable tissue was assessed at 1 week. Angiograms of the flaps and histological preparations of flap tissue were assessed for evidence of angiogenesis. The survival of flaps treated with VEGF A165 or B167 cDNA was significantly greater than that of controls (P < 0.05). The survival of flaps treated with VEGF B186 cDNA was greater than that of controls, but statistical significance was not reached. Angiograms and microvessel density counts failed to produce evidence of angiogenesis. With improved delivery strategies, VEGF may have a role in the management of surgical ischaemia.

Analysis of Variance↗
PubMed2001

Incidence of Guillain-Barré syndrome following infection with Campylobacter jejuni.

Evidence of recent or ongoing Campylobacter jejuni infection has been found in approximately one out of every four cases of Guillain-Barré syndrome (GBS). It is increasingly accepted that C. jejuni infection is an important causal factor for GBS. However, the likelihood of GBS' occurring following an episode of C. jejuni gastroenteritis has not been measured. The authors measured the incidence of GBS in a large cohort of persons with laboratory-confirmed C. jejuni infection. Cases of C. jejuni infection were derived from the Swedish national laboratory reporting system for the years 1987--1995. Follow-up for GBS was carried out using the Swedish national hospital inpatient register. Nine cases of GBS were detected in the cohort, which comprised 29,563 cases of C. jejuni infection--a rate of 30.4 per 100,000 (95% confidence interval: 13.9, 57.8). This compares with an expected incidence of 0.3 per 100,000 in a 2-month period in the general population. GBS is an important but rare complication of C. jejuni infection. The risk of developing GBS during the 2 months following a symptomatic episode of C. jejuni infection is approximately 100 times higher than the risk in the general population.

Adult↗
PubMed2001

Low birthweight in schizophrenia: prematurity or poor fetal growth?

In the general population, low birthweight (LBW) is associated with neurological and psychological problems during childhood and adolescence. LBW may result from premature birth or poor fetal growth, and the independent effects of these two events on childhood development are not fully understood. The rate of low weight births is increased in schizophrenia and is associated with social withdrawal during childhood and an early onset of illness. However, it is unclear whether this LBW reflects poor fetal growth or premature birth, or whether these two risk factors have distinct implications for childhood functioning and age at onset of schizophrenia. Subjects included 270 patients with schizophrenia for whom a detailed history of obstetric events could be obtained. The rate of low weight births was high and was associated with poorer premorbid functioning and an earlier age at illness onset. The rate of both premature births and poor fetal growth was high relative to the normal population. Prematurity, but not poor fetal growth, was associated with premorbid social withdrawal and an early age at illness onset. Poor fetal growth, but not prematurity, was associated with low educational achievement. These results suggest that poor fetal growth and prematurity are associated with distinct patterns of childhood maladjustment in individuals who develop schizophrenia.

Adolescent↗
PubMed2001

Apoptotic proteins. p53 and c-myc related pathways.

c-Myc and p53 are two proteins that have critical roles in the regulation of apoptosis and the cell cycle. The authors review how these two proteins are thought to control the opposing events of proliferation and apoptosis and examine whether their well-documented biological roles in tumorigenesis can be applied to the vascular system.

Apoptosis↗
PubMed2001

Postoperative changes in visual evoked potentials and cognitive function tests following sevoflurane anaesthesia.

We tested the hypothesis that minor disturbance of the visual pathway persists following general anaesthesia even when clinical discharge criteria are met. To test this, we measured visual evoked potentials (VEPs) in 13 ASA I or II patients who did not receive any pre-anaesthetic medication and underwent sevoflurane anaesthesia. VEPs were recorded on four occasions, before anaesthesia and at 30, 60, and 90 min after emergence from anaesthesia. Patients completed visual analogue scales (VAS) for sedation and anxiety, a Trieger Dot Test (TDT) and a Digit Symbol Substitution Test (DSST) immediately before each VEP recording. These results were compared using Student's t-test. P<0.05 was considered significant. VEP latency was prolonged (P<0.001) and amplitude diminished (P<0.05) at 30, 60, and 90 min after emergence from anaesthesia, when VAS scores for sedation and anxiety, TDT, and DSST had returned to pre-anaesthetic levels.

Adolescent↗
PubMed2001

Violence in treatment resistant psychotic inpatients.

This study sought to: a) ascertain the effect on rates of violence by varying its operational definition and b) compare characteristics of violent and nonviolent patients. Aggressive behavior was recorded daily for every patient (N = 78) during a 2-year period. Standardized rating scales were used to rate psychopathology and functioning. Almost two thirds of patients were aggressive to others, and 26% violently assaulted another person. Official incident reports underestimated rates of violence to others, self- harm, and property damage. Multivariate predictive models that greatly improved accuracy over base rates showed that violent patients tended to be female, schizophrenic (nonparanoid type), and abusive of alcohol before admission. Violence is more common in treatment resistant psychotic inpatients than suggested by incident reports. Standardized definitions of violence are urged in order to accurately study its prevalence and correlates. Models combining both historical/demographic and clinical data may enhance prediction of violence.

Adolescent↗
PubMed2001

Perspectives in post-transplantation immunotherapy in breast cancer.

High risk and metastatic breast cancer remain a major therapeutic challenge. Although the role of high dose chemotherapy followed by stem cell transplantation (SCT) in the overall treatment strategy is not yet well defined, it is clear that new forms of therapy such as immunotherapy will be needed to cure the majority of patients with advanced disease. We review important considerations for immunotherapy in the post-transplantation period. Experimental and clinical data suggest that immunotherapy may be most effective in a state of minimal residual disease such as that achieved following SCT. However, high dose therapy and autologous SCT result in an iatrogenic immune deficiency, which compounds the suppression of the immune system associated with tumor itself. Understanding reconstitution of a functional immune system post transplantation is critical in devising clinically effective immune interventions. A review of the clinical studies of post transplant immunotherapy for breast cancer is presented including autologous and allogeneic strategies, as well as perspectives for future development.

Journal Article↗
PubMed2000

Diagnosis and management of subdural haematoma complicating bone marrow transplantation.

Subdural haematoma (SDH) is a known complication of bone marrow transplantation (BMT). A retrospective review of 657 consecutive patients undergoing allogeneic or autologous bone marrow/stem cell transplantation at the Royal Brisbane Hospital between January 1991 and December 1998 is reported. Seventeen cases of subdural haematoma/hygroma were identified (2.6%). Eleven of these (65%) were bilateral. Four required surgical drainage, with two developing re-accumulation of SDH. All cases presented with a headache and eight of these had associated neurological complications. Diagnosis was made predominately by CT scan: however in 25% of cases definitive diagnosis could only be made in MRI studies. An association with intrathecal methorexate-containing conditioning therapy, post lumbar puncture headache, prolonged thrombocytopenia and coagulopathy was noted. In our experience, conservative management with platelet support and correction of coagulopathy achieved resolution of subdural haematoma in most cases, with surgical intervention being reserved for neurological deterioration. Bone Marrow Transplantation (2000) 25, 549-552.

Adolescent↗
PubMed1999

Continuous subcutaneous infusion of morphine vs. hydromorphone: a controlled trial.

Seventy-four patients were included in a double-blind, randomized, controlled trial comparing the analgesic efficacy and adverse effects of hydromorphone and morphine delivered by continuous subcutaneous infusion. Patients completed the Memorial Pain Assessment Card and a checklist of opioid-related adverse effects immediately before commencing subcutaneous infusion and 24, 48, and 72 hours later. An assessment tool was developed for the 60 patients who were too ill to complete their own questionnaire. The tool demonstrated excellent inter-rater reliability. Thirty-four percent of patients in the hydromorphone group and 27% of those in the morphine group died before completion of the study (P = 0.66). The hydromorphone group required more analgesia for breakthrough pain in the first 24 hours of the study (P = 0.03) and had a greater improvement in the behavior of frowning on movement and the comfort visual analogue scale (P = 0.08) over the course of the study. Adverse effects were rare and similar in both groups. This study found hydromorphone to be at least as effective as morphine when delivered by continuous subcutaneous infusion.

Adult↗
PubMed1999

The risk of Guillain-Barré syndrome following infection with Campylobacter jejuni.

To estimate the incidence of Guillain-Barré syndrome (GBS) following Campylobacter jejuni infection (CI) we studied three populations where outbreaks of CI had occurred involving an estimated 8000 cases. No case of GBS was detected in the 6 months following the outbreaks in the local populations. The point estimate for the risk of GBS following CI estimated in this study was 0 in 8000 (95% confidence interval 0-3).

Campylobacter Infections↗
PubMed1999

An international outbreak of Vero cytotoxin-producing Escherichia coli O157 infection amongst tourists; a challenge for the European infectious disease surveillance network.

In March 1997, an outbreak of Vero cytotoxin-producing Escherichia coli O157 (VTEC) infection occurred amongst holidaymakers returning from Fuerteventura, Canary Islands. For the investigation, a confirmed case was an individual staying in Fuerteventura during March 1997, with either E. coli O157 VTEC isolated in stool, HUS or serological evidence of recent infection; a probable case was an individual with bloody diarrhoea without laboratory confirmation. Local and Europe-wide active case finding was undertaken through national centres, Salm-Net and the European Programme of Intervention Epidemiology, followed by a case-control study. Fourteen confirmed and one probable case were identified from England (7), Finland (5), Wales (1), Sweden (1) and Denmark (1) staying in four hotels. Three of the four hotels were supplied with water from a private well which appeared to be the probable vehicle of transmission. The case-control study showed illness was associated with consumption of raw vegetables (OR 8.4, 95% CI 1-5-48.2) which may have been washed in well water. This investigation shows the importance of international collaboration in the detection and investigation of clusters of enteric infection.

Adolescent↗
PubMed1999

Analgesic infiltration at the site of bone marrow harvest significantly reduces donor morbidity.

Little information has been published concerning the severity of pain experienced by bone marrow donors or the use of local analgesia following bone marrow harvesting procedures. The aims of this study were to assess duration and severity of pain experienced by bone marrow donors and the effectiveness of bupivacaine as a local analgesic agent following bone marrow harvest. During a single blinded randomised study of 24 bone marrow donors, 10 ml of 0.5% bupivacaine was infiltrated either into the right or left posterior iliac crest of the donor immediately following bone marrow harvest. Donors were requested to record the level of pain experienced at the right and left harvest sites on a pain rating score sheet (0-10) at time intervals of 4, 8, 12, 24, 48 and 72 h following harvest. A significant reduction in pain was experienced at the harvest site infiltrated with bupivacaine when compared with the control site during the first 3 days post-harvest. It is recommended that bupivacaine be infiltrated routinely into the harvest sites of all bone marrow donors to reduce the pain experienced in the 3 days following harvest.

Anesthetics, Local↗
PubMed1999

Case-case comparisons to study causation of common infectious diseases.

BACKGROUND: Analytical studies of reportable infectious diseases often use the small minority of cases detected through surveillance systems. For many diseases, notification of cases represents a non-random selection process. Apparent differences in exposure histories may be due to biases involved in the surveillance system selection of cases compared to randomly selected controls. In addition, differential recall between cases and controls may occur. One way to avoid these problems is to compare cases with another group of cases with a different disorder selected by a similar surveillance system, although this can introduce new biases. METHODS: In infectious diseases cases with the same disease can be divided into aetiologically meaningful subgroups by subtyping the pathogen. Exposure history can then be compared between these subgroups. RESULTS: Several biases are removed. The control group composed of other cases does not represent the exposure history of the study base but differs from it in a predictable and useful way. People considered as controls will have a higher incidence of general predisposing factors than the general population. Analysis is limited to factors associated with exposure to the infecting agent. CONCLUSIONS: Case-case comparison is a development of case-control methodology made possible by laboratory typing techniques. These comparisons allow a more restricted but more refined analysis of the association of some exposures with infection. Determination of how exposure to the infectious agent occurred is more efficient and unbiased than in standard case-control studies but general factors determining whether disease occurs after an infectious exposure can not be studied.

Bias↗