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Biomedical subjects

T Matthews

Publications and source records attributed to T Matthews.

At least 37 records · Page 2Linked to original sources
PubMed2001

Questionnaire on practices and priorities in neonatal care in Ireland.

As part of a process of audit of neonatal practice, a questionnaire on clinical practice and priorities which need to be addressed was sent to all consultant neonatologists, and to a consultant paediatrician in all other units caring for newborn infants, in the Republic of Ireland. The response rate was 88% (22 out of 25 replied). Thirteen respondents specified greater than 24 weeks and/or greater than 500 grams as the criteria at which infants were resuscitated. Eleven routinely intubated very premature infants. Seven treated any infant intubated for respiratory distress syndrome with surfactant, and seven sometimes used prophylactic surfactant. Poor perfusion or low blood pressure was the most common criterion for volume expansion during the first hour, using albumen (15 of 22), fresh frozen plasma (10), whole blood (9), normal saline (20 and haemacell (1). Most (18 of 22) used steroids for established bronchopulmonary dysplasia. Oral feeds were generally begun "as soon as possible". Persistent foetal circulation was treated with various vasodilators, tolazoline (14 of 22), magnesium sulphate (8) and nitric oxide (4). The main local priorities noted are the need for more neonatally trained nursing and / or medical staff. Almost all respondents noted the need for a national neonatal transport system. While this summary reveals a considerable variation in clinical practice this variation reflects the lack of evidence on which to base clinical decision making. Where evidence exists from clinical trials considerable uniformity exists in clinical decision making and practice. This study highlights the need for continued audit of clinical practice and the essential role clinical research plays in informing decision making in practice.

Birth Weight↗
PubMed2000

A phase II study of two HIV type 1 envelope vaccines, comparing their immunogenicity in populations at risk for acquiring HIV type 1 infection. AIDS Vaccine Evaluation Group.

Several immunogens induce HIV-specific neutralization and in vitro lymphoproliferation in adults at low HIV-1 risk, but responses in persons at high HIV-1 risk are not known. We performed a multicenter, double-blinded, adjuvant-controlled trial with two gp120 vaccines in 296 HIV-1-uninfected volunteers, including 176 reporting higher HIV-1 risk activities. The immunogens were remarkably well tolerated. After three immunizations, 210 of 241 vaccinees (87%) developed neutralizing antibodies, which persisted in 59% after 2 years. The injection drug users receiving SF-2/gp120 had decreased antibody responses relative to the lower risk groups. Envelope-specific lymphoproliferation peaked after two immunizations, and 54% of vaccinees mounted a DTH reaction to gp120 after 4 years. In summary, these immunogens have low adverse reactogenicity and induce durable antibody and T cell responses to the prototype strains. Unexpected differences in antibody responses among diverse HIV-1 risk strata lend support to the conduct of expanded phase II trials in populations other than low-risk volunteers.

AIDS Vaccines↗
PubMed2000

Identification of gp120 regions targeted by a highly potent neutralizing antiserum elicited in a chimpanzee inoculated with a primary human immunodeficiency virus type 1 isolate.

We have previously reported that a chimpanzee infected with a primary human immunodeficiency virus type 1 (HIV-1) isolate (HIV-1(DH12)) developed an extremely potent virus-neutralizing antibody. Immunoglobulin G purified from this animal conferred sterilizing immunity following passive transfer to macaques which were subsequently challenged with simian immunodeficiency virus/HIV-1 chimeric virus strain DH12. In addition to being highly strain specific, the chimpanzee antiserum did not bind to the V3 loop peptide of HIV-1(DH12), nor did it block the interaction of gp120 with the CD4 receptor. When neutralization was examined in the context of virus particles carrying chimeric envelope glycoproteins, the presence of all five hypervariable regions (V1 to V5) was required for optimal neutralization. Virions bearing chimeric gp120 containing the V1-V2 and V4 regions of HIV-1(DH12) could also be neutralized, but larger quantities of the chimpanzee antiserum were needed to block infection. These results indicate that the HIV-1 gp120 epitope(s) targeted by the chimpanzee antiserum is highly conformational, involving surface elements contributed by all of the hypervariable domains of the envelope glycoprotein.

Animals↗
PubMed2000

Effect of prone sleeping on circulatory control in infants.

BACKGROUND: The mechanism of death in sudden infant death syndrome (SIDS) remains unclear. Progressive bradycardia is the pre-eminent terminal event, suggesting that circulatory failure might be a crucial factor. Vasomotor tone regulates the circulatory system by controlling blood volume distribution while maintaining venous return and blood pressure. AIM: To examine whether prone sleeping, the most consistently identified risk factor for SIDS, has a measurable influence on vasomotor/circulatory control. METHODS: 44 full term infants (mean age, 7.9 weeks) were studied during an overnight sleep. Recordings were made while the infants were horizontal and asleep in the supine and prone positions, and repeated after a head up tilt to 60 degrees, maintained for 30 minutes, while in both sleep positions. Blood pressure, heart rate, anterior shin, and anterior abdominal wall skin temperatures were measured. RESULTS: Systolic blood pressure was lower, but peripheral skin temperature and heart rate were higher during sleep, while horizontal, in the prone rather than the supine position. After tilting, there was a greater reduction in blood pressure and a greater increase in peripheral skin temperature and heart rate when in the prone position. Anterior abdominal wall skin temperature did not vary in either sleeping positions while horizontal or tilted. CONCLUSION: Prone sleeping has a measurable effect on circulatory control, with a reduction in vasomotor tone resulting in peripheral vasodilatation, a higher peripheral skin temperature, a lower blood pressure, and a higher resting heart rate. Because vasomotor tone is crucially important in circulatory control this could be a factor in increasing the risk of SIDS.

Autonomic Nervous System↗
PubMed2000

Responses of seventh grade students to "do you have a partner with whom you would like to have a baby?".

This study investigated differences in demographic data, self-esteem, and coping skills for 225 students in Grade 7 who reported having a partner with whom they wanted to have a baby and 946 students who did not. Data were collected on the Rosenberg Self-esteem Scale, the Family Crisis-oriented Personal Evaluation Scale, and questions related to attitudes towards teen pregnancy and demographic data. The sample included 548 (46.8%) boys and 624 (53.2%) girls whose mean age was 13.2 yr. Students with a partner had significantly lower scores on the curriculum questions, self-esteem, and family coping skills, combined with higher scores in passivity. They indicated a desire to have a greater number of children, beginning by having their first child at a younger age and believed that having a baby improves a couple's relationship. Possible approaches may include effective teaching methods to overcome passivity through boosting self-confidence, goal-setting, and acquiring a purpose in life besides parenting a child.

Adolescent↗
PubMed2000

Feeding infants - an investment in the future.

Because nutrition during infancy not only determines growth but also impacts on future adult health, it is essential that healthy eating habits be promoted from a very young age. This study examines current feeding practices among Irish infants in the first year of life. Although 51% of Irish mothers commenced breast-feeding their infants at birth, the number of women who continued to breast-feed their infants at 3 months of age was among the lowest in Europe. Over two-thirds of infants (70%) received some formula by 4 weeks of age and the majority of infants changed formulas at least once or twice in the first year. The use of follow-up milk formulas was particularly prevalent in Ireland. Only 16% of infants were given unmodified cow's milk in their first year of life but none had been prescribed supplemental iron or vitamins. On average, Irish infants were weaned between 3 and 4 months of age but few families used home-prepared foods in the initial weaning period. Areas for future intervention include the encouragement of a longer duration of breast-feeding, appropriate vitamin and iron supplementation and the promotion of home-prepared foods.

Adult↗
PubMed2000

The current epidemiology of SIDS in Ireland.

This paper examines some epidemiological factors associated with SIDS to give a general profile of SIDS cases occurring in Ireland between the years 1993 to 1997. There has been a dramatic decrease in the incidence of the Sudden Infant Death Syndrome (SIDS) in the Republic of Ireland in the last decade from an average rate of 2.2/1000 live-births in the 1980s to 0.8/1000 live-births in the years 1993-1997, a decrease of 100 deaths a year. The fall in the SIDS rate has been seen in many countries and is felt to be associated with Reduce The Risks (RTR) of SIDS campaigns and the avoidance of the prone sleeping position. The use of the prone sleep position averaged at 6% of children being put prone in the years 1993-1997 but the prone position has progressively decreased from 13% of children being put prone in 1994 to only 2% in 1997. The profile of the Irish SIDS cases is similar to that of SIDS cases in other countries following similar RTR campaigns with a male predominance, the characteristic clustering of deaths in the first six months of life and the majority of cases (75%) occuring in the night sleep period. The loss of the seasonal variation of the time of death is also shown and factors such as lower socio-economic status, unemployment and medical card eligibility were seen in higher proportions in SIDS families than in the general population. A high percentage of SIDS mothers smoked (73%). Higher smoking rates were seen among younger and single mothers and smoking rates were inversely related to educational level and socioeconomic grouping. An urgent question that needs to be addressed is how socioeconomic disadvantage increases the SIDS risk and what factors influence socioeconomically disadvantaged families to adopt life style and parenting practices such as smoking that influence their children's health.

Adult↗
PubMed1998

Potent suppression of HIV-1 replication in humans by T-20, a peptide inhibitor of gp41-mediated virus entry.

T-20, a synthetic peptide corresponding to a region of the transmembrane subunit of the HIV-1 envelope protein, blocks cell fusion and viral entry at concentrations of less than 2 ng/ml in vitro. We administered intravenous T-20 (monotherapy) for 14 days to sixteen HIV-infected adults in four dose groups (3, 10, 30 and 100 mg twice daily). There were significant, dose-related declines in plasma HIV RNA in all subjects who received higher dose levels. All four subjects receiving 100 mg twice daily had a decline in plasma HIV RNA to less than 500 copies/ml, by bDNA assay. A sensitive RT-PCR assay (detection threshold 40 copies/ml) demonstrated that, although undetectable levels were not achieved in the 14-day dosing period, there was a 1.96 log10 median decline in plasma HIV RNA in these subjects. This study provides proof-of-concept that viral entry can be successfully blocked in vivo. Short-term administration of T-20 seems safe and provides potent inhibition of HIV replication comparable to anti-retroviral regimens approved at present.

Adult↗
PubMed1998

An audit of care provided for children with epilepsy in the South Tees area.

This study examined the knowledge carers of children with epilepsy have of the condition and its management. It also examined their experience of medical services for their child and the attitude of staff at their schools. A school nursing sister using a semi-structured technique interviewed 48 carers of 53 children. A majority expressed dissatisfaction with outpatient medical care, especially that outpatient visits did not improve their knowledge of the condition or its treatment. Twenty-eight carers were not satisfied with the attitude of staff at schools. Ways to improve the service are discussed, including the role of the specialist community children's nurse and the need to see children with epilepsy in a dedicated clinic.

Activities of Daily Living↗
PubMed1998

Perinatal factors influencing survival in extremely low-birthweight infants.

The majority of deaths in normally formed infants occur in extremely low birth weight infants (< 1000 g). Survival rates for these infants have improved greatly but still vary from centre to centre and accurate local outcome figures are important for counselling parents and upholding standards of care. In the Rotunda Hospital, Dublin, over the 6 year period from 1 January 1990 to 31 December 1995, there were 34 474 deliveries over 500 g birthweight. One hundred and twenty-six of these were normally formed infants between 500 g and 999 g. Our objective was to analyse the factors influencing survival in these extremely low birthweight (ELBW) infants. Overall survival in the group was 63%. The most significant factors influencing survival to 28 days were gestation and birthweight. Survival increased from 33% at 24 weeks to 100% at 28 weeks' gestation and from 29% at 500-599 g to 87% at 900-999 g birthweight. Having controlled for gestational age, none of the following variables had a significant effect on survival: year of birth; gender; multiple pregnancy; 1-minute Apgar score; maternal age; parity; use of antenatal steroids; a history of antepartum haemorrhage, pre-eclamptic toxaemia or prolonged rupture of membranes. A 5-min Apgar score > 5 increased the chance of survival by 3.97 (95% CI: 1.46- 10). Both mode of delivery and incidence of chorioamnionitis had an influence on survival which varied according to the gestational age. A larger cohort of survivors would illustrate the effect of these variables more clearly.

Journal Article↗
PubMed1998

Cytotoxic T cell and neutralizing antibody responses to human immunodeficiency virus type 1 envelope with a combination vaccine regimen. AIDS Vaccine Evaluation Group.

Effective human immunodeficiency virus (HIV) vaccination may require induction of neutralizing antibodies (NAs) and CD8+ cytotoxic T lymphocytes (CTL) to prevent transmission and control early infection. Recombinant envelope proteins induce NAs but rarely CD8+ CTL responses, and vaccinia vectors containing HIV-1 envelope elicit CD8+ cytotoxicity but few NAs. To benefit from both approaches, 56 vaccinia-naive subjects were randomized to a regimen of priming with recombinant vaccinia gp160LAI and boosting with recombinant gp120SF-2, gp120LAI, gp120MN, or gp160MN. Of 51 persons for whom assays were done, 26 demonstrated envelope-specific CTL. Boosting with gp120, compared with gp160, elicited significantly more NAs and CD4-blocking antibodies. Neutralization of the homologous and heterologous HIV-1 laboratory strains occurred in all subjects receiving vac/env and gp120 and was detectable in 91% of the subjects for >6 months. Thus, vaccine regimens in which one component elicits primarily CTL and the other NAs offer promise for the development of an effective HIV-1 vaccine strategy.

AIDS Vaccines↗
PubMed1998

Induction of neutralizing antibodies to T-cell line-adapted and primary human immunodeficiency virus type 1 isolates with a prime-boost vaccine regimen in chimpanzees.

Five chimpanzees were immunized by administration of one or more intranasal priming doses of one to three recombinant adenoviruses containing a gp160 insert from human immunodeficiency virus type 1 (HIV-1) MN (HIV-1MN) followed by one or more boosts of recombinant HIV-1SF2 gp120 delivered intramuscularly with MF59 adjuvant. This regimen resulted in humoral immune responses in three of five animals. Humoral responses included immunochemically active anti-H1V-1 antibodies (Abs) directed to recombinant gp120 and neutralizing Abs reactive with T-cell-line-adapted HIV-1MN and HIV-1SF2. In addition, neutralizing activity was detected to the two homologous primary isolates and to two of three heterologous primary isolates which, like the immunizing strains, can use CXCR4 as a coreceptor for infection. The three animals with detectable neutralizing Abs and a fourth exhibiting the best cytotoxic T-lymphocyte response were protected from a low-dose intravenous challenge with a cell-free HIV-1SF2 primary isolate administered 4 weeks after the last boost. Animals were rested for 46 weeks and then rechallenged, without a boost, with an eightfold-higher challenge dose of HIV-1SF2. The three animals with persistent neutralizing Abs were again protected. These data show that a strong, long-lived protective Ab response can be induced with a prime-boost regimen in chimpanzees. The data suggest that in chimpanzees, the presence of neutralizing Abs correlates with protection for animals challenged intravenously with a high dose of a homologous strain of HIV-1, and they demonstrate for the first time the induction of neutralizing Abs to homologous and heterologous primary isolates.

Animals↗
PubMed1998

Neurocardiogenic syncope: a model for SIDS.

A 5 1/2 month old male infant who had suffered three acute life threatening episodes was admitted for overnight sleep studies but was found dead after their completion while still in hospital. A necropsy classified the cause of death as sudden infant death syndrome (SIDS). The sleep studies had shown no periods of apnoea (> 20 seconds) or bradycardia (< 90 beats/min), and a rapid response to nasal occlusion (5 seconds). However, autonomic function during sleep was poor, with reduced heart rate variability (6 beats/min v control 24 beats/min, SD 6.2) and postural hypotension (a 12-14% fall in resting systolic blood pressure) associated with a fall in heart rate when tilted to a vertical position. Postural hypotension with bradycardia occurs in adults with unexplained syncopal episodes and is called a neurocardiac reflex. It involves poor vasomotor tone with peripheral pooling of blood, a consequent reduction in central venous return and cardiac distension, and in some individuals a neurally mediated bradycardia, as seen in this infant, rather than the expected tachycardia. A progressive bradycardia is the predominant mechanism of death seen in SIDS infants dying on cardiorespiratory monitors at home. This case suggests that a neurocardiac reflex occurs in infants, may have been involved in this infant's death, and deserves further study in the context of SIDS.

Hospitalization↗
PubMed1998

Antimony in blood and urine of infants.

AIM: To establish a reference range for antimony in the serum and urine of infants in the first year of life. METHODS: 100 infants were selected randomly from the population. Each infant had a single blood and urine sample taken. Antimony was assayed using inductively coupled plasma mass spectrometry. RESULTS: The reference range for antimony in the serum of infants in the first year of life was established as 0.09-0.25 microgram/l. The upper 95% centile for urinary antimony, corrected for creatinine, in the same population was 2.6 ng/mg creatinine. There was a very weak correlation between the serum and urine concentrations. CONCLUSIONS: This study confirms the presence of low concentrations of antimony in the serum and urine of healthy infants.

Age Factors↗
PubMed1998

Advancing AIDSVAX to phase 3. Safety, immunogenicity, and plans for phase 3.

AIDSVAX (VaxGen, Inc., South San Francisco, CA), a possible vaccine to protect against human immunodeficiency virus type 1 (HIV-1) infection, is being tested for efficacy in phase 3 studies. It has been tested for potential efficacy in chimpanzees, and tested for safety and immunogenicity in human clinical studies. Four candidate vaccines, each with a different envelope protein antigen or combination of antigens, have been produced in alum formulations. In both design and clinical testing, AIDSVAX has an excellent safety profile. Because these highly purified proteins were prepared using recombinant DNA technology, there is no possibility of these vaccines causing HIV infection. Having been administered to over 1200 people, the only side effects attributable to AIDSVAX have been local pain and inflammation at the injection site. After immunization, essentially all recipients developed a robust antibody response, including binding and neutralizing antibodies. The neutralizing antibodies peaked after a 12-month boost. Excellent memory is induced. Two phase 3 trials of two bivalent formulations will evaluate their efficacy. One trial will use a bivalent subtype B formulation. This trial in North America will involve 5000 men who have sex with men and heterosexual women at high risk. The other study will use a bivalent subtype B/subtype E formulation. This trial in Thailand and will involve 2500 intravenous drug users. Both studies will be randomized, double-blinded and placebo controlled. The volunteers will be followed for 3 years. The end points of the studies are infection, as defined by seroconversion to standard diagnostic tests, and viral load, as defined by commercial polymerase chain reaction (PCR) tests.

AIDS Vaccines↗