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Biomedical subjects

T Quinn

Publications and source records attributed to T Quinn.

At least 19 recordsLinked to original sources
PubMed1999

Short-term effects of large-dose vitamin A supplementation on viral load and immune response in HIV-infected women.

Vitamin A supplementation has been suggested for treatment and prevention of HIV infection. However, some in vitro data indicate that vitamin A may activate HIV. Randomly, 40 HIV-seropositive women of reproductive age were allocated to receive a single oral dose of 9900 micromol (300,000 IU) vitamin A or placebo. Plasma HIV-1 RNA concentration, total lymphocytes, selected lymphocyte subsets and activation markers, and in vitro lymphocyte proliferation to phytohemagglutinin (PHA) and Candida were measured before dosing and at various time points over an 8-week follow-up period. No differences were found between treatment groups in the frequency of signs or symptoms of acute vitamin A toxicity, nor were differences evident in any lymphocyte subset or activation marker at any time during follow-up. Mean and median viral load concentration at each time point and change in viral load from baseline to each follow-up point did not differ between treatment groups. No difference was measured between treatment groups in the proportion of women who responded to PHA or Candida. This study provides no evidence that high dose vitamin A supplementation of HIV-infected women is associated with significant clinical or immunologic adverse effects.

Adult↗
PubMed1999

Mutations in a gene encoding a new oxygen-regulated photoreceptor protein cause dominant retinitis pigmentosa.

The autosomal dominant retinitis pigmentosa (RP) locus, designated RP1, has been mapped through linkage studies to a 4-cM interval at 8q11-13. Here we describe a new photoreceptor-specific gene that maps in this interval and whose expression is modulated by retinal oxygen levels in vivo. This gene consists of at least 4 exons that encode a predicted protein of 2,156 amino acids. A nonsense mutation at codon 677 of this gene is present in approximately 3% of cases of dominant RP in North America. We also detected two deletion mutations that cause frameshifts and introduce premature termination codons in three other families with dominant RP. Our data suggest that mutations in this gene cause dominant RP, and that the encoded protein has an important but unknown role in photoreceptor biology.

Amino Acid Sequence↗
PubMed1998

Patterns of HIV-1 evolution in individuals with differing rates of CD4 T cell decline.

Evolution of HIV-1 env sequences was studied in 15 seroconverting injection drug users selected for differences in the extent of CD4 T cell decline. The rates of increase of either sequence diversity at a given visit or divergence from the first seropositive visit were both higher in progressors than in nonprogressors. Viral evolution in individuals with rapid or moderate disease progression showed selection favoring nonsynonymous mutations, while nonprogressors with low viral loads selected against the nonsynonymous mutations that might have resulted in viruses with higher levels of replication. For 10 of the 15 subjects no single variant predominated over time. Evolution away from a dominant variant was followed frequently at a later time point by return to dominance of strains closely related to that variant. The observed evolutionary pattern is consistent with either selection against only the predominant virus or independent evolution occurring in different environments within the host. Differences in the level to which CD4 T cells fall in a given time period reflect not only quantitative differences in accumulation of mutations, but differences in the types of mutations that provide the best adaptation to the host environment.

Base Sequence↗
PubMed1998

Determining patients' suitability for thrombolysis: coronary care nurses' agreement with an expert cardiological 'gold standard' as assessed by clinical and electrocardiographic 'vignettes'.

BACKGROUND: Thrombolytic therapy is an established treatment for acute myocardial infarction, the benefits of which are time-dependent. Coronary care nurses are often the first professionals to assess patients with suspected myocardial infarction on hospital admission, and there are a number of reports of nurseled practices for immediate assessment and 'cardiac triage'. OBJECTIVE: To assess coronary care nurses' ability to determine patients' suitability for thrombolysis as judged by an expert cardiological 'gold standard'. METHODS: Ten coronary care units in the Northern and Yorkshire region of England were sent packs comprising 10 sets of 10 'vignettes' and accompanying electrocardiograms together with a questionnaire regarding treatment decisions. An expert 'gold standard' for correct responses to the questionnaire was derived following independent assessment of the vignettes by three nurse specialists and three consultant cardiologists. Respondents' treatment decisions were subsequently compared with the 'gold standard'. RESULTS: Of 42 (42%) completed sets of questionnaires returned for analysis, 37 (87%) of respondents indicated management decisions in absolute agreement with the 'gold standard'. Where there was not absolute agreement, most treatment decisions were acceptable as safe practice. CONCLUSION: The majority of nurses indicated safe and appropriate management decisions. These limited data provide further support for ongoing developments of nurse-initiated thrombolysis, although there is a need for further, larger trials to determine the safety and efficacy of such an approach to patient care.

Cardiology↗
PubMed1998

Evaluation of vaginal infections in adolescent women: can it be done without a speculum?

OBJECTIVE: Given that highly sensitive urine-based nucleic acid amplification tests may eliminate the need for speculum exam to diagnose gonorrhea and chlamydia cervicitis, we sought to determine if vaginal infections could be diagnosed without using a speculum. METHODS: Matched pairs of vaginal specimens were collected from participants before and during speculum exam for diagnosis of trichomoniasis, bacterial vaginosis, and vulvovaginal candidiasis. Females age 12 to 22 years presenting to the Johns Hopkins adolescent primary care clinics who required a pelvic examination were eligible to participate. A convenience sample of 686 patients was recruited between July 1995 and August 1996. Paired vaginal specimens were evaluated with blinded microscopic evaluation. Analysis consisted of: 1) comparison of collection method sensitivities; and 2) assessment of proportions of infections detected by one method that were also detected by the other method. RESULTS: Sensitivities of speculum and nonspeculum collection methods were 75% and 77% (difference = -2%; 95% confidence interval, -11%, 7%) for trichomoniasis, 64% and 68% (difference = -4% [-10%, 3%]) for bacterial vaginosis, and 85% and 80% (difference = 5% [-12%, 22%]) for vulvovaginal candidiasis. The speculum method identified 88% (trichomoniasis), 90% (bacterial vaginosis), and 81% (vulvovaginal candidiasis) of infections detected by the nonspeculum method. The nonspeculum method identified 91% (trichomoniasis), 95% (bacterial vaginosis), and 76% (vulvovaginal candidiasis) of infections detected by the speculum method. CONCLUSIONS: Vaginal infections can be adequately diagnosed without a speculum. Once urine-based diagnosis of gonorrhea and chlamydia becomes well established, it may be possible to perform evaluations for uncomplicated genitourinary complaints without using a speculum.

Adolescent↗
PubMed1997

Assessment of the patient with chest pain in the accident and emergency department.

This article will review measures enabling emergency staff to identify patients with chest pain who are likely to need admission to a cardiac care unit, in particular those with manifestations of acute ischaemic heart disease--acute myocardial infarction and unstable angina. Other non-cardiac causes of chest pain will also be discussed.

Chest Pain↗
PubMed1997

Adenovirus-mediated in vivo gene transfer rapidly protects ornithine transcarbamylase-deficient mice from an ammonium challenge.

The purpose of this study was to determine the time of onset, duration, and the efficacy of in vivo gene transfer in protecting the ornithine transcarbamylase deficient spf/Y mouse from an acute ammonium challenge. The animals were challenged with ammonia (10 mmol/kg NH4Cl) 1, 2, 7, 14, or 28 d after the administration of a recombinant adenoviral construct deleted in E1 and with a temperature sensitive mutation in E2. Although there was no protection with the control LacZ virus, the ornithine transcarbamylase (OTC)-containing vector provided partial protection from both behavioral symptoms (ataxia, seizures, and abnormal response to sound) and biochemical abnormalities (ammonium, aspartate, alanine, and glutamine) within 24 h and complete protection by 48 h. Mortality was also decreased. Animals receiving the vector 7 and 14 d before the ammonium load were also protected, whereas those treated 28 d before the challenge were not. OTC enzyme activity in liver of untreated spf/Y mice was 5% of control C3H mice. After gene transfer, activity was increased to near control levels through 14 d but had returned to baseline by 28 d. These studies indicate that adenovirus-mediated gene transfer confers a metabolic benefit within 24 h of administration and provides protection against an acute metabolic insult for at least 2 wk.

Adenoviridae↗
PubMed1996

Estimating the timing of mother-to-child transmission of human immunodeficiency virus in a breast-feeding population in Kinshasa, Zaire.

Breast-fed infants born to human immunodeficiency virus (HIV)-infected mothers in Kinshasa, Zaire, were monitored a mean of 18 months. HIV infection in infants was determined by polymerase chain reaction (PCR), HIV culture, or ELISA. PCR test results for HIV DNA on venous blood drawn from children ages 0-2 days and 3-5 months were used to estimate proportions of mother-to-child transmission and transmission risks during the intrauterine, intrapartum/early postpartum, and late postpartum periods. Among 69 HIV-infected children (26% of the cohort), 23% (95% confidence interval [CI], 14%-35%) were estimated to have had intrauterine, 65% (CI, 53%-76%) intrapartum/early postpartum, and 12% (CI, 5%-22%) late postpartum transmission. The estimated risks for intrauterine, intrapartum/early postpartum, and late postpartum infection, respectively, were 6% (16/261; CI, 4%-10%), 18% (45/245; CI, 14%-24%), and 4% (8/189; CI, 2%-8%). These results support earlier studies indicating that most transmission occurs during labor and delivery or in the early postpartum period and that the risk of HIV transmission through breast-feeding during the postpartum period is substantial.

Breast Feeding↗
PubMed1996

A library of organic landscapes on filamentous phage.

A billion-clone library of filamentous phage with different surface structures ("landscapes') was generated by fusing random octapeptides to the N-terminus of all 4000 copies of the major coat protein. Such a "landscape library' might include clones exhibiting emergent properties that inhere in the entire surface architecture, not in the peptides by themselves. Because the diverse surface landscapes are displayed on viable phage, they can be surveyed for exceedingly rare functions using microbiological selection methods. Clones with several emergent properties of the sort envisioned were successfully selected, suggesting that landscape libraries have promise as a novel source of nanomaterials with exploitable surface properties.

Amino Acid Sequence↗
PubMed1996

Homing in Pacific salmon: mechanisms and ecological basis

Pacific salmon (Oncorhynchus spp.) are famous for their homing migrations from oceanic feeding grounds to their natal river to spawn. During these migrations, salmon travel through diverse habitats (e.g. oceans, lakes, rivers), each offering distinct orientation clues and, perhaps, requiring distinct sensory capabilities for navigation. Despite these challenges, homing is generally precise and this philopatry has resulted in reproductively isolated spawning populations with specialized adaptations for their natal habitat. This paper reviews the mechanisms underlying all aspects of salmon homing but emphasizes the final, freshwater phase governed by olfactory recognition of homestream water. Prior to their seaward migration, juvenile salmon learn (imprint on) odors associated with their natal site and later, as adults, use these odor memories for homing. Our understanding of this imprinting process is derived primarily from studies using artificial odorants and hatchery-reared salmon. Recent findings suggest, however, that such studies may underestimate the complexity of the imprinting process in nature.

Journal Article↗
PubMed1995

The AIDS epidemic in India: a new method for estimating current human immunodeficiency virus (HIV) incidence rates.

Human immunodeficiency virus (HIV) incidence rates in India were estimated using a new method that accounts for follow-up bias. Follow-up bias arises in epidemiologic cohort studies when the incidence rate among individuals who do and do not return for follow-up are different. The new method combines data on the prevalence of p24 antigenemia among all those initially screened together with the longitudinal follow-up data on the subset of patients who returned for follow-up. Using these methods, the current HIV incidence rate among patients attending sexually transmitted disease clinics in Pune, India, was 18.6% per year. It was found that follow-up bias can cause significant underestimation in HIV incidence rates, perhaps by as much as 60%. These incidence estimates, together with other HIV seroprevalence studies, suggest the HIV epidemic in India is growing rapidly.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Site-directed mutagenesis of P2U purinoceptors. Positively charged amino acids in transmembrane helices 6 and 7 affect agonist potency and specificity.

Two subtypes of G protein-coupled receptors for nucleotides (P2U and P2Y purinoreceptors) contain several conserved positively charged amino acids in the third, sixth, and seventh putative transmembrane helices (TMHs). Since the fully ionized form of nucleotides has been shown to be an activating ligand for both P2U and P2Y purinoceptors (P2UR and P2YR), we postulated that some of these positively charged amino acids are involved in binding of the negatively charged phosphate groups of nucleotides. To investigate the role of the conserved positively charged amino acids in purinoceptor function, a series of mutant P2UR cDNAs were constructed so that lysine 107 and arginine 110 in TMH 3, histidine 262 and arginine 265 in TMH 6, and arginine 292 in TMH 7 were changed to the neutral amino acid leucine or isoleucine. The mutated P2UR cDNAs were stably expressed in 1321N1 astrocytoma cells and receptor activity was monitored by quantitating changes in the concentration of intracellular Ca2+ upon stimulation with full (ATP, UTP) or partial (ADP, UDP) P2UR agonists. Neutralization of His262, Arg265, or Arg292 caused a 100-850-fold decrease in the potency of ATP and UTP relative to the unmutated P2UR and rendered ADP and UDP ineffective. In contrast, neutralization of Lys107 or Arg110 did not alter the agonist potency or specificity of the P2UR. Neutralization of Lys289 in the P2UR, which is expressed as a glutamine residue in the P2Y subtype, did not alter receptor activity; however, a conservative change from lysine to arginine at this position altered the rank order of agonist potency so that ADP and UDP were approximately 100-fold more potent than ATP and UTP. A three-dimensional model of the P2UR indicates the feasibility of His262, Arg265, and Arg292 interactions with the phosphate groups of nucleotides.

Amino Acid Sequence↗
PubMed1995

Administration of thrombolytic therapy to patients with acute myocardial infarction.

The publication of large randomised trials such as ISIS 2 (1988) and AIMS (1990), provided striking evidence as to the effectiveness of thrombolytic therapy in reducing early mortality and morbidity in patients suffering acute myocardial infarction. This article will provide an overview of the use of thrombolytic agents in modern cardiac care, with particular reference to their impact on the Accident and Emergency department.

Electrocardiography↗