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Biomedical subjects

T Quinn

Publications and source records attributed to T Quinn.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1995

Can nurses safely assess suitability for thrombolytic therapy? A pilot study.

Thrombolytic therapy reduces mortality in patients with acute myocardial infarction. Early treatment is crucial and any system which reduces 'door-to-needle' time without placing the patient at risk is to be encouraged. A group of 20 patients with suspected heart attack was assessed by coronary care nurses and preregistration house officers with regard to: time of symptom onset; admission 12 lead electrocardiogram, presence of contraindications to thrombolytic therapy. Nurses and house officers were asked to state whether or not they considered thrombolysis indicated, and if so, which agent they would recommend on an 'intention to treat' basis. Participating staff were given the option of referral for senior medical opinion. There was no difference in nurses' and house officers' stated intentions regarding thrombolytic therapy. A group of 46 patients was assessed by nurses alone on an 'intention to treat' basis; in this latter group nurses' management intentions were identical to those of the responsible doctor prescribing treatment. Appropriately trained nurses can assess patients with suspected heart attack accurately and safely for thrombolytic therapy. In practice, this could reduce delays to thrombolysis and merits further scrutiny.

Coronary Care Units↗
PubMed1995

Safety of thrombolytic treatment in patients with central venous cannulation.

OBJECTIVES: To determine the safety of thrombolytic treatment in patients with central venous cannulation. BACKGROUND: Thrombolytic treatment significantly reduces mortality in patients with myocardial infarction. Because of the fibrinolytic state induced and the potential for haemorrhagic complications, thrombolysis is currently considered a strong relative contraindication in patients who have had central venous cannulation. There are few data available to support this practice. METHODS: Complications in 56 consecutive patients admitted between 1989 and 1992 with infarction and who had cannulation shortly before, or within 24 h of thrombolysis were studied. RESULTS: Central venous access was achieved via the subclavian route in 52 patients, the internal jugular in three, and the supraclavicular in one. The main indications were for inotropic drugs in 15 patients, pacing in 17, amiodarone infusion in 19, and pressure monitoring in five. Minor haemorrhagic complications occurred in five patients. Two of these patients required either blood or plasma transfusion. Possible major haemorrhagic complications occurred in one patient who became hypotensive shortly after cannulation. Two further patients with severe cardiac failure became hypotensive after cannulation but there was no radiological evidence of effusion and the hypotension was attributed to worsening cardiac failure. Importantly, none of the 19 patients who had cannulas for amiodarone infusion developed significant bleeding complications. CONCLUSION: Central cannulation in the fibrinolytic state is associated with a low incidence of important bleeding complications. Thrombolysis should not be withheld in these patients. Cannulation via the subclavian route, however, should be avoided in patients undergoing thrombolysis.

Adult↗
PubMed1994

Trial of immunosuppression in amyotrophic lateral sclerosis using total lymphoid irradiation.

Although the cause of amyotrophic lateral sclerosis (ALS) remains unknown, recent studies have suggested an autoimmune mechanism of pathogenesis. Previous trials of immunosuppressive treatment have yielded inconclusive results. Our study was designed to determine whether more powerful and prolonged immunosuppression, produced by total lymphoid irradiation (TLI), would alter the course of ALS. In a double-blind, randomized, placebo-controlled study, 30 patients with classic ALS were treated with TLI, and 31 were given sham radiation. Quantitative measurements of muscle strength, functional motor activity, and humoral and cellular immune status were followed for 2 years, or until death or respirator dependence. Motor function in the TLI-treated and control groups showed no significant differences throughout the study. Overall survival was not significantly different in the TLI-treated and control groups. TLI effectively suppressed cellular and humoral immune function throughout the 2-year study period. Analysis of the relationship between immunosuppression and motor functions showed no consistent effect of treatment. We conclude that powerful and prolonged immunosuppression produced by TLI did not benefit patients with ALS. This fails to support the concept of an autoimmune mechanism of pathogenesis of ALS.

Amyotrophic Lateral Sclerosis↗
PubMed1994

Absence of recoverable infectious virus and unique immune responses in an asymptomatic HIV+ long-term survivor.

We have studied a woman with transfusion-acquired HIV who appears to have contained infectious virus to consistently undetectable levels over a 13-year period without antiviral treatment. She received the infected transfusion for intra- and postpartum blood loss immediately after delivery of her second child in 1981. She had no acute febrile syndrome and has never had HIV-associated clinical signs or symptoms in the 13 years since infection. She was first tested and found positive for HIV antibodies in 1985, and the infected blood donor was diagnosed with AIDS in 1986 and died of AIDS-related complications in 1989. Two other recipients of packed erythrocytes from this donor (in 1980 and 1982) also became infected and were subsequently diagnosed with AIDS. Between January 1986 and April 1994, in the setting of continuous and unambiguous Western blot HIV-specific antibodies and intermittently positive low-level HIV DNA signal after polymerase chain reaction (PCR) amplification, more than 30 separate cell cocultures performed in several independent laboratories failed to yield evidence of infectious virus, despite special efforts to induce and detect HIV replication. Immunologically, a strong in vitro proliferative response to HIV envelope proteins also distinguished this subject from other asymptomatic HIV+ individuals.

Adult↗
PubMed1994

Prevalence of HIV-1 DNA and p24 antigen in breast milk and correlation with maternal factors.

Breast milk specimens from human immunodeficiency virus type 1 (HIV-1)-seropositive and HIV-1-seronegative women were examined for the presence of HIV-1 p24 antigen by the antigen capture method and for viral DNA using the polymerase chain reaction. HIV-1 DNA was present in 70% of milk specimens collected from 47 HIV-seropositive women 0-4 days after delivery and in approximately 50% of specimens collected 6 and 12 months postpartum. p24 antigen, present in 24% of milk specimens collected from 37 seropositive women within the first 4 days postpartum, was not detected in any of the subsequent specimens. The presence of HIV-1 DNA or p24 antigen in milk was not significantly associated with maternal CD4 lymphocyte count, beta 2-microglobulin level, or fulfillment of the AIDS clinical case definition. Although the correlation of either HIV-1 proviral DNA or p24 antigen with the presence of infectious virus is not known, these data indicate the need for additional studies examining the role of breastfeeding in maternal-infant transmission of HIV-1.

Breast Feeding↗
PubMed1994

Expression of early and late activation markers on peripheral blood T lymphocytes does not reliably reflect immune events in transplanted hearts.

Monoclonal antibodies directed against early (receptors for interleukin-2 and transferrin [IL-2R, TfR]) and late (PTA1, alpha 1 integrin VLA-1) activation antigens were used as probes to monitor cardiac transplant patients for episodes of acute graft rejection. Age- and sex-matched patient control groups consisting of 11 patients awaiting cardiac transplantation and 13 kidney transplant recipients with long-term grafts, respectively, were used to define an upper limit for normal activation antigen expression (mean + 3 SD) in patients. Expression of all cell markers was significantly higher in both patient control groups than in healthy control individuals. Therefore, the level of activation marker expression in heart patients awaiting transplantation was used as comparison for the patient population under study. Sequential monitoring of 24 heart transplant recipients failed to demonstrate a significant correlation of increased activation marker expression with clinical events of immune activation. Subsequently 62 consecutive endomyocardial biopsy scores in 36 patients were compared with the expression of IL-2R, TfR and VLA-1 on peripheral blood T cells. Neither increased cellular infiltration of the endocardium, nor of the myocardium, was associated with increasing proportions of IL-2R, TfR, or VLA-1 positive T cells. Elevated T-cell expression of the three markers combined indicated acute graft rejection with a sensitivity, specificity, and overall accuracy of 38%, 52%, and 43%, respectively. Acute graft rejection in biopsies with associated myofiber damage (biopsy rejection scores 2 and 3A,B) was not associated with a change in the proportion of activated T cells in circulation within the first 6 months after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Patterns of sedation and analgesia in the postoperative ICU patient.

Control of pain, discomfort, and agitation is an integral part of the postoperative management of critically ill patients. We examined the sedative and analgesic practices in a surgical ICU during two six-month periods, one in 1986-1987 and the other in 1989-1990. Narcotics, especially morphine and Fentanyl, were the most commonly used drugs. The amount of Fentanyl received by the endotracheal patients in the 1986-1987 group was quite large, 5.5 +/- 4.3 (SD) mg/day. The use of midazolam during the second survey period was associated with a reduced dose of narcotics in artificially ventilated patients receiving continuous intravenous Fentanyl and morphine. The use of epidural Fentanyl, especially following thoracic surgery, was greatly increased during the second study period. More work is needed to assess the effects and effectiveness of ICU sedative and analgesic regimens.

Adult↗
PubMed1991

Diagnosis of Chlamydia trachomatis eye infection in Tanzania by polymerase chain reaction/enzyme immunoassay.

Detection of Chlamydia trachomatis eye infection is largely unsatisfactory by standard laboratory methods. A polymerase chain reaction/enzyme immunoassay (PCR-EIA) that had previously been successful for diagnosis of genital C trachomatis infection was compared with direct antibody immunofluorescence (DFA) for detection of the organism in conjunctival scrapes. 234 Tanzanian children aged 1-7 years living in a village that had had no previous trachoma control programme were classified clinically as having no sign of trachoma (0) n = 97, follicular trachoma (TF) n = 100, or intense inflammatory trachoma with or without TF (TI +/- TF) n = 37. PCR-EIA detected C trachomatis in 24%, 54%, and 95% of subjects, respectively, compared with elementary body (EB) detection by DFA of 1%, 28%, and 60%, respectively. Overall prevalence of chlamydial eye infection was 22% by DFA compared with 48% by PCR-EIA. Of subjects with chlamydial DNA at pretreatment, 103 (92%) had no detectable chlamydial DNA at the end of 4 weeks of ocular tetracycline. The findings show that PCR-EIA is likely to affect trachoma diagnosis and epidemiology because of the increased sensitivity for detection of C trachomatis in all clinical groups; the less stringent requirements for specimen collection and transport make this method suitable for field use. Moreover, the semi-quantitative aspect of PCR-EIA may be useful for monitoring a decrease in chlamydial DNA after treatment.

Administration, Topical↗
PubMed1991

Avian myeloblastosis virus reverse transcriptase. Effect of glycerol on its hydrodynamic properties.

Although reverse transcriptase has been the subject of intensive investigation, minimal information is available regarding the physical properties of the enzyme. The basic hydrodynamic properties of avian myeloblastosis virus reverse transcriptase in solution were measured by both sedimentation velocity and equilibrium measurements in two buffer systems. In a 0.3 M potassium phosphate buffer system, pH 7.8, the enzyme sedimented as a homogenous particle with a sedimentation coefficient of (7.1 +/- 0.3) S with a weight-average molecular weight, Mw, of (1.52 +/- 0.05) x 10(5). Since the enzyme consists of an alpha and beta subunit of equal molar ratio with Mw of 6.3 x 10(4) and 9.4 x 10(4), respectively, it was concluded that the enzyme exists as an alpha beta heterodimer in this buffer system. In a Tris buffer system, pH 7.9, containing 0.46 M NaCl and 4% glycerol, the native enzyme also sedimented as a homogeneous particle with an apparent sedimentation coefficient of (10.1 +/- 0.5) S, without considering the effect of glycerol on solvent-protein interaction. Based on the results of Gekko and Timasheff (Gekko, K., and Timasheff, S. N. (1981) Biochemistry 20, 4667-4676) and the polarity of the enzyme, it was estimated that there is significant solvent-protein interaction even at 4% glycerol leading to a value of -0.06 g/g in the preferential solvent interaction parameter. When the solvent effect was taken into consideration, the value for s020,w increased from 10.1 to 11.9 S, implying that the native enzyme dimerizes in the presence of 4% glycerol. The combined results of gel filtration and sedimentation velocity showed that the dimerization of the enzyme to form (alpha beta)2 is favored at 20 degrees C with the alpha beta form predominating at 4 degrees C. The secondary structure of the reverse transcriptase was measured by circular dichroism. Results showed that the enzyme consists of (16 +/- 2)% alpha-helix, (24 +/- 2)% beta-sheet, (24 +/- 2)% beta-turn, and (36 +/- 4)% undefined structures.

Avian Myeloblastosis Virus↗
PubMed1990

Frequency of indeterminate western blot tests in healthy adults at low risk for human immunodeficiency virus infection. The NIAID AIDS Vaccine Clinical Trails Network.

As part of a phase 1 trial of a candidate AIDS vaccine, blood specimens were collected from 168 healthy adult volunteers at minimal or no risk for becoming infected with human immunodeficiency virus type 1 (HIV-1). These specimens were screened for evidence of HIV-1 infection by enzyme immunoassay (EIA) and the Biotech/Du Pont Western blot (n = 168), culture (n = 122), and polymerase chain reaction assay (n = 20). None of the subjects had a positive test result by any of these assays, but 32% had indeterminate Western blot tests, most of which demonstrated a single band of low intensity. The most common bands were p24 (47%), p55 (34%), and p66 (36%); envelope bands were unusual (gp41, 2%; gp120, 2%). No serum specimen collected after 2-11 months from individuals with indeterminate Western blot results was positive by EIA or Western blot. There was 91% agreement in the test results of the first and second serum samples when the same lot of Western blot kit was used but only 36% agreement when different lots were used. The Biotech/Du Pont Western blot kit thus frequently yields indeterminate test results in the absence of HIV-1 infection, the reproducibility of which is subject to lot-to-lot variability.

Adult↗
PubMed1990

Diagnosis of Chlamydia trachomatis cervical infection by detection of amplified DNA with an enzyme immunoassay.

A sensitive and specific system for detection of amplified Chlamydia trachomatis DNA from cervical specimens by fluorometric quantitation in an enzyme immunoassay (EIA) format (polymerase chain reaction [PCR]-EIA) is described. The primers selected for PCR-amplified DNA were from the 15 serovars of C. trachomatis and two strains of Chlamydia pneumoniae (TWAR). One strain of Chlamydia psittaci (Borg) was not amplified. One hundred four previously cultured cervical specimens were evaluated. Forty-six culture-positive specimens containing from 1+ to 4+ inclusion bodies were all positive by PCR-EIA. Of 58 culture-negative specimens, 2 were repeatedly positive and were nonreactive with control probes. This assay system represents a sensitive and specific combination of technologies for the quantitative detection of C. trachomatis DNA directly from a body fluid.

Base Sequence↗