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Biomedical subjects

J M Burns

Publications and source records attributed to J M Burns.

At least 19 recordsLinked to original sources
PubMed1994

Denver Potable Water Reuse Demonstration Project: comprehensive chronic rat study.

The health effects testing program for the Denver Water Department's Potable Water Reuse Demonstration Project was designed to evaluate the relative health effects of highly treated reclaimed water derived from secondary wastewater in comparison with Denver's present high-quality drinking water. The 1 x 10(6) gal/day treatment plant provided 500-fold concentrates of water that had been treated by multiple processes to remove microbial and chemical contaminants. Fischer 344 rats were exposed to the complex mixture solutions for up to 2 yr to evaluate chronic toxicity and oncogenicity effects. The following parameters were evaluated: clinical observations, survival rate, growth, food and water consumption, haematology, clinical chemistry, urinalysis, organ weights, gross autopsy and histopathological examination of all lesions, major tissues and organs. Clinical pathology, gross pathology, and microscopic pathology conducted at wk 26 and 65 and at the end of the study did not reveal any findings that could be considered to be treatment related. Administration of drinking water concentrates at up to 500 times the original concentration in the original water samples to F344 rats for up to 104 wk did not result in any overt toxicological or carcinogenic effects.

Animals↗
PubMed1994

Antigens shared by Leishmania species and Trypanosoma cruzi: immunological comparison of the acidic ribosomal P0 proteins.

Patients with visceral leishmaniasis produce high levels of immunoglobulin, but the specificities of antibodies produced are not well characterized. In an effort to identify leishmania antigens that are specific to Leishmania species or are cross-reactive with other parasitic protozoa, we have cloned and characterized full-length genomic and cDNA clones encoding a Leishmania chagasi acidic ribosomal antigen, LcP0, recognized during human infections. The protein is homologous to the Trypanosoma cruzi and human ribosomal proteins TcP0 and HuP0, respectively. Unlike most higher eukaryotes, but similar to TcP0, LcP0 has a C-terminal heptapeptide sequence resembling those of the archaebacterial acidic (P-like) proteins. The highly charged C-terminal acidic domain of LcP0 contains a serine residue typically found in most eukaryotes but lacking in all T. cruzi P proteins we have characterized thus far. L. chagasi-infected individuals as well as those with T. cruzi infections have antibodies cross-reactive with recombinant LcP0 and TcP0 as well as HuP0. However, the properties of anti-P0 antibodies in T. cruzi and L. chagasi infection sera are quite different. Through the use of synthetic peptides, we showed that while T. cruzi infection anti-TcP0 antibodies are exclusively directed against the C-terminal domain of TcP0, L. chagasi infection sera contain antibodies reactive with epitopes other than the C-terminal sequence of LcP0. Thus, anti-LcP0 antibodies in L. chagasi infection sera represent the first characterized deviation from the restricted immunodominant C-terminal epitope involved in the generation of anti-P0 antibodies following infection or autoimmune diseases.

Amino Acid Sequence↗
PubMed1994

Serodiagnosis of Chagas' disease by enzyme-linked immunosorbent assay using two synthetic peptides as antigens.

An enzyme-linked immunosorbent assay (ELISA) was developed for detecting antibodies against Trypanosoma cruzi. Two synthetic T. cruzi peptides, TcD and PEP2, were used. The specificity and sensitivity of the peptide ELISA were determined with 260 serum samples from individuals living in an area in which Chagas' disease is endemic. ELISAs were performed with the peptides singly or in combination. The evaluation of these tests showed that 168 (93.8%) of 179 serum samples from T. cruzi-infected patients were positive when TcD peptide was used as antigen; 164 (91.6%) samples were positive with PEP2, and 178 (99.4%) samples were positive when the two peptides were combined. Thus, the sensitivity of the ELISA using the two peptides exceeded 99%. The specificity was evaluated by using a panel of 118 serum samples that included samples from 81 individuals living in an area of endemicity with negative serology for Chagas' disease and from 37 patients from areas in which T. cruzi was not endemic but with other pathologies, such as leishmaniasis, tuberculosis, and leprosy. Only two false-positive serum samples were found in this group of individuals, giving a test specificity of more than 98%. Because these peptides can be synthesized and are very stable at room temperature, the use of such reagents can improve the standardization and reproducibility of ELISAs for the serodiagnosis of T. cruzi infection.

Amino Acid Sequence↗
PubMed1993

Antibody responses of visceral leishmaniasis patients to gp63, a major surface glycoprotein of Leishmania species.

A major surface glycoprotein of Leishmania parasites, gp63, is highly conserved among species and is expressed in both infective and intracellular stages. Although much is known about its role in entry and survival in host macrophages, patient antibody responses to this glycoprotein have not been well characterized. The prevalence of anti-gp63 antibody in sera of leishmaniasis patients was evaluated by ELISA. Sera from most acute visceral leishmaniasis patients (84%) from Brazil and Sudan had notably high levels of antibody to recombinant (r) gp63. Sera from other forms of leishmaniasis and from other diseases did not contain significantly elevated levels of anti-gp63 antibody. These results indicate that rgp63 might be a useful constituent of a defined serologic test for visceral leishmaniasis.

Animals↗
PubMed1992

Identification and synthesis of a major conserved antigenic epitope of Trypanosoma cruzi.

A gene sequence encoding an immunodominant protein with a repetitive epitope from the protozoan Trypanosoma cruzi, the causative agent of Chagas disease, was cloned and expressed. The identified 10-amino acid repeat is present within a high-molecular-weight trypomastigote antigen that appears specific to and conserved among T. cruzi isolates. More importantly, greater than 95% of T. cruzi infection sera, including both chronic and acute Chagas disease, contained elevated levels of antibody to a 15-amino acid synthetic peptide bearing the repetitive B-cell epitope. Considering the wide diversity of T. cruzi parasites, as well as the broad spectrum of clinical manifestations of Chagas disease, such a prevalent immune response among patients is significant and applicable to the control of Chagas disease through the diagnosis of T. cruzi infection.

Amino Acid Sequence↗
PubMed1992

Stimulation of human T lymphocytes by Leishmania lipophosphoglycan-associated proteins.

Lipophosphoglycan (LPG) is a glycoconjugate present on the surface of Leishmania promastigotes that has been reported to promote intracellular survival of these parasites, to protect mice against leishmaniasis, and to elicit T cell responses in infected mice and humans. We investigated whether LPG and its components could elicit proliferative responses and cytokine secretion from leishmaniasis patient PBMC. LPG prepared by standard methods (LPG-1) stimulated patients T cells to proliferate and secrete IFN-gamma. LPG was fractionated into several components. An LPG-1-specific T cell line was shown to respond to the core region but not to the repeating saccharide units. LPG-1 was fractionated to yield an LPG-free- associated protein complex and an LPG-2 fraction that was more than 95% depleted of associated protein. The ability of LPG-2 to stimulate T cells was significantly decreased over that of LPG-1. In contrast, LPG-AP stimulated T cell proliferation and IFN-gamma production. Therefore, proteins associated with LPG were effective in eliciting patient T cell responses, whereas the glycolipid enriched moiety was weakly effective or ineffective at stimulating these responses.

Animals↗
PubMed1992

Elderly patients and their medication: a post-discharge follow-up study.

Fifty-six elderly patients (age range 65-98 years) discharged from a geriatric unit were visited at home on or after the 5th post-discharge day (median day 8) and their medication assessed. By the day of the visit, 15 of the 56 had not had a new prescription issued (27%) and 27 patients (48%) had old prescribed medication at home. Forty-one new scripts, issued by general practitioners, should have contained 128 medications if the general practitioners wished to continue unchanged the medication given on hospital discharge. Fourteen drugs (11%) had been added and 17 drugs (13%) omitted. The number of prescriptions issued unchanged was 26/41 (63%). Inaccurately labelled containers and/or changed drug names were found in 28%. Contrary to hospital advice, 47% of medications were issued in childproof containers. Poor communication between hospital and general practitioners is only part of the problem. Methods to expedite the delivery of new prescriptions should be developed.

Aged↗
PubMed1992

Monitoring of streptokinase resistance titre in acute myocardial infarction patients up to 30 months after giving streptokinase or anistreplase and related studies to measure specific antistreptokinase IgG.

OBJECTIVE: To examine the induction of antistreptokinase antibodies after giving streptokinase or anistreplase to patients with acute myocardial infarction. DESIGN: Patients were randomly allocated to receive either 1.5 x 10(6) IU, streptokinase or 30U anistreplase in a double blind study. Blood samples were collected immediately before treatment and subsequently at intervals up to 30 months; plasma samples were assayed for streptokinase resistance titre (functional assay) and streptokinase binding by IgG (microradioimmunoassay). SETTING: Cardiology department in a general hospital. PATIENTS: 128 consecutive eligible patients. Samples were collected for up to one year according to a prospective design: a subsection of 47 patients was selected for intensive study over the first 14 days. After one year, all available patients (67) were sampled on one further occasion. RESULTS: Antibody responses to streptokinase and anistreplase were similar. Streptokinase resistance titres exceeded pretreatment concentrations five days after dosing, and values peaked at 14 days. By 12 months after dosing, 92% of resistance titres (n = 84) had returned to within the pretreatment range. Antistreptokinase IgG concentrations also exceeded baseline concentrations within five days and peaked at 14 days. Half of the individual values had returned to within the pretreatment range by 12 months (n = 84) and 89% by 30 months (n = 18). CONCLUSION: Although we cannot be sure of the clinical significance, because of the increased likelihood of resistance due to antistreptokinase antibody, streptokinase and anistreplase may not be effective if administered more than five days after an earlier dose of streptokinase or anistreplase, particularly between five days and 12 months, and increased antistreptokinase antibody may increase the risk of allergic-type reactions.

Adult↗
PubMed1992

The roles of general and geriatric medicine in the provision of acute medical care for elderly patients.

To determine whether there are differences between elderly patients admitted acutely to general medicine and those admitted to geriatric medical wards, and whether the patients are appropriately referred, a prospective survey of 426 consecutive patients aged 65 years or over admitted acutely to general medical and geriatric wards over a three month period was performed. A total of 286 patients were admitted to general medicine (GM) and 140 to the geriatric unit (GER). GER patients were older (81.0 v. 75.8 years) and had greater pre-morbid functional impairment and incontinence. Fewer GER patients presented with readily apparent organ specific diagnoses (56% v. 94%). Median length of stay was longer in GER patients (23 days v. 9 days). Variables independently predictive of GER admission were increasing age, increasing duration of illness, poor pre-morbid functional status and prior reliance on a carer. Length of stay was not associated with unit of admission allowing for the variables described above. GER patients are a different population. They have more chronic illness and functional impairment, and are more likely to require multidisciplinary assessment and rehabilitation in addition to treatment of presenting illness. Elderly patients are appropriately referred by General Practitioners (GPs) without a formal admissions policy.

Aged↗
PubMed1991

Human T cell responses to gp63, a surface antigen of Leishmania.

gp63, an abundant and conserved leishmania cell surface protein, has been implicated in the ability of these parasitic protozoa to infect macrophages in vitro and has shown potential as a protective immunogen in mice. However, little is known regarding human immune responses to this glycoprotein Ag. In this study, human T lymphocyte responses to Leishmania amazonensis native gp63 and to recombinant gp63 (rgp63) produced in Escherichia coli were evaluated in individuals with active or cured cutaneous, mucosal or visceral leishmaniasis. Both native and rgp63 elicited strong proliferative responses in all patients tested. In addition, IFN-gamma was produced in response to stimulation with both forms of the protein. T cell lines generated from PBMC by stimulation with native or rgp63 were phenotypically similar, and proliferated and produced IFN-gamma in response to stimulation with both forms of the molecule. These results suggest that gp63 is a strong T cell immunogen and that the recombinant and native forms can elicit the same type of T cell response from infected patients. In order to compare the immunogenic properties of these two forms of gp63, PBMC from naive (uninfected) donors were sensitized in vitro with native or rgp63. T cell lines generated against rgp63 proliferated in response to rgp63, but failed to proliferate in response to native gp63 or to promastigote lysate. Thus, rgp63 was effective in eliciting T cell responses from patients with active or cured leishmania infection, but did not effectively induce T cell responses under the conditions used.

Animals↗
PubMed1991

Characterization of a membrane antigen of Leishmania amazonensis that stimulates human immune responses.

To investigate human immune responses to defined leishmania Ag we have begun to characterize biochemically and immunologically, an abundant 42-kDa surface Ag of Leishmania amazonensis, a causative agent of human leishmaniasis. We have shown that this Ag, La gp42, is expressed on the surface of L. amazonensis promastigotes, being anchored to the membrane by a glycosyl-phosphatidylinositol moiety. As demonstrated by lectin blotting studies, La gp42 is glycosylated, binding both Con A and wheat germ agglutinin. Immunologically, La gp42 is strongly recognized by sera from patients with different forms of leishmaniasis as well as by patients with Chagas' disease. In addition, we show that purified La gp42 stimulates the proliferation of human T lymphocytes obtained from several leishmaniasis patients. Finally, the N-terminal sequence of La gp42 was obtained and a serologically cross-reactive 42-kDa protein with a homologous sequence was identified in Leishmania major.

Amino Acid Sequence↗
PubMed1991

Left ventricular hypertrophy in hypertension.

Major advances in left ventricular hypertrophy (LVH) and hypertension have occurred in recent years. The ability to diagnose LVH has been improved by echocardiography, and with this technique it has been shown that evidence of LVH is an important independent risk factor for cardiovascular disease. The major cause of death in patients with hypertension and LVH is coronary artery disease. Therefore an understanding of the interrelationships between these two disorders is fundamental, and it is now clear that the hypertrophied ventricle is vulnerable to myocardial ischemia. Appreciation of the mechanisms of sudden death has also increased, although the exact situation in patients with LVH remains to be clarified. Regression of LVH is known to occur with the use of several different antihypertensive drugs. Recent studies indicate that the calcium blocking agent nicardipine, in addition to beta-blocking drugs and angiotensin-converting enzyme inhibitors, brings about LVH regression without any deterioration of left ventricular function. However, further studies are needed to assess the long-term benefits of this regression.

Calcium Channel Blockers↗
PubMed1991

A comparison of the pharmacokinetic properties of streptokinase and anistreplase in acute myocardial infarction.

1. The pharmacokinetics of streptokinase (SK) and anistreplase in conventional dosage regimens of 1.5 x 10(6) i.u. of SK infused over 60 min and 30 units of anistreplase over 5 min were studied in 24 consecutive patients presenting with acute myocardial infarction, using a functional bioassay to assess concentrations. 2. The two agents were found to have similar volumes of distribution (5.68 and 5.90 l), but SK was cleared significantly more rapidly than anistreplase, resulting in a shorter terminal phase half-life (0.61 vs 1.16 h) and a shorter mean residence time (0.76 vs 1.55 h).

Aged↗
PubMed1991

Doppler echocardiography in elderly patients with ejection systolic murmurs.

Thirty-nine elderly patients, mean age 77 years (range 65 to 96), with ejection systolic murmurs were studied to evaluate the functional significance of these murmurs. Subjects were evaluated clinically, by 2-D echocardiography, and by a full Doppler echocardiography study. Good quality Doppler signals were obtained in 35 subjects. Mitral regurgitation was found to be the only significant valvular lesion in 6 patients (17%). Doppler gradients in systole across the aortic valve were less than 30 mmHg in 28 subjects (80%) and were considered not significant. Gradients of greater than 30 mmHg representing significant aortic stenosis were found in 7 subjects (20%). The clinical sensitivity in detecting significant aortic stenosis was 44% and specificity was 81%. Doppler evidence of significant aortic stenosis was found in a substantial proportion of these elderly subjects. Neither clinical assessment nor 2-D echocardiography can be relied on to exclude this condition.

Aged↗
PubMed1990

Angiographic patency study of anistreplase versus streptokinase in acute myocardial infarction.

128 patients with acute myocardial infarction of duration 6 h or less were randomised in double-blind fashion to receive 30 U anistreplase over 5 min or 1.5 MU streptokinase over 1 h, both intravenously. Angiographic patency was assessed 90 min and 24 h from the start of therapy. 55% of patients who received anistreplase and 53% of patients who received streptokinase had patent infarct-related arteries (TIMI grade 2-3) at 90 min (95% CI 42-68% and 40-66%, respectively). At 24 h 81% and 87.5% of arteries were patent respectively (95% CI, 71-91% and 83.5-91.5%). Time to therapy had no significant effect on patency rates. There was one early reocclusion within 24 h in each treatment group and clinical evidence of reocclusion was recorded between 24 h and hospital discharge in a further 5 patients (streptokinase 3, anistreplase 2). With these regimens, therefore, anistreplase and streptokinase gave the same patency rates.

Adult↗
PubMed1990

Colour Doppler flow mapping in the diagnosis of traumatic ventricular septal defect.

The use of colour Doppler flow mapping allows noninvasive diagnosis and gives haemodynamic information on the severity of ventricular septal defects. We describe the case of a man with delayed presentation of a traumatic ventricular septal defect in whom colour Doppler flow mapping permitted conservative management after accurate noninvasive diagnosis.

Adult↗