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Biomedical subjects

L Evans

Publications and source records attributed to L Evans.

At least 19 recordsLinked to original sources
PubMed1992

Long-term symptomless HIV-1 infection in recipients of blood products from a single donor.

There have been reported cases of long-term symptomless human immunodeficiency virus type 1 (HIV-1) infection, but it is not clear whether the benign course of infection was due to host, viral, or other unknown factors. During follow-up of subjects with transfusion-acquired HIV-1 infection in New South Wales, Australia, we identified a group of 6 subjects who had been infected through a single common donor. We were therefore able to study the contributions of various factors to the course of infection. Throughout follow-up (range 6.8-10.1 years after infection), 5 of the recipients and the donor (last follow-up 10.2 years after infection of the first recipient) remained clinically free of symptoms, with normal CD4 cell counts and no p24 antigenaemia. HIV-1 was isolated from only 1 recipient; the isolate did not induce syncytia in a SUPT1 co-culture assay and had a limited in-vitro host range. 1 infected recipient (who had received extensive immunosuppressive treatment for systemic lupus erythematosus) developed Pneumocystis carinii pneumonia and died 4.3 years after infection. The frequency of progression to AIDS or a CD4 cell count below 0.50 x 10(9)/l was significantly lower among the 6 subjects with a common donor (1/6) than among 101 other HIV-infected transfusion recipients for whom data from 7 years of follow-up were available (94/101; p less than 0.0001). These findings suggest that the subjects were infected by a less virulent strain of HIV-1. The identification of this group of subjects should stimulate a search for other similar groups, which will provide important information on the immunopathogenesis of HIV-1 disease.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Modified nucleosides in human serum.

Methylated purines and pyrimidines derived from the degradation of transfer ribonucleic acid have been shown to be excreted in abnormal amounts in the urine of patients with cancer. Recent technology developed by Gehrke and Kuo has allowed the separation and quantification of modified nucleosides in serum using reversed-phase high-performance liquid chromatography with diode-array measurement. Serum levels of ten modified nucleosides were measured in 37 normal healthy adults to establish normal values and to correlate activity with age and sex. In addition, serum levels of patients with several malignancies were measured to determine activity in these diseases. Levels of modified nucleosides in normal individuals were consistently reproducible and showed no significant variation among males versus females or with age. Patients with malignant diseases showed consistent elevations and these were highest in patients with more advanced disease. The evidence of no significant differences in the mean levels of modified nucleosides in serum with age or sex in normal adults and elevations in patients with malignancies demonstrate the potential value of modified nucleosides as cancer biomarkers.

Adult↗
PubMed1992

Expression of B-type Epstein-Barr virus in HIV-infected patients and cardiac transplant recipients.

In the present study, peripheral blood mononuclear cells (PBMCs) were obtained from HIV+ subjects as well as cardiac transplant recipients, and the presence of A- and B-type Epstein-Barr virus (EBV) was determined using the polymerase chain reaction (PCR). Of the HIV+ patients studied, 24% were found to be infected with A-type EBV, 27% with B-type EBV, and 39% with both A and B virus types. Analysis of PBMCs from cardiac transplant recipients revealed that 39% were infected with A-type EBV, 33% with B-type EBV, and 28% with both EBV types. These results demonstrate a higher prevalence of infection with B-type EBV in HIV+ patients, than had been found previously by an analysis of spontaneously generated lymphoblastoid cell lines. The data indicated that it is not HIV per se which is responsible for the high incidence of B-type EBV in HIV+ individuals.

Australia↗
PubMed1992

Identification of HIV-1 in semen following primary HIV-1 infection.

OBJECTIVE: To determine whether HIV could be identified in semen samples during the first few weeks after infection. DESIGN: A series of three homosexual men with symptomatic primary HIV-1 infection. METHODS: Each subject provided a series of semen samples that was examined for HIV-1 by virus culture, polymerase chain reaction (PCR) and transmission electron micrography. RESULTS: The first samples obtained for each subject (17, 22 and 24 days following onset of primary HIV-1 infection) were all positive by PCR and negative by viral culture. Of 13 samples obtained during the first 80 days after onset of primary HIV-1 infection and analysed by PCR, 10 were positive. Only one of these samples was virus culture-positive. Four semen samples obtained from two subjects during treatment with zidovudine were PCR-positive. Eight samples were examined for presence of HIV-1 by electron microscopy and one was found to be positive. CONCLUSIONS: These results indicate that men with HIV-1 infection are potentially infectious through sexual transmission during the first few weeks after infection. The findings emphasize that individuals in all stages of HIV-1 infection should practise safer sex to reduce transmission of HIV-1.

Adult↗
PubMed1992

The latent structure of anxiety symptoms in anxiety disorders.

OBJECTIVE: Research in the psychopathology of panic and anxiety disorders, particularly agoraphobia, suggests that fear of fear may be the basis of these conditions. However, there is little empirical research on the definition and validity of the concept of fear of fear in a clinical study group. The authors' aims are 1) to determine empirically if particular associations between symptoms and beliefs exist in a group of patients with anxiety disorders and what underlying dimensions of perceived threat they represent and 2) to assess the relative importance of these associations in agoraphobia with panic attacks, panic disorder, social phobia, and generalized anxiety disorder. METHOD: In an anxiety disorders treatment unit, 390 outpatients with anxiety disorders diagnosed according to DSM-III criteria completed the Anxiety Symptoms and Beliefs Scale. RESULTS: A principal components analysis of the patients' ratings on the Anxiety Symptoms and Beliefs Scale produced a four-factor solution in which specific sets of anxiety symptoms loaded with specific beliefs. These four factors were interpreted as respiratory symptoms, vestibular symptoms, autonomic arousal, and psychological threat. Respiratory and vestibular symptoms were more associated with panic disorder diagnoses than with social phobia and generalized anxiety disorder diagnoses. CONCLUSIONS: These findings support a conception of fear of fear in anxiety disorders as fearful beliefs concerning the experience of anxiety symptoms. Associations between symptoms and fear of fear are present across anxiety disorders but are most pronounced in agoraphobia with panic attacks.

Adult↗
PubMed1992

Car size or car mass: which has greater influence on fatality risk?

OBJECTIVES: Proposed increases in corporate average fuel economy standards would probably lead to lighter cars. Well-established relationships between occupant risk and car mass predict consequent additional casualties. However, if size, not mass, is the causative factor in these relationships, then decreasing car mass need not increase risk. This study examines whether mass or size is the causative factor. METHODS: Data from the Fatal Accident Reporting System are used to explore relationships between car mass, car size (as represented by wheelbase), and driver fatality risk in two-car crashes. RESULTS: When cars of identical (or similar) wheelbase but different mass crash into each other, driver fatality risk depends strongly on mass; the relationship is quantitatively similar to that found in studies that ignore wheelbase. On the other hand, when cars of similar mass but different wheelbase crash into each other, the data reveal no dependence of driver fatality risk on wheelbase. CONCLUSIONS: Mass is the dominant causative factor in relationships between driver risk and car size in two-car crashes, with size, as such, playing at most a secondary role. Reducing car mass increases occupant risk.

Accidents, Traffic↗
PubMed1992

An Australian multicentre study of moclobemide versus amitriptyline in the treatment of depression.

This paper reports the results of a multicentre study of the new monoamine oxidase inhibitor, moclobemide, in the treatment of major depression. Moclobemide is a specific monoamine oxidase-A inhibitor which does not bind irreversibly to the enzyme, unlike the currently available MAOIs. Recent studies would suggest that in subjects taking moclobemide blood pressure elevation caused by tyramine is significantly less than that induced by the irreversible MAOIs, particularly when tyramine is administered in an oral form. Forty-eight patients with major depression were randomly allocated to treatment with either moclobemide or amitriptyline for 4 weeks in a double-blind comparison. There were no statistically significant differences between the two groups on measures of efficacy. Patients taking amitriptyline reported a greater number of side-effects and more patients in the amitriptyline group dropped out because of these. There were no reports of interactions with tyramine-containing foods.

Adult↗
PubMed1991

A phase II study alternating alpha-2a-interferon and gamma-interferon therapy in patients with chronic myelogenous leukemia.

Patients with Philadelphia chromosome-positive chronic myelogenous leukemia (CML) were treated with a combination of alpha-interferon and gamma-interferon. Recombinant alpha-2a-interferon (Roferon-A, Hoffmann-LaRoche, Inc., Nutley, NJ) and recombinant gamma-interferon (Genentech, Inc., South San Francisco, CA) were administered on alternating weeks each at doses ranging from 2 to 10 MU/m2 given intramuscularly. Of the 27 patients, 11 (41%) achieved complete hematologic remission (CHR) and 3 (11%) achieved partial hematologic remission (PHR). Responses were seen among 9 of 22 (41%) patients treated during the chronic phase of the disease and in 2 of 5 (40%) patients treated during the accelerated phase/second chronic phase. Cytogenetic responses were seen in six patients, including one complete response and five minor responses. Toxicities included flu-like symptoms, which appeared to be more severe with gamma-interferon than with alpha-interferon, hypertriglyceridemia, and thrombocytopenia. In this limited study, an improved outcome was not observed for the combination regimen compared with alpha-interferon alone.

Adolescent↗
PubMed1991

Gamma-tubulin is a highly conserved component of the centrosome.

We have cloned and characterized gamma-tubulin genes from both X. laevis and S. pombe, and partial genes from maize, diatom, and a budding yeast. The proteins encoded by these genes are very similar to each other and to the original Aspergillus protein, indicating that gamma-tubulins are an ubiquitous and highly conserved subfamily of the tubulin family. A null mutation of the S. pombe gene is lethal. gamma-tubulin is a minor protein, present at less than 1% the level of alpha- and beta-tubulin, and is limited to the centrosome. In particular, gamma-tubulin is associated with the pericentriolar material, the microtubule-nucleating material of the centrosome. gamma-Tubulin remains associated with the centrosome when microtubules are depolymerized, suggesting that it is an integral component that might play a role in microtubule organization.

Amino Acid Sequence↗
PubMed1991

Airbag effectiveness in preventing fatalities predicted according to type of crash, driver age, and blood alcohol concentration.

The effectiveness of airbags was estimated in a recent paper by assuming that they do not affect ejection probability and protect only in frontal and near-frontal crashes; the impact-reducing effectiveness in such crashes was assumed equal to that of lap/shoulder belts. The effectiveness, estimated as 18%, thus depends on the distribution of crashes by direction of impact and the incidence of ejection. Ejection rates and impact directions are markedly different for single-car as compared to two-car crashes and as a function of driver age and alcohol use. This raises the possibility that the overall effectiveness estimates might reflect an average of higher effectiveness for drivers more likely to be responsible for crashes (youths, drunks, those involved in single-car crashes) and a lower effectiveness for those less likely to be responsible (non-youths, the sober, and those involved in two-car crashes). By using FARS data for 1975-1986 to distribute fatal crashes by impact direction under various conditions, airbag effectiveness was calculated under these same conditions. Although substantial dependencies on impact direction were found, the fraction of all fatalities that were frontals remained surprisingly constant. It is concluded that effectiveness does not depend much on driver age or alcohol consumption, but is greater for two-car crashes than for single-car crashes (21% compared to 16%).

Accidents, Traffic↗
PubMed1991

Microtubule behavior during guidance of pioneer neuron growth cones in situ.

The growth of an axon toward its target results from the reorganization of the cytoskeleton in response to environmental guidance cues. Recently developed imaging technology makes it possible to address the effect of such cues on the neural cytoskeleton directly. Although high resolution studies can be carried out on neurons in vitro, these circumstances do not recreate the complexity of the natural environment. We report here on the arrangement and dynamics of microtubules in live neurons pathfinding in response to natural guidance cues in situ using the embryonic grasshopper limb fillet preparation. A rich microtubule network was present within the body of the growth cone and normally extended into the distal growth cone margin. Complex microtubule loops often formed transiently within the growth cone. Branches both with and without microtubules were regularly observed. Microtubules did not extend into filopodia. During growth cone steering events in response to identified guidance cues, microtubule behaviour could be monitored. In turns towards guidepost cells, microtubules selectively invaded branches derived from filopodia that had contacted the guidepost cell. At limb segment boundaries, microtubules displayed a variety of behaviors, including selective branch invasion, and also invasion of multiple branches followed by selective retention in branches oriented in the correct direction. Microtubule invasion of multiple branches also was seen in growth cones migrating on intrasegmental epithelium. Both selective invasion and selective retention generate asymmetrical microtubule arrangements within the growth cone, and may play a key role in growth cone steering events.

Animals↗
PubMed1991

Reduction of cat eye movements using retrobulbar botulinum toxin.

We studied the effects of a single retrobulbar injection of Botulinum toxin on the motility of cat eyes. Four cats were sedated and the opposite eye served as a control. Eye movements were plotted by reflecting a laser beam from a mirror fixed to the cornea. We found the mean degrees of deviation per eye per day and summarized these results as mean degrees of deviation per eye per week +/- standard deviation. Statistical analysis was accomplished using Student's t test for independent measures, since measurement of the treated eye pairs was done in a randomized manner on different test days. (table; see text) These results indicate that a single retrobulbar dose of Botulinum toxin can produce a paralysis of the ocular musculature lasting in excess of four weeks in a specific and reproducible manner. In addition, this methodology should prove useful in future experiments in which ocular motility might prove to be a technical concern.

Animals↗
PubMed1991

GM-CSF as an alternative to dose modification of the combination zidovudine and interferon-alpha in the treatment of AIDS-associated Kaposi's sarcoma.

Combined zidovudine (ZDV) and interferon-alpha (IFN) is an appealing therapy for AIDS-associated Kaposi's sarcoma because of the antiretroviral as well as antitumor potential of this combination. Overlapping myelotoxicity of these agents, however, frequently complicates their clinical use. This phase I/II study was undertaken to test the safety and efficacy of granulocyte-macrophage colony stimulating factor (GM-CSF) in those patients who became neutropenic while receiving ZDV (1,200 mg/day) and IFN (9 MU/day). Despite a "high-risk" population of patients, the tumor response rate among evaluable patients was 50% (33% overall). Sixty-four percent of patients required GM-CSF and all patients receiving GM-CSF had a prompt improvement in their absolute neutrophil count (ANC). The use of GM-CSF was associated with an improved end of study ANC (p less than 0.05), but was not associated with tumor response, CD4 count improvement, or improved change in hemoglobin concentration. GM-CSF/ZDV/IFN was not associated with increased toxicity over ZDV/IFN; however, two unusual events occurred in the GM-CSF/ZDV/IFN group: erythema multiforme and glucose intolerance. Dose-limiting thrombocytopenia and anemia were seen in two patients and anemia in one patient on GM-CSF/ZDV/IFN. No consistent alterations in serum HIV p24 antigenemia were noted in either group. The use of GM-CSF mitigated the neutropenia of combined ZDV and IFN. Further study evaluating the utility of this hematopoietic growth factor in combination therapies for AIDS patients is warranted.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Issues in gynecologic radiation oncology.

Radiation therapy has a number of established roles in the curative, adjuvant, and palliative management of gynecologic malignancies. Specific indications for use of radiation therapy, concepts of integration of radiation therapy with other modalities, and techniques of radiation therapy, however, continue to evolve. Rather than discuss the use of radiation therapy in specific diseases, this paper reviews recent studies dealing with current issues in gynecologic radiation oncology.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Zidovudine in the management of primary HIV-1 infection.

Eleven subjects who presented with a clinical illness characteristic of primary HIV-1 infection were treated with 1 g zidovudine daily for a median period of 56 days (range, 28-111 days). Primary HIV-1 infection was confirmed in each subject by seroconversion and virus isolation. The acute phase of the illness resolved a median of 4 days (range, 3-14 days) from commencement of zidovudine. Six subjects reported symptoms that may have been side-effects of zidovudine, the most common being nausea in four subjects and headache in two. Treatment was discontinued in one subject who had persistent headache and nausea. Haemoglobin, haematocrit and erythrocyte counts decreased and mean corpuscular volume increased significantly during the treatment. None of the subjects developed anaemia and none required dose modification or blood transfusion as a result of haematological side-effects. There were no significant differences in the granulocyte count or the lymphocyte count during any week of treatment when compared with baseline levels. There were no significant differences in T-cell subset numbers of the subjects during treatment compared with a group of historical controls. HIV-1 was isolated from several subjects during and after termination of zidovudine treatment. The results of this investigation indicate that zidovudine is a safe drug to administer to people with primary HIV-1 infection. There was no clear evidence, however, of any clinical benefit in terms of resolution of the acute illness and no indication that the treatment would prevent development of persistent infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1991

Granulocyte-macrophage colony-stimulating factor mitigates the neutropenia of combined interferon alfa and zidovudine treatment of acquired immune deficiency syndrome-associated Kaposi's sarcoma.

The combined use of zidovudine (ZDV) and interferon (IFN) alfa-2a has been shown to have antiretroviral and antitumor potential benefit in the treatment of acquired immune deficiency syndrome (AIDS)-associated Kaposi's sarcoma (KS). However, the clinical use of this combination is frequently complicated by the overlapping myelotoxicity of these agents. We report here the results of a phase I/II study in which granulocyte-macrophage colony-stimulating factor (GM-CSF) was used for those KS patients who became neutropenic while receiving ZDV (1,200 mg/d) and IFN (9 x 10(6) U/d). Nineteen of 29 patients (66%) developed an absolute neutrophil count (ANC) of less than 1,000 cells per cubic millimeter and were begun on GM-CSF. All experienced a prompt increase in the ANC. Those patients receiving GM-CSF/ZDV/IFN alfa-2a had an improved end of study ANC when compared with the ZDV/IFN alfa-2a group, but did not have an increased rate of tumor response, end of study CD4 cell count, or improvement in any other hematologic variable. The use of GM-CSF was not associated with increased toxicity and, in particular, was not associated with a change in serum human immunodeficiency virus (HIV) p24 antigen. Tumor response was noted in 50% of the assessable patients (33% overall) despite "high-risk" characteristics in 80%. Of the responding patients, seven were on GM-CSF and might have otherwise required an alteration in ZDV/IFN alfa-2a dose level. Further study of GM-CSF as an alternate to dose modification of this (ZDV/IFN alfa-2a) and other combination therapies for AIDS patients is warranted.

Acquired Immunodeficiency Syndrome↗