Biomedical subjects
Publications and source records attributed to M Doyle.
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The prevalence of human immunodeficiency virus (HIV) risk factors was evaluated by questionnaire survey in 1565 consecutive patients who attended an adult A&E department in Brisbane over a 2-month period. The survey revealed that a total of 144 (9.2%) patients could be considered at risk of HIV infection (high-risk group) because of known seropositivity, admission to HIV high-risk factors or engaging in high-risk activities. The remaining 1421 patients who did not acknowledge any high-risk behaviour were classified as an 'unknown-risk' group. More than 70% of the HIV high-risk patient group were under the age of 30 years. A total of 275 (17.6%) patients presented with open wounds and/or needed hospitalization (23 [1.5%] high-risk patients). Of the 490 respondents who engaged in short term sexual relationships, 310 (63.3%) practised unprotected coitus, 32 of these including four seropositives were classified in the high-risk group. The patients were asked if they were in favour of an HIV testing service at their local A&E department; 1324 (86.6%) were in agreement 121 of whom were in the high-risk group. There was no significant difference (chi 2 = 0.093: P greater than 0.7) in opinion between the 'unknown risk' and high-risk patient groups on this matter.
Previously we showed that mononuclear cells from about half of human T-lymphotropic virus (HTLV)-seropositive persons exhibit spontaneous proliferation in vitro. We sought to determine if proliferation was associated with other immunologic changes characteristic of HTLV infection. The parameters assessed were (1) percentages of lymphocytes expressing CD4 and/or CD25 (interleukin-2 receptor), (2) serum levels of soluble CD25, (3) serostatus for other viruses, (4) anti-HTLV antibody levels, and (5) HTLV type determined by polymerase chain reaction or serologic reactivity with type-specific peptides. The proliferation+ HTLV (PROL+) group, proliferation HTLV (PROL-) group, and control group showed similar percentages of CD4+, CD25+, and CD4+CD25+ lymphocytes; serum levels of soluble CD25 were also similar. Antibodies to cytomegalovirus, hepatitis B core, and hepatitis C were present in similar proportions of PROL+ and PROL+ groups. However, a significant association was found between spontaneous proliferation and anti-HTLV antibody levels; sera from 67% of PROL+ persons, but only 18% of PROL- persons, required dilution to yield absorbance values within the linear range of the anti-HTLV antibody assay. In the PROL+ group, persons whose sera required the most dilution had proliferative responses significantly higher than those whose sera required no dilution. The PROL+ and PROL groups were similar with regard to the relative distribution of HTLV-I and HTLV-II infection. These findings indicate that HTLV-related spontaneous lymphocyte proliferation is related to levels of circulating anti-HTLV antibodies, and characterizes both HTLV-I and HTLV-II infection.
Acute myocardial infarction is associated with an accumulation of lipids. Spectroscopic and chemical-shift imaging strategies which can depict the spatial distribution of these chemical species are evolving. The present study was undertaken to test whether the Dixon method could detect spatially lipids known to accumulate in myocardium after an ischemic insult. Seven dogs underwent a 24-h coronary artery occlusion (LAD = 4, Cx = 3). Post mortem, hearts were removed and imaged ex vivo. Myocardial samples were also evaluated by high-resolution 1H NMR spectroscopy. Lipid images revealed regions of increased signal intensity, in the regions corresponding to the myocardial infarction, particularly in the periphery of the infarction. An increase in mobile lipids was observed by 1H NMR spectroscopy of myocardial samples with moderately reduced blood flow and corresponding to regions with increased signal intensity on the lipid image. This study shows that chemical-shift imaging may be useful for detecting alterations in myocardial lipid levels following an ischemic insult.
Time-of-flight angiography methods rely on blood/tissue contrast generated when fresh blood spins enter a partially saturated region. A series of projective angiographic views is generated by application of a maximum intensity projection algorithm to data acquired from a 3D volume. When the data are acquired as a set of 2D slices, the angiograms exhibit sensitivity to body motion, resulting in the generation of artifacts. We present a new 2D time-of-flight angiographic technique, STREAM, Suppressed Tissue with Refreshment Angiography Method. It exhibits low sensitivity to internal body motion, thus allowing acquisition of good quality, single average angiograms. To suppress the static tissue signal a unique "active" suppression strategy is employed. Additionally, to further suppress the lipid signal, the chemical-shift phenomenon is exploited in the STREAM sequence.
To enhance contrast between flow and static tissue, NMR projective angiographic methods usually require data subtraction, or alternatively the application of special data processing routines such as the "maximum intensity projection" algorithm. We have successfully developed a direct projection method which yields sufficient flow/static contrast in a single acquisition, producing angiograms in under 4 s. Direct projection angiograms of the cervical and abdominal vessels were obtained. The cervical vessels were uniformly depicted in a number of different projection views. The abdominal vessels exhibit intensity variations due to the pulsatile flow pattern. A series of abdominal angiograms were acquired, each triggered at a different starting cardiac phase. When displayed as a movie sequence the pulsatile flow pattern was seen to advance along the arteries. To more uniformly represent the abdominal vessels a 24-s average was adequate. This new technique should allow NMR angiograms to be obtained in a "fluoroscopic" mode.
In rapidly acquired gradient echo images, lipid regions usually appear as areas of high signal intensity. In 2D inflow angiograms processed by the maximum intensity projection algorithm, this high lipid signal may prevent angiographic visualization of some blood vessels. We present a new approach to suppress the lipid signal, SLIP, spatially separated lipid presaturation. The SLIP technique suppresses lipid signal over a narrow region by exploiting the chemical-shift effect. SLIP requires an arrangement of a thin slice and a wide presaturation slab already available in 2D inflow refreshment angiography. Thus SLIP was incorporated to an inflow angiography sequence without increasing the acquisition time. The use of SLIP resulted in considerable improvement in angiographic contrast and increased the number of vessels detected in projection angiograms. The SLIP technique does not require high homogeneity of the main magnet field.
Conventional angiography, two-dimensional inflow magnetic resonance (MR) angiography, and color duplex ultrasound (US) were performed on 12 patients in a blinded, prospective study. The ability to grade arterial lesions and plan revascularization interventions were compared. Arterial lesions were categorized as nonsignificant (0%-49% diameter reduction) or significant (50%-100% diameter reduction). Determination of nonsignificant and significant lesions with MR angiography was in agreement with that at conventional angiography in 100 of 140 lesions (71%). Agreement between results of conventional angiography and color duplex US occurred with 114 of 123 infrainguinal lesions (93%). Twenty-one vascular interventions were planned by using conventional angiography; there was agreement with color duplex US in 11 cases and MR angiography in five. Color duplex US performed well in the assessment of infrainguinal disease but was limited in the evaluation of iliac segments because of nonvisualization. The iliac region was visualized in more patients with MR angiography than with color duplex US, but image quality with MR angiography was inconsistent. Strategies to improve MR angiography of the peripheral vasculature merit further study.
The Doppler probe was used to identify the dominant cutaneous perforating arteries in a series of 10 patients. The results were compared with our previous total body fresh cadaver anatomical studies and a close correlation was found. The instrument was used in a series of patients to plan the base, the axis and the dimensions of skin flaps for local, distant and free transfer. A dominant perforator was located at the base of the flap, the surrounding skin was scanned to identify the next dominant perforator in each direction and the appropriate axis was chosen by drawing a line between two nominated perforators. Often the flap was based distally or its axis departed from the main course of the supplying vessel. The technique proved to be simple and reliable and in many cases flaps of unusual dimensions and directions were transferred successfully. The instrument provides a useful link between the anatomical dissecting room and the operating theatre.
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Interleukin-2 (IL-2) and beta-interferon (beta-IFN) are cytokines with profound immunobiological effects on T-cell and natural killer (NK) cell activity; IL-2 also induces lymphokine-activated killer (LAK) cell cytotoxicity in humans. Both lymphokines induce antineoplastic activity against several refractory tumors. This Phase I study of 50 patients assessed the toxicities, maximally tolerated dose (MTD), effects on certain immune effector cells, pharmacokinetics of IL-2, and development of antibodies to the combination of subcutaneously administered IL-2 and intravenously administered beta-IFN. Fever was common. Indomethacin reduced the incidence and severity of fever and was necessary to prevent it from becoming dose-limiting. Hypotension occurred but never required pressors or produced complications. Constitutional symptoms, local skin toxicity at the site of IL-2 injection, generalized desquamation, eosinophilia, nausea, and vomiting were also observed. One patient had reversible renal dysfunction. Two patients experienced drug-related dyspnea without evidence of capillary leak syndrome; neither required intubation. Fluid retention and cardiotoxicity were not observed. The MTD was 5 x 10(6) U/m2 s.c. of IL-2 and 2 x 10(6) U/m2 i.v. of beta-IFN when given in combination. Enhancement of in vivo NK cell cytotoxicity and proliferation of T4+, T8+, and NK cells occurred. In vivo induction of LAK cell cytotoxicity was observed in three patients. Four patients developed nonneutralizing anti-IL-2 IgG antibodies, but none developed antibodies to beta-IFN. Peak IL-2 serum levels typically occurred 4 h following drug administration. Serum levels were within a factor of 3 of the peak level in the period studied, 1-6 h postinjection. No complete responses occurred. One patient with rectal cancer and one with transitional cell carcinoma each had a partial response, and 13 other patients (5 with renal cell, 4 with colorectal, and 4 other cancers) had stable disease. Induction of NK cell cytotoxicity was seen more commonly in patients with stable disease than in those with progressive disease. Combined administration of these agents is feasible with acceptable toxicity, and Phase II trials are warranted.
Using a 1-m-bore superconductive magnet at 0.1 T, whole-body transverse images through adult humans have been obtained at repetition times of 57 ms. The techniques used were minor variations of echo-planar imaging (EPI) employing large pulsed gradients to provide complete coverage of the plane in phase space, and low-angle RF excitation sequences allowing rapid repetition of the experiment. In addition active magnetic screening of the gradient coils was implemented to protect the surrounding magnet from the eddy currents induced by the necessarily fast switching of the large gradient fields.
The hybrid technique of projection-reconstruction echo-planar (PREP) imaging for obtaining chemical-shift images is demonstrated experimentally using a fluorine sample. The technique which is a variation on echo-planar imaging (EPI) relies on a multipass procedure. It is nevertheless quite efficient and consequently chemical-shift images may be produced in a few minutes. The method produces images in 64 chemical-shift regions, each region mapped spatially by 64 X 64 pixels. The imaging time was just over 4 min. These 64 chemical-shifted images can be straightforwardly added together to form an undistorted image of the complete object. In addition the chemical-shift spectrum can be extracted and the various chemical-shift images can be unambiguously assigned to the spectral peaks.
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