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Biomedical subjects

P Gibbs

Publications and source records attributed to P Gibbs.

At least 91 records · Page 5Linked to original sources

Major extended hepatic resections in diseased livers using hypothermic protection: preliminary results from the first 12 patients treated with this new technique.

BACKGROUND: Hepatic vascular exclusion allows the performance of major hepatic resections with minimal intraoperative blood loss. We have previously shown that normothermic ischemia can be tolerated by a healthy liver for up to 90 minutes, and this period is increased to 4 hours if the liver is cooled to 4 degrees C using University of Wisconsin solution. STUDY DESIGN: This study assessed whether these techniques could be successfully applied for patients requiring resection of a diseased liver, which is more sensitive to ischemic damage. Between July 1990 and May 1994, 12 patients (6 men, 6 women; mean age, 57.8 years) in whom the planned hepatic resection was believed to require hepatic vascular exclusion for more than 1 hour were treated with perfusion with the University of Wisconsin solution. The surgical procedures were right hepatectomy (one patient), extended right hepatectomy (seven patients), and extended left hepatectomy (four patients). The underlying hepatic disease was cirrhosis or severe fibrosis with hepatocellular carcinoma (four patients), cholestasis (due to cholangiocarcinoma and biliary stricture, one patient each), and more than 30 percent steatosis after treatment of hepatic metastases with chemotherapy (six patients). The University of Wisconsin solution that had been cooled to 4 degrees C was perfused through a cannula placed in the portal vein or the hepatic arterial branch of the segment to be resected, but with flow directed toward the liver that should be retained and effluent fluid drained through a cavotomy. Before reperfusion, the liver was rinsed with Ringer's lactate solution, which was also 4 degrees C. RESULTS: The mean duration of hepatic ischemia was 121 minutes (range, 65 to 250 minutes), and venovenous bypass was used in three cases. The mean amount of blood transfused intraoperatively was 4.3 +/- 4 U; four cases required no transfusion. One patient died on postoperative day seven of portal vein thrombosis. The median hospital stay was 21 days (range, 12 to 56 days). Postoperative complications consisted of pneumonia (one patient), liver insufficiency (one patient, who recovered spontaneously), and subphrenic abscess (one patient). The postoperative tests of hepatic function were altered to the same degree as that seen after hepatic vascular exclusion of less than 1-hour duration in healthy livers. All patients who left the hospital were alive at 1 year. CONCLUSIONS: Cooling of the hepatic parenchyma allowed us to perform major hepatic resection in patients with diseased livers using hepatic vascular exclusion for longer than 1 hour without increased morbidity or mortality. However, because of particular difficulties due to the size or location of the lesions, the application of these new techniques should only be considered for the largest and most complex hepatic resections for which hepatic vascular exclusions longer than 1 hour are foreseen.

Adenosine↗

The flow cytometric crossmatch in liver transplantation.

The role of the cytotoxic crossmatch in liver transplantation is generally considered controversial. The development of the flow cytometric crossmatch has allowed the detection of lower levels of donor-directed IgG than is possible with the conventional crossmatch. This assay has been shown to be useful in renal transplantation. However, with the controversial role of the standard cytotoxic crossmatch, the flow cytometric crossmatch has not been used in liver transplantation. Twenty-seven human orthotopic liver allograft recipients were tested for donor-directed IgG using the flow cytometric crossmatch. Thirteen recipients were identified with either T or B lymphocyte-directed IgG. This group had a significantly increased incidence of clinical rejection (75%) as compared with the negative group (29%, P = 0.02, Fisher's exact test). The differences were greatest with B lymphocyte-directed IgG and the rejections were generally steroid sensitive. In this series, the flow cytometric crossmatch proved to be a better prognostic indicator of rejection than the conventional cytotoxic crossmatch. In addition, the association of a positive flow cytometric crossmatch with rejection indicates that the liver follows the same pattern seen in renal and cardiac grafts.

Adult↗

Immunogenicity of biliary epithelial cells: study of the expression of B7 molecules.

Efficient antigen presentation requires the provision of a co-stimulatory signal, the best characterized of which is provided by the B7 molecules. It is unclear whether biliary epithelial cells expressing Class II major histocompatibility complex molecules can function as antigen presenting cells, although this has been suggested as an important mechanism in the initiation and/or perpetuation of some immune-mediated liver diseases, including primary biliary cirrhosis and liver allograft rejection. We have found that human intrahepatic biliary epithelial cells do not express B7-1 (CD80) or B7-2 in vitro, even after activation with high doses of interferon-gamma, tumour necrosis factor-alpha or phorbol myristate acetate, or in vivo. However, they express similar levels of class II major histocompatibility complex antigens to those expressed by professional antigen presenting cells (Epstein-Barr virus transformed B cells). It is therefore unlikely that biliary epithelial cells stimulate efficient primary T cell activation. It may be possible that these non co-stimulatory class II major histocompatibility complex positive cells play a role in modulating immune responses in the liver.

Antigen-Presenting Cells↗

Experimental anthrax vaccines: efficacy of adjuvants combined with protective antigen against an aerosol Bacillus anthracis spore challenge in guinea pigs.

The efficacy of several human anthrax vaccine candidates comprised of different adjuvants together with Bacillus anthracis protective antigen (PA) was evaluated in guinea pigs challenged by an aerosol of virulent B. anthracis spores. The most efficacious vaccines tested were formulated with PA plus monophosphoryl lipid A (MPL) in a squalene/lecithin/Tween 80 emulsion (SLT) and PA plus the saponin QS-21. The PA+MPL in SLT vaccine, which was lyophilized and then reconstituted before use, demonstrated strong protective immunogenicity, even after storage for 2 years at 4 degrees C. The MPL component was required for maximum efficacy of the vaccine. Eliminating lyophilization of the vaccine did not diminish its protective efficacy. No significant alteration in efficacy was observed when PA was dialyzed against different buffers before preparation of vaccine. PA+MPL in SLT proved superior in efficacy to the licensed United States human anthrax vaccine in the guinea pig model.

Adjuvants, Immunologic↗

A review of heavy metal and organochlorine levels in marine mammals in Australia.

Study of toxic contaminants in marine mammal specimens collected around Australia is currently uncoordinated and piecemeal. Most states collect samples but there is little or no financial support for their analysis. This study combines data, published or unpublished, from 13 sources. Heavy metals have been analysed in about 676 specimens; over 400 were for mercury levels in P. macrocephalus taken at a whaling station. The remaining samples were mostly from toothed whales, a few baleen whales (< 20), pinnipeds (41) and dugongs (49). The most consistently analysed metals were lead, mercury and cadmium. Liver and kidney lead levels ranged from < 1-3 ppm; levels in bone were 0-418 ppm, with most less than 10 ppm. Mercury levels in a large sample of P. macrocephalus muscle were < 12.2 ppm. Mercury levels in the small number of samples from other species were 0.51-143 ppm (kidney), 1.52-479 ppm (liver) and < 0.1-36 ppm (muscle). Cadmium levels in liver (0-52 ppm) and kidney (0-106 ppm) were extremely variable. Levels greater than 10 ppm were recorded in many species and were especially high in Hydrurga leptonyx, Dugong dugon, Mesoplodon layardii and Pseudorca crassidens. Adult Tursiops truncatus inhabiting the inshore gulfs of South Australia had considerably higher levels of cadmium compared with other regions. Information on organochlorine levels is sparse (approximately 39 specimens) and suggest low levels when compared to other parts of the world. Total DDT was highest (28.4 ppm) in a neonatal Orcinus orca. Some high levels of DDT were recorded in Tursiops truncatus, Delphinus delphis and Arctocephalus pusillus doriferus. PCBs ranged from < 0.05 to 3.87 ppm. A comprehensive pathological assessment of marine mammals is needed in order to evaluate the effects of toxic contaminants.

Animals↗

Fingers: three-dimensional MR imaging and angiography with a local gradient coil.

The authors interfaced a 12-cm-diameter local gradient coil with a solenoid radio-frequency coil (2.2-cm internal diameter, 1.4-cm long) to a recalibrated clinical magnetic resonance imaging system. Three-dimensional gradient-echo imaging and phase-contrast angiography were performed on the fingers of five healthy volunteers (four men and one woman, aged 23-33 years). Data sets (256 x 256 x 28) were acquired with spatial resolution of 100 x 100 x 500 microns in 6 minutes 51 seconds. The angiograms clearly delineated blood vessels that were less than 1 mm in diameter.

Adult↗

The relationship of angulation to translation in fracture deformities.

We measured both angulation and translation on anteroposterior and lateral roentgenograms of 100 fixed post-traumatic deformities (either malunions or stiff [hypertrophic] non-unions) of long bones. We used trigonometric formulae to calculate the true planes and actual magnitude of both the angulation and the transverse translation of each deformity. We found that the planes of angulation and translation for each osseous deformity were rotated 43 +/- 25 degrees (mean and standard deviation) with respect to each other; in fact, we found almost as many instances in which the planes of angulation and translation of the fragments were within 10 degrees of perpendicular to each other as we did instances in which the angulation and translation were within 10 degrees of being in the same plane. Only seven angular deformities and six translational deformities occurred along either the sagittal or the coronal plane; the remaining deformities were in planes that were oblique to the standard reference planes.

Biomechanical Phenomena↗

Adhesion molecule expression (ICAM-1, VCAM-1, E-selectin and PECAM) in human kidney allografts.

Expression of the cellular adhesion molecules ICAM-1, VCAM-1, E-selectin and PECAM in human kidney allografts was assessed by immunoperoxidase labelling of cryostat sections. Biopsies from 10 kidneys immediately prior to transplantation and 58 biopsies from 51 kidney transplants with graft dysfunction were studied. Allograft dysfunction was due to acute tubular necrosis (n = 5), acute rejection (n = 30), cyclosporin A (CyA) nephrotoxicity (n = 6), acute pyelonephritis (n = 3), recurrent glomerulonephritis (n = 4) and chronic rejection (n = 10). There was variability in the distribution of ICAM-1, VCAM-1 and E-selectin expression in pretransplant kidneys but the principal observation was a marked increase in the expression of ICAM-1 and VCAM-1 by the renal vasculature and the proximal tubules during acute rejection. By contrast, grafts with dysfunction not attributed to rejection showed a pattern of ICAM-1 and VCAM-1 expression similar to that observed prior to transplantation. E-selectin was expressed only weakly by occasional intertubular capillaries during acute rejection but the three grafts with pyelonephritis displayed strong expression of E-selectin on intertubular capillaries. There was no change in the pattern of PECAM expression following transplantation. The induction of ICAM-1 and VCAM-1 during rejection may contribute to the recruitment of mononuclear cells and render endothelial and tubular renal cells more susceptible to cell-mediated injury.

Adolescent↗

Prolonged monitoring of the upper gastrointestinal tract using echo planar magnetic resonance imaging.

Upper gastrointestinal motility and transit has been studied in five human volunteers with the ultra high speed, magnetic resonance imaging (MRI) technique MBEST (Modulus Blipped Echo-planar Single pulse Technique), a variant of echo planar imaging. Snapshot images requiring a data acquisition time of only 64-128 msec allowed visualisation of peristalsis in the antrum and duodenum in real time, without motional image degradation, as would normally be seen using conventional MRI. Gastroduodenal flow of the luminal contents was visualised using water as a contrast medium, with appropriate adjustment of the time constant (T2) weighting of the system. Rapid (0.3 Hz) imaging of gastroduodenal motility in both transverse and coronal planes was achieved by respiratory gating to the imaging frequency, allowing repetition rates of up to 20 frames per minute for 2-3 hours. Fast replay of stored images, to produce a 'movie loop', allowed identification of fasting motility patterns of the gastric antrum and proximal small intestine, with depiction of the phases of the migrating motor complex. Images of the fed patterns after the ingestion of a test meal showed good separation of solid and liquid particulate matter and mixing waves in the gastric body. The potential for quantitative measurements with this new imaging modality of the gastrointestinal tract is under development, which will allow us to measure transit and correlate this with motility data.

Adult↗

Real-time flow measurements using echo-planar imaging.

The ultra-high-speed echo-planar imaging (EPI) method is combined with velocity encoding prior to EPI read-out, thereby allowing real-time measurement of flow. Results of EPI flow measurement experiments are presented on phantoms and human volunteers.

Blood Flow Velocity↗

Observation of cerebrospinal fluid flow with echo-planar magnetic resonance imaging.

Using echo-planar (EP) magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) flow patterns have been demonstrated in the normal subject and patients with pathological conditions including communicating hydrocephalus, aqueduct stenosis and syringohydromyelia. Snap-shot imaging times of 128 ms allow detailed demonstration of transient intraventricular CSF flow patterns, which is not possible with conventional MRI. The potential of EPI as a method for qualitative and quantitative assessment of CSF dynamics is illustrated.

Cerebral Aqueduct↗

Echo-planar imaging of the human fetus in utero.

We have demonstrated that echo-planar imaging can be used to produce high-quality snapshot images of the human fetus in utero in a fraction of a second. These images are free of motional artifact or blurring and allow detailed depiction of fetal structures in normal and pathological pregnancies.

Fetal Heart↗

High-speed multislice T1 mapping using inversion-recovery echo-planar imaging.

Tissue contrast in MR images is a strong function of spin-lattice (T1) and spin-spin (T2) relaxation times. However, the T1 relaxation time is rarely quantified because of the long scan time required to produce an accurate T1 map of the subject. In a standard 2D FT technique, this procedure may take up to 30 min. Modifications of the echo-planar imaging (EPI) technique which incorporate the principle of inversion recovery (IR) enable multislice T1 maps to be produced in total scan times varying from a few seconds up to a minute. Using IR-EPI, rapid quantification of T1 values may thus lead to better discrimination between tissue types in an acceptable scan time.

Fourier Analysis↗

Electron paramagnetic resonance spectroscopic investigation of the inhibition of the phosphoroclastic system of Clostridium sporogenes by nitrite.

The proposal that nitrite exerts its inhibitory effect on anaerobic bacteria by direct interaction with the iron-sulphur proteins of the phosphoroclastic system was investigated. The effects of nitrate, nitrite with or without ascorbate, and nitric oxide on the growth of Clostridium sporogenes in liquid cultures at pH 7.4, on the rates of hydrogen production, and on the activities of the enzymes pyruvate-ferredoxin oxidoreductase and hydrogenase, and of ferredoxin were investigated. In agreement with previous studies, nitrate was the least effective inhibitor of cell growth, and nitric oxide the most effective. Nitrite reductase activity was very low in C. sporogenes, indicating that the presence of external reducing agents would be necessary for the reduction of nitrite to nitric oxide. Inhibition by nitrite was enhanced by ascorbate; 0.5 mM-nitrite with 10 mM-ascorbate stopped growth completely. In partially-purified preparations 4.1 mM-NaNO2 and equimolar ascorbate caused complete inactivation of hydrogenase activity but only partial (up to 78%) inactivation of pyruvate-ferredoxin oxidoreductase. This agreed with the loss of hydrogen production observed with nitrite in vivo. Inhibition occurred within 5 min, and was irreversible in each case. Electron paramagnetic resonance (EPR) spectroscopy showed that paramagnetic [Fe(NO)2(SR)2] species were formed during growth in the presence of nitrite, and were associated with cells. However, the intensity of these EPR signals did not correlate with the inhibition of cell growth. The [4Fe-4S] clusters in ferredoxin were shown by EPR spectroscopy to be resistant to treatment with 3.6 mM-NaNO2 and 3.6 mM-ascorbate. It is concluded that the effects of nitrite on pre-formed iron-sulphur proteins are not convincing as a basis for the lethal effects on bacterial cells.

Ascorbic Acid↗

Ultrafast magnetic resonance scanning of the liver with echo-planar imaging.

Echo-planar imaging (EPI) is a magnetic resonance imaging (MRI) technique which provides MR images in, typically, 50-100 ms. The potential of EPI as an imaging modality for the liver has been investigated in volunteers and patients with liver disease. Images with improved quality are presented. Obtained at a field strength of 0.52 Tesla, these true unaveraged snap-shot images have larger data arrays, comprising 128 X 128 pixels.

Aged↗

Echo planar imaging of the human fetus in utero at 0.5 T.

The snap-shot capability of the echo-planar imaging technique is used to freeze motion effectively in human fetal studies in utero. These first results obtained at 0.5 T demonstrate diagnostic quality images without the need for averaging. Although averaging improves the image signal to noise ratio, it is shown that significant image blurring is produced even when only eight separate images are averaged over a period of a few seconds. Results are presented showing anatomical detail of the internal organs of the fetus. Some pathology is also demonstrated. These results were obtained using the modulus blipped echo-planar single-pulse technique (MBEST). Running at 10 frames/second, the modulus version of the fast low-angle excitation echo-planar technique (FLEET) is used to produce ungated fetal cardiac movies.

Female↗