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Biomedical subjects

P Gibbs

Publications and source records attributed to P Gibbs.

At least 19 recordsLinked to original sources
PubMed1999

Cardiac metastases from malignant melanoma.

BACKGROUND: Cardiac metastases are uncommon, with the exception of malignant melanoma. More cases of cardiac involvement are being diagnosed in association with the rising incidence and increasing survival of patients with melanoma. Surgical intervention may be an effective palliative measure and should be considered for selected patients who present with this problem. METHODS: In this article, the authors present clinical, laboratory, and imaging data from two patients with malignant melanoma who presented with cardiac metastases. A discussion of these patients is accompanied by a review of the current literature on this topic. RESULTS: Two females with known metastatic malignant melanoma presented with nonspecific pulmonary symptoms and were found to have intracardiac metastases involving the right heart. One patient underwent successful surgical removal of a large tumor mass, which resulted in relief of symptoms and prevention of imminent death from cardiac complications. Together with the literature review, these cases demonstrate the important clinical features of cardiac metastases from melanoma and define the best means of diagnosis as well as the potential benefits of surgical intervention. CONCLUSIONS: Cardiac involvement by malignant melanoma is now diagnosed with increasing frequency. A diagnosis can be made with relative ease, but clinical suspicion must precede it. Surgery may be useful to palliate symptoms and prevent death from cardiac complications.

Aged↗
PubMed1998

Basic anatomical and physiological differences between species should be considered when choosing combinations for use in models of hepatic xenotransplantation: an investigation of the guinea pig-to-rat combination.

Published data on the guinea pig-to-rat hepatic xenotransplant model describe problems concerning poor graft reperfusion. To further investigate this phenomenon, orthotopic liver xenotransplantation between weight-matched guinea pigs and rats were performed using Kamada's technique. On reperfusion, all cases had portal venous inflow block with hypoperfusion of the hepatic parenchyma. Histological examination showed no evidence of hyperacute rejection, although deposits of IgG2a and C3 but not IgM were identified within the central area of the liver. To increase blood inflow, arterialized partial liver grafts were performed without changing the outcome. We hypothesize that the hypoperfusion may be related to anatomical and physiological differences between the species. Guinea pig portal vein branches were found to have muscular walls susceptible to spasm, and portal blood flow is four times greater in the guinea pig than in the rat because the guinea pig intestine is both longer (two times as long) and of greater diameter. The combination of reperfusion injury, early immunological events, and the rat's lower portal blood flow induces spasm of the intrahepatic portal system resulting in hypoperfusion. These findings demonstrate the importance of recognizing basic anatomical and physiological differences between species when selecting xenotransplantation models.

Animals↗
PubMed1998

Technical details for safer venous and biliary anastomoses for liver transplantation in the rat.

Although orthotopic liver transplantation in the rat is a well-established experimental model, no detailed illustrated description of the procedure is available in the literature. As a result, achieving success in the technique without prolonged learning time requires training in specialized centers where the step-by-step details essential to success in the technique can be learnt. The aim of this paper is to provide beginners with the culminative experience of 15 years of improvements made to Kamada's original model, clearly illustrating the necessary steps and fine detail of each anastomosis to help beginners avoid unnecessary complications. We hope that this complete description of orthotopic liver transplantation in the rat, which remains the most difficult rodent transplant model to master, will greatly help microsurgeons acquire this demanding procedure.

Anastomosis, Surgical↗
PubMed1998

New technique of complete thymectomy in adult rats without tracheal intubation.

Adult rat thymectomy is frequently performed as part of the protocol for experiments in transplant immunology. Current methods used are either imprecise (suction methods) or require tracheal intubation (surgical technique) and are thus difficult to master. We have developed a safe technique of surgical removal of the thymus with resolution of any pneumothorax by suction through the xyphoid insertions of the diaphragm. This method is easy to learn and gives a 95% success rate.

Animals↗
PubMed1998

Biliary reconstruction with or without an internal biliary stent in orthotopic liver transplantation: a prospective randomised trial.

Choledochocholedochostomy (CCD) with a 7 fr/8 fr Cotton Leung internal biliary stent removed at endoscopic retrograde cholangiography (ERC) 3 months following orthotopic liver transplantation (OLT) was the technique used on our unit for biliary reconstruction. From June 1995 to July 1996, we randomised 37 OLT patients with CCDs to receive either an internal stent (group I, nd = 18) or no stent (group II, n = 19). Patients in group I had an ERC at 3 months for stent removal whereas patients in group II had an ERC if indicated. The mean follow up was 19 (13-26) months. Biliary complications occurred in 9 out of 18 patients in group 1 compared to 1 out of 19 patients in group II (P = 0.007). In group I, ERC was required for complications in 8 patients and early surgery in 2, compared to 1 ERC for abnormal liver function tests in group II. Five of the early complications in group I were stent related. Late biliary stenosis occurred in 1 patient at 9 months. There was one stent-related death. The use of stents contributes to biliary complications and CCD without stenting is safe after OLT.

Adolescent↗
PubMed1998

Spontaneous T cell responses to melanoma differentiation antigens from melanoma patients and healthy subjects.

The spontaneous cytotoxic T cell responses to melanoma differentiation antigens and influenza matrix peptide were compared in 20 HLA-A2+ melanoma patients and 17 healthy A2+ individuals. Cytotoxic T lymphocyte (CTL) responses were determined by mixed lymphocyte peptide culture (MLPC) involving two stimulations of unfractionated peripheral blood lymphocytes (PBLs) with peptide in vitro. CTL responses to Melan-A 9-mer (amino acids 27-35, AAGIGILTV) peptide were detected in 4 out of 16 normal individuals, but in none of the melanoma patients. CTL specific for influenza matrix peptide were frequently found in both normal individuals and melanoma patients, suggesting that generalized immuno-suppression was not responsible for this difference. No significant responses were observed in either normal individuals or melanoma patients to Melan-A 10-mer (26-35, EAAGIGILTV), two gp1OO epitopes (280-288, YLEPGPVTA; 457466, LLDGTATLRL) and two tyrosinase epitopes (1-9, MLLAVLYCL; 368-376, YMDGMSQV). Melan-A (27-35)-specific CTL cells generated by normal individuals and melanoma patients recognized both synthetic peptide-pulsed T2 cells and two HLA-A2+, Melan-A+ melanoma cell lines (ME272, LAR1) in an antigen-specific, MHC class I restricted manner. T cells generated against Melan-A 9-mer were also able to recognize Melan-A 10-mer-pulsed target cells. Spontaneous CTL responses to Melan-A 9-mer from three known responder normal individuals were further evaluated over a prolonged time course (6-11 months). All 3 subjects demonstrated specific Melan-A 9-mer responses throughout the study period, although lytic activity fluctuated over time for a given individual. We found the MLPC assay to be reliable and easy to perform for monitoring T cell responses, although it may still not be sufficiently sensitive to detect low numbers of precursor T cells.

Adjuvants, Immunologic↗
PubMed1998

Pathway selection's utility for control of word recognition.

Regularity effects signify assembled phonology: the nonlexical pathway in word recognition. Assembled phonology may be strategically controlled. When task conditions do not favor its use, such as when a lexical decision task includes pseudohomophone (durt) foils, an alternative pathway is selected. Consequently, regularity effects will be reduced or absent. This prediction was tested in 3 lexical decision experiments using several definitions of word regularity. Word regularity was crossed in factorial designs with nonword lexicality, the degree to which nonword foils mimic the properties of actual words. Regularity effects to words were large and most reliable in pseudohomophone conditions, opposite to the tested prediction. Instead, the observed pattern corroborated a resonance account with parametric control.

Humans↗
PubMed1998

Split liver transplantation: King's College Hospital experience.

BACKGROUND: The purpose of split liver transplantation is to increase the source of pediatric grafts without compromising the adult donor pool. Early results have been discouraging because of technical complications and selection of poor risk patients. METHODS: The results of a single center experience of 41 split liver transplantations were analyzed. Patient and graft survival and complications related to the technique were analyzed. RESULTS: Patient and graft survival for the whole group was 90% and 88% respectively at a median follow up of 12 months (range 6-70 months). Patient and graft survival for the right lobe graft was 95% and the left lateral segment 86% and 82% respectively. Four patients died, of which two of the patients were first two splits following technical complications. Two others died, one from cerebral lymphoma and the other of multiorgan failure secondary to sepsis. One patient has been retransplanted for chronic biliary sepsis. CONCLUSION: Split liver transplantation has now become an acceptable treatment option for both adult and pediatric recipients with end stage liver disease. Right lobe recipients are not disadvantaged by the procedure. Good results can be achieved with better patient selection and by the use of good quality organs.

Adolescent↗
PubMed1998

Effects of oncostatin M and tamoxifen on human melanoma cells.

New agents are required in the treatment of malignant melanoma, to be used alone or in combination with established therapies. Oncostatin M (OSM), a member of the gp130 family of cytokines, has previously been shown to inhibit the growth of melanoma cell lines. Tamoxifen (TAM) is widely used in the treatment of melanoma, typically in combination with chemo- and/or immunotherapy. A component of the antitumour activity of TAM is via modulation of transforming growth factor-beta (TGF beta) which has previously been shown to be synergistic with OSM in vitro. To further investigate the clinical potential of OSM, alone and in combination with TAM, set concentrations of each were added to nine fresh and two well-established melanoma cell lines. The proliferation of seven of the 11 cell lines was inhibited by OSM, while two were unresponsive at the dose range tested. Of particular interest was the finding that the growth of two of the cell lines was significantly stimulated at low doses of OSM. The combination of OSM with TAM produced widely divergent results, most frequently resembling the effects of OSM alone. No synergism between the two was evident in any of the cell lines tested. Our results indicate that a combination of OSM and TAM in clinical trials needs further evaluation before it can be recommended. Furthermore, while OSM alone may be useful in the treatment of melanoma, this may be complicated by the possibility of stimulating tumour growth in some instances.

Antineoplastic Agents↗
PubMed1998

Primary breast abnormalities: selective pixel sampling on dynamic gadolinium-enhanced MR images.

PURPOSE: To evaluate a region-of-interest (ROI) analytic method that involves selective sampling of pixels within predetermined ranges of contrast material enhancement values ("thresholding") on magnetic resonance (MR) images of primary breast abnormalities. MATERIALS AND METHODS: Dynamic gadolinium-enhanced MR images were obtained in 105 women. ROIs were drawn to outline the full extent of lesions. Relative signal intensity increase was determined on a pixel-by-pixel basis on 1- and 2-minute postcontrast images, as was the maximum relative signal intensity increase. Thresholding was used to analyze each ROI, with the upper boundary defined by the highest pixel value and lower boundaries of 0%-100%. RESULTS: Seventy-one invasive carcinomas and 37 benign lesions were analyzed. Narrower thresholding (i.e., larger percentage) resulted in an increase in all enhancement ratios (P < .0005). The enhancement ratio on 1-minute postcontrast images differed between benign lesions and carcinomas (P < .0005), but there were no significant differences in 2-minute and maximum ratios. Mean enhancement differences between benign and malignant lesions increased with narrower thresholding, but variability also increased linearly. Results of receiver operating characteristic analysis showed that thresholding did not affect the diagnostic usefulness of enhancement ratios. CONCLUSION: Contrary to current opinion, selective sampling of the most enhancing areas of breast abnormalities may not provide any diagnostic advantage over the use of easily drawn, lesion-encompassing ROIs.

Biopsy↗
PubMed1998

Radiotherapy treatment planning of brain tumours using MRI alone.

MRI of the brain can provide images of very high quality revealing detailed information especially concerning the extent of abnormalities. As such MRI has great potential in the radiotherapy (RT) planning of brain tumours. However MRI has rarely been used alone as the basis for treatment planning primarily due to concern over potential geometric distortions. Treatment planning using MRI has therefore usually been carried out in conjunction with CT images. This work demonstrates that geometric distortions can be minimized by using a relatively small field-of-view, an increased receiver bandwidth, and a fast spin echo acquisition sequence, and that it is thus possible to perform RT planning using MRI.

Brain Neoplasms↗
PubMed1998

Periodontitis: a risk factor for coronary heart disease?

This paper evaluates the current information on the relationship between oral disease (specifically periodontitis) and atherosclerosis/coronary heart disease (CHD) to determine whether the information is sufficient to conclude that periodontitis is a risk factor for atherosclerosis/CHD. As background for this evaluation, the term "risk factor" is defined, and the 3 criteria used to establish exposures as risk factors are reviewed. In addition, epidemiologic criteria for defining an exposure as causal are presented. The available evidence then is evaluated according to the criteria for causality, which are extensions of the criteria for establishing a risk factor. This review is done in the context of the relationship between atherosclerosis/CHD and inflammation. A number of findings are briefly reviewed that link inflammation and atherosclerosis/CHD, such as: 1) prior flu-like symptoms were more common in cases of myocardial infarction than in concurrently sampled controls; 2) high levels of cytomegalovirus antibody titers were associated with elevated carotid intimal-medial wall thickness 18 years later; 3) prior infection with cytomegalovirus was a strong independent risk factor for restenosis after coronary atherectomy; 4) dental infections were more common in cases of cerebral infarction compared to community controls matched on age and sex; and 5) the gingival index was significantly correlated with fibrinogen and white cell counts in periodontal patients and controls, adjusted for age, smoking, and socioeconomic status. Three case-control studies and 5 longitudinal studies investigating the relationship between dental conditions and atherosclerosis/CHD are reviewed in terms of strength of associations, consistency of associations, specificity. of associations, time sequence between exposure and outcome, and degree of exposure and outcome. Related to the last criterion, new findings are presented which indicate that the extent of the periodontal infection, a measure reflecting microbial burden, also is related to onset of new CHD events. Our previously published model describing the potential biological mechanisms underlying the associations found is reviewed. This model places the associations into a context of an intrinsic or acquired hyperinflammatory monocyte trait that results in a more intense inflammatory response to lipopolysaccharide (LPS) challenges, such as periodontal infections. This hyperinflammatory response may promote atheroma formation and thromboembolic events. finally, new findings from ongoing animal studies are presented, indicating that high fat diets in atherosclerotic-susceptible mice induce greater inflammatory responses to Porphyromonas gingivalis challenges. We conclude that the available evidence does allow an interpretation of periodontitis being a risk factor for atherosclerosis/CHD. This conclusion, however. is made with some qualifications. While the associations found across a wide variety of subjects are remarkably consistent, for the most part they are represented by incidence odds ratios around 2.0. While this level of association would result in oral conditions contributing to a large number of CHD cases, it is possible that associations of this magnitude are due to bias in the study designs. In addition, some studies report that periodontitis is associated with all-cause mortality and low birth weight infants. These multiple associations detract from the credibility of periodontitis as a risk factor, as specificity of association is more often related to causality. However, all-cause mortality may largely be driven by mortality from cardiovascular events: and some exposures, such as smoking. are indeed risk factors for multiple conditions. On the other hand, current findings regarding the associations between oral conditions and atherosclerosis/CHD imply that the criteria for causality may be met in the not-too-distant future.

Animals↗
PubMed1997

Cavocaval liver transplantation without venovenous bypass and without temporary portocaval shunting: the ideal technique for adult liver grafting?

The influence of the implantation technique on the outcome was studied prospectively in a series of 116 consecutive adult patients undergoing primary liver transplantation during the period January 1991-June 1994. Thirty-eight patients (32.8%; group 1) underwent classical orthotopic liver transplantation (OLT) with replacement of the recipient's inferior vena cava (R-IVC) and with venovenous bypass (VVB). Thirty-nine patients (33.56%) had a piggy-back OLT with preservation of the R-IVC (group 2); bypass was used in 17 of them (43.6%) because of poor hemodynamic tolerance of R-IVC occlusion. Thirty-nine patients (33.6%) had OLT without VVB and with side-to-side cavocaval anastomosis (group 3). The three techniques were performed irrespective of the anatomical situation and of the status of the recipient at the time of transplantation. The following parameters were assessed in all patients: implantation time, blood product use, morbidity (e.g., hemorrhagic, thoracic, gastrointestinal, neurological, and renal complications), and outcome. Thirty-one patients underwent detailed intraoperative hemodynamic assessment. The early (< 3 months) post-transplant mortality of 10.3% (12/116 patients) was unrelated to the implantation technique. Group 3 had a significantly shorter mean implantation time, a reduced need for intraoperative blood products, and a lower rate of reoperation due to intra-abdominal bleeding. After excluding two immediate perioperative deaths and eight patients requiring early retransplantation because of primary nonfunction, the frequency of immediate extubation was significantly higher in group 3. Detailed hemodynamic assessment did not show a difference between 6 group 1 patients and 17 group 3 patients, indicating that partial lateral clamping of the IVC fulfills the function of venous bypass. Similar results were obtained in 6 group 2 patients who did not have IVC occlusion. Cavocaval OLT has become our preferred method of liver implantation. It allows the transplantation to be performed without VVB, regardless of the anatomical situation and of the condition of the patient at the time of transplantation. Moreover, it avoids all of the potential complications and costs of VVB.

Adult↗
PubMed1997

Hepatic transplantation in children under 3 months of age: a single centre's experience.

Liver transplantation in neonates represents a major medical and technical challenge particularly in babies weighing less than 5 kg. The authors report the experience of 10 liver transplants in 9 babies (6 boys and 3 girls), mean age, 6 weeks (range, 2 to 11); median weight, 3.7 kg (range, 2.4 to 5). All had fulminant hepatic failure caused by neonatal haemochromatosis (n = 3), non-A non-B hepatitis (n = 3), total parenteral nutrition induced (n = 1), hepatitis B (n = 1), and hepatic haemangio-endothelioma (n = 1). One child underwent retransplantation for hepatic artery thrombosis. Immunosuppression was by Cyclosporine A-based triple therapy in all cases. All received a reduced size graft consisting of left lobe (n = 1), left lateral segment (n = 6) and monosegment III (n = 3). In nine cases the donor hepatic artery was anastomosed to an iliac artery conduit from the infrarenal aorta, and a Roux loop was used for bile duct reconstruction. Primary abdominal wound closure was possible in six patients, skin closure alone in one, and a silastic patch was used in three. Complications included infection (n = 5), bowel perforation (n = 2), diaphragmatic perforation (n = 2), bile leak (n = 1), hepatic artery thrombosis (n = 1), and portal vein thrombosis (n = 1). None of the babies experienced acute rejection. Currently five of the nine recipients are alive with good graft function at a mean follow-up of 22 months (range, 5 to 58). Of the four deaths, two were related to infection (one in combination with portal vein thrombosis), one to multiorgan failure and fluid overload, and one to early graft dysfunction and sepsis after undergoing retransplantation for hepatic artery thrombosis. From our experience liver transplantation offers a promising option for the treatment of severe liver disease in children less than 3 months old.

Age Factors↗
PubMed1997

Hirschsprung's disease: a 20-year experience.

During the period from 1972 to 1992, 59 children received surgical treatment at the University of Louvain Medical School for biopsy-proven Hirschsprung's disease (HD). The extent of aganglionosis was as follows: short segment restricted to the rectosigmoid or descending colon (n = 44, 75%); long segment (n = 9,15%); ultra-short segment (n = 3, 5%); unknown length because of death without autopsy (n = 3, 5%). The median age at operation was 7 months for short-segment disease compared with 14 months for those with long-segment disease. Surgical procedures used for short-segment disease were Swenson with colostomy (n = 16), Swenson-Pellerin without colostomy (n = 27), Duhamel (n = 1), and for long-segment disease were Martin (n = 3), Swenson-Deloyers (n = 2), Swenson-Boley (n = 2) and ileostomy only in = 2). Lynn's sphincteromyotomy was performed in the three ultra-short cases. There were six deaths (10%) at a median age of 86 days (range, 28 to 1545 days), three had long-segment disease, and the others were not classified because of death before curative surgery. Enterocolitis (EC) was the most common cause of death (five cases) and was also the major source of morbidity after curative surgery (12 of 44, 27%) in short-segment patients, three of seven (43%) in long-segment patients. The functional success of the procedure was evaluated in 70% of the surviving patients (37 of 53; mean follow-up, 8.7 years; range, 1.2 to 21.5), using a novel semiquantitative scoring system, specifically designed for children who have HD. This system assesses normal stool evacuation, abdominal distention, soiling, and severe incontinence. The results were compared with those from a population of 39 healthy children and adolescents and demonstrated progressive improvement in function during childhood and adolescence (P = .04) for patients treated for short-segment disease. However, function was found to be consistently poorer in all age groups when compared with healthy controls (5 to 10 years, P < .01; 10 to 15 years, P < .05; > 15 years, P < .01).

Enterocolitis↗
PubMed1997

Immunogenicity of biliary epithelium: study of the adhesive interaction with lymphocytes.

BACKGROUND & AIMS: Intrahepatic bile ducts express a range of lymphocyte adhesion molecules during episodes of inflammation. This may contribute to the susceptibility of biliary epithelium to immunologic damage during liver allograft rejection, graft-versus-host disease, and primary biliary cirrhosis. However, no previous study has shown that these adhesion molecules are functional. The aim of this study was to define the molecular basis of lymphoepithelial interactions within the intrahepatic bile ducts. METHODS: Human intrahepatic biliary epithelial cells (HIBECs) were cultured, and their interaction with resting and activated lymphocytes was studied using a flow-cytometric assay that allowed characterization of the adherent cells and functional investigation of individual adhesive interactions. The capacity of adherent cytotoxic lymphoid cells to damage HIBEC was studied using a standard 51Cr release assay. RESULTS: Allogeneic lymphocytes were bound by HIBECs; this adherence was increased by activation of either participating cell type. Cells with cytotoxic capacity were bound preferentially. At least 50% of the overall adhesion was dependent on lymphocyte function-associated antigen 1. Cytotoxicity assays showed that HIBECs were susceptible to lysis by lymphokine-activated natural killer cells. CONCLUSIONS: This study shows that the adhesion molecules expressed by HIBECs are functional and necessary for the activity of cytotoxic effector lymphocytes.

Bile Ducts, Intrahepatic↗
PubMed1997

Immunologic responses to vaccinia vaccines administered by different parenteral routes.

To develop a less reactogenic but equally immunogenic vaccine, this study of 91 human volunteers compared the safety and immunogenic potency of a new, cell culture-derived vaccinia virus vaccine administered intradermally and intramuscularly with the licensed vaccinia vaccine administered by scarification. Cutaneous pox lesions developed in a higher proportion of scarification vaccinees. Scarification and intradermal vaccine recipients who developed cutaneous pox lesions had more local reactions but also achieved significantly higher cell-mediated and neutralizing antibody responses than those who did not develop pox lesions. Although less reactogenic, intradermal or intramuscular administration of vaccinia vaccine without the concomitant development of a cutaneous pox lesion induced lower immune responses.

Antibodies, Viral↗