Biomedical subjects

P Gibbs

Publications and source records attributed to P Gibbs.

At least 55 records · Page 3Linked to original sources

PubMed2000

A direct comparison of cytolytic T-lymphocyte responses to Melan-A peptides in vitro: differential immunogenicity of Melan-A27-35 and Melan-A26-35.

In this study we directly compared the in vitro responses of T-cells from normal donors and melanoma patients to Melan-A27-35 and Melan-A26-35. These peptides have been previously used in peptide-based vaccination studies. Following three stimulations with peptide-pulsed antigen-presenting cells in vitro, Melan-A-specific cytolytic T-lymphocytes (CTLs) were generated from seven of 20 subjects; two of the seven subjects responded reproducibly to both Melan-A27-35 and Melan-A26-35, three to only Melan-A27-35 and two to only Melan-A26-35. However, CTLs generated with either Melan-A27-35 or Melan-A26-35 showed cross recognition, and both types of CTL could recognize naturally processed antigen displayed on HLA-A2+ tumour cells. Furthermore, Melan-A-specific CTLs could also be generated by stimulating peripheral blood mononuclear cells with autologous melanoma cells. Our results suggest that some subjects may have a bias in their CTL repertoire which favours the generation of Melan-A27-35 specific CTLs, while others may favour Melan-A26-35 specific CTLs. It is also likely that CTL precursors capable of detecting both peptides may have different affinities to the two Melan-A peptides. Since it is difficult to predict the CTL responses to Melan-A peptide in a given individual, we suggest vaccinating with both Melan-A27-35 and Melan-A26-35 peptides in clinical trials.

Cancer Vaccines↗

PubMed2000

A phase II study of biochemotherapy for the treatment of metastatic malignant melanoma.

The use of interleukin-2 (IL-2) and interferon-alpha (IFNalpha) in combination with chemotherapy for the treatment of advanced malignant melanoma has generated considerable interest. In particular, the relatively high number of durable complete responses has suggested this may be a significant advance in the treatment of malignant melanoma. We report our experience at the University of Colorado in 43 patients, including many with poor prognostic factors. Patients received cisplatin 20 mg/m2 on days 1-4, vinblastine 1.6 mg/m2 on days 1-4, dacarbazine 800 mg/m2 on day 1, IL-2 9 x 10(6) IU/m2 per day intravenously over 24h on days 1-4 and IFNalpha 5 x 10(6) IU/m2 per day subcutaneously on days 1-5 every 3 weeks. The median follow-up for all patients was 34 months. Responses were seen in 20 patients (47%, 95% confidence interval 31-62%) and comprised five complete responses (CRs) (12%) and 15 partial responses (PRs) (35%). Two patients achieving a CR remain disease free at 45 and 47 months follow-up. In addition three patients who obtained a surgical CR and another with only minor residual changes on computed tomography scan have not progressed at 27, 30, 40 and 27 months, respectively. Toxicity was manageable, but all patients had at least one grade 3 or 4 toxicity, predominantly hypotension and neutropenia. There were no treatment-related deaths. In conclusion, the response rate and duration is within the range previously reported for biochemotherapy. The results of ongoing randomized studies are awaited to better define the value of biochemotherapy in the treatment of advanced melanoma.

Abdominal Neoplasms↗

PubMed2000

MAGE-12 and MAGE-6 are frequently expressed in malignant melanoma.

MAGE proteins have been identified as potential specific targets for cancer vaccination. Although MAGE-6 and MAGE-12 were originally identified in malignant melanoma there are no studies reporting the frequency of expression of these antigens in this malignancy. These are of relevance particularly for MAGE-6 as recent studies have identified CTL activity against several epitopes. We have studied MAGE-1, -2, -3, -4, -6 and -12 gene expression using reverse transcription-polymerase chain reaction in 47 melanoma samples and 11 melanoma cell lines established from these tumours. The tumour samples expressed MAGE-12 (74%) and MAGE-6 (64%) mRNA at much higher frequencies than the other MAGE genes. MAGE-12 and MAGE-6 were expressed at the highest frequencies, relative to the other MAGE antigens, in early stage lesions. The frequency of expression of all the MAGE genes was found to be higher in samples from metastatic deposits compared to those from locoregional disease. The cell lines all expressed the same or more MAGE antigens than the tumours from which they were derived. In only one cell line was expression of a MAGE antigen lost. Certain recurring patterns of MAGE expression were observed in the tumour samples. MAGE-6 and/or -12 expression were detected in all of those 26 tumour samples that were positive for one or more of MAGE-1, -2, -3 and -4. Twenty of these 26 samples expressed both antigens. These findings suggest that protocols targeting MAGE-12 and -6 would permit many more patients to be included into clinical cancer vaccination trials.

Adult↗

PubMed2000

Underwater disorientation as induced by two helicopter ditching devices.

BACKGROUND: Spatial orientation is based on the integration of concordant and redundant information from the visual, vestibular, and somatosensory systems. When a person is submerged underwater, somatosensory cues are reduced, and vestibular cues are ambiguous with respect to upright or inverted position. Visual cues may be lost as a result of reduced ambient light. Underwater disorientation has been cited as one of the major factors that could inhibit emergency egress after a helicopter ditching into water. One countermeasure to familiarize aircrew with underwater disorientation is emergency egress training. This study examined the relative degree of underwater disorientation induced by the Modular Egress Training Simulator (METS) and the Shallow Water Egress Trainer (SWET). METHODS: There were 36 healthy subjects (28 males and 8 females) who participated in the study. Underwater disorientation was quantified by measuring the deviation of subjective vertical-pointing from the gravitational vertical, time to egress, and subjective reports of disorientation and ease of egress. A repeated measure design was employed with seat position (SWET chair, METS window, and METS aisle) as the sole factor. RESULTS: Subjective response data indicated that the degree of disorientation is rated significantly higher, and the ease of egress is rated worse from the two METS seat positions than from the SWET. This is supported by the findings that subjective vertical-pointing accuracy is worse in the METS seat positions than in the SWET (p < 0.01). The time to egress is longer from the two METS seat positions than from SWET (p < 0.01). CONCLUSION: Our results indicate that the METS device is effective for inducing underwater disorientation as provoked by simulated helicopter ditching. disorientation, vestibular, subjective pointing.

Accidents, Aviation↗

PubMed1999

Efficiency of four secondary enrichment protocols in differentiation and isolation of Listeria spp. and Listeria monocytogenes from smoked fish processing chains.

Four secondary enrichment protocols (conventional methods: UVM II, Fraser 24 h and Fraser 48 h: Impedimetric method: Listeria electrical detection medium) were studied for their ability to isolate Listeria spp. and Listeria monocytogenes from fish and environmental samples collected along the processing chain of cold-smoked fish. From all methods, Listeria spp. and L. monocytogenes were respectively present in 56 and 34 of 315 samples analysed. Fraser broth incubated for 48 h gave the fewest false negative Listeria spp. results [4/56; (7.1%)], but concurrently only 15/34 (44.1%) samples were correctly identified as containing L. monocytogenes, Listeria electrical detection (LED) medium detected only 36/56 (64.3%) Listeria spp. positive samples. Despite this lower isolation rate, LED identified 20/34 (58.8%) L. monocytogenes positive samples correctly and gave fewer false positive results. The overall conclusion was that more than one isolation method is needed to accurately estimate L. monocytogenes contamination rates.

Animals↗

PubMed1999

Thermal inactivation of Alicyclobacillus acidoterrestris spores under different temperature, soluble solids and pH conditions for the design of fruit processes.

Alicyclobacillus acidoterrestris, a thermoacidophilic, non-pathogenic and spore-forming bacterium has been detected in several spoiled commercial pasteurised fruit juices. A. acidoterrestris spores, besides being resistant to the pasteurisation treatment conditions normally applied to acidic fruit products, can germinate and grow causing spoilage. Therefore, this microorganism was suggested as the target to be used in the design of adequate pasteurisation processes. The objectives of this work were to investigate the influence of temperature (T: 85-97 degrees C), total soluble solids (SS: 5-60 degrees Brix or % by weight) and pH (2.5-6.0) on D-values (decimal reduction time) of Alicyclobacillus acidoterrestris (type strain, NCIMB 13137) spores, and to fit a model using response surface methodology. A central composite face-centred experimental design was used, and the response, D-value determined in malt extract broth, ranged between 0.498+/-0.045 and 94.9+/-6.7 min. Within the factor ranges studied, temperature was the parameter that most affected the D-value. Following this was the SS and, lastly, the pH value. A linear decrease in D-value was observed with decreasing SS and pH, and a non-linear decrease in D-value was noticed with increasing temperature. A second order polynomial was successfully fitted to the data (R2 = 0.98). In general, D-values measured in real fruit systems, such as orange, apple and grape juices, blackcurrant concentrates, cupuaçu (exotic fruit) extract and orange juice drink, were higher than those predicted by the malt extract broth model. This result emphasises the importance of experimental validation of any model-derived process.

Bacillaceae↗

PubMed1999

An investigation into the risk of air embolus during veno-venous bypass in orthotopic liver transplantation.

After observing micro-bubble activity in the venovenous bypass system during liver transplantation, an experiment was designed to investigate the origin of these bubbles and to define the conditions under which they occurred. Using a Biomedicus constrained vortex pump and a customized circuit design, microbubble activity was measured in saline and blood media during varying pre- and post-head pressures. The data show that air emboli can be generated from this pump and the rate at which they develop is directly related to the pre- and post-head pressure and hematocrit.

Anastomosis, Surgical↗

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↗

PubMed1999

Dynamic contrast-enhanced MRI in the differentiation of breast tumors: user-defined versus semi-automated region-of-interest analysis.

Dynamic contrast-enhanced MR mammography is an increasingly used method of evaluating breast pathology. The purpose of this study was to compare two semi-automated methods of region of interest (ROI) analysis with a user-defined method, in the discrimination of breast tumors using dynamic contrast-enhanced MRI. Results are presented from the retrospective analysis of 81 malignant and 36 benign breast lesions. The study demonstrates the importance of a consistent ROI strategy and also shows that semi-automated approaches offer a standardized method, which may improve the discrimination of primary breast tumors. J. Magn. Reson. Imaging 1999; 10:945-949.

Adenocarcinoma↗

PubMed1999

Living-related liver transplantation: is Doppler sonography sufficient to define the hepatic artery anatomy before surgery?

OBJECTIVE: to evaluate the accuracy of colour Doppler sonography (CDS) in the assessment of the left hepatic arterial supply in living donors before hepatic transplantation. MATERIAL AND METHODS: Pre-operative sonographic Doppler data of the left hepatic artery (LHA) were compared retrospectively with the selective hepatic angiographic data and the intra-operative observations in 60 living donors. RESULTS: Pre-operative Doppler data of the LHA were available in 53 cases and incomplete or absent in seven cases. In 51 cases (96%) the origin of the LHA or an accessory LHA were correctly described at Doppler sonography (44 classical LHA in anatomic position, seven accessory LHA). In 11 cases (21%), Doppler data were insufficient or incorrect to define the arterial supply of the hepatic segments II, III and IV. Doppler studies were unable to determine the length or the diameter of the LHA. CONCLUSION: Doppler sonography seems to be able to define the main left hepatic artery anatomy. Selective hepatic angiography is still indicated to determine the length, diameter and intra-hepatic segmental supply.

Hepatic Artery↗

PubMed1999

Evaluation of cynomolgus (Macaca fascicularis) and rhesus (Macaca mulatta) monkeys as experimental models of acute Q fever after aerosol exposure to phase-I Coxiella burnetii.

BACKGROUND AND PURPOSE: Q fever is a disease of humans. Vaccines to prevent this disease have demonstrated efficacy in rodents and must also be evaluated for efficacy in a nonhuman primate model. Preliminary to vaccine efficacy experiments, cynomolgus and rhesus monkeys were evaluated as suitable experimental models of acute Q fever. METHODS: Both species of monkeys were challenged with aerosolized 10(5) virulent phase-I Coxiella burnetii Henzerling strain, and clinical and serologic responses were determined. RESULTS: Radiographic changes were observed in seven of eight monkeys of both species; however, changes in cynomolgus monkeys tended to be more significant. Between 7 and 10 days after challenge, all rhesus monkeys and 88% of cynomolgus monkeys were bacteremic. Sequential increases in antibody responses to C. burnetii phase-I and phase-II whole cells and phase-I lipopolysaccharide were observed in both species. Although the maximal rectal temperature increase was similar in both species, duration of fever was slightly longer in rhesus monkeys. Clinical features were similar to those described in human acute Q fever patients. CONCLUSIONS: On the basis of the more pronounced radiographic changes in cynomolgus monkeys, we favor use of this species for future studies of vaccine efficacy.

Acute Disease↗

PubMed1999

Non-BSNs provide quality cancer care.

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Clinical Competence↗

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↗