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Biomedical subjects

M Gibson

Publications and source records attributed to M Gibson.

At least 91 records · Page 5Linked to original sources

Incidence, risk factors, management, and outcome of portal vein abnormalities at orthotopic liver transplantation.

Portal vein thrombosis is often considered a contraindication to orthotopic liver transplantation. We have analyzed the incidence, risk factors, management and outcome of patients with portal vein thrombosis undergoing orthotopic liver transplantation. During the period from October 1988 to October 1992 140 grafts were performed on 132 patients. Fourteen had portal vein thrombosis with either partial (n = 7) or complete (n = 7) occlusion of the portal vein at surgery. Portal vein thrombosis was more common in patients with autoimmune chronic active hepatitis (3/5 vs. 11/127, chi 2 = 13.3, P < 0.001), cryptogenic cirrhosis (4/12 vs. 10/120, chi 2 = 7.2, P < 0.01), or those with tumors (6/22 vs. 10/110, chi 2 = 5.7, P < 0.05). In 13 of the 14 portal inflow was reestablished by flushing, balloon thrombectomy, or passage of a graduated dilator. In one patient complete fibrous obliteration necessitated a portal vein to right gastroepiploic vein anastomosis. On follow-up there have been 6 deaths in this group (6/14 = 43%) from recurrent cancer (n = 1), sepsis (n = 4), and cardiac and renal failure (n = 1). Four of these 6 patients had confirmation of PV patency on imaging. The remaining 8 patients are alive and well (median follow-up 37 months, range 6-53 months). Post-transplant portal vein thrombosis occurred in 3 of the 14 patients (21%) with a portal vein abnormality at surgery and in two of the 118 patients with a normal portal vein (3/14 vs. 2/118, chi 2 = 8.5, P < 0.01). Four of the 5 cases were successfully treated by surgical thrombectomy.

Adolescent↗

Low-dose intra-arterial thrombolysis in the treatment of phlegmasia caerulea dolens.

Three patients with phlegmasia caerulea dolens treated successfully by low-dose intra-arterial thrombolysis are presented. In all patients a rapid improvement was observed and amputation avoided. The risk of pulmonary embolus was reduced by the use of a retrievable vena cava filter in one patient and thrombolytic therapy in the presence of a previously inserted cava filter in the other two.

Adult↗

The mouse Fas-ligand gene is mutated in gld mice and is part of a TNF family gene cluster.

The gene for the mouse Fas ligand was cloned and its chromosomal position determined. Fasl was tightly linked to gld (no crossovers in 567 meiotic events) on mouse chromosome 1 and closely linked with a novel member of the same TNF family of ligands, the Ox40 ligand (Ox40l, 1 crossover in 567 meiotic events). Southern blot analysis did not reveal any difference between the Fasl gene from gld and wild-type mice and levels of Fasl mRNA transcripts were similar in PMA and ionomycin induced wild-type and coisogenic gld T cells. Sequence analysis of the gld gene indicated a single amino acid change (Phe Leu) in the COOH terminal portion of this type II transmembrane protein, and COS cells transfected with Fasl cDNA from gld mice failed to induce apoptosis of Fas-expressing target cells. Thus, the data demonstrate that the gld phenotype is the result of a point mutation in the Fasl gene and that Fasl is part of a complex of ligands structurally related to TNF mapping within a small region of mouse chromosome 1.

Amino Acid Sequence↗

Design and implementation of a new radiology consultation service in a teaching hospital.

The steady increase in costs related to testing has been a major factor in the overall growth of health care expenses. Concern is substantial about the excessive number of tests ordered by physicians without measurable improvement in patients' outcomes. This is of particular concern in teaching hospitals, because in addition to the direct impact on national health care expenditures, these are the institutions in which young physicians train and formulate test-ordering practices. Proper selection of imaging tests is a complex process that requires detailed information about the patient; specific questions to be answered; and knowledge of the characteristics of the test, including sensitivity, specificity, risks, and cost. To date, no systematic method exists for combining the expertise of the radiologist with that of the referring physician before the tests are selected. Therefore, we designed a new clinical service within the radiology department that allows formal, on-the-ward consultation to assist internal medicine housestaff in the selection of radiologic tests. The goal of this study was to assess the feasibility of this formal radiology consultation service and to determine how often its imaging recommendations were implemented for patients with complicated medical conditions.

Boston↗

Molecular cloning and characterization of 13 out genes from Erwinia carotovora subspecies carotovora: genes encoding members of a general secretion pathway (GSP) widespread in gram-negative bacteria.

The chemical mutagen ethylmethanesulphonate (EMS) has been used to generate mutants of Erwinia carotovora subspecies carotovora which are defective in the secretion of pectinases (Pel) and cellulases (Cel) but unaltered for protease (Prt) secretion. Such mutants, called Out-, still synthesize Pel and Cel but these enzymes accumulate within the periplasm. Cosmid clones carrying wild-type E. carotovora ssp. carotovora DNA, identified by their ability to restore the Out+ phenotype when transferred to some Out- mutants, were classified into six complementation groups using cosmids and cosmid derivatives. Analysis of the nucleotide sequence of a 12.7 kb DNA fragment, encompassing complementing cosmid inserts, revealed a coding capacity for 13 potential open reading frames (ORFs), and these were designated outC-outO. Some of the out gene products were visualized using a T7 gene 10 expression system. The predicted Out proteins are highly similar to components of extracellular enzyme secretion systems from a diverse range of eubacteria including Erwinia chrysanthemi, Klebsiella oxytoca, Aeromonas hydrophila, Pseudomonas aeruginosa and Xanthomonas campestris. Lower levels of similarity exist between Ecc Out proteins and components of macromolecular trafficking systems from Bacillus subtilis, Haemophilus influenzae, Agrobacterium tumefaciens, Yersinia pestis and a protein involved in the morphogenesis of filamentous bacteriophages such as M13.

Amino Acid Sequence↗

Measurement of insulin-like growth factor-II in human plasma using a specific monoclonal antibody-based two-site immunoradiometric assay.

An immunoradiometric assay (IRMA) for the measurement of insulin-like growth factor-II (IGF-II) in human plasma has been developed, optimized and evaluated clinically in normal subjects and patients with disorders of the GH/IGF-I axis. Six monoclonal antibodies (MAbs) to recombinant human IGF-II (rhIGF-II) were produced, all of which had low cross-reactivity with rhIGF-I (< 0.01%) and insulin (< 0.01%). Compatibility of pairs of MAbs was tested in two-site IRMAs using three radioiodinated MAbs and three MAbs linked to Sephacryl S-300 (with separation of bound and free radiolabelled MAb by sucrose layering). Seven pairs of MAbs bound rhIGF-II and the combination of 125I-labelled W3D9 and W2H1 linked to solid phase was selected. The optimized assay had a completion time of 4 h, a minimum detection limit of 30 ng/ml (2.5 standard deviations from the zero standard) and detected a single peak of endogenous IGF-II in normal plasma which co-eluted with rhIGF-II after acid gel chromatography. IGF-II was measured in formic acid/acetone extracts of plasma from 16 normal subjects (mean 685, range 516-1008 micrograms/l), four acromegalic patients (mean 637, range 553-700 micrograms/l), fourteen patients with type-1 diabetes (mean 635, range 247-753 micrograms/l), nine patients with uraemia (mean 423, range 78-850 micrograms/l), and three patients with Laron-type GH insensitivity (75, 35 and 36 micrograms/l). No significant fluctuations were detected between samples obtained hourly from 08.00 to 19.00 h in normal subjects. Low levels of IGF-binding proteins (IGFBPs) remaining in plasma extracts may interfere with the measurement of IGF-II and give rise to falsely elevated IGF-II levels in radioimmunoassays or falsely suppressed levels in IRMAs. Such interference did not occur with the IRMA when used to measure IGF-II in extracts from normal subjects, acromegalic patients and patients with type-1 diabetes, and the addition of excess rhIGF-I in order to displace IGF-II from residual IGFBPs had no effect on IGF-II measurements in these samples. However, levels of IGF-II measured in extracts from patients with Laron-type GH insensitivity and patients with uraemia increased markedly after preincubation with excess rhIGF-I. The accurate measurement of IGF-II by IRMA in extracts from these subjects therefore requires the displacement of IGF-II from IGFBPs prior to assay. We conclude that, in contrast to radioimmunoassays, the two-site IRMA developed here provides a practical, rapid and specific method for the measurement of IGF-II in human plasma.

Antibodies, Monoclonal↗

Shipping stress and social status effects on pig performance, plasma cortisol, natural killer cell activity, and leukocyte numbers.

Crossbred pigs were used to evaluate the effects of shipping stress on natural killer (NK) cell activity, leukocyte numbers, plasma cortisol, and BW changes. In the first study, pigs were bled at a commercial farm and, after shipping, resident and shipped pigs were bled again. Plasma cortisol concentrations were not different (P > .10) because of large variation in cortisol concentrations. Furthermore, NK cytotoxicity was nondetectable among all pigs. A second study showed that plasma cortisol concentration rose by approximately 2.6 ng/mL (P = .018) for each minute after pigs were aroused. In the third, more controlled study, pigs were housed in pens of three pigs each. Video recordings were made during the first 24 h pigs were grouped to identify socially dominant, intermediate, and submissive pigs. At time zero (before shipping), resident pigs and those to be shipped had similar plasma cortisol concentrations. However, after the 4-h shipping experience, shipped pigs had elevated (P < .05) plasma cortisol compared with resident control pigs. Shipped pigs lost 5.1% of their BW (P < .05) compared with resident pigs, which gained .02% of their BW. Body weight change during shipping and plasma cortisol were negatively correlated (r = -.34, P = .04), indicating pigs that had greater adrenal response to shipping also lost more weight during shipping. Shipping reduced (P < .05) NK cytotoxicity among pigs of intermediate and submissive social status compared with shipped, dominant pigs. At the end of shipping or control treatments, the correlation between NK cytotoxicity and plasma cortisol was positive (r = .35, P = .036), indicating that pigs with greater cortisol response had greater NK cytotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Ovulation after intravenous and intramuscular human chorionic gonadotropin.

OBJECTIVE: To define the time interval from intravenous and intramuscular hCG administration to follicular wall rupture and the endocrinologic events associated with ovulation. DESIGN: Subjects were studied in two cycles and received hCG either 10,000 IU IM or 500 IU IV in a random sequence with an intervening spontaneous menstrual cycle. PATIENTS: Thirty women from the University of Vermont Reproductive Endocrinology Service with unexplained, male, or cervical factor infertility. INTERVENTIONS: Subjects underwent superovulation with clomiphene citrate followed by hCG administration when the lead follicle reached a mean diameter of 18 mm. Follicular rupture was determined by ultrasound monitoring every 2 hours starting 31 and 30 hours after intravenous and intramuscular hCG, respectively. Serum samples were obtained hourly for hormone measurements. The study was completed 2 hours after follicular rupture or 48 hours after hCG administration. RESULTS: Twenty-five subjects received both intramuscular and intravenous hCG. The mean time to ovulation was 40.4 hours after intramuscular hCG (range, < or = 36 to > or = 48 hours) and 38.3 hours after intravenous hCG (range, 33 to > or = 48 hours). No differences were noted in the time interval to ovulation or rate of change in circulating E2 and P levels after IM versus IV hCG administration. CONCLUSIONS: These findings suggest (1) ovulation occurs over a broad range of time after hCG administration; (2) ovulation does not occur in a more specific time interval after intravenous than intramuscular hCG; and (3) the rate of change in circulating E2 and P levels are not different after intravenous than intramuscular hCG.

Chorionic Gonadotropin↗

Somatostatin inhibits vasopressin-stimulated phosphoinositide hydrolysis and influx of extracellular calcium in clonal hamster beta (HIT) cells.

Vasopressin (VP) stimulates insulin secretion and inositol phosphate (InsP) production in clonal hamster beta cells (HIT) via a cyclic AMP-independent V1-receptor-mediated signal-transduction pathway. Somatostatin (SRIF) inhibited VP-stimulated insulin secretion, and the effects of SRIF were abolished by pretreatment with pertussis toxin. The Ca(2+)-channel blockers verapamil and nifedipine also inhibited VP-stimulated insulin secretion during 20 min incubations, but verapamil was ineffective at 2 min, and the effects of SRIF and nifedipine together were not addictive. SRIF failed to inhibit further the attenuated insulin response to VP in Ca(2+)-free medium. VP-stimulated InsP production was also inhibited by SRIF in a pertussis-toxin-sensitive manner. Whereas VP-stimulated insulin secretion was almost completely inhibited by SRIF at an equimolar concentration, VP-stimulated InsP production was much less sensitive to inhibition by SRIF, even at a 100-fold excess concentration. VP increased cytosolic Ca2+ in HIT cells loaded with fura 2, the fluorescent Ca2+ indicator. The increase was biphasic, with an initial rapid spike increase followed by a prolonged second phase. Both SRIF, at a concentration which inhibited VP-stimulated insulin secretion but not InsP production, and verapamil failed to inhibit the rapid spike increase in intracellular Ca2+, but did inhibit the second phase. We conclude that VP induces biphasic changes in cytosolic Ca2+, secondary to mobilization of intracellular Ca2+ and influx of extracellular Ca2+. SRIF inhibits insulin secretion by interrupting influx of extracellular Ca2+, likely by inhibiting Gi-subunit activity. Inhibition of VP-stimulated phosphoinositide hydrolysis, which is also pertussis-toxin-sensitive, may represent an additional mechanism of action of SRIF.

Animals↗

A method for the independent assessment of the accuracy of hematology whole-blood calibrators.

An independent assessment of the accuracy with which a large manufacturer assigned values to hematologic calibrators was performed. Data were collected from 1,767 hospitals and clinics distributed over North America. Statistical analysis of the mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration of these patient data confirmed the accuracy of the values for hemoglobin, erythrocyte count, hematocrit, and erythrocyte indices for the calibrators manufactured and released during a 9-month period. This approach proved both workable and effective in detecting inaccuracies of less than 1%. Few technologist-users have the time or the equipment to verify independently the accuracy of hematologic calibrators. The manufacturers should perform ongoing, independent assessments of the accuracy of their products. The statistical analysis of patient data provides manufacturers with a suitable method.

Calibration↗

A preliminary evaluation of the use of a redox agent in the treatment of chronic periodontitis.

A small-scale clinical trial was carried out to evaluate the effect of a redox agent, methylene blue, on microbiological and clinical indices of chronic periodontitis. Methylene blue was applied subgingivally on a daily basis for 7 d to 25 test sites in 7 patients and the sites evaluated clinically and microbiologically for up to 14 d: 25 control sites in the same patients received sterile water. The test sites showed statistically significant differences from the control sites in terms of changes in a number of clinical and microbiological indices. In the test sites the proportions of anaerobes, Gram-negative anaerobes, spirochetes and motile bacteria decreased, as did the crevicular fluid flow, while the proportions of facultative anaerobes and cocci increased. These changes are indicative of a shift towards periodontal health. No significant differences were observed between the test and control sites in terms of bleeding on probing or pocket depth. The encouraging results of this preliminary study suggest that the use of redox agents in the treatment of chronic periodontitis warrants further investigation.

Adult↗

Radiography for back pain presenting to accident and emergency departments.

In order to determine the relevance of radiographs of the lumbar spine in an A&E department 225 consecutive patients presenting in a 6-month period with acute back pain were studied. An analysis of the number of radiographs performed and their association with particular factors in the history and examination of the patient was performed. A total of 108 patients had radiographs (48%), with a total of seven fractures (6% of radiographs). All the patients with fractures had a history of direct trauma. Radiographs had no bearing on the decision to admit the patient. The indications for radiography of the lumbar spine in the A&E department are discussed.

Adolescent↗