The pedicled tensor fasciae latae flap as a salvage procedure for an infected abdominal mesh.
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Abdominal Muscles↗
Biomedical subjects
A D'Hoore
Publications and source records attributed to A D'Hoore.
Interactions of a bicyclic analog of colchicine with beta-tubulin isoforms alphabeta(II), alphabeta(III) and alphabeta(IV).
Tubulin exists as various isoforms, which differ in their assembly, drug-binding properties, and the dynamic properties of the microtubules they compose. One of the most striking differences in drug binding among the isoforms is observed with colchicine, which binds much better to the alphabeta(II) and alphabeta(IV) isoforms than to the alphabeta(III) isoform. Here we have studied the interaction of these isoforms with 2-methoxy-5-(2',3',4'-trimethoxyphenyl) tropone (MTPT), an analog of colchicine that lacks the B-ring. The kinetics of association and dissociation were studied fluorometrically, and the kinetic parameters for the two-step binding were determined for different beta-tubulin isoforms. The apparent on-rate constants for alphabeta(II), alphabeta(III) and alphabeta(IV) were 13358, 4558 and 10828 M(-1) s(-1), the off-rate constants (k(-2)) were 0.04, 0.03 and 0.02 s(-1), and the affinity constants are 3.33 x 10(5), 1.56 x 10(5) and 5.44 x 10(5) M(-1), respectively. The differences in kinetic parameters among different beta-tubulin isoforms are greatly reduced when the B-ring is removed. Our results indicate that the B-ring plays a major role in determining the isoform differences, and the results might be of importance for designing tissue-specific analogs of colchicine for cancer chemotherapy.
Colchicine↗
Abdominal resection rectopexy versus Delorme's procedure for rectal prolapse: a predictable outcome.
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Evaluation Studies as Topic↗
Surgery for gastric remnant carcinoma following Billroth II gastrectomy.
Between January 1983 and December 1995, 31 patients with gastric remnant carcinoma were operated on 6-45 years after a Billroth II resection for peptic ulcer disease. Total gastrectomy with Roux-en-Y reconstruction was performed in all cases. In 16 patients (52%) extended resection with removal of one or more adjacent organs was necessary for oncological reasons. In this elderly population with a high incidence of pre-operative risk factors (55%), most tumours were classified as stage III or IV (45%). Although total gastrectomy should be the surgical option of first choice for gastric remnant carcinoma, it resulted in high levels of post-operative mortality and morbidity (13% and 35%, respectively), especially in patients with stage III and IV tumours who underwent resection of an adjacent organ. Despite extended surgery, if necessary, the recurrence rate after 'curative' surgery is high (8/20 patients) and the cumulative disease-free 5-year survival rate was 48%. Detection of the tumour at an earlier stage not only limits the extent of resection and lowers the complication rate, but also improves survival.
Aged↗
Kinetics of association and dissociation of two enantiomers, NSC 613863 (R)-(+) and NSC 613862 (S)-(-) (CI 980), to tubulin.
The kinetics of binding of R- and S-enantiomers were studied by the fluorescence stopped-flow technique. For the R-enantiomer, the time course of the increase in fluorescence is best fitted by a sum of two exponentials. In pseudo-first-order conditions, the first observed rate constant showed a linear concentration dependence whereas the second showed a hyperbolic one. The dissociation rate constants were determined independently by displacement experiments with 2-methoxy-5-(2,3,4-trimethoxyphenyl)-2,4,6-cycloheptatrien-1-one (MTC). The two exponential phases were assumed to be due to a two-step binding mechanism: an initial binding followed by a conformational change. This is different from colchicine and MTC binding, where the two phases show a hyperbolic concentration dependence and are attributed to the parallel binding to different isoforms of tubulin [Banerjee, A., & Luduena, R. F. (1992) J. Biol. Chem. 267, 13335-13339]. R-isomer binding did not discriminate between the tubulin isoforms. The temperature dependence of all the rate constants were measured, and the entire thermodynamic reaction path was constructed. For the S-isomer, the direct fluorescence stopped-flow study showed that the signals were largely imputable to the fluorescence of the binding at low-affinity sites [Leynadier, D., Peyrot, V., Sarrazin, M., Briand, C., Andreu, J. M., Rener, G. A., & Temple, C., Jr. (1993) Biochemistry 32, 10674-10682]. Therefore, we exploited the competition between R- and S-isomers to determine the binding kinetics of the S-isomer to the R-site. The observed rate constants for competitive binding showed a linear concentration dependence, thus allowing us to calculate the association rate constant of the S-isomer to the R-site. The kinetics of displacement of the S-isomer by MTC allowed the dissociation rate constant for the S-isomer to be determined. The binding of both enantiomers to tubulin in presence of tropolone methyl ether (analog of the colchicine C ring) was decreased, indicating the involvement of the C subsite.
Animals↗
Immobilizing and imaging microtubules by atomic force microscopy.
Microtubules isolated from pig brains have been immobilized on an inorganic substrate for use in AFM studies. The method employs 4-aminobutyldimethylmethoxysilane and glutaraldehyde to activate a silicon wafer for binding the biopolymer. The covalent bond ensures the positional stability of the tubules on the substrate, and allows reproducible scanning probe experiments. Microtubules have been imaged both by atomic force and scanning tunneling microscopy, yielding results very similar to electron microscopy. The average apparent height of the tubules is smaller than observed with transmission electron microscopy (25 nm) and is smaller in buffer solution (10 nm) than in air (15 nm). The biopolymer surface is softer under buffer than in air. The highest resolution was obtained with the tapping mode where surface features as small as 10 nm in X and Y have been resolved. Gold-coated tubules bound on silicon have been successfully imaged by STM, while images of uncertain origin were generated for tubules deposited on graphite. It is shown that artefacts imaged on a blank graphite surface can easily be confounded with collapsed tubules.
Animals↗
Interaction of desacetamidocolchicine, a fast binding analogue of colchicine with isotypically pure tubulin dimers alpha beta II, alpha beta III, and alpha beta IV.
Desacetamidocolchicine (DAAC) is a colchicine analogue that lacks the acetamido side chain in the ring-B of colchicine. Unlike colchicine, it binds to tubulin very quickly, and yet it has powerful antimitotic properties. It has been demonstrated that the beta-tubulin isoforms differ significantly in their interactions with colchicine. In an effort to understand the role of the ring-B of colchicine, we have studied the interaction of DAAC with purified beta-tubulin isoforms. The association was studied fluorometrically using a stopped-flow instrument under pseudo-first-order conditions in the presence of a large excess of drug. The observed pseudo-first-order rate constants increased in a nonlinear way with the drug concentration, indicating that the binding of DAAC to tubulin isoforms occur in two steps as is true for the binding of colchicine to tubulin (Garland, D.L. (1978) Biochemistry 17, 4266-4272), [formula: see text] where the first step is a fast reversible binding and the second step is a slow conformational change leading to the formation of the stable complex (T.DAAC)*. Kinetic analysis shows that the tubulin isoforms exhibit very little differences in their K1 values, which are 5794 +/- 670, 7109 +/- 1800, and 8993 +/- 1780 M-1 for alpha beta II, alpha beta III, and alpha beta IV, respectively. The k2 values for alpha beta II, alpha beta III, and alpha beta IV are 0.67 +/- 0.05, 0.05 +/- 0.006, and 0.59 +/- 0.07 s-1, respectively. The apparent on-rate constants (k(on,app) = K1k2) for alpha beta II, alpha beta III, and alpha beta IV are 3907 +/- 530, 376 +/- 80, and 5305 +/- 1200 M-1 s-1, respectively. The off-rate constants as measured by the loss of fluorescence of drug-tubulin complexes in the presence of a large excess of podophyllotoxin are 6.3 x 10(-4), 5.2 x 10(-4), and 5.7 x 10(-4) s-1, respectively, for alpha beta II, alpha beta III, and alpha beta IV. The affinity constants as determined by Scatchard analyses are 2.5 x 10(6), 1.5 x 10(6), and 4 x 10(6) M-1 for alpha beta II, alpha beta III, and alpha beta IV, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Evidence for an alternative pathway for colchicine binding to tubulin, based on the binding kinetics of the constituent rings.
The kinetics of tropolone methyl ether binding to tubulin were measured by following the loss of colchicine binding capacity upon preincubation of tubulin with tropolone methyl ether. At 25 degrees C a bimolecular association rate constant of 2.7 (+/- 0.2) M-1 min-1 was determined, and from the temperature dependence an activation energy of 37 (+/- 8) kJ.mol-1 was calculated. By displacement experiments a dissociation rate constant of 2.9 (+/- 0.6) x 10(-2) min-1 was determined at 25 degrees C. The effect of 3',4',5'-trimethoxyacetophenone (TMA) is 2-fold. TMA reduces the apparent association rate constant of colchicine, indicating that it equilibrates very rapidly and reversibly with the colchicine binding site. From this reduction the binding constant for TMA can be obtained. At 25 degrees C a value of 112 (+/- 13) M-1 is estimated. The binding of TMA is practically thermoneutral. Preincubation of tubulin with TMA over 30 min not only reduces the subsequent binding rate constant of colchicine but also the amplitude. This indicates that TMA also binds slowly in a second mode or site. Stopped-flow kinetic studies reveal that fast TMA binding competes for the initial binding of colchicine. From these results it is concluded that colchicine binds initially with its trimethoxybenzene ring and in a subsequent step with the tropolone ring.
Acetophenones↗
Major pulmonary resections: pneumonectomies and lobectomies.
We report on our experience in 20 patients who underwent major thoracoscopic pulmonary resections between October 1991 and November 1992. These consist of 2 left pneumonectomies, 17 lobectomies, and 1 segmentectomy. The indications were strictly limited to benign pulmonary diseases and stage I (TNM) primary lung cancer. A hilar lymphadenectomy was performed in all cases of malignancy. Our surgical technique is described. Our findings demonstrate the feasibility of performing major video-assisted thoracoscopic pulmonary resections, even though the definite role of this procedure in the management of lung cancer must still be defined.
Female↗
Multiple trauma in elderly patients. Factors influencing outcome: importance of aggressive care.
From 1978 to 1991, 126 multiply-injured patients of 65 years and over were admitted to the Department of Traumatology and Emergency Surgery of the University Hospitals of Leuven. The seriousness of the injury was evaluated using the Injury Severity Score (ISS) and the Glasgow Coma Scale (GCS). Traffic accident (57 per cent) and a simple fall at home (30 per cent) were the main causes of injury. The overall mortality rate within 6 months was 17 per cent. Multiple system organ failure (MSOF) was responsible for the fatal outcome in 48 per cent of the cases and in 71 per cent of the deaths more than 7 days after trauma. Of the survivors still living at home before injury, 78 per cent were able to go back to their normal surroundings. Survivors were compared with non-survivors. There was no significant difference in age or in ISS, nor in pre-existing diseases. On the other hand, the GCS was of important prognostic value, both for survival and functional recovery (P < 0.001). Also, the need for early intubation and continued ventilation were predictive of survival (P < 0.001). Nevertheless, this need for respiratory assistance was not an indication for withdrawing support as 9 per cent of the survivors also required endotracheal intubation for 5 days or longer. In our opinion, aggressive trauma care for the elderly is justified.
Accidental Falls↗
Fluorescence stopped-flow study of the interaction of tubulin with the antimitotic drug MDL 27048.
The kinetics of the binding of MDL 27048 to tubulin have been studied by fluorescence stopped flow. The binding is accompanied by a fluorescence increase. The time course can be described by a sum of two exponentials, assumed to be due to the presence of two major tubulin isoforms. The observed rate constants depend in a nonlinear way on the concentration of MDL in pseudo-first-order conditions. This concentration dependence can be described by the presence of a fast equilibrium of low affinity, followed by an isomerization of the initial complex. The dissociation kinetics have been studied by displacement experiments, in which MTC was used as a competitive ligand. The reaction enthalpy change for the first binding equilibrium and the activation energies for the forward and reverse steps of the isomerization were determined from the temperature dependence. This was possible for the two tubulin isotype populations. The kinetics of the binding of MDL to tubulin are slowed down in the presence of 3',4',5'-trimethoxyacetophenone, a fast binding analog of the colchicine A-ring, but are not influenced by the binding of tropolone methyl ether, indicating that the binding site of MDL has the A-subsite in common with colchicine, but not the C-subsite.
Animals↗
Radioimmunoguided surgery for colorectal carcinoma.
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Adult↗
The pathology of complex fistula in ano.
Anal fistulae do not heal spontaneously without surgery. Knowledge of anorectal anatomy and function, and diligent examination frequently requiring anaesthesia are prerequisites for adequate assessment, classification and treatment of the pathology. Fistulography, endoanal ultrasound and MRI of the anorectum may have additional diagnostic value with therapeutic impact in complex and recurrent fistulae. Parks' classification is most useful because it is the best guide for surgical therapy. In the modern treatment of trans- or suprasphincteric fistula in ano fast or slow division of any part of the striated perianal musculature is to be avoided in order to prevent anal incontinence.
Anal Canal↗
Restorative resections for ulcerative colitis.
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Age Factors↗
Advancement flap plasty for the closure of anal and recto-vaginal fistulas in Crohn's disease.
The management of anal fistulas in patients with IBD continues to be extremely challenging and, indeed, somewhat frustrating. Despite a global closure rate of about 75%, all patients should be informed about the risk of infection, early failure, eventual temporary disfunctioning stoma and the possibility of late recurrence (about 15%). Closure of a RVF in Crohn's disease should not be considered an easy undertaking, especially in patients with several Crohn localisations. The technique can be adapted to the local situation. Construction of a temporary stoma is not mandatory. However, stoma construction seems to be beneficial when extensive perianal or recto-vaginal dissection including eventual tissue interposition is required. Advancement flaps are an attractive surgical alternative for the management of all anal transsphincteric fistulas, also in Crohn's disease, because sphincter architecture and function are well preserved. Improved medical treatment and the changed approach from conservative to reparative surgery may well have resulted in a decreased need or at least in a delay of the need for a proctectomy. Although the surgical principles of advancement flap techniques are sound, these techniques have not been used for many decades. Skills needed, problematic approach, suboptimal quality of local tissues have contributed to its selective use and to the absence of prospective randomised studies.
Crohn Disease↗
Miliary tuberculosis following infliximab therapy for Crohn disease: A case report and review of the literature.
We present a case of miliary tuberculosis diagnosed 15 months after infliximab treatment despite negative screening for previous exposure to Mycobacteria on skin PPD and chest X-ray. This case shows that--although screening for TB with a skin PPD and a chest X-ray should be performed in all patients--this is not 100% effective and may be a problem in patients on concomitant immunosuppression. The clinical course of this patient further shows that in a patient treated with anti-TNF antibodies who's condition does not improve one should always be aware of the possibility of a tuberculosis infection. Even though tuberculosis is usually not rapidly fatal, the disease may show a fulminant course in immunocompromised patients.
Aged↗
Multiple trauma in patients of 65 and over. Injury patterns. Factors influencing outcome. The importance of an aggressive care.
In a first study of 416 polytrauma patients, 49 were aged 65 years or older. These "old patients" (mean age 72.1) were compared with the remaining 367 "young patients" (mean age 31.3). In a second study concerning 126 polytrauma patients of 65 and over, the survivors and non survivors were profiled and compared. The typical injured old patient was a pedestrian hit by a car or a motorbike or someone who had simply fallen at home. Despite the fact that the mean Injury Severity Score (ISS) was significantly lower in the old patients' groups (33.2 versus 42.1 degrees) (p < 0.0001) the mortality rate was higher (18% versus 7.6%) (p < 0.05). In old trauma victims multiple system organ failure (MSOF) was responsible for the fatal outcome in 48% of the cases and in 71% of the deaths more than 7 days after trauma. Seventy eight percent of the surviving old patients still living at home pre-injury were able to go back to their normal surroundings. In the old patients groups there was no significant difference in age nor in ISS nor in pre-existing diseases between survivors and non-survivors. On the other hand the Glasgow Coma Scale (GCS) was of important prognostic value, as well as to survival as to functional recovery (p < 0.001). Also the need for early intubation and continued ventilation were predictive of survival (p < 0.001). Nevertheless this need for respiratory assistance was not an indication for withdrawing support as also 9% of the survivors required endotracheal intubation for 5 days or longer.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗