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Biomedical subjects

G Pron

Publications and source records attributed to G Pron.

17 recordsLinked to original sources

Therapeutic failure of uterine fibroid embolization caused by underlying leiomyosarcoma.

The authors describe an unusual case in which continued growth of uterine fibroids in a postmenopausal patient after polyvinyl alcohol embolization therapy prompted hysterectomy, which revealed an underlying leiomyosarcoma. The surgery was nearly fatal as a result of venous bleeding, and parasitization of blood from adjacent bowel by the tumor was noted. The difficulty of preoperative diagnosis of leiomyosarcoma and the need for diligent follow-up after uterine fibroid embolization are discussed.

Embolization, Therapeutic↗

Screening for oropharyngeal dysphagia in stroke: insufficient evidence for guidelines.

There is no evaluation of the evidence for the screening of oropharyngeal dysphagia in stroke. We reviewed the literature on clinical screening for oropharyngeal dysphagia in adults with stroke to determine (a) the accuracy of different screening tests used to detect dysphagia defined by abnormal oropharyngeal physiology on videofluoroscopy and (b) the health outcomes reported and whether screening alters those outcomes. Peer-reviewed English-language and human studies were sought through Medline (from 1966 to July 1997) by using the key words cerebrovascular disorders and deglutition disorders, relevant Internet addresses, and extensive hand searching of bibliographies of identified articles. Of the 154 sources identified, 89 articles were original, peer-reviewed, and focused on oropharyngeal dysphagia in stroke patients. To evaluate the evidence, the next selection identified 10 articles on the comparison of screening and videofluoroscopic findings and three articles on screening and health outcomes. Evidence was rated according to the level of study design by using the values of the Canadian Task Force on Periodic Health Examination. From the identified screening tests, most of the screenings were related to laryngeal signs (63%) and most of the outcomes were related to physiology (74%). Evidence for screening accuracy was limited because of poor study design and the predominant use of aspiration as the diagnostic reference. Only two screening tests were identified as accurate: failure on the 50-ml water test (likelihood ratio = 5.7, 95% confidence interval = 2.5-12.9) and impaired pharyngeal sensation (likelihood ratio = 2.5, 95% confidence interval = 1.7-3.7). Limited evidence for screening benefit suggested a reduction in pneumonia, length of hospital stay, personnel costs, and patient charges. In conclusion, screening accuracy needs to be assessed by using both abnormal physiology and aspiration as diagnostic markers for dysphagia. Large well-designed trials are needed for more conclusive evidence of screening benefit.

Adult↗

Internalisation of the bleomycin molecules responsible for bleomycin toxicity: a receptor-mediated endocytosis mechanism.

Bleomycin (BLM) does not diffuse through the plasma membrane but nevertheless displays cytotoxic activity due to DNA break generation. The aim of the study was to describe the mechanism of BLM internalisation. We previously provided evidence for the existence of BLM-binding sites at the surface of DC-3F Chinese hamster fibroblasts, as well as of their involvement in BLM cytotoxicity on DC-3F cells and related BLM-resistant sublines. Here we report that A253 human cells and their BLM-resistant subline C-10E also possessed a membrane protein of ca. 250 kDa specifically binding BLM. Part of this C-10E cell resistance could be explained by a decrease in the number of BLM-binding sites exposed at the cell surface with respect to A253 cells. The comparison between A253 and DC-3F cells exposing a similar number of BLM-binding sites revealed that the faster the fluid phase endocytosis, the greater the cell sensitivity to BLM. Moreover, the experimental modification of endocytotic vesicle size showed that BLM cytotoxicity was directly correlated with the flux of plasma membrane area engulfed during endocytosis rather than with the fluid phase volume incorporated. Thus, BLM would be internalised by a receptor-mediated endocytosis mechanism which would first require BLM binding to its membrane receptor and then the transfer of the complex into intracellular endocytotic vesicles, followed by BLM entry into the cytosol, probably from a nonacidic compartment.

Animals↗

Interventional radiology and the use of metal stents in nonvascular clinical practice: a systematic overview.

PURPOSE: The intent of this systematic overview was to describe the clinical role of metal stents in nonvascular health care interventions and the level of evidence supporting their use. MATERIALS AND METHODS: Structured searches of Medline were conducted and limited to original peer-reviewed articles published in English. RESULTS: Clinical practice involving metal stents was reported in more than 109 clinical series involving 4,753 patients. Stents were placed mainly for palliation of malignant biliary, esophageal, and airway obstruction in patients who were untreatable or had surgically unresectable lesions. Assessment of these interventions has so far centered on safety and technical success. Efficacy, quality of life, and costing factors were not routinely reported. Randomized trial evidence was available but limited; six randomized trials involving metal stents have been reported. Three trials involved biliary malignant obstruction, and all three reported metal stent (132 patients) palliation to be superior to plastic stent palliation (136 patients) based on longer patency and lower reintervention costs. Safety and complication differences between stents, however, were inconsistent across trials. In three trials involving esophageal malignant obstruction, metal stent (82 patients) palliation was reported to be superior to plastic stent (41 patients), based on lower complication and reintervention rates, and superior to laser therapy (18 patients), based on better dysphagia relief. CONCLUSION: Use of metal stents has been reported for obstructed ducts and passageways of most body systems. There is, however, limited controlled trial evidence confirming the advantages of their use over plastic stents or other forms of treatment.

Cholestasis↗

Improved retroperitoneal and gastrointestinal sonography using oral contrast agents in a porcine model.

OBJECTIVE: Abdominal sonography can be compromised by the presence of air within the scanning field. Gas-displacing oral contrast agents have the potential to improve the diagnostic yield of routine abdominal sonography. The purpose of this study was to investigate two oral contrast agents and water and to compare their ability to improve abdominal sonography with an unenhanced baseline study and each other in a porcine model. MATERIALS AND METHODS: The acoustic properties of agent 1 (Oralex; Molecular Biosystems, San Diego, CA), a suspension of polydextrose in purified water; agent 2, a homemade agent (named BMW), a suspension of polysaccharide particles in water; and water were assessed in finger phantoms under laboratory conditions. Each solution was subsequently evaluated in 10 pigs, for a total of 30 animals. The bolus character, gas artifact, abdominal viscera, vessels, and gut wall were graded from 1 (nondiagnostic) to 5 (excellent) in the unenhanced and postcontrast states. Postcontrast grades were compared with unenhanced baseline grades using the Wilcoxon signed-rank correlation. Agents were compared with each other using the Mann-Whitney U test (Wilcoxon rank sum test). RESULTS: All three solutions were hypoechoic, were homogeneous, and showed minimal attenuation and backscatter. Both oral contrast agents had excellent bolus characteristics (agent 1, grade 5.0 +/- 0; agent 2, grade 4.6 +/- 0.5), displaced gas from the scanning field, and significantly improved visibility in all categories, particularly the gut. No difference in performance was found between agents 1 and agent 2. Water had poor bolus characteristics (grade 1.3 +/- 0.48) and did not improve visibility over baseline. CONCLUSION: The acoustic in vitro properties of agent 1 and agent 2 approach that of an ideal sonographic contrast agent. Both agents are superior to water in their improvement of direct visualization of the retroperitoneum and the gut in abdominal sonography in a porcine model.

Administration, Oral↗

Case for active physician involvement in US practice.

PURPOSE: To assess the benefit of active physician involvement in ultrasound (US) examinations. MATERIALS AND METHODS: Concordance of findings by technologists and physicians was assessed prospectively for examinations of 1,510 consecutive patients who underwent US during regular working hours. RESULTS: Overall concordance was generally good (74%). However, in cases in which a major or minor new diagnosis was made from the US scan, concordance rates were substantially lower (36% and 32%, respectively). Agreement varied with the type of examination. The discordance rate for obstetric examinations (17%) was only half that for abdominal and pelvic examinations (31%). Concordance improved with increasing years of experience of the technologist. CONCLUSION: An active role of physicians in the overall conduct of US examinations is essential to optimize provision of a complete, accurate report.

Diagnostic Errors↗

Monobloc and facial bipartition osteotomies: quantitative assessment of presenting deformity and surgical results based on computed tomography scans.

PURPOSE: The results of monobloc (MB) or facial bipartition (FB) osteotomies on 23 consecutive patients operated on between 1987 and 1991 were evaluated. PATIENTS AND METHODS: A previously described method of clinically relevant linear measurements taken from preoperative and postoperative computed tomographic scans of these patients was used to document their presenting dysmorphology and the results of surgical correction initially and 1 year after operation. These data were compared with control values, and a percentage of normal for each measurement was derived for each patient. RESULTS: In the patients with craniofacial dysostosis undergoing an MB osteotomy, the initial cranial vault length (87% of normal), medial orbital wall length (87%), zygomatic arch length (84%), and extent of globe protrusion (134%) all indicated horizontal (anterior-posterior) deficiency of the upper and middle face. After surgery, these measurements moved closer to age-matched control values. At the 1-year interval a minor degree of relapse was evident. In the patients with craniofacial dysostosis who were believed to need an FB osteotomy, the globe protrusion (142% of normal), medial orbital wall length (85%), and zygomatic arch lengths (83%) all indicated horizontal (anterior-posterior) deficiency in the upper and middle face. In addition, the anterior interorbital distance (123% of normal), mid-interorbital distance (122%), and intertemporal distance (126%) all indicated upper face hypertelorism. As a result of the FB osteotomy, anterior bony projection was achieved, and the hypertelorism was improved, but fell short of age-matched normal values. In the patients with frontonasal dysplasia, cranio-orbital clefting, and isolated orbital hypertelorism who underwent an FB osteotomy, preoperative measurements showed a distinct widening of the whole upper midface with forward projection of the medial relative to the lateral orbital walls. The orbital measurements revealed a substantially widened anterior interorbital distance (175% of normal), increased mid-interorbital distance (123%), and an increased distance between the lateral orbital walls (106%). After the surgical procedure, these measurements were improved and relatively stable but not completely normalized. CONCLUSION: The use of quantitative measurements in the initial evaluation, intraoperative skeletal reshaping, and assessment of early and late reconstructive results provides useful benchmarks.

Acrocephalosyndactylia↗

Involvement of membrane bleomycin-binding sites in bleomycin cytotoxicity.

The authors have recently shown the existence of bleomycin (BLM)-binding sites at the surface of DC-3F cells. In order to study the involvement of these sites in the sensitivity of the cells to bleomycin several BLM-resistant cell lines from DC-3F cells were analysed. These mutants were obtained by electrotransfection of the Sh ble gene (D/BlmI cells) or the Sh ble-beta Gal fusion gene (D/BlmII cells) and/or by continuous culture in the presence of BLM (D/BlmIR and D/Blm40 cells). The resistance levels of the D/BlmII and D/Blm40 cells were 50- and 22-fold, respectively, determined at the EC50 level. The D/BlmI cells were only 2-fold resistant, whereas D/BlmIR cells were so resistant that almost no cytotoxicity was detected up to 200 microM BLM external concentration. Electropermeabilization was used in an attempt to bypass the plasma membrane of the cells and permit the distinction between internal resistance and membrane resistance. The former was observed when the products of the transfected genes were present. With respect to membrane resistance, differences were detected in the number of BLM-binding sites in several mutant cell lines, which could account for the differences in cell sensitivity to BLM. This suggests that the BLM-binding sites found at the cell surface may play a crucial role in BLM internalization and consequently in its cytotoxicity.

Animals↗

Electropermeabilization of cells in tissues assessed by the qualitative and quantitative electroloading of bleomycin.

Using cells in suspension, electropermeabilization is a technique extensively used to transfect living cells or to introduce a variety of compounds inside the cells. Here we demonstrate the reality of the tissue electropermeabilization using qualitative and quantitative determinations of the electroloading of bleomycin considered as an nonpermeant molecule that serves as an indicator of the permeabilization. In tissues, cell electropermeabilization is achieved for electric field intensities lower than those necessary to permeabilize the same cells in suspension. We also emphasize the importance of the geometry of the electric field lines defined by the electrodes for permeabilizing a whole tissue, for example a tumor.

Animals↗

Facial sensibility in adolescents with and without clefts 1 year after undergoing Le Fort I osteotomy.

Static two-point discrimination, pressure, and vibratory threshold values were measured at standard coordinates in the area corresponding to the infraorbital nerve distribution in 59 adolescents 1 year after undergoing LeFort I osteotomy. The patients were divided into three groups: those born with unilateral cleft lip and palate (n = 30; mean age, 18 years; SD = 2); those with bilateral cleft lip and palate (n = 12; mean age, 19 years; SD = 3); and those without a cleft (n = 17; mean age, 19 years; SD = 3). One year after the osteotomy, none of the patients complained of altered sensibility in the maxillary vestibular mucosa, gingiva, or upper lip and cheek regions. No significant differences were found between the mean postoperative sensibility values of patients with and without clefts, indicating that the presence of clefting did not affect sensory recovery. Mean postoperative static two-point discrimination values were higher than preoperative values in all areas tested and in all patient groups. These results suggest that the sensory recovery, although incomplete, was strong enough to mask any subjective feelings of changes in sensory function.

Adolescent↗

Bleomycin, an apoptosis-mimetic drug that induces two types of cell death depending on the number of molecules internalized.

Bleomycin (BLM), a compound currently used in anticancer therapy, is unable to cross the plasma membrane efficiently. Electropermeabilization allows a defined number of BLM molecules to enter directly into the cell cytoplasm. Such a procedure has revealed that BLM is intrinsicly highly cytotoxic. Here we show that the mechanisms of the cell death caused by BLM are closely related to the number of BLM molecules introduced into the cell cytoplasm. When only a few thousand BLM molecules are internalized, cells display an arrest in the G2-M phase of the cell cycle and become enlarged and polynucleated before dying. These observations parallel the "mitotic death" seen with ionizing radiations. By contrast, when several million molecules of BLM are internalized, morphological changes identical to those usually associated with apoptosis are observed as well as very rapid DNA fragmentation into oligonucleosomal-sized fragments. We demonstrate that this fragmentation, which occurs within a few seconds after BLM internalization, is consistent with the direct internucleosomal cleavage of chromatin by BLM. Our findings reinforce the importance of DNA digestion as an early and essential step in the morphological changes associated with apoptosis.

Animals↗

Identification of a plasma membrane protein that specifically binds bleomycin.

In this paper, the association of radiolabelled bleomycin on the plasma membrane of DC-3F cells is shown to be saturable, displaying classical features of a ligand-receptor binding. This association corresponds to the presence of 140,000 to 400,000 binding sites at the surface of the cells with a half-saturating concentration of 5 microM. Moreover, using a gel electrophoresis procedure to separate membrane proteins incubated with radiolabelled bleomycin, we demonstrate the existence of a membrane protein of about 250kDa able to specifically bind bleomycin. This membrane bleomycin-binding protein could play a major part in the association of bleomycin with the cells and in its further internalization, a process that has not been elucidated yet.

Animals↗

Ear malformation and hearing loss in patients with Treacher Collins syndrome.

Although the hearing loss of patients with Treacher Collins syndrome is well documented, few studies have reported jointly on their hearing loss and ear pathology. This paper reports on the hearing loss and computerized tomography (CT) assessments of ear malformations in a large pediatric series of patients with Treacher Collins. Of the 29 subjects assessed by the Craniofacial Program between 1986 and 1990, paired audiologic and complete CT assessments were available for 23 subjects. The external ear canal abnormalities were largely symmetric, either bilaterally stenotic or atretic. In most cases, the middle ear cavity was bilaterally hypoplastic and dysmorphic, and ossicles were symmetrically dysmorphic or missing. Inner ear structures were normal in all patients. The majority of patients had a unilateral or bilateral moderate or greater degree of hearing loss and almost half had an asymmetric hearing loss. The hearing loss of all subjects was conductive, except for three whose loss was bilateral mixed. Two types of bilaterally symmetric hearing loss configurations, flat and reverse sloping, were noted. Conductive hearing loss in patients with Treacher Collins is mainly attributable to their middle ear malformations, which are similar for those of patients with malformed or missing ossicles.

Adolescent↗

Cranio-orbito-zygomatic measurements from standard CT scans in unoperated Crouzon and Apert infants: comparison with normal controls.

Cranio-orbito-zygomatic measurements taken from standard axial computed tomographic (CT) scans of unoperated patients with Crouzon syndrome (6 males, 14 females) and Apert syndrome (6 males, 10 females) under 1 year of age were compared to each other and to normal controls (40 males, 35 females). Fifteen cranio-orbito-zygomatic variables were measured and repeated. Means and standard deviations were computed for each sex, and means were pooled since they were not significantly different. Correlation coefficients for repeat measures (intra-observer error) of each variable showed good reproducibility. Only the lateral orbital wall angle differed between the syndromes (p = .034), suggesting that upper facial differences (as measured by these variables) do not manifest themselves at this young age. All measurements for both syndromes, except one, were outside the 95 percent confidence range for age-matched controls. Measurements taken from standard CT scans provide an objective comparison between specific syndromes and the normal population.

Acrocephalosyndactylia↗

Recurrent Crohn's disease in the duodenum and jejunum following extensive small bowel resection and jejunocolonic anastamosis: radiologic findings in twenty-five patients.

BACKGROUND: To evaluate the radiologic features of recurrent Crohn's disease after extensive enteric resection and jejunocolostomy. METHODS: We reviewed the small bowel studies of 25 patients with recurrent enteritis and less than 125 cm of jejunum following enteric resection and jejunocolostomy and the studies of 27 patients with jejunitis in an intact jejunum. RESULTS: Twenty-three patients with recurrences had neoterminal jejunitis, six under 10 cm, 10 over 10 cm and continuous, and seven with skip lesions (six jejunal, one duodenal). Two had isolated jejunitis or duodenitis. Three with continuous disease had lengthy recurrences. Enteritis showed only one or two abnormalities in 12 of 25 patients with recurrences and in two of 27 with disease in the intact jejunum. Recurrent jejunitis and jejunitis in the intact jejunum showed similar frequencies of mucosal thickening, strictures, ulceration and its complications, skip lesions, sacculation, obstructive dilatation, featureless mucosa, and polyps, and significantly different frequencies only of mesenteric masses. Recurrent jejunitis and terminal ileitis showed significantly different frequencies of mucosal thickening, strictures, ulceration and its complications, skip lesions, sacculation, obstructive dilatation, and mesenteric masses, and similar frequencies only of a featureless mucosa. CONCLUSIONS: The neoterminal jejunum is the most common site of recurrence and the only site in almost 25%. Jejunitis remote from the fecal stream is also frequent, but duodenitis is not. Recurrences are seldom extensive and often show only one or two radiographic findings. The frequencies of most lesions in recurrent jejunitis do not differ significantly from those in jejunitis in the intact jejunum but do differ from those in terminal ileitis.

Adolescent↗

Fluoroscopically-guided manipulation of malfunctioning peritoneal dialysis catheters.

OBJECTIVE: To review our experience with fluoroscopic evaluation and manipulation of malpositioned, malfunctioning, peritoneal dialysis (PD) catheters. MATERIALS AND METHODS: Thirty-one patients, over a 5-year period (1 May 1992 to 30 April 1997) with malfunctioning PD catheters, who had fluoroscopically-guided manipulation were reviewed. Catheters were manipulated using a malleable aluminum bar and, if necessary, guide wires or other stiffeners. Technical success was assessed on the basis of adequate, fluoroscopically verified, catheter placement at the time of the procedure and improved flows. A functional PD catheter at 30 days post manipulation was considered to be a clinically successful manipulation. RESULTS: There were 41 manipulations [33 initial (IM) and 8 remanipulations (RM)] for malpositioned or kinked catheters. In 31 (19 male, 12 female) patients ranging in age from 31 to 76 years (mean age 60 years), the initial technical success rate was 85% for IM (n = 28/33) and 63% (n = 5/8) for RM. The overall clinical success rate, or 30-day primary patency, was 55% for IM (n = 18/33) and 63% for RM. Catheter function (combined IM and RM) continued for a median 869 days (95% CI: 118, 1620). No early complications were noted. CONCLUSIONS: Fluoroscopic manipulation, including attempts at remanipulation, of PD catheters is a safe procedure. The technique is a simple, inexpensive, and effective way of prolonging PD catheter life, thereby reducing the number of surgical interventions.

Adult↗