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Biomedical subjects

M Cremer

Publications and source records attributed to M Cremer.

At least 19 recordsLinked to original sources
PubMed2002

Long-term follow-up and factors predictive of recurrence in Barrett's esophagus treated by argon plasma coagulation and acid suppression.

BACKGROUND AND STUDY AIMS: In several series, argon plasma coagulation (APC) combined with acid suppression has led to short- or medium-term eradication of Barrett's esophagus. The present study was designed to assess the long-term outcome after this treatment. PATIENTS AND METHODS: 39 patients with Barrett's esophagus, seven of them with low-grade dysplasia, underwent APC and received 40 mg omeprazole daily for eradication of the metaplastic epithelium. After the treatment period, patients were randomly assigned to receive 20 or 40 mg omeprazole daily for long-term acid suppression. Histological and endoscopic changes were evaluated annually. Univariate and multivariate analyses were used to test the following 10 variables as predictors of sustained reversal of Barrett's esophagus at the end of follow-up: age, gender, length of diseased segment, presence of hiatal hernia, circumferential nature of lesion, presence of low-grade dysplasia at initial biopsy, number of coagulation sessions, result of pH monitoring under protein pump inhibitor (PPI) treatment, omeprazole dosage, and initial response to therapy (after 1 month). RESULTS: The median follow-up period was 36 months (range 12 - 48). The endoscopic and histological relapse rates at 1, 12, and 24 months, and end of follow-up were, respectively, 30 % and 44 % (12/39 and 17/39), 57 % and 54 % (16/28 and 15/28), 60 % and 57 % (17/28 and 16/28), and 62 % for both rates (23/37). According to multivariate analysis, shorter length of diseased segment and normalization of pH with PPI treatment were the only independent predictors of sustained long-term re-epithelialization. Among the seven patients with low-grade dysplasia, four experienced relapse after 1 month, and during the long-term follow-up, one was lost to follow-up and all the others experienced relapse, but only one developed low-grade dysplasia again. Cancer was found in two cases after 12 and 18 months, respectively. CONCLUSIONS: Persistence of acid reflux and greater length of diseased segment are the major factors associated with a high relapse rate after successful initial reversal. APC for ablation of Barrett's esophagus cannot be recommended.

Adult↗
PubMed2001

Quantification of corrosion phenomena in plastic processing machines.

In a model platelet system the corrosion of metallic materials was studied by processing polyethylene, polyphenylene sulfide, and glass-fibre-reinforced polyphenylene sulfide. The measurement methods used were scanning electron microscopy (images), electron-probe microanalysis (lateral element maps), secondary-ion mass spectrometry (depth profiles), X-ray photoelectron spectroscopy (chemical bonding), and grazing-incidence X-ray diffraction (structures of crystalline compounds). As nondestructive measure of corrosive attack, grazing-incidence X-ray diffraction, using the intensity ratio (IFe-O/IFe), was found to be the method of choice. The reproducibility for the total procedure was found to range between 6 and 13% (rel.). The intensity ratio was examined as function of depth, of the time of stress, of material composition, and of the surrounding atmosphere. Oxides were identified as main corrosion products. The extent of oxide formation is proportional to the time elapsed after processing.

Journal Article↗
PubMed2001

Arrangements of macro- and microchromosomes in chicken cells.

Arrangements of chromosome territories in nuclei of chicken fibroblasts and neurons were analysed employing multicolour chromosome painting, laser confocal scanning microscopy and three-dimensional (3D) reconstruction. The chicken karyotype consists of 9 pairs of macrochromosomes and 30 pairs of microchromosomes. Although the latter represent only 23% of the chicken genome they containalmost 50% of its genes. We show that territories of microchromosomes in fibroblasts and neurons were clustered within the centre of the nucleus, while territories of the macrochromosomes were preferentially located towards the nuclear periphery. In contrast to these highly consistent radial arrangements, the relative arrangements of macrochromosome territories with respect to each other (side-by-side arrangements) were variable. A stringent radial arrangement of macro- and microchromosomes was found in mitotic cells. Replication labelling studies revealed a pattern of DNA replication similar to mammalian cell nuclei: gene dense, early replicating chromatin mostly represented by microchromosomes, was located within the nuclear interior, surrounded by a rim of late replicating chromatin. These results support the evolutionary conservation of several features of higher-order chromatin organization between mammals and birds despite the differences in their karyotypes.

Animals↗
PubMed2001

Non-random radial higher-order chromatin arrangements in nuclei of diploid human cells.

A quantitative comparison of higher-order chromatin arrangements was performed in human cell types with three-dimensionally (3D) preserved, differently shaped nuclei. These cell types included flat-ellipsoid nuclei of diploid amniotic fluid cells and fibroblasts and spherical nuclei of B and T lymphocytes from peripheral human blood. Fluorescence in-situ hybridization (FISH) was performed with chromosome paint probes for large (#1-5) and small (#17-20) autosomes, and for the two sex chromosomes. Other probes delineated heterochromatin blocks of numerous larger and smaller human chromosomes. Shape differences correlated with distinct differences in higher order chromatin arrangements: in the spherically shaped lymphocyte nuclei we noted the preferential positioning of the small, gene dense #17, 19 and 20 chromosome territories (CTs) in the 3D nuclear interior--typically without any apparent connection to the nuclear envelope. In contrast, CTs of the gene-poor small chromosomes #18 and Y were apparently attached at the nuclear envelope. CTs of large chromosomes were also preferentially located towards the nuclear periphery. In the ellipsoid nuclei of amniotic fluid cells and fibroblasts, all tested CTs showed attachments to the upper and/or lower part of the nuclear envelope: CTs of small chromosomes, including #18 and Y, were located towards the centre of the nuclear projection (CNP), while the large chromosomes were positioned towards the 2D nuclear rim. In contrast to these highly reproducible radial arrangements, 2D distances measured between heterochromatin blocks of homologous and heterologous CTs were strikingly variable. These results as well as CT painting let us conclude that nuclear functions in the studied cell types may not require reproducible side-by-side arrangements of specific homologous or non-homologous CTs. 3D-modelling of statistical arrangements of 46 human CTs in spherical nuclei was performed under the assumption of a linear correlation between DNA content of each chromosome and its CT volume. In a set of modelled nuclei, we noted the preferential localization of smaller CTs towards the 3D periphery and of larger CTs towards the 3D centre. This distribution is in clear contrast to the experimentally observed distribution in lymphocyte nuclei. We conclude that presently unknown factors (other than topological constraints) may play a decisive role to enforce the different radial arrangements of large and small CTs observed in ellipsoid and spherical human cell nuclei.

Amniotic Fluid↗
PubMed2001

Argon plasma coagulation in the treatment of Barrett's high-grade dysplasia and in situ adenocarcinoma.

BACKGROUND AND STUDY AIMS: Endoscopic therapy of high-grade dysplasia (HGD) and superficial adenocarcinoma associated with Barrett's esophagus (BE), using Nd:YAG laser, KTP laser, or photodynamic therapy (PDT), has been reported to be effective in a curative role. Argon plasma coagulation (APC) appears to be effective in the eradication of nondysplastic Barrett's mucosa, but no results are available in the management of early neoplasms complicating BE. We report our initial experience in the application of APC in this indication. PATIENTS AND METHODS: Ten patients (mean age 74.2) with histologically proven HGD (n = 7) or in situ adenocarcinoma (n = 3) associated with BE (mean length 6 cm) and unfit for surgery were treated using APC and high-dose omeprazole (40 mg daily) until squamous re-epithelialization or complete eradication of the initially apparent lesions. Endoscopic follow-up was maintained at every 3 months. RESULTS: Complete eradication of HGD and in situ adenocarcinoma was achieved after a mean number of 3.3+/-1.5 APC sessions in 8/10 patients (80%). The eight patients with complete clearance of the neoplastic areas did not show any evidence of local recurrence during a median follow-up of 24 months (range 12-36 months). One patient with initial HGD had persistence of HGD 30 months after initial diagnosis, and one patient progressed to invasive adenocarcinoma after failure of APC and PDT. CONCLUSIONS: APC is safe and effective in the management of HGD and in situ adenocarcinoma associated with BE, and might represent an interesting alternative in selected patients who are not candidates for surgery.

Adenocarcinoma↗
PubMed2001

Concentrations of thrombopoietin and interleukin-11 in the umbilical cord blood of patients with fetal alloimmune thrombocytopenia.

The objective of this study is to determine whether the fetus compensates for fetal alloimmune thrombocytopenia (FAITP) by increasing serum concentrations of thrombopoietin (TPO) and interleukin-11 (IL-11). TPO and IL-11 concentrations were measured in cord blood sera of 12 neonates with FAITP, and 35 preterm and 25 term controls. TPO concentrations in the 12 patients (median 129 pg/mL, range 73 to 325 pg/mL) were similar to those of 35 healthy preterm neonates (median 183 pg/mL, range 71 to 290 pg/mL) and the 25 term controls (median 180 pg/mL, range 93 to 302 pg/mL), although the platelet counts were significantly lower in FAITP. TPO concentrations did not correlate with the platelet counts, platelet nadir after birth, or time to recovery of normal platelet count. IL-11 reached detectable concentrations only in four patients with FAITP (median 54 pg/mL). After birth, these patients had a more rapid recovery of the platelet count. Cord blood serum concentrations of TPO are not significantly elevated in FAITP and do not predict the severity of the thrombocytopenia. Elevated IL-11 may signal a more rapid platelet recovery in FAITP.

Fetal Blood↗
PubMed2001

Pancreas divisum: evaluation with secretin-enhanced magnetic resonance cholangiopancreatography.

BACKGROUND: The clinical significance of pancreas divisum (PD) remains controversial. Secretin-enhanced magnetic resonance cholangiopancreatography (S-MRCP) is a noninvasive diagnostic procedure that relies on the dynamic response of the main pancreatic duct (MPD) to secretin stimulation. The aim of this study was to determine the frequency of PD and to analyze the dynamic changes of the MPD by using S-MRCP in patients referred for suspected pancreatic diseases before ERCP. METHODS: MRCP was obtained before and at 30-second intervals over 10 minutes after secretin stimulation in consecutive patients with idiopathic acute pancreatitis (n = 67), persistent hydrolasemia (n = 42), recurrent abdominal pain thought to be of pancreatic origin (n = 48), severe chronic pancreatitis (n = 68), and in a control group (n = 54). RESULTS: Thirty patients (10.8%) had a PD at S-MRCP. Secretin stimulation improved the detection of PD in 23% (7/30). The frequency of PD was not significantly different (p > 0.2) between these groups. The occurrence of an abnormal response at S-MRCP (persistent dilatation of the MPD) did not significantly differ in patients with or without PD (p > 0.4). CONCLUSION: The frequency of PD did not differ between groups, and the dynamic changes of the MPD during S-MRCP were similar in patients with and without PD.

Adolescent↗
PubMed2000

Association of nonsense mutation of dystrophin gene with disruption of sarcoglycan complex in X-linked dilated cardiomyopathy.

BACKGROUND: In a systematic analysis of inherited forms of cardiomyopathy, we previously identified a family with X-linked dilated cardiomyopathy characterised by a mutation in the rod region of dystrophin. We have now attempted to eludicate the genetic mechanism involved in this disease, as well as the role of dystrophin-associated glycoproteins. METHODS: The affected dystrophin epitope, which lacks binding to the dys-1 antibody, was analysed by single-strand conformation polymorphism analysis, reverse-transcription PCR, and DNA sequencing. Effects on dystrophin-associated glycoproteins were studied by immunohistochemistry and western blotting. FINDINGS: A translation-termination mutation (C4148T) in exon 29 of the dystrophin gene was found in all affected family members. Alternative splicing rescued the reading frame and led to the expression of a dystrophin molecule lacking 50 aminoacids both in cardiac and skeletal muscle. Immunohistochemical analysis of the dystrophin-associated proteins revealed a reduction of beta-sarcoglycan and delta-sarcoglycan in the sarcolemma of cardiac muscle but not skeletal muscle tissue. However, western blotting revealed similar amounts of sarcoglycan subunits in both tissues. INTERPRETATION: The molecular mechanism of this subtype of X-linked cardiomyopathy may be explained by a conformational change in exon-29-deleted dystrophin, resulting in disruption of the sarcoglycan assembly in heart muscle but not skeletal muscle.

Cardiomyopathy, Dilated↗
PubMed2000

Prevalence and clinical evolution of isolated ventral pancreatitis in alcoholic chronic pancreatitis.

BACKGROUND: The role of pancreas divisum in chronic pancreatitis is controversial. Ductal changes limited to the pancreatic ventral duct (isolated ventral pancreatitis) have only been described as isolated case reports. METHODS: In a cohort of 542 patients with chronic pancreatitis we determined the frequency of ventral chronic pancreatitis among patients with pancreas divisum and analyzed the clinical presentation of 10 patients with isolated ventral alcohol-induced pancreatitis compared with 10 patients with isolated dorsal alcohol-induced pancreatitis and 30 patients with chronic pancreatitis and without pancreas divisum. Magnetic resonance pancreatography under secretin stimulation was used to evaluate the status of the dorsal pancreatic duct in some patients during follow-up. RESULTS: We identified 62 (11.4%) patients with pancreas divisum and 16 (2.9%) patients with incomplete pancreas divisum. The ventral duct was affected by chronic pancreatitis in 74% of these patients. Isolated ventral or dorsal duct alterations were identified in 14% and 26%, respectively, of patients with pancreas divisum. Patients with isolated ventral pancreatitis had pain symptoms similar to those of the two other groups but had no endocrine or exocrine insufficiency on initial presentation. After a mean follow-up of 44 months, 83% of patients studied with isolated ventral pancreatitis developed alterations of the dorsal ductal part of the gland. CONCLUSION: We conclude that isolated ventral alcohol-induced pancreatitis is one of the first manifestations of generalized pancreatic disease where the anatomic factor of pancreas divisum plays only a marginal role.

Acute Disease↗
PubMed2000

Outcome after surgical resection of intraductal papillary and mucinous tumors of the pancreas.

OBJECTIVE: Treatment of intraductal papillary and mucinous tumors of pancreas (IPMT) usually requires surgery. The objective of this study was to evaluate the risk of recurrence in patients after surgery according to the histological nature of the neoplasm and the type of surgery. METHODS: The outcome of 45 patients who underwent partial pancreatectomy (n = 35) or total pancreatectomy (n = 10) for IPMT was studied according to the nature of the neoplasm (invasive carcinoma or noninvasive neoplasm), type of surgery (partial or total pancreatectomy), and lymph nodes status. RESULTS: The overall 3-yr actuarial survival rate was 83%. Death occurred in seven of 20 (35%) patients with invasive carcinoma and in one of 26 (4%) patients with noninvasive tumors (p<0.05). There were two recurrences in the seven patients with noninvasive neoplasm who underwent partial pancreatectomy with involved resection margins, and none in the 13 patients with disease-free margins. In patients with invasive carcinoma, there was one recurrence after total pancreatectomy, six after partial pancreatectomy with disease-free margins and six after partial pancreatectomy with involved margins. In patients with invasive carcinoma, total pancreatectomy and the absence of lymph nodes involvement were independently associated with a low risk of recurrence. CONCLUSIONS: IPMT may be managed as follows: 1) in patients with noninvasive neoplasms, partial pancreatic resection should be guided by frozen section examination until disease-free margins are obtained; and 2) in patients with invasive carcinoma, total pancreatectomy seems most likely to cure the patient, but should be discussed according to the general status and the age.

Actuarial Analysis↗
PubMed2000

A comparison of Ultraflex Diamond stents and Wallstents for palliation of distal malignant biliary strictures.

OBJECTIVE: The objective of this study was to compare the effectiveness of the Ultraflex Diamond stent and the Wallstent for the drainage of distal malignant biliary strictures. METHODS: The results obtained in 23 consecutive patients in whom the insertion of a Ultraflex Diamond stent had been attempted were compared with those obtained in 23 patients matched for age, gender, serum bilirubin, and diagnosis who had been treated with Wallstents. RESULTS: Biliary drainage was obtained in 100% of cases. More than one stent was required in 4% and 12% of patients treated with Ultraflex Diamond stents and Wallstents, respectively (p > 0.05). The first stent inserted did not provide adequate biliary drainage in four patients, because of the impaction of the proximal end of Wallstents into the bile duct wall (n = 2) and obstruction of the stent lumen by tumor tissue (one in each group). Procedure-related morbidity and mortality were 4%. Patients were followed-up for a mean of 228 days (range, 1 to 1262 days). During follow-up, bile duct obstruction relapsed in 5/22 and 6/21 patients treated with Ultraflex Diamond stents and Wallstents, respectively. Life table analysis of bile duct patency was similar with both stent models. CONCLUSIONS: Ultraflex Diamond stents are easy to insert and provide a high success rate of biliary drainage with minimal complication. Although long-term patency rates obtained with this stent were similar to those observed with Wallstents, no firm conclusion can be drawn in this regard due to the relatively small number of patients studied.

Adult↗
PubMed2000

Intramucosal adenocarcinoma arising under squamous re-epithelialisation of Barrett's oesophagus.

BACKGROUND: Eradication of Barrett's mucosa by thermal or photoablation combined with high doses of proton pump inhibitors is a potentially attractive strategy in the management of this preneoplastic condition. However, major concerns of this method are the persistence of residual metaplastic glands beneath the new squamous epithelium and the absence of any knowledge of its impact on long term outcome. CASE REPORT: The case of an intramucosal adenocarcinoma diagnosed 18 months after apparently complete squamous re-epithelialisation achieved using argon plasma coagulation and high dose omeprazole (40 mg/daily) is reported in a 68 year old patient presenting initially with a Barrett's oesophagus without dysplasia. Intramucosal adenocarcinoma was located under the new squamous layer and presented as a bulging area covered by the squamous epithelium. It probably originates from residual metaplastic glands after therapy although a pre-existing tumour cannot be definitely excluded. CONCLUSION: This observation might question future application of this experimental endotherapy in non-dysplastic Barrett's oesophagus. It suggests that the residual glands might still be premalignant and that the early diagnosis of neoplastic changes might be compromised by the squamous re-epithelialisation.

Adenocarcinoma↗
PubMed2000

Chronic pancreatitis: evaluation of pancreatic exocrine function with MR pancreatography after secretin stimulation.

PURPOSE: To compare duodenal filling seen at magnetic resonance (MR) pancreatography after secretin stimulation and biochemical parameters determined with the intraductal secretin test (IDST) for evaluation of pancreatic exocrine function. MATERIALS AND METHODS: MR pancreatography after secretin stimulation and IDST were performed in 41 patients with chronic pancreatitis (group 1) and eight patients with other pancreatic disease (group 2). A control group (group 3, n = 28) underwent MR pancreatography after secretin stimulation only. MR pancreatograms were acquired before and every 30 seconds for 10 minutes after secretin injection. Duodenal filling was graded from least amount of filling (grade 1) to normal filling (grade 3) on the last MR pancreatogram. Pancreatic exocrine function was determined at IDST. Main pancreatic ductal diameter was compared between groups 1 and 3. RESULTS: All ductal diameters were significantly larger in group 1 (P <.001). The maximal diameter variation after secretin stimulation was significantly higher in the control group (P =.001). Pancreatic exocrine function parameters determined at IDST were significantly lower in patients with grade 1 duodenal filling than in those with grade 2 or 3 (P <.05). Maximal bicarbonate concentration alone was independently associated with all grades of duodenal filling (P =.007). The sensitivity and specificity of reduced duodenal filling for assessment of reduced pancreatic exocrine function were 72% and 87%, respectively. CONCLUSION: Duodenal filling grade determined at MR pancreatography after secretin stimulation allows specific estimation of pancreatic exocrine function.

Adolescent↗
PubMed2000

Discrimination between dysplastic and malignant epithelium of the ampulla of vater based on quantitative image cytometric data.

OBJECTIVE: To assess the ability to associate histopathologic grading with objective criteria obtained by nuclear image cytometry in epithelium of the ampulla of Vater. STUDY DESIGN: Forty-one resected ampullary specimens were studied, including 8 dysplastic ampullomas together with 22 well-differentiated and 11 poorly differentiated ampullary adenocarcinomas. The nuclei were Feulgen stained and analyzed using a computer-assisted microscope, which generated 38 quantitative variables describing chromatin texture and nuclear DNA content (DNA ploidy level). These variables were explored by discriminant analysis to determine the most stable and informative variables. Univariate analysis was performed on the four most informative ones. The whole set of variables was also subjected to principal component analysis in order to characterize intragroup and intergroup heterogeneity. RESULTS: The univariate analysis defined two morphonuclear variables (related to nuclear chromatin distribution) discriminating between dysplasia and well-differentiated cancers. Aneuploidy occurrence was associated with discrimination between well-differentiated and poorly differentiated cancers. CONCLUSION: While alterations in chromatin distribution may be an early event in the malignant degeneration of this epithelium, alterations in nuclear DNA content should correspond to a later phenomenon. Quantification of these features can be exploited to assist in diagnosis.

Ampulla of Vater↗
PubMed2000

[Treatment of pain in chronic calcifying pancreatitis with endoscopy and extracorporeal shock wave lithotripsy. A case report].

Abdominal pain is the most frequent symptom of chronic pancreatitis and may, on occasions, lead to great treatment problems. The case of a 56-years-old patient with idiopathic chronic pancreatitis calcifying who showed intracanalicular lithiasis is reported. Treatment with endoscopy and extracorporal shock wave lithotripsy (ESWL) was successful.

Abdominal Pain↗
PubMed2000

Chromosome territories, interchromatin domain compartment, and nuclear matrix: an integrated view of the functional nuclear architecture.

Advances in the specific fluorescent labeling of chromatin in fixed and living human cells in combination with three-dimensional (3D) and 4D (space plus time) fluorescence microscopy and image analysis have opened the way for detailed studies of the dynamic, higher-order architecture of chromatin in the human cell nucleus and its potential role in gene regulation. Several features of this architecture are now well established: 1. Chromosomes occupy distinct territories in the cell nucleus with preferred nuclear locations, although there is no evidence of a rigid suprachromosomal order. 2. Chromosome territories (CTs) in turn contain distinct chromosome arm domains and smaller chromatin foci or domains with diameters of some 300 to 800 nm and a DNA content in the order of 1 Mbp. 3. Gene-dense, early-replicating and gene-poor, middle-to-late-replicating chromatin domains exhibit different higher-order nuclear patterns that persist through all stages of interphase. In mitotic chromosomes early replicating chromatin domains give rise to Giemsa light bands, whereas middle-to-late-replicating domains form Giemsa dark bands and C-bands. In an attempt to integrate these experimental data into a unified view of the functional nuclear architecture, we present a model of a modular and dynamic chromosome territory (CT) organization. We propose that basically three nuclear compartments exist, an "open" higher-order chromatin compartment with chromatin domains containing active genes, a "closed" chromatin compartment comprising inactive genes, and an interchromatin domain (ICD) compartment (Cremer et al., 1993; Zirbel et al., 1993) that contains macromolecular complexes for transcription, splicing, DNA replication, and repair. Genes in "open," but not in "closed" higher-order chromatin compartments have access to transcription and splicing complexes located in the ICD compartment. Chromatin domains that build the "open" chromatin compartment are organized in a way that allows the direct contact of genes and nascent RNA to transcription and splicing complexes, respectively, preformed in the ICD compartment. In contrast, chromatin domains that belong to the "closed" compartment are topologically arranged and compacted in a way that precludes the accessibility of genes to transcription complexes. We argue that the content of the ICD compartment is highly enriched in DNA depleted biochemical matrix preparations. The ICD compartment may be considered as the structural and functional equivalent of the in vivo nuclear matrix. A matrix in this functional sense is compatible with but does not necessitate the concept of a 3D nuclear skeleton existing of long, extensively arborized filaments. In the absence of unequivocal evidence for such a structural matrix in the nucleus of living cells we keep an agnostic attitude about its existence and possible properties in maintaining the higher-order nuclear architecture. Quantitative modeling of the 3D and 4D human genome architecture in situ shows that such an assumption is not necessary to explain presently known aspects of the higher-order nuclear architecture. We expect that the interplay of quantitative modeling and experimental tests will result in a better understanding of the compartmentalized nuclear architecture and its functional consequences.

Animals↗