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Biomedical subjects

M Cremer

Publications and source records attributed to M Cremer.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1999

Effects of long-term administration of methotrexate on bone mineral density in rheumatoid arthritis.

Because previous studies of high-dose methotrexate usage have demonstrated an effect on bone formation and resorption, this study was done to determine whether long-term, low-dose use of methotrexate for the treatment of rheumatoid arthritis causes bone loss. Bone mineral density (BMD) of the lumbar spine and hip was measured in 10 Caucasian postmenopausal women who had never received methotrexate and 10 Caucasian postmenopausal women who had received the drug for 3 or more years. There were no significant differences in BMD at the lumbar spine (L2-L4) between patients who had used long-term methotrexate compared with patients never treated with methotrexate (1.08 +/- 0.08 g/cm2 versus 0.98 +/- 0.14 g/cm2, respectively; P = 0.08). Similarly, there were no significant differences in BMD at the femoral neck between methotrexate users and nonusers (0.81 +/- 0.08 g/cm2 versus 0.76 +/- 0.15 g/cm2, respectively; P = 0.42). These results suggest that long-term low-dose methotrexate treatment for rheumatoid arthritis is not associated with accelerated bone loss.

Antirheumatic Agents↗
PubMed1999

Serum levels of thrombopoietin, IL-11, and IL-6 in pediatric thrombocytopenias.

We measured serum levels of thrombopoietin (TPO), interleukin (IL)-11, and IL-6 in 90 different samples from 67 pediatric patients with thrombocytopenia (TP). The cytokine levels were determined by enzyme-linked immunosorbent assays (ELISA), and the biological activity of TPO was measured using a cell line transfected with human c-mpl. In patients with impaired megakaryocytopoiesis, as found in diseases such as aplastic anemia, amegakaryocytic TP, or TP with absent radii, we found TPO levels which were highly elevated compared with normal values (mean=261 AU/ml, n=52, vs. 22 AU/ml in healthy controls). In contrast, patients suffering from idiopathic thrombocytopenic purpura (mean=16 AU/ml, n=31) or platelet function defects (mean=23 AU/ml, n=7) demonstrated normal TPO levels. The biological activity tested in the bioassay correlated well with the ELISA data. However, sera of some patients with amegakaryocytic TP demonstrated a remarkably higher biological activity of TPO than expected from the ELISA data. Within the different groups there was no correlation between platelet counts and TPO levels. Only 27% of all samples had elevated levels of IL-11 (mean=450 pg/ml, n=20). Elevated IL-6 serum levels were detected in only 13% of all samples analyzed (mean=42 pg/ml, n=12). We conclude that megakaryocytopoiesis is regulated mainly by TPO, that it is dependent on the platelet and the megakaryocytic mass, and that IL-11 plays an additional role in supporting the platelet production. IL-6 does not appear to be up-regulated in children with thrombocytopenia.

Adolescent↗
PubMed1999

Esophageal fistula sealing: choice of stent, practical management, and cost.

BACKGROUND: Three models of covered metal stents are available to seal esophageal fistulas. METHODS: Stainless steel covered stents were inserted in 5 patients (group I); nitinol covered stents were inserted in 12 patients (group II) with malignant (n = 14) or benign (n = 3) esophageal fistulas. RESULTS: Stent positioning was satisfactory in all cases. Fistula sealing was complete in 1 of 5 (20%) and 12 of 12 (100%) patients of groups I and II, respectively (p < 0.005). Continued esophageal leakage was initially related to the passage of fluids alongside the stent covering (n = 3) and to early stent migration (n = 1). Complications related to stent placement were observed in 2 of 17 (12%) patients and were fatal. During follow-up (mean 153 +/- 143 days), esophageal fistulas relapsed after initial sealing in 5 of 13 (38%) patients. Further treatment (glue or fibrin sealant injection, additional stent insertion) was attempted in 7 cases of persistent or relapsing esophageal fistula, with sealing obtained in 5 of them. The costs per patient and per day free from symptoms due to the esophageal fistula were $106 and $57 in groups I and II, respectively. CONCLUSION: Nitinol covered stents more frequently provided complete esophageal fistula sealing, as compared with stainless steel covered stents. Further treatments tailored to the mechanisms of fistula persistence or relapse often provided sealing.

Adolescent↗
PubMed1999

Secretin-enhanced MR pancreatography.

MR cholangiopancreatography has now emerged as a noninvasive diagnostic technique that can replace diagnostic endoscopic retrograde cholangiopancreatography in many instances. Recent technical issues include the use of fast single-shot T2-weighted single-slice projections in combination with a negative oral contrast agent and secretin stimulation for assessment of pancreatic flow dynamics and duodenal filling. Potential clinical applications include the evaluation of patients with recurrent pancreatitis and inconclusive CT examination as well as the evaluation of chronic pancreatitis complications whenever endoscopic treatment is suggested. In combination with cross-sectional MR sequences, secretin-enhanced MR pancreatography offers the possibility of a comprehensive examination of the pancreas that provides parenchymal, ductal, and functional information within a single diagnostic modality.

Humans↗
PubMed1999

Chronic pancreatic alterations in AIDS patients.

Patients with acquired immunodeficiency syndrome (AIDS) can develop biliary and pancreatic disorders, like sclerosing cholangitis and acute pancreatitis. Chronic pancreatic changes are rare and only poorly described. In this study, we report our endoscopic retrograde cholangiopancreatography (ERCP) findings in 20 patients with AIDS, focusing on pancreatographic changes. ERCP findings from 20 patients with advanced disease were analyzed. Patients with history of chronic alcoholism were ruled out. ERCP findings were correlated to the coexistence of an opportunistic infection and the taking of antiviral therapies. Bile duct and pancreatic duct abnormalities were observed in 11 (55%) of 20 and seven (37%) of 19 patients, respectively. Bile duct lesions were mainly sclerosing cholangitis, and chronic pancreatic alterations consisted of side-branch involvement (n = 4), multiple and diffuse strictures of the main duct (n = 1), and diffuse dilatation of the main pancreatic duct (n = 2). The presence of an opportunistic infection was correlated with sclerosing cholangitis but not with chronic pancreatic changes. Similarly, there was no association between the finding of an abnormal cholangiogram and the presence of pancreatic alterations. This population of patients with AIDS had a significant proportion (37%) of chronic pancreatic ductal changes, which do not seem to be related to morphologic alterations and/or opportunistic infections of the biliary tract.

AIDS-Related Opportunistic Infections↗
PubMed1999

Laser microdissection and laser pressure catapulting for the generation of chromosome-specific paint probes.

Chromosome-specific paint probes provide a powerful tool with wide applications in cytogenetic analysis. Here, we present a new approach using UV-laser microbeam microdissection in combination with laser-pressure catapulting, which allows the fast isolation of single chromosomes for the generation of chromosome-specific paint probes. To demonstrate the feasibility of this approach, single chromosomes were collected and amplified with degenerate oligonucleotide-primed PCR, hapten-labeled and hybridized onto normal metaphase spreads. Fluorescence in situ hybridization signals revealed specific painting of the respective chromosomes.

Animals↗
PubMed1998

Defective c-Mpl signaling in the syndrome of thrombocytopenia with absent radii.

Thrombocytopenia with absent radii (TAR) syndrome is a rare congenital defect with severe hypomegakaryocytic thrombocytopenia and bilateral radial aplasia. To elucidate a possible relationship between thrombocytopenia in TAR and defects in the thrombopoietin (TPO)/c-Mpl system, we examined TPO activity in sera from six patients and in vitro reactivity of the patients' platelets to recombinant human TPO. We found elevated TPO serum levels in all patients, excluding a TPO production defect as a pathomechanism for the thrombocytopenia. In contrast to healthy controls, however, platelets of TAR patients failed to respond to recombinant TPO as measured by testing TPO synergism to suboptimal concentration of platelet activators. Most interestingly, TPO-induced tyrosine phosphorylation of platelet proteins was completely absent (four out of five) or markedly decreased (one out of five). More detailed investigations of the signal cascades of c-Mpl demonstrated the absence of Jak2 phosphorylation after TPO stimulation in a TAR patient's platelets. A defect in the early events of c-Mpl signal transduction might be the reason for impaired megakaryocytopoiesis in TAR syndrome.

Blood Platelets↗
PubMed1998

A guiding catheter to facilitate accurate stent length determination.

BACKGROUND: Endoscopic stenting is widely used for drainage in benign and malignant strictures of the bile and pancreatic ducts. Accurate fitting of the stent to the anatomic ductal features is essential, although this is often done by visual assessment alone. METHODS: A new guiding catheter, the measuring-mounting catheter, with radiopaque bands at 1 cm intervals from its distal end, was used in 10 patients. Visual estimates, based on fluoroscopic images, of the length of the duct segments considered for stenting were compared with measurements obtained with the catheter. RESULTS: There was a significant difference between duct length estimations based on visual assessment and lengths determined objectively using the catheter (mean +/- SD, 17 +/- 11 mm; p < 0.0005). In one half of the cases, the operator rejected the stent he chose before using the catheter. CONCLUSIONS: The measuring-mounting catheter improves the precision of plastic stent implantation without loss of time during the procedure. It is particularly useful in technically difficult situations such as hilar or main pancreatic duct strictures.

Bile Ducts↗