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Biomedical subjects

M Stahl

Publications and source records attributed to M Stahl.

At least 55 records · Page 3Linked to original sources
PubMed2000

Induction chemotherapy followed by concurrent chemotherapy and high-dose radiotherapy for locally advanced squamous cell carcinoma of the upper-thoracic and midthoracic esophagus.

The purpose of this study was to evaluate the efficacy and toxicity of an induction chemotherapy schedule followed by high-dose radiotherapy and concurrent chemotherapy for locally advanced squamous cell carcinomas of the upper and midthoracic esophagus. Patients were treated with three courses of fluorouracil, leucovorin, etoposide, and cisplatin-containing induction chemotherapy followed by high-dose external beam radiotherapy to 65 Gy in 6 weeks for T4 and obstructing T3 tumors. Transversable T3 tumors received 60 Gy in 6 weeks by external radiotherapy, followed by two high-dose-rate esophageal brachytherapy fractions of 4 Gy in 5-mm tissue depth. Concurrent to radiotherapy, cisplatin and etoposide were given. Long-term survival of 22 patients was 41% and 31% at 2 and 3 years, respectively, with a median follow-up of 39 months. The probability of locoregional tumor recurrence was 60% at 3 years for all patients and 30% for those with a partial or complete response to induction chemotherapy. Acute toxicity of this schedule was moderate. Long-term survivors had a good swallowing function. This schedule offers a considerable chance of long-term survival for patients with locally advanced squamous cell carcinomas of the upper and midthoracic esophagus. Local in-field recurrences are the main risk after definitive radiochemotherapy. Dose escalation of radiotherapy is possible because of the observed low late toxicity.

Adult↗
PubMed2000

The heart-brain connection.

We have long known that patients with vascular disease in one system are at risk for vascular disease in other systems. Beyond this, we are recognizing the increased risk for cardiovascular patients to develop stroke not only as the result of arrhythmia, but also at the time of cardiovascular events or procedures. This presents clinical challenges to nurses with either neurological or cardiovascular expertise, requiring development of new awareness, clinical and critical thinking skills, and collaboration with their colleagues in other specialties. Three case studies illustrate patient presentations ranging from the subtle to the obvious. Pathophysiology of stroke is reviewed. Leading-edge management strategies and supporting literature highlight the benefits of prompt identification and management of the stroke patient. The Stroke Watch Action Team (SWAT) has proved to be an effective means of expediting patient identification and access to effective stroke treatment.

Adolescent↗
PubMed2000

Digital radiography enhancement by nonlinear multiscale processing.

Today's digital radiography systems mostly use unsharp maskinglike enhancement algorithms based on splitting input images into two or three frequency channels. This method allows fine detail enhancement as well as processing of global contrast (harmonization). However, structures of medium size are not accessible. In extension of a standard algorithm of such type, we develop and test a new enhancement algorithm based on hierarchically repeated unsharp masking, resulting in a multiscale architecture allowing consistent access to structures of all sizes. Our algorithm decomposes a radiograph by a pyramid-architecture, dividing it into eight or more channels representing structures of different sizes, known as "scales." At each scale, weakly contrasting structures are then enhanced by suitable nonlinear processing. We emphasize two points: first, backward compatibility to the standard algorithm which is used routinely in clinical practice. This allows reuse of current parametrization know-how as well as a smooth transition from current to new processing. Second, our enhancement is noise-resistant in the sense that it prevents unacceptable noise amplification. A prototype implementation of the algorithm is undergoing trials in the clinical routine of radiology departments of major German hospitals. Results strongly indicate the superior performance and high acceptance of the new processing.

Algorithms↗
PubMed2000

[Infusiontherapy with 5-fluorouracil ("infusional" 5-FU) in solid tumors].

BACKGROUND: 5-FU is an important anticancer agent for many tumor entities. Because of the historical development of this compound it was predominantly administered as a bolus application, although it was well known that the antineoplastic activity of this antimetabolite is improved by prolonged administration schedules (protracted infusion ["infusional"] of 5-FU). Since port-a-cath systems and portable pumps became available, "infusional" 5-FU containing chemotherapies were intensively investigated in various tumors known to be susceptible to 5-FU. INDICATIONS: The largest experience with "infusional" 5-FU +/- folinic acid +/- other cytostatic drugs exists in gastrointestinal tumors. Meanwhile this way of 5-FU application is well established in the first- and second-line chemotherapy of metastatic colorectal and gastric cancer where it contributes to a clinically relevant improvement of the prognosis of these tumors. Other tumor entities where "infusional" 5-FU-based chemotherapies showed first positive results are i.e. breast cancer and esophageal cancers.

Antimetabolites, Antineoplastic↗
PubMed1999

Stereochemical course and steady state mechanism of the reaction catalyzed by the GDP-fucose synthetase from Escherichia coli.

Recently the genes encoding the human and Escherichia coli GDP-mannose dehydratase and GDP-fucose synthetase (GFS) protein have been cloned and it has been shown that these two proteins alone are sufficient to convert GDP mannose to GDP fucose in vitro. GDP-fucose synthetase from E. coli is a novel dual function enzyme in that it catalyzes epimerizations and a reduction reaction at the same active site. This aspect separates fucose biosynthesis from that of other deoxy and dideoxy sugars in which the epimerase and reductase activities are present on separate enzymes encoded by separate genes. By NMR spectroscopy we have shown that GFS catalyzes the stereospecific hydride transfer of the ProS hydrogen from NADPH to carbon 4 of the mannose sugar. This is consistent with the stereospecificity observed for other members of the short chain dehydrogenase reductase family of enzymes of which GFS is a member. Additionally the enzyme is able to catalyze the epimerization reaction in the absence of NADP or NADPH. The kinetic mechanism of GFS as determined by product inhibition and fluorescence binding studies is consistent with a random mechanism. The dissociation constants determined from fluorescence studies indicate that the enzyme displays a 40-fold stronger affinity for the substrate NADPH as compared with the product NADP and utilizes NADPH preferentially as compared with NADH. This study on GFS, a unique member of the short chain dehydrogenase reductase family, coupled with that of its recently published crystal structure should aid in the development of antimicrobial or anti-inflammatory compounds that act by blocking selectin-mediated cell adhesion.

Carbohydrate Epimerases↗
PubMed1999

Crystal structure of human cytosolic phospholipase A2 reveals a novel topology and catalytic mechanism.

Cytosolic phospholipase A2 initiates the biosynthesis of prostaglandins, leukotrienes, and platelet-activating factor (PAF), mediators of the pathophysiology of asthma and arthritis. Here, we report the X-ray crystal structure of human cPLA2 at 2.5 A. cPLA2 consists of an N-terminal calcium-dependent lipid-binding/C2 domain and a catalytic unit whose topology is distinct from that of other lipases. An unusual Ser-Asp dyad located in a deep cleft at the center of a predominantly hydrophobic funnel selectively cleaves arachidonyl phospholipids. The structure reveals a flexible lid that must move to allow substrate access to the active site, thus explaining the interfacial activation of this important lipase.

Animals↗
PubMed1999

Prognostic significance of cyclin D1 in esophageal squamous cell carcinoma patients treated with surgery alone or combined therapy modalities.

In the present study, the expression of cyclin D1, as detected by immunohistochemistry, was compared with other prognostic variables and its prognostic impact was evaluated in a group of 172 patients with squamous cell carcinoma (SCC) of the esophagus who underwent potentially curative resection therapy and in a second group of 38 patients with SCC of the esophagus who were treated by combined modality therapy (radiochemotherapy +/- surgery). Expression of cyclin D1 in surgically treated carcinomas correlated negatively with tumor differentiation (p = 0.026) but positively with mitotic activity (p = 0.0199) and nodal status (p = 0.040). There were no significant correlations with pT category. Patients with cyclin D1-positive carcinomas showed significantly worse overall survival than patients with cyclin D1-negative carcinomas, both in univariate (p = 0.0016) and in multivariate survival analyses (p = 0.0038). Expression of cyclin D1 in carcinomas with multimodal treatment was correlated with poor response to chemotherapy (p = 0.026) but not with overall survival. We thus consider expression of cyclin D1 to be an important parameter, predicting an unfavorable overall survival of surgically treated esophageal cancer patients.

Adult↗
PubMed1999

Enhanced intestinal expression of heat shock protein 70 in patients with inflammatory bowel diseases.

Heat shock protein (Hsp) 70 is stress-inducible and exhibits both protective and antigenic properties. This study investigated the mucosal expression of the constitutive (Hsp70c) and inducible form (Hsp70i) as well as antibodies against human Hsp70 in inflammatory bowel disease and controls. Biopsies were assessed by immunoblot and immunofluorescence, resection specimens by immunohistochemistry, and mucosal antibody content by isoelectric focusing. Compared to controls, expression of Hsp70 was enhanced in ulcerative colitis (P<0.05), less so in Crohn's disease and infectious colitis. Strong epithelial staining was found for Hsp70c and Hsp70i in both diseases. Mucosal and submucosal mononuclear cells showed enhanced Hsp70c expression in Crohn's disease and to a lesser degree in ulcerative colitis. Antibodies of isotypes A or M were detected in nearly all patients and controls. The different pattern of Hsp70 expression in Crohn's disease compared to ulcerative colitis points to a distinct protective and immunological function, whereas a role in autoimmunity seems unlikely.

Adult↗
PubMed1999

Prognostically orientated multimodality treatment including surgery for selected patients of small-cell lung cancer patients stages IB to IIIB: long-term results of a phase II trial.

Following mediastinoscopy, a prognostically orientated multimodality approach was chosen in selected small-cell lung cancer (SCLC) patients with hyperfractionated accelerated chemoradiotherapy (Hf-RTx) and definitive surgery (S). Stage IB/IIA patients had four cycles of cisplatin/etoposide (PE) and surgery. Stage IIB/IIIA patients had three cycles PE followed by one cycle concurrent chemoradiation including Hf-RTx and surgery. Most stage IIIB patients were not planned for surgery and had CTx followed by sequential RTx or one cycle concurrent CTx/RTx. Of 46 consecutive patients (stage IB six, IIA two, IIB/IIIA 22, IIIB 16) 43 (94%) showed an objective response. Twenty-three of patients (72%) planned for inclusion of S were completely resected (R0) (IB 6/6, IIA 2/2, IIB/IIIA 13/22, IIIB 2/2). Overall toxicity was acceptable--one patient died of septicaemia, no perioperative deaths occurred. Median follow-up of patients alive (n = 21) is 52 months (30+ - 75+). Median survival and 5-year survival rate of all patients are 36 months and 46%, in R0 patients 68 months and 63% (R0-IIB/IIIA/IIIB: not yet reached and 67%). This multimodality treatment including surgery proved highly effective with 100% local control and remarkable long-term survival after complete resection, even in locally advanced SCLC stages IIB/IIIA patients.

Adolescent↗
PubMed1999

Identification of a novel promoter mutation in the human pyruvate kinase (PK) LR gene of a patient with severe haemolytic anaemia.

Using direct sequencing we analysed the pyruvate kinase (PK) LR gene of a patient with severe haemolytic anaemia due to PK deficiency. A novel promoter mutation -249delA relative to the translation initiation site and the common 1529A mutation in exon 11 of the gene could be identified. Reverse transcription (RT)-PCR analysis combined with restriction digestion revealed that the -249delA mutation leads to a reduction in the amount of mRNA produced from this allele to about 6% of normal. We assume that both mutations would account for the PK deficiency in the compound heterozygous patient.

Anemia, Hemolytic↗
PubMed1999

Higher incidence of severe hypoglycaemia leading to hospital admission in Type 2 diabetic patients treated with long-acting versus short-acting sulphonylureas.

AIMS: A comparison of the frequency of severe hypoglycaemia leading to hospital admission in people with Type 2 diabetes mellitus (DM) treated with long vs. short-acting sulphonylureas. METHODS: A community based study over a 12-year period in the population of the city of Basle, Switzerland. The number of diabetic patients treated with oral hypoglycaemic agents was established on the basis of tablet consumption and a defined daily dose, e.g. 7.5 mg for glibenclamide, and 50 mg for glibornuride. RESULTS: Twenty-eight Type 2 diabetic patients were admitted for severe hypoglycaemia, with a median age of 73 years. There were no deaths. Sixteen of these admissions were patients treated with long-acting sulphonylureas and 12 were patients treated with short-acting forms. Only 23.5% of the population with Type 2 DM in Basle were treated with long-acting sulphonylureas. With 30345 person-years of observation, the incidence of severe hypoglycaemia was 2.24 per 1000 person-years for long-acting sulphonylureas vs. 0.75 per 1000 person-year for short-acting forms, odds ratio 3.01 (95% confidence interval 1.35-6.77). Decreased food intake (nine patients) was a major contributing factor. CONCLUSIONS: Severe hypoglycaemia leading to hospital admission is more common in elderly Type 2 diabetic patients treated with long-acting compared to short-acting sulphonylureas. Such long-acting sulphonylureas should be avoided.

Aged↗
PubMed1999

Elevated serum thrombopoietin and interleukin-6 concentrations in thrombocytosis associated with inflammatory bowel disease.

Reactive thrombocytosis is a typical feature in inflammatory bowel disease (IBD). The question arose as to whether the normal negative feedback regulation of the concentration of thrombopoietin (TPO) in blood was altered in IBD patients. We measured serum immunoreactive TPO in 30 patients with active IBD, 29 patients with inactive IBD, and 56 healthy controls. The results were related to platelet and leukocyte counts and to the serum concentration of interleukin 6 (IL-6). Patients with active IBD exhibited significantly increased TPO levels (medians 112 pg/ml vs. 90 pg/ml in controls, p < 0.05) in association with thrombocytosis (428 platelets/nl blood vs. 241 platelets/nl blood in controls), leukocytosis, and increased IL-6 levels (12.9 pg/ml vs. 2.5 pg/nl in controls). In patients with inactive IBD, only platelets (322/nl) and leukocytes were above normal. Although the observation of increased TPO and IL-6 levels provides an explanation for the occurrence of thrombocytosis in IBD, the pathogenetic mechanisms underlying the elevated TPO level still need to be identified.

Adolescent↗
PubMed1999

Mesenteric blood flow is related to disease activity and risk of relapse in ulcerative colitis: a prospective follow up study.

BACKGROUND: The diagnostic significance of increased splanchnic blood flow in ulcerative colitis is unclear. This prospective study was therefore undertaken to define the role of Doppler sonography in the assessment of disease activity and in the prediction of early relapse. SUBJECTS/METHODS: Splanchnic flowmetry was performed in 76 patients with ulcerative colitis (47 with active disease and 29 in remission), six with infectious colitis, and 13 healthy controls during fasting and 30 minutes after ingestion of a standardised meal. Twenty seven of the patients with ulcerative colitis and all patients with infectious colitis were investigated during the active state as well as in clinical remission and followed up for six months. Flow velocity and pulsatility index (PI) of the superior (SMA) and inferior (IMA) mesenteric arteries and the portal vein were related to clinical (Truelove index), laboratory (C-reactive protein), and endoscopic (Sutherland index) parameters of disease activity. RESULTS: The mean flow velocity of the IMA correlated closest with clinical activity (Truelove, r = 0.41, p<0.005), the PI with C-reactive protein (r = 0.30, p<0.05), and endoscopic activity (r = 0.45, p<0.001). All patients in remission after six months (14/14) or with infectious colitis (6/6) showed an increase in PI of the IMA compared with the initial measurement during active disease (mean increase for ulcerative colitis +36% and for infectious colitis +77%). In contrast, most patients with later relapse or surgery (11/13) had decreased PI during initial remission (mean decrease -12%). The positive predictive value of this index for maintenance of remission was 0.77. Flow variables of the SMA and portal vein displayed weaker correlations. CONCLUSIONS: Flow measurements in the IMA are closely related to clinical and endoscopic disease activity in patients with ulcerative colitis. Repeated measurement of the PI allows estimation of the risk of recurrence.

Adolescent↗
PubMed1999

Induction chemotherapy followed by concurrent chemotherapy and high-dose radiotherapy for locally advanced squamous cell carcinoma of the cervical oesophagus.

The efficacy and toxicity of combined radiochemotherapy for locally advanced squamous cell carcinomas of the cervical oesophagus was evaluated retrospectively. Induction chemotherapy consisted of three courses of 5-fluorouracil (5-FU), leucovorin, etoposide and cisplatin (FLEP) or two courses weekly six times of 5-FU and leucovorin combined with biweekly cisplatin. This induction regimen was followed by high-dose external beam radiotherapy up to 60-66 Gy and concurrent chemotherapy with cisplatin and etoposide. Median follow-up of the recruited 17 patients was 37 months (13-73 months). Long-term survival was 24% at 2 and 3 years. The probabilities of locoregional tumour recurrences and distant metastases as sites of first relapse were 67 and 39% at 2 years. Acute and late toxicity of this schedule was moderate. The protocol offers a definitive chance of long-term survival for patients with locally advanced carcinomas of the cervical oesophagus, but local in-field recurrences remain the predominant risk after treatment. Intensification of the regimen seems possible because no dose-limiting late toxicities were observed.

Adult↗
PubMed1999

Root coverage employing an envelope technique or guided tissue regeneration with a bioabsorbable membrane.

BACKGROUND: Different treatment modalities have been described for root coverage in cases of gingival recession. The aim of the present study was to evaluate the postsurgical outcome of 2 modes of surgical root coverage of predominantly shallow, Class I or II, gingival recessions. METHODS: Fourteen buccal recession sites in 13 patients were treated with free connective tissue grafts employing a modified envelope technique; 14 sites in 9 patients were subjected to a coronally repositioned flap in combination with a bioabsorbable membrane. Immediately before surgery as well as after 6 months, gingival dimensions, i.e., width and thickness, as well as root coverage and attachment gain, were assessed to the next 0.1 mm employing a caliper, an ultrasonic device, and a pressure calibrated, computerized periodontal probe. RESULTS: At the outset, mean recession depths amounted to 2.48+/-1.06 and 3.00+/-1.95 mm for patients treated with a free connective tissue graft and a bioabsorbable membrane, respectively. With the former technique, 80+/-24% root surface could be covered after 6 months, while the latter resulted in only 45+/-40% coverage. The contrast in reduction of recession width was even more pronounced (77+/-35% versus 18+/-37%). In both groups, an increase of gingival thickness of 0.6 to 0.7 mm was noticed. CONCLUSIONS: Small recessions may be covered more predictably with the modified envelope technique. 751.

Absorbable Implants↗
PubMed1998

Molecular cloning of human GDP-mannose 4,6-dehydratase and reconstitution of GDP-fucose biosynthesis in vitro.

We have cloned the cDNA encoding human GDP-mannose 4,6-dehydratase, the first enzyme in the pathway converting GDP-mannose to GDP-fucose. The message is expressed in all tissues and cell lines examined, and the cDNA complements Lec13, a Chinese Hamster Ovary cell line deficient in GDP-mannose 4,6-dehydratase activity. The human GDP-mannose 4,6-dehydratase polypeptide shares 61% identity with the enzyme from Escherichia coli, suggesting broad evolutionary conservation. Purified recombinant enzyme utilizes NADP+ as a cofactor and, like its E. coli counterpart, is inhibited by GDP-fucose, suggesting that this aspect of regulation is also conserved. We have isolated the product of the dehydratase reaction, GDP-4-keto-6-deoxymannose, and confirmed its structure by electrospray ionization-mass spectrometry and high field NMR. Using purified recombinant human GDP-mannose 4,6-dehydratase and FX protein (GDP-keto-6-deoxymannose 3,5-epimerase, 4-reductase), we show that the two proteins alone are sufficient to convert GDP-mannose to GDP-fucose in vitro. This unequivocally demonstrates that the epimerase and reductase activities are on a single polypeptide. Finally, we show that the two homologous enzymes from E. coli are sufficient to carry out the same enzymatic pathway in bacteria.

Amino Acid Sequence↗