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M Stahl

Publications and source records attributed to M Stahl.

At least 91 records · Page 5Linked to original sources
PubMed1997

Down-regulation of topoisomerase II by camptothecin does not prevent additive activity of the topoisomerase II inhibitor etoposide in vitro.

Topoisomerases (Topo) I and II are cellular enzymes that catalyze the relaxation of topologically strained DNA and that are involved in a number of DNA-related processes. Their complete inhibition by Topo I and II inhibitors gives promise for improvements in the treatment of malignant diseases. However, preclinical studies showed down-regulation of Topo II protein expression by Topo I inhibitors, which may preclude the useful application of combined topoisomerase inhibition in the clinic. We investigated the efficacy of the combination of etoposide (ETP) and camptothecin (CPT) in human gastric and lung cancer cell lines with different sensitivity towards ETP. The cytotoxicity of different drugs was assessed by the sulforhodamine B assay. Drug interactions were evaluated by isobologram analysis. The polymerase chain reaction and flow cytometry were employed for examination of the mdr1 (multidrug resistance type 1) phenotype. As reported by others, incubation of the P glycoprotein (P-gp)-negative tumor cell lines with the Topo I inhibitor CPT resulted in a significant down-regulation of Topo II protein expression. This was obviously due to changes in the cell cycle distribution of the cells induced by the treatment, with a marked increase of cells in G2/M phase and a consecutive decrease of S phase cells. Despite these biochemical changes, isobologram analysis showed additive cytotoxic activity of CPT and ETP in all the cell lines, independent of whether the drug incubation was performed simultaneously or sequentially. These data indicate that down-regulation of Topo II protein by CPT does not prevent additive activity of CPT and ETP in vitro, and therefore combined Topo I and II inhibition may be useful for investigation in clinical trials.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Crohn's disease and sarcoidosis: systemic granulomatosis?

We report an unusual case of severe Crohn's disease with involvement of the lung. In 1993 at age 21 a male patient experienced a Helicobacter-negative duodenitis. A routine chest radiograph revealed spotted opacities in the right upper lobe without discomfort and normal pulmonary function except for a reduced diffusion capacity. Bronchoalveolar lavage showed mild lymphocytosis and biopsies from the macroscopically normal bronchi displayed non-caseating granulomas. In 1995 he had symptoms of peptic ulcer disease with a gastric outlet stenosis. He underwent Billroth I resection with only temporary improvement. Three months later the symptoms had recurred and a stenosing inflammatory process of the duodenum was seen on endoscopy suggesting Crohn's disease. A chest radiograph demonstrated infiltrations in parts of the left lung and bronchoalveolar lavage again revealed alveolar lymphocytosis (CD4/CD8 ratio 3.1). Both the gastrointestinal and pulmonary affections responded to corticosteroids but the duodenal stricture had to be resected. The association of Crohn's disease and pulmonary disorders is discussed.

Adrenal Cortex Hormones↗
PubMed1997

Quality assessment of blood glucose testing in general practitioners' offices improves quality.

Measurement of blood glucose is a frequent test in Danish physicians' offices. We describe here a new design of external quality assessment wherein fresh, unstabilized whole-blood samples were analyzed by the physicians' office methods and by a hospital laboratory comparison method (glucose dehydrogenase assay, calibrated against NIST 909a). This approach was used in the offices of 171 general practitioners in our county during a 5-year period. The first survey, in 1992, revealed unsatisfactory performance in terms of our criterion that no difference between the physician's office and the hospital laboratory's single result should exceed +/-20% of the laboratory result. After initiation of a program of consultation and assistance, the proficiency testing rounds of 1994 and 1996 showed considerable improvement. Thus, whereas in 1992 12% of the values were outside the acceptance limits, in 1994 and 1996 the respective values were 4% and 3%. We believe the effect was mainly related to improvements in choice of technology, procedures, and handling of specimens. We conclude that the use of bedside instruments should be restricted to diagnosis of only severe hypo- or hyperglycemia and to monitoring glucose >5 mmo/L in already diagnosed diabetics. Our program differs from previous approaches to quality assessment and could also be useful for large hospitals' in-house proficiency testing.

Blood Glucose↗
PubMed1996

[Preoperative radiochemotherapy in esophageal carcinoma].

Patients with esophageal cancer still have on unfavourable prognosis. After standard treatment, only 10% will survive five years. During the last years a lot of study groups intended to improve patient's prognosis by the use of multimodality treatment including chemotherapy. The concept of preoperative chemotherapy seems to be most promising. In the case of stage I and II cancer (potentially resectable tumors) multimodal therapy has not proved superior to surgery alone, so far. The results of well done phase III trials have to be waited for. Prognosis of patients with locally advanced tumors has been significantly improved by preoperative radiochemotherapy compared to surgery alone. In general, patients with localized esophageal cancer should be treated in experienced cancer centers within prospective trials.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Complete 1H, 15N and 13C assignments, secondary structure, and topology of recombinant human interleukin-6.

Essentially complete backbone and side-chain 1H, 15N and 13C resonance assignments for the 185-amino-acid cytokine interleukin-6 (IL-6) are presented. NMR experiments were performed on uniformly [15N]- and [15N,13C]-labeled recombinant human IL-6 (rIL-6) using a variety of heteronuclear NMR experiments. A combination of 13C-chemical shift, amide hydrogen-bond exchange, and 15N-edited NOESY data allowed for analysis of the secondary structure of IL-6. The observed secondary structure of IL-6 is composed of loop regions connecting five alpha-helices, four of which are consistent in their length and disposition with the four-helix bundle motif present in other related cytokines and previously postulated for IL-6. In addition, the topology of the overall fold was found to be consistent with a left-handed up-up-down-down four-helix bundle based on a number of long-range interhelical NOEs. The results presented here provide deeper insight into structure-function relationships among members of the four-helix bundle family of proteins.

Amino Acid Sequence↗
PubMed1996

Liver glycogen synthase deficiency: a rarely diagnosed entity.

UNLABELLED: Three children from two German families are described and the observation compared with the previously published three families comprising eight patients. The two index cases presented with morning fatigue, had ketotic hypoglycaemia when fasting which rapidly disappeared after eating, and hepatic glycogen deficiency and absent or very low hepatic glycogen synthase activity. Metabolic profiles comprising glucose, lactate, alanine, and ketones in blood were typical for hepatic glycogen synthase deficiency. Symptoms were rapidly relieved and chemical signs corrected by introducing frequent protein-rich meals and night-time feedings of suspension of uncooked corn (maize) starch. The discovery of oligosymptomatic and asymptomatic siblings suggests that there are more persons with undiagnosed hepatic glycogen synthase deficiency. CONCLUSION: Liver glycogen synthase deficiency is likely to be more common than is believed today. It should be sought in children who, before the first meal of the day, present with drowsiness, lack of attention, pallor, uncoordinated eye movements, disorientation or convulsions and who have hypoglycaemia and acetone in urine.

Age of Onset↗
PubMed1996

Phase I/II study with a weekly 24-hour infusion of 5-fluorouracil plus high-dose folinic acid (HD-FU/FA) in intensively pretreated patients with metastatic breast cancer.

BACKGROUND: In metastatic breast cancer patients who have had prior exposure to anthracyclines, single agents induce less than 15% and combination chemotherapy less than 20%-30% of objective responses. Therefore more active and tolerable salvage regimens are needed. PATIENTS AND METHODS: Forty-three patients with advanced breast cancer pretreated with 1-5 (median 2) different chemotherapy regimens were entered into this phase I/II trial. Treatment consisted of folinic acid (FA) (500 mg/m2, i.v., 2-hour infusion) followed by a 24-hour infusion of 5-fluorouracil (FU) which was escalated from 1.5 g/m2 (dose level (dl 1)), to 1.8 g/m2 (dl 2) to 2.1 g/m2 (dl 3). Therapy was given as outpatient treatment once weekly times 6 followed by a 2-week rest. RESULTS: HD-FU/FA was well tolerated. No dose-limiting toxicity occurred at dl 1 or 2. Only 3/32 (9%) patients had WHO grade 3/4 toxicities (gastrointestinal toxicities, hand-foot-syndrome) at dl 3. The response rate for all 32 of the patients treated at dl 3 was 41% (13/32). In the 24 patients with anthracycline-refractory disease, a response rate of 41% (10/24) was achieved. The median remission duration was 11 months and the median survival time 19 months. CONCLUSIONS: This schedule of FU/FA is a safe outpatient treatment with substantial activity in intensively pretreated breast cancer patients.

Adult↗
PubMed1996

Combined preoperative chemotherapy and radiotherapy in patients with locally advanced esophageal cancer. Interim analysis of a phase II trial.

PURPOSE: The prognosis of patients with locally advanced esophageal cancer (LAEC) remains poor when treated with local modalities. An intensive preoperative program with chemoradiotherapy was used to evaluate the curative resection rate, pathologic response, and survival of patients with LAEC. PATIENTS AND METHODS: Ninety patients with LAEC were treated preoperatively with chemotherapy (three courses of fluorouracil, leucovorin, etoposide, and cisplatin [FLEP]) followed by concurrent chemoradiotherapy (one course of cisplatin plus etoposide in combination with 40 Gy of radiation). Transthoracic esophagectomy was performed 4 weeks after the end of radiation. RESULTS: Seventy-two patients were included in this evaluation. Forty-four (61%) underwent a complete tumor resection, and 16 (22%) had no tumor in the resected specimen (pathologic complete response [PCR]). The operative mortality rate was 15%. At a median follow-up time of 22 months (range, 12 to 41), the median survival duration of all 72 patients was 17 months (range, 1 to 41+). The calculated survival rates at 3 years were 33%, 42%, and 68% for all patients, patients after complete resection, and patients with PCR, respectively. CONCLUSION: This combined treatment modality is active in LAEC, with a PCR in 33% of the patients undergoing surgery. The results appear improved compared with those reported with surgery alone, by approximately doubling the 3-year survival rate. The high efficacy of preoperative chemoradiation warrants evaluation of the role of surgery in LAEC.

Adenocarcinoma↗
PubMed1996

[Not Available].

This work presents a series of homeopathical doctors who were associated with the lay doctor Clemens von Bönninghausen (1785-1864) in the area Westfalen and introduces "Vereinigung homöopathischer Aerzte Rheinlands und Westphalens" which was founded in 1849. This is followed by biographical sketches of the chairmen until 1921.

Germany↗
PubMed1996

[Adjuvant and neoadjuvant methods: what is their value--do they change surgical procedure?].

Despite advances in surgical treatment for gastrointestinal tumors, in general, improvements in prognosis could not be achieved; therefore other therapeutical options were evaluated in a multimodal concept. Stage III or II/III disease of colorectal cancer appears to benefit from adjuvant chemo/radiotherapy by reduced relapse and mortality rates. After application of preoperative therapy for locally advanced tumors of the upper gastrointestinal tract and rectum tumor debulking and better local tumor control was achieved resulting in an increased curative resection and survival rate. Surgical procedures and the extent of resection should not be modified in multimodal treatment: the aim must be a complete tumor (R0)-resection.

Chemotherapy, Adjuvant↗
PubMed1996

Weekly infusional 5-fluorouracil plus/minus other drugs for the treatment of advanced gastric cancer.

Based on preclinical data and the promising results being achieved with infusional 5-FU in colorectal and breast cancer, we investigated a weekly schedule of a 24-hour infusion of 5-FU plus folinic acid (HD-FU/FA) in patients failing to first-line chemotherapy and HD-FU/FA plus cisplatin (C) or plus cisplatin/epidoxorubicin (C/E) in chemo-naive patients with advanced gastric cancer. In all three trials the results achieved with the tested chemotherapy regimens indicated high activity and good tolerability. All three protocols were administered as outpatient treatment. With HD-FU/FA and overall response rate of 24% and a median survival time of 5 months was observed in 17 patients refractory to or relapsing after first-line chemotherapy. HD-FU/FA/C induced an overall response rate of 66% and a median survival time of 13 months. Of note was the high activity of this regimen in patients with malignant ascites. HD-FU/FA/C/E also proved to be an interesting regimen similar active as HD-FU/FA/C but it was subjectively less well tolerated. In patients with locally advanced disease the response rate was 90% (10/11), and in patients with distant metastases 50% (8/16).

Adult↗
PubMed1995

Two unrelated children with developmental delay, short stature and anterior chamber cleavage disorder, cerebellar hypoplasia, endocrine disturbances and tracheostenosis: a new entity?

Two unrelated children with developmental delay, anterior chamber-cleavage disorder, proportionate short stature and striking similarity in facial appearance appear to have an identical syndrome. Peters' plus syndrome has to be considered but additional abnormalities not described in this syndrome and their apparently different facies may be evidence for a hitherto undescribed condition. The further malformations both children have in common are cerebellar hypoplasia, hypothyroidism, tracheostenosis and dislocated hips.

Abnormalities, Multiple↗
PubMed1994

Inactivation of a cytosolic phospholipase A2 by thiol-modifying reagents: cysteine residues as potential targets of phospholipase A2.

The cytosolic phospholipase A2 (cPLA2) from the human monocytic cell line U937 contains nine cysteine residues and is subject to oxidation. Iodoacetamide and 5,5'-dithiobis(2-nitrobenzoic acid) were used to explore the susceptibility of cysteine residues to thiol modification agents as outlined in Schemes 2 and 3. In the absence of thiol reducing agents such as DTT, cPLA2 takes up only 2.8 equiv of [1-14C]iodoacetamide at pH 8.03/37 degrees C. With DTT present, cPLA2 is in its fully reduced form, and 4-5 equiv of acetamide are taken up without altering enzyme activity to give IA-cPLA2. A single equivalent of DTNB suffices to inactivate IA-cPLA2, giving a TNB-labeled enzyme, with the loss of activity correlating with release of an equivalent of 5-thio-2-nitrobenzoate. The TNB-labeled enzyme is quite stable up to 33 degrees C; enzyme activity is recoverable with DTT, even after this disulfide-enzyme adduct is incubated with iodoacetamide at pH 9.5, conditions that inactivate the free enzyme. At pH 9.5/37 degrees C, a single equivalent of 14C-labeled iodoacetamide is incorporated by IA-cPLA2 concomitant with complete loss of enzyme activity. Amino acid analysis of the 14C-labeled enzyme indicates that only cysteine residues are labeled. Lys-C digestion of labeled enzyme with 2 M guanidine at pH 8.0 yields a 40-mer peptide. Amino acid sequencing establishes that the label resides primarily in Cys324, although Cys331 is also labeled. These results identify a region of the enzyme that is susceptible to labeling by group modification reagents and may represent a suitable target for small molecule inhibitors.

Amino Acid Sequence↗
PubMed1994

5-Fluorouracil, folinic acid, etoposide and cisplatin chemotherapy for locally advanced or metastatic carcinoma of the oesophagus.

38 patients with advanced oesophageal carcinoma were treated with intravenous (i.v.) folinic acid (300 mg/m2), 5-fluorouracil (500 mg/m2), etoposide (100 mg/m2), and cisplatin (30 mg/m2) (FLEP), on days 1, 2 and 3, every 22-28 days. 26 patients had locally advanced disease (LAD) and 12 had metastatic disease (M1). Oesophagectomy was planned for patients with LAD in case of tumour regression after chemotherapy, while patients with M1 disease received chemotherapy only. The overall remission rate was 45% (17/38) including four clinical and two pathologically confirmed complete remissions. 16 patients underwent oesophagectomy, 12 after response to FLEP, and 4 after FLEP and subsequent irradiation +/- 5-fluorouracil/mitomycin. Toxicity was mainly haematological, with WHO grade 3 and 4 leukocytopenia in 50% and thrombocytopenia in 31% of the patients. Two treatment-related deaths were observed; one due to chemotherapy and one postoperatively. Median survival time of LAD patients was 13 months, and actuarial 2-year survival was 31%. Patients with complete tumour resection after FLEP had a median survival time of 18 months and a 2-year survival rate of 42%. Median survival of M1 patients was 6 months. FLEP is an active combination for oesophageal cancer, especially when used preoperatively in LAD.

Adenocarcinoma↗
PubMed1994

Current status and future directions in the treatment of localized esophageal cancer.

Due to insufficient local tumor control in the majority of esophageal carcinoma (EC) patients and due to distant recurrences, the dismal prognosis of patients with EC has not essentially changed during the past two decades. This holds true despite extended surgical procedures and improved radiation techniques. The 2-year survival rates in stage IIB/III which represent two-thirds of the patients with localized EC is still less than 20%. Therefore, clinical efforts in the management of EC focus on combined modality treatment (CTM), usually preoperative chemotherapy (CTx)/chemoradiotherapy (CTx/RTx) or CTx/RTx alone. Up to now, results of CTM in potentially resectable EC have not shown that preoperative CTx or CTx/RTx is superior to surgery alone with respect to resectability, local tumor control and overall survival. However, CTx responders who subsequently underwent a complete tumor resection had a markedly improved long term survival indicating that the inclusion of CTx in the treatment of EC may improve the prognosis. The benefit of CTx could also be demonstrated in a randomized trial comparing RTx alone versus CTx/RTx with a reduction of local and distant failures and significantly improved survival in the CTM arm. Similar observations were made with CTM in locally advanced disease. To date, there is sufficient evidence that preoperative treatment of EC may improve prognosis at least of subgroups of patients with this tumor. However, this has to be confirmed in well designed (proper staging including endoscopic ultrasound, etc.) randomized trials.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents↗
PubMed1994

Weekly high-dose 5-fluorouracil and folinic acid as salvage treatment in advanced gastric cancer.

BACKGROUND: A weekly schedule of a 24-h high-dose 5-FU infusion in combination with folinic acid was investigated as salvage therapy in patients with advanced gastric cancer. PATIENTS AND METHODS: Seventeen patients with progressive disease after chemotherapy were treated with a weekly schedule of 500 mg folinic acid/sqm by i.v. 2-h infusion followed by an i.v. 24-h infusion of 2.6 g 5-FU/sqm times six. Fourteen of the 17 patients (82%) had been pretreated in regimens which included 5-FU/folinic acid i.v. bolus. RESULTS: Toxicity was mild, with diarrhea, mucositis and nausea; WHO grade III/IV diarrhea was observed in only two patients. Three patients achieved partial remissions (18%; 95% confidence interval: 0%-38%) and 7 patients stable disease (41%; 95% confidence interval: 17%-64%). Their median survival time was five months (range 1.5-10 months) after the onset of salvage therapy. CONCLUSIONS: This schedule of weekly 24-h infusions of high-dose 5-FU and folinic acid is effective, even in patients pretreated with or resistant to regimens including 5-FU/folinic acid i.v. bolus. Based on these data, it appears that this schedule of high-dose 5-FU/folinic acid in first-line combination chemotherapy merits investigation.

Adult↗