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Biomedical subjects

M Maier

Publications and source records attributed to M Maier.

At least 127 records · Page 7Linked to original sources

Design and implementation of an electronic point-of-contact oncology clinical record.

An electronic point-of-contact narrative clinical record was developed and implemented in a multidisciplinary regional cancer center with an annual new caseload of 1,200. Design principles included (1) natural clinician-intuitive interface with pen, touch, and sound input options; (2) structure and processes enabling direct input of both clinician-reported and patient-reported data; (3) embedding of decision support and practice guidelines directly into the interface; (4) incorporation of automated cancer staging algorithms; (5) automatic production of consultation and progress notes, limiting transcription requirements to sound fields; (6) outcomes--focused report formats; and (7) integrated billing and activity reporting. The system was implemented in Windows, both on a local area network and on mobile devices. Evaluation parameters included feasibility, acceptance, performance, cost of hardware and software development and/or customization, cost of system maintenance, and comparison of net clinician time for encounter documentation relative to a paper-based standard. Feasibility, acceptance, and cost-effectiveness were established.

Decision Making, Computer-Assisted↗

Enzymatic degradation of various antisense oligonucleotides: monitoring and fragment identification by MECC and ES-MS.

Efficacy and sequence specific behaviour of antisense oligonucleotides in biological systems are attenuated by enzymatic degradation, which is predominantly dependent on the oligonucleotide modification. Quantitative data relating to the kinetics and pattern of enzymatic digestion are thus valuable for the interpretation of biological tests with novel antisense oligonucleotides. To study the stability of modified oligonucleotides against nuclease attack, in vitro experiments of enzymatic degradation have been carried out using micellar electrokinetic capillary chromatography (MECC) as a quantitative control and electrospray mass spectrometry (ES-MS) for fragment identification. In contrast to gel electrophoresis, which is commonly applied, monitoring of enzymatic digestion by MECC can be carried out directly from the incubated sample without the need for labeled substrate. Furthermore, exact quantitative analysis becomes possible. Phosphodiester oligonucleotides terminally conjugated with hexaethylene glycol have been prepared to investigate the stability and degradation process of 3'- and 5'-protected oligomers with natural backbones in serum-containing medium. The results demonstrate that 3'-protection is much more effective than 5'-protection for nuclease stability, both in fetal calf serum and in human blood serum. To examine the influence of backbone modification on nuclease stability, the digestion of dodecanucleotides containing different numbers of phosphorothioate groups has been investigated by MECC and ES-MS. Degradation rates vary by a factor of approximately 50. Most fragments have been identified and the degradation patterns allow conclusions about the variations of nucleolytic activity with changing substrates.

Base Sequence↗

Analysis of double-stranded oligonucleotides by electrospray mass spectrometry.

Double-stranded oligonucleotides of different lengths and chemical modification have been analyzed by ion spray mass spectrometry. The non-covalent-bonded duplexes can be detected. Therefore, ion spray mass spectrometry is a useful method for investigation of hybridizations of natural and chemically modified oligonucleotides. Since the exact mass of the double strand can be detected, this method can distinguish between specific and nonspecific interaction.

Base Sequence↗

[Benign bile duct stenosis--conservative management as long as possible?].

The clinical course of 37 patients (15 female, 22 male) treated endoscopically for benign biliary stenosis was analyzed retrospectively. Patients with chronic pancreatitis (n = 20) were compared to those (n = 17) with biliary stenosis due to other reasons, postoperative strictures in most cases. Each patient received at least one 10- or 11.5-French endoprosthesis. The liver enzyme and serum bilirubin levels returned to normal or slightly elevated levels. The average time until exchange or extraction of the prosthesis was 11.4 (range 2 to 33) months in patients with chronic pancreatitis and 5.1 (0.5 to 21) months in patients with postoperative strictures. The therapy was completed by extraction of prosthesis in six patients with chronic pancreatitis (30%) and in 14 patients with stenosis due other reasons (82.3%). None of the patients died of complications related to endoscopic therapy.

Adult↗

[Acute pancreatitis due to the rupture of an echinococcal cyst into the bile duct system].

A 47-year-old woman with stones in the gall-bladder suddenly developed severe upper abdominal pain. Cholesterol concentration was elevated, as were amylase (555 U/l) and lipase (408 U/l) concentrations, suggesting biliary pancreatitis. Endoscopic retrograde cholangiography demonstrated a cyst, about 10 cm in diameter, in the left lobe of the liver, connected to the biliary tract system. Ultrasonography and computed tomography additionally showed a smaller cyst in the right lobe. Infection with Echinococcus granulosus was proven microbiologically on bile (demonstration of hooklets and protoscolices) as well as serologically. Transpapillary cholangioscopy demonstrated daughter cysts within the echinococcal cyst. The main cyst was rinsed with 20% NaCl for 10 days via a nasocystic catheter. In addition, mebendazole (three times daily 1000 mg) was administered for 13 months. The signs if inflammation receded and the cyst shrank to a small residual volume. Surgical intervention became unnecessary.

Acute Disease↗

Hypoxia-induced accumulation of erythropoietin mRNA in isolated hepatocytes is inhibited by protein kinase C.

To define the role of protein kinase C (PKC) in oxygen-dependent production of erythropoietin (EPO) in the liver, we have determined EPO messenger ribonucleic acid (mRNA) expression in primary cultures of juvenile rat hepatocytes incubated at different oxygen tensions in the absence and presence of phorbol esters, vasopressin, and structurally different kinase inhibitors. Upon reduction of oxygen concentrations from 40% to 3% EPO mRNA in cultured hepatocytes increased markedly within 1.25 h, reached maximal values after 2.5 h and remained elevated for up to 72 h. Treatment of hepatocytes during 1.25-5 h of hypoxic exposure with phorbol 12-myristate-13 acetate (PMA) attenuated hypoxia-induced EPO mRNA levels dose-dependently by a maximum of approximately 50%. This inhibitory effect of PMA disappeared upon treatment for more than 5 h and was completely lost after incubation for 9 and 18 h in the presence of 10(-6) M and 10(-7) M PMA, respectively. Phorbol 12,13-dibutyrate and vasopressin also inhibited EPO mRNA accumulation, whereas 4 alpha-phorbol 12,13-didecanoate was ineffective. Western blot analysis of PKC isozymes revealed the presence of PKC alpha, beta II, delta, epsilon and zeta and provided no evidence that the PMA-induced inhibition of EPO expression was associated with depletion of any of these isozymes. Conversely, PMA-induced inhibition of EPO mRNA accumulation was paralleled by translocation of PKC alpha from cytosol to membranes and the time- and dose-dependent attenuation of the inhibitory effect of PMA on EPO mRNA levels was paralleled by down-regulation of PKC alpha. A dose-dependent inhibition of EPO mRNA formation, independent of effects on total RNA synthesis, as determined by [3H]uridine incorporation, was also found in the presence of the kinase inhibitor staurosporine (ED50 approximately 2 x 10(-8) M) and three structurally related derivatives with increased selectivity for PKC (RO 317549, ED50 approximately 1 x 10(-6) M; RO 318220, ED50 approximately 1 x 10(-6) M and CGP 41251, ED50 approximately 4 x 10(-6) M). The markedly lower potency of the latter three compounds as compared to staurosporine suggests that this suppression of EPO gene induction was not mediated by inhibition of PKC. In summary the data indicate that PKC alpha is a negative modulator of EPO gene expression in hepatocytes. A kinase other than PKC, however, appears to be an essential element of hypoxic signalling.

Alkaloids↗

Combination therapy with a synthetic peptide of C-reactive protein and interleukin 2: augmented survival and eradication of pulmonary metastases.

A synthetic peptide (RS-83277) derived from the structure of human C-reactive protein (CRP) was previously shown to have antitumor activity in three different murine tumor models when administered in multilamellar vesicles (MLV). The therapeutic effects were comparable to those seen with MLV-encapsulated native CRP. The present study evaluated the therapeutic and immunomodulatory effects of administering CRP peptide RS-83277 MLV simultaneously with low-dose recombinant interleukin-2 (IL-2) to C57Bl/6 mice bearing established pulmonary metastases of fibrosarcoma T241. Results demonstrated that the capacity of RS-83277 MLV to inhibit tumor metastases and prolong survival was significantly augmented by combination with 10,000 U/day IL-2 i.p. Treated animals showed no evidence of toxicity. By immunohistochemistry, increased Thy 1.2+ cells were detectable in lungs of RS-83277 MLV/IL-2-treated animals compared to those receiving RS-83277 MLV alone. Circulating tumor necrosis factor alpha (TNF) and interferon (IFN) were not detectable in animals receiving RS-83277 MLV alone, but TNF was significantly elevated in animals receiving IL-2. In the presence of combination therapy, however, circulating TNF was not detectable. Results suggest that the combination of synthetic CRP peptide RS-83277 MLV and low-dose IL-2 offers a therapeutic advantage over either agent alone.

Animals↗

Fluoroscopically guided laser lithotripsy of a pancreatic duct stone.

A 54-year-old man with early stage chronic pancreatitis and an impacted ductal stone in the pancreatic head complicated by a 2 cm abscess was treated with pulsed dye laser lithotripsy using an automatic stone tissue differentiation system under fluoroscopic control. This system automatically switches off the laser on contact with tissue. The 0.25 mm quartz fiber introduced into the pancreatic duct via a 5 French teflon catheter delivered 165 out of 1000 pulses at contact with the stone (100 mJ, 10 Hz). Partial stone disintegration was achieved making mechanical stone removal possible which initially failed. No major side-effect occurred. This new laser with a stone detection system seems to render fluoroscopically guided laser lithotripsy in the pancreatic duct safer thus warranting further clinical trials.

Calculi↗

[Barrett esophagus with severe epithelial dysplasia--always surgery? A case report].

A 57 year-old patient presented with a Barrett's epithelium over the length of 18 cm. We found the typical functional changes of acid reflux and hypomotility in the distal esophagus. There was a history of chemotherapy for seminoma 30 years ago. Because of the repeated finding of severe dysplasia surgery was proposed. The patient died in the postoperative period with the signs and symptoms of pulmonary embolism. There was no invasive tumor found in the resected part of the esophagus. Main aspects of the etiology and histological characterism of Barrett's esophagus and the indication for surgery in cases with severe dysplasia are discussed.

Barrett Esophagus↗

[Carcinoid tumor of the lung. An unusual form of ocular metastasis].

Carcinoid tumors are slowly and locally invasive growing neoplasms. Their main localization is in the ileum or in organs derived from the embryonic foregut, i.e. bronchus, stomach, pancreas and thyroid. The low rate of metastatic manifestation of about 10% indicates their potential malignancy. The endocrine effects vary. We describe the case of a 30-year-old female patient, who had had a carcinoid tumor of the bronchus with infiltration of a hilar lymph node, which had been resected two years previously. The postoperative course was marked by an increased level of urine 5-hydroxyindolacetic acid (5-HIAA). Finally, the patient complained a 4-month history of recurrent episodes of refractory conjunctival hyperemia, visual loss and visual field defects in both eyes. Examination revealed bilateral multiple choroidal masses associated with retinal detachment. As various authors have reported, carcinoid tumor metastases to the eye are extremely rare. Diagnostic approaches and therapeutic considerations are described. Ultrasonic examination of the choroidal lesion, applying standardized A-scan echography at tissue sensitivity, showed solid tissue masses and bilateral circumscribed exudative retinal detachment. The tumor was characterized by medium to high reflectivity and slight sound attenuation. The internal structure showed less irregularity than is usually seen in metastases.

Adult↗

Direct dissolution of gallstones with methyl tert-butyl ether by endoscopic cannulation of the gallbladder.

Methyl tert-butyl ether (MTBE) rapidly and effectively dissolves cholesterol gallbladder stones. Due to the invasive nature of transhepatic catheterization, we studied the safety and efficacy of MTBE stone dissolution, delivered by endoscopic, retrograde cannulation of the gallbladder. Extracorporeal shock-wave lithotripsy (ESWL) was employed in patients with multiple stones, to increase contact surface area and facilitate dissolution. We successfully cannulated the gallbladder in 13/17 patients (76.5%) attempted, with no associated complications. After cannulation, MTBE lysis was then conducted on all patients, and 10/13 patients (77%) cannulated were either stone-free at completion, or had only residual gallbladder sludge. Predissolution ESWL successfully fragmented stones in 6/7 patients (86%) in which it was attempted. Both ESWL and MTBE were well tolerated by all patients. Endoscopic retrograde cannulation of the gallbladder and MTBE dissolution is a promising alternative for the treatment of gallbladder stones in patients who will not receive surgery.

Aged↗

Inhibition of tissue kallikrein by protein C inhibitor. Evidence for identity of protein C inhibitor with the kallikrein binding protein.

We studied the inhibition of tissue kallikrein by protein C inhibitor (PCI), a relatively unspecific heparin-dependent serine protease inhibitor present in plasma and urine. PCI inhibited the amidolytic activity (cleavage of H-D-valyl-L-leucyl-arginine-p-nitroaniline) of urinary kallikrein with an apparent second order rate constant of 2.3 x 10(4) M-1 s-1 and formed stable complexes (85 kDa) with urinary kallikrein as judged from silver-stained sodium dodecyl sulfate-polyacrylamide gels. Complex formation was time-dependent and was paralleled by a decrease in the intensity of the main PCI protein band (Mr = 57,000) and an increase in the intensity of the lower Mr (54,000) PCI form (cleaved inhibitor). Heparin interfered with the inhibition of tissue kallikrein by PCI and with the formation of tissue kallikrein-PCI complexes in a dose-dependent fashion and completely abolished PCI-tissue kallikrein interaction at 300 micrograms/ml. This is in contrast to findings on the interaction of PCI with all other target proteases studied so far (i.e. stimulation of inhibition by heparin) but is similar to the reaction pattern of 125I-labeled tissue kallikrein with so called kallikrein binding protein described in serum and other systems. To study a possible relationship between PCI and this kallikrein binding protein we incubated 125I-labeled urinary kallikrein in serum and in PCI-immunodepleted serum in the absence and presence of heparin and analyzed complex formation using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In normal serum, formed complexes co-migrated with complexes of purified PCI and 125I-kallikrein and were less intense in the presence of heparin. No complex formation at all was seen in PCI-depleted serum. Our data indicate that PCI may be a physiologically important endogenous inhibitor of tissue kallikrein and provide evidence that PCI may be identical to the previously described kallikrein binding protein.

Amides↗

Possible identity of kallikrein binding protein with protein C inhibitor.

Protein C inhibitor (PCI) inhibits tissue kallikrein by forming stable 1:1 complexes (k1 = 2.3 x 10(4)M-1s-1). Heparin inhibits the tissue kallikrein/PCI-interaction and complex formation of 125I-tissue kallikrein in serum. 125I-tissue kallikrein complexes formed in plasma can be immunoprecipitated with monoclonal anti-PCI IgG suggesting that PCI might be identical to the kallikrein binding protein described previously (J. Chao et al. 1986, Biochem. J. 239, 325-331).

Carrier Proteins↗

Determination of human low molecular weight kininogen by immunoassay.

It was the aim of the present investigation to develop a convenient method for determination of human kininogens. Using mono- and polyclonal antibody preparations an ELISA-system for specific determination of LMWK could be developed. In addition, the specificity of the monoclonal antibody suggests that their epitope in HMWK and its heavy chain is different to that in LMWK.

Antibodies, Monoclonal↗

[Pearson's syndrome. Pancytopenia with exocrine pancreatic insufficiency: new mitochondrial disease in the first childhood].

Pearson's syndrome is a lethal disorder of a still unknown cause, responsible for pancytopenia and exocrine pancreatic dysfunction in the first months of life. Permanent hyperlactacidemia and increased mitochondrial and cytoplasmic oxidoreduction ratios were observed in 6 unrelated children presenting with this disease. This led to study the oxidative phosphorylation in lymphocytes and thus to relate Pearson's syndrome to an enzymatic disease of the respiratory chain (NADH oxidase activity deficiency). The study of the mitochondrial genome allowed identifying major changes in mitochondrial DNA in all patients and all studied tissues. Thus, Pearson's syndrome is the first mitochondriopathy with a non neuromuscular expression reported to date.

DNA, Mitochondrial↗

[Erythrocyte morphology in asymptomatic microhematuria: experimental studies and clinical significance].

Renal and postrenal origin of hematuria can be differentiated by analysis of the morphology of the erythrocytes in the urinary sediment. In order to investigate the mechanisms which cause the membrane changes in dysmorphic erythrocytes, indicating renal origin of bleeding, normal red blood cells were exposed in vitro to an osmotic environment similar to that of the nephron. Upon exposure of osmotically challenged erythrocytes to a hemolytic environment, 50 to 90% of the cells became dysmorphic in a time- and dose-dependent manner and were indistinguishable on light and electron microscopy from those obtained in vivo from a patient with proven glomerular microhematuria. The reliability of erythrocyte morphology in differentiating between renal and postrenal microhematuria was evaluated by performing microscopic analysis as the initial step in the investigation of 316 consecutive patients. In 123 patients with eumorphic red cells in their urine complete urological investigation revealed a postrenal source of bleeding in 85%. Out of 193 patients with dysmorphic erythrocytes, 132 were followed up for at least 2 years after only minimal diagnostic evaluation. An additional postrenal source of bleeding developed in two patients, which was easily diagnosed by the change in erythrocyte morphology. Our studies, representing experience over 6 years with asymptomatic microhematuria, show that microscopic examination of erythrocyte morphology as initial diagnostic step is a safe, inexpensive and efficient method which renders invasive investigations superfluous in the majority of patients.

Adolescent↗