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Biomedical subjects

C Riedel

Publications and source records attributed to C Riedel.

At least 37 records · Page 2Linked to original sources
PubMed2001

Phase II study of a weekly 24-hour infusion with 5-fluorouracil and simultaneous sodium-folinic acid in the first-line treatment of metastatic colorectal cancer.

BACKGROUND: A weekly continuous 24-hour infusion therapy with 5-fluorouracil (5-FU) and calcium - folinic acid (CA-FA) was shown to be an effective first-line treatment in advanced metastatic colorectal cancer. Sodium - folinic acid (S-FA) is a new formulation which, in contrast to CA-FA allows the simultaneous i.v. administration in combination with 5-FU in one pump. PATIENTS AND METHODS: From 1997 to 1998, 51 patients [median age 60 (range 24-77) years; 38 male, 13 female] with metastatic colorectal cancer were recruited in 5 centers to receive weekly 24-hour infusions of 5-FU (2,600 mg/m(2)) and S-FA (500 mg/m(2)) dissolved in one pump for 6 weeks as first-line treatment. The treatment cycle was repeated after a 2-week rest period. RESULTS: 1,178 administrations (median 24, range 3-54) were performed during the study. Out of 51 patients (median follow-up 20.2 months), 2 (3.9%) achieved complete remission (CR), 17 (33.3%) partial remission (PR), and 21 (41.2%) no change (NC). Progressive disease (PD) was observed in 11/51 (21.6%) patients, including 6 patients who did not complete the first cycle. Median time to tumor progression (TTP) was 8.5 months (95% CI: 5.8-11.3). 32/51 (62.7%) patients survived for more than 1 year, the median survival was reached at 16.5 months (95%CI: 10.2-22.8). Among major toxicities, NCICTC grade III/IV diarrhea occurred in 13/51 (25.4%), grade III hand-foot syndrome in 6/51 (11.7%) patients. Grade III/IV stomatitis was observed in 4/51 (7.8%), cardiac toxicity occurred in 2/51 patients (3.9%). CONCLUSION: Similar to conventional 24-hour 5-FU + CA-FA treatment, the combination with S-FA induced 37.2% objective responses with moderate toxicity. However, TTP seems favorable and the administration of S-FA is convenient, while saving costs and time for the patient in outpatient units.

Adult↗
PubMed2001

Characterization of the phosphoenolpyruvate carboxykinase gene from Corynebacterium glutamicum and significance of the enzyme for growth and amino acid production.

Corynebacterium glutamicum possesses phosphoenolpyruvate (PEP) carboxykinase, oxaloacetate decarboxylase and malic enzyme, all three in principle being able to catalyze the first step in gluconeogenesis. To investigate the role of PEP carboxykinase for growth and amino acid production, the respective pck gene was isolated, characterized and used for construction and analysis of mutants and overexpressing strains. Sequence analysis of the pck gene predicts a polypeptide of 610 amino acids showing up to 64% identity with ITP-/GTP-dependent PEP carboxykinases from other organisms. C. glutamicum cells harbouring pck on plasmid showed about tenfold higher specific PEP carboxykinase activities than the wildtype. Inactivation of the chromosomal pck gene led to the absence of PEP carboxykinase activity and the inability to grow on acetate or lactate indicating that the enzyme is essential for growth on these carbon sources and thus, for gluconeogenesis. The growth on glucose was not affected. Examination of glutamate production by the recombinant C. glutamicum strains revealed that the PEP carboxykinase-deficient mutant showed about fourfold higher, the pck-overexpressing strain two- to threefold lower glutamate production than the parental strain. Inactivation and overexpression of pck in a lysine-producer of C. glutamicum led to an only 20% higher and lower lysine accumulation, respectively. The results show that PEP carboxykinase activity in C. glutamicum is counteractive to the production of glutamate and lysine and indicate that the enzyme is an important target in the development of strains producing amino acids derived from citric acid cycle intermediates.

Amino Acid Sequence↗
PubMed2000

Exact invariants for a class of three-dimensional time-dependent classical hamiltonians

An exact invariant is derived for three-dimensional Hamiltonian systems of N particles confined within a general velocity-independent potential. The invariant is found to contain a time-dependent function f(2)(t), embodying a solution of a third-order differential equation whose coefficients depend on the explicitly known trajectories of the particle ensemble. Our result is applied to a one-dimensional time-dependent nonlinear oscillator and to a system of Coulomb interacting particles in a time-dependent quadratic external potential.

Journal Article↗
PubMed2000

[Retroperitoneal desmoid tumor with kidney failure in familial adenomatous polyposis].

HISTORY AND FINDINGS: A 39-year-old man was hospitalized because of continually rising urinary creatinine and blood urea nitrogen concentration. He was known to have familial adenomatous polyposis (FAP), first diagnosed 18 years previously and re-Physical examination was unremarkable except for pain on percussion over both kidney regions. There was a well-healed laparotomy scar. INVESTIGATIONS: Ultrasound revealed chronic bilateral obstructive renal disease, grade II-III, and computed tomography showed a conglomerate retroperitoneal tumour with obstruction of both ureters at the level of the lower pelvis. This tumour had first been noted first 3 years after the colectomy when the patient complained of abdominal pain. It had been identified histologically as a nonresectable retroperitoneal desmoid tumour. TREATMENT AND COURSE: An external fistula was made, relieving the renal retention. To suppress growth of the desmoid tumour Sulindac, a nonsteroid anti-inflammatory drug, was administered. Genetic molecular analysis revealed a germ line defect in codon 1690 of the APC gene. It is intended to examine other members of the family for the presence of this defect. CONCLUSION: Desmoid tumours are more common in persons with FAP and are among the most frequent extracolic causes of their death. Treatment options are critically analysed.

Adenomatous Polyposis Coli↗
PubMed1998

N-linked glycosylation of the thyroid Na+/I- symporter (NIS). Implications for its secondary structure model.

The Na+/I- symporter (NIS), a 618-amino acid membrane glycoprotein that catalyzes the active accumulation of I- into thyroid cells, was identified and characterized at the molecular level in our laboratory (Dai, G., Levy, O., and Carrasco, N. (1996) Nature 379, 458-460). Because mature NIS is highly glycosylated, it migrates in SDS-polyacrylamide gel electrophoresis as a broad polypeptide of higher molecular mass (approximately 90-110 kDa) than nonglycosylated NIS (approximately 50 kDa). Using site-directed mutagenesis, we substituted both separately and simultaneously the asparagine residues in all three putative N-linked glycosylation consensus sequences of NIS with glutamine and assessed the effects of the mutations on function and stability of NIS in COS cells. All mutants were active and displayed 50-90% of wild-type NIS activity, including the completely nonglycosylated triple mutant. This demonstrates that to a considerable extent, function and stability of NIS are preserved in the partial or even total absence of N-linked glycosylation. We also found that Asn225 is glycosylated, thus proving that the hydrophilic loop that contains this amino acid residue faces the extracellular milieu rather than the cytosol as previously suggested. We demonstrated that the NH2 terminus faces extracellularly as well. A new secondary structure model consistent with these findings is proposed.

Amino Acid Sequence↗
PubMed1998

Qualitative and quantitative analysis of synapses in Hirschsprung's disease.

In Hirschsprung's disease (HD), certain intestinal nervous plexuses are absent. Sprouting nerve endings contain different amounts of synaptophysin (SY), a protein and main constituent of acetylcholinesterase (AChE) storage compartments. Due to the lack of specific markers for synapses, a qualitative analysis of nerve endings of intestinal segments affected by HD has not yet been undertaken. For this study, resected colorectal specimens from patients with HD (n = 8, mean age 2.1 years) were investigated in parallel for AChE, SY, and content of small synaptic vesicles by biochemical, immunohistochemical, and electronmicroscopic means. In the microdissected muscular layer, reduced SY (1.4 microgram/mg total protein, normal 24 +/- 0.3) was observed. Immunohistochemistry showed in affected tissues reduced numbers of SY-positive nerve fibers and nerve endings, which in turn were thickened and distorted, in both the muscle proper and the muscularis mucosae. Combining both morphologic and biochemical findings, in HD the number of cholinergic vesicles in the remaining nerve endings seems to be increased as measured by SY, a marker molecule specific for synaptic vesicles. Our data also suggest that nerve endings in HD may contain high concentrations of cholinergic vesicles, paralleling the known high amounts of acetylcholine and AChE found in intestinal segments of patients with HD.

Acetylcholinesterase↗
PubMed1998

Evaluation of mechanism of increased intracranial pressure with insufflation.

BACKGROUND: Previous studies have documented an increase in intracranial pressure with abdominal insufflation, but the mechanism has not been explained. METHODS: Nine 30-35-kg domestic pigs underwent carbon dioxide insufflation at 1.5 l/min. Intracranial pressure (ICP), lumbar spinal pressure (LP), central venous pressure (CVP), inferior vena cava pressure (IVCP), heart rate, systemic arterial blood pressure, pulmonary arterial pressure, cardiac output, heart rate, respiratory rate, temperature, and end-tidal CO2 were continuously measured. Mechanical ventilation was used to maintain a constant pCO2. Measurements were recorded at 0, 5, 10, and 15 mmHg of abdominal pressure with animals in supine, Trendelenburg (T), and reverse Trendelenburg (RT) positions. Prior to recording measurements, the animals were allowed to stabilize for 40 min after each increase in abdominal pressure and for 20 min after each position change. RESULTS: The animals showed a significant increase in ICP (mmHg) with each 5-mmHg increase in abdominal pressure (0 mmHg: 14 +/- 1.7; 5 mmHg: 19.8 +/- 2.3, p < 0.001; 10 mmHg: 24.8 +/- 2.5, p < 0.001; 15 mmHg: 29.8 +/- 4.7, p < 0.01). The ICP at 15 mmHg abdominal pressure increased further in the T position (39 +/- 4, p < 0.01). Insufflating in the RT position did not significantly reduce the increase in ICP. The IVCP (mmHg) increased with increased abdominal pressure (0 mmHg: 11.5 +/- 6.2, 15 mmHg: 22.1 +/- 3.5, p < 0.01). This increase correlated with the increase in ICP and LP (r of mean pressures >/=0.95). There was no significant change in CVP. CONCLUSIONS: This study suggests that care may be needed with laparoscopy in patients at risk for increased ICP due to head injury or a space occupying lesion. The mechanism of increased ICP associated with insufflation is most likely impaired venous drainage of the lumbar venous plexus at increased intraabdominal pressure. Further studies of cerebral spinal fluid movement during insufflation are currently underway to confirm this hypothesis.

Animals↗
PubMed1997

Characterization of the thyroid Na+/I- symporter with an anti-COOH terminus antibody.

The Na+/I- symporter (NIS) is the plasma membrane protein that catalyzes active I- transport in the thyroid, the first step in thyroid hormone biogenesis. The cDNA encoding NIS was recently cloned in our laboratory and a secondary structure model proposed, suggesting that NIS is an intrinsic membrane protein (618 amino acids; approximately 65.2 kDa predicted molecular mass) with 12 putative transmembrane domains. Here we report the generation of a site-directed polyclonal anti-COOH terminus NIS antibody (Ab) that immunoreacts with a approximately 87 kDa-polypeptide present in membrane fractions from a rat thyroid cell line (FRTL-5). The model-predicted cytosolic-side location of the COOH terminus was confirmed by indirect immunofluorescence experiments using anti-COOH terminus NIS Ab in permeabilized FRTL-5 cells. Immunoreactivity was competitively blocked by the presence of excess synthetic peptide. Treatment of membrane fractions from FRTL-5 cells, Xenopus laevis oocytes, and COS cells expressing NIS with peptidyl N-glycanase F converted the approximately 87 kDa-polypeptide into a approximately 50 kDa-species, the same relative molecular weight exhibited by NIS expressed in E. coli. Anti-NIS Ab immunoprecipitated both the NIS precursor molecule (approximately 56 kDa) and the mature approximately 87 kDa form. Furthermore, a direct correlation between circulating levels of thyroid-stimulating hormone and NIS expression in vivo was demonstrated.

Amino Acid Sequence↗
PubMed1996

Fibrinolytic treatment with ultra-high streptokinase infusion via the dorsalis pedis vein offers no advantage over systemic infusion via the brachial vein in patients with deep vein thrombosis of the leg.

The present study into the fibrinolytic therapy of deep vein thrombosis (DVT) considers whether streptokinase infusion into the dorsalis pedis vein of the affected leg (ipsipedal infusion) yields higher lysis rates than systemic infusion via the brachial vein (systemic infusion). In both cases the dosage regimen selected was a short-term ultra-high streptokinase (UHSK) infusion of 1.5 million IUSK/hour over a period of 6 hours (total SK dose: 9 million IU). A series of one to three UHSK infusions was given on one to three consecutive days. Forty patients were randomised to either systemic (Group S) or ipsipedal (Group IP) treatment. The distribution of important parameters determining a fibrinolytic response (e.g. the age, site and extent of DVT, and number of UHSK infusion series) was virtually identical in the two treatment groups. The rates for total and partial thrombolysis in the systemic infusion group were 50% and 10% respectively compared with 30% and 20% respectively in the ipsipedal group. The distribution of side-effects was approximately identical in the two groups. The results show that ipsipedal UHSK lysis via the dorsalis pedis vein confers no advantage over systemic infusion via the brachial vein.

Adult↗
PubMed1995

Video-assisted endoscopic spinal surgery: thoracoscopic discectomy.

The use of new endoscopic techniques to conduct a thoracic discectomy is presented. The development of these endoscopic techniques through live porcine and cadaver models are outlined. It is concluded that the use of multiple ports for the endoscopic approach to the thoracic spine provides an exposure to the anterior and lateral spinal theca that is equal to the exposure afforded by the more extensive thoracotomy. Current techniques are being developed for transperitoneal and retroperitoneal endoscopic lumbar spine surgery.

Adult↗
PubMed1994

Lysis block treatment: a new form of local thrombolysis.

Lysis block treatment (LBT) is a new form of fibrinolytic therapy for deep vein thrombosis and arterial occlusion in the distal parts of the limbs. Strictly local lysis was achieved by placing a cuff around the thigh or the upper arm, inflating the cuff to a pressure of 500 mmHg ("Bier's blockade"), and giving heparin and tissue plasminogen activator (rt-PA) by intravenous injection into the dorsal pedis or antecubital veins. Occlusion lasted for one hour. This new technique was demonstrated in 22 patients. Six patients presented with popliteal vein thromboses and 1 patient with a distal femoral vein thrombosis. In addition, 15 arterial occlusions were treated comprising 3 calf, 6 popliteal, 3 distal femoral, and 2 digital sites and 1 brachial site. Five of 7 venous and 9 of 15 arterial occlusions were partially or totally removed. The activated partial thromboplastin time remained nearly unchanged during LBT and only a limited and short-term lengthening was recorded after restoration of blood flow. This was of importance for patients with bleeding tendencies, which are normally a contraindication for systemic lysis. LBT may therefore be considered as a useful alternative to systemic fibrinolytic treatment.

Aged↗
PubMed1993

[Lysis block technique--a new method of fibrinolytic treatment with tissue-type plasminogen activator (rt-PA)].

With lysis-block technique an over-systolic tourniquet is put on the thigh or upper arm. The fibrinolytic substance is injected into a dorsal foot vein or forearm vein. By using this strictly local lysis it was possible to remove distal venous and arterial occlusions. During over-systolic blockade there was only a minimal link between the blocked part of the limb and systemic circulation. By choosing a lytic substance with a short half-life-period (rt-PA) the systemic effect after loosening the blockade was small. LBT is a new and interesting method for the fibrinolytic treatment of peripheral venous and arterial occlusions. The procedure is characterized by minimal systemic reactions and it can probably be applied in those patients with contraindications for systemic lysis.

Adult↗