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Biomedical subjects

U Seitz

Publications and source records attributed to U Seitz.

At least 55 records · Page 3Linked to original sources

Relaxation of evoked contractile activity of isolated guinea-pig ileum by (+/-)-kavain.

Kava pyrones are the pharmacologically active compounds of Piper methysticum Forst. In the present study, the effect of the synthetic kava pyrone (+/-)-kavain was investigated on evoked contractile activity of isolated guinea-pig ileum. (+/-)-Kavain (1 microM-1 mM) dose-dependently reduced contractions of ileum evoked by carbachol (10 microM), by BAY K 8644 (0.3 microM), or by substance P (0.05 microM). (+/-)-Kavain also inhibited the contractile responses induced by raising the extracellular K+ concentration from 4 to 20 mM and by blocking the K+ channel by barium chloride (1 mM) or 4-aminopyridine (0.3 mM). After pre-incubation with 1 microM nifedipine, carbachol (1 microM) evoked 18.2 +/- 14.3% of contraction at control (i.e. prior pre-incubation with nifedipine). This remaining response was completely abolished by high concentrations of (+/-)-kavain (400 microM). After treatment of the longitudinal ileum strips with pertussis toxin (PTX), carbachol (1 microM) evoked 27.0 +/- 6.2% of the control response in untreated ileum. These contractions were also blocked by (+/-)-kavain (400 microM). However, (+/-)-kavain had no effect on the caffeine-induced (20 mM) contractions of ileum strips, which were permeabilized with digitonin or beta-escin. Moreover, it failed to affect Ca(2+)-evoked contractions of skinned muscles. These results suggest that the kava pyrone (+/-)-kavain may act in a non-specific musculotropic way on the smooth muscle membrane.

Animals↗

[3H]-monoamine uptake inhibition properties of kava pyrones.

Three kava pyrones, the natural compounds (+)-methysticine and (+)-kavain, and the synthetic racemate (+/-)-kavain, were tested concerning their action on in vitro uptake of monoamines in synaptosomes prepared from the cerebral cortex and hippocampus of rats. (+/-)-Kavain and (+)-kavain were found to potently inhibit the uptake of [3H]-noradrenaline. Uptake of [3H]-noradrenaline was inhibited in the following order of potency: (+/-)-kavain = (+)-kavain > (+)-methysticine, whereas none of the kava pyrones efficiently blocked the uptake of [3H]-serotonin. The results indicate a pyrone-specific non-stereo-selective inhibition of the [3H]-noradrenaline uptake which might be responsible for or, at least, contribute to the psychotropic properties of kava pyrones.

Animals↗

Endoscopic snare mucosectomy in the esophagus without any additional equipment: a simple technique for resection of flat early cancer.

BACKGROUND AND STUDY AIMS: Endoscopic mucosal resection of early esophageal cancer has increasingly proved to be an effective treatment modality, especially if the tumor has not invaded the muscularis mucosae. Different techniques have been introduced, using an overtube, double-channel endoscope, or suction cap. We have not found that these devices are required for snare resection in the esophagus. PATIENTS AND METHODS: Over a period of two years (1994-1996), seven patients (five men and two women, age range 59-88) with early esophageal cancer defined by endosonography (3 cm or less in size, limited to the submucosal layer) were treated using a simplified technique of endoscopic snare resection using a monopolar diathermic polypectomy snare made of monofilament steel wire. The snare was positioned around the lesion, and then closed while pressing the snare against the mucosa and applying suction to draw the lesion into the snare. Pure coagulation current was used for resection. If necessary, a piecemeal technique was used to achieve complete removal. RESULTS: Complete removal was achieved in one session in all seven cases. No complications were observed. Two patients underwent radical surgery with no tumor remnant or metastatic lymph node in the resected specimen. All patients have remained free of recurrence during a median follow-up period of seven months (range 3-22 months). Two patients died of cardiovascular disease four and eight months after endoscopic mucosal resection. CONCLUSION: Small early esophageal cancer can be safely removed with a simplified method of endoscopic snare resection using a standard monofilament polypectomy snare.

Adenocarcinoma↗

[Life threatening salicylate poisoning caused by percutaneous absorption in severe ichthyosis vulgaris].

In a 7-year-old boy, ichthyosis vulgaris was treated with a 10% ointment for application over a large area of the body surface. In this way, the child received 400 g salicylic acid (0.6 g/kg body weight per day) percutaneously over a period of 4 weeks. The patient was referred to hospital by the family doctor: he was in a deep somnolent state, apparently caused by hyperventilation following wheezing, vomiting, tinnitus and vertigo. Salicylate intoxication was suspected because of metabolic acidosis, an anion gap and respiratory overcompensation. The diagnosis was confirmed by a serum salicylate level of 985 micrograms/ml (therapeutic level 150-300 micrograms/ml). Following forced diuresis and alkalization with sodium bicarbonate, haemodialysis was unnecessary. As the salicylate level declined to values within the therapeutic range, the patient started to recover consciousness, waking on the 4th day. By day 6 there were still obvious neurological deficiencies. Fecal incontinence, bilateral ptosis and intermittent diverging strabismus on the right persisted for some weeks. It was 6 months before complete neurological resolution was achieved. The pathogenesis of salicylate toxicity and the need for safer therapies for ichthyosis vulgaris are discussed.

Acid-Base Equilibrium↗

Papillary roof incision using the Erlangen-type pre-cut papillotome to achieve selective bile duct cannulation.

BACKGROUND: Prior studies evaluating pre-cutting the major papilla to access the bile duct when standard cannulation falls have usually used the needle-knife papillotome. We conducted a prospective study to evaluate the efficacy and safety of an Erlangen-type pre-cut papillotome for pre-cutting. PATIENTS AND METHODS: Three hundred twenty-seven patients (114 men, mean age 67 years) who underwent first-time sphincterotomy at our institution were included. Pre-cutting was performed if free and wire-guided cannulation of the bile duct failed according to an algorithm. RESULTS: Pre-cutting was performed in 123 patients (38%) and selective cannulation was successful in all. Post-ERCP serum pancreatic enzyme levels were more frequently elevated in the pre-cut group (50%) than the non-pre-cut group (27%, p < 0.001); however, there was no difference in the incidence of post-ERCP pancreatitis (pre-cut = 2.7%, 95% CI: 0.66% to 7.6%; non-pre-cut = 1.6%, 95% CI: 0.3% to 4.7%). The incidence of bleeding was similar (pre-cut, 2.4%, non-pre-cut, 3.9%; p > 0.05). CONCLUSION: Pre-cutting the major papilla for biliary access using the Erlangen-type pre-cut papillotome is an effective and reasonably safe procedure when performed by endoscopists with extensive experience in pancreatobiliary endoscopy.

Aged↗

Ultrasonic esophagoprobe for TNM staging of highly stenosing esophageal carcinoma.

BACKGROUND: Endosonographic staging of esophageal carcinoma may be limited in one third of cases by tumor stenoses that cannot be traversed with conventional echoendoscopes. We designed and evaluated a new endosonographic instrument (ultrasonic esophagoprobe) for TNM staging of highly stenosing esophageal carcinomas. METHODS: Eighty-seven consecutive patients (64 men, mean age 61 years) with highly stenosing esophageal carcinomas were studied with the esophagoprobe (features: diameter of 7.9 mm, bougie-shaped tip, no fiber optics, insertion over a guide wire). RESULTS: The esophagoprobe was successfully inserted past the stenosis without complication in all patients. Nine patients (10%) required preliminary bougienage to 33 F. The imaging quality was high and allowed for complete T and N staging in all patients. M staging was indeterminate in 15 patients because of inadequate visualization of the celiac axis region. Histopathologic correlation in 38 patients who underwent surgery showed an overall T stage accuracy rate of 89% (T2 = 80%, T3 = 95%, T4 = 87%), and N and M stage accuracies of 79% (N0 = 44%, N1 = 90%) and 91% (M0 = 94%, M1 = 75%), respectively. CONCLUSIONS: The esophagoprobe enables safe passage of highly stenosing esophageal carcinomas for TNM staging. Accuracy rates are similar to those reported for conventional echoendoscopes.

Adult↗

The Tannenbaum stent: a new plastic biliary stent without side holes.

OBJECTIVE: Clogging of plastic biliary stents used in malignant biliary obstruction remains a major problem. In vitro studies have shown that side holes, a standard feature of commercially available stents, may contribute to stent clogging. In a pilot study, we designed and prospectively evaluated a new biliary stent without side holes (Tannenbaum stent). METHODS: Over a 12-month period, 55 consecutive patients (mean age 75 yr) with malignant distal common bile duct obstruction and without papillary or duodenal tumor infiltration underwent endoscopic placement of the Tannenbaum stent for the palliative treatment of jaundice. RESULTS: Tannenbaum stent insertion was technically successful on the first attempt in all patients and was accompanied by a significant reduction in mean serum bilirubin levels (10.1-1.6 mg%). Fifty-one patients were followed until death (median survival of 130 days); the symptomatic occlusion rate was 16%, the dislocation rate was 8%, and the median stent patency was 64 wk. Aside from stent clogging, there were no complications. CONCLUSION: The Tannenbaum stent provided effective palliative biliary decompression in all patients. The patency rate was longer than that reported in the literature for conventional plastic stents with side holes and compared favorably with patency rates that have been reported for the metallic expandable biliary stents. The results of this pilot study are encouraging and warrant further studies.

Aged↗

Prolonged patency with a new-design Teflon biliary prosthesis.

Clogging of biliary endoprosthesis has been a persistent problem faced by endoscopists over many years. Evidence suggests that incorporating sideholes increases the risk of plastic stents clogging. We conducted a prospective, nonrandomized study comparing 10 Fr Teflon pigtail (PT) stents with sideholes to a new design 10Fr Teflon straight stent without sideholes, designated as the "Tannenbaum" (TB) stent. Seventy-four consecutive patients were treated with the PT stent and 55 consecutive patients with the TB stent in two different periods. All patients had malignant distal biliary obstruction with jaundice. Stent insertion was successful in all patients, and a significant reduction in serum bilirubin levels was achieved. All follow-up patients, except one in the TB group, had died at the time of reporting. Median survival in the PT group was 100 days (range: 6-636 days) and 130 days (range: 3-703 days) in the TB group. Median follow-up in the PT group was 104 days (range: 6-636 days) and 141 days (range: 3-537 days) in the TB group. Statistical analysis shows significantly longer patency for the TB stent (p < 0.02). Moreover, the results of the TB stent compared favorably with the published results of metallic self-expandable biliary stents. We believe the TB stent holds great promise for the future of endoscopic biliary stenting. Prospective randomized studies comparing the TB stent with existing plastic and metal stents are, however, necessary.

Aged↗

[Endoscopic techniques in therapy of choledocholithiasis].

Endoscopically, approximately 85% of all bile duct stones can be removed immediately after successful papillotomy. For the remaining cases, complete clearance of the bile duct is achieved by lithotripsy techniques. Due to the lower risks, endoscopic treatment is preferable.

Cholecystectomy, Laparoscopic↗

Characterization of monoclonal antibodies directed against domains of pertussis toxin involved in receptor recognition.

The exotoxin pertussis toxin (PT) produced by virulent Bordetella pertussis bacteria is regarded as the main virulence factor of the organism and held responsible for most of its pathological effects. Identification of functional sites on PT would greatly facilitate site-specific detoxification and thus also the development of a new vaccine. For the investigation of structure-function aspects of PT we have prepared and characterized eleven monoclonal antibodies (mAbs) (UB-A1, UB-A2, UB-A10, UB-B7, UB-B12, UB-D4, UB-D7, UB-D10, UB-F7, UB-G1, and UB-G12) directed at the native toxin. Only UB-B12 and UB-D10 recognized PT in Western blotting indicating that most of the mAbs were directed against conformational epitopes. The mAbs were assayed for their ability to interfere with the binding of PT in model receptor systems like a solid phase binding assay using fetuin as receptor moiety, hemagglutination of chymotrypsin-sensitized goose erythrocytes, and the PT-mediated induction of the clustered growth pattern (CGP) of Chinese hamster ovary (CHO) cells. Five of the eleven mAbs (UB-A1, UB-A2, UB-B7, UB-B12, and UB-D7) interfered with the binding of PT to fetuin on solid phase and with PT-mediated hemagglutination. UB-A2, UB-B7, and UB-B12 also inhibited the induction of the clustered growth pattern of CHO-cells. This indicates that the determinants recognized by these mAbs are associated with the formation of the carbohydrate recognition sites of PT. Thus, the monoclonal antibodies described in this study will be valuable tools in the further analysis of the structure-function relationship of pertussis toxin with respect to receptor recognition and binding.

Animals↗

Purification and characterization of chromatin-bound DNA-dependent RNA polymerase I from parsley (Petroselinum crispum). Influence of nucleoside triphosphates.

The isolation and purification of DNA-dependent RNA polymerase I (EC 2.7.7.6) from parsley (Petroselinum crispum) callus cells grown in suspension culture is described. The enzyme was solubilized from isolated chromatin. Purification was achieved by using DEAE- and phospho-cellulose in batches, followed by column chromatography on DEAE- and phospho-cellulose (two columns) and density-gradient centrifugation. The highly purified enzyme was stable over several months. The properties of purified parsley RNA polymerase I were investigated. Optimum concentration for Mn2+ was 1 mM, and for Mg2+ 4-6 mM, Mn2+ was slightly more stimulatory than Mg2+. The enzyme was most active at low ionic strengths [10-20 mM-(NH4)SO4]. The influence of various phosphates was tested: pyrophosphate inhibited RNA polymerase at low concentrations, whereas orthophosphate had no effect on the enzyme activity. ADP was slightly inhibitory, and AMP had no effect on the enzyme reaction. Nucleoside triphosphates and bivalent cations in equimolar concentrations in the range 4-11 mM did not influence the RNA synthesis in vitro. Free nucleoside triphosphates in excess of this 1:1 ratio inhibited the enzyme activity, unlike free bivalent cations, which stimulated RNA polymerase I.

Cells, Cultured↗

RNA polymerase I from higher plants. Evidence for allosteric regulation and interaction with a nuclear phosphatase activity controlled NTP pool.

RNA polymerase I was isolated from parsley cells grown in suspension culture and from soybean hypocotyls. Kinetic studies of the enzyme revealed that RNA polymerase I is an allosteric regulated enzyme. The enzyme activity was influenced by nucleoside triphosphates (NTP) and divalent cations. NTP exceeding a 1:1 ratio of these two components acted as allosteric inhibitors, contrary to free divalent cations, which had promotive effects on the RNA polymerase I. Furthermore, isolated nuclei from parsley exhibited a powerful nucleoside triphosphatase (NTPase) activity. Contrary to RNA polymerase I, this enzyme was stimulated by NTP exceeding the 1:1 ratio of NTP and divalent cations. Free divalent cations had an inhibitory effect. Assuming that a causal connection of these two processes does exist, a possible role of this NTPase would be the control of NTP pools in relation to divalent cations and thus regulating RNA synthesis.

Allosteric Regulation↗