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Biomedical subjects

T Schubert

Publications and source records attributed to T Schubert.

At least 19 recordsLinked to original sources

Levoprotiline ((-)-oxaprotiline) effects on inositol phosphate generation in human peripheral lymphocytes.

The effects of the atypical antidepressant levoprotiline (LPT) on inositol phosphate metabolism were investigated in N-formyl-methionyl-leucylphenylalanine (fMLP) activated human lymphocytes. In the presence of LPT, stimulation of phosphoinositide hydrolysis by fMLP lead to an increased accumulation of inositol bisphosphates, an effect which could be detected within the range of therapuetic plasma concentrations and which is exerted by lithium in a similar way. Furthermore, incubation of lymphocytes with LPT and subsequent stimulation with fMLP lead to a pronounced decrease in the level of free intracellular [3H]inositol. Both LPT effects, the increased accumulation of inositol bisphosphates and the reduction of free intracellular [3H]inositol, were found to be more pronounced for LPT than for its enantiomer (+)-oxaprotiline. The results are discussed in view of a possible biochemical mechanism which may contribute to the antidepressive activity of LPT.

Antidepressive Agents

Therapeutic concentrations of lithium and carbamazepine inhibit cGMP accumulation in human lymphocytes. A clinical model for a possible common mechanism of action?

Although a large variety of biochemical effects have been reported for lithium (Li) and carbamazepine (Cbm), the final molecular mechanism underlying their therapeutic efficacy for recurrent affective disorders is still unknown. The data presented here clearly indicate that therapeutic concentrations of both drugs inhibit sodium nitroprusside-induced accumulation of cGMP in human lymphocytes to about the same extent. The effect is not seen for other antidepressants, and shows pronounced interindividual variations in healthy volunteers. A similar effect of lithium and carbamazepine can also be demonstrated for the cGMP accumulation of central neurons using the model of dissociated cells of the mouse brain. The results are discussed in view of a common mechanism of action of both drugs. Furthermore, it is speculated that the individual sensitivity of the cGMP generating system of human lymphocytes to both drugs might be used to predict therapeutic response or nonresponse of the individual patient.

Animals

[Modification of tear film break-up time by beta blocker eyedrops without preservatives].

Traditional beta-blocking eye drops preserved with benzalkonium chloride show an adverse effect on the precorneal tear film, which can be measured by checking the break-up-time (BUT). To decide, whether this adverse effect is caused more by the beta-blocking drug or the preservative, we tested the influence of timolol eye drops without preservative in single dose units Timosine) on the BUT in a prospective, open study. These eyedrops caused no significant shortening of the BUT in persons, which where untreated before. Patients using preserved beta-blocking eye drops and having irritations of their eyes showed significant prolongation of the BUT after changing the therapy to Timosine. Preservative-free beta-blocking eye drops are a real improvement in the therapy of glaucoma patients with irritated eyes.

Glaucoma

Central cholinergic functioning and aging.

Normal aging in experimental animals and humans has been demonstrated to affect various aspects of central cholinergic functions. Although deficits at the levels of the number of cholinergic neurons, the acetylcholine synthesis, and the number of muscarinic cholinergic receptors are probably less relevant, deficits at the levels of acetylcholine release, muscarinic cholinergic receptor plasticity, as well as muscarinic cholinergic receptor function are fairly pronounced and seem to justify the assumption that the functioning of the central cholinergic system is impaired by aging. However, whether these cholinergic deficits of normal aging are the sole neurochemical basis to explain age-associated memory impairment or whether other transmitter systems also play a role is still a matter of controversy.

Aging

Lithium but not cholinergic ligands influence guanylate cyclase activity in intact human lymphocytes.

The presence of guanylate cyclase in intact circulating human lymphocytes and the sensitivity of this enzyme to stimulation by sodium nitroprusside could be confirmed. However, in contrast to other observations all attempts failed to stimulate the enzyme by cholinergic agonists, despite the use of M1 as well as M2 selective agonists. These findings do not support the assumption that cholinergic recognition sites on human lymphocytes described by many groups are part of a functioning muscarinic transducing mechanism. While several other neuroreceptor agonists were also unable to affect lymphocyte guanylate cyclase activity, lithium was found to potently inhibit the stimulation of guanylate cyclase by sodium nitroprusside at an intracellular concentration close to the therapeutic plasma levels. It is suggested that the effects of lithium on guanylate cyclase activity in human lymphocytes could be related to a possible mechanism of action of lithium in affective disorders.

Adult

[Plate osteosynthesis of the femur in patients with multiple and mono-trauma].

In multiple trauma patients successful treatment of femur shaft fractures depends more on timing of osteosynthesis than on choosing a specific type of fracture stabilization. Because of theoretical and practical reasons early osteosynthesis within 24 to 48 hours seems to be advantageous. In our experience it led to a significant decrease in complications. However, concomitant thorax trauma mandates special consideration. The two fatalities in our study belonged to this subgroup. With adequate indication for therapeutic intervention, correct operative technique and consideration of the patient's general status good results can be expected with every type of fracture treatment available (external fixation, plate fixation, intramedullary nailing).

Adult

[Use of UV radiation for the disinfection of water. V. Microbiological studies of the behavior of bacterial cells from the logarithmic and from the stationary phase in cold and warm drinking water].

The u.v.-susceptibility of E. cloacae, E. coli and E. faecium was tested with a flow-through u.v. light treatment apparatus. Drinking water of three ranges of temperature (ca. 13 degrees C, ca. 33 degrees C, and ca. 48 degrees C) was used. The u.v.-susceptibility was tested with bacteria harvested in the exponential phase of growth as well as with bacteria harvested in the stationary phase. In all ranges of temperature and both phases of growth reductions of at least 99.9999% of E. cloacae and E. coli were obtained by a dosage of less than or equal to 25 mWs/cm2. For E. faecium harvested in the exponential phase of growth this could be confirmed in cold water of 13 degrees C, while in warm water of 48 degrees C a dosage of ca. 47 mWs/cm2 for a reduction of 99.9999% was necessary. To kill E. faecium-cells, which were harvested in the stationary phase, dosage between 39 and 45 mWs/cm2 were necessary in water of the three ranges of temperature.

Bacteria

[Hypothermia and polytrauma. A case report (28 degrees C)].

In a 29-year-old polytraumatised motorbike driver, massive blood transfusion led to a decrease of the body temperature to 28.1 degrees C rectal on the second day after admission. We could rewarm the patient using only a Clinitron bed, although he had persisting blood loss due to an intravasal coagulopathy. This method has proven to be noninvasive, effective and without any side effects.

Adult

Endoscopic therapy and early elective operation as a therapeutic regimen in ulcer bleeding.

In a prospective protocol we treated 63 consecutive patients admitted to our surgical department with bleeding gastroduodenal ulcers between January 1986 and December 1987. The therapeutic regimen included emergency endoscopy in all cases. Active Forrest Ia or II hemorrhage was treated endoscopically with submucosal injection. Endoscopic control of hemorrhage was achieved in all but one case. Low-risk ulcers, e.g. Forrest II without visible vessel and III or ulcers caused by antirheumatic drug medication were treated definitively by therapeutic endoscopy (31 patients). Ulcers with high risk of rebleeding even after endoscopic therapy underwent additional early elective operation. Thirty patients were treated surgically by this means. Two patients required emergency operation because of failure to control the bleeding (Ia and second rebleeding) endoscopically. The overall mortality of the surgically treated patients was 6% (2/32). The mortality of the therapeutic endoscopy was 0%. Thus, the mortality of the overall group was 3%. The major advantages of this concept were: low mortality rates, elimination of rebleeding in the follow-up period, optimal conditions for the surgical therapy resulting in low death-rates and a reduced need for transfusions.

Adult

N-formyl-methionyl-leucyl-phenylalanine induced accumulation of inositol phosphates indicates the presence of oligopeptide chemoattractant receptors on circulating human lymphocytes.

Using [3H]-inositol-labeled human lymphocytes, formation of inositolphosphates was found as a specific response to the chemotactic formylpeptide, N-formyl-methionyl-leucyl-phenylalanine (fMLP), in a fashion similar to the effects of fMLP in human granulocytes. Inositol phosphate formation could be significantly augmented by lithium ions. The results suggest that fMLP-mediated hydrolysis of phosphoinositides is involved in its chemotactic effects on human lymphocytes.

Adult

Twice-daily sucralfate dosing to heal acute duodenal ulcer. Multicenter Study Group.

Twice-daily dosing with sucralfate was evaluated by two multicenter trials, trial 1 (eight weeks) and trial 2 (four weeks). Both trials demonstrated significantly better ulcer healing at study completion for the 2-g twice daily (B.I.D.) regimen compared with placebo. Both trials were double-blind, randomized, and placebo-controlled, with parallel groups. Patients received two doses daily consisting of sucralfate 2 g B.I.D., placebo/sucralfate 2 g at bedtime (H.S.), or placebo/placebo. Ulcer healing was assessed by scheduled endoscopy and symptom assessment. Healing was defined as complete absence of erosion or ulceration. Trial 1 evaluations were conducted at four and eight weeks, trial 2 evaluations at two and four weeks. Interim examinations were performed at investigator discretion. Treatment groups were comparable with regard to number of patients, age, sex, smoking status, ulcer size, and presence/absence of baseline symptoms. Sucralfate 2 g B.I.D. was significantly better than H.S. or placebo dosing at the completion of each trial. H.S. dosing was better than placebo only at the four-week analysis of trial 1. At Week 4 of trial 1, 14 of 54 patients (26 percent) were healed with the B.I.D. sucralfate regimen, whereas at Week 8, 41 of 54 (76 percent) were healed (p less than 0.001). For the placebo/sucralfate H.S. group, 17 of 57 patients (30 percent) were healed at Week 4 (p less than 0.05), and 32 of 56 patients (57 percent) were healed at Week 8. For the placebo group, six of 52 (12 percent) and 20 of 51 patients (39 percent) were healed at Weeks 4 and 8, respectively. In trial 2, the B.I.D. group had a 21 percent healing rate at Week 2 (13 of 61 patients) and 62 percent were healed at Week 4 (38 of 61 patients; p less than 0.05). The H.S. group had an 8 percent healing rate (five of 66 patients) at Week 2 and 50 percent (33 of 66 patients) at Week 4. For the placebo group, 10 of 62 patients (16 percent) and 26 of 62 patients (42 percent) were healed at Weeks 2 and 4, respectively. Trial 1 demonstrated significant symptom improvement for active treatment groups at both four and eight weeks, whereas no differences were found in trial 2. Sucralfate 2 g B.I.D. was found to be safe and effective for the treatment of acute duodenal ulcer.

Acute Disease

Intraabdominal abscesses--percutaneous catheter drainage versus operative treatment.

From 65 patients with 73 abscesses 38 were treated by operation and 27 by PCD. The mean duration of drainage was 6.8 days (OP) and 7.4 days (PCD) respectively. In the surgical group 2 patients needed reintervention and 1 died due to sepsis. In the PCD group 1 patient had to be operated on because of insufficient drainage and 1 died after perforation of the colon. With modern techniques of imaging (Ultrasound, CT) PCD is a useful tool in the therapeutic regimen of intraabdominal abscesses. PCD has to be considered as definitive treatment or preparation for surgical eradication. Above all indication to PCD depends on localization and cause of the abscess.

Abdomen

A multicenter, randomized, double-blind trial of somatostatin in the management of acute hemorrhage from esophageal varices.

A prospective, randomized, placebo-controlled, double-blind, multicenter clinical trial of intravenous somatostatin (Stilamin; Serono Laboratories, Inc., Randolph, MA) was performed in 102 patients with actively bleeding esophageal varices from August, 1985, to November, 1986. Patients had major hemorrhage indicated by hematemesis or melena and evidence of significant blood loss. For entry, patients had to have endoscopic demonstration of active bleeding from esophageal varices or stigmata of recent hemorrhage and bright red blood in the gastric aspirate with no other source of bleeding found. Randomized patients received identical-appearing somatostatin or placebo for a 30-hr study period. Those given somatostatin received a 250-micrograms bolus and a 250-micrograms per hr infusion with repeat bolus and doubling of the infusion if the bleeding was not controlled. In retrospect, 18 patients could not be evaluated. Of the 84 evaluable patients, 48 received somatostatin and 36 placebo. They were comparable in age, gender, severity of liver disease and history of variceal bleeding. Transfusion requirements were similar in both groups. Bleeding stopped for 12 consecutive hr during 30 hr of the study period in 31 (65%) of the somatostatin group vs. 30 (83%) of the placebo group (p = 0.06). The median time to cessation of bleeding was 2 hr in the placebo group and 3 hr in the somatostatin group. Deaths following the study period were nine (25%) in the placebo group and 15 (31%) in the somatostatin group. Within the limitations of the present study, we conclude that somatostatin was ineffective in the management of active bleeding of esophageal varices.

Adult

Adenosine cardioplegia. Adenosine versus potassium cardioplegia: effects on cardiac arrest and postischemic recovery in the isolated rat heart.

Adenosine is a potential cardioplegic agent by virtue of its specific inhibitory properties on nodal tissue. We tested the hypothesis that adenosine could be more effective than potassium in inducing rapid cardiac arrest and enhancing postischemic hemodynamic recovery. Isolated rat hearts were perfused with Krebs-Henseleit buffer or cardioplegic solutions to determine the time to cardiac arrest and the high-energy phosphate levels at the end of cardioplegia. Cardioplegic solutions contained adenosine 10 mmol/L, potassium 20 mmol/L, or adenosine 10 mmol/L + potassium 20 mmol/L and were infused at a rate of 2 ml/min for 3 minutes at 10 degrees C. Both time taken and total number of beats to cardiac arrest during 3 minutes of cardioplegia were reduced by adenosine 10 mmol/L and adenosine 10 mmol/L + potassium 20 mmol/L when compared with potassium 20 mmol/L alone (p less than 0.001). Tissue phosphocreatine was conserved by adenosine 10 mmol/L when compared with potassium 20 mmol/L, being 7.1 +/- 0.2 (mumol/gm wet weight (n = 7) and 6.0 +/- 0.3 mumol/gm wet weight (n = 5), respectively (p less than 0.05). Postischemic hemodynamic recovery was tested in isolated working rat hearts. After initial cardiac arrest, the cardioplegic solution was removed with Krebs-Henseleit buffer at a rate of 2 ml/min for 3 minutes at 10 degrees C, and thereafter total ischemia was maintained for 30 or 90 minutes at 10 degrees C before reperfusion. Adenosine 10 mmol/L enhanced recovery of aortic output when compared with potassium 20 mmol/L or adenosine 10 mmol/L + potassium 20 mmol/L, the percentage recovery after 30 minutes of ischemia being 103.0% +/- 4.4% (n = 6), 89.0% +/- 5.8% (n = 6), and 86.6% +/- 4.3% (n = 6), respectively (p less than 0.05 for comparison between adenosine 10 mmol/L and potassium 20 mmol/L). Thus adenosine cardioplegia caused rapid cardiac arrest and improved postischemic recovery when compared with potassium cardioplegia and with a combination of these two agents.

Adenosine

[The production of eluates for testing acute cytotoxicity by a new method].

In vitro tests of new biomaterials require internationally and nationally eluates increasingly. Only the extracted substances become effective in the cells in that way. The material surface has the greatest influence on the quantity of the released substances by elution. The surface of diverse undefined mixture quantities is definable exactly by means of a gas adsorption method (BET method). The influence of the secondary technologies was tested by the atom adsorption spectrometry. The Jena bioglass ceramics could be estimated successfully by this method.

Biocompatible Materials

[Parasitic liver cyst. Indications and choice of procedure in cystic echinococcosis].

About 60-90% of clinically diagnosed cases of echinococcosis are found in the liver. Half of these patients show episodes of acute abdominal or back pain. The others complain about discrete and unspecific symptoms. Diagnosis is confirmed by combination of imaging techniques and serologic tests. Operation still is the only way for eradication of the parasite. This paper presents a summary of the literature and clinical data of 27 patients treated in our hospital from 1966 to March 1988. Cystectomy with omentoplasty is confirmed to be a simple and effective surgical method in operative treatment of echinococcosis.

Adolescent

Radiology and pathology in canine acalculous cholecystitis.

Although the value of hepatobiliary scan and ultrasonography are well established in calculous cholecystitis, their role in acute acalculous cholecystitis (AAC) is less certain. This study assesses the diagnostic reliability of these tests in AAC chemically induced in 10 dogs with rutin, a compound known to induce AAC. Ultrasonography demonstrated pericholecystic fluid or wall thickening in 8 of 10 dogs. Hepatobiliary scans were abnormal in only 2 of 9 dogs. Pathologic evaluation showed significant abnormalities in all gallbladders. Our studies confirm the usefulness of ultrasonography in diagnosing AAC and suggest caution in using a normal hepatobiliary scan to exclude the diagnosis of AAC.

Animals