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Biomedical subjects

L Kramer

Publications and source records attributed to L Kramer.

At least 37 records · Page 2Linked to original sources
PubMed1996

Modulation of protein kinase C activity and calcium-sensitive isoform expression in human myeloid leukemia cells by bryostatin 1: relationship to differentiation and ara-C-induced apoptosis.

Previous studies have shown that pretreatment of human myeloid leukemia cells (HL-60) with the protein kinase C (PKC) activator bryostatin 1 potentiates ara-C-induced apoptosis. To test the hypothesis that this capacity stems from down-regulation of PKC activity and/or Ca2+-dependent (group-I; cPKC) isoform expression, comparisons were made between the effects of this agent and the stage-2 tumor promoter mezerein under conditions favoring either cellular differentiation or drug-induced apoptosis. Twenty-four-hour pretreatment of HL-60 cells with 10 nM bryostatin 1, which does not induce differentiation in this cell line, led to a profound reduction in membrane and cytosolic PKC activity, decreased expression of cPKC isoforms (alpha, betaI, betaII, gamma), and a marked increase in ara-C induced apoptosis. In contrast, 10 nM mezerein, which induces HL-60 cell differentiation, was less effective in down-regulating membrane and cytosolic PKC activity as well as alpha, betaI, and gamma cPKC isoform expression, and failed to potentiate ara-C-related apoptosis. The effects of bryostatin 1 were dominant to those of mezerein, in that the combination resulted in down-regulation of PKC activity and expression and potentiation of ara-C-induced apoptosis, but not cellular maturation. However, coadministration of the Ca2+ ionophore A23187 (250 nM) restored bryostatin 1's differentiating ability while antagonizing its capacity to augment apoptosis, despite failing to reverse bryostatin 1-induced down-regulation of PKC activity and cPKC isoform expression. Furthermore, pretreatment of differentiation-responsive monocytic leukemia cells (U937) with bryostatin 1 substantially reduced PKC activity and cPKC isoform expression, but exerted minimal effects on ara-C-related apoptosis. In contrast, exposure of U937 cells to bryostatin 1 after ara-C dramatically increased apoptosis, a phenomenon that did not occur in differentiation-unresponsive HL-60 cells. Collectively, these observations indicate that down-regulation of total assayable PKC activity and cPKC expression by bryostatin 1 are insufficient, by themselves, to account for potentiation of leukemic cell apoptosis, at least under conditions in which differentiation occurs. They also provide further evidence that a reciprocal and highly schedule-dependent relationship exists between leukemic cell differentiation and drug-induced apoptosis.

Antimetabolites, Antineoplastic↗
PubMed1996

Cyclosporine may affect improvement of cognitive brain function after successful cardiac transplantation.

BACKGROUND: The effects of cardiac transplantation on cognitive brain function are uncertain. METHODS AND RESULTS: We measured cognitive brain function and quality of life in out-of-hospital cardiac transplant candidates (n = 55; ejection fraction, 19.9%; age, 54.8 years [means]). After transplantation, the patients were serially reevaluated at 4 months (n = 25) and at 12 months (n = 19). Brain function was measured objectively by cognitive P300 evoked potentials. Additionally, standard psychometric tests (Trail Making Test A, Mini-Mental State Examination, and Profile of Mood State test) were performed. Cognitive P300 evoked potentials were impaired in cardiac transplant candidates (359 ms, recorded at vertex) compared with 55 age- and sex-matched healthy subjects (345 ms, P < .01). Trail Making Test A was also abnormal (45 versus 31 seconds in 55 healthy subjects, P < .01). After transplantation, P300 measures were normalized at 4 months (345 ms, P < .05 versus before transplantation) but declined again at 12 months (352 ms, P = NS versus before transplantation). Stepwise multiple regression analysis revealed that cumulative cyclosporine dosage was the only predictor of individual cognitive brain function 4 months (753 mg/kg body wt, P < .05) and 12 months (2006 mg/kg body wt, P < .01) after transplantation, respectively. CONCLUSIONS: Objective cognitive P300 auditory evoked potential measurements indicate that cognitive brain function is significantly impaired in patients suffering from stable end-stage heart failure. Successful cardiac transplantation is effective to fully normalize impaired brain function. Subsequent relative long-term decline of cognitive brain function after successful cardiac transplantation is strongly suggested to be related to cumulative cyclosporine neurotoxicity.

Affect↗
PubMed1996

Detection of nontraumatic comatose patients with no benefit of intensive care treatment by recording of sensory evoked potentials.

OBJECTIVES: To determine the predictive ability of sensory evoked potential recordings in nontraumatic comatose patients. To evaluate the hypothesis that patients with bilateral absent cortical responses ultimately die despite long-term intensive care treatment. DESIGN: Prospective cohort study. SETTING: Medical intensive care unit (ICU) of a university hospital. PATIENTS: Four hundred forty-one adult nontraumatic comatose patients (unarousable unresponsiveness to external stimulation, Glasgow Coma Score < or = 7) from various causes. Six hundred seventy-six sensory evoked potential measurements were performed within 7 days after onset of coma. MAIN OUTCOME MEASURES: Death or survival to hospital discharge. RESULTS: Eighty-six patients (20%) had a bilateral loss of the cortical evoked potential N20 peak. Despite long-term intensive care treatment, all died without awakening from coma (mortality rate, 100%; 95% confidence interval, 96-100). The mean stay at the ICU after evoked potential measurement until death was 8.1 days (697 patient days). The overall cost of ICU management for these 86 patients accounted for approximately $1,324,300. In the remaining 355 comatose patients with preserved cortical N20 peak, 148 (42%) survived and 207 (58%) died. In this latter group of patients, cervicomedullary N13 to cortical N20 conduction time was prolonged in nonsurvivors (mean +/- SD, 6.7 +/- 1.3 milliseconds) compared with that in survivors (mean +/- SD, 6.4 +/- 1.2 milliseconds, P < .05) and healthy controls (mean +/- SD, 5.5 +/- 0.4 milliseconds, P < .05). Although this difference is statistically significant, a preserved N20 peak is not useful to discriminate whether the individual patient will survive (N13-N20 conduction time of > 7 milliseconds had a positive predictive value of correct prediction of death of 0.67). CONCLUSIONS: Recording of sensory evoked potentials identifies a subgroup of adult nontraumatic comatose patients with a mortality rate of 100% in our sample. In these patients, advanced intensive care treatment should be withdrawn to provide limited ICU resources for patients with higher probability of favorable outcome. We emphasize that these results are not applicable to comatose patients following closed head trauma and particularly not to children.

Adolescent↗
PubMed1996

Outcome prediction for patients with cirrhosis of the liver in a medical ICU: a comparison of the APACHE scores and liver-specific scoringsystems.

OBJECTIVE: To find the most adequate prognostic scoring system for predicting ICU-outcome in patients with decompensated liver cirrhosis in a medical intensive care unit (ICU). DESIGN: Retrospective analysis of patients' records over a 10-year period. SETTING: A medical ICU at the university medical center of Vienna. PATIENTS AND PARTICIPANTS: 94% (n = 198) of all patients with cirrhosis admitted to our medical ICU throughout the 10-year study period. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: From data obtained at admission and at 48 h after admission, scores were calculated using the following scoring systems: Acute Physiology and Chronic Health Evaluation (APACHE) II and III, Scale for Composite Clinical and Laboratory Index Scoring (CCLI), Mayo Risk Score, and Child's Classification. Statistical analysis for the prognostic variables was performed using the chi-square test, t-test, Youden index, and area under a receiver operating characteristic (ROC) curve. APACHE III was found to be the most reliable outcome predictor at admission and after 48 h for patients with decompensated liver cirrhosis (AUC = 0.75 and 0.8, respectively). CONCLUSIONS: To predict the outcome for patients with decompensated cirrhosis of the liver admitted to a medical ICU liver failure alone is not decisive. Liver-specific scoring systems (Mayo Risk Score, CCLI) are adequate, but the APACHE II and III proved to be more powerful, because they include additional physiologic parameters and therefore also take into account additional complications associated with this liver disorder.

APACHE↗
PubMed1996

Beneficial effect of renal transplantation on cognitive brain function.

Cognitive brain dysfunction is a common complication of end-stage renal disease. To investigate the cerebral effect of renal transplantation, we studied P300 event-related potentials--an objective marker of cognitive brain function--trailmaking test and Mini-mental state in 15 chronic hemodialysis patients and 45 matched healthy subjects. Before transplantation, patients showed prolonged P300 latency (364 vs. 337 ms, P < 0.01), smaller amplitude (15.2 vs. 19.1 microV) and scored lower (P < 0.05) in trailmaking test and Mini-mental state as compared to healthy subjects. Following renal transplantation (14 months), P300 latency decreased (337 ms, P < 0.01 vs. before) and amplitude increased (17.4 microV, P < 0.05 vs. before), indicating improved cognitive brain function. The trailmaking test and Mini-mental state tended to improve. Following transplantation, P300 findings, trailmaking test and Mini-mental state were not different from healthy subjects. Additional studies following erythropoietin treatment in 6 of the 15 hemodialysis patients revealed decreased (improved) P300 latency (351 vs. 379 ms before, P < 0.05) with further decrease following transplantation (341 ms, P = 0.06). Our findings indicate that cognitive brain dysfunction in hemodialysis patients may be fully reversed by successful renal transplantation.

Adult↗
PubMed1996

What's real in children's fantasy play?: fantasy play across the transition to becoming a sibling.

This study examined children's fantasy enactments during the critical life transition of becoming a sibling to determine the degree to which the thematic content of fantasy play reflects children's realistic concerns. Thirty 3-5-year-old children played with their best friend at two pre- and three post-birth intervals. Mothers kept diary records of children's concerns, worries, and events they were excited about during 3-day periods surrounding the five play sessions. Raters then evaluated the degree to which the thematic content of the fantasy play was consistent with their concerns as reported by mothers. Overall, little convergence was apparent between the themes of fantasy play and children's perceived concerns. However, a modest relationship was found between acting out positive concerns in play and sibling relationship quality. Although these results lend limited support for the notion that children's concerns are reflected in the content of their spontaneous play, they do suggest that 'playing it out' is beneficial for children.

Adaptation, Psychological↗
PubMed1996

Double-blind, placebo-controlled trial of topiramate as add-on therapy in patients with refractory partial seizures.

In a double-blind, randomized, parallel-group trial, we compared topiramate (TPM) with placebo as add-on therapy in patients with refractory partial epilepsy. TPM was titrated either to the target dosage of 800 mg/ day [400 mg twice daily (b.i.d)] or to the maximal tolerated dose if lower. Twenty-eight (28) patients were randomized to each treatment group. In the intent-to-treat analysis, the net median percent reduction relative to placebo in average monthly seizure rate was 54% for patients in the TPM group (p < 0.001). None of the placebo-treated patients and 43% of the patients treated with TPM experienced > or = 50% reduction in seizures (p = 0.001), and 36% of patients assigned to TPM had a 75-100% reduction in seizures (p < 0.01). Secondarily generalized seizures were also significantly reduced in the TPM group (p = 0.044). The most common adverse events (AE) reported in the TPM group were fatigue, impaired concentration, weight loss, dizziness, and paresthesias. AE occurring either during the rapid titration of TPM or at high dosages led 21% of TPM-treated patients to withdraw from the study. Half of these occurred during the titration study period. No serious AE or clinically important changes in clinical laboratory measures were observed. The present study further establishes the favorable profile and good benefit/risk ratio of TPM in resistant partial epilepsy.

Adolescent↗
PubMed1996

Topiramate placebo-controlled dose-ranging trial in refractory partial epilepsy using 600-, 800-, and 1,000-mg daily dosages. Topiramate YE Study Group.

We conducted a multicenter, double-blind, randomized, parallel, placebo-controlled trial in 190 patients to evaluate the safety and efficacy of three dosages of topiramate (600, 800, and 1,000 mg/day) as adjunctive therapy for patients with refractory partial epilepsy. During an 18-week double-blind treatment period, median percent reductions from baseline in average monthly seizure rates were 1% for placebo, 41% for topiramate 600 mg/day and topiramate 800 mg/day, and 38% for topiramate 1,000 mg/day. There was a 50% or greater reduction from baseline in seizure frequency in 9% of patients in the placebo group and in 44% for topiramate 600 mg/day, 40% for topiramate 800 mg/day, and 38% for topiramate 1,000 mg/day. No placebo patients were improved by 75 to 100% in seizure frequency, whereas 20% of the topiramate patients were improved to this degree. All intent-to-treat drug-placebo comparisons including seizure reduction, percent responders, and investigator and patient global evaluations significantly (p < or = 0.02) favored topiramate. Treatment-emergent adverse events consisted mainly of neurologic symptoms commonly observed during antiepileptic drug (AED) therapy. Sixteen percent of patients on topiramate discontinued therapy due to adverse events. Results of this study indicate that topiramate is a highly efficacious and generally well tolerated new AED. When large groups of patients are compared, incremental efficacy in the add-on setting is not observed at topiramate dosages above 600 mg/day; however, higher doses may prove beneficial to individual patients who tolerate them.

Adolescent↗
PubMed1996

[Effect of prostaglandin E1 on extravascular lung water in patients with severe heart failure].

Prostaglandin E1 (PGE1) is a physiologic vasodilator, which is broadly used in the therapy of peripheral arterial occlusive disease. In addition, the successful use of PGE1 in patients with severe heart failure has been described in several studies, where a decrease in pulmonary artery pressure and an increase in cardiac output were observed. In contrast to these positive effects, the development of lung edema was reported in individual cases after the infusion of PGE1 in patients with heart disease. We therefore conducted a double-blind study to evaluate the effect of PGE1 on extravascular lung water (EVLW) in patients with heart failure (NYHA III-IV) and borderline increased EVLW. Seven patients received an infusion of PGE1 (Prostavasin) at a dosage of 60 micrograms over 2 hours, while in 6 patients (control group) isotonic saline was given as placebo. EVLW was measured using a double indicator method at time points -15 h, -9 h before and at the start of the infusion, 1 h and 2 h during infusion, as well as +1 h, +4 h, +7 h, and +22 h after termination of the infusion. Infusion of PGE1 did not alter EVLW both in comparison to pre-study values (9.8 +/- 4.3 ml/kg bw preinfusion. 9.3 +/- 3.2 ml/kg bw after 1 hour and 9.4 +/- 3.5 ml/kg bw after 2 hours) or to the control group (6.5 +/- 3.3 ml/kg bw preinfusion, 7.1 +/- 2.7 ml/kg bw after 1 hour and 7.0 +/- 3.2 ml/kg bw after 2 hours). We conclude that there is no evidence that PGE1 might contribute to the development, or worsening of lung edema by inducing extravascular lung water accumulation and can, thus, be savely given to patients with even a severe degree of heart failure (NYHA III-IV).

Alprostadil↗
PubMed1996

[Acute rhabdomyolysis in status asthmaticus].

Acute rhabdomyolysis is a rare complication in patients with status asthmaticus receiving mechanical ventilation. Individual reports implicate several factors, whereby the simultaneous use of high-dose glucocorticoids and non-depolarizing muscle blocking agents appears to be the major patho-physiological mechanism. A 48 year-old female patient with a 3-year history of granulomatous vasculitis Churg-Strauss was admitted to the intensive care unit (ICU) due to severe status asthmaticus, which necessitated endotracheal intubation and mechanical ventilation. Antiobstructive therapy consisted of beta 2-sympathomimetics, theophylline and high-dose intravenous prednisolone (5440 mg in 10 days). Additionally, the patient was treated with non-depolarizing muscle blocking agents (atracurium 2070 mg over 7 days). Six days after admission to the ICU the patient developed severe rhabdomyolysis, with an increased creatine kinase (CK) level and myoglobinuria. The maximum CK value occurred 12 days after ICU admission (3810 U/l), accompanied by a serum myoglobin level of 13,900 ng/ml. 5 days after cessation of muscle relaxant therapy and reduction of intravenous glucocorticoids, the serum CK level decreased, reaching normal values 9 days later.

Acute Disease↗
PubMed1995

Platelet disorders in uraemia before and after haemodialysis under the influence of low dose aspirin.

Thrombocyte dysfunction and increased bleeding time (BT) are well documented in uraemic patients. However, these patients are frequently medicated with low dose aspirin (ASA) in order to maintain shunt patency and prevent cardiovascular events. Recently, life- threatening gastrointestinal haemorrhage in an uraemic subject taking low dose aspirin has been reported. In this work ASA related bleeding risk in uraemic patients and the effect of haemodialysis on their bleeding tendency was studied by measuring in vitro bleeding time (BT) using the Thrombostat 4000 in 34 uraemic patients on chronic haemodialysis compared to 50 healthy subjects. Our results indicate that low dose aspirin does not influence uraemic thrombopathia 8 to 10h after ingestion but seems to increase bleeding risk shortly after ingestion. Moreover, haemodialysis alters uraemic in vitro BT with regard to the time after ingestion of ASA.

Adult↗
PubMed1995

Renal and hepatic family 3A cytochromes P450 (CYP3A) in spontaneously hypertensive rats.

Troleandomycin (TAO), a selective family 3A cytochromes P450 (CYP3A) inhibitor, decreases enhanced in vivo corticosterone 6 beta-hydroxylation and blood pressure in spontaneously hypertensive rats (SHR). Corticosterone 6 beta-hydroxylation was measured in liver and kidney microsomes, to determine ontogeny and the effect of TAO on CYP3A activity at the organ level. SHR kidney CYP3A activity increased from 4 to 8 weeks, stabilized at 11 and 16 weeks, and was much higher than in control (Wistar-Kyoto, WKY) rats at all ages. Hepatic activity showed less consistency in strain difference. TAO produced a relatively large decrease in renal CYP3A activity compared with liver. Although renal CYP3A mRNA was not present in sufficient quantity for detection by northern blot analysis of total RNA, its presence was demonstrated in SHR by reverse transcriptase-polymerase chain reaction amplification. Correlations between renal CYP3A activity and systolic blood pressure in SHR and WKY rats with variations in age, strain and drug treatment are consistent with the role of the enzyme in the pathogenesis of blood pressure elevation in SHR.

Animals↗