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Biomedical subjects

G Stark

Publications and source records attributed to G Stark.

At least 55 records · Page 3Linked to original sources
PubMed1998

Saw palmetto extracts for treatment of benign prostatic hyperplasia: a systematic review.

OBJECTIVE: To conduct a systematic review and, where possible, quantitative meta-analysis of the existing evidence regarding the therapeutic efficacy and safety of the saw palmetto plant extract, Serenoa repens, in men with symptomatic benign prostatic hyperplasia (BPH). DATA SOURCES: Studies were identified through the search of MEDLINE (1966-1997), EMBASE, Phytodok, the Cochrane Library, bibliographies of identified trials and review articles, and contact with relevant authors and drug companies. STUDY SELECTION: Randomized trials were included if participants had symptomatic BPH, the intervention was a preparation of S repens alone or in combination with other phytotherapeutic agents, a control group received placebo or other pharmacological therapies for BPH, and the treatment duration was at least 30 days. DATA EXTRACTION: Two investigators for each article (T.J.W., A.I., G.S., and R.M.) independently extracted key data on design features, subject characteristics, therapy allocation, and outcomes of the studies. DATA SYNTHESIS: A total of 18 randomized controlled trials involving 2939 men met inclusion criteria and were analyzed. Many studies did not report results in a method that permitted meta-analysis. Treatment allocation concealment was adequate in 9 studies; 16 were double-blinded. The mean study duration was 9 weeks (range, 4-48 weeks). As compared with men receiving placebo, men treated with S repens had decreased urinary tract symptom scores (weighted mean difference [WMD], -1.41 points [scale range, 0-19] [95% confidence interval (CI), -2.52 to -0.30] [n = 1 study]), nocturia (WMD, -0.76 times per evening [95% CI, -1.22 to -0.32] [n = 10 studies]), and improvement in self-rating of urinary tract symptoms; risk ratio for improvement (1.72 [95% CI, 1.21-2.44] [n = 6 studies]), and peak urine flow (WMD, 1.93 mL/s [95% CI, 0.72-3.14] [n = 8 studies]). Compared with men receiving finasteride, men treated with S repens had similar improvements in urinary tract symptom scores (WMD, 0.37 International Prostate Symptom Score points [scale range, 0-35] [95% CI, -0.45 to 1.19] [n = 2 studies]) and peak urine flow (WMD, -0.74 mL/s [95% CI, -1.66 to 0.18] [n = 2 studies]). Adverse effects due to S repens were mild and infrequent; erectile dysfunction was more frequent with finasteride (4.9%) than with S repens (1.1%; P<.001). Withdrawal rates in men assigned to placebo, S repens, or finasteride were 7%, 9%, and 11%, respectively. CONCLUSIONS: The existing literature on S repens for treatment of BPH is limited in terms of the short duration of studies and variability in study design, use of phytotherapeutic preparations, and reports of outcomes. However, the evidence suggests that S repens improves urologic symptoms and flow measures. Compared with finasteride, S repens produces similar improvement in urinary tract symptoms and urinary flow and was associated with fewer adverse treatment events. Further research is needed using standardized preparations of S repens to determine its long-term effectiveness and ability to prevent BPH complications.

Enzyme Inhibitors↗
PubMed1998

A new high-resolution esophageal electrocardiography recording technique: an experimental approach for the detection of myocardial ischemia.

UNLABELLED: Criteria for ischemic changes in the esophageal electrocardiograph (E-ECG) have not been standardized and validated. The main goal of this study was to evaluate the experimental esophageal recording of myocardial ischemia and to assess the association between ST segment alternans in the E-ECG and ischemia. Experiments were performed on 18 anesthetized sheep with occlusion of a branch of the left anterior descending artery. The bipolar signals were recorded via an esophageal lead containing three chloridized silver electrodes. Electrical signals were amplified in a self-designed, battery-supported preamplifier (gain 1000, frequency range 0.01-2000 Hz, common mode rejection 140 dB, signal noise 5-7 microV p-p), then sent to a digital oscilloscope for display and to a pulse code-modulated recorder. Surface electrocardiography (S-ECG) data were also recorded. Ischemia E-ECG revealed homogenous ST segments without any beat-to-beat alternans. Two minutes after occlusion, 14 of 15 sheep (93%) showed repetitive beat-to-beat fluctuations within the ST segment on the E-ECG. Of the 15 sheep, 7 (47%) showed ischemia in the S-ECG (P < 0.01). For calculation of the dynamic changes in the ST segment in the E-ECG, the difference in the amplitudes of the ST segment of five successive beats to the next beat, performed for 200 consecutive beats, was calculated. The central tendency of the sum of these values before versus during ischemia was 2000 mV/ms versus 5000 mV/ms (Hodges-Lehmann point estimator) (95% confidence intervals 1700/2500 versus 3350/9250 [lower limit/upper limit]). The authors have established a close temporal relationship between the magnitude of ST segment alternans recorded via E-ECG and myocardial ischemia. IMPLICATIONS: The study presents the use of an esophageal electrocardiograph for detection of progressive changes of myocardial ischemia and infarction. During acute myocardial ischemia and infarction in sheep, the esophageal electrocardiograph has visually apparent ST alternans of amplitude in the millivolt range, in part due to a special amplifier (0.01-2000 Hz). This is therefore one very promising technique for better evaluation of electrocardiographic changes of ischemia.

Animals↗
PubMed1998

Successful thrombolysis in massive pulmonary embolism with right ventricular thrombus.

Systemic thrombolytic therapy for pulmonary embolism (PAE) is an established and common procedure. Due to increased risk, however, it is not much used in pulmonary embolism combined with thrombotic mass in the right ventricle. We applied it in a 59-year-old male patient with small intracardiac thrombus in the right ventricle (diameter = 1 cm) and peripheral pulmonary embolism whose diagnosis was obtained with transthoracal echocardiography (TTE) and helix lung CT. Twelve hours after thrombolytic treatment, helix lung CT scan showed a reduction in the size of the pulmonary embolism and no thrombotic masses in the right ventricle. In this patient with a small cardiac thrombus and rather peripheral pulmonary emboli, a systemic thrombolytic therapy proved to be effective and safe.

Diagnostic Imaging↗
PubMed1997

Photodynamic membrane damage at the level of single ion channels.

Illumination of cellular membranes by visible light in the presence of appropriate photosensitizers is known to inactivate specific ionic pathways and to increase the unspecific leak conductance of the membranes. While previous studies have concentrated on the macroscopic ionic currents, the present study separates the two phenomena at the microscopic level. Using opossum kidney (OK) cells as epithelial model system and photofrin II as sensitizer, the patch-clamp technique in inside-out configuration has been applied to show the inactivation of single ion channels immediately after start of illumination and the subsequent strong increase of the leak conductance. Inactivation is shown for two kinds of channels: the large-conductance Ca2+-dependent K+ channel (maxi-K(Ca)) and the stretch-activated nonselective cation channel (SA-cat).

Animals↗
PubMed1997

Effects of free radicals on partial reactions of the Na,K-ATPase.

The function of the Na,K-ATPase is known to be considerably impaired in the presence of free radicals such as OH.. While previous experiments were largely based on the loss of enzymatic activity of the protein, this is the first communication dealing with partial reactions of the pump cycle in the presence of free radicals produced by water radiolysis. Three different system states, which are directly involved in ion transfer catalyzed by the enzyme, showed similar sensitivity to free radical action. This is indicated by largely identical D37-doses of the decay of the reaction amplitudes investigated. The decrease in the efficiency of the enzyme functions was largely due to a lethal damage of pump molecules. A kinetic analysis of the ATP-induced conformational transition E1-->E2 revealed, however, that a minor component of the inactivation is due to a reduction of the transition rate constant. The decrease of the enzymatic activity could be simulated by the decay of the rate-limiting conformational transition. This finding indicates the conservation of a close coupling between ATP-hydrolysis and sodium translocation process throughout free-radical induced inactivation. As a result of the tight coupling, enzyme modification at different system states leads to similar functional consequences for the protein.

Adenosine Triphosphate↗
PubMed1997

The inner membrane barrier of lipid membranes experienced by the valinomycin/Rb+ complex: charge pulse experiments at high membrane voltages.

The kinetic analysis of charge pulse experiments at planar lipid membranes in the presence of macrocyclic ion carriers has been limited so far to the low voltage range, where, under certain simplifying conditions, an analytical solution is available. In the present study, initial voltages of up to 300 mV were applied to the membrane, and the voltage decay through the conductive pathways of the membrane was followed as a function of time. The system of differential equations derived from the transport model was solved numerically and was compared with the experimental data. The generalized kinetic analysis of charge pulse experiments and of steady-state current-voltage curves was used to study the voltage dependence of the individual transport steps and to obtain information on the shape of the inner membrane barrier. The data were found to be consistent with a comparatively broad inner barrier such as a trapezoidal barrier or an image force barrier. The inner barrier was found to sense 70-76% of the voltage applied to the membrane. As a consequence, 24-30% of the voltage acts on the two interfacial barriers between membrane and water. The data refer to membranes formed from monoolein, monoeicosenoin, or monoerucin in n-decane.

Cations, Monovalent↗
PubMed1997

Magnesium abolishes inadequate kinetics of frequency adaptation of the Q-aT interval in the presence of sotalol.

OBJECTIVE: It has been well established that class III antiarrhythmic drugs can also induce ventricular arrhythmias. Marked changes in the QT interval are correlated with an increased dispersion of repolarization which is an important factor for the induction of ventricular arrhythmias. The aim of the present study was to investigate the effects of sotalol alone and in combination with MgSO4 and the Q-aT interval during abrupt changes in heart rate. METHODS: The experiments were performed on isolated guinea-pig hearts perfused by the method of Langendorff. The rate adaptation of the Q-aT interval was estimated after abruptly changing the ventricular pacing rate from 220 to 180 ms and back to 220 ms. RESULTS: In the presence of 10 microM sotalol, at a constant pacing cycle length of 220 ms, the QT interval was prolonged significantly (P < 0.01) from 152 +/- 4 to 166 +/- 3 ms (mean +/- s.e.m., n = 8 in each group). The addition of 3.4 mM MgSO4 caused a slight further prolongation of the QT interval. After abruptly shortening the pacing cycle length from 220 to 180 ms, the Q-aT interval shortened within 2 min by 11.3 +/- 0.5 ms with a time constant (tau) of 77 +/9 beats under control conditions, by 15.4 +/- 0.9 ms (P < 0.05 vs. control with tau = 52 +/- 7 beats (P < 0.05 vs. control) in the presence of sotalol, and by 13.1 +/- 1.2 ms with tau = 158 +/- 13 beats under the combination of sotalol (10 microM) and MgSO4 (3.4 mM). After abrupt shortening of the pacing cycle length the Q-aT interval of the first beat was shortened by 3.3 +/- 0.3 ms under control conditions, by 7.1 +/- 0.2 ms (P < 0.01 vs. control) under sotalol, and by 4.2 +/- 0.2 ms with the combination of sotalol and MgSO4. If the pacing cycle length was abruptly increased from 180 to 220 ms, the effects were comparable to those described above. CONCLUSIONS: Sotalol led to inadequate kinetics of fate adaptation of the Q-aT interval indicated by a high amplitude of Q-aT interval change, especially within the first beat after abrupt change in the pacing rate. MgSO4 abolished this effect of sotalol. These findings suggest that MgSO4 could reduce sotalol-induced inadequate kinetics of rate adaptation and therefore also dispersion of repolarization, which may result in a reduction of sotalol-induced ventricular arrhythmias.

Animals↗
PubMed1997

A high-resolution esophageal electrocardiogram for monitoring atrial activity in the hypothermic potassium-arrested heart.

Atrial electrical activities during hypothermic, K(+)-induced cardioplegic arrest correlate with an increased incidence of postoperative supraventricular dysrhythmias in coronary artery bypass graft patients. Surface electrocardiogram (ECG) (S-ECG) may be insufficiently sensitive to detect such activity intraoperatively, and invasive methods are impractical and traumatic. From induction of anesthesia until the end of surgery, esophageal ECG signals were detected with a new bipolar esophageal probe and a new high-resolution preamplifier (frequency range 0.01-2000 Hz). The S-ECG and the esophageal ECG (E-ECG) were evaluated independently in 18 patients. Eight of 18 patients presented during cardioplegic arrest a mean of 483 +/- 119 high-amplitude, biphasic P components (mean amplitude 0.7 +/- 0.1 mV, range 0.35-1.15 mV) per patient (mean 36 +/- 6 [5-59] potentials/min) similar to those coinciding with the surface ECG P-waves during sinus rhythm. Six of these eight patients presented a mean of 29 +/- 11 low atrial activities (mean amplitude 0.14 +/- 0.023 mV; range 0.1-0.25 mV) per patient (mean 8.4 +/- 5.6 [2.3-48] potentials/min) in the E-ECG. In the S-ECG, one patient of these eight presented 26 P waves during cardioplegic arrest simultaneously with activities in the E-ECG. During the first 5 days, seven of eight (88%) patients with atrial activities in the E-ECG versus 3 of 10 (30%) patients without atrial activities developed supraventricular tachyarrhythmias postoperatively (P < 0.05). This new high-resolution E-ECG device detected in a beat-to-beat technique more atrial activity during cardioplegic arrest than a S-ECG and offered the advantages of artifact exclusion and better prediction of postoperative supraventricular dysrhythmias.

Aged↗
PubMed1997

Influence of duration of rapid ventricular pacing on ventricular refractoriness in the presence of propafenone and lidocaine.

Propafenone and lidocaine have a rate dependent negative dromotropic effect on intraventricular conduction. We investigated the use dependent actions of propafenone and lidocaine on intraventricular conduction in isolated guinea pig hearts perfused by the method of Langendorff. Of primary interest was how the number of stimuli of the conditioning train (S1) might influence the ventricular effective refractory period (VERP) when refractoriness is assessed at a high pacing rate. Propafenone (0.3 microM) and lidocaine (50 microM) caused a comparable prolongation of the intraventricular conduction time during sinus rhythm. During ventricular pacing in the presence of propafenone an abrupt decrease of the pacing cycle length (220 to 120 ms) resulted in an initial peak of rate dependent prolongation of the QRS interval that subsequently decreased to a stable steady-state level. Lidocaine also induced a rate dependent increase of the intraventricular conduction time up to a steady-state level. The time constant, characterizing the changes of the intraventricular conduction time after shortening the ventricular pacing cycle length from 220 to 120 ms was significantly (P < 0.01) longer in the presence of propafenone (tau = 31 +/- 4 beats; mean +/- SEM; n = 11) than for lidocaine (tau = 3 +/- 1; n = 10). Both drugs caused the greatest increase of the VERP when the number of conditioning stimuli (S1, interstimulus interval = 120 ms) was in the range of their respective time constant. However, when the number of conditioning stimuli was further increased, VERP progressively diminished. These effects may be explained by a shortening of the action potential during high rates that results in a decreased binding of propafenone to Na+ channels and by the direct shortening of repolarization period by lidocaine (Class IB drug).

Action Potentials↗
PubMed1997

Fatal bupropion overdose.

BACKGROUND: Bupropion is a unique monocyclic antidepressant that has been known to cause seizures in high therapeutic doses and in acute overdoses. Death due to ingestion, however, is a rare occurrence. CASE REPORT: We report a case of a 26-year-old man who ingested 23 g bupropion, developed seizures and hypoxia, and presented in cardiac arrest. The patient was resuscitated in the emergency department, but died 4 d after supportive intensive care. CONCLUSIONS: Bupropion overdose may lead to recurrent seizures, hypoxia and death. Aggressive management of severe bupropion overdose is recommended.

Adult↗
PubMed1996

Glucocorticoids regulate the expression of the stressprotein alpha B-crystallin.

alpha B-crystallin is a major component of the eye lens but is also found in many extralenticular tissues. In established fibroblasts it is synthesized in response to stress such as hyperthermia. Here we report that the treatment of NIH3T3 fibroblasts with the synthetic glucocorticoid hormone dexamethasone resulted in the accumulation of substantial amounts of alpha B-crystallin, alpha B-crystallin mRNA accumulated slowly and over a period of many days in response to prolonged hormone treatment. alpha B-crystallin promoter-reporter constructs were hormone responsive. A putative glucocorticoid response element (GRE) within the analysed promoter region could bind the glucocorticoid receptor as revealed from in vitro footprint analysis but is not involved in the hormone-mediated gene activation. Deletions of 5' flanking regions to position -465 relative to the transcription start allowed for full hormone responsiveness. A deletion from -465 to -389 abolish hormone-mediated gene induction. No sequence element closely resembling a classical GRE is present within that hormone-responsive region.

3T3 Cells↗
PubMed1996

Rate-dependent effects of ajmaline and propafenone on atrioventricular conduction.

The aim of the present study was to characterize the time dependence of the depressant effects of ajmaline and propafenone on the Ca(2+)-channel-dependent tissue of the atrioventricular node in isolated guinea pig hearts perfused by the method of Langendorff. Ajmaline at a concentration of 0.03 microM and propafenone at a concentration of 0.3 microM caused a significant and comparable prolongation of the His bundle and atrioventricular conduction time (AVCT). When the pacing cycle length was abruptly shortened from 240 to 180 ms, the mean time constant (tau on) of the rate-dependent AVCT prolongation was comparable for ajmaline and propafenone. In contrast, if the pacing cycle length was abruptly increased from 180 to 240 ms the mean time constant (tau off) for ajmaline was significantly higher than for propafenone. The rate-dependent increase of the atrioventricular effective refractory period was significantly more pronounced in the presence of ajmaline than of propafenone. Ajmaline and propafenone affect the Ca(2+)-channel-dependent tissue of the myocardium. The more pronounced rate-dependent effect of ajmaline on the atrioventricular effective refractory period may be explained by a slower dissociation kinetic from the channel.

Ajmaline↗
PubMed1996

Generation of mice with a 200-kb amyloid precursor protein gene deletion by Cre recombinase-mediated site-specific recombination in embryonic stem cells.

Gene disruptions and deletions of up to 20kb have been generated by homologous recombination with appropriate targeting vectors in murine embryonic stem (ES) cells. Because we could not obtain a deletion of about 200 kb in the mouse amyloid precursor protein gene by the classical technique, we employed strategies involving the insertion of loxP sites upstream and downstream of the region to be deleted by homologous recombination and elicited excision of the loxP-flanked region by introduction of a Cre expression vector into the ES cells. In the first approach, the loxP sequences were inserted in two successive steps and after each step, ES cell clones were isolated and characterized. Deletion of the loxP-flanked sequence was accomplished by introducing the cre gene in a third step. In the second approach, ES cells containing the upstream loxP cassette were electroporated simultaneously with the downstream loxP targeting vector and the Cre expression plasmid. ES cells were obtained that gave rise to chimeric mice capable of germ-line transmission of the deleted amyloid precursor protein allele.

Amino Acid Sequence↗
PubMed1996

The effect of free radicals on the conductance induced by alamethicin in planar lipid membranes: activation and inactivation.

Exposure to ionizing radiation of planar lipid membranes doped with alamethicin gives rise to an increase and to a subsequent decrease of the membrane conductance. Both effects are due to the presence of radiation-induced free radicals of water radiolysis as was shown by addition of various radical scavengers. The increase of the conductance was found to be a consequence of free radical-initiated lipid peroxidation favouring the formation of active ion channels. The decrease of the conductance observed at larger radiation doses is due to an inactivation of alamethicin monomers. The characteristic D37 dose of inactivation was found to be about two orders of magnitude larger than in the case of gramicidin A. The comparatively high sensitivity of the latter is due to the presence of its four tryptophan residues. Inactivation of trichorzianine AIIIc, an analogue of alamethicin with a C-terminal tryptophanol residue, occurs at radiation doses two orders of magnitude lower than observed with alamethicin.

Alamethicin↗
PubMed1996

Effects of AWD 23-111, a new antiarrhythmic substance, on cardiac conduction and refractoriness.

In isolated spontaneously beating guinea pig hearts, the effects of AWD 23-111 (N-(dicyclohexylcarbamoylmethyl)-N-(3-diethylamino-propyl)-4-nit robenzamid -hydrochloride), a new synthetic class III antiarrhythmic agent with sodium antagonistic properties, were investigated on cardiac electrophysiological parameters, that is, conduction and refractoriness. Concentration-dependent prolongation of the atrioventricular, intraventricular, and His bundle conduction times and of sinus node cycle length were present. At 0.3 microM the repolarization period was prolonged significantly. No reverse use-dependent effect on the repolarization period was observed. During rapid pacing (pacing cycle length = 120 ms for the ventricle and 180 ms for the atrium) the rate-dependent intraventricular (QRS) or atrioventricular conduction time (AVCT) prolongation follows an exponential function of the beat number and is characterized by a drug-specific time constant. The time constant for the intraventricular conduction time prolongation in the presence of 0.1 microM AWD 23-111 was very long at 150 +/- 29 beats (mean +/- SEM; n = 6), indicating a slow binding kinetic to the sodium channel. At 0.1 microM AWD 23-111, a significant increase in the ventricular effective refractory period was reached when the interstimulus interval (S1-S1) was 120 ms and the number of conditioning stimuli (S1) was higher than the time constant. The time constant for the rate-dependent AVCT prolongation in the presence of 0.3 microM AWD 23-111 was 34 +/- 6 beats (n = 6). The effective refractory period of the atrioventricular conduction significantly increased with the number of conditioning stimuli (S1), until the number was comparable with the time constant. In conclusion, AWD 23-111 exerts a wide variety of actions on the cardiac conduction system. Its combined effects on the potassium and sodium channels seem to be responsible for the marked rate-dependent effect on ventricular refractoriness and for the lack of a reverse use-dependency on JT prolongation.

Animals↗
PubMed1996

Exercise increases plasma concentrations of (R)- and (S)-propranolol.

OBJECTIVE: We recently reported a highly stereoselective increase in plasma concentrations of (S)-atenolol during exercise which is most likely due to a release of the drug from adrenergic cells. The objective of the present study was to investigate the influence of physical exercise on plasma concentrations of the (R)- and (S)-enantiomers of propranolol. METHODS: Blood samples were taken immediately before and at the end of exercise in 12 patients receiving chronic treatment with racemic (R, S)-propranolol. Plasma concentrations of (R)- and (S)-propranolol were determined by HPLC. RESULTS: In contrast to atenolol, mean plasma concentrations of (S)-propranolol were significantly higher (+20%) than those of (R)-propranolol at rest. During exercise there was an increase in plasma concentrations of both (R)-propranolol (+129%) and (S)-propranolol (+109%). CONCLUSION: Based on information from in vitro studies we conclude that the increase in plasma concentrations of (S)-propranolol during exercise is caused by a release of the drug from adrenergic nerves, whereas the reason for the increase in (R)-propranolol remains to be determined. This release of the beta-adrenoceptor blocking (S)-enantiomer directly at the synaptic gaps might be one reason for the poor correlation between plasma concentration and effect of beta-adrenoceptor antagonists repeatedly described in the literature.

Adrenergic beta-Antagonists↗