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Biomedical subjects

G Stark

Publications and source records attributed to G Stark.

At least 37 records · Page 2Linked to original sources
PubMed2000

Serenoa repens for benign prostatic hyperplasia.

OBJECTIVES: This systematic review aimed to assess the effects of Serenoa repens in the treatment of Benign Prostatic Hyperplasia (BPH). SEARCH STRATEGY: Trials were searched in computerized general and specialized databases (MEDLINE, EMBASE, Cochrane Library, Phytodok), by checking bibliographies, and by contacting manufacturers and researchers. SELECTION CRITERIA: Trials were eligible if they (1) randomized men with BPH to receive preparations of Serenoa repens (alone or in combination) in comparison with placebo or other BPH medications, and (2) included clinical outcomes such as urologic symptom scales, symptoms, or urodynamic measurements. Eligibility was assessed by at least two independent observers. DATA COLLECTION AND ANALYSIS: Information on patients, interventions, and outcomes was extracted by at least two independent reviewers using a standard form. The main outcome measure for comparing the effectiveness of Serenoa repens with placebo or other BPH medications was the change in urologic symptom scale scores. Secondary outcomes included changes in nocturia and urodynamic measures. The main outcome measure for side effects was the number of men reporting side effects. MAIN RESULTS: 2939 men from18 randomized trials lasting 4 to 48 weeks were assessed. 16 trials were double-blinded and treatment allocation concealment was adequate in 9 studies. Compared with placebo, Serenoa repens improved urinary symptom scores, symptoms, and urinary flow measures. The weighted mean difference (WMD) for the urinary symptom score was -1.41 points (scale range 0-19), (95%CI = -2.52, -0.30, n = 1 study) and the risk ratio (RR) for self rated improvement was 1.75 (95%CI = 1.21, 2.54, n = 6 studies). The WMD for nocturia was -0.76 times per evening (95%CI = -1.22, -0.32; n = 10 studies). The WMD for peak urine flow was 1.93 ml/sec (95%CI = 0.72, 3.14, n = 8 studies). Compared with finasteride, Serenoa repens produced similar improvements in urinary symptom scores (WMD = 0.37 IPSS points (scale range 0-35), 95%CI = -0.45, 1.19, n = 2 studies) and peak urine flow (WMD = -0.74 ml/sec, 95%CI = -1.66, 0.18, n = 2 studies). Adverse effects due to Serenoa repens were mild and infrequent. Withdrawal rates in men assigned to placebo, Serenoa repens or finasteride were 7%, 9%, and 11%, respectively. REVIEWER'S CONCLUSIONS: The evidence suggests that Serenoa repens improves urologic symptoms and flow measures compared with placebo. Serenoa repens produced similar improvement in urinary symptoms and flow compared to finasteride and is associated with fewer adverse treatment events. The long term effectiveness, safety and ability to prevent BPH complications are not known.

Androgen Antagonists↗
PubMed2000

T1-deficient and T1-Fc-transgenic mice develop a normal protective Th2-type immune response following infection with Nippostrongylus brasiliensis.

The IL-1 receptor-related protein T1 is expressed on the surface of Th2, but not Th1 cells. Studies with anti-T1 monoclonal antibodies have suggested that T1 is critical for development of normal Th2-type responses. To elucidate the role of T1 in vivo, we generated T1-deficient mice and a T1-transgenic strain which secretes soluble T1-Fc fusion protein into the serum. These were analyzed for the Th2 immune response induced by infection with the parasitic nematode Nippostrongylus brasiliensis. Although Th2 cytokine production by lymph node cells was similar in all groups of N. brasiliensis-infected mice, a decrease in IL-5 production by lung lymphocytes was detected in both T1-deficient and T1-Fc-transgenic mice compared to control littermates. This difference in IL-5 production did not influence blood eosinophilia, but recruitment of eosinophils into lung tissue, especially in T1-Fc-transgenic mice was slightly decreased. However, induction of all other immune parameters was normal and both T1-deficient and T1-Fc-transgenic mice were able to clear the parasite infection within 12 days with kinetics similar to those in control mice. Therefore, in contrast to previous suggestions, we conclude that the T1 protein is not obligatory for normal development of Th2 immune responses.

Animals↗
PubMed2000

Inverse dose-rate effects at the level of proteins observed in the presence of lipids.

PURPOSE: Radical-chain mechanisms such as lipid peroxidation are known to show an inverse dose-rate effect, i.e. the radiation effect increases with decreasing dose rate at identical doses applied. The present study was intended to investigate whether an inverse dose-rate effect can be transferred from the level of lipids to the level of proteins. METHOD: Functional inactivation or structural modification by 80kV X-rays of two classes of proteins was investigated: membrane proteins with a natural environment of lipids like the Ca-ATPase of the sarcoplasmic reticulum, succinate dehydrogenase and F0F1-ATPase from the inner mitochondrial membrane. The second class comprises the water-soluble proteins cytosolic creatine kinase (MM-CK) and bovine serum albumin (BSA). Their modification by free radicals of water radiolysis was investigated in the absence and presence of lipid vesicles. RESULTS: For all proteins investigated, an inverse dose-rate effect was observed in the presence of lipids. This also holds for the water-soluble proteins MM-CK and BSA. In the latter two cases, the dose-rate effect disappeared either in the absence of (unsaturated) lipids or in the presence of alpha-tocopherol. CONCLUSION: The largely identical results obtained for a variety of different proteins indicate that inverse dose-rate effects are a normal consequence of radiation induced protein damage in the presence of lipids. In view of the high amount of cellular lipids, this should also hold for the situation in vivo, although due to the comparatively high concentration of intracellular antioxidants the dose-rate dependence might be strongly reduced or even virtually abolished.

Animals↗
PubMed2000

Efficacy of the novel calcium antagonist R(+)-semotiadil in limiting the ventricular rate during atrial flutter in isolated guinea pig hearts.

Ca2+ antagonists slow the ventricular rate by blocking conduction in the anterograde direction through the atrioventricular (AV) node. The aim of this study was to investigate the efficacy of the novel Ca2+ antagonist semotiadil compared with verapamil and diltiazem on the filtering capacity of the AV node during simulated atrial flutter in isolated guinea-pig hearts perfused by the method of Langendorff. During sinus rhythm, semotiadil as well as verapamil and diltiazem induced comparable depressant effects on AV-nodal conduction time and, during tachycardia, a comparable enhancement of this effect. The time constant (tau-on) for the drug-specific rate-dependent effect on AV-nodal conduction slowing was longest in the presence of verapamil compared with the long tau-on of semotiadil and the short tau-on of diltiazem. Verapamil and semotiadil exhibited a significantly greater effect than diltiazem on the mean ventricular cycle length (VCLmeun), on the maximal ventricular cycle length (VCLmax) and on the standard deviation of the VCL (SD(VCL)) during atrial flutter. Therefore the kinetics of the rate adaptation of AV-nodal conduction time in the presence of Ca2+ antagonists predicts the filtering capacity of the AV node during atrial flutter. Semotiadil has a verapamil type of action on ventricular cycle length during atrial flutter, whereas the disadvantageous prolongation of maximal VCL as well as the dispersion of VCL with semotiadil was only about half those found with verapamil.

Animals↗
PubMed2000

Pulmonary embolism and intracardiac thrombi--individual therapeutic procedures.

Mobile right heart thrombus is a severe but rare presentation of thromboembolic disease and usually coexists with an already massive pulmonary embolism (PE). But looking at the literature there is no clear consensus on therapeutic management. We therefore tried to find possible therapeutic guidelines and to evaluate an optimal diagnostic procedure looking at three patients who presented at our department with mobile right heart thrombus in the last year. The first patient with a small (diameter = 1 cm) thrombus in the right ventricle and peripheral pulmonary embolism underwent successful thrombolytic therapy without any complications. Patients II and III showed large intracardiac masses, in patient III extending into the superior vena cava, with central PE. These two patients underwent pulmonary arteriotomy. The diagnostic line in each case was transthoracal echocardiography followed by a helix lung CT scan. Only patients with small intracardiac thrombi and thrombotic masses in the peripheral pulmonary arteries but with hemodynamically significant PE should be treated with thrombolytic agents.

Coronary Thrombosis↗
PubMed2000

Osteomyelitis of the spine and abscess formation in the left thigh after stent-graft implantation in the superficial femoral artery.

PURPOSE: To present a rare case of abscess formation around a covered stent in the superficial femoral artery. METHODS AND RESULTS: Two weeks after balloon dilation of a left superficial femoral artery (SFA) occlusion, during which a Hemobahn covered stent had been placed to treat dissection, a 77-year-old nondiabetic male developed intolerable pain and swelling of his left thigh. An abscess had formed around the stent, which was patent; intravenous antibiotic therapy quelled the symptoms, and the patient discontinued his oral antibiotic regimen weeks after discharge. General septicemia ensued. Acute lower limb ischemia and excruciating back pain prompted readmission. The SFA stent-graft occlusion required femoropopliteal bypass; the abscess and spondylodiskitis that had developed in the T12 and L1 vertebrae responded to intravenous antibiotics. The patient is without signs of infection at 6 months. CONCLUSIONS: Local and systemic infections associated with intraluminal prostheses are rare, and prophylactic antibiotic therapy is not commonly employed. Balloon- or device-induced arterial injury may expose the arterial wall to bacterial colonization, suggesting that patients receiving lengthy stents or experiencing arterial injury during angioplasty should receive antibiotics as a precautionary measure.

Abscess↗
PubMed1999

Free radical-induced inactivation of creatine kinase: influence on the octameric and dimeric states of the mitochondrial enzyme (Mib-CK).

Free radicals of X-ray-induced water radiolysis, either directly or indirectly via their reaction products, reduce the activity of both dimeric cytoplasmic muscle-type creatine kinase (MM-CK) and octameric mitochondrial creatine kinase (Mi-CK) to virtually zero. Similarly values of the characteristic D(37)-dose of enzyme inactivation (dose required to reduce enzyme activity to 37%) were found for the two isoenzymes of CK under identical conditions. Octamer stability was not significantly affected within the dose range considered. However, both the dissociation of octamers into dimers by a transition-state analogue complex (TSAC), and the reassociation of the dimers into octamers, showed dose-dependent reduction. Binding of the TSAC to the active centre was found to protect the enzyme against inactivation by free radicals. No protection was observed for the radiation-induced decrease of the endogenous tryptophan fluorescence. The experimental results are in line with the following interpretation: (i) the reduction of Mi(b)-CK dimer association is due to free radical-induced modification of Trp-264, situated at the dimer/dimer interface; (ii) the active-site Trp-223 is not a prime target for free radicals and is not involved in the inactivation of the enzyme; (iii) the inhibition of TSAC-induced dissociation of Mi(b)-CK, like enzyme inactivation, is primarily due to a modification of the active-site Cys-278.

Animals↗
PubMed1999

Deficient T cell fate specification in mice with an induced inactivation of Notch1.

Notch proteins are cell surface receptors that mediate developmental cell specification events. To explore the function of murine Notch1, an essential portion of the gene was flanked with loxP sites and inactivation induced via interferon-regulated Cre recombinase. Mice with a neonatally induced loss of Notch1 function were transiently growth retarded and had a severe deficiency in thymocyte development. Competitive repopulation of lethally irradiated wild-type hosts with wild-type- and Notch1-deficient bone marrow revealed a cell autonomous blockage in T cell development at an early stage, before expression of T cell lineage markers. Notch1-deficient bone marrow did, however, contribute normally to all other hematopoietic lineages. These findings suggest that Notch1 plays an obligatory and selective role in T cell lineage induction.

Animals↗
PubMed1999

Radiolytic and photodynamic modifications of ion transport through the plasma membrane of OK cells: a comparison.

PURPOSE: This study seeks to compare functional modifications of the plasma membrane induced either by water radiolysis (80 kV X-rays) or by visible light in the presence of the photosensitizer photofrin II. The two methods generate different kinds of free radicals and other reactive species such as singlet oxygen. Their effect on the electrical properties of the plasma membrane is investigated. METHOD: The patch-clamp technique (whole-cell and inside-out configuration) was applied to the plasma membrane of an epithelial cell line (opossum kidney (OK) cells). RESULTS: Generation of the reactive species gave rise to a decay of the membrane potential, to an inactivation of K+-channels, and to an increase of the leak conductance of the membrane. All three effects were strongly involved in photomodification of the membrane. Following X-ray exposure (doses up to 1000 Gy) on the other hand, the decay of the membrane conductance caused by inactivation of ion channels was predominant, while the increase of the leak conductance and the depolarization were comparatively minor responses. CONCLUSION: Photomodification of the plasma membrane by visible light in the presence of the membrane-active sensitizer photofrin II is of considerably greater consequence for the electrical properties of the membrane, compared with exposure to ionizing radiation of the membrane and its aqueous environment. The differences are thought to reflect the types of reactive species produced by the two methods and their site of generation.

Animals↗
PubMed1999

[Marine toxins].

The consumption of seafood, which is contaminated by toxines of red tides, is a common cause of disease in tropic regions. The most important diseases, which are caused by red tides are Paralytic Shellfish Poisoning (PSP), Diarrhetic Shellfish Poisoning (DSP), Neurotoxic Shellfish Poisoning (NSP), Amnesic Shellfish Poisoning (ASP), Ciguatera Fish Poisoning (CFP).

Americas↗
PubMed1998

Photofrin II sensitized modifications of ion transport across the plasma membrane of an epithelial cell line: I. Electrical measurements at the whole-cell level.

Photofrin II is a photosensitizer frequently applied in photodynamic therapy. Light-induced tumor cell inactivation observed in the presence of this substance has been suggested to start with modifications at the level of cellular membranes. In the present study electrophysiological techniques are applied in order to investigate the action of photofrin II on functional properties of the plasma membrane of opossum kidney (OK) cells (as an epithelial model system) and of fibroblasts. Illumination of the cells in the presence of photofrin II (or Zn-phthalocyanine) leads to comparatively fast depolarization of the membrane potential. It is caused by a strong change of the membrane conductance which proceeds in two phases. Both phases contribute to a loss of ion selectivity of the plasma membrane between K+ and Na+. In the first phase, specific pathways for K+, which determine the resting potential under physiological conditions, are inactivated. The second phase is distinguished by a marked increase of a nonselective conductance. The increase of the latter - after light-induced initiation - continues in the dark. The conclusions are derived from light-induced, time-dependent changes of the membrane conductance and of the shape of the current-voltage relationship detected under different experimental conditions.

Animals↗
PubMed1998

Photofrin II sensitized modifications of ion transport across the plasma membrane of an epithelial cell line: II. Analysis at the level of membrane patches.

In the first part of this study, photofrin II sensitized membrane modifications of OK-cells were investigated at the level of macroscopic membrane currents. In this second part, the inside-out configuration of the patch-clamp technique is applied to analyze the phenomena at the microscopic level. It is shown that the characteristic single channel fluctuations of the electric current disappear after the start of illumination of membrane patches in the presence of photofrin II. This holds for all three types of ion channels investigated: the large-conductance Ca2+-dependent K+ channel (maxi-KCa), a K+ channel of small conductance (sK), and a stretch-activated nonselective cation channel (SA-cat). Part of the experiments show a transient activation of the channels (indicated by an increase of the probability in the open-channel state) before the channels are converted into a closed nonconductive state. Inactivation of all three channel types proceeds by a continuous reduction of their open probability, while the single channel conductance values are not affected. The process of photodynamically induced channel inactivation is followed by a pronounced increase of the leak conductance of the plasma membrane. The latter process - after light-induced initiation - is found to continue in the dark. The ionic pathways underlying the leak conductance also allow permeation of Ca2+ ions. The resulting Ca2+-flux may contribute to the photodynamically induced increase of the intracellular Ca2+ concentration observed in various cell lines.

Animals↗
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↗