Botulinum-A toxin for treating detrusor hyperreflexia in spinal cord injured patients: a new alternative to anticholinergic drugs? Preliminary results.

PURPOSE: We evaluated the efficacy of botulinum-A toxin injections into the detrusor muscle in patients with spinal cord injury, detrusor hyperreflexia and urge incontinence resistant to anticholinergic drugs. The purpose of treatment was to suppress incontinence episodes and increase functional bladder capacity. MATERIALS AND METHODS: Included in our prospective nonrandomized study done at 2 clinics were 31 patients with traumatic spinal cord injury who emptied the bladder by intermittent self-catheterization. These patients had severe detrusor hyperreflexia and incontinence despite a high dose of anticholinergic medication. Pretreatment evaluation included a clinical examination and complete urodynamic investigation. Under cystoscopic control a total of 200 to 300 units of botulinum-A toxin were injected into the detrusor muscle at 20 to 30 sites (10 units per ml. per site), sparing the trigone. Clinical and urodynamic followup was planned for 6, 16 and 36 weeks after treatment. Patients were asked to decrease their intake of anticholinergic drugs during week 1 after treatment. RESULTS: Of the 21 patients 19 underwent a complete examination 6 weeks after the botulinum-A toxin injections, and 11 at 16 and 36 weeks. At the 6-week followup complete continence was restored in 17 of 19 cases in which anticholinergic medication was markedly decreased or withdrawn. Less satisfactory results in 2 cases were associated with an insufficient dose of 200 units botulinum-A toxin. After the injections overall mean reflex volume and mean maximum cystometric bladder capacity plus or minus standard deviation significantly increased from 215.8 +/- 90.4 ml. to 415.7 +/- 211.1 (p <0.016) and 296.3 +/- 145.2 to 480.5 +/- 134.1 (p <0.016), respectively. There was also a significant decrease after treatment in mean maximum detrusor voiding pressure from 65.6 +/- 29.2 cm. water to 35 +/- 32. 1 (p <0.016). Mean post-void residual urine volume catheterized at the end of the urodynamic examination increased significantly from a mean of 261.8 +/- 241.3 ml. to 490.5 +/- 204.8 (p <0.016). Moreover, autonomic dysreflexia associated with bladder emptying that manifested as a hypertensive crisis during voiding disappeared after treatment in the 3 patients with tetraplegia. Satisfaction was high in all successfully treated patients and no side effects were observed. Ongoing improvement in urodynamic parameters and incontinence was already present in all patients reevaluated at 16 and 36 weeks. CONCLUSIONS: Botulinum-A toxin injections into the detrusor seem to be a safe and valuable therapeutic option in spinal cord injured patients with incontinence resistant to anticholinergic medication who perform clean intermittent self-catheterization. Successfully treated patients become continent again and may withdraw from or markedly decrease anticholinergic drug intake. A dose of 300 units botulinum-A toxin seems to be needed to counteract an overactive detrusor. The duration of bladder paresis induced by the toxin is at least 9 months, when repeat injections are required.

[Secondary prevention following coronary intervention. Survey of 13 intervention centers in Austria]. / Sekundärprävention nach Koronarintervention. Vorgangsweise an 13 Interventionellen Zentren in Osterreich.

Risk factor control has been shown to reduce the incidence of coronary events in patients with or without preceding infarction. Secondary prevention should therefore be borne in mind by every cardiologist. In order to test this concept and/or to promote secondary prevention in our country, the following survey was conducted by our working group for epidemiology and prevention. All interventional centres of the country (7 million inhabitants) were asked to report relevant data of 50 consecutive patients with PTCA in a structured questionnaire. Thirteen centres responded and we report the data of 650 patients. The mean proportion of women was 28%, the mean age 61.1 years and the mean stent rate 49.8%. The indications for PTCA varied widely: stable angina 10-74%, unstable angina 10-86%, primary PTCA 0-22%. The risk factor history was distributed as follows: diabetes 12-46% (mean 22.3%), hypertension 32-68% (mean 54.2%), current smoking 6-56% (mean 21.9%), and total cholesterol (TChol) > 200 mg/dl: 30-78% (mean 60.3%). Current lipid values were available for T chol. in 44-100% (mean 84.5%) and for LDL in 4-100% (mean 67.1%). Dietary counselling by a dietician was done in 4-100% of patients (mean 35.6%) Information concerning the hazards of smoking was given to 25-100% (mean 83.6%) of current smokers. Drug treatment at hospital discharge was as follows: 84-100% (mean 93.1%) received ASA, 24-74% (mean 49.8%) ticlopidine, 6-84% (mean 53.3%) nitrates, 34-82% (mean 60.2%) beta blockers, 10-70% (mean 39.5%) ACE inhibitors, 4-74% (mean 4 7.2%) lipid lowering drugs, 7-48% (mean 17.8%) calcium antagonists, 0-12% (mean 6.1%) digitalis and 0-28% (mean 13.6%) diuretics. Follow-up data were collected in 4 centres at 6 months post discharge and were available for 174 patients. Here we found an increase in the prescription of calcium antagonists, digitalis and statins. The following conclusions were drawn at a conference in which all centres participated: lipid values should be available for each patient at PTCA, dietary counselling should be initiated for every patient during hospitalisation (and continued by the family physician) and the national cardiac society should promote guidelines for the use of drugs in which the variation in use is too wide at present. It should be ensured that these guidelines are implemented not only in patients after AMI but also in those after PTCA.

Percutaneous transluminal therapy of occluded saphenous vein grafts: can the challenge be met with ultrasound thrombolysis?

BACKGROUND: Percutaneous transluminal treatment of a thrombotic vein graft yields poor results. We have previously reported our experience with transluminal percutaneous coronary ultrasound thrombolysis (CUT) in the setting of acute myocardial infarction (AMI). This report describes the first experience with ultrasound thrombolysis in thrombus-rich lesions in saphenous vein grafts (SVGs), most of which were occluded. METHODS AND RESULTS: The patients (n=20) were mostly male (85%), aged 64+/-4 years old. The presenting symptom was AMI in 2 patients (10%) and unstable angina in the rest. Fifteen patients (75%) had totally occluded SVGs. The median age of clots was 6 days (range, 0 to 100 days). The ultrasound thrombolysis device has a 1.6-mm-long tip and fits into a 7F guiding catheter over a 0.014-in guidewire in a "rapid-exchange" system. CUT (41 kHz, 18 W,

Ultrasound thrombolysis.

The possibility of lysing clots by the direct intravascular application of ultrasound was described first in 1974 in an animal experiment. However research on therapeutic ultrasound for thrombolysis gained momentum in the early 1980s and is now divided into several directions: 1) pharmacological thrombolysis supported by externally applied ultrasound; 2) pharmacological thrombolysis accelerated by intravascular ultrasound; 3) lysis of intravascular clots by intravascular ultrasound applied as singular treatment; 4) facilitating angioplasty by intravascular ultrasound which may smoothen the rigid surface of calcified arteries by lysing calcified structures out of sclerotic plaques. In acute myocardial infarction first evidence of efficacy in lysing clots by ultrasound was described in two small series of 15 patients in 1997. Furthermore, ultrasound thrombolysis seems to be efficient also in occluded saphenous vein grafts and in completely obstructed peripheral arteries, where the latest clinical experience gives very promising results.

Application of pulsed-Doppler tissue imaging in patients with dual chamber pacing: the importance of conduction time and AV delay on regional left ventricular wall dynamics.

UNLABELLED: Pulsed-Doppler tissue imaging (pDTI) is able to measure myocardial wall velocities (systolic: S; early diastolic: E; late diastolic: A) and their timings. Relationships have been demonstrated between the pre-ejection period and indexes of left ventricular systolic function. This study was designed to examine with pDTI the effects of variations in atrioventricular delay (AVD) (100 ms, 150 ms, 200 ms) on myocardial dynamics and on their timings at the basal interventricular septum (IVS) from an apical approach and at the posterior wall (PW) from the parasternal view. These data were compared with stroke volume measurements recorded from the left ventricular outflow tract. Seventeen patients with dual chamber pacemakers (7 because of complete heart block, 10 with sick sinus syndrome and first-degree AV block) were studied; full atrial and ventricular capture was present at any AVD. These data were also compared with those obtained in 10 age-matched healthy volunteers with comparable heart rates. RESULTS: Optimal atrial contribution to left ventricular filling and, consequently, best systolic performance were achieved when AVD was programmed such that a mean interval of 77 ms was allowed between the end of the A wave and the beginning of the S wave, similar to what was measured in the healthy control group by pDTI. CONCLUSION: The noninvasive measurement of timings of the cardiac cycle by pDTI is helpful to determine the optimal AVD in individual patients.

Prediction of survival after out-of-hospital cardiac arrest: results of a community-based study in Vienna.

The objective of this study was the assessment of out-of-hospital cardiac arrest and the definition of possible predictive factors for final hospital discharge. Out of a database of 89,557 consecutive missions of the Vienna emergency medical system (EMS) during 1990, there were 623 missions due to a collapse of non-traumatic origin: in 374 cases (60.0%) the patients were declared dead without further attempts at resuscitation. The remaining 249 patients were analysed for predictive factors at site. Survival to hospital admission: 109 patients survived to hospital admission (43.7%); bystander support had a small impact (P < 0.05) on survival to hospital arrival whereas age and gender had no predictive power. Most patients with ventricular tachycardia/fibrillation (VT/VF) survived primarily (69 of 117, i.e. 59.0%). Survival to hospital discharge: 27 patients were discharged from hospital care (10.8%). ECG findings on arrival of the EMS physician at the site proved to be the only powerful predictor for survival: 24 of 117 patients with VT/VF survived compared with only one of 81 with primary asystole, two of 39 with severe bradycardia, and no patient with electromechanical dissociation.

[Psychosomatic determinants of restenosis after percutaneous transluminal coronary angioplasty]. / Psychosomatische Einflussgrössen auf die Restenosierung nach Percutaner Transluminaler Koronarangioplastie (PTCA).

Coronary Angioplasty (PTCA) has become one of the standard procedures in the therapy of coronary heart disease. One of the main issues is the 20-40% incidence of restenosis of the dilated vessel. Up to now, the subject of predictors of restenosis has not yet been sufficiently clarified. Our study is concerned with two questions; first, is it possible to prove any connections between the amount of restenosis and psychosocial factors? Second, is it possible to distinguish groups of patients with and without subsequent restenosis on the basis of psychosocial variables, even before the diagnostic coronary angiography? 138 (91m, 47f) patients were assessed before the diagnostic coronarangiography, the 25 PTCA-patients (20m, 5f) were furthermore reassessed three months after the PTCA (the time of the angiographic control). Somatic and social data were collected and a semistandardised interview was conducted. In addition, coping, stress-coping control over disease and health and life-contentment were determined. Highly significant correlations was found between the amount of restenosis and resignative stress-coping, self-pity, depressive coping and flight-tendency. With the help of stress-coping-subtests (which were given at the first examination) it was possible to separate the group of patients with restenosis from the group without it.

APP RNA splicing is not affected by differentiation of neurons and glia in culture.

Amyloid precursor protein (APP) gene expression was investigated in primary cultures of neurons, astrocytes, microglial cells and oligodendrocytes. Neurons from various rat brain regions, as well as oligodendrocytes, contained RNA encoding APP695, while astrocytes and microglial cells expressed high levels of RNAs for APP770 and APP751. It was studied whether the cell type-specific regulation of APP gene expression could be modified by induction of cellular differentiation in vitro. While neuronal differentiation of PC12 cells has been shown to correspond with an altered pattern of APP splicing, in the primary cultures neither the time in culture nor a treatment of the cells with appropriate differentiation factors affected this pattern.

Cortical astrocytes activated by basic fibroblast growth factor secrete molecules that stimulate differentiation of mesencephalic dopaminergic neurons.

In reactive gliosis, astrocytes undergo morphological and biochemical changes which can be mimicked in vitro by treatment with bFGF (basic fibroblast growth factor) or cAMP. To investigate the influence of activated cortical astrocytes on central nervous system (CNSD) neurons, we studied the effect of the supernatant from bFGF-treated astrocytes on the development of dopaminergic neurons from rat mesencephalon. Conditioned medium of untreated astrocytes stimulated dopamine uptake of mesencephalic cultures. After activation of astrocytes with bFGF this effect was greatly enhanced. It was significantly more potent than stimulating effects of other neurotrophic factors. The supernatant of these astrocytes increased the biochemical differentiation but not the survival of dopaminergic neurons in our cell culture system. Trypsin digestion and gel chromatography revealed that the activity was due to one or several proteins with molecular mass above 5 kDa. We excluded the participation of several factors known to be produced by astrocytes or that are neurotrophic for substantia nigra cultures. In particular, we provide evidence that bFGF, BDNF, NT-3, Il-1, Il-6, S100 beta and alpha 2-macroglobulin were not involved in the effect of the conditioned medium. In vitro stimulation of astrocytes therefore triggers the expression of currently uncharacterized factors which influence the biochemical differentiation of mesencephalic dopaminergic neurons, the cells that degenerate in Parkinson's disease.

Efficacy, safety and tolerability of lovastatin and bezafibrate retard in patients with hypercholesterolemia.

Hyperlipidemia has turned out to be the most important risk factor for coronary heart disease and necessitates frequently lipid lowering long-term treatment. Therefore, efficacy and tolerability of hypolipemic drugs are of great interest. The objective of the present study was to compare the safety, tolerability and effect on plasma lipids of Lovastatin and Bezafibrate retard in patients with hypercholesterolemia. 99 patients with total cholesterol of > or = 250 mg/dl after a 4 week standard lipid-lowering diet were treated another 4 weeks with placebo and then randomized to 400 mg Bezafibrate retard or 20 to 80 mg Lovastatin given once a day for 12 weeks. Mean changes from baseline in total cholesterol, LDL cholesterol and triglycerides were significantly reduced, in HDL cholesterol increased in both treatment-groups (p < or = 0.01). The effects of Lovastatin on total cholesterol and LDL cholesterol were more pronounced than those of Bezafibrate retard (p < or = 0.01), while Bezafibrate had a larger effect on triglycerides (p < or = 0.05). The frequency of clinical adverse experiences was low and similar among treatment groups, the frequency of laboratory adverse experiences was higher in the Lovastatin group. One patient in the Bezafibrate group was withdrawn because of nausea, one patient in the Lovastatin group because of GGT elevation.

Comparison of a noncardioselective beta-adrenoceptor blocker and a cardioselective blocker in reducing aqueous flow in humans.

In a double-masked crossover study, the dose-response relationship for aqueous flow was determined for four concentrations of betaxolol hydrochloride and levobunolol hydrochloride in 19 normal subjects. One eye of each subject received every concentration of both drugs. Each concentration was administered once daily for 1 week. The fellow eye received a placebo. Aqueous flow was measured for several hours on the last day of administration of each concentration beginning immediately after drug administration. For levobunolol, the mean decrease in aqueous flow compared with baseline was 8% after 1 week's treatment with 0.017% levobunolol, 15% after treatment with 0.05%, 20% after treatment with 0.167%, and 32% after treatment with 0.5%. For betaxolol, the mean decrease in aqueous flow compared with baseline was 3% after 1 week's treatment with 0.017% betaxolol, 12% after treatment with 0.05%, 18% after treatment with 0.167%, and 17% after treatment with 0.5%. Levobunolol-treated eyes but not betaxolol-treated eyes showed a significant drug effect 1 week after discontinuing the drug therapy. The relative potency of the noncardioselective drug was greater than that of the beta 1-cardioselective drug, but the difference in potency was much less than would be expected solely based on their relative affinity for beta 2-receptors in other species and tissues.

Acute occlusion in multiple lesion coronary angioplasty: frequency and management.

Among 3,548 patients undergoing a percutaneous transluminal coronary angioplasty procedure, 714 had multilesion angioplasty (1,550 lesions) in a single session. Acute occlusion occurred in 22 patients (3.1%) and 29 lesions (1.9%). The patients were classified into a group undergoing multivessel angioplasty (348 patients, 785 lesions) and a group undergoing multilesion single vessel angioplasty (366 patients, 765 lesions). The rate of acute occlusion was similar in both patient groups. The multivessel angioplasty group had a 2.9% rate per patient (n = 10) and a 1.7% rate per vessel; the multilesion single vessel group had a 3.3% rate per patient (n = 12) and a 2.1% rate per lesion. Five of the 10 patients from the multivessel group with acute occlusion, but only 1 of the 12 patients with occlusion in the single vessel multilesion group, required emergency open heart surgery. No patient in either group died as a consequence of coronary angioplasty. Occlusion occurred during angioplasty in 15 of the 22 patients, and 1 to 24 h after angioplasty in 7 of 22 patients. In the group with multivessel angioplasty, acute occlusion during the procedure was mainly linked with hypotension during the second vessel dilation, whereas in this group with delayed vessel closure and in the multilesion single vessel group, existence of intimal tearing constituted the most important factor for acute occlusion (12 of 16 patients). Closure of vessel per major coronary system was evenly distributed in the multivessel group, whereas significantly more left circumflex vessels closed in the single vessel multilesion group (6.1% versus 1.3% in the left anterior descending coronary artery and 1.1% in the right coronary artery; p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Pertussis toxin inhibits angiotensin II-mediated phosphatidylinositol breakdown and ADP-ribosylates a 40 Kd protein in cultured smooth muscle cells.

Angiotensin II causes an increase of inositol phosphate production in cultured vascular smooth muscle cells from rat aorta. Pretreatment of the cells with pertussis toxin attenuates this effect. Pertussis toxin ADP-ribosylates a protein of about 40 kD in a crude membrane fraction. These data demonstrate the possible involvement of a GTP-binding protein (G-protein) in the angiotensin II-induced activation of phosphoinositidase in vascular smooth muscle cells.

Measurement of aqueous flow in rabbits with corneal and vitreous depots of fluorescent dye.

Using pigmented rabbits, two fluorophotometric methods for measuring aqueous flow were compared. A corneal depot of dye was used to measure aqueous flow in one eye of each rabbit while the vitreous depot method of Johnson and Maurice was used to measure aqueous flow over the same period in the fellow eye. After intravenous administration of acetazolamide or mannitol, during the first hour after drug delivery a decrease in aqueous flow was observed in the eye with the corneal depot of dye that was undetected in the eye with the vitreous depot of dye. In rabbits which were water-loaded by orogastric tube, an increase in aqueous flow was observed by the corneal depot method, while the vitreous depot method indicated a decrease in aqueous flow. The vitreous depot method depends on the assumption that the rate of loss of dye from the vitreous remains stable. It is shown that movement of water into or out of the vitreous can cause large changes in the rate of movement of dye from the vitreous to the anterior chamber and can make interpretation of the vitreous method ambiguous. While the vitreous depot method is probably superior for measuring sustained changes of the rate of aqueous flow over tens of hours or days, it is concluded that it cannot be used for measuring changes over shorter periods.

Pharmacokinetics of an extended-release dosage form of molsidomine in patients with coronary heart disease.

Molsidomine (N-carboxy-3-morpholino-sydnonimine-ethylester; Cassella-Riedel Pharma GmbH, Frankfurt/M. FRG) has an antianginal effect for up to 3-5 h after oral administration of 2 mg Corvaton [1]. Plasma levels of the parent drug can be measured during this interval. A new galenic formulation (Corvaton retard) has been developed to prolong the duration of the therapeutic action and to improve patient compliance. The present study was carried out to establish whether the in vitro dissolution profile of the tablet was reflected in vivo, thus permitting prediction of plasma molsidomine levels in patients with coronary heart disease.

Stress testing in persons above the age of 65 years: applicability and diagnostic value of a standardized maximal symptom-limited testing protocol.

A standardized symptom-limited stress test on a bicycle ergometer in semisupine position is examined in regard to its applicability in patients over the age of 65. The test protocol allows for exercise at full capacity in the elderly. Its value for diagnosis of coronary heart disease is equivalent with its value in the younger patients' group. In 167 patients above 65 years, there occurred only one case of pulmonary rales with exercise, no other complication could be observed (0.568%). Standardized, symptom-limited stress testing appears to be a simple, highly diagnostic and safe method for testing exercise capacity or diagnosing coronary heart disease in the elderly as in younger persons.

[Complications of the use of microcatheters using Grandjean's technic in ergometry]. / Komplikationen beim Gebrauch von Einschwemmkathetern nach Grandjean während der Ergometrie.

The method of microcatheterism was described in the now usual form first by Grandjean in 1967. It offers an appropriate information about pressures in the pulmonary circulation at rest and during stress. This report gives a comprehensive survey about the complications with this method in a time range of seven years, from 1976 until 1982, in 4901 patients. The total rate of complications was very low (0.67%). Compared with a study about complications with Swan-Ganz-catheters in similar patients from Roskamm and co-workers, we found in our investigation a lower rate of dangerous arrhythmias. We conclude that microcatheterism is a simple, and cheap method, which is poor of risks. It is suitable ideally either for screening and control investigations or for the quantification of a cardiopulmonary disease.