Pulsatile tinnitus —a review of 84 patients

Pulsatile tinnitus can be annoying for a patient and can also be the only clue to a potentially devastating and life-threatening disease. In order to understand its clinical spectrum and management better we analysed the files of 84 patients seen at our institution over a 10-year period. Noninvasive techniques (ultrasound, computed tomography, magnetic resonance imaging) and angiography were employed as investigations tailored to the individual patient. A vascular disorder [i.e. arteriovenous fistula, dissection of the internal carotid artery (ICA), fibromuscular dysplasia, aneurysm of the ICA and sinus thrombosis] was found in 36 patients (42%), most commonly a dural arteriovenous fistula or a carotid-cavernous sinus fistula. In 26 patients with a vascular abnormality, pulsatile tinnitus was the presenting symptom. In 12 patients (14%), nonvascular disorders such as glomus tumour or intracranial hypertension with a variety of causes explained the tinnitus. We conclude that patients with pulsatile tinnitus should be investigated with noninvasive techniques. If these are negative or to clarify abnormal findings of noninvasive techniques selective angiography is needed for diagnosis and to guide treatment Received: 18 August 1997 Received in revised form: 29 October 1997 Accepted: 12 November 1997     

Influence of pulse repetition frequency and high pass filter on color Doppler maps of converging flow in vitro

Assessment of regurgitant flow by the flow convergence method is based on reading absolute velocities from color Doppler maps. Velocity overestimation by high pass filtering above 100 Hz has been reported. An extremely low filter, however, is inpracticable in patients. A ratio of pulse repetition frequency (PRF)/filter of 10/1 usually results in good quality color maps as judged visually. We studied in vitro the influence of PRF and filter on the absolute velocities within color maps of the flow convergence, keeping PRF/filter at 10/1. The color maps were also compared with computerized flow simulations. Flow across different orifice plates was scanned using two different setups for each flow condition: low velocity setup (PRF 600–2500 Hz, filter 50–300 Hz) and high (PRF 1500–6000 Hz, filter 200–600 Hz). From the color maps, velocity profile curves were read along the flow center line across the flow convergence. The high velocity setup provided artefact-free color maps at a distanced=2–4 through 8–11 mm to the orifice, the low setup atd=6–8 through 18 mm. Within the overlapping range (d=6–8 through 8–11 mm), the resulting curves showed no significant differences in local velocity, with a slight trend towards higher velocities with the high velocity setup (2.2–2.9%). The simulations agreed well with color Doppler except for slightly lower values at d>10–12 mm. Changes in PRF and filter have no significant influence on the absolute velocities displayed within color maps as long as PRF/filter is kept close to 10/1.     

Violent attacks on public figures by persons suffering from psychiatric disorders

In connection with two attempts on the lives of prominent politicians committed by mentally ill individuals during 1990 there occurred a marked increase in social distance towards the mentally ill among the German public. Even though the level of social distance subsided again during the 2 years following the attacks, it had not yet completely returned to its initial level by the end of 1992. The negative effects of these incidents on the attitude of the general public were able to be replicated on a regional level, after yet another violent attack by a mentally ill assailant in 1993, this time on the life of a famous female athlete.     

Klinik und Differentialdiagnose der cranialen Migrationshemmung des Rückenmarks

Zusammenfassung Nach einer Literatur-und pathomorphologischen Übersicht wird an Hand von 23 Fällen einer spinalen Malformation unterschiedlicher Genese das klinische Bild der cranialen Migrationshemmung herausgearbeitet. Für die Diagnose ist neben Hautveränderungen über der dorsalen Mittellinie, wie sie für den dysrhaphischen Formenkreis typisch sind, die neurologische Symptomatik der unteren Extremitäten richtungweisen. Der Beweis einer Aszensionshemmung kann nur durch die Myelographie erbracht werden. Die Bedeutung frühzeitiger operativer Maßnahmen zur Verhinderung progredienter Ausfälle wird besonders herausgestellt.

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Clinical features and differential diagnosis of the restricted cranial migration of the spinal cord

After a review of the literature on, and the pathology of spinal malformations the clinical features of a restricted ascent of the spinal cord are described with reference to 23 cases of spinal dysrhaphism of varying genesis. The suppression of cranial migration is caused either by a diastematomyelia, a lipoma, or a dermoid sinus with direct connection to the spinal cord, or else by myelomeningoceles and cicatrices after arachnitis.The symptoms occur particularly during the early years of life and in the age group of between 20 and 30.The manifestations of the disease are changes over the dorsal midline which are typical for spinal dysraphism, neurological defects of the lower limbs, and abnormalities in the function of bladder and rectum. Deformations of the feet and trophic disturbances have been encountered.Important for the diagnosis is a radiographic investigation of the spine since a restriction of the cranial migration can only be proved by myelography. Operation with view of a release of the spinal cord is the method of choice. The importance of early operative measures for the prevention of progredient deficiencies is particularly stressed.

     

Buchbesprechungen

Ohne Zusammenfassung     

Modelling cost effectiveness and cost utility of sequential DMARD therapy including leflunomide for rheumatoid arthritis in Germany: II. The contribution of leflunomide to efficiency

OBJECTIVE: To estimate the 3-year incremental cost effectiveness and cost utility of introducing leflunomide into sequential therapy, consisting of the most frequently used disease-modifying antirheumatic drugs (DMARDs), for patients with rheumatoid arthritis in specialised, i.e. rheumatological, care in Germany. DESIGN AND SETTING: The analysis was conducted from the societal perspective in Germany using an existing 3-year simulation model, which was adapted to the German healthcare system after secondary analysis of relevant publications and data. DMARD sequences including leflunomide were compared with those excluding leflunomide. Costs comprised direct costs incurred by treatment and indirect costs incurred by loss of productivity (sick leave and premature retirement) of rheumatoid arthritis patients. Effectiveness parameters were given by response years gained (RYGs) according to the American College of Rheumatology (ACR) criteria for 20%, 50% and 70% improvement (ACR20/50/70RYGs) and by QALYs gained (QALYGs). Costs, effects and QALYs were discounted by 5% per annum. In the base-case analysis, average values of costs, response years and QALYs were applied. Costs were in 1998-2001 values (euro 1 approximately equal to $US 0.91, average of the period from the year 2000 through 2001). MAIN OUTCOME MEASURES AND RESULTS: After 3 years, adding leflunomide was less costly and more effective than the strategy excluding leflunomide when total (direct and indirect) costs were considered. There were savings of euro 271,777 and 8.1, 4.3, 5.1 and 4.9 ACR20RYGs, ACR50RYGs, ACR70RYGs and QALYGs per 100 patients, respectively, obtained through adding leflunomide. Focusing on direct costs, adding leflunomide was more costly and more effective compared with excluding leflunomide, with an incremental cost effectiveness of euro 5004 per ACR20RYG, euro 9535 per ACR50RYG, euro 7996 per ACR70RYG, and an incremental cost utility of euro8301 per QALYG, after 3 years. The robustness of the results was shown in comprehensive sensitivity analyses. In the analysis of extremes, different combinations of the limits of cost, effectiveness and utility parameters were investigated. Adding leflunomide to sequential DMARD therapy remained dominant in 79% of the possible cases, i.e. was less costly and more effective than the strategy excluding leflunomide. Focusing on direct costs, adding leflunomide became dominant in 29% and remained more costly and more effective in 50% of possible cases. CONCLUSIONS: Our analysis suggests, with its underlying data and assumptions, that having leflunomide as an additional option in a DMARD treatment sequence extends the time patients benefit from DMARD therapy at reasonable additional direct costs. Adding leflunomide may even be cost saving when total (direct and indirect) costs are considered. As data on DMARD effectiveness were extracted from the results of clinical trials, real-world data from observational studies would be needed to corroborate the findings of the present analysis.     

A secondary metabolite, 4,5-dibromopyrrole-2-carboxylic acid, from marine sponges of the genus Agelas alters cellular calcium signals

A secondary metabolite from sponges of the genus Agelas, 4,5-dibromopyrrole-2-carboxylic acid, which is well known as feeding deterrent, was investigated for effects on the cellular calcium homeostasis in PC12 cells. 4,5-Dibromopyrrole-2-carboxylic acid did not change intracellular calcium levels if applied alone without cell depolarization. During depolarization of the cellular membrane using high potassium solution, a dose dependent reduction of intracellular calcium elevation was revealed utilizing Fura II as calcium indicator. Significant reduction was seen at concentrations higher than 30 μM in a series of experiments, but in single experiments a concentration of 300 nM was still reversible effective. In the same concentration range, the onset of depolarization induced calcium elevations was significantly delayed by 4,5-dibromopyrrole-2-carboxylic acid. Dose dependent reduction and delay of depolarization evoked calcium elevations are probably due to a reduction of calcium entry via voltage operated calcium channels. One cellular mode of action of the feeding deterrent potential of 4,5-dibromopyrrole-2-carboxylic acid to fishes may be an interaction with the cellular calcium homeostasis of exposed cells.     

E1-INT (Transition Therapeutics/Novo Nordisk)

Transition Therapeutics (through its acquisition of Waratah Pharmaceuticals), in collaboration with Novo Nordisk, is developing E1-INT, an injectable islet neogenesis therapy comprising an epidermal growth factor analog and a gastrin analog, for the treatment of insulin-dependent (type 1) and non-insulin-dependent (type 2) diabetes. The compound is currently undergoing phase II clinical trials.