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Biomedical subjects

E Munch

Publications and source records attributed to E Munch.

13 recordsLinked to original sources

Effect of intra-arterial papaverine on regional cerebral blood flow in hemodynamically relevant cerebral vasospasm.

BACKGROUND AND PURPOSE: It remains controversial whether the intra-arterial administration of papaverine (IAP) is effective in reversing vasospasm-associated cerebral hypoperfusion after aneurysmal subarachnoid hemorrhage. The aim of the present study was to continuously assess regional cerebral blood flow (rCBF) during and after IAP with the use of quantitative, bedside thermal diffusion flowmetry. METHODS: Eight patients with cerebral vasospasm after subarachnoid hemorrhage (mean flow velocity >120 cm/s; angiographic vessel constriction >33%; hemispheric cerebral blood flow [CBF] <32 mL/100 g per minute) were prospectively entered into the study. Before IAP, thermal diffusion microprobes were implanted into the white matter of each affected vascular territory (n=10) for rCBF monitoring. During and after IAP (300 mg papaverine/50 mL saline over 1 hour), mean arterial blood pressure, intracranial pressure, cerebral perfusion pressure, thermal diffusion rCBF (TD-rCBF), and cerebrovascular resistance (CVR) were recorded continuously. RESULTS: IAP significantly increased TD-rCBF from 7.3+/-1.6 to 37.9+/-6.6 mL/100 g per minute (mean+/-SEM), indicating reversal of cerebral hypoperfusion. This TD-rCBF response was dependent on the degree of cerebral vasospasm and reduced perfusion within the vascular territory. Long-term analysis of TD-rCBF, however, demonstrated that this beneficial effect of IAP on cerebral hypoperfusion was only transient: within 3 hours after treatment, TD-rCBF and CVR returned to baseline values. Furthermore, a lack of correlation between transcranial Doppler sonography and thermal diffusion flowmetry suggested that transcranial Doppler sonography is not suited for CBF-based neuromonitoring after IAP. CONCLUSIONS: IAP is not effective in permanently reversing cerebral hypoperfusion in patients with cerebral vasospasm. The need to validate alternative therapeutic strategies that seek to improve cerebral perfusion in vasospasm warrants continued development of CBF-based neuromonitoring strategies.

Adult↗

Comparative study of budesonide as a nebulized suspension vs pressurized metered-dose inhaler in adult asthmatics.

The study objective was to compare the effect of budesonide administered as a nebulized suspension as compared to a spray with a spacer in adult asthmatics. In a double-blind, double-dummy crossover study, 26 adult patients with moderately severe unstable asthma were randomized to three 4-week treatment periods with budesonide 0.8 mg b.i.d. administered by a pressurized metered-dose inhaler (pMDI) with spacer (Nebuhaler) and budesonide 1 mg and 4 mg b.i.d. administered by a Pari Inhalier Boy jet nebulizer. The nebulizer was activated only during inspiration. The total mass output was similar from the two devices but their fraction of small particles differed by a factor of 2 in favour of pMDI. Effect was evaluated from daily home measurements of peak expiratory flow (PEF), need of beta 2-agonist and symptom scores. Plasma cortisol and budesonide levels were measured in a subgroup of 10 patients. A consistent trend showed the nebulizer treatment to be at least as efficient as the pMDI plus spacer treatment. In actual fact, the apparent order of effect was: 4 mg nebulized suspension treatment > or = 1 mg nebulized suspension treatment > or = 0.8 mg pMDI with spacer treatment. Plasma budesonide and plasma cortisol also exhibited dose-related levels independent of device. The adverse effects reported appeared to be related to the dose rather than delivery device. Accordingly, the effect was related to total mass output, rather than to the small particle fraction of the budesonide aerosol. These results attest to the efficiency of jet-nebulized budesonide suspension, and indicate nebulized budesonide to be equipotent to standard budesonide therapy delivered by pMDI with Nebuhaler, provided nebulization is synchronized with inspiration and no loss of aerosol occurs during expiration.

Adult↗

NS 004--an activator of Ca(2+)-dependent K+ channels in cerebellar granule cells.

The large-conductance Ca(2+)-dependent K+ channels or BK channels in cerebellar granule cells were studied by patch-clamp technique, and the effects on channel activity of the molecule NS 004 (1-(2-hydroxy-5-chlorophenyl)-5-trifluoromethyl-2- benzimidazolone) were investigated. The channels had a unit conductance of 187 pS, were blocked by charybdotoxin and activated by internal Ca2+. NS 004 (10-30 microM) significantly increased the single channel opening frequency as well as the mean open time. In whole-cell recordings the compound shifted the BK current-voltage relationship by up to 40 mV towards negative membrane potentials. NS 004 is an efficient BK channel opener, which may represent a novel approach to relaxation of neuronal cells expressing this type of K+ channel.

Action Potentials↗

Selective activation of Ca(2+)-dependent K+ channels by novel benzimidazolone.

Activators and blockers of specific ion channels are important pharmacological tools for characterizing ion channels and their influence on cell function. The large-conductance Ca(2+)-dependent K+ channel (BK channel) is blocked by peptides such as charybdotoxin and iberiotoxin, but no selective activator of the channel has been described. Here we report single-channel and whole-cell patch-clamp experiments on the specific activation of BK channels in aortic smooth muscle cells with a new heterocyclic molecule, NS 1619 (1-(2'-hydroxy-5'-trifluoromethylphenyl)-5-trifluoromethyl- 2(3H)benzimidazolone). The effect of NS 1619 on the BK channel was dose-dependent, resulting in a shift of the activation curve by up to -50 mV towards negative membrane potentials. The effect was fully reversible and was antagonized by charybdotoxin as well as by tetraethylammonium ions. The compound hyperpolarized the smooth muscle cells. NS 1619 is a selective and new type of K+ channel activator, which may significantly modulate cell excitability.

Animals↗

No effect of high-dose inhaled steroids in pulmonary sarcoidosis: a double-blind, placebo-controlled study.

OBJECTIVE: To evaluate whether inhaled steroids in high doses might be of therapeutic value in pulmonary sarcoidosis. DESIGN: Randomized, double blind and placebo controlled parallel study. SETTING: The out-patient clinic of the Department of Pulmonary Medicine, Gentofte Hospital, Copenhagen, Denmark. SUBJECTS: Twenty-one untreated patients (17 males, 4 females, median age 33 years, range 21-65) and eight patients treated with systemic prednisolone. All patients had biopsy proven pulmonary sarcoidosis radiological stage I-III. INTERVENTIONS: Treatment with either inhaled budesonide 1.2 mg day-1-2.0 mg day-1 (n = 9) or placebo (n = 12) for 12 months. MAIN OUTCOME MEASURES: Clinical (cough, chest pain, dyspnoea) and paraclinical variables (chest X-ray, gallium scintigraphy, pulmonary function tests, and biochemical markers of disease activity: blood leukocytes, lymphocytes, serum (S-) angiotensin converting enzyme (ACE), S-1,25-OH-cholecalciferol, plasma (P-) calcium, P-immunoglobulins) were recorded before treatment, every three months during treatment, and 6 months after treatment had been discontinued. RESULTS: There were no significant differences between the recorded variables in the budesonide and placebo groups. In general, a regression of disease activity was observed in both groups. Two patients in the treatment group, treated with 2.0 mg budesonide/day, and two in the placebo group had progression in disease and were put on systemic steroids. CONCLUSION: Inhaled budesonide in doses of 1.2-2.0 mg day-1 had no recognizable therapeutic effect on pulmonary sarcoidosis.

Administration, Inhalation↗

Hyposensitization in hay fever with grass pollen extracts: a three-year study comparing a dialysed alum adsorbed extract with allpyral.

Immunotherapy with a dialysed aqueous extracted alum absorbed extract of grass pollens and with undialysed pyridine extracted alum precipitated extract of grass pollens (Allpyral) was compared in 58 patients with hay fever over a three year period in a randomized open study. Both types of treatment resulted in similar immunological responses as measured by changes in grass specific serum IgE and IgG. The dialysis of the grass pollen material did not decrease or increase the stimulation of specific immunoglobulins. The incidence of both local and systemic side effects was similar in both treatments. More injection site granulomata occurred in patients treated with the new alum adsorbed extract, although the difference did not achieve statistical significance. Symptom-medication data showed that patients who received the conventional pyridine extracted materials obtained a better clinical response, but all treatments gave continuing clinical benefit in each successive year.

Adolescent↗

A cumulative dose response study for the comparison of the effect of inhalation of two dose sequences of fenoterol inhalation powder.

The effect of inhalation of two dose sequences of fenoterol inhalation powder were compared in a double-blind cumulative dose response investigation. Nine patients with stable asthma participated in the study. In dose sequence I, 50 + 50 + 100 + 200 micrograms of fenoterol powder were inhaled and in dose sequence II, 200 + 50 + 50 + 50 micrograms fenoterol inhalation powder. There was no significant difference in the effect on lung function or tremor at any point following the two methods of inhalation.

Dose-Response Relationship, Drug↗

An open comparison of dosage frequencies of beclomethasone dipropionate in seasonal allergic rhinitis.

In an open group-comparative study, 123 adult patients with seasonal allergic rhinitis were allocated at random to one of three treatment groups; each of which received a daily dose of 400 micrograms beclomethasone dipropionate as (1) one puff in each nostril four times daily, (2) two puffs in each nostril twice daily and (3) four puffs in each nostril once per day. The result of treatment was assessed on daily symptom scores and the use of antihistamine tablets. There were no statistically significant differences between the three groups. The results indicate that it is unnecessary to give beclomethasone dipropionate nasal spray four times daily, and treatment in the morning and in the evening is recommended.

Adolescent↗