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Biomedical subjects

S Behrens

Publications and source records attributed to S Behrens.

At least 55 records · Page 3Linked to original sources
PubMed1999

The erg-like potassium current in rat lactotrophs.

1. The ether-à-go-go-related gene (erg)-like K+ current in rat lactotrophs from primary culture was characterized and compared with that in clonal rat pituitary cells (GH3/B6). The class III antiarrhythmic E-4031 known to block specifically erg K+ channels was used to isolate the erg-like current as the E-4031-sensitive current. The experiments were performed in 150 mM K+ external solution using the patch-clamp technique. 2. The erg-like K+ current elicited with hyperpolarizing pulses negative to -100 mV consisted of a fast and a pronounced slowly deactivating current component. The contribution of the slow component to the total current amplitude was potential dependent and varied from cell to cell. At -100 mV it ranged from 50 to 85% and at -140 mV from 21 to 45%. 3. The potential-dependent channel availability curves determined with 2 s prepulses were fitted with the sum of two Boltzmann functions. The function related to the slowly deactivating component of the erg-like current was shifted by more than 40 mV to more negative membrane potentials compared with that of the fast component. 4. In contrast to that of native lactotrophs studied under identical conditions, the erg-like K+ current of GH3/B6 cells was characterized by a predominant fast deactivating current component, with similar kinetic and steady-state properties to the fast deactivating current component of native lactotrophs. 5. Thyrotrophin-releasing hormone reduced the erg-like current in native lactotrophs via an intracellular signal cascade which seemed to involve a pathway independent from protein kinase A and protein kinase C. 6. RT-PCR studies on cytoplasm from single lactotrophs revealed the presence of mRNA of the rat homologue of the human ether-à-go-go-related gene HERG (r-erg1) as well as mRNA of the two other cloned r-erg cDNAs (r-erg2 and r-erg3) in different combinations. In GH3/B6 cells, only the transcripts of r-erg1 and r-erg2 were found.

Animals↗
PubMed1999

Long-term follow-up and outcome in patients treated for spinal dural arteriovenous fistula.

Clinical outcome was examined in 21 patients treated for spinal dural arteriovenous fistula after 5-50 months. We compared the neurological condition (motor function, pain, sensory disturbance, vegetative dysfunction) and Barthel index before and after fistula occlusion. Neurological impairment was assessed as improved, unchanged, or deteriorated. All patients initially showed paraparesis of varying degree, and a sensory loss with a defined level in 81% before treatment. The greatest postoperative change that we measured was in motor activity (67% improved), and the most important deterioration was in male potency (28% deteriorated). We observed unchanged or absent symptoms in pain in 71% of our patients. We were thus able not only to stop but even to reverse the progression of symptoms and the degree of disability. On average, neurological symptoms stabilized within 1 year. The results of this study confirm that spinal dural arteriovenous fistula should be treated as early as possible after diagnosis.

Adult↗
PubMed1999

Mycophenolate mofetil: a new therapeutic option in the treatment of blistering autoimmune diseases.

BACKGROUND: Mycophenolate mofetil (MMF), an ester of mycophenolic acid (MPA), was approved by the Food and Drug Administration in 1995 and is currently primarily indicated for the prophylaxis of rejection in renal transplant patients. The drug seems also to be of value in the treatment of psoriasis and rheumatic arthritis. Recently there have been 6 reported cases of successful treatment of blistering autoimmune diseases with MMF in combination with high dose prednisone therapy. OBJECTIVE: On the basis of these reports we administered this new treatment regimen to several patients with blistering autoimmune diseases. Besides using a combination of MMF and high-dose prednisone we wanted to evaluate whether MMF monotherapy is also effective in the treatment of blistering autoimmune diseases. METHODS: We administered MMF to 5 patients who had severe pemphigus vulgaris or bullous pemphigoid. Two patients received MMF in combination with high-dose prednisone therapy and 3 patients received MMF monotherapy. To our knowledge, this is the first report of successful treatment of pemphigus vulgaris and bullous pemphigoid with MMF monotherapy. RESULTS: All patients were completely free of symptoms within 8 to 11 weeks of therapy. Patients who had received MMF monotherapy responded as well to treatment as those who received a combination of MMF and high-dose prednisone. CONCLUSION: Our experiences strongly suggest that MMF monotherapy may be effective for patients even with severe pemphigus vulgaris and bullous pemphigoid. In addition, MMF monotherapy, at least over the short term, offers the advantage of fewer side effects in comparison to immunosuppressive combination therapy and was well tolerated by our patients.

Aged↗
PubMed1999

Phototherapy for atopic eczema with narrow-band UVB.

Management of atopic dermatitis has been less than satisfactory. Conventional therapy has not been particularly successful, and prolonged use of topical corticosteroids and systemic immunosuppressant drugs (eg, corticosteroids, cyclosporine, azathioprine) can result in severe cutaneous and systemic effects. We decided to evaluate the effect of UVB at 311 nm to treat 5 patients with moderate to severe atopic dermatitis. In each patient a mean cumulative dose of 9.2 J/cm2 was applied over a mean of 19 irradiations. Narrow-band UVB notably reduced atopic dermatitis after 3 weeks in all patients.

Adult↗
PubMed1999

Low-frequency, low-intensity ultrasound accelerates thrombolysis through the skull.

Systemic thrombolysis of acute ischemic stroke with recombinant tissue plasminogen activator (rt-PA) has been established recently. Whereas the delay to and the rate of vessel recanalization are unknown, they are likely slower and smaller than for local application of rt-PA. This may contribute to the small benefits of recovery reported and stimulate further investigations to improve clot lysis. Pilot studies indicate that continuous-wave low-frequency ultrasound (US) can accelerate rt-PA-mediated recanalization of peripheral thrombotic vessel occlusion. For the hypothesized therapeutical purpose in stroke treatment, we measured the attenuation of ultrasound through the skull at different frequencies and intensities (33.3 and 71.4 kHz; 0.5 and 3.4 W/cm2), and investigated thrombolysis in vitro (n = 125 clots). Attenuation was lowest by transtemporal insonation of 33.3 kHz, 0.1 dB (0.9). Thrombolysis (artificial fibrin-rich clots) was significantly increased after 1 h (p < 0.025) and after 3 h (p < 0.01) for US treatment in combination with rt-PA vs. rt-PA alone. Results suggest that US increases rt-PA-mediated thrombolysis through the skull and may improve benefits of thrombolytic stroke treatment in vivo.

Brain Ischemia↗
PubMed1999

Risk stratification following myocardial infarction in the thrombolytic era: a two-step strategy using noninvasive and invasive methods.

OBJECTIVES: We prospectively performed a two-step risk assessment in patients in the early phase after acute myocardial infarction (MI). BACKGROUND: Noninvasive methods like Holter electrocardiographic monitoring (HM) and determination of the left ventricular ejection fraction (EF) as well as the invasive technique of programmed ventricular stimulation (PVS) have been used to identify patients in the late phase after MI as candidates for prophylactic implantation of a cardioverter/defibrillator. However, it is unclear whether these results can be transferred to patients following acute MI. METHODS: A series of 657 patients with acute MI (< or = 75 years) underwent HM and EF. If one of the two methods yielded abnormal findings (HM > or = 20 ventricular ectopic beats/h/> or =10 ventricular pairs/day/ventricular tachycardia; EF < or = 40%), PVS was done (abnormal PVS: induction of monomorphic ventricular tachycardia, duration >10 s, cycle length > or = 230 ms). RESULTS: Of 657 patients, 304 (46%) had either an abnormal HM or EF. The PVS performed in 146 of 304 patients was abnormal in 22. During a mean follow-up of 37 months, there were 106 (16%) deaths, being sudden in 24 (3.6%), nonsudden cardiac in 45 (6.8%). The incidence of arrhythmic events (sudden cardiac death, symptomatic ventricular tachycardia, cardiac arrest) was 18% (4/22) with an abnormal PVS and only 4% (5/124) with a normal PVS (odds ratio 4.0, p=0.032). CONCLUSIONS: The rate of arrhythmic events is low in post-MI patients in the 1990s. Nevertheless, a two-step risk stratification is helpful in selecting candidates for a defibrillator trial aiming at primary prevention of sudden cardiac death after MI.

Combined Modality Therapy↗
PubMed1999

Structure of the phylogenetically most conserved domain of SRP RNA.

The signal recognition particle (SRP) is a phylogenetically conserved ribonucleoprotein required for cotranslational targeting of proteins to the membrane of the endoplasmic reticulum of the bacterial plasma membrane. Domain IV of SRP RNA consists of a short stem-loop structure with two internal loops that contain the most conserved nucleotides of the molecule. All known essential interactions of SRP occur in that moiety containing domain IV. The solution structure of a 43-nt RNA comprising the complete Escherichia coli domain IV was determined by multidimensional NMR and restrained molecular dynamics refinement. Our data confirm the previously determined rigid structure of a smaller subfragment containing the most conserved, symmetric internal loop A (Schmitz et al., Nat Struct Biol, 1999, 6:634-638), where all conserved nucleotides are involved in nucleotide-specific structural interactions. Asymmetric internal loop B provides a hinge in the RNA molecule; it is partially flexible, yet also uniquely structured. The longer strand of internal loop B extends the major groove by creating a ledge-like arrangement; for loop B however, there is no obvious structural role for the conserved nucleotides. The structure of domain IV suggests that loop A is the initial site for the RNA/protein interaction creating specificity, whereas loop B provides a secondary interaction site.

Base Sequence↗
PubMed1999

PUVA-bath photochemotherapy (PUVA-soak therapy) of recalcitrant dermatoses of the palms and soles.

PUVA-bath therapy has proven to avoid many side effects associated with oral 8-methoxypsoralen (8-MOP) treatment. In order to investigate the effectiveness of topical PUVA-bath therapy (PUVA-soak therapy) on chronic palmoplantar dermatoses, 30 patients with plaque-type psoriasis, pustular psoriasis, endogenous eczema, dyshidrotic eczema and hyperkeratotic dermatitis of the palms and soles were treated over 8 weeks with PUVA-soak using 8-MOP. No additional treatment except skin moisturising cream such as unguentum emulsificans aquosum was used during the study period. The single UVA-doses applied ranged from 0.3 to 3.0 J/cm2 (mean single dose of 1.8 J/cm2), with a mean cumulative dose of 48.6 J/cm2 per patient. Altogether 26 of 30 patients responded well within 8 weeks of treatment with 63% of all patients showing a complete remission and 23% showing considerable improvement, as shown by flattening of plaques, decreased scaling and erythema, as well as decreased vesicle and pustule formation. The condition responding best to our therapy was palmoplantar psoriasis followed by atopic eczema. Hyperkeratotic dermatitis displayed the poorest responding rates in this study. Unwanted side effects such as erythema, pain, blistering or patchy hyperpigmentation were not observed in any of the patients. We conclude that PUVA-soak therapy can be highly efficient in the treatment of palmoplantar dermatoses, especially in the management of palmoplantar psoriasis.

Administration, Cutaneous↗
PubMed1999

Treatment of severe recalcitrant dermatoses of the palms and soles with PUVA-bath versus PUVA-cream therapy.

PUVA-bath therapy developed into a first line topical PUVA therapy, and gel and cream preparations have been described as alternative modes of topical 8-MOP application. Because bath-PUVA can be difficult to manage, topical PUVA therapy using 8-MOP gel or cream preparations may become an important alternative when treating localised skin diseases. However, controlled comparisons of efficacy with this alternative topical PUVA therapy are lacking. We therefore compared the efficacy of PUVA-cream therapy with PUVA-bath therapy in 12 patients with recalcitrant dermatoses of the palms and soles using a left/right trial design. These patients responded well to both treatment modalities, meaning that both could be used successfully to treat recalcitrant dermatoses of the palms and soles.

Administration, Cutaneous↗
PubMed1999

Establishment and characterization of cytopathogenic and noncytopathogenic pestivirus replicons.

Defective interfering particles (DIs) of bovine viral diarrhea virus (BVDV) have been identified and shown to be cytopathogenic (cp) in the presence of noncytopathogenic (noncp) helper virus. Moreover, a subgenomic (sg) RNA corresponding in its genome structure to one of those BVDV DIs (DI9) was replication competent in the absence of helper virus. We report here that an sg BVDV replicon which encodes from the viral proteins only the first three amino acids of the autoprotease N(pro) in addition to nonstructural (NS) proteins NS3 to NS5B replicates autonomously and also induces lysis of its host cells. This demonstrates that the presence of a helper virus is not required for the lysis of the host cell. On the basis of two infectious BVDV cDNA clones, namely, BVDV CP7 (cp) and CP7ins- (noncp), bicistronic replicons expressing proteins NS2-3 to NS5B were established. These replicons express, in addition to the viral proteins, the reporter gene encoding beta-glucuronidase; the release of this enzyme from transfected culture cells was used to monitor cell lysis. Applying these tools, we were able to show that the replicon derived from CP7ins- does not induce cell lysis. Accordingly, neither N(pro) nor any of the structural proteins are necessary to maintain the noncp phenotype. Furthermore, these sg RNAs represent the first pair of cp and noncp replicons which mimic complete BVDV CP7 and CP7ins- with respect to cytopathogenicity. These replicons will facilitate future studies aimed at the determination of the molecular basis for the cytopathogenicity of BVDV.

Animals↗
PubMed1998

[Bleomycin-induced PSS-like pseudoscleroderma. Case report and review of the literature].

Although the association between administration of the antitumor agent bleomycin and the development of cutaneous fibrosis is established, there are only a small number of cases of bleomycin-induced scleroderma described in the literature. We report the development of generalised scleroderma with wide spread hyperpigmentation in a 52-year-old male patient, who received a total dose of 360 mg bleomycin in combination with cisplatin and etoposid for therapy of a malignant testicular seminoma. The clinical cutaneous alterations as well as the histological findings were indistinguishable from those encountered in progressive systemic sclerosis (PSS). In contrast to PSS however, Raynaud's phenomenon, cutaneous calcinosis, teleangiectasia, arthritis and involvement of additional organs were all absent. PSS-typical auto-antibodies were negative. Even 18 months after discontinuation of the drug and treatment with UVA1 phototherapy (3-4 times per week with 20 J/cm2) as well as physiotherapy, the skin changes had still not resolved. Based on our case and a detailed review of the literature, we discuss characteristics of bleomycin-induced scleroderma including pathogenesis, treatment modalities and course.

Antibiotics, Antineoplastic↗