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Biomedical subjects

R Neuhaus

Publications and source records attributed to R Neuhaus.

At least 109 records · Page 6Linked to original sources

[Randomized, double-blind comparison of isosorbide-5-mononitrate and delayed-action nifedipine in patients with stable exertional angina. Multicenter Study Group].

The therapeutic effects of IS-5-MN and s.r. nifedipine were investigated in this double-blind, randomized, group-comparative, multicenter study over 2 weeks, in 251 patients with stable reproducible exercise-induced angina. After 2 weeks' treatment with IS-5-MN 20 mg b.i.d. or t.i.d., 61% of the patients were responders who showed an increase in total exercise time (to moderately severe angina) of greater than or equal to 20% in comparison with placebo in the run-in phase. The corresponding responder rate after s.r. nifedipine 20 mg b.i.d. or 40 mg b.i.d. was 53%. Both IS-5-MN and s.r. nifedipine significantly increased the total exercise time, the time to angina onset and to greater than or equal to 1 mm ST-depression, and significantly reduced the rate pressure product and the ST-segment depression at peak exercise in comparison with placebo in the run-in phase. The improvement in quality of life as indicated by the reduction in anginal episodes and intake of short-acting nitrates was comparable with both drugs. The pattern and incidence of all AEs were as expected in the two active treatment groups. The daily treatment costs for a 20 mg b.i.d. dosing regimen for both drugs in the Federal Republic of Germany was 64% higher for s.r. nifedipine than with IS-5-MN.

Angina Pectoris↗

Follow-up of recurrent hepatitis B and delta infection in liver allograft recipients after treatment with recombinant interferon-alpha.

Reinfection of the graft with hepatitis B virus (HBV) and hepatitis delta virus (HDV) is a potential complication in patients undergoing orthotopic liver transplantation (OLT). Therefore, we added recombinant interferon-alpha (rIFNa) to the standard immunosuppressive regimen in 11 patients who received transplants following liver failure attributed to cirrhosis B (n = 10, with HDV co-infection in four cases) or fulminant hepatitis B (n = 1). Patients were treated with rIFNa for periods ranging from 2 to 3 months between the first and the 13th month after OLT. All patients received immunosuppressive treatment with low-dose corticosteroids, azathioprine and cyclosporine. Anti-HBs hyperimmune globulin was also administered. None of the patients showed evidence of severe allograft rejection. Seven patients suffered HBV reinfection of the graft with histological signs of acute hepatitis in five cases and transition to chronic hepatitis in one patient. Treatment with rIFNa did not prevent or reduce HBV replication. Reinfection of the graft with HDV was demonstrated by PCR in four patients co-infected with HDV. During treatment with rIFNa liver biopsy specimens from three reinfected patients were transiently negative for HDV antigen but not for HDV RNA, and the sera from two patients were transiently negative for HDV RNA. The data indicate that rIFNa can reduce HDV replication in reinfected liver allografts.

Adrenal Cortex Hormones↗

Regulation of bradykinin- and ATP-activated Ca(2+)-permeable channels in rat pheochromocytoma (PC12) cells.

Membrane currents activated by bradykinin (500 nM) and by extracellular ATP (50 microM) were studied in voltage-clamped, NGF-treated rat pheochromocytoma (PC12) cells. Under quasiphysiological ionic conditions, both substances caused an outward current due to opening of Ca(2+)-activated K+ channels. Bradykinin caused an additional inward current that could be studied after blockade by internal Cs+ of the initial transient outward current. The inward current became larger when the extracellular Ca2+ concentration was increased. Neither inositol-1,4,5-trisphosphate, dioctanoylglycerol, phorbol 12-myristat 13-acetate, forskolin, GTP, GTP-gamma-S, or pretreatment with pertussis toxin affected this current component. Increasing the internal Ca buffer concentration [EGTA or bis-(o-aminophenoxy)-ethane-N,N,N',N'-tetra-acetic acid] from 1 to 10 mM had no effect on the inward current as long as the free [Ca2+]i was kept constant. However, it was modulated by the resting free [Ca2+]i. Elevation of [Ca2+]i from nominally 0 to 60 or to 180 nM increased the bradykinin-induced average peak current density from 0.14 to 1.04 or to 2.29 pA/pF, respectively. This regulation may depend on a calmodulin-dependent pathway, since CGS 9343B, a calmodulin inhibitor, blocked the effect of elevated [Ca2+]i. With ATP as an agonist, outward current was preceded by a large inward current that was partially blocked by extracellular Ca2+ in the millimolar range. Extracellular Ca2+ was also found to reduce the single-channel conductance estimated from outside-out patches treated with ATP.

Adenosine Triphosphate↗

Changes in the conductance of the neuronal nicotinic acetylcholine receptor channel induced by magnesium.

We have investigated the effect of magnesium on the single-channel conductance of neuronal nicotinic acetylcholine receptors (nAChRs) in nerve growth-factor treated rat pheochromocytoma (PC12) cells. The patch-clamp technique was used to record single-channel currents from cell attached and excised, outside-out patches in the presence of various internal and external Mg2+ concentrations. Mg2+ reduced the single-channel conductance in a concentration-dependent manner with an IC50 of 9.2 mM for external Mg2+ (inward conductance) and 0.69 mM for external Mg2+ (outward conductance). Both estimated and measured conductances for divalent cation-free CsCl solutions were around 60 pS. We also find that divalent cations are not involved in the inward rectification of whole-cell ACh-induced currents in these cells. Our results imply that the amino acids screened by divalent cations sense electric fields only weakly and are presumably outside the lipid bilayer. They also suggest that the density and the number of charges (or both) differ on either side of the ion pore.

Acetylcholine↗

The effects of dihydropyridine derivatives on force and Ca2+ current in frog skeletal muscle fibres.

1. The effects of dihydropyridine (DHP) derivatives on current through the slow Ca2+ channel and on isometric force were investigated in short toe muscle fibres of the frog (Rana temporaria). The experiments were performed under voltage-clamp conditions with two flexible internal microelectrodes. 2. The non-chiral DHP derivative nifedipine was used mainly because it allowed control measurements after the inactivation of the drug with UV light. 3. In a TEA sulphate solution containing 4 mM-free Ca2+, nifedipine (1 microM) caused no relevant alterations in the time course of successive contractures induced by depolarizing steps to 0 mV of 3.5 min duration followed by a restoration time at -90 mV of 1.5 min. 4. When external Ca2+ was replaced by Mg2+, nifedipine caused a dose-dependent shortening of contractures. The effect reached saturation at about 50% of shortening with 1-5 microM-nifedipine. In the absence of divalent cations and with Na+ being the only metallic cation in the solution, shortening became more pronounced and maximum force decreased. 5. The application of 2 microM-nifedipine to a Ca2(+)-free, Mg2(+)-containing solution shifted the voltage dependence of force inactivation by 5-10 mV to more negative potentials. 6. Force activation was facilitated by nifedipine. In the presence of 2 microM-nifedipine in a Ca2(+)-containing solution, threshold potentials (rheobase) as negative as -75 mV were measured under microscopical observation. UV irradiation shifted the threshold potential back to the normal value of about -50 mV. 7. The slow Ca2+ inward current was blocked almost completely by approximately 5 microM-nifedipine, even when induced from negative holding potentials (-90 to -120 mV), i.e. under conditions where normal phasic contractures could still be observed. 8. Nifedipine (0.8 microM) caused a shift of the voltage dependence of current inactivation (V0.5) by 4 mV from -26 to -30 mV and at negative holding potentials (-90 mV), a reduction of maximum current by 35%. 9. The voltage dependence of current activation was not significantly altered by nifedipine (2 microM). 10. It is assumed that nifedipine binds with low affinity to the resting state of the DHP receptor (KD 0.8 microM) and with high affinity (KD 1 nM) to the inactivated and the active state (or to a precursor of this state). These assumptions could explain the relatively small shift of the inactivation curves (points 5 and 8) to more negative potentials and the facilitation of force activation (point 6).

Animals↗

Comparative clinical trial of isosorbide 5-mononitrate and sustained-release isosorbide dinitrate in ischaemic heart disease.

A double-blind crossover study, with placebo periods preceding each active treatment, was carried out in 29 patients with ischaemic heart disease to compare the clinical efficacy of isosorbide 5-mononitrate 40 mg twice daily and the same regimen of sustained-release isosorbide dinitrate. Assessment was by bicycle ergometry, symptomatology and blood nitrate level measurements. After 2-weeks' therapy with isosorbide 5-mononitrate, mean ST segment depression at the highest comparable exercise level for each patient was reduced by 32.5% (p less than 0.01), the mean maximum exercise level was increased from 87 to 102 Watts (17.8%, p less than 0.01), and mean work capacity was increased from 581 Watts-minutes to 783 Watts-minutes (34.6%, p less than 0.01). With sustained-release isosorbide dinitrate, ST segment depression was reduced by 16.5% (p less than 0.05); maximum exercise level showed only a small non-significant increase, from 89 to 97 Watts (8.6%), but work capacity increased (p less than 0.05) from 593 Watts-minutes to 705 Watts-minutes (18.9%). There was no significant difference between drugs as regards ST segment reduction but a slight difference in favour of isosorbide 5-mononitrate (p less than 0.05) in terms of maximal exercise level and work capacity. Both drugs resulted in very small reductions in blood pressure (p less than 0.001 for systolic with isosorbide 5-mononitrate; p less than 0.01 for systolic and p less than 0.05 for diastolic with sustained-release isosorbide dinitrate). Heart rate and rate-pressure product changed little with either drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗

Planning and management of public health in the Federal Republic of Germany.

In the Federal Republic of Germany, the debate on public health is dominated by the question as to the cost and the financing of good health care. Indeed, expenditure planning has now become the main area of planning in the public health sector. By contrast, the plans to improve health standards and to intensify health protection as well as to improve the quality and efficacy of health provision are somewhat neglected. This is probably due, in the main, to the strong position held by the providers of medicines and medical services and thus, by the same token, to the weak position of the consumers. Although there exists a well known set of statistics and indicators to describe the state of public health in this country, there is an almost complete absence of any attempt to evaluate them for planning purposes. The scope of intervening in the sphere of health care is thus left to a large number of protagonists characterized by completely heterogeneous interests. What we lack is a system of target-oriented plans and concrete measures. In the field of providing health care and combating disease, the only available systematic planning concerns the provision of in-patient and out-patient medical services: there is no planning for the quality of such facilities or for the range and quality of psychosocial and nursing services. As regards health-expenditure planning--which has made the biggest advances--the participants enjoy a great deal of independence: the volume of spending and increases in expenditure are thus the outcome of a process of negotiation. Under the current planning philosophy, consensual decision-making enjoys a high status.

Germany, West↗

Malignant syringoma of the eyelid.

Two cases of malignant syringoma of the eyelid are reported. The first patient, a 20-year-old woman, presented with a one year history of a slowly growing nodule in the left lower eyelid. The lesion recurred five months after excision, slowly grew over the ensuing two and one-half years, and was reexcised. The second case was an 18-year-old man who was first examined by an ophthalmologist because of a slowly enlarging, painless induration of his right lower eyelid for two years. Histologic examination of the excised lesions from both patients disclosed proliferated ducts lined by two layers of epithelium infiltrating the dermis and subcutaneous tissue; there was skeletal muscle and perineural invasion, but only minimal cellular atypia. Malignant syringomas are rare forms of sweat gland carcinoma, which most often occur on the upper lip and to our knowledge have not been reported on the eyelid. These tumors probably arise from eccrine ducts, are more common in women, and have a peak incidence in the fifth decade. The histologic feature that best indicates prognosis is the degree of cellular atypia. Patients with cytologically well-differentiated tumors do well following complete local excision. Features that help to distinguish malignant syringoma from its benign counterpart are the larger size, solitary nature, and subcutaneous, muscular, and perineural invasion.

Adenoma↗

An alternative technique of biliary reconstruction after liver transplantation.

In ten pigs ligature dissection and side-to-side reanastomosis was performed as a model for biliary reconstruction after liver transplantation. Results were satisfying with no complications, such as bile leakage, cholangitis, obstruction, or stenosis in a follow-up of 3-12 months. The same technique was used in a transplantation program with rhesus monkeys so far showing the same good results.

Animals↗

The technique of kidney transplantation in rhesus monkeys.

The technique of kidney transplantation in rhesus monkeys is described in detail. The rate of successful transplantations can be increased to 90-100% if several technical aspects are considered. These include adequate perfusion of the organ to be preserved, measures to prevent a sharp decrease in body temperature, doing the arterial anastomosis with interrupted sutures and prevention of low blood pressure after revascularization.

Animals↗

[Respiratory training with intermittent positive pressure in acute respiratory disturbances (author's transl)].

In a clinical study the applicability and effectiveness of breathing therapy with intermittent positive pressure in cases of incipient or already established pulmonary complications are evaluated. The case material was divided into four groups: 1. Imminent respiratory complications (haemorrhagic shock, flail chest); 2. acute postoperative pulmonary insufficiency in old patients; 3. postoperative alveolar or interstitial pulmonary oedema; 4. postoperative pneumonia. Individual respiratory training succeeded in all patients in significantly improving the arterial blood gases; prolonged artificial ventilation could be dispensed with. The method and its limitations and indications for its use are reviewed.

Abdomen↗

[Epidural morphine analgesia. Postoperative period (author's transl)].

50 patients after abdominal surgery received peridural morphine for postoperative pain relief. At the end of operation, 2-3 mg morphine in 10-15 ml 0,9% saline were injected peridurally by a catheter, which was placed preoperatively. The injection was followed by a dissociated analgesia. Diffuse pain and wound pain were diminished. Pin prick and temperature were still perceived. Analgesia started within 2-5 min after injection and lasted 14 h in the mean (range 1-49 h). The degree of analgesia was determined by a visual analogue scoring system. The patients reported a marked pain relief. A new dose of 2 mg morphine was given on demand, when the patients felt pain again. This procedure was continued until the second postoperative day. The overall amount of morphine by peridural application was 8 mg within 3 days. Neither clinically nor by blood gas analyzes here were signs of respiratory depression. There were no severe side effects. The advantages of epidural morphine analgesia are: low dose, long duration, lack of sedation and motor block, lack of respiratory depression, tachyphylaxia and sympathetic block. No pneumonia were seen in the epidural morphine group, whereas 4 cases of pneumonia were seen in the control group (n = 50) with conventional analgetics.

Abdomen↗

Analysis of microdissected cataractous human lenses.

The potential of high-performance liquid chromatography (HPLC) as a technique for studying human cataractogenesis by analyzing minute quantities of lens proteins was demonstrated in a human retinitis pigmentosa (RP) lens. Individual human cortical cataractous lenses were microdissected. A well-defined opaque section was identified, the lens capsule was cut, and the section was removed. A nearby clear lens section was dissected out to serve as a control. Soluble crystallins from the cataractous and adjacent normal sections were subjected separately to gel filtration on a HPLC system. In the RP lens, the protein profiles obtained from an opaque polar-posterior subcapsular section and from nearby clear sections of the same lens were significantly different. The protein profile of an opaque area near the equator of the same RP lens was similar to nearby clear sections. These results show that different opaque zones in a single lens may have unique biochemical and biophysical properties.

Cataract↗