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Biomedical subjects

J Buch

Publications and source records attributed to J Buch.

At least 19 recordsLinked to original sources

Evaluation of the efficacy of emodepside+praziquantel topical solution against cestode (Dipylidium caninum, Taenia taeniaeformis, and Echinococcus multilocularis) infections in cats.

Emodepside+praziquantel topical solution was developed to provide broad-spectrum anthelmintic activity against gastrointestinal parasites in cats. Eight controlled studies were conducted to evaluate the efficacy of a topical solution of emodepside (3 mg/kg) and praziquantel (12 mg/kg) (Profender, BayerAG, Leverkusen, Germany) against feline infections with three species of cestodes. Studies featured naturally acquired infections of Dipylidium caninum or Taenia taeniaeformis, or experimental infections with Echinococcus multilocularis that were placebo-controlled, randomized and blinded. Cats were euthanatized and necropsied between 2 and 11 days after treatment, depending on the target parasite. The efficacy of emodepside+praziquantel topical solution was 100% against D. caninum and T. taeniaeformis, and 98.5- 100% against E. multilocularis. No significant systemic or local adverse reactions to treatment were noted in cats that received the combination. Topical treatment of cats with emodepside+praziquantel topical solution was safe and highly effective against cestode infections.

Administration, Topical↗

Evaluation of the efficacy of emodepside plus praziquantel topical solution against ascarid infections (Toxocara cati or Toxascaris leonina) in cats.

Eleven controlled studies were conducted in the United States and Europe to evaluate the efficacy of a topical solution of emodepside (3 mg/kg)+praziquantel (12 mg/kg) (Profender, Bayer AG, Leverkusen, Germany) against infection with various stages of the ascarid nematodes Toxocara cati and Toxascaris leonina. Infections were induced by administration of larvated ascarid eggs, and stage-specific efficacy was evaluated by treating cats at scheduled intervals post-inoculation. All studies featured random allocation to treatment groups, placebo-treated control animals and assessment of outcome measures by masked personnel. The product (emodepside+praziquantel topical solution) was 100% effective against mature adults and immature adult T. cati. In addition, it was 96.8% effective against third stage larvae and at least 99.4% effective against fourth stage larvae of T. cati, respectively. Efficacy against mature, immature adult and L4 stages of T. leonina exceeded 93.4%, but regulatory "adequacy of infection" criteria were not met in some studies. No adverse reactions to treatment were noted in cats treated with the emodepside+praziquantel topical solution.

Administration, Topical↗

Efficacy of a topically administered combination of emodepside and praziquantel against mature and immature Ancylostoma tubaeforme in domestic cats.

This paper reports the efficacy of emodepside/praziquantel spot-on (Profender), Bayer AG, Leverkusen, Germany), a novel broad-spectrum anthelmintic for dermal application, against L4 larvae and immature adult and adult stages of Ancylostoma tubaeforme in cats. The formulation contains 2.14% (w/w) emodepside and 8.58% (w/v) praziquantel, with emodepside being active against gastrointestinal nematodes and praziquantel against cestodes. Five randomized, blinded and controlled laboratory studies demonstrated 100% efficacy of emodepside/praziquantel spot-on against mature A. tubaeforme and an efficacy of >95% and >97%, respectively, against L4 larvae and immature adults (based on worm counts after necropsy) at approximately the minimum proposed dose rate in cats of 3.0 mg emodepside and 12.0 mg praziquantel/kg body weight. No adverse reactions to the treatment were observed. It is concluded that emodepside/praziquantel spot-on is an effective and safe treatment against infections with mature and immature A. tubaeforme. Emodepside/praziquantel spot-on will considerably facilitate the treatment of cats against nematodes and cestodes compared with orally administered preparations.

Administration, Topical↗

Field evaluation of the efficacy and safety of emodepside/praziquantel spot-on solution against naturally acquired nematode and cestode infections in domestic cats.

Two controlled, blinded and randomized multi-site clinical field studies evaluated the efficacy and safety of emodepside/praziquantel spot-on in the treatment of gastrointestinal nematode and cestode infections in cats. In a study conducted in Europe, faecal egg count reductions of >98% for all nematode eggs and eggs of Toxocara cati, respectively, were observed in cats treated with emodepside/praziquantel spot-on (Profender, Bayer AG, Leverkusen, Germany). For a positive-control product containing selamectin (Stronghold) reductions of >95% were observed. A 100% reduction of faecal eggs and proglottids was observed in cats treated with emodepside/praziquantel spot-on that were infected with cestodes. In a study conducted in North America, cats were treated with either emodepside/praziquantel spot-on plus a placebo tablet or a combination of two control products containing, respectively, selamectin (Revolution) and epsiprantel (Cestex). Faecal egg count reduction for eggs of T. cati was >99% for both treatments. For faecal eggs and proglottids of Dipylidium caninum reductions of >99 and >97% were recorded for cats treated with emodepside/praziquantel spot-on and the control group, respectively. No adverse reactions were observed in the European study, and only mild ones of short duration in a few cats from both treatment groups of the North American study. The two studies demonstrated that emodepside/praziquantel spot-on is highly efficacious and safe under field conditions.

Administration, Topical↗

Mutations in apoptosis genes: a pathogenetic factor for human disease.

Cell death by apoptosis is exerted by the coordinated action of many different gene products. Mutations in some of them, acting at different levels in the apoptosis process, have been identified as cause or contributing factor for human diseases. Defects in the transmembrane tumor necrosis factor receptor 1 (TNF-R1) lead to the development of familial periodic fever syndromes. Mutations in the homologous receptor Fas (also named CD95; Apo-1) are observed in malignant lymphomas, solid tumors and the autoimmune lymphoproliferative syndrome type I (ALPS I). A mutation in the ligand for Fas (Fas ligand; CD95 ligand, Apo-1 ligand), which induces apoptosis upon binding to Fas, was described in a patient with systemic lupus erythematodes and lymphadenopathy. Perforin, an other cytotoxic protein employed by T- and NK-cells for target cell killing, is mutated in chromosome 10 linked cases of familial hemophagocytic lymphohistiocytosis. Caspase 10, a representative of the caspase family of proteases, which plays a central role in the execution of apoptosis, is defect in autoimmune lymphoproliferative syndrome type II (ALPS II). The intracellular pro-apoptotic molecule bcl-10 is frequently mutated in mucosa-associated lymphoid tissue (MALT) lymphomas and various non-hematologic malignancies. The p53, an executioner of DNA damage triggered apoptosis, and Bax, a pro-apoptotic molecule with the ability to perturb mitochondrial membrane integrity, are frequently mutated in malignant neoplasms. Anti-apoptotic proteins like bcl-2, cellular-inhibitor of apoptosis protein 2 (c-IAP2) and neuronal apoptosis inhibitory protein 1 (NAIP1) are often altered in follicular lymphomas, MALT lymphomas and spinal muscular atrophy (SMA), respectively. This article reviews the current knowledge on mutations of apoptosis genes involved in the pathogenesis of human diseases and summarises the gradual transformation of discoveries in apoptosis research into benefits for the clinical management of diseases.

Adaptor Proteins, Signal Transducing↗

Can superoxide organic chemistry be observed within the liposomal bilayer?

--2-(Dimethylamino) fluorene (1a) and 5-benzoyloxy-2,3,7,8,12,13,17,18-octaethylporphyrin (4) react with superoxide anion radical (generated from KO2/18-crown-6 polyether) in aprotic media. Yet, when incorporated into the lipid bilayer of dimyristoyl phosphatidylcholine liposomes, these two substrates are inert to superoxide, generated enzymatically (xanthine oxidase/acetaldehyde) or radiolytically (60Co or 137Cs source/formate solution). On the other hand, 7-acetoxy-4-methylcoumarin (6), which reacts with superoxide in aprotic media yielding the corresponding 4-methylumbelliferone (7), also gives the same product when incorporated within the liposomal bilayer and reacted with radiolytically or enzymatically generated superoxide. In the latter case, the reaction is inhibited by SOD. NMR studies indicate that in contradistinction to the highly lipophilic 1a and 4, which presumably lie well within the lipid bilayer, 7 lies in a highly polar region of the bilayer. These results suggest that superoxide anion does not penetrate deep into the liposomal bilayer; nevertheless, superoxide reactions can, indeed, be observed, provided the active site of the substrate lies at or near the lipid-water interface.

Binding Sites↗

[Intramedullary nailing of unstable forearm shaft fractures in children].

Forearm diaphyseal fractures in children are commonly treated by conservative management. In about 5% of cases, however, unstable fractures occur and require surgical intervention. We prefer the intramedullary pinning procedure, which has already been published in a similar version in 1913 by Schöne and in 1947 by Bsteh. 41 patients were followed up between 1979 and 1988. One instance with a severe infection of a second-degree open fracture required two reoperations and was completely restored with a very good result. An overall assessment of our collective yielded 31 patients with findings rated as very good, four patients rated as good, five as satisfactory and one as moderate.

Adolescent↗

Functional properties in vitro of systemic small arteries from rabbits fed a cholesterol-rich diet for 12 weeks.

1. Recent evidence has suggested that the impairment of endothelium-dependent cholinergic relaxation in vitro, which is seen in atherosclerotic large arteries of animals and man, could be part of a general deleterious effect to the endothelium of hypercholesterolaemia. 2. This possibility has been investigated in vitro by measuring the response to acetylcholine, sodium nitroprusside, 5-hydroxytryptamine and noradrenaline in segments of aorta and of femoral, mesenteric and cerebral small arteries (internal diameter approximately 200 microns) from control rabbits (n = 12) and from rabbits fed a 1% (w/w) cholesterol and 3% (w/w) coconut oil diet (n = 12) for 12 weeks. 3. Thoracic aorta segments from the control rabbits exhibited a maximal relaxation in response to acetylcholine of 64 +/- 11% compared with 10 +/- 5% (P less than 0.01) for thoracic segments from cholesterol-fed animals. Cerebral, femoral and mesenteric small arteries exposed to acetylcholine (10(-9)-10(-4) mol/l) relaxed to the same degree as arteries from control rabbits. The responses to sodium nitroprusside and bradykinin of the small arteries from the cholesterol-fed rabbits remained unaffected. 5-Hydroxytryptamine evoked comparable contractions in the small arteries, while the sensitivity to noradrenaline of the femoral small arteries was significantly decreased and the response of cerebral small arteries to noradrenaline in cholesterol-fed rabbits slightly increased compared with control rabbits. 4. Aorta from the cholesterol-fed rabbits had extensive atheromatous lesions. Morphological measurements and histological examination showed unchanged thickness and light microscopic appearance of intima and media of small arteries from cholesterol-fed animals compared with control animals. 5. The present study indicates that hypercholesterolaemia in this rabbit model is followed by atherosclerotic lesions and changed function of large arteries, but that both function and structure of systemic small arteries are largely unaffected.

Animals↗

[Radiographic examination of the thorax, fluoroscopy and echocardiography in cardiac calcification].

The value of radiographic examination of the thorax, fluoroscopy and echocardiography in demonstration and localization of intracardiac calcifications were compared in an investigation of 40 patients with valvular heart disease prior to planned cardiac catheterization or operation. Radiographic examination of the thorax revealed only the most severe calcifications. By means of echocardiography it proved possible to undertake a simple semi-quantitative characterisation of the calcified tissue with acceptable intra- and inter-observer variation. Echocardiography and fluoroscopy were found to be of equal value in demonstration of the degree of calcification of the heart. Echocardiography was, however, superior to fluoroscopy in fine localization of the calcifications. The relative and additive values of the methods could be illustrated employing Bayes' theorem and could be represented graphically provided that the observations carried out with the three methods could be considered independent of one another. It is concluded that radiographic examinations of the thorax is unsuitable for screening for cardiac calcifications. Fluoroscopy can no longer be considered to be the method of choice in assessing lesions of this type but should be employed in cases where echocardiography does not provide sufficient information or is not available. The greatest certainty in demonstration of calcifications is obtained with combined employment of fluoroscopy and echocardiography.

Adult↗

[Conservative treatment of calcaneus fracture versus repositioning and percutaneous bore wire fixation. A comparison of 2 methods].

From 1976 to 1985 we treated 236 patients with fractures of the calcaneum without additional injuries to the legs or pelvis. Among 129 patients, 22 female/107 male, with an average age of 50 and 42 years, respectively, we performed a total of 141 fractures of the calcaneum. The average post-traumatic follow-up was 6 years. For 62 fractures we performed conservative therapy with immobilization in plaster and for 79 fractures, reduction and percutaneous drill wire fixation. The fractures were classified according to Boehler, Watson Jones, and Essex Lopresti, and on the basis of the tuber joint angle (Boehler's angle). The resulting groups, however, were not homogeneously structured. Of 82 intraarticular fractures with fragment dislocation, 19 were treated conservatively and 63 surgically. Boehler's angle at trauma was 14 degrees in the conservative group and 2 degrees in the surgical group. The more severe types of fractures were thus treated by surgery. There were two Sudeck's dystrophies with conservative and three with surgical treatment. Inadequate surgical technique (drill wires extending greater than 2 mm over the bone and insufficient compression) led to the following complications: 10 drill wire perforations without subsequent complications, 8 drill wire migrations, 2 deep infections. In four patients drill wires had to be shortened, and in 1 patient drill wires had to be shortened, and in 1 patient drill wires were misplaced and had to be corrected. Surgically treated fractures were followed by arthrodesis in 2 patients, medialization of the lateral wall of the calcaneum in 1 patient, and peroneal tendon revision in 1 patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Long-term follow-up of right ventricular function after Mustard operation for transposition of the great arteries.

As development of right ventricular (RV) failure is a potential risk after Mustard operation for transposition of the great arteries, 17 patients were reexamined 5-13 years postoperatively. Comparisons were made with healthy controls. There were no clinical signs of heart failure. Echocardiographically determined RV end-diastolic diameter was increased to 2.5 +/- 0.8 cm (controls: 1.5 +/- 0.4 cm, p less than 0.001). Comparison of RV systolic time intervals (STI) in patients with normal left ventricular (LV) STI revealed decreased RV function, with RPEPI 165 +/- 19 msec (controls 126 +/- 12, p less than 0.001) and RPEP/RVET 0.484 +/- 0.096 (controls 0.284 +/- 0.045, p less than 0.001). Nuclear angiography demonstrated decreased RV ejection fraction (EF), viz. 42.8 +/- 6.6% (normal RV 53 +/- 6%, LV 68 +/- 9%, p less than 0.001). Only two patients showed normal (5%) rise in RV-EF during exercise. There was no evidence of deterioration with passage of time. The results do not justify use of anatomic repair at our center, since the perioperative mortality might then be higher than in the Mustard or Senning procedures.

Angiography↗

[Aseptic bone necroses in leukemia patients in childhood and adolescence].

Four children with leukemia (1.6% of all leukemia patients) treated between 1979 and 1984 developed aseptic bone necroses, all of them at multiple sites. The average time from starting chemotherapy to developing bone necroses has been 19 months (range 9 to 28 months). This is a well known complication of corticoid therapy, but corticoids may not be the only aetiological factor. Other antineoplastic agents and leukemia for itself have been associated with aseptic bone necroses. Bone and joint pain caused by aseptic bone necroses can mimic leukemic relapse, so the diagnosis may be difficult. The increasing number of long term survivors in childhood leukemia, who underwent aggressive polychemotherapy, could make this problem more common in the near future.

Adolescent↗

Systolic time interval. Heart rate relationship during atrial or ventricular pacing.

In order to evaluate the relative importance of heart rate (HR) and A-V synchrony during pacing, 16 patients with VVI pacemakers were compared with 8 patients with AAI pacemakers using systolic time intervals. The patients were examined at rest at increasing HR with increments of 10 beats/min until a maximum of 150 beats/min was reached or for AAI pacing until 2 degrees A-V block occurred. The slopes of the linear regression equations for PEP versus HR and PEP/LVET versus HR were used. To compensate for differences in baseline values, delta PEP% versus delta HR% and delta PEP/LVET% versus delta HR% were also calculated and used to evaluate the response to the two different pacing modes. PEP seemed in this situation to be less dependent on HR than expected from earlier data concerning spontaneous differences in heart rate. This is probably due to a lower catecholamine level during pacing. During AAI pacing the slopes were slightly more normal than during VVI pacing, but the differences did only reach statistical significance using PEP/LVET versus HR (p less than 0.05). At heart rates above 80 blood pressure had a tendency to be higher during AAI pacing, a trend which was only significant for the diastolic blood pressure at HR from 130-150. These results support the view, that the ability to increase heart rate is more crucial for left ventricular function than A-V synchrony in these patients.

Adult↗

[Posterior shoulder dislocation].

Posterior dislocations of the shoulder can be caused by various mechanisms, the most common one, being epileptic seizures. Therefore many patients or their relatives hesitate to admit, how the injury has actually occurred. Spängler et al. published in 1975 several reasons why the diagnosis of "posterior subluxation of the humeral head" is often missed. Usually very typical errors in the evaluation of the clinical findings lead to misinterpretation of the radiograms. In spite of the fact that long-term results of untreated posterior subluxations can be surprisingly good, reduction must be achieved as soon as possible. Deep impression-fracture of the humeral head are the cause of recurrent dislocations. Various methods have been described to treat this condition by filling the defect with subscapularis tendon or cancellous bone. Avulsion-fractures of the posterior rim of the glenoid can successfully be refixed with small screws. In case of dislocation fractures through the anatomical neck, prosthetic replacement of the head leeds to satisfying results. So-called habitually dislocations are more common in boys and do usually not require surgery, as the inclination to dislocate becomes less frequent in later years. Only in adults operation may be indicated. Posterior apposition of a bone graft can be recommended.

Adult↗

Different patterns of hemodynamic abnormalities in patients with ischemic heart disease compared with patients with congestive cardiomyopathy.

48 patients with chest pain or unexplained heart failure were examined with exercise test, systolic time intervals, apexcardiogram and left- and right-sided heart catheterization including coronary arteriography. The 23 patients with ischemic heart disease (IHD) and 19 patients with congestive cardiomyopathy (COCM) could as groups be separated by several of the parameters. Two major patterns of change were present when using the whole range of parameters, probably reflecting that the heart and circulation had compensated for left ventricular dysfunction in different ways in IHD and COCM. Comparing patients with the same ejection fraction (EF), preejection-period index (PEPI) pre-ejection-period/left ventricular ejection time (PEP/LVET) and systolic blood pressure/left ventricular end systolic volume index (SBP/LVESVI), were all more abnormal in patients with COCM than with IHD at most EF levels. The best separation between the diseases was obtained using exercise capacity in combination with PEP/LVET. The correlations between invasive and noninvasive parameters underlined that no single parameter can satisfactorily characterize the circulatory function in patients with individual differences in preload, afterload, pulse rate, cardiac volumes, compliance and contractility. No or poor correlations were found between exercise capacity and the different function parameters used.

Adult↗

Late infections of pacemaker units due to silicone rubber insulation boots.

Early in 1980, there was an increase at our hospital of late infections of pulse generator pockets not due to perforation. No source of contamination could be found; then, late in 1981, the infection rate decreased. The only change in procedure during this period was the introduction of silicone rubber boots around the pacemaker unit to prevent muscle pacing. The risk of late infection was 13.8%, when using a rubber boot, while otherwise it was only 2.6% (p less than 0.001). The infections were usually caused by ordinary skin bacteria. The authors believe that the infections were due to bacteria introduced inside the rubber boot, where they were practically out of reach of the ordinary defense mechanisms. The decrease in infection rate occurred after the introduction of silicone-coated pacemakers.

Bacterial Infections↗

Influence of atenolol and nifedipine on digoxin-induced inotropism in humans.

Short term effect of digoxin on left ventricular performance was studied in six healthy volunteers before and during atenolol or nifedipine administration. Left ventricular function was evaluated by systolic time intervals and echocardiography. No changes in left ventricular end diastolic or systolic dimensions occurred throughout the study, indicating unchanged ventricular pre- and afterload. Thus, changes in the systolic time intervals must be attributed to changes in cardiac contractility. Changes in the pre-ejection period index (PEPI) obtained from the systolic time intervals were used as a measure of digoxin-induced inotropism. A concentration-response relationship between plasma digoxin level and changes in PEPI was revealed when digoxin was given alone. Atenolol did not influence the digoxin-induced inotropism at a given serum digoxin level. During nifedipine administration no inotropic effect of digoxin could be demonstrated. Thus, it is concluded that nifedipine attenuates digoxin-induced inotropism, while atenolol seems without this effect. These results are in accordance with previous experiments and reflect the different pharmacological sites of action of beta-adrenoceptor antagonists and calcium channel blocking agents. Plasma digoxin concentration, renal digoxin clearance and creatinine clearance did not change during atenolol or nifedipine.

Adult↗