Measurements of echocardiographic indices and biomarkers of kidney injury in dogs with chronic kidney disease.

Pathophysiological cardiac and renal interactions are termed cardiovascular-renal disorder (CvRD). Cardiovascular disease/dysfunction secondary to kidney disease (CvRDK), is a leading cause of death in human chronic kidney disease (CKD) patients. The presence and clinical impact of CvRDK in dogs with CKD is unknown. We hypothesized that echocardiographic measurements, and cardiac and renal biomarkers, will be altered in dogs with CKD and associated with survival. Eleven dogs with CKD (n = 6 IRIS stage 2, n = 5 IRIS stage 3) and without primary cardiac disease, plus 12 healthy age-matched control dogs, were recruited to this prospective observational study. Dogs underwent standard echocardiography, glomerular filtration rate (GFR) estimation by iohexol clearance, and measurement of plasma cardiac troponin I and N-terminal pro-B-type natriuretic peptide (NT-proBNP), plasma and urinary cystatin B, and urinary clusterin and neutrophil gelatinase-associated lipocalin (NGAL). Values were compared between groups, and their association with all-cause mortality explored. Dogs with CKD had significantly lower GFR and higher NT-proBNP, urinary cystatin B, clusterin, and NGAL, compared to controls (P < 0.05). Echocardiographic measurements were similar between dogs with CKD and controls. Median follow-up time was 666 days, during which six dogs with CKD died. Risk of death was associated with increasing age, serum total protein, and normalized left ventricular posterior wall thickness (LVPWDN) and decreasing bodyweight and packed cell volume. Although baseline differences in echocardiographic measurements were not evident between dogs with moderate CKD and controls, the presence of CvRDK was suggested by the association between LVPWDN and survival.

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.

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.

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.

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.

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.

Effect of level of anastomosis and quality of intraepididymal sperm on the outcome of end-to-side epididymovasostomy.

OBJECTIVES: Epididymovasostomy is commonly performed at the most distal site of the epididymis where whole sperm are present within the lumen, regardless of their motility status. Although more fresh and motile sperm can be found more proximally within the epididymis, it is believed that the outcome of epididymovasostomy is better more distally. Because the current results of epididymovasostomy are far from perfect, it would be ideal to be able to harvest motile sperm for cryopreservation at the time of surgery in case the patient remains azoospermic postoperatively. The objective of this study was to determine the effect of the level of epididymal anastomosis and quality of sperm on the outcome of surgery. METHODS: An end-to-side epididymovasostomy was performed on 131 azoospermic men with a mean age of 39 years and a mean obstructive interval of 18 years. The etiology of obstruction was vasectomy in 48%, infectious in 19%, congenital in 20%, and unknown in 13%. The average duration of follow-up was 32 months. The overall patency rate was 67% and pregnancy rate was 27%. Subgroups of patients with an anastomosis to the same level of the epididymis on all functional sides were identified as follows: caput (56), corpus (28), and cauda (13). These groups were compared in regard to the presence of motile sperm within the epididymal lumen at the time of surgery, patency rates, postoperative semen quality, and pregnancy rates. RESULTS: Motile sperm were present more often in both the caput (54%) and corpus (61%) than in the cauda epididymis (25%) (P < 0.05). The patency rates for the three subgroups were not significantly different. The postoperative total motile sperm count and pregnancy rate for the corpus epididymis (13 x 10(6) and 45%) was significantly (P < 0.05) better than for the caput (4.4 x 10(6) and 22%) but no different than that of the cauda (10 x 10(6) and 23%). The patency and pregnancy rates for anastomoses performed at levels demonstrating motile sperm were not significantly better than at sites with nonmotile sperm, but the postoperative total motile sperm count was better (P < 0.05). CONCLUSIONS: The results of this study suggest that the outcomes of epididymovasostomy to the corpus and cauda epididymis are roughly equivalent and superior to the caput. Therefore, it may be reasonable to move more proximally from the cauda to corpus in the search for motile sperm for cryopreservation during an end-to-side epididymovasostomy. In contrast, moving from the corpus to the caput epididymis has a significant adverse effect upon outcome; it is, therefore, not worthwhile to search for viable sperm for cryopreservation in this clinical setting.

La necesidad de adecuar en cada paciente el tratamiento antihipertensivo y antianginoso: papel de los bloqueantes cálcicos de acción prolongada / The necessity of tailoring antihypertensive and antianginal therapy to the individual patient: the place of long-actin calcium channel blockers

La patología cardiovascular afecta a más de uno de cada cuatro habitantes en los países desarrollados y es la causa principal de mortalidad, en varones y mujeres, los avances en su tratamiento han contribuído a disminuir las tasas de mortalidad por enfermedad cardiovascular, pero las tasas de morbimortalidad asociadas a hipertensión, enfermedad coronaria y accidente cerebrovascular todavía son preocupantes. El manejo óptimo de la enfermedad cardiovascular requiere una elección individualizada del tratamiento para cada paciente en particular, de manera que, además de los efectos terapéuticos, se consiga una buena tolerancia durante largos períodos. Los bloqueantes cálcicos de acción prolongada, tales como la amlodipina, representan una opción importante en el tratamiento de la hipertensión y la angina. Los bloqueantes cálcicos de acción prolongada como la amlodipina son drogas de primera línea para el tratamiento individualizado de la enfermedad cardiovascular

Cytokines stimulate lipid membrane peroxidation of human sperm.

Reactive oxygen species production has been demonstrated to impair sperm function. We have noted the potential for the cytokines IL-1 alpha, IL-1 beta, and TNF alpha to stimulate reactive oxygen species production by fertile donor sperm at levels that are consistent with the levels of IL-1 occurring in human seminal plasma. Reactive oxygen species-related sperm membrane peroxidation may be one mechanism by which cytokines can exert a detrimental effect on male fertility. This study suggests a new mechanism by which cell-mediated immunological male infertility may occur.

[Conservative treatment of calcaneus fracture versus repositioning and percutaneous bore wire fixation. A comparison of 2 methods]. / Konservative Behandlung des Fersenbeinbruches versus Reposition und perkutane Bohrdrahtfixation. Vergleich zweier Methoden.

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)

[Radiographic examination of the thorax, fluoroscopy and echocardiography in cardiac calcification]. / Røntgenundersøgelse af thorax, fluoroskopi og ekkokardiografi ved kardiale forkalkninger.

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.

Partial characterization of a unique growth factor secreted by human Sertoli cells.

Human Sertoli cells were grown in a serum-free environment, and the Sertoli cell conditioned medium (hSCCM) was tested for mitogenic activity. The presence of a potent growth factor(s), termed Sertoli cell secreted growth factor (SCSGF), in hSCCM was confirmed and supports previous observations based on experiments using rat SCCM. Mitogenicity of hSCSGF was demonstrated in cell proliferation assays with the A431 (human epidermoid carcinoma) cell line and in [methyl-3H]-thymidine incorporation (DNA synthesis) assays with the Swiss 3T3 (mouse embryo fibroblast) cell line. In a dose-dependent manner, hSCSGF stimulated A431 cell growth up to 4-fold over control values (P less than 0.0001) and stimulated thymidine incorporation up to 4.5-fold over control values (P less than 0.0002). Importantly, SCSGF stimulated A431 proliferation 2-fold over control values (P less than 0.0002) in the presence of 5% serum. With the exception of rat SCSGF, human SCSGF is the only growth factor known to stimulate A431 cells. SCSGF also demonstrated epidermal growth factor (EGF)-like activity based upon displacement of EGF from its receptor in a radioreceptor assay. However, SCSGF is not EGF since it is a potent stimulator of A431 cells, whereas EGF is inhibitory. The growth factor was stable to heat, freeze-thaw, acid (pH 3), and trypsin treatment. Furthermore, it did not bind heparin agarose and is thus distinct from the endothelial cell growth factor family. High-pressure liquid chromatography on size exclusion (TSK G2000 SW) columns revealed an approximate size of 8000 daltons. Human SCSGF is a unique growth factor and may play a key role in the regulation of normal spermatogenesis.

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.

Effect of tobacco consumption on semen quality of a population of hypofertile males.

Effect of tobacco use (by chewing or smoking) on semen quality has been seen. Semen analysis of 119 tobacco chewers and 219 smokers was compared with those of 288 control patients. Some decrease in the ejaculate volume, sperm density, and total count was observed in tobacco users, but it was statistically insignificant. No difference was found in other parameters, like motility and morphology. It is concluded that tobacco use by chewing or smoking is not associated with impaired semen quality in males selected from an idiopathically hypofertile population.

[Aseptic bone necroses in leukemia patients in childhood and adolescence]. / Zum Problem der aseptischen Knochennekrosen bei Leukämiepatienten im Kindes- und Jugendalter.

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.

[Posterior shoulder dislocation]. / Die hintere Schulterverrenkung.

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.

Development of aortic stenosis in a patient with formerly pure aortic incompetence.

A 42 year old man with severe aortic incompetence and hypertension, but no aortic stenosis, responded so well to medical treatment that the planned operative treatment was postponed. 8 years later he was re-admitted with severe aortic stenosis and only minimal aortic incompetence. It is concluded, that a short trail of medical treatment may be warranted even in patients with severe aortic incompetence, before surgery is performed, especially if the patient is hypertensive.