Efficacy of Procox® oral suspension for dogs (0.1% emodepside and 2% toltrazuril) against experimental nematode (Toxocara cati and Ancylostoma tubaeforme) infections in cats

Two exploratory studies were performed to determine the optimum therapeutic dose of Procox(?) for the removal of experimental infection with mature adult Toxocara (T.) cati and Ancylostoma (A.) tubaeforme in kittens. Procox(?) is a new oral suspension containing a combination of the nematocidal and coccidiocidal active principles emodepside (0.1 %) and toltrazuril (2 %).In the first study, 18 eight-weeks-old kittens were inoculated with 450 L3 larvae of T. cati. 56 days after infection, the kittens were allocated to three treatment groups and were treated with 0.5 mg emodepside/kg body weight (group 1), 0.25 mg emodepside/kg body weight (group 2) and 0.1 mg emodepside/kg body weight (group 3), respectively. In the second study, 10 eight-weeks-old kittens were inoculated with 350 L3 larvae of A. tubaeforme. Four weeks after infection, the kittens were allocated to two treatment groups and were treated with 0.1 mg emodepside/kg body weight (group 1) or 0.25 mg emodepside/kg body weight (group 2). In both studies, all kittens received a reference treatment with Drontal(?) (230 mg pyrantel embonate and 20 mg praziquantel per tablet) at the recommended dose of one tablet/4 kg body weight 5 days after treatment with Procox(?). Anthelmintic efficacy was calculated by reduction in worm numbers expelled with the faeces following treatment with Procox(?) as compared with faecal worm numbers after reference treatment with Drontal(?), by thus avoiding necropsy of the animals.In the T. cati study, emodepside was at 99.9 %, 100 % and 96.5 % effective at a dosage of 0.5 mg, 0.25 mg and 0.1 mg per kg body weight, respectively. Against A. tubaeforme emodepside was at 95.7 % and 100 % effective at a dosage of 0.1 mg and 0.25 mg per kg body weight. No adverse events were seen during either study.It can be concluded that Procox(?) is efficacious for the control of mature adult T. cati and A. tubaeforme infections in cats at a single-dose rate of 0.25 mg emodepside/kg body weight.     

Outcomes of Transplanting Deceased-Donor Kidneys between Elderly Donors and Recipients

Rate of acceptance of deceased-donor kidneys decreases with donor age despite the growing number of aged transplant candidates on the waiting list. In the Eurotransplant Senior Program, HLA-unmatched kidneys from deceased donors aged ≥65 yr are transplanted regionally into recipients aged ≥65 yr. Because we have become more willing to accept kidneys from donors aged ≥75 yr than previous years, we performed a retrospective analysis of this subgroup. Kidneys were accepted from donors aged ≥75 yr provided a normal creatinine on admission to the hospital, a Cockcroft-Gault creatinine clearance >80 ml/min, and an absence of comorbidities. We compared outcomes of kidneys from donors aged ≥75 yr with both younger-donor kidneys transplanted in the Eurotransplant Senior Program and with younger-donor HLA-matched kidneys transplanted into recipients ≥60 yr. There were no differences in 5-yr graft and patient survival or rate of delayed graft function between groups. Graft function, measured by creatinine and creatinine clearance, differed without pattern at only three of 12 time points during 5 yr of follow-up. In conclusion, our data suggest that kidneys from deceased donors aged ≥75 yr can be transplanted safely into recipients aged ≥65 yr if similar donor criteria and local allocation practices are used.Kidney transplantations (KTX) are beneficial also for old recipients.^1,2 Because the number of aged kidney donors is constantly rising^3,4 and donor shortage is the limiting factor for a timely transplant, Eurotransplant initiated the Eurotransplant Senior Program (ESP) in 1999. In this program, kidneys from deceased donors aged ≥65 are allocated according to waiting time and blood group compatibility without HLA matching to recipients ≥65. Because susceptibility to damage through cold ischemic time increases with donor age, transport time is kept short by local allocation.^5,6 Donors of the age of the ESP are defined as expanded criteria donors (ECD), and kidneys were found to have a 1.7 times higher risk for graft failure compared with normal donors, and >50% of kidneys from deceased donors aged ≥60 are discarded in the United States.^7,8 Discarding these donor kidneys is despite an increasing number of old patients on the waiting list⁹ and the findings of some authors who could show that kidneys refused because of donor age were successfully transplanted in other centers. Also, ECD kidneys were transplanted successfully into recipients aged ≥40.^10,11Our department has taken part in the ESP since its start in 1999.¹² Our center criteria for acceptance of kidneys from ESP donors include absence of comorbidities (uncontrolled arterial hypertension, diabetes, proteinuria), creatinine on admission to the hospital in the normal range, and creatinine clearance (Cockcroft-Gault) of >80 ml/min. Because we observed an increasing number of donors aged ≥75 accepted into this program and because no publication on this subgroup of “very old for old” KTX exists, we performed a retrospective, single-center analysis.During the studied period, kidneys from 48 deceased donors aged ≥75 yr were allocated locally to our center by Eurotransplant (mean number of offers per year 5.3 [0 to 12]). Fifteen (31%) donors fulfilled the inclusion criteria. We transplanted 18 kidneys into 18 recipients aged ≥65 yr (study group [“very old for old”]). Control group 1 were recipients in the ESP who received donor kidneys aged 65 to 74 yr (“old for old”; n = 73), control group 2 were recipients who were ≥60 and received a kidney from a donor in the usually applied Eurotransplant kidney allocation system (ETKAS), which also includes HLA matching (“ETKAS for old”; n = 30).The surgical technique was extraperitoneal with intermittent ureteral stenting of the antirefluxive ureteral implantation, immunosuppression consisted of a standardized triple therapy (calcineurin inhibitor, mycophenolate mofetil, corticosteroids) with dosage reduction over time. Selected patients received an induction therapy with an IL receptor antibody. Rejections were treated by pulsed methylprednisolone bolus therapy, followed by conversion to tacrolimus and/or treatment with ATG in steroid-resistant cases. Delayed graft function (DGF) was defined as the need for dialysis in the first week after KTX. Data for the study were retrieved from our computer database, which stores all patient data, including the follow-up visits, in an electronic patient record system.For demographic data, see

Myocardial uptake and biodistribution of newly designed technetium-labelled fatty acid analogues

PURPOSE: In an effort to develop 99mTc-labelled fatty acids (FAs) for myocardial metabolism and flow imaging, several Tc analogues according to the '3+1' and the '4+1' mixed-ligand approach were synthesized and myocardial extraction was evaluated in non-working isolated guinea pig hearts. An example of biodistribution patterns in guinea pigs was determined by using one FA analogue. METHODS: The coordination moieties contain a +5, respectively +3, oxidation state metal core attached to the end position of a FA chain. FA complexes of the '3+1' and the '4+1' mixed-ligand type were prepared and investigated using the isolated heart model. To estimate the diagnostic value of the analogue 99mTc-FAs, the biodistribution of one well-extracted FA was evaluated. RESULTS: The '4+1' FA compounds achieved the highest uptake rates of all the technetium FAs investigated. In particular, the '4+1' 99mTc-C11-FA achieved at least a 2-fold higher ventricular extraction of the applied activity than the established control tracers including omega-(p-[123I]iodophenyl)pentadecanoic FAs (BMIPP and IPPA) and Tc-MIBI. Furthermore, the '4+1' dodecanoic FA derivative and the thiadodecanoic FA derivative showed an extraction comparable to established 123I-labelled tracers. Biodistribution experiments performed for the thiadodecanoic FA derivative indicated a good heart/blood and heart/lung ratio and also a high uptake in the liver. In contrast, '3+1' 99mTc complexes showed a low myocardial extraction rate. Nevertheless, the differentiation in the extraction profile, which depends on the FA chain length and structure, indicates a specific heart uptake of these 99mTc-labelled FA derivatives as well. CONCLUSIONS: The excellent extraction rates found for '4+1' 99mTc-FAs indicate possibly promising structures for innovative myocardial tracers.     

Effects of IGM-enriched solution on polymorphonuclear neutrophil function, bacterial clearance, and lung histology in endotoxemia

Immunological interventions in endotoxemia and sepsis have been tested in experimental and clinical studies. Our group evaluated the effects of an immunoglobulin (Ig)M-enriched solution in an established model of Gram-negative bacteraemia. Ten New Zealand White rabbits (2-3 kg) were randomized to a treatment or control group. In both groups, LPS was infused at a rate of 40 mg kg(-1) h(-1). Immunoglobulin M-enriched solution (Pentaglobin; 2 mL kg(-1) h(-1)) was applied in the intervention group 15 min after beginning LPS infusion. 1 x 10(8) colony forming units of Escherichia coli were injected 30 min after LPS infusion was commenced. Baseline hemodynamic and respiratory parameters, blood E. coli concentration (30 min before and 1, 15, 30, 60, 90, 120, and 180 min after E. coli injection), polymorphonuclear neutrophil oxidative burst activity, and phagocytosis dead space (both 30 min before and 1, 15, 60, 120, and 180 min postinjection) were measured. Ex vivo phagocytosis activity was measured in a separate experiment and evaluated by electron microscopy. Diffuse alveolar damage (DAD) was measured. Organ colonization (kidney, lung, liver, spleen) was assessed in aseptic organ samples. Hemodynamic parameters did not differ between the two groups. Bacterial blood clearance was not influenced by application of IgM-enriched solution. Liver and spleen colonization was significantly reduced in the IgM group. Immunoglobulin M-enriched solution reduced in vitro residual phagocytosis capacity at 30, 90, and 180 min and improved respiratory burst at 180 min. Correspondingly, ex vivo phagocytosis activity as documented by electron microscopy was increased in the IgM group. The sum of all weighted DAD scores (except overdistension) was significantly better in the IgM group (23+/-5 vs. 30+/-8). Immunoglobulin M-enriched solution significantly improved six of seven DAD score parameters and reduced liver and spleen E. coli count. Residual phagocytosis capacity was significantly decreased in the IgM group, whereas burst activity was increased, pointing to an increased in vivo phagocytosis efficiency. Short-term IgM-enriched solution intervention had an especially beneficial effect on LPS-induced pulmonary histological changes.     

Treatment of the wrist in rheumatoid arthritis

Wrist involvement is common in rheumatoid arthritis and affects up to 50% of patients within the first 2 years after the onset of the disease, including bilateral involvement. It is a progressive disease that destroys the articular cartilage and surrounding soft tissues, thus leading to severe deformities. Radiological changes are characteristic and include narrowing of the joint line, cysts, and periarticular osteoporosis. Clinical changes are characterized by different scoring systems, indicating different therapeutic options. Surgical orthopedic treatment options include joint-preserving techniques to prevent further damage (radiosynoviorthesis, synovectomy, or axial correction with tendon transfers in earlier stages) and joint replacing techniques to restore function (arthrodesis, resection arthroplasty or total joint arthroplasty in later stages). This article reviews pathologic changes in the rheumatoid hand and their surgical treatment alternatives.     

Lymphocytoma cutis benigna

Infectious conditions of the infantile genitals are a diagnostic challenge. One of the rare differential diagnoses is lymphocytoma cutis benigna. We report a case of borrelial lymphocytoma of the glans penis in a 9 year old boy. Based on this case, the clinical, diagnostic and therapeutic aspects of this rare form of dermatoborreliosis are discussed.     

Steroid- and calcineurin inhibitor free immunosuppression in kidney transplantation: state of the art and future developments

Owing to the increasing disparity of organ demand and organ supply the search for optimal immunosuppressive strategies has become a central issue in kidney transplantation (KTX). In the focus today are modifications of the use of calcineurin-inhibitors (CNIs, Cyclosporine A/Tacrolimus) and steroids, as they are nephrotoxic and promote cardiovascular risk factors like arterial hypertension, hyperlipidemia and diabetes mellitus. These modifications can either be withdrawal or avoidance of these substances in combination with new and/or established immunosuppressants. Because about half of all KTXs are performed by or with the help of urologists’ knowledge of modern immunosuppressive regimens is crucial also for urologists. We performed a literature research (PubMed, DIMDI, medline) for CNI- and steroid-sparing protocols and studies to elucidate their influence on graft-function and graft- and patient-survival. New substances and actual studies were also evaluated. Several published reports on CNI- and steroid-sparing protocols after KTX exist, including withdrawal, reduction or avoidance. The time of reduction seems to be crucial: an initially increased immune response should be counterbalanced by an initially intensified immunosuppression. Therefore, late steroid withdrawal seems to be safer than early withdrawal especially in Cyclosporine-based immunosuppression. Steroid avoidance also seems feasible on a CNI based regimen, especially in context with induction therapy. Withdrawal or avoidance of CNIs seems feasible with mycophenolate acid and/or induction therapy with IL 2-receptor antibodies as co-immunosuppressants. This is of interest in grafts with deteriorating function or from donors with extended criteria. Also, CNI- and steroid-free immunosuppression can be successfully performed with new immunosuppressants but results are yet premature. CNI- and/or steroid reduction, withdrawal or even avoidance is feasible. As long-term graft function is the goal of KTX and as more kidneys from donors with extended criteria are transplanted “tailored immunosuppression” will replace standards in the future.