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Biomedical subjects

W R Klein

Publications and source records attributed to W R Klein.

At least 19 recordsLinked to original sources
PubMed2005

Gentamicin nephrotoxicity--a comparison of in vitro findings with in vivo experiments in equines.

The aminoglycoside gentamicin is often used in equine practice. Despite its clinical use, concerns remain regarding the potential toxic side-effects, such as nephrotoxicity, in equine patients, particularly after repeated dosing. The aim of the study was to investigate first in vitro the mechanisms contributing to the renal toxicity of gentamicin and to identify sensitive biomarkers indicating proximal tubule damage. To this end, the kidney-derived cell lines LLC-PKI and MDCK were treated with gentamicin at different concentrations. Toxicity was assessed by measuring the release of gamma-glutamyl transferase (GGT), and the production of reactive oxygen species (ROS). Cell viability was measured using Alamar blue (AB) and Neutral red (NR) cytotoxicity assays. Gentamicin exerted a dose-dependent toxicity. Primarily, loss of brush border membrane integrity, indicated by GGT leakage, and an increased ROS production were observed. As GGT was found to be a sensitive marker for gentamicin-induced renal cell injury, in the subsequent in vivo experiments, in which ponies were given gentamicin (3.0 mg/kg bw three times daily and 4.5 mg/kg bw twice daily) for five consecutive days, plasma levels and the urinary excretion of GGT and creatinine were measured and the GGT:creatinine ratio was calculated. Elevated GGT levels in urine following gentamicin therapy were observed, but this enzyme leakage was transient and returned to baseline values after cessation of therapy. It could thus be concluded that even a conservative dose regimen of gentamicin did not result in significant renal toxicity in healthy ponies.

Animals↗
PubMed2005

Influence of fluid therapy on gentamicin pharmacokinetics in colic horses.

The aminoglycoside antibiotic gentamicin is commonly used in equine medicine for the prevention and treatment of Gram-negative and staphylococcal bacteria in surgically treated colic patients. The pharmacokinetics of gentamicin in these patients might be altered by the disease status, and/or under the influence of fluid therapy. The purpose of this study was to investigate the effect of intravenous fluid treatment on gentamicin kinetics in colic patients. Colic patients subjected to laparotomy were given fluid infusions according to clinical status. Following gentamicin administration, blood samples were taken for gentamicin analysis at different time points, and the main pharmacokinetic parameters including Vc, Vss, t(1/2) and MRT were calculated. Horses undergoing fluid therapy showed a significantly different t(1/2), clearance and MRT as compared to non-infused patients. However, taking into account the clinical status of the patients receiving fluid support, the data suggest that endotoxaemia, rather than fluid therapy, influence gentamicin pharmacokinetics following laparotomy.

Animals↗
PubMed2003

Comparison of the efficacy of local treatment of equine sarcoids with IL-2 or cisplatin/IL-2.

Local interleukin-2 (IL-2) is effective in a number of experimental animal models and in veterinary and human cancer patients without discomforting side effects. The primary goal of this study was to compare the therapeutic effects and side effects of the local intratumoral administration of five or ten low doses of IL-2 with those of a combination of cisplatin and a single high dose of IL-2 in the treatment of equine sarcoids. The therapeutic effect (complete and partial regression) of local cisplatin together with a single high dose of IL-2 was significantly better than the combined effect of low doses of local IL-2 administered daily over 5 or 10 days (80% and 43%, respectively; P=0.02). Cisplatin/IL-2 and low doses of IL-2 induced 53% and 14% complete regressions, respectively ( P=0.02). Histological changes after cisplatin/IL-2 treatment were far more pronounced than after IL-2 only treatment and in several cases showed an enormous eosinophilic infiltrate.

Animals↗
PubMed2002

[Treatment of equine sarcoids with cisplatin in arachid oil: a useful alternative?].

At the Department of Equine Sciences at Utrecht University a study was performed on the treatment of sarcoids with the cytostatic drug cisplatin. Fourteen horses with 23 sarcoids were treated in the period 2000-2001. Complete regression was seen in 78% of the tumours. No systemic side-effects were encountered. Although treatment was easy to perform, the ALARA (As Low As Reasonably Achievable) principle should be followed when using cytostatics.

Animals↗
PubMed2002

High volume continuous venovenous haemofiltration (HV-CVVH) in an equine endotoxaemic shock model.

Equine acute abdominal disease is often associated with shock. Important aspects in the onset of this complication include hypovolaemia, the translocation of endotoxins from the gut and the subsequent activation of the cytokine network. The clinical efficacy of high volume continuous venovenous haemofiltration (HV-CVVH) and the clearance of cytokines were therefore investigated in an equine endotoxaemic model. Ten male Shetland ponies received a slow infusion of LPS (2 microg/kg bwt) under general anaesthesia. The treatment group (n = 5) received HV-CVVH (2 ml/kg bwt/min) using a 75 kD polymethylmethacrylate (PMMA filter). Haemodynamic, blood variable and cytokine (TNF, IL-1 and IL-6) measurements were performed every 30 min for a 6 h period. The ponies showed a typical reaction in mean pulmonary arterial pressure, blood chemical and haematological markers after LPS challenge. No significant differences were found between the treatment group and the control group. Only a slight increase in cardiac index and no marked decrease in mean arterial pressure were seen. A clear cytokine response was found in all ponies, though substantially different in magnitude between individuals. The clearance of cytokines from the blood increased in time, but did not lead to significant decrease in serum levels. In this study, HV-CVVH with a PMMA filter did not prove to have a significant beneficial effect on the course of experimental endotoxaemia in horses. However, in a more severe model, better efficacy might be obtained. Testing additional filters might lead to a more suitable therapy for horses.

Animals↗
PubMed2001

Factors influencing the occurrence of thrombophlebitis after post-surgical long-term intravenous catheterization of colic horses: a study of 38 cases.

Thrombophlebitis is a well-known complication of the use of long-term in-dwelling catheters. In humans, catheter material has been shown to strongly influence the occurrence of thrombophlebitis. In the horse, the influence of catheter material has been studied in healthy experimental animals, but information on the relative importance of this factor is lacking. To investigate which factors have most impact on the frequency of jugular vein thrombosis in post-surgical colic horses, a clinical study was performed on 38 animals. Horses were randomly divided into two groups. In one group a polytetrafluoroethylene catheter was used, in the other a polyurethane catheter. Both groups were clinically monitored and screened for signs of thrombophlebitis. Seven out of 38 horses developed thrombophlebitis. The type of catheter material used had no influence on thrombophlebitis development. Dwell time was significantly longer in horses that developed thrombophlebitis compared with those that did not. There was no relationship between the occurrence of thrombophlebitis and underlying disease or surgical treatment, suggesting that the general state of debilitation these horses experienced was the most important determinant for the development of thrombophlebiris. This was further stressed by the fact that seven horses developed thrombophlebitis of the contralateral vein that had been used for the induction of anaesthesia (this incidence is much higher than in horses anaesthetized for elective surgery). It is concluded that the state of debilitation is the most important determining factor for the occurrence of thrombophlebitis after the use of long-term in-dwelling intravenous catheters. This makes a substantial reduction of the incidence of thrombophlebitis difficult, but some progress can be made by consequently restricting dwell time.

Animals↗
PubMed1999

Local low-dose IL-2 therapy.

Interleukin-2 (IL-2) is a powerful drug for treating cancer. However, it is only powerful if it is properly applied. That is, IL-2 should be applied at the tumor site, because at the transition of normal and malignant tissue are the tumor infiltrating cells. These should be activated by IL-2. Local application implies that IL-2 can be used in relatively low doses. It is becoming clear that even a single injection of IL-2 can cure cancer. IL-2 can also enhance the therapeutic effects of irradiation and Cisplatin. Locally applied IL-2 therapy is virtually non-toxic.

Animals↗
PubMed1996

Optimal regimes for local IL-2 tumour therapy.

In this report we present studies on optimal regimes for regional IL-2 therapy, focused on dose, schedule and site of injection. Original data obtained in 2 murine tumour models show that all 3 factors are of importance. Anti-tumour responses were most effective when IL-2 was administered regionally 5 to 10 times, at doses ranging from 7,000 to 33,000 IU/day every day or every other day. This resulted in cure rates of more than 40% in mice bearing ascitic tumour that had also disseminated to liver and lungs. The importance of these data is discussed in the light of previous results of our group. These results illustrate that the doses and schedules used in this study are not effective exclusively in these 2 tumour models but may have a more general applicability.

Animals↗
PubMed1996

Side effects of oral antimicrobial agents in the horse: a comparison of pivampicillin and trimethoprim/sulphadiazine.

To evaluate the side effects of oral pivampicillin and trimethoprim/ sulphadiazine, 200 horses receiving these antimicrobial agents were studied. The horses received either trimethoprim/ sulphadiazine (30 mg/kg twice daily) or pivampicillin (25 mg/kg twice daily) for three or more days. No adverse effects other than loose faeces and diarrhoea were detected. The risk of diarrhoea was significantly less after the oral administration of pivampicillin (3 per cent) than after trimethoprim/ sulphadiazine (7 per cent). Horses whose appetite was reduced appeared to be predisposed to develop diarrhoea after the administration of either oral antimicrobial agent.

Administration, Oral↗
PubMed1996

Distribution of penicillins into subcutaneous tissue chambers in ponies.

The distribution of penicillins into a tissue chamber implanted subcutaneously in ponies was studied. Ampicillin sodium (equivalent to 15 mg/kg ampicillin) was administered intravenously. Pivampicillin, a prodrug of ampicillin, was administered by nasogastric tube to fed ponies at a dose of 19.9 mg/kg (equivalent to 15 mg/kg ampicillin). Procaine penicillin G was administered intramuscularly at a dose of 12 mg/kg (equivalent to 12000 IU/kg). Six ponies were used for each medication. Antibiotic concentrations in plasma and tissue chamber fluid (TCF) were measured for 24 h after administration. Mean peak concentrations of ampicillin in TCF were 7.3 micrograms/mL, reached at 1.7 h, and 1.3 micrograms/mL, reached at 2.7 h, after administration of ampicillin sodium and pivampicillin respectively. The mean peak concentration of penicillin G of 0.3 microgram/mL was reached 12.3 h after administration of procaine penicillin G. Concentrations in TCF remained above the minimum inhibitory concentration of Streptococcus zooepidemicus for the proposed dosing intervals of 8, 12 and 24 h for ampicillin sodium, pivampicillin and procaine penicillin G respectively.

Ampicillin↗
PubMed1996

Clinical efficacy of ampicillin, pivampicillin and procaine penicillin G in a soft tissue infection model in ponies.

Tissue chambers, implanted subcutaneously in ponies, were inoculated with Streptococcus zooepidemicus. The animals received either no antibiotics or one of the following treatments: pivampicillin per os (19.9 mg/kg, equivalent to 15 mg/kg ampicillin, every 12 h) for 7 or 21 days (7 and 5 ponies, respectively), procaine penicillin G intramuscularly (12 mg/kg = 12,000 IU/kg, every 24 h) for 7 days (7 ponies), or ampicillin sodium intravenously (equivalent to 15 mg/ kg ampicillin, every 8 h) for 1 day (5 ponies). Only intravenous administration was started before infection (prophylactically), the other treatments were started 20 h after infection (curatively). A total of 7 ponies received no antibiotics. In untreated controls, the infection led to abscessation of the tissue chamber in 4 to 10 days. Curative treatment with either pivampicillin or procaine penicillin G for 7 days resulted in a reduction of viable bacteria in the tissue chamber but did not eliminate the infection, resulting in abscessation in 5 to 14 days. However, administration of pivampicillin for 21 days eliminated the streptococci in five out of five ponies and prophylactic administration of ampicillin was successful in three out of five ponies.

Ampicillin↗
PubMed1996

Three cases of carcinoid in the equine nasal cavity and maxillary sinuses: histologic and immunohistochemical features.

Three cases of carcinoid tumor in horses are described. The tumors originated from the maxillary sinuses and the retrobulbar region and caused exophthalmos. Histologically, they had a characteristic endocrine pattern and were argyrophilic with the Grimelius stain. All tumors contained reactivity for neuron-specific enolase and synaptophysin. Two of three tumors were reactive for both bovine and porcine chromogranin A. These immunohistochemical results confirm the neuroendocrine nature of these tumors. Neuroendocrine cells could not be detected in the nasal mucosa and maxillary sinuses of a normal horse; therefore, the origin of these carcinoid tumors remains obscure.

Animals↗
PubMed1995

Therapy of bovine ocular squamous-cell carcinoma with local doses of interleukin-2: 67% complete regressions after 20 months of follow-up.

We have tested the therapeutic potency of peritumorally injected low doses of interleukin-2 (IL-2). Seventy tumours of the bovine ocular squamous-cell carcinoma (BOSCC), 1-3 cm in diameter, were treated with 5000, 20,000 or 200,000 U IL-2 from Eurocetus (Chiron) to find the optimal dose for treatment. Injections were given peritumorally on Monday to Friday on 2 consecutive weeks. The size of the tumours was measured before treatment and 1, 3, 4, 9 and 20 months after treatment. After 9 months complete regression was observed in 89% of the tumours treated with 5000 U IL-2, 80% treated with 20,000 U and 67% treated with 200,000 U. After 20 months, there was complete regression of 35%, 31% and 67% of the tumours respectively. The 9- and 20-month results of the 200,000-U treatment are significantly better than those of the 5000-U and 20,000-U treatments taken together. This protocol may be useful to treat advanced inoperable tumours (e.g. of the nasopharynx or skin) of human patients.

Animals↗
PubMed1995

Ocular squamous cell carcinoma in Simmental cattle in Zimbabwe.

In Zimbabwe, ocular squamous cell carcinoma (OSCC) was frequently observed in 5 breeding herds of Simmental cattle, a Bos taurus breed originating from Switzerland. In these herds, initial signs of OSCC were already noticeable in cattle about 3 years old. Gradually, OSCC prevalence increased, and 36 to 53% of cattle over 7 years old had 1 or more tumors. More tumors developed in Simmental cattle with periorbital white skin than in cattle with periorbital pigmented skin. Other breeds of cattle (eg, Friesian) also are partly white-faced and live in Zimbabwe in a comparable environment; yet, OSCC prevalence was lower in those breeds.

Aging↗
PubMed1994

[Differential diagnosis of non-healing 'fungal'patches in horses].

Dermatophytosis is the most common equine skin disease. Mycotic-like lesions that do not disappear are suspected of being sarcoids. The clinical symptoms and therapeutic interventions for both affections are discussed. A short review of the differential diagnoses is presented.

Animals↗