Large granular lymphocyte lymphoma with leukemic phase and suspicion of leptomeningeal lymphomatosis in a cat - a case report.

INTRODUCTION: In this case report we present a feline large granular lymphocyte (LGL) lymphoma, a rare morphologically distinct subtype of lymphoma, in a twelve-year-old female spayed domestic short hair cat, with high suspicion of leptomeningeal lymphomatosis due to magnetic resonance imaging findings and results of cerebral spinal fluid analyses. Diagnosis of LGL lymphoma was confirmed by means of blood cytology and polymerase chain reaction for antigen receptor rearrangements.

INTRODUCTION: Dans ce rapport de cas, nous présentons un Large Granular Lymphocyte (LGL) lymphome, un sous-type rare de lymphome, chez une chatte domestique à poil court stérilisée de douze ans, avec une forte suspicion de lymphomatose leptoméningée en raison des résultats de l'imagerie par résonance magnétique et de l'analyse du liquide céphalo-rachidien. Le diagnostic de LGL-lymphome a été confirmé par une cytologie sanguine et une réaction en chaîne de la polymérase pour les réarrangements des récepteurs d'antigènes.

Informed Consent in Contrast-Enhanced CT: Understanding of Risks and Identification of Possible Prognostic Factors.

PURPOSE: Aim of our study was to assess understanding of risks associated with intravascular application of contrast media in patients undergoing CT examination. We wanted to evaluate epidemiologic and socio-economic prognostic factors for a higher understanding of risks. Additionally, we evaluated a possible correlation between an extensive, outcome-oriented oral informed consent and better understanding of risks. MATERIALS AND METHODS: 120 patients distributed in 2 study arms participated in this prospective study. In study arm I, the treating physician was not informed that his patients participated in a study whereas the physician in study arm II knew about the survey. After the informed consent we performed a standardized, semi-structured interview to enquire the 3 most frequent risks of intravascular application of contrast agents (anaphylactoid reactions, nephropathy and thyrotoxic crisis) and epidemiologic data. The understanding of the risks was evaluated using a 6 point scale. RESULTS: Patients scored 3.73 points in study arm I and 4.93 points in arm II on average. The statistical difference between both study arms was highly significant (p <0.001). In a combined logistic regression analysis, only "higher education" (p = 0.001) and participation in study arm II (p =0 .001) showed a significant connection to a better understanding of risks. CONCLUSION: Patients profit from an outcome-oriented and individualized informed consent. Due to the significant correlation between educational level and understanding of risks, informed consent should be adjusted to the educational status of the individual patient, e. g. by using didactic aids or individualized information sheets.

[Necrotizing granulomatous pneumonia caused by fungal infection in a goat]. / Granulomatös-nekrotisierende Pneumonie durch Schimmelpilzinfektion bei einer Ziege.

This case report describes the clinical and postmortem findings in a 2.5-year-old goat with necrotizing granulomatous pneumonia. The goat was referred to our clinic because of swelling of the head and neck, which was unresponsive to treatment, dysphagia, and deterioration in general condition. Thoracic radiographs showed two soft tissue densities, about 10 cm in diameter, in the left caudodorsal lung. The goat was euthanized and a necropsy was carried out. The two lesions in the left caudodorsal lung were round, firm and clearly demarcated from the surrounding lung tissue. They contained purulent material and compromised about 70 % of the diaphragmatic lung lobe. Histological examination of the lesions revealed a dense network of hyphae characteristic of Mucorales spp.

[Aorto-iliac thrombosis in a gelding: treatment with the anticoagulant Phenprocoumon (Marcoumar)]. / Aortenthrombose bei einem Wallach: Behandlung mit dem Antikoagulans Phenprocoumon (Marcoumar).

A 14-year old Swiss warmblood gelding was presented to the equine hospital of the University of Zurich because of therapy-resistant fever. An intermittent lameness suggested the presence of an intravascular aorto-iliac thrombus which was confirmed sonographically. Subsequently, treatment was initiated with Heparin s.c. and continued for 7 months with Phenprocoumon (Marcoumar). The dosage was monitored and adjusted according to the prothrombin time, which was initially measured every week, and later maximally biweekly. The lameness improved and the regression of the thrombus could be followed sonographically. Seven months later the horse had to be euthanized due to acute colic.

Contrast-enhanced power and color Doppler ultrasonography of the pancreas in healthy and diseased cats.

BACKGROUND: The diagnosis of feline pancreatic disease is difficult, because clinical abnormalities and routine noninvasive diagnostic tests are unreliable. OBJECTIVE: The purpose of this study was to investigate by Doppler ultrasonography if vascularity and blood volume differs in the otherwise ultrasonographically normal and diseased feline pancreas. ANIMALS: Thirty-six client owned cats. METHODS: The pancreas was examined with B-mode and contrast-enhanced color and power Doppler ultrasonography. Doppler images were analyzed with a computer program: parameter fractional area represents a vascularity index and color-weighted fractional area assesses blood volume. RESULTS: Based on the B-mode findings, the pancreas was considered normal in 11 clinically healthy cats and diseased in 25 cats of which 4 were clinically healthy and 21 had clinical signs consistent with pancreatic disease. Histologic or cytologic samples were taken in all diseased pancreata. Fifteen samples were of diagnostic quality: purulent or mixed cellular inflammation (8), nodular hyperplasia (4), and neoplasia (3) were identified. Vascularity and blood volume for all Doppler methods was significantly higher in cats with pancreatic disease. Significantly higher Doppler values were detected with power Doppler than with color Doppler, and with postcontrast color and power Doppler than with precontrast Doppler technologies. CONCLUSION: Contrast-enhanced Doppler ultrasonography appears feasible in the feline pancreas. Significant differences were found between normal cats and those with evidence of pancreatic pathology. Further studies are needed to evaluate its use for the differentiation of pancreatic disorders and in cats suspected to have pancreatic disease but without B-mode ultrasonographic changes of the pancreas.

[A case of alveolar hydatid disease in a dog: domestic animals as rare incidental intermediate hosts for Echinococcus multilocularis]. / Ein Fall von alveolärer Echinococcose beim Hund: Haustiere als seltene Fehlzwischenwirte von Echinococcus multilocularis.

A 2-years old male Labrador retriever dog was presented with intermittent therapy-resistant diarrhoea, accompanied by vomiting, inappetence, apathy, and mild fever. The blood analysis showed an anaemia, neutrophilia, eosinophilia, and increased liver enzymes. Abdominal palpation was slightly painful. X-rays and echography revealed a severely enlarged liver with multiple cavernous structures. Histopathologic examination of liver biopsies showed a severe chronic granulomatous hepatitis with numerous parasitic cysts. Morphology of the cysts was compatible with the metacestode stage of Echinococcus multilocularis. The dog was only 2-years old at the time of diagnosis. Although alveolar hydatid disease of the liver is rare in dogs, it should be envisaged as a possible differential diagnosis in cases of space-occupying processes in the liver, even in young animals, as the incubation period of this disease in the dog can be considerably shorter than in humans.

Glenoid dysplasia and bicipital tenosynovitis in a Maine coon cat.

This report describes a rare case of bicipital tenosynovitis in a Maine coon cat. The cat, a three-and-half-year-old neutered female, presented with chronic weightbearing lameness of the left forelimb. Flexion of the left glenohumeral joint and extension of the left cubital joint were resented, and palpation of the biceps brachii tendon in the bicipital groove elicited pain. A mild incongruity of the joint with mild degenerative changes was seen radiographically. Glenohumeral joint dysplasia was suspected. Ultrasound examination revealed marked thickening of the bicipital tendon and moderate effusion of the left bicipital tendon sheath. Positive contrast radiography of the joint confirmed dilation of the tendon sheath. A tentative diagnosis of bicipital tenosynovitis was made and confirmed on arthrotomy. Surgical removal of osteophytes resulted in the cat being free from pain but a mild lameness recurred six months after surgery.

The lumbosacral junction in working german shepherd dogs -- neurological and radiological evaluation.

The clinical and radiological incidence of lumbosacral (LS) disease was studied on 57 German Shepherd dogs (GSDs) used in active service. The study included a clinical history, a neurological examination, and plain radiographs of the caudal lumbar vertebrae. The neurological examinations revealed lower back pain and/or neural deficits in 21 dogs, of which 14 had a history of pain or pelvic gait abnormalities. Radiographic findings were spondylosis at L7-S1, degeneration of L7-S1 disc, LS malalignment, transitional LS vertebrae and/or primary spinal canal stenosis in 15 dogs with neurological abnormalities and/or back pain and in 18 dogs with no clinical signs. No correlation between the neurological and the radiographic findings were found. This study demonstrates that even prominent radiographic LS abnormalities are of minimal value in the evaluation of LS disease in the GSD.

Persistent truncus arteriosus and patent foramen ovale in a Simmentaler x Braunvieh calf.

A Simmentaler x Braunvieh calf had been anorexic during its first 36 hours of life, had a loud heart murmur and was suspected to have pneumonia. In the light of the results of radiographic and echocardiographic examinations, right heart catheterisation and angiography, a diagnosis of persistent truncus arteriosus and patent foramen ovale was made. The diagnosis was confirmed on postmortem examination.

Search for dietary antimutagens and anticarcinogens: methodological aspects and extrapolation problems.

It is well documented that dietary factors play a crucial role in the aetiology of human cancer and strong efforts have been made to identify protective (antimutagenic and anticarcinogenic) substances in foods. Although numerous studies have been published, it is problematic to use these results for the development of nutritional strategies. The aim of this article is a critical discussion of the pitfalls and problems associated with the search for protective compounds. The main obstacles in regard to the extrapolation of the data to the human situation arise from: (i) the use of inadequate experimental in vitro models, which do not reflect protective mechanisms in man and therefore give misleading results; (ii) the use of genotoxins and carcinogens that are not relevant for humans; (iii) the lack of knowledge about dose-effect relationships of DNA-protective and cancer protective dietary constituents; (iv) the use of exposure concentrations in animal models which exceed by far the human exposure levels; and finally (v) the lack of knowledge on the time-kinetics of protective effects. More relevant data can be expected from in vitro experiments with cells possessing inducible phase I and phase II enzymes, short-term in vivo models with laboratory animals which enable the measurement of effects in organs that are targets for tumour formation, and human biomonitoring studies in which endpoints are used that are related to DNA damage and cancer.

Protective effects of Brussels sprouts towards B[a]P-induced DNA damage: a model study with the single-cell gel electrophoresis (SCGE)/Hep G2 assay.

The aim of this study was to investigate the chemoprotective effects of Brussels sprouts juice towards benzo[a]pyrene (B(a)P)-induced DNA damage in the single-cell gel electrophoresis (SCGE)/Hep G2 test system. This assay combines the advantages of the SCGE assay with that of the use of human-derived cells possessing inducible phase I and phase II enzymes. Co-treatment of Hep G2 cells with small amounts of Brussels sprouts juice (0.25-2.0 microl/ml) and B(a)P reduced the genotoxic effect of the latter in a dose-dependent manner. Contrary to the results with the crude juice, unexpected synergistic effects were observed with allyl isothiocyanate (AITC, 1.0-6.0 microM), a breakdown product of sinigrin, which is the most abundant glucosinolate in Brussels sprouts. Although these concentrations of AITC did not cause DNA damage per se, at higher concentrations (> or =25 microM), the compound caused a pronounced dose-dependent DNA damage by itself. Mechanistic studies showed that Brussels sprouts juice causes induction of activities of ethoxyresorufin O-deethylase (EROD) and glutathione S-transferase (GST) at dose levels which were protective towards B(a)P. In combined treatment experiments with (+/-)-anti-benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE, 5.0 microM), the main genotoxic metabolite of B(a)P, and Brussels sprouts juice, only weak protection was found indicating that the mechanism of chemoprotection of Brussels sprouts is not mediated through inactivation of this metabolite. In conclusion, our findings show that Brussels sprouts are highly protective against B(a)P-induced DNA damage in human-derived cells.

Cafestol and kahweol, two coffee specific diterpenes with anticarcinogenic activity.

Epidemiological studies have found an inverse association between coffee consumption and the risk of certain types of cancers such as colorectal cancers. Animal data support such a chemopreventive effect of coffee. Substantial research has been devoted to the identification of coffee components that may be responsible for these beneficial effects. In animal models and cell culture systems, the coffee diterpenes cafestol and kahweol (C+K) were shown to produce a broad range of biochemical effects resulting in a reduction of the genotoxicity of several carcinogens including 7,12-dimethylbenz[a]anthracene (DMBA), aflatoxin B(1) (AFB(1)), benzo[a]pyrene (B[a]P) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Different mechanisms appear to be involved in these chemoprotective effects: an induction of conjugating enzymes (e.g. glutathione S-transferases, glucuronosyl S-transferases), an increased expression of proteins involved in cellular antioxidant defense (e.g. gamma-glutamyl cysteine synthetase and heme oxygenase-1) and an inhibition of the expression and/or activity of cytochromes P450 involved in carcinogen activation (e.g. CYP2C11, CYP3A2). In animal models, the C+K-mediated induction of conjugating and antioxidant enzymes has been observed in hepatic, intestinal and kidney tissues. In the small intestine, these inductions were shown to be mediated by Nrf2-dependent transcriptional activation. In vitro investigations obtained in cell cultures of human origin indicate that the effects and mechanisms observed in animal test systems with C+K are likely to be of relevance for humans. In human liver epithelial cell lines transfected to express AFB(1)-activating P450s, C+K treatment resulted in a reduction of AFB(1)-DNA binding. This protection was correlated with an induction of GST-mu, an enzyme known to be involved in AFB(1) detoxification. In addition, C+K was found to inhibit P450 2B6, one of the human enzymes responsible for AFB(1) activation. Altogether, the data on the biological effects of C+K provide a plausible hypothesis to explain some of the anticarcinogenic effects of coffee observed in human epidemiological studies and in animal experiments.

Effects of cruciferous vegetables and their constituents on drug metabolizing enzymes involved in the bioactivation of DNA-reactive dietary carcinogens.

Epidemiological studies give evidence that cruciferous vegetables (CF) protect humans against cancer, and also results from animal experiments show that they reduce chemically induced tumor formation. These properties have been attributed to alterations in the metabolism of carcinogens by breakdown products of glucosinolates, which are constituents of CF. The present article gives an overview on the present state of knowledge on the impact of CF and their constituents on enzymes that are involved in the metabolism of DNA-reactive carcinogens. The development of in vitro models with metabolically competent cell lines led to the detection of potent enzyme inducers contained in CF such as sulforaphane. Recently, we showed that Brassica juices induce glutathione-S-transferases (GST) and cytochrome P-450 1A2 in human hepatoma cells (HepG2) and protect against the genotoxic effects of B(a)P and other carcinogens. Earlier in vivo experiments with rodents indicated that indoles and isothiocyanates, two major groups of glucosinolate breakdown products, attenuate the effects of polycyclic aromatic hydrocarbons (PAHs) and nitrosamines via induction of GST and inhibition of cytochrome-P450 isoenzymes, respectively. Our own investigations showed that CF are also protective towards heterocyclic amines (HAs): Brussels sprouts- and garden cress juices attenuated IQ-induced DNA-damage and preneoplastic lesions in colon and liver of rats. These effects were paralleled by induction of uridine-di-phospho-glucuronosyl transferase (UDPGT) which is very probably the mechanism of protection against HAs by cruciferous vegetables. There is also evidence that consumption of CF might protect humans against cancer. In matched control intervention studies with these vegetables, it was shown that they induce GST-activities in humans but overall, results were inconclusive. Recently, we carried out crossover intervention studies and found pronounced GST-induction upon consumption of Brussels sprouts and red cabbage, whereas no effects were seen with white cabbage and broccoli. Furthermore, we found that the isoenzyme induced was GST-pi which plays an important role in protection against breast, bladder, colon and testicular cancer. No induction of the GST-alpha isoform could be detected. Urinary mutagenicity experiments gave further evidence that CF affect drug metabolism in humans. Consumption of red cabbage led to changes in the pattern of meat-derived urinary mutagenicity. Overall, CF are among the most promising chemopreventive dietary constituents and further elucidation of their protective mechanisms and the identification of active constituents may contribute to the development of highly protective Brassica varieties.

Comparison of the effect of native glucagon-like peptide 1 and dipeptidyl peptidase IV-resistant analogues on insulin release from rat pancreatic islets.

BACKGROUND: Glucagon-like peptide 1 (GLP-1) stimulates insulin secretion and may improve glycaemic control in type 2 diabetes. Therapeutic use is limited by its rapid degradation, primarily by dipeptidyl peptidase IV. MATERIALS AND METHODS: Five GLP-1 analogues with alterations at cleavage positions were synthesized according to the Fmoc strategy and tested for metabolic stability by incubation with rat kidney membranes containing dipeptidyl peptidase IV activity. Their insulinotropic effect was compared in isolated rat pancreatic islets after 24 h maintenance in tissue culture. Ten islets per vial were incubated for 30 min; insulin was measured radioimmunologically. Each analogue was compared with GLP-1 in the same experiment. RESULTS: All analogues were biologically active in isolated islets in the potency order da2d8 = da2 > d2d9 > da2ds8 > desamino. At 16.7 mmol L-1 glucose, GLP-1 and GLP-1 analogues altered as position 2, or 2 and 8 significantly (P < 0.05) increased insulin release at 10(-9) mol L-1. N-terminal modification of GLP-1 confers resistance to dipeptidyl peptidase IV degradation in rat kidney membranes in vitro. CONCLUSIONS: The analogues tested are biologically active and resistant to degradation by dipeptidyl peptidase IV. Their greater metabolic stability may help to realize the potential of GLP-1 analogues in diabetes therapy.

Biological activity of GLP-1-analogues with N-terminal modifications.

Glucagon-like peptide-1 (GLP-1) stimulates insulin secretion and improves glycemic control in type 2 diabetes. In serum the peptide is degraded by dipeptidyl peptidase IV (DPP IV). The resulting short biological half-time limits the therapeutic use of GLP-1. Therefore, various GLP-1 analogues with alterations in cleavage positions were synthesized. GLP-1-receptor binding was investigated in RINm5F cells. Biological activity of the GLP-1 analogues was investigated in vitro by measuring cAMP production in RINm5F cells. GLP-1 analogues with modifications in position 2 were not cleaved by DPP IV and showed receptor affinity and in vitro biological activity comparable to native GLP-1. Analogues with alterations in positions 2 and 8, 2 and 9 or 8 and 9 showed a significant decrease in receptor affinity and biological activity. In vivo biological activity was tested in pigs. GLP-1 analogues were administered subcutaneously followed by an intravenous bolus injection of glucose. Plasma glucose and insulin were monitored over 4 h. Compared to native GLP-1, analogues with an altered position 2 showed similar or increased potency and biological half-time. Other GLP-1 analogues were less active. Despite the lack of degradation of these GLP-1 analogues by DPP IV in vitro, their biological action is as short as that of GLP-1, except for desamino-GLP-1, indicating that other degradation enzymes are important in vivo. Alterations of GLP-1 in positions 8 or 9 result in a loss of biological activity without extending biological half-time.