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Biomedical subjects

Urs Giger

Publications and source records attributed to Urs Giger.

At least 19 recordsLinked to original sources

Inherited metabolic disease in companion animals: searching for nature's mistakes.

Inborn errors of metabolism are caused by genetic defects in intermediary metabolic pathways. Although long considered to be the domain of human paediatric medicine, they are also recognised with increasing frequency in companion animals. The diagnosis of diseased animals can be achieved by searching for abnormal metabolites in body fluids, although such screening programmes have, until now, not been widely available to the small animal clinician. A comprehensive battery of analytical tools exists for screening for inborn metabolic diseases in humans which can be applied to animals and serve not only for the diagnosis of affected patients but also to detect asymptomatic carriers and further our understanding of metabolic pathways in dogs and cats. Moreover, naturally occurring animal models of inherited metabolic diseases provide a unique opportunity to study the biochemical and molecular pathogenesis of these disorders and to investigate possible therapeutic options.

Animals↗

Prevalence of DNA of Mycoplasma haemofelis, 'Candidatus Mycoplasma haemominutum,' Anaplasma phagocytophilum, and species of Bartonella, Neorickettsia, and Ehrlichia in cats used as blood donors in the United States.

OBJECTIVE: To identify the prevalence of DNA of Mycoplasma haemofelis; 'Candidatus Mycoplasma haemominutum'; Anaplasma phagocytophilum; and species of Bartonella, Neorickettsia, and Ehrlichia in blood of cats used as blood donors in the United States. DESIGN: Prospective study. ANIMALS: 146 cats that were active blood donors. PROCEDURES: Environmental history was requested for each blood-donor cat from which a blood sample (mixed with EDTA) was available. Polymerase chain reaction assays capable of amplifying the DNA of the microorganisms of interest following DNA extraction from blood were performed. RESULTS: Overall, DNA of one or more of the infectious agents was detected in blood samples from 16 of 146 (11%) feline blood donors. Twenty-eight laboratory-reared cats housed in a teaching hospital had negative results for DNA of all organisms investigated. The DNA of at least 1 infectious agent was amplified from blood samples collected from 16 of 118 (13.6%) community-source cats; assay results were positive for 'Candidatus M haemominutum,' M haemofelis, or Bartonella henselae alone or in various combinations. Of the community-source cats allowed outdoors (n = 61) or with known flea exposure (44), DNA for a hemoplasma or B henselae was detected in 21.3% and 22.7%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: When community-source cats, cats allowed outdoors, or cats exposed to fleas are to be used as blood donors, they should be regularly assessed for infection with M haemofelis, 'Candidatus M haemominutum,' and Bartonella spp, and flea-control treatment should be regularly provided.

Anaplasma phagocytophilum↗

A frame shift mutation in canine TPP1 (the ortholog of human CLN2) in a juvenile Dachshund with neuronal ceroid lipofuscinosis.

The neuronal ceroid lipofuscinoses (NCLs) are inherited lysosomal storage diseases characterized by progressive neuropathy and the accumulation of autofluorescent cytoplasmic granules. Clinical signs of a new canine NCL began in a 9-month-old male Dachshund with vomiting, mental dullness, and loss of previously learned commands and rapidly progressed to include disorientation, ataxia, visual deficits, generalized myoclonic seizures, and death at 12 months of age. Neurons throughout the CNS contained autofluorescent storage granules that stained with periodic acid-Schiff and Luxol fast blue stains. Electron microscopy revealed that the storage granule contents consisted of curvilinear-appearing material characteristic of human late infantile NCL caused by CLN2 mutations. Nucleotide sequence analysis of canine TPP1, the ortholog of human CLN2, revealed a single nucleotide deletion in exon 4 which predicted a frame shift with a premature stop codon. Brain tissue from the affected dog lacked detectable activity of the tripeptidyl-peptidase enzyme encoded by TPP1, whereas the specific activities of 15 other lysosomal enzymes were higher than those in the brains of three control dogs. The affected Dachshund was homozygous for the mutant c.325delC allele, his sire and dam were heterozygotes, and 181 unrelated dogs, including 77 Dachshunds, were all homozygous for the wild-type allele. A DNA assay that detects the mutant allele will help Dachshund breeders avoid producing affected puppies in future generations. Furthermore, this Dachshund NCL may prove to be a useful model for studying the pathogenesis of neurodegeneration in human late infantile NCL and for evaluating novel therapeutic interventions for this disease.

Aminopeptidases↗

Laparoscopic surgery for benign lesions of the pancreas.

BACKGROUND: Minimally invasive pancreatic surgery, although known to be feasible and safe, is still not considered a standard procedure. We report our experience with laparoscopic pancreatic surgery in a retrospective case series. MATERIALS AND METHODS: Fifteen consecutive patients (3 male, 12 female) underwent primarily laparoscopic pancreatic surgery from February 2000 to June 2005. Histologically confirmed diagnoses were: neuroendocrine pancreatic tumors (n = 11), adult nesidioblastosis (n = 1), serous cystadenoma (n = 1), and pseudocysts due to chronic pancreatitis (n = 2). RESULTS: Enucleation (n = 3) or left pancreatic resection with spleen preservation (n = 6) was performed laparoscopically in 9 patients. The mean (+/-standard deviation) operative time was 173 +/- 48 minutes (range, 120-250 minutes) and the mean postoperative hospital stay was 5.5 +/- 1.2 days (range, 5-8 days) for the laparoscopic cases. Conversion to open surgery was necessary in 6 patients because of: closeness of the lesion to the portal/mesenteric vein (n = 3), inadequate intraoperative tumor localization (n = 2), or stapler device dysfunction (n = 1). In these patients, open enucleation (n = 1), middle segment pancreatectomy (n = 2), left pancreatic resection (n = 2), and pylorus-preserving Whipple resection (n = 1) were performed. The mean operative time was 268 +/- 74 minutes (range, 150-360 minutes) with a mean postoperative hospital stay of 8 +/- 2 days (range, 6-10 days). Both operative time and hospital stay were significantly longer in patients with secondary open surgery compared to patients with successful laparoscopic operations. CONCLUSION: Laparoscopic enucleation or distal pancreatectomy with spleen preservation for benign lesions located in the body or tail of the pancreas can be performed safely, with all the potential benefits of minimally invasive surgery. Preoperative tumor localization is of utmost importance to limit pancreatic mobilization and to avoid blind pancreatic resection and conversion to open surgery.

Adult↗

Impact of time-limited feeding and dietary carbohydrate content on weight loss in group-housed cats.

Twenty-four adult cats were transitioned to time-limited feeding and randomized to either a dry low carbohydrate diet (LC) or a dry reduced energy diet (HC). In Trial 1 the LC and HC groups received equal amounts of food (by weight) for 13 weeks. Both groups consumed all food offered, hence the LC group received more energy/day than the HC group. In Trial 2 all cats were fed the LC diet for 12 weeks, but each group received the energy that the opposite group had received in Trial 1. In Trial 1 only the overweight HC cats (body condition score> 6/9) experienced a significant change in body weight (-0.52 +/- 0.08 kg). In Trial 2, LC/Low Calorie overweight cats lost 0.62 +/- 0.10 kg, whereas, the LC/High Calorie normal weight cats gained 0.68 +/- 0.05 kg. In conclusion, body condition and energy intake but not type of diet influenced weight in this cohort of group-housed cats.

Animals↗

Amnionless function is required for cubilin brush-border expression and intrinsic factor-cobalamin (vitamin B12) absorption in vivo.

Amnionless (AMN) and cubilin gene products appear to be essential functional subunits of an endocytic receptor called cubam. Mutation of either gene causes autosomal recessive Imerslund-Gräsbeck syndrome (I-GS, OMIM no. 261100) in humans, a disorder characterized by selective intestinal malabsorption of cobalamin (vitamin B12) and urinary loss of several specific low-molecular-weight proteins. Vital insight into the molecular pathology of I-GS has been obtained from studies of dogs with a similar syndrome. In this work, we show that I-GS segregates in a large canine kindred due to an in-frame deletion of 33 nucleotides in exon 10 of AMN. In a second, unrelated I-GS kindred, affected dogs exhibit a homozygous substitution in the AMN translation initiation codon. Studies in vivo demonstrated that both mutations abrogate AMN expression and block cubilin processing and targeting to the apical membrane. The essential features of AMN dysfunction observed in vivo are recapitulated in a heterologous cell-transfection system, thus validating the system for analysis of AMN-cubilin interactions. Characterization of canine AMN mutations that cause I-GS establishes the canine model as an ortholog of the human disorder well suited to studies of AMN function and coevolution with cubilin.

Animals↗

Bleeding remains a major complication during laparoscopic surgery: analysis of the SALTS database.

BACKGROUND AND AIMS: The aim of this study was to determine the incidence of bleeding complications from various laparoscopic procedures in a nationwide prospective multicentre study in Switzerland from 1995 to 2001 following an initial learning curve. PATIENTS AND METHODS: Since 1989, the Swiss Association of Laparoscopic and Thoracoscopic Surgery (SALTS) has prospectively collected data from patients undergoing laparoscopic or thoracoscopic surgery at 114 surgical institutions (university, county and district hospitals, private practice). More than 130 items of data, including indication for surgery, intraoperative course, local as well as general postoperative complications, mortality and follow-up were recorded on a computerised data sheet. RESULTS: Some 43,028 procedures were assessed and analysed. Local morbidity (e.g. wound infections) occurred in 0.05% of the whole patient group, whereas 3.3% developed general postoperative complications. The overall mortality rate was 0.2%. In 1.7% of the cases, the intraoperative course was complicated by internal bleeding or haematoma of the abdominal wall. In the postoperative course, 1.5% of the patients presented with internal bleeding or bleeding of the abdominal wall. Major vascular injury occurred in 0.09%. This patient group with bleeding complications was analysed in the context of the operator's experience, instrumental lesions (Veress needle or trocar) and conversion incidence. Furthermore, a trend analysis of the complication rate from 1995 to 2001 was performed. CONCLUSION: Although the initial learning curve of laparoscopic procedures is probably finished, the rate of bleeding complications is still substantial. These results demonstrate that the collection of data in the form of multicentre studies is essential for quality control. It permits recognition and understanding of the current problems in laparoscopic surgery in order to improve the quality of daily surgical practice. The fact that the operator's experience seems to play an important role shows that improvement in learning and teaching programmes is still necessary and should be coordinated on a national basis.

Adolescent↗

Comparison of various canine blood-typing methods.

OBJECTIVE: To compare canine blood-typing results determined by use of the card (CARD), gel (GEL), Michigan State University (MSU), and tube (TUBE) tests. SAMPLE POPULATION: Blood samples from 23 healthy dogs. PROCEDURES: Blood samples anticoagulated with EDTA were screened by use of each blood-typing method according to manufacturers' protocols. RESULTS: Strong RBC agglutination reactions were observed with dog erythrocyte antigen (DEA) 1.1 reagents of the CARD and GEL tests as well as MSU test (only after adding Coombs' reagent) in 9 blood samples. By use of the CARD test, RBCs from 4 additional dogs agglutinated weakly; on the basis of MSU test results, these 4 dogs were classified as DEA 1.2 positive. All blood samples agglutinated with the B antigen reagent of the TUBE test. All but 2 blood samples had strong positive reactions with the DEA 4 reagent of the MSU test. All but 3 blood samples reacted with the E antigen reagent of the TUBE test. Three blood samples agglutinated with the DEA 3 reagent of the MSU test and A antigen reagent of the TUBE test. Five blood samples had strong agglutination reactions with the DEA 5 reagent of the MSU test. CONCLUSIONS AND CLINICAL RELEVANCE: Use of the CARD test allows for rapid identification of DEA 1.1 but may produce weak reactions with blood from DEA 1.2-positive dogs. The GEL test is a reliable and rapid clinical laboratory method for identification of DEA 1.1. The MSU test requires Coombs' reagent for identification of DEA 1.1 and 1.2.

Animals↗

Comparison of various blood-typing methods for the feline AB blood group system.

OBJECTIVE: To compare feline blood-typing results determined by use of the card (CARD), gel (GEL), tube (TUBE), University of Pennsylvania (Penn) tube, and Penn slide tests. SAMPLE POPULATION: Blood samples from 38 healthy cats. PROCEDURES: Blood samples, anticoagulated with EDTA, were screened by use of each blood-typing method according to manufacturers' protocols. RESULTS: On the basis of the standard Penn tube and slide test results, 20, 11, and 7 cats were classified as type A positive, type B positive, and type AB positive, respectively. The same results were obtained with the anti-B and anti-B reagents of the TUBE test. Use of anti-A antibodies of original polyclonal and current monoclonal CARD tests resulted in mostly 2+ to 3+ (scale, 0 to 4+) agglutination reactions with blood samples from type A-positive cats; agglutination reactions with blood samples from type AB-positive cats were weak (1+). The anti-B lectin of the CARD test induced a 2+ to 4+ reaction with blood from all type B- and type AB-positive cats. Use of the GEL test allowed recognition of type A and type B blood samples; following addition of anti-A serum to control columns, type B blood was differentiated from type AB blood. CONCLUSIONS AND CLINICAL RELEVANCE: Use of the in-practice CARD test allows identification of type A- and type B-positive cats, but weak reactions of type AB blood with the anti-A monoclonal antibody raise concerns. The modified GEL and TUBE tests appear to be reliable clinical laboratory methods for feline blood typing.

Animals↗

Effect of desmopressin on von Willebrand factor multimers in Doberman Pinschers with type 1 von Willebrand disease.

OBJECTIVE: To assess the effect of desmopressin (DDAVP) administration in Doberman Pinschers with type 1 von Willebrand disease (vWD) on plasma von Willebrand factor (vWF) multimers through determination of vWF collagen binding activity (vWF:CBA; a functional vWF assay dependent on the presence of high-molecular-weight [HMWI multimers), comparison of vWF antigen concentration (vWF:Ag) to vWF:CBA, and vWF multimer size distribution. ANIMALS: 16 Doberman Pinschers with type 1 vWD and 5 clinically normal control dogs. PROCEDURE: Plasma vWF:Ag and vWF:CBA assays and vWF multimer analysis were performed before and 1 hour after administration of DDAVP (1 microg/kg, SC). RESULTS: Following DDAVP administration, dogs with type 1 vWD had an increase in mean baseline values of plasma vWF:Ag and vWF:CBA from 10% to 17% for both variables. The mean vWF Ag:CBA ratio at baseline (0.95) was similar after DDAVP administration (0.97), indicating concordant increases in plasma vWF concentration and activity. In control dogs, mean plasma vWF:Ag and vWF:CBA increased from baseline values of 64% to 113% and 58% to 114%, respectively, and the vWF Ag:CBA ratios were unchanged (1.1 vs 1.0) after DDAVP administration. Plasma vWF multimer analysis revealed proportional increases in band intensity for all multimer sizes following DDAVP administration, in comparison to baseline for the control dogs and Doberman Pinschers with vWD, consistent with vWF Ag:CBA ratios of approximately 1. CONCLUSIONS AND CLINICAL RELEVANCE: Beneficial effects of DDAVP on primary hemostasis in Doberman Pinschers with type 1 vWD cannot be explained by preferential increases in HMW vWF multimers.

Animals↗

Mucopolysaccharidosis type VII in a German Shepherd Dog.

A 12-week-old male German Shepherd Dog was evaluated because of a 3-week history of a progressive inability to ambulate. Clinical and laboratory findings included skeletal deformities, corneal cloudiness, cytoplasmic granules in the neutrophils and lymphocytes of blood and CSF and glycosaminoglycans in a urine sample (detected via a toluidine blue spot test). Enzyme activity and DNA analyses confirmed mucopolysaccharidosis type VII as a result of severe beta-glucuronidase deficiency; this condition had been identified in a mixed-breed dog (likely of German Shepherd Dog descent) that was reported 20 years earlier and caused by the same missense mutation. Because of the progressive nature of this disease, the puppy was euthanatized and all tissues examined contained evidence of lysosomal storage leading to marked cellular distention. Mucopolysaccharidosis type VII is only one of many hereditary lysosomal storage diseases identified in companion animals. It is important that clinicians recognize the typical signs of lysosomal storage diseases and are aware of the cytologic and urinary screening tests for mucopolysaccharidosis disorders. Furthermore, there are specific blood enzyme and DNA-based tests to distinguish the forms of mucopolysaccharidosis in affected and carrier animals.

Animals↗

Management of chronic pancreatitis.

Chronic pancreatitis (CP) is an inflammatory disorder that results in permanent impairment of the glandular anatomy of the pancreas with or without functional abnormalities. The pathogenesis of CP is usually unclear, except in the case of alcohol-induced disease. The most common symptoms of CP are abdominal pain, diarrhea, and weight loss often requiring recurring hospitalization. Over time, pancreatic endocrine and exocrine dysfunction may develop as the disease progresses, and a variety of complications can occur. Among the possible complications are nutrient malabsorption and diabetes mellitus. The treatment of CP is difficult and challenging for every physician. Relieving pain is the first step in treating CP. This symptom needs to be controlled, often with narcotics, which can cause dependence. Diarrhea usually indicates the presence of steatorrhea, which is often treated with a high-calorie, high-protein, and low-fat diet to minimize symptoms of the underlying disease and to promote weight retention or gain. Pancreatic replacement therapy is used to combat maldigestion and malabsorption. Patients with diabetes may need insulin therapy for glycemic control. The use of parenteral nutrition for bowel rest is a standard approach in patients with symptomatic CP. The use of jejunal enteral feeding recently has been evaluated for efficacy in CP patients. The role of pancreatic endotherapy in the management of CP is evolving. Several reports have suggested that endoscopic therapy aimed at decompressing the obstructed pancreatic duct can be associated with pain relief in some patients. Surgery should be considered in patients who fail medical therapy.

Journal Article↗

Evaluation of erythropoiesis and changes in serum erythropoietin concentration in cats after renal transplantation.

OBJECTIVE: To investigate the clinicopathologic patterns of the erythropoietic response after renal transplantation in cats with chronic renal failure (CRF). ANIMALS: 14 cats with CRF undergoing renal transplantation. PROCEDURE: Before and at intervals during a 6-month period after transplantation, serum creatinine and erythropoietin concentrations, Hct, erythrocyte indices, aggregate reticulocyte percentage, and iron variables were measured. Additionally, the number of transfusions administered to and any complications that developed in each cat were recorded. RESULTS: In all cats, preoperative azotemia resolved within 6 days after renal transplantation. Two cats had a temporary increase in serum creatinine concentration secondary to an acute graft rejection episode. Anemia (defined as Hct < 28%) resolved in 10 cats 3 to 49 days after surgery. Resolution of anemia was delayed in 2 cats that had acute rejection episodes. Serum erythropoietin concentration and reticulocyte percentage were low preoperatively; values after surgery were highly variable. Compared with preoperative values, serum erythropoietin concentration increased 1 to 4 days after surgery in 11 cats; between days 5 and 58, another increase was detected in 9 cats. Serum iron concentrations were generally low before and 14 days after transplantation. CONCLUSION AND CLINICAL RELEVANCE: The erythropoietic response was highly variable in cats after renal transplantation, but anemia typically resolved within 1 month after surgery. A delay in resolution of anemia in cats may indicate poor graft function and inadequate iron stores, suggesting the need for further evaluation for concurrent illness.

Animals↗

Evaluation of a canine D-dimer point-of-care test kit for use in samples obtained from dogs with disseminated intravascular coagulation, thromboembolic disease, and hemorrhage.

OBJECTIVE: To evaluate a canine D-dimer point-of-care (cD-d POC) test kit for use in healthy dogs and dogs with disseminated intravascular coagulation (DIC), thromboembolic disease (TED), and hemorrhage. ANIMALS: 12 healthy dogs, 18 dogs with DIC, 23 dogs with TED (19 acute and 4 chronic), and 18 dogs with hemorrhage. PROCEDURE: The cD-d POC, canine D-dimer ELISA (cD-d ELISA), human D-dimer latex agglutination (hD-d LA), and fibrin degradation product (FDP) tests were performed on citrated plasma. RESULTS: All healthy dogs had negative cD-d POC test results and mean cD-d ELISA value of 0.2 U/mL. All dogs with DIC had positive cD-d POC test results and mean cD-d ELISA value of 44 U/mL. Dogs with acuteTED had a mean cD-d ELISA value of 34 U/mL, and 17 of 19 had positive cD-d POC test results. Mean cD-d ELISA value in dogs with hemorrhage was 14 units/mL, and 15 of 18 had positive cD-d POC test results. The cD-d ELISA values in dogs with hemorrhage were significantly higher than those of healthy dogs but lower than those of dogs with DIC and acute TED. The cD-d POC, cD-d ELISA, and hD-d LA tests were comparable in differentiating healthy dogs from dogs with DIC, acute TED, or hemorrhage and appeared to be superior to measurement of FDPs. CONCLUSIONS AND CLINICAL RELEVANCE: The cD-d POC test kit can be quickly and easily used and reliably detects dogs with DIC or acute TED. Positive results may also be seen in dogs with internal hemorrhage.

Animals↗

Use of a hemoglobin-based oxygen-carrying solution in cats: 72 cases (1998-2000).

OBJECTIVE: To determine clinical features and outcome associated with use of a hemoglobin-based oxygen-carrying (HBOC) solution in cats. DESIGN: Retrospective study. ANIMALS: 72 cats. PROCEDURE: Medical records of cats that received an HBOC solution were reviewed. RESULTS: The most common clinical signs and physical examination findings prior to infusion of the HBOC solution were associated with anemia; vomiting, neurologic signs, and respiratory abnormalities were also detected. The HBOC solution was given as a supportive measure in treatment of anemia in 70 cats, most often because compatible blood was not readily available. There were 80 separate HBOC solution infusion events (mean dose, 14.6 ml/kg [6.6 mg/lb]; mean rate of infusion, 4.8 ml/kg [2.2 ml/lb] per hour). Improvements in 37 of 43 of the more closely monitored cats included increased rectal temperature, blood hemoglobin concentration, blood pressure, appetite, and activity. Adverse events in 44 cats included pulmonary edema (n = 8), pleural effusion (21), mucous membrane discoloration (21), pigmenturia (11), vomiting (4), and neurologic abnormalities (4). Twenty-three cats were discharged from the hospital, and 49 cats died or were euthanatized. Necropsy examination of 23 cats did not reveal evidence of renal or hepatic toxicosis associated with HBOC administration. CONCLUSIONS AND CLINICAL RELEVANCE: Although administration of an HBOC solution may provide temporary support to anemic cats, the development of pulmonary edema or pleural effusion potentially associated with rapid infusion rate and large volume of infusion of the HBOC solution should be investigated further before use of the solution can be recommended in cats.

Anemia↗

Comparison of platelet count recovery with use of vincristine and prednisone or prednisone alone for treatment for severe immune-mediated thrombocytopenia in dogs.

OBJECTIVE: To evaluate the effect of prednisone alone, compared with a combination of prednisone and vincristine, on platelet counts in bleeding dogs with severe primary immune-mediated thrombocytopenia (IMT). DESIGN: Prospective case study. ANIMALS: 24 dogs with severe primary IMT PROCEDURE: All dogs received immunosuppressive doses of prednisone (1.5 to 2 mg/kg [0.7 to 0.9 mg/lb] of body weight, PO, q 12 h). In addition, 12 dogs received a single dose of vincristine (0.02 mg/kg [0.01 mg/lb], IV). Platelet count, transfusion requirement, and outcome were monitored. A response was defined as an increase in platelet count to > or = 40,000/microl. Dogs in the prednisone group that failed to respond received 1 dose of vincristine on day 7. RESULTS: Dogs that received prednisone and vincristine had a significantly faster increase in platelet count to > or = 40,000 platelets/microl than dogs that received prednisone alone (mean +/- SD, 4.9 +/- 1.1 vs 6.8 +/- 4.5 days, respectively). A similarly rapid response was observed in dogs that received vincristine on day 7 after treatment with prednisone alone failed. Furthermore, duration of hospitalization was reduced in the vincristine group, compared with the prednisone group (5.4 +/- 0.3 vs 7.3 +/- 0.5 days, respectively). No adverse effects attributable to vincristine were observed in any dog. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of combined vincristine and prednisone is associated with more rapid increase in platelet numbers and shortened duration of hospitalization in dogs with IMT, compared with use of prednisone alone. Early use of vincristine seems warranted in dogs with severe primary IMT.

Animals↗