Early Biochemical and Clinical Responses to Cobalamin Supplementation in Cats with Signs of Gastrointestinal Disease and Severe Hypocobalaminemia
ABSTRACT Domestic cats with small intestinal disease may develop cobalamin deficiency because of reduced small intestinal uptake of this vitamin. This study assessed the impact of cobalamin deficiency on biochemical and clinical findings in cats with intestinal disease. Nineteen pet cats, all with severe hypocobalaminemia (< or =100 ng/L) and histories of gastrointestinal signs, were studied. Cats received cobalamin, 250 microg SC once weekly, for 4 weeks. Biochemical indices of cobalamin availability (e.g., serum methylmalonic acid, homocysteine, and cysteine concentrations), serum feline trypsinlike immunoreactivity (fTLI) and serum folate concentrations, and clinical findings were recorded at the start of the study and after 4 weeks of cobalamin therapy. Serum methylmalonic acid (MMA) concentrations (median; range) decreased after cobalamin supplementation (5373.0; 708.5-29,329.0 versus 423.5; 214.0-7219.0 nmol/L, P < .0001). Serum homocysteine concentrations were not significantly altered (mean +/- SD 8.2 +/- 2.9 versus 10.3 +/- 4.5 micromol/L, P = .1198), whereas cysteine concentrations increased significantly (122.3 +/- 38.8 versus 191.5 +/- 29.4 micromol/L, P < .0001). Mean body weight increased significantly after cobalamin therapy (3.8 +/- 1.1 versus 4.1 +/- 1 kg, P < .01), and the average body weight gain was 8.2%. Significant linear relationships were observed between alterations in serum MMA and fTLI concentrations and the percentage body weight change (P < .05 for both, Pearson r2 = 0.26 and 0.245, respectively). Mean serum folate concentration decreased significantly (mean +/- SD 19 +/- 5 microg/L versus 15.4 +/- 6.2 microg/L, P < .001). Reduced vomiting and diarrhea were observed in 7 of 9 and 5 of 13 cats, respectively. These results suggest that cobalamin supplementation in cats with small intestinal disease and severe hypocobalaminemia is associated with normalization of biochemical test results and improvements in clinical findings in most affected cats.
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- "has been shown to normalize serum MMA concentrations after 4 weeks of therapy (Ruaux et al., 2005). The recommendations for dose frequency and recheck schedule beyond 4 weeks are empirical, and are based on the author's own clinical experience and that of collaborators/co-investigators at the Gastrointestinal Laboratory at Texas A&M University. "
ABSTRACT: Measurement of the water-soluble vitamin cobalamin has long been of interest as a marker of gastrointestinal disease in companion animals due to the highly localized presence of cobalamin receptors in the ileum. An increasing body of evidence suggests that cobalamin deficiency is an important co-morbidity in many companion animal patients with gastrointestinal and pancreatic disease. Congenital disorders of cobalamin absorption and cellular metabolism are also increasingly recognized in companion animal breeds. The early recognition of these disorders and timely treatment with parenteral cobalamin can be life-saving. In this article, the normal mechanisms of cobalamin absorption, the use of cobalamin as a marker of intestinal disease and data on the prevalence of hypocobalaminemia in a variety of diseases are described. The prognostic impact of and rational therapy for hypocobalaminemia in domestic animals are discussed.The Veterinary Journal 03/2013; 196. DOI:10.1016/j.tvjl.2013.01.025 · 2.17 Impact Factor
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ABSTRACT: INTRODUCTION Diseases of the gastrointestinal tract are a common cause for dogs and cats to be presented to a veterinarian. In a recent study of new insurance claims for pets in the UK, 13.9% of new claims for dogs and 11.8% of all new claims for cats were related to gastrointestinal problems. 1 There are a wide variety of causes of clinical signs of gastrointestinal disease, such as vomiting, diarrhea, weight loss, and others. In order to arrive at the most appropriate diagnosis, veterinarians need to employ diagnostic tests. While no diagnostic test is always positive in a patient with a certain disease and no diagnostic test is always negative in a patient without the disease, the clinician needs to strive to use the tests with the highest clinical accuracy possible. In addition to a high accuracy, diagnostic tests should also be economical and as minimally invasive as possible. Folate is a water-soluble B-vitamin (vitamin B 9) that is plentiful in most commercial pet foods. However, folate in the diet is mostly supplied as folate polyglutamate, which cannot be readily absorbed. In the proximal small intestine folate polyglutamate is deconjugated by folate deconjugase and the resulting folate monoglutamate is absorbed by specific folate carriers in the proximal small intestine. In patients with proximal small intestinal disease, both folate deconjugase and folate carriers can be destroyed. If the disease process is severe enough either folate polyglutamate is no longer deconjugated or folate monoglutamate is no longer absorbed, leading to folate malabsorption. If the condition continues for a significant period of time, folate body stores are depleted and serum folate concentration decreases. The same is true in patients with diffuse small intestinal disease as long as the proximal small intestine is involved in the disease process. Many bacterial species synthesize folate and it is believed that an increased number of bacterial species (i.e., small intestinal bacterial overgrowth) can lead to significant increases in serum folate concentrations.
Conference Paper: Clocking design and analysis for a 600 MHz Alpha microprocessor[Show abstract] [Hide abstract]
ABSTRACT: The clocking methodology for the 600 MHz Alpha microprocessor allows increased performance goals to be met through multi-level buffering. In addition power savings are realized through reduced metal usage and conditional clocks. Two distinct analysis methods are required to verify the clock design. One is used for large, globally distributed clocks and the other is applied to small, locally distributed clocks. The clock is generated from an 80-200 MHz reference clock multiplied by an on-chip phase-locked loop (PLL) to a nominal frequency of 600 MHz. The clock distribution network up to and including the global clock (GCLK) is included in the feedback loop of the PLL to control phase alignment. GCLK is the primary timing reference for the chip. The generation of GCLK begins at the PLL and is routed through a high-gain buffer network to a central point on the die. From there the clock is driven through buffered X, H and RC trees to distributed GCLK drivers located in a windowpane pattern across the chip. The final physical stage of the global clock distribution network is a grid of upper-level low-impedance metal that covers the entire dieSolid-State Circuits Conference, 1998. Digest of Technical Papers. 1998 IEEE International; 03/1998