Mark E. Peterson

Quality of life indexes for national policy: review and agenda for research

A number of governments and public policy institutes have developed “Quality of Life Indexes” – statistics that attempt to measure the quality of life for entire states or regions. We develop 14 criteria for determining the validity and usefulness of such QOL indexes to public policy. We then review 22 of the most-used QOL indexes from around the world. We conclude that many of the indexes are successful in that they are reliable, have established time series measures, and can be disaggregated to study subpopulations. However, many fall short in four areas: (1) indexes vary greatly in their coverage and definitions of domains of QOL, (2) none of the indexes distinguish among the concepts of input, throughput, and output that are used by public policy analysts, (3) they fail to show how QOL outputs are sensitive to public policy inputs, and (4) none have examined convergent validity against each other. We conclude that many of these indexes are potentially very useful for public policy and recommend research to further improve them.

Comparison of a low carbohydrate–low fiber diet and a moderate carbohydrate–high fiber diet in the management of feline diabetes mellitus⋆:

This study compared the effects of a moderate carbohydrate–high fiber (MC–HF) food and a low carbohydrate–low fiber (LC–LF) food on glycemic control in cats with diabetes mellitus. Sixty-three diabetic cats (48 male castrated, 15 female spayed) were randomly assigned to be fed either a canned MC–HF (n=32) food or a canned LC–LF (n=31) food for 16 weeks. Owners were blinded to the type of diet fed. CBC, urinalysis, serum chemistry panel, fructosamine concentration and thyroxine concentration were determined on initial examination, and a complete blood count, serum chemistry panel, urinalysis and serum fructosamine concentration were repeated every 4 weeks for 16 weeks. Insulin doses were adjusted as needed to resolve clinical signs and lower serum fructosamine concentrations. Serum glucose (P=0.0001) and fructosamine (P=0.0001) concentrations significantly decreased from week 0 to week 16 in both dietary groups. By week 16, significantly more of the cats fed the LC–LF food (68%, 22/31), compared to the cats fed the MC–HF food (41%, 13/32), had reverted to a non-insulin-dependent state (P=0.03). Cats in both groups were successfully taken off of insulin regardless of age, sex, type of insulin administered or duration of clinical disease before entering the study. There was no significant difference in the initial or final mean body weights or in the mean change in body weight from week 0 to week 16 between dietary groups. Diabetic cats in this study were significantly more likely to revert to a non-insulin-dependent state when fed the canned LC–LF food versus the MC–HF food.

Tranexamic acid concentrations associated with human seizures inhibit glycine receptors

Antifibrinolytic drugs are widely used to reduce blood loss during surgery. One serious adverse effect of these drugs is convulsive seizures; however, the mechanisms underlying such seizures remain poorly understood. The antifibrinolytic drugs tranexamic acid (TXA) and ε-aminocaproic acid (EACA) are structurally similar to the inhibitory neurotransmitter glycine. Since reduced function of glycine receptors causes seizures, we hypothesized that TXA and EACA inhibit the activity of glycine receptors. Here we demonstrate that TXA and EACA are competitive antagonists of glycine receptors in mice. We also showed that the general anesthetic isoflurane, and to a lesser extent propofol, reverses TXA inhibition of glycine receptor-mediated current, suggesting that these drugs could potentially be used to treat TXA-induced seizures. Finally, we measured the concentration of TXA in the cerebrospinal fluid (CSF) of patients undergoing major cardiovascular surgery. Surprisingly, peak TXA concentration in the CSF occurred after termination of drug infusion and in one patient coincided with the onset of seizures. Collectively, these results show that concentrations of TXA equivalent to those measured in the CSF of patients inhibited glycine receptors. Furthermore, isoflurane or propofol may prevent or reverse TXA-induced seizures.

Etiopathology of Feline Toxic Nodular Goiter

We have discussed the etiopathology of feline toxic nodular goiter in the context of human nodular goiter pathogenesis. We have reviewed thyroid heterogeneity, growth regulation, functional and growth autonomy, nodule and tumor formation, and the evolution of toxic nodular goiter in the human being. By addressing toxic nodular goiter of the cat, the history, morphologic findings, xenotransplantation and cell culture studies, evidence for and against circulating thyroid stimulators and epizootiological studies of the feline disease have been summarized. Due to its structure, the thyroid gland offers some unique possibilities to study the mechanisms that are responsible for cellular heterogeneity, the emergence of autonomous nodular growth and function, and, ultimately, the development of tumors. The demonstration of naturally occurring clones of cells with high intrinsic proliferation potential within the follicular epithelium of the thyroid has fostered promising new concepts on the genesis of nodular growth of benign and possibly malignant endocrine tumors. Hyperthyroid cat goiters contain single or multiple, autonomously (i.e., TSH-independently) functioning and growing nodules. Neither hyperfunction nor growth of these nodules depends on extrathyroidal circulating stimulators. The basic lesion appears to be an excessive intrinsic growth capacity of some thyroid cells. The factors enhancing the transformation of a normal thyroid into a nodular hyperfunctioning goiter over many years are still unknown. Immunological, environmental, and nutritional factors are the focus of ongoing studies, but an infectious agent can not yet be excluded.

Hyperthyroidism in cats: what's causing this epidemic of thyroid disease and can we prevent it?

Practical relevance: Since first being reported in the late 1970s, there has been a dramatic increase in the prevalence of hyperthyroidism in cats. It is now recognized worldwide as the most common feline endocrine disorder. Patient group: Hyperthyroidism is an important cause of morbidity in cats older than 10 years of age. It is estimated that over 10% of all senior cats will develop the disorder. Clinical challenges: Despite its frequency, the underlying cause(s) of this common disease is/are not known, and no one has suggested a means to prevent the disorder. Because of the multiple risk factors that have been described for feline hyperthyroidism, it is likely that more than one factor is involved in its pathogenesis. Continuous, lifelong exposure to environmental thyroid disruptor chemicals or goitrogens in food or water, acting together in an additive or synergistic manner, may first lead to euthyroid goiter and then to autonomous adenomatous hyperplasia, thyroid adenoma and hyperthyroidism. Evidence base: This review draws on published research studies to summarize the available evidence about the risk factors for feline hyperthyroidism. Based on the known goitrogens that may be present in the cat’s food, drinking water or environment, it proposes measures that cat owners can implement that might prevent, or reduce the prevalence of, thyroid tumors and hyperthyroidism in their cats.

Increased serum D-lactate associated with diabetic ketoacidosis.

We hypothesized that serum D-lactate may be increased in vivo in diabetes mellitus as a result of increased glucose flux through the glyoxalase pathway and/or via hepatic ketone metabolism. Levels of D-lactate and related metabolic intermediates were measured in 30 cats with spontaneous diabetes mellitus and in one ketoacidotic nondiabetic cat. Serum D-lactate was significantly (P = .0051) elevated in cats with ketoacidosis (337.2 +/- 70.2 mumol/L) as compared with nonketoacidotic diabetic (140.3 +/- 58.8) and control (25.0 + 6.5) cats. Two nonketoacidotic cats also had high levels of D-lactate. There was a significant linear correlation (r = .684, P = .0001) between D-lactate and beta-hydroxybutyrate concentrations. Serum D-lactate did not correlate with serum glucose (r = .078, P = .6825), and in vitro erythrocyte D-lactate formation did not increase in the presence of hyperglycemia. These data suggest that hepatic ketone metabolism, rather than hyperglycemia, may be a major source of serum D-lactate in diabetics.

Autonomy of growth and of iodine metabolism in hyperthyroid feline goiters transplanted onto nude mice.

Hyperthyroidism caused by nodular goiters is a common disease of aging cats. Growth and iodine metabolism were studied by autoradiography in normal and hyperfunctioning thyroid tissue obtained from cats injected with 125I before surgery, and in xenografts, grown in nude mice, after double-labeling with 131I and [3H]thymidine. Hyperthyroid cat goiters contain single or multiple hyperplastic nodules, consisting of highly cellular tissue with an iodine metabolism exceeding that of the surrounding normal tissue. Xenografts of hyperplastic hot tissue in thyroxine-treated nude mice retain their original histologic pattern and continue to accumulate radioiodine intensely. Autoradiographs assessed for [3H]thymidine incorporation reveal autonomously proliferating follicular cells within the hyperplastic foci but not within the normal tissue. Administration of sera from donor cats into host mice fails to stimulate the xenografts. Neither hyperfunction nor growth of toxic cat goiters depends on extrathyroidal stimulators. The basic lesion appears to be an excessive intrinsic growth capacity of some thyroid cells.

Mesenchymal cells isolated after acute lung injury manifest an enhanced proliferative phenotype.

After acute lung injury, mesenchymal cells migrate into the alveolar airspace where they proliferate and deposit connective tissue macromolecules. Early in the disease process, inflammatory cell-derived trophic factors modulate these mesenchymal cell functions. However, in those patients who die, even as the inflammatory response abates, the fibroproliferative response continues, resulting in extensive intraalveolar fibrosis. We therefore hypothesized that lung mesenchymal cells obtained from individuals dying with acute alveolar fibrosis would manifest an enhanced proliferative capacity that was independent of persistent exogenous signals. To examine this hypothesis, the in vitro growth properties of mesenchymal cells prepared from patients dying with acute lung injury (n = 3) were analyzed in defined medium and compared with those of mesenchymal cells similarly prepared from patients dying with histologically normal lungs (n = 3). Isolates were characterized as mesenchymal cells by using morphological and immunohistochemical criteria. In accord with the hypothesis, mesenchymal cells isolated from lung-injured patients doubled within 3 d in the complete absence of exogenous peptide growth factors, reaching a saturation density of approximately 15 x 10(3) cells/cm2. As expected, lung mesenchymal cells from normal individuals failed to significantly increase in number. Consistent with this proliferative phenotype, the immediate early cell division cycle genes c-fos and c-jun were constitutively expressed in each cell strain prepared from injured lungs, but not in those from control lungs. The observed proliferative phenotype was stable through the fifth subcultivation of the cells. Despite these proliferative properties, three separate criteria indicated the mesenchymal cells from injured lungs were not transformed: normal karyotype; finite lifespan in vitro (9-10 subcultivations); and inability to disseminate in mice with severe combined immunodeficiency. These data support the hypothesis that mesenchymal cells manifest an enhanced proliferative state after acute lung injury.

IgA deficiency in shar-pei dogs

Two shar-pei puppies examined because of signs of sinopulmonary disease, one of which also had skin disease, had deficient IgA concentrations. Deficient serum IgA concentrations also were confirmed in 30 of 39 (76.9%) clinically normal adult dogs in two colonies of shar-peis. Both courses of disease--sinopulmonary signs and chronic skin disease and a benign clinical course--have been reported in human patients with IgA deficiency. Thus, the shar-pei might be an appropriate model for studying the immunopathology of IgA deficiency in man.

Preservative effect of aprotinin on canine plasma immunoreactive adrenocorticotropin concentrations

The susceptibility of adrenocorticotropin (ACTH) in canine blood and plasma to enzymatic degradation has limited the availability of endogenous ACTH assay for veterinary use. This study examined if a proteinase (enzyme) inhibitor, aprotinin, mixed with blood at the time of collection, would limit the loss of immunoreactive (IR) ACTH from canine plasma stored at various temperatures. Blood was collected from laboratory-maintained dogs or dogs with hyperadrenocorticism and placed into EDTA-containing tubes in the presence or absence of aprotinin. Plasma obtained was stored for 4 d at temperatures ranging from -86 degrees C to room temperature (22 degrees C). Results showed that addition of aprotinin preserved IR-ACTH concentrations in plasma stored for 4 d at temperatures < or = 4 degrees C, or in unfrozen plasma stored inside insulated shipping containers containing frozen refrigerant packs. Plasma collected with aprotinin and stored at 22 degrees C showed a slight (17-23%) but significant (P < 0.05) decline in IR-ACTH. Unfrozen plasma collected without aprotinin showed significant (P < 0.05) loss of IR-ACTH during storage under identical conditions. These data indicate that aprotinin has a profound preservative effect upon canine plasma IR-ACTH and that it may be possible to submit unfrozen samples collected with this inhibitor to appropriate reference laboratories for analysis of IR-ACTH.