Prognostic understanding, quality of life and mood in patients undergoing hematopoietic stem cell transplantation.

Little is known about how patients undergoing hematopoietic stem cell transplantation (HCT) and their family caregivers (FC) perceive their prognosis. We examined prognostic understanding in patients undergoing HCT and their FC and its relationship with quality of life (QOL) and mood. We conducted a longitudinal study of patients (and FC) hospitalized for HCT. We used a questionnaire to measure participants' prognostic understanding and asked the oncologists to estimate patients' prognosis prior to HCT. We assessed QOL and mood weekly and evaluated the relationship between prognostic understanding, and QOL and mood using multivariable linear mixed models. We enrolled 90 patients undergoing (autologous (n=30), myeloablative (n=30) or reduced intensity allogeneic (n=30)) HCT. About 88.9% of patients and 87.1% of FC reported it is 'extremely' or 'very' important to know about prognosis. However, 77.6% of patients and 71.7% of FC reported a discordance and more optimistic prognostic perception compared to the oncologist (P<0.0001). Patients with a concordant prognostic understanding with their oncologists reported worse QOL (ß=-9.4, P=0.01) and greater depression at baseline (ß=1.7, P=0.02) and over time ((ß=1.2, P<0.0001). Therefore, Interventions are needed to improve prognostic understanding, while providing patients with adequate psychological support.

DNA-based animal models of human disease: from genotype to phenotype.

Biomedical research utilizes animal models to elucidate human disease processes at the cellular and molecular level and for the development of new therapies. Traditionally, mammalian models have been limited to the mouse, primarily because of well characterized genetic lines and the ability to manipulate the genome to directly test hypotheses regarding causal mutations and disease phenotypes. The emerging availability of genome sequences of other mammals (bovine, canine, equine, feline, and porcine) now permits utilization of the mammal in which the phenotype best approximates the human condition. Equally important is the use of somatic cell nuclear cloning (SCNT) coupled with targeted germline manipulation to create animals to resolve the molecular mechanisms of the disease state. Our efforts have focused on the pig, which has emerged as an important biomedical mammalian model due to its closer physiology to humans. The utility of porcine genetically-defined tumour, cardiovascular and neurological disease models is described.

Genetic induction of tumorigenesis in swine.

The transition from basic to clinical cancer research for a number of experimental therapeutics is hampered by the lack of a genetically malleable, large animal model. To this end, we genetically engineered primary porcine cells to be tumorigenic by expression of proteins known to perturb pathways commonly corrupted in human cancer. Akin to human cells, these porcine cells were quite resistant to transformation, requiring multiple genetic changes. Moreover, the transformed porcine cells produced tumors when returned to the isogenic host animal. The ability to now rapidly and reproducibly genetically induce tumors of sizes similar to those treated clinically in a large mammal similar to humans in many respects will provide a robust cancer model for preclinical studies dependent on generating large tumors.

Diet affects nutrient digestibility, hematology, and serum chemistry of senior and weanling dogs.

The objective of this experiment was to determine the effects of age and diet on serum chemistry, hematology, and nutrient digestibility in healthy dogs. Twelve senior (11 yr old; six males and six females) and 12 weanling (age = 8 wk old; six males and six females) beagles were randomly assigned to one of two dietary treatments: 1) an animal product-based (APB) diet or 2) a plant product-based (PPB) diet. The APB diet was primarily composed of brewer's rice, chicken by-product meal, and poultry fat, whereas the primary ingredients of the PPB diet included corn, soybean meal, wheat middlings, and meat and bone meal. Dogs remained on experiment for 12 mo. A 4-d total fecal collection was performed to determine apparent macronutrient digestibilities after 3 and 10 mo. Blood samples were collected at baseline and after 3, 6, 9, and 12 mo on study. After 3 mo, dogs fed the APB diet had greater (P < 0.001) DM (6 percentage units) and OM (7 percentage units) digestibilities than dogs fed the PPB diet. Senior dogs had greater DM (2.5 percentage units; P = 0.07) and OM (3 percentage units; P < 0.01) digestibilities than young dogs. Dogs fed the PPB diet had a lower (P < 0.001) fecal DM percentage (7.5 percentage units) and greater (P < 0.001) fecal output (253 vs. 97 g/d, as-is basis). After 10 mo, age did not affect nutrient digestibility or fecal characteristics. However, the effect of diet after 10 mo was similar to that observed after 3 mo, as dogs fed the PPB diet had a lower (P < 0.001) fecal DM percentage (7 percentage units), lower OM (4 percentage units; P = 0.09) and fat (6 percentage units; P < 0.001) digestibilities, and greater (P < 0.005) fecal output (235 vs. 108 g/d, as-is basis). At baseline, most serum metabolites were different between age groups, with weanlings having several metabolite concentrations outside the reference ranges for adult dogs. Blood cholesterol, red blood cells, hemoglobin, hematocrit, creatinine, total protein, albumin, bilirubin, sodium, chloride, and alanine transaminase were present in greater (P < 0.05) concentrations in senior dogs, but weanling dogs had greater (P < 0.05) concentrations of glucose, platelets, Ca, P, K, and alkaline phosphatase. Over time, blood cholesterol concentrations were affected by age (P < 0.05) and diet (P < 0.01). Senior dogs had greater (P < 0.05) cholesterol concentrations than weanling dogs. Moreover, dogs fed the APB diet had greater (P < 0.05) cholesterol concentrations than dogs fed the PPB diet. Overall, although serum metabolite concentrations of weanlings were different from senior dogs at baseline, as weanlings matured into young adults, metabolite concentrations were similar to those of senior dogs. Diet had the largest effects on nutrient digestibilities and fecal characteristics. Canine age and diet must be considered when interpreting experimental and clinical data.