Infusion of butyrate affects plasma glucose, butyrate, and ß-hydroxybutyrate but not plasma insulin in lactating dairy cows.

The objective of this study was to investigate the effects on plasma metabolites and rumen traits when butyrate was infused into the rumen or abomasum of lactating cows. Jugular catheters were inserted into 5 ruminally fistulated Holstein cows [94.2 ± 26.3 DIM; 717 ± 45 kg of body weight (BW); mean ± SD] in a 5 × 5 Latin square with 3-d periods. Cows were infused for 24 h with 1 of 5 treatments: water (CON), 1 g/kg of BW of butyrate infused into either the abomasum (A1) or rumen (R1), or 2 g/kg of BW of butyrate infused into either the abomasum or rumen. Sodium butyrate was the source of butyrate and NaCl was added to the CON, A1, and R1 treatments to provide the same amount of sodium as supplied by the sodium butyrate treatment in the 2-g treatments. Plastisol flanges were inserted into the abomasum to allow infusion to the abomasum and peristaltic pumps provided continuous infusion at 9.3 mL/min for all treatments. The concentration of NaCl and sodium butyrate was varied in the infusate to provide the correct infusion amount. Rumen fluid samples were collected at -2, -1, 0, 1, 2, 3, 4, 6, 8, 12, 18, 24, 28, and 32 h relative to start of infusion. Serial blood samples were collected at -2, -1, 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 18, 24, 26, 28, and 32 h relative to start of infusion. Compared with CON, infusing butyrate increased both plasma butyrate and plasma ß-hydroxybutyrate (BHB), whereas plasma glucose decreased. Increasing butyrate infusion from 1 to 2 g increased plasma butyrate, tended to decrease plasma glucose, and tended to increase plasma BHB. Compared with abomasal infusion, rumen infusion of butyrate increased rumen butyrate, did not affect plasma glucose, and tended to increase plasma BHB. Treatment had no effect on plasma insulin. Results demonstrated that site of infusion and amount of butyrate affected several plasma metabolites when butyrate was infused in lactating dairy cows over a period of 24 h.

Single-dose infusion of sodium butyrate, but not lactose, increases plasma ß-hydroxybutyrate and insulin in lactating dairy cows.

Several studies have identified beneficial effects of butyrate on rumen development and intestinal health in preruminants. These encouraging findings led to further investigations related to butyrate supplementation in the mature ruminant. However, the effects of elevated butyrate concentrations on rumen metabolism have not been investigated, and consequently the maximum tolerable dosage rate of butyrate has not been established. Therefore, the first objective of this work was to evaluate the effect of a short-term increase in rumen butyrate concentration on key metabolic indicators. The second objective was to evaluate the source of butyrate, either directly dosed in the rumen or indirectly supplied via lactose fermentation in the rumen. Jugular catheters were inserted into 4 ruminally fistulated Holstein cows in a 4×4 Latin square with 3-d periods. On d 1 of each period, 1h after feeding, cows were ruminally dosed with 1 of 4 treatments: (1) 2L of water (CON), (2) 3.5g/kg of body weight (BW) of lactose (LAC), (3) 1g/kg of BW of butyrate (1GB), or (4) 2g/kg of BW of butyrate (2GB). Sodium butyrate was the source of butyrate, and NaCl was added to CON (1.34g/kg of BW), LAC (1.34g/kg of BW), and 1GB (0.67g/kg of BW) to provide equal amounts of sodium as the 2GB treatment. Serial plasma and rumen fluid samples were collected during d 1 of each period. Rumen fluid pH was greater in cows given the 1GB and 2GB treatments compared with the cows given the LAC treatment. Cows administered the 1GB and 2GB treatments had greater rumen butyrate concentrations compared with LAC. Those cows also had greater plasma butyrate concentrations compared with cows given the LAC treatment. Plasma ß-hydroxybutyrate was greater and insulin tended to be greater for butyrate treatments compared with LAC. No difference in insulin was found between the 1GB and 2GB treatments. Based on plasma and rumen metabolites, singly infusing 3.5g/kg of BW of lactose into the rumen is not as effective at providing a source of butyrate as compared with singly infusing 1 or 2g/kg of BW of butyrate into the rumen. Additionally, rumen pH, rumen butyrate, plasma ß-hydroxybutyrate, glucose, and plasma butyrate were less affected in cows administered the 1GB treatment than in cows given the 2GB treatment. This finding suggests that singly dosing 1g/kg of BW of butyrate could serve as the maximum tolerable concentration for future research.

True ileal amino acid digestibility and endogenous ileal amino acid losses in growing pigs fed wheat shorts- or casein-based diets.

Use of dietary AA in growing pigs reflects digestion and use of digested AA for various body functions. Before evaluating dietary effects on use of digestible AA intake for body protein deposition, a digestibility study was conducted to investigate true ileal AA digestibility and endogenous ileal AA losses in growing pigs fed graded levels of wheat shorts (WS) or casein (CS; control). A casein-based basal diet (basal) was formulated to contain 0.27 g of standardized ileal digestible (SID) Lys per MJ of DE, to which extra Lys was added from WS (WS2, +0.10 g of SID Lys per MJ of DE; WS3, +0.20 g of SID Lys per MJ of DE) or casein (CS3, +0.20 g of SID Lys per MJ of DE). A fifth diet was formulated to be similar in CP level and source as CS3 but in which 6% pectin, a source of soluble non-starch polysaccharides (NSP), was included at the expense of cornstarch (CS3 + pectin). Five Yorkshire barrows (17.5 +/- 1.5 kg of BW) were fitted with a T-cannula at the distal ileum and randomly assigned to 1 of the 5 experimental diets in a 5 x 5 Latin Square design. Apparent ileal digestibility (AID), true ileal digestibility (TID), and endogenous ileal protein losses (EPL) were determined using the homoarginine method. Diet CS level did not influence (P > or = 0.10) TID of most essential AA or EPL (10.4 g/kg of DM intake). Including pectin in the diet did not influence TID of AA (P > or = 0.10) but increased EPL (15.6 g/kg of DM intake; P > or = 0.01). Inclusion of WS in the diet reduced TID of most essential AA (P < 0.01). The TID values for most essential AA, however, were the same (P > or = 0.10) for both dietary WS levels, except for Lys and Met, which were further reduced at the greatest dietary WS level. Increased EPL (P < 0.01) was only observed for WS3 (16 g/kg of DMI). We concluded that (1) the effects of dietary protein source on AID of AA can be attributed both to reduced TID of AA and increased EPL, (2) the impact of dietary WS level on TID of AA and EPL does not seem to be linear, (3) soluble NSP from pectin or WS exerts a greater effect on EPL than insoluble NSP, and (4) because of the metabolic cost associated with EPL and the impacts of feed composition on microbial fermentation in the gut lumen, the effects of feed ingredients on the use of ileal digestible AA for protein deposition should be investigated further.

Duodenal glucose increases glucose fluxes and lactose synthesis in grass silage-fed dairy cows.

The effect of intestinal glucose supply on whole body rate of glucose appearance (WBGRa) and mammary utilization of glucose was studied in four lactating dairy cows. Glucose (0, 443, 963 and 2398 g/d) was continuously infused in the duodenum over 14-d periods using a Latin square design. A grass silage-based diet was formulated so that treatments were isoenergetic and isonitrogenous and contained 100 and 110% of energy and protein requirements according to INRA (1989). The WBGRa was measured by the [6,6-(2)H2]glucose dilution technique, and mammary glucose balance by arteriovenous differences and blood flow measurements. Duodenal glucose infusion increased arterial glucose concentrations linearly, whereas arterial concentrations of insulin, growth hormone, and glucagon were not changed. The WBGRa increased linearly with increasing glucose loads. The increase represented 42% of the intestinal glucose supplement. Mammary blood flow dramatically increased (up to 45%) and was associated with a significant increase of arterial insulin-like growth factor-1 concentrations. Mammary gland rate of glucose disappearance ([6,6-(2)H2]glucose measurement) increased linearly, whereas net mammary balance of glucose, lactose, and milk yields increased quadratically. Net mammary balance of glucose accounted for 60% of WBGRa, except for the greatest dose (47.6%). The decrease in milk yield with 2398 g/d of glucose may be explained by an imbalance in intracellular intermediate concentrations. The milk ratio of glucose-1-phosphate to glucose-6-phosphate decreased significantly at the greatest infusion of glucose. In conclusion, exogenous glucose supply to a grass silage-based diet increased WBGRa, mammary utilization of glucose and milk synthesis.

Benefits of nutritional intervention on nutritional status, quality of life and survival.

Most cancers in children are acute diseases. Therefore, the incidence of malnutrition, in general, is not different from the incidence in the referral population. Some specific tumors, such as neuroblastoma and those resulting in the diencephalic syndrome, can be exceptions. By contrast, malnutrition is a frequent problem during modern intensive cancer treatment as the result of the associated anorexia, altered taste sensations and catabolic effects of drugs. In addition, there are psychogenic factors and metabolic consequences associated with the tumor itself. Nutritional support does improve the feeling of well-being and performance status, while maintaining or improving the immune competence, thereby potentially affecting survival by limiting infectious episodes. There is no convincing evidence to date that nutritional support has an antineoplastic effect per se, but deficiency of a specific nutrient might be beneficial because of a differential requirement between tumor and normal cells. Theoretically, nutritional support might enhance tumor growth but also susceptibility to chemotherapy. In either case, nutrition is a support modality that must be given with appropriate tumor-directed therapy if curative intent is the goal of treatment. Nutrition remains a consideration after therapy is completed. This generates different challenges. If further tumor-directed therapy is futile, the decision to continue nutritional support is difficult, but if the child is well, nutritional rehabilitation must be pursued. Finally, the cured child continues to benefit from dietary advice. Nutrition should be viewed for what it is: supplying the most basic need of children.

MOPP chemotherapy without irradiation as primary postsurgical therapy for brain tumors in infants and young children.

Infants and young children who have brain tumors have a poor rate of survival and high treatment associated morbidity. A trial of mechlorethamine, vincristine (oncovin), procarbazine, and prednisone (MOPP) was performed to test the hypothesis that replacing radiotherapy with chemotherapy would improve survival and decrease long term morbidity of infants who have brain tumors. Between 1976 and 1988, 17 consecutive children less than 36 months old when diagnosed with medulloblastoma or ependymoma were treated with MOPP chemotherapy as primary therapy following surgical excision or biopsy of the tumor. Radiotherapy was reserved for recurrent disease. Ten of 17 children have survived without evidence of disease: medulloblastoma eight of 12 with median survival time of 10.6 years (range, 6.2 to 15.2 yrs); and ependymoma, 2 of 5 (at 13.0 and 16.0 yrs). Four of the 10 children with medulloblastoma and ependymoma who relapsed are now disease free at 7.5, 11.7, 12.2 and 13.5 yrs post relapse after receiving salvage therapy with cisplatin (n = 1) or irradiation (n = 3). All relapses occurred within 26 months of diagnosis. Data on growth demonstrated height less than the 5th percentile in all children who received cranial irradiation compared to 25 to 95th percentile for nonirradiated children. Intellectual ability for the group who did not require radiation was within normal range (mean IQ 100.1) and stable across annual assessments. Those who required radiation had lower IOs which continued to decline over time (mean IQ 85 at mean age of 5.8 years, declining to 63 at 10 years). In young children with brain tumors, primary chemotherapy with MOPP, omitting radiotherapy, provides improved neurodevelopmental outcome and survival.

Early hospital discharge and the timing of newborn metabolic screening.

Cost containment measures have reduced dramatically the length of stay for normal newborns, in some cases jeopardizing the ability to obtain appropriate newborn screens. In our hospital, we found that an unacceptable number of patients had mistakenly been screened before 24 hours of age. As pressures to shorten hospitalization increase, health-care providers must examine the impact of such changes on their ability to obtain adequate newborn screens. Potential solutions include continued vigilance in gathering specimens after 24 hours of age, interpretation of time-sensitive tests in an age-adjusted manner, and repeating newborn screens after 24 hours of age.

Extended triple intrathecal chemotherapy trial for prevention of CNS relapse in good-risk and poor-risk patients with B-progenitor acute lymphoblastic leukemia: a Pediatric Oncology Group study.

PURPOSE: The Pediatric Oncology Group (POG) acute leukemia in childhood (ALinC) 13 study tested two treatment regimens that used different CNS chemoprophylaxis for children older than 12 months with non-T, non-B acute lymphoblastic leukemia (ALL) and with no demonstrable CNS disease at diagnosis. PATIENTS AND METHODS: With the first regimen, standard (S), six injections of triple intrathecal chemotherapy (TIC), consisting of methotrexate (MTX), hydrocortisone (HC), and cytarabine (ara-C), were administered during intensification treatment and at every-8-week intervals throughout the maintenance phase for 17 additional doses. The second regimen, standard and MTX pulses (SAM), also specified six TICs during intensification, but substituted every-8-week pulses of intermediate-dose parenteral methotrexate (IDM; 1 g/m2) for the 17 maintenance TIC injections, with a low-dose intrathecal (IT) MTX boost administered with the first four maintenance IDM pulses. Otherwise, systemic therapy on regimen SAM was identical to regimen S. There were 1,152 patients randomized to the S and SAM regimens after stratification by risk group (age/leukocyte count) and immunophenotype. RESULTS: The 5-year probabilities (+/- SE) of an isolated CNS relapse were regimen S: good risk (n = 381), 2.8% +/- 1.3%; poor risk (n = 196), 7.7% +/- 3.2%; good + poor risk (n = 577), 4.7% +/- 1.5%; regimen SAM: good risk (n = 388), 9.6% +/- 2.2%; poor risk (n = 187), 12.7% +/- 4.2%; good + poor risk (n = 575), 10.9% +/- 2.2%. In poor-risk patients, approximately one third of the isolated CNS relapses occurred before preventive CNS therapy was begun at week 9. Hence, regimen S has provided better CNS preventive therapy for both good- and poor-risk patients (P < .001 overall). The difference is statistically significant for good-risk patients (P < .001), but not for poor-risk patients (P = .20). Neither treatment has shown a significant advantage in terms of general outcome. CONCLUSION: TIC injections extended throughout the intensification and maintenance periods are superior to IDM pulses for prevention of CNS leukemia. Our results with TIC seem comparable with those achieved with other contemporary methods of CNS preventative therapy. Thus, extended TIC affords a reasonable alternative to CNS irradiation plus upfront IT MTX for patients with B-progenitor ALL.

Intracranial ependymoma in children: analysis of prognostic factors.

Between 1955 and 1986, 25 children (aged 2 weeks to 15 years) were treated for intracranial ependymoma at M.D. Anderson Cancer Center. Nine patients had supratentorial primaries (5 high-grade, 4 low-grade), and 16 had infratentorial primaries (9 high-grade, 7 low-grade). Five patients had gross complete resection and 20 had incomplete resection. Seven patients received craniospinal irradiation (25-36 Gy to the neuro-axis, 45-55 Gy to tumor bed), 12 received local field irradiation (29-60 Gy, median 50 Gy). Five infants had adjuvant chemotherapy without radiotherapy, and 6 children had post-radiotherapy adjuvant chemotherapy, and 12 patients had salvage chemotherapy with various agents and number of courses. Eight patients are alive, disease-free and without relapse from 1 year to 12 1/2 years from diagnosis (median 42 months). The primary failure pattern was local recurrence. The data suggest that 1) the long-term cure rate of children with ependymoma is suboptimal; 2) histologic grade may be of prognostic importance for supratentorial tumors; 3) prognosis appears worse for girls and infants under 3 years of age; 4) in well-staged patients routine spinal irradiation could be omitted; 5) the role of adjuvant chemotherapy is unclear.

Clinical characteristics and treatment outcome of children with acute lymphocytic leukemia and Down's syndrome. A Pediatric Oncology Group study.

Of 2947 children with acute lymphocytic leukemia (ALL), treated during three consecutive studies of the Pediatric Oncology Group (1974-1986), 52 (1.8%) had Down's Syndrome (DS). Comparison of clinical and laboratory characteristics showed no significant differences in leukocyte count, racial distribution, sex ratio, platelet count, incidence of mediastinal mass, lymphadenopathy or hepatosplenomegaly, or percentage of blood or bone marrow blasts for children with ALL with or without Down's Syndrome (DS-ALL or NDS-ALL, respectively). However, children with DS-ALL were slightly older at the time of presentation and had higher hemoglobin values. The relative frequency of each major immunophenotype (early pre-B, pre-B, T, or B) was also comparable for patients with or without DS. For this report, treatment regimens were categorized as either conventional (no consolidation therapy) or intensive. Cox regression analysis revealed that the presence of DS, a higher leukocyte count, black race, or age older than 10 years was independently associated with a poorer event-free survival (EFS) for children treated with conventional chemotherapy. However, for the cohort of children who received intensive chemotherapy, DS was no longer an independent risk factor. In fact, event-free survival (EFS) was markedly improved to a level comparable with that observed in the children diagnosed as having NDS-ALL. On the other hand, serious toxicity, requiring interruption of treatment, was significantly more frequent in the intensively treated children with DS compared with similarly treated patients with NDS-ALL, although deaths resulting from toxicity occurred infrequently.

The truly cured child?

The concept of the truly cured child, denoting a child on par with his or her peers in development, maturation, achievement, and aspirations, was introduced in 1977. 'Cure' is the norm in pediatric oncology. However, the cure of a disease and the consequences of that disease are complex concepts. Cure has at least three components: a biological cure, a psychological cure, and a social cure. Biological and psychological cures have been realized, but the social cure is yet to be achieved. The concept of the truly cured child is widely accepted. School reintegration is the primary method by which psychosocial cure is approached. The characteristics of psychosocial cure and the obstacles that hinder uniformly achieving the goal should be recognized so that the truly cured child can be a realistic goal in pediatric oncology.

The impact of Medicaid on research-based care in pediatric hematology/oncology.

The dilemmas posed by Medicaid's inadequate reimbursement for health care are discussed. A short history of the intent of Medicaid is presented and Medicaid is contrasted with indigent care and care provided by health maintenance organizations or similar programs. Research care is expensive, and it is therefore often difficult to support Medicaid patients in research protocols. Current trends in research care delivery are summarized, and a potential solution is presented in which the support of the clinical research structure is transferred to support of the patient enrolled in a research protocol.

Special nutritional needs of children with malignancies: a review.

Nutrition support for the patient with cancer is an important part of the overall treatment regimen. Nutrition support for the child with cancer poses a special challenge. For the purpose of reviewing the special nutritional needs of children with cancer, a Task Force was formed by the American Academy of Pediatrics to review the current state of knowledge. The work of the Task Force was supported by the Food and Drug Administration through its Liaison Representative, Joginder Chopra, M.D., Staff support from the Academy was provided by Jean D. Lockhart, M.D., This review is prepared from the Task Force Report to the FDA. It is designed to review factors enhancing nutritional risks for the child with cancer and to discuss nutritional intervention strategies and their efficacies.