Cyclic parenteral nutrition during allogeneic bone marrow transplantation

Two adolescents who underwent successful allogeneic bone marrow transplantation were nutritionally managed on a fat-free cyclic parenteral nutrition (PN) regimen. Serum concentrations of prealbumin, albumin, and transferrin were prospectively evaluated to assess the efficacy of nutritional therapy. Both patients tolerated the cyclic PN metabolically. Serial albumin and transferrin concentrations varied slightly and were less sensitive indices of changing nutritional status. In contrast, prealbumin concentrations decreased uniformly during periods of metabolic stress. At the cessation of Pn therapy, all serum proteins were within the normal range. Cyclic PN appears to be a safe, practical approach to the nutritional management of patients undergoing bone marrow transplantation.     

Use of total parenteral nutrition in pediatric bone marrow transplantation

To evaluate the extent of the nutritional stress of pediatric bone marrow transplantation (BMT) and to evaluate the use of total parenteral nutrition (TPN), 35 consecutive pediatric patients who received BMT were studied retrospectively. Voluntary cessation of oral nutrition in almost all patients was observed, and significant decreases of serum albumin levels were seen after BMT. In 85% of these patients, TPN was necessary in response to severe wasting and fasting. No deaths were related to indwelling central venous catheters during the period of 2968 catheter-use days in these severely myelosuppressed patients. The mean of the total daily energy intake was 104% of basal energy expenditure (BEE), and 70% of patients lost their weight. Predicted energy requirement to maintain body weight after BMT would be 128% of BEE from a simple linear regression step in this study. Significant correlations were found between the marrow recovery time and the initial nutritional state, expressed as the percentage of ideal weight height ratio, as well as benign nature of the disease. The use of TPN did not show any beneficial effects on the time course of marrow recovery, although it showed favorable effects on the maintenance of body weight.     

Nutritional and metabolic support in patients undergoing bone marrow transplantation

Bone marrow transplantation (BMT) is a sophisticated procedure consisting of the administration of high-dose chemoradiotherapy followed by intravenous infusion of hemopoietic stem cells to reestablish marrow function when bone marrow is damaged or defective. BMT is used in the treatment of solid tumors, hematologic diseases, and autoimmune disorders. Artificial nutrition, total parenteral nutrition in particular, is provided to patients undergoing BMT to minimize the nutritional consequences of both the conditioning regimens (eg, mucositis of the gastrointestinal tract) and complications resulting from the procedure (eg, graft versus host disease and venoocclusive disease of the liver). Although artificial nutrition is now recognized as the standard of care for BMT patients, defined guidelines for the use of artificial nutrition in this clinical setting are lacking. During the past 2 decades, artificial nutrition in BMT patients has moved from simple supportive care to adjunctive therapy because of the possible benefits, not strictly nutritional, of specialized nutritional intervention. Although data exist documenting the beneficial role of special nutrients, such as lipids and glutamine, in the management of BMT recipients, the results obtained to date are controversial. The reasons for this controversy may reside in the heterogeneity of the patients studied and of the study designs. This review focuses on the need to correctly identify the different patterns of BMT to achieve reproducible and reliable data, which may in turn be used to devise precise guidelines for the use of specialized artificial nutrition in BMT patients.     

Continuous versus cyclic parenteral nutrition during bone marrow transplantation: assessment and follow-up

The aim of this prospective, randomized clinical trial was to compare the efficacy of parenteral nutrition (PN) in adult bone marrow transplant (BMT) patients on a continuous (CON) versus a cyclic (CYC) regimen. Twelve patients received CON PN and 12 CYC PN. The groups were homogeneous. CON PN received 27.2 +/- 3.7 kcal/kg/day and for CYC PN 25.9 +/- 4.2 kcal/kg/day (P= 0.45). The duration of PN was 20.4 +/- 7.9 days and 27.3 +/- 13.4 days respectively (P = 0.14). There were no differences between initial and final body weights, either within or between groups. The initial pre-albumin levels were 16.1 +/- 7.5 mg/dl and 20.1 +/- 4.9 mg/dl in CON PN and CYC PN, respectively (P= 0.22), and these were maintained throughout the study. Blood glucose levels did not differ between groups. Measures of liver function were moderately increased, but with no significant differences between groups. There were no significant differences regarding the efficacy of PN or the appearance of complications between CON PN and CYC PN in patients with BMT.     

Acute cytomegalovirus colitis after bone marrow transplantation]

Cytomegalovirus infection of the digestive tract is rare and particularly severe after transplantation. Colon is the most often affected part of the digestive tube. We present the case of acute cytomegalovirus colitis that occurred five months after a bone marrow transplantation. An emergency subtotal colectomy with sigmoidostomy and ileostomy was performed followed six weeks later by an ileorectal anastomosis. The pathologic specimen showed cytomegalovirus inclusion bodies proving the diagnosis.     

Plasma antioxidant status after high-dose chemotherapy: a randomized trial of parenteral nutrition in bone marrow transplantation patients

BACKGROUND: Chemotherapy and radiation therapy result in increased free radical formation and depletion of tissue antioxidants. It is not known whether parenteral nutrition (PN) administered during bone marrow transplantation (BMT) supports systemic antioxidant status. OBJECTIVE: The aims of the study were to determine 1) whether high-dose chemotherapy decreases concentrations of major circulating antioxidants in patients undergoing BMT and 2) whether administration of standard PN maintains systemic antioxidant concentrations compared with PN containing micronutrients and minimal lipids alone. DESIGN: Twenty-four BMT patients were randomly assigned to receive either standard PN containing conventional amounts of dextrose, amino acids, micronutrients, and lipid (120 kJ/d) or a solution containing only micronutrients (identical to those in standard PN) and a small amount of lipid (12 kJ/d). Plasma antioxidant status was measured before conditioning therapy and serially at days 1, 3, 7, 10, and 14 after BMT. RESULTS: Plasma glutathione (GSH) and alpha- and gamma-tocopherol concentrations decreased and the GSH redox state became more oxidized after conditioning chemotherapy. Plasma cysteine concentrations were unchanged, whereas cystine concentrations increased. Plasma vitamin C and zinc concentrations and GSH peroxidase activity increased over time. Plasma alpha-tocopherol concentrations were lower in patients given standard PN. There were no differences in other plasma antioxidants between groups. CONCLUSIONS: A significant decline in GSH-glutathione disulfide, cysteine-cystine, and vitamin E status occurs after chemotherapy and BMT. Standard PN does not improve antioxidant status compared with administration of micronutrients alone. Further evaluation of PN formulations to support patients undergoing high-dose chemotherapy and BMT are needed.     

Donor-cell-derived acute leukemias after allogeneic bone marrow transplantation

The authors survey the clinical, immunophenotypic, cytogenetic, molecular genetic spectrum and pathogenetic mechanisms of donor cell derived acute leukemias after allogeneic bone marrow transplantation. The main aspects for detection of donor cell origin and the available therapeutic approaches are discussed through demonstration of one documented patient and data of the literature. Several hypotheses are summarized which try to explain how donor cell leukemia might arise including occult leukemia in the donor cells, transfer of oncogene from host to donor cells and the role of impaired immune surveillance. Investigation of donor cell leukemia cases might bring closer to understand the pathogenesis of leukemia serving as a model for studying the leukemiagenesis in vivo.     

Low protein intake: the impact on calcium and bone homeostasis in humans

Increasing dietary protein results in an increase in urinary calcium. Despite over 80 y of research, the source of the additional urinary calcium remains unclear. Because most calcium balance studies found little effect of dietary protein on intestinal calcium absorption, it was assumed that the skeleton was the source of the calcium. The hypothesis was that the high endogenous acid load generated by a protein-rich diet would increase bone resorption and skeletal fracture. However, there are no definitive nutrition intervention studies that show a detrimental effect of a high protein diet on the skeleton and the hypothesis remains unproven. Recent studies from our laboratory demonstrate that dietary protein affects intestinal calcium absorption. We conducted a series of short-term nutrition intervention trials in healthy adults where dietary protein was adjusted to either low, medium or high. The highest protein diet resulted in hypercalciuria with no change in serum parathyroid hormone. Surprisingly, within 4 d, the low protein diet induced secondary hyperparathyroidism that persisted for 2 wk. The secondary hyperparathyroidism induced by the low protein diet was attributed to a reduction in intestinal calcium absorption (as assessed by dual stable calcium isotopes). The long-term consequences of these low protein-induced changes in calcium metabolism are not known, but they could be detrimental to skeletal health. Several recent epidemiological studies demonstrate reduced bone density and increased rates of bone loss in individuals habitually consuming low protein diets. Therefore, studies are needed to determine whether low protein intakes directly affect rates of bone resorption, bone formation or both.     

Parenteral nutrition support after bone marrow transplantation: comparison of total and partial parenteral nutrition during the early posttransplantation period

OBJECTIVE: Bone marrow transplantation (BMT) usually is indicated if the patient's malignant disease involves the marrow or if hazard to the normal marrow is the limiting factor in the aggressive treatment of disease. The success of BMT depends on a complete team with all the resources needed to ensure optimal results. Aggressive nutrition support after BMT is very important. Adequate parenteral nutrition, total (TPN) or partial, followed by enteral nutrition according to the patient's gastrointestinal function is the important principle. METHODS: Between 1996 and 2000, 60 patients, 46 male and 14 female, received BMT in Chang Gung Memorial Hospital. Their ages ranged from 6 to 54 y. Standard TPN was used in 40 patients after BMT, and partial parenteral nutrition was used in the remaining 20 patients. TPN was enriched with branched-chain amino acids (BCAA) when the patient's liver functions were impaired, and cyclic TPN was shifted when the patient's liver functions persistently deteriorated. RESULTS: Most patients improved their nutrition status and increased their body weights, especially those receiving TPN. The patients receiving partial parenteral nutrition decreased their visceral proteins significantly during the course of parenteral nutrition. The BCAA-TPN can maintain a patient's visceral protein better than standard TPN. Only two patients expired because of graft rejection and sepsis; their body weights and nutrition status showed deterioration despite aggressive nutrition support. CONCLUSIONS: We conclude that the nutrition support for patients with BMT is related to the success of marrow transplantation. Parenteral nutrition support, especially with TPN, is important because of frequent gastrointestinal dysfunction during the posttransplantational period, and it is better at maintaining the nutrition status and body weights of patients after BMT. An oral diet can be resumed after the patient's gastrointestinal function has improved and it can be tolerated.     

Oral and parenteral glutamine in bone marrow transplantation: a randomized, double-blind study.

BACKGROUND: Total parenteral nutrition (TPN) supplemented with glutamine (GLN) has been reported to be effective for patients with bone marrow transplantation (BMT). Our aim was to evaluate enteral and parenteral glutamine in patients undergoing BMT. METHODS: For evaluation of GLN in BMT, 66 patients with 43 hematologic and 23 solid malignancies (21 breast carcinomas), were randomized, double-blinded, to either oral GLN (n = 35) or glycine-control (GLY) (n = 31), 10 g three times daily. When TPN became necessary, patients who received GLN orally were given TPN with GLN (0.57 g/kg). Those who received GLY received standard TPN, isocaloric and isonitrogenous. Patients with hematologic malignancies received high-dose chemotherapy, total body irradiation, and either allogeneic (ALLO) BMT (n = 18) or autologous (AUTO) stem cell transplantation (n = 25). Patients with solid malignancies (n = 23) received AUTO. RESULTS: There were 14 in-hospital deaths without relationship to GLN administration. For respective comparisons of ALLO and AUTO transplants in the GLN and GLY hematologic groups and AUTO in the solid tumor groups, there were no significant differences in hospital stay, duration of stay after BMT, TPN days, neutrophil recovery >500/mm3, incidence of positive blood cultures, sepsis, mucositis, and diarrhea. Acute graft us host disease occurred in 1 of 10 hematologic patients receiving GLN and in 3 of 8 patients receiving GLY placebo (p > .05). Possible reduction in need for TPN and a suggestion of improved long-term survival were associated with GLN. CONCLUSIONS: Oral and parenteral GLN seemed to be of limited benefit for patients having AUTO or ALLO BMT for hematologic or solid malignancies. Further study of long-term effects of GLN in BMT seems warranted.     

Regeneration of the immune system after bone marrow transplantation

After haematopoietic stem cell transplantation, reconstitution of bone marrow consists of two distinct phenomena, numerical recovery of bone marrow cellular elements on the one hand and functional recovery of cellular interactions on the other. Immune reactivity during the first month postgrafting is extremely low. Cytotoxic and phagocytic functions usually recover by day 100, while more specialized and cooperative functions of T and B cells remain impaired up to one year or more postgrafting. Regeneration of total CD4+ T cell number in adult (and especially in elderly) transplant recipients is severely limited and occurs largely by peripheral expansion of mature CD4+ T cells. While restoration of total CD8+ T cell number is commonly seen in adults, potentially important alterations in the subset composition of CD8+ populations remain. Contracted T cell repertoires for CD4+ and CD8+ T cells are consistently found in adults after T cell regeneration. This suggests that thymic function is frequently limiting in adults and that thymic-independent pathways are insufficient for restoring host immunocompetence. Although there are similarities in immune reconstitution after alllo- and autologous haematopoietic stem cell transplantations, allogeneic transplantation involves graft versus host disease and the use of immunosuppressive therapy to control it, both of which further interfere in the early developmental stages of immune reconstitution.     

Influence of ghrelin on food intake and energy homeostasis

PURPOSE OF REVIEW: The purpose of this review is to provide updated information on the role of ghrelin in food intake and energy homeostasis, and on its mechanism of action. Moreover, the potential of ghrelin as a target for drugs to treat cachexia and obesity will be discussed. RECENT FINDINGS: Whereas the effects of ghrelin in the regulation of appetite, food intake and energy homeostasis have been fairly well documented, the pathways responsible for the effects of ghrelin are now increasingly being understood. As a consequence, clinical applications of ghrelin are now being developed. SUMMARY: Ghrelin is an endogenous orexigenic peptide recently discovered in the stomach. Ghrelin is involved in short-term regulation of food intake since its plasma levels increase before meals and decrease strongly postprandially. Ghrelin is also involved in long-term body-weight regulation by inducing adiposity. Ghrelin might be useful for cachexia and obesity treatment.     

Ghrelin: a hormone regulating food intake and energy homeostasis

Regulation of energy homeostasis requires precise coordination between peripheral nutrient-sensing molecules and central regulatory networks. Ghrelin is a twenty-eight-amino acid orexigenic peptide acylated at the serine 3 position mainly with an n-octanoic acid, which is produced mainly in the stomach. It is the endogenous ligand of the growth hormone secretagogue (GHS) receptors. Since plasma ghrelin levels are strictly dependent on recent food intake, this hormone plays an essential role in appetite and meal initiation. In addition, ghrelin is involved in the regulation of energy homeostasis. The ghrelin gene is composed of four exons and three introns and renders a diversity of orexigenic peptides as well as des-acyl ghrelin and obestatin, which exhibit anorexigenic properties. Ghrelin stimulates the synthesis of neuropeptide Y (NPY) and agouti-related protein (AgRP) in the arcuate nucleus neurons of the hypothalamus and hindbrain, which in turn enhance food intake. Ghrelin-expressing neurons modulate the action of both orexigenic NPY/AgRP and anorexigenic pro-opiomelanocortin neurons. AMP-activated protein kinase is activated by ghrelin in the hypothalamus, which contributes to lower intracellular long-chain fatty acids, and this appears to be the molecular signal for the expression of NPY and AgRP. Recent data suggest that ghrelin has an important role in the regulation of leptin and insulin secretion and vice versa. The present paper updates the effects of ghrelin on the control of energy homeostasis and reviews the molecular mechanisms of ghrelin synthesis, as well as interaction with GHS receptors and signalling. Relationships with leptin and insulin in the regulation of energy homeostasis are addressed.     

骨髓间充质干细胞促进异基因骨髓移植后造血恢复

目的探讨骨髓间充质干细胞(BMMSC)对异基因骨髓移植小鼠造血功能恢复的影响。方法将供鼠C57BL/6(H-2b)的骨髓细胞和体外培养的BMMSC联合输给致死量照射的受鼠BalB/c(H-2d)。在移植后第1、7、14天检测受鼠外周血红细胞(RBC)、白细胞(WBC)、血小板(BPC);移植后第7、14天检测受鼠骨髓中的脾集落形成单位(CFU-S)。结果联合移植组小鼠第7、14天的外周血红细胞、白细胞、血小板、CFU-S数均显著高于单纯移植组(P<0.01)。结论BMMSC能促进异基因骨髓移植后造血功能重建。