The burden and consequences of inherited blood disorders among young children in western Kenya.

Although inherited blood disorders are common among children in many parts of Africa, limited data are available about their prevalence or contribution to childhood anaemia. We conducted a cross-sectional survey of 858 children aged 6-35 months who were randomly selected from 60 villages in western Kenya. Haemoglobin (Hb), ferritin, malaria, C-reactive protein (CRP) and retinol binding protein (RBP) were measured from capillary blood. Using polymerase chain reaction (PCR), Hb type, -3.7 kb alpha-globin chain deletion, glucose-6-phosphate dehydrogenase (G6PD) genotype and haptoglobin (Hp) genotype were determined. More than 2 out of 3 children had at least one measured blood disorder. Sickle cell trait (HbAS) and disease (HbSS) were found in 17.1% and 1.6% of children, respectively; 38.5% were heterozygotes and 9.6% were homozygotes for α(+) -thalassaemia. The Hp 2-2 genotype was found in 20.4% of children, whereas 8.2% of males and 6.8% of children overall had G6PD deficiency. There were no significant differences in the distribution of malaria by the measured blood disorders, except among males with G6PD deficiency who had a lower prevalence of clinical malaria than males of normal G6PD genotype (P = 0.005). After excluding children with malaria parasitaemia, inflammation (CRP > 5 mg L(-1) ), iron deficiency (ferritin < 12 µg L(-1) ) or vitamin A deficiency (RBP < 0.7 µg L(-1) ), the prevalence of anaemia among those without α(+) -thalassaemia (43.0%) remained significantly lower than that among children who were either heterozygotes (53.5%) or homozygotes (67.7%, P = 0.03). Inherited blood disorders are common among pre-school children in western Kenya and are important contributors to anaemia.

The importance of controlling for the acute-phase response in the population-based assessment of vitamin A status: a study in children of pre-school age in Uganda.

OBJECTIVE: To improve estimates of vitamin A deficiency in children of pre-school age in the 2006 Uganda Demographic and Health Survey (UDHS 2006). DESIGN: A cross-sectional study in which dried blood spot samples were analysed for C-reactive protein (CRP). Retinol-binding protein (RBP) had previously been analysed using a commercial enzyme immunoassay. SETTING: A population-based study in Uganda. SUBJECTS: A systematically selected subset of the dried blood spot samples collected from children aged 6­59 months for UDHS 2006. Children were categorized into 'normal CRP' (Group A) and 'raised CRP' (Group B) using a CRP cut-off of 5mg/l. A correction factor was calculated to adjust the Group B RBP values for the influence of the acute-phase response. RESULTS: Geometric mean CRP was 6.2 (95% CI 5.5, 7.0) mg/l, 1.6 (95% CI 1.5, 1.8) mg/l and 17.9 (95% CI 16.4, 19.6) mg/l in all children, in Group A and in Group B, respectively. Geometric mean RBP in all children, in Group A and in Group B was 1.18 (95% CI 1.14, 1.22)mmol/l, 1.26 (95% CI 1.20, 1.33)mmol/l and 1.12 (95% CI 1.07, 1.17)mmol/l, respectively, before correction. Correction increased mean RBP in Group B to 1.26 (95% CI 1.21, 1.31)mmol/l. The prevalence of vitamin A deficiency (RBP,0.825mmol/l) reduced from 18.4% (95% CI 17.2, 23.0%) to 13.9% (95% CI 11.3, 16.5%). CONCLUSIONS: Correcting for the acute-phase response significantly reduced the prevalence of vitamin A deficiency; thus, the acute-phase response should be considered when vitamin A status is assessed using RBP in order to improve population-level estimates of vitamin A deficiency.

Biochemical indices for the assessment of nutritional status during hematopoietic stem cell transplantation: are they worth using? A single center experience.

Hematopoietic stem cell transplantation (HSCT) is being used increasingly in an attempt to cure many hematological disorders, solid tumors and autoimmune diseases. One of the major challenges in the post-transplant period is nutrition. The purpose of this investigation was to assess changes in the biochemical indices of nutritional status during HSCT and compare them with acute-phase protein levels to find the best parameters for nutritional support qualification. Nutritional status was assessed in 54 patients during autologous (30 cases) and allogeneic (24 cases) transplantation. Fifteen patients had to be treated with total parenteral nutrition (TPN), eight of them needing prolonged hospitalization. All nutritional indices and acute-phase protein levels were evaluated during the day before the beginning of conditioning regimen, after chemotherapy completion and every 7 days until engraftment, at least three times after stem cells infusion. Wilcoxon test and canonical analysis were used for statistical analyses. The measurement of retinol-binding protein and transferrin can be useful for nutritional assessment during autologous and allogeneic HSCT, respectively. Prealbumin level, measured 8 days after the end of conditioning regimen, is helpful in making a decision about starting TPN.

Assessment of vitamin A nutritional status in newborn preterm infants.

OBJECTIVE: This study assessed the vitamin A nutritional status of preterm infants determined by the vitamin A relative dose-response test (RDR) compared with serum levels of vitamin A, retinol-binding protein (RBP), transthyretin (TTR), and retinol relations with carrier proteins. METHODS: Serum levels of retinol, RBP, and TTR and retinol/RBP, retinol/TTR, and RBP/TTR molar ratios were determined in 120 infants at 7 d and in 92 at 28 d. For the determination of the performance of the tests, the RDR was considered the reference method. The sensitivity and specificity for all possible cutoff values were determined by constructing receiver operator characteristic curves. The areas under the curves were used to estimate the overall accuracy of the tests. The best cutoff values to be used for the calculation of sensitivity and specificity were determined with 95% confidence intervals. RESULTS: RDR indicated vitamin A deficiency in 60% of the infants at 7 d and in 51.1% at 28 d. In the receiver operator characteristic curves, the best area under the curve was 0.710 obtained for serum retinol at 28 d of postnatal age and considered moderately accurate. The least inadequate cutoff level was set at 25 mg/dL, but no value was considered adequate due to low sensitivity and/or low specificity. CONCLUSION: Compared with RDR, the determination of serum levels of retinol, RBP, and TTR and their molar ratios are not adequate to assess nutritional vitamin A status in preterm infants.

Usefulness of oral mucosal epithelial cell apoptosis rate in nutritional assessment.

OBJECTIVE: This preliminary study was designed to explore a new method for nutritional assessment by measuring oral mucosal cell apoptosis or proliferation. METHODS: Forty-two consecutive patients with gastrointestinal malignant tumors were hospitalized on the surgical wards and studied prospectively. Patient-Generated Subjective Global Assessment was used to identify malnourished patients. Anthropometric measurements including weight, body mass index, triceps skinfold thickness, and midarm muscle circumference were recorded. The serum proteins measured were retinol-binding protein (RBP), transferrin, prealbumin (PA), and albumin. Simultaneously, the rates of oral epithelial cell apoptosis and proliferation were measured by flow cytometry. Of the 20 malnourished patients, 14 were followed up in a serial study with a 3-d nutritional support therapy. Nutritional indices and oral epithelial cell apoptosis rate were measured after 3 d of nutritional support. RESULTS: Malnutrition was diagnosed in 20 of 42 patients (47.6%). Oral epithelial apoptosis and proliferation rates were significantly decreased (P < 0.01 and P < 0.05, respectively) in malnourished compared with non-malnourished patients, although there were no significant differences between their anthropometric data. Malnourished patients had lower serum levels of RBP, albumin, and PA and rates of oral epithelial cell apoptosis and proliferation. The rate of oral epithelial cell apoptosis positively correlated with serum RBP (R = 0.32, P < 0.05) and PA (R = 0.33, P < 0.05). The rate of oral epithelial cell apoptosis and serum RBP and PA increased significantly in the malnourished patients who received nutritional support for 3 days. CONCLUSIONS: Measuring the rate of oral epithelial cell apoptosis may be another non-invasive technique to determine nutritional assessment and is worthy of further exploration.

The role of visceral proteins in the nutritional assessment of intensive care unit patients.

PURPOSE OF REVIEW: This review analyses the recently published literature focusing on nutritional assessment in intensive care unit patients. The metabolic response to nutritional intervention is difficult to evaluate in critically ill patients whose body weight is influenced largely by massive fluid administration or losses. Visceral protein plasma levels have been proposed for this purpose, because they reflect hepatic synthesis in response to nutrient supply. However, in acute inflammatory states, liver activity is converted to the synthesis of acute-phase response proteins, resulting in a dramatic drop in visceral proteins, despite nutritional support. RECENT FINDINGS: The data regarding visceral protein levels were examined in relation to nutritional supplementation, and compared with other nutritional parameters and clinical outcomes. Transthyretin and retinol-binding protein levels seem to be the most sensitive to nutritional intervention. They are also the earliest to rise at the decrease of acute-phase protein levels, therefore representing a good index of the reversing reprioritization of hepatic protein synthesis. An inconsistent relationship was found between visceral protein plasma levels and clinical outcome in intensive care unit patients, probably because of the difficulty in demonstrating clearly a beneficial effect of nutritional supplementation in highly catabolic conditions. SUMMARY: In the acute stage of critical illness, the bi-weekly measurement of transthyretin together with acute-phase response protein plasma levels seems to be a 'window' on the metabolic condition (anabolism versus catabolism). However, only in the presence of stable inflammatory parameters do transthyretin levels reflect the adequacy of nutritional coverage.

Parenteral with enteral nutrition in the critically ill.

OBJECTIVE: To determine whether nutrient intake by early enteral nutrition with parenteral nutrition improves levels of retinol-binding protein and prealbumin (primary endpoint) and reduce morbidity and mortality (secondary endpoint) in ICU patients. DESIGN: Prospective, double-blind, and randomized, placebo-controlled study. SETTING: Two intensive care units in a tertiary institution. PATIENTS AND PARTICIPANTS: 120 patients in two groups of 60. INTERVENTIONS: Patients received either enteral plus parenteral nutrition (treatment group) or enteral nutrition plus placebo (placebo group) for 4-7 days after initiation of nutritional support. MEASUREMENTS AND RESULTS: Retinol-binding protein (P = 0.0496) and prealbumin (P = 0.0369) increased significantly in the treatment group from day 0 to day 7. There was no reduction in morbidity in ICU. There was no difference in OMEGA score (263 vs. 244) and length of stay in the ICU (16.9 vs. 17.3), but a reduction in length of stay at hospital (31.2+/-18.5 vs. 33.7+/-27.7, P = 0.0022). Mortality on day 90 (17 vs. 18) and after 2 years (24 vs. 24) was identical. CONCLUSIONS: Although it enhances nutrient intake and corrects nutritional parameters such as RBP and prealbumin more rapidly, within 1 week, supplemental parenteral nutrition has no clinically relevant effect on outcome in ICU patients at the early phase of nutritional support.

Use of the retinol-binding protein: transthyretin ratio for assessment of vitamin A status during the acute-phase response.

The ratio plasma retinol-binding protein (RBP):transthyretin (TTR) has been proposed as a means to improve the assessment of vitamin A status of individuals with concurrent infection or inflammation. We have measured RBP and TTR in stored sera from South African children who had accidentally ingested kerosene. Samples were collected from these children in hospital when suffering acute inflammation and respiratory distress, and from them and neighbourhood control children 3 months later. Vitamin A status was defined by modified relative dose response (MRDR) tests of liver retinol stores at 3 months and by serum retinol concentration both when children were ill and when they were well. Illness was defined as either being in hospital or, at follow-up, as having a raised plasma alpha 1-acid glycoprotein (AGP) level. The RBP:TTR value was significantly decreased by both illness and low liver retinol stores. When the effects on RBP:TTR of illness and vitamin A stores were considered together for the 3-month follow-up samples, only vitamin A status significantly decreased the value. We calculated sensitivity and specificity of the RBP:TTR ratio against established measures of vitamin A status using a cut-off value of 0.3 for RBP:TTR and standard cut-off values for MRDR (0.06) and plasma retinol (0.7 mumol/l). Compared with MRDR, RBP:TTR had sensitivities of 76% and 43% and specificities of 22% and 81% to detect vitamin A deficiency in hospitalized and well children respectively. Compared with plasma retinol, sensitivities were 88% and 44% and specificities were 55% and 64% in hospitalized and well children respectively. Only for the case of clinically well children with biochemical evidence of subclinical inflammation did sensitivity (62% and 100% against MRDR and plasma retinol respectively) and specificity (100% and 60% against MRDR and retinol) approach useful levels for an assessment tool. Overall, although a trend supporting the theory behind the use of the RBP:TTR for assessment of vitamin A status in infection was observed in the current study, the ratio did not provide adequate sensitivity and specificity to be a useful assessment tool.

Nutritional assessment of peripheral blood stem cell transplantation in children.

Peripheral blood stem cell transplantation (PBSCT) has many advantages for patients because hematopoiesis and general condition return to normal more rapidly than they do following bone marrow transplantation. Thus, the authors hypothesize that the nutritional condition of patients also returns to normal more rapidly after PBSCT. The duration of insufficient nutrition was investigated in children undergoing PBSCT. The subjects of this study were 8 patients with malignant diseases. The factors measured were body weight, body fat, cholesterol, albumin, pre-albumin, and retinol-binding protein. These parameters were measured a day before transplantation, and then once a week for 4 weeks after transplantation. All parameters were recovered until day 28 from the lowest level in transplantation. In this study, all parameters returned to normal comparatively early. PBSCT causes little damage to patients' nutrition.

Nutritional assessment in head injured patients through the study of rapid turnover visceral proteins.

BACKGROUND & AIMS: Nutritional monitoring of rapid turnover visceral protein is important in the recognition of malnutrition in patients admitted to the Intensive Care Unit (ICU). We studied prealbumin and retinol-binding protein in patients who received three different kinds of artificial nutrition in order to evaluate the appropriateness of artificial nutrition. METHODS: 45 consecutive head injury patients received enteral (Group A), parenteral (Group B) or both enteral and parenteral nutrition (Group C) at random. We considered these parameters: prealbumin, retinol binding protein and nitrogen balance before (T1), after 3 (T2), 7 (T3) and 11 (T4) days after the beginning of study. Statistical analysis was performed with Kruskal-Wallis test and Bonferroni's t -test. RESULTS: Plasma prealbumin and Retinol binding protein (RBP) showed an increasing of basal values during the study period in all groups (<< 0.0001) and more significantly in group A (Enteral nutrition P < 0. 001 vs Total parenteral nutrition (TPN) and Enteral P<< 0.01 vs Enteral and parenteral nutrition). CONCLUSION: Data obtained in the present study indicate that a laboratory is essential for monitoring nutritional assessment and for checking the appropriateness of nutritional therapy. We found prealbumin to be the most sensitive measure and found it to be the test of choice for early assessment and intervention.

Biochemical assessment of the nutritional status of cystic fibrosis patients treated with pancreatic enzyme extracts.

We examined the protein and fat nutritional status of 65 cystic fibrosis patients aged 4-26 y (x +/- SD: 11.2 +/- 5.6 y). Patients were treated with pancreatic enzyme extracts to improve nutrient absorption; in addition, most patients were supplemented with vitamins A and E. Results were compared with those in a control group of 39 subjects aged 5-29 y (x: 14.3 +/- 5.6 y) with no digestive diseases or nutritional deficiencies. Protein determination showed low albumin concentrations in 42% of the cystic fibrosis patients and decreased blood concentrations of retinol binding protein in 12% of the patients. Lipoprotein components were characterized by decreased cholesterol concentrations in 25% of the cystic fibrosis group. Also, mean concentrations of apolipoprotein A-I were significantly lower in the cystic fibrosis group than in control subjects. The results of fatty acid status, expressed in relative (%) and absolute (mg/L) values, showed concentrations of essential fatty acids, represented by linoleic and arachidonic acids, to be significantly decreased in cystic fibrosis patients; this decrease was markedly significant for fatty acid status expressed in absolute values, especially in the cholesteryl ester subfraction. Serum retinol and alpha-tocopherol concentrations were lowered by 8% and 46% in cystic fibrosis patients and control subjects, respectively: retinol, 1.80 +/- 0.50 and 2.37 +/- 0.60 micromol/L, P < 0.001, and alpha-tocopherol, 18.1 +/- 8.7 and 25.7 +/- 5.0 micromol/L, P < 0.001. In conclusion, despite regular treatment with pancreatic enzyme replacements, neither protein nor fat malnutrition in cystic fibrosis patients was completely corrected.

Comparison of the modified relative dose response (MRDR) and the relative dose response (RDR) in the assessment of vitamin A status in malnourished children.

The modified-relative-dose-response (MRDR) test and the relative-dose-response (RDR) test were compared in 49 mildly to moderately malnourished Bangladeshi children. The MRDR test had a significantly lower sensitivity, detecting only 71% of children with very low serum retinol (< or = 0.35 mumol/L) and 33% of children with low serum retinol (0.355-0.70 mumol/L) compared with 100% and 80% for the RDR test, respectively. The MRDR test showed a very strong dependency on retinol-binding protein (RBP) saturation (ie, percent saturation of RBP with retinol) compared with the RDR test. Only 3 (23%) of 13 children with RBP saturation > or = 55% but low vitamin A stores were diagnosed as abnormal by the MRDR test. This suggests that when apo-RBP concentration is limiting, as it is in malnourished children, didehydroretinol, the analog used in the MRDR test cannot effectively compete with retinol for binding to apo-RBP. Under these circumstances, the MRDR test is rendered ineffective. The possibility of increasing the sensitivity of the test by using a high dose of didehydroretinol needs to be investigated.

[Nutritional assessment and rapid turnover protein in the elderly].

Nutritional assessment with respect to rapid turnover protein (RTP) in the elderly was performed in 22 outpatients (7 males and 15 females, mean age 77 years) who suffered from slight illnesses such as mild hypertension and osteoporosis. Their nutritional parameters were almost within the normal range, judging from body mass index (BMI) and their plasma levels of total protein, albumin, lipids and RTP (transferrin, pre-albumin and retinol-binding protein). Statistically, BMI had a significantly positive correlation with subcutaneous fats and total protein and had a significantly negative correlation with HDL-cholesterol. Retinol-binding protein had a significantly positive correlation with prealbumin, ferritin and vitamin A. Conversely, in 12 bedridden patients the nutritional status was very poor, with their plasma levels of the above markers being significantly lower than those of the controls. We administered an enteral diet (EWH330) to 10 bedridden patients in an effort to restore their nutritional status. As a result, their nutritional parameters, especially RTP showed a significant increase after 4 and 8 weeks of the administration of EWH330. These results suggest that RTP is a very sensitive parameter of nutritional assessment in the elderly.

Total parenteral nutrition and nutritional assessment and leukaemic children undergoing bone marrow transplantation.

The aggressive radiotherapy and chemotherapy used in conditioning regimens for children with leukaemia undergoing bone marrow transplantation (BMT) cause a severe catabolic state. Total parenteral nutrition (TPN) is indispensable in the management of these patients. 25 children with leukaemia undergoing BMT were studied to evaluate the efficacy of TPN and the value of anthropometric parameters and biochemical variables (albumin, retinol-binding protein and prealbumin) in monitoring nutritional status in the critical post-BMT phase. The complications of TPN were mainly metabolic, generally mild and easily controlled. The hyperalimentation solution and infusion line were not responsible for infection in any patient. The marked variations in anthropometric parameters and albumin expected in such patients were not observed in our children due to the nutritional support given. Prealbumin and retinol-binding protein showed statistically significant, positive variations (P less than 0.01), thus proving sensitive indices of the response to nutritional repletion.

Assessment of vitamin A status in an elderly French population using impression cytology with transfer.

The vitamin A status of 105 elderly French people was assessed by ocular impression cytology with transfer (ICT). 5 patients (4.8%) had a negative ICT defined by the absence of goblet cells and the enlargement of the epithelial cells (deficient vitamin A status). 100 patients had a positive ICT with goblet cells and small, numerous epithelial cells (sufficient vitamin A status). ICT results were compared to serum biochemical parameters. Mean serum levels of retinol, retinol-binding protein (RBP) and transthyretin (TTR) were significantly lower while C-reactive protein (CRP) and orosomucoid were significantly higher in negative ICT than in positive one. The etiology of vitamin A deficiency is difficult to conclude (malnutrition, vitamin A deficiency, inflammation). ICT is a good indicator of peripheral vitamin A deficiency in our experience.

Assessing the efficacy of intravenous nutrition in general surgical patients: dynamic nutritional assessment with plasma proteins.

We have compared the direction of changes in four plasma transport proteins measured weekly with the direction of nitrogen balance in general surgical patients receiving intravenous nutrition (IVN). Fifty four patients had IVN for 2 weeks, and 15 had IVN for 3 or 4 weeks. Change in plasma prealbumin followed the direction of nitrogen balance in both weeks of IVN in 39 of 54 of the former group, whereas none of the other plasma proteins achieved 50% accuracy. A weekly rise in plasma prealbumin had a sensitivity of 88%, specificity of 70%, positive predictive value of 93%, and negative predictive value of 56% in detecting positive nitrogen balance. Results in the patients who received 3 or 4 weeks of IVN showed an improvement in negative predictive value to 79%. None of the other plasma proteins performed as well. Twelve patients suffered a major complication of their disease or died, following their course of IVN. Nitrogen balance was the best prognostic indicator of these patients, whereas a fall in prealbumin was the best of the plasma proteins, with a sensitivity of 67%, specificity of 79%, positive predictive value of 40%, and negative predictive value of 92% in determining the incidence of complications. Prealbumin was the most suitable plasma protein for use as a dynamic index of nutritional progress in the type of patient seen in this study.

[Assessment of nutritional status for surgical planning]. / Die Erfassung des Ernährungszustands zur Operationsplanung.

72 patients with gastro-intestinal carcinomas were involved in a retrospective study in which 97 metabolic parameters were pre-operatively determined from each of them and subsequently tested by stepwise discriminant analysis for their bearings on clinical mortality. A discriminant function of seven parameters was obtained and can be used as a prognostic nutritional index for successful subdivision of patients into differentiated risk groups. Two prospective control studies were conducted into 605 patients consecutively operated on for benign and malignant diseases for the purpose of testing the nutritional index for its prognostic information potential. The discriminant function proved to be applicable to differentiation between patients with high, moderate, and low surgical risk. Findings were unambiguous. The nutritional index can thus be used as an aid for decision-making in cases in which alternatives exist between several surgical approaches. The importance of malnutrition as a possible causative factor of complications is likely to grow along with the invasiveness of the intervention.

The roles of vitamin A in the prevention of neoplastic diseases: a critical assessment.

The role of vitamin A and its analogs (retinoids) in the prevention and therapy of neoplastic diseases is discussed. Epidemiological data showing a relationship between vitamin A deficiency and increased frequency of tumors in man and animals are examined and the experimental models demonstrating the protective action of retinoids in the respect of both spontaneous and induced neoplasias of animals are reviewed. Among the possible mechanisms responsible of the antineoplastic activity, the immunopotentiating effect is underlined. Some toxicological aspects of retinoids administration and the consequent application of the experimental results in human medicine are finally discussed.