Comparison of standard of care treatment with a low steroid and mycophenolate mofetil regimen for lupus nephritis in the ALMS and AURA studies.

Lupus nephritis is the most common organ-threatening manifestation of systemic lupus erythematosus. The current standard of care for patients is treatment with a combination of steroids plus either mycophenolate mofetil (MMF) or cyclophosphamide. However, these medications are associated with considerable toxicity and suboptimal efficacy. This retrospective propensity analysis of data from 63 matched patients enrolled in two of the largest active lupus nephritis controlled trials, ALMS and AURA, suggests that the high dose regimen of MMF and steroids as described in the 2012 American College of Rheumatology lupus nephritis guidelines may not be necessary in all lupus nephritis patients. A lower dose regimen may result in better long-term safety, including a reduction in lymphoproliferative disorders, skin cancers and steroid related side effects, without compromising efficacy. An ongoing randomized controlled double-blind phase 3 study, AURORA (NCT03021499), is investigating renal response in 358 patients randomized to receive a low dose regimen containing voclosporin, MMF and steroid therapy as used in the AURA trial. It is anticipated that the AURORA study and its blinded two-year extension will provide important long-term outcome data.

The potential double-burden of vitamin A malnutrition: under- and overconsumption of fortified table sugar in the Guatemalan highlands.

BACKGROUND/OBJECTIVES: In Guatemala, population-wide vitamin A fortification of table sugar has been operating for two decades. The objective of this study was to estimate the adequacy of vitamin A intakes in pregnant and lactating women from low-income, urban and rural communities. SUBJECTS/METHODS: One or two previous-day dietary recalls were collected in a convenience sample of 234 pregnant and lactating women in the Western Highlands of Guatemala. Estimated daily intakes and main sources of total vitamin A, provitamin A and preformed vitamin A were calculated. Total intakes, adjusted for day-to-day variation, were examined in relation to estimated average requirements (EAR). RESULTS: Median estimated 1-day total vitamin A intake was 1177 µg retinol activity equivalents (RAE) (interquartile range (IQR) 832-1782) in the urban site and 567 µg RAE (IQR 441-737) in the rural site. Women not meeting their status-specific vitamin A requirement were 3.5 times more common in the rural communities (31%) than in the urban confines (9%). In the urban area, 26 women (21%) had preformed vitamin A intakes above 1500 µg on the day of data collection. Preformed vitamin A accounted for a median of 83.9% and 60.9% of the daily total vitamin A intake in the urban and rural sites, respectively. Sugar was the principal source of vitamin A, contributing 512 µg RAE (IQR 343-749) in the urban site and 256 µg RAE (IQR 189-363 µg) in the rural area. CONCLUSIONS: The vitamin A contribution from fortified sugar can be a determinant of reaching adequacy; nevertheless, a significant proportion of pregnant and lactating women do not meet the EAR, especially in the rural setting.

Nutrient density in complementary feeding of infants and toddlers.

The paradigm of the first 1000 days of life, the period from conception to the second birthday, has been advanced as a critical window of opportunity to save a life and a child's future. Infancy and toddler life, through the first 24 months after birth, is a unique period during which human milk is recommended as either the exclusive source of nutrition (6 months) or a variable component thereof. After the maternal delivery of milk is accounted for, the remainder of the energy and nutrients needs come from complementary foods. There is an intrinsic gap left by the maternal milk supply in volume and micronutrient content in relation to expanding infant and toddler needs. The nutrient density approach provides us with a mathematical framework to manage the closing of the nutrient gap. The intrinsic nutrient content of the unprocessed foods appropriate for young children is limited. The most problematic nutrients are calcium, iron and zinc. Some manner to enhance the nutrient density of the complementary foods is an incontestable necessity. The nutrient density consideration, which identifies for us the nature of the problem, offers a tool for the titrating of the fortification to an adequate--but safe--addition.

Several 'problem nutrients' are identified in complementary feeding of Guatemalan infants with continued breastfeeding using the concept of 'critical nutrient density'.

BACKGROUND/OBJECTIVES: The World Health Organization (WHO) recommends nutritionally adequate complementary feeding (CF) through the introduction of indigenous foodstuffs and local foods while breastfeeding for at least 2 years. To determine the adequacy of the contribution of CF to the diets of Guatemalan infants at the 7th-12th month of life receiving high-intensity continued breastfeeding. SUBJECTS/METHODS: Critical nutrient densities for CF were modelled using age- and sex-specific energy and protein requirements assuming children to be at the 50th weight percentile of local peers and 15th weight percentiles of the 2006 WHO standards. Nutrient requirements for the total diet were determined using the recommended nutrient intakes. Breast milk was assumed to provide 75% of total energy at the 7th-9th month and 50% at the 10th-12th month. Gaps between computed critical nutrient densities and the CF consumption of 128 Guatemalan infants based on data collected by means of three nonconsecutive 24-h quantitative intake recalls were examined. Locally consumed foods with nutrient densities above the modelled critical densities were identified. RESULTS: Observed non-breast milk complementation would result in total diets providing inadequate nutrient density for vitamin A, niacin and vitamin C in some age groups. Major gaps for calcium, iron and zinc were ubiquitous across all groups. Few foods commonly consumed among Guatemalan infants had adequate densities of 'problem nutrients'. CONCLUSIONS: The critical nutrient density concept is useful to evaluate the nutrient adequacy of the infant's diet. Fortified foods are essential sources of the main 'problem nutrients', namely calcium, iron and zinc, given that natural sources are scarce.

Daily consumption of foods and nutrients from institutional and home sources among young children attending two contrasting day-care centers in Guatemala City

Adequate nutrition is critical to child development and institutions such as day-care centers could potentially complement children’s diets to achieve optimal daily intakes. The aim of the study was to describe the full-day diet of children, examining and contrasting the relative contribution of home-derived versus institutional energy and nutrient sources. The present comparison should be considered in the domain of a case-study format. The diets of 33, 3-6 y old children attending low-income day-care centers serving either 3 or a single meal were examined. The home-diet was assessed by means of 3 non-consecutive 24-hr recalls. Estimated energy and nutrient intakes at the centers and at home were assessed and related to Recommended Nutrient Intakes (RNI). Nutrient densities, critical densities and main sources of nutrients were computed. We observed that in children attending the day-care center serving three meals, home-foods contributed less than half the daily energy (47.7%) and between 29.9% and 53.5% of daily nutrients. In children receiving only lunch outside the home, energy contribution from the home was 83.9% and 304 kcal lower than for children receiving 3 meals. Furthermore, between 59.0% and 94.8% of daily nutrients were provided at home. Daily energy, nutrient intakes and nutrient densities were well above the nutrient requirements for this age group, and particularly high for vitamin A. The overall dietary variety was superior in the situation of greater contribution of home fare, but overall the nutrient density and adequacy of the aggregate intakes did not differ in any important manner.

Ingesta diaria de alimentos y nutrientes provenientes de la dieta institucional y del hogar en niños que asisten a dos centros de cuidado infantil contrastantes en la ciudad de Guatemala. Una adecuada nutrición es crítica para el desarrollo infantil. Los centros de cuidado infantiles (CCI) podrían jugar un papel fundamental en la complementación de la ingesta de alimentos y nutrientes. El propósito de este estudio fue describir la dieta de niños, comparando la contribución relativa de energía y nutrientes de la dieta-hogar e institucional. El presente estudio debe ser considerado como una presentación de caso. Se examinó la dieta de 33 niños de 3-6 años que asisten a dos CCI utilizados por familias de escasos recursos y con diferencias en número de comidas servidas. Se determinó la dieta-hogar utilizando 3 recordatorios de 24-horas en días no-consecutivos. Se calculó la ingesta estimada de energía y nutrientes en las instituciones y en casa y se comparó con las Ingestas Recomendadas de Nutrientes. Se determinó la densidad de nutrientes y principales fuentes. Se observó que los alimentos consumidos en el hogar contribuyeron 47.7% de la energía diaria y entre 29.9% y 53.5% de los nutrientes diarios requeridos para los niños con 3 comidas en el CCI y de 83.9%, 59.0 y 94.8%, respectivamente, para los niños que consumen únicamente el almuerzo en el CCI. La ingesta diaria de energía fue 304 kcal mayor en los niños que consumieron 3 comidas fuera del hogar. No hubo mayor variación en las dietas cuando mayor era el consumo de alimentos en el hogar, sin embargo la densidad nutricional y la adecuación de la dieta completa fue adecuada en ambos centros, y particularmente elevadas para la vitamina A.

Efficacy of mycophenolate mofetil in adolescent patients with lupus nephritis: evidence from a two-phase, prospective randomized trial.

The safety and efficacy of mycophenolate mofetil (MMF) were evaluated in adolescent patients with systemic lupus erythematosus and active or active/chronic class III-V lupus nephritis. During the 24-week induction phase, patients were randomized to oral MMF (target dose 3.0 g/day) or intravenous cyclophosphamide (IVC) (0.5-1.0 g/m(2)/month), plus prednisone. Response was defined as a decrease in 24-hour urine protein:creatinine ratio (P:Cr) to < 3 in patients with baseline nephrotic range proteinuria, or by ≥ 50% if subnephrotic baseline proteinuria, and stabilization (± 25%) or improvement in serum creatinine. In the 36-month maintenance phase, induction therapy responders were randomized 1:1 to MMF (1.0 g twice daily) or oral azathioprine (AZA) (2 mg/kg/day), plus prednisone. In the induction phase, 10 patients received MMF and 14 received IVC; 15 (62.5%) achieved treatment response (MMF, 7 (70%); IVC, 8/15 (57.1%); p = 0.53, odds ratio (95% confidence interval) 2.0 (0.2, 15.5)). There was a non-statistically significant difference in maintenance of response to MMF (7/8; 87.5%) versus AZA (3/8; 37.5%). Seven patients withdrew (MMF, 2; AZA, 5). During both phases, rates of serious adverse events were similar in both arms. During both phases treatment response with MMF was as effective as the comparator.

Daily consumption of foods and nutrients from institutional and home sources among young children attending two contrasting day-care centers in Guatemala City.

Adequate nutrition is critical to child development and institutions such as day-care centers could potentially complement children's diets to achieve optimal daily intakes. The aim of the study was to describe the full-day diet of children, examining and contrasting the relative contribution of home-derived versus institutional energy and nutrient sources. The present comparison should be considered in the domain of a case-study format. The diets of 33, 3-6 y old children attending low-income day-care centers serving either 3 or a single meal were examined. The home-diet was assessed by means of 3 non-consecutive 24-hr recalls. Estimated energy and nutrient intakes at the centers and at home were assessed and related to Recommended Nutrient Intakes (RNI). Nutrient densities, critical densities and main sources of nutrients were computed. We observed that in children attending the day-care center serving three meals, home-foods contributed less than half the daily energy (47.7%) and between 29.9% and 53.5% of daily nutrients. In children receiving only lunch outside the home, energy contribution from the home was 83.9% and 304 kcal lower than for children receiving 3 meals. Furthermore, between 59.0% and 94.8% of daily nutrients were provided at home. Daily energy, nutrient intakes and nutrient densities were well above the nutrient requirements for this age group, and particularly high for vitamin A. The overall dietary variety was superior in the situation of greater contribution of home fare, but overall the nutrient density and adequacy of the aggregate intakes did not differ in any important manner.

Bioavailability of zinc from NutriSet zinc tablets compared with aqueous zinc sulfate.

BACKGROUND/OBJECTIVES: The apparent widespread extent of zinc (Zn) deficiency in developing countries and the efficacy of oral Zn supplements as an adjunct to oral rehydration therapy make oral Zn supplementation an increasingly important modality in clinical medicine and public health. In this study we aimed to compare the relative bioavailability of oral doses of 30 mg of Zn in two dosing forms. SUBJECTS/METHODS: In total, 10 healthy male volunteers ingested oral Zn doses with 200 ml plain water at about 0830 hours in the fasting state on two occasions, once as 30 mg of Zn in an aqueous solution of reagent grade zinc sulfate (ZnSO(4)) and another time as 1.5 NutriSet Zn tablets (Nutriset, Malaunay, France); on a third occasion, only plain water was consumed. Venous blood specimens were collected at baseline, 60, 120, 180 and 240 min after ingestion and the plasma Zn was measured for each sample. RESULTS: The relative bioavailability of oral Zn from a commonly used, tableted (NutriSet) form is only about half of that of a reference dose of aqueous ZnSO(4) as indicated by the area under the curve of serial plasma Zn excursion and maximal change in circulating Zn. CONCLUSIONS: Reduced or absent functional outcomes in Zn intervention trials may derive, in part, from a lower than anticipated intestinal uptake of the Zn in the tableted form.

Contribution of complementary foods to the total daily water needs of urban Guatemalan infants.

BACKGROUND: Estimates of adequate intake (AI) for water only became available in 2005. The daily water AI for 6-12-month-old infants of both sexes is 800 mL. The present study aimed to estimate the water intake of urban infants receiving both breast milk and complementary feeding (CF) and to compare them with the reference AI. METHODS: Sixty-four infants, 42 boys and 22 girls, aged 6-12 months on enrollment, from a low-income district of Guatemala City, were recruited to the study. Quantitative 24-h recalls and breastfeeding histories were collected in three serial interviews. The quantity of water was estimated from recipes and food composition moisture values for the CF items reported. The amount of breast milk needed to complement foods and beverages in meeting the individual energy needs was calculated, and breast milk's water contribution was derived accordingly. The total quantity of water in beverages, including human milk, liquids in recipes and moisture of foods, was tabulated as the infants' daily intake. RESULTS: Some 56.3% of the water needs for boys and 41.1% for girls were satisfied by just water obtained from plain water, other complementary beverages and moisture of foods within CF, exclusive of breast milk. Adding the estimated breast milk intake, the median water intake for the infant sample was essentially equal to the 800 mL of the AI. CONCLUSIONS: The infants in this low-income community are approximating the recommended AI for daily water through the currently selected pattern of lactation and CF.

Practical limitations to a positive deviance approach for identifying dietary patterns compatible with the reduction of cancer risk.

BACKGROUND: The positive deviance (PD) approach seeks to devise and promote health-promoting practices identified within the most successful member of a society. The World Cancer Research Fund and the American Institute for Cancer Research (WCRF/AICR) recommendations indicate the need for specific dietary behaviours, which may be considered impractical. Thus, it is important to demonstrate ways in which these dietary practices have been achieved from concordant individuals. The present study aimed to assess the feasibility of constructing healthy eating guides in four international settings. METHODS: Adult participants from the Netherlands (n = 1052), Scotland (n = 849), Mexico (n = 790) and Guatemala (n = 873) enrolled in an international diet survey project. Participants with inadequate diets and current smokers were excluded from the analysis. Concordance with selected WCRF/AICR individual guideline components related to diet and lifestyle were evaluated. A selection of participants was made towards making a set of 14 rotating menus for a cancer-prevention healthy-eating guide. RESULTS: Overall concordance with the WCRF/AICR recommendations was low in all four nations and no participants with an ideal behaviour were found. The selection of candidates for constructing 14 daily menus for a single national guide identified 51, 13 and 12 individuals concordant with 11 of 14 WCRF/AICR recommendation components in Guatemala, Scotland and Mexico, respectively, and 24 individuals concordant with eight of 14 WCRF/AICR components in the Netherlands. CONCLUSIONS: The basis for PD guidance for developing dietary recommendations for cancer prevention was strong across all social classes in Guatemala, marginal for Mexico and Scotland, and effectively impossible for the Netherlands.

Efficacy and safety of twice-weekly administration of three RDAs of iron and folic acid with and without complement of 14 essential micronutrients at one or two RDAs: a placebo-controlled intervention trial in anemic Cambodian infants 6 to 24 months of age.

OBJECTIVE: To determine the differential efficacy and safety of twice-weekly administration of 3 RDAs of iron and folic acid, with and without a complement of 2 RDAs of 11, and 1 RDA of 3 additional essential micronutrients as compared to a placebo control (PlbCON) given as foodLETs. SUBJECTS/METHODS: A total of 250 children aged 6-24 months were enrolled after recruitment by village health workers; 19 of them dropped out during the trial. Children were assigned to one of three treatment arms and followed for 20.5 weeks; 41 supervised twice-weekly dosings of 30 mg of iron plus folic acid, either with or without accompanying micronutrients or placebo were given as foodLETs, a tool for ready-to-eat fortification in infant food. Initial and final measurements of anthropometry and blood biomarkers for hematological, iron stores and inflammatory status, as well as for abnormal hemoglobin (Hb), were obtained. Symptoms of listlessness, vomiting, watery stools and acute respiratory infections were monitored weekly. RESULTS: Iron-containing supplements increased Hb concentrations significantly (P<0.0001) and virtually eradicated any IDA, as compared to no change in hematological status in the PlbCON group (P=0.011). Iron stores, as reflected by ferritin, increased significantly with iron-containing treatments (P<0.0001). Responses were as effective in individuals with HbE as in those with exclusively HbA phenotypes. Watery stools (P=0.002) and listlessness (P=0.001) were significantly more frequent in those receiving iron and folic acid alone than in the PlbCON group. In contrast, acute respiratory infections (P=0.014) and listlessness (P=0.001) were significantly less frequent in those receiving the multiple micronutrient formulation than in the PlbCON group. CONCLUSIONS: Supplementation of micronutrients along with iron and folic acid mitigates the excess morbidity of iron-folate alone, without reducing its efficacy in correcting anemia and building iron stores. FoodLETs are a suitable vehicle to provide micronutrient supplementation to infants.

An international, phase III, randomized trial of mycophenolate mofetil in myasthenia gravis.

BACKGROUND: This prospective, randomized, double-blind, placebo-controlled, phase III trial assessed the efficacy, safety, and tolerability of mycophenolate mofetil (MMF) as a steroid-sparing agent in patients with myasthenia gravis (MG). METHODS: Patients with acetylcholine receptor antibody-positive class II-IVa MG (MG Foundation of America [MGFA] criteria) taking corticosteroids for at least 4 weeks were randomized to MMF (2 g/day) or placebo for 36 weeks. The primary endpoint was a composite measure defined as achievement of minimal manifestations or pharmacologic remission (MGFA post-intervention status), with reduction of corticosteroid dose on a set schedule. Secondary endpoints included disease severity, quality-of-life scores, and safety. RESULTS: A total of 44% of MMF-treated (n = 88) and 39% of placebo-receiving (n = 88) patients achieved the primary endpoint (p = 0.541). Improvements in mean quantitative MG, MG activities of daily living, and 36-item Short-Form health survey scores were similar in both groups. Numbers of adverse events were similar in both groups. The most commonly reported adverse events in the MMF-treated group were headache (12.5%) and worsening of MG (11.4%), and in the placebo group, worsening of MG (20.5%) and diarrhea (10.2%). CONCLUSIONS: Initiation of mycophenolate mofetil (MMF) treatment was not superior to placebo in maintaining myasthenia gravis (MG) control during a 36-week schedule of prednisone tapering. There were no significant differences in the primary or secondary endpoints between the study groups. MMF was well tolerated and adverse events were consistent with previous studies. Experience from this large, international, multicenter, phase III study employing full MG Foundation of America guidelines will aid the design of future MG studies.

Mycophenolate mofetil as induction and maintenance therapy for lupus nephritis: rationale and protocol for the randomized, controlled Aspreva Lupus Management Study (ALMS).

The Phase III Aspreva Lupus Management Study (ALMS) will investigate mycophenolate mofetil (MMF) therapy for lupus nephritis (LN). Eligibility criteria include: 12-75 years of age; diagnosis of systemic lupus erythematosus according to revised American College of Rheumatology criteria; and biopsy-demonstrated LN (Class III-V). Randomized patients will receive open-label induction therapy with MMF or cyclophosphamide in combination with corticosteroids for 24 weeks. The primary efficacy endpoint is treatment response [decreased proteinuria and stabilized (within 25% of baseline) or improved serum creatinine level]. Patients achieving response or complete remission (normalization of all parameters) will be rerandomized to double-blind, placebo-controlled maintenance treatment with MMF or azathioprine, both plus corticosteroids. The maintenance phase primary endpoint is time to treatment failure. To detect a 15% rate improvement in the MMF group compared with cyclophosphamide, and to provide 90% power, a total of 358 patients will be required for the induction phase. On the basis of a projected 278 rerandomized patients, the maintenance phase will have 90% power to detect a difference between treatment groups assuming azathioprine and MMF three-year failure rates of 59.5% and 40.7%, respectively. Aspreva Lupus Management Study may provide invaluable comparative data on the efficacy and safety of MMF as LN induction and maintenance therapy.

Haematological response to haem iron or ferrous sulphate mixed with refried black beans in moderately anaemic Guatemalan pre-school children.

OBJECTIVE: Combating iron deficiency in toddlers with iron-fortified food has proved difficult in countries with phytate-rich diets. For this purpose, a new haem iron preparation was developed. The study compared changes in iron status after administration of refried beans with beans fortified with a haem iron preparation or ferrous sulphate (FeSO4). DESIGN: In a masked, stratified-randomised intervention trial, children received five 156-g cans of refried black beans per week for 10 consecutive weeks. The beans-only (control), FeSO4 and haem iron groups were offered a cumulative dose of 155 mg, 1625 mg and 1700 mg of iron from the bean intervention, respectively. Haemoglobin (Hb) and ferritin concentrations were determined at baseline and after 5 and 10 weeks. Compliance was examined weekly. SETTING: A low-income community in Guatemala City. SUBJECTS: One hundred and ten children aged 12-36 months with initial Hb values between 100 and 115 g l(-1). RESULTS: The cumulative intake of beans was approximately 80% of that offered, signifying an additional approximately 1300 mg of either haem or inorganic iron in the corresponding treatment groups over 10 weeks. Hb concentrations increased by the order of 7.3-11.4 g l(-1) during the intervention, but without significant differences across treatments. Average ferritin concentrations were unaffected by treatment assignment. However, post hoc analysis by subgroups of initial high ferritin and initial low ferritin found the Hb increments after 10 weeks in the haem iron group (13.1+/-7.7 g l(-1)) to be significantly greater than the respective increases (6.8+/-11.2 and 6.4+/-8.5 g l(-1)) in the inorganic iron and beans-only groups. CONCLUSIONS: Canned refried beans are a candidate vehicle for fortificant iron. Given the improved colour and organoleptic properties imparted by haem iron added to refried beans, its additional potential for benefiting the iron status of consumers with iron deficiency may recommend it over FeSO4.

Monitoring of hematological, inflammatory and oxidative reactions to acute oral iron exposure in human volunteers: preliminary screening for selection of potentially-responsive biomarkers.

BACKGROUND: Iron is an essential micronutrient but also a major catalyst of oxidative and inflammatory reactions. OBJECTIVE: To evaluate the potential utility of selected biomarkers in blood or urine to indicate in vivo oxidative or inflammatory response to oral iron intake at pharmacological doses. METHODS: Three healthy volunteers provided morning, fasting samples of blood and urine on up to 13 study days--3 before, 7 during and 3 following a 7-consecutive-day period of receiving 120 mg of iron per day as ferrous sulfate in commercially available syrup. A series of 23 biomarkers were measured on each collection of biological fluids to monitor iron-responsive changes in biomarkers related to hematological or iron status, inflammation and in vivo oxidation. RESULTS: Among the inflammatory biomarkers measured, white blood cells, serum CRP and urinary neopterin showed no response to iron dosing. Only circulating interleukin-4 (IL-4) and TNF-alpha had abnormal responses with a time association to the oral iron intake. Among the oxidative biomarkers, expression of blood superoxide dismutase (SOD), hemoxygenase-1, catalase as well as circulating thiobarbituric acid reactive substances (TBARS), total oxidative capacity and carbonyl proteins were stable in response to iron exposure. Only urinary TBARS, 8-hydroxy-2-desoxyguanosine and isoprostanes evidenced consistent or suggestive responses to ingestion of the iron challenge. Serum hepcidin concentration increased dramatically in all three subjects after only the first 120 mg dose of iron, and remained elevated even 9 days after cessation of the iron intervention. CONCLUSIONS: Most of the candidate biomarkers show very limited promise as response-indicators to oral iron dosing at the 120 mg dosages or lower, but circulating IL-4, TNF-alpha as well as urinary TBARS, 8-hydroxy-2-desoxyguanosine and isoprostanes showed potential utility as reliable indicators of oxidative and inflammatory response to oral ferrous sulfate.

Modulation of the immune system and the response against pathogens with bovine colostrum concentrates.

The growth, development and health conditions for children living under deprived conditions in developing countries are so adverse that immediate public health measures to reduce morbidity and improve nutrition are urgently needed. Preventing and shortening the course of diarrhoeal episodes, eliminating protozoal colonization, and balancing intestinal microflora would all contribute to these goals. The consumption by humans of part of the colostrum produced when a dairy animal gives birth is an established tradition in many traditional societies. Recent advances in food technology in industrial dairying allow for continuous availability of stabilized bovine colostrum concentrate, both natural and hyperimmunized against specific human pathogens. This is safe for the calves of the producers themselves, for laboratory animals, and generally for humans, with the caveat of the milk-allergic. Moreover, substantial amounts of orally ingested bovine colostrum concentrate survive their passage through the stomach to remain intact and active in the lower reaches of the bowel. Studies in animals, human volunteers and naturally infected humans have demonstrated a therapeutic efficacy of oral bovine colostrum with certain infections. Similarly, attempts to prevent gastrointestinal infections in animals, exposed volunteers and at-risk populations have met with limited success with specific pathogens. It is time to begin to assess the feasibility and potential effectiveness and efficiency of employing seasonal or chronic bovine colostrum feeding in populations of deprived infantile populations to reduce the rates of recurrent gastroenteritis and decrease immunostimulation to improve vitality and nutritional status in early life.

A base of skull fracture presenting as haematemesis.

In a patient presenting with haematemesis, known to have oesophageal varices, the bleeding would be expected to be from those varices. This case demonstrates an unusual presentation of a base of skull fracture; blood from a fracture of the temporal bone had run from the middle ear through the eustachian tube to the pharynx. It demonstrates the need to remain vigilant even when the diagnosis appears to be obvious.

Fermentation, fermented foods and lactose intolerance.

Lactose (milk sugar) is a fermentable substrate. It can be fermented outside of the body to produce cheeses, yoghurts and acidified milks. It can be fermented within the large intestine in those people who have insufficient expression of lactase enzyme on the intestinal mucosa to ferment this disaccharide to its absorbable, simple hexose sugars: glucose and galactose. In this way, the issues of lactose intolerance and of fermented foods are joined. It is only at the extremes of life, in infancy and old age, in which severe and life-threatening consequences from lactose maldigestion may occur. Fermentation as part of food processing can be used for preservation, for liberation of pre-digested nutrients, or to create ethanolic beverages. Almost all cultures and ethnic groups have developed some typical forms of fermented foods. Lessons from fermentation of non-dairy items may be applicable to fermentation of milk, and vice versa.

Can the degree of concordance with recommendations for a cancer prevention diet and lifestyle be assessed from existing survey information data?

BACKGROUND: The World Cancer Research Fund convened an expert committee who analyzed the literature related to the causation of human cancers. Recommendations for preventing cancer through behavioral practices were formatted into a 14-point guideline. OBJECTIVE: We parsed the cancer prevention guidelines to determine to what extent relevant information on individual behavior could be assessed from conventional food-frequency questionnaires, which are being used in surveys conducted in developing countries. DESIGN: We examined a convenience sample of archival forms completed during 2 independent studies (a case-control and a field study) that used an adapted Willett food-frequency questionnaire that was translated into Spanish for use in Guatemala. RESULTS: All dietary related guidelines, except for salt, were evaluated by both questionnaires. Physical activity, food handling, and food preparation were not addressed by either of the questionnaires, although body mass index and dietary supplements were addressed in the case-control study and field-study questionnaires, respectively. CONCLUSIONS: Although concordance with some of the cancer prevention goals and guidelines can be evaluated from the existing questionnaires, adjustments and additions must be made with respect to salt and supplement use, physical activity, and food handling. Actual weight and height measurements are also needed, particularly in low-income populations.

Self-rated health and its relationship to functional status and well-being in a group of elderly Guatemalan subjects.

This study examined the association of self-rated health with physical function and emotional well-being, while controlling for differences in sex, age and anthropometry. Subjects were participants in a multicentre study originated by the International Union of Nutritional Sciences (IUNS). A total of 151 elderly Guatemalan subjects were examined using a questionnaire which included information on self-rated health, activities of daily living, well-being, and a common battery of anthropometric variables. Adjusted odds ratios (OR) obtained with polytomous logistic regression showed that subjects with the highest score on the well-being index compared with those with the lowest were 1.67 times more likely (P-value <0.001, confidence interval (C.I.) = 1.31-2.14) to rate themselves in 'good' health versus 'fair' and 'poor' health. Subjects with the highest score versus those with the lowest on the mobility index were 1.15 times more likely (P-value <0.05, (C.I.) = 1.00-1.32) to rate themselves in 'good' health versus the other health ratings. These are the first results to examine the relationship of self-rated health to physical function and emotional well-being of elderly, free-living Guatemalans.