León Cintra's contribution to the field of protein malnutrition effects on sleep and the brain.

On June 19 2009, everyone who knew Leon Cintra was shocked by the terrible news of the automobile accident that took his life. The feeling within the scientific community was that his passing was not only a great loss for Mexican science but also the loss of a beloved friend. He will be missed and forever remembered for his brilliant mind and noble heart. His scientific career was focused, since the beginning, on the study of protein malnutrition effects on brain morphometry, somato-sensory transmission, sleep, circadian rhythms and behavior. His findings showed that malnutrition has long lasting adverse effects on morphometry of systems involved in sleep regulation such as locus coeruleus, nucleus raphe dorsalis and susprachiasmatic nucleus, and on hippocampal circuit implicated in theta activity generation. His results on spectral analysis of electrical field potential at every 4 sec from 24-h baseline recording and 72-h of recovery sleep after total sleep deprivation or selective REM sleep deprivation demonstrated that protein malnutrition induced alterations on homeostatic as well as on circadian sleep regulation; brain oscillations and theta coherent activity between left and right hemisphere and between hippocampus and cerebral cortex are also affected by malnutrition.

INCAP studies of kwashiorkor and marasmus.

This article summarizes thirty years of intensive clinical metabolic and therapeutic studies of the consequences of severe protein deficiency relative to calories, which results in kwashiorkor, and of a balanced deficiency of protein and calories that results in marasmus. Evidence is provided that these are two different metabolic diseases, but kwashiorkor is usually superimposed on some degree of chronic marasmus and hence most cases studied were marasmic kwashiorkor. The value of the creatinine/height index to indicate the degree of lean body cell mass with any disease is demonstrated.

INCAP studies of energy, amino acids, and protein.

This Special Issue summarizes the results of several studies aimed at providing information on a series of questions related to the adequate protein and energy intakes that allow adequate growth and function in children and work performance and productivity in adults. The effect of different sources of protein on nitrogen balance and the requirements of essential amino acids in young children were also explored in fully recovered, previously malnourished children housed in the Metabolic Ward of the Biomedical Division of INCAP. The following are the main results of these investigations: Animal experiments and studies in children recovering from protein-energy malnutrition (PEM) strongly suggest that even when requirements of all nutrients are satisfied, inactivity reduces the rate of linear growth and physical activity improves it as well as lean body mass repletion. The effects of different energy intakes on nitrogen balance demonstrated how energy intake modifies the need to ingest different amounts of protein to satisfy protein requirements. Insensible nitrogen losses in preschool children and their relation to protein intake was demonstrated. The quality of even "good protein sources" modifies the amount needed to satisfy nitrogen requirements, and corn and bean-based diets can satisfy protein needs for health and even growth of young children. Essential amino acid requirements of 2-year-old children was assessed by diverse measurements of nitrogen metabolism and amino acid levels in blood, and were found lower than those recommended by FAO-WHO. In rural adult populations the relationship between energy and protein intake, productivity and body composition, and the impact of environmental hygiene on nitrogen balance was demonstrated and measured.

INCAP studies of hematologic and gastrointestinal function in healthy individuals and those with protein-energy malnutrition and infection.

Anemia is highly prevalent, especially in poorly nourished populations living in unsanitary conditions. Studies of the Central American population showed that iron was the predominant deficient hematopoietic micronutrient and that correction of nutrient deficiencies led to hematological normality as defined by WHO. The bioavailability of diverse iron compounds added to the mostly vegetable diets of such populations showed the superior absorption of chelated iron (NaFeEDTA) and its strong effectiveness in correcting iron deficiency when added to sugar. The consequences on development and mental behavioral functions as well as on work capacity of iron deficiency and anemia in infants, children and adults, and the positive effects of their correction was demonstrated. In protein-energy malnourished (PEM) children, the deficit in active tissue mass (basal oxygen consumption) and in total hemoglobin content were closely related. This relationship persisted as the rates of active tissue mass repletion was modified by levels of protein intake. This demonstrated the strong adaptive nature of hemoglobin content in response to oxygen needs in PEM and during recovery. Gastrointestinal functions in PEM and in populations demonstrated the bacterial invasion of the upper GI tract and how this resulted in secondary bile acids that are toxic to the intestinal mucosal cells impairing their absorptive functions. Environmental hygiene in populations reversed gut bacterial migration and improved GI function.

Diagnosing clinical malnutrition: Perspectives from the past and implications for the future.

This review, intended for both researchers and clinicians, provides a history of the definition of clinical malnutrition. Despite global efforts, we remain without one clear, objective, internationally accepted definition; clarity in this regard will ultimately improve our evaluation and monitoring of nutritional status to achieve optimal patient outcomes. In this review we explore the development of the term malnutrition and its diagnosis and application in the setting of acute and chronic disease. We begin in the second century A.D. with the work of the Greek physician Galen who is credited as the first to apply the term marasmus to characterize three categories of malnutrition, which are surprisingly similar to components of current international definitions. We then highlight significant developments over the next 2000 years culminating in our current application of the clinical diagnosis of malnutrition. A perspective on historical practices may inform current efforts toward a global definition and diagnosis of malnutrition.

Malnutrition in a Modernising Economy: The Changing Aetiology and Epidemiology of Malnutrition in an African Kingdom, Buganda c.1940-73.

The ecological fecundity of the northern shore of Lake Victoria was vital to Buganda's dominance of the interlacustrine region during the pre-colonial period. Despite this, protein-energy malnutrition was notoriously common throughout the twentieth century. This paper charts changes in nutritional illness in a relatively wealthy, food-secure area of Africa during a time of vast social, economic and medical change. In Buganda at least, it appears that both the causation and epidemiology of malnutrition moved away from the endemic societal causes described by early colonial doctors and became instead more defined by individual position within a rapidly modernising economy.

A history of noma, the "Face of Poverty".

Noma (necrotizing ulcerative stomatitis, stomatitis gangrenosa, or cancrum oris) is a devastating orofacial gangrene that occurs mainly among children. The disease has a global yearly incidence of 140,000 cases and a mortality rate of approximately 90 percent. Patients who survive noma generally suffer from its sequelae, including serious facial disfigurement, trismus, oral incontinence, and speech problems. The medical history of noma indicates that the disease was already known in classical and medieval civilizations in Europe. In the sixteenth and seventeenth centuries, Dutch chirurgeons clearly described noma as a clinical entity and realized that the popular name "water canker" was not sufficient, because this quickly spreading ulceration in the faces of children was different from "cancer." In the eighteenth century, awareness that noma is related to poverty, malnutrition, and preceding diseases such as measles increased in northwestern Europe. In the first half of the nineteenth century, extensive surgical procedures were described for the treatment of the sequelae of noma. At the end of that century, noma gradually disappeared in the Western world because of economic progress, which gave the poorest in society the opportunity to feed their children sufficiently. Only in the twentieth century were effective drugs (sulfonamides and penicillin) against noma developed, as well as adequate surgical treatment for the sequelae of noma. These modes of treatment remain inaccessible for the many present-day victims of noma because of their extreme poverty. The only truly effective approach to the problem of noma throughout the world is prevention, namely, combating the extreme poverty with measures that lead to economic progress. In the meantime, medical doctors in the Western world should not forget their own history and ignore this global health problem; rather, they should face "the face of poverty" with the eyes of mercy and concern suited to their profession.

Protein-energy malnutrition and immunological responses.

Historical accounts have suggested a temporal relationship between famines and epidemics. More recently, careful epidemiologic studies have shown a relationship between nutritional deficiencies and heightened risk of morbidity and mortality due to infectious disease. These observations led to studies that examined the effect of protein-energy malnutrition on immunocompetence. The lymphoid tissues, particularly the thymus, were found to be atrophied. There was a reduction in delayed cutaneous hypersensitivity, fewer T cells, especially T helper cells, decreased thymulin activity, impaired secretory immunoglobulin A antibody response, decreased antibody affinity, reduced concentration and activity of complement components and phagocyte dysfunction. These observations were then applied to the study of individual nutrient deficiencies. The interactions of protein-energy malnutrition and the immune system have generated many practical and clinical applications.

Biochemical and palaeopathological investigations on weaning and infant mortality in the early Middle Ages.

Weaning age of the children of the early medieval population at Wenigumstadt (Ldkr. Aschaffenburg, southern Germany, 500-700 AD) was estimated by stable nitrogen isotope analysis of bone collagen. The onset of weaning was by one year of age, when solid vegetal food subsequently replaced breast milk. In total, the change from mother's milk to solid adult food took about three years, the infants being fully weaned at this age. While the growing infant was sufficiently supported in utero and during the first months of life, the weanling's diet was insufficient for further growth and development. Starting with about 18 months of age, more and more symptoms of malnutrition are detectable on the skeletal remains, and the peak of both morbidity and mortality is reached at four years of age. Especially unspecific stress markers like Harris' lines and enamel hypoplasia clearly indicate the infants' risk of falling ill or die between three and four years of age. Malnutrition weakens the immune response, therefore the majority of inflammations detectable on the skeleton are found among the inadequately nourished children. The assumption that weaning is responsible for pathological skeletal lesions and early death in history is thus supported by archaeometry.

Two-century perspective of some major nutritional deficiency diseases in childhood.

In this review, dealing with historical aspects and the present day situation in developing countries, three major nutritional deficiencies among children are discussed, namely rickets, iron deficiency anaemia and protein energy malnutrition (PEM).

[Conceptual milestones in the history of protein-energy malnutrition]. / Hitos conceptuales en la historia de la desnutrición proteico-energética.

Although the biblical horsemen of hunger, plague and war have proverbially ridden together, the consequences of these adversities, i.e. malnutrition and death, may have been secularly interpreted as natural as life itself. This may be the reason why the first clinical description of what is now known as protein-energy malnutrition, did not appear until the 19th century, in 1865 to be precise. The limited dissemination of this finding, originally written in Spanish, brought about a rediscovery and successful description of the disease in English in 1933. In 1949, one year after their creation, the World Health Organization (WHO) and the Food and Agriculture Organization (FAO) decided to unify their diagnostic criteria of malnutrition, and endorse further research. The present assay describes some of the major conceptual landmarks in the history of the scientific knowledge of this disease.

Radiopaque transverse lines (Harris lines) in the prehispanic population of El Hierro (Canary Islands).

Harris lines were assessed in 48 right tibiae of prehispanic inhabitants of El Hierro (one of the Canary Islands), belonging to 23 adult females and 25 adult males. No Harris lines were detected in sixteen (33%) of the adult individuals (7 females = 30% and 9 males = 36%), these differences are not statistically significant. Female tibiae showed a slightly higher mean number of Harris lines at the distal end than male ones (2.091 +/- 1.9 in females vs 1.417 +/- in males). Ages at which Harris lines were formed show two peaks, a major one at the age of 2 years, and another one between 11 and 13, particularly in the females. Harris lines were more frequently observed at the proximal than at the distal end of the bone. No relation was found between the number of Harris lines and stature. The relative high number of lines detected in our population speak for several stressful episodes suffered during growth.

Endemic disease patterns in paleopathology: porotic hyperostosis.

Recent research has shown that constitutional factors can elicit a porotic skeletal lesion pattern related to iron-deficiency anemia, even when adequate dietary iron is available. This study considers the pattern of skeletal involvement under conditions of chronic or endemic dietary stress. Analysis focused on 54 subadults aged 0-10 years at death from the Arroyo Hondo site. Early age of onset is documented in the pattern of coincident active periosteal reactions and porotic lesions under 6 months. Endemically inadequate diets affecting pregnant females and their fetuses, acting synergistically with immediately acquired infections, not weaning diets, are the probable major underlying causes for the early onset of iron-deficiency anemia at Arroyo Hondo.