Historical Perspective on Clinical Trials of Carnitine in Children and Adults.

The metabolic roles of carnitine have been greatly clarified over the past 50 years, and it is now well established that carnitine is a key player in mitochondrial generation of energy and metabolism of acetyl coenzyme A. A therapeutic role for carnitine in treatment of nutritional deficiencies in infants and children was first demonstrated in 1958, and since that time it has been used to treat a number of inborn errors of metabolism. Carnitine was approved by the US Food and Drug Administration in 1985 for treatment of 'primary carnitine deficiency', and later in 1992 for treatment of 'secondary carnitine deficiency', a definition that included the majority of relevant metabolic disorders associated with low or abnormal plasma carnitine levels. Today, carnitine treatment of inborn errors of metabolism is a safe and integral part of many treatment protocols, and a growing interest in carnitine has resulted in greater recognition of many causes of carnitine depletion. Notwithstanding, there is still a lack of data from randomized clinical trials, even on the use of carnitine in inborn errors of metabolism, although ethical issues may be a contributing factor in this regard.

Global Update and Trends of Hidden Hunger, 1995-2011: The Hidden Hunger Index.

BACKGROUND: Deficiencies in essential vitamins and minerals-also termed hidden hunger-are pervasive and hold negative consequences for the cognitive and physical development of children. METHODS: This analysis evaluates the change in hidden hunger over time in the form of one composite indicator-the Hidden Hunger Index (HHI)-using an unweighted average of prevalence estimates from the Nutrition Impact Model Study for anemia due to iron deficiency, vitamin A deficiency, and stunting (used as a proxy indicator for zinc deficiency). Net changes from 1995-2011 and population weighted regional means for various time periods are measured. FINDINGS: Globally, hidden hunger improved (-6.7 net change in HHI) from 1995-2011. Africa was the only region to see a deterioration in hidden hunger (+1.9) over the studied time period; East Asia and the Pacific performed exceptionally well (-13.0), while other regions improved only slightly. Improvements in HHI were mostly due to reductions in zinc and vitamin A deficiencies, while anemia due to iron deficiency persisted and even increased. INTERPRETATION: This analysis is critical for informing and tracking the impact of policy and programmatic efforts to reduce micronutrient deficiencies, to advance the global nutrition agenda, and to achieve the Millennium Development Goals (MDGs). However, there remains an unmet need to invest in gathering frequent, nationally representative, high-quality micronutrient data as we renew our efforts to scale up nutrition, and as we enter the post-2015 development agenda. FUNDING: Preparation of this manuscript was funded by Sight and Life. There was no funding involved in the study design, data collection, analysis, or decision to publish.

"Sick and unable to march:" life and death in the army of the Dutch West India Company in the Northeast of Brazil, 1630-1654.

Of the many evils that were inflicted upon the army of the West India Company in its years of activity in Brazil, few could be compared to diseases. However, there is little quantitative data in the field of historiography regarding the impact of disease on these troops. Apart from the limited amount of information about the diseases that affected many soldiers, little is known about the medical treatments that were available, the main diseases that affected the troops, and what were the causes. This article provides information to understand aspects that have been little studied in quantitative and systematic terms in the field of historiography, and demonstrates how the diseases afflicted the Company and affected its actions in the territory.

“ Doentes e incapazes para marchar”: vida e morte no exército da Companhia Neerlandesa das Índias Ocidentais no Nordeste do Brasil, 1630-1654 / “ Sick and unable to march: ” life and death in the army of the Dutch West India Company in the Northeast of Brazil, 1630-1654

Dos diversos males que infligiram o exército da Companhia das Índias Ocidentais em seus anos de atividade no Brasil, poucos podem ser comparados às doenças. São escassos, todavia, os dados quantitativos apresentados na historiografia para mostrar seu impacto nas tropas. Além dos índices de baixas por doença que ceifavam muitos militares, sabe-se pouco sobre os tratamentos médicos oferecidos, as principais doenças que atingiam a tropa e suas causas. Este artigo traz elementos que ajudam a compreender aspectos pouco trabalhados em termos quantitativos e sistemáticos pela historiografia e demonstra como as doenças afligiam a companhia e embaraçavam suas ações no território.

Of the many evils that were inflicted upon the army of the West India Company in its years of activity in Brazil, few could be compared to diseases. However, there is little quantitative data in the field of historiography regarding the impact of disease on these troops. Apart from the limited amount of information about the diseases that affected many soldiers, little is known about the medical treatments that were available, the main diseases that affected the troops, and what were the causes. This article provides information to understand aspects that have been little studied in quantitative and systematic terms in the field of historiography, and demonstrates how the diseases afflicted the Company and affected its actions in the territory.

[Neurological changes related to malnutrition during the spanish civil war (1936-1939)]. / Trastornos neurológicos relacionados con la malnutrición en la Guerra Civil Española (1936-1939).

In this lecture, given at the International Conferences on Neuroscience, in Quito, May 31st-June 1st of 2013, the topic of famine situations during the Spanish Civil War, 1936-1939, was approached. Madrid, the capital of Spain, was under food, water and milk rationing during that period. This situation led to conditions that showed the relationships between the nervous system and nutrition. The Madrilenian population was submitted to a real experiment of hyponutrition, similar to the one that may be reproduced at the laboratory. At the end of the war, the National Direction on Health and the Institute of Medical Investigations, with the collaboration of the Rockefeller Foundation, carried out a series of clinical and food consumption surveys among the Madrilenian population. There were three medical situations that were of particular relevance during the Civil War and after it: the pellagra epidemics, the onset of lathyrism, and the socalled Vallecas syndrome. The occurrence of pellagra cases was paramount because it allowed reconsidering all the unspecific symptoms observed from an already known vitamin deficiency. Pellagra became the most prevalent deficitrelated disease, and most clearly related to nutrition. Lathyrism is a chronic intoxication produced by the accumulation of neurotoxins. It is due to common intake of chickling peas (Lathyrus sativus). Chickling peas are toxic only if they represent more than 30% of the daily calories consumed for a prolonged period greater than two to three months. Lathyrism would reoccur in the Spanish population after the war, in 1941 and 1942, the so called "famine years", when due to the scarcity of foods chickling pea flour was again consumed in high amounts. Deficiency-related neuropathies observed in Madrid during the Civil War led to new and original clinical descriptions. In children from schools of the Vallecas neighborhood, a deficiency syndrome, likely related to vitamin B complex deficiency, was described, which manifested by muscle cramps and weakness, and was termed the Vallecas syndrome. Poor fat content in the diet and a light decrease in calcium levels, which were already very low, were observed in the group with cramps. Both the administration of tablets containing an adequate amount of calcium and phosphorus and the daily intake of 4-6 milligrams of thiamine, achieved a considerable reduction in the frequency and severity of the cramps, or their complete resolution.

En esta conferencia, dictada en el marco de las Jornadas Internacionales de Neurociencias, Quito, Mayo 31 a Junio 1, 2013, se hizo una exposición de lo que fueron las situaciones de hambruna acaecidas en España durante la Guerra Civil de 1936-39. Su capital, Madrid sufrió durante todo ese periodo racionamientos de alimentos, agua y leche. Esta situación dio lugar a unas condiciones que pusieron de manifiesto las relaciones entre sistema nervioso y alimentación. La población madrileña estuvo sometida a un verdadero experimento de hipo alimentación, análogo al que se puede realizar en el laboratorio. Al concluir la guerra, la Dirección General de Sanidad y el Instituto de Investigaciones Médicas, con la colaboración de la Fundación Rockefeller, realizaron una serie de encuestas clínicas y de consumo alimentario entre la población de Madrid. Hubo tres situaciones médicas que tuvieron especial relevancia durante la Guerra Civil y durante la posguerra: La epidemia de pelagra, la aparición de latirismo y el denominado síndrome de Vallecas. La aparición de casos de pelagra fue trascendental porque permitió, a partir de una avitaminosis conocida, replantearse toda la sintomatología inespecífica que se había estado observando. La pelagra pasó a ser la enfermedad carencial más prevalente, y la más claramente vinculada a la alimentación. El latirismo es una intoxicación crónica producida por la acumulación de neurotoxinas. Se debe al consumo frecuente de almortas (Lathyrus sativus) . La almorta es toxica solo cuando constituye más del 30% de las calorías diarias consumidas durante un período continuado de dos a tres meses. El Latirismo volvería a afectar a los españoles durante los años 1941 y 1942, en los llamados "años del hambre" de la posguerra, cuando, debido a la escasez de alimentos, fue consumida gran cantidad de harina de almortas. Las neuropatías carenciales observadas en Madrid durante la Guerra Civil dieron lugar a descripciones clínicas novedosas y originales. En niños de colegios del barrio de Vallecas se describió un síndrome carencial, probable mente de vitaminas del complejo B, que originaba calambres musculares y debilidad muscular, que se dio en llamar síndrome de Vallecas. Se destacó la pobreza en grasas de la dieta y una ligera disminución de la cifra de calcio, ya muy pobre, en el grupo con calambres. Tanto con la administración de tabletas conteniendo una proporción adecuada de calcio y fósforo como con la ingestión diaria de 4 a 6 miligramos de tiamina, consiguieron hacer desaparecer los calambres musculares o aminorar considerablemente su frecuencia e intensidad.

History of zinc in agriculture.

Zinc was established as essential for green plants in 1926 and for mammals in 1934. However, >20 y would pass before the first descriptions of zinc deficiencies in farm animals appeared. In 1955, it was reported that zinc supplementation would cure parakeratosis in swine. In 1958, it was reported that zinc deficiency induced poor growth, leg abnormalities, poor feathering, and parakeratosis in chicks. In the 1960s, zinc supplementation was found to alleviate parakeratosis in grazing cattle and sheep. Within 35 y, it was established that nearly one half of the soils in the world may be zinc deficient, causing decreased plant zinc content and production that can be prevented by zinc fertilization. In many of these areas, zinc deficiency is prevented in grazing livestock by zinc fertilization of pastures or by providing salt licks. For livestock under more defined conditions, such as poultry, swine, and dairy and finishing cattle, feeds are easily supplemented with zinc salts to prevent deficiency. Today, the causes and consequences of zinc deficiency and methods and effects of overcoming the deficiency are well established for agriculture. The history of zinc in agriculture is an outstanding demonstration of the translation of research into practical application.

What's out there making us sick?

Throughout the continuum of medical and scientific history, repeated evidence has confirmed that the main etiological determinants of disease are nutritional deficiency, toxicant exposures, genetic predisposition, infectious agents, and psychological dysfunction. Contemporary conventional medicine generally operates within a genetic predestination paradigm, attributing most chronic and degenerative illness to genomic factors, while incorporating pathogens and psychological disorder in specific situations. Toxicity and deficiency states often receive insufficient attention as common source causes of chronic disease in the developed world. Recent scientific evidence in health disciplines including molecular medicine, epigenetics, and environmental health sciences, however, reveal ineluctable evidence that deficiency and toxicity states feature prominently as common etiological determinants of contemporary ill-health. Incorporating evidence from historical and emerging science, it is evident that a reevaluation of conventional wisdom on the current construct of disease origins should be considered and that new knowledge should receive expeditious translation into clinical strategies for disease management and health promotion. An analysis of almost any scientific problem leads automatically to a study of its history.--Ernst Mayr.

Vitamins for the soul: John Bowlby's thesis of maternal deprivation, biomedical metaphors and the deficiency model of disease.

In 1951 John Bowlby, British psychoanalyst and child psychiatrist, published his now famous report, Maternal Care and Mental Health, commissioned by the World Health Organization. In this report, Bowlby coined the term 'maternal deprivation', which quickly permeated into Western psychiatry and psychology. The implications of Bowlby's writings, while widely criticized and contested, generated a considerable amount of research and brought about significant changes in perceptions of separation between children and their mothers. This article examines the origins of the 'maternal deprivation' hypothesis, focusing on how the deficiency theory of disease influenced psychiatric discourse, and framed Bowlby's theory of maternal care. We argue that developments in paediatric medicine, and particularly in the field of nutritional deficiencies, provided Bowlby a prototype for conceptualizing his early views on the psychological needs of children and the development of psychopathology.

[New trends of medicine manifested at Naeuiwon in the late Chosun period].

Tonifying method has been used to treat various types of deficiency syndrome in traditional Korean medicine. Tonifying medicinal including ginseng and deer horns is one of the various methods of the treatments, but they are recognized as a representative of traditional Korean remedies nowadays in Korea. That is concerned with the new trends of medicine manifested at Naeuiwon (Royal Infirmary) in the late Chosun period. The period that manifested the tonifying method obviously was the reign of King Youngjo (r.1724-1776). King Youngjo who lived longest among Chosun kings considered tonifying yang very important in keeping him healthy. He had taken a large quantity of ginseng, he and others considered the reason for his longevity as taking ginseng. From that time, the method of tonifying yang became one of the principles in health care and treatment as well. In the 19th century, the theory of tonifying method had been changed, in that tonifying yin was considered more important among Naeuiwon physicians. Tonifying yang alone was thought to be harmful because of its warm and dry nature. The main cause of prevalence of tonifying method in Naeuiwon was the fact that it was safe and had little side effects. The method of health care and treatments of the kings was considered as an ideal model by the ordinary people at that time. The new trends of medicine manifested at Naeuiwon in the late Chosun period had a strong influence on traditional Korean medicine, which emphasized the importance of tonifying method.

New Trends of Medicine Manifested at Naeuiwon in the Late Chosun Period / 의사학

Tonifying method has been used to treat various types of deficiency syndrome in traditional Korean medicine. Tonifying medicinal including ginseng and deer horns is one of the various methods of the treatments, but they are recognized as a representative of traditional Korean remedies nowadays in Korea. That is concerned with the new trends of medicine manifested at Naeuiwon(Royal Infirmary) in the late Chosun period. The period that manifested the tonifying method obviously was the reign of King Youngjo(r.1724-1776). King Youngjo who lived longest among Chosun kings considered tonifying yang very important in keeping him healthy. He had taken a large quantity of ginseng, he and others considered the reason for his longevity as taking ginseng. From that time, the method of tonifying yang became one of the principles in health care and treatment as well. In the 19th century, the theory of tonifying method had been changed, in that tonifying yin was considered more important among Naeuiwon physicians. Tonifying yang alone was thought to be harmful because of its warm and dry nature. The main cause of prevalence of tonifying method in Naeuiwon was the fact that it was safe and had little side effects. The method of health care and treatments of the kings was considered as an ideal model by the ordinary people at that time. The new trends of medicine manifested at Naeuiwon in the late Chosun period had a strong influence on traditional Korean medicine, which emphasized the importance of tonifying method.

Gaspar Casal: descripción ecológica de la pelagra, primera enfermedad carencial / Gaspar Casal: ecological description of pellagra, the leading deficiency disease

Tercera de una serie de notas sobre clásicos de la salud pública enEspaña. Se refiere a Gaspar Casal (1680-1759), que describió lapelagra, primera entidad nosológica carencial, en sus condicionesambientales

The third in a series of highlights from public health classics inSpain features Gaspar Casal (1680-1759), who discovered pellagra,the leading deficiency disease, in nosological terms, in his surroundingenvironment

[Deficiency neuropathies in Madrid during the Civil War period]. / Las neuropatías carenciales en Madrid durante la Guerra Civil.

During the Spanish Civil War Madrid was submitted to a prolonged siege. The civilians were only fed with the official diet and suffered severe malnutrition. A group of physicians, represented by Manuel Peraita, studied the epidemic of deficiency diseases in detail. The majority of the complications were neurological. Peraita isolated a relatively unknown paresthesic syndrome possibly related to pellagra. The present is a small homage to a forgotten generation of neurologists.