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Our objective was to determine the prevalence, severity and preventability of adverse drug reactions (ADRs), ADRs causing or contributing to hospitalization (cADRs) and preventable ADRs (pADRs) in middle-aged patients aged 45–64 years presenting acutely to hospital. This was a prospective observational pilot study. The sampling frame was middle-aged patients in the acute medical unit of an Irish university teaching hospital. In total, 100 patients using three or more medicines were screened for ADRs present at hospitalization. Potential ADRs were assessed for causality, preventability, severity and relationship to hospitalization using validated tools and clinician assessment. The associations between ADRs and potentially inappropriate prescribing (PIP) and polypharmacy (five or more medicines) were investigated using Pearson’s χ2 test. Multivariate logistic regression analyses examined associations between ADRs and sex, age, polypharmacy, comorbidity and PIP. Of the 100 patients, 21 experienced 23 ADRs. The prevalence of cADRs and pADRs was 14% and 11% of patients, respectively. Over one-half of ADRs identified (n = 14) were sufficiently severe to prompt presentation to hospital for urgent medical review. PIP was associated with the occurrence of any ADR (adjusted odds ratio 3.49; 95% confidence interval 1.22–9.93) but not with cADR. Excessive polypharmacy (ten or more medicines) (χ2 = 5.73, p = 0.02), but not polypharmacy, was associated with any ADR occurrence. One in five patients had an ADR and experienced short-term morbidity as a result. For 11 patients, the ADR was preventable. These findings illustrate that middle-aged patients are vulnerable to medicine-related harm. Additional research in larger studies is needed to more comprehensively describe the prevalence and risk factors for ADRs in middle-aged patients.

Aging is characterized by shrinkage of muscle fibers and loss of protein from them. Bone is also lost, and matrix and mineral are lost together. The predominance of breakdown over synthesis is probably the fundamental cause of both muscle and bone loss. Little can be done to prevent this by dietary means, but physical activity is of vital importance in helping to maintain the integrity of both muscle and bone. McCay's finding that rats underfed from weaning lived longer than those that had adequate food has been confirmed by others, but this is only true if the rats remain free of infections and other hazards, particularly during growth. The mechanisms by which underfeeding delays the aging process in rats may apply to the human body but, if so, this is completely offset by other considerations. For their present and future well-being, children should be fed in the best possible way.

The composition of body tissues is a function of the age, nutrition, state of health and physical activity of the individual. In this paper, the effects of age on the composition of healthy tissues are reviewed. Eleven soft tissues (adipose tissue, blood--whole, brain--whole, heart, kidney, liver, lung, muscle--skeletal, placenta, skin and spleen) and cortical bone are considered. Elemental compositions, mass and electron densities are tabulated for the tissues, as a function of age, from fetus to young adult. Although the compositions given here are predominantly for healthy tissues, reported changes because of dietary influences are briefly discussed.

EDITOR—As a practising clinician in New Zealand, I was interested to read the New Zealand perspective on the management-clinician interface in the article by Malcolm et al.1 However, even after several careful …

Contemporary human diets are probably as diverse now as they have ever been in the history of mankind. The abundance of food in the western world is in stark contrast to the lack of food and near starvation in parts of Africa, the continent where Homo sapiens evolved. The development of agriculture has enabled the population of the world to expand and to colonize almost the whole of its land surface, but the dependence on one staple food has introduced problems. If the staple crop fails, for example because of drought, there may be no alternative, and undernutrition and starvation are the result. Further, if the rest of the diet does not provide the nutrients that the staple food lacks, diseases due to specific nutrient deficiencies become widespread. Vitamin deficiencies among adults are less common now than they were 50 years ago, but even today millions of children in the poor rice-eating areas of the world are blind because their diets were deficient in vitamin A. For physiological reasons infants and young children will suffer most wherever there is a scarcity of food, of water, or of specific nutrients.

The results are presented for the first 4 years of the Multiple Risk Factor Intervention Trial (MRFIT) nutrition intervention program. Study participants were at high risk (upper 10–15%) for Coronary Heart Disease (CHD). The Special Intervention (SI) group reached and sustained the goals of an eating pattern originally designed to limit cholesterol intake to less than 300 mg/day, with less than 10% of calories as saturated fat and not more than 10% as polyunsaturated fat. By the end of the first year, mean serum total cholesterol had fallen by 6.3% from the mean initial value of 254 mg/dl. The magnitude of the decrease became slightly greater in the ensuing years, reaching 7.4% by the fourth annual visit. Substantially larger decreases in mean serum cholesterol level were observed in the subgroups with the highest baseline level, greatest weight loss, in those who did not smoke, and in those who had normal blood pressure on entry. The changes in cholesterol level were accompanied by parallel changes in mean plasma LDL cholesterol, which also fell by 6.6% over the 4 years, but mean HDL cholesterol was not substantially altered. Comparison with earlier population data suggests that the overall responses to the MRFIT eating pattern were limited by the apparent fact that participants had already made self-initiated changes toward the fatcontrolled dietary pattern before they entered the study.

1. The diets and living conditions of nine Asian boys with biochemical, and in most instances also radiological, signs of rickets were compared with those of nine other boys who appeared to be normal. The groups were matched according to age, religion, place of father's origin and boy's own place of birth.2. There were no outstanding differences between the diets of the boys with, and of those without signs of rickets. All had adequate to high calcium intakes. Most of the boys had low intakes of vitamin D, and those with signs of rickets generally had lower intakes than the normal boys. The food tables used for making the calculations of vitamin D intakes report the amount of the vitamin in the lipid fraction of milk. If it proves to be true that most of the vitamin D activity of milk is in the aqueous fraction, the boys would have been getting considerably more vitamin D than the results suggested, and their average intake may have been about 3.5 μg/d.3. It was not possible to make any quantitative measure of the exposure of the boys to sunlight. All Asian boys studied appeared to have their bodies more completely covered than British or West Indian boys.4. The problem of why nine boys had signs of rickets and nine had none has not been solved. It is suggested that those with signs of rickets may have had higher requirements for vitamin D than the others. When the intake of vitamin D is low and exposure to sunlight is minimal, those with high requirements will be the ones to develop signs of rickets.

Expired air carbon monoxide (CO) and serum thiocyanate (SCN) were used to asses exposure to cigarettes in 139 middle-aged men. Subjects who reported smoking cigarettes generally had CO levels exceeding 8ppm and SCN levels exceeding 100umol/L; non-smokers had lower levels. For both tests the mean concentration among men smoking more than one pack daily was three times that of non-smokers. The is a high correlation between the two tests (r=.571 for smokers), an association that was largely independent of the smaller correlations between either test and reported smoking frequency (r=.476 for CO; r=.479 for SCN). The ability to distinguish between individuals who reported "typical" smoking habits and non-smokers was best when the CO and SCN analyses were used together to take advantage of their separate sources of variance; it was 99 per cent when the two tests were mutually concordant (91 per cent of cases). The CO and SCN measurements allowed 16 individuals who reported light smoking habits to be categorized into high and low presumptive tobacco exposure groups. The two tests are inexpensive and suitable for use in epidemiologic and health care delivery programs.

Dr Widdowson began her lecture by pointing out that sex influences body weight and survival rates from the moment of conception. It is well known that the average birth weight of boys is greater than that of girls, but why should this be so? Many more boys than girls are conceived and slightly more boys than girls are actually born. The fact that so many male foetuses ‘fall by the wayside’ leads to the assumption that the larger, stronger male babies survive.

Egon Hynek Kodicek was born on 3 August 1908 at Kamenny Ujezd, a little village on the river Moldau in southern Bohemia, which at that time was part of the Austro -Hungarian Empire. He was an only child and his father was a general medical practitioner, trained in Vienna. Egon’s father was widely known in the region for his expert diagnostic skills. Using only his senses of touch, vision and smell he was able correctly to identify disease processes where other doctors would need the help of hospital facilities. As a doctor he was much influenced by the teaching of Sigmund Freud and he was one of the first to use psychological methods, when appropriate, in the treatment of disease. Egon admired and had an enormous respect for his father and sometimes would accompany him in his horse-drawn carriage on visits to patients. When Egon was 6 years old the family moved to nearby Budweis, where his father had been appointed doctor-in-charge of the military hospital there. Although his grandparents on both sides w ere orthodox Jews, Egon’s parents were not religious and he described him self and his father as ‘Czech liberals’

Cows' milk--fresh, boiled, and processed in different ways for the domestic market, and various infant milk formulae--was investigated for its sensitising capacity in the guinea-pig after being fed for 37 days. The anaphylactic sensitising capacity was considerably reduced by heat-treatment. As heat becomes more intense and more prolonged so beta-lactoglobulin and casein become less sensitising. It should be stressed that these were results from experiments on guinea-pigs drinking milk. Should they be found to apply to the human infant too, it seems that it would not be impossible to manufacture a non-sensitising but fully nutritive milk product. The sensitising capacity of fresh and boiled goats' milk was examined too, and it was found that boiling reduced the sensitising capacity to an even greater extent than was the case with cows' milk.

Summary Cow's milk differs from human milk in a number of important ways, and manufactures of dried milk preparations for infants have used various methods to make the composition of the diluted product more like that of human milk. The first was to add lactose, or to recommend the mother to add sucrose. This not only increased the carbohydrate, but also ‘diluted’ the protein and inorganic constituents which are more concentrated in cow's than in human milk. The second was to replace all or part of the cow's milk fat with animal and vegetable fats, and so make the fatty acid composition more like that of human milk fat. In particular the proportion of linoleic acid was increased and that of stearic acid decreased, and this made the fat more easily digested and absorbed by the young infant. The third modification of cow's milk has been more fundamental. Its aim has been to make a product containing less sodium and phosphorus than cow's milk and with a higher lactalbumin: casein ratio. Whey, which contains lactalbumin but not casein, is used as the starting material. This is dialysed to remove soluble inorganic constituents. Some skimmed milk is then added to supply casein and some minerals, and the composition is adjusted as required with further minerals and vitamins. Lactose is added and a mixture of animal and vegetable fats. Dried milks on sale in Britain contain added vitamins A,D, and C and also iron. Some have added copper and zinc.

Quality control was emphasized in the screening and clinic laboratory during the early stages of the trial to cover all aspects of screening, and in the later stages to cover local testing used to monitor the participant in the clinic and to guarantee collection of valid specimens to be shipped to the Central Laboratory. Special attention throughout the trial was focused on techniques for collection of specimens, since it was recognized that analytical results could not be better than the quality of the specimens. Training courses, on-site visits, and newsletters were used to sensitize the staff of the clinic laboratory about the necessity to follow protocol. Any monitoring evidence of carelessness, use of deteriorated supplies, failure to follow safety rules, and deviation from directions in the MRFIT Manual of Operations resulted in memoranda from the Coordinating Center or the Central Laboratory.

The acquisition of quality biochemical data in the MRFIT was enhanced by writing detailed protocols, instituting strict rules for collecting and shipping specimens, setting high goals for analytical performance, using reliable means to transfer data, employing dedicated and competent analysts, and having a director of the Central Laboratory who believed in and enforced an effective quality control system. A Laboratory Quality Control Subcommittee was formed to work with this director in solving laboratory problems, with the Coordinating Center in conducting appropriate monitoring, with the Quality Control Committee in documenting the quality of data and investigating any laboratory problems, and with other committees of the directors and Program Office in responding to any questions raised about laboratory aspects of the trial. All of these efforts culminated in reliable biochemical data.

1. The diets of 120 pregnant women at different economic levels have been studied by the individual method.2. The intake of calories was found to be little affected by income, and this was true also of fat and carbohydrate. The intakes of protein, animal protein, calcium, phosphorus, iron and vitamin B1rose convincingly with income.3. These differences were due to the fact that a rise in spending power led to an increased consumption of milk, fruit, vegetables and meat, and to a decreased consumption of bread and total cereals. Details are given in Table V.4. Women taking the better diets were found on average to be taller and less anaemic than those taking the poorer diets. The differences were significant.5. A comparison of the diets of the well-to-do women with the requirements suggested by the League of Nations and other authorities suggests that the requirement for calories has been set too high. The intake of calcium was suboptimal throughout and the diets of the poorer women were deficient in many respects.

The behaviour and nervous activity of rats which had been made to grow fast by a super-abundance of food in the first week or two of life were compared with the same characteristics in litter-mates which had been suckled in large litters, and gained weight much more slowly. The rapidly growing animals were more active and inquisitive at each chronological age than their slow-growing litter-mates, and they appeared to profit more by previous experience, which indicates that they learned more quickly. It is suggested that nutritional variables may underlie some of the correlations which have been found by others to exist between physical and mental development at similar chronological ages in children. It is also possible that children today, who are admittedly growing faster than they did 50 years ago, should be expected to display a correspondingly greater mental activity and ability to learn.

The total amount of DNA and the protein/DNA ratio have been measured in the kidneys, heart, liver, and gastrocnemius muscles of 56 human fetuses and newborn infants of 13-42 weeks' gestational age. The total amount of DNA in each organ approximately doubled every week up to the 25th; thereafter the rate of increase was slower. The protein/DNA ratio in each organ increased rapidly in the last 10 weeks of intrauterine life. Before 30 weeks there was some increase in the protein/DNA ratio in the kidneys, heart, and gastrocnemius muscles, but no significant change in the liver. In 5 small-for-dates infants the protein/DNA ratio was normal, whereas the total DNA tended to be low.

Specimens of urine were obtained during the forenoon from 45 Ugandan and 45 British boys and girls below 4 years of age who were attending clinics for healthy children. By employing known facts about the excretion of creatinine, and by making certain assumptions, it was possible to obtain a surprising amount of information about the nature of the food consumed. This agreed well with what was already known about it. The method has distinct possibilities and could be made more quantitative by using a reference group about which more was known.

Summary 1. Sodium chloride was added to the milk given to premature infants and newborn piglets which were then reared by hand. 2. The addition of salt led to (a) an abnormal increase of weight; (b) a rise in the serum sodium and chloride; (c) an expansion of the extracellular volume and ultimately massive oedema; (d) a reduction in the catabolism of tissue protein; (e) no increased excretion of potassium, if anything the reverse. 3. Similar and. even more clear cut results were obtained when the piglets were given water and salted water instead of milk and salted milk. 4. When the administration of salt was stopped the infants rapidly regained their healthy status. Expansion hypertonique des liquides extracellulaires. Du chlorure de sodium a ete ajoute au lait destinea des enfants nes avant terme ainsi qu' a des porcelets nouveaunes qui furent alors eleves au biberon. L'addition de chlorure de sodium au lait amena: a) une augmentation anormale du poids oorporel, b) une augmentation du taux du sodium et des ions chlores dans le serum, c) une augmentation du volume des liquides extracellulaires et subsidiairement un œdeme massif, d) une reduction du catabolisme des proteines tissulaires, e) une diminution plutot qu'une augmentation de l'elimination du potassium. Des resultats analogues et meme plus nets encore ont ete obtenus chez des porcelets nourris d'eau et d'eau salee au lieu de lait et de lait sale. Une fois que le sel eut ete supprime, les bebes redevinrent rapidement bien portants. Hypertonische Ausdehnung der intracellularen Flussigkeiten. Kochsalz wurde zur Milch zugesetzt, die fruhgeborenen Sauglingen und neugeborenen Schweinchen verabreicht wurde. Der Salzzusatz bewirkte: a. eine abnormale Gewichtszunahme, b. eine Steigerung im Natrium-und Chloridgehalt im Serum, c. eine Expansion des aussercellularen Volumens und schliesslich massives Oedem, d. eine Reduzierung im Abbau der Gewebsproteine, e. keine Erhohung, wenn nicht Herabsetzung der Kaliumausscheidung. Ahnliche und sogar eindeutigere Resultate wurden erzielt, wenn die Schweinchen Wasser und Salzwasser anstatt der Milch und der gesalzenen Milch erhielten. Wenn die Verabreichung des Kochsalzes unterbrochen wurde, kehrten die Sauglinge rasch zu ihrem gesunden Zustand zuruck. Expansion hipertonica de los liquidos extracelulares. Se anadio cloruro de sodio a la leche suministrada a prematuros y tambien a lechoncillos recien nacidos criados a mano. La adicion de la sal condujo a: (a) aumentacion anormal de peso, (b) ascenso del sodio y cloruro sericos, (c) expanson del volumen extracelular y finalmente edematizacion masiva, (d) reduccion catabolica proteicotisular, (e) aumento nulo de excrecion potasica y mas bien lo contrario. Resultados analogos y todavia inas pronunciados obtenidos cuando se suministro a los lechoncillos agua y agua salada en lugar de leohe y leche salada. Al suspenderse la administracion de sal, los ninitos recobraron rapidamente las condiciones de la salud.

An investigation has been made of the iron intake of sixty-three men and sixty-three women of the English middle class, living on freely chosen diets. Their intakes of total iron have been found to have mean values of 16·8 and 11·4 mg. per day respectively. The highest value found for any woman was only just above the average for the men, and 30 per cent, of the women were taking less than 10 mg. of iron a day.“Available” or inorganic iron in the diets has also been calculated, and has been found to average 10·8 mg. per day for men and 7·9 mg. for women. If fairly large amounts of meat are eaten, the available iron may be less than half the total iron in the diet. If, on the other hand, the diet is mainly vegetarian, about 90 per cent, of the total iron may be available.Haemoglobin determinations were made on more than 50 per cent, of the subjects. The men's average was 102 per cent, and the women's 93 per cent. No significant correlation could be found between the total or available iron intake and the haemoglobin level.The effect of large doses of iron (100 mg. of iron a day as ferrous sulphate or ferric ammonium citrate) on normal haemoglobin levels has been investigated. This has scarcely altered the haemoglobin percentages of men, but has increased the values for women by 4–17 per cent, and a mean rise of over 10 per cent, has been observed.

At the Nutricia Symposium in Groningen in 1973 Professor Visser et al. gave a paper on “Parenteral nutrition in low birth weight infants” (I). In the discussion afterwards the question was raised as to whether the low birth weight infant should receive an amino acid mixture corresponding to human milk, or to fetal plasma, and it was suggested that the best mixture might be one corresponding to that of the baby’s body itself. At that time there were no figures for the amino acid make-up of the protein in the body of the human fetus. I promised that such information would be forthcoming, and this is the main subject of our paper today.

If food is plentiful the requirement for energy is met by an accurate system of control so that intake balances expenditure. Energy requirements are therefore often assessed by measuring energy intakes. Intakes of protein, however, are no measure of protein requirements and the amounts customarily taken in Western diets are considerably more than man needs. The requirements for calcium are difficult to assess, for they are affected not only by age, but by other constituents of the diet, by the time of year, by individual peculiarities and by the previous intake. There is a physiological loss of calcium from the body starting in middle age which is not prevented by a high calcium intake.

The physical arrangement of radiographs and a method for their retrieval is discussed. The aim is to facilitate access to examples of various conditions from several possible approaches by a method of specific classification of each item and a comprehensive card index. A system to maintain consistency and to achieve relevance for the potential user is described.

Thirty-two dried milk preparations, designed for infant feeding and obtained from 7 European countries, have been analysed for nitrogen, carbohydrate, fat, the distribution of fatty acids in the fat, and 8 inorganic constituents. The composition of the milks differed considerably. Some were full-cream dried milks. Many had carbohydrate added in the form of lactose, sucrose, or dextrimaltose. Some were `half-cream9, others had had all the milk fat removed and replaced by a mixture of animal and vegetable fats or, in one instance, by maize oil alone. The fatty acid composition of these milks varied considerably, and linoleic acid accounted for up to 58% of the total fat in one as compared with 9% of the fat in human milk and 1 to 2% of that in cow9s milk. All the milks contained considerably more calcium and phosphorus per 100 g solids than human milk, some of them four times as much. Some milks had had an iron salt added during manufacture, and a few contained added copper.

Male hooded rats were divided into 3 equal groups: (1) controls were given a complete diet ad libitum at all times; (2) for 8 weeks from the age of 28 days, undernourished (UN) rats received the complete diet in restricted amounts; (3) low protein (LP) rats received a low-protein, high-carbohydrate diet for the same period. From 12 weeks all rats were given the complete diet ad libitum, until tested at 35 weeks. Each rat was then put alone, for 12 days, in a residential “plus-maze” with a central nest box and 4 arms radiating from it; food was supplied at the end of one arm, water in the nest box. On Days 4 to 9 each rat had access to the arms for only 1 hr daily. Entries into the arms, and duration of stay, were recorded automatically. All arms were regularly visited by rats of all classes, even when access was only for 1 hr. Visits per day to the 3 nonfood arms combined were usually higher than visits to the food arm, but duration of stay in the food arm was higher than the total duration in the other 3 arms. LP rats made most visits to the arms and were especially active after the 6 days of restriction; but they were less adaptable than the control and UN rats in adjusting food intake during the period of restricted access. In contrast, the UN rats spent most time in the arms.

Sudanese men and women were flown to Cambridge in the winter of 1966/67 and at once began to take part in an experiment there lasting for 8 days with a corresponding number of British subjects. The Sudanese conformed to the British way of life. Time was provided for relaxation and exercise and the intakes and expenditures of water, salt and energy were measured. The British party were flown to Khartoum in the spring of 1968-not, for political reasons, as was originally planned in June 1967. They matched up again with the Sudanese subjects and adopted the daily routine of the latter while a similar programme of relaxation exercise and measurements was being carried out. The dry-bulb temperatures out of doors in England ranged from - 5.6 to 12.5 $^\circ$ C but the rooms were warmed. The dry-bulb temperatures ranged from 14.8 to 38.7 $^\circ$ C in Khartoum and none of the rooms were cooled. The food in Khartoum provided more protein and less salt than in Cambridge. The subjects ate more and expended more energy in Cambridge than in Khartoum and they also tended to gain weight, particularly the Sudanese. The British food intakes were considerably lower in Khartoum and, in spite of expending less energy, the subjects lost weight. To live the lives they did the British males had an obligatory water expenditure of around 2223 ml/day in Cambridge and 2920 ml. in Khartoum; the figures for the Sudanese were 2278 and 3381. All the subjects would have required about 7 to 8 g of sodium chloride/day in Khartoum to make their food palatable and to provide for the obligatory losses. The women ate less, expended less energy and had considerably lower obligatory losses of water and salt than the men. Neither the British nor the Sudanese showed impaired ability to perform arithmetic or prolonged vigilence tests in their unaccustomed environment. The Sudanese were less cautious than the British in that they made more false reports of signals in the vigilance task.