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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.

This Special Publication is a collection of papers which identifies, describes, and interprets the occurrence of palaeosurfaces in the geological record. The concept of a palaeo surface is one which is generally understood across the geomorphological and geological sciences but, according to discipline and application, often differs in the emphasis and detail of its interpretation. In order to encompass the widest range of contributions and views upon the subject of palaeosurfaces, a broad remit was deliberately adopted during the preparation of this volume. cations of ancient palaeosurfaces. The research areas represented are geographically widespread and include examples from Australia, Africa, South America, India, and Europe.

IN their original communication about BAL-lntrav, Danielli, Danielli, Mitchell, Owen and Shaw1 referred to some of the work on man which we had at that time begun. Since we have been forced to abandon this work for the time being, owing to the desirability of studying some of the nutritional problems in Germany, we have decided to publish our preliminary observations for the benefit of those who may be interested in the subject.

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.

Studies in the 1930s on the absorption and excretion of iron by adults with an excess of iron inside them showed conclusively that the amount of iron in the body is regulated, not by active excretion into the intestine as was believed at that time, but by controlled absorption. The same is true of manganese. One-week-old breast-fed infants excreted far more iron and managanese in their faeces than they took in the milk. Meconium also contains iron and manganese and it is suggested that the elements reach the intestine in the bile. The urine normally contains very little zinc, but patients with albuminurea excrete larger amounts. The faeces of young infants contain more zinc than the milk; a loss of zinc from the body may continue for some months. The kidneys control the amount of strontium in the body as they do of calcium. Young breast-fed infants did not retain strontium but formula-fed infants, with much higher intakes, retained 70%. Silver and gold within the body were excreted only in traces. Lithium and boron were readily absorbed and excreted in the urine. The urine was the main route of excretion of vanadium, cobalt, nickel and tin.

Hooded and harbor seals are unique among true seals (family Phocidae) in that the lanugo (fetal pelage) is typically shed in utero. Shedding had occurred in all newborn hooded seals examined off the Labrador coast (n = 62) and in 94% of newborn harbor seals on Sable Island, Nova Scotia (n = 110), although in one-fifth of the latter the molt was incomplete. In hooded seals the shed hair in the amniotic sac was organized into tightly woven disks, whereas in harbor seals the shed hair formed a loose mat with no evident structure. We examined hair masses in the intestines of pups of both species but could find no evidence that the intestines were involved in hair disk formation. We argue that fetal shedding, like prenatal blubber deposition, is an adaptation enabling newborn pups to enter cold water without adverse consequences. This ability allows the use of pupping substrates that are unstable or regularly inundated with water.

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.

Lactation makes considerably greater demands on the mother's body than pregnancy does in species where the young are helpless at birth and depend on mother's milk for a comparatively long time. These species include many rodents and carnivores and also man. The requirements for the production of milk are met partly from within, by the mobilization of the mother's body tissues, and partly from without, by an increased food intake. Both ways lead to alterations in the composition of the mother's body which may or may not be permanent. Fat laid down in the body during pregnancy is used and there may also be losses of calcium from the skeleton, especially if the calcium intake is low. Whether extra protein is deposited during human pregnancy and lost again during lactation still remains an open question. In rats, the answer depends partly on the intake of protein and energy. The increase in food intake during lactation in some species is so great that the gastrointestinal tract grows considerably to deal with it. In the rat, the small intestine more than doubles its weight. The intestinal wall dilates and the area of mucosa almost doubles. The liver also increases considerably in size owing to an increase in both number and size of cells. After lactation, the liver becomes smaller again, and so does the amount of protein in it, but there is no loss of cells, so that rats that have reared litters have more cellular livers than those that have not. There is no indication whether similar changes occur in women.

A meeting embracing current research on palaeosurfaces in the geological record was convened by M. Widdowson at the Department of Earth Sciences, Sheffield University on the 15–16 April 1994. The meeting attracted over 40 participants from Europe, and comprised 16 talks in five sessions. A discussion forum followed the final presentation. The meeting aimed to provide a UK venue for presentation of current palaeosurface research, and a forum for multi-disciplinary discussion. It forms part of the UK contribution to the current IGCP 317 Paleoweathering Records and Paleosurfaces. Contributions from the fields of geomorphology, geology, geochemistry, palynology, and palaeoenvironmental studies were represented and included studies of lateritization and bauxitization, palaeokarstification, geochemistry of rock alteration, and the preservation of ancient palaeosurface elements in both glaciated and tropical terrains. The areas of study were widespread and included research from Australia, Africa, Europe, Scandinavia, Sri Lanka, and India. Presentations incorporated discussion of aspects of evolution, reconstruction, and palaeo-environmental interpretation of ancient palaeosurfaces Following a brief welcome by D. A. Spears on behalf .of the Sheffield University Earth Sciences Department, the morning sessions were chaired by M. Widdowson, the first of which began with a presentation by D. Subasinghe (PRIS, Reading University), who outlined the effects of silicification and associated phophatization in a Sri Lankan saprolite derived from Precambrian apatite-bearing marbles. Diagenetic processes involving the chemical replacement of primary apatite crystals during the silicification have lead to mobilization of phosphorus resulting in complex patterns of phosphate depletion and enrichment: these currently form the economically

In black bears the last 6–8 weeks of gestation and the first 10–12 weeks of lactation occur in winter while the mother is in a dormant state, and reportedly does not eat, drink, urinate or defaecate. Measurements were made of the body composition and organ weights of cubs, of the composition of milk, and of milk intake (by dilution of 2H2O), in the first 3 months after birth. Additional milk samples were collected until 10 months postpartum. Bear cubs were small at birth, only 3·7 g/kg maternal weight, and chemically immature, as indicated by the high concentration of water (840 g/kg) in their bodies. Organ weights at birth were similar to those of puppies. In the first month after birth cubs gained 22 g/d or 0·23 g/g milk consumed; the milk was high in fat (220 g/kg) and low in water (670 g/kg). About 30% of the ingested energy and 51% of the ingested N were retained in the body. Over the entire 12-week period bear cubs required about 11 kg milk, containing (kg) water 7, fat 2·5, protein 0·8 and total sugar 0·25, to achieve a 2·5 kg weight gain. The birth of immature young and the production of high-fat, low-carbohydrate milk seem to be maternal adaptations to limit the utilization of glucogenic substrates during a long fast. Isotope recycling indicates that mothers may also recover most of the water (and perhaps much of the N) exported in milk by ingesting the excreta of the cubs. Lactation represents another aspect of the profound metabolic economy of the fasting bear in its winter den.

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.

Goa state lies between those of Maharashtra and Karnataka on the west coast of India. A few tens of kilometers to the north and east lies the southern margin of the immense Deccan Traps CFB province covering much of NW peninsular India. The Deccan succession has been the subject of much detailed chemostratigraphic study (Mitchell and Widdowson 1991 and references therein), and the structure and stratigraphy (Table 1) of the southern region of the province is now well established. In the south this succession can be considered essentially lensoid in character with the greatest thicknesses exposed inland of the coast along the Western Ghats escarpment. It thins noticably eastward and southward and displays a southerly overstep of older formations with the stratigraphically youngest basalts occurring at the southernmost edge. These latter cap the Western Ghats escarpment and inland of Goa.

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. Male and female rats aged 3 weeks were divided into two groups. One group of each sex was allowed unlimited access to the stock diet, the other group was given the stock diet in restricted amounts for 10 weeks so that the males gained only 19 g and the females 21 g in comparison with 176 g and 116 g for the well-nourished males and females respectively. The undernourished animals were then rehabilitated by being allowed the stock dietad lib.2. Five animals of each sex were killed at various stages of the experiment, their bodies analysed for fat and nitrogen, and the size and number of fat cells determined in specific fat depots.3. The undernourished rats failed to make a complete recovery and were significantly smaller than the controls of the same sex at 172 d of age when the experiment terminated.4. The previously undernourished rats deposited significantly more fat in their bodies during rehabilitation than the control animals in the same number of days and over the same gain in body-weight.5. There were no significant differences in the number of cells containing fat at the abdominal fat site between the undernourished and rehabilitated animals and the controls at any stage, nor were there any significant differences in apparent fat cell numbers between the control and rehabilitated animals at any of the other sites studied when the experiment ended at 172 d.

A chemical test to distinguish smokers and nonsmokers is important in many epidemiologic studies. We have developed an automated method for determining serum thiocyanate by use of the reaction between thiocyanate and ferric ions to form a colored complex. Our data show that this method distinguishes cigarette smokers and nonsmokers: of 197 healthy individuals studied, 1.8% false-positive and 6.7% false-negative results were obtained when 85 µmol of SCN- per liter was the critical value used to distinguish the two populations.

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.

Variation in the assays of uniform control serum commonly are assumed to represent day-to-day analytical variation. To test this assumption, we compared the differences between results of serum aliquots assayed immediately for 12 constituents and frozen aliquots accumulated and assayed on a single day with the results of control serum variation from the same period. One aliquot of each weekly sample was stored frozen. Eleven subjects were sampled for 12 weeks. Storage at --20 degrees C for 15 weeks had a mild destructive effect on two enzymes in serum. The control serum data revealed significant linear trends in magnesium (upwards) and alkaline phosphatase (downwards) that substantially increased the respective variances. In the other 10 constituents tested, comparison of variances indicated that long-term (weeks) variation in control serum assays is similar to the difference of variation between aliquots assayed immediately and those frozen and assayed at the same time. For these constituents, this finding justifies the use of control serum to estimate long term analytical variation.

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.

59 young male and female rats were injected with crude papain for 28 days and this hindered the growth of the skeleton. Two kinds of controls were used as comparisons: (1) littermates were pair-fed with those receiving papain, which kept them in a state of moderate undernutrition, and this was revealed in their physical characteristics; (2) other littermates were fed ad libitum throughout the whole experiment. Some rats in each of these three groups were killed at the end of the period of injection, the remainder were given unlimited food and no other treatment till they were 6 or 12 months old. The bodies and tails of the papain-treated rats were short compared with those of pair-fed animals of the same body weight; the long bones were also short, but of similar width. The composition of the bone appeared to be normal. The muscles attached to the long bones were necessarily short, but they, like the bones, were wide for their length. The weights of the heart, lungs and brain were similar in the papain-treated and pair-fed animals of the same body weight, but the kidneys, spleens and pituitaries were consistently larger in the papain-treated ones. The livers were also larger, but the undernutrition of the pair-fed animals was responsible for the small size of their livers. Papain hindered the growth of the stomach and small intestine but promoted the growth of the large intestine Most of these differential effects on the organs were still evident when the animals were killed at 6 months of age. The testes, moreover, had now become heavier in the animals previously treated with papain than in either of the two control groups, although the rats themselves were much smaller. Papain is known to act on the mucopolysaccharide-protein complexes in the epiphyseal plates and this is what hinders the growth of the bones. It is suggested that papain also acts on similar mucopolysaccharide-protein complexes in the elastic capsules surrounding the kidneys, spleen and testes so that there is no longer the usual restricting influence on the blood supply and growth of these organs.

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.

The weights of harp seal pups quadruple during 13 days of suckling while hooded seal pups double in weight in a lactation period of just 4 days. Pups of both species then fast for a month or longer. As a first measure of tissue responses to this ‘feast and famine’ pattern, we weighed the body, sculp (blubber and attached skin), core (carcass including viscera) and major internal organs of seal pups at birth, at the end of suckling, and at the end of the fast. When expressed as a percentage of body weight, the weights of the internal organs of newborn harp and hooded seals were within the range reported for newborn land mammals. During suckling, harp and hooded seals gained 2.3 and 6.5 kg/day body weight, respectively, but a large part (64–73 %) of this gain was blubber and skin rather than core. Even though pups were ingesting great quantities of fat, their digestive organs (stomach, small and large intestines, pancreas) were neither particularly large at birth nor did these organs gain in weight or length unusually rapidly. Most organs increased in weight in proportion to the increase in core weight, but the liver and spleen increased proportionately more than the core, and the stomach, heart and kidneys increased proportionately less. At the end of suckling, sculp accounted for more than half of the body weight in both species. The subsequent 4-week fast resulted in weight loss from both the sculp and core, and the liver and spleen decreased in weight by about 70%. The net effect of sequential suckling and fasting was particularly striking in the hooded seal pup, which had a lighter core, heart, liver and spleen at 1 month postpartum than at birth. These data illustrate a remarkable cycle of nutrient deposition and depletion which is undoubtedly central to the survival of young seals in the harsh pack-ice environment.