Do rates of hospital admission for falls and hip fracture in elderly people vary by socio-economic status?

OBJECTIVE: To determine the relationship between hospital admissions for falls and hip fracture in elderly people and area characteristics such as socio-economic deprivation. STUDY DESIGN: Ecological study of routinely collected hospital admissions data for falls and hip fracture in people aged 75 years or over for 1992-1997, linked at electoral ward level with characteristics from census data. METHODS: In total, 42,293 and 17,390 admissions were identified for falls and hip fracture, respectively, from 858 electoral wards in Trent. Rate ratios (RRs) for hospital admissions for falls and hip fracture were calculated by the electoral wards' Townsend score divided by quintiles. RRs were estimated by negative binomial regression and adjusted for the ward characteristics of age, gender, ethnicity, rurality, proportion of elderly people living alone and distance from hospital. RESULTS: There was a small but statistically significant association at electoral ward level between hospital admissions for falls and the Townsend score, with the most deprived wards having a 10% higher admission rate for falls compared with the most affluent wards (adjusted RR 1.10, 95% CI 1.01-1.19). No association was found between hospital admission for hip fracture and deprivation (adjusted RR 1.05, 95% CI 0.95-1.16). CONCLUSION: There is some evidence of an association at electoral ward level between hospital admissions for falls and socio-economic deprivation, with higher rates in deprived areas. No such association was found for hip fracture. Further work is required to assess the impact of interventions on reducing inequalities in hospital admission rates for falls in elderly people.

A potentially useful distribution model for dietary intake data.

BACKGROUND: Conventional mixed models for the analysis of diet diary data have introduced several simplifying assumptions, such as that of a single standard deviation for within-person day-to-day variation which is common to all individuals. OBJECTIVE: We developed a model in which the within-person standard deviation was allowed to differ from person to person. DESIGN: The model was demonstrated using data on daily retinol intake from the Dietary and Nutritional Survey of British Adults. The data were from 7-day weighed dietary diaries. Estimation was performed by Markov chain Monte Carlo. Reliability of the model was assessed from the accuracy of estimation of the percentage of days on which various intakes were exceeded. For levels above the median retinol intake, estimation of percentages of days with excessive intakes was most accurate using the model with varying within-person standard deviation. SETTING: A survey of British adults aged 16-64 years. SUBJECTS: In total 2197 adults living in the UK, 1087 males and 1110 females. RESULTS: Under the traditional model, estimated daily intake ranged from 716.4 to 1421.8 microg depending on age and sex, with a within-person standard deviation of 4298.9 microg. Under the new model, estimated average daily intake ranged from 388.9 to 518.3 microg depending on age and sex, but with a within-person standard deviation varying between subjects with a 95% range of 29 to 8384 microg. The new model was shown to predict the percentage of days of exceeding large intakes more successfully than the traditional model. For example, the percentage of days of exceeding the maximum recommended intake (9000 microg for men and 7500 microg for women) was 2.4%. The traditional model predicted no excessive intakes, whereas the new model predicted 2.9%. CONCLUSIONS: This model is potentially useful in dietary research in general and for analysis of data on chemical contaminants in foods, in particular.

Food and nutrient intake of a national sample of 4-year-old children in 1950: comparison with the 1990s.

OBJECTIVE: To evaluate the food and nutrient intake of members of a birth cohort study when young children in 1950 and investigate differences from present-day children's diets. DESIGN: One-day recall diet records from the MRC National Survey of Health and Development (NSHD) (1946 Birth Cohort) at age 4 years were analysed for energy and selected nutrients and compared to the published results for 4-year-olds in the 1992/93 National Diet and Nutrition Survey (NDNS). SETTING: England, Scotland and Wales in 1950 and 1992/93. SUBJECTS: 4,599 children in 1950 and 493 children in 1992/93. RESULTS: Mean (SD) daily intakes in 1950 were energy 1,445 (343) kcal, or 6.1 (1.4) MJ, protein 46 (11)g, fat 64 (20)g, starch 117 (33)g, sugar 62 (24)g, unavailable carbohydrate 13 (4)g, calcium 736 (230) mg, iron 7.7 (2.1) mg, retinol 738 (1,273) microg, carotene 1,049 (1,130) microg and vitamin C 40 (26) mg. Compared to 1992/93, the 1950 diet contained substantially more bread and vegetables and less sugar and soft drinks, giving it a higher starch and fibre content and making it more in line with current recommendations on healthy eating. However, fat provided 40% of energy in 1950, compared to 35% in 1992/93. In 1950, red meat was an important source of iron, but by 1992 most iron came from fortified breakfast cereals. Vitamin C came mainly from vegetables in 1950, but from soft drinks in 1992. CONCLUSIONS: The relative austerity of post-war food supplies resulted in food and nutrient intakes in 1950 which in many respects may well have been beneficial to the health of young children, despite fat intake being higher than present-day recommendations.

Characteristics of the low-energy reporters in a longitudinal national dietary survey.

The aim of the present study was to establish whether the characteristics of members of a large national birth cohort study who submitted diet diaries with implausibly low-energy intake differed from those whose recorded energy intake was more plausible. Survey members (n 1898) recorded their diets in a 7 d diary in household measures. Those whose reported energy intake (EI) as a fraction of their estimated BMR was less than 1.10, here termed low-energy reporters (LER) but often called under-reporters, constituted 20.6% of the study population. None of the variables describing dietary, smoking or exercise behaviour bore a significant relationship with low EI/BMR (< 1.10), neither did those describing region of residence, subjective adequacy of income, current social class, social relations or the social environment of the subjects. Results of logistic regression analysis showed that the only independently significant characteristic for men was higher BMI. In women, in addition to higher BMI, having been overweight or obese as an adult independently, but less significantly, predicted low EI/BMR, while membership as a child of social class III (non-manual), having more children in the household and having a paid job marginally but independently decreased the probability of reporting low EI/BMR. Submission of a diary with EI/BMR < 1.10 7 years earlier in the same survey was an even more powerful predictor of current low EI/BMR than higher BMI in both sexes. The average reported diet-composition of LER was more micronutrient- and protein-rich than that of the others, indicating different dietary, or diet-recording, behaviour in this group of subjects. LER are not a random sample of the survey population, and their characteristics, definable to some extent, put them at risk for lower health status. Although EI/BMR cut-off points can be used to identify LER, the problem of how to use their data is still unresolved.

Nitrogen homoeostasis in man: diurnal changes in nitrogen excretion, leucine oxidation and whole body leucine kinetics during a reduction from a high to a moderate protein intake.

1. The adaptation of the diurnal cycle of nitrogen (N) homeostasis during a change in protein intake was investigated with diurnal measurements of N and leucine balance and turnover during a reduction from a high to a moderate protein intake in normal adults. 2. In experiment 1, during a 9 day period after a reduction from 1.82 to 0.77 g of protein day-1 kg-1, N excretion fell slowly at a similar rate in fed and fasted states so that the lowered intake was unable to replete any of the postabsorptive losses for 3 days. There was a marked negative N balance, which persisted throughout the study, although with a significant reduction in N losses in both fed and fasted states on day 4, balances during days 4-9 (-32.8 +/- 28.3 mg of N day-1 kg-1) were less negative than during days 1-3 (-79.1 +/- 60.4 mg of N day-1 kg-1). 3. In experiment 2, during a 14 day period after a reduction from 1.89 to 0.77 g of protein day-1 kg-1, [1-13C]leucine oxidation and turnover were measured by primed intravenous infusion, during fasting and feeding in subjects before and on days 3, 7 and 14 after the dietary change. Leucine oxidation fell by 32% (P < 0.05) on day 3 in the fed state and by 12% (P < 0.05) during fasting, falling further in each case by day 7 with improved balance.(ABSTRACT TRUNCATED AT 250 WORDS)

Nitrogen homeostasis in man: the diurnal responses of protein synthesis and degradation and amino acid oxidation to diets with increasing protein intakes.

1. The diurnal changes in whole body protein turnover associated with the increasing fasting body nitrogen (N) losses and feeding gains with increasing protein intake were investigated in normal adults. [13C]Leucine, [2H5]phenylalanine and [2H2]tyrosine kinetics were measured during an 8 h primed, continuous infusion during the fasting and feeding phase together with fed-state N turnover assessed with [15N]glycine after 12 days of adaptation to diets containing 0.36 (LP), 0.77 (MP), 1.59 (GP) and 2.07 (HP) g of protein day-1 kg-1. Measurements were also made of fasting and fed resting metabolic rate and plasma hormone levels. 2. Resting metabolic rate in the fasted and fed state was not influenced by dietary protein intake, but was increased by feeding (11-13%, P < 0.01) with no influence of dietary protein concentration. Fasting plasma insulin levels were not influenced by protein intake and were increased by feeding independent of protein intake. Fasted but not fed values of insulin-like growth factor-1 increased with protein intake, although no feeding response was observed. Thyroid hormones (free and total tri-iodothyronine) did not change in any state. 3. For leucine with increasing protein intake the increasing fasting losses reflected increasing rates of protein degradation, although the changes were small and only significant between GP and MP intakes. The increasing leucine gain on feeding was associated with increasing rates of protein synthesis and falling rates of protein degradation, reflecting a progressive inhibition of degradation with feeding, and a change from inhibition of synthesis (LP diet) to stimulation (GP and HP diets). Mean daily rates of synthesis and degradation did not change with protein intake. 4. Phenylalanine and tyrosine kinetics were calculated from adjusted values based on leucine kinetics and published data of the hepatic/plasma enrichment ratio. With the increased protein intake, the increasing fasting losses of phenylalanine (GP > MP) were mediated by increasing rates of degradation (paired t-tests). The increasing phenylalanine gain (GP > MP > LP) was due to increasing fed-state rates of synthesis and falling rates of degradation, reflecting a progressive inhibition of degradation, a stimulation of hydroxylation and a variable response of synthesis ranging from inhibition at the lowest intake to stimulation at higher intakes. For tyrosine a similar progressive inhibition of degradation with intake was shown. Mean daily rates of synthesis and degradation (phenylalanine) and degradation (tyrosine) did not change with protein intake.(ABSTRACT TRUNCATED AT 400 WORDS)

Nitrogen homeostasis in man: influence of protein intake on the amplitude of diurnal cycling of body nitrogen.

1. The diurnal nature of nitrogen (N) homoeostasis was investigated in adults fed increasing protein intakes. N balance was estimated during a 48 h period of consecutive 12 h periods of feeding hourly meals and fasting, after 12 days of adaptation to diets containing 0.36 +/- 0.01, 0.77 +/- 0.03, 1.59 +/- 0.08 and 2.31 +/- 0.65 g of protein day-1 kg-1. N losses were determined from measured urinary N excretion corrected for changes in the body urea pool, and estimated faecal and miscellaneous losses. [13C]Leucine and [2H5]phenylalanine balances were measured during a primed, continuous infusion of the two amino acids during the fasting and feeding phase on the second day. 2. Increasing fasting N losses were observed (47 +/- 7, 60 +/- 6, 95 +/- 15 and 140 +/- 36 mg day-1 kg-1) on the four intakes, with corresponding increasing fed gains of 8.2 +/- 3.9, 40.2 +/- 7.1, 112 +/- 24 and 180 +/- 56 mg day-1 kg-1. 3. Increasing fed-state amino acid gains with increasing protein intake were observed with both [13C]leucine and [2H5]phenylalanine, whereas increasing fasting amino acid losses were confirmed with [13C]leucine. 4. The N equivalent of the leucine oxidation rate was mostly in the range of 10-50% lower than expected from the N excretion rates. This may reflect the timing of the amino acid balance measurements and non-uniform rates of gain and loss throughout the diurnal cycle. 5. We conclude on the basis of both N and amino acid balances that the amplitude of the diurnal cycling of body protein N in human adults increases with increasing dietary protein intake. Thus one component of the protein requirement for N balance reflects a demand for repletion of fasting losses which increases with increasing habitual protein intake.

Effects of dopamine, high potassium concentration and field stimulation on the secretion of aldosterone by the perfused rat adrenal gland.

The rat adrenal cortex contains quantities of dopamine that are compatible with its function as a neurotransmitter, suggesting that locally released dopamine may act as a neuroregulator within the gland. This possibility has been tested by comparing the effects of dopamine on aldosterone secretion in the perfused adrenal with the effects of stimuli designed to provoke the release of intraglandular dopamine. Infusion of dopamine (0.1-100 mumol/l for 10-min periods) into the isolated perfused rat adrenal gland resulted in a transient, dose-related reduction of aldosterone secretion to a minimum of approximately 50% of the basal value at 1 mumol dopamine/l (ratio of experimental to control measurements, R = 0.53 +/- 0.06 (S.E.M.); n = 5). In contrast, dopamine (1-100 mumol/l) had no effect on aldosterone production by dispersed zona glomerulosa cell preparations incubated in vitro. The effects of changes in K+ concentration (3.9-52 mmol/l) on aldosterone secretion in the perfused gland and dispersed cell preparations were also compared. A similar bell-shaped dose-response relationship was seen in both preparations between 6 and 32 mmol K+/l, with a maximum at 8.4 mmol K+/l and a return to control values with 16, 24 or 32 mmol K+/l. However, infusion of media with very high K+ concentrations (42 or 52 mmol K+/l) reduced the secretion of aldosterone by the perfused gland to approximately 50% of the basal value (R = 0.51 +/- 0.05, n = 9; R = 0.49 +/- 0.08, n = 9; respectively) but produced no change in aldosterone production by zona glomerulosa cells.(ABSTRACT TRUNCATED AT 250 WORDS)

The nutritional sensitivity of the diurnal cycling of body protein enables protein deposition to be measured in subjects at nitrogen equilibrium.

In adults in overall protein balance on intakes of protein equal to or greater than minimum requirements, the diurnal pattern of feeding and fasting results in cycling of body protein, with fasted losses and fed state gains of increasing amplitude with increasing habitual protein intake. Measurement of the slope of the fed state gain-intake relationship enables investigation of the ability of various patient groups to utilise dietary protein, without the need to impose negative nitrogen balance due to sub-maintenance protein intakes.

Studies on the mechanisms of ACTH-induced inhibition of aldosterone biosynthesis in the rat adrenal cortex.

In rats, chronic treatment with high doses of ACTH (10-40 micrograms/100 g body weight per day) leads to a marked reduction in aldosterone synthesis by adrenal capsules. The possibility that this inhibition is secondary to a decrease in plasma potassium levels or in renin angiotensin system (RAS) activity has been explored. The effects of chronic ACTH treatment were compared in (I) animals in which the endogenous RAS activity was stimulated by restricting dietary sodium intake, (II) animals in which plasma angiotensin II was increased by infusion from implanted osmotic minipumps and (III) animals which received supplementary potassium and in which hypokalaemia was prevented. In all cases, rates of aldosterone biosynthesis in vitro by adrenal capsules were decreased in ACTH-treated animals to an extent similar to those in untreated controls. In addition, ACTH treatment of hypophysectomized rats resulted in a similar inhibition of aldosterone biosynthesis to that found in sham-operated controls. It may be concluded that the ACTH-induced reduction of aldosterone biosynthesis is independent of the secretion of other pituitary hormones, and cannot be simply ascribed to either a reduction in RAS activity or in plasma potassium levels. The results are consistent with the view that the effects of chronic ACTH treatment are mediated by a direct action on the zona glomerulosa cell, which leads to its transformation into a zona fasciculata-like form.

In vitro analysis of the interactions of recombinant IL-2 with regenerating lymphoid and myeloid cells after allogeneic marrow transplantation.

Although administration of rIL-2 post-T depleted allogeneic bone marrow transplantation (TD-BMT) offers the prospect of augmenting immune reconstitution and thereby reducing the risks of infection and relapse, it has been unclear what direct or indirect effects this agent would have on the regenerating myeloid system. We find that addition of 200 IU or rIL-2 to patient lymphocytes obtained within 6 wk of TD-BMT results in a substantial (2 to 3 log) increase in INF-gamma secretion and the production of TNF. Cytokines present in supernatants obtained from IL-2-stimulated patient lymphocytes have two contrasting effects on myeloid cells from normal donors and from marrow recipients. They prime granulocytes for enhanced oxidative metabolism as measured by ability to generate chemiluminescence in response to FMLP, whereas IL-2 added directly to neutrophils has no effect. However, these IL-2-induced cytokines also act to inhibit myeloid progenitor growth and reduce granulocyte macrophage (GM) colony formation by a mean of 53%. Preincubation of supernatants with anti-IFN-gamma antibody partially abrogates both enhancement of granulocyte chemiluminescence and suppression of marrow CFU-GM. Addition of IL-2 directly to recipient marrow also produces inhibition, leading to a 25% reduction of GM-colony growth. This effect is not due to direct interaction between myeloid progenitor cells and IL-2, because it is completely abrogated by removal of CD8 and Leu-7+ lymphocytes from the marrow. Although the suppressive effects on marrow growth in vitro are of particular concern after BMT, the potential of IL-2 to promote granulocyte function, immune reconstitution, and anti-leukemic activity after TD-BMT justify further consideration of IL-2 therapy in this setting.

Inosine monophosphate dehydrogenase activity in acute leukaemia.

Inosine monophosphate dehydrogenase (IMPD) is an important enzyme in de-novo purine synthesis. The level of IMPD activity has been suggested to determine whether acute leukaemia cells proliferate (if the activity is high) or differentiate (if IMPD activity is low). IMPD activity measured by the conversion of inosine monophosphate to xanthine monophosphate ranged from 12.5 to 87.0 (mean 49.4) pmol/h/10(6) cells in normal bone marrow. The levels were significantly raised in AML (range 14-374, mean 184 pmol/h/10(6) cells) and ALL (range 65-228, mean 172 pmol/h/10(6) cells). Normal tonsillar (B) lymphocytes showed higher levels (range 78-159, mean 110 pmol/h/10(6) cells) than resting peripheral blood T lymphocytes (range 8.8-51.2, mean 28.1 pmol/h/10(6) cells). In CLL, the results (range 19-173, mean 64.3 pmol/h/10(6) cells) were comparable to those of normal tonsillar B lymphocytes. IMPD levels could be related to cell cycle in PHA-stimulated lymphocytes, since IMPD activity increased in parallel with increase in DNA synthesis measured by labelled thymidine incorporation. On the other hand, IMPD activity did not correlate with the proportion of proliferating cells measured on a FACS sorter in either AML or ALL or in normal tonsillar B cells. We conclude that IMPD levels are higher in B than T lymphocytes and in acute leukaemia blasts compared to more differentiated mixed bone marrow cells. The results do not suggest, however, that IMPD assay will be of value in differentiation of the various subtypes of acute leukaemia or of malignant haemopoietic cells from the equivalent normal cell at the same level of differentiation.

Effects of stimulation on steroid output and perfusion medium flow rate in the isolated perfused rat adrenal gland in situ.

Using the in-situ, isolated, perfused rat adrenal system, the actions of adrenal stimulants on steroidogenesis and perfusion medium flow rates (under constant perfusion pump conditions) have been studied. In a series of 100 experiments, initial rates of corticosterone output and flow rates were found to be positively correlated, although there was no such relationship between initial rates of aldosterone output and flow rates. Furthermore, in stable perfusion conditions, bolus injections of ACTH increased both flow rate and steroid output in a dose-related manner. In individual experiments there was a clear correlation between corticosterone and flow, but the association between aldosterone secretion rate and flow was less evident. It is possible that this discrepancy arises because of temporal differences in the responses of these two steroids. Flow was also stimulated by dibutyryl cyclic AMP (dbcAMP), with correlations with steroid output similar to ACTH, but the specific zona glomerulosa stimulants angiotensin II amide and potassium ions had, if anything, inhibitory effects on flow, but only at high concentrations. The data suggest that ACTH and dbcAMP evoke specific responses in the adrenal vasculature, resulting in relatively decreased intraglandular vascular resistance. They furthermore suggest that the secretory functions of the inner adrenocortical zones are subject to the additional control of vascular elements in the intact gland.

The role of platelet-derived growth factor on human pluripotent progenitor (CFU-GEMM) growth in vitro.

The effect of serum on the proliferation of human bone marrow pluripotent progenitor cells (CFU-GEMM), was compared to that of fresh frozen plasma (FFP). Serum significantly increased the number of mixed erythroid-granulocytic-megakaryocytic colonies (CFU-GEMM) and erythrocytic bursts (BFU-E) in this assay system (p less than 0.01 and 0.02, respectively). Two possible explanations for this finding were considered: first the presence of citrate-phosphate-dextrose (CPD) in plasma but not in serum, and second the presence of platelet-derived growth factor (PDGF) in serum but not in plasma. CPD was indeed found to have an inhibitory effect on growth of colonies of all types when added to serum-stimulated cultures. Nevertheless, when heparinized plasma was compared to serum from the same donors, growth of CFU-GEMM and BFU-E was higher in the serum-stimulated cultures (p less than 0.001 and p less than 0.05, respectively). PDGF at concentrations of 120-240 pM was found to enhance the formation of CFU-GEMM and BFU-E by three- and four-fold respectively when added to cultures containing FFP but not when added to cultures containing serum derived from whole blood (WBS). Purified PDGF added at the same concentrations, to cultures containing platelet-poor derived serum (PDS), promoted similar increases in growth of CFU-GEMM and BFU-E but not of granulocytic-macrophage or megakaryocytic colonies. Whether PDGF has a direct action on CFU-GEMM or its growth promoting activity is via an interacting cell population is currently being studied.

Effects of chronic ACTH stimulation on the morphology of the rat adrenal cortex.

The effects of chronic ACTH treatment (Depot Synacthen, 100 micrograms/day) on the morphology of the rat adrenal were studied in animals treated for 1 to 18 days. The gross weight of the adrenal increased up to tenfold, but although mitotic figures were seen after 3 days in the glomerulosa region, most of this is attributable to a vast increase in blood content. After 3 days of treatment the sinusoids in the reticularis became extremely dilated, and red blood cells penetrated the endothelial wall to become tightly packed around the cortical cells. This led to the gross distortion of the organization of the cortical tissue and after 7 days the cells in the reticularis region were isolated from each other by the continual infiltration of red blood cells. These changes gradually progressed outward so that other regions of the cortex became similarly affected. Eventually the cord-like arrangement of the fasciculata was disrupted. After 18 days of treatment, most of the cortex was involved and only a very thin layer of cells lying beneath the adrenal capsule was seemingly unaffected. Another major effect of corticotrophin treatment was the gradual loss of cellular differentiation, particularly of glomerulosa cells. Although the glomerulosa appeared normal after 1 day of treatment, cells of the fasciculata abut directly on the connective tissue capsule following 3 days of ACTH administration. Eventually glomerulosa cells disappeared almost completely, although there was no sign of cellular necrosis. It is likely that glomerulosa cells are transformed into fasciculata-type cells under ACTH treatment. This interpretation is consistent with functional changes that occur at the same time, including the loss of aldosterone synthetic capacity.