The effect of exercise on behavioral and psychological symptoms of dementia: towards a research agenda.

BACKGROUND: Behavioral and psychological symptoms of dementia (BPSD) are common and are core symptoms of the condition. They cause considerable distress to the person with dementia and their carers and predict early institutionalization and death. Historically, these symptoms have been managed with anxiolytic and antipsychotic medication. Although potentially effective, such medication has been used too widely and is associated with serious adverse side-effects and increased mortality. Consequently, there is a need to evaluate non-pharmacological therapies for behavioral and psychological symptoms in this population. One such therapy is physical activity, which has widespread health benefits. The aim of this review is to summarize the current findings of the efficacy of physical activity on BPSD. METHOD: Published articles were identified using electronic and manual searches. Rather than systematically aggregating data, this review adopted a rapid critical interpretive approach to synthesize the literature. RESULTS: Exercise appears to be beneficial in reducing some BPSD, especially depressed mood, agitation, and wandering, and may also improve night-time sleep. Evidence of the efficacy of exercise on improving other symptoms such as anxiety, apathy, and repetitive behaviors is currently weak or lacking. CONCLUSION: The beneficial effect of exercise type, its duration, and frequency is unclear although some studies suggest that walking for at least 30 minutes, several times a week, may enhance outcome. The methodological shortcomings of current work in this area are substantial. The research and clinical implications of current findings are discussed.

Religious coping strategies in patients diagnosed with breast cancer in the UK.

OBJECTIVES: The use of religious/spiritual coping strategies may be particularly prevalent when dealing with the stress of a cancer diagnosis. There has, however, been very little research conducted on this topic outside the USA. Existing measures of coping largely ignore the complexity of religious/spiritual coping and its potential to be adaptive as well as maladaptive. The aim of this study was to examine the prevalence of various religious coping strategies in a UK cancer sample. METHOD: A longitudinal design assessed religious coping strategies in patients newly diagnosed with breast cancer at the time of surgery and at 3 and 12 months post surgery. We recruited 202 patients of which, at 12 months, 160 remained. A non-religious coping measure was included for comparison. RESULTS: The use of religious coping strategies was overall common; up to 73% of patients used positive religious coping to some degree at surgery and up to 53% experienced various religious/spiritual struggles. The use of some religious coping strategies showed differing patterns of change across time while others remained stable. CONCLUSION: Using religious/spiritual resources in the coping process during the early stages of breast cancer appears common in the UK. Patients may benefit from having their spiritual needs addressed as experiencing some form of religious/spiritual struggle may serve as a barrier to illness adjustment. Health-care professionals should also be aware that some religious coping strategies may be more prevalent at different times during the first year of illness.

The impact of a breast cancer diagnosis on religious/spiritual beliefs and practices in the UK.

The use of religious/spiritual resources may increase when dealing with the stress of a cancer diagnosis. However, there has been very little research conducted into changes in religious/spiritual beliefs and practices as a result of a cancer diagnosis outside the USA. The aim of this study was to examine the impact of a breast cancer diagnosis on patients' religious/spiritual beliefs and practices in the UK where religious practice is different. The study used two methods. One compared the religious/spiritual beliefs and practices of 202 patients newly diagnosed with breast cancer with those of a control group of healthy women (n = 110). The other examined patients' perceived change in religious/spiritual beliefs and practices at the time of surgery with those in the year prior to surgery. The aspects of religiousness/spirituality assessed were: levels of religiosity/spirituality, strength of faith, belief in God as well as private and public practices. Patient's perceived their belief in God, strength of faith and private religious/spiritual practices to have significantly increased shortly after surgery compared with the year prior to surgery. However, there were no significant differences in religious/spiritual beliefs and practices between patients and healthy participants. Change scores demonstrated both a reduction and an increase in religious/spiritual beliefs and practices. Although belief in God, strength of faith and private religious/spiritual practices were perceived by patients to be significantly higher after their cancer diagnosis, no significant differences in religious/spiritual beliefs and practices were found between the cancer group at the time of surgery and the control group. Different methodologies appear to produce different results and may explain contradictions in past US studies. Limitations of this study are discussed and suggestions for future research are made.

The effect of varying levels of population control on the prevalence of tuberculosis in badgers in Ireland.

We examined the effect of varying levels of badger population control on the prevalence of Mycobacterium bovis infection in badgers in four counties of Ireland. In the 'Removal' and 'Buffer' areas, proactive culling was conducted to substantially reduce and subsequently maintain badger populations at a low level for five years. In the 'Reference' areas, localised reactive culling was conducted in association with herd breakdowns. The infection status of badgers was determined using bacteriology. A total of 2696 badgers were recruited into the study, and 19.0% were found to be infected with M. bovis. The two population control strategies had differing effects on the subsequent prevalence of tuberculosis in badger populations. Proactive culling led to a long term decrease in the prevalence of tuberculosis in the re-emergent populations. Although there was an overall decline in the disease prevalence, no consistent trend in disease prevalence as a result of reactive culling was observed.

The impact of badger removal on the control of tuberculosis in cattle herds in Ireland.

In Ireland, the herd prevalence of bovine tuberculosis has remained stable for several decades, and in common with several other countries, progress towards eradication has stalled. There is evidence in support of the potential role of infected badgers (Meles meles, a protected species) in bovine tuberculosis in Ireland and Britain. However, this evidence on its own has not been sufficient to prove disease causation. Field trials are likely to offer the best opportunity to define this role. Building on the earlier East Offaly project, our objectives were to assess the impact of badger removal on the control of tuberculosis in cattle herds in Ireland. The study was conducted from September 1997 to August 2002 in matched removal and reference areas (average area of 245.1km(2)) in four counties: Cork, Donegal, Kilkenny and Monaghan. Badger removal was intensive and proactive throughout the study period in the removal areas, but reactive (in response to severe tuberculosis outbreaks in cattle) in the reference areas. Removal intensity in the removal and reference areas during the first 2 years of the study averaged 0.57 and 0.07 badgers/km(2)/year, respectively. The outcome of interest was restriction of cattle herds due to confirmed tuberculosis, where tuberculous lesions were detected in one or more animals. Data were analysed using logistic regression (modelling the probability of a confirmed herd restriction) and survival analysis (modelling time to a confirmed herd restriction). During the study period, there was a significant difference between the removal and reference areas in all four counties in both the probability of and the time to a confirmed herd restriction due to tuberculosis. In the final year of the study, the odds of a confirmed herd restriction in the removal (as compared to the reference areas) were 0.25 in Cork, 0.04 in Donegal, 0.26 in Kilkenny and 0.43 in Monaghan. Further, the hazard ratios (removal over reference) ranged from 0.4 to 0.04 (a 60-96% decrease in the rate at which herds were becoming the subject of a confirmed restriction).

Alteration of the circadian rhythm of intact parathyroid hormone and serum phosphate in women with established postmenopausal osteoporosis.

Several studies have established that the circulating concentration of intact parathyroid hormone, PTH (1-84), over 24 h follows a circadian rhythm. The importance of this circadian rhythm is not known although some authors have detected alterations in the rhythm in metabolic bone disease and following dietary manipulation. We have studied the circadian rhythm of PTH (1-84) in 8 premenopausal women, 8 postmenopausal women with established osteoporosis and 8 postmenopausal women with no evidence of osteoporosis. Blood samples were obtained at 30-min intervals over a 24-h period and significant differences were found in the profiles of PTH (1-84) and serum phosphate in the three groups studied. Premenopausal women possessed a nocturnal/early morning increase in PTH (1-84) and phosphate (between 2200 and 0700 hours), as did postmenopausal women without osteoporosis. In postmenopausal women with osteoporosis the nocturnal increase in PTH (1-84) and serum phosphate was absent and PTH (1-84) decreased during the period 2200-0700 hours. A shift in acrophase is observed between premenopausal and postmenopausal women without osteoporosis. No acrophase was found in postmenopausal women with osteoporosis for either PTH (1-84) or serum phosphate. No circadian rhythm, acrophase or significant amplitude was observed in serum adjusted calcium or ionized calcium in any group studied. Alterations in the circadian rhythms for PTH (1-84) and serum phosphate occur in patients with postmenopausal osteoporosis that suggest that normal dynamics of PTH (1-84) secretion may play a role in both calcium and phosphate metabolism and the bone remodelling process. Whether these changes are causative or a response to the pathology will require further investigation.

Management of male osteoporosis: report of the UK Consensus Group.

Although osteoporosis is generally regarded as a disease of women, up to 30% of hip fractures and 20% of vertebral fractures occur in men. Risk factors for osteoporotic fractures in men include low body mass index, smoking, high alcohol consumption, corticosteroid therapy, physical inactivity, diseases that predispose to low bone mass, and conditions increasing the risk of falls. The key drugs and diseases that definitely produce a decrease in bone mineral density (BMD) and/or an increase in fracture rate in men are long-term corticosteroid use, hypogonadism, alcoholism and transplantation. Age-related bone loss may be a result of declining renal function, vitamin D deficiency, increased parathyroid hormone levels, low serum testosterone levels, low calcium intake and absorption. Osteoporosis can be diagnosed on the basis of radiological assessments of bone mass, or clinically when it becomes symptomatic. Various biochemical markers have been related to bone loss in healthy and osteoporotic men. Their use as diagnostic tools, however, needs further investigation. A practical approach would be to consider a bone density more than one SD below the age-matched mean value (Z < -1) as an indication for therapy. The treatment options for men with osteoporosis include agents to influence bone resorption or formation and specific therapy for any underlying pathological condition. Testosterone treatment increases BMD in hypogonadal men, and is most effective in those whose epiphyses have not closed completely. Bisphosphonates are the treatment of choice in idiopathic osteoporosis, with sodium fluoride and anabolic steroids to be used as alternatives.

A comparison of the effects of alfacalcidol treatment and vitamin D2 supplementation on calcium absorption in elderly women with vertebral fractures.

Although vitamin D supplementation in the frail elderly improves calcium absorption, suppresses parathyroid hormone, decreases bone loss and reduces the risk of fractures, such treatment may be ineffective in patients with vertebral osteoporosis, because of impaired vitamin D metabolism or resistance to the action of vitamin D metabolites on the bowel. We have therefore performed a randomized, single masked study comparing the effects of alfacalcidol treatment (0.25 micrograms twice daily) and vitamin D2 supplementation (500-1000 units daily) on calcium absorption and bone turnover in 46 elderly women (median age 69 years, range 64-79 years) with radiological evidence of vertebral fractures. Serum 25-hydroxyvitamin D increased significantly after 3 and 6 months of treatment with vitamin D2 (p < 0.001), but was unchanged in the group receiving alfacalcidol. Serum 1,25-dihydroxyvitamin D did not change significantly in either group over the study period. Fractional 45Ca absorption increased after 3 months of treatment with alfacalcidol (p < 0.05), but was unchanged with vitamin D2. There was also a reduction in plasma intact parathyroid hormone and serum alkaline phosphatase after 6 months of treatment with alfacalcidol (p < 0.05) which was not seen in the group receiving vitamin D2. Our study shows that vitamin D2 supplementation is ineffective in stimulating calcium absorption in elderly women with vertebral osteoporosis. By increasing calcium absorption in such patients, alfacalcidol may prove more effective than vitamin D in the management of vertebral osteoporosis.

Changes in calciotrophic hormones and biochemical markers of bone turnover in normal human pregnancy.

Plasma concentrations of parathyroid hormone-related protein (PTHrP), parathyroid hormone, alkaline phosphatase, osteocalcin and albumin-adjusted calcium were measured along with nephrogenous cyclic adenosine monophosphate (NcAMP) in 10 normal women longitudinally through pregnancy. In addition, an assessment of bone resorption was made in these same subjects by the measurement in true fasting urine specimens of the calcium/creatinine ratio (Ca/Cr), hydroxyproline/creatinine ratio (HP/Cr), pyridinoline/creatinine ratio (Pyr/Cr) and deoxypyridinoline/creatine ratio (Dpyr/Cr). The PTHrP level rose through pregnancy from (mean +/- SEM) 0.8 +/- 0.2 pmol/l in the first trimester to 2.7 +/- 0.2 pmol/l 6 weeks postpartum (p < 0.0001). Serum alkaline phosphatase rose from 94 +/- 8 U/l (first trimester) to 347 +/- 25 U/l at term (p < 0.0001). A significant positive correlation was evident between PTHrP and alkaline phosphatase up to term (r = 0.44, p < 0.005). Parathyroid hormone concentrations remained unchanged during pregnancy but rose significantly postpartum from 1.8 +/- 0.2 pmol/l (first trimester) to 3.1 +/- 0.5 pmol/l (p < 0.0001). Similarly, osteocalcin, a marker of bone formative activity, remained unchanged through pregnancy but rose significantly at 6 weeks after delivery to 0.38 +/- 0.05 nmol/l from 0.19 +/- 0.03 nmol/l (first trimester) (p = 0.019). No significant change was noted in serum-adjusted calcium or NcAMP, either through pregnancy or at the postpartum assessment. Fasting urinary Ca/Cr fell through pregnancy from 0.70 +/- 0.11 (first trimester) to a nadir of 0.19 +/- 0.04 6 weeks postpartum (p = 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)

Recurrent chylothorax in a woman with primary amenorrhoea.

A 47 year old woman receiving oestrogen replacement therapy for primary amenorrhoea presented with recurrent chylothorax. The clinical and radiological features of her illness were characteristic of pulmonary lymphangio-leiomyomatosis, a rare hormone-dependent disease. The condition was treated with pleurodesis and withdrawal of oestrogen therapy.

Cytokine and growth factor expression in Paget's disease: analysis by reverse-transcription/polymerase chain reaction.

We investigated expression of several cytokines and growth factors in explants of Pagetic and non-Pagetic bone samples using the technique of reverse-transcription/polymerase chain reaction (RT/PCR). Transcripts for IL-1 alpha and IL-1 beta, TNF-alpha, TNF-beta, IL-6, basic fibroblast growth factor (bFGF), transforming growth factor beta (TGF-beta) and insulin-like growth factor-I (IGF-I) were found to a variable degree in both Pagetic and non-Pagetic bone samples, but there was no significant difference in the patterns of expression for these factors in Pagetic bone (n = 18) as compared with non-Pagetic bone (n = 51). There was furthermore, no significant difference in the patterns of expression for the various factors studied when patients were subdivided into mild and severe categories of disease activity using markers of bone formation (serum alkaline phosphatase) or bone resorption (osteoclast counts on adjacent biopsy specimens). Although IL-6 and IL-1 have previously been implicated as bone resorbing factors in Pagetic bone, 40% of our patients with severe disease had not detectable IL-6 transcripts, 70% had no detectable IL-1 alpha transcripts and 50% no IL-1 beta transcripts. We conclude that patterns of expression for cytokine and growth factor mRNAs are not disturbed in Paget's disease. Although we cannot exclude the possibility that post-transcriptional processing of the mRNAs may differ in Pagetic and normal bone cells, our data raise the possibility that the abnormalities of bone turnover which are characteristic of active Paget's disease may be due to local elaboration of other, possibly novel osteotropic factors, which stimulate bone formation and resorption.

Association of severe haemophilia A with osteoporosis: a densitometric and biochemical study.

Following a femoral neck fracture and vertebral compression fractures in two patients with severe haemophilia A, bone density and turnover were measured in 19 males with severe haemophilia A (all HIV negative, 18/19 hepatitis C antibody positive) and in 19 age/sex matched controls. Bone density at the lumbar spine (L2-4), measured by dual energy X-ray absorptiometry, was significantly lower in the haemophiliac patients (HPs) at (mean +/- SEM) 1.109 +/- 0.042 g/cm2 vs. 1.234 +/- 0.027 in controls; p = 0.018. Femoral neck density was also lower at 0.877 +/- 0.034 g/cm2 (HPs) vs. 1.067 +/- 0.032; p < 0.0005. No significant differences were evident between the groups for serum calcium, parathyroid hormone, luteinizing hormone, follicle-stimulating hormone or 1,25 dihydroxyvitamin D3, nor for fasting urinary hydroxyproline, pyridinoline or deoxypyridinoline excretion. Serum total alkaline phosphatases was elevated in HPs at 200 +/- 10 U/l vs. 158 +/- 8; p = 0.004. Similarly, gamma-glutamyl transferase was elevated at 42 +/- 7 U/l (HPs) vs. 20 +/- 2; p = 0.007. Serum total testosterone and sex-hormone-binding globulin (SHBG) were higher in HPs at 26 +/- 2.5 nmol/l vs. 17.4 +/- 1.6 (p = 0.009) and 56 +/- 6 nmol/l vs. 27 +/- 3 (p = 0.0005), respectively. Free androgen index, however, was lower in HPs at 44 +/- 5 vs 69 +/- 7; p = 0.008. These results suggest significant osteopenia associated with haemophilia A. This may be partly due to liver dysfunction in HPs, but other factors, e.g. relative immobilization, may also be relevant.

Acute effects of intravenous 1 alpha-hydroxycholecalciferol on parathyroid hormone, osteocalcin and calcitriol in man.

The acute effects of a single intravenous injection of 2 micrograms of 1 alpha-hydroxycholecalciferol (alfacalcidol) were studied for a 24-h period in six normal males (mean age 33 years), six women with primary hyperparathyroidism (mean age 72 years) and six women with established osteoporosis (mean age 63 years). In all three groups, serum calcitriol levels rose to a peak 2-3 h after administration of alfacalcidol. Basal levels were highest in the primary hyperparathyroidism group at (mean +/- SEM) 81 +/- 2 vs 62 +/- 12 (normal males) (p < 0.05) and 56 +/- 5 pmol/l (osteoporosis) (p < 0.01). Highest peak levels were found also in the primary hyperparathyroidism group at 150 +/- 15 vs 114 +/- 15 (normal males) (p < 0.05) and 127 +/- 15 pmol/l (osteoporosis) (p < 0.01). The rise in calcitriol was higher in the primary hyperparathyroidism group than either the normal males or osteoporotic patients (p < 0.05). No significant differences were evident in basal serum calcidiol concentrations among the three treatment groups. As might be expected, highest basal concentrations of parathyroid hormone (PTH), serum calcium and serum osteocalcin were noted in the primary hyperparathyroid group (PTH: 17.1 +/- 7.7 vs 1.9 +/- 0.5 (normal males) (p < 0.01) and 2.1 +/- 0.3 pmol/l (osteoporosis) (p < 0.01); calcium: 3.06 +/- 0.08 vs 2.50 +/- 0.02 (normal males) (p < 0.01) and 2.43 +/- 0.02 mmol/l (osteoporosis) (p < 0.01); osteocalcin: 1.10 +/- 0.08 vs 0.56 +/- 0.16 (normal males) (p < 0.05) and 0.53 +/- 0.21 nmol/l (osteoporosis) (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Mineralisation defects with pamidronate therapy for Paget's disease.

Bone biopsy samples were taken from 20 patients with Paget's disease before and after intravenous pamidronate therapy. In 10 patients given 180 or 360 mg during 6 or 9 weeks, bone turnover decreased as measured biochemically and histologically, but osteomalacia developed in 1 patient and mineralisation defects in 3. 10 other patients received 45 mg every 3 months for 1 year. Bone turnover decreased biochemically but not histologically, and osteoid thickness increased, suggesting impaired mineralisation. Despite overall efficacy, pamidronate has a narrow therapeutic range between resorption inhibition and mineralisation defects. Short courses given to achieve biochemical remission should be administered with caution.

Central nervous system histiocytosis X--imaging and responses to chemotherapy.

Histiocytosis X is the term first coined by Lichtenstein in 1953 to describe a heterogeneous group of disorders which is considered now to include Hand-Schuller-Christian disease, Letterer-Siwe disease and Eosinophilic Granuloma of bone. Gagel, in 1941, first described involvement of the central nervous system (CNS) in Histiocytosis X--in this case the hypothalamus and posterior pituitary were the areas principally affected. CNS involvement outwith these areas is rare, generally difficult to diagnose, and little information on treatment is available. In this case we describe a man with cranial histiocytosis X who was treated with intrathecal and systemic chemotherapy and cranial irradiation, and we comment upon the value of magnetic resonance imaging (MRI) in this condition.

Secondary osteoporosis.

Osteoporosis with attendant increased fracture risk is a common complication of many other diseases. Indeed, almost all chronic diseases make some impact on life-style, usually by restricting physical activity and hence reducing the anabolic effect of exercise and gravitational strains on the skeleton. Restricted appetite and modified gastrointestinal tract function is another commonplace finding that has an impact on bone nutrition and synthesis, as on other systems. Sex hormone status is of particular importance for the maintenance of the normal skeleton, and the postmenopausal woman is at particular risk for most causes of secondary osteoporosis. In dealing with secondary osteoporosis in the hypo-oestrogenic woman, the question of giving hormone replacement therapy in addition to other disease-specific therapy should always be considered, as, for example, in a young amenorrhoeic woman with Crohn's disease. Similarly, in hypogonadal men the administration of testosterone is useful for bone conservation. The wider availability of bone densitometry ought to make us more aware of the presence of osteoporosis in the many disease states discussed above. This is particularly important as the life span of such patients is now increased by improved management of the underlying disease process in many instances. Even in steroid-induced osteoporosis--one of the commonest and most severe forms of osteoporosis--we now have some effective therapy in the form of the bisphosphonates and other anti-bone-resorbing drug classes. The possibility of prophylaxis against secondary osteoporosis has therefore become a possibility, although the very long-term effects of such drug regimens are still unknown. In some situations, such as thyrotoxicosis, Cushing's syndrome and immobilization, spontaneous resolution of at least part of the osteoporosis is possible after cure of the underlying problem. The shorter the existence of the basic problem, the more successful the restoration of the skeleton appears to be. A useful credo for clinicians with respect to secondary osteoporosis is: to think of it; to use specific therapy for the underlying disease; to reduce or remove completely any relevant drug or toxic material; to optimize physical activity and general nutrition; to treat hypogonadism if present and feasible; and to consider the use of specific anti-bone-resorbing or other bone active drugs.