Authors defend their study to develop tool to predict falls in elderly people.
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Accidental Falls↗
Biomedical subjects
F C Martin
Publications and source records attributed to F C Martin.
A study of force and cross-sectional area of adductor pollicis muscle in female hip fracture patients.
OBJECTIVES: To determine the extent of muscle weakness in older female hip fracture patients compared with healthy older and young women; to determine the extent to which this weakness is caused by a decline of the force produced per unit area of muscle rather than by a decline in muscle bulk; and to investigate the mechanism of the decline in force per unit area. DESIGN: This was an open study of three groups of subjects, two age matched older groups and one young group. SETTING: University College London, Royal Free Hospital, and St. Thomas's Hospital, London. PARTICIPANTS: Twenty-nine older female hip fracture patients (mean age 85.6 +/- 0.9 SEM), 18 healthy older women (mean age 84.7 +/- 1.2 SEM), and 43 young women (mean age 28.9 +/- 1.2 SEM). MEASUREMENTS: Adductor pollicis muscle maximum voluntary force (MVF) during isometric and pliometric contractions and cross-sectional area (CSA), body weight, height, and demi-span. RESULTS: Isometric MVF was lowest in the hip fracture group. In both older groups, isometric MVF and CSA were lower than in the young women. Only part of this weakness in the older groups could be explained by the smaller CSAs. The isometric force per unit area (MVF/CSA) was also lower in both older groups, the hip fracture patients again having the lowest values. Analysis of variance showed a significant difference between groups. The age-related declines in pliometric force were much less than the declines in isometric force. This resulted in an increase in the pliometric/isometric force ratio both for the hip fracture patients and for the healthy older women compared with that for young women. CONCLUSION: In comparison with the results from young women, the adductor pollicis muscles of female hip fracture patients were even weaker than those of healthy older women when normalized for muscle size. This decline in isometric MVF/CSA accounted for at least half of the overall weakness in the hip fracture patients. Inasmuch as pliometric force is maintained in situations where weakness is caused by a decline in the force produced per muscle cross-bridge, this is the likely mechanism of the declines in isometric MVF/CSA observed in this study.
Adult↗
Development and evaluation of evidence based risk assessment tool (STRATIFY) to predict which elderly inpatients will fall: case-control and cohort studies.
OBJECTIVES: To identify clinical characteristics of elderly inpatients that predict their chance of falling (phase 1) and to use these characteristics to derive a risk assessment tool and to evaluate its power in predicting falls (phases 2 and 3). DESIGN: Phase 1: a prospective case-control study. Phases 2 and 3: prospective evaluations of the derived risk assessment tool in predicting falls in two cohorts. SETTING: Elderly care units of St Thomas's Hospital (phase 1 and 2) and Kent and Canterbury Hospital (phase 3). SUBJECTS: Elderly hospital inpatients (aged > or = 65 years): 116 cases and 116 controls in phase 1,217 patients in phase 2, and 331 in phase 3. MAIN OUTCOME MEASURES: 21 separate clinical characteristics were assessed in phase 1, including the abbreviated mental test score, modified Barthel index, a transfer and mobility score obtained by combining the transfer and mobility sections of the Barthel index, and several nursing judgements. RESULTS: In phase 1 five factors were independently associated with a higher risk of falls: fall as a presenting complaint (odds ratio 4.64 (95% confidence interval 2.59 to 8.33); a transfer and mobility score of 3 or 4 (2.10 (1.22 to 3.61)); and primary nurses' judgment that a patient was agitated (20.9 (9.62 to 45.62)), needed frequent toileting (2.48 (1.08 to 5.70)), and was visually impaired (3.56 (1.26 to 10.05)). A risk assessment score (range 0-5) was derived by scoring one point for each of these five factors. In phases 2 and 3 a risk assessment score > 2 was used to define high risk: the sensitivity and specificity of the score to predict falls during the following week was 93% and 88% respectively in phase 2 and 92% and 68% respectively in phase 3. CONCLUSION: This simple risk assessment tool predicted with clinically useful sensitivity and specificity a high percentage of falls among elderly hospital inpatients.
Accidental Falls↗
Growth hormone secretion in the elderly: ageing and the somatopause.
The syndrome associated with lack of growth hormone (GH) in adults can be reversed by treatment with recombinant human GH (rhGH) with apparently beneficial clinical effects. This syndrome is strikingly similar to the characteristics of normal older adults which are known as the somatopause. GH secretion and insulin-like growth factor I levels are reduced in healthy older people and it has been suggested that the somatopause is an age-related GH deficiency state. This review describes the physiological control of GH secretion in adults and seeks an explanation for the age-related decline, considering the impact of other factors such as nutrition and mobility, and particularly whether exercise offers a physiological approach to changing both the GH decline and the somatopause. The benefits and side-effects of treatment with rhGH for normal older people or older patients facing catabolic stresses are reviewed together with alternative approaches to stimulate GH such as GH-releasing hormone and the new pharmaceutical GH secretagogues.
Aged↗
Delay in the diagnosis of bacteraemic urinary tract infection in elderly patients.
Collaboration between clinicians and microbiologists revealed that many patients with subsequently proven urinary tract infection (UTI) present with symptoms suggestive of chest infection. A retrospective analysis was performed on patients over 50 years old with community acquired bacteraemic UTI proven by blood cultures. The main presenting features were confusion (30%), cough (27%), dyspnoea (28%) and new urinary symptoms (20%). The initial clinical diagnosis was UTI in 43% and chest infection in 24%. Chest infection was diagnosed more often in those over 70 years old than those aged 50-70 years old (chi 2 = 7.2, p = 0.007). The majority had pyuria but less than half of the urine samples arrived in the laboratory on the day of admission, fewer from the older patients than the younger (chi 2 = 2.57, p = 0.10). These results demonstrate that UTI frequently presents with respiratory features and that the diagnosis of UTI is often delayed. Sampling the urine with a catheter may be justified to enable diagnosis on the day of admission.
Aged↗
A serum-free, pyruvate-free medium that supports neonatal neural/glial cultures.
Tissue culture media with serum generally cause excessive astrocyte proliferation in neonatal brain cultures, and often fail to support neonatal neurons. Published serum-free media for brain cultures contain sodium pyruvate, which interferes with lactate dehydrogenase (LDH) assays for cell death. We wanted to use neonatal neural-glial cultures in LDH assays while avoiding astrocyte proliferation, so we developed a serum-free medium without sodium pyruvate. Our initial medium was based on that of Romijn et al. (J Neurosci Methods 23:75-83, 1988), testing selected additives. Cell survival in 8-10-day-old cultures was measured using 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT). N-acetylcysteine, citrate, superoxide dismutase, ascorbate, supplemental amino acids, and high levels of transferrin improved survival. The optimized medium supported neonatal brain cells in reaggregates or in monolayers of 400 cells/mm2 for several weeks with large, healthy-appearing neurons and very little astrocyte proliferation. Neurons stained strongly for the neuronal marker class III beta-tubulin and the synapse marker synaptophysin. Electron microscopy of reaggregate cultures demonstrated abundant neurons with synapses in a dense neuropil. This medium will be useful for various in vitro applications, especially those using LDH assays or requiring the use of neonatal cells.
Animals↗
An alternative method for obtaining high-viability cell suspensions from neonatal mouse brain.
Cultured brain cells have contributed greatly to our understanding of a variety of neurobiological processes. The ability to culture brain tissue is important for studying cellular processes underlying unique neural properties. Traditional culturing techniques commonly involve triturating tissue through glass Pastuer pipets, which are inappropriate for use with potentially biohazardous materials. We therefore developed an alternative method for dissociating brain tissue. The protocol combines enzymatic digestion and mechanical dissociation with additives to the dissection medium that protect the cells against other sources of injury, including glutamate neurotoxicity, oxidative damage, and excessively alkaline pH. We find this method works well with post-natal mouse brain, consistently giving cell viabilities in the range of 92-99% and an average yield of 3.1 x 10(6) cells per mouse.
Animals↗
Neurotransmitters and cytokines in CNS pathology.
In summary, we have demonstrated an in vitro model for oligodendrocyte cell death that may be relevant to events in formation of lesions in MS. It involves cell contact to oligodendrocytes with activated, viable microglia (or inflammatory macrophages), surface TNF-alpha, surface adhesion molecules, and production of NO. Precise mechanisms of TNF-alpha and ICAM-1/LFA-1 participation and the nature of the susceptibility of the oligodendrocyte are currently being studied.
AIDS Dementia Complex↗
Lymphokine induction of rat microglia multinucleated giant cell formation.
Multinucleated giant cell formation (MNGC) occurs in central nervous system AIDS. The mechanism of fusion of microglia in these cases is unknown. We investigated the ability of lymphokines to induce fusion and found that interleukin-3 (IL-3), interleukin-4 (IL-4), gamma interferon (gamma-IFN), and granulocyte-macrophage colony stimulating factor (GM-CSF) induced MNGC formation in cultures of rat microglia in vitro. The diacylglycerol analogue phorbol myristate acetate (PMA) also induced MNGC. Interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF alpha) failed to induce fusion. Preincubation of the IL-3 treated cultures with anti-IL-3, anti-leukocyte function associated antigen-1 (LFA-1) alpha-chain (CD11a), and anti-intercellular adhesion molecule-1 (ICAM-1) inhibited cell fusion. Antibody to polymorphic Class II major histocompatibility complex (MHC) determinants also inhibited MNGCs. Cell surface LFA-1 was predominantly observed on MNGC, suggesting that LFA-1 expression is involved in microglia fusion. We thus propose that MNGC formation of microglia result from the effects of T cell-derived cytokines probably through the induction of cell surface adhesion molecules.
Animals↗
Production of interleukin-1 by microglia in response to substance P: role for a non-classical NK-1 receptor.
Substance P (SP) is a central and peripheral neurotransmitter which has been found in multiple sclerosis plaques. SP stimulates peripheral immune cells and may play a role in some chronic inflammatory diseases. Human peripheral monocyte/macrophages have been shown to produce the inflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha) in response to SP. Therefore, in this study we examined rat brain microglia for the presence of SP receptors and production of IL-1 and TNF alpha in response to SP. Microglia had 4900 +/- 950 (mean +/- SE) receptors per cell fitting a two-site model. Four percent of these were high-affinity receptors with a Kd of 8.2 x 10(-8) M +/- 3.6 x 10(-8) M (mean +/- SE), and 96% of them were low-affinity receptors with a Kd of 2.1 x 10(-6) M +/- 5.2 x 10(-7) M (mean +/- SE). Competitive studies with CP 96,345 and other SP analogs demonstrate these to be non-classical NK-1 receptors. SP alone did not stimulate IL-1 or TNF alpha production. However, SP in synergy with lipopolysaccharide (LPS) quadrupled IL-1 production compared to LPS alone, but did not affect TNF alpha production. These results have implications for certain inflammatory conditions in the central nervous system.
Animals↗
Pubic osteomyelitis caused by Staphylococcus simulans.
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Aged↗
In vivo model of HIV infection of the human brain.
Approximately one quarter of the AIDS patients have severe HIV encephalitis with diffuse neuronal damage that may be mediated by immune factors secreted by CNS macrophages. Based on an in vitro brain microsphere model, we developed an in vivo system in which human embryonic brain tissue survives for several months in the interscapular fat pad of SCID mice. Coculture of human brain tissue with macrophages prior to transplantation resulted in infiltration of the microspheres by activated macrophages. When the macrophages were infected in vitro with a neurotropic HIV strain, viral particles were detected in vivo up to 3 months after transplantation. HIV-infected transplants contained multinucleated giant cells similar to those seen in HIV encephalitis. However, the neuroglial component degenerated in the fat pad of SCID mice. The absence of synaptogenesis in the human transplants suggests that the murine fat pad lacks adequate stimuli or support for human neuronal differentiation. To study neurologic damage associated with HIV infection, sites of implantation that stimulate synaptogenesis (e.g. murine CNS) will need to be explored. Based on these findings we conclude that transplantation of brain microspheres with HIV-infected macrophages into SCID mice may be an achievable model of HIV encephalitis.
AIDS Dementia Complex↗
Substance P stimulates IL-1 production by astrocytes via intracellular calcium.
There is increasing evidence that local substance P (SP) exacerbates peripheral inflammations, partly by stimulating production of inflammatory cytokines such as interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha). SP may play similar roles in certain central nervous system inflammations. Multiple sclerosis plaques, for example, form around veins which are innervated by unmyelinated SP-containing fibers, and astrocytes in multiple sclerosis plaques stain for SP. We tested whether SP could stimulate IL-1 and TNF alpha production by cultured astrocytes and whether calcium was the second messenger in this process. We found that both SP and the calcium ionophore A23187 raised intracellular calcium ([Ca2+]i) and stimulated IL-1 production in astrocytes. SP also nonsignificantly increased TNF alpha production by astrocytes. Treatment with dibromo BAPTA/AM, an intracellular calcium buffer, blocked SP-induced IL-1 production. These findings indicate that SP induces IL-1 production by astrocytes and uses calcium as a second messenger. Our results indicate local SP may play a role in multiple sclerosis and certain other central nervous system inflammations.
Animals↗
Contrasting effects of centromedial and basolateral amygdaloid lesions on stress-related responses in the rat.
The effects of lesions in the centromedial and basolateral amygdala were examined using three different tests sensitive to the following stress-related responses: exploratory behavior, pain reactivity, and immune responses. The most clear-cut results were found with exploratory behavior. Rats with lesions of the centromedial amygdala tended to explore a radial-arm maze more quickly and entered more novel arms of the maze than controls. Those with lesions of the basolateral amygdala were generally too hesitant to explore at all. No significant differences were found between groups on measurements of natural killer cell activity. In tests of pain perception, rats in the control group displayed an analgesic response on the hot plate following an injection of the anxiogenic drug, RO 15-1788, whereas rats with centromedial lesions tended to exhibit a blunted response. These findings provide modest support for the view that the central and lateral regions of the amygdala play complementary roles in aversively motivated behaviors and in stress-related response patterns.
Amygdala↗
Natural killer cell activity in vasopressin-deficient rats (Brattleboro strain).
Several lines of evidence suggest that the neuropeptide vasopressin is involved in the regulation of the immune system. We explored this possibility by comparing the cytotoxic activity of natural killer (NK) cells in Brattleboro (DI) rats, which are homozygous for diabetes insipidus and lack vasopressin, and Long-Evans (LE) rats, the strain from which DI rats were derived. Additionally, we compared the effects of swim stress, morphine administration and vasopressin replacement on NK cell activity in these two strains. In DI rats, NK cell activity, determined by a standard 4-h chromium-release assay, was significantly higher than in LE rats. Both swim stress and morphine administration suppressed NK activity in DI and LE rats. There was no difference in the level of suppression between the two strains. Vasopressin replacement normalized water intake in DI rats, but had no significant effect on NK cell activity. DI rats exhibited lower plasma corticosterone levels, which were not elevated by vasopressin replacement. The results suggest that the lack of vasopressin in DI rats elevates baseline NK cell activity, probably via mechanisms that are secondary to the vasopressin deficiency (e.g. lower corticosterone levels). Neither vasopressin nor other hormones affected by vasopressin deficiency seem to be involved in the acute modulating effects of stress and morphine on NK cells.
Animals↗
Suppression of natural killer cell activity by high-dose narcotic anesthesia in rats.
Suppression of natural killer (NK) cell activity in the postoperative period has been reported in several clinical studies. Endogenous opioids and cerebral injection of morphine have been shown to suppress NK cell activity. Since high-dose opiates are commonly used in anesthetic practice, we sought to determine the effects of three narcotic agents on NK cell activity. Male rats were injected subcutaneously with morphine (30 mg/kg), fentanyl (0.3 mg/kg), or sufentanil (0.06 mg/kg). Three, 12, or 24 h later the cytotoxic activity of splenic NK cells was measured in a 4-h chromium-51 release assay using radiolabeled target cells. All three drugs significantly suppressed NK cytotoxicity at 3 h after administration; this effect was blocked by an opiate antagonist, naltrexone. Fentanyl and sufentanil also caused a significant suppression 12 h after drug administration. By 24 h NK activity of all groups returned to normal values. Interferon is known to augment NK cell activity. Therefore, in another experiment rats were given an interferon inducer, polyinosinic:polycytidylic acid (poly I:C), to determine if it would alter the effects of these narcotics on splenic NK activity. Poly I:C treatment increased NK cytotoxicity to above baseline; fentanyl in these animals reduced NK activity and brought it back to control levels. These findings suggest that clinically used high-dose narcotic anesthesia can suppress NK cytotoxic activity and that pretreatment with interferon can attenuate this suppression.
Anesthesia↗
Effects of a single administration of morphine or footshock stress on natural killer cell cytotoxicity.
We previously reported that daily exposure for 4 days to an inescapable form of footshock stress, known to cause opioid-mediated analgesia, suppressed the cytotoxic activity of splenic natural killer (NK) cells in rats. Similarly, daily injection of high doses of morphine (greater than or equal to 30 mg/kg) for 4 days also suppressed splenic NK cell activity. We now report that a single exposure to the opioid form of footshock stress or a single high dose of morphine induces suppression of splenic NK cell cytotoxicity. This effect is evident 3 h after treatment, returning to normal by 24 h. Morphine-induced NK suppression is evident in both male and female rats, is blocked by the opiate antagonist naltrexone, and develops tolerance. Morphine-induced NK suppression is seen in cells derived simultaneously from the spleen, bone marrow, and peripheral blood, suggesting that this suppression does not result from a selective egress of NK cells from the spleen.
Animals↗
Diagnosis and management of acute confusional states.
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Aged↗