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Biomedical subjects

M A Horan

Publications and source records attributed to M A Horan.

At least 19 recordsLinked to original sources
PubMed2001

Clinical features of dementia associated with apolipoprotein epsilon4: discrimination with a neural network genetic algorithm.

BACKGROUND: It is unclear whether the APOE epsilon4 allele is associated with distinct clinical features in dementia. METHOD: 100 cases meeting ICD criteria for dementia were interviewed using standardized instruments and genotyped for APOE. The presence of the epsilon4 allele was used by a genetic algorithm neural network (GANN) to discriminate symptoms and signs. RESULTS: The GANN selected six features: gender, systolic blood pressure, absence of ankle tendon reflexes, history of weight loss, history of falls, and interviewer observed lability of mood. Using these features, a neural network discriminated cases according to epsilon4 highly accurately (area under receiver operating characteristic=0.83, sensitivity=0.78, specificity=0.78). CONCLUSIONS: A GANN is able to discriminate a clinically distinct group of features among dementia patients who express the epsilon4 allele.

Accidental Falls↗
PubMed2000

Disrupted cortisol-ACTH relationships in elderly women given corticotrophin-releasing hormone two weeks after proximal femur fracture.

OBJECTIVE: In elderly women with hip fractures plasma cortisol is persistently higher than in healthy elderly women, possibly causing undesirable catabolic effects. A lack of corresponding changes in plasma ACTH or in the cortisol response to exogenous ACTH has prompted us to study cortisol-ACTH relationships after giving corticotrophin-releasing hormone (CRH) to such subjects. SUBJECTS: Seventeen women aged 70-90 years who had sustained a hip fracture about two weeks previously were compared with 19 healthy women aged 68-85 years. MEASUREMENTS: 100 microg CRH was injected into each subject and ACTH and cortisol concentrations were measured at intervals for 90 minutes beforehand and 180 minutes afterwards. The concentrations of vasopressin and various cytokines and related peptides were also measured during the baseline period. RESULTS: Under baseline conditions plasma cortisol was higher and plasma ACTH lower in the injured patients than in the healthy subjects. The patients showed smaller incremental ACTH and cortisol responses to CRF but because of the higher baseline value the peak cortisol concentration was enhanced. A strong correlation between the cortisol and ACTH responses in the healthy subjects was completely lost in the patients and the slope of the ACTH-cortisol dose-response relationship varied greatly between individuals, with no overall increase. The concentrations of vasopressin, interleukin-1 receptor antagonist and soluble tumour necrosis factor receptors were higher in the patients but did not correlate with the responses to CRH. CONCLUSIONS: The results are not consistent with increased sensitivity to ACTH and suggest an independent stimulus to the adrenals of hip-fracture patients. Its identity is unknown as the non-ACTH stimuli proposed hitherto are reported to enhance sensitivity to ACTH.

Adrenocorticotropic Hormone↗
PubMed2000

Hypocapnia and its relation to fear of falling.

OBJECTIVE: To determine if hypocapnia occurs in patients with fear of falling and to explore potential causes of hypocapnia. DESIGN: Observational study in patients who fall with and without fear of falling. SETTING: Rehabilitation wards of an elderly care unit. PATIENTS: Consecutive fallers with (n = 20) and without (n = 10) fear of falling. MAIN OUTCOME MEASURES: End-tidal CO2 (PETCO2) and respiratory rate (RR) responses were measured during sustained isometric muscle contraction (SIMC) (40% of maximum voluntary contraction of quadriceps for 2 min) and during a 5-meter walk. Falls efficacy scale (FES) and Hospital anxiety and depression scale (HAD). RESULTS: Patients with fear of falling had significantly higher FES and HAD scores (p < .01). During SIMC, baseline and nadir PETCO2 levels were significantly lower in patients with a fear of falling (p < .01). During the 5-meter walk, PETCO2 was lower at baseline, at nadir, and at the end of the walk in the fear of falling group than in controls (p < .01). RR was higher at nadir and end of the walk in the fear of falling group than in controls (p < .02). CONCLUSIONS: Hypocapnia may occur in patients with a fear of falling during SIMC and walking. Anxiety seems to be the main cause, but muscle weakness may contribute. Breathing or relaxation techniques and reconditioning may have a role in treating fear of falling in the rehabilitation setting.

Accidental Falls↗
PubMed2000

New approach to risk determination: development of risk profile for new falls among community-dwelling older people by use of a Genetic Algorithm Neural Network (GANN).

BACKGROUND: Falls risk in older people is multifactorial and complex. There is uncertainty about the importance of specific risk factors. Genetic algorithm neural networks (GANNs) can examine all available data and select the best nonlinear combination of variables for predicting falls. The aim of this work was to develop a risk profile for operationally defined new falls in a random sample of older people by use of a GANN approach. METHODS: A random sample of 1042 community-dwelling people aged 65 and older, living in Nottingham, England, were interviewed at baseline (1985) and survivors reinterviewed at a 4-year follow-up (n = 690). The at-risk group (n = 435) was defined as those survivors who had not fallen in the year before the baseline interview. A GANN was used to examine all available attributes and, from these, to select the best nonlinear combination of variables that predicted those people who fell 4 years later. RESULTS: The GANN selected a combination of 16 from a potential 253 variables and correctly predicted 35/114 new fallers (sensitivity = 31%; positive predictive value = 57%) and 295/321 nonfallers (specificity = 92%; negative predictive value = 79%); total correct = 76%. The variables selected by the GANN related to personal health, opportunity, and personal circumstances. CONCLUSIONS: This study demonstrates the capacity of GANNs to examine all available data and then to identify the best 16 variables for predicting falls. The risk profile complements risk factors in the current literature identified by use of standard and conventional statistical methods. Additional data about environmental factors might enhance the sensitivity of the GANN approach and help identify those older people who are at risk of falling.

Accidental Falls↗
PubMed1999

Topical estrogen accelerates cutaneous wound healing in aged humans associated with an altered inflammatory response.

The effects of intrinsic aging on the cutaneous wound healing process are profound, and the resulting acute and chronic wound morbidity imposes a substantial burden on health services. We have investigated the effects of topical estrogen on cutaneous wound healing in healthy elderly men and women, and related these effects to the inflammatory response and local elastase levels, an enzyme known to be up-regulated in impaired wound healing states. Eighteen health status-defined females (mean age, 74.4 years) and eighteen males (mean age, 70.7 years) were randomized in a double-blind study to either active estrogen patch or identical placebo patch attached for 24 hours to the upper inner arm, through which two 4-mm punch biopsies were made. The wounds were excised at either day 7 or day 80 post-wounding. Compared to placebo, estrogen treatment increased the extent of wound healing in both males and females with a decrease in wound size at day 7, increased collagen levels at both days 7 and 80, and increased day 7 fibronectin levels. In addition, estrogen enhanced the strength of day 80 wounds. Estrogen treatment was associated with a decrease in wound elastase levels secondary to reduced neutrophil numbers, and decreased fibronectin degradation. In vitro studies using isolated human neutrophils indicate that one mechanism underlying the altered inflammatory response involves both a direct inhibition of neutrophil chemotaxis by estrogen and an altered expression of neutrophil adhesion molecules. These data demonstrate that delays in wound healing in the elderly can be significantly diminished by topical estrogen in both male and female subjects.

Aged↗
PubMed1999

Difficulties in measuring the effect of testosterone replacement therapy on muscle function in older men.

Muscle wasting in older men may be related to androgen deficiency. We have assessed the effect of testosterone replacement therapy on muscle function in the upper and lower limbs of older (age > 60 years) men with blood testosterone levels < 14 nmol/L. Subjects (n = 7 per group) received testosterone enanthate 200 mg i.m. or placebo every 2 weeks in a double blind study over a 12-week period and underwent muscle testing every 4 weeks. A significant increase in blood levels of testosterone and a reduction in levels of sex hormone binding globulin occurred in the treatment group. Total body mass, haemoglobin and packed cell volume also increased significantly (p < 0.05). No improvements in handgrip strength, isometric strength of knee flexors and extensors or leg extensor power were seen in either group. Wide variability in all measures of muscle function were observed in these elderly men suggesting that very large study groups would be required to determine potential treatment benefits on muscle function.

Aged↗
PubMed1999

A study of infection in elderly nursing/residential home and community-based residents.

It is commonly believed that patients admitted to hospital from nursing homes/residential homes (NHRH) with infections are less likely to respond to treatment and have a higher fatality rate than counterparts admitted from their own homes ('the Community'). It is also believed that NHRH's harbour a reservoir of unusual and resistant organisms. These preconceptions may influence how these patients are managed. A database of 10593 sequential admissions to a Geriatric Medical unit over a three-year period was used to identify NHRH and community populations with a principal diagnosis of infection. They were investigated using the Department of Microbiology's database. The admission rate in the NHRH group was twice that of the community group. There were no significant differences in length of stay (LOS) [16 +/- 2 vs 17 +/- 2 days (s.e.m.)], or mean survival time (ST)(61 days (37-84) vs 48 days (25-72): 95% confidence intervals) between the two groups. Subgroups of the NHRH group did have significantly different survival times. Fatality rate was not significantly different between the NHRH (40%) or Community (35%) groups. Both the NHRH and community group underwent very similar levels of investigation (189 vs 200 investigations performed). The types and frequencies of pathogen seen in the two groups were very similar.

Aged↗
PubMed1999

The effect of aging on skeletal muscle capillarization in a murine model.

Capillarization of skeletal muscle has been reported to be both maintained and reduced with advancing age. This conflict may represent methodological differences between biopsy studies. We have examined capillarization throughout two muscles, soleus and extensor digitorum longus (EDL), from a well-established colony of aging mice, and related this to fiber number (C/F ratio) and type. Labeling of muscle capillaries was performed with the biotinylated Griffonia (Bandeiraea) simplicifolia lectin (GSL 1) using immunochemistry. The results showed a significant increase in the C/F ratio in the aged mice when compared with the younger (6-month mice soleus = 1.296, 95% CI 1.226-1.366 vs 28-month mice soleus = 1.530, 95% CI 1.488-1.572, p <.001; 6-month mice EDL = 0.881, 95% CI 0.751-1.011 vs 28-month mice EDL = 1.124, 95% CI 1.028-1.220, p = .017). These differences could not be accounted for by changes in fiber type but may reflect loss of fibers. Alternatively, there may be increased angiogenic drive or a failure of downregulation of angiogenesis.

Aging↗
PubMed1999

Serum transferrin receptor assay in iron deficiency anaemia and anaemia of chronic disease in the elderly.

The most common cause of anaemia in the elderly is anaemia of chronic disease (ACD). However, iron deficiency anaemia (IDA) may coexist, and can be difficult to diagnose. The serum transferrin receptor (sTfR) blood test may be a better indicator of iron status as it is not affected by inflammation nor by advancing age. We evaluated it in four groups (10 males, 10 females each): 'young' controls, 'elderly' controls, IDA and ACD. All patients in the IDA group had elevated sTfR levels (mean +/- SD 65.2 +/- 17.7 nmol/l). All 'young' controls had normal sTfR (22.3 +/- 7.3 nmol/l) and ferritin levels (92.7 +/- 61.1 micrograms/l). Although all subjects in the 'elderly' controls and ACD group had normal, and raised or normal serum ferritin, respectively (88 +/- 62.3 micrograms/l; 631.2 +/- 509.5 micrograms/l), three (15%) 'elderly' controls and four (20%) ACD patients had raised sTfR levels, suggesting depleted iron stores. Bone-marrow aspirates were available in 3/4 ACD patients with raised sTfR. Haemosiderin was absent in two. The sTfR blood test is comparable to serum ferritin in diagnosing IDA in the elderly but also seems capable of differentiating ACD from IDA. Its potential as a non-invasive test of iron status, especially in elderly anaemic patients, deserves further evaluation.

Adult↗
PubMed1999

Injury in the aging: recovery and rehabilitation.

Interest in how victims of traumatic injuries recover is increasing and a number of observational studies have now been done. There are very few intervention studies aimed at enhancing recovery, but there will be more as our knowledge base grows. Older recipients of traumatic injuries differ from the young in the types of injuries they sustain, in the way they respond to their injuries and in the consequences of even relatively minor injuries on their future independence. In this paper, we summarise our understanding of recovery after injury and consider this in more depth for older people with specific injuries.

Accidental Falls↗
PubMed1998

Use of stroke distance in the early detection of simulated blood loss.

OBJECTIVES: To compare the effects of simulated and mild actual hemorrhage on parameters used traditionally to assess hemorrhaging patients: heart rate (HR), blood pressure (BP), and Shock Index (SI = HR/systolic BP), with stroke distance (SD) measured ultrasonically as an index of cardiac stroke volume. MATERIALS AND METHODS: Hemorrhage was simulated in 19 healthy volunteers by the application of graded lower-body negative pressure (LBNP) (0, -20, -40, and -60 mm Hg) to pool blood in the lower body and reduce venous return. Measurements were also made before and after a standard blood donation (450 mL) in nine healthy volunteers. MEASUREMENTS AND MAIN RESULTS: SD decreased significantly and progressively from the baseline level of 23.8+/-5.7 cm (mean+/-SD) at each level of LBNP: by 3.4+/-1.9, 7.4+/-2.5, and 11.8+/-3.2 cm at LBNP of -20, -40, and -60 mm Hg, respectively. Neither HR nor SI changed significantly at the lowest level of LBNP (-20 mm Hg), but they showed progressive, significant increases thereafter. Mean BP did not change significantly at any level of LBNP. Similarly, after a controlled hemorrhage of 450 mL, SD decreased significantly by 3.3+/-1.6 cm from 22.2+/-2.8 cm, whereas HR and SI remained unchanged and mean BP increased slightly. CONCLUSION: Changes in SD may provide an earlier indication of progressive blood loss than either HR or BP alone or in combination.

Adult↗
PubMed1998

Prediction of hemorrhagic blood loss with a genetic algorithm neural network.

There is no established method for accurately predicting how much blood loss has occurred during hemorrhage. In the present study, we examine whether a genetic algorithm neural network (GANN) can predict volume of hemorrhage in an experimental model in rats and we compare its accuracy to stepwise linear regression (SLR). Serial measurements of heart period; diastolic, systolic, and mean blood pressures; hemoglobin; pH; arterial PO2; arterial PCO2; bicarbonate; base deficit; and blood loss as percent of total estimated blood volume were made in 33 male Wistar rats during a stepwise hemorrhage. The GANN and SLR used a randomly assigned training set to predict actual volume of hemorrhage in a test set. Diastolic blood pressure, arterial PO2, and base deficit were selected by the GANN as the optimal predictors set. Root mean square error in prediction of estimated blood volume by GANN was significantly lower than by SLR (2.63%, SD 1.44, and 4.22%, SD 3.48, respectively; P < 0.001). A GANN can predict highly accurately and significantly better than SLR volume of hemorrhage without knowledge of prehemorrhage status, rate of blood loss, or trend in physiological variables.

Algorithms↗
PubMed1998

Sensitivity of mononuclear leucocytes to glucocorticoids in elderly hip-fracture patients resistant to suppression of plasma cortisol by dexamethasone.

OBJECTIVE: Elderly women with proximal femur fracture show a prolonged increase in plasma cortisol, which could have undesirable catabolic effects. Suppression of cortisol by dexamethasone is impaired, suggesting resistance to glucocorticoid effects at feedback inhibitory sites. We therefore wished to find out whether peripheral glucocorticoid sensitivity is normal. DESIGN: Peripheral blood mononuclear leucocytes were used as a model tissue. Blood samples were taken from elderly women about 2 weeks after hip fracture and from elderly control women. Each patient was then given 1 mg dexamethasone at 2300 h followed by further sampling at 0800 and 1600 h the next day. METHODS: Glucocorticoid-receptor binding parameters were measured by incubating whole cells with [3H]dexamethasone for 2 h at 37 degrees C. Inhibition of cell proliferation by dexamethasone was assessed by addition of [3H]thymidine to cells cultured for 65 h with concanavalin A. Cortisol and dexamethasone concentrations were measured in the dexamethasone suppression test. RESULTS: As expected, the hip-fracture patients had raised morning cortisol concentrations and impaired suppression by dexamethasone. The cells of the patients had similar numbers of glucocorticoid receptors to those of the control subjects but higher values for Kd (i.e. a lower binding affinity). The cells of the patients incorporated less [3H]thymidine than the control cells in the absence of dexamethasone. The percentage inhibition by a saturating concentration of dexamethasone was unchanged but the concentration giving half-maximal inhibition was decreased (sensitivity was increased) at the higher of the two concanavalin A concentrations used. CONCLUSIONS: These experiments in mononuclear leucocytes give no evidence of peripheral resistance to glucocorticoids in hip-fracture patients with impaired suppression of cortisol by dexamethasone.

Aged↗
PubMed1998

Aging alters the inflammatory and endothelial cell adhesion molecule profiles during human cutaneous wound healing.

Age-related changes in the human inflammatory response in vivo have been largely ignored, resulting in a lack of understanding of the patho-physiologic processes involving inflammation that become increasingly important with age, of which wound repair is an important example. We have tested the hypothesis that the delay in wound healing resulting from old age is associated with an altered inflammatory response and endothelial cell adhesion molecule (CAM) profile, because CAMs influence the temporal and lineage profiles of extravasated leukocytes within a wound. Cutaneous punch biopsies were taken from 138 healthy subjects, aged 19 to 96 years; the wounds were rebiopsied at fixed time-points from Day 1 up to 3 months postwounding. Quantitative image analysis showed that there was a marked early increase in the neutrophil response in the aged with a less pronounced peak in the wounds of young subjects. Monocyte/macrophage and lymphocyte appearance was delayed in the aged with cell numbers peaking at Day 84, compared to Day 7 for monocytes and Day 21 for lymphocytes in the young, but with increased numbers of mature macrophages in the aged. E-selectin was strongly expressed in a perivascular distribution in the early wounds of the aged; however, only faint staining was seen from Day 3 to 7 in the wounds of the young. Intracellular CAM-1 and vascular CAM-1 expression exhibited an age-related delay in appearance and a reduction in staining intensity. This altered CAM profile may affect the early inflammatory wound healing response in aged humans and suggests a target for future therapeutic manipulations.

Adult↗
PubMed1998

Evolution of artificial neural network architecture: prediction of depression after mania.

Artificial neural networks (ANNs) are compared to standard statistical methods for outcome prediction in biomedical problems. A general method for using genetic algorithms to "evolve" ANN architecture (EANN) is presented. Accuracy of logistic regression, a fully interconnected ANN, and an EANN for predicting depression after mania are examined. All methods showed very good agreement (training set accuracy, chi-square all p < 0.01). However, significant differences were found for stability (test set accuracy); logistic regression being the most unstable and EANN being significantly more stable than a fully interconnected ANN (McNemar p < 0.01). We conclude that the EANN method enhances ANN stability. This approach may have particular relevance for biomedical prediction problems, such as predicting depression after mania.

Algorithms↗