Dario Maggio

Manometric investigation of anorectal function in early and late stage Parkinson's disease

Abnormal gastrointestinal function is relatively frequent in Parkinsons disease, and constipation is a disturbing symptom in many patients. However, it remains to be established whether anorectal abnormalities are characteristic of the late stages of the disease. Clinical and anorectal manometric function were investigated in groups of early and late stage parkinsonian patients. Thirty one patients (19 men, 12 women, age range 22 to 89 years) entered the study. The disease severity was assessed by Hoehn and Yahr staging: there were four (12.9%) stage I, seven (22.6%) stage II, 10 (32.2%) stage III, and 10 (32.2%) stage IV patients. Anorectal variables were measured by standard manometric equipment and techniques. Values obtained in early stage patients (Hoehn and Yahr stage I and II) were compared with those obtained in late stage patients (Hoehn and Yahr stage III and IV). Overall, more than 70% of patients complained of chronic constipation, with chronic laxative use reported in more than 30%. Late stage patients were slightly older than their early stage counterparts. Pelvic floor dyssynergia was documented in more than 60% of patients. Manometric variables were not different in the two groups. In conclusion, defecatory dysfunction is frequent in Parkinsons disease, it is not confined to late stage patients, and it is found early in the course of the disease. This has potential implications for a targeted therapeutic approach.

Age related cortical bone loss at the metacarpal

In order to evaluate in vivo the entity of endosteal and periosteal changes with age in the two sexes, and their relative contribution to age-related cortical bone loss, we undertook a cross-sectional study on a population of normal Caucasian subjects. The group included 189 women and 107 men who were studied by photodensitometry and radiogrammetry of the second metacarpal bone, derived from the same standard hand X-ray. Of the subjects, 134 were 65 years of age or older (75 women and 59 men). Metacarpal bone mineral density (BMD) correlated with age in both sexes, with an annual bone loss rate of 0.5% in women and 0.15% in men. In the over 65 group, correlation was significant only in women, who underwent an acceleration in the rate of bone loss (1 % per year). Marrow cavity width (M), cortical index at the second metacarpal shaft (MI) and external width (W) all correlated with age in both sexes, although generally better in the female than in the male sex. M almost doubled from the fourth to the ninth decade in women and increased 50% in men. In the same age interval, MI showed an annual decrease of 0.49% in females and 0.33% in males. In the over 65 group, cortical thinning rate was significant in women (0.39% per annum) but not in men (0.14% per annum), whereas correlation of W was not significant in either sex. Finally, MI correlated with BMD in the whole study population and in the over 65, with a female prevalence in correlation strength maintained throughout life. The following conclusions can be derived for metacarpal aging: (1) an acceleration in cortical bone loss occurs in females after age 65; (2) age-related growth in periosteal diameter, although significant in the whole population, is negligible in the elderly of both sexes; (3) age-related cortical bone loss is generally more dependent on cortical thinning in women than in men.

Cathepsin B activity in normal human osteoblast-like cells and human osteoblastic osteosarcoma cells (MG-63) : regulation by interleukin-1 β and parathyroid hormone

Cathepsin B activity and its regulation by interleukin 1 beta (IL-1 beta) and parathyroid hormone (PTH) was investigated in normal human osteoblast-like cells (hOB) and in the human osteoblastic osteosarcoma cell line MG-63. Cathepsin B activity was measured using a fluorescent synthetic substrate, 7-N-benzyloxycarbonyl-L-arginyl-L-arginylamide-4-methylcoumarin, and its specificity was checked with E-64, a specific inhibitor of cysteine proteinases and CA074, a specific inhibitor of the enzyme. Cathepsin B activity was detected in crude extracts of cell monolayers and in conditioned media. In both cell types, basal activity was detected essentially in cell extracts, since in media only approximately 1.2% (hOB) and approximately 6% (MG-63) of the total activity was released. IL-1 beta (1-100 U/ml) and PTH (10(-9) M-10(-6) M) significantly stimulated cathepsin B activity in cell extracts and in conditioned media. In both cell types, the increase in proteolytic activity appeared to require RNA and protein synthesis after adding IL-1 beta or PTH. Using the above substrate, we also evaluated some biochemical properties of the enzyme, and its pH-stability and pH-optimum. In both cell types, intracellular cathepsin B activity was not resistant to neutral or slightly alkaline pH, whereas extracellular cathepsin B activity was stable. This study provides evidence that osteoblast-like cells produce and secrete active cathepsin B. The production and secretion was stimulated by IL-1 beta and PTH. The physiological role of cathepsin B produced by osteoblasts and stimulated by the bone resorbing agents remains to be elucidated. Since extracellular activity is stable under relatively physiological conditions, it is possible that the extracellular as well as intracellular form of the enzyme may play a role in matrix turnover.

Botulinum toxin treatment of oesophageal achalasia in the old old and oldest old: a 1-year follow-up study.

BackgroundIntrasphincteric injection of botulinum toxin (BTX) has become one of the most frequent therapeutic approaches for the treatment of oesophageal achalasia. This treatment seems particularly effective in elderly patients who are not candidates for more invasive procedures.AimsThere are few or no data on BTX treatment of achalasia in the old old and oldest old. Therefore, we evaluated BTX treatment in a group of patients with achalasia in the extreme age range who were too ill or frail to undergo surgery or pneumatic dilatation.Patients and MethodsTwelve elderly achalasic patients (age range 81–94 years, average age 86 years) with American Society of Anesthesiologists (ASA) class III–IV status were recruited for the study. After baseline clinical and instrumental evaluations, BTX 100U was injected at time 0 and 1 month later. Clinical follow-up was carried out after 3, 6 and 12 months.ResultsA significant improvement in symptom score was documented at each follow-up step. On the basis of improvements in scores, approximately 70% of patients were considered responders at the end of follow-up.ConclusionsBTX treatment is an effective treatment in a substantial proportion of achalasic patients >80 years of age, in whom benefits are still detectable after 12 months. BTX is a therapeutic option in patients unsuitable for surgery or pneumatic dilatation.

Cathepsin B in osteoblasts

Active cathepsin B has been found in cell extract and medium of human osteoblast-like cells and MG-63 cells. The released form is stable at neutral and alkaline pH and, in both cell types, intracellular and extracellular cathepsin B activities are increased by interleukin-1 beta (IL-1beta) and parathyroid hormone (PTH). To evaluate the physiological role of cathepsin B in osteoblasts, we investigated the production and secretion of this enzyme in normal human synovial fibroblasts and modulation by IL-1beta and PTH. Lactate secretion concurrent with release of cathepsin B and comparable responses in osteoblasts were also examined. Our data show that synovial fibroblasts respond differently to treatment with the two agents, suggesting a cell-specific regulation of cathepsin B and possible involvement in osteoblast physiology. Cathepsin B involvement was then evaluated in the activation of plasminogen activator (PA) in MG-63 cells using two specific inhibitors of cathepsin B, CA074 and CA074-Me, in constitutive conditions and after treatment with IL-1beta. As results of PA activity obtained in the presence of IL-beta were in contrast with previous reports, we examined the activities of PA, pro-PA activated with trypsin, and plasmin in cell extract and media of MG-63 cells after 24-h treatment with IL-1beta. Results show that in normal conditions and in the presence of IL-1beta, cathepsin B is involved in the activation of PA. Moreover, IL-1beta stimulates PA, pro-PA activated by trypsin, and plasmin activity in medium, whereas in cell extract it stimulates pro-PA activated by trypsin and plasmin activity. IL-1beta has no effect on cell extract-associated PA.

Short-term Reproducibility of Proximal Femur Bone Mineral Density in the Elderly

Abstract. Densitometric measurements are prone to imprecision in elderly subjects and the present study was primarily designed to dissect out the effects of age and bone mineral density on proximal femur dual energy x-ray absorptiometry (DXA) reproducibility. The study comprised 17 elderly women (mean age 74.6 years, range 65–84 years), 13 early postmenopausal women with osteopenia (mean age 56.2 years, range 50-63 years), and 17 elderly men (mean age 73.8 years, range 65-86 years). Each subject was given triplicate proximal femur scans by a QDR 2000 Densitometer (Hologic Inc., Waltham, MA) with repositioning between scans. Because of subject selection in the early postmenopausal women there were no significant differences in bone mineral density (BMD) at any site among the three groups. Despite this, reproducibility errors expressed as either coefficient of variation (CV) % or mean standard deviation (SD) were greater in the elderly subjects, regardless of gender, when compared with the younger female subjects. The variability in measurement errors with age were least marked for the total hip and trochanteric sites. Within the elderly subjects, BMD appeared to exert little influence on measurement errors. We conclude that short-term proximal femur reproducibility is dependent on age-related factors other than BMD. There is no influence of gender on the measurement errors. It is likely that local factors (e.g., hip osteoarthritis) or general frailty may influence repositioning but this needs further exploration. In the meantime, the total hip and trochanteric sites should be used as they provide the most reproducible measurements in the elderly.

Hip fracture in nursing homes: an Italian study on prevalence, latency, risk factors, and impact on mobility.

Hip fracture may cause and/or complicate institutionalization. We undertook this study to define its overall prevalence among the residents of four nursing homes in Central Italy as well as its latency and impact on mobility when it occurred within institutions. We also performed a case control analysis with the aim of identifying potential risk factors for hip fracture in nursing home. Among the 211 residents (160 women, mean age 82.2 +/- 9.29 years, and 51 men, mean age 77.1 +/- 8.9 years), 42 were hip fracture cases, with a prevalence of almost 20%, and a female/male ratio of 6/1.23 fractures preceded institutionalization; of these 19 (17 females and 2 males) occurred within the nursing homes (mean age 83.2 +/- 6.3 years). The average interval between institutionalization and fracture was 74.2 months. The impact of hip fracture on mobility was relevant. The percentage of residents ambulating autonomously fell from 95% to 32% among those who had fractured. Fractured subjects were characterized by worse mobility and function than unfractured subjects, while comorbidity, cognitive functions, and use of psychotropic drugs were similar. Prefracture mobility of fractured subjects was better than that of age-and sex-matched residents who had never fractured their hip. Regarding hip fracture in our nursing home population we can conclude that (1) hip fracture is one of the main causes of institutionalization; (2) in most cases hip fracture occurred late in the course of the nursing home stay; (3) the functional impact of the fracture was relevant when it occurred in institutions. We also suggest that preserved mobility may represent an additional risk factor for hip fracture in nursing homes.

Appendicular cortical bone loss after age 65: sex-dependent event?

Distal radius photodensitometric and second metacarpal radiogrammetric measurements were obtained from computerized analyses of standard hand X-Ray films of 296 Caucasian subjects (189 women and 107 men). This sample included 134 subjects ≥65 years old (75 women and 59 men). Distal radius bone density and metacarpal index showed a significant linear decrease with age in both sexes. Rates of bone loss, calculated from the regression curves, were-0.7% per year in women and-0.5% per year in men by distal radial photodensitometry, and-0.49% per year in women and-0.33% per year in men by metacarpal radiogrammetry. In the elderly subgroup, women ≥65 years of age showed an even faster bone loss, with an annual decrease of-1.4% by distal radial photodensitometry. Conversely, men ≥65 years of age had no significant bone loss, not even by metacarpal radiogrammetry. In conclusion, these data suggest that appendicular cortical bone loss ocurs at a higher rate in elderly females than in the elderly males, both at the distal radial and at the metacarpal site.

Physical activity and cardiovascular health in the elderly

People over the age of 65 constitute a growing proportion of the world population both in western and in developing countries. A unique feature of this group is the high prevalence of cardiovascular diseases, which negatively affect its quality of life as well as its life expectancy. Among the interventions able to reduce the health burden of cardiovascular diseases is physical activity. The benefits of physical activity have been demonstrated both in healthy and chronically ill elderly subjects, while the risks have been found to be modest. Physicians should recommend moderate-intensity physical activity to sedentary older subjects, who are still the majority within the elderly population.

Emotional and psychological distress of persons involved in the care of patients with Alzheimer disease predicts falls and fractures in their care recipients.

Background/Aims: Elderly patients with dementia have a higher risk of falls and fractures as compared to cognitively intact elderly subjects. To investigate whether psychological distress of the caregiver might predispose older persons with Alzheimer disease (AD) to falls and fractures, we performed a prospective cohort study. Methods: A consecutive series of 110 subjects with dementia underwent baseline and follow-up clinical and functional evaluations. The burden of the caregivers was recorded at baseline. Any intervening fall or fracture was ascertained at the 1-year follow-up. Results: The caregiver burden was significantly higher in persons involved in the care of patients with AD who subsequently fell. In a multivariate regression model, the caregiver burden score predicted falls and fractures. Conclusion: Part of the increased risk of falls and fractures in AD might be due to the distress of caregivers, a factor potentially amenable to treatment.