Multimorbidity and functional impairment–bidirectional interplay,synergistic effects and common pathways

This review discusses the interplay between multimorbidity (i.e. co‐occurrence of more than one chronic health condition in an individual) and functional impairment (i.e. limitations in mobility, strength or cognition that may eventually hamper a person's ability to perform everyday tasks). On the one hand, diseases belonging to common patterns of multimorbidity may interact, curtailing compensatory mechanisms and resulting in physical and cognitive decline. On the other hand, physical and cognitive impairment impact the severity and burden of multimorbidity, contributing to the establishment of a vicious circle. The circle may be further exacerbated by people's reduced ability to cope with treatment and care burden and physicians’ fragmented view of health problems, which cause suboptimal use of health services and reduced quality of life and survival. Thus, the synergistic effects of medical diagnoses and functional status in adults, particularly older adults, emerge as central to assessing their health and care needs. Furthermore, common pathways seem to underlie multimorbidity, functional impairment and their interplay. For example, older age, obesity, involuntary weight loss and sedentarism can accelerate damage accumulation in organs and physiological systems by fostering inflammatory status. Inappropriate use or overuse of specific medications and drug–drug and drug–disease interactions also contribute to the bidirectional association between multimorbidity and functional impairment. Additionally, psychosocial factors such as low socioeconomic status and the direct or indirect effects of negative life events, weak social networks and an external locus of control may underlie the complex interactions between multimorbidity, functional decline and negative outcomes. Identifying modifiable risk factors and pathways common to multimorbidity and functional impairment could aid in the design of interventions to delay, prevent or alleviate age‐related health deterioration; this review provides an overview of knowledge gaps and future directions.     

Free insulin-like growth factor-I and cognitive function in older persons living in community.

CONTEXT: Increasing evidences from experimental and human studies suggest that the activity of the growth hormone (GH/insulin-like growth factor-I) axis may contribute to the age-related cognitive decline and poor cognition in late life. OBJECTIVE: The aim of the present study was to evaluate the relationship of total serum free IGF-I and its binding protein-3 with cognitive performance in older persons aged 80 years or older. DESIGN: Data are from baseline evaluation of the ilSIRENTE study (n=353). Cognitive performance was evaluated using five items enclosed in the Minimum Data Set for Home Care assessment form: short-term memory, procedural memory, cognitive skills in daily decision making, verbal expression, comprehension. Free insulin-like growth factor-I (free IGF-I) and IGF-binding protein-3 (IGFBP-3) in blood were measured. Analysis of covariance (ANCOVA) was used to examine the relationship between cognitive impairment and the serum free IGF-I and IGFBP-3 concentrations, after adjustment for potential confounding variables. RESULTS: After adjustment for potential confounders, which included age, gender, education, cerebrovascular disease, ischemic heart disease, congestive heart failure, hypertension, diabetes, depression, Parkinson diseases, thyroid diseases, smoking status, alcohol abuse, body mass index, and number of medications, individuals with verbal expression problems (n=20) and individuals with comprehension problems (n=24) had a significantly lower serum levels of readily dissociable IGF-I than participants without cognitive impairments. The serum IGFBP-3 presented the same behavior of free IGF-I. CONCLUSION: The present study suggests that among old-old subjects living in the community lower levels of total serum free IGF-I and IGFBP-3 are associated with impairment of cognitive performance. This finding suggests that the GH/IGF-I axis may play an important role in the age-related decline of cognitive performance.     

Analysis of epidermal growth factor receptor and activated epidermal growth factor receptor expression in pituitary adenomas and carcinomas.

Epidermal growth factor receptor plays an important role in the pathogenesis of many malignancies. Various growth factors, including epidermal growth factor receptor, have been shown to influence pituitary tumor growth and differentiation. To analyze the role of epidermal growth factor receptor in pituitary tumor development, we examined normal pituitaries (n=8), pituitary adenomas (n=158), and pituitary carcinomas (n=7) for expression of epidermal growth factor receptor protein and messenger RNA using tissue microarrays and RT-PCR. We also examined (a) the expression of phospho-epidermal growth factor receptor, the activated form of epidermal growth factor receptor, in pituitary tumors and normal pituitaries by immunohistochemistry and (b) the effects on epidermal growth factor receptor expression of treating pituitary cells (HP75 cell line) with epidermal growth factor. Epidermal growth factor receptor and the phosphorylated variant expression were present in normal pituitary cells. Epidermal growth factor receptor messenger RNA was also detected in normal pituitaries, pituitary adenomas, and carcinomas by in situ hybridization and RT-PCR. Most pituitary adenomas showed expression of epidermal growth factor receptor and the phosphorylated variant. Nonfunctional adenomas showed higher levels of expression of epidermal growth factor receptor (76 vs 34%) and of phospho-epidermal growth factor receptor (26 vs 8%) as compared to functional adenomas. Five of seven pituitary carcinomas showed strong expression of both epidermal growth factor receptor and phospho-epidermal growth factor receptor. When a human pituitary cell line (HP75) was cultured in the presence of epidermal growth factor receptor, there was an increase in the levels of both epidermal growth factor receptor and phospho-epidermal growth factor receptor after 5 h of treatment, thus confirming that epidermal growth factor receptor signaling was active in pituitary tumors. These results indicate that activated epidermal growth factor receptor is expressed in pituitary adenomas and carcinomas. Higher levels in pituitary carcinomas suggest a role in pituitary tumor progression.     

Effect of haemodynamic variables on surgically created arteriovenous fistula flow

Background: The immediate success and flow rate of a newly constructed arteriovenous fistula is dependent on several haemodynamic factors affecting te inflow and outflow of the fistula. Method: In this study we evaluated the effect of preoperative arterial blood pressure, arterial inflow, subclavian venous flow, and operative venous outflow resistance on the immediate success, with special reference to the quantity of the fistula flow in 32 patients undergoing internal arteriovenous fistula operation. Flow measurements were done by utilizing colour flow duplex imaging and measurement of venous resistance of the fistula vein was accomplished indirectly by a newly developed simple system. Results: A preoperative subclavian venous flow rate of less than 400 ml/min was associated with higher rate of immediate failures (P<0.05) with a negative predictive value of 100% with 100% sensitivity. Regarding immediate failures, no other haemodynamic measurement was found to affect the success of a newly constructed fistula significantly. A linear correlation between the measured haemodynamic values and the quantity of postoperative fistula flow was not found. However, an arterial inflow value of ⩾40 ml/min was associated with higher fistula flow rates (P<0.05) Conclusion: The immedate success and flow of a newly constructed arteriovenous fistula is mainly dependent on arterial inflow and subclavian venous flow. An arterial inflow rate of 40 ml/min or more and subclavian venous flow rate of 400 ml/min or more measured by colour flow duplex imaging prior to the operation will be associated with better outcomes, and therefore the use of colour flow duplex imaging is warranted during the evaluation of patients who are candidates for an arteriovenous fistula operation.     

Functional decline in frail community-dwelling stroke patients

Patients who suffer a stroke event are at high risk of functional decline after the post-acute rehabilitation period. The aim of the present study was the evaluation of factors associated with functional decline in a large sample of older patients with stroke living in the community. The study population consisted of all patients admitted to home care programs after a post-acute rehabilitation program--with at least 1 year of follow-up--in twenty-two Italian Home Health Agencies from 2000 to 2002 (n=1338). For the present study we selected 355 (26%) patients with diagnosis of stroke. After 1 year of in-home care program, 149 out of 355 stroke survivors (42%) had presented a worsening in the activities of daily living (ADL) scale score. In the final adjusted model, patients with cognitive impairment (OR 2.59, 95% CI, 1.45-4.64), pressure ulcer (OR 2.74, 95% CI, 1.45-5.18), urinary incontinence (OR 1.64, 95% CI, 1.01-3.29), or hearing impairment (OR 1.83, 95% CI, 1.02-3.29) were more likely to significantly decline in physical functioning after a period of 1 year in-home care program. Our study documents that functional decline of stroke patients was largely dependent on specific subjects' clinical characteristics. Three of four concomitant disabling conditions associated in our sample with functional decline--pressure ulcer, urinary incontinence, hearing--can be prevented and eventually treated or modified. Appropriate post-acute rehabilitation programs and adequate home care interventions focused on the prevention and treatment of these conditions might be correlated to better outcomes in older post-stroke patients.     

Bilateral adrenal hemorrhage associated with bilateral renal vein and vena cava thrombosis

Idiopathic bilateral adrenal hemorrhage with thrombosis of both renal veins and inferior vena cava are presented using US and CT in a newborn. To our knowledge such bilateral involvement of the adrenal glands and the renal veins have not been reported previously.     

Effects of gamma-hydroxybutyrate on cerebrospinal fluid lactate and glucose levels after spinal cord trauma.

This study aims to evaluate the effects of gamma-hydroxybutyrate (GHB) after spinal cord trauma (SCT). Twenty rabbits were divided equally into four groups: group I was the sham-operated group, group II suffered from SCT but received no treatment, group III was given a dose of 400 mg/kg of GHB intravenously before SCT and group IV received the same dose after SCT. Cerebrospinal fluid (CSF) samples were obtained 30 min before SCT (T(0)), at 60 (T(1)) and 120 min (T(2)) after SCT. There was a threefold increase in lactate levels from baseline value at T(2) in group II, while statistically significant elevation of the lactate levels were not observed in groups III and IV. Glucose levels at T(1) and T(2) were significantly lower in groups III and IV compared with the control group. The findings of this study demonstrate that GHB can control the increase of CSF lactate and glucose levels following SCT and that this metabolic effect may be associated with neuroprotective physiological changes.     

Is there any relationship between human leucocyte antigen class II and chronic urticaria? (chronic urticaria and HLA class II)

The Human Leukocyte Antigen (HLA) typing of large groups of patients with various autoimmune diseases has demonstrated that some HLA alleles occur at higher frequencies in specific diseases than in the general population. Chronic urticaria has been shown to have an autoimmune basis by a previous study which found an association between chronic urticaria and specific HLA groups. We investigated the HLA subtypes of Turkish chronic urticaria patients. For this purpose 42 Turkish patients with chronic urticaria and 115 healthy controls were typed for HLA-DR and DQ by PCR-SSP (Polymerase Chain Reaction Sequence Specific Primers) low resolution DNA technique. We found an increased frequency of DR4 (42.9%, p=0.01) in chronic urticaria patients in comparison with that in healthy controls. This study supports the hypothesis that HLA alleles may be involved in the pathogenesis of chronic urticaria and that they appear to be directly involved in the initiation of the immune response.     

Sensitization to common allergens, especially pollens, among children with respiratory allergy in the Trakya region of Turkey

Asthma and allergic rhinitis are common problems in children and the causative pollen allergens vary according to the geographical area. The aim of this study was to investigate patterns of sensitization to common inhalant allergens, especially pollens, in Turkish children living in the Trakya region and to determine differences between rural and urban areas. Allergen skin testing was prospectively performed on 539 children aged between 4 and 17 years with respiratory allergy. The reaction was considered to be positive if the mean wheal diameter was at least 3 mm greater than that of the negative controls. We detected positive skin reactions in 420 (77.9%) children. Two hundred and eighty-one (52.1%) mite, 277 (51.4%) pollen, 174 (32.3%) mold, 65 (12.1%) animal dander, 12 (2.2%) cockroach and 6 (1.1%) latex skin sensitivities were detected. Among the pollen allergies 173 were cereal pollen (32.1%), 170 grass pollen (31.5%) and 144 tree pollen allergies (26.7%). The most common positive skin test among the pollens was to cultivated wheat (Titicum vulgare) (n = 116, 21,5%), followed by rye grass (Lolium perenne) and orchard grass (Dactylis glomerata). Positive skin reactions to Alternaria, to Candida albicans, and to all pollens except Ulmus competris, Pinus sylvetris, Platanus vulgaris and Tilia platyphyllos, were higher in children with allergic rhinitis than in those with asthma. In children from rural areas, allergic skin reactivity was found to be more common against Candida albicans, sheep dander and all pollens except Corylus avellana, Fraxinus excelsior, Populus alba, Pinus sylvetris, Platanus vulgaris and Chenopodium album, than in urban children. Although Trakya is close to Greece and other Mediterranean countries, this study suggests that the pollens, which sensitize children, are not similar.     

Neuronal nuclear antigen (NeuN): a new tool in the diagnosis of central neurocytoma

The use of neuronal nuclear antigen (NeuN) as a reliable neuronal marker in the differential diagnosis of clear cell neoplasms of the central nervous system was determined in a biopsy series of 23 cases. Immunohistochemical analyses were carried out by antisera against neuronal nuclear antigen, synaptophysin, neuron-specific enolase, microtubule-associated protein 2, and glial fibrillary acidic protein. All eight central neurocytomas were characteristically immunolabeled by NeuN. NeuN immunoreactivity was uniformly strong and basically located in the nuclei of neurocytes. Despite this uniform staining pattern of central neurocytomas, 12 cases of oligodendrogliomas and three cases of ependymoma were negative for NeuN. As the diagnostic criteria for central neurocytoma include immunohistochemical and/or ultrastructural evidence for neuronal differentiation, NeuN as a sensitive and specific neuronal marker in formalin-fixed, paraffin-embedded tissues may greatly facilitate the differential diagnosis of central neurocytomas.