Presence Of Significant Pathology Research Articles

Resistance and Resilience to Alzheimer's Disease.

Dementia is a significant public health crisis; the most common underlying cause of age-related cognitive decline and dementia is Alzheimer's disease neuropathologic change (ADNC). As such, there is an urgent need to identify novel therapeutic targets for the treatment and prevention of the underlying pathologic processes that contribute to the development of AD dementia. Although age is the top risk factor for dementia in general and AD specifically, these are not inevitable consequences of advanced age. Some individuals are able to live to advanced age without accumulating significant pathology (resistance to ADNC), whereas others are able to maintain cognitive function despite the presence of significant pathology (resilience to ADNC). Understanding mechanisms of resistance and resilience will inform therapeutic strategies to promote these processes to prevent or delay AD dementia. This article will highlight what is currently known about resistance and resilience to AD, including our current understanding of possible underlying mechanisms that may lead to candidate preventive and treatment interventions for this devastating neurodegenerative disease.

Should chronic catarrh patients seen in primary care be referred for further investigations?

Chronic catarrh is commonly encountered in primary care, but often presents a quandary to the clinician because the history of postnasal or pharyngeal mucus build-up is frequently at odds with the absence of physical findings. As with certain other medically mysterious syndromes, the value of often costly investigation remains unclear in both the primary and the secondary care settings. Indeed, investigation may reassure the physician more than the patient (1) and could even prove counter-productive through reinforcement of the patient's belief about the presence of significant pathology (2). To establish the benefit of referral of chronic catarrh patients for specialist investigation. A cross-sectional survey. A total of 138 patients referred to secondary care with chronic catarrh, postnasal drip or throat clearing in the north of England. Subjects completed three disease-specific symptom-scoring questionnaires (RSI, SNOT-20 and GETS). Investigations performed were saccharin clearance time, nasendoscopy, skinprick allergy testing and CT of sinuses. Results were compared with published values. Catarrh patients scored highly on all three symptom questionnaires. Nasendoscopy was normal in 70% of patients, with the remainder demonstrating mostly simple mucus (20%), lymphoid tissue (6%) or mucopus (2%). Only 6 of the 136 patients tested had a prolonged saccharin clearance time greater than 30 min. The mean score of the 63 sinus CT scans obtained was 2.6 (normal range = 0-5). Of patients undergoing skinprick testing (n = 45), 30% reacted to one or more inhaled allergen. No rhinological investigation yielded results above that expected in the general population. Chronic catarrh appears to be related more to pharyngeal symptom awareness than to pathological postnasal drip or mucus over-production. Rhinological investigations have a limited role in the management of chronic catarrh patients. The principal outcome of ENT referral is likely to be reassurance and direction towards patient self-help information.

Tubulovesicular particles occur early in the incubation period of murine scrapie.

Tubulovesicular bodies are structures, apparently specific to the transmissible spongiform encephalopathies, which are of unknown composition and significance. Prion protein (PrP) is absent from tubulovesicular bodies when tissues are examined by immunogold electron microscopy. In the F1 cross of C57 and VM mice (CVF1) infected with ME7 scrapie there is a marked degeneration of hippocampal CA1 neurons. In this model the earliest changes seen, at about 100 days post inoculation (dpi) are a degeneration of axon terminals and synaptic loss. Terminal disease is around 250 dpi. In blind coded trials we counted the number of tubulovesicular particles and estimated their density in 56-76 electron micrographs taken from the stratum radiatum of each of one or two CVF1 ME7-infected mice at 84, 100, 126, 154 and 181 dpi and from four normal brain inoculated control mice. Tubulovesicular particles were present from 98 dpi and the density of particles increased with increasing incubation period. The very early occurrence of tubulovesicular particles, before the presence of significant pathology, argues that tubulovesicular particles are a part of the primary disease and are not epiphenomena.

Back Pain in Children

Back pain in a young child or adolescent is an unusual complaint and must be regarded as a possible indication of the presence of significant pathology. Functional and mechanical causes of back pain in this age group are uncommon; therefore, it is most important that a vigorous attempt be made to establish the primary diagnosis. The purpose of this paper is to review the distinctive features of the history and physical examination that may lead to accurate diagnosis, and to outline a logical approach to the laboratory and radiographic evaluation for each of the major causes of back pain. HISTORY A carefully obtained medical history is frequently the most helpful factor in establishing a diagnosis. In addition to providing important information, it also establishes an attitude of mutual trust and understanding between the physician and patient. A skillfully taken history can help the physician gain vital insight into the patient's attitude toward his or her disease and suggest areas to be emphasized for further evaluation. Specific aspects of the history that are most revealing include: the mode of onset, nature and severity of the pain; a change in symptoms; and associated systemic complaints (Table 1). The mode of onset should be determined as specifically as possible.