A new transthyretin variant (Glu61Gly) associated with cardiomyopathy.

We report the identification of a new transthyretin (TTR) gene mutation and variant protein, Glu61Gly, in a 55-year-old man with progressive cardiomyopathy, mild peripheral neuropathy and bilateral carpal tunnel syndrome. A diagnosis of TTR-associated familial amyloidosis (ATTR) was considered after an endomyocardial biopsy revealed amyloid deposits in the heart of a patient who had no family history of amyloidosis and no evidence of a plasma cell dyscrasia. Serum screening for a TTR variant by isoelectric focusing (IEF) was positive and prompted further studies to identify the genetic abnormality and to characterize the amyloidogenic protein. Direct DNA sequence analysis of all four coding regions in the TTR gene demonstrated heterozygosity in exon 3. Near equal amounts of guanine (G) and adenine (A) were observed at the second base position of codon 61. The wild-type (GAG) and mutated (GGG) sequences found in codon 61 correspond to glutamic acid (Glu) and glycine (Gly) residues, amino acids which differ in mass by -72 Da. Mass spectrometric analyses of TTR immunoprecipitated from serum showed the presence of both wild-type and variant proteins. The observed mass results for the wild-type and variant proteins were consistent with the predicted values calculated from the genetic analysis data.     

A qualitative investigation of seniors' and caregivers' views on pain assessment and management.

The literature suggests that pain in the elderly, especially among seniors with dementia, is under-assessed and under-treated.This qualitative study solicited the perspectives of seniors, front-line nursing staff, nursing-home administrators, and informal caregivers of seniors with dementia on the current status of pain assessment and management. The views of these participants complement the research findings reported in the literature. While some of their explanations and potential solutions concerning under-treatment of pain in seniors echo views that have been presented in the literature, the participants also pointed to factors and avenues that have been given less formal consideration (e.g., systemic barriers to effective assessment and treatment of pain).They also highlighted the need for pain-control strategies beyond medication. The implications of these findings are discussed.     

Metabolic syndrome: contributing factors and treatment strategies.

Metabolic syndrome is associated with increased risk for cardiovascular and cerebrovascular disease. The World Health Organization and National Cholesterol Education Program Adult Treatment Panel III have identified physiologic abnormalities associated with metabolic syndrome, including impaired glucose metabolism, high blood pressure, elevated cholesterol levels, and abdominal obesity. It is estimated that 47 million Americans have metabolic syndrome. A variety of therapies may help reduce the incidence and risk, including diet, weight loss, physical exercise, glycemic control, and pharmacological treatments. Nursing care is focused on developing an individualized plan of care that includes family members and providing education, psychosocial support, close monitoring, and continued follow-up to ensure adherence and success in achieving patient outcomes.     

Tissue physiology and the response to heat.

The most important physiological parameter influencing tissue response to heat is blood flow. At mild hyperthermia temperatures blood perfusion increases in many tumours and this effect is heating time-, temperature- and tumour-dependent. These flow increases can improve tumour oxygenation. When heating is terminated, perfusion and oxygenation commonly recover, although how quickly this occurs appears to be tumour-specific. While these effects are unlikely to have any anti-tumour activity they can be exploited to improve the combination of heat with other therapies. However, since similar physiological effects should occur in normal tissues, such combination therapies must be carefully applied. Heating tumours to higher temperatures typically causes a transient increase in perfusion during heating, followed by vascular collapse which if sufficient will increase tumour necrosis. The speed and degree of vascular collapse is dependent on heating time, temperature and tumour model used. Such vascular collapse generally occurs at temperatures that cause a substantial blood flow increase in certain normal tissues, thus preferential anti-tumour effects can be achieved. The tumour vascular supply can also be exploited to improve the response to heat. Decreasing blood flow, using transient physiological modifiers or longer acting vascular disrupting agents prior to the initiation of heating, can both increase the accumulation of physical heat in the tumour, as well as increase heat sensitivity by changing the tumour micro-environmental parameters, primarily an increase in tumour acidity. Such changes are generally not seen in normal tissues, thus resulting in a therapeutic benefit.