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.     

Toxicity, inflammation, and anti-human immunodeficiency virus type 1 activity following exposure to chemical moieties of C31G.

C31G, which has potent activity against the human immunodeficiency virus type 1 (HIV-1) and an established record of safety in animal studies and human trials, is a microbicidal agent comprised of a buffered equimolar mixture of two amphoteric, surface-active agents: an alkyl amine oxide (C14AO) and an alkyl betaine (C16B). Studies of long-term in vitro exposure to C31G and its constituents have suggested that the components of C31G may contribute differentially to its toxicity and efficacy. In the present studies, in vitro assays of cytotoxicity and anti-HIV-1 activity demonstrated that C16B was slightly less cytotoxic compared to either C31G or C14AO, whereas the anti-HIV-1 activities of C31G and its individual constituents were similar. In the murine model of cervicovaginal microbicide toxicity, in vivo exposure to C14AO resulted in severe cervical inflammation followed by a delayed disruption of the columnar epithelium. In contrast, exposure to C16B caused severe cervical epithelial disruption and a secondary, less intense inflammatory response. These results demonstrate that (i) there are both mechanistic and temporal differences in toxicity associated with the components of C31G not necessarily predicted by in vitro assessments of cytotoxicity and (ii) contributions of each component to the anti-HIV-1 activity of C31G appear to be equal. In addition, these findings indicate that direct and indirect mechanisms of in vivo toxicity can be observed as separate but interrelated events. These results provide further insight into the activity of C31G, as well as mechanisms potentially associated with microbicide toxicity.     

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.     

Statistical clues to postoperative blood loss: Moving averages applied to medical data

With the advent of computerized databases, medical data has become easy to accumulate; however, effective use of this data continues to pose significant problems. In other circumstances, smoothing algorithms have been used to uncover non-obvious correlations, trends and relationships in noisy data. We have applied four such algorithms to a large dataset of postoperative blood replacement in cardiopulmonary bypass patients. When applied to this dataset, one of the algorithms proved surprisingly effective. It confirmed several previously observed correlations, and also provided an additional series of counterintuitive and apparently unrelated associations. These associations have been explored in an accompanying paper.     

Family-oriented nutrition intervention for a lipid clinic population

We have developed a unique, family-oriented approach to lowering plasma cholesterol concentrations in persons with familial hyperlipidemias. The approach includes individual clinic visits and group nutrition classes and uses dietary goals outlined in The New American Diet. A series of 13 nutrition classes is presented to small groups, usually composed of relatives from pedigrees with familial hypercholesterolemia or other familial hyperlipidemias. Dietary action goals, cooking demonstrations, food tasting, and finger-stick plasma cholesterol determinations are important components of the classes. Problem-solving discussion is encouraged in the group. Over the past 4 years, 143 hyperlipidemic individuals, along with at least 94 unaffected family members, have participated in 31 groups, which have met for at least six classes. Many clinic participants lower plasma cholesterol by 20% or more. Keys to the success of this program include emphasizing dietary therapy, using the family setting for nutrition intervention, providing hands-on experience with food and recipes, promoting problem solving for dietary action goals, measuring blood cholesterol during classes, and encouraging long-term follow-up for participants with physicians and dietitians.     

An experiment in medical education. A critical analysis using traditional criteria

In 1984, in addition to its standard traditional curriculum, Rush Medical College (Chicago, Ill) developed a Socratic problem-based method of teaching basic science material called the alternative curriculum. As part of an evaluation of this new curriculum, students in the two curricula were compared using three traditional measurements: (1) test scores from the National Board of Medical Examiners, Part I; (2) test scores from the National Board of Medical Examiners, Part II; and (3) performance on an oral examination. Alternative curriculum students did not differ significantly from their traditional curriculum classmates on National Board of Medical Examiners, Part I and Part II total scores, although their subset scores on Part I did tend to be lower, reaching significance in one subset area. Differences in performance favoring the traditional curriculum were primarily seen in the early years of the program. Alternative curriculum students in the class matriculated in 1987 scored significantly higher in three of five categories on the oral examination.