The Framingham Disability Study: physical disability among community-dwelling survivors of stroke

The relationship between stroke and physical disability was examined in a cohort of adult, Framingham, Massachusetts, residents who, between 1948 and 1951, were assembled for a longitudinal examination of cardiovascular disease. Multivariate analyses examined the amount of residual disability attributable to stroke among 2540 community-dwelling survivors, 27 years after their initial examination, after controlling for age, cardiovascular risk factors, other cardiovascular diseases, and eight general health conditions related to physical disability. Among men living in the community, a history of stroke explained 12% of the variance in physical disability. Suffering a stroke, however, was not as strongly related to physical disability among women living in the community, accounting for only 3% of the variance. Results suggest that although older men and women die from the same major causes, they may not be disabled by the same conditions.     

Extracorporeal membrane oxygenation for the circulatory support of children after repair of congenital heart disease

We have treated 39 infants and children with congenital heart disease with extracorporeal membrane oxygenation during the past 5 years. Thirty-six were treated for low cardiac output or pulmonary vasoreactive crisis after repair of congenital heart defects. Twenty-two (61%) survived. Most patients were cannulated from the neck via the right internal jugular vein and the right common carotid artery. Six patients were cannulated from the chest, including three who had separate drainage of the left side of the heart with a left atrial cannula. Two of these patients survived and were the only survivors of the nine patients cannulated in the operating room because they could not be weaned from cardiopulmonary bypass after open cardiac operations. We also reviewed 312 patients (the predictor study series) having open cardiac operations before the availability of extracorporeal membrane oxygenation; 27 of these patients died. Data were collected at 1 and 8 hours postoperatively to determine if any parameters might predict early mortality. With these parameters used as criteria, patients who went on extracorporeal membrane oxygenation were as sick as those who died before extracorporeal membrane oxygenation was available. The most common complication was bleeding related to heparinization. The mean transfusion requirement in survivors was 1.50 +/- 1.13 ml/kg/hr, 5.63 +/- 7.0 ml/kg/hr in the nonsurvivors, and 7.46 +/- 8.29 ml/kg/hr in those cannulated in the operating room because they could not be weaned from bypass. Four children had intracranial hemorrhage, and two of them died. There was one late death. Nine of the 22 survivors are entirely normal. All survivors who do not have Down's syndrome are considered to have normal central nervous system function. We conclude that extracorporeal membrane oxygenation can improve survival in patients with both pulmonary artery hypertension and low cardiac output after operations for congenital heart disease.     

Maculopapular eruption with enlarged macrophages in eight patients receiving G-CSF or GM-CSF

In the last years, granulocyte and granulocyte-macrophage colony-stimulating factors (G-CSF and GM-CSF) are being increasingly used and several cutaneous eruptions have been reported in relation to these treatments. In 1991 Horn et al. described three patients with maculopapular eruption that paralleled the time of infusion of GM-CSF. Two of the cases showed an increase in the number and size of macrophages in the biopsy specimen. Since then, several cases have been reported showing this histopathological alteration that has been considered characteristic of reaction to G-CSF or GM-CSF. Although maculopapular eruption with enlarged macrophages can appear after chemotherapy treatment, we have found that the presentation of this eruption after the beginning of cytokine treatment is suggestive of the involvement of G-CSF and GM-CSF in the eruption. We described eight cases of patients treated with G-CSF or GM-CSF that developed maculopapular eruptions with enlarged macrophages.     

Effect of Multiple Freeze-Thaw Cycles on Detection of Measles, Mumps, and Rubella Virus Antibodies

We investigated the effect of multiple freeze-thaw cycles on mumps, measles, and rubella virus serum antibody levels with whole-virus immunoglobulin G enzyme-linked immunoassays. Fresh serum samples from nine healthy adult volunteers were divided into six sets of five aliquots each. Samples were taken through a total of 10 freeze-thaw cycles and stored at 4°C until assayed. Each assay measurement was done in replicates of five, and the mean value was reported. After completing 10 freeze-thaw cycles, we found no clinically or statistically significant effect on measured antibody levels and found no discernible detrimental effect on the ability to measure these antibodies by enzyme-linked immunoassays.     

X-linked muscular atrophy and the androgen receptor

X-linked muscular atrophy is a form of adult-onset, usually slowly progressive spinal and bulbar motor neuron degenerative disease that is uniquely associated with male hypogonadism. The mutation responsible for this syndrome is expansion of the trinucleotide repeat—cytosine (C), adenine (A), guanine (G)—in a 5′-translated portion of the androgen receptor (AR) gene from a normal, polymorphic length of n = 11–31 to n ≥ 40. The resulting androgen receptor (AR) protein has an expanded polyglutamine tract in its NH₂-terminal modulatory domain, and is postulated to lose a basic, intrinsic function that causes a mild form of androgen insensitivity; however, almost certainly, it also gains a novel, extrinsic function that is selectively neuronotoxic. The unexplained mechanism that culminates in this form of neuronspecific death is the prototype for three different adult-onset neuronopathies that are caused by (CAG)_n expansions in other genes.     

Enhanced sensitivity and specificity of thallium-201 imaging for the detection of regional ischemic coronary disease by combining SPECT with "bull's eye" analysis

Previous studies have indicated that the combination of single photon emission computed tomography (SPECT) and quantitative "bull's eye" analysis (QBA) TI-201 cardiac stress imaging may improve the detection of myocardial ischemia over that achieved with planar (PLN) imaging. This study will evaluate the sensitivity and specificity of SPECT and QBA in the detection of disease in the left anterior descending (LAD), left circumflex (LCX), and right coronary artery. Ninety-nine patients who underwent both TI-201 stress imaging and coronary arteriography were evaluated retrospectively. Of the 99, 62 had PLN imaging and 37 were evaluated with SPECT; 23 of these 37 had QBA. The overall sensitivity and specificity were as follows: PLN, 94% and 50%; SPECT, 90% and 67%; QBA, 100% and 20%; and SPECT with QBA, 92% and 72%, respectively. The regional sensitivity and specificity of PLN for individual coronary arteries were as follows: RCA, 78% and 74%; LAD, 89% and 60%; LCX, 50% and 89%, respectively. For SPECT, the results were: RCA, 86% and 93%; LAD, 85% and 88%; and LCX, 60% and 88%. For QBA alone, the results were: RCA, 100% and 75%; LAD, 88% and 53%; and LCX, 100% and 89%. The results for QBA with SPECT were: RCA, 100% and 94%; LAD, 88% and 80%; and LCX, 67% and 95%. Thus, SPECT interpreted on conjunction with QBA showed higher sensitivity for evaluation of ischemia in the RCA and LCX arteries and higher specificity in the detection of LAD and RCA disease than did PLN TI-201 imaging. Because of the low specificity of QBA (20%), caution is advised in the interpretation of QBA alone without reviewing SPECT images.     

Survey of the Distribution of a Newly Characterized Receptor for Advanced Glycation End Products in Tissues

Advanced glycation end products (AGEs), the final products of nonenzymatic glycation and oxidation of proteins, are found in the plasma and accumulate in the tissues during aging and at an accelerated rate in diabetes. A novel integral membrane protein, termed receptor for AGE (RAGE), forms a central part of the cell surface binding site for AGEs. Using monospecific, polyclonal antibody raised to human recombinant and bovine RAGE, immunostaining of bovine tissues showed RAGE in the vasculature, endothelium, and smooth muscle cells and in mononuclear cells in the tissues. Consistent with these data, RAGE antigen and mRNA were identified in cultured bovine endothelium, vascular smooth muscle, and monocyte-derived macrophages. RAGE antigen was also visualized in bovine cardiac myocytes as well as in cultures of neonatal rat cardiac myocytes and in neural tissue where motor neurons, peripheral nerves, and a population of cortical neurons were positive. In situ hybridization confirmed the presence of RAGE mRNA in the tissues, and studies with rat PC12 pheochromocytes indicated that they provide a neuronal-related cell culture model for examining RAGE expression. Pathological studies of human atherosclerotic plaques showed infiltration of RAGE-expressing cells in the expanded intima. These results indicate that RAGE is present in multiple tissues and suggest the potential relevance of AGE-RAGE interactions for modulating properties of the vasculature as well as neural and cardiac function, prominent areas of involvement in diabetes and in the normal aging process.