Endomyocardial biopsy in 30 patients with primary amyloidosis and suspected cardiac involvement

Thirty patients with primary amyloidosis in whom cardiac involvement was suspected underwent endomyocardial biopsies. Medical records and biopsies were reviewed and echocardiograms were interpreted by observers who were unaware of the recorded findings. Cardiac amyloidosis was documented by endomyocardial biopsy in 30 (100%) of the patients. In two patients, amyloid was present in only one of four specimens, suggesting that a minimum of four biopsy samples is necessary to eliminate the possibility of sampling error. Only 36 (55%) of 65 biopsy specimens of extracardiac tissues contained amyloid. Findings were positive for amyloidosis in 11 (58%) of 19 rectal biopsies and in 16 (52%) of 31 bone marrow biopsies. Of interest, only the endomyocardial biopsy tissues were positive for amyloid in eight (27%) of the 30 patients, among whom 12 extracardiac biopsies had been performed. Two-dimensional echocardiography was consistent with the diagnosis of amyloidosis in 19 (68%) of 28 patients and was abnormal but nonspecific in the remainder. Endomyocardial biopsy frequently provides information about cardiac involvement with amyloid when biopsy of other organs is negative or echocardiography is nonspecific.     

Primary systemic amyloidosis: comparison of melphalan and prednisone versus placebo.

Satisfactory treatment for primary amyloidosis does not exist. Because the amyloid fibrils consist of a portion of a monoclonal light chain, it appears reasonable to treat amyloidosis with alkylating agents that are effective against the plasma cells that synthesize monoclonal light chains. Fifty-five patients with primary systemic amyloidosis were randomized (double blind) to melphalan-prednisone or placebo. In comparison with the placebo group, patients given melphalan-prednisone were able to continue on treatment for a longer time and to receive larger doses before the code was broken. Among this group, the nephrotic syndrome disappeared in two patients and urinary excretion of protein was reduced by more than 50% in eight others. Of 13 patients who received melphalan-prednisone for more than 12 mo, 6 improved, 3 were stable, and 4 had progression of disease. Survival did not differ significantly between the groups.     

Emerging lifestyles and proactive options for successful ageing

Maintenance of functional health and high quality of late life are crucial concerns for gerontologists and health researchers, as rapidly growing numbers of very old adults face the challenges and opportunities of increasing longevity and frailty in the twenty-first century (Atchley, 1995; Institute of Medicine [IOM], 1991). The present formulation outlines how older adults of tomorrow can enhance their own quality of life through a broad array of proactive adaptations. By recognizing and accepting older adults’ right to, and preference for, proactive involvement in shaping their own destiny, we can make important strides toward facilitating elders’ successful ageing. Successful ageing, based on our model, is an attainable goal within reach of even those aged traditionally relegated to ranks of passive and stigmatized recipients of care. The awards she has received include the Gerontological Society of America (GSA) Distinguished Mentorship Award; Mary E. Switzer Distinguished Fellowship; Ohio Distinguished Gerontological Researcher; Distinguished Scholar Award, Section on Aging & the Life Course of the American Sociological Association (ASA); and Polisher Award of the GSA for her outstanding contribution to applied gerontology. She has published extensively in the area of stress, coping, and health of the aged. Dr. Kahana has been honored throughout his career, including Fellow of the American Psychological Society, a Heller Award for Contributions to Gerontology, the State of Ohio Distinguished Gerontological Researcher Award, and a Publishers Prize for Research Excellence. His extensive list of publications covers the fields of psychology, coping, trauma, stress, and health of the aged. Dr. Kercher acts as statistical and research methods consultant to the School of Medicine, Frances Payne Bolton School of Nursing, Mandel School of Applied Social Sciences, Department of Communication, and University Center on Aging and Health at Case Western Reserve University. Dr. Kercher has served as the co-director of the Education, Epidemiology, and Health Services Research Administration for the Northeast, and serves as Director of the Invitational Research Seminar Series for Case Western Reserve University.     

Sequential deregulation of NK cell subset distribution and function starting in acute HIV-1 infection

Natural killer (NK) cells are critical in the first-line defense against viral infections. Chronic HIV-1 infection leads to a perturbation in the NK cell compartment, yet the kinetics of this deregulation and the functional consequences are unclear. Here, we characterized changes in the NK cell compartment longitudinally by multiparameter flow cytometry, starting in acute HIV-1 infection. Acute HIV-1 infection was associated with elevated NK cell numbers, with an expansion of CD3(neg)CD56(dim)CD16(pos) NK cells and an early depletion of CD3(neg)CD56(bright)CD16(neg) NK cells. Ongoing viral replication resulted in a depletion of CD3(neg)CD56(dim)CD16(pos) NK cells with a paralleled increase in functionally anergic CD3(neg)CD56(neg)CD16(pos) NK cells, accompanied by reduced functional activity, as measured by CD107a expression and cytokine secretion. Taken together, these studies demonstrate a sequential impairment of NK cell function with persistent viral replication resulting from a progressive deregulation of NK cell subsets with distinct functional properties.     

Effect of complete response on outcome following autologous stem cell transplantation for myeloma

We studied the effect of complete response (CR) among 126 consecutive patients who underwent stem cell transplantation (SCT) for myeloma. The CR rate with SCT was 33%. Median overall survival (OS) from diagnosis of myeloma was 56 months. OS following SCT was 22 months. Progression-free survival (PFS) was 12 months. OS was not different between patients who achieved CR and those who did not, median survival 25 vs 24 months, P = 0.5. Corresponding median times for PFS were 15 and 11 months, P = 0.2. The plasma cell labeling index (PCLI) was high (> or = 1%) in 36% (high risk group) and was associated with poor OS and PFS (P < 0.001). Achieving CR did not influence OS or PFS in either the high or the low risk group. In contrast, OS and PFS were significantly influenced by high PCLI both in patients who achieved CR and those who did not. OS was poor (< 30 months) in high risk patients regardless of CR status and in low risk patients who did not achieve CR, compared to low risk patients achieving CR (57 months), making them candidates for novel post-transplant treatment options. Outcome following SCT is dependent more on biological variables such as the PCLI than on CR status.     

Multiple myeloma: current therapy and a glimpse of the future

Patients with benign monoclonal gammopathy or smouldering multiple myeloma should not be treated. The plasma cell labelling index utilizing tritiated thymidine or a monoclonal antibody to 5-bromo-2-deoxyuridine is helpful in differentiating patients with benign monoclonal gammopathy or smouldering myeloma from those with overt myeloma. Although combinations of chemotherapeutic agents seem to produce a greater number of objective responses than does melphalan-prednisone, a significant difference in survival has not been proved. Possibilities for future treatment include chemotherapy with large intravenous doses of melphalan, very small doses of cyclophosphamide or melphalan, the administration of hydroxyurea before chemotherapy, combination of interferon with alkylating agents, autologous bone marrow transplantation, and improvement of the soft-agar colony-forming assay for myeloma cells. The therapeutic use of monoclonal antibodies to plasma cell antigens may be possible in the future. Much more needs to be learned about the biologic basis of myeloma before real progress can be made.     

Peripheral and intracardiac levels of atrial natriuretic factor during cardiothoracic surgery.

Immunoreactive atrial natriuretic factor (ANF) levels were measured in blood taken from superior vena cava, right atrium, pulmonary artery, pulmonary vein, left atrium, and radial arteries in patients undergoing cardiac surgery. Significant (p less than 0.05) differences were seen between sites. Levels of atrial natriuretic factor were seen to rise from superior vena cava (27.5 pmol/L) to right atrium (54.3 pmol/L) and then fall in pulmonary artery (38.5 pmol/L). A further significant fall was seen in pulmonary vein (32.7 pmol/L) samples. There was no significant change in levels in left atrium (32.1 pmol/L) or radial artery (30 pmol/L). The fall between radial artery levels and superior vena caval levels was also significant. The rise from superior vena cava to right atrium is to be expected as this represents the major site of addition of atrial natriuretic factor to the circulation. We propose that the fall in levels from right atrium to pulmonary artery and from pulmonary artery to pulmonary vein suggests uptake and therefore possible local hormonal action on both right ventricle and pulmonary vasculature. The fall from radial artery to vena cava would be in keeping with atrial natriuretic factor's known systemic uptake and action.     

Host defense and bacterial pneumonia

Despite advances in antibiotic therapy, bacterial pneumonia remains a significant cause of morbidity and mortality. Pulmonary host defense has both an innate component, consisting of nonspecific antimicrobial factors, as well as an acquired component, which is pathogen-specific. Defects in either arm of the immune system can have a profound impact on the other because these are highly interactive systems. From the upper airway to the respiratory alveolus, defense mechanisms are in place to maintain sterility of the lower respiratory tract. These features include anatomical barriers, nonspecific antimicrobial peptides, the mucociliary escalator, and the airway lining fluid. In the airspaces, the alveolar macrophage is the cell responsible for early pathogen clearance and subsequent initiation of the acute inflammatory response. Neutrophil recruitment and acquired immune responses are dependent on cytokine secretion by these resident tissue phagocytes. This article reviews the salient features of innate and acquired immunity against bacterial pathogens and how host factors (such as alcoholism) undermine these antibacterial defenses.