Improvement in quality of life in patients with heart failure who undergo transplantation

BACKGROUND: Very few studies have examined quality of life longitudinally in heart failure patients from before or after heart transplantation. The purpose of this study was to compare quality of life of patients with heart failure at the time of listing for a heart transplant with that 1 year after the operation. Major dimensions of quality of life measured in this study were health, physical and emotional functioning, and psychosocial functioning. METHODS: A convenience sample of 148 patients (80% male and mean age 52 years) was recruited from a midwestern and southern medical center. Data were collected from chart review and six patient-completed instruments: the Heart Transplant Symptom Checklist, Sickness Impact Profile, Heart Transplant Stressor Scale, Jalowiec Coping Scale, Quality of Life Index, and Rating Question Form. Informed consent was obtained, and patients who agreed to participate in the study completed the booklet of self-administered instruments. Statistical analyses included frequencies, measures of central tendency, paired t-tests, and Wilcoxon signed-ranks tests. RESULTS: Total symptom distress decreased significantly overall from before to after heart transplantation (before = 0.19 versus after = 0.15, p < 0.0001). Patients rated themselves as having significantly poorer health while listed as a heart transplant candidate than at 1 year after surgery (before = 4.5 versus after = 7.5, p < 0.0001). Although the overall level of functional disability was fairly low before and 1 year after transplantation, patients still reported significant improvement after surgery (before = 0.21 versus 1 year after = 0.13, p < 0.0001). No significant differences were found in total stress, which was low to moderate (before = .026 versus 1 year after = 0.26, p = not significant), coping use (before = 0.48 versus 1 year after = 0.48, p = not significant), or coping effectiveness (before = 0.40) versus 1 year after = 0.42, p = not significant), from before to 1 year after heart transplantation. However, changes in types of symptoms, functional disability, stressors, and coping were noted over time. Overall satisfaction with life, which was fairly high at both time periods, increased significantly from the time of listing for a transplant to 1 year after surgery (before = 0.72 versus 1 year after = 0.82, p <0.0001), and overall quality of life improved significantly from before to after heart transplantation (before = 5.5 versus after = 7.8, p < 0.0001). CONCLUSIONS: End-stage heart failure patients had improved quality of life from before to 1 year after heart transplant due to less total symptom distress, better health perception, better overall functional status, more overall satisfaction with life, and improved overall quality of life. However, post-transplant patients still experienced some symptom distress, functional disability, and stress, but were coping well.     

Allelic deletion on chromosome 17p13.3 in early ovarian cancer

Multiple chromosome 17 loci may be involved in ovarian carcinogenesis. Fifty-seven sporadic ovarian epithelial tumors were examined for loss of heterozygosity at 15 loci on chromosomes 17p. Eighty % (39 of 49) of informative tumors had allelic loss in 17p13.3 at D17S30, D17S28, or both loci within this region, including 3 of 7 tumors of low malignant potential and 4 of 5 nonmetastatic carcinomas. The smallest region of overlapping deletions extends from D17S28 to D17S30, a distance of 15 kb. Furthermore, several tumors have breakpoints within the region detected by the D17S30 probe. Chromosome 17p13.3 genes with potential tumor suppressor function include HIC-1, DPH2L (N. J. Phillips et al. Isolation of a human diphthamide biosynthesis gene on chromosome 17p13.3, submitted for publication)/OVCA1, PEDF, and CRK. The HIC-1 coding sequence lies i kb centromeric to the D17S28-S17S30 region of deletion (M. Makos Wales et al., Nat. Med., 1:570-577, 1995) but remains a candidate because 5'-regulatory elements may lie within the critical region. Portions of the DPH2L/OVCA1 coding sequence lie within the D17S28-D17S30 interval. Somatic cell hybrid analysis places PEDF in an interval including D17S28, D17S30, and D17S54, whereas CRK is excluded from this interval. Chromosome 17p13.3 loss precedes TP53 and BRCA1 region deletions because the latter changes are see only in high-stage carcinomas. Microsatellite instability plays only a minor role in sporadic ovarian carcinogenesis because only 1 of 57 tumors showed this finding.     

The genetics of human systemic lupus erythematosus

The present study, using confocal laser scanning microscopy and immunoelectron microscopy, examined the intracellular localization of tyrosine-phosphorylated proteins in cultured mouse dorsal root ganglion neurons with special reference to their growth cones. The growth cone is the specialized structure formed at the growing tip of the axon; characteristically highly motile with filopodia on the surface, it is responsible for the extension and guidance of the neurites to the appropriate targets during nerve regeneration. It has been suggested that protein-tyrosine phosphorylation plays an important role in the intracellular signal transduction that regulates the extension and motility of growth cones. By fluorescence immunocytochemistry, phosphotyrosine immunoreactivity was found in the growth cones and neurites. Some of the filopodia exhibited strong immunoreactivity at their tips. By immunoelectron microscopy, a large number of immunogold particles (gold particles conjugated to the secondary antibody) were seen to be distributed in the cytoplasm and some were observed on the plasma membrane in the growth cones, whereas in the neurites the density of immunogold particles was the same in the axoplasm as on the plasma membranes. These findings suggest that in the growth cones phosphotyrosines might mainly be involved in intracellular signaling for maintaining their high motility whereas in the neurites they might mostly be associated with the receptor proteins at the plasma membrane for adhesion as well as for growth of neurites. Thus, tyrosine phosphorylation might contribute to different functions for growth cones and neurites.     

Evaluation of phosphorus-containing inhibitors of gamma-glutamyl hydrolase

Several putative, phosphorus-containing inhibitors of gamma-glutamyl hydrolase were synthesized and evaluated for inhibitory activity. The phosphonamidoic acids were shown to be weak competitive inhibitors while both a phosphoramidate diester and a phosphonamidate ester were shown to be potent time-dependent inactivators, presumably through irreversible phosphorylation of an active site nucleophile.     

Managed care workers' compensation outcome measurements: how can a clinic compete?

Clear guidelines and standards established for physicians by managed care organizations are not similarly applied to clinics. Generally, measures of quality of care and service for clinics are ill-defined. Dr. Mueller details six steps to creating a meaningful, achievable set of outcome measures so that clinic organizations can improve and promote their care.     

State-dependent stimulus control: cuing attributes of acute cocaine rebound in rats

General and rapid methods were developed for determining the extent of non-covalent binding between small molecules and proteins, using the model system of human cytomegalovirus protease and several drug candidates which inhibit the protease by non-covalently binding to it. The assay was performed by off-line coupling of size-exclusion methods with mass spectrometry in the following manner. The protease and inhibitor were incubated together under native conditions and then subjected to separation based on size, by use of a spin column (gel permeation chromatography) and/or a microconcentrator (ultrafiltration). The spin column selectively passed the high molecular mass (M(r)) protease and trapped low M(r) molecules. Alternatively, the microconcentrator passed low M(r) molecules and retained the protease. If the inhibitor bound non-covalently to the protease, both the inhibitor and protease passed through the spin column (or were retained by the microconcentrator). Electrospray ionization mass spectrometry was used to assay the spin column eluate (or the microconcentrator retentate) and to characterize the amounts of protease and inhibitor based on known standards. An advantage of these techniques is that a mixture containing inhibitors can be analyzed in the presence of the protease, and inhibitors with the greatest binding affinity can be identified. Non-covalent binding specificity was demonstrated using spin columns by comparing the binding affinity of inhibitors using several mutants of cytomegalovirus protease. The techniques described are applicable to the rapid screening of compound libraries for selecting substances which bind non-covalently to a known protein.     

Frequency, distribution and clonality of chromosome damage in human lymphocytes by multi-color FISH

Behavioral studies and reports in the pediatric medical literature suggest that children, particularly those younger than 4 years, frequently place foreign objects such as toys and small parts of consumer products in their mouths, nasal cavities and ear canals. These actions not infrequently lead to injury or death. Accurate models of the anatomical areas most often severely injured by foreign body impaction (oral cavity, orbit, ear canal and nasal passages) would greatly facilitate assessment of the risks of impaction. Because models of these anatomic regions in children of the ages when they are most at risk are not widely available, Intertek Testing Services, Risk Analysis and Management (ITS RAM), in association with faculty at the University of Pittsburgh and the Pittsburgh Supercomputing Center at Carnegie Mellon University, developed computerized models of these anatomical areas of interest in children at the critical stages of child development. Computer models were also developed of proposed or existing products and of objects represented in the ITS RAM Small Parts Aspiration and Ingestion Database (comprised of data from 17 children's hospitals) and fatality data from the Consumer Product Safety Commission. The computer models of products and computer anatomical models can be used to assess the possible hazards inherent in the product designs and to communicate the risks associated with product designs to manufacturers and marketing groups.     

Delivery of extremely large infants

The purpose of this retrospective study was to find out if more effort should be applied to the diagnosis of extremely large infants, with a birth weight of 5,000 grams or more, and if elective caesarean section can be recommended. In the Department of Obstetrics, Herning Central Hospital, Denmark, 67 mothers delivered an infant with a birth weight of 5000 g or more over a ten year period. This index group was compared with a matched group with infants of normal weight. The result showed significantly more caesarean sections in the index group (24% versus 5%, p = 0.002). Shoulder dystocia and Duchenne-Erb's palsy were more frequent as well. Sixteen percent in the index group were admitted to the paediatric department, but the Apgar scores were not significantly lower. Except for one, all the infants showed complete recovery. In conclusion, elective caesarean section can not be generally recommended for an estimated birthweight exceeding 5,000 g, if a trained obstetrician is present at delivery.     

A phase II "window" study of topotecan in untreated patients with high risk adult acute lymphoblastic leukemia

To further evaluate the activity of topotecan (TPT) in acute leukemia, TPT was administered (2.1 mg/m2/day for 5 days by continuous i.v. infusion) to adult patients with previously untreated acute lymphoblastic leukemia (ALL) with high-risk features (13 patients) or relapsed ALL (1 patient). Patients achieving a partial response or significant hematological improvement received a second course. All patients subsequently received standard treatment for ALL. Because complete response was achieved in only 1 of 14 patients, the study was terminated prematurely. An additional patient achieved minimal response, and a third patient normalized her hemogram despite ongoing leukemia in the marrow. Overall, six patients had significant hematological improvement (normalization of platelet and/or absolute neutrophil count). Two patients expired due to infections during induction chemotherapy. The primary nonhematological toxicities were mucositis and diarrhea. Exposure to TPT did not appear to influence the response to subsequent standard chemotherapy. The mean steady-state TPT plasma concentration, 16.1+/-1 nM, overlapped the range of LD90 values of primary human leukemia specimens. Cellular topo I content varied over a 3-fold range, encompassing levels found previously in relapsed patients. No relationship was found between topo I expression and markers of cellular proliferation or response to therapy. In contrast, low expression of the apoptosis inhibitor Bcl-2 was associated with response to TPT therapy. TPT has significant, albeit modest, single-agent activity against high-risk adult ALL. This study demonstrates the feasibility of evaluating promising new therapeutic agents in untreated patients with acute leukemia at high risk for failure with conventional therapy.     

Neoplastic transformation and DNA-binding of 4,4''-methylenebis(2-chloroaniline) in SV40-immortalized human uroepithelial cell lines

1. The effects of cyclopiazonic acid (CPA) and thapsigargin (TG), both of which are known to inhibit sarcoplasmic reticular Ca(2+)-ATPase, on the mechanical activities, intracellular Ca2+ level and electrical activities of smooth muscle of the carotid artery of stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar Kyoto rats (WKY) were compared. 2. Both CPA and TG induced elevation of tension of the smooth muscle, which was composed of a phasic and a tonic component. The level of tension attained, especially the tonic component, was greater in the preparation from SHRSP. 3. The elevation of tension was associated with an increased intracellular Ca2+ level. Both the elevation of tension and the increase in intracellular Ca2+ were diminished by the removal of extracellular Ca2+ or by the application of verapamil. 4. The resting membrane potential of the preparations from SHRSP were depolarized to a greater extent than those from WKY.CPA depolarized the smooth muscle from both SHRSP and WKY, and the final level was also more depolarized in the preparation from SHRSP. 5. These results indicate that the elevation of tension induced by these drugs is mainly due to increased Ca2+ influx through voltage-dependent Ca2+ channels, and the difference in the action between the preparation from SHRSP and that from WKY can be explained mainly by the changes in the channels. 6. Thus, differences in the action of these drugs on the tension of smooth muscle between preparations from WKY and SHRSP can mainly be explained by the difference in the membrane potential which is related to the difference in voltage-dependent Ca2+ influx.