Using health status surveys in medical consultations

The goal of this research was to identify patients' preferences for physician inquiry into various aspects of health status and to examine whether the preconsultation availability of health status data (collected from the SF-36 Health Status Questionnaire) influenced the physician's conduct during the consultation. Results from 58 prenatal patient visits yielded the following findings. First, patients expressed strong preferences for physicians to ask about the patient's perceptions of health in general and about physical dimensions of health status such as pain, vitality, and role limitations due to physical functioning. Patients also were more satisfied when doctors were perceived as having asked about these issues. Second, patients varied considerably in their preferences for physician inquiries into psychosocial issues such as social functioning, mental health, and role limitations due to emotional problems. Approximately half the patients wanted these matters discussed, whereas the remainder either did not care or preferred that doctors not ask about these topics. Third, the preconsultation availability of health status information had little effect on the degree to which physicians asked about the patient's health-related quality of life. Clinical implications are discussed.     

Adoptive immunotherapy for leukemia: donor lymphocytes transduced with the herpes simplex thymidine kinase gene for remission induction. HGTRI 0103

This study will evaluate the safety and efficacy of allogenic donor lymphocyte infusions in patients who have relapsed hematologic malignancies after allogeneic bone marrow transplantation (BMT). Donor lymphocyte transfusions have resulted in the cure of some patients with relapsed leukemia or lymphoproliferative disorder after allogeneic BMT, but has been complicated by the development of graft versus host disease (GvHD). We hypothesize that a retroviral vector containing the Herpes simplex thymidine kinase (HStk) gene will allow for retention of the anti-leukemia response of transfused donor lymphocytes while allowing for the adverse effects of GVHD to be mitigated. Patients with relapsed hematologic malignancies after allogeneic BMT will be infused with ex vivo gene modified donor lymphocytes. The Herpes Simplex thymidine kinase (HStk) gene will be transduced into the cells ex vivo using LTKOSN. 1 vector supernate. Insertion of the HStk gene into lymphocytes confers a sensitivity to the anti-herpes drug ganciclovir (GCV). This selective destruction of donor lymphocytes in situ will be used to abrogate the effect of graft versus host disease, if it develops.     

Myocardial acoustics in pediatric allograft rejection

BACKGROUND: Ultrasonographic tissue characterization is the assessment of physical properties of biologic tissue on the basis of quantitative analysis of its acoustic characteristics. Abnormalities in microscopic structure that occur with cardiac allograft rejection may result in characteristic alterations in myocardial acoustics. Ultrasonographic tissue characterization may allow noninvasive detection of rejection. METHODS: Findings in 22 pediatric heart transplant patients undergoing routine surveillance for rejection by endomyocardial biopsy were prospectively evaluated. Off-line ultrasonographic tissue characterization analysis was done on transthoracic echocardiograms obtained at each biopsy. Within patients, tissue characterization texture measures derived from the ultrasonographic image data were compared with histologic findings. Univariate multiple regression analysis was used to identify texture measures associated with acute allograft rejection in a subgroup (n = 8) with at least one biopsy-proven episode of moderate rejection. RESULTS: Measures of homogeneity (co-occurrence matrix correlation and heterogeneity (run-length nonuniformity) decreased with moderate rejection (p < 0.03). Homogeneity measures decreased if the patient had a previous episode of rejection. Several measures of heterogeneity (gray level difference and run-length statistics) were affected by the presence of edema. Run-length nonuniformity was the only measure that differentiated moderate rejection from edema. Discriminant analysis on all 22 patients correctly identified 96% of first rejection episodes (sensitivity 80%, specificity 64%), 93% of moderate and severe rejection episodes (sensitivity 71%; specificity 62%), and 69% of all rejection episodes (sensitivity 51%, specificity 91%). CONCLUSIONS: Histologic changes associated with moderate and severe pediatric allograft rejection as reflected by characteristic alterations in myocardial acoustics can be assessed with ultrasonographic tissue characterization. Histologic changes associated with transplantation itself (resolution of rejection and edema) also affect myocardial acoustics and must be taken into account in rejection surveillance.     

Paracrine expression of a native soluble vascular endothelial growth factor receptor inhibits tumor growth, metastasis, and mortality rate

Vascular endothelial growth factor (VEGF) is a potent and selective vascular endothelial cell mitogen and angiogenic factor. VEGF expression is elevated in a wide variety of solid tumors and is thought to support their growth by enhancing tumor neovascularization. To block VEGF-dependent angiogenesis, tumor cells were transfected with cDNA encoding the native soluble FLT-1 (sFLT-1) truncated VEGF receptor which can function both by sequestering VEGF and, in a dominant negative fashion, by forming inactive heterodimers with membrane-spanning VEGF receptors. Transient transfection of HT-1080 human fibrosarcoma cells with a gene encoding sFLT-1 significantly inhibited their implantation and growth in the lungs of nude mice following i.v. injection and their growth as nodules from cells injected s.c. High sFLT-1 expressing stably transfected HT-1080 clones grew even slower as s.c. tumors. Finally, survival was significantly prolonged in mice injected intracranially with human glioblastoma cells stably transfected with the sflt-1 gene. The ability of sFLT-1 protein to inhibit tumor growth is presumably attributable to its paracrine inhibition of tumor angiogenesis in vivo, since it did not affect tumor cell mitogenesis in vitro. These results not only support VEGF receptors as antiangiogenic targets but also demonstrate that sflt-1 gene therapy might be a feasible approach for inhibiting tumor angiogenesis and growth.     

Antimutagenic and anticarcinogenic potentials of some Thai vegetables

HPLC assays were developed and validated for the quantitation of the novel orally active nonsteroidal antiestrogen EM-800 ?(S)-(+)-4-[7-(2,2-dimethyl-l-oxopropoxy)-4-methyl-2-[4-[2-(1-pipe ridinyl)- ethoxy]phenyl]-2H-l-benzopyran-3-yl]-phenyl 2,2-dimethylpropanoate?. The assay involves reversed-phase C18 or C4 columns using different mobile phases with ammonium acetate buffers and UV detection at lambda = 240 nm. The standard curve was linear over the concentration range of 10-1100 micrograms/ml. The precision (% relative standard deviation) values of these methods were in the range of 0.38-0.52 and 1.89-3.45% with C4 and C18 reversed phases, respectively. The limit of detection was found to be 1 microgram/ml. Enantiomeric separation was also obtained using a chiral method (ChiralPak AD column) using a mixture of hexane-reagent alcohol-diethylamine (94.9:5.0:0.1) as mobile phase. These methods were applied to stability studies, evaluation of pharmaceutical dosage forms and in the framework of toxicological studies. Details of some of these applications will be presented.     

Complications resulting from saphenous vein patch graft after carotid endarterectomy

OBJECTIVE: Reducing surgical risks to the minimum in carotid endarterectomy has become crucial, especially with the results of recent clinical trials extending indications to asymptomatic patients. The use of the saphenous vein patch graft (SVPG) has been suggested to reduce early postoperative thrombosis and cerebral infarct as well as late recurrent stenosis. However, the exact risks and complications involved in this technique are not known. METHODS: During a 23-year period (1972-1994), 2888 carotid endarterectomies with SVPG for primary carotid stenosis were performed by the Neurosurgical Cerebrovascular Service at the Mayo Clinic. The data from all patients were retrospectively analyzed, emphasizing postoperative complications related to SVPG. RESULTS: There were five postoperative vein ruptures (0.17%), four cases of aneurysm formation, and three cases of deep infection necessitating surgical intervention. The vein patch ruptured in one male patient and four female patients (mean age, 69 yr). All ruptures occurred within 4 days of the primary operation, including two during the first 24 hours. All patients with rupture underwent emergency surgery and were found to have intact suture lines and tears in the middle of the grafts. Two patients recovered without deficits, one suffered major disability, and the other two died. Aneurysm of the patch developed in two male patients and two female patients (mean age, 71 yr). All of the patients developed painless pulsatile neck masses 1 to 9 years after the initial surgery; two also had recurrent ischemic symptoms. All of the patients with aneurysms underwent surgical correction without consequences. CONCLUSION: Although the benefit of routine use of SVPG in carotid endarterectomy is still the focus of debate, this analysis showed that its use adds a small but definite risk of serious complications related to inherent weakness of the venous tissue. If a surgeon chooses to use a patch graft, our recommendation is for use of a synthetic material rather than vein.     

Effects of removal of weight-bearing function on contractility and myosin isoform composition in single human skeletal muscle cells

The purpose of this study was to investigate the effects of a 6-week period without weight bearing, achieved by bed rest, on the contractile behaviour, myosin isoform expression and myofibrillar protein content of single human muscle fibres. Percutaneous biopsied specimens of the quadriceps muscle were taken from three healthy male volunteers before and at the end of the experimental period. Maximum force normalised to cross-sectional area (specific tension), maximum velocity of unloaded shortening (V0), and myosin heavy chain (MyHC) and light chain (MyLC) isoform composition were measured in single membrane-permeabilised muscle cells obtained from these specimens. At the end of the experimental period, specific tension was reduced (P < 0.001) by 40% and there was a parallel decline in myofibrillar protein content per muscle cell volume. V0 did not change significantly in response to bed rest when data from all muscle cells were pooled. In two of the subjects, however, V0 decreased (P < 0.01-0.001) in muscle cells expressing the beta/slow (type I) MyHC isoform, but there was no change in fibres expressing type IIA or a combination of type IIA and IIB MyHCs. The slowing in type I MyHC fibres was associated with a change in the isoform composition of the regulatory MyLC.