The last phase of life: innovative approaches improve end-of-life care inexpensively.
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Biomedical subjects
Publications and source records attributed to D Weber.
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PURPOSE: To clarify the natural history of solitary plasmacytoma of bone (SBP) after radiation treatment. METHODS AND MATERIALS: Between 1965-1996, we identified 57 previously untreated patients with a SBP. A serum myeloma protein was present in 33 patients (58%) and Bence Jones proteinuria was present in an additional eight patients (14%). The median radiotherapy dose was 50 Gy (range, 30-70 Gy). Overall survival, cause-specific survival, and freedom from progression to multiple myeloma were calculated actuarially. RESULTS: Local control was achieved in 55 of 57 patients (96%). For those 29 patients (51%) who subsequently developed multiple myeloma, the median time to progression was 1.8 years. There was a direct correlation between persistence of abnormal protein following radiotherapy and the likelihood of developing multiple myeloma. Among 11 patients with disappearance of myeloma protein, only two developed multiple myeloma after 4 and 12 years, in contrast to progression in 57% of patients with a persistent protein peak and 63 % of those with nonsecretory disease (p = 0.02). Among 23 patients with thoracolumbar spine disease, 7 of 8 patients staged with plain radiographs alone developed multiple myeloma in comparison with 1 of 7 patients who also had magnetic resonance imaging (MRI) (p = 0.08). For all patients, the median survival from radiotherapy was 11.0 years. The median cause-specific survival of patients with disappearance of myeloma protein was significantly longer than that of the remaining patients (p = 0.004). CONCLUSION: Results supported the importance of precise staging that includes MRI of the spine for optimum patient selection and the application of definitive radiotherapy. Those patients with myeloma protein that disappears following radiotherapy represent a category with a high likelihood of cure.
The rat protein farnesyltransferase crystal structure has been solved by multiple isomorphous replacement methods at a resolution of 2.75 A. The three-dimensional structure, together with recent data on the effects of several mutations, led us to propose a model for substrate binding which differs from the model presented by Park et al. based on their independent structure determination [Park, H. -W., Boduluri, S. R., Moomaw, J. F., Casey, P. J., and Beese, L. S. (1997) Science 275, 1800-1804]. Both farnesyl diphosphate and peptide substrates can be accommodated in the hydrophobic active-site barrel, with the sole charged residue inside the barrel, Arg202 of the beta-subunit, forming a salt bridge with the negatively charged carboxy terminus of peptide substrates. Our proposals are based in part on the observation of electron density in the active site which can be modeled as bound farnesyl diphosphate carried through the enzyme purification. In addition, our model explains in structural terms the results of mutational studies which have identified several residues critical for substrate specificity and catalysis.
Relative shortening of the fibula may occur after any type of ankle fracture when the lateral malleolus is involved. Patients complain of pain and restriction of their daily and sporting activities. Clinically, there is valgus of the hind foot due to abduction and lateral rotation of the talus. The goal of treatment is to restore the initial length of the fibula by a horizontal or Z-osteotomy, which will also correct the malposition of the talus. This study shows that the operative reconstruction of a widened mortise is a relatively safe procedure, independent of the type of osteotomy used. Lengthening of the fibula is an important step in the treatment of the painful ankle when the fibula is short after trauma, even when degenerative changes of the joint are already present.
We performed an observational cohort study to test the ability of a short-form screening procedure to detect unrecognized functional disability, as well as its capacity to predict clinical outcome. This screening procedure was administered to 198 consecutive patients within 48 hours of admission. Clinical outcomes upon discharge from the acute care hospital and at 3 months were analyzed according to the number of functional disabilities present on admission. This brief test identified a mean of 1.8 and a median of 1 previously unrecognized functional disabilities per patient. The presence of two or more functional disabilities on admission (48% of the study population) was significantly associated with a negative outcome upon discharge (relative risk = 1.73; CI, 1.33-2.25; p = 0.0001) and at 3 months after discharge (relative risk = 1.34; CI, 1.10-1.64; p = 0.003) confirming the reliability of the short-form screening procedure.
Karyotypic studies of bone marrow were conducted in 79 previously untreated patients with multiple myeloma who received a standard programme of chemotherapy. An abnormal karyotype was observed in 46% of patients, virtually all showing multiple abnormalities consistent with a long period of preclinical clonal evolution. Patients with an abnormal pattern showed various aberrations with hyperdiploidy in 64%, pseudodiploidy in 5% and hypodiploidy in 31%. The number of chromosomes affected ranged from two to 19 (median 10), with at least one trisomy in 83%, one monosomy in 75%, and one translocation in 42% of patients. Lymphoma-like karyotypes were present in 17% of patients with an abnormality but were not associated with atypical clinical features, such as an extramedullary mass, leukaemia, or increased serum lactate dehydrogenase. Monosomy or deletion of chromosome 13 was present in 47% of patients with an abnormal pattern, who lived for a shorter duration (median 10 months) than patients with other abnormalities (median 34 months) or with diploidy (median 35 months). The cause of the short survival of patients with monosomy or deletion of chromosome 13 was not clear, but further studies on the relationship with specific oncogenes are indicated.
We report one patient who presented with a spontaneous bleeding complication under phenprocoumon therapy. Oral anticoagulation was initiated due to deep-vein thrombosis which was attributed to an antiphospholipid antibody syndrome. Coagulation analysis revealed a strong and selective reduction of factor IX (F IX) activity to 1%, whereas the other vitamin K-dependent factors (II, VII, X), the prothrombin time and International Normalized Ratio (INR) were within the therapeutic range. After withdrawal of phenprocoumon, all vitamin K-dependent factors including F IX normalized. Because the patient suffered from a recurrence of thrombotic events, he was re-exposed to phenprocoumon and the disproportionate decline of F IX was observed again. These findings indicate an increased sensitivity of F IX to vitamin K antagonists, representing an uncommon mechanism associated with bleeding complications under oral anticoagulant treatment.
A prospective phase II study was carried out in 48 patients with relapsed or refractory non-Hodgkin's lymphoma using paclitaxel 27.5 mg/M2 i.v. by continuous infusion over 24 hours daily on days 1, 2, 3, and 4 in combination with mitoxantrone 8 mg/M2 i.v. on day 1 and ifosfamide/mesna 1.33 grams/M2 i.v. daily on days 1, 2, and 3 (MINT). Responding patients completed four cycles of MINT and were consolidated with etoposide, solumedrol [methylprednisolone], high-dose cytarabine [Ara-C], and platinum (ESHAP). Forty-eight patients were entered in the study between 1994 and 1996 at The University of Texas M. D. Anderson Cancer Center. Overall response after the first four cycles of MINT was 67% (16% complete response [CR]+ 51% partial response [PR]) and after consolidation with ESHAP it was 49% (26% CR + 23% PR). Variables associated with an improved CR rate and better failure-free survival included the number of prior treatments and the response to prior treatment. A comparison with a similar group of patients treated with mesna, ifosfamide, mitoxantrone, and etoposide (MINE)-ESHAP revealed no major differences in outcome.
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Heptafluorobutyrate (HFB) derivatives have not previously been used for GC of Alternaria mycotoxins. Capillary (0.5 micron film) GC-mass spectrometry (MS) showed that full and partial derivatives of alternariol (AOH), alternariol monomethyl ether (AME) and altenuene (ALT); a structurally uncharacterized derivative of altertoxin I (ALTX-I); and a tris-HFB derivative of tenuazonic acid (TA) were formed with heptafluorobutyric anhydride and a basic catalyst. Full and partial trimethylsilyl (TMS) ethers of these mycotoxins were formed with Tri-Sil TBT. Apple juice extracts caused increased response in GC-MS of AOH bis-HFB and bis-TMS derivatives. Natural occurrence of AOH in apple juice has been demonstrated.
We have developed a portable and extensible set of tools and applications for control of a remote transmission electron microscope (TEM). These tools will be used to develop a system for automatically acquiring large numbers of high quality images from a TEM in a routine, robust, and efficient manner. In particular we plan to develop applications that allow for data collection from specimens preserved in vitreous ice. Copyright 1997 Academic Press. Copyright 1997 Academic Press
BACKGROUND: The risk of lung cancer is increased with cigarette smoking and obstructive lung disease. Patients having a lung volume reduction operation represent a high-risk population for cancer. METHODS: Between March 1994 and December 1996, 281 patients underwent a lung volume reduction operation. All had severe obstructive lung disease with hyperinflation. The incidence of lung nodules and their management were addressed. RESULTS: Of the 281 patients, 39.5% had at least one lung nodule identified. Fifty-two nodules had typical benign calcification patterns. Of the remaining nodules, 78 were resected and 20 were followed up. Seventeen nodules resected were cancerous, of which 13 were primary lung cancers. Of the resected nodules there were 28 nodules not identified by the preoperative radiologic evaluation. CONCLUSIONS: Nodules are frequently seen in patients undergoing lung volume reduction operations. The overall incidence of cancer was 6.4%, with several only identified in the pathologic examination. Survival at short follow-up has been excellent for those with primary lung cancer. Nodules seen in this group of patients should be aggressively diagnosed and managed.