Citations

Abstract Previous studies have reported mortality rates of about 80% in hematopoietic stem cell transplant recipients with diffuse alveolar hemorrhage. This retrospective study describes the clinical course of 48 such patients: mean age 47.7 years, 52% autologous transplant and 67% peripheral stem cell source. The hemorrhage occurred within one month of transplant in 28 patients. Symptoms included dyspnea in 92%, fever in 67%, cough in 56%, and hemoptysis in 15%. Intensive care unit admission was required in 85% and mechanical ventilation in 77%. Most of the patients were treated with intravenous methylprednisolone 1 g daily for 3 days and then tapered off after a median of 22 days. The hospital mortality was 48%. The cause of death was respiratory failure in 15 of the 23 deaths. Mortality was 28% in autologous compared with 70% in allogeneic transplant recipients (p = 0.0040). The mortality rate of patients whose hemorrhage occurred within the first 30 days of transplant was 32% compared with 70% of those with late hemorrhage (p = 0.0096). This study shows that survival rate of hematopoietic stem cell transplant recipients with diffuse alveolar hemorrhage is better than previously reported, and that early onset and autologous transplant are favorable prognostic indicators.

Abstract Cells experience plasma membrane stress failure when the matrix to which they adhere undergoes large deformations. In the lung, such a mechanism might explain mechanical ventilation–associated cell injury. We have previously shown that in alveolar epithelial cells, deformation induces lipid trafficking to the plasma membrane, thereby accommodating the required increase in the cell surface area. We now show that cell wounding is strain amplitude and rate dependent and that under conditions of impaired exocytosis strain-induced cell wounding is significantly increased. In addition, the susceptibility of cells to mechanical injury was not correlated with changes in cell stiffness. Using a dual-labeling technique, we differentiated between cell populations that were reversibly and irreversibly injured and showed that interventions that impair deformation-induced lipid trafficking also reduce the likelihood of plasma membrane resealing. Our findings suggest that cell plasticity and remodeling responses such as deformation-induced lipid trafficking are more important for cytoprotection from strain injury than are the innate mechanical properties of the cell. We also conclude that in deformation experiments, tests of cell membrane integrity cannot be interpreted as tests of cell viability because an intact plasma membrane after deformation does not mean that no injury had occurred.

ABSTRACT Gene therapy in eukaryotes has met many obstacles. Research into the design of suitable nonviral vectors has been slow. To our knowledge, no nonviral vector has been proposed that allows for the possibility of highly efficient, site‐selective integration into the genome of mammalian cells. On the basis of prior studies investigating the components necessary for transposon, retrovirus‐like retrotransposon, and retroviral integration, we propose a nonviral system that would potentially allow for site‐selective, efficient integration into the mammalian genome. Transposons have been developed that can transform a variety of cell lines. For example, the Sleeping Beauty transposon (SB) can transform a wide range of vertebrate cells from fish to human, and it mediates stable integration and long‐term transgene expression in mice. However, the efficiency of transposition varies significantly among cell lines, suggesting the possible involvement of host factors in SB transposition. Here, we propose the use of a chimeric transposase (i.e., transposase‐host DNA binding domain) to bypass the potential requirement of a host DNA‐directing factor (or factors) for efficient, site‐selective integration. We also discuss another potential method of docking the transposonbased vector adjacent to the host DNA, utilizing repetitive sequences for homologous recombination to promote efficient site‐selective integration, as well as other site‐selective nonviral approaches.—Kaminski, J. M., Huber, M. R., Summers, J. B., Ward, M. B. Design of a nonviral vector for site‐selective, efficient integration into the human genome. FASEB J . 16, 1242–1247 (2002)

ABSTRACT Studies that detected an association between Streptococcus bovis endocarditis and colon carcinoma have not taken into account the recently identified genetic diversity among organisms historically classified as S. bovis . With near full-length 16S ribosomal DNA sequence analysis, organisms cultured from the blood of endocarditis patients at the Mayo Clinic from 1975 to 1985 and previously identified as S. bovis or streptococcus group D nonenterococci were shown to represent S. bovis biotypes I (11 isolates) and II/2 (1 isolate), S. salivarius (1 isolate), and S. macedonicus (1 isolate). Two of the S. bovis biotype I cases were associated with colon cancer. Whether S. bovis biotype II or other organisms closely related to and historically identified as S. bovis (e.g., S. macedonicus ) are associated with malignant (or premalignant) colon lesions in humans remains to be definitively determined.

AbstractSurgical treatment for adrenal disease may be withheld from elderly patients because of concern about prohibitive operative morbidity and mortality. To obtain objective data in our practice, we analyzed the results of adrenalectomy for patients aged 65 years and older. From 1984 to 1993 there were 85 patients (41 men, 44 women) with ages ranging from 65 to 84 years (median 69 years) who underwent adrenalectomy for Cushing syndrome (n= 19), pheochromocytoma (n= 16), adrenocortical carcinoma (n= 7), benign adenoma (n= 26), or primary hyperaldosteronism (n= 17) at our institution. Median follow‐up was 26 months (range 1 month to 9.1 years). A retrospective review with respect to preoperative risks and postoperative morbidity and mortality was performed utilizing the American Society of Anesthesiologists (ASA) physical status classification and the modified Goldman multifactorial cardiac risk scheme. Survival was estimated by the Kaplan‐Meier methods. Operative mortality was 7% (six patients). No patients with pheochromocytoma or primary hyperaldosteronism died during the postoperative period. Patients undergoing adrenalectomy for adrenocortical carcinoma had a significantly higher operative mortality (43%) (p= 0.006). Postoperative complications developed in 19 patients (22%), and there was a reoperation rate of 6% (5 patients). Nineteen percent of patients required postoperative intensive care admission and had a median stay of 2 days (range, 1–38 days). Median hospital stay was 7 days (range 3–47 days). Seventy‐three patients (86%) remained alive at study completion. Two‐ and five‐year survivals were 86% and 84%, respectively. Goldman class II or greater was an excellent predictor of increased morbidity (p= 0.032) and mortality (p= 0.036). With the exception of adrenocortical carcinoma, adrenal surgery for elderly patients can be performed with acceptable morbidity and mortality. The Goldman multifactorial cardiac risk scheme reliably predicts postoperative outcome in this elderly group of patients.

Background — The Multicenter Unsustained Tachycardia Trial (MUSTT) was designed to evaluate an antiarrhythmic treatment strategy, including drugs and implantable defibrillators (ICDs), guided by electrophysiological (EP) testing. We performed several statistical analyses to assess the contribution of defibrillators to the observed treatment benefit. Methods and Results — First, the effects of defibrillators were indirectly examined by comparing the randomized treatment arms (EP-guided therapy versus no antiarrhythmic therapy) within subgroups that varied according to ICD usage. Use of ICDs increased during the trial; hence, the randomized treatments were compared according to date of enrollment. There were also site-specific differences in ICD use; hence, the randomized arms were compared within groups of sites defined by level of ICD use. There was a distinct “dose response” in relation to ICD use. Where ICD use was high, EP-guided therapy produced significant reductions in arrhythmic death or cardiac arrest ( P <0.004). Where ICD use was low, there was no benefit of EP-guided therapy. Finally, outcomes of EP-guided therapy patients who received an ICD were directly compared with outcomes of other patients using the Cox proportional hazards model with receipt of an ICD as a time-dependent covariate. Adjusted for other prognostic factors, patients who received an ICD had risk reductions of >70% in arrhythmic death or cardiac arrest and >50% in total mortality ( P <0.001 for both end points). Conclusions — The benefit of EP-guided antiarrhythmic therapy observed in MUSTT was due to improved outcomes among patients who received an ICD but not among patients who received antiarrhythmic drugs.

AbstractAutologous stem cell transplantation (ASCT) improves survival in patients with previously untreated multiple myeloma (MM) and relapsed, chemotherapy-sensitive, aggressive non-Hodgkin lymphoma (NHL). Lower relapse rates seen in allogeneic stem cell transplantation have been related to early absolute lymphocyte count (ALC) recovery as a manifestation of early graft-verus-tumor effect. In ASCT, the relation between ALC recovery and clinical outcomes in MM and NHL was not previously described. This is a retrospective study of patients with MM and NHL who underwent ASCT at the Mayo Clinic between 1987 and 1999. The ALC threshold was determined at 500 cells/μL on day 15 after ASCT. The study identified 126 patients with MM and 104 patients with NHL. The median overall survival (OS) and progression-free survival (PFS) times for patients with MM were significantly longer in patients with an ALC of 500 cells/μL or more than patients with an ALC of fewer than 500 cells/μL (33 vs 12 months,P &lt; .0001; 16 vs 8 months, P &lt; .0003, respectively). For patients with NHL, the median OS and PFS times were significantly longer in patients with an ALC of 500 cells/μL or more versus those with fewer than 500 cells/μL (not reached vs 6 months, P &lt; .0001; not reached vs 4 months,P &lt; .0001, respectively). Multivariate analysis demonstrated day 15 ALC to be an independent prognostic indicator for OS and PFS rates for both groups of patients. In conclusion, ALC is correlated with clinical outcome and requires further study.

ABSTRACT A 300-bp plasmid fragment of the hemagglutinin gene was used as target DNA to develop a rapid real-time LightCycler (Roche Applied Science, Indianapolis, Ind.) PCR assay for laboratory detection of smallpox virus. PCR primers and probes were designed specifically for detection of smallpox virus DNA, but all viruses of the genus Orthopoxvirus tested could be detected by use of the hemagglutinin gene target sequence. Base pair mismatches in the 204-bp amplicon allowed discrimination of cowpox virus (melting temperature [ T m ], 56.40°C), monkeypox virus ( T m , 56.24°C), and vaccinia virus ( T m , 56.72°C), including the Dryvax vaccine strain, from smallpox virus ( T m , 62.45°C) by melting curve analysis. The analytical sensitivity was 5 to 10 copies of target DNA per sample. The assay was specific for members of the genus Orthopoxvirus ; the DNAs of herpes simplex virus and varicella-zoster virus were not detected by the smallpox virus LightCycler PCR.

ABSTRACT We compared the activities of linezolid (25 mg/kg of body weight, administered intraperitoneally every 8 h) and of vancomycin (25 mg/kg of body weight, administered intraperitoneally every 8 h) in a rat model of vanA vancomycin-resistant Enterococcus faecium experimental endocarditis. Results were expressed as median log 10 CFU per gram of vegetation after 3 days of treatment. The median log 10 CFU per gram of vegetation was 10.1 among 7 untreated control animals, 10.2 among 9 vancomycin-treated animals, and 7.9 among 10 linezolid-treated animals. Linezolid treatment was more active ( P < 0.05) than vancomycin treatment or no treatment.