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Biomedical subjects

C A Keller

Publications and source records attributed to C A Keller.

At least 19 recordsLinked to original sources

Atelectasis--an unusual and late complication of lung transplant.

We report a previously unrecognized late complication of allograft lung transplantation - persistent recurrent atelectasis of the transplanted lung. The patient developed sudden, severe respiratory distress about 2 yr after a right lung transplant, because of acute atelectasis of her transplanted lung. Multiple transbronchial biopsies at the time revealed minimal inflammation and no evidence of rejection. She was treated with surfactant replacement therapy, and her collapsed lung fully expanded following surfactant installation. To eliminate the possibility of acquired deficiency of surfactant lipids or proteins, ultrastructural examination and immunostains for surfactant proteins were performed in a transbronchial lung biopsy. No deficiency of surfactant lipids or proteins was found. On ultrastructural examination of the lung biopsy, the number of Type II cells per alveolus and the number of lamellar bodies per square micron of Type II cell cross-sectional area was increased compared with an age-matched control. We conclude that synthesis of surfactant lipids and proteins was unimpaired and because of the patient's response to surfactant replacement therapy, that the increase in number of lamellar bodies could reflect a compensatory mechanism for a surfactant functional defect. The patient later developed breast carcinoma to which she succumbed. We raise the possibility that the functional surfactant defect is a hitherto unrecognized non-metastatic manifestation of malignancy.

Female↗

Loss-of-function mutations reveal that the Drosophila nautilus gene is not essential for embryonic myogenesis or viability.

nautilus (nau), the single Drosophila member of the bHLH-containing myogenic regulatory family of genes, is expressed in a subset of muscle precursors and differentiated fibers. It is capable of inducing muscle-specific transcription as well as myogenic transformation, and plays a role in the differentiation of a subset of muscle precursors into mature muscle fibers. In previous studies, the nau zygotic loss-of-function phenotype was determined using genetic deficiencies in which the gene is deleted. We note that this genetic loss-of-function phenotype differs from the loss-of-function phenotype determined using RNA interference (L. Misquitta and B. M. Paterson, 1999, Proc. Natl. Acad. Sci. USA 96, 1451-1456). The present study re-examines this loss-of-function phenotype using EMS-induced mutations that specifically alter the nau gene, and extends the genetic analysis to include the loss of both maternal and zygotic nau function. In brief, embryos lacking nau both maternally and zygotically are missing a distinct subset of muscle fibers, consistent with its apparent expression in a subset of muscle fibers. The muscle loss is tolerated, however, such that the loss of nau both maternally and zygotically does not result in lethality at any stage of development.

Animals↗

Pneumomediastinum and subcutaneous emphysema from pacemaker placement.

Percutaneous insertion of permanent pacemaker leads through the subclavian vein is an alternative to the cephalic vein approach. A rare occurrence and successful conservative management of extensive pneumomediastinum and subcutaneous emphysema without concomitant pneumothorax resulting from permanent transvenous pacemaker insertion in an 80-year-old man with syncope and arrhythmia is reported.

Aged↗

Endoluminal graft repair for abdominal aortic aneurysms in high-risk patients and octogenarians: is it better than open repair?

OBJECTIVE: To analyze the short-term and midterm results of open and endoluminal repair of abdominal aortic aneurysms (AAA) in a large single-center series and specifically in octogenarians. METHODS: Between January 1997 and October 2000, 470 consecutive patients underwent elective repair of AAA. Conventional open repair (COR) was performed in 210 patients and endoluminal graft (ELG) repair in 260 patients. Ninety of the patients were 80 years of age or older; of these, 38 underwent COR and 52 ELG repair. RESULTS: Patient characteristics and risk factors were similar for both the entire series and the subgroup of patients 80 years or older. The overall complication rate was reduced by 70% or more in the ELG versus the COR groups. The postoperative death rate was similar for the COR and ELG groups in the entire series and lower (but not significantly) in the ELG 80 years or older subgroup versus the COR group. The 36-month rates of freedom from endoleaks, surgical conversion, and secondary intervention were 81%, 98.2%, and 88%, respectively. CONCLUSION: The short-term and midterm results of AAA repair by COR or ELG are similar. The death rate associated with this new technique is low and comparable, whereas the complication rate associated with COR in all patients and those 80 years or older in particular is greater and more serious than ELG repair. Long-term results will establish the role of ELG repair of AAA, especially in elderly and high-risk patients.

Adult↗

The use of endoscopic argon plasma coagulation in airway complications after solid organ transplantation.

The objective of the study was to describe a safe and effective treatment option for endobronchial complications after solid organ transplantation. A retrospective analysis was performed in a tertiary-care university hospital. The use of bronchoscopic argon plasma coagulation (APC) for the treatment of endobronchial lesions was studied in five solid organ transplant recipients. Four patients presented with variable degrees of endobronchial obstruction, and one patient presented with massive hemoptysis. Two of the patients with endobronchial obstruction were double lung transplant recipients who developed anastomotic strictures. The strictures were opened with endobronchial stents but became obstructed again by inflammatory granulation tissue overgrowth through the stent mesh. APC was used to maintain airway patency. One kidney transplant recipient developed pulmonary zygomycosis with secondary obstruction of the left main bronchus because of granulation tissue growth through endobronchial stents. Airway patency was reestablished with several treatments with APC. Another kidney transplant recipient developed subglottic and tracheal papillomatosis that was effectively removed with APC. A heart transplant recipient was referred with recurrent massive hemoptysis refractory to bronchial artery embolization. The bleeding was caused by hemorrhagic polypoid lesions, which were completely ablated by APC. Bronchoscopic use of the argon plasma coagulator is a safe and simple technique that can be used effectively to treat endobronchial pathology in solid organ transplant patients.

Adult↗

Formation of supported membranes from vesicles.

Using a combination of the quartz crystal microbalance and surface plasmon resonance techniques, we have studied the spontaneous formation of supported lipid bilayers from small (approximately 25 nm) unilamellar vesicles. Together these experimental methods measure the amount of lipid adsorbed on the surface and the amount of water trapped by the lipid. With this approach, we have, for the first time, been able to observe in detail the progression from the adsorption of intact vesicles to rupture and bilayer formation. Monte Carlo simulations reproduce the data.

Adsorption↗

Outcome of bedside percutaneous tracheostomy with bronchoscopic guidance.

OBJECTIVE: To determine the morbidity and mortality of percutaneous dilational tracheostomy with bronchoscopic guidance when performed by medical intensivists. DESIGN: A retrospective analysis. SETTING: A tertiary care university hospital. PATIENTS: Fifty consecutive patients who underwent percutaneous dilational tracheostomy for prolonged mechanical ventilation. INTERVENTION: Bedside percutaneous dilational tracheostomy with bronchoscopic guidance. RESULTS: Seventeen women and 33 men with a mean age of 62 +/- 17 years. Operative mortality was 0 with four (8%) operative complications. Complications included one posterior tracheal abrasion, one anterior tracheal laceration, one episode of endobronchial hemorrhage requiring bronchoscopy, and one pneumothorax. Thirty-day mortality was 28% and overall mortality was 40%. All deaths were related to the patients' underlying disease. CONCLUSIONS: Percutaneous dilational tracheostomy with bronchoscopic guidance is a safe procedure when performed by experienced medical intensive care personnel in tertiary care institutions. Bronchoscopy helps to reduce the risk of major complications and aids in the management of minor complications.

Aged↗

Comparison of clinical results for unilateral and bilateral thoracoscopic lung volume reduction.

BACKGROUND: It is widely believed that bilateral thoracoscopic lung volume reduction (BTLVR) yields superior results when compared with unilateral thoracoscopic lung volume reduction (UTLVR) with regard to spirometry, functional capacity, oxygenation and quality of life results. METHODS: To address these issues, we compared the results of patients undergoing UTLVR (N = 338 patients) and BTLVR (N = 344 patients) from 1993 to 1998 at five institutions. Follow-up data were available on 671 patients (98.4%) between 6 and 12 months after surgery, and a patient self-assessment was obtained at a mean of 24 months. RESULTS: It was found that BTLVR provides superior improvement in measured postoperative percent change in FEV1 (L) (UTLVR 23.3% +/- 55.3 vs BTLVR 33% +/- 41, p = 0.04), FVC(L) (10.5% +/- 31.6 vs 20.3% +/- 34.3, p = 0.002) and RV(L) (-13% +/- -22 vs -22% +/- 17.9, p = 0.015). BTLVR also provides a slight improvement over UTLVR in patient's perception regarding improved quality of life (UTLVR 79% vs BTLVR 88%, p = 0.03) and dyspnea relief (71% vs 61%, p = 0.03). There was no difference in mean changes in PO2 (mm Hg) (UTLV 4.5 +/- 12.3 vs BTLVR 4.9 +/- 13.3, p = NS), 6-minute walk (UTLVR 26% +/- 66.1 vs BTLVR 31% +/- 59.6, p = NS) or decreased oxygen utilization (UTLVR 78% vs BTLVR 74%, p = NS). CONCLUSIONS: These data suggest that both UTLVR and BTLVR yield significant improvement, but the results of BTLVR seem to be superior with regard to spirometry, lung volumes, and quality of life.

Adult↗

Risk analysis for thoracoscopic lung volume reduction: a multi-institutional experience.

OBJECTIVE: Most reports of thoracoscopic lung volume reduction (TLVR) are relatively small and early experiences from a single institution, factors which limit both the statistical validity and the applicability to the population at large. In order to address these shortcomings we undertook an analysis of the TLVR experience at five separate institutions to assess operative morbidity and identify predictors of mortality. METHODS: Questionnaires were sent to four groups of surgical investigators at five institutions actively performing TLVR. Data was requested regarding preoperative, operative and postoperative parameters. Twenty-five potential predictors of mortality were analyzed and seven proved to be at least marginally significant (P<0.10). These parameters were entered into a stepwise logistic regression analysis to identify independent predictors. RESULTS: The 682 patients (415 males, 267 females, mean age 64.0 years) underwent unilateral (410) or bilateral (272) TLVRs. Overall, operative mortality was 6% with half of the deaths resulting from respiratory causes. The remaining patients were discharged to home (88%), a rehabilitation facility (4%) or a ventilator facility (2%). There were 25 perioperative factors chosen representing clinically important indices such as spirometry, oxygenation, functional status, clinical and demographic variables. Univariate analysis identified seven variables as predictors of mortality (P<0.10) and these were entered into a stepwise logistic regression analysis. Only age, 6-min walk, gender (male 8%, female 3% mortality) and the procedure performed (unilateral 4.6%, bilateral 8%) were independent predictors while preoperative steroid therapy, preoperative oxygen administration, and time since smoking cessation dropped out of the model. The specific institution, learning curve (early vs. late experience), type of lung disease, spirometric indices and predicted maximum VO(2) were not significant predictors. CONCLUSION: This experience suggests that unilateral and bilateral lung volume reduction procedure can be performed with acceptable morbidity and mortality. Although age, gender, exercise capacity and the procedure performed are all independent predictors of mortality, the risk of operative death did not appear excessive in this fragile patient subset.

Adult↗

Pulmonary alveolar proteinosis in association with household exposure to fibrous insulation material.

We report the case of a 35-year-old woman who developed pulmonary alveolar proteinosis requiring multiple lavage treatments, in association with household exposure to ventilation system dust comprised at least partially by a cellulose fire-resistant fibrous insulation material. Scanning electron microscopy with energy-dispersive x-ray analysis documented the presence of spectral peaks consistent with the insulation material in transbronchial biopsy tissue. The patient showed symptomatic improvement once exposure to the insulation material had ceased. We believe that this case demonstrates an unusual association with pulmonary alveolar proteinosis. This case emphasizes the broad differential diagnosis for this histologic injury pattern and the need to thoroughly investigate environmental exposures in patients with unexplained pulmonary disease.

Adult↗

Current status of thoracoscopic lung volume reduction.

Surgical therapy has recently been reintroduced for the treatment of emphysema, and a number of investigators have used video-assisted thoracic surgical (VATS) techniques to accomplish lung volume reduction. The published reports differ with regard to patient selection, preoperative preparation, operative approach, and surgical technique. The results of these reports are reviewed and compared. Thoracoscopic lung volume reduction appears to be a useful part of the surgeon's armamentarium in managing patients with severe pulmonary emphysema.

Humans↗

Long-term survival after thoracoscopic lung volume reduction: a multiinstitutional review.

BACKGROUND: It has been suggested that bilateral thoracoscopic lung volume reduction (BTLVR) yields significantly better long-term survival than unilateral thoracoscopic lung volume reduction (UTLVR). METHODS: All perioperative data were collected at the time of the procedure. Follow-up data were obtained during office visits or by telephone. RESULTS: A total of 673 patients underwent thoracoscopic LVR: 343 had either simultaneous or staged BTLVR and 330, UTLVR. As of July 1998, follow-up was available on 667 (99%) of the 673 patients with a mean follow-up of 24.3 months. The patients in the BTLVR group were significantly younger (62.6+/-8.0 years versus 65.4+/-8.1 years; p < 0.0001), had a higher preoperative arterial oxygen tension (69.7+/-12 mm Hg versus 65.3+/-11 mm Hg; p < 0.0001), and had a superior preoperative 6-minute walk performance (279.9+/-93.6 m [933+/-312 feet] versus 244.5+/-101.4 m [815+/-338 feet] p < 0.0001). There was no difference in the operative mortality rate between the two groups (UTLVR, 5.1%, and BTLVR, 7%). Actuarial survival rates for the UTLVR group at 1 year, 2 years, and 3 years were 86%, 75%, and 69%, respectively versus 90%, 81%, and 74%, respectively, for the BTLVR group (p = not significant). CONCLUSIONS: Contrary to previous reports, survival after BTLVR was not superior to that after UTLVR even though the former group appeared to have a lower risk preoperatively because of younger age, higher arterial oxygen tension, more advantageous anatomy, and better functional status. Despite thoracoscopic LVR, the actuarial mortality rate approached 30% at 3 years, and this calls into question whether this procedure offers any survival advantage to patients with end-stage emphysema.

Aged↗

A role for nautilus in the differentiation of muscle precursors.

In the Drosophila embryo, nautilus is expressed in a subset of muscle precursors and differentiated fibers and is capable of inducing muscle-specific transcription, as well as myogenic transformation. In this study, we examine the consequences of nautilus loss-of-function on the development of the somatic musculature. Genetic and molecular characterization of two overlapping deficiencies, Df(3R)nau-9 and Df(3R)nau-11a4, revealed that both of these deficiencies remove the nautilus gene without affecting a common lethal complementation group. Individuals transheterozygous for these deficiencies survive to adulthood, indicating that nautilus is not an essential gene. These embryos are, however, missing a subset of muscle fibers, providing evidence that (1) some muscle loss can be tolerated throughout larval development and (2) nautilus does play a role in muscle development. Examination of muscle precursors in these embryos revealed that nautilus is not required for the formation of muscle precursors, but rather plays a role in their differentiation into mature muscle fibers. Thus, we suggest that nautilus functions in a subset of muscle precursors to implement their specific differentiation programs.

Animals↗

Endovascular stent grafts for aneurysmal and occlusive vascular disease.

BACKGROUND: This report details our initial experience with two types of endovascular grafts- one for the treatment of infrarenal abdominal aortic aneurysms and the other for the treatment of iliac artery occlusive disease. METHODS: An abdominal aortic aneurysm was repaired in 34 patients using 3 different types of Ancure endografts (Menlo Park, California). Control patients (n = 9) had a standard aneurysm repair. Patients with chronic lower extremity ischemia (n = 7) secondary to iliac artery occlusive disease were treated with a Hemobahn endograft (W. L. Gore & Associates, Flagstaff, Arizona). RESULTS: Ancure graft deployment was achieved in 33 of 34 (97.1%) patients. Perioperative mortality for the Ancure and control group patients was 2.9% and 0%, respectively. Periprosthetic leaks were identified within 48 hours of deployment in 6 (18.2%) Ancure graft patients. All but 2 of the leaks resolved on serial follow-up. Additional endovascular procedures were required in 11 (32.4%) Ancure graft patients at the initial procedure or during follow-up to correct graft or arterial stenoses. Patients treated with an endovascular graft had significantly less blood loss and shorter hospital stays than control group patients. For Hemobahn patients, the technical success for graft deployment was 100%. There were no perioperative deaths. The ankle/brachial index increased from a mean of 0.52 preoperatively to 0.86 postoperatively (P = 0.004). One patient required a Wallstent in follow-up to correct a graft wrinkle. Angiography at 6 months demonstrated mild intimal hyperplasia in the stent graft in 5 of 6 patients. CONCLUSIONS: These early results support the potential for endovascular grafts in the treatment of aneurysmal and occlusive vascular disease. Further modifications in the devices and deployment techniques are necessary to reduce the incidence of periprosthetic leaks, graft limb stenoses, and intimal hyperplasia.

Aged↗

Surface specific kinetics of lipid vesicle adsorption measured with a quartz crystal microbalance.

We have measured the kinetics of adsorption of small (12.5-nm radius) unilamellar vesicles onto SiO2, oxidized gold, and a self-assembled monolayer of methyl-terminated thiols, using a quartz crystal microbalance (QCM). Simultaneous measurements of the shift in resonant frequency and the change in energy dissipation as a function of time provide a simple way of characterizing the adsorption process. The measured parameters correspond, respectively, to adsorbed mass and to the mechanical properties of the adsorbed layer as it is formed. The adsorption kinetics are surface specific; different surfaces cause monolayer, bilayer, and intact vesicle adsorption. The formation of a lipid bilayer on SiO2 is a two-phase process in which adsorption of a layer of intact vesicles precedes the formation of the bilayer. This is, to our knowledge, the first direct evidence of intact vesicles as a precursor to bilayer formation on a planar substrate. On an oxidized gold surface, the vesicles adsorb intact. The intact adsorption of such small vesicles has not previously been demonstrated. Based on these results, we discuss the capacity of QCM measurements to provide information about the kinetics of formation and the properties of adsorbed layers.

Adsorption↗