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Biomedical subjects

Dan M Meyer

Publications and source records attributed to Dan M Meyer.

13 recordsLinked to original sources

Effects of early steroid withdrawal after heart transplantation.

BACKGROUND: Managing immunosuppression is a significant aspect of posttransplantation patient care. Previously, our institution reported that prednisone could be withdrawn in cardiac allograft recipients without jeopardizing midterm survival. We returned to this group of patients to investigate the long-term effects of our steroid taper protocol. METHODS: We reviewed the records of 162 consecutive cardiac transplant recipients from our institution. Patients who underwent transplantation between 1988 and 1990 were treated with traditional triple-therapy immunosuppression (cyclosporine, azathioprine, and prednisone). Beginning June 1990, we instituted a protocol of early steroid taper with discontinuation by 6 months after transplant. The two groups were comparable with respect to age, sex, ethnicity, cause of heart failure, ischemic time, body mass index, and creatinine at the time of transplantation. RESULTS: Fifty-seven percent of the patients in the early steroid taper group were successfully withdrawn from steroids at 6 months after transplantation. This group had a decreased freedom from and increased frequency of acute rejection (p < 0.01 for each) when compared with the traditional therapy group. There was, however, no difference in freedom from posttransplant coronary artery disease (p = 0.53). The early steroid taper group enjoyed an increased freedom from malignancy (p = 0.01) and trended toward a decreased frequency of infection (p = 0.10) and improved survival (p = 0.06). CONCLUSIONS: Steroid withdrawal is possible in 57% of patients at 6 months after transplantation. The institution of an early steroid taper protocol improves the overall freedom from malignancies and may decrease the frequency of infection and prolong overall survival without increasing the risk of posttransplant coronary artery disease.

Adult↗

Lung preservation solution substrate composition affects rat lung oxidative metabolism during hypothermic storage.

Lungs harvested for transplantation utilize oxygen after procurement. We investigated the effects of storage solution substrate composition on pulmonary oxidative metabolism and energetics during the preservation interval. Rat lungs were harvested and stored at 10 degrees C in low-potassium dextran (LPD) solution. Groups of lungs were preserved with preservation solution containing 5mM carbon-13 ((13)C) labeled glucose or increasing concentrations of (13)C labeled pyruvate. Additional groups of rat lungs were studied with dichloroacetate (DCA) added to the pyruvate-modified preservation solutions. Oxidative metabolism (measured by (13)C-enrichment of glutamate) and adenine nucleotide levels were quantified. Increasing preservation solution pyruvate concentration augmented glutamate (13)C-enrichment up to a concentration of 32mM pyruvate. DCA further stimulated oxidative metabolism only at lower concentrations of pyruvate (4 and 8mM). ATP and ADP were not different among groups, but AMP levels were higher in the glucose group. These data suggest that altering the substrate composition of the preservation solution influences lung metabolism during allograft preservation for transplantation.

Adenosine Triphosphate↗

Characterizing lung metabolism with carbon-13 magnetic resonance spectroscopy in a small-animal model: evidence of gluconeogenesis during hypothermic storage.

Experimental evidence suggests storing lungs inflated with oxygen and with oxidizable substrate improves results of lung transplantation. Glucose is included in the low-potassium-dextran (LPD) solution Perfadex to achieve this goal. The authors hypothesized that other substrates might be more effective. Rat lungs were stored for 6 or 24 hr in LPD solution with the following carbon-13--labeled substrates: 5 mM glucose (Perfadex group), 32 mM pyruvate (pyruvate group), or both (combination group). Metabolism was assessed by magnetic resonance spectroscopy. Small amounts of exogenous glucose were oxidized in the Perfadex group. In contrast, exogenous pyruvate was the major substrate oxidized in the pyruvate and combination groups (P<0.01 vs. Perfadex). Carbon-13--labeled glucose and glycogen were detected in the pyruvate group, suggesting that gluconeogenesis and glycogen synthesis occur in glucose-deprived lungs. Lungs for transplantation metabolize substrates through both anabolic and catabolic pathways. These reactions may be important in designing improved solutions for lung preservation.

Animals↗

Health insurance and cardiac transplantation: a call for reform.

Cardiac transplantation is an accepted therapy for patients with end-stage heart failure (ESHF). Presently in the U.S., patients with ESHF need to have health insurance or another funding source to be considered eligible for cardiac transplantation. Whether it is appropriate to exclude potential recipients solely due to lack of finances has received considerable interest including being the subject of a recent major motion picture (John Q, New Line Cinema, 2002). However, one important aspect of this debate has been underappreciated and insufficiently addressed. Specifically, organ donation does not require the donor to have health insurance. Thus, individuals donate their hearts although they themselves would not have been eligible to receive a transplant had they needed one. By querying Siminoff's National Study of Family Consent to Organ Donation database, we find that this situation is not uncommon as approximately 23% of organ donors are uninsured. Herein we also discuss how the funding requirement for cardiac transplantation has been addressed by the federal government in the past, its implications on the organ donor consent process, and its potential impact on organ donation rates. We call for a government-sponsored, multidisciplinary task force to address this situation in hopes of remedying the inequities in the present system of organ allocation.

Health Care Reform↗

Impact of recipient age and procedure type on survival after lung transplantation for pulmonary fibrosis.

BACKGROUND: The decision to perform single-lung (SLT) or bilateral sequential lung (BSLT) transplantation in patients with pulmonary fibrosis is controversial. Some centers use recipient age (<50 years) as a criterion to select BSLT over SLT, but the rationale for this approach is not well established. METHODS: Eight hundred twenty-one patients (636 SLT, 185 BSLT), aged 30 to 69 years, who were recipients of transplants for pulmonary fibrosis in the United States between 1994 and 2000 were reported to the United Network for Organ Sharing. Survival was compared by procedure type within three age groups (30 to 49 years, 50 to 59 years, and 60 to 69 years) using the Kaplan-Meier method. Multivariate logistic regression analysis was used to calculate risk-adjusted mortality within 1-month after transplantation, and proportional hazards regression was used to calculate risk-adjusted mortality after 1 month. RESULTS: Early (1-month) and late (3-year) survival in recipients aged 30 to 49 years was significantly better with SLT than BSLT (early, 90.9% versus 77.1%; late, 63.8% versus 46.2%, respectively; p = 0.02). Survival was also significantly better with SLT than BSLT at these time points in those patients aged 50 to 59 years (early, 89.5% versus 81.7%; late, 53.6% versus 46.7%, respectively; p = 0.03). When posttransplant survival was reanalyzed contingent on survival to 1 month, no significant difference in survival by procedure type (SLT versus BSLT) was detected for any age group. Multivariate analysis of survival, adjusted for other known risk factors, as well as propensity analysis, yielded similar results. CONCLUSIONS: Patients younger than 60 years of age who were recipients of transplants for pulmonary fibrosis appear to have better survival with SLT than with BSLT. Although the basis for this observation is unclear, events occurring in the early period (first month) after transplantation may play a role. Further studies will be needed, but these data do not appear to support the preferential use of BSLT for younger patients with pulmonary fibrosis.

Adult↗

Pyruvate-modified perfadex improves lung function after long-term hypothermic storage.

BACKGROUND: Lungs harvested for transplantation are stored while inflated with oxygen, which can serve to support oxidative metabolism. However, strategies aimed at increasing graft metabolism during storage have received little attention. In this study, we added pyruvate to the preservation solution Perfadex and measured the effects on oxidative metabolism and reperfusion lung function. METHODS: Rat lungs were stored for 6 and 24 hours in low-potassium dextran solution at 10 degrees C containing either 5 mmol/liter uniformly carbon-13 (U-(13)C) labeled glucose (Perfadex), 32 mmol/liter 3-(13)C pyruvate (pyruvate), or both (combined). Oxidation of exogenous substrates was measured as the incorporation of (13)C into tricarboxylic acid cycle intermediates by magnetic resonance spectroscopy. Additional groups of lungs with each substrate modification were preserved for 6 or 24 hours and then reperfused. RESULTS: Enrichment of tricarboxylic acid cycle intermediates was low in the Perfadex group (9% at 6 hours and 32% at 24 hours of storage, respectively). In contrast, enrichment was significantly increased in both the pyruvate group (50% and 59%, respectively) and combined group (39% and 54%, respectively) compared with the Perfadex group (p<0.01). Graft function was excellent after 6-hour storage in all groups. All lungs stored for 24 hours exhibited inferior lung function, but oxygenation, pulmonary artery pressures, and airway pressures in the combined group were significantly improved compared with the Perfadex group (p<0.05). CONCLUSIONS: Preservation solution substrate composition influences graft metabolism during storage. The addition of pyruvate to Perfadex increases metabolism during storage and improves reperfusion lung function.

Animals↗

Routine computed tomography screening of the chest in high-risk cardiac transplant recipients may improve survival.

BACKGROUND: Multiple studies have demonstrated an increased incidence of lung cancer in the heart transplant population. We reviewed our cardiac transplantation experience with respect to the development of bronchogenic carcinoma and explored the role of routine chest computed tomography (CT) in its surveillance. METHODS: We performed a review of our cardiac transplantation experience, highlighting the incidence of lung cancer, and we analyzed our recent experience with screening chest CT in lung cancer surveillance in this patient group. RESULTS: Eighteen patients developed 20 cases of bronchogenic carcinoma for an incidence of 6.83%. In 10 cases, the patients underwent surgical resection; however, in the remaining cases, the patients were either treated with chemotherapy and/or radiation or they died before initiation of therapy. The actuarial 1-, 2- and 5-year overall survival rates were 49%, 29% and 13%, respectively. The median survival of patients who underwent surgical resection was 28 months (3 to 85 months), whereas the median survival of patients who were either ineligible for surgery or died before initiation of treatment was only 1 month (1 to 13 months). All patients diagnosed with lung cancer by chest CT underwent surgical resection; however, only 37.5% of patients diagnosed with lung cancer by chest X-ray were found at an appropriate stage for resection (p = 0.025). CONCLUSIONS: Cardiac transplant recipients have a significant risk of developing bronchogenic carcinoma. Routine chest CT screening in high-risk patients may enable clinicians to identify disease earlier, which is essential for the option of surgical resection and, therefore, prolonged survival.

Adolescent↗

Contemporary assessment of laryngotracheal trauma.

OBJECTIVES: Laryngotracheal trauma is a rare and potentially deadly spectrum of injuries. We sought to characterize the contemporary mechanisms, diagnostic modalities, and outcomes common in laryngotracheal trauma today. METHODS: We performed a retrospective analysis of all laryngotracheal trauma cases at 2 major metropolitan hospitals between 1996 and 2004, detailing mechanisms, associated injuries, diagnostic modalities, and outcomes of laryngotracheal trauma. RESULTS: We identified 71 patients with a mean age of 32.8 +/- 13.3 years (range, 15-71 years). In our series penetrating trauma was the cause in 73.2% of patients; however, blunt trauma had a significantly higher mortality (63.2% vs 13.5%, respectively; P < .0001). Blunt mechanisms involved older patients (38.5 +/- 15.2 years vs 30.1 +/- 11.9 years, P = .017), and these patients were more likely to require emergency airways than those with penetrating trauma (78.9% vs 46.2%, P = .017). The requirement of an emergency airway was an independent predictor of mortality (P = .0066). CONCLUSION: Laryngotracheal trauma is a deadly spectrum of injuries with a mortality of 26.8%. Blunt mechanisms are decreasing in frequency. This might reflect improvements in automobile safety. Additionally, violent crime is on the increase, producing penetrating injuries with increasing frequency. The most fundamental intervention for patients with laryngotracheal injury is airway control. Either routine intubation or a tracheostomy can secure the airway. Blunt trauma and the requirement of an emergency airway are independent predictors of mortality. Laryngotracheal trauma requires prompt recognition, airway protection, and skillful management to lessen the mortality of this deadly spectrum of injuries.

Adolescent↗

Improved pain management outcomes with continuous infusion of a local anesthetic after thoracotomy.

OBJECTIVE: We sought to determine the effectiveness of an incisional infusion of local anesthetics through a continuous-infusion elastomeric pump for the management of postoperative pain after thoracotomy. METHODS: We performed a retrospective comparative analysis of 110 patients undergoing thoracotomies between November 1999 and March 2003. Postoperative pain management with a continuous-infusion elastomeric pump providing local anesthetic into the incisional area was compared with a single-shot epidural in combination with continuous local anesthetic infusion and continuous thoracic epidural infusion. Data sources were reviewed for mean narcotic use, pain score, and complications. RESULTS: After thoracotomy procedures, 38 patients received the ON-Q Pain Relief System (I-Flow Corp, Lake Forest, Calif), 32 received the ON-Q device and single-shot epidural infusion, and 40 received continuous epidural infusion. Demographic attributes, including age, body mass index, and sex were similar between the groups. Preoperative American Society of Anesthesiologists status was significantly higher in the ON-Q group compared with that in the other groups (P = .02). Narcotic use and pain scores were significantly reduced in the ON-Q group compared with that in the epidural group at all time points (P < .001). There were no wound-healing complications or infections associated with the use of the pump. CONCLUSION: A continuous infusion of 0.25% bupivacaine at 4 mL/h through the ON-Q elastomeric infusion pump is a safe and effective adjunct in postoperative pain management after thoracotomy. The use of the ON-Q Pain Relief System results in decreased narcotic use and lower pain scores compared with continuous epidural infusion.

Adult↗

Perfusion preservation maintains myocardial ATP levels and reduces apoptosis in an ex vivo rat heart transplantation model.

BACKGROUND: Machine perfusion preservation improves reperfusion function of many solid organs, compared with conventional storage, but has received limited clinical attention in preserving hearts for transplantation. We evaluated representative extracellular (Celsior) and intracellular (University of Wisconsion) storage solutions using static and perfusion protective strategies over a clinically relevant preservation period. METHODS: Rat hearts were preserved for 200 minutes by either static storage or perfusion preservation in Celsior or University of Wisconsin solutions. Three conditions were studied: conventional static storage; static storage using either solution with 5.5 mmol/L glucose added; and perfusion preservation using either solution with 5.5 mmol/L glucose added. Glucose was provided as U-13C-labeled glucose, and glycolysis and oxidative metabolism during preservation were quantified from incorporation of (13)C into glycolytic and tricarboxylic acid cycle intermediates. Adenosine triphosphate levels after preservation, and apoptosis and cardiac function after reperfusion were measured. RESULTS: Both perfusion preservation groups had higher myocardial oxygen consumption during storage and better early graft function, compared with static preservation groups (P < .05). Adenosine triphosphate levels were higher after storage in the perfusion groups (P < .01). Apoptosis was reduced in the perfusion groups (P < .01). Comparing perfusion groups, hearts preserved with Celsior had higher myocardial oxygen consumption and glucose utilization during perfusion storage and exhibited decreased reperfusion coronary vascular resistance and myocardial water content, compared with the UW perfusion group (P < .05). CONCLUSIONS: Perfusion preservation results in greater metabolism during storage and superior cardiac function with improved myocyte survival, compared with static storage. Extracellular preservation solutions appear more effective for perfusion preservation, possibly by augmenting cellular metabolism.

Adenosine Triphosphate↗

Palmar skin blood flow and temperature responses throughout endoscopic sympathectomy.

Thoracic surgical sympathectomy is often performed to treat primary palmar and axillary hyperhidrosis. An increase in palmar skin temperature is frequently used to identify the success of the procedure. Because changes in palmar skin temperature occur secondary to changes in skin blood flow, the objective of this study was to test the hypothesis that monitoring palmar skin blood flow would provide greater temporal resolution relative to monitoring palmar skin temperature. In 11 patients with palmar and/or axillary hyperhidrosis, we measured palmar skin temperature and blood flow (via laser Doppler flowmetry) throughout the sympathectomy procedure. Five minutes after the initial cautery, skin blood flow increased from 48 +/- 7 perfusion units to 121 +/- 17 perfusion units (P <0.001), whereas no significant change in temperature was observed (31.0 degrees C +/- 0.5 degrees C to 31.3 degrees C +/- 0.5 degrees C; P >0.05). The time required to reach peak skin blood flow (22 +/- 3 min) was significantly less than the time required to reach peak skin temperature (34 +/- 0.3 min; P <0.001). Finally at 5, 10, and 15 min after the initial cautery, skin blood flow increased to a larger percentage of the total increase in skin blood flow relative skin temperature (all P <0.006). These data suggest that monitoring skin blood flow provides greater temporal resolution when compared with monitoring skin temperature during thoracic sympathectomy. However, the initial cautery of the parietal pleura over the ganglion may result in increases in skin blood flow before physical disruption of the ganglion. This occurrence may limit the utility of skin blood-flow measurements in identifying the success of the procedure.

Adult↗

Thoracoscopic sympathectomy for hyperhidrosis: indications and results.

BACKGROUND: Hyperhidrosis can cause significant professional and social handicaps. Although treatments such as oral medication, botox, and iontophoresis are available, surgical sympathectomy is being increasingly utilized. METHODS: Between January 1997 and December 2002, 180 patients with palmar, axillary, facial, or plantar hyperhidrosis underwent a thoracoscopic sympathectomy. Surgical technique evolved during our study period and included excision of the sympathetic ganglia at T(2), T(3), or T(4) depending on the location of the sweating using monopolar cautery. RESULTS: Patient demographics included 33% males (59/180) and 67% females (121/180), with a mean age of 29.2 years old (range 12 to 76 years old). Ethnic origin was 67% white (122/180), 19% Asian (34/180), 8% Black (14/180), and 6% Hispanic (10/180). Positive family history of hyperhidrosis was noted in 57%. Preoperatively, 49% patients (86/180) had palmar sweating only, 7% patients (12/180) axillary only, 24% patients (43/180) palmar and axillary, 16% patients (28/180) face/scalp only, and 7% patients (11/180) all of the above; additionally 69% patients (125/180) had plantar hyperhidrosis. All procedures were performed through 3-mm and 5-mm ports, and 98% (177/180) were completed as an outpatient procedure. Complications included a mild temporary Horner's Syndrome (n = 1; 0.5%), air leak requiring chest drainage (n = 9; 5%), and bleeding (n = 3; 1.6%) requiring thoracoscopic reexploration (n = 1) and chest drainage (n = 2). Success rates were palmar 100% (109/109), axillary 98% (48/49), and face/scalp 93% (26/28). Plantar hyperhidrosis responded with improvement in 82% (72/88) of all patients. Seventy-eight percent patients (96/123) experienced compensatory hyperhidrosis, usually affecting the stomach, chest, back, and neck. Overall satisfaction was 94% (139/148). CONCLUSIONS: Thoracoscopic sympathectomy is a safe and effective outpatient method for managing hyperhidrosis. Although overall satisfaction is high, patients should be fully informed about the potential for compensatory sweating.

Adolescent↗