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Biomedical subjects

Joseph B Zwischenberger

Publications and source records attributed to Joseph B Zwischenberger.

At least 19 recordsLinked to original sources
PubMed2006

Hemodynamic analysis and design of a paracorporeal artificial lung device.

We have extended our model of the ovine pulmonary circulation to include a model of a paracorporeal artificial lung (AL) and its attachments to the natural pulmonary circulation in two configurations: in series and in parallel. Our model of the natural lung (NL) circulation is first shown to be in agreement with hemodynamic and input impedance data from the open literature. We then study design efficacy of the AL in terms of its housing and attachments. A sensitivity analysis of the modified pulmonary circulation model reveals that there are three key parameters: inlet graft length (IGL) and the compliances of the inlet compliance chamber (CC) and housing of the artificial lung. Based on literature reports, we assume the right ventricle is well-matched to the impedance of the natural pulmonary circulation and adjust the parameters of the modeled AL circuit to achieve the best least-squares fit to natural pulmonary input impedance data. Best-fit parameters produce impedance curves that fit natural impedance well, particularly below 3 Hz, where both compliance and graft length have their largest effects. Of these parameters, the impedance profile is most sensitive to IGL. However, the compliances are important, as well, particularly at low frequencies.

Animals↗
PubMed2006

Transthoracic closure of a postpneumonectomy bronchopleural fistula with coils and cyanoacrylate.

Standard treatment for persistent bronchopleural fistulas involves thoracotomy with primary closure and transposition of a vascularized muscle flap to the bronchial leak site. This major operation may be ineffective or medically contraindicated. We successfully treated 2 patients by insertion of coils and cyanoacrylate glue into and adjacent to the fistula of a postpneumonectomy bronchial stump with computed tomographic-guided transthoracic needle. The coils served as scaffolding for cyanoacrylate glue to control the bronchopleural fistula.

Adenocarcinoma↗
PubMed2006

Adjuncts to mechanical ventilation in ARDS.

Since its first description, acute respiratory distress syndrome has been characterized by abnormal physiologic and gas exchange properties of the lungs. Many adjunctive therapies have been developed to reduce the stresses of mechanical ventilation on already damaged lungs. We examined the mechanism of action and the latest clinical trial information of several adjunctive therapies including prone positioning, nitric oxide, extracorporeal membrane oxygenation, arterial venous carbon dioxide removal, and liquid ventilation. While all of these therapies have demonstrated short-term improvements in arterial blood gases and in the limitation of lung injury, none have shown an evidence-based survival benefit.

Carbon Dioxide↗
PubMed2006

Nonlinear multiscale wavelet diffusion for speckle suppression and edge enhancement in ultrasound images.

This paper introduces a novel nonlinear multiscale wavelet diffusion method for ultrasound speckle suppression and edge enhancement. This method is designed to utilize the favorable denoising properties of two frequently used techniques: the sparsity and multiresolution properties of the wavelet, and the iterative edge enhancement feature of nonlinear diffusion. With fully exploited knowledge of speckle image models, the edges of images are detected using normalized wavelet modulus. Relying on this feature, both the envelope-detected speckle image and the log-compressed ultrasonic image can be directly processed by the algorithm without need for additional preprocessing. Speckle is suppressed by employing the iterative multiscale diffusion on the wavelet coefficients. With a tuning diffusion threshold strategy, the proposed method can improve the image quality for both visualization and auto-segmentation applications. We validate our method using synthetic speckle images and real ultrasonic images. Performance improvement over other despeckling filters is quantified in terms of noise suppression and edge preservation indices.

Algorithms↗
PubMed2006

Artificial lung: progress and prototypes.

Lung disease is the fourth leading cause of death (one in seven deaths) in the USA. Acute respiratory distress syndrome (ARDS) affects approximately 150,000 patients a year in the USA, and an estimated 16 million Americans are afflicted with chronic lung disease, accounting for 100,000 deaths per year. Medical management is the standard of care for initial therapy, but is limited by the progression of disease. Chronic mechanical ventilation is readily available, but is cumbersome, expensive and often requires tracheotomy with loss of upper airway defense mechanisms and normal speech. Lung transplantation is an option for less than 1100 patients per year since demand has steadily outgrown supply. For the last 15 years, the authors' group has studied ARDS in order to develop viable alternative treatments. Both extracorporeal gas exchange techniques, including extracorporeal membrane oxygenation, extracorporeal and arteriovenous CO(2) removal, and intravenous oxygenation, aim to allow for a less injurious ventilatory strategy during lung recovery while maintaining near-normal arterial blood gases, but precludes ambulation. The paracorporeal artificial lung (PAL), however, redefines the treatment of both acute and chronic respiratory failure with the goal of ambulatory total respiratory support. PAL prototypes tested on both normal sheep and the absolute lethal dose smoke/burn-induced ARDS sheep model have demonstrated initial success in achieving total gas exchange. Still, clinical trials cannot begin until bio- and hemodynamic compatibility challenges are reconciled. The PAL initial design goals are for a short-term (weeks) bridge to recovery or transplant, but eventually, for long-term support (months).

Animals↗
PubMed2005

Pertussis with severe pulmonary hypertension and leukocytosis treated with extracorporeal membrane oxygenation.

Pertussis, or "whooping cough," is a highly communicable disease caused by the coccobacillus Bordetella pertussis. Pertussis remains one of the most common causes of death from infectious diseases worldwide. We describe a 5-week-old infant girl who presented with severe pertussis infection associated with extreme leukocytosis and required prolonged extracorporeal membrane oxygenation (ECMO). Nitric oxide therapy resolved the pulmonary hypertension, and she was successfully weaned from ECMO and discharged home after 3 months. We report successful application of ECMO for severe pertussis-induced respiratory failure despite multiple grave prognostic indicators (<1 year age, leukocytosis, pulmonary hypertension) and discuss the role of extracorporeal life support in treating pertussis.

Extracorporeal Membrane Oxygenation↗
PubMed2005

Synergistic interaction of hyperthermia and Gemcitabine in lung cancer.

Hyperthermia increases cytotoxicity of various antineoplastic agents. We investigated the cytotoxic effects of Gemcitabine and/or hyperthermia on BZR-T33 (human non-small-cell lung cancer cells) in vitro and in immune-suppressed athymic nude mice. Isobologram analysis of monolayer cell cultures for cytotoxicity demonstrates a synergistic interaction between hyperthermia and Gemcitabine. Clonogenic results show significant reductions in surviving fractions and colony size for both therapies; greatest reduction was for the combined therapy group. Using cell cycle analysis, hyperthermia enhanced Gemcitabine-induced G2-M arrest resulting in destruction of 3.5 log cells. Apoptotic studies (Annexin-V FITC staining) showed that hyperthermia augmented Gemcitabine-induced apoptosis. Transmission electron microscopy demonstrated pathology observed in cultures exposed to either therapy present in cultures exposed to both therapies. Studies in nude mice show that the combination therapy group had both an initial decrease in tumor size, and a significantly delayed rate of growth. Additionally, using tumor material harvested from nude mice two days after end to treatment reveals a significantly greater apoptotic index and significantly smaller mitotic index for the combined therapy group. Western blots of the same tumor material, showed that heat shock protein 70 was not significantly increased, however, caspase-3 activity of was significantly increased because of the combined therapy. In conclusion, the combined therapy is synergistic in effect because of hyperthermia enhancing Gemcitabine-induced apoptosis.

Antimetabolites, Antineoplastic↗
PubMed2005

A mechanism of hyperthermia-induced apoptosis in ras-transformed lung cells.

Lung cancer, the leading cause of cancer-related deaths in both men and women, is the consequence of disordered apoptosis, induction of which may have therapeutic utility. Hyperthermia has been identified as a stimulus for apoptosis. We investigated the mechanism of hyperthermia-induced cell death in ras-transformed lung cells. Effect of hyperthermia (43 degrees C for 180 min) was compared between two cell lines, an immortalized (sv-40) normal human bronchial epithelial (BEAS2-B) and its malignant transformed (H-ras transfected) counterpart (BZR-T33). Survival after hyperthermia: 7-d growth culture BEAS2-B, 1.03 +/- 0.007 and BZR-T33, 0.39 +/- 0.008 (P < 0.05); clonogenic assays BEAS2-B, 0.76 +/- 0.003 and BZR-T33, 0.41 +/- 0.004 (P < 0.05). Hoechst positive (apoptotic) cells: BEAS2-B, 11 +/- 3% and BZR-T33, 78 +/- 5% (P < 0.05). TUNEL, DNA fragmentation, and Annexin-V all corroborate this result. Western blot comparing the effect of hyperthermia in BZR-T33 cells to BEAS2-B cells revealed: TRAIL and FAS-L displayed significant increases (threefold and twofold, respectively); caspase-3 showed a decrease in uncleaved form and an increase in cleaved form, and a 50-fold increase in activity effectively blocked with the caspase-3 inhibitor DEVD-fmk; caspase-9 showed near depletion of uncleaved; poly (ADP-ribose) polymerase (PARP) degradation was clearly visible during heating. After hyperthermia, gene expression demonstrates a 5.7-fold increase in TRAIL and insignificant changes in tumor necrosis factor-alpha (TNF-alpha), FAS-L, and caspases 3, 8, 9 in transformed cells. Data demonstrated that hyperthermia induces apoptosis in transformed cells, and that apoptosis is mediated by caspase-3 as a result of activation of cell-death membrane receptors of the tumor-necrosis-factor family. In summary, these data suggest that hyperthermia could become an additional modality in the multidisciplinary approach to the treatment of lung cancer.

Apoptosis↗
PubMed2005

Perioperative management of special populations: the geriatric patient.

Americans over age 65 represent the fastest growing segment of the United States population. As a result, the demographic landscape of America is changing. Knowledge of aged physiology is necessary to construct a risk-benefit analysis tailored for each patient to improve perioperative outcomes and lower the morbidity and mortality rates among the elderly. Benefit estimates should account for a patient's life expectancy and quality of life before and after surgery. With aging, baseline functions of almost every organ system undergo progressive decline resulting in a decreased physiologic reserve and ability to compensate for stress. Pain control, postoperative cognitive dysfunction, end-of-life issues, and realistic expectations after surgery are paramount issues throughout the perioperative period.

Aged↗
PubMed2005

A model of the pacemaking neuron of the respiratory central pattern generator.

We have developed a model of the mammalian respiratory central pattern generator (rCPG) to mimic the salient characteristics of its constituent medullary neurons. This model is designed as a network of Hodgkin-Huxley-type medullary neurons driven by a pacemaking neuron from the pre-Bötzinger complex. Here, we present the results of our model of this pacemaking neuron, based on available voltage clamp data. Implications for the behavior of the rCPG are discussed.

Action Potentials↗
PubMed2005

A survey for pain and sedation medications in pediatric patients during extracorporeal membrane oxygenation.

Routine administration of large amounts of pain and sedative medication is common to critically ill pediatric patients undergoing extracorporeal membrane oxygenation (ECMO) for cardiopulmonary failure. It has been our experience that pediatric patients are the most difficult age group in which to achieve an ideal pain and sedative control due to the narrow margin of safety. The purpose of this study was to determine the general practice guideline used for pain and anxiolytic pharmacotherapy for pediatric patients at ECMO centers. We sent a survey questionnaire to all ECMO centers in the USA that treat pediatric respiratory failure patients. Of the 46 responding centers (including telephone follow-ups), 37 (80%) centers had an active pediatric ECMO programs for patients with severe respiratory failure. Fentanyl was the most commonly used pain medication and continuous infusion, administered directly to the patient, was preferred. Subjective effectiveness of various pharmacological agents was variable without clear consensus; however, midazolam was considered to be the most effective agent used.

Anesthetics↗
PubMed2005

Seventy-two hour gas exchange performance and hemodynamic properties of NOVALUNG iLA as a gas exchanger for arteriovenous carbon dioxide removal.

OBJECTIVE: Acute respiratory failure is complicated by acidosis and altered end-organ perfusion. NOVA-LUNG iLA is an interventional lung assist (ILA) device for arteriovenous carbon dioxide removal (AVCO2R). The present study was conducted to evaluate the device for short-term CO2 removal performance and hemodynamic response. METHODS: Six adult sheep received cannulation of the jugular vein and carotid artery. The ILA-AVCO2R circuit was placed on the sheep for 72 hours. Hemodynamics and PaCO2 were measured; CO2 removal was calculated while varying sweep gas flow rates (Qg), device blood flow rates (Qb), and PaCO2. RESULTS: Hemodynamic variables remained normal throughout the 72 hour study. CO2 removal increased with increases in Qg or Qb. Mean CO2 removal was 119.3 ml/min for Qb 1 L/ min, Qg 5 L/min, and PaCO2 40-50 mmHg. PaCO2 was directly proportional to CO2 clearance (R=0.72, p <0.001). CONCLUSION: NOVALUNG iLA can provide near total CO2 removal with Qb 1-2 L/min, Qg 5 L/min, and minimal flow resistance (3.88+/-0.82 mmHg/L/min). PaCO2 correlates with CO2 removal and is dependent on Qb and Qg.

Animals↗
PubMed2004

Percutaneous venovenous perfusion-induced systemic hyperthermia for lung cancer: a phase I safety study.

BACKGROUND: Veno-venous perfusion-induced systemic hyperthermia (VV-PISH) homogeneously raises core body temperature potentially improving outcomes from metastatic lung cancer. METHODS: Patients (n = 10) with stage IV lung cancer, received VV-PISH (>or= 42 degrees C to or= 70. Time to target temperature was 47 +/- 2 minutes, as electrolytes remained normal, without patient or circuit complications. Extubation occurred between 6 and 18 hours. Hospital stay was 4.6 +/- 1.1 days; median length-of-survival after hyperthermia was 271 days. For concurrent controls (n = 16, stage IV lung cancer), median length-of-survival from time of diagnosis to death was 96 days, but for the VV-PISH patients it was significantly longer at 450 days (p < 0.05). All patients returned to pretreatment status following treatment and died from progression of lung cancer. CONCLUSIONS: Venovenous perfusion-induced systemic hyperthermia is safe, technically feasible, and achieves target temperature. Survival may be enhanced in stage IV lung cancer.

Adenocarcinoma↗