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Biomedical subjects

B J Roth

Publications and source records attributed to B J Roth.

At least 55 records · Page 3Linked to original sources

Modeling of spreading cortical depression using a realistic head model.

Barkley and colleagues in 1990 reported large amplitude waves (LAWs) in time series magnetoencephalography (MEG) recordings from migraine patients and inferred that these LAWs arose from spreading cortical depression (SCD). SCD propagates slowly across the cortex in all species in which it has been observed. Previously, we reported that LAWs could be simulated and compared with the recorded signals using the four-sphere model (Wijesinghe and Tepley 1997). We showed that LAWs could arise from the propagation of SCD across a sulcus. In this paper, we model LAWs using a realistically shaped head model based on magnetic resonance images (MRI) (Roth et al. 1993). Simulated signals using this model are similar to the recorded signals. In this model, current dipoles represent the excitable neurons in the cortex and magnetic fields created by these individual dipoles are calculated. The magnetic field arising from the excited area of cortex is obtained by summing the fields due to these individual dipoles.

Brain Mapping↗

Electrical stimulation of cardiac tissue by a bipolar electrode in a conductive bath.

A three-dimensional (3-D) computer simulation of the electrical stimulation of passive cardiac tissue from a bipolar electrode placed within a conductive bath is presented. Through the bidomain model, the syncytial and anisotropic properties of cardiac tissue are taken into account; tissues with equal anisotropy and no transverse coupling are also considered. The membrane is represented by a capacitor and passive resistor in parallel. Located within an isotropic bath, the bipolar electrode is oriented either perpendicular or parallel to the tissue surface. For anisotropic tissue with a small cathode-tissue separation, the tissue surface is highly depolarized under the cathode with the depolarization persisting a considerable distance from the electrode in the transverse fiber direction. Adjacent to this region in the longitudinal direction, areas of hyperpolarization exist. At large distances from the cathode, the tissue surface is hyperpolarized in all directions when the electrode axis is perpendicular to the tissue. In the parallel case, surface depolarization creates buried regions of hyperpolarization. For the perpendicular configuration, the ratio of the steady-state maximum depolarization to steady-state maximum hyperpolarization, an estimate of the ratio of anodal to cathodal threshold, decreases rapidly with increasing cathode-tissue separation. In the parallel case, the depth of the conductive bath significantly affected the transmembrane potential distribution in the tissue. The use of a 3-D model more realistically simulates real-life electrical stimulation (such as stimulation with an implantable pacemaker) and provides insight into the effect of the volume conductor adjacent to the tissue.

Algorithms↗

Clinical stage I nonseminoma: surgery versus surveillance.

The presentation of nonseminomatous germ cell tumor confined clinically to the testicle (clinical stage I) is associated with a 30% incidence of occult retroperitoneal metastases. For decades, the standard of care in these patients has been a retroperitoneal lymph node dissection (RPLND), both for staging purposes, and, in the pre-modern chemotherapy era, it was performed with curative intent. The improvements in combination chemotherapy during the past 20 years have resulted in the cure of most individuals with small volume recurrent disease, calling into question the continued need for RPLND. The strategy of surveillance and chemotherapy for the 30% who relapse has gained acceptance, and, with meticulous follow-up, can result in the same excellent cure rates seen in patients treated with the surgical option. Although primary chemotherapy has also been suggested as a treatment option, the majority of patients will receive that chemotherapy unnecessarily, and cure rates with this strategy will not surpass those for surveillance or RPLND. Prognostic factors have been developed that can successfully identify a group of patients who are at an extremely low risk of relapse, thus potentially sparing these individuals any additional therapy. However, attempts to define a very high risk population have been unsuccessful to date, and we await the development of newer biologic markers able to predict which patients are most likely to have occult retroperitoneal disease and therefore most likely to benefit from additional "adjuvant" therapy post-orchiectomy.

Germinoma↗

Is pH paper an acceptable, low-cost alternative to the blood gas analyzer for determining pleural fluid pH?

BACKGROUND: Our laboratory uses pH paper rather than a blood gas analyzer to measure pleural fluid pH to decrease cost and avoid analyzer malfunction due to viscous fluids. METHODS: To compare these two methods of determining pleural fluid pH, 42 patients undergoing diagnostic or therapeutic thoracentesis had two 1-mL aliquots of pleural fluid anaerobically collected in a heparinized syringe and placed on ice. pH measurements were made using litmus paper (pHydron Vivid 6-8 brand litmus paper; MicroEssential Labs; Brooklyn, NY) and the model 995-Hb blood gas analyzer (AVL Instruments; Roswell, GA) within 1 h of collection. Agreement analysis was performed in three ways: on the entire group; in subcategories of complicated or uncomplicated parapneumonic effusions (<7.1, 7.1 to 7.3, >7.3); and in subcategories of poor prognosis or better prognosis malignant effusions(<7.3, >7.3). RESULTS: pH measured with pH paper was significantly more variable (SD=0.55, coefficient of variation [CV]=7.5%) than was pH measured with the blood gas analyzer (SD=0.11, CV=1.5%). There was no significant correlation between values obtained with the two techniques (r=-0.26, SD of the differences=0.59). Using the pH subcategories, there was 72% discordance in classification between litmus paper and arterial blood gas (ABG) determinations for patients with parapneumonic effusions. In patients with malignant effusions, there was 30% discordance. The pH values obtained by the ABG analyzer predicted tube thoracostomy 72% of the time, whereas the pH values obtained using pH paper were consistent only 36% of the time. CONCLUSION: Determination of pleural fluid pH using pH paper is unreliable and should not be considered an acceptable alternative to the blood gas analyzer. There is no need to determine pH on purulent samples. Hospital laboratories will be more likely to allow the use of the ABG analyzer on fluids other than blood if clinicians keep this in mind.

Blood Gas Analysis↗

Vinblastine, ifosfamide, and gallium nitrate--an active new regimen in patients with advanced carcinoma of the urothelium. A phase II trial of the Eastern Cooperative Oncology Group (E5892).

BACKGROUND: This study was conducted to assess the efficacy and toxicity of vinblastine, ifosfamide, and gallium nitrate (VIG) as first-line chemotherapy in patients with locally advanced or metastatic carcinoma of the urothelium. METHODS: Forty-five eligible patients were enrolled and stratified into good and poor risk groups. Poor risk was defined as age > or = 70 years, 1 functioning kidney, and prior adjuvant or neoadjuvant chemotherapy. Good risk patients were treated with vinblastine, 0.11 mg/kg, on Days 1 and 2; ifosfamide, 1.2 g/m2, on Days 1-5 with mesna uroprotection; and gallium nitrate, 300 mg/m2, as a continuous infusion on Days 1-5. Poor risk patients received similar therapy with doses decreased by 20% and administered over 4 days. All patients received recombinant human granulocyte-colony stimulating factor. Cycles were repeated at 21-day intervals until disease progression or to a maximum of 6 cycles. RESULTS: Twenty of 45 patients (44%; 95% confidence interval, 30-60%) demonstrated an objective response, with 6 patients (13%) achieving a complete clinical response. The median duration of response was 47 weeks and the median survival duration for all patients was 10 months. Hematologic toxicity was significant, with 28 patients and 31 patients experiencing Grade 3 or 4 leukopenia and anemia, respectively. Six patients had clinically significant cardiac events (primarily atrial arrhythmias). There were two early deaths that were possibly treatment related. CONCLUSIONS: VIG is an active regimen in patients with advanced urothelial carcinoma. Toxicity is significant but acceptable. Patients with significant cardiac disease (especially arrhythmias) should be treated with extra care. The 4-day regimen appears to have similar therapeutic efficacy with less toxicity.

Adenocarcinoma↗

Dipole localization in patients with epilepsy using the realistically shaped head model.

Dipole sources were localized in 3 patients with epilepsy using both the realistically shaped head model and the 3-sphere model. Interictal spikes were recorded from 63 closely spaced scalp electrodes. The scalp, skull, and brain surfaces were digitized from a MRI of each patient's head, and each surface was tessellated by 1600 triangles. Single dipole fits to the EEG were performed using both the realistically shaped head model and the 3-sphere model. The 2 models localized dipoles to positions that differed from one another by 1-3 cm. For dipoles localized to the temporal lobe, the most important difference between models was that the realistically shaped head model localized the dipole lower in the brain than the 3-sphere model. The realistically shaped head model was more in accordance with the ECoG findings than the 3-sphere model.

Adolescent↗

Postchemotherapy retroperitoneal lymph node dissection is effective therapy in selected patients with elevated tumor markers after primary chemotherapy alone.

OBJECTIVES: Elevated tumor markers after primary chemotherapy for metastatic testis cancer are usually an indication of persistent cancer. Subsequent treatment has usually been salvage chemotherapy. This article examines the possibility that selected patients can achieve long-term disease-free survival with surgery alone. METHODS: Using a computerized data base of 627 postinduction chemotherapy retroperitoneal lymph node dissections (PC-RPLND), 23 patients with elevated tumor markers who have undergone PC-RPLND after induction chemotherapy alone were identified. Of the 23 patients, 15 were considered candidates for salvage chemotherapy, but instead underwent salvage surgery. Case histories were reviewed to establish selection criteria for PC-RPLND. RESULTS: Eight patients originally presented as clinical Stage C, 6 as clinical Stage B-3, and 1 as clinical Stage B-2. All patients initially received cisplatin combination chemotherapy. Twelve patients had an elevated alpha-fetoprotein level and 3 patients had an elevated beta human chorionic gonadotropin level prior to PC-RPLND. Seven patients had rising markers at the time of PC-RPLND. Seven patients had teratoma only in their resected specimen and all have no evidence of disease (NED) at a median of 35 months. Two patients had necrosis only in their RPLND specimen and both are NED at 10 and 42 months. Six patients had cancer in their resected specimen and 2 are NED, 1 is alive with disease, and 3 are dead of disease. Five of the 6 patients with cancer in their resected specimen were the only patients who received postoperative chemotherapy. CONCLUSIONS: Some patients with modest elevations of tumor markers after induction chemotherapy may only have teratoma or necrosis in the postchemotherapy resected specimen. These patients (n = 9) remain continuously NED. Patients who undergo salvage surgery and have cancer in the resected specimen do less well, but selected patients can be cured with this modality and thus avoid the morbidity of salvage chemotherapy.

Adolescent↗

Bedside videoscopic placement of feeding tubes: development of fiberoptics through the tube.

OBJECTIVE: Transpyloric small intestine feeding tube placement can be difficult and tedious. Currently accepted techniques are associated with disadvantages and risk. The purpose of this study is to describe the development of a new technique: bedside videoscopic placement using fiberoptics through the tube. DESIGN: Prospective, descriptive case study. SETTING: Intensive care unit in a teaching hospital. PATIENTS: Subjects were divided into two groups: a) group 1: eight healthy volunteers (seven male, one female); b) group 2: nine critically ill patients (six male, three female; eight of these patients were intubated). INTERVENTIONS: Standard 12-Fr (4.0-mm) feeding tubes (n = 19) were placed. Two patients from group 2 had feeding tubes placed on two separate occasions. The feeding tubes were inserted by the oral (n = 8) or nasal (n = 11) route under direct vision, using a 6.7-Fr (2.2-mm) fiberoptic scope through the feeding tube. MEASUREMENTS AND MAIN RESULTS: We visualized enteric structures clearly through the feeding tube in all subjects and patients. Based on visual landmarks, we advanced the feeding tube through the pylorus and into the duodenum in all individuals. Transpyloric tube placement was confirmed videoscopically (n = 19) and radiographically (n = 18). In three subjects from group 1, the feeding tube entered the first part of the duodenum, while, in the remainder of the subjects, the tube passed into or beyond the second portion of the duodenum. In eight (73%) of 11 attempts on the nine critically ill patients from group 2, the feeding tubes were advanced to the distal duodenum or jejunum. The time required for placement in group 2 ranged from 2 to 43 mins (mean 18 +/- 12 [SD]). The feeding tubes remained in place 10 +/- 4 days and patients met their estimated caloric needs within 24 hrs. Residual volumes of nutrition in the small bowel were < 5 mL. There were no documented episodes of aspiration. CONCLUSION: This new technique has the potential for rapid, accurate, and safe feeding tube placement in patients requiring nutritional support.

Adult↗

Electrical conductivity values used with the bidomain model of cardiac tissue.

Electrical conductivities in the bidomain model of cardiac tissue are expressed as functions of four parameters. These expressions allow simulations to be performed using nominal, equal, and reciprocal anisotropy without introducing undesired effects, such as length constant variations. Relative values of the bidomain conductivities are estimated to be: sigma iL = 1, sigma iT = 0.1, sigma eL = 1, and sigma eT = 0.4.

Animals↗

Nonsustained reentry following successive stimulation of cardiac tissue through a unipolar electrode.

INTRODUCTION: Using numerical simulations, we predict that nonsustained reentry occurs following a strong, premature stimulus through a unipolar electrode. METHODS AND RESULTS: Our simulations were based on the bidomain model of cardiac tissue, and the active membrane properties were represented by the Beeler-Reuter model. An outwardly propagating wavefront was excited by an initial stimulus (S1). A second stimulus (S2) was then applied through the same electrode. Nonsustained reentry or reentrant-like behavior followed the S2 stimulus for both cathodal and anodal stimulation, and were associated with "break" stimulation but not with "make" stimulation. The direction of spiral-wave rotation was reversed when the polarity of the stimulus was reversed. These complex dynamics occur only for a narrow window of S1-S2 intervals. During anodal S2 stimulation, two different modes of reentry exist. Our simulations also explain the "no response" phenomenon. CONCLUSION: Our mathematical model predicts that both anodal and cathodal unipolar S2 stimulation results in reentry. This behavior arises from an interaction of virtual anodes and cathodes surrounding the stimulating electrode.

Computer Simulation↗

Cost- and risk-benefit considerations in the management of clinical stage I nonseminomatous testicular tumors.

BACKGROUND: The high curability of clinical stage I nonseminomatous germ cell tumors (NSGCTs) and the availability of equally effective management options (retroperitoneal lymph node dissection [RPLND] and surveillance) allows for treatment decisions based on secondary end points, including sort- and long-term toxicity and cost relative to benefit. The purpose of this study was to perform cost-benefit and risk-benefit analyses of management options in clinical stage I NSGCT using data from the literature and Indiana University. METHODS: The overall costs for 100 patients undergoing a primary RPLND were compared with the total costs of 100 patients managed by surveillance for clinical stage I disease. These two options were then analyzed in terms of survival, late relapse, acute and chronic toxicity (including fertility), and perioperative morbidity. RESULTS: The overall costs of these two approaches were essentially identical. The two options were similar in terms of survival, although RPLND demonstrated superiority in terms of fertility, toxicity, and late relapse. CONCLUSIONS: The choice of nerve-sparing RPLND or surveillance in clinical stage I NSGCT patient cannot be made on the basis of cost as a discriminator. Instead, the decision should be made based on patient desires, physician expertise, biological predictors, and short- and long-term toxicity.

Combined Modality Therapy↗

Strength-interval curves for cardiac tissue predicted using the bidomain model.

INTRODUCTION: Strength-interval curves are predicted for unipolar anodal and cathodal stimulation of cardiac muscle. METHODS AND RESULTS: Cardiac tissue is represented by the bidomain model, and the active properties of the membrane are described by the Beeler-Reuter model. Two successive stimuli (S1 and S2) are delivered through a single extracellular electrode. The S2 threshold is determined as a function of the S1-S2 interval, for anodal and cathodal S2 stimuli with 2-, 5-, 10-, and 20-msec durations. Each of the resulting cathodal and anodal strength-interval curves is divided into two parts: one section corresponding to make stimulation (long intervals) and the other section corresponding to break stimulation (short intervals). Generally, the cathodal strength-interval curves are decreasing functions of interval, except for an anomalous section of the 20-msec duration cathodal curve in the interval range from 310 to 318 msec. At short intervals, the anodal strength-interval curve contains a deep dip, which is more prominent for longer S2 durations. The cathodal threshold is less than the anodal threshold for all intervals except those corresponding to the end of the refractory period. CONCLUSION: The bidomain model predicts complex anodal and cathodal strength-interval curves, with the anodal curve containing a dip (supernormal stimulation). These results resemble the experimental observations of Dekker.

Action Potentials↗

Sulfasalazine pulmonary toxicity in ulcerative colitis mimicking clinical features of Wegener's granulomatosis.

The centrally accentuated antineutrophil cytoplasmic antibody test (c-ANCA) is widely regarded as a sensitive and specific marker for Wegener's granulomatosis (WG). There are increasing reports, however, of false-positive c-ANCAs, usually in the setting of other vasculidities. We report a case of a 27-year-old man with ulcerative colitis who developed pulmonary symptoms, peripheral nodular lung infiltrates, and an elevated c-ANCA suggesting WG. Chest CT and open lung biopsy specimens were consistent with WG. The symptoms and pulmonary infiltrates resolved after discontinuation of sulfasalazine therapy. The c-ANCA remained elevated due to the occurrence of false-positive values in ulcerative colitis. We conclude sulfasalazine toxicity can mimic clinical aspects of WG and that c-ANCA testing should be interpreted with caution in patients with ulcerative colitis.

Adult↗

Ifosfamide in the treatment of bladder cancer.

Although chemotherapy for advanced bladder cancer has historically been based on cisplatin-based combination regimens, the limitations of these regimens both in terms of efficacy and toxicity are now widely appreciated. In response to these limitations, other single agents have been studied, and a number have demonstrated significant activity, including ifosfamide. Older single-agent phase II trials of ifosfamide in previously untreated patients suggested a response rate as high as 40%, including objective responses in nontransitional histologies. More recently, the Eastern Cooperative Oncology Group has defined the response rate for ifosfamide in patients with one prior chemotherapy regimen to be 20%, with central nervous system toxicity, nephrotoxicity, and myelosuppression as the dose-limiting toxicities. Phase II trials of ifosfamide in combination with vinblastine and gallium nitrate have been completed, while others, including trials with paclitaxel alone or paclitaxel plus cisplatin, are ongoing. The precise role of ifosfamide in the therapy of advanced bladder cancer is in the process of being defined. However, the frequency of occult or clinically evident renal insufficiency in this patient population may limit ifosfamide's role in this disease.

Antineoplastic Agents↗

The role of ifosfamide in the treatment of testicular and urothelial malignancies.

The activity of ifosfamide in genitourinary malignancies has been documented in testicular cancer and bladder cancer. The use of ifosfamide in germ cell tumors spans 20 years and has involved three distinct clinical settings: as a component of salvage therapy in cisplatin-resistant or recurrent disease, as part of initial therapy for patients with poor-risk disease, and as part of an ablative regimen for patients undergoing high-dose therapy with stem cell support. The use of ifosfamide in salvage therapy is well established, with approximately 40% to 50% of patients treated with a second-line ifosfamide-based regimen expected to achieve a complete response; however, only 25% of these patients will be long-term disease-free survivors. The drug's incorporation into standard-dose first-line regimens in patients with poor-risk disease has failed to improve the efficacy of therapy over standard, less toxic regimens. The value of ifosfamide as a component of high-dose salvage therapy with stem cell support in patients with refractory disease or of its increasing use as first-line therapy in patients with poor-risk features remains to be demonstrated. In urothelial carcinoma, data on the activity of ifosfamide are more sparse. Older trials in previously untreated patients in Japan and Egypt suggest an overall response rate of 30% to 40%, while a recent Eastern Cooperative Oncology Group trial in patients with prior chemotherapy reported a response rate of 20%. Ifosfamide has therefore been identified as one of six new active agents in urothelial cancer, and trials of combination regimens including ifosfamide are under way. The vinblastine/ifosfamide/gallium nitrate (VIG) combination was tested in a pilot study at Indiana University with a 67% overall response rate and in a confirmatory Eastern Cooperative Oncology Group phase II trial with a 56% response rate. Trials of ifosfamide plus paclitaxel with or without cisplatin are ongoing, but the role of ifosfamide in the routine therapy of urothelial malignancies remains to be determined.

Antineoplastic Combined Chemotherapy Protocols↗