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Biomedical subjects

B J Roth

Publications and source records attributed to B J Roth.

At least 91 records · Page 5Linked to original sources
PubMed1994

Electrical stimulation of cardiac tissue: a bidomain model with active membrane properties.

Numerical calculations simulated the response of cardiac muscle to stimulation by electrical current. The bidomain model with unequal anisotropy ratios represented the tissue, and parallel leak and active sodium channels represented the membrane conductance. The speed of the wavefront was faster in the direction parallel to the myocardial fibers than in the direction perpendicular to them. However, for cathodal stimulation well above threshold, the wavefront originated farther from the cathode in the direction perpendicular to the myocardial fibers than in the direction parallel to them, consistent with observations of a dog-bone-shaped virtual cathode made by Wikswo et al., Circ. Res. 68:513-530, 1991. The model showed that the virtual cathode size and shape were dependent upon both membrane and tissue conductivities. Increasing the peak sodium conductance or reducing the transverse intracellular conductivity accentuated the dog-bone shape, while the opposite change caused the virtual cathode to become more elliptical, with the major axis of the ellipse transverse to the fiber direction. A cathodal stimulus created regions of hyperpolarization that slowed conduction of the wavefront propagating parallel to the fibers. An anodal stimulus evoked a wavefront with a complex shape; activation originated from two depolarized regions 1 to 2 mm from the stimulus site along the fiber direction. The threshold current strength (0.5 ms duration pulse) for a cathodal stimulus was 0.048 mA, and for an anodal stimulus was 0.67 mA. When the model was modified to simulate the effect of electropermeabilization, which may be present when the transmembrane potential reaches very large values near the stimulating electrode, our qualitative conclusions remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

A theoretical model for magneto-acoustic imaging of bioelectric currents.

A theoretical model of magneto-acoustic current imaging is derived, based on fundamental equations of continuum mechanics and electromagnetism. In electrically active tissue, the interaction between an applied magnetic field, B, and action currents, J, creates a pressure distribution. In the near field limit, this pressure obeys Poisson's equation, with a source term (delta x J).B. The displacement and pressure fields are calculated for a dipole (q), oriented either parallel or perpendicular to the applied magnetic field (B), at the center of an elastic, conducting sphere (radius a, shear modulus G). Surface displacements are on the order of qB/(4 pi Ga), which is about 1 nm for typical biological parameters. If the applied magnetic field is changing with time, eddy currents induced in the tissue may be larger than the action currents themselves. The frequency of the pressure and displacement arising from these eddy currents, however, is twice the frequency of the applied magnetic field, so it may be possible to eliminate this artifact by filtering or lock-in techniques. Magneto-acoustic and biomagnetic measurements both image delta x J in a similar way, although magneto-acoustic current imaging has the disadvantage that acoustic properties vary among tissues to a greater degree than do magnetic properties.

Acoustics↗
PubMed1994

Significant activity of paclitaxel in advanced transitional-cell carcinoma of the urothelium: a phase II trial of the Eastern Cooperative Oncology Group.

PURPOSE: To assess the efficacy and toxicity of single-agent paclitaxel as first-line chemotherapy in patients with locally advanced or metastatic transitional-cell carcinoma of the urothelium. PATIENTS AND METHODS: Twenty-six eligible patients were enrolled onto this cooperative group study and treated with paclitaxel at a dosage of 250 mg/m2 by 24-hour continuous infusion every 21 days until progression or patient intolerance. All patients received recombinant human granulocyte colony-stimulating factor (rhG-CSF) at 5 micrograms/kg/d for at least 10 days during each cycle. RESULTS: Eleven of 26 patients (42%; 95% confidence interval [CI], 23% to 63%) demonstrated an objective response, with seven achieving a complete clinical response (CR) (27%; 95% CI, 12% to 48%) and four (15%) a partial response (PR). The median duration of response in the 11 responders is 7+ months (range, 4 to 17), with five responders (four CRs, one PR) remaining progression-free at 5, 6, 10, 12, and 16 months from the start of therapy. The estimated median survival duration for all patients is 8.4 months. Hematologic toxicity consisted of anemia (12% grade 3) and granulocytopenia (4% grade 3, 19% grade 4), with two patients developing granulocytopenic fevers. Nonhematologic toxicity included grade 3 mucositis in 11%, grade 3 neuropathy in 11%, and grade 4 diarrhea in 4%. CONCLUSION: Single-agent paclitaxel at this dosage and schedule is one of the most active single agents in previously untreated patients with advanced urothelial carcinoma, and is well tolerated by this patient population when given with hematopoetic growth factor support.

Adult↗
PubMed1994

Phase II trial of vinblastine, ifosfamide, and gallium combination chemotherapy in metastatic urothelial carcinoma.

PURPOSE: Phase II trial in metastatic urothelial carcinoma using a novel combination chemotherapy regimen consisting of vinblastine, ifosfamide, and gallium nitrate (VIG). PATIENTS AND METHODS: Twenty-seven patients were entered onto this phase II study. Dosages were vinblastine 0.11 mg/kg days 1 and 2, ifosfamide 1.2 gm/m2 days 1 through 5 (with mesna), and gallium 300 mg/m2 as a 24-hour infusion days 1 through 5, with calcitriol (1,25-dihydroxycholecalciferol) 0.5 microgram/d orally starting 3 days before each course (except the first) and continuing throughout gallium administration, plus recombinant human granulocyte colony-stimulating factor (rhG-CSF) (filgrastim) 5 micrograms/kg/d days 7 through 16. Courses were repeated every 21 days for a maximum of six cycles. RESULTS: The major toxicity was granulocytopenia. Fifteen patients (55.6%) had grade 3 or 4 granulocytopenia, including eight patients with granulocytopenic fevers. Eleven patients had grade 3 or 4 anemia and four had grade 3 or 4 nephrotoxicity, which was reversible. Other grade 3 to 4 toxicities included hypocalcemia (three patients), thrombocytopenia (two), encephalopathy (one), and temporary blindness (one). There was one treatment-related mortality. Toxicity was more severe in patients older than 70 years and those with prior pelvic irradiation, prior cisplatin adjuvant therapy, or prior nephrectomy. We now decrease VIG by 20% in this patient population. Eighteen patients (67%) achieved an objective response, including 11 (41%) who attained a disease-free status (five with VIG alone and six with subsequent surgery). Median duration of remission was 20 weeks, with five patients still in remission at 22+ to 56+ weeks. CONCLUSION: VIG combination chemotherapy is very active in patients with metastatic urothelial carcinoma. Toxicity was significant but manageable.

Adult↗
PubMed1994

Incidence of neutropenic fever in patients treated with standard-dose combination chemotherapy for small-cell lung cancer and the cost impact of treatment with granulocyte colony-stimulating factor.

PURPOSE: We sought to determine the incidence of neutropenic fever associated with the use of standard-dose combination chemotherapy for small-cell lung cancer (SCLC) and to use these data as a template to analyze the costs and benefits of the routine use of granulocyte colony-stimulating factor (G-CSF). PATIENTS AND METHODS: We retrospectively reviewed records of 137 consecutive, unselected patients with SCLC treated with combination chemotherapy from January 1987 to March 1992. Admission criteria for neutropenic fever were temperature > or = 38.5 degrees C and an absolute neutrophil count < or = 500/microL. Neutropenic fevers were managed with a 25% dose reduction of the myelosuppressive drugs in subsequent cycles. Charge estimates for hospitalization ($1,244 per day) and G-CSF use ($2,027 per course) were estimated by reviewing charges to patients at Indiana University hospitalized for neutropenic fever or treated with outpatient G-CSF. We imposed assumptions from the Neupogen (filgrastim; Amgen Inc, Thousand Oaks, CA) licensing trial regarding the effectiveness of G-CSF and the Indiana University charge estimates on three models of G-CSF use: (1) preemptive--with all courses of chemotherapy, (2) reactive--with all cycles of chemotherapy following a neutropenic fever, and (3) dose reduction only (no G-CSF)--to derive charge estimates for G-CSF use. RESULTS: Records of 137 patients with SCLC were identified and reviewed. The incidence of neutropenic fever was 12% in the first cycle of chemotherapy, and 18% overall, compared with the placebo- and G-CSF-treated arms of the Neupogen licensing trial, in which the incidence of neutropenic fever was 77% and 40%, respectively. Other therapeutic outcomes, such as neutropenic septic deaths, response rates, and survival, were comparable. We derived the following charge estimates for the three models of G-CSF: (1) preemptive--total charges = $1,287,481; (2) reactive--total charges = $276,154; and (3) dose reduction only--total charges = $192,820. CONCLUSION: The incidence of neutropenic fever with standard-dose chemotherapy for SCLC was 18%. Routine use of G-CSF in SCLC patients treated with standard-dose chemotherapy appears to be expensive and is not associated with an obvious therapeutic benefit or cost savings. We suggest that careful analysis of the incidence of infectious complications, rather than granulocyte nadir and duration, be performed, and that clinical guidelines for the use of these effective, but expensive, products be developed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Salvage chemotherapy for recurrent germ cell cancer.

Clinical trials of chemotherapy in germ cell cancer have explored the full range of the relationship of chemotherapy dose and intensity. In good-risk patients, successful efforts have diminished the duration of treatment or number of drugs required to reliably cure the illness. In patients with a poor prognosis, efforts to intensify therapy have been undertaken. In the setting of disease recurrence after primary chemotherapy, the outlook is considerably less hopeful, as only 20% to 30% of patients survive recurrent illness. Current standard treatment in this setting is combination therapy with ifosfamide and cisplatin, given with either etoposide or vinblastine. High-dose chemotherapy with bone marrow or peripheral blood stem cell support can cure a small portion of selected patients with multiple recurrences of germ cell cancer. The impact of earlier treatment with high-dose chemotherapy (either as initial salvage therapy or primary treatment) is less certain. Clinical trials in these settings have not yet demonstrated a definite advantage over less toxic conventional-dose therapies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Mechanisms for electrical stimulation of excitable tissue.

Electric fields excite electrically active tissue by several mechanisms. A long, straight, uniform fiber is polarized by an activating function, proportional to the axial gradient of the axial electric field. During unipolar anodal stimulation, the activating function results in two areas of depolarization (virtual cathodes) that are responsible for anode-make stimulation. During unipolar cathodal stimulation, the virtual anodes can be exploited to produce unidirectional propagation and physiological recruitment of axons. Anode-break stimulation of nerves arises from the intrinsic properties of the sodium channel kinetics; cathode-break stimulation in nerves is anode-break stimulation at a virtual anode. The activating function applies to magnetic stimulation as well as to electric stimulation. Other important mechanisms of stimulation arise if the fiber is terminated, nonuniform, or curved. In the brain, cortical neurons are excited when the electric field is directed from the dendrites toward the axon. Possible mechanisms for cortical excitation are the impedance mismatch between the axon and dendritic tree, and the axon bending as it enters the white matter. Transcranial magnetic stimulation differs from transcranial electric stimulation because during magnetic stimulation the electric field is parallel to the brain surface, whereas during electric stimulation the electric field has components both parallel and perpendicular to the brain surface. Cardiac tissue can be represented by use of the bidomain model. This model predicts that a point-source stimulus results in adjacent areas of depolarized and hyperpolarized tissue. The presence of virtual anodes during cathodal stimulation is analogous to the creation of virtual anodes along a one-dimensional fiber by the activating function. Anode- and cathode-break stimulation both occur in cardiac tissue, but the mechanism may be different than for nerve and may depend on diffusion of depolarization into a previously hyperpolarized region. Electrical stimulation of cardiac tissue can cause reentry through a critical point mechanism. Two mechanisms for defibrillation have been hypothesized: (1) the relatively high junctional resistance between cardiac cells causes each cell to be depolarized on one side and hyperpolarized on the other; and (2) the fiber tracts within the heart behave like individual fibers, with fiber curvature providing a mechanism for polarization. Similarities among nerve, brain, and cardiac stimulation are emphasized.

Animals↗
PubMed1993

Taxol in advanced, hormone-refractory carcinoma of the prostate. A phase II trial of the Eastern Cooperative Oncology Group.

BACKGROUND: Recent clinical trials have documented activity for combinations of chemotherapeutic agents that target the microtubular apparatus in patients with hormone-refractory prostate cancer. Taxol has a novel antimicrotubular mechanism, acting by stabilizing polymerized tubulin. METHODS: Twenty-three patients with hormone-refractory prostate cancer and bidimensionally measurable disease were treated with Taxol by 24-hour continuous infusion at 135-170 mg/M2 every 21 days for a maximum of 6 cycles. RESULTS: Eighty-five courses of Taxol were administered to 23 patients. One patient (4.3%) experienced a partial response lasting 9 months, and four other patients with radiographically stable disease had minor reductions in the serum prostate-specific antigen (PSA) of 16-24%. Eleven patients (47.8%) had stable disease, and progressive disease developed in 9 patients (39.1%) during therapy. Median survival was 9 months. Leukopenia was the dose-limiting toxicity with 13% of patients having Grade 3 and 61% having Grade 4 toxicity, and granulocytopenic fever developed in 26%. Three patients experienced sudden cardiovascular events while participating in the study, including one patient with a nonfatal, non-Q-wave myocardial infarction that occurred during a taxol infusion, and two patients who had sudden deaths 9 days and 30 days after receiving their last taxol dose, respectively. CONCLUSIONS: In the subset of patients with hormone-refractory prostate cancer and bidimensionally measurable disease, Taxol at this dosage has only minor activity.

Aged↗
PubMed1993

Source analysis of scalp-recorded movement-related electrical potentials.

We used brain electric source analysis to study the sources generating the movement-related cortical potentials during the interval from 200 msec before to 200 msec after the movement onset. Dipole solutions were obtained for the peak of the negative slope (pNS') and the frontal peak of the motor potential (fpMP) on scalp-recorded movement-related electrical potentials elicited by self-paced, repetitive unilateral finger movements in 10 normal volunteers. Two sources in homologous areas on each side of a spherical head model provided a satisfactory solution for the activity occurring at the instant of the pNS' in all subjects. The fpMP was modeled by a contralateral source and a midline source in 6 subjects and by a single contralateral source in the remaining 4 subjects. The percentage of the residual variance, or goodness-of-fit, over the interval from -200 to 200 msec, using the derived at pNS' and fpMP, was low. The results support the hypothesis that the NS' originates from the activity of bilateral generators in the sensorimotor cortex, and the motor potential arises from the combined activity of sources in the contralateral postcentral regions and the supplementary motor area.

Adult↗
PubMed1993

How well does a three-sphere model predict positions of dipoles in a realistically shaped head?

The electrical potential produced by a dipole in the temporal or frontal lobe was calculated for a realistically shaped scalp, skull, and brain. This potential distribution was then used with a 3-sphere model to predict the position, orientation, and strength of the dipole source. The original and predicted dipole positions differed by an average of 1.97 cm, with a difference of more than 4 cm in some cases. Control calculations demonstrated that this difference was not caused by numerical artifacts in the computation, but instead was due to a true difference between the 3-sphere and realistically shaped head models.

Brain↗
PubMed1993

The use of a cap-shaped coil for transcranial magnetic stimulation of the motor cortex.

A cap-shaped coil is introduced as a superior design for inducing transcranial magnetic motor evoked potentials for spinal cord monitoring. Evaluation of the magnetic characteristics of the cap coil showed higher induced electrical fields at and below the depth of the cortical surface, compared to a 9-cm, butterfly-shaped coil. Twenty normal adults were stimulated with the cap coil and a 9-cm round coil in three positions. Compound muscle action potentials were recorded from the left and right abductor digiti minimi and anterior tibialis muscles. The cap coil induced potentials with higher intensities and lower variability between consecutive stimuli. The cap coil was also more able to simultaneously induce motor evoked potentials from the four muscles studied. This coil design should provide superior means of inducing transcranial magnetic motor evoked potentials in multiple muscles.

Arm↗
PubMed1993

The response of a spherical heart to a uniform electric field: a bidomain analysis of cardiac stimulation.

A mathematical model describing electrical stimulation of the heart is developed, in which a uniform electric field is applied to a spherical shell of cardiac tissue. The electrical properties of the tissue are characterized using the bidomain model. Analytical expressions for the induced transmembrane potential are derived for the cases of equal anisotropy ratios in the intracellular and interstitial (extracellular) spaces, and no transverse coupling between fibers. Numerical calculations of the transmembrane potential are also performed using realistic electrical conductivities. The model illustrates several mechanisms for polarization of the cell membrane, which can be divided into two categories, depending on if they polarize fibers at the heart surface only or if they polarize fibers both at the surface and within the bulk of the tissue. The latter mechanisms can be classified further according to whether they originate from continuous or discrete properties of cardiac tissue. If cardiac tissue had equal anisotropy ratios, a large membrane polarization would be induced at the heart surface that would become negligible a few length constants into the tissue. If cardiac tissue were continuous and had no transverse coupling between fibers, a membrane polarization would be induced throughout the bulk that would arise from an "activating function" similar to the one used to describe neural stimulation. Polarization would occur if the fibers were curving, if the cross-sectional area of the tissue were changing (fiber branching), or both. The numerically calculated transmembrane potential is intermediate between those predicted using the assumptions of equal anisotropy ratios and no transverse coupling between fibers. Although discrete properties of cardiac tissue are not incorporated into this model, an estimate of their effect indicates that the amplitude of the polarization caused by the resistance of the cellular junctions is similar to that caused by fiber curvature and branching. The spatial distribution of the polarization, however, is quite different.

Electric Conductivity↗
PubMed1993

Dose intensity in germ cell cancer: continued lessons from a model neoplasm.

Clinical trials of chemotherapy in germ cell cancer have explored the full range of dose intensity. In good risk patients, efforts have been successful in diminishing duration of treatment or number of drugs required to cure the illness reliably. In patients with poor prognosis, efforts to intensify therapy have been undertaken. It has been difficult to demonstrate improved outcome using higher doses of conventional agents in the setting of primary treatment of poor risk disease. It is more likely that improvement will come with the discovery of new active agents. High dose chemotherapy with bone marrow or peripheral blood stem cell support can cure a small portion of selected patients with multiple recurrences of germ cell cancer. The impact of earlier treatment with high dose chemotherapy as initial salvage therapy or even primary treatment is less certain. Clinical trials in these settings have not yet demonstrated a definite advantage over less toxic conventional dose therapies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Surgical salvage of chemorefractory germ cell tumors.

PURPOSE: Patients with disseminated germ cell tumors who relapse after salvage chemotherapy, or who progress during cisplatin-based therapy, have chemorefractory disease and a very poor prognosis. A subset of these patients will have chemorefractory but resectable disease. We have therefore evaluated the role of salvage surgery in this patient population. PATIENTS AND METHODS: We performed a retrospective review of all patients with disseminated germ cell tumors who were felt to have chemorefractory disease and underwent salvage surgery from 1977 to 1990 at Indiana University. All patients had elevated serum markers or other signs of progressive carcinoma. A total of 48 patients underwent surgery (33 retroperitoneal lymph node dissections [RPLNDs], six thoracotomies, three thoracoabdominal resections, and multiple asynchronous procedures in six patients). RESULTS: Thirty-eight of 48 patients (79%) were rendered grossly free of disease and 29 (60%) obtained a serologic remission. Ten patients (21%) remain continuously disease-free with no postoperative treatment with a median follow-up of 46 months (range, 31 to 89). Six additional patients who relapsed after salvage surgery are currently disease-free with further treatment (four with repeat surgery and two with high-dose chemotherapy and autologous bone marrow transplantation [ABMT]). CONCLUSION: Selected patients with chemorefractory but resectable germ cell tumors have definite potential for cure with salvage surgery.

Adolescent↗
PubMed1992

Comparison of N-acetylcysteine and mesna as uroprotectors with ifosfamide combination chemotherapy in refractory germ cell tumors.

From January 1983 through August 1988, 318 consecutive patients with refractory germ cell neoplasms were treated with ifosfamide-containing combination chemotherapy. The patients received ifosfamide at 1.2 gm/m2/day with cis-platin 20 mg/m2/day for 5 days and etoposide 75 mg/m2/day for 5 days or vinblastine 0.11 mg/kg on days 1 and 2 for each cycle. Of 277 evaluable patients, NAC was used as an uroprotector in the initial 86 patients while the latter 191 consecutive patients received mesna to reduce urothelial toxicity. Dosages of NAC was 2.0 gm po q 6 hr and for mesna 120 mg/m2 IV push prior to ifosfamide and then 1200 mg/m2/day as continuous infusion of 5 consecutive days. All patients received 3.0 liters of normal saline per day. The number of courses of chemotherapy given in the two groups were similar. Twenty-four of the 86 patients (27.9%) receiving NAC developed hematuria (13 patients - grade 1, 4 patients - grade 2, and 7 patients - grade 3 toxicity). While 8 out of 191 (4.2%) mesna patients developed hematuria (6 - grade 1 and 2 - grade 3) (p < 0.0001). The incidence of severity of renal toxicity was similar in the two groups. Ifosfamide dosage was reduced solely for urothelial toxicity in 11 patients receiving NAC compared with none of the patients receiving mesna (p < 0.0001). Chemotherapy response was similar in the two groups. In conclusion, mesna provides better urothelial protection from ifosfamide-induced toxicity than NAC and allows better maintenance of the drug dosage.

Acetylcysteine↗
PubMed1992

Steady-state point-source stimulation of a nerve containing axons with an arbitrary distribution of diameters.

The paper extends a mathematical model for point-source electrical stimulation of a nerve. In the original model, it was assumed that all the axons in the nerve have the same diameter. In this paper the model is extended to represent a nerve with an arbitrary distribution of axon diameters. It is shown that the assumption of identical axons is justified for a typical human nerve if the 'representative' axon diameter is taken as the area-weighted average of the diameter distribution.

Axons↗
PubMed1992

The heating of metal electrodes during rapid-rate magnetic stimulation: a possible safety hazard.

The temperature of electrodes and metal disks positioned close to a coil was measured during rapid-rate magnetic stimulation. The temperature rise ranged from a fraction of a degree to almost half a degree per stimulus pulse and increased with the electrical conductivity of the metal, the square of the electrode radius and the square of the stimulus strength, and was independent of the electrode thickness. During a brief high-frequency train, the temperature increase from each pulse added; during a long, high-frequency train the temperature increase approached a steady state. After the stimulus ended, an electrode on the arm cooled with a time constant of about 45 sec. A standard silver EEG electrode on the surface of the skin did not increase in temperature enough to induce a skin burn if the stimulating rate was below 0.4 Hz or the total number of stimuli was less than 20. Heating was reduced by cutting gaps in the electrode.

Alloys↗