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Biomedical subjects

B J Roth

Publications and source records attributed to B J Roth.

At least 19 recordsLinked to original sources
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↗
PubMed1992

Relevance of stimulus duration for activation of motor and sensory fibers: implications for the study of H-reflexes and magnetic stimulation.

Electric stimuli with durations of 0.5-1.0 msec are optimal for studies of H-reflexes. It is more difficult to obtain H-reflexes with shorter duration stimuli or with magnetic stimulation. In order to understand this behavior, we studied the excitation thresholds for motor and sensory fibers in the ulnar, median and tibial nerves using both electric and magnetic stimulation. For short duration electrical stimuli (0.1 msec) the threshold for motor fibers is lower than for sensory fibers. For longer duration electric stimuli (1.0 msec) the threshold for sensory fibers is lower. For magnetic stimulation the threshold for motor fibers is much lower than for sensory fibers. Thus, stimulus duration is a critical parameter for sensory fiber excitation, and current magnetic stimulators are not optimal.

Adult↗
PubMed1992

Determining the site of stimulation during magnetic stimulation of a peripheral nerve.

Magnetic stimulation has not been routinely used for studies of peripheral nerve conduction primarily because of uncertainty about the location of the stimulation site. We performed several experiments to locate the site of nerve stimulation. Uniform latency shifts, similar to those that can be obtained during electrical stimulation, were observed when a magnetic coil was moved along the median nerve in the region of the elbow, thereby ensuring that the properties of the nerve and surrounding volume conductor were uniform. By evoking muscle responses both electrically and magnetically and matching their latencies, amplitudes and shapes, the site of stimulation was determined to be 3.0 +/- 0.5 cm from the center of an 8-shaped coil toward the coil handle. When the polarity of the current was reversed by rotating the coil, the latency of the evoked response shifted by 0.65 +/- 0.05 msec, which implies that the site of stimulation was displaced 4.1 +/- 0.5 cm. Additional evidence of cathode- and anode-like behavior during magnetic stimulation comes from observations of preferential activation of motor responses over H-reflexes with stimulation of a distal site, and of preferential activation of H-reflexes over motor responses with stimulation of a proximal site. Analogous behavior is observed with electrical stimulation. These experiments were motivated by, and are qualitatively consistent with, a mathematical model of magnetic stimulation of an axon.

Adult↗
PubMed1992

The activating function for magnetic stimulation derived from a three-dimensional volume conductor model.

A three-dimensional volume conductor model of magnetic stimulation is proposed that relates transmembrane potential of an axon to the induced electric field in a uniform volume conductor. This model validates assumptions used to derive a one-dimensional cable model of magnetic stimulation (Roth & Basser, IEEE Trans. Biomed. Eng., vol. 37, pp. 588-597, 1990) of unmyelinated axons. The three-dimensional volume conductor model reduces to this one-dimensional cable equation forced by the activating function, -delta EzA/delta z.

Axons↗
PubMed1992

Randomized study of cyclophosphamide, doxorubicin, and vincristine versus etoposide and cisplatin versus alternation of these two regimens in extensive small-cell lung cancer: a phase III trial of the Southeastern Cancer Study Group.

PURPOSE: The trial was undertaken to determine (1) the relative efficacy/toxicity of two commonly used combination chemotherapy regimens in patients with extensive small-cell lung cancer (SCLC) and (2) whether the rapid alternation of these two regimens could provide superior therapeutic results compared with either regimen alone. PATIENTS AND METHODS: In this phase III trial, 437 eligible patients were stratified by performance status (PS) and sex and were randomly assigned to receive either 12 weeks of cisplatin and etoposide (EP); 18 weeks of cyclophosphamide, doxorubicin, and vincristine (CAV); or 18 weeks of alternation of these two regimens (CAV/EP). RESULTS: There were no significant differences in treatment outcome for EP, CAV, or CAV/EP in terms of response rate (61%, 51%, 59%, respectively), complete response rate (10%, 7%, 7%, respectively), or median survival (8.6 months, 8.3 months, 8.1 months, respectively), with a non-statistically significant trend toward a longer median time to progression with alternating therapy (4.3 months, 4.0 months, 5.2 months, respectively). Crossover second-line chemotherapy given at progression produced low response rates and short survival, regardless of the regimen used. Myelosuppression was the dose-limiting toxicity for all patients, although the pattern and severity differed among the treatment arms. CONCLUSIONS: The combination regimens EP and CAV can be considered equivalently effective induction therapies in extensive SCLC, and these two regimens are, to some degree, crossresistant. Alternating therapy provides no therapeutic advantage compared with the use of either of these regimens alone and should not be considered as standard treatment in this clinical setting.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

No evidence of acute cardiovascular complications of chemotherapy for testicular cancer: an analysis of the Testicular Cancer Intergroup Study.

PURPOSE: The purpose of this study is to evaluate the risk of acute vascular events in patients receiving cisplatin-based chemotherapy for testicular cancer. PATIENTS AND METHODS: A questionnaire assessing cardiovascular toxicity was distributed to all participants in the Testicular Cancer Intergroup study and details of toxicity from the chemotherapy flow sheets were reviewed. Patients with pathologic stage I testicular cancer were registered on to the study and observed after retroperitoneal lymphadenectomy. Patients with pathologic stage II disease were randomized to receive two postoperative courses of adjuvant cisplatin-based chemotherapy or observation. Any patient who had disease recurrence after observation or adjuvant therapy was given four cycles of cisplatin-based chemotherapy. RESULTS: Review treatment-related toxicity for those patients receiving adjuvant chemotherapy (n = 97) or chemotherapy for recurrent disease (n = 83) showed no cases of acute cardiovascular toxicity. The median follow-up period after study enrollment was 5.1 years; 459 questionnaires were mailed and 270 were returned. The percent return was equal among the observed adjuvant and recurrent groups (59%, 54%, and 64%). There was a significant increase in the incidence of extremity paresthesias in the two groups receiving chemotherapy. Fatal myocardial infarction was reported in two patients in the observation group and one nonfatal infarction was reported in the adjuvant treatment group. No patient in any group reported an incidence of stroke. Three patients in the observation group and one patient in the recurrent group experienced a thromboembolic event. CONCLUSION: Despite sporadic case reports suggesting a causal association between chemotherapy for testicular cancer and acute vascular events, this retrospective analysis provides no evidence of an increased risk for subsequent cardiovascular disease in this patient population.

Acute Disease↗
PubMed1992

Acute respiratory compromise resulting from tracheal mucous impaction secondary to a transtracheal oxygen catheter.

Transtracheal oxygen catheters are being increasingly used because of savings in oxygen usage and patient preference. The complications of the catheter are believed to be minor and easily managed. Inspissated mucous collections that form at the tip of the SCOOP 1 (Transtracheal Systems, Denver, Colorado) catheter have been reported but are usually easily expectorated by the patient. This report describes a patient who had development of acute respiratory compromise from crusted mucoid impaction of the trachea secondary to transtracheal catheter use. General anesthesia and rigid bronchoscopy were required for removal of the obstructing impaction. Unexplained worsening of respiratory symptoms in patients with transtracheal oxygen catheters should be addressed by prompt stripping of the catheter.

Acute Disease↗
PubMed1992

Optimal focal transcranial magnetic activation of the human motor cortex: effects of coil orientation, shape of the induced current pulse, and stimulus intensity.

We studied the effects of coil orientation, stimulus intensity, and shape of the induced current pulse on the amplitudes of motor evoked potentials in the left abductor pollicis brevis of 10 normal adults who had transcranial magnetic stimulation. The optimal direction of currents induced in the brain is approximately perpendicular to the central sulcus, flowing diagonally from back to front. The most effective coil orientation depends on the shape of the induced current pulse and, when the first and second phases of the pulse are of similar size, also on the intensity of stimulation. Optimal mapping of the human motor cortex with magnetic stimulation requires knowledge of the influences of all these factors.

Adolescent↗
PubMed1992

How the anisotropy of the intracellular and extracellular conductivities influences stimulation of cardiac muscle.

The bidomain model, which describes the behavior of many electrically active tissues, is equivalent to a multi-dimensional cable model and can be represented by a network of resistors and capacitors. For a two-dimensional sheet of tissue, the intracellular and extracellular conductivity tensors can be visualized as two ellipses. For any pair of conductivity tensors, a coordinate transformation can be found that reduces the extracellular ellipse to a circle and aligns the intracellular ellipse with the coordinate axes. The eccentricity of the intracellular ellipse in this new coordinate system is an important parameter. It can have two special values: zero (in which case the tissue has equal anisotropy ratios) or one (in which case the tissue is comprised of one-dimensional fibers coupled through the two-dimensional extracellular space). Thus the bidomain model provides a unifying framework within which the electrical behavior of a wide variety of nerve and muscle tissues can be studied. When the anisotropy ratios in the intracellular and extracellular domains are not equal, stimulation with an anode always causes depolarization of some region of tissue. An analogous effect occurs in models that describe one-dimensional fibers, in which an "activating function" determines the site of stimulation. Experiments indicate that cardiac muscle does not have equal anisotropy ratios. Therefore, models developed to describe stimulation of axons may also help in understanding stimulation of two- or three-dimensional cardiac tissue, and may explain the concept of anodal stimulation of cardiac tissue through a "virtual cathode".

Anisotropy↗
PubMed1991

Binding of insulin-like growth factors to Tera-2 human embryonal carcinoma cells during differentiation.

Differentiation of Tera-2 human embryonal carcinoma cells by exposure to 2.1 mM alpha-difluoromethylornithine resulted in changes in morphology, a decrease in growth rate, and changes in the expression of SSEA-1 differentiation antigen. While the binding of 125I-insulin-like growth factor I (IGF-I) remained relatively constant during differentiation, binding of 125I-IGF-II increased 2-3-fold. Further, the binding of IGF-II was 87 times greater than IGF-I in both undifferentiated and differentiated cells. Undifferentiated Tera-2 cells exhibited a single class of binding sites for both IGF-I (KD = 1.2 nM, 7.0 x 10(3) sites/cell) and IGF-II (KD = 8.3 nM, 3.4 x 10(5) sites/cell). Following differentiation, IGF-I continued to bind to a single class of binding sites (KD 1.0 nM, 6.7 x 10(3) sites/cell) whereas IGF-II bound to both high-affinity sites (KDH 0.3 nM, 2.2 x 10(5) sites/cell) and low-affinity sites (KDL 15.1 nM, 1.6 x 10(7) sites/cell). The binding of iodinated IGF-II was blocked by unlabeled IGF-II but not IGF-I. In contrast, 125I-IGF-I binding was prevented by either IGF-I or IGF-II. Affinity cross-linking experiments demonstrated the presence of both type I and type II IGF receptors along with a number of IGF binding proteins. IGF-I failed to stimulate the incorporation of [3H]thymidine in both undifferentiated and differentiated cells. Although IGF-II caused a significant increase in [3H]thymidine incorporation in both undifferentiated and differentiated Tera-2 cells, the magnitude of the response and the sensitivity of the cells to IGF-II stimulation was diminished following differentiation. The observed changes in IGF-II binding, which occur in conjunction with cellular differentiation, may be an important feature of the expression of the differentiated phenotype by human germ cell tumors.

Binding Sites↗
PubMed1991

Methotrexate, vinblastine, doxorubicin, and cisplatin in metastatic breast cancer. A phase II trial of the Hoosier Oncology Group.

Forty-six eligible patients with metastatic breast cancer (MBC) were treated with a combination of methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) as first-line chemotherapy. Of 44 patients evaluable for response, 28 (64%) had an objective response, including seven (16%) who had a complete response. The median duration of response was 4 months (range, 0 to 38 months), and the median survival from the time of entry was 14 months (range, less than 1 to greater than 45 months). Myelosuppression was the most common dose-limiting toxicity, with 54% of patients experiencing Grade 3 or 4 leukopenia (including 28% with granulocytopenic fever and one septic death), and cumulative Grade 3 anemia occurred in 28% of patients. Grades 3 to 4 stomatitis was observed in 18% of patients. An active, although highly toxic regimen when used as first-line therapy in MBC, M-VAC has a response rate and survival duration similar to existing, less toxic combination regimens. As such, M-VAC cannot be recommended in preference to other combination chemotherapy regimens in this clinical setting.

Adenocarcinoma↗
PubMed1991

A comparison of two boundary conditions used with the bidomain model of cardiac tissue.

In the bidomain model, two alternative sets of boundary conditions at the interface between cardiac tissue and a saline bath have been used. It is shown that these boundary conditions are equivalent if the length constant of the tissue in the direction transverse to the fibers is much larger than the radius of the individual cardiac cells. If this is not the case, the relative merits of the two boundary conditions are closely related to the question of the applicability of a continuum model, such as the bidomain model, to describe a discrete multicellular tissue.

Animals↗
PubMed1991

Stimulation of a myelinated nerve axon by electromagnetic induction.

A model of electromagnetic stimulation predicts the transmembrane potential distribution along a myelinated nerve axon and the volume of stimulated tissue within a limb. Threshold stimulus strength is shown to be inversely proportional to the square of the axon diameter. It is inversely proportional to pulse duration for short pulses and independent of pulse duration for long ones. These results are also predicted by dimensional analysis. Two dimensionless numbers, Sem, the ratio of the induced transmembrane potential to the axon's threshold potential, and Tc/T, the ratio of the pulse duration to the membrane time constant, summarise the dependence of threshold stimulus strength on pulse duration and axon diameter.

Axons↗