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Biomedical subjects

B J Roth

Publications and source records attributed to B J Roth.

At least 73 records · Page 4Linked to original sources
PubMed1996

Chemotherapy for advanced bladder cancer.

For the past 10 years, chemotherapy for advanced urothelial carcinoma has centered on cisplatin-based combination regimens such as methotrexate, vinblastine, doxorubicin and cisplatin (MVAC). Although such regimens have provided modest improvements in response rates, time to progression and survival, this has been achieved with moderate to severe toxicity. The median survival of patients with advanced disease remains at 12 to 13 months, and attempts to increase the dose intensity of existing regimens have been unsuccessful. Increasingly, attention has turned to the identification of new active agents, and a number have been recently identified, including paclitaxel, gemcitabine, ifosfamide, trimetrexate, piritrexim, and gallium nitrate. These agents will form the basis of new combination regimens that will attempt to improve on the advances in response and survival achieved with combination chemotherapy during the past decade.

Antineoplastic Agents↗
PubMed1996

Highlights of abstracts on hormone-refractory prostate cancer presented at the 1996 annual meeting of the American Society of Clinical Oncology.

Among the more interesting studies at the 1996 annual meeting of the American Society of Clinical Oncology that related to hormone-refractory prostate cancer were several that reported on the use of cis-retinoic acid both alone and in combination with interferon-alpha. Interferon-alpha and interferon-alpha plus cis-retinoic acid have antiproliferative effects in vitro against both PC3 and D-145 prostate cancer cells in culture. BCL2 expression is increased in androgen-independent cells, which may block apoptosis, and retinoids induce transforming growth factor-beta and apoptosis in prostate cancer cell lines. This regimen raises many questions. For example, it is difficult to determine what prostate-specific antigen (PSA) level one should expect from cis-retinoic acid, 4HPR, or any of the other differentiating agents. Should there be an increase in PSA1 Should one expect a slower decline in PSA when giving additional agents that are in fact cytotoxic? What is the significance of a changing level of PSA after this and other types of treatment? These and other questions remain to be determined in future studies.

Antineoplastic Agents↗
PubMed1996

New therapeutic agents for hormone-refractory prostate cancer.

The identification of active chemotherapeutic agents for use in the treatment of advanced hormone-refractory prostate cancer remains a priority of clinical research. An estimated 317,100 new cases will be diagnosed in 1996. This increased diagnosis of disease can be directly attributed to the widespread use of screening serum prostate-specific antigen. However, this has not been associated with a reduction in mortality; more than 41,000 men in the United States are expected to die of the disease this year. The natural history of hormone-resistant disease has remained unaltered, with patients having a median survival of only approximately 12 months. Use of surrogate endpoints, such as a reduction in prostate-specific antigen or improvement in pain, may be appropriate for the evaluation of novel agents or combinations. A number of promising new approaches have been recently tested and brought to trial, including combined antimicrotubular therapy, camptothecins, and matrix metalloproteinase inhibitors. It is only through the development of these and other novel compounds that we can hope to affect the natural course of prostate cancer.

Antineoplastic Agents↗
PubMed1995

Cost and risk benefit in the management of clinical stage II nonseminomatous testicular tumors.

BACKGROUND: Two similarly effective treatment options exist for managing clinical low volume Stage II nonseminomatous germ cell testis tumors (NSGCT). Primary retroperitoneal lymph node dissection (RPLND) (with immediate adjuvant chemotherapy or chemotherapy at relapse) and primary chemotherapy have resulted in similar survival rates in large series. Because the chance for cure is similar with either approach, the cost and morbidity of therapy should be considered important discriminating factors in deciding which option to pursue for an individual patient. The purpose of this study was to undertake a cost/benefit and risk/benefit analysis of these two options using data and costs from the Indiana University experience. METHODS: The overall direct costs for 100 patients undergoing primary RPLND were compared with the total direct costs of 100 patients receiving primary chemotherapy for low volume Stage II disease, including the costs of adjuvant chemotherapy, salvage chemotherapy in relapsing patients, and routine follow-up for a 5-year period. In addition, the two treatment options were analyzed relative to survival, late relapse, acute and chronic toxicity, (including fertility), and perioperative morbidity. RESULTS: In this analysis, the overall 5-year costs of RPLND were significantly less than the costs of primary chemotherapy. The two options did not differ significantly in terms of survival or quality of life. Patients receiving RPLND were found to have an advantage also in terms of fertility, toxicity, and late relapse. CONCLUSIONS: Treatment decisions for patients with clinical low volume Stage II NSGCT may be based on cost/benefit and risk/benefit considerations, including relative toxicity, long term cure rate, and individual patient preference. Patient compliance with follow-up, the specific expertise of the physicians, and the availability of specialized therapeutic care ultimately may influence such decisions.

Algorithms↗
PubMed1995

A mathematical model of agonist-induced propagation of calcium waves in astrocytes.

In astrocytes, calcium signals evoked by neurotransmitters appear as waves within single cells, which spread to other cells in the network. Recent analysis has shown that waves are initiated at a single invariant site in the cell and propagated within the cell in a nonlinear and saltatory manner by regenerative amplification at specific predestined cellular sites. In order to gain insight into local cellular waves and wave collisions we have developed a mathematical model of cellular wave amplification loci. This model is in good agreement with experimental data which includes: ambient calcium gradients in resting cells, wave origination and local amplification and generation of local waves. As observed in experiments, the model also predicts that different locations in the cell can have different frequencies of oscillation. The amplification loci are thought to be specialized areas of the endoplasmic reticulum membrane containing a higher density or higher sensitivity of IP3 receptors. Our analysis suggests that the cellular loci act as weakly coupled oscillators each with its intrinsic latency and frequency of oscillation. Thus the appearance of the propagated calcium wave may be a reflection of these differences rather than an actual diffusional wave propagation.

Animals↗
PubMed1995

A mathematical model of make and break electrical stimulation of cardiac tissue by a unipolar anode or cathode.

Numerical simulations of electrical stimulation of cardiac tissue using a unipolar extracellular electrode were performed. The bidomain model with unequal anisotropy ratios represented the tissue, and the Beeler-Reuter model represented the active membrane properties. Four types of excitation were considered: cathode make (CM), anode make (AM), cathode break (CB), and anode break (AB). The mechanisms of excitation were: for CM, tissue under the cathode was depolarized to threshold; for AM, tissue at a virtual cathode was depolarized to threshold; for CB, a long cathodal pulse produced a steady-state depolarization under the cathode and hyperpolarization at a virtual anode. At the end (break) of the pulse, the depolarization diffused into the hyperpolarized tissue, resulting in excitation. For AB, a long anodal pulse produced a steady-state hyperpolarization under the anode and depolarization at a virtual cathode. At the end (break) of the pulse, the depolarization diffused into the hyperpolarized tissue, resulting in excitation. For AB stimulation, decay of the hyperpolarization faster than that of the depolarization was necessary. The thresholds for rheobase and diastolic CM, AM, CB, and AB stimulation were 0.038, 0.41, 0.49, and 5.3 mA, respectively, for an electrode length of 1 mm and a surface area of 1.5 mm2. Threshold increased as the size of the electrode increased. The strength-duration curves for CM and AM were similar except when the duration was shorter than 0.2 ms, in which case the AM threshold rose more quickly with decreasing duration than did the CM threshold. CM and AM resulted in similar strength-frequency curves. The model agrees qualitatively, but (in some cases) not quantitatively, with experiments.

Animals↗
PubMed1995

Eosinophilic pneumonia and respiratory failure associated with a trazodone overdose.

Drug-induced eosinophilic lung disease commonly presents as a simple pulmonary eosinophilia-like syndrome consisting of transient pulmonary infiltrates, peripheral eosinophilia, and mild pulmonary symptoms that disappear promptly upon withdrawal of the offending medication. However, a more fulminant presentation most resembling acute eosinophilic pneumonia has been recently described. We present a patient with BAL-confirmed eosinophilic pneumonia (EP) and respiratory failure after a trazodone overdose. This is the first case of EP associated with trazodone and only the third drug-mediated EP reported to precipitate respiratory failure.

Acute Disease↗
PubMed1995

Digital clubbing associated with polymyositis and interstitial lung disease.

Clubbing of the fingers is commonly associated with interstitial lung diseases (ILDs). Although ILD occurs in as many as 40% of patients with polymyositis/dermatomyositis (PM/DM), clubbing of the digits has never been reported to occur in patients with PM/DM and ILD. We report the first case of clubbing associated with PM/DM and ILD.

Adult↗
PubMed1995

The role of paclitaxel in the therapy of bladder cancer.

Although significant strides have been made in the development of effective chemotherapy for metastatic bladder cancer, those benefits have plateaued and prompted a search for new, active agents. The most active of a new generation of investigational agents is paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ). The only single-agent phase II trial to date, which used paclitaxel at a dose of 250 mg/m2 by 24-hour infusion every 3 weeks, resulted in a 42% response rate and a 27% complete response rate in previously untreated patients. With granulocyte colony-stimulating factor support, this therapy was well tolerated, with fewer than 10% of patients developing neurtropenic fever during therapy. Paclitaxel's potential as a radiation sensitizer and its relatively low renal excretion make it an attractive agent for use in patients with urothelial carcinoma. The goal of ongoing and planned clinical trials will be to (1) identify potential paclitaxel-containing combination regimens, (2) define the optimal dose and schedule of administration in patients with bladder cancer, and (3) define the activity of paclitaxel in previously treated patients.

Aged↗
PubMed1995

Palliative chemotherapy in advanced bladder cancer.

Transitional cell carcinoma of the urothelium is a chemosensitive tumor, and combination chemotherapy can provide not only palliation but a modest survival advantage in patients with advanced disease. While the four-drug regimen methotrexate/vinblastine/doxorubicin/cisplatin remains the standard combination therapy, its toxicity can be formidable. The overall response rate in phase III trials with this combination is in the 35% to 45% range, with a median survival duration in treated patients of only 12 months. Although attempts to decrease the toxicity of the regimen with the addition of hematopoietic growth factors have been successful, attempts to increase its efficacy by dose escalation have not. This has prompted a search for new active agents that can be incorporated into alternative combination regimens. Recently, activity has been noted for several drugs (including gallium nitrate, ifosfamide, and gemcitabine). In untreated patients, paclitaxel has demonstrated significant activity and is certainly among the most active single agents in the treatment of advanced bladder cancer. Studies incorporating these new agents into novel combination regimens are ongoing, with the goal of providing a regimen that has superior efficacy in advanced disease and, ultimately, in earlier stages of disease with curative intent.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Preliminary experience with paclitaxel in advanced bladder cancer.

In a phase II Eastern Cooperative Oncology Group trial, single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) was administered to 26 patients with advanced urothelial cancer who had not received prior systemic chemotherapy. Paclitaxel was given at a dose of 250 mg/m2 by 24-hour continuous infusion along with prophylactic granulocyte colony-stimulating factor. Despite a 23% incidence of grade 3 or 4 neutropenia, only two patients developed febrile neutropenia; other hematologic toxicity was mild and not dose limiting. Nonhematologic toxicity included grade 3 neurologic toxicity in three patients, grade 3 mucositis in three patients, and grade 4 diarrhea in one patient. Eleven of 26 (42%) patients had an objective response (seven clinical complete responses, four partial responses), two had stable disease as their best response, and 13 patients progressed while on therapy. Preliminary response data suggest significant single-agent activity for paclitaxel in transitional cell carcinoma of the bladder. Future studies will evaluate paclitaxel-containing combination regimens as first-line therapy for advanced disease and define the role of paclitaxel in salvage therapy following conventional chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Early salvage therapy for germ cell cancer using high dose chemotherapy with autologous bone marrow support.

BACKGROUND: Patients with relapsed germ cell cancer (GCT) have a poor prognosis when treated solely with conventional chemotherapy; high dose chemotherapy with autologous bone marrow rescue (ABMR) has shown curative potential in patients with relapsed and refractory GCT. This protocol was designed to incorporate high dose therapy with initial salvage therapy. METHODS: Twenty-three patients in the first relapse of GCT received two cycles of conventional dose cisplatin-based therapy (either vinblastine, ifosfamide and cisplatin [VeIP] or cisplatin, vinblastine, and bleomycin) followed by carboplatin (1500-2100 mg/m2) and etoposide (1200-2250 mg/m2) given in divided doses with ABMR. RESULTS: Eighteen of 23 patients completed protocol therapy including high dose therapy. Five of 23 did not undergo high dose therapy due to: insurance refusal (1); patient refusal (1); active infection (1); central nervous system metastasis (1); death on induction therapy (1). Response to two courses of conventional dose induction therapy (N = 23) was complete response (CR), 8; partial response (PR), 12; stable disease (SD), 2; and toxic death, 1. Two of five individuals who did not continue with high dose therapy are alive and progression free after conventional salvage therapy and surgery with at least 24 months of follow-up. Outcome after high dose therapy (N = 18) was CR, 9, PR, 6, SD, 1, and PD, 2. Two patients who were in PR after receiving two cycles of conventional dose therapy were converted to CR using high dose therapy. There was only one treatment-related death in this cohort, a septic death during VeIP induction therapy. There were no transplant related deaths. Of those patients completing high dose therapy, 7 of 18 (39%) survived, progression free with a median follow-up of 26 months, 2 of 18 are alive with active disease, and 9 of 18 died of recurrent disease. CONCLUSIONS: Conventional dose induction therapy followed by consolidation with high dose therapy and ABMR is well tolerated and provides prolonged disease-free survival in some patients with chemosensitive relapsed germ cell cancer.

Adolescent↗
PubMed1994

Roentgenographic evaluation of the cervical spine. A selective approach.

BACKGROUND: To determine if routine radiographic evaluation of the cervical spine could be eliminated in the alert, sober trauma patient who has no neck pain, tenderness, or other major injuries without a significant increase in missed occult injury. DESIGN: Prospective cohort study. SETTING: Emergency department and general surgery service at a military tertiary medical center. MAIN OUTCOME MEASURE: Those patients with cervical spine injuries. RESULTS: Sixteen patients (2%) had cervical spine injuries, all had signs and/or symptoms of their injury on presentation. Ninety-six patients (14%) who were not intoxicated and had no neck pain, tenderness, or other major injuries were evaluated. None of these patients had abnormal cervical spine studies. Two hundred ninety patients (43%) were followed up between 30 to 150 days. No missed injuries were noted. CONCLUSIONS: These results indicate that blunt trauma patients may not require cervical spine roentgenography if they meet the following criteria: absence of mental status changes, intoxication, neck pain or tenderness, neurologic signs or symptoms, or simultaneous major distracting injury. Because of the small incidence of cervical spine injuries, further studies are necessary to evaluate the positive predictive value of history and physical examination of the cervical spine in a trauma patient.

Alcoholic Intoxication↗
PubMed1994

The time constants of motor and sensory peripheral nerve fibers measured with the method of latent addition.

The time constants of motor and sensory fibers in the human ulnar, median and tibial nerves were determined using the method of latent addition. Two square-wave stimuli were applied: the first one was subthreshold and the second, at various delays relative to the first, was adjusted to achieve threshold activation. Strength-delay curves were obtained, from which the time constant was determined using a mathematical model. Sensory fibers had time constants that were about 3 times the time constant for motor fibers. The strength-delay curves gave similar time constants as those obtained from strength-duration curves.

Adolescent↗