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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

Bilateral testicular tumors: management and outcome in 21 patients.

BACKGROUND: The authors examined the clinical course of patients with bilateral testicular tumors to determine whether the outcome after treatment was different from patients with unilateral tumors. METHODS: Using a computerized data base of 2088 patients with testicular carcinoma at Indiana University, 21 patients (1%) were identified with bilateral testicular carcinoma. A retrospective review of hospital and clinic charts was performed. Sixteen patients with metachronous and 5 patients with synchronous testicular tumors were identified. RESULTS: Treatment was based on clinical stage and was similar to therapy given for unilateral disease. The mean age at presentation of the first testicular tumor was 28.4 years (range, 16-47 years). Approximately 50% of the second primary tumors presented > 5 years after the contralateral tumor. At a mean follow-up of 49.9 months (range, 1-276 months), 18 patients were without evidence of disease, 2 were alive with disease, and 1 patient had died of disease. CONCLUSIONS: The treatment of patients with bilateral germ cell tumors is based on the pathology and clinical stage and should not be different from the traditional management of unilateral testicular carcinoma. Patients with unilateral testicular carcinoma should be informed of the necessity of long term follow-up because contralateral testicular carcinoma may occur as long as 25 years later.

Adolescent

Effects of doxycycline on human prostate cancer cells in vitro.

Prostate cancer is the most common form of cancer in older men and the major cause of death from prostate cancer is metastatic disease. The matrix metalloproteinases (MMPs) play a significant role in the growth, invasion and metastasis of many tumors, including those of the prostate. We previously demonstrated that doxycycline, a synthetic tetracycline, inhibits MMPs and cell proliferation and induces apoptosis in several cancer cell lines. We also demonstrated that in an in vivo model of metastatic breast cancer in athymic mice doxycycline inhibits tumor size and regrowth after resection. In the present study, gelatinolytic activity in the human prostate cancer cell line, LNCaP, was suppressed and significant inhibition of cell growth occurred after exposure to 5 or 10 microg/ml of doxycycline, while cell growth was normal in untreated cells. Radioisotope incorporation into proteins was reduced by doxycycline. DNA fragmentation, consistent with apoptosis, was demonstrated in cells treated with doxycycline. These data suggest that doxycycline may have potential utility in the management of prostate cancer.

Adenocarcinoma

A phase II trial of paclitaxel in refractory germ cell tumors.

BACKGROUND: A significant percentage of patients with refractory germ cell tumors will not respond to standard salvage regimens. Thus there is a need for new active agents. Paclitaxel has demonstrated activity against a variety of solid tumors in both laboratory and clinical studies. METHODS: Eighteen patients with refractory germ cell tumors who failed initial cisplatin-based chemotherapy and a maximum of 2 salvage regimens were enrolled into a Phase II trial of paclitaxel at a dose of 170 mg/m2 by intravenous infusion over 24 hours every 21 days without growth factor support. The median age of the patients was 32.5 years (range, 18-49 years). The testis was the primary site of tumor for 13 patients (72%) and the tumor was extragonadal in 5 patients (28%). Six patients (33%) were late recurrences. Twelve patients (67%) had > or = 2 metastatic sites. The median number of previous chemotherapy cycles was six (range, four to nine). Three patients (17%) previously had undergone autologous bone marrow transplantation. RESULTS: Two patients (11%) responded to paclitaxel. Major toxicities were Grade 3-4 neutropenia (55% of patients) and Grade 3-4 neurotoxicity (2 patients). Neutropenic fever occurred in 3 patients (17%). CONCLUSIONS: Paclitaxel demonstrated minimal activity in heavily pretreated patients with multiple, poor risk clinical features. These results in part may be due to the unfavorable characteristics of the patients in the current study, specifically the high percentage of patients with late recurrences and extragonadal primary tumors, both of which are known to respond poorly to salvage therapy. Other trials with different patient populations and doses of paclitaxel reported response rates ranging from 13.3%-26%. The role of paclitaxel in the treatment of patients with refractory germ cell tumors remains to be defined in future studies.

Adolescent

The pinwheel experiment revisited.

The critical point hypothesis explains the origin of some cardiac arrhythmias, and the bidomain model describes electrical stimulation of the heart. In this paper, the critical point hypothesis is combined with the bidomain model. The result is four new predictions about the pinwheel experiment, a fundamental experiment in cardiac electrophysiology. These are: (1) The duration of the vulnerable period during cathodal S2 stimulation is longer for an S1 wavefront propagating perpendicular to the fibers than for an S1 wavefront propagating parallel to the fibers. (2) For anodal S2 stimulation with the S1 wavefront propagating parallel to the fibers, the vulnerable period splits into two periods with an "invulnerable period" between them. (3) For anodal S2 stimulation with the S1 wavefront propagating perpendicular to the fibers, the vulnerable period consists of only one period. (4) A previously suggested mechanism for the upper limit of vulnerability (S2 is so strong that the entire tissue is depolarized by an amount greater than S*) is no longer applicable.

Animals

Differences between the time constant of sensory and motor peripheral nerve fibers: further studies and considerations.

Using a method of latent addition, we previously demonstrated that sensory fibers had time constants that were about three times longer than those of motor fibers. The aim of the present work was to confirm this difference by determining the time constants for single sensory axons by using microneurography and for single motor axons by recording single motor units with bipolar concentric needle electrodes. To determine the influence of the conditioning pulse on the neural time constant, we used both depolarizing and hyperpolarizing conditioning pulses. When hyperpolarizing conditioning pulses at comparable intensity were applied, the tendency was to find shorter time constants than when depolarizing pulses were applied, although still with the motor time constant being slightly shorter. Although the absolute values varied with the different methods, the sensory time constant was generally three times the motor time constant for depolarizing conditioning stimuli, whereas for hyperpolarizing conditioning stimuli the difference dropped to about one and a half. These characteristics improve understanding of the behavior of sensory and motor axons, and, in particular, explain the differential excitability. Determination of neural time constants might prove valuable for clinical use.

Adult

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