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Biomedical subjects

D H Johnson

Publications and source records attributed to D H Johnson.

At least 145 records · Page 8Linked to original sources
PubMed1995

Combined modality therapy in non-small cell lung cancer.

Lung cancer kills more Americans annually than the next four most frequently diagnosed malignancies combined. Single-modality therapy is the standard for most cases of limited and metastatic non-small cell lung cancer, but treatment of locally advanced disease remains controversial. Historically, radiotherapy alone was used; more recent approaches include single-agent or combination chemotherapy. The combined chemoradiotherapy approach, versus single-modality chemotherapy or irradiation, has improved on survival. Investigators have also recently shown an advantage to adding chemotherapy with or without radiotherapy to definitive surgery. Better staging systems and definitions of biologic prognostic factors may help determine the optimal therapy for locally advanced non-small cell lung cancer patients.

Carcinoma, Non-Small-Cell Lung↗
PubMed1995

Transient effects during the chopping response of LSO neurons.

The initial transient chopping response of LSO neuron discharges to both monaural and binaural tone-burst stimuli in the context of a previously developed point process model of the later sustained response is analyzed and modeled. The analysis reveals the nature of the initial transient response to stimulus onset: The model's stimulus-dependent parameters vary with poststimulus-onset time while the neuron's intrinsic recovery characteristics remain constant throughout the response. By applying maximum-likelihood estimation techniques to determine the time course of the stimulus-dependent parameters, it was found that the initial excitatory and inhibitory effects decay exponentially, with their ratio determining the instantaneous rate of firing and their relative latency determining the extent of the initial chopping pattern. The "absolute" and apparent deadtime also vary exponentially during the transient portion of the response. It is concluded that the recovery characteristics of LSO neurons and, the exponential nature of the transient effects give rise to a tightly distributed latency period and a regular chopping response pattern that could encode azimuthal information.

Acoustic Stimulation↗
PubMed1995

Phase II study of paclitaxel in patients with extensive-disease small-cell lung cancer: an Eastern Cooperative Oncology Group study.

PURPOSE: To evaluate the efficacy and safety of paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ), a novel diterpene plant product in the treatment of previously untreated patients with extensive-disease small-cell lung cancer (SCLC). PATIENTS AND METHODS: Patients with extensive-disease SCLC received paclitaxel 250 mg/m2 intravenously over 24 hours every 3 weeks. Nonresponders or partial responders, who received the maximum number of cycles (n = 4) of paclitaxel received salvage chemotherapy that consisted of etoposide (VP-16) 120 mg/m2 intravenously over 45 minutes on days 1, 2, and 3, and cisplatin 60 mg/m2 intravenously as a short infusion on day 1. Cycles were repeated every 3 weeks. RESULTS: Of 36 patients entered onto the study, 34 and 32 patients were assessable for toxicity and response, respectively. No complete responses (CRs) were observed. Eleven patients (34%) had a partial response (PR) and six (19%) had stable disease (SD). In three of six patients categorized as having SD, there was greater than 50% tumor shrinkage. However, no 4-week follow-up measurements were made, so these could not be considered PRs, in part because patients received salvage chemotherapy by study design. In this trial, induction and salvage chemotherapy resulted in a response (two CRs and 15 PRs) (53%) in 17 patients. The estimated median survival duration was 43 weeks. Dose-limiting toxicity was leukopenia, with 19 patients (56%) having grade 4 leukopenia. The numbers of patients who experienced other grade 4 toxicities were as follows: pulmonary, three (9%); liver, two (6%); cardiac, one (3%); thrombocytopenia, one (3%); metabolic, one (3%); stomatitis, one (3%); and allergic reaction, one (3%). Four additional patients had grade 3 leukopenia and one patient (3%) died of sepsis (grade 5 toxicity). CONCLUSION: Paclitaxel is an active new agent in the treatment of SCLC. Further investigation of this agent in combination with other active agents is appropriate.

Adult↗
PubMed1995

Phase II study of ifosfamide, carboplatin, and oral etoposide chemotherapy for extensive-disease small-cell lung cancer: an Eastern Cooperative Oncology Group pilot study.

PURPOSE: A phase II study of ifosfamide, carboplatin, and prolonged oral administration of etoposide (ICE) in patients with untreated extensive-disease (ED) small-cell lung cancer (SCLC) was conducted to assess toxicities, response, and median survival. PATIENTS AND METHODS: Between July 1990 and August 1992, 35 patients were treated. ICE doses were ifosfamide 5 g/m2 by 24-hour continuous intravenous (CIV) infusion with mesna on day 1, carboplatin 300 mg/m2 intravenously (IV) on day 1, and etoposide 50 mg/m2 orally on days 1 to 21 every 4 weeks for up to six to eight cycles (schedule I). Because of severe hematologic toxicity in the first 18 patients, the last 17 patients received ifosfamide 3.75 mg/m2 IV on day 1, carboplatin 300 mg/m2 IV on day 1, and etoposide 50 mg orally on days 1 to 14 (schedule II). RESULTS: Nine of 18 patients (50%) on schedule I had 13 episodes of severe hematologic toxicity (one death), and only two (11%) received full doses on cycle 2. However, with schedule II, only four of 17 patients (24%) developed severe hematologic toxicity, and eight (47%) received full doses on cycle 2. Objective responses were observed in 29 of 35 patients (83%) (schedule 1, 16 of 18 patients [89%]; schedule II, 13 of 17 patients [76%]). There were eight (23%) complete responses (CRs) and 21 (60%) partial responses (PRs). The median survival duration was 8.3 months, and 1- and 2-year survival rates were 37% and 14%, respectively. CONCLUSION: ICE with oral etoposide has comparable activity with other regimens in ED SCLC. However, the 2-year survival rate may be higher and ICE with the lower doses of schedule II could be given safely with acceptable toxicity. Further studies of ICE compared with standard two-drug regimens are warranted.

Administration, Oral↗
PubMed1995

Phase III trial (E5592) comparing cisplatin plus etoposide with cisplatin plus paclitaxel at two dose levels for treatment of advanced non-small-cell lung cancer. Eastern Cooperative Oncology Group.

Non-small-cell lung cancer (NSCLC) is the most common cause of cancer-related death in the United States. Only about 30% of patients present with surgically resectable (and thus curable) disease. Because existing chemotherapeutic regimens are never curative in advanced NSCLC and because the median survival time is only modestly increased, the Eastern Cooperative Oncology Group (ECOG) has concentrated on a broad phase II testing program designed to identify new agents with activity against the disease. Of the more than one dozen drugs that have been thus evaluated during the past 10 years, only paclitaxel (Taxol) has been shown to result in an objective response rate of more than 20%. To determine if the paclitaxel-containing regimen can increase survival, ECOG has, therefore, embarked on a phase III trial (E5592) in which patients with stage IV NSCLC are randomly assigned to receive either cisplatin plus etoposide (the current standard chemotherapy) or cisplatin plus paclitaxel. The trial design should also help to determine the appropriate dose of paclitaxel in this clinical setting.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Paclitaxel plus carboplatin for advanced lung cancer: preliminary results of a Vanderbilt University phase II trial--LUN-46.

Based on their good activity and minimal toxicity in non-small cell lung cancer and other cancers, we initiated a phase II trial of carboplatin plus paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in the treatment of patients with previously untreated stage IIIB and IV non-small cell lung cancer. Among 51 patients treated, the overall response rate was 27.5% (14 partial responses). Seventeen patients had stable disease, while 16 patients experienced disease progression after two cycles of treatment. Apart from myelosuppression, toxicity has been modest, with fewer than 5% of patients experiencing grade 3 or greater nonhematologic toxicity. Objective response and survival rates were modestly improved among patients given the higher of two paclitaxel doses (175 mg/m2 v 135 mg/m2). These data suggest that paclitaxel plus carboplatin warrants further study in metastatic non-small cell lung cancer.

Adult↗
PubMed1994

High-dose, brief duration, multiagent chemotherapy for metastatic breast cancer.

BACKGROUND: The authors evaluated a high-intensity inpatient regimen using augmented but subtransplantation doses of multiple agents in patients with metastatic breast cancer. Two high-dose courses were given in an attempt to improve the efficacy of high-dose regimens using a single course. METHODS: Forty women received treatment between October 1988 and October 1991. The median age was 38 years (range, 24-56 years). Twenty-five patients were receiving their first chemotherapy for metastatic disease; 15 patients had received one or more prior regimens. The patients received two courses of chemotherapy, which consisted of the following: cyclophosphamide 1500 mg/m2 intravenously (i.v.) on days 1 and 2; doxorubicin 45 mg/m2 i.v. on days 1 and 2; cisplatin 20 mg/m2 i.v. on days 1, 2, 3, 8, 9, and 10; 5-fluorouracil 1000 mg/m2 on days 8, 9, and 10 (continuous infusion); methotrexate 100 mg/m2 i.v. on days 15 and 22; leucovorin 15 mg/m2 i.v. or by mouth for four doses beginning 24 hours after methotrexate. Etoposide 400 mg/m2 i.v. on days 1, 2, and 3 was substituted for doxorubicin in 14 patients who had received prior doxorubicin. RESULTS: Twenty-nine of 40 patients (73%) had objective response to therapy, with 10 (25%) complete responses. Four patients who obtained a complete response remain disease-free at 14, 21, 28, and 32 months, respectively; all of these patients received this regimen as first-line therapy for metastatic disease. Myelosuppression was severe, with median durations of leukocytes less than 1000/microliters and platelets less than 50,000/microliters of 15 days (range, 7-48 days) and 13 days (range, 3-49 days), respectively. Moderate or severe mucositis occurred in 56 of 68 courses. Four patients (10%) had treatment-related deaths. CONCLUSIONS: This regimen produced high overall response and complete response rates compared with standard regimens. However, only 15% of patients who received this therapy as first-line treatment for metastatic breast cancer remain disease-free, and median response duration was shorter than that reported using high-dose therapy with bone marrow support. Toxicity with this regimen was greater than anticipated, although myelosuppression and stomatitis would be reduced by the use of cytokines. This regimen does not improve results achieved with standard therapy sufficiently to justify its toxicity and expense.

Adult↗
PubMed1994

The effect of long-term medical therapy on the outcome of filtration surgery.

Long-term medical therapy and laser trabeculoplasty have been implicated as risk factors in the outcome of glaucoma filtration surgery. A retrospective analysis was performed of patients undergoing primary trabeculectomy during three key periods: before use of beta-blockers and laser trabeculoplasty (1975 and 1976), after introduction of beta-blocker therapy but before use of the laser (1980), and after common use of beta-blockers and laser (1985 and 1986). A total of 150 patients were included in the analysis. Eyes treated with laser trabeculoplasty at some time before filtration surgery had a decreased probability of successful filtration surgery (intraocular pressure less than 21 mm Hg, 75% vs 91% at one year, P = .05; 50% vs 86% at five years, P = .01). It is unknown whether laser was detrimental to subsequent filtration surgery or merely acted as a selection factor in identifying patients who would have less successful surgical outcomes. Preoperative use of topical medication did not influence the outcome of surgery. Patients having bilateral filtration surgery had similar outcomes between fellow eyes despite the longer use of therapy in the second eye (mean of 1.8 years between operations). In the subgroup of eyes with low preoperative intraocular pressures (less than 21 mm Hg), surgery was successful in reducing pressure to a lower level in 70% of eyes at one year (preoperative pressure, 17.8 mm; one-year postoperative pressure, 13.3 mm, P = .007).

Adult↗
PubMed1994

A nonstationary Poisson point process describes the sequence of action potentials over long time scales in lateral-superior-olive auditory neurons.

The behavior of lateral-superior-olive (LSO) auditory neurons over large time scales was investigated. Of particular interest was the determination as to whether LSO neurons exhibit the same type of fractal behavior as that observed in primary VIII-nerve auditory neurons. It has been suggested that this fractal behavior, apparent on long time scales, may play a role in optimally coding natural sounds. We found that a nonfractal model, the nonstationary dead-time-modified Poisson point process (DTMP), describes the LSO firing patterns well for time scales greater than a few tens of milliseconds, a region where the specific details of refractoriness are unimportant. The rate is given by the sum of two decaying exponential functions. The process is completely specified by the initial values and time constants of the two exponentials and by the dead-time relation. Specific measures of the firing patterns investigated were the interspike-interval (ISI) histogram, the Fano-factor time curve (FFC), and the serial count correlation coefficient (SCC) with the number of action potentials in successive counting times serving as the random variable. For all the data sets we examined, the latter portion of the recording was well approximated by a single exponential rate function since the initial exponential portion rapidly decreases to a negligible value. Analytical expressions available for the statistics of a DTMP with a single exponential rate function can therefore be used for this portion of the data. Good agreement was obtained among the analytical results, the computer simulation, and the experimental data on time scales where the details of refractoriness are insignificant.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1994

Challenges of preoperative chemotherapy in non-small cell lung cancer.

Surgical extirpation of a non-small cell lung cancer (NSCLC) represents an individual's best opportunity for cure. Unfortunately, only a small percentage of patients present with surgically resectable disease. Many patients are diagnosed with tumor confined to the thorax but which is technically unresectable. In the setting of locally advanced disease, combination chemotherapy is capable of effecting tumor shrinkage in a majority of cases. When this occurs, it is tempting to subject the patient to thoracotomy in an attempt to resect the previously unresectable lesion. Use of chemotherapy in this manner is generally referred to as neoadjuvant or preoperative chemotherapy. Recently, several groups have demonstrated that such an approach is feasible but the impact on patient survival remains ill defined. Further studies designed to ascertain the feasibility of neoadjuvant chemotherapy are no longer warranted. It is time for a prospective, randomized trial designed to determine the true potential of neoadjuvant chemotherapy. The optimal design of such a trial is a matter of debate but several options are reasonable. This article will review the available data on preoperative chemotherapy in locally advanced non-small cell lung cancer and will review areas of controversy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Combined modality treatment for locally advanced non-small cell lung cancer--which control arm?

Up to one-third of newly diagnosed patients with non-small cell lung cancer (NSCLC) present with locally advanced, unresectable disease. Traditionally, these patients have been treated with thoracic radiotherapy alone. Unfortunately, the vast majority eventually die as a result of the development of distant, extrathoracic metastases. While chemotherapy is not particularly effective against clinically obvious metastatic disease, there are good theoretical reasons why the use of this modality in earlier stage disease may be beneficial. Several recently completed pilot studies of combined modality therapy have yielded promising results suggesting improved survival. Indeed, the combination of chemotherapy and thoracic radiotherapy has been shown to be marginally superior to radiotherapy alone in a few recently completed randomized trials. However, this has not been a uniform observation. Thus, further study is needed to firmly establish the role of combined modality treatment in Stage III, unresectable non-small cell lung cancer. In these future trials, the best control arm is a matter of some controversy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Phase II trial of oral etoposide plus cisplatin in extensive stage small cell carcinoma of the lung: an Eastern Cooperative Oncology Group study.

Based upon the schedule specificity of etoposide and the in vitro and clinical synergy observed with cisplatin, the Eastern Cooperative Oncology Group conducted a phase II trial of oral etoposide and cisplatin in newly diagnosed, untreated patients with extensive stage small cell carcinoma of the lung. 35 patients received 100 mg/m2 of cisplatin intravenously on day 1 and 50 mg/m2 of etoposide orally for 21 consecutive days. Cycles were repeated every 28 days. The most common toxicity observed was myelosuppression. Sixty-seven per cent of patients had grade 3 or 4 leukopenia and 34% had grade 3 or 4 thrombocytopenia during cycle one. Of 26 evaluable patients, 4 had a complete response (15%) and 17 had a partial response (65%). The median survival for the group as a whole was 8.5 months. We conclude that this regimen was associated with significant myelosuppression, and offered no therapeutic advantage to other commonly administered chemotherapeutic regimens for small cell carcinoma of the lung.

Adult↗