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Biomedical subjects

D H Johnson

Publications and source records attributed to D H Johnson.

At least 163 records · Page 9Linked to original sources
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

Adjuvant chemotherapy for non-small cell lung cancer.

In the late 1970s and early 1980s, the Lung Cancer Study Group conducted a series of adjuvant chemotherapy trials in patients with resected non-small cell lung cancer. Although some of these trials yielded modest survival benefit, the length of improved survival essentially equaled the time spent receiving chemotherapy. Consequently, few physicians routinely employ postoperative chemotherapy in spite of its theoretical appeal. Possible explanations for the failure of adjuvant chemotherapy to provide meaningful prolongation of survival in non-small cell lung cancer include lack of effective chemotherapy, incorrect chemotherapy regimen, inadequate dose intensity, and possibly inadequate trial design. Future postoperative adjuvant trials should focus on treating patients with resected early stage lesions (T1N1, T2N1, T2N0). What role, if any, newer antineoplastic agents will play in the postoperative setting remains to be determined. Neoadjuvant induction chemotherapy may well prove to be a superior treatment strategy and deserves further investigation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Taxol (paclitaxel) in the treatment of lung cancer: the Eastern Cooperative Oncology Group experience.

Two phase II studies of paclitaxel involving patients with advanced non-small cell lung cancer (NSCLC) have been completed. The first study, conducted by the Eastern Cooperative Oncology Group (ECOG), involved 25 previously untreated patients who received intravenous (i.v.) paclitaxel 250 mg/m2 over 24 hours every 3 weeks. Among 24 evaluable patients with stage IV disease, 5 partial responses (21%) were observed, median survival was 24.1 weeks, and 1-year survival was approximately 45%. Common toxicities included leukopenia (66% grade 4), neurotoxicity (28% grade 3), and cardiotoxicity (12.5% grade 3). The second trial, conducted at the M.D. Anderson Cancer Center, yielded similar results. Twenty-seven previously untreated patients with stage IV disease received paclitaxel 200 to 250 mg/m2 i.v. over 24 hours every 3 weeks, yielding 1 complete response and 5 partial responses (24%) in 25 evaluable patients. The major toxicity was leukopenia. No cardiac toxicity was seen. For the past several years ECOG has tested several agents against previously untreated NSCLC, and none has demonstrated a response rate greater than 10%, other than paclitaxel. Given these results, the ECOG plans to conduct a three-arm phase III study involving patients with advanced NSCLC comparing 'standard' cisplatin/etoposide chemotherapy to two paclitaxel-containing arms: (1) paclitaxel 135 mg/m2 i.v. over 24 hours plus cisplatin 75 mg/m2 i.v.; (2) paclitaxel 250 mg/m2 i.v. over 24 hours plus cisplatin 75 mg/m2 i.v. plus recombinant human granulocyte colony-stimulating factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Atypical pneumonias. Clinical and extrapulmonary features of Chlamydia, Mycoplasma, and Legionella infections.

Pneumonias caused by atypical organisms usually have extra-pulmonary features. Chlamydial pneumonia often starts with hoarseness and fever, and respiratory tract symptoms may not appear for days. Mycoplasmal pneumonia may manifest with ear pain and a nonproductive cough. Legionnaires' disease presents with high fevers and central nervous system and gastrointestinal abnormalities. Diagnosis of chlamydial infection is accomplished with serologic testing. Patients are unresponsive to erythromycin treatment and should be started on empirical doxycycline (Doryx, Vibramycin) therapy. The presence of cold agglutinins in the appropriate clinical setting permits a presumptive diagnosis of mycoplasmal infection. Clinical diagnosis of Legionella pneumonia may be made in patients with pneumonia who also have relative bradycardia with elevated serum transaminases or hypophosphatemia with gastrointestinal or central nervous system symptoms. Erythromycin is the mainstay of treatment of legionnaires' disease, but treatment failures have been reported. Doxycycline is less expensive, has a better safety profile, and is better tolerated than erythromycin.

Anti-Bacterial Agents↗
PubMed1993

Adenine phosphoribosyltransferase genes in two Drosophila species: dosage compensation, a nuclear matrix attachment site, and a novel intron position.

The Aprt locus of Drosophila encodes the structural gene for the purine salvage enzyme adenine phosphoribosyltransferase. Aprt is autosomal and enzyme activity is gene-dose-dependent in Drosophila melanogaster. However, Aprt is X-linked and dosage compensated in Drosophila pseudoobscura, as shown here. The Aprt genes of both Drosophila species contain a DNA sequence associated with nuclear matrix attachment sites and these Aprt sequences specifically bind to nuclear matrix in vitro. Putative promoter sequences positioned upstream of the predicted transcriptional start site in the two Aprt genes have a similar structure of direct repeats with an overlapping dyad symmetry, but the DNA sequence of these motifs is not conserved between the two species. Biological features in mutants of Aprt as well as natural variants suggest that dosage compensation of this gene in Drosophila pseudoobscura is due to a general control mechanism on X-linked genes rather than a gene-specific mechanism.

Adenine Phosphoribosyltransferase↗
PubMed1993

Preliminary results with neoadjuvant therapy and resection for esophageal carcinoma.

Between December 1988 and August 1992, 68 patients with adenocarcinoma (n = 39) and squamous carcinoma (n = 29) of the esophagus were entered prospectively in a treatment protocol to receive two cycles of cisplatin, 5-fluorouracil, etoposide, leucovorin, and 3,000 cGy of radiation to the involved esophagus and adjacent mediastinum, followed by resection. There were four deaths during chemotherapy, and 7 patients had a decline in condition or were denied operation. Fifty-six patients have come to operation, and 1 awaits resection. Twenty-two patients had transhiatal esophagectomy and 29 patients had esophagogastrostomy with a combined abdominal and right thoracic approach. Five patients did not undergo resection at operation. There was one hospital death (2%). A complete response to preoperative therapy was seen in 12 patients (21%): 5 of 20 with squamous cancer (25%) and 7 of 36 with adenocarcinoma (19%). Average follow-up is 19 months. Median survival in these patients after entrance in the protocol is 24 months. Actuarial survival at 12, 18, and 24 months is 72% (confidence limits, 66% and 78%), 53% (confidence limits, 46% and 60%), and 51% (confidence limits, 44% and 58%). Significantly better survival was associated with adenocarcinoma (p = 0.041). There is no survival advantage based on complete response to preoperative therapy. This neoadjuvant regimen is effective in patients with squamous carcinoma and adenocarcinoma. These preliminary results demonstrate an improved median and actuarial survival compared with historical controls in 137 patients operated on between 1966 and 1985 at our institution.

Adenocarcinoma↗
PubMed1993

Excitation effects on LSO unit sustained responses: point process characterization.

LSO units recover from a spike discharge in a characteristic way, modeled by an intrinsic recovery function that is stimulus invariant up to a scaling factor and a shifting constant. Data analysis shows that the effect of increasing excitatory stimulus level can be described by amplifying the intrinsic recovery function and by shifting it toward shorter intervals. The shifting process secondarily interacts with the absolute deadtime to produce the response characteristics of the three LSO unit types. Decreased excitation is clearly distinguished from inhibition, which affects the scaling, but not the time origin, of the recovery. We conclude that both excitatory and inhibitory stimulus levels are encoded in the timing of LSO unit discharges.

Action Potentials↗
PubMed1993

Postarthroscopy analgesia with intraarticular bupivacaine/morphine. A randomized clinical trial.

BACKGROUND: Postarthroscopy analgesia has been provided with intraarticular bupivacaine, but the duration of analgesia may be only a few hours. More recently, longer-lasting analgesia has been achieved using intraarticular morphine, although the onset of analgesia may be delayed. The combination of intraarticular morphine and bupivacaine has been suggested as an ideal analgesic after knee arthroscopy. METHODS: One hundred and twenty ASA Physical Status 1-2 outpatients, age 18-60 yr, having knee arthroscopy, were randomized into one of four treatment groups. Exclusion criteria included relevant drug allergy, extensive debridement or synovectomy, arthrotomy, postoperative intraarticular drainage, tracheal intubation, and patient refusal. All patients received general anesthesia with intravenous fentanyl, propofol, N2O, O2, and isoflurane. At the end of surgery, before tourniquet release, the following were injected intraarticularly through the arthroscope: group 1, 0.25% bupivacaine; group 2, 1 mg morphine in saline; group 3, 2 mg morphine in saline; and group 4, 1 mg morphine in 0.25% bupivacaine. The volume injected was 30 ml, and all solutions contained 1:200,000 epinephrine. Postoperative analgesia was provided with intravenous fentanyl and/or oral acetaminophen/codeine, and was recorded for 24 h. Visual analog pain scale (VAPS) scores and the McGill Pain Questionnaire (MPQ) were performed hourly from 1-6 h, and at 24 h postoperatively. RESULTS: Visual analog pain scale and MPQ scores were lowest in groups 1 and 4 at 1-6 h, but at 24 h, VAPS scores were lowest in groups 2, 3, and 4. Analgesic requirements were lower for the first 12 h in groups 1 and 4, but no difference was seen between groups over the 24-h study period. No adverse effects were noted. CONCLUSIONS: Morphine, 1 mg intraarticular, in 30 ml 0.25% bupivacaine, with 1:200,000 epinephrine, may provide superior postoperative analgesia for up to 24 h versus bupivacaine or morphine alone.

Adolescent↗
PubMed1993

Improved survival with neoadjuvant therapy and resection for adenocarcinoma of the esophagus.

OBJECTIVE: This study sought to determine the impact of preoperative chemotherapy and radiation therapy (neoadjuvant therapy) followed by resection in patients with adenocarcinoma of the esophagus. SUMMARY BACKGROUND DATA: Long-term survival in patients with carcinoma of the esophagus has been poor. An increase in the incidence of adenocarcinoma of the esophagus has been reported recently. METHODS: Fifty-eight patients with biopsy-proven adenocarcinoma of the esophagus treated at this institution from January 1951 through February 1993 were studied. Since 1989, 24 patients were entered prospectively into a multimodality treatment protocol consisting of preoperative cisplatin, 5-fluorouracil (5-FU), and leucovorin with or without etoposide, and concomitant mediastinal radiation (30 Gy). Patients were re-evaluated and offered resection. RESULTS: There were no deaths related to neoadjuvant therapy and toxicity was minimal. Before multimodality therapy was used, the operative mortality rate was 19% (3 of 16 patients). With multimodality therapy, there have been no operative deaths (0 of 23 patients). The median survival time in patients treated before multimodality therapy was 8 months and has yet to be reached for those treated with the neoadjuvant regimen (> 26 months, p < 0.0001). The actuarial survival rate at 24 months was 15% before multimodality therapy and 76% with multimodality therapy. No difference in survival was noted in neoadjuvant protocols with or without etoposide (p = 0.827). CONCLUSIONS: Multimodality therapy with preoperative chemotherapy and radiation therapy followed by resection appears to offer a survival advantage to patients with adenocarcinoma of the esophagus.

Actuarial Analysis↗
PubMed1993

Analyzing and modeling fractal intensity point processes.

Fractal intensity point processes--doubly stochastic point processes with a fractal waveform intensity process--are required to describe the discharge patterns recorded from the auditory and visual systems. The Fano factor--the ratio of the variance of the number of events in an interval to the mean of this number--captures the self-similar characteristics of the intensity via two quantities: fractal dimension and fractal time. The fractal dimension is the exponent of the asymptotic power law behavior of the Fano factor with interval duration. The fractal time delineates long-term fractal behavior from short-term characteristics of the data. The average rate and self-similarity parameter of the intensity process, absolute and relative refractory effects, and serial dependence all modify the fractal time. To generate fractal intensity point processes, stochastic fractal processes are derived by applying memoryless, nonlinear transformations to fractional Gaussian noise. The intensity's amplitude distribution in combination with the Fano factor form criteria to choose the transformation that best describes data.

Auditory Perception↗
PubMed1993

Function-based modeling of binaural processing: level and time cues.

From theoretical considerations, function-based modeling predicts the input-output characteristics of a neural system intended to perform a signal processing task within a sensory system. The sensory task under study here is the time- and level-based localization of a high-frequency, possibly amplitude-modulated, sound source in the horizontal plane. The stimulus is assumed to be represented by each ear's primary-like discharge pattern. An optimal system that extracts azimuthal angle from these discharge patterns, which represent acoustic time and level localization cues, has been derived. This system can be described as the maximization of a sum of three subsystems' outputs. The stimulus cues employed by these systems are interaural level difference for the level-based subsystem, the interaural onset-time difference for the time-based subsystem, and the interaural envelope-phase difference for the phase-based subsystem. The system encompassing all these cues is shown to trade-off the level, time, and envelope-phase cues depending upon the time since stimulus onset, the observation time, and the incident signal's level. How this system might correspond to known structures in the lower auditory pathway is described.

Acoustic Stimulation↗
PubMed1993

Using memory for pain in analgesic research.

OBJECTIVE: To determine the validity of pain intensity recall at 24 and 48 hours as a substitute for hourly pain assessments in repeated-dose analgesic studies. SETTING: Orthopedic unit of an acute care teaching hospital. PARTICIPANTS: Eighty-four patients undergoing arthroscopic reconstruction of the anterior cruciate ligament, using the patellar tendon, who were participating in a randomized, double-blind, parallel-group analgesic study. INTERVENTIONS: Patients rated their pain intensity every hour (while awake) for 48 hours and their recall of worst, least, and usual pain intensity at 24 and 48 hours using a visual analog scale (VAS). MAIN OUTCOME MEASURES: This study examined the relationship between recall of worst, least, and usual pain intensity at 24 and 48 hours and the experienced maximum, minimum, and mean pain intensity VAS scores obtained from hourly assessments over the 0-24- and 0-48-hour periods, respectively. The significance of differences between recalled and experienced pain intensity variables was assessed. RESULTS: Worst, least, and usual pain recall at 24 and 48 hours were highly correlated with experienced maximum, minimum, and mean pain from hourly reports, respectively, over the 0-24- and 0-48-hour periods (Pearson correlation coefficients, r = 0.80-0.89, p < 0.0001). Among the three pain recall variables, usual pain showed the highest correlation with hourly measurements. There were no significant differences between recalled pain and the corresponding measures of pain from the hourly VAS scores, except in the case of 48-hour recall of worst pain (Student's t-test, p = 0.001). CONCLUSIONS: The close agreement between actual pain experience and recall of pain provides support for the use of pain recall in assessing analgesic efficacy in clinical trials.

Acetaminophen↗