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J L Lewis

Publications and source records attributed to J L Lewis.

At least 145 records · Page 8Linked to original sources
PubMed1992

6R instrumented spatial linkages for anatomical joint motion measurement--Part 2: Calibration.

The six-revolute-joint instrumented spatial linkage (6R ISL) is often the measurement system of choice for monitoring motion of anatomical joints. However, due to tolerances of the linkage parameters, the system may not be as accurate as desired. A calibration algorithm and associated calibration device have been developed to refine the initial measurements of the ISL's mechanical and electrical parameters so that the measurement of six-degree-of-freedom motion will be most accurate within the workspace of the anatomical joint. The algorithm adjusts the magnitudes of selected linkage parameters to reduce the squared differences between the six known and calculated anatomical position parameters at all the calibration positions. Weighting is permitted so as to obtain a linkage parameter set that is specialized for measuring certain anatomical position parameters. Output of the algorithm includes estimates of the measuring system accuracy. For a particular knee-motion-measuring ISL and calibration device, several interdependent design parameter relationships have been identified. These interdependent relationships are due to the configuration of the ISL and calibration device, the number of calibration positions, and the limited resolution of the devices that monitor the position of the linkage joints. It is shown that if interdependence is not eliminated, then the resulting ISL parameter set will not be accurate in measuring motion outside of the calibration positions, even though these positions are within the ISL workspace.

Algorithms↗
PubMed1992

6R instrumented spatial linkages for anatomical joint motion measurement--Part 1: Design.

Six-revolute-joint instrumented spatial linkages (6R ISLs) have become often-used devices to measure the complete six-degree-of-freedom motion of anatomical joints. Accuracy of motion measurement depends on ISL design and calibration technique. In this paper, a design process is outlined that uses computer graphics and numerical methods as aids in developing 6R ISLs that (i) physically assemble within the desired range of motion of the joint; (ii) do not collide with either the experimental apparatus or the subject joint; (iii) avoid singular linkage configurations that can cause forces to be applied to the joint; and (iv) measure selected anatomical motions most accurately. It is found that a certain subgroup of 6R linkages are suitable for accurate measurement of specific motions, and can be the basis for new ISL designs. General guidelines are developed that can assist in the generation of unique linkage designs for different anatomical joints. The design process is demonstrated in the creation of an ISL to measure knee motion.

Computer Simulation↗
PubMed1992

Ifosfamide and mesna in previously treated advanced epithelial ovarian cancer: activity in platinum-resistant disease.

PURPOSE: There is a critical need to find new antineoplastic drugs that are active in platinum-refractory ovarian cancer. We conducted a phase II trial of single-agent ifosfamide with mesna uroprotection in patients with ovarian cancer previously treated with an organoplatinum compound to assess its activity in this clinical setting. PATIENTS AND METHODS: Ifosfamide (1.0 or 1.2 g/m2/d for 5 days, delivered on a monthly schedule) was administered to the 57 patients entered onto this trial. Dose reductions were permitted for unacceptable toxicities. RESULTS: Toxicity included severe bone marrow suppression (WBC count less than 1,000/microL and/or platelet count less than 50,000/microL), renal dysfunction (serum creatinine level greater than 2.0 mg/dL), and reversible CNS dysfunction (disorientation, hallucinations, somnolence, and agitation), which occurred in 20%, 14%, and 12% of patients, respectively. Of 41 patients with strictly defined platinum-refractory ovarian cancer, five (12%) demonstrated a partial (four) or complete (one) response to this treatment program. CONCLUSION: Single-agent ifosfamide has modest but unequivocal activity in platinum-resistant ovarian cancer. Further studies of this drug used as a front-line agent along with an organoplatinum compound or as part of a dose-intensification program with bone marrow, peripheral stem cell, or colony-stimulating factor support are indicated. In addition, single-agent ifosfamide is a reasonable standard second-line treatment strategy in appropriately selected patients with platinum-refractory ovarian cancer.

Acute Kidney Injury↗
PubMed1992

Impact on survival of surgically defined favorable responses to salvage intraperitoneal chemotherapy in small-volume residual ovarian cancer.

PURPOSE: To evaluate the impact on survival of the attainment of surgically defined favorable responses (S-R) to salvage intraperitoneal (IP) chemotherapy after initial systemic cytotoxic drug delivery. PATIENTS AND METHODS: We examined the survival of patients who were treated on one of three phase II IP trials that were conducted at the Memorial Sloan-Kettering Cancer Center. A total of 58 patients whose largest residual tumor masses measured less than or equal to 0.5 cm in maximum diameter at the initiation of this salvage therapy were assessable for response, 28 of whom (48%) demonstrated a S-R, which included 19 (33%) who achieved a surgically defined complete response (S-CR). RESULTS: With a median follow-up of 43+ months (range, 33+ to 58+ months) from the initiation of IP therapy, 12 of 19 (63%) have recurred. The median duration of S-CR for the 10 patients with microscopic residual disease was 32 months compared with 15 months for the nine patients with macroscopic residual disease (largest tumor mass less than or equal to 0.5 cm; P greater than .1). For patients with microscopic residual disease who experienced a S-CR (n = 10) after salvage IP therapy, the median overall survival from the initiation of therapy has not been reached, but will exceed 4 years compared with a 25-month median survival for the nonresponding patients (n = 13; P = .004). The median survival for the 18 patients with small-volume macroscopic disease who responded to therapy was 40 months compared with 19 months for the nonresponders (P = .009). CONCLUSION: Although the results of this evaluation are encouraging and suggest that the attainment of a S-R, particularly a S-CR, after IP chemotherapy may result in a clinically meaningful favorable impact on survival, a randomized controlled trial will be required to address definitively this important issue.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Phase I trial of intraperitoneal taxol: a Gynecoloic Oncology Group study.

PURPOSE: To evaluate the safety and pharmacology of the intraperitoneal (IP) administration of the antineoplastic agent taxol. PATIENTS AND METHODS: Twenty-five pretreated patients who were entered onto a phase I clinical trial; 24 had advanced ovarian cancer. Patients were treated with taxol administered IP in 2 L of normal saline every 3 to 4 weeks. The starting dose was 25 mg/m2. There were no intrapatient dose escalations. RESULTS: The dose-limiting toxicity was the development of severe abdominal pain at taxol doses more than 175 mg/m2. Moderate leukopenia (WBC count less than 2,000/mm3) was observed at IP doses of greater than or equal to 175 mg/m2. The exposure of the peritoneal cavity (peak levels and area under the time-versus-concentration curve [AUC]) to taxol after IP delivery exceeded that of the plasma by approximately 1,000-fold. However, concentrations of the agent previously shown to produce cytotoxicity in experimental systems were demonstrated in the systemic compartment after regional delivery, which was considered important. Significant concentrations of taxol persisted within the peritoneal cavity for more than 24 to 48 hours after a single IP installation. Several antitumor responses, which included control of platinum-refractory ascites, were documented. CONCLUSION: Taxol can be delivered by the IP route with both an acceptable toxicity profile and a major pharmacokinetic advantage for cavity exposure.

Alkaloids↗
PubMed1992

Exploring the use of chronic low-dose oral etoposide in ovarian cancer: is there a role for this "new drug" in the management of platinum-refractory disease?

Despite showing high objective response rates (70% to 80%) to cisplatin- or carboplatin-based chemotherapy, most patients with ovarian cancer ultimately die of complications of their disease. Etoposide, given either as a single agent or in combination with the organoplatinum compounds, has produced disappointingly low response rates in the salvage setting. Based on recent data that suggest chronic administration of oral etoposide is superior to single daily dosing every 3 to 4 weeks, and the failure of previous trials to evaluate etoposide's activity in cisplatin-resistant malignancies, we have begun a phase II trial of chronic, low-dose oral etoposide in patients with clinically defined, platinum-resistant ovarian cancer. Thus far, 11 patients have been entered into the study. Neutropenia, the most prevalent toxicity, has precluded several patients from receiving the full 20-day course of 50 mg/d. No responses to treatment have been observed in nine evaluable patients. The study continues to accrue patients. The final results of this study and other trials should help determine the efficacy of chronic low-dose oral etoposide administration in patients with ovarian cancer.

Administration, Oral↗
PubMed1992

Leaders fostering leaders.

Explore the source record for details and available documents.

American Speech-Language-Hearing Association↗
PubMed1991

The cyanide-metabolizing enzyme rhodanese in human nasal respiratory mucosa.

The cyanide-metabolizing enzyme rhodanese is present in rat nasal epithelium at high activity levels. Cyanide is a common environmental pollutant. It is both toxic and an odorant. The high rhodanese activity in rat nasal epithelium may provide a mechanism for detoxicating inhaled hydrogen cyanide and may also play a role in olfaction by limiting the concentrations of cyanide in the nasal epithelium. The objective of this study was to determine whether high levels of rhodanese activity are also present in human nasal epithelium. On a per milligram mitochondrial protein basis, the rhodanese in human nasal tissue exhibited both a lower affinity (higher Km) for cyanide and a lower maximum velocity (Vmax) for cyanide metabolism than did rhodanese from rat nasal tissue. As in human liver, the human nasal enzyme appeared to exhibit substrate activation by cyanide. Rhodanese activity in the maxilloturbinates of nonsmokers was statistically higher than in smokers although only three samples per group were available. The Vmax/Km ratios for rhodanese from the nasal tissue of nonsmokers were consistently greater, thus suggesting the possibility of higher rates of cyanide metabolism in nonsmokers than in smokers.

Cyanides↗
PubMed1991

Endometrial cancer and age at last delivery: evidence for an association.

Because the role hormonal and reproductive factors play in the etiology of endometrial cancer is incompletely understood, the authors evaluated the risk of this cancer in relation to age at last delivery. The data were obtained in a hospital-based case-control study of 483 women with endometrial cancer (cases) and 693 women with other conditions (controls) conducted in a number of hospitals in the United States and Canada from 1978 to 1985. There was an inverse association between age at last delivery and endometrial cancer risk: Compared with women who last gave birth before age 25 years, the rate ratio was 0.9 (95% confidence interval (CI) 0.5-1.6) for last delivery at ages 25-29 years, 0.6 (95% CI 0.3-1.0) for last delivery at ages 30-34 years, 0.5 (95% CI 0.3-1.0) for last delivery at ages 35-39 years, and 0.4 (95% CI 0.1-0.9) for last delivery at age 40 years or older. The trend of decreasing rate ratio with increasing age at last delivery was statistically significant (p = 0.02). The association was apparent regardless of parity or menopausal status. There was no evidence for an association between age at first pregnancy and risk. These data suggest that women who bear children late in reproductive life may be at lower risk for endometrial cancer than those who complete their families early.

Adult↗
PubMed1991

Persistent hypomagnesemia following cisplatin chemotherapy in patients with ovarian cancer.

The development of acute hypomagnesemia following cisplatin administration is a well-recognized complication associated with the use of this chemotherapeutic agent. However, there is limited information available in the medical literature concerning how long this abnormality may persist following the discontinuation of cisplatin. Of 13 patients with ovarian cancer who had a baseline serum magnesium determination obtained prior to the initiation of a second-line cisplatin-based chemotherapy regimen, 9 (69%) were found to be hypomagnesemic (serum magnesium less than 1.4 mg/l), including 3 patients with serum magnesium values less than 1.0 mequiv/l. The median cisplatin-free interval for these 9 patients was 19 months (range 6-40 months). We conclude that persistent, and possibly permanent, hypomagnesemia is common following cisplatin chemotherapy.

Cisplatin↗
PubMed1991

Phase II trial of high-dose cisplatin with sodium thiosulfate nephroprotection in patients with advanced carcinoma of the uterine cervix previously untreated with chemotherapy.

Cisplatin is one of the most active single agents in the treatment of advanced cancer of the cervix. The concurrent administration of the nephroprotective agent, sodium thiosulfate, has enabled exploitation of the therapeutic potential of cisplatin. To explore the role of cisplatin dose intensity in the treatment of patients with cancer of the uterine cervix, patients with persistent/recurrent measurable disease were treated with cisplatin at 200 mg/m2 as a 2-hr infusion with sodium thiosulfate given at 3.3 g/m2 1 hr prior to cisplatin and 6.6 g/m2 during the cisplatin infusion. Treatment was repeated monthly. Due to the known cumulative toxicity of cisplatin, treatment beyond two cycles (400 mg/m2) was given only to those patients who had at least demonstrated a PR. Audiologic evaluation was done prior to each cycle of treatment. Eleven patients were entered with a median age of 43 years (range, 25-57), a median KPS of 80% (range, 60-90%), and nine epidermoid and two adenocarcinoma, and all patients had received previous pelvic irradiation. Twenty-eight cycles of treatment were given: 1, five cycles; 3, three cycles; 7, two cycles. No greater than or equal to 3+ hematologic, neurologic, or renal toxicity was demonstrated. Ototoxicity was demonstrated in the mild to moderate hearing loss range (3000-8000 Hz). The greatest threshold shift occurred after the first course of cisplatin. There were three PRs with a maximum duration of 4 months. Due to the significant toxicities encountered, the low response rate, and the limited duration of responses, this trial was closed early to accrual.

Adult↗
PubMed1991

Chemotherapy-induced neutropenia and fever in patients receiving cisplatin-based chemotherapy for ovarian malignancy.

Fifty-six episodes of chemotherapy-induced neutropenia and fever occurred in forty-three patients receiving cisplatin-based combination chemotherapy for ovarian cancer. All patients were treated with broad-spectrum antibiotics including gentamicin. Twelve of fifty-six episodes were associated with positive cultures; in six patients a single organism was isolated, and the other six patients had polymicrobial infection. The mean duration of antibiotic therapy was 6.5 days. One patient died of sepsis. Fifty-five episodes had a successful outcome. There was no antibiotic-related morbidity. Based on this review we recommend broad-spectrum antibiotic therapy for chemotherapy-induced neutropenia with fever. The regimen of gentamicin plus ticarcillin and clavulanic acid (ceftazidime for penicillin-allergic patients) is effective as initial therapy. Additional agents (i.e., vancomycin) may be necessary in culture-positive patients based on sensitivity testing of bacterial isolates. Gentamicin can be safely administered to patients receiving cisplatin-based chemotherapy without compromising ability to continue cisplatin therapy in subsequent treatment cycles.

Adult↗
PubMed1991

Intraperitoneal chemotherapy: analysis of complications with an implanted subcutaneous port and catheter system.

To determine the morbidity associated with delivery of intraperitoneal chemotherapy via subcutaneous semipermanent infusion catheters, we analyzed the data on 227 patients treated from April 1985 through December 1989. A total of 249 catheters were inserted and used to administer chemotherapy in these patients. There were 40 (17.6%) complications associated with the use of 230 original catheters, with 20 patients experiencing catheter inflow obstruction and 20 developing catheter-related infections; the latter group included 8 patients with bowel perforations. Although there was a trend toward an increase in catheter-related infections in association with large bowel surgery and appendectomies, sample size limited statistical analysis. There were 7 (36.8%) complications associated with the use of 19 replacement catheters. This rate was significantly increased (P = 0.03) when compared with the complication rate of original catheters. This system functions well and has an acceptable level of morbidity for delivery of intraperitoneal chemotherapy in gynecologic cancer patients.

Catheterization↗
PubMed1991

Late effects of cisplatin-based chemotherapy on renal function in patients with ovarian carcinoma.

While the acute toxicity of cisplatin on renal function is well described, the long-term effects have received little attention in the medical literature. In an effort to examine this important issue, we evaluated the renal function of a group of 60 women with ovarian cancer who received a second-line cisplatin-based chemotherapy program at the Memorial Sloan-Kettering Cancer Center longer than 6 months following the completion of their initial cisplatin-based chemotherapeutic regimen. These patients had not received any cisplatin for a median of 19 months (range, 6-57 months) prior to beginning the second-line program. Only 4 patients (7%) had a serum creatinine value greater than 1.3 mg/dl (upper limit of normal in our laboratory) at the time of initiation of the second-line program. In each case, the serum creatinine was less than or equal to 1.6 mg/dl. An additional 6 patients (10%) had a greater than 50% increase in serum creatinine above the initial baseline value prior to any treatment, but were still within the normal range. Following second-line cisplatin therapy, only 1 of the 60 patients (2%) experienced a serum creatinine rise to greater than 2.0 mg/dl. We conclude that a limited number of patients with ovarian cancer who are long-term survivors following cisplatin-based chemotherapy exhibit evidence of a mild persistent compromise of renal function and, in general, second-line cisplatin can be administered to previously treated patients without the development of serious renal dysfunction.

Adult↗
PubMed1991

Prognostic factors for recurrence following negative second-look laparotomy in ovarian cancer patients treated with platinum-based chemotherapy.

Prior studies of the risk of recurrence following negative second-look laparotomy have included patients treated with a variety of chemotherapeutic regimens, including nonplatinum regimens. We have examined the long-term outcome and risk factors for recurrence among a homogeneous group of platinum-treated patients. During the years 1978-1987, 91 patients at Memorial Sloan-Kettering Cancer Center had a negative second-look laparotomy following platinum-based chemotherapy for epithelial ovarian cancer. The mean age at diagnosis was 57 years, with a range of 30 to 79. Distribution by stage was as follows: I, 10; II, 18; III, 57; IV, 6. The mean number of cycles of platinum prior to second-look surgery was 6.3. The mean number of biopsies taken at negative second-look laparotomy was 12. Lymph node biopsies were done in 47/91 (52%) of patients. Median follow-up from the date of second-look laparotomy was 54.6 months among survivors. Forty of ninety-one patients (44%) have had recurrence, almost 40% of which were outside the peritoneal cavity. The mean interval from negative second-look laparotomy to recurrence was 24 months (range, 2-70 months). By multivariate analysis the risk of recurrence was significantly related to stage (P = 0.017), histologic grade (P = 0.041), and the amount of tumor remaining after the first operation for ovarian cancer (P = 0.015). Recurrence by stage was as follows: stage I, 1/10 (10%); stage II, 5/18 (28%); stage III, 31/57 (54%); stage IV, 3/6 (50%). Recurrence by grade was as follows: grade 1, 4/18 (22%); grade 2, 11/28 (39%); grade 3, 25/45 (56%). There was no relationship between the risk of recurrence and the number of cycles of platinum, the number of biopsies performed at second-look, or the number of months from primary surgery to second-look. Patients having negative second-look laparotomy following platinum-based chemotherapy for advanced epithelial ovarian cancer have a substantial risk of recurrence, particularly within the first 3 years. Such patients should be offered participation in clinical trials of consolidation therapy directed against both intraperitoneal and extraperitoneal disease.

Adult↗
PubMed1991

Cisplatin-based combination chemotherapy in carcinoma of the fallopian tube.

Forty-three cases of primary tubal adenocarcinoma were treated at Memorial Sloan-Kettering Cancer Center between 1979 and 1989. Thirty-eight patients who received cisplatin-based combination chemotherapy following primary surgery were reviewed. The mean patient age was 59 years, with 86% postmenopausal. Distribution by stage was as follows: I, 3 (7%); II, 4 (11%); III, 27 (71%); and IV, 4 (11%). Median follow-up from the time of diagnosis was 62 months (range, 5-132). Overall survival for all 38 patients by Kaplan-Meier analysis was 51% at 5 years. Excluding stage I, patients with no residual disease following surgery had a significantly higher 5-year survival (83%) than those left with gross residual disease (28%). Twenty-six patients underwent a second-look procedure. Of the 21 patients with advanced (stages III, IV) disease undergoing reexploration, 11 (52%) had a negative second-look and 10 (48%) were positive. Ten of the eleven patients with a negative second-look remain clinically free of disease with a median follow-up of 49 months. One patient with stage III disease had recurred after 47 months. Carcinoma of the fallopian tube appears to respond favorably to cisplatin-based multiagent chemotherapy. Patients with advanced-stage disease who achieve a negative second-look appear to have an improved possibility of remaining disease-free over similar-stage patients with ovarian cancer.

Adult↗
PubMed1991

Analysis of antigen expression at multiple tumor sites in epithelial ovarian cancer.

The question of whether the antigenic phenotype of human epithelial ovarian cancer varies in a given patient between the primary tumor and metastatic sites or among metastatic sites themselves is an important issue in planning potential therapeutic strategies for ovarian cancer. We have obtained tumor specimens from at least two separate sites during operations on 12 patients with epithelial ovarian cancer, and we have typed these specimens with a group of 18 monoclonal antibodies that react with cell-surface glycoprotein and carbohydrate antigens, including blood group antigens. Antibodies with relative specificity for malignant cells as well as those that detect more widely distributed epithelial antigens were used. A total of 31 specimens from 12 patients with advanced adenocarcinoma (8 serous, 3 undifferentiated, 1 endometrioid) of the ovary were studied, including fresh ascites cells in two patients. Frozen sections of tumor specimens were stained with the antibodies by the indirect immunoperoxidase technique and graded semiquantitatively. Little difference was seen in antigenic expression of tumors that were obtained from various sites in the same patient for either the epithelial cell markers or blood group markers. Intratumoral antigenic heterogeneity was seen, but this was generally quite consistent within a given patient's specimens. As anticipated, variations in antigen expression were seen among specimens from different patients. The antigenic phenotype of the tumor specimens in a given patient, as determined immunohistochemically by our group of antibodies, showed only minor variation among primary and metastatic sites.

Antibodies, Monoclonal↗