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Biomedical subjects

J L Lewis

Publications and source records attributed to J L Lewis.

At least 199 records · Page 11Linked to original sources

Knee mechanics after repair of the anterior cruciate ligament. A cadaver study of ligament augmentation.

An experimental knee-testing system was used to investigate the immediate postoperative mechanical state in knees with nonaugmented and augmented repairs of the anterior cruciate ligament. Ligament, repair tissue, and augmentation forces were measured using buckle transducers, and joint motion was measured using an instrumented spatial linkage during the application of 90 N anteriorly-directed tibial loads to seven fresh knee specimens at 0-90 degrees of flexion. Force and motion data were collected from each knee with an intact and excised anterior cruciate ligament, and after performing (1) a nonaugmented repair and an augmented repair using the Ligament Augmentation Device (3M Company) placed either (2) anatomically through the lateral femoral condyle or (3) in the over-the-top position. The forces in the nonaugmented repair and the repair with the augmentation in the two positions were greater than the forces in the intact anterior cruciate ligament with the knee under the same anterior loads; this difference from normal was not significant with the over-the-top augmentation. With the augmentation anatomically placed, the load sharing did not reduce the force in the repair tissue as compared with the nonaugmented case. The over-the-top augmentation, on the other hand, lowered the repair tissue forces at extension while avoiding high repair tissue forces in flexion. The tibia was consistently in an externally rotated configuration compared with normal in both the unloaded and anterior load states with all three repair procedures.

Biomechanical Phenomena↗

Second-look laparotomy in endodermal sinus tumor: a report of two patients with normal levels of alpha-fetoprotein and residual tumor at reexploration.

The role of second-look laparotomy in the management of patients with endodermal sinus tumor of the ovary is controversial. We report two women who converted to a normal alpha-fetoprotein (AFP) level during treatment with combination chemotherapy, yet were found to have residual endodermal sinus tumor at second-look laparotomy. In view of the limited experience with this rare disease, we continue to recommend second-look laparotomy for patients who have completed chemotherapy for endodermal sinus tumor of the ovary, regardless of the serum AFP level.

Adolescent↗

Intraperitoneal chemotherapy as treatment for ovarian carcinoma and gastrointestinal malignancies: the Memorial Sloan-Kettering Cancer Center experience).

Several different chemotherapy trials via either combined systemic and intraperitoneal or only via the intraperitoneal route were investigated. The administration of systemically and intraperitoneally infused 5-fluorouracil (5-FU) in patients with ovarial carcinoma did not shown in any patient a complete or partial remission, but showed severe side effects. In a patient with a metastasizing adeno carcinoma of the appendix this chemotherapy protocol led to a complete remission. Investigations with intraperitoneally infused cisplatin showed that 50% of all patients came into remission with tumor nodules less than 0.5 cm, but showed only 20% objective remissions in patients with tumor nodules greater than 0.5 cm. The intraperitoneal administration of mitoxantrone showed in several patients with cisplatin refractory ovarial carcinoma tumor remission with, however, severe local toxicity.

Antineoplastic Combined Chemotherapy Protocols↗

Recurrence after negative second-look laparotomy for ovarian cancer: analysis of risk factors.

To determine the long-term rate of recurrence and define risk factors for recurrence, we have analyzed clinical information on 83 patients followed up for a minimum of 4 years (median, 69 months) after negative second-look laparotomy. Overall, 21 of 83 patients (25.3%) had a recurrence. Median interval to recurrence was 14 months. Stage, grade, and type of chemotherapy were significantly related to risk of recurrence. In patients with stage I disease only one of 27 (3.7%) had a recurrence. Patients with stage I disease were not included in further analysis of risk factors. In stages II, III, and IV, 20 of 56 patients (35.7%) had a recurrence. Recurrence rates by grade (excluding stage I) are as follows: grade 1, three of 21 (14.3%); grade 2, six of 17 (35.5%), and grade 3, 11 of 17 (64.7%). Platinum-treated patients in stages II, III, and IV had a 50% (12/24) recurrence rate compared with 25% in nonplatinum-treated patients (8/32) (p = 0.05). Differences in disease-free survival between platinum- and nonplatinum-treated patients were significant at the p = 0.02 level. When treated with platinum-based regimens, more patients will achieve complete clinical remission and subsequently negative second-look laparotomy. However, the recurrence rate in these patients is considerably higher than that in patients treated for longer durations with nonplatinum regimens.

Antineoplastic Agents↗

Primary chemotherapy and the role of second-look laparotomy in non-dysgerminomatous germ cell malignancies of the ovary.

In view of the rarity of germ cell tumors of the ovary, it is not surprising that little information exists about the indications for and significance of findings at second-look laparotomy in patients with these tumors. For this reason, we have reviewed 16 patients who received primary chemotherapy for malignant germ cell tumors of the ovary at Memorial Sloan-Kettering Cancer Center (MSKCC) between 1976 and 1983. Eleven of them underwent a second-look laparotomy after completion of their therapy. Primary therapy consisted of surgery, usually unilateral oophorectomy, and cis-platinum-based VAB chemotherapy. The histologic diagnoses were six immature teratomas, five endodermal sinus tumors, four mixed germ cell tumors, and one nongestational choriocarcinoma. Stage distribution was as follows: Stage IA, eight patients; Stage IC, one patient; Stage IIA, one patient; Stage III, four patients, and unstaged, two patients. The ages ranged from 15 to 56 years, with the mean of 29 years. All of the 11 patients undergoing second-look laparotomy were found to be free of disease. They are alive and have been continuously free of disease from 9 to 77 months (mean 39 months). This paper discusses primary chemotherapy and the role of the second-look laparotomy and suggests its value in modifying treatment, predicting cure, and safely stopping therapy in patients with germ cell malignancies of the ovary.

Adolescent↗

Description and error evaluation of an in vitro knee joint testing system.

An experimental system for the analysis of knee joint biomechanics is presented. The system provides for the simultaneous recording of ligament forces using buckle transducers and three-dimensional joint motion using an instrumented spatial linkage, as in vitro specimens are subjected to a variety of external loads by a pneumatic loading apparatus with associated force transducers. The system components are described, and results of an evaluation of system errors and accuracy are presented. The experimental setup has been successfully used in the analysis of normal knee ligament mechanics, as well as surgical reconstructions of the anterior cruciate ligament. The system can also be adapted to test other human or animal in vitro joints.

Biomechanical Phenomena↗

Phase I trial of concurrent intraperitoneal and continuous intravenous infusion of fluorouracil in patients with refractory cancer.

In an effort to maximize both local-regional and systemic drug exposure to tumor in the peritoneal cavity, a phase I study was conducted that examined the simultaneous daily intraperitoneal (IP) and continuous intravenous infusion (CVI) of fluorouracil (5-FU) to 32 patients with refractory cancer. IP 5-FU administered at 1,000 mg/d with concurrent 5-FU by CVI at 1,000 mg/m2/d for four consecutive days was well tolerated. One patient with a primary gastrointestinal (GI) malignancy with minimal volume disease experienced a surgically defined complete remission. In theory, this regimen may demonstrate clinical utility as an adjuvant treatment of certain GI malignancies. Future studies are planned in this clinical setting.

Drug Administration Schedule↗

A phase I trial of intraperitoneal recombinant gamma-interferon in advanced ovarian carcinoma.

The interferons are a class of biological agents that have demonstrated antineoplastic activity in a variety of tumors both in vitro and in vivo. Previous reports have suggested that interferons can be safely administered by the intraperitoneal (IP) route with a pharmacokinetic advantage for peritoneal cavity exposure compared with the systemic circulation and with objective antitumor activity being demonstrated. On the basis of these reports and laboratory data suggesting activity for recombinant gamma-interferon (r-GIFN) against several malignant cell lines, we treated 27 refractory ovarian carcinoma patients, including six with very-small-volume residual disease, with this agent delivered by the IP route. While r-GIFN was found to be remarkably well tolerated, with a 150- to 200-fold pharmacokinetic advantage for peak levels achieved in the peritoneal cavity compared with the plasma, no objective responses were observed. Despite the lack of demonstrated activity for single-agent IP-administered r-GIFN in this clinical setting, there remains considerable interest in this agent when delivered by the IP route because of in vitro data suggesting concentration-dependent synergy between r-GIFN and other biological agents.

Adult↗

Treatment of uterine leiomyosarcoma.

We reviewed 46 cases treated at the Gynecology Service of Memorial Sloan-Kettering Cancer Center from 1970-1984 to evaluate the impact of modern multimodal therapy on survival of patients with uterine leiomyosarcoma. Eighteen patients had their primary treatment at Memorial Hospital, whereas the remaining 28 patients were referred either after primary surgery (ten) or after the development of recurrent disease (18). Thirty-four patients initially had disease confined to the uterus. Twelve of these patients received various adjuvant treatment regimens after hysterectomy, and 83.3% developed recurrent disease; 68.2% of 22 patients who received no adjuvant therapy developed recurrent disease. Twelve patients who presented with extrauterine disease all died within two years of initial treatment. Thirty-seven patients were treated for persistent or recurrent disease after primary treatment. No objective responses to radiation therapy were seen in these patients. Doxorubicin used alone or in combination produced a 16.7% response rate (average duration four months), whereas there were no responses to chemotherapeutic regimens not containing doxorubicin. The disease-free survival rate for all patients in this study was 22%; those patients who presented with stage I and II disease had a 29% survival rate.

Adult↗

Integration of surgery and other techniques in the management of trophoblastic malignancy.

The role of surgery in the management of gestational trophoblastic neoplasms has changed over the years and warrants continuous re-evaluation. Surgical removal of the bulk of the disease in an attempt to shorten the hospital course and decrease the amount of chemotherapy required appears to be of value. This approach to therapy should therefore be considered in most patients with nonmetastatic disease without regard to the histologic diagnosis if they have completed their families. "Debulking" of primary uterine disease in the presence of metastases may decrease the chemotherapy necessary for cure and removes a potential source of resistant disease. Pulmonary surgery improves survival rates for patients with a solitary, resistant lung tumor and is advisable under the circumstances outlined herein. Craniotomy is rarely of value in the management of tumor in the brain but may be necessary in emergency situations caused by intracerebral hemorrhage. Surgery to control complications of the disease has been proved to be safe with acceptable morbidity even if performed during chemotherapy. Thus, although chemotherapy has replaced surgery as the primary management of patients with gestational trophoblastic disease, there remain a significant number of patients in whom surgery plays a significant role.

Combined Modality Therapy↗

Peritoneal cytology as an indicator of disease in patients with residual ovarian carcinoma.

Cytologic assessment of peritoneal washings or ascites in ovarian cancer patients has been suggested as a method of evaluating response to therapy or disease status, although the accuracy of this technique has not been clearly established. Ascitic fluid or peritoneal washings were obtained during 96 reassessment laparotomies that were biopsy-positive for residual intraperitoneal ovarian cancer. Cytologic studies done on these samples failed to detect malignant cells in 66% of the cases with gross residual disease and 78% of the cases with only microscopic residual disease on biopsy. The accuracy of peritoneal cytology in detecting residual ovarian cancer was unrelated to residual tumor size, original clinical stage, histologic tumor grade, and tumor cell type. Examination of ascitic fluid found at the time of surgery was somewhat more reliable than assessment of peritoneal washings, although this difference was of borderline statistical significance. Peritoneal cytology cannot reliably detect residual ovarian cancer after initial treatment with surgery and chemotherapy. Negative peritoneal cytology is frequently seen in the presence of gross residual tumor.

Ascitic Fluid↗

Mouse monoclonal antibodies to human epithelial differentiation antigens expressed on the surface of ovarian carcinoma ascites cells.

Four different human epithelial differentiation antigens (MT179, MW162, MW207, and MX35) have been defined by mouse monoclonal antibodies obtained from mice immunized with either an ovarian carcinoma cell line or fresh ovarian carcinoma cells. In an attempt to identify tissue-specific antigens restricted to ovarian epithelial cells, sections of a benign ovarian cyst were used as the initial target for screening hybridoma supernatants. The distribution of the antigens detected by these monoclonal antibodies was determined on frozen sections of 24 normal tissues and on 103 cultured cell lines of various histological types. In spite of the method used to select these monoclonal antibodies, they all reacted to some degree with normal epithelial cells in tissues other than ovary. All antibodies were unreactive with nonepithelial cells in frozen sections. These antibodies also reacted with frozen sections of most or all fresh ovarian carcinomas and benign ovarian cysts. All antibodies were unreactive with ABH, Lewis blood group-related antigens and appeared to be different in specificity from previously described well-characterized antigens of ovarian carcinoma cells. MW162 was characterized as a high-molecular-weight mucin-like molecule, and the determinant recognized is probably carbohydrate in nature. MW207 was identified as a Mr 37,000 protein. These monoclonal antibodies and 24 other previously derived antibodies that react with epithelial differentiation antigens were tested for reactivity with the surface of fresh ovarian carcinoma ascites cells and for nonreactivity with normal mesothelial cells. This assay was designed to select monoclonal antibodies that might be effective agents for i.p. therapy or radioimmunodetection of human ovarian carcinoma. Five antibodies with the desired specificity were selected; these were the four new antibodies described herein and MH99, which was characterized previously and recognizes a glycoprotein having Mr 38,000 and 29,000 subunits. The degree of heterogeneity of antigen expression on ascites carcinoma cell was dependent on the particular antigen being examined and was related to the biochemical nature of the antigen. In particular, most ABH and Lewis blood group-related antigens showed a striking degree of heterogeneity.

Animals↗

Elastic moduli, yield stress, and ultimate stress of cancellous bone in the canine proximal femur.

Elastic moduli, yield stress and ultimate compressive stress were determined for cancellous bone from the femoral head and neck regions of the canine femur. Unconfined compression tests were performed on 5 mm cubic samples which were cut from two femurs. Elastic moduli were measured in three orthogonal directions, and the yield stress and ultimate stress were measured along the proximal-distal axis. The results from this investigation support previous assumptions that the mechanical behavior of canine cancellous bone is qualitatively similar to human cancellous bone. The canine cancellous bone was observed to be anisotropic in elastic modulus. For two thirds of the cubic specimens tested, the elastic modulus was largest in the load-bearing, proximal-distal direction. A linear relationship between yield stress and elastic modulus was observed for canine bone, as is typical of human bone. A similar linear relationship between ultimate stress and elastic modulus was observed. Thus, for canine bone as well as for human bone, failure appears to be governed by a strain level which is position independent. The yield strain of 0.0259 and ultimate strain of 0.0288 for canine bone were both less than the yield strain of 0.0395 reported for human bone.

Animals↗

Pharmacokinetics of 2'-deoxycoformycin, an inhibitor of adenosine deaminase, in the rat.

The distribution of the potent inhibitor of adenosine deaminase (ADA), 2'-deoxycoformycin (DCF), in the brain of the rat and its inhibition of ADA in brain and gut was determined. The accumulation of [3H]DCF in brain was maximal 2 hr after intraperitoneal injection and elimination was best described by a two compartment model having t1/2 phases of about 1-5 hr and 50 hr. The activity of ADA in gut exhibited dose-related inhibition at 1.9, 3.7 and 18.6 mumol/kg (i.p.) and returned to normal by 16 days. In brain, ADA was inhibited by about 95% at all three of these doses of DCF 2 hr after injection and activity returned to control levels by 30 days with the two smaller doses, but remained at 66% of control levels at 50 days with 18.6 mumol/kg. The t1/2 of the recovery of the activity of ADA in both brain and gut was found to be dose-dependent. The failure of the activity of ADA in brain to recover after treatment with 18.6 mumol/kg suggests either long-term down-regulation of the expression of ADA or irreversible damage to ADA-containing neurons.

Adenosine Deaminase↗

Radical hysterectomy for recurrent cervical cancer following radiation therapy.

In patients with small central recurrences following radiation therapy for cervical cancer the surgeon may have to make a judgment as to when radical hysterectomy is preferable to exenteration. During the years 1968-1984 there were 21 radical hysterectomies performed at Memorial Sloan-Kettering Cancer Center for recurrent cervical cancer. The original clinical stage distribution is as follows: IB-4, IIA-4, IIB-11, IIIB-1, IVA-1. The median interval from initial diagnosis to recurrence was 10 months. There were two operative deaths; both were from sepsis. Ten of the 21 patients developed postoperative fistulas, with 9 requiring surgical diversion of the urinary or both urinary and intestinal tracts. Thirteen of 21 patients (62%) have survived with a median follow-up of 73 months. Seven patients suffered recurrences following radical hysterectomy. All developed recurrence in the central pelvis. Four had sidewall disease as well, but none had distant disease at the time recurrence was diagnosed. Of 11 patients with cervical tumors of 2 cm or less in size at the time of radical hysterectomy, none experienced recurrence, while among 10 patients with tumor size of greater than 2 cm, 7 had recurrence. All patients whose initial clinical stage was IB or IIA have survived without recurrence. There was only 1 survivor among 5 patients with positive parametrial or vaginal margins. Six of the 13 survivors required urinary diversion, and 2 required colostomy as well. Radical hysterectomy for this indication is a morbid procedure which should be undertaken only by the most experienced of pelvic surgeons and limited to patients of early clinical stage with central recurrences of less than 2 cm in size.

Adult↗

Modification of an infant incubator for exposure of experimental animals to nitrous oxide.

Research with N2O is hampered because it is a gas and must be inhaled by the test subject rather than injected. Described herein is the development of a practical and efficient exposure chamber for such research. A Model C-35 Isolette infant incubator was modified by installation of a manifold system for distribution and opposed-suction fans for a circulation of the gas mixture (N2O in oxygen). An exponential model was developed, predicated on gas concentration uniformity, to track the increasing concentration of N2O during chamber filling and to predict the time required for the chamber to assume a steady-state level of N2O. This model requires that three things be known: the volumetric flow rate of administered gas mixture, the concentration of N2O in that mixture, and the volume of the chamber. The model predicts that X(t)/X infinity = 1 - exp(-t/tau), where X(t) is the concentration of N2O of an instant t; X infinity, the concentration of N2O administered; and tau, the time constant--the ratio of chamber volume to volumetric flow rate. This model was confirmed via mass spectroscopy analysis of gas from the chamber during filling.

Air↗

Combined surgery and radiation in endometrial carcinoma: an analysis of prognostic factors.

From 1969 to 1979, 300 patients with the diagnosis of endometrial cancer operated elsewhere were referred for treatment to the Department of Radiation Oncology at Memorial Sloan-Kettering Cancer Center. All the patients were staged according to FIGO classification. One hundred and seventy-three patients were Stage IA, 105 patients were Stage IB, and 22 patients were Stage II. Within Stage IA, 141 patients had well differentiated tumor (G1), 20 had moderately well differentiated tumor (G2), and 12 patients had poorly differentiated (G3). One hundred and thirty-three patients had superficial myometrial invasion and 40 patients had deep myometrial invasion. Within Stage IB, 69 patients had G1 tumor, 23 had G2, and 13 had G3 tumors. Seventy-four patients in this group had superficial myometrial invasion and 31 patients had deep myometrial invasion. Two hundred and eighty-three patients had adenocarcinoma, 13 patients had adenoacanthoma, 4 patients had adenosquamous and other histological types. All of the patients received combined surgery (total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH/BSO) and radiation. The radiation treatments consisted of external pelvic radiation and intravaginal vault radiation. External pelvic radiation was delivered with a megavoltage apparatus for a total dose of 4,000 cGy in 4 weeks preoperatively (47 patients) or postoperatively (105 patients) in patients presenting with high grade (G2,G3), more than 1/3 myometrial invasion, Stage II and extrauterine extension of disease at surgery. All patients received in addition, postoperative intravaginal vault irradiation consisting of 2100 cGy in 3 fractions over 4 weeks with a high dose rate remote afterloading technique. The follow-up in these patients ranged from 5-14 years. Survival data was calculated according to Kaplan-Meier Method and Cox regression multivariate analysis to identify the prognostic factors. The 10-year survival rate in Stage IA was 91%; in Stage IB 75%; and in Stage II it was 71%. Eleven patients (4%) developed recurrent disease with either local and/or distant metastasis. Nine-percent of the patients developed mild to moderate complications which resolved with conservative treatment. Patients with gross extra-uterine pelvic extension of disease had a poor survival compared with those presenting with microscopic involvement (40% vs. 80% at 5-years). No statistically significant difference in survival was observed between patients who received either preoperative or postoperative external pelvic irradiation.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗