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Biomedical subjects

J L Lewis

Publications and source records attributed to J L Lewis.

At least 181 records · Page 10Linked to original sources
PubMed1990

Immunohistochemical localization of P-glycoprotein in adult human ovary and female genital tract of patients with benign gynecological conditions.

The multidrug-resistance gene, MDR1, encodes a plasma membrane glycoprotein termed P-glycoprotein, which mediates active cellular efflux of certain cytotoxic agents. Two mouse monoclonal antibodies (MAb), C219 and JSB-1, were used to identify P-glycoprotein in frozen tissue from the female genital tract of 14 women with benign gynecological conditions; multiple samples from several sites in the genital tract were available from seven patients. P-glycoprotein was detected in the ovarian surface epithelium in four of 14 cases, in the Fallopian tube in three of five cases, in occasional epithelial cells of the endometrial glands in two of five cases, in some endocervical glandular epithelium in three of five cases, in ectocervical squamous epithelium in one of the two cases, and in luteinized cells of the eight cases in which a corpus luteum was present in the specimen. Positive staining with these two MAb was also observed in some endothelial cells in the cortex of the ovary and in the stromal tissue of the myometrium, endometrium, and endocervix. These studies suggest that, if epithelial ovarian cancers are derived from the surface epithelial cells of the ovary, a small proportion of the cancers might be expected to retain the phenotype found in non-cancerous cells and to express P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1990

Phase II trial of intraperitoneal mitoxantrone in the management of refractory ovarian cancer.

To define both the toxicity and efficacy of intraperitoneal mitoxantrone in the treatment of refractory ovarian carcinoma, 31 patients were entered onto a phase II trial of this agent delivered in a 2 L treatment volume on a monthly basis. Due to excessive local pain at the initial dose level (30 mg/m2), the amount of drug delivered with each treatment course was reduced to 20 mg/m2. Despite this reduction, 74% of patients required narcotic analgesia during treatment. In addition, there were four episodes of bowel obstruction (one requiring surgical intervention) during therapy, and two patients developed bowel obstruction and intraabdominal abscesses following the completion of treatment. Six of 18 evaluable patients (33%) whose largest tumor diameter was less than or equal to 1 cm at protocol initiation experienced surgically documented responses, compared with one of 11 patients (9%) whose largest tumor was greater than 1 cm in diameter. If the two patients exhibiting what we called a mixed response to treatment are included, seven of 21 patients previously treated with intraperitoneal cisplatin responded to this treatment program, including four patients who had failed to respond to intraperitoneal cisplatin. No responding patient has demonstrated clinical evidence of relapse with a median follow-up of 7 months (range, 3+ to 13+ months) from response laparotomy. Intraperitoneal mitoxantrone is an active treatment program in patients with small-volume refractory ovarian carcinoma, but local toxicity can be severe. Due to the toxicity encountered with this specific program, its use cannot be recommended for standard clinical practice. However, in view of the activity observed in refractory ovarian carcinoma, including responses in patients who had previously failed intraperitoneal cisplatin, it is important to continue to explore alternative therapeutic regimens using intraperitoneal mitoxantrone to reduce local toxicity while maintaining or improving efficacy.

Carcinoma↗
PubMed1990

Anterolateral rotatory instability of the knee. Cadaver study of extraarticular patellar-tendon transposition.

A cadaver knee-testing system was used to analyze the effect of an extraarticular reconstruction for anterolateral rotatory instability in which the lateral one third of the patellar tendon with a patellar bone block was transposed to the lateral femoral condyle. Ligament and reconstruction tendon forces were measured using buckle transducers, and joint motion was measured using an instrumented spatial linkage as 90 N anteriorly directed tibial loads were applied to seven knee specimens at 0 degree, 30 degrees, 60 degrees, and 90 degrees of flexion by a pneumatic load apparatus. This was done for each knee with first an intact, then an excised anterior cruciate ligament, and finally the extraarticular reconstruction. Forces in the transposed graft exhibited an isotonic pattern over the flexion range, unlike the intact anterior cruciate ligament, which was more highly loaded in extension than in flexion. The transposition of the patellar tendon led to external rotation of the tibia in both unloaded and anterior load conditions throughout flexion. Collateral ligament forces increased with anterior cruciate ligament excision, with the force in the medial ligament remaining higher than normal with the reconstruction, while the lateral forces became lower than normal.

Biomechanical Phenomena↗
PubMed1989

Experimental method for the measurement of the elastic modulus of trabecular bone tissue.

A procedure has been developed to measure the elastic modulus of small, irregularly shaped specimens without significantly disturbing the specimen's internal or surface structure. This procedure was developed to measure the average elastic modulus of isolated trabeculae from human cancellous bone tissue. The procedure combines direct testing of a cantilever beam-type specimen, along with finite element modeling of the specimen and the testing conditions. Initial estimates for the bone tissue material properties are input into the finite element model; differences between the calculated finite element displacement and the experimentally observed displacement allows the actual material modulus to be determined. Machined aluminum and cortical bone specimens were used to test the accuracy and repeatability of the procedure. Manipulations of the finite element models were performed to examine the effect that mesh construction errors might have on the accuracy of the results. None of the parameters examined resulted in changes in the measured finite element displacements of greater than 8%. In tests on six trabecular bone specimens, an average elastic modulus of 7.8 GPa was calculated. Even taking into account the possible sources of error, this value remains significantly less than the accepted value for cortical bone.

Bone and Bones↗
PubMed1989

Binding parameters of monoclonal antibodies reacting with ovarian carcinoma ascites cells.

Binding parameters were determined for four mouse monoclonal antibodies reacting with three antigens on the surface of fresh human ovarian carcinoma ascites cells, under nearly physiological conditions. The object of these experiments was to aid in the selection of the optimal monoclonal antibodies for intraperitoneal immunotherapy. The number of antigenic sites per cell, the effective equilibrium association constant (affinity) and the half-life for dissociation were: for Ab MH99, 1.2 x 10(6) sites/cell, (1.9-4.1) x 10(8) M-1, and 4 h; for Ab MX35, (3.2-4.1) x 10(5) sites/cell, (3.4-4.8) x 10(8) M-1, and greater than 10 h; and for Ab MW207, 1.3 x 10(5) sites/cell, (3.6-4.1) x 10(9) M-1, and 3.1 h, respectively. One of the antigens, MH99, is recognized by five different monoclonal antibodies, and competitive inhibition experiments demonstrated that two distinct determinants are present; this antigen is also recognized by the previously described Ab 17-1A. These binding data will aid the rational design of immunotherapy strategies.

Animals↗
PubMed1989

Mechanisms of general anesthesia: brain regional responses to baclofen.

The GABAB agonist baclofen is reported to produce general anesthesia when administered either centrally into the lateral ventricles of rats or peripherally to mice. Previously we demonstrated that beta-endorphin given intracerebrally produces anesthesia in rats, a response localized to sites in or adjacent to the inferior third and fourth ventricles. In order to compare the anatomical localization of these two anesthetic responses, we administered baclofen into the inferior or superior lateral or third ventricles, the aqueduct, or fourth ventricle in rats. Although 10 micrograms baclofen infusions into several regions caused loss of the righting reflex, in no case did animals exhibit an unconscious state which satisfied strict criteria of anesthesia. Infusions of 20 micrograms into the inferior third and fourth ventricles elicited seizures followed by a postictal depression. Although unresponsive to some stimuli, these animals showed no impairment in the corneal reflex. Since this dose was often lethal, higher doses not tested. Baclofen, given to mice intraperitoneally at doses of 25, 50, or 75 mg/kg, failed to elicit strictly defined anesthesia, although, to varying degrees, animals exhibited analgesia, loss of the righting reflex, and loss of behavioral responses to loud sounds. Animals continued to show motor responses when handled and retained corneal reflexes. Baclofen does not evoke an unconscious anesthetic state when administered centrally or systemically, emphasizing the need for strict criteria to define general anesthesia and to categorize drugs that promote this state.

Anesthesia, General↗
PubMed1989

Palliative surgery for intestinal obstruction in advanced ovarian cancer.

Intestinal obstruction in ovarian cancer patients is a major complication which frequently affects survival and quality of life. After a reasonable trial of conservative management fails, surgery is the only hope for relief of obstruction. In an effort to evaluate the success of such surgery we have reviewed the outcome of 54 operations (52 patients) for relief of intestinal obstruction performed over the 3-year period 1983-1985. Possible predictive factors for success and survival following surgery were analyzed. The sites of intestinal obstruction in the 54 procedures were as follows: small intestine 24 (44%); large intestine 18 (33%); combined small and large intestine 12 (22%). In 11 operations no surgical correction of the obstruction was possible. In 43, major intestinal procedures were performed, including 14 bypasses, 13 resections, and 20 colostomies. Of the 43 instances in which intestinal procedures were performed, 4 patients expired without leaving the hospital. At the time of discharge from the hospital the remaining 34 of these 43 patients were eating a regular or low-residue diet. Successful palliation of intestinal obstruction was thus achieved in 79% of the 43 instances in which a definitive procedure could be performed, and in 63% of the total of 54 operations. Mean survival following surgery was 6.8 months for the group undergoing a definitive procedure, and 1.8 months for the group undergoing exploration only. There was no significant difference between the two groups with regard to age, time from diagnosis, prior radiotherapy, number of prior laparotomies, site of obstruction, or use of total parenteral nutrition. None of the multiple clinical variables analyzed correlated with survival following definitive surgery. Most patients explored for intestinal obstruction due to advanced ovarian cancer can have their obstruction relieved and be discharged from the hospital. We were not able to define criteria that would allow selection of patients unlikely to benefit from surgery.

Adult↗
PubMed1989

Intestinal surgery in gynecologic oncology.

Intestinal surgery is frequently required in the management of patients with gynecologic malignancies. During a recent 3-year period 10.4% of all laparotomies performed on the Gynecology Service at Memorial Sloan-Kettering Cancer Center included major intestinal surgery. A total of 215 separate intestinal procedures were performed during 171 operations on 158 patients. The majority of operations were performed in patients with ovarian (42.7%), cervical (24%), and endometrial (12.3%) malignancies. Seventy-nine of 171 (46.2%) of operations were performed on previously irradiated patients. The most frequent indications for intestinal surgery were intestinal obstruction (43.2%) and intestinal fistula (21%). Procedures performed included 87 intestinal resections, 26 intestinal bypasses, 82 colostomies, and 20 intestinal conduit urinary diversions. Hand suturing was used in 71% of anastomoses; automatic stapling instruments were used in 29%. There was a single surgical mortality. Complications including infections, obstruction, and fistula formation were infrequent. These difficult intestinal procedures can be performed safely in the context of a fellowship training program. Since a significant proportion of all laparotomies done in gynecologic cancer patients will include major intestinal surgery, physicians managing patients with these diseases should have both the technical skills necessary to perform these procedures, as well as a thorough understanding of the diseases themselves.

Female↗
PubMed1989

Synergistic activity of tumor necrosis factor and interferon in a nude mouse model of human ovarian cancer.

In vitro and in vivo studies suggest a synergistic inhibition of tumor growth by the combination of certain interferons and tumor necrosis factors. We have examined the activity of two of these agents in an animal model of human ovarian cancer. The human ovarian cancer cell line SK-OV3 was grown subcutaneously in immunodeficient mice. Mean relative tumor volume was determined weekly by external tumor measurements and a standard formula. Animals were treated by intraperitoneal injection with (1) recombinant human tumor necrosis factor alpha (rHTNF) 5 or 10 micrograms/day; (2) recombinant murine interferon gamma (rMIFN) 5 x 10(4) units per day; or (3) a combination of rHTNF 5 micrograms/day and rMIFN 5 x 10(4) units/day. Simultaneous control groups were run for all experiments. Administration of rHTNF alone in either dose had no effect on rate of tumor growth. Administration of rMIFN at a dose of 5 x 10(4) units/day produced a marginal decrease in rate of tumor growth. Animals receiving both rHTNF 5 micrograms/day and rMIFN 5 x 10(4) units daily showed marked inhibition of tumor growth, with the mean relative tumor volume after 4 weeks of treatment measuring 0.75 +/- 0.91 in the treatment group and 11.06 +/- 2.96 in the control group. rHTNF and rMIFN demonstrate a synergistic inhibition of tumor growth in this animal model of human ovarian cancer.

Animals↗
PubMed1989

A longitudinal study of antigen expression in epithelial ovarian cancer.

The extent to which the antigenic phenotype of human epithelial ovarian cancer changes during the course of the disease is an issue that must be addressed in order to maximize the potential of antibody-directed imaging and therapy. We have obtained tumor specimens at two separate operations from ten patients with epithelial ovarian cancer and typed these specimens with a panel of 19 monoclonal antibodies to cell surface glycoprotein and carbohydrate antigens including blood group antigens. Antibodies with relatively high specificity for malignant cells as well as those detecting more widely distributed epithelial antigens were used in the study. Mean time between the two operations was 8.5 months. Five patients received intraperitoneal therapy during the interval between the two operations, including platinum-based regimens (four patients) and tumor necrosis factor (one patient). Four patients received intravenous platinum-based chemotherapy; one received no treatment. Frozen sections of specimens were stained with the antibodies by the indirect immunoperoxidase technique. Antigenic phenotypes were found to be unrelated to the patient's age, stage, tumor grade, histologic cell type, prior chemotherapy, and interval between operations. Most significantly, little difference was seen in antigenic expression between tumors obtained at the two operations for either the cell surface or blood group markers. Variations in the staining pattern were seen with antibody B72.3 and, to some extent, with the anti-blood group antibodies, which are known for producing heterogeneous staining. The antigenic phenotype of the tumor specimens in a given patient as determined immunohistochemically by our panel of antibodies showed only minor variation between operations, even under the selective pressures of chemotherapy and immunotherapy.

Adenocarcinoma↗
PubMed1989

Pelvic exenteration for recurrent or persistent gynecologic malignancies: a 10-year review of the Memorial Sloan-Kettering Cancer Center experience (1972-1981).

From January 1, 1972 to December 31, 1981, sixty-five patients underwent pelvic exenteration as treatment for recurrent or persistent gynecologic malignancy at Memorial Sloan-Kettering Cancer Center. Cervical carcinoma was the disease most commonly treated by exenteration. The operative mortality of 9.2% represents an improvement over previous reports from this institution. After routine use of prophylactic minidose heparin, no cases of thrombophlebitis or pulmonary embolus occurred postoperatively. A 5-year survival rate of 23% warrants continued use of exenteration in carefully selected patients. The significant mortality and morbidity associated with pelvic exenteration preclude its use as a palliative procedure.

Female↗
PubMed1989

Determinants of increased risk for recurrence in patients undergoing radical hysterectomy for stage IB and IIA carcinoma of the cervix.

From 1939 to 1977, 431 patients underwent radical hysterectomy as primary therapy for Stage IB or IIA carcinoma of the cervix at Memorial Sloan-Kettering Cancer Center. Only 11 patients were lost to follow-up at intervals of from 1 to 94 months. Assessment of gross and histologic extent of disease was correlated with the prevalence of nodal metastases and survival. Increasing tumor size, depth of invasion, and histologic grade were covariable and predictive of both lymph node metastases and recurrence. After stratifying for nodal metastases, adenocarcinoma cell type, the size of the primary tumor, depth of invasion into the cervix, and histologic grade were associated with decreased survival. For the 85 patients with documented recurrence of their carcinoma, the time to recurrence varied inversely with primary tumor size. Of 56 patients with documented recurrence and negative nodes at the time of their initial therapy, 10 patients (18%) were ultimately salvaged. None of the 29 patients with recurrent carcinoma and positive nodes at the time of their initial lymphadenectomy was successfully treated. Analysis of prognostic factors identifies a group of patients at high risk for recurrence and decreased survival for whom prospective trials of adjunctive treatment should be considered.

Adenocarcinoma↗
PubMed1989

Long-term access to the peritoneal cavity in ovarian cancer patients.

One hundred thirty-six totally implanted peritoneal catheter systems were placed in 130 patients. No complications occurred at catheter placement. A total of 629 courses of intraperitoneal therapy were administered. The average catheter has remained in place for 4.5 months (range 1-19 months). Seven catheters (5.1%) were removed for infection. An additional 7 catheters were removed because of blockage, for a total removal rate due to complications of 10.2%. Catheters were not used for drainage of the peritoneal cavity. The totally implanted peritoneal catheter system provides a reliable means for long-term access to the peritoneal cavity in patients with ovarian cancer.

Antineoplastic Agents↗
PubMed1989

Evidence for the efficacy of adjuvant therapy in epithelial ovarian tumors of low malignant potential.

During the 10-year period from January 1975 through December 1985, 48 patients with low malignant potential epithelial ovarian tumors were treated on the Gynecology Service at Memorial Sloan-Kettering Cancer Center. No patients were lost to follow-up and the mean duration of follow-up was 42 months. Twenty-nine patients were Stage I, 5 patients were Stage II, 11 patients were Stage III, 1 patient was Stage IV, and 2 patients were unstaged. Patients were divided into those with no residual disease after initial surgical treatment (29), microscopic residual disease (7), and gross residual disease (12). No patient without residual disease died from cancer. Of the 19 patients with residual disease, all received adjunctive chemotherapy alone, radiation therapy alone, or a combination of both. Three of 19 patients died from cancer. Twelve patients with residual disease were found to be free of disease at second-look surgical reassessment following adjunctive therapy. This review indicates that adjunctive therapy can eradicate residual disease in patients with epithelial ovarian tumors of low malignant potential.

Adult↗
PubMed1989

Serum CA 125 levels and surgical findings in patients undergoing secondary operations for epithelial ovarian cancer.

Serum CA 125 levels and surgical findings were prospectively compared in 96 secondary laparotomies performed on patients with epithelial ovarian cancer. All patients had documentation of an elevated CA 125 level (greater than 35 U/ml) at a time when ovarian cancer was present, and thus the tumors were known to be "marker positive." Operation was performed in 45 patients who were clinically free of disease and in 51 patients in whom there was clinical evidence of disease. At the time of operation, 29 patients had normal CA 125 levels; persistent disease was documented in 18 (62%) of these. Of the patients with normal CA 125 levels at the time of operation, those with persistent disease had a significantly higher mean CA 125 level (16.9) than those with no disease detected (8.8, p = 0.001). At exploration, cancer was found in 84 patients. There was a correlation between the maximum diameter of the largest residual tumor mass and the accuracy of the CA 125 level as follows: microscopic to 1 cm disease, 55% accuracy; greater than 1 to 5 cm disease, 80% accuracy; greater than 5 cm disease, 92% accuracy (p = 0.013). There was no correlation of CA 125 accuracy with the patient's age, number of months from initial diagnosis, tumor stage, grade, or cell type, or the highest-ever level of CA 125. Of the 84 patients with tumor found at exploration, 66 had elevated CA 125 levels, yielding a sensitivity of 78.5%. There were 12 patients with no tumor found at exploration; 11 of these had normal CA 125 levels. The one patient who had an elevated CA 125 level subsequently had a recurrence; the corrected specificity is thus 100%. An elevated CA 125 level is an accurate predictor of persistent disease. Most of these patients will have gross tumor present. The accuracy of the CA 125 level in detecting disease is related to the amount of tumor present. In our population, the predictive value of an elevated CA 125 level was 100%; the predictive value of a normal CA 125 level was 38%.

Adult↗
PubMed1989

Knee joint motion and ligament forces before and after ACL reconstruction.

The goal of this in vitro study was to investigate the initial postoperative mechanical state of the knee with various types of anterior cruciate ligament (ACL) reconstructions. An experimental knee testing system was developed for the in vitro measurement of ligament forces and three-dimensional joint motion as external loads were applied to fresh knee specimens. Two groups of knee specimens were tested. In test series #1, two intraarticular reconstructions were performed in each of five specimens using semifree and free patellar tendon grafts with bone blocks. In test series #2, a more carefully controlled intraarticular reconstruction was performed in five specimens using a semifree composite graft consisting of the semitendinosus and gracilis tendons augmented with the Ligament Augmentation Device. Ligament force and joint motion data were collected as anteriorly directed tibial loads were applied to the normal joint, the joint with a cut ACL and the reconstructed joint. These knee joint states were compared on the basis of ACL or graft forces, joint motion and load sharing by the collateral ligaments. The dominate result of the study was that the forces and motions defining the mechanical state of the knee after the ACL reconstructions in both test series were highly variable and abnormal when compared to the normal knee state. The higher level of surgical control series #2 did not decrease this variability. There was a poor correlation between motion of the reconstructed knee relative to normal, and the ACL graft force. There was little consistent difference in force and motion results between the surgical procedures tested.

Humans↗
PubMed1989

An improved culture medium supports development of random-bred 1-cell mouse embryos in vitro.

One-cell CF-1 x B6SJLF1/J embryos, which usually exhibit a 2-cell block to development in vitro, have been cultured to the blastocyst stage using CZB medium and a glucose washing procedure. CZB medium is a further modification of modified BMOC-2 containing an increased lactate/pyruvate ratio of 116, 1 mM-glutamine and 0.1 mM-EDTA but lacking glucose. Continuous culture of one-cell embryos in CZB medium allowed 83% of embryos to develop beyond the 2-cell stage of which 63% were morulae at 72 h of culture, but blastocysts did not develop. However, washing embryos into CZB medium containing glucose after 48 h of culture (3-4-cell stage) was sufficient to allow development to proceed, with 48% of embryos reaching the blastocyst stage by 96 h of culture. Exposure of embryos to glucose was only necessary from the 3-4-cell stage through the early morula stage since washing back into medium CZB without glucose at 72 h of culture still promoted the development of 50% of embryos to the blastocyst stage. The presence of glucose in this medium for the first 48 h of culture (1-cell to 4-cell stage) was detrimental to embryo development. Glutamine, however, exerted a beneficial effect on embryo development from the 1-cell to the 4-cell stage although its presence was not required for development to proceed during the final 48 h of culture. Blastocysts which developed under optimum conditions contained an average of 33.7 total cells. The in-vitro development of 1-cell embryos beyond the 2-cell stage in response to the removal of glucose and the addition of glutamine to the culture medium suggests that glucose may block some essential metabolic process, and that glutamine may be a preferred energy substrate during early development for these mouse embryos.

Animals↗