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Biomedical subjects

J L Lewis

Publications and source records attributed to J L Lewis.

At least 235 records · Page 13Linked to original sources

Three mouse monoclonal antibodies to human differentiation antigens: reactivity with two mucin-like antigens and with connective tissue fibers.

Three human differentiation antigens (MU78, MT334, and MQ49) have been defined by mouse monoclonal antibodies developed from mice immunized with ovarian carcinoma cell lines. Their distribution was determined on 148 cultured cell lines of various histologic types and on frozen sections of 16 normal tissues. MU78 was found in fibrillar structures in soft connective tissue with a distribution resembling that of elastin fibers; however, elastin fibers in elastic cartilage and in the aorta were nonreactive. MU78 was detected in cultured carcinoma cells of various histologic types, where it had a nonfibrillar, cytoplasmic distribution, but was not detected in normal epithelial cells in frozen sections. Cultured fibroblasts, astrocytomas, melanomas, and lymphomas did not contain MU78. In cell lines, MU78 appears to be a protein of 2000-5000 daltons. The other two antigens, MT334 and MQ49, are both mucin-like molecules, and the determinants are probably carbohydrate in nature. Of the normal tissues examined, MT334 was detected only in goblet cells of the colon, though it was present in a variety of carcinomas in culture. It was detected as both a cytoplasmic and secreted component. MQ49 was detected in various secretory epithelial cells, in Hassall's corpuscles in the thymus, and in cultured carcinomas of various histologic types. It was found on the cell surface as well as in the cytoplasm and is present on a glycolipid as well as on a sulfated mucin. These results, and results of other recent studies, demonstrate the importance of mucin-like molecules as antigens in epithelial cells and secretions.

Animals↗

A pilot study of adjuvant therapy in patients with cervical cancer at high risk of recurrence after radical hysterectomy and pelvic lymphadenectomy.

The prognosis after surgical therapy (radical hysterectomy and pelvic lymphadenectomy) of stages IB and IIA carcinoma of the cervix is affected by several histopathologic findings within the resected specimen. Patients at high risk of recurrence include those with involved pelvic lymph nodes, lymphatic or vascular invasion in the cervix, tumor size greater than 4 cm, grade 3 lesions, adenosquamous histology, parametrial invasion, and evidence of locally metastatic (noncontiguous) disease. We report the results of adjuvant chemotherapy (cisplatin and bleomycin) and pelvic radiotherapy in 32 patients with cervix cancer deemed to be at high risk of recurrence after radical hysterectomy and pelvic lymphadenectomy. The continuous disease-free survival rate for the 32 evaluable patients in 84% at a mean and median follow-up time of 28 months. Three patients are dead of disease and two patients are alive after treatment of local recurrences giving a survival rate of 91%. The two patients who are alive after disease recurrence demonstrated only locally recurrent disease while the three patients who have died with recurrent disease relapsed both locally and systemically. Complications of this treatment program were not significantly greater than those observed in prior studies using the combination of surgery and adjuvant radiotherapy without chemotherapy. When compared with the results from historical controls in a large series of similar patients at the same institution, the results in this pilot study are encouraging and would seem to justify a randomized prospective clinical trial.

Antineoplastic Combined Chemotherapy Protocols↗

Effect of cement pressure and bone strength on polymethylmethacrylate fixation.

The effect of the quality of the bone and of the cement pressurization magnitude and duration on the fixation achieved with polymethylmethacrylate (PMMA) bone cement is studied in vitro. Seventy-one cement-bone interface specimens, prepared under various conditions of pressurization of low-viscosity bone cement, are tested in tension. The load at failure and the maximum cement penetration are measured to assess the fixation achieved, and the quality of the bone is assessed by determining the compressive strength of each of the bone specimens. Statistical analysis of the data indicates that the pressure magnitude is the most influential of the factors considered in the cement penetration behavior and in the development of failure load capacity. The duration of the pressure does not appear to be a significant factor. The cement penetration is a decreasing function of the bone strength, reflecting a decrease in the porosity and an increase in the area fraction. Although not directly measured in these tests, these latter bone properties are indirectly measured by the bone compressive strength. The effect of increasing bone strength on the failure load is nonlinear. The development of adequate failure load capacity is the result of a balance between the cement penetration allowed by the porosity of the bone and the inherent strength of the cancellous bone itself. Weak bone, although adequately penetrated by cement, cannot provide strong fixation. Stronger, denser bone limits cement penetration, but pressurization enhances development of failure load capacity through more complete infusion and interlocking of the cement in the available pore space. The strength of the fixation achievable for any bone is limited by the intrinsic strength of the bone.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomechanical Phenomena↗

The role of fluid hydrostatic pressure in bone-implant interface load transfer.

Permeability of the soft tissue-bone system surrounding artificial joints fixed in cancellous bone was measured in four adult dogs after implants had been in place 2 months. Fluid was forced through a cavity formed by removal of the implant, the cavity was capped with a stopper to allow for pressure generation. Surface permeability of the 2-month-old implant cavity was 45 times less than the permeability of freshly drilled holes in cancellous bone. A mathematical model of a rigid implant resting on a biphasic solid-fluid layer showed the fluid carried 90% of the load when the implant cavity permeability was assumed, but only 27% when the freshly drilled permeability was used. The results suggest caution in interpreting finite-element models with bonded interfaces and suggest a possible role of the fluid in biological response at the interface.

Animals↗

Cell surface antigens of human ovarian and endometrial carcinoma defined by mouse monoclonal antibodies.

Mouse monoclonal antibodies to several cell surface antigens of human ovarian and endometrial carcinomas have been produced. The distribution of the antigens was determined by mixed hemagglutination assays on 153 normal and malignant cell cultures of various types and by immuno-peroxidase staining of frozen sections of 27 normal adult and 24 fetal tissues. Five distinct antigens were characterized. MD144 antigen was detected on only a single ovarian carcinoma cell line and has the biochemical properties of a lipid. MH55 antigen is weakly expressed on ovarian and uterine cancer cell lines but not on other cells and tissues tested. MF61 antigen was detected on an ovarian carcinoma and some renal carcinoma cell lines but not on other cell lines tested. It was also detected by immunoperoxidase staining in the noncellular follicles of the thyroid and in uterine glandular epithelial cells. This antigen also has the properties of a lipid. MF116 antigen was detected on a proportion of ovarian, uterine, renal, and bladder carcinoma and neuroblastoma cell lines and on normal kidney epithelial cell cultures but not on other cell lines tested. It was not detected in sections of any normal tissue tested using the immunoperoxidase method. MF116 was readily detected in the spent culture medium but not in detergent-solubilized extracts of metabolically radiolabeled cells. This shed antigen is a glycoprotein of Mr 105,000 and isoelectric point lower than pH 4.0. MH94 antigen was detected on a proportion of ovarian, uterine, colon, breast, lung, cervical, and pancreatic carcinoma cell lines. In tissue sections it was detected in many but not all epithelia, predominantly in secretory epithelial cells. Antibody MH94 did not immunoprecipitate a detectable antigen.

Antibodies, Monoclonal↗

A crack model of a bone cement interface.

This paper is concerned with the fracture mechanics of a bone-cement interface that includes a cohesive zone effect on the crack faces. This accounts for the experimentally observed strengthening mechanism due to the mechanical interlock between the crack faces. Edge crack models are developed where the cohesive zone is simulated by a continuous or a discrete distribution of linear or nonlinear springs. It is shown that the solution obtained by assuming a homogeneous material is fairly close to the exact solution for the bimaterial interface edge crack problem. On the basis of that approximation, the analysis is conducted for the problem of two interacting edge cracks, one at the interface, and the other one in the cement. The small crack that was observed to initiate in the cement, close to the bone-cement interface, does not affect much the mode I stress-intensity factor at the tip of the interface crack. However it may grow, leading to a catastrophic breakdown of the cement. The analysis and following discussion point out an interdependency between bone-cement interface strength and cement strength not previously appreciated. The suggested crack models provide a framework for quantifying the fracture mechanisms at the bone-cement interface.

Biomedical Engineering↗

Enteric fistulas encountered on a gynecologic oncology service from 1969 through 1980.

In the 12 year period from 1969 to 1980, 56 patients with a total of 68 enteric fistulas were seen at the Gynecology Service of the Memorial Sloan-Kettering Cancer Center. Prior therapy was common, with 98 per cent of the patients having had previous surgical treatment and 88 per cent of the patients had had prior surgical treatment and radiation therapy. Management consisted of three phases: stabilization, definition and surgical therapy. Of the surgically treated patients, 89 per cent had successful fistula closure. Although TPN as a primary therapy was unsuccessful, adequate nutrition was essential in the management of these patients. In our series, surgical care was the final step in successful management. Of the possible types of operation, those providing total exclusion of the fistula from the intestinal stream proved to be most effective.

Colectomy↗

The influence of prosthetic stem stiffness and of a calcar collar on stresses in the proximal end of the femur with a cemented femoral component.

UNLABELLED: We used three-dimensional finite-element models of the proximal end of the femur to examine the influence of stem material, stem geometry, and the use of a calcar collar on the stresses in and around implanted total hip-replacement femoral components. Anatomical bone geometries and realistic prosthetic geometries were considered. A slender titanium-alloy stem with a collar allows creation of calcar stresses of approximately 80 per cent of the anticipated normal levels. A similar stem of cobalt-chromium alloy creates calcar stresses of 67 per cent of these normal values. Stem designs without a collar were shown to generate no more than 40 per cent of normal values while larger, stiffer stems were seen to create less than 30 per cent of normal values, with or without a collar. Proximal cement stresses were increased by the use of titanium-alloy stems, but were reduced to low levels by a functioning collar. The highest cement stresses in the system were found near the tip of the stem, where titanium-alloy stems create lower stresses than do corresponding cobalt-chromium-alloy stems. The achievability of calcar loading with a titanium prosthesis was demonstrated in in vitro strain-gauge tests. CLINICAL RELEVANCE: Loosening of the femoral stem and calcar resorption are problems that are seen in many long-term clinical series of total hip prostheses. In order to reduce the incidence of these problems, the goal of the designer of a prosthesis is to reduce cement and cement interface stresses around the femoral stem and to create stress distributions in the bone that will prevent resorption.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Cements↗

The measurement of form and variation in form: an application of three-dimensional quantitative morphology by finite-element methods.

D'Arcy Thompson developed a method of coordinates which allowed for a geometrical presentation of form and form change. While his grid transformations have received much attention, little work in the geometry of form and form change has occurred since. We present a three-dimensional nonhomogeneous finite-element scaling method which allows for the mathematical and geometrical measurement of form change in addition to the graphical representation of these deformations as D'Arcy Thompson grids. This allows a reconciliation between geometrical and statistical methods for analyzing form. The method involves quantification of the transformation of one form into another in three dimensions without special registration and contains algorithms for obtaining a mean form. The method is applied to an analysis of variation in cranial form among adult male rhesus macaques from the Cayo Santiago skeletal collection. Variation was greatest in the superior-inferior direction, followed by the anterior-posterior and medial-lateral directions. The upper facial region is particularly variable. An analysis of allometry relative to local size variation shows that the larger any particular region is, the relatively greater its height, narrower its width, and shorter its length. An analysis of allometry relative to overall size showed that the upper face is positively allometric, the occipital region is strongly negatively allometric, and the other regions are isometric. After within-group variation is characterized, as described here, between-group studies, such as growth series and phylogenetic series, can be performed.

Animals↗

Metronidazole as a radiosensitizer and high-dose radiation in advanced vulvovaginal malignancies, a pilot study.

Advanced vulvovaginal cancers have a survival of less than 25% in 5 years when treated with radiotherapy alone. The radiosensitizer metronidazole was used with unconventional radiation fractions in 10 patients. Local control was achieved in 9 out of 10 patients treated. Five of 10 patients have remained free of disease 9-30 months postdiagnosis. Two patients died with metastatic disease, but with local control. In only 1 patient did this approach fail to control local disease. The outcome of these 10 patients represents a significant improvement over conventional radiation. A randomized prospective study has been started on the basis of this pilot study.

Adult↗

The role of radioactive colloids in malignant peritoneal mesotheliomas.

Malignant peritoneal mesothelioma remains a therapeutic problem. A review of the use of intraperitoneal 32P and a review of the status of therapy for this disease are presented. Six patients treated with 32P and combinations of external radiation therapy, surgery, and chemotherapy are reviewed with survival times from 5 months to 18 years. Overall survival in this disease is poor, about 44.2 months. This series suggests that with combined therapy with intraperitoneal 32P and chemotherapy, longer survivals can be achieved.

Adolescent↗

Cervix carcinoma: treatment with combination cisplatin and bleomycin.

Thirty patients with metastatic carcinoma of the cervix were treated with a combination of cisplatin and bleomycin. Thirty patients were evaluable for toxicity and 24 were evaluable for response. Thirteen patients achieved a partial remission for an objective response rate of 54% with a median duration of 3.5 months. The response rate for extrapelvic disease without prior radiation was 57% while the response rate for disease recurring in the previously irradiated pelvic area was only 36%. Response rates were higher in tumors with nonsquamous histology. Survival times for responders and nonresponders were not significantly different. Significant toxicity was observed. It is concluded that the combination of high-dose cisplatin and bleomycin infusion in patients with recurrent cervix cancer has an improved response rate. However, these responses are of short duration and drug toxicity is significant. The role of this combination for adjuvant studies is discussed.

Adult↗

Radiation therapy of primary vaginal carcinoma.

Primary carcinoma of the vagina is rare, constituting only 1 to 2% of all neoplasms arising in the female genital tract. From 1950-1974, 36 patients with carcinoma of the vagina were treated with radiation at Memorial Sloan-Kettering Cancer Center (MSKCC); 35 (96%) had epidermoid carcinoma and one patient (4%) had adenocarcinoma. These patients were staged according to FIGO. Fourteen patients (39%) were Stage I; six patients (17%) were Stage II; three patients (8%) were Stage III; and 13 patients (36%) were Stage IV. Nine patients (25%) were treated with external radiation and interstitial implant; seven patients (20%) were treated with interstitial implant alone; nine patients (25%) were treated with external radiation alone and 11 patients (30%) with external radiation and intracavitary radiation. The five year NED survival was 71% in Stage I, 66% in Stage II, 33% in Stage III and 0% in Stage IV. This paper discusses radiotherapy management of primary carcinoma of the vagina.

Adenocarcinoma↗

Role of radiation therapy in the treatment of advanced vulvar carcinoma.

To evaluate different methods of radiation therapy for advanced vulvar malignancy, a retrospective study was done on 33 patients treated with radiation between 1950 and 1979. Group I consisted of 18 patients treated with surgery and radiation and group II of 15 patients treated with radiation alone. The patients received several kinds of radiation therapy. Group I received radiotherapy because of local recurrence or positive lymph nodes found in the groin and/or pelvis; the overall survival in that group ranged from 3 months to 11 years. Group II received radiation only because of locally advanced disease and/or associated medical problems; the overall survival in that group ranged from 2 to 40 months. We concluded that megavoltage radiation minimized the local reaction and that better local control was obtained with a combination of photons and electrons and an interstitial implant. Postoperative radiation for positive lymph nodes prevented local recurrence but did not seem to improve survival.

Adenocarcinoma↗