Biomedical subjects

J L Lewis

Publications and source records attributed to J L Lewis.

At least 163 records · Page 9Linked to original sources

PubMed1991

An experimental method for measuring force on the spinal facet joint: description and application of the method.

A technique is described for measuring load magnitude and resultant load contact location in the facet joint in response to applied loads and moments, and the technique applied to the canine lumbar spine motion segment. Due to the cantilever beam geometry of the cranial articular process, facet joint loads result in surface strains on the lateral aspect of the cranial articular process. Strains were quantified by four strain gages cemented to the bony surface of the process. Strain measured at any one gage depended on the loading site on the articular surface of the caudal facet and on the magnitude of the facet load. Determination of facet loads during in vitro motion segment testing required calibration of the strains to known loads of various magnitudes applied to multiple sites on the caudal facet. The technique is described in detail, including placement of the strain gages. There is good repeatability of strains to applied facet loads and the strains appear independent of load distribution area. Error in the technique depends on the location of the applied facet loads, but is only significant in nonphysiologic locations. The technique was validated by two independent methods in axial torsion. Application of the technique to five in vitro canine L2-3 motion segments testing resulted in facet loads (in newtons, N) of 74+ / -23 N (mean + / -STD) in 2 newton-meter, Nm, extension, to unloaded in flexion. Lateral bending resulted in loads in the right facet of 40+ / -32 N for 1 Nm right lateral bending and 54+ / -29 N for 1 Nm left lateral bending. 4 Nm Torsion with and without 100 N axial compression resulted in facet loads of 92+ / -27 N and 69+ / -19 N, respectively. The technique is applicable to dynamic and in vivo studies.

Animals↗

PubMed1991

Normal contact of elastic spheres with two elastic layers as a model of joint articulation.

An analytical model of two elastic spheres with two elastic layers in normal, frictionless contact is developed which simulates contact of articulating joints, and allows for the calculation of stresses and displacements in the layered region of contact. Using various layer/layer/substrate combinations, the effects of variations in layer and substrate properties are determined in relation to the occurrence of tensile and shear stresses as the source of crack initiation in joint cartilage and bone. Vertical cracking at the cartilage surface and horizontal splitting at the tidemark have been observed in joints with primary osteoarthritis. Deep vertical cracks in the calcified cartilage and underlying bone have been observed in blunt trauma experiments. The current model shows that cartilage stresses for a particular system are a function of the ratio of contact radius to total layer thickness (a/h). Surface tension, which is observed for a/h small, is alleviated as a/h is increased due to increased load, softening and/or thinning of the cartilage layer. Decreases in a/h due to cartilage stiffening lead to increased global compressive stresses and increased incidence of surface tension, consistent with impact-induced surface cracks. Cartilage stresses are not significantly affected by variations in stiffness of the underlying material. Tensile radial strains in the cartilage layer approach one-third of the normal compressive strains, and increase significantly with cartilage softening. For cases where the middle layer stiffness exceeds that of the underlying substrate, tensile stresses occur at the base of the middle layer, consistent with impact induced cracks in the zone of calcified cartilage and subchondral bone. The presence of the superficial tangential zone appears to have little effect on underlying cartilage stresses.

Cartilage, Articular↗

PubMed1991

Responses to second-line cisplatin-based intraperitoneal therapy in ovarian cancer: influence of a prior response to intravenous cisplatin.

Phase II trials of second-line intraperitoneal (IP) cisplatin-based therapy in patients with ovarian cancer have demonstrated the ability of this approach to produce objective antitumor responses, including surgically defined complete responses (CRs), in individuals with persistent small-volume disease after front-line cisplatin-based intravenous (IV) treatment. To examine the influence of a prior response to systemic cisplatin on the activity of second-line IP cisplatin, we retrospectively analyzed two phase II trials of cisplatin-based IP therapy in persistent/recurrent ovarian cancer conducted at our institution. Of the 89 assessable patients on the two trials, 52 (58%) had previously responded to IV cisplatin. The overall response and CR rates to second-line IP cisplatin-based therapy in this previously responding population were 56% and 33%, respectively, compared with overall response and CR rates in the 37 nonresponders to IV cisplatin of 11% and 3%, respectively (P less than .001; chi 2, 1 df). In the 36 patients responding to systemic cisplatin and whose largest tumor mass measured less than 1 cm at IP cisplatin initiation, a 42% CR rate was observed, compared with a 7% CR rate in the 14 patients with the same bulk of disease who had previously failed to respond to systemic cisplatin (P less than .025). We conclude that a prior response to systemic cisplatin strongly influences the antineoplastic activity of second-line IP cisplatin in ovarian cancer.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1991

Intraperitoneal cisplatin and cytarabine in the treatment of refractory or recurrent ovarian carcinoma.

Preclinical evaluation has suggested impressive concentration-dependent cytotoxic synergy between cisplatin and cytarabine in ovarian carcinoma. To further evaluate the clinical relevance of these observations, 39 patients with refractory or recurrent ovarian carcinoma were entered onto a phase II trial of intraperitoneal (IP) cisplatin (100 to 105 mg/m2 per course) plus cytarabine (600 to 900 mg per course). Treatment was administered over 2 or 3 days for a maximum of five monthly courses, followed by surgical reevaluation in patients without clinical evidence of disease. The 3-day regimen was discontinued secondary to the development of severe thrombocytopenia (five of 12 courses platelets decreased to less than 50,000/mm3). Additional toxicities included abdominal pain (moderate to severe at some time during therapy in 46% of patients), fever without evidence of infection (44%), and bacterial peritonitis (10%). Three patients declined surgical reassessment. Fourteen of 36 (39%; 95% confidence interval [CI], 23% to 55%) assessable patients demonstrated surgically defined responses, including 12 of 23 (52%; 95% CI, 32% to 72%) patients with tumor nodules less than 1 cm in diameter and only two of 13 (15%; 95% CI, 0% to 34%) patients with any lesion greater than 1 cm. There were seven (30%; 95% CI, 11% to 49%) surgically defined complete responses (CRs) in patients with less than 1 cm disease and none in patients with larger tumor nodules. IP cisplatin/cytarabine results in a high surgically defined response rate in patients with minimal residual ovarian carcinoma, but activity is low in patients with bulky intraabdominal disease.

Adult↗

PubMed1991

Second-line platinum therapy in patients with ovarian cancer previously treated with cisplatin.

In an effort to critically define the incidence and clinical characteristics of secondary responses to cisplatin-based therapy in patients with ovarian cancer previously treated with a cisplatin-based program, a retrospective review was undertaken of patients at the Memorial Sloan-Kettering Cancer Center who received greater than or equal to two cisplatin/carboplatin-based programs. Eighty-two patients were identified who met the entry criteria of having had a cisplatin-free interval (CFI) of more than 4 months between the completion of their first regimen and the institution of a second cisplatin/carboplatin program. Of the 72 assessable patients (10 had no measurable disease, and a laparotomy was not performed to assess response), 31 (43%) responded, including 10 surgically defined complete responses (S-CRs). The overall response rates (and S-CR rate), based on duration of CFI, were 5 to 12 months, 27% (5%); 13 to 24 months, 33% (11%); and more than 24 months, 59% (22%). Twenty-nine patients (35%) received noncisplatin/carboplatin-containing treatments between the cisplatin programs. Patients without any treatment for more than 24 months from the completion of their initial therapy experienced a 77% (17 of 22) response rate and a 32% (seven of 22) S-CR rate. In conclusion, secondary responses to cisplatin/carboplatin-based treatment are common in patients with ovarian cancer who have previously responded to the agents and increase in frequency with greater distance from the initial therapy.

Adult↗

PubMed1991

Phase II trial of weekly or biweekly intraperitoneal mitoxantrone in epithelial ovarian cancer.

Previous experimental and clinical evaluation has suggested that ovarian cancer is sensitive to the cytotoxic effects of mitoxantrone at concentrations achievable within the peritoneal cavity after intraperitoneal (IP) administration. Unfortunately, the use of the drug delivered IP at high doses (20 mg/m2 in 2 L normal saline [NS]) on a monthly schedule is compromised by severe local effects secondary to the irritant properties of the drug. To reduce toxicity and take advantage of minimal systemic drug exposure following IP administration, we treated 28 patients with a lower drug concentration of mitoxantrone (10 mg/m2 in 2 L NS), but on a weekly or every other week schedule (total, 12 courses). Compared with the monthly program, this regimen caused less pain, allowed for a higher cumulative dose of mitoxantrone to be delivered, and resulted in less serious treatment-related morbidity. Four of 13 assessable patients (31%) whose largest tumor was less than or equal to 1 cm in diameter demonstrated a surgically defined response. All responding patients had failed previously or exhibited a minimal response to cisplatin. Despite the improved toxicity profile of this regimen, the overall response rate was similar to the monthly program, probably secondary to inadequate IP drug distribution in many patients. Future investigative efforts using IP mitoxantrone as therapy for ovarian cancer might focus on developing methods to improve drug delivery to all sites of tumor within the peritoneal cavity (eg, intraoperative therapy, increased treatment volumes, and antiinflammatory agents to reduce adhesion formation).

Adult↗

PubMed1991

Osteoarthrotic changes after acute transarticular load. An animal model.

The canine patellofemoral joint was subjected to a standardized transarticular load of 2170 newtons for two milliseconds, and the gross and histological changes were examined at two, twelve, and twenty-four weeks after injury. Initially, the load creates fractures in the zone of calcified cartilage, with minimum damage to the articular cartilage surface. Surface fissures were visible in all patellae only after staining with India ink. Histologically, these surface clefts extended into the transitional or superficial radial zone, and they did not communicate with the subchondral bone except in two patellae. However, there were reproducible clefts in the region of the subchondral bone and the zone of calcified cartilage in all patellae. Six months after loading, there was a loss of safranin-O staining above the deep clefts, and there was new-bone formation in the subchondral region and fibrillation of the cartilaginous surface. Thus, the initial changes had progressed to osteoarthrotic-like conditions at six months. In this animal model, the joint is not invaded and the changes that result from loading are reproducible. The injury to the joint creates superficial disruption of the cartilage and subchondral changes that lead to arthritic-like degeneration of the cartilage within six months.

Animals↗

PubMed1990

Factors affecting graft force in surgical reconstruction of the anterior cruciate ligament.

The effect of the maximum unloaded graft length (Lo) and femoral fixation hole location on graft force with the knee under anteriorly directed tibial loads was measured in five fresh cadaver knees with a reconstruction of the anterior cruciate ligament (ACL). The reconstruction was performed using a composite graft consisting of the semitendinosus and gracilis tendons augmented with the Kennedy ligament augmentation device (LAD). Buckle transducers were used to measure ligament and graft forces. The total graft force was adjusted to match the intact ACL at 30 degrees flexion using a force-setting method so that a standardized reference configuration could be repeatedly obtained. The graft force was highly sensitive to Lo, typically changing by 50% with a change in Lo of 3 mm. Variation in femoral hole location of 5 mm anterior, posterior, proximal, and distal to the anatomic position produced changes in graft force, particularly at 60 degrees and 90 degrees flexion; however, these changes were not statistically significant. The effect of femoral hole location varied considerably between knees. This variability makes predicting proper hole placement difficult, and suggests the need to adjust each knee at surgery to account for this variable femoral hole position sensitivity.

Adult↗

PubMed1990

Method for setting total graft force and load sharing in augmented ACL grafts.

The objective of this study was to develop a method for obtaining a controllable and reproducible immediate postoperative mechanical state in a knee with an anterior cruciate ligament (ACL) reconstruction. This method, called the force-setting technique, was demonstrated using a composite graft consisting of the middle third of the patellar tendon with bone blocks (PT) and the ligament augmentation device (LAD). The total graft force was set to match the force in the intact ACL at 30 degrees flexion with the knee under the same standardized external load, while at the same time the load sharing between the biologic and augmentation components was controlled. The total graft force was set to match the ACL force three separate times in each knee, with ratios of load sharing set at the following levels: 50% PT-50% LAD, 25% PT-75% LAD, and 75% PT-25% LAD. ACL, PT, LAD, and collateral forces were measured using buckle transducers, and three-dimensional knee motion was measured using an instrumented spatial linkage as 90 N anteriorly directed tibial loads were applied to eight specimens at 0 degree, 30 degrees, 60 degrees, and 90 degrees flexion with an intact ACL, an excised ACL, and the three load-sharing reconstruction states. The total graft force could be consistently set to within an average of 2% of the intact ACL force at 30 degrees flexion, and load sharing between the graft segments could be set to within an average of 5.1% of the desired ratio at 30 degrees.(ABSTRACT TRUNCATED AT 250 WORDS)

Cadaver↗

PubMed1990

Intracerebral choriocarcinoma.

Nineteen patients with gestational trophoblastic disease (GTD) metastatic to the brain are reviewed. These patients constituted 9.0% of 210 [corrected] patients with GTD treated between November 1967 and December 1987. Four patients (21%) presented with primary neurological symptoms of GTD; four patients developed brain metastases during or after treatment with first drug(s) therapy; and 11 patients developed CNS metastases after resistance to initial chemotherapy. The initial chemotherapy in three of four patients who presented with brain metastases was with the combination of methotrexate, actinomycin D, and chlorambucil (MAC). Of the 15 patients who developed brain metastases after prior chemotherapy, 12 had received MAC at least once prior to the diagnosis of brain metastases, and in 5 patients, MAC was the first chemotherapy given after the diagnosis of brain metastases. All of the patients received whole-brain radiotherapy. Five of nineteen patients (26.3%) are living and well 4 to 15 years after the diagnosis of brain metastases. One of four patients (25%) who presented with brain metastases survived. These results suggest that MAC chemotherapy did not prevent the development of brain metastases in some of the patients and was less than optimal therapy in those whose brain tumor had become resistant to other cytotoxic agents.

Adult↗

PubMed1990

Aggressive chemosurgical debulking in patients with advanced ovarian cancer.

From July 1986 to June 1989, 43 evaluable patients with advanced ovarian cancer were treated on protocol with initial cytoreductive surgery, two courses of high-intensity intravenous Cytoxan (1000 mg/m2) and cisplatin (120-200 mg/m2) chemotherapy, and repeat debulking laparotomy in an effort to maximize response to a subsequent four cycles of intraperitoneal platinum-based chemotherapy. Two patients were stage IIIA, 2 stage IIIB, 28 stage IIIC, and 11 stage IV. Five tumors were grade 1, 9 grade 2, and 29 grade 3. Thirty-eight (88%) patients had bulky tumor (5-25 cm) found at first laparotomy; 25 of these had greater than 1-cm residual after initial debulking. Following two cycles of intensive intravenous chemotherapy 18 of these 25 had greater than 1-cm disease found at second laparotomy; 12 of 18 underwent secondary cytoreduction to less than 1 cm. Thus, 30 of these 38 (79%) patients entered the intraperitoneal phase of the protocol with less than 1-cm disease. Four patients had 2- to 5-cm tumor at initial laparotomy; two of four were debulked to less than 1-cm residual. All four were found to have less than 1-cm disease at second laparotomy. This combination regimen was well tolerated. There was one treatment-related death. In sum, 42 of 43 patients had tumor greater than 2 cm at staging laparotomy and 38 (88%) had large, bulky disease (5-25 cm); 34 of 43 (79%) entered the intraperitoneal phase of the protocol with optimal (less than 1-cm) disease. Aggressive chemosurgical cytoreduction in patients with bulky advanced ovarian cancer can leave a large proportion of patients with minimal residual disease and maximize their chances of responding to subsequent intraperitoneal chemotherapy.

Cisplatin↗

PubMed1990

Treatment of endometrial stromal tumors.

We reviewed 31 cases of endometrial stromal tumors treated on the Gynecology Service at Memorial Sloan-Kettering Cancer Center from 1970 to 1984. Twenty-two patients had endolymphatic stromal myosis and 9 patients had endometrial stromal sarcoma. Twenty-six patients initially had disease confined to the uterus. Following hysterectomy, 7 patients received various adjuvant therapies, but no active adjuvant regimen was identified. All 3 patients who presented with advanced endometrial stromal sarcoma died of rapidly progressive disease; only 2 of 6 patients with stage I endometrial stromal sarcoma developed recurrence. Among patients with endolymphatic stromal myosis, a higher recurrence rate was noted in patients with residual ovarian tissue (100%) than in those without residual ovarian tissue (43%). Fifteen patients were treated for recurrent disease (13 with endolymphatic stromal myosis, 2 with endometrial stromal sarcoma). Following attempts to resect disease surgically, objective responses were attained with both chemotherapy (57%) and radiation (40%). The median survival following treatment of recurrent disease was 46 months. Actuarial survival for all patients in this study was 76% at 5 years and 69% at 10 years.

Adult↗

PubMed1990

Paget's disease of the vulva.

Thirty-six patients with Paget's disease of the vulva were reviewed. Median age of the patients at diagnosis was 64 years (range 41-84 years). Five patients (14%) had an associated invasive adenocarcinoma of the vulva at the time of diagnosis. Of 31 patients with superficial noninvasive Paget's disease, 28 were available for follow-up. Treatment of patients with superficial Paget's disease was surgical and based on the extent of disease. Procedures performed included total vulvectomy (25), wide local excision (4), and skinning vulvectomy with skin graft (1). The median follow-up was 108 months (range 6-266 months). Twenty-two of twenty-eight patients remained free of disease. Six patients have required multiple procedures for recurrent superficial Paget's disease. Treatment of Paget's disease of the vulva is surgical. Radical surgery is the preferred treatment of patients with an associated invasive adenocarcinoma; three of five patients with an invasive adenocarcinoma were long-term survivors. Patients with superficial Paget's disease of the vulva should be treated by local excision utilizing frozen-section margin evaluation as a guide to extent of excision. Only one patient with an initial diagnosis of superficial Paget's disease of the vulva developed invasive adenocarcinoma.

Adenocarcinoma↗

PubMed1990

Development of 1-cell embryos from different strains of mice in CZB medium.

One-cell embryos from several different strains of mice have been cultured to the blastocyst stage in CZB medium. CZB medium can be used to culture CF1 x B6SJLF1/J 1-cell embryos to the blastocyst stage provided glucose is introduced into the medium on Day 3 of culture. The amount of glucose required for embryo development was titrated using a concentration range of 5.5 to 49.5 mM. With the exception of the highest concentration, all glucose levels tested supported 65-85% development to the morula and blastocyst stages. Variations of CZB medium were tested for their ability to support the development of 1-cell embryos from 4 strains of mice. For embryos from CF1 and DBA/2J (both x B6SJLF1/J) mice, which exhibit a "2-cell block" to development in vitro, CZB medium containing glutamine with the addition of glucose on Day 3 supported optimum development from the 1-cell stage to morula and blastocysts (79% and 87%). For embryos from B6D2F1/J and CD1 female mice (both x B6SJLF1/J males), which do not exhibit a "2-cell block" to in vitro development, optimum development to morula and blastocyst stages (95% and 50%) was in CZB medium containing both glutamine and glucose from the start of culture.

Animals↗

PubMed1990

Facet loads in the canine lumbar spine before and after disc alteration.

The effect of externally applied spinal loads on facet mechanics before and after facet capsulectomy and disc alteration was investigated. Four control and four chymopapain-treated specimens were tested. Facet load and resultant load location were determined in the unaltered state, after facet capsulectomy, and after discectomy using a newly developed, noninvasive measurement technique. Resultant contact load locations shifted in a predictable manner. Caudal shift in contact locations occurred with chymopapain treatment or discectomy but was variable with capsulectomy. Facet load changed with applied load magnitude and direction; no significant change was noted after intradiscal chymopapain, discectomy, or capsulectomy. The significance of the lack of force change with disc narrowing is unknown. Perhaps, observed facet degeneration results from a change in the joint motion and contact location rather than change in facet load.

Animals↗

PubMed1990

Cracks emanating from circular voids or elastic inclusions in PMMA near a bone-implant interface.

Mechanical fracture is believed to be a primary reason for loss of fixation at the bone-cement-implant interface. In addition to the expected cracks at the bone-cement interface, cracks are also observed to be formed at voids and inclusions within the cement. An analytical solution is presented for cracks emanating from circular voids or elastic inclusions under uniaxial tension using the solution for a single dislocation as a Green's function. Stress intensity factors are calculated for arbitrary orientations of the cracks, and for varying relative stiffnesses of the inclusion and the matrix, to determine the most favorable combination of parameters for crack growth.

Biomechanical Phenomena↗

PubMed1990

An analytical model of joint contact.

The stress distribution in the region of contact between a layered elastic sphere and a layered elastic cavity is determined using an analytical model to stimulate contact of articulating joints. The purpose is to use the solution to analyze the effects of cartilage thickness and stiffness, bone stiffness and joint curvature on the resulting stress field, and investigate the possibility of cracking of the material due to tensile and shear stresses. Vertical cracking of cartilage as well as horizontal splitting at the cartilage-calcified cartilage interface has been observed in osteoarthritic joints. The current results indicate that for a given system (material properties mu and nu constant), the stress distribution is a function of the ratio of contact radius to layer thickness (a/h), and while tensile stresses are seen to occur only when a/h is small, tensile strain is observed for all a/h values. Significant shear stresses are observed at the cartilage-bone interface. Softening of cartilage results in an increase in a/h, and a decrease in maximum normal stress. Cartilage thinning increases a/h and the maximum contact stress, while thickening has the opposite effect. A reduction in the indenting radius reduces a/h and increases the maximum normal stress. Bone softening is seen to have negligible effect on the resulting contact parameters and stress distribution.

Biomechanical Phenomena↗

PubMed1990

MR imaging of the knee with a 0.064-T permanent magnet.

Magnetic resonance (MR) imaging has proved beneficial in the evaluation of internal derangements of the knee. A limitation to general acceptance of MR imaging of the knee has been availability and cost. The recent introduction of low-field-strength MR imaging has shown promise in decreasing the cost and increasing the availability of this modality. High-resolution (pixel size, 0.7 mm2), three-dimensional Fourier transform (3DFT), thin-section (3.5 mm) imaging performed on a 0.064-T permanent magnet was used to evaluate 117 knees in 114 consecutive patients. The appearance of normal anatomy and internal derangements of the knee at low-field-strength imaging is described. Arthroscopic correlation was available for 28 knees. Findings from low-field-strength MR imaging and arthroscopy agreed in 79% of cases in the determination of meniscal tears. Partial-flip-angle techniques with 3DFT produced thin-section images of the knee of diagnostic quality. The authors conclude that in patients with internal derangements of the knee, low-field-strength (0.064-T) MR imaging may provide useful information.

Adolescent↗