Biomedical subjects

J L Lewis

Publications and source records attributed to J L Lewis.

At least 73 records · Page 4Linked to original sources

PubMed1995

Cytoreductive surgery in ovarian carcinoma patients with a documented previously complete surgical response.

Recurrent ovarian cancer after negative findings at second-look laparotomy is common. A retrospective review of 57 patients who developed recurrent tumor after a negative second-look laparotomy was undertaken to evaluate treatment efficacy and prognostic factors. All patients received primary platinum-based chemotherapy. Recurrences occurred in the abdomen or pelvis (40 patients), lymph nodes (7), liver (4), lungs (3), and vagina (3). Recurrent disease was diagnosed at a mean interval of 20 months after second-look surgery. Of the 38 patients who underwent laparotomy for recurrence, 36 (95%) had > 0.5 cm disease. After cytoreductive surgery 14 patients (37%) were left with minimal (< 0.5 cm) residual disease. Intestinal resection or bypass was performed on 10/38 patients (26%) with one requiring a colostomy. There was no operative mortality and one complication (small bowel obstruction). Treatment after recurrence consisted of platinum-based chemotherapy (88%), with the remaining patients receiving irradiation or hormonal therapy. At a mean follow-up from recurrence for the entire group of 20 months, 18/38 (47%) explored patients are alive. All 19 patients who were not explored died with a median survival time from recurrence of 9 months. Patients who underwent a laparotomy and patients with < 0.5 cm residual disease had a significant survival advantage (P < 0.0001). Initial stage, grade, disease-free interval, and disease found at laparotomy did not influence survival. Recurrent ovarian carcinoma after platinum-based chemotherapy is associated with a grave prognosis when the patient is deemed inoperable or when distant metastasis are found. Patients with disease reduced to < 0.5 cm showed a significant survival advantage.

Abdominal Neoplasms↗

PubMed1995

Platinum-based chemotherapy for advanced-stage serous ovarian carcinoma of low malignant potential.

PURPOSE: To evaluate the effect of platinum-based chemotherapy on tumor response in patients with advanced-stage serous ovarian carcinoma of low malignant potential. PATIENTS AND METHODS: We conducted a retrospective review of hospital records, pathology slides, and office charts of patients identified as having Stage III or IV serous ovarian cancer of low malignant potential. RESULTS: Between November 1979 and April 1993, 21 patients with advanced-stage serous ovarian carcinoma of low malignant potential received platinum-based chemotherapy following initial cytoreductive surgery. The amount of residual disease was recorded in 20 patients; 8 (40%) had macroscopic residual tumor < 2 cm in largest diameter, and 12 (60%) had only microscopic disease. Sixteen patients underwent a second-look laparotomy following chemotherapy; 10 (62.5%) had no evidence of disease, 1 (6%) had a partial response, 2 (12.5%) had stable disease, and 3 (19%) had progressive disease. During a mean follow-up of 64 months, only 1 patient had died of disease. She had progressive disease noted at second-look laparotomy. Five of 6 patients who did not have a complete response to initial chemotherapy underwent further therapy with oral etoposide (1), intraperitoneal platinum (2), intraperitoneal mitoxantrone (1), or both (1). The sixth patient received no further therapy. Three of the patients subsequently receiving salvage intraperitoneal therapy underwent a third-look laparotomy. Two had partial responses noted, while the third patient had stable disease. CONCLUSIONS: Platinum-based chemotherapy is effective in achieving surgically documented responses in patients with advanced-stage serous ovarian tumors of low malignant potential. The benefit of this therapy in improving survival is unproven.

Adult↗

PubMed1995

Design and biomechanics of a plate for the distal radius.

A dorsal plate for the distal radius was designed to provide rigid fixation and thus allow early motion. It functions as a blade plate, lessening the role of metaphyseal screws, and providing internal neutralization rather than compression. The rigidity and strength of the plate were compared to the existing T-plate in an unstable, extra-articular fracture model in paired, fresh-cadaver, axially loaded radii. The dorsal plate construct was significantly stronger and more rigid than the T-plate construct. The failure mode was similar for both plate types; 8 of 10 constructs failed with plate bending and screw loosening, while the oldest specimen pair showed primary bone failure. Compared to the T-plate, the dorsal plate transmitted a greater single axial load from the articular surface to the shaft.

Aged↗

PubMed1995

Probability of progenitor renewal (PPR) and production of clonogenic progeny (CFU-GM) by primitive adherent progenitor cells in adult human bone marrow and umbilical cord blood.

Human haemopoietic tissues contain primitive plastic-adherent progenitor cells (P delta cells) that can be detected by measurement of their granulocyte-macrophage colony-forming cell (CFU-GM) progeny. Limiting dilution analysis and Poisson statistics are necessary for determining the frequency of P delta cells because each of them produces several CFU-GM. Limiting dilution also permits measurement of the abilities of individual P delta progenitors to produce CFU-GM. Here we report that the frequencies of P delta progenitors in cord blood and adult marrow are similar (5.6 and 7.8/10(5) mononuclear cells respectively) and individual cord blood P delta progenitors produce fewer CFU-GM than adult P delta progenitors. To test the possibility that the lower production of differentiated progeny by cord blood cells was the result of a higher rate of self-renewal, we devised a two-stage limiting dilution assay relying on the relative production of CFU-GM after two consecutive weeks of incubation. The probability of progenitor renewal (PPR) was derived from the number of wells (progenitors) that produced CFU-GM on both occasions compared with the number that produced CFU-GM on the first occasion only. The total number of CFU-GM produced on the second occasion compared with the number produced on the first occasion provided an index of the overall change in the size of the P delta cell population. The data indicate that P delta cells in cord blood have a higher PPR (0.59) than those in adult marrow (0.36). Also, the relative numbers of CFU-GM produced in the second and first weeks were greater for cord blood (1.2) than for adult marrow (0.36). Therefore P delta cells in cord blood have a greater capacity for self-maintenance and possibly for expansion than P delta cells in adult marrow.

Adult↗

PubMed1995

Apoptosis in chronic myeloid leukaemia: normal responses by progenitor cells to growth factor deprivation, X-irradiation and glucocorticoids.

Inhibition of apoptosis (genetically programmed active cell death) by p210 BCR-ABL expression is a mechanism that might contribute to clonal expansion in chronic myeloid leukaemia (CML). Since cell death following exposure to ionizing radiation and many chemotherapeutic agents can occur by the apoptotic pathway, inhibition of apoptosis would be expected to confer a relative resistance to these treatments. Similarly, cells deprived of growth factors in vitro die by apoptosis, and inhibition of apoptosis would therefore be expected to allow cells to survive better in growth factor-deprived conditions. We found that the survival of normal and CML myeloid progenitors was the same after in vitro incubation in deprived conditions and after treatment with X-irradiation or glucocorticoids. We also found that mature cells in colonies produced by CML progenitors (CFU-GM) did not survive better than those produced by normal progenitor cells. Flow cytometric analysis of propidium iodide-stained cells provided a direct indication that the degree of apoptosis may correspond to the degree of deprivation. These results suggest that inhibition of apoptosis may not be the primary mechanism whereby BCR-ABL influences the expansion of the malignant clone in CML.

Apoptosis↗

PubMed1995

Induction of nasal carboxylesterase in F344 rats following inhalation exposure to pyridine.

Carboxylesterases (CEs) in the nasal mucosa metabolize some inhaled esters, including industrially important acrylates and acetates, to toxic acid metabolites that produce site-specific lesions in the nasal epithelium. The metabolic capacity of CEs in the normal nasal mucosa is theoretically sufficient to protect the lower respiratory tract from toxicant-induced injury at concentrations of acrylates and acetates likely to be inhaled in industrial environments. Thus, alterations in the metabolism and toxicity of these substrates would be predicted with changes in the amount or activity of CE in the nasal mucosa. Although many other nasal enzymes have been reported to be relatively refractory to induction, the amount of CE in the nasal mucosa can be increased by inhalant exposure. In the liver, expression of CEs may be elevated in response to exposure to P450 inducers. To examine this phenomenon in the nose with the widely used industrial solvent pyridine, we examined the effect of pyridine inhalation at the threshold limit value concentration of 5 ppm, or at 444 ppm, 6 hr/day for 4 days on the localization and amount of immunoreactive CE in olfactory mucosas of F344/N rats. CE immunoreactivity was increased in Bowman's glands following exposure to 5 or 444 ppm pyridine, and in sustentacular cells most notably following the 5 ppm exposure. Quantitative densitometry showed a statistically significant, dose-related increase in the density of immunoreactive CE in Bowman's glands of pyridine-exposed rats. These results indicate pyridine, and possibly other solvents, can induce nasal CE, an enzyme not directly involved in the metabolism of those solvents, following low-dose, short-term exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

PubMed1995

Evidence for a mechanism that can provide both short-term and long-term haemopoietic repopulation by a seemingly uniform population of primitive human haemopoietic precursor cells.

One of the controversies surrounding the repopulating capacities of haemopoietic stem cells is whether or not the same or different populations are responsible for short-term and long-term repopulation after transplantation. To address this question, we analysed results obtained from an in vitro model for the clonal production of granulocyte-macrophage colony-forming cells (CFU-GM) by individual primitive multilineage precursors in adult human bone marrow. The primitive precursors adhere to plastic and produce CFU-GM in a 1-week long 'delta' type culture. The clones that form are classified as having short maturation pathways (clones containing predominantly day 7 CFU-GM) or long maturation pathways (clones containing predominantly day 21 CFU-GM). The results indicate that individual primitive (P delta) cells produce clones that reach full maturity after different periods of time so that cells corresponding to a range of maturational stages can become available simultaneously. Consequently, transplanted stem cells may be able to provide both rapid and long-term mature cell recovery whilst at the same time reconstituting the stem cell pool. These results suggest that it might be possible to use highly purified stem cell populations, devoid of committed progenitors, for clinical transplantation.

Bone Marrow Cells↗

PubMed1995

Dental practice considerations.

Treating young children, working through an intermediary (the parenting adult), obtaining informed consent, and reporting suspected child abuse bring extra pressures to the dentist and staff members unless the protocol for each step is established and followed precisely. Managing for fiscal soundness and making a profit are other professional responsibilities. Counterbalancing the many pressures, the dentist who treats young children enjoys an added measure of pleasure beyond that experienced by many colleagues by helping a young child cope with the stresses of treatment, leading a child into a lifetime free of dental disease, and winning the trust and approval of parents or guardians. All of these aspects make dentistry a profession that provides a lifetime of excitement, fulfillment, learning, and constant opportunities for growth.

Adult↗

PubMed1995

Expression of cell-surface lectins on haemopoietic progenitor cells.

The expression of lectins on the surface of the murine multi-myeloid progenitor cell line FDCP-Mix, and the human leukaemic cell line KG1, was assessed and compared to the pattern of lectin expression observed on human bone marrow mononuclear cells. Using flow cytometry, cell-surface lectins were identified by their ability to recognise fluorescein isothiocyanate-labelled neoglycoproteins. Both cell lines recognised neoglycoproteins expressing alpha-D-glucose and alpha-D-galactose residues. Inhibition studies suggested that recognition of these neoglycoproteins was via two independent receptors, each displaying characteristic sugar-binding properties. The CD34+ population of bone marrow mononuclear cells, identified by positive staining with the anti-CD34 antibody QBend10, were shown to interact with alpha-glucose-, alpha-galactose- and alpha-D-mannose-expressing neoglycoproteins. Similarly, binding of these probes to lymphocyte and monocyte sub-populations of CD34- bone marrow mononuclear cells was observed. In contrast, CD34- granulocytic cells did not appear to recognise these probes. It is suggested that the alpha-D-galactose binding activity observed for both cell lines and the alpha-D-galactose and alpha-D-mannose binding activity observed for bone marrow mononuclear cells represent expression of the component polypeptides of the previously reported galactosyl/mannosyl receptor. The glucosyl-specific receptor, observed on both cell lines and on bone marrow mononuclear cells, has not been reported previously. It is suggested that this receptor may mediate glucose transport or cell adhesion through recognition of glucosyl-containing compounds such as heparan sulphate.

Bone Marrow Cells↗

PubMed1994

An improved technique for measuring in vivo intervertebral motion in the canine.

STUDY DESIGN: An experimental animal study using an established technique for measuring in vivo motion in canines was designed to improve measurement techniques and to eliminate the effects of the instrument mounting technique on the tissue and subsequently on the motion being measured. OBJECTIVES: The purpose of this study was to improve a technique for measuring in vivo intervertebral motion in canines, so that the measuring technique did not affect the motion being measured. SUMMARY OF BACKGROUND DATA: Biplanar radiography has been used to measure in vivo intervertebral motion, but involves radiation exposure and expensive equipment. Electromechanical devices have been used more recently but have had significant effects on the motion over extended time periods. METHODS: Intervertebral motion was measured using an instrumented spatial linkage in eight adult canines divided into two groups that differed regarding the method of "mounting pin" placement. Group I had open surgical placement of the pins and Group II had pins placed into the spinous processes. After pin implantation, the instrumented spatial linkage was attached and motion data were recorded during walking. This testing sequence was repeated 3 weeks later. Animals were killed and intervertebral and facet motion were calculated from the experimental data and compared statistically. RESULTS: Facet motion decreased 1 to 3 weeks after pin implantation for animals of group I (3.4 +/- 0.2 mm to 1.1 +/- 0.3 mm), whereas the facet excursion of animals in Group II showed no change (3.0 +/- 0.2 mm and 3.1 +/- 0.3 mm). CONCLUSIONS: A new method of measuring in vivo intervertebral motion in canines has been developed and shown to have no significant affect on the segment mechanics.

Animals↗

PubMed1994

Comparison of in vivo and in vitro adjacent segment motion after lumbar fusion.

STUDY DESIGN: For in vitro studies, there is no basis for choosing a "load control study" over a "displacement control" study. This study qualitatively compared results from in vitro and in vivo tests, allowing the authors to address the experimental assumptions that in vitro testing contributes to the understanding of the in vivo condition. OBJECTIVES: To compare motion changes at segments adjacent to fusions for in vitro and in vivo tests. SUMMARY OF BACKGROUND DATA: Investigators have measured the effects of spinal fusions on the adjacent segment in a human cadaver model and found greater adjacent facet joint load after fusions. Others have found significant increases in motion and facet loads at segments adjacent to in vitro lumbosacral and long fusions, when the same range of motion was repeated before and after immobilization of lumbar segments. METHODS: L2-L3 motion was measured in vitro by an instrumented spatial linkage under load and displacement control before and after immobilization of segments (L3-L7). In vivo, L2-L3 motion was measured while animals walked on a treadmill. L3-L7 was fused and the L2-L3 motion testing was repeated. The change in in vivo adjacent segment motion was qualitatively compared with the in vitro change under "load" and "displacement" control. RESULTS: Under "load" control, in vitro facet motion did not significantly change after immobilization, whereas under "displacement" control, the facet motion significantly increased from 2.2 +/- 0.4 mm to 4.1 +/- 0.6 mm. Post-instrumentation, in vivo L2-L3 facet motion increased significantly. This change in vivo related better to the changes seen in the in vitro "displacement" control test than to the in vitro "load" control test.

Animals↗

PubMed1994

A case-control study of oral contraceptive use and invasive epithelial ovarian cancer.

The relation of oral contraceptive use to the risk of ovarian cancer was assessed with data collected during 1977-1991 from patients under 65 years of age in hospitals in Boston, New York, Philadelphia, and Baltimore. We compared 441 women with recently diagnosed invasive epithelial ovarian cancer to 2,065 control women. Logistic regression was used to control risk factors for ovarian cancer. The multivariate relative risk estimate decreased with the increasing duration of oral contraceptive use (p < 0.05): the estimate was close to 1.0 for duration categories of less than 3 years; it was reduced for the categories of 3-4 years of use and greater, but it did not decline further as the duration of use increased. For > or = 3 years of use, the estimate was 0.6 (95% confidence interval 0.4-0.8). The inverse association of risk with > or = 3 years of use was consistently present across categories of age, parity, interview year, and geographic area. It was apparent for as long as 15-19 years after cessation. Many different specific oral contraceptive formulations appeared related to a decreased risk; however, data were sparse for the newer types, particularly phasic preparations, and the ability to assess specific preparations in the context of use of multiple preparations was limited. The present data confirm previous reports of an inverse association of ovarian cancer risk with oral contraceptive use of several years in duration. They also suggest that the association may persist for as long as two decades and that it is not confined to any particular type of oral contraceptive formulation.

Adult↗

PubMed1994

Comparative localization of carboxylesterase in F344 rat, beagle dog, and human nasal tissue.

BACKGROUND: Carboxylesterases (CE) exhibit high activity in the nasal mucosae and produce acid metabolites toxic to the olfactory epithelium following exposures to inhaled esters. The regional distribution and activity of CE have been studied in rodents, but no comparative studies have examined regional localization or activity in dog or human nasal tissues. METHODS: We determined the immunohistochemical distributions of CE in the nasal respiratory and olfactory mucosae of Beagle dogs, and the nasal respiratory mucosa of the human nose and compared these distributions to those in the F344 rat. RESULTS: In the dog respiratory mucosa, the greatest CE immunoreactivity was in the subepithelial glands and surface epithelial cells. In the olfactory mucosa, immunoreactivity was observed in the apical portion of the sustentacular cells, and in duct cells and acinar cells of Bowman's glands. This distribution is similar to that found in rat, except the subepithelial glands of the rat respiratory mucosa showed little to no immunoreactive CE. The human respiratory mucosa showed immunostaining in surface epithelial cells as well as glandular cells. Immunostaining in the human tissue samples was dramatically reduced in the presence of hyperplastic lesions and virtually eliminated in samples with squamous metaplasia. CONCLUSIONS: The data indicate that the distribution of CE is very similar in healthy nasal mucosae across the three species studied. However, the loss of CE immunoreactivity correlated with nasal epithelial lesions in the human samples suggests enzymatic activity may be compromised by insults to nasal tissues. Further studies of CE activity in animals following nasal insult could improve the ability to predict human responses to inhaled esters.

Adolescent↗

PubMed1994

Alteration in multijoint dynamics in patients with bilateral knee osteoarthritis.

OBJECTIVE: To document the alterations of joint motion and torque in patients with bilateral knee osteoarthritis (OA), using a well-defined functional maneuver, the sit-to-stand (STS) task. METHODS: Twelve patients with bilateral knee OA and 12 age-, sex-, and height-matched control subjects performed the STS maneuver from a stool of a standard height at their natural speeds. A motion analysis system and 2 force platforms were employed to determine the dynamic joint motion and the resultant joint torques at the ankle, knee, and hip joints. RESULTS: The results showed that OA patients exhibited substantially reduced knee extension torques, accompanied by other alterations in initial sitting posture (more extended knee and more plantar-flexed ankle), movement duration (increased), dynamic range of motion at the knee (reduced), and extension torques at the hip (increased). CONCLUSION: The alterations in joint dynamics among patients with knee OA may have revealed an adaptive motor behavior characterized by redistributing the load from impaired to less-impaired or nonimpaired joints through multijoint dynamics. Two major potential pitfalls of such a movement strategy have subsequently been postulated.

Aged↗

PubMed1994

Load affects remodeling of transplanted, autogenous bone-patellar tendon-bone segments in a rabbit model.

The question of whether or not load affects the remodeling of a transplanted autogenous free graft was addressed by removal of the patella-patellar tendon-tibial tubercle complex from the right knees of 15 New Zealand White rabbits. The tubercle was split, and the tendon was divided with each half trimmed to an equal width. The autograft complex was transplanted into a subcutaneous tunnel on the back of the rabbit. Controlled cyclic loads were applied via transcutaneous sutures to half of the graft, while the other half remained unloaded. The mechanical stiffness and strength and the cell density of loaded and unloaded halves of the autograft were measured in nine animals at 3 weeks and in six animals at 6 weeks. Five autografts from four additional rabbits served as unimplanted controls. An analysis of variance showed that the loaded portions of the autografts had a significantly higher failure strength (mean of 90%) and were significantly stiffer (mean of 62%) than the unloaded halves at 3 and 6 weeks. Failure strength was significantly greater (mean of 90%) at 3 weeks than at 6 weeks. The autografts were less stiff and had a lower failure strength than the unimplanted controls, with the greatest difference occurring in the unloaded segments at 6 weeks. Histology revealed that both loaded and unloaded segments demonstrated an increase in cellularity at 6 weeks compared with 3 weeks. This report introduces a model for the study of the effect of load on soft-tissue grafts and demonstrates that loading affects the remodeling process of a transferred autograft.

Animals↗

PubMed1994

Elastic modulus of calcified cartilage is an order of magnitude less than that of subchondral bone.

The elastic moduli of calcified cartilage and subchondral bone tissues were measured experimentally with use of a three-point bending test. Specimens were obtained from a bovine patella and the distal end of a bovine femur, from two different animals. Fifteen specimens were tested as "pure" subchondral bone beams, and 15 were tested as composite calcified cartilage/subchondral bone beams. A least-squares optimization scheme was used to obtain modulus values from the composite beams. The elastic modulus for subchondral bone calculated from the "pure" subchondral bone beams was 2.3 +/- 1.5 GPa (3.9 +/- 1.5 GPa for specimens from the femur and 1.6 +/- 0.7 GPa for specimens from the patella). The composite beam optimization resulted in a modulus for subchondral bone of 5.7 +/- 1.9 GPa and a modulus for calcified cartilage of 0.32 +/- 0.25 GPa. The modulus for the calcified cartilage was more than an order of magnitude lower than the modulus of the underlying subchondral bone. This supports the idea that the zone of calcified cartilage forms a transitional zone of intermediate stiffness between the articular cartilage and the subchondral bone.

Animals↗

PubMed1994

Method for establishing and measuring in vivo forces in an anterior cruciate ligament composite graft: response to differing levels of load sharing in a goat model.

In order to determine the appropriate load history for optimal remodeling of an anterior cruciate ligament graft, methods for establishing and measuring the graft force due to an external load could be set to a preselected value in in vivo are required. Our objectives with this study were to (a) develop a method in which the graft force due to an external load could be set to a preselected value in a living animal, (b) show that this force could be maintained after fixation, and (c) determine what happens to the forces after the animal has functioned for as long as 2 weeks postoperatively, when differing levels of load sharing between the segments had been set at surgery. The anterior cruciate ligament was reconstructed in 12 goats with use of a bone-patellar tendon-bone graft and a synthetic augmentation device. The forces in the graft segments were established, at the time of surgical fixation, with use of a force-setting technique. In five animals, the tendon segment was set to carry 90% of the total graft force; in the remaining seven animals, the augmentation segment was set to share 90% of the total graft force. Graft forces were measured, with the use of buckle transducers mounted extra-articularly over the anterior tibia, under a 67 N anterior tibial load at 60 degrees of knee flexion before and after fixation and at 2 weeks postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Olfactory mucosal lesions in F344 rats following inhalation exposure to pyridine at threshold limit value concentrations.

Pyridine is a volatile solvent used as an intermediate in the production of insecticides, herbicides, pharmaceuticals, and dyes. Pyridine is also found in tobacco smoke. Because inhalation is a primary route of exposure to pyridine, we examined the effect of inhaled pyridine on morphology at the portal of entry, the nose. Nasal tissues from F344/N rats exposed using a nose-only mode 6 hr/day for 4 days to either filtered air (controls) or one of two concentrations of pyridine vapor were examined histologically. The rats had been killed 18 hr after the last exposure. The two pyridine concentrations were the current threshold limit value (TLV, 5 ppm) and a high concentration (444 ppm). Olfactory epithelial lesions in rats exposed to both concentrations of pyridine included vacuolar degeneration of sustentacular cells; focal, marked attenuation of the epithelium; loss of vacuolar degeneration of sustentacular cells; focal, marked attenuation of the epithelium; loss of neurons; and the presence of intraepithelial luminal structures. The lesions were only slightly more severe in the rats exposed to 444 ppm compared to those rats exposed to 5 ppm pyridine. The results show that inhalation of pyridine at the current TLV concentration of 5 or 444 ppm causes lesions in the olfactory epithelium of rats.

Administration, Inhalation↗