Biomedical subjects

J L Lewis

Publications and source records attributed to J L Lewis.

At least 91 records · Page 5Linked to original sources

PubMed1994

Description and application of instrumented staples for measuring in vivo bone strain.

In vivo bone strain measurements using strain gages cemented to bony surfaces with cyanoacrylate polymers are limited in duration due to debonding of the gages from bone. As an alternative to the bone bonded strain gages, a technique was developed in which strain gages were first bonded to miniature staples and then the staples embedded into bone. The instrumented staples may be calibrated so that staple strain is directly proportional to bone strain. The method was first validated by comparing the staple output with cemented surface strain gages. Comparison of instrumented staples to cemented strain gages revealed only a 3% deviation from linearity during longitudinal bending; the staples were insensitive to transverse loading. The instrumented staples were then applied to the in vitro canine lumbar spine to determine L2-3 facet loads. Load testing, repeatibility of facet calibration, and validity testing of the in vitro instrumented staples were found to be comparable to that of the previous cemented strain gage techniques. In vivo facet joint application of the instrumented staples for periods of greater than 5 weeks gave load measurements comparable to our previous short-term in vivo studies obtained with cemented strain gages. The advantages of the instrumented staples are a more secure bonding to the bone, and less traumatic surgery for fixation.

Animals↗

PubMed1994

A microstructural model for the elastic response of articular cartilage.

A model of articular cartilage is developed in which the continuum stiffness tensor is related to the tissue's microstructure. The model consists of bilinear elastic fibers embedded in an elastic matrix. Homogenization techniques are used to relate this level of organization to the macroscopic response of the tissue. The model includes the effects of spatial orientation of fibers, pre-stress in the fibers and matrix resulting from matrix swelling, slipping at the interface between the fibers and the matrix, fiber buckling in compression, and deformation-induced fiber reorientation. The model predicts increased axial stiffness with increasing stretch due to fiber reorientation, reduced axial and shear stiffness with slipping between fiber and matrix and a sensitivity of the tissue response to the swelling pressure in the matrix, the matrix modulus and the bonding of the fiber matrix interface.

Algorithms↗

PubMed1994

The kinetics of colony formation by CFU-GM in vitro.

Video-recordings of whole normal bone marrow granulocyte-macrophage colony (CFU-GM) cultures were made after 7, 14 and 21 d. Retrospective viewing of the tapes allowed the relationships to each other of the colonies scored on the three different occasions to be documented. The results show that, according to our scoring criteria, there is very little overlap between the numbers of colonies scored on days 7, 14 and 21. Moreover, only about 10% of the progenitors in a sample form day 21 colonies. The remaining progenitors form colonies earlier in the culture period and either disappear before day 21 or remain small.

Bone Marrow Cells↗

PubMed1994

Analysis of the genetic contamination of salt-sensitive Dahl/Rapp rats.

Genetic contamination of Dahl/Rapp salt-sensitive rats (SS/JrHsd) was recently discovered in animals received from Harlan Sprague Dawley, Inc, the main supplier of this strain to researchers in the United States. We were interested in determining how this problem occurred and the extent of contamination in the breeding colony in hopes of quickly correcting the problem and reestablishing the supply of this important model of genetic hypertension. DNA was extracted from whole blood obtained from each rat in the Harlan foundation colony and their offspring, the pedigree expansion colony. Several microsatellite-based genetic markers that were polymorphic between the normal and contaminant alleles were used to test these two colonies. All 10 breeder pairs in the foundation colony were tested at six different loci and found to be homozygous for the normal allele in each case. All 60 members of the pedigree expansion colony were also tested, and several rats carrying contaminant alleles were found, thus localizing the origin of the contamination to this colony. We offer several recommendations regarding precautions researchers using inbred animals should take in designing future experiments.

Alleles↗

PubMed1994

Renal apical membrane sodium-hydrogen exchange in genetic salt-sensitive hypertension.

Inbred Dahl/Rapp salt-sensitive and salt-resistant rats differ in their blood pressure response to dietary salt. We studied sodium-hydrogen (Na-H) exchanger kinetics in renal brush border membrane vesicles prepared from both strains on either a 1% or 8% NaCl diet. Kinetics measurements were made with the acridine orange fluorescence quenching technique in vesicles prepared at pH 6.0. The initial Na-H exchange rate was measured using preparations with similar initial quench values. The maximal transport rate (Vmax, fluorescence units per second per milligram protein [+/- SEM]) in salt-sensitive rats on a 1% NaCl diet was significantly lower than that in salt-resistant rats (36.9 +/- 4.4 versus 51.8 +/- 5.5, respectively, P < .0005). With the 8% NaCl diet for 1 week, the Vmax of salt-resistant rats decreased and became similar to that of salt-sensitive rats. The affinity for sodium (Km, millimoles per liter [+/- SEM]) was also lower in salt-sensitive rats than in salt-resistant rats while on a 1% NaCl diet (11.8 +/- 1.0 versus 19.6 +/- 2.3, respectively, P < .002). These values converged when both strains were fed an 8% NaCl diet for 1 week. Inhibition by 25 mumol/L amiloride was less in salt-sensitive rats than in salt-resistant rats on the 1% NaCl diet. These results show that salt-sensitive rats have lower renal apical membrane Na-H exchange activity than salt-resistant rats on a 1% NaCl diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗

PubMed1994

Intraperitoneal Taxol (paclitaxel) in the management of ovarian cancer.

In an effort to examine the safety and pharmacology of the intraperitoneal (i.p.) delivery of paclitaxel, 25 patients (24 with ovarian cancer) were treated in a phase I dose escalation trial. The drug was administered in normal saline every 3 to 4 weeks, starting at a dose of 25 mg/m2. The dose-limiting toxicity at doses at or above 175 mg/m2 was abdominal pain. A 3-log pharmacokinetic advantage for peritoneal cavity exposure to paclitaxel, compared with the systemic compartment, was observed. High levels of drug persisted within the cavity for longer than 48 hours following a single treatment. In addition, significant paclitaxel concentrations were found in the systemic compartment after i.p. treatment, despite the pharmacokinetic advantage demonstrated for cavity exposure. Several patients exhibited clinical and laboratory evidence of an antitumor response. On the basis of these data, further exploration of a potential role for i.p. paclitaxel in the management of ovarian cancer appears justified.

Dexamethasone↗

PubMed1994

Blood transfusion for radical hysterectomy before and after the discovery of transfusion-related human immunodeficiency virus infection.

OBJECTIVE: To compare the patterns of perioperative blood transfusion in patients undergoing radical hysterectomy in time periods before and after the discovery of transfusion-related human immunodeficiency virus (HIV) infection. METHODS: We reviewed the medical records of all patients who underwent radical hysterectomy and pelvic lymphadenectomy at Memorial Sloan-Kettering Cancer Center during two time periods, an early period (January 1, 1980 through December 31, 1993) and a late period (July 1, 1991 through June 30, 1993). The early period preceded and the late period coincided with the era of increased awareness of transfusion-related HIV infections. RESULTS: One hundred twenty-eight patients underwent radical hysterectomy in the early period and 71 in the late period. In the late period, markedly fewer units of blood were transfused per patient (0.62 versus 3.5). Most patients in the early period received at least one unit (117 of 128, 91%), compared with less than half (31 of 71, 44%) in the late period. For patients who received transfusions, notably fewer received homologous blood during the late (6 of 31, 19%) versus the early period (117 of 117, 100%). Using an unpaired t test and the 95% confidence interval (CI), we found that the patients in the late period had a shorter mean postoperative length of stay (11 versus 14 days, P < .0001, 95% CI +/- 1.3) and were discharged with a significantly lower mean hemoglobin level (9.7 versus 11.4 g/dL, P < .0001, 95% CI +/- 0.35). The mean estimated blood loss was lower in the late period (756 versus 1598 mL). We defined the transfusion index as the number of units transfused per 500 mL of estimated blood loss. The mean transfusion index was significantly lower during the late period (0.38 versus 1.1, P < .001, 95% CI +/- 0.19). CONCLUSIONS: During the perioperative period for radical hysterectomy and pelvic lymphadenectomy, the incidence of blood transfusion at our institution has markedly decreased over the past decade without immediate adverse effects on postoperative recovery. The reasons for this are probably multifactorial. However, the contribution of increased concern about transfusion-related HIV infections must be considered. Preoperative autologous donation can notably decrease the need for homologous transfusion.

Adult↗

PubMed1994

Laparoscopic knot substitutes. An assessment of techniques of securing sutures through the laparoscope.

Advanced interventional laparoscopy has required the development of new methods of securing sutures as alternatives to the three-throw reef knot. A tensiometer was designed to measure the forces required for distraction of various knots or securing devices with different sutures. A three-throw reef knot was used as a control. Each device was tested 15 times, and the tension at which the "knot" slipped was recorded. Titanium clips (Ligaclip, Ethicon), locking polydioxanone clips (Absolok and Lapra-ty, Ethicon), malleable collars, Roeder knots and biocompatible glue (Histoacryl, B Braun Melsungen AG) were all assessed. Sutures secured with Ligaclips, Absolok clips and glue were significantly weaker than the three-throw reef knot. Sutures secured with malleable collars and Lapra-ty clips were as strong as the three-throw reef knot and have potential for use as knot substitutes.

Enbucrilate↗

PubMed1993

Thoracotomy in the management of gestational choriocarcinoma. A clinicopathologic study.

BACKGROUND: Pulmonary metastases occur frequently in patients with gestational choriocarcinoma and most of these patients achieve remission with chemotherapy alone. Thus, the indications for surgical intervention are limited, but in appropriately selected patients, resection of a chemotherapy-resistant lung lesion can be curative. METHODS: Nine patients with choriocarcinoma metastatic to the lung underwent 11 thoracotomies. The procedure was done in two patients for diagnosis and in seven to remove a resistant focus of tumor in the lung. The excised resistant tumors in six patients were studied histopathologically, immunohistochemically, and by electron microscopic examination (one patient). RESULTS: Six (66.6%) patients achieved complete remission for periods ranging from 3 months to 18 years, and three patients died of their disease. The residual lung nodules in these patients with chemotherapy-resistant tumors were characterized by the presence of large mononucleated tumor cells that showed features intermediate between those of cytotrophoblasts and syncytiotrophoblasts but lacking ultrastructural and immunohistochemical features of the intermediate trophoblasts seen in placental site tumors. CONCLUSION: A major role for operative treatment of chemotherapy-resistant choriocarcinoma in the lung is suggested by the observation that some of the resistant tumors contain a unique variant of trophoblastic cells that show a decreased sensitivity to chemotherapy but are amenable to surgical resection.

Adult↗

PubMed1993

Chromosomal localization of angiotensin II type 1 receptor isoforms in the rat.

The cDNA sequences of two different isoforms of the rat angiotensin II type 1 receptors, AT1A and AT1B, have been reported. A single set of polymerase chain reaction primers was used to amplify sequence from both AT1A and AT1B from rat genomic DNA. Genomic DNA from a panel of rat x mouse somatic hybrid cell lines which had been characterized as to the rat chromosomal content was then amplified with these primers. The amplified products from rat AT1A and AT1B were distinguished from each other and those of the mouse by the use of differential restriction patterns. Using this method, AT1A was localized to rat chromosome 17 and AT1B to rat chromosome 2.

Angiotensin II↗

PubMed1993

Intraperitoneal chemotherapy in the management of ovarian cancer.

During the past decade, intraperitoneal therapy of ovarian cancer has evolved from a pharmacologic model into an established treatment technique for women with this malignancy. Approximately 40% of patients with small-volume residual ovarian cancer (microscopic disease or macroscopic tumor, < or = 0.5 cm in maximum tumor diameter), after an objective response to initial organoplatinum-based systemic chemotherapy, may have a surgically documented complete response to platinum-based intraperitoneal chemotherapy. Patients who have not responded to systemic platinum administration rarely will respond to the drug given intraperitoneally, despite the presence of only small-volume residual disease when this regional treatment strategy is used. Other agents with antineoplastic activity after intraperitoneal administration in women with ovarian cancer include mitoxantrone, taxol, alpha-interferon and gamma-interferon, and interleukin-2. Although intraperitoneal therapy currently is being examined as a component of the initial chemotherapeutic program for patients with ovarian cancer, a precise role for regional drug delivery in this clinical setting remains to be defined.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1993

Diagnosis and management of gestational trophoblastic disease.

Gestational trophoblastic disease is a term that describes a group of tumors that share several characteristics as follows: (1) they arise in fetal chorion, (2) they produce human chorionic gonadotropin (hCG), and (3) they respond extremely well to chemotherapy. Although rare, they have received a disproportionate amount of attention because they were the first metastatic solid tumor to be cured using chemotherapy. Also, hCG was the first reliable tumor marker. Finally, because they arise in fetal tissue, they have the potential for a strong immune response against paternal antigens in the tumor. This potential for immunologic rejection was thought initially to explain the success of chemotherapy in this disease. The early detection of gestational trophoblastic disease is successful in patients who have had a hydatidiform mole as the pregnancy event that begins the process but unsuccessful in the early detection of the development of choriocarcinoma after a normal term delivery, abortion (spontaneous or elective), or ectopic pregnancy. Surveillance after evacuation of a molar pregnancy (whether complete or a partial mole) consists of regular evaluation of hCG production and the detection of metastatic disease. However, the development of gestational choriocarcinoma after term pregnancy or an abortion (no molar tissue can develop as a consequence of these pregnancies) is detectable only by signs or symptoms of metastatic disease in any of the many organs to which this tissue can spread. Unlike most staging classifications in gynecologic cancers, which are based on histologic findings and tumor location, the classification used in gestational trophoblastic disease stresses other features that are more useful for treatment selection. Both the National Institutes of Health and the World Health Organization classifications emphasize the importance of recognizing factors that predict the likelihood of a tumor responding to chemotherapy. Currently available treatment can cure all patients except those who are in the very high-risk group, which usually is characterized by metastasis to the brain or liver or a history of prior chemotherapy. Even in this category, approximately 80% of patients are curable.

Adult↗

PubMed1993

Epithelial ovarian cancer in the elderly. The Memorial Sloan-Kettering Cancer Center experience.

BACKGROUND: There is evidence of differences between older (> or = 65 years of age) and younger (< 65 years of age) women with ovarian cancer. METHODS: To evaluate differences in the care of older versus younger patients with ovarian cancer, a retrospective review was conducted of the records of 146 patients who had their initial surgery for ovarian cancer at the Memorial Sloan-Kettering Cancer Center from January 1987-January 1991. RESULTS: There was a significant difference in stage at presentation between the older (48 patients) and younger (98 patients) populations (Stage I/II: older 10%; younger 25%; P < 0.05). Although there was no statistically significant difference in the distributions of patients according to tumor grade between the two groups, 10% of the younger patients had ovarian cancer of low malignant potential, compared to only 2% of older patients (P < 0.1). Forty-six percent of the younger patients entered an intensive initial chemotherapy trial compared to only 17% of the older patients (P < 0.001), principally due to comorbid medical conditions (e.g., heart disease). Finally, whereas the relative number of younger to older patients with ovarian cancer undergoing initial surgery at this institution was 2:1, the relative number of totally new patients to the service (including referral for initial treatment or salvage programs) was 4:1 (P < 0.001), suggesting that older patients with ovarian cancer are less likely to be referred for secondary experimental programs than for initial treatment. CONCLUSIONS: These data suggest that there are major differences between the presentation and treatment strategies of older compared to younger patients with ovarian cancer.

Adult↗

PubMed1993

Maintenance of set force in anterior cruciate ligament grafts.

This study was undertaken to determine how accurately total graft force and load-sharing between graft segments could be set and maintained during augmented anterior cruciate ligament (ACL) reconstruction in the goat knee. Special procedures were developed to reduce the effect of tissue creep and to overcome difficulties in the setting of graft force. Five knees from goat cadavers were reconstructed using a bone-tendon-bone graft (PT) and a synthetic augmentation device (LAD). Prescribed levels of total graft force and load-sharing between the autograft and LAD were set under a standardized external joint load. Immediately after fixation, the set force declined an average of 9 and 3% in the LAD and PT, respectively. After three subsequent exercise sequences, the set forces fell from their initial level by an average of 25% for the LAD and 28% for the PT. An analysis of variance did not show the loss of force with exercise to be statistically significant. We conclude from this in vitro study that our method can be used to set forces in an ACL reconstruction with reasonable maintenance of load-sharing but that losses of approximately 30% of total graft force after exercise of the reconstructed joint are to be expected.

Animals↗

PubMed1993

High-resolution positron emission tomography of human ovarian cancer in nude rats using 124I-labeled monoclonal antibodies.

PET has inherently high resolution and excellent contrast imaging and accurately measures radioactivity concentrations in vivo. When combined with specific immunological targeting it might provide a highly specific and sensitive radioimmunoscintigraphic tool. To investigate this we injected 124I-labeled MAb MX35 or MAb MH99 monoclonal antibodies (doses 200-400 mu Ci) intravenously into nude rats bearing subcutaneous human ovarian cancer xenografts (SK-OV-7 and SK-OV-3 cell lines). A melanoma cell line (SK-MEL-30) was used as a control tumor. These murine monoclonal antibodies react with cell-surface antigens expressed by most ovarian cancer cells, including the ovarian cell line used. Imaging was performed at 1-6 days using a high-resolution positron emission tomograph (PCR-I) with a spatial resolution of 4.5 mm. The slice thicknesses were 0.5 and 1.0 cm. Forty to seventy thousand coincident pulses were obtained per frame. The PET results were compared with those of autopsy and histology. Samples of blood, tumor, and normal tissues were obtained at various time points. PET calculation of isotope uptake ratios demonstrated specific localization of the antibodies in tumor, with ratios of tumor to normal tissue uptake as high as 6:1. Subcutaneous ovarian cancer nodules as small as 7 mm were identified with PET imaging. The results corresponded well with tissue sampling. Our findings suggest that PET imaging of tumors with 124I-labeled monoclonal antibodies may be useful in human diagnostic and therapeutic applications in ovarian cancer as well as other diseases.

Animals↗

PubMed1993

Evidence for persistence of mitoxantrone within the peritoneal cavity following intraperitoneal delivery.

In clinical trials examining the intraperitoneal (ip) administration of mitoxantrone as therapy of platinum-refractory small-volume residual ovarian cancer, the characteristic "blue color" of the agent has been demonstrated to stain the surface of the peritoneal cavity and to persist for > or = 1 month following the last course of therapy. To determine if this blue staining material contains potentially cytotoxic concentrations of mitoxantrone, we analyzed tissue obtained at exploratory laparotomy in six women who had last received the agent administered ip from 6-22 weeks prior to surgery. Concentrations of mitoxantrone ranged from < 0.1 to 13.8 micrograms/g of tissue examined. Since any mitoxantrone present on the peritoneal surface will be highly protein bound, any residual drug may not have cytotoxic potential. The dose-response curves of mitoxantrone in a human clonogenic cytotoxicity assay against the RPMI 2780/S human ovarian cell line were virtually identical when the cells were incubated in either 5 or 50% fetal bovine serum, suggesting that protein binding will not significantly impair mitoxantrone-induced tumor cell killing. We conclude that the ip administration of mitoxantrone may lead to prolonged exposure of surface tumor to the high local concentrations of the active cytotoxic agent. This effect may contribute significantly to the antineoplastic potential of ip mitoxantrone in patients with small-volume residual ovarian cancer.

Dose-Response Relationship, Drug↗

PubMed1993

The use of recombinant human erythropoietin to prevent carboplatin-induced anemia.

Anemia is a frequent and potentially serious toxicity associated with the use of carboplatin, particularly when this agent is administered in the salvage setting. In an effort to evaluate a possible role for human erythropoietin (rh-E) in preventing or minimizing carboplatin-induced anemia we analyzed the impact of the agent on anemia and transfusion requirements of women with ovarian cancer who were treated on one of two nonrandomized trials employing identical second-line carboplatin-based intraperitoneal regimens, with the only difference in the regimens being the addition of rh-E (Study 1, without rh-E; Study 2, with rh-E). There was a statistically significant difference in the incidence of documented nadir hemoglobin levels of < 9 g/dl (Study 1, 60%; Study 2, 13%; P < 0.005) and < 8 g/dl (Study 1, 33%; Study 3, 6%; P < 0.05). We also observed a threefold reduction in transfusion requirements with the use of rh-E (Study 1, 23%; Study 2, 6%), but this difference was not statistically significant with the limited sample size evaluated. In this nonrandomized comparison of two identical chemotherapy programs we have demonstrated that rh-E significantly reduced the incidence and severity of anemia associated with carboplatin-based chemotherapy. A randomized trial examining the potential impact of rh-E on carboplatin-induced anemia and transfusion requirements is warranted.

Adult↗

PubMed1993

Salvage intraperitoneal mitoxantrone therapy of ovarian cancer: influence of increasing the volume of treatment.

Despite the demonstrated activity of intraperitoneal mitoxantrone in patients with small volume-platinum-refractory ovarian cancer, previous reports have revealed that many patients fail to achieve adequate distribution of the cytotoxic drug throughout the peritoneal cavity when delivered in a "standard" 2-liter treatment volume. In an effort to improve the distribution and therapeutic efficacy of intraperitoneal mitoxantrone, 22 patients with platinum-refractory ovarian cancer were treated with the drug at a dose of 10 mg/m2 given in 2 liters of normal saline followed by an additional 1-2 liters every 2 weeks for eight cycles. The surgically defined complete response rate in 17 patients evaluable for response with platinum-refractory ovarian cancer was 24%, with an overall response rate of 29%. Of 18 in which the influence of treatment volume could be examined (4 patients developed catheter failure), 12 (67%) were able to tolerate a 4-liter treatment volume for > 80% of courses, with a total of 15 patients (83%) receiving treatment with a minimum of a 3-liter treatment volume. We conclude that it is possible to safely increase the intraperitoneal treatment volume to 3-4 liters in most patients undergoing this therapeutic strategy. While the impact on therapeutic efficacy of expanding the volume employed for cytotoxic drug delivery remains to be defined, in theory this approach may optimize the opportunity for agents achieving high-intraperitoneal concentrations to produce their maximal cytotoxic effect.

Adult↗