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Biomedical subjects

N Lane

Publications and source records attributed to N Lane.

At least 19 recordsLinked to original sources
PubMed1994

Physician-determined patient risk of toxic effects: impact on enrollment and decision making in phase I cancer trials.

BACKGROUND: The conventional phase I trial design yields an estimate of the maximum tolerated dose (MTD) of a new drug defined from treatment toxic effects observed in a small heterogeneous cohort of patients. The MTD is specific for those patients treated in the study and may not be reproducible in another patient series, a limitation known as cohort dependency. PURPOSE: We conducted an opinion survey of phase I investigators in an attempt to characterize physician attitudes and clinical practices regarding assessment of risk of toxic effects in patients. METHODS: A physician opinion survey of scaled multiple choice and open-ended questions was distributed to oncologists (faculty and fellows) at National Cancer Institute (NCI)-funded phase I contract institutions. The target sample was narrowed to these specific institutions because of their experience in conducting various phase I trials. Each NCI-funded phase I contractor received an instruction sheet and 25 surveys and envelopes that were made available to oncologists enrolling patients in phase I trials. RESULTS: Of the 75 surveys distributed, 67 (89%) were returned. Most respondents agreed that unexplained variability in toxicity exists in phase I trials. However, opinion varied considerably among five participating institutions (two-sided P = .001). Informal scoring of patients for toxicity risk prior to treatment was a common practice (85% overall), although the prevalence of this practice varied somewhat among the institutions (two-sided P = .01). Physicians' opinions were mixed regarding the practice of becoming increasingly selective in enrolling patients as the MTD was approached, with strong disagreement noted among institutions (two-sided P = .001). Given background on a hypothetical phase I trial, respondents were asked to rank the usefulness of 27 patient factors for predicting the risk of dose-limiting leukopenia. Eight factors were perceived as strongly informative: Eastern Cooperative Oncology Group performance status of 2 or worse, recent weight loss of more than 10%, multiple bone marrow metastases, two or more prior chemotherapy regimens, history of treatment toxic effects, and prior treatment with carboplatin, mitomycin, or nitrosoureas. CONCLUSIONS: Informal assessment of the risk of toxic effects in a patient was found to be common practice among oncologists who enroll patients on phase I trials, and there was strong agreement on the usefulness of several key patient factors for such assessments. Interestingly, interinstitutional variation in opinions and practices were noted, specifically regarding patient-selection bias. Follow-up studies are required to establish if physician-determined assessments of patient risk are consistent and accurate.

Adult↗
PubMed1994

Mechanical and biochemical changes in the superficial zone of articular cartilage in canine experimental osteoarthritis.

The changes in the tensile mechanical properties and biochemical composition of the superficial zone of articular cartilage were examined in a canine model of early osteoarthritis generated by transection of the anterior cruciate ligament. Sixteen weeks following ligament transection, the tensile stiffness of the articular cartilage was decreased by 44% and the ion-induced stress relaxation of the tissue was increased by 57% compared with the contralateral control. Biochemical analyses indicated that the water content of the experimental tissue was increased by 13%, which was reflected as an apparent 37% decrease in the proteoglycan content and a 36% decrease in the collagen content (expressed per wet weight). The hydroxypyridinium crosslink density was decreased in the experimental tissue by 11%. A significant negative correlation was found between the ion-induced stress relaxation and the hydroxypyridinium crosslink density in both control tissue (R = -0.56) and experimental tissue (R = -0.70). No correlation was noted between the tensile stiffness and the biochemical composition of the tissue. These results suggest that, in the superficial zone of articular cartilage, the structure of the tissue may play a more important role than the composition in the determination of its mechanical properties. A major event observed in the model of early osteoarthritis appears to be the disruption and remodeling of the collagen network in the superficial zone of the articular cartilage.

Animals↗
PubMed1994

Cancellous bone behavior in hindlimb immobilized rats during and after naproxen treatment.

Temporary immobilization creates bone loss. The purpose of this investigation was to use an agent to protect the skeleton from bone loss bone during temporary immobilization. Eighty-nine 6-month-old retired breeder Sprague-Dawley female rats were used. Animals were randomly divided into six groups of equal numbers. Four groups were given drinking water from day 0, containing naproxen (100 or 200 mg/l). At day 7, half the animals in all groups had their right hindlimb immobilized. At day 49, half the immobilized rats and non-immobilized controls were sacrificed. The remaining rats were remobilized and the drug was stopped. At day 91, all remaining rats were sacrificed. Gastrocnemius and soleus muscle weights were determined. Right tibiae were analyzed for cancellous bone mass, bone structural and bone dynamic variables. At the close of immobilization, bone mass was lower in the right (immobilized) hindlimb of the immobilized group than in the non-immobilized group. Immobilized rats drinking 100 mg/l naproxen water had significantly higher bone mass in their immobilized limbs than did untreated immobilized rats, but all rats drinking 200 mg/l naproxen water had lower bone mass than controls. After 6 weeks of recovery, bone mass in the immobilized limb of untreated formerly immobilized rats improved, but remained below untreated never-immobilized rats. Formerly immobilized rats that had been treated with 100 mg/l naproxen water had normal bone mass after 6 weeks of recovery. Naproxen, an agent that mildly depresses activation frequency, prevents some of the transient bone mass and structural deterioration during temporary immobilization. Such treatment facilitates a more rapid return to normal bone mass, though not to normal structure. The more rapid recovery occurs because the difference from normal is less, not because of more rapid formation in recovering animals.

Analysis of Variance↗
PubMed1994

Transient bacteremia due to Mycobacterium avium complex in patients with AIDS.

It is generally assumed that Mycobacterium avium complex (MAC) bacteremia, once it develops, is unremitting. On the basis of this presumption, changes in the level of mycobacteremia are used to gauge therapeutic response. In 7 (12%) of 60 patients enrolled in a prospective trial of MAC bacteremia and AIDS, bacteremia became undetectable before the initiation of antimycobacterial therapy. Patients with transient bacteremia reported fewer and shorter symptoms and survived longer than those with sustained bacteremia (59 vs. 31 weeks; P = .022). There was no difference in the duration of AIDS, CD4+ cell count, hematocrit, or body weight between groups. Two additional patients with transient bacteremia were identified outside this study setting. Despite disappearance of detectable mycobacteremia and subsequent administration of antimycobacterial agent(s), bacteremia once again became detectable in 6 patients 4-45 weeks after their negative pretreatment cultures. Patients with disseminated MAC may have fluctuating levels of mycobacteremia that become undetectable in the absence of antimycobacterial therapy.

AIDS-Related Opportunistic Infections↗
PubMed1992

Synovium-like tissue from loose joint replacement prosthesis: comparison of human material with a canine model.

The formation of synovium-like tissue is a biological response to a loose joint replacement prosthesis. Histological examination of this tissue has shown a synovial lining with a predominance of fibroblasts and macrophages, some multinucleated giant cells, and dispersed particles from the implant. Previous studies have reported elevated interleukin 1 (IL-1), prostaglandin E2 (PGE2), and collagenase in this tissue. We developed a canine model for the loose cemented femoral stem. Tissue harvested from the canine model was compared with human tissue retrieved at revision arthroplasty. Histology showed synovium, similar to that observed around loose human prostheses, adjacent to the canine cement sheath. Cells were isolated from this tissue and incubated in culture medium with or without naproxen for 3 days. Aliquots of the conditioned media were tested in the thymocyte proliferation assay to determine IL-1-like activity. IL-1 beta levels in human cell-conditioned media were analyzed by enzyme-linked immunosorbent assay, and PGE2 levels were measured by radioimmunoassay (RIA) using a PGE2 RIA kit (New England Nuclear). Human tissue contained levels of IL-1 beta in the range of 150 to 7,040 pg/mL and PGE2 levels of 82 to 952 ng/mL. The canine specimens contained IL-1-like activity and significant amounts of PGE2 (76 to 1,720 ng/mL). Naproxen decreased PGE2 levels in vitro. This animal model provides the means to investigate the in vivo and in vitro activity of the synovial cells around loose total joint prostheses.

Adult↗
PubMed1992

Long-term effect of naproxen on cancellous bone in ovariectomized rats.

Previous work shows that at 42 d post-ovariectomy (OX) in aged rats, naproxen, a nonsteriodal anti-inflammatory drug (NSAID) prevents cancellous bone loss. The purpose of this study was to evaluate the effects of naproxen on cancellous bone of aged OX and sham-OX rats, at 90 days post-OX. Six-month-old Sprague-Dawley retired breeder female rats underwent either sham-OX (n = 49) or OX (n = 65). Sham-OX rats were randomized into five groups and OX rats into six groups. The first five groups of both were given ad lib access to water containing 0, 4, 10, 25, or 62.5 mg/l of naproxen sodium. The sixth group of OX rats was given water containing 156.25 mg naproxen sodium/l. After ninety days, the rats were killed following in vivo dual calcein labeling. Terminal serum naproxen was measured by HPLC. In the proximal tibial metaphysis, trabecular bone volume, trabecular thickness, trabecular number, mineralizing surface (double label), osteoclast surface, and bone formation rate were measured. Sham-OX and OX rats were compared by t-test of means. Kruskal-Wallis tests and, as necessary, Dunnett's t-tests, were applied separately to the groups of Sham-OX and OX rats. Dose-related serum levels of naproxen up to 9.4 mcg/ml were achieved in the 156.25 mg/ml group. OX rats had significantly lower bone volume, trabecular thickness, and trabecular number than Sham-OX groups (p less than .001). OX rats had significantly higher mineralizing surface, formation rate, and osteoclast surface than sham-OX rats (p less than .001). No differences related to naproxen treatment existed in sham-OX rats. Naproxen treatment producing a serum level of 9.4 mcg/ml reduced bone volume in OX rats consuming water with 156.25 mg/l (p less than .05). At 90 days post-OX, naproxen, at serum levels of 9.4 mcg/ml or less, did not diminish estrogen-depletion cancellous bone loss in rats. Naproxen lacks lasting ability to halt estrogen-depletion bone loss in aged OX rats.

Animals↗
PubMed1991

Bone mineral density of the lumbar spine in women with endometriosis.

Young women with endometriosis have reduced cortical and trabecular bone mineral density of the wrist compared with age-matched controls. This conclusion was based on 41 subjects from one geographical location. The purpose of this study was to test this finding in a larger, more geographically diverse population. One hundred women with laparoscopically proven endometriosis were enrolled in this study for the evaluation of the efficacy of nafarelin, a gonadotropin-releasing hormone agonist. Patients were recruited from nine investigators across the United States and Canada, and bone mineral density of the lumbar spine was obtained at baseline, with 6 Hologic QDR (Hologic Inc., Waltham, MA) and a Lunar DPX (Lunar Radiation Corp., Madison, WI) instrument. The age of the women was 30.3 +/- 5.8 years (mean +/- SD); 91% were white. Bone mineral density of the lumbar spine was 1.1 +/- 0.11 g/cm2 (n = 85 Hologic QDR) and 1.2 +/- 0.93 g/cm2 (n = 15 Lunar DPX). Hologic bone mineral density was 104.8 +/- 11.0 and Lunar bone mineral density was 103.4% +/- 7.8% of normal values for age. To conclude, in a population based cross-sectional study of patients with endometriosis, we do not observe low bone mineral density of the lumbar spine by techniques that measure a combination of cortical and trabecular bone.

Adult↗
PubMed1991

Bone mineral density of the lumbar spine in endometriosis subjects compared to an age-similar control population.

The purpose of this study was to compare the lumbar bone mineral density (BMD) between women with endometriosis and age-similar controls. Eighty-five women from nine North American centers (mean age, 30.7 yr) with laparoscopically proven endometriosis (study patients) were enrolled in a study of the efficacy of nafarelin, a GnRH agonist. Fifty-two women (mean age, 32 yr) from the Palo Alto area, with regular menstrual cycles and no major medical problems, served as age-similar controls. Both groups were predominantly (greater than 92%) white. The mean BMD of the lumbar spine was 1.1 g/cm2 in both the study subjects and the controls. Study patients were 104.8% and controls were 104.8% of normal values for age. BMD was not significantly different in the two groups. BMD was not correlated with severity or time from diagnosis of endometriosis. BMD was positively correlated with weight (r = 0.28; P less than 0.05) in both groups, with height (r = 0.30; P less than 0.01) in study patients, and marginally with height (r = 0.26; P less than 0.07) in controls. This study showed no difference in BMD between endometriosis patients and age-similar controls; both groups had normal BMD.

Adolescent↗
PubMed1990

Effect of naproxen on cancellous bone in ovariectomized rats.

Nonsteroidal anti-inflammatory drugs (NSAIDs) affect bone metabolism in vitro and in vivo. They delay but do not alter the outcome of healing processes in bone. In some bone loss models, they block bone resorption and slow the rate of loss. We studied the effect of naproxen, a potent NSAID, on cancellous bone of the proximal tibial metaphysis of 6-month-old adult female ovariectomized rats. Animals were ovariectomized, divided into groups, and fed standard diets differing only in naproxen content for 42 days. The rats of the groups ate 2.0, 5.5, 12.7, and 32 mg naproxen per kg body weight per day, respectively. Serum levels of naproxen were determined. Bone volume, mineralizing surface, osteoblast activity, osteoclast surface, and bone resorption rate were determined by bone histomorphometric techniques. The rats' dose-related serum naproxen levels ranged from 4 to 28 micrograms/ml. Naproxen inhibited up to 70% of the bone loss occurring after ovariectomy at a serum level of 4 micrograms/ml. We deduced that naproxen blocked bone resorption in ovariectomized rats by slowing osteoclast activity at all doses. In contrast, naproxen slowed bone formation only at serum levels greater than 20 micrograms/ml in ovariectomized rats. These findings may have clinical relevance in helping to prevent postmenopausal bone loss in women.

Animals↗
PubMed1990

Tissue changes around loose prostheses. A canine model to investigate the effects of an antiinflammatory agent.

The aseptically loosened prosthesis provided a means for investigating the in vivo and in vitro activity of the cells associated with the loosening process in seven dogs. The cells were isolated and maintained in culture for sufficient periods of time so that their biologic activity could be studied as well as the effect of different agents added to the cells in vivo or in vitro. The biologic response as determined by interleukin-1 and prostaglandin E2 activity paralleled the roentgenographic appearance of loosening and the technetium images and observations made at the time of revision surgery. The correlation between clinical, roentgenographic, histologic, and biochemical loosening indicates that the canine model is suitable for investigating the mechanisms of prosthetic failure. A canine model permits the study of possible nonsurgical therapeutic interventions with the ultimate hope of stopping or slowing the loosening process.

Animals↗
PubMed1988

Dissection of the mechanisms of immune injury in rheumatoid arthritis, using total lymphoid irradiation.

Eleven patients with intractable rheumatoid arthritis were treated with total lymphoid irradiation. After radiotherapy, there was a marked decrease in the number and function of peripheral blood helper/inducer (Leu-3+) T lymphocytes, in the spontaneous secretion of interleukin-1 by synovial biopsy specimens, and in the activity of the joint disease. In contrast, levels of IgM, IgA, and IgG rheumatoid factors and C3 concentrations in blood and synovial fluid samples did not change significantly after therapy with total lymphoid irradiation.

Arthritis, Rheumatoid↗
PubMed1983

Coexisting lobular neoplasia and carcinoma of the breast.

In a review of 3040 cases of carcinoma of the breast of all types in the files of the Laboratory of Surgical Pathology at Columbia for the years 1960 to 1980, 267 cases were found in which the lobular neoplasia lesion coexisted with one of the usual forms of breast carcinoma. These patients had a separate and distinct, and of course malignant, clinicopathologic entity which is distinguished from benign lobular neoplasia occurring alone. Comparing these findings in lobular neoplasia coexisting with one of the usual forms of carcinoma with our findings in lobular neoplasia occurring alone, it was found that the patients with the latter lesion were younger. Three of the nine microscopic features studied in both forms of lobular proliferation were considerably more frequent in lobular neoplasia coexisting with carcinoma: (1) loss of cohesion of the cells filling up the lobules; (2) macroacini; and (3) a maximal amount of lobular neoplasia. The great majority of the forms of carcinoma that were found coexisting with lobular neoplasia were well differentiated, small cell, intraductal, and tubular, and metastasized less often than carcinomas usually do. Carcinoma developed in the second breast three times more frequently in patients with lobular neoplasia preceding or coexisting with unilateral carcinoma than it did in patients without lobular neoplasia.

Adenocarcinoma↗
PubMed1982

Bone involvement in hairy-cell leukemia.

Destructive bone involvement is a rarely recognized complication of hairy-cell leukemia (leukemic reticuloendotheliosis). We report a case in which localized hip pain and lytic bone lesions were the presenting manifestations. A second case of bone involvement in a patient with previously diagnosed hairy-cell leukemia is also described. These cases are compared with the nine cases of hairy-cell leukemia with bone involvement previously published in the medical literature.

Adult↗
PubMed1978

Lobular neoplasia (so-called lobular carcinoma in situ) of the breast.

In a review and reclassification of 5,560 benign epithelial lesions of the breast entered in the files of the Laboratory of Surgical Pathology at Columbia, we found 211 examples of the type of lobular proliferation occurring alone without co-existing infiltrating carcinoma, which we prefer to call lobular neoplasia, but which is generally referred to as noninfiltrating lobular carcinoma in situ. We regard this lesion as a separate distinctive pathological-clinical entity. These 211 cases are studied from a number of parameters, including the ages of the patients, the breast affected, the length of the follow-up, the interval between the initial diagnosis and the frank carcinoma which eventually developed in 17.1 percent of the patients. The relationship of microscopic qualitative and quantitative variations in the lobular neoplasia to subsequent carcinoma was studied; the variations were not found to have any value in predicting subsequent carcinoma. This study is unique in that we have data as to the frequency of a family history of carcinoma in a mother or sister, and also as to the occurrence of gross cystic disease in our patients with lobular neoplasia. We have determined the ratio between the observed and expected numbers of patients developing carcinoma in the several possible combinations of these three factors which predispose to carcinoma. We report that the predisposition is cumulative: in patients in whom all three predisposing factors were present the ratio of observed to expected risk of carcinoma was 13:8. We do not recommend mastectomy for lobular neoplasia, but only systematic follow-up by palpation of the patients' breasts every four months.

Adult↗