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Biomedical subjects

L Schuman

Publications and source records attributed to L Schuman.

At least 19 recordsLinked to original sources
PubMed2002

Alcohol, tobacco and breast cancer--collaborative reanalysis of individual data from 53 epidemiological studies, including 58,515 women with breast cancer and 95,067 women without the disease.

Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58,515 women with invasive breast cancer and 95,067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women's age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19-1.45, P<0.00001) for an intake of 35-44 g per day alcohol, and 1.46 (1.33-1.61, P<0.00001) for >/=45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5-8.7%; P<0.00001) for each additional 10 g per day intake of alcohol, i.e. for each extra unit or drink of alcohol consumed on a daily basis. This increase was the same in ever-smokers and never-smokers (7.1% per 10 g per day, P<0.00001, in each group). By contrast, the relationship between smoking and breast cancer was substantially confounded by the effect of alcohol. When analyses were restricted to 22 255 women with breast cancer and 40 832 controls who reported drinking no alcohol, smoking was not associated with breast cancer (compared to never-smokers, relative risk for ever-smokers=1.03, 95% CI 0.98-1.07, and for current smokers=0.99, 0.92-1.05). The results for alcohol and for tobacco did not vary substantially across studies, study designs, or according to 15 personal characteristics of the women; nor were the findings materially confounded by any of these factors. If the observed relationship for alcohol is causal, these results suggest that about 4% of the breast cancers in developed countries are attributable to alcohol. In developing countries, where alcohol consumption among controls averaged only 0.4 g per day, alcohol would have a negligible effect on the incidence of breast cancer. In conclusion, smoking has little or no independent effect on the risk of developing breast cancer; the effect of alcohol on breast cancer needs to be interpreted in the context of its beneficial effects, in moderation, on cardiovascular disease and its harmful effects on cirrhosis and cancers of the mouth, larynx, oesophagus and liver.

Adult↗
PubMed2002

Arthroscopic treatment for osteochondral defects of the talus. Results at follow-up at 2 to 11 years.

We reviewed 38 patients who had been treated for an osteochondral defect of the talus by arthroscopic curettage and drilling. The indication for surgical treatment was persistent symptoms after conservative treatment for at least six months. A total of 22 patients had received primary surgical treatment (primary group) and 16 had had failed previous surgery (revision group). The mean follow-up was 4.8 years (2 to 11). Good or excellent results, as assessed by the Ogilvie-Harris score, were found in 86% in the primary group and in 75% in the revision group. Two further procedures were required, one in each group. Radiological degenerative changes were seen in one ankle in the revision group after ten years. Arthroscopic curettage and drilling are recommended for both primary and revision treatment of an osteochondral defect of the talus.

Adolescent↗
PubMed2001

[Treatment strategies in osteochondral lesions of the talus. Review of the literature].

The aim of this study was to compare the results of different treatment strategies for osteochondral defects (OCD) of the talus. Electronic databases from 1966 to June 2000 were systematically screened. Thirty-nine studies fulfilled our inclusion criteria. No randomized clinical trials could be identified. The results of nonoperative treatment were described in 14 studies, of excision alone in 4, of excision and curettage in 10, of excision, curettage and drilling in 21, of cancellous bone grafting in 2, of fixation in 3, and of osteochondral transplantation in 1. Good or excellent results were found in 45% of the cases. Comparison of different surgical procedures showed that excision, curettage and drilling resulted in the highest mean success rate (86%), followed by excision and curettage (76%) and excision alone (38%). From the results of this systematic review we conclude that nonoperative treatment and excision alone are not to be recommended for treatment of talar OCD. Excision, curettage and drilling produced a high percentage of good or excellent results. Further randomized, controlled trials are required to compare the outcome of these two surgical strategies for OCD of the talus.

Ankle Injuries↗
PubMed2001

[Traumatic osteochondral lesions of the talar dome].

Trauma is currently accepted to be the main etiologic factor causing OCL of the talus. Displaced lesions are easily recognized clinically and radiographically and treated surgically. In other cases, radiographic findings are often remarkably discrete or even absent. If symptoms persist, surgical treatment is warranted. In our series of 27 patients with traumatic talar OCL, operative treatment achieved good/excellent results in 88% of primary cases and good/excellent results in 80% of recurrent cases. The interval between trauma and surgery averaged 20 months (6-60). No radiographic signs of arthritic changes were observed at 2-11 years follow-up. All lesions were treated by arthroscopic excision, curettage and drilling, and this is currently the treatment of choice.

Adolescent↗
PubMed1999

Resurfacing potential of heterologous chondrocytes suspended in fibrin glue in large full-thickness defects of femoral articular cartilage: an experimental study in the goat.

A large full-thickness articular-cartilage defect was created in the medial femoral condyle of 32 adult goats. The defects were xenografted with isolated rabbit chondrocytes suspended in fibrin glue. Sham operated goats, where only a standardized defect was created, were used as controls. Results of cartilage repair were assessed after 3, 8, 13, 26 and 52 weeks. The repair tissue was evaluated macroscopically, histologically and biochemically. Results indicated that xenografted rabbit chondrocytes survived the transplantation and maintained their potential to produce matrix in fibrin glue, particularly if they were located in a non-weight-bearing area. In terms of an immunological reaction to xenografted chondrocytes, only mild signs of synovitis were observed in both groups and rejection of transplanted cells did not occur. From 3 weeks gradually progressive resolvement of the fibrin glue was observed with subsequent replacement by fibrous tissue. Initially xenografted defects histologically showed better tendency for cartilage regeneration, however, 52 weeks after surgery no significant differences could be detected in the repair tissue of both groups macroscopically, histologically and on biochemical scoring. The amount of collagen type II in the newly synthesized matrix was 75% 1 year after surgery. This study shows that isolated heterologous chondrocytes can be used for transplantation in articular cartilage defects, however, fibrin glue does not offer enough biomechanical support to the cells to maintain its function as a three-dimensional scaffold.

Animals↗
PubMed1996

Chronic inhalation toxicity and carcinogenicity testing of respirable fibrous particles. Workshop report.

On May 8-10, 1995, a workshop on chronic inhalation toxicity and carcinogenicity testing of respirable fibrous particles was held in Chapel Hill, North Carolina. The workshop was sponsored by the Office of Pollution Prevention and Toxics, U.S. Environmental Protection Agency (EPA), in collaboration with the National Institute of Environmental Health Sciences (NIEHS), the National Institute for Occupational Safety and Health (NIOSH), and the Occupational Safety and Health Administration (OSHA). The goal of the workshop was to obtain input from the scientific community on a number of issues related to fiber testing. Major issues for discussion were: (i) the optimal design and conduct of studies of the health effects of chronic inhalation exposure of animals to fibers; (ii) preliminary studies which would be useful guides in designing the chronic exposure study; (iii) mechanistic studies which would be important adjuncts to the chronic exposure study to enable better interpretation of study results and extrapolation of potential effects in exposed humans; and (iv) available screening tests which can be used to develop a minimum data set for (a) making decisions about the potential health hazard of the fibers and (b) prioritizing the need for further testing in a chronic inhalation study. After extensive discussion and debate of the workshop issues, the general consensus of the expert panel is that chronic inhalation studies of fibers in the rat are the most appropriate tests for predicting inhalation hazard and risk of fibers to humans. A number of guidances specific for the design and conduct of prechronic and chronic inhalation studies of fibers in rodents were recommended. For instance, it was recommended that along with other information (decrease in body weight, systemic toxicity, etc.), data should be obtained on lung burdens and bronchoalveolar lavage fluid analysis to assist in establishing the chronic exposure levels. Lung burden data are also important for quantifying aspects of risk assessment related to dosimetric adjustments before extrapolation. Although mechanistic studies are not recommended as part of the standard chronic inhalation studies, the expert panel stressed the need for obtaining mechanistic information as far as possible during the course of subchronic or chronic inhalation studies. At present, no single assay and battery of short-term assays can predict the outcome of a chronic inhalation bioassay with respect to carcinogenic effects. Meanwhile, several short-term in vitro and in vivo studies that may be useful to assess the relative potential of fibrous substances to cause lung toxicity/carcinogenicity have been identified.

Administration, Inhalation↗
PubMed1995

Chondrocyte behaviour within different types of collagen gel in vitro.

In cartilage repair experiments chondrocytes are transplanted into osteochondral defects. Biological substances are used as cell vehicles and are likely to play an important role in the outcome of these studies. Collagen gel is formed by polymerization of type I collagen and is used in plastic surgery and for three-dimensional culture systems. To test collagen gel as a potential vehicle for transplantation, we evaluated chondrocyte behaviour in vitro in different collagen gels. Collagen type I was extracted and purified from rat tail tendon and fetal calf skin and compared with commercially available collagen type I. After suspension of bovine chondrocytes, five different collagen gels were cultured for 14 days and evaluated by light and electron microscopy. Cells proliferated within all gels and synthesized proteoglycans as assessed by 35S incorporation; 40-90% of cells maintained a chondrocyte-like morphology after 1 week in culture depending on the type of collagen gel. Synthetic and secretory activity was confirmed by electron microscopy. Based on these results, calf skin collagen is recommended for culturing chondrocytes for implantation.

Animals↗
PubMed1994

Regulation of protein kinase C by transforming growth factor beta 1 in rat costochondral chondrocyte cultures.

Transforming growth factor beta (TGF-beta) regulates the proliferation and differentiation of chondrocytes; however, the mechanism of TGF-beta signal transduction remains unclear. We examined whether the response to TGF-beta is mediated by protein kinase C activity in chondrocytes at different stages of maturation. The aims were to examine the effect of recombinant human TGF-beta 1 (rhTGF-beta 1) on protein kinase C in rat costochondral chondrocyte cultures; determine the major isoform present; assess the involvement of phospholipase C or tyrosine kinases; determine whether genomic or nongenomic pathways are involved; and test whether these mechanisms differ as a function of the stage of cell maturation. Dose-dependent increases in protein kinase C activity were observed in confluent, fourth-passage cultures of rat costochondral growth zone and resting zone chondrocytes treated with rhTGF-beta 1. In growth zone cells, elevated activity was observed at 12 h and decreased markedly by 24 h. In resting zone cells, elevated activity was observed at 9 h, maximum stimulation occurred at 12 h, and activity returned to baseline levels after 48 h. Immunoprecipitation studies showed protein kinase C alpha is the major isoform present in both untreated and treated cells. Neither the phospholipase C inhibitor, U73122, nor the tyrosine kinase inhibitor, genistein, significantly reduced the protein kinase C response to rhTGF-beta 1. Actinomycin D and cycloheximide, inhibitors of transcription and translation, produced dose-dependent inhibition of rhTGF-beta 1 stimulated protein kinase C activity in both resting zone and growth zone chondrocytes. The time course of activation and insensitivity to U73122 suggest that phospholipase C-mediated events are not involved in rhTGF-beta 1 stimulation of protein kinase C in costochondral chondrocytes. Similarly, because genistein had no effect, tyrosine kinases are not implicated. Rather, the reduction in protein kinase C activity observed when rhTGF-beta 1 is administered along with actinomycin D or cycloheximide indicates that new gene expression and protein synthesis are required for the response. These results indicate that the effect of rhTGF-beta 1 is mediated by protein kinase C; however, it is very slow and may require new protein kinase C production, perhaps via a cytokine cascade. Moreover, the classic mechanism of activation of protein kinase C by phospholipase C was not found, suggesting a novel mechanism of activation. Finally, the effects of rhTGF-beta 1 on protein kinase C are dependent on the state of cell maturation with respect to onset and duration of response.

Animals↗
PubMed1993

Evaluation of risks for non-Hodgkin's lymphoma by occupation and industry exposures from a case-control study.

The etiology of non-Hodgkin's lymphoma (NHL) is not well understood. To develop hypotheses on causes of this tumor, data from a population-based case-control interview study of 1,867 white men (622 cases and 1,245 controls) in Iowa and Minnesota conducted during 1980-1983 were examined. Subjects, or their next of kin, were interviewed to obtain information on agricultural exposures, work history, medical conditions, and family history. This analysis focuses on risks of NHL by occupation, by industry, and by selected exposures. Although many comparisons were made, few significant associations were observed. Small numbers and limitations in exposure assessment, however, would tend to reduce opportunities to detect associations. The strongest finding was with various occupations that work in metals and metal products. The analysis by exposure estimates also uncovered a significant association with metals, but risks did not increase with estimated intensity of exposure. Slightly elevated risks were also noted among persons employed as painters and construction workers, agricultural and forestry workers, printers and typesetters, funeral directors and embalmers, and dry cleaners. Although the overall risks for benzene and other solvents were small, they increased slightly with level of assigned exposure. Although some associations may be due to chance, several of these occupations and industries have been linked to lymphoma in other investigations and deserve further attention.

Adult↗
PubMed1993

Maturation-dependent regulation of protein kinase C activity by vitamin D3 metabolites in chondrocyte cultures.

Vitamin D3 metabolites regulate the differentiation of chondrocytes isolated from the growth zone or resting zone of rat costochondral cartilage. Since some of the direct membrane effects of vitamin D metabolites are nongenomic, we hypothesized that protein kinase C (PKC) plays a role in signal transduction for these chondrocyte differentiation factors and that the regulation of PKC by the vitamin D metabolites is cell maturation dependent. Confluent, fourth passage cultures of growth zone and resting zone chondrocytes were treated with vitamin D3 metabolites for up to 24 h, lysed, and cell extracts assayed for kinase activity using a specific PKC substrate peptide. The addition of 1,25-(OH)2D3 to growth zone cell cultures resulted in a rapid dose-dependent stimulation of PKC, significant at 10(-9)-10(-7) M, beginning at 3 min and sustained until 90 min; 1,25-(OH)2D3 had no effect on PKC activity in resting zone chondrocyte cultures. The addition of 24,25-(OH)2D3 to resting zone cultures showed a slower PKC activation, with significant stimulation seen at 90-360 min for 10(-8)-10(-7) M 24,25-(OH)2D3. However, 24,25-(OH)2D3 had no effect on PKC activity in growth zone cell cultures at all times and concentrations examined. The specificity of PKC stimulation by the vitamin D3 metabolites was verified using a specific pseudosubstrate region peptide inhibitor, which reduced PKC activity when included in the reaction mixture. Pretreatment of the cultures with U73, 122, a phospholipase C inhibitor, decreased 1,25-(OH)2D3-stimulated PKC activity but had no effect upon 24,25-(OH)2D3-induced activity. The tyrosine kinase inhibitor, genistein, did not inhibit the PKC response in either vitamin D3 metabolites-treated culture. Neither actinomycin D nor cycloheximide affected 1,25-(OH)2D3-induced PKC activity in growth zone chondrocyte cultures, while both compounds inhibited 24,25-(OH)2D3-induced activity in resting zone chondrocyte cultures. The results of this study indicate that vitamin D metabolites stimulate PKC activity in a metabolite- and cell-maturation-specific manner. Effects of 1,25-(OH)2D3 appear to be nongenomic, whereas the effects of 24,25-(OH)2D3 probably involve a genomic mechanism.

24,25-Dihydroxyvitamin D 3↗
PubMed1993

Consistent lack of association between breast cancer and oral contraceptives using either hospital or neighborhood controls.

BACKGROUND: Case-control studies of oral contraceptive use and breast cancer have used neighborhood, population, or hospital controls. METHODS: To determine whether this association differs according to type of controls, interview data from 131 incident cases of breast cancer were compared with those of 189 hospital controls and 182 neighborhood controls Study subjects were white females recruited between 1973 and 1975 from among residents of Baltimore City and County ages 18 to 59 years. RESULTS: Adjusted relative odds of breast cancer related to ever versus never use of oral contraceptives were 1.0 and 0.8, using hospital and neighborhood controls, respectively. Relative odds did not increase proportionally to duration of oral contraceptive use or to progestogen potency. Although few subjects had used oral contraceptives for more than 2 years, almost all pill brands contained more than 49 micrograms of ethinyl estradiol or of mestranol. CONCLUSIONS: Results from the present study do not support the hypothesis that early preparations of oral contraceptives increased breast cancer risk among white women, regardless of whether controls are neighbors of the cases or hospital patients. However, its conclusions cannot be generalized to women who began taking the pill before their first full-term birth or took it for more than 2 years.

Adolescent↗
PubMed1992

Comments on occupational and environmental factors in the origin of non-Hodgkin's lymphoma.

The review of the literature regarding non-Hodgkin's lymphoma and occupational and environmental factors presented at this workshop suggested associations with viruses, solvents, and hair dyes. A population-based case-control study among men from Iowa and Minnesota notes similar associations. Workers engaged in metal working, hair care, painting, and dry cleaning experienced nonsignificant excesses. Risks from specific exposures showed some variation by histological type. Both follicular and diffuse non-Hodgkin's lymphoma were associated with benzene. The diffuse type was linked to solvents other than benzene and formaldehyde, while the follicular was excessive among workers exposed to oils and greases.

Adult↗
PubMed1992

Pesticides and other agricultural risk factors for non-Hodgkin's lymphoma among men in Iowa and Minnesota.

Data from an in-person interview study of 622 white men with newly diagnosed non-Hodgkin's lymphoma and 1245 population-based controls in Iowa and Minnesota were used to measure the risk associated with farming occupation and specific agricultural exposures. Men who ever farmed were at slightly elevated risk of non-Hodgkin's lymphoma (odds ratio = 1.2, 95% confidence interval = 1.0-1.5) that was not linked to specific crops or particular animals. Elevated risks were found, with odds ratio generally 1.5-fold or greater, for personal handling, mixing, or application of several pesticide groups and for individual insecticides, including carbaryl, chlordane, dichlorodiphenyltrichloroethane, diazinon, dichlorvos, lindane, malathion, nicotine, and toxaphene. Associations were generally stronger for first use prior to 1965 than more recently, and when protective clothing or equipment was not used. Small risks were associated with the use of the phenoxyacetic acid herbicide 2,4-dichlorophenoxyacetic acid, but the risks did not increase with latency or failure to use protective equipment. Exposure to numerous pesticides poses problems of interpreting risk associated with a particular chemical, and multiple comparisons increase the chances of false-positive findings. In contrast, nondifferential exposure misclassification due to inaccurate recall can bias risk estimates toward the null and mask positive associations. In the face of these methodological and statistical issues, the consistency of several findings, both within this study and with observations of others, suggests an important role for several insecticides in the etiology of non-Hodgkin's lymphoma among farmers.

Adult↗
PubMed1990

Assessment of pupillary light reflex latency and darkness adapted pupil size in control subjects and in diabetic patients with and without cardiovascular autonomic neuropathy.

Increased pupillary light reflex latencies were found more often than a reduced darkness pupil size in diabetic patients with and without abnormal cardiovascular reflexes. This finding suggests that parasympathetic pupillary dysfunction precedes sympathetic pupillary denervation in diabetic autonomic neuropathy.

Adolescent↗
PubMed1988

Hair dye use and risk of leukemia and lymphoma.

Data from a population-based case-control study of incident leukemia and non-Hodgkin's lymphoma among adult men in Iowa and Minnesota were used to evaluate risk associated with hair dye use. The relative risk for ever using hair dyes was 1.8 (95% confidence interval [CI] = 1.1-2.7) among leukemia patients, and 2.0 (CI = 1.3-3.0) among cases with non-Hodgkin's lymphoma. There was a suggestion of increased risk with extent of hair dye use. Given the widespread use of hair coloring products, these observations deserve more detailed evaluation in populations where the exposure is relatively common.

Adult↗
PubMed1987

Use of the working formulation for non-Hodgkin's lymphoma in epidemiologic studies: agreement between reported diagnoses and a panel of experienced pathologists.

Independent review of slides of 668 cases of non-Hodgkin's lymphoma (NHL) by a panel of 4 experienced pathologists using the Working Formulation (WF) allowed determination of the agreement between reported diagnoses and panel review of slides. The panel agreed with the reported diagnosis of NHL in 93% of cases, but with the NHL subtype in only 55% of cases overall. The ability of the panelists to agree among themselves, however, was only slightly better than the panelists' agreement with the reported diagnosis (60% vs. 54%, respectively). Agreement of the panel with the reported subtype diagnosis varied from 14% to over 90%. The best agreement was with small lymphocytic lymphoma and follicular subtypes. Conclusions from this study are: 1) The WF functions well as common language for translation and comparison of diagnoses of subtypes of NHL. 2) Relative to time and cost involved, panel review using only light microscopy may not be useful in epidemiologic studies of NHL. 3) Small lymphocytic and follicular subtypes of NHL can be used more confidently in epidemiologic studies than can other subtypes whether the subtyping is done from abstracted reports or by panel review.

Humans↗