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Biomedical subjects

M Coleman

Publications and source records attributed to M Coleman.

At least 109 records · Page 6Linked to original sources

Effects of dietary fatty acids on DU145 human prostate cancer cell growth in athymic nude mice.

The purpose of this study was to examine the effects of diets containing different unsaturated fatty acids (FAs) on DU145 human prostate cancer cell growth in nude mice. In Experiment 1, groups of 25 mice were fed 23% (wt/wt) fat diets containing 18% corn oil (CO)-5% linseed oil (18:2n-6 FA-rich), 18% linseed oil (LO)-5% CO (18:3n-3 FA-rich), or 18% menhaden oil (MO)-5% CO (20:5 and 22:6n-3 FA-rich), and seven days later they were injected subcutaneously with 1 x 10(6) DU145 cells. The diets were continued for six weeks. The growth rates and final weights of tumors from the 18% CO-5% LO and 18% LO-5% CO mice were similar; there was a 30% reduction in tumor growth in the 18% MO-5% CO group (p < 0.001). The tumor phospholipid FA patterns suggested that the inhibitory effect of the high-MO diet was due, at least in part, to a reduction of arachidonic acid available for prostaglandin biosynthesis. In Experiment 2, groups of 25 mice were injected with 5 x 10(5) or 1 x 10(6) DU145 cells directly into the prostate gland and fed a high-fat linoleic acid (n-6 FA)-rich or a low-fat diet for 10 weeks. At necropsy, macroscopic cancers and microscopic intraprostatic tumors were evaluated. When the initial tumor load was 1 x 10(6) cells, all but 7 of the 50 mice had developed large macroscopic tumors; the mean tumor weight in the high-fat group was twice that in the low-fat group (p = 0.047). A stimulatory effect of dietary n-6 FA on DU145 prostate cancer cell growth may require a critical initial tumor cell mass.

Animals↗

Correlates of child care providers' interpretation of pediatric AIDS: implications for education and training.

A total of 212 child care providers residing in a southeastern state were surveyed about their knowledge and attitudes toward AIDS and child care policies. Providers' feeling about caring for an HIV-infected child, rather than their perceived knowledge of AIDS, were most consistently correlated with their factual knowledge and positive attitudes toward AIDS. These results suggest that providers may pay more attention to AIDS information and become more accepting of recommended child care policies when they are able to personalize AIDS within the context of their work with young children. Implications for education are discussed within the context of the Health Belief Model.

Acquired Immunodeficiency Syndrome↗

Starvation-induced genes of the tomato pathogen Cladosporium fulvum are also induced during growth in planta.

The pathogenicity of fungal pathogens is presumably dependent on genes that are expressed during infection. In order to isolate such genes from the tomato pathogen Cladosporium fulvum, and to test the hypothesis that starvation-induced genes are also plant induced, a cDNA library was prepared from mycelia grown in a defined medium and then transferred to a starvation medium. The library was then screened with cDNA prepared from starved and replete fungal mycelium. Five unique, differentially expressed cDNAs were isolated from 1,000 clones screened. Northern (RNA) hybridization confirmed that all five were starvation induced. Interestingly, all five were also found to be plant induced. The identity of two of the clones was indicated by partial DNA sequencing as alcohol and aldehyde dehydrogenase. The observed correlation between starvation induction and plant induction in discussed.

Amino Acid Sequence↗

CODBLAM IV chemotherapy for large cell lymphoma: sequential use of infusional vincristine and bleomycin and "high dose" consolidation.

BACKGROUND: Based on prior results in large cell lymphoma (LCL) with COPBLAM (Cyclophosphamide, Oncovin, Prednisone, Bleomycin, Adriamycin, Matulane) I and COPBLAM III, CODBLAM (Cyclophosphamide, Oncovin, Dexamethasone, Bleomycin, Adriamycin, Matulane) IV was developed to intensify treatment further by utilizing four sequential cycles of infusional chemotherapy followed by high-dose chemotherapy and cycle active agents. METHODS: Sixty-one patients with LCL, mostly B-cell lymphoma, with 54% >60 years of age, were treated with daily continuous infusion of vincristine 1.0 mg/m2 days 1-2, bleomycin 4 mg/m2 i.v. push x 1 only followed by daily infusion 4 mg/m2 days 1-5, dexamethasone 10 mg/m2 days 1-5, procarbazine 100 mg/m2 orally days 1-5, doxorubicin 35 mg/m2 i.v. push day 1 (escalated), and cyclophosphamide 350 mg/m2 i.v. push day 1 (escalated), all given every 3 weeks for four cycles. After infusions, patients were restaged and treated with single courses of doxorubicin 90 mg/ m2 i.v. push followed at 3 weeks with cyclophosphamide 1500 mg/m2 i.v. push (both with concomitant vincristine 1 mg/m2 i.v. push and dexamethasone 10 mg/m2 p.o. daily for 5 days). Remaining treatment consisted of methotrexate 120 mg/m2 i.v. push with citrovorum rescue, cytarabine 250 mg/m2 i.v. push, and etoposide 100 mg/m2 i.v. infusion over 1 h, all given every 10 days for six cycles. RESULTS: The overall complete response (CR) rate was 88%. Of all patients, 36 (59%) are sustained disease free at a median follow-up time of 55 months. In patients age < or = 60 years, 89% achieved CR and 85% of patients age >60 years attained CR. CR was achieved in 83% of patients with constitutional B-type symptoms, 69% of patients with bulky adenopathy, and 86% of patients with immunoblastic histology. Toxicity was primarily pulmonary, occuring in 15% of patients. One toxic death was observed. CONCLUSIONS: Infusional CODBLAM IV may represent an effective and unique treatment for LCL.

Adult↗

The molecular mechanisms of term and preterm labor: recent progress and clinical implications.

Current tocolytic protocols rely largely on the use of beta-mimetics to induce myometrial quiescence and delay delivery. Unfortunately, the rapid transplacental passage and poor receptor specificity of the commonly used beta-mimetics results in widespread activation of intrauterine and extrauterine beta 1 and beta 2 receptors. The use of beta-mimetics is associated with a range of well-recognized and potentially dangerous side effects for mother and fetus. The value of continued use of beta-agonists after obtaining uterine quiescence also has been the subject of recent debate. In this article we have attempted to explore the biochemical and molecular rationale for the use of alternative therapeutic modalities in the treatment and prevention of PTL. In the light of the current view that the term "preterm labor" covers a considerable diversity of causes, we propose that a range of treatment regimes should be chosen on the basis of the diagnosis and classification of the patient according to the their particular condition. Although the measurement of several biochemical parameters have been suggested to be of use in predicting PTL, we believe that a panel of diagnostic indicators (e.g., free or total CRH, IL-6, extracellular matrix proteases, fetal fibronectin) is more likely to provide useful diagnostic information on which appropriate treatment modalities can be selected (Table 1). Because of the complex and interactive nature of the mechanisms operating within the intrauterine environment to regulate myometrial activation and uterotonin production, we speculate that a combination of tocolytics, anti-inflammatory agents, uterotonic antagonists, and receptor blockers is likely to be more effective than a monotherapeutic approach, which focuses on only one facet of the process of uterine activation for pharmacologic intervention. For example, the use of antibiotics, PGHS inhibitors, and/or beta-mimetics might be an appropriate first line of treatment for infection-associated PTL in extreme prematurity. If it is successful, this treatment might be followed by longer term use of a progestagen and/or NO donor to maintain myometrial quiescence until closer to term. Alternatively, use of progesterone or oxytocin antagonists may be effective in augmenting the actions of beta-mimetics while reducing their side effects, whereas other combinations may be useful as long-term prophylactics in women with a high risk of developing PTL. Improvements continue in our diagnostic ability to correctly identify the different causes of preterm labor. We anticipate that careful selection of differing combinations of therapeutic options will result in significant reductions in the morbidity, mortality, and healthcare costs associated with preterm birth.

Female↗

A nonradioactive method of in situ hybridization that uses riboprobes and paraffin-embedded tissue and its combination with immunohistochemistry.

Current research into cytokine production in tissue sections relies on the detection of cytokine proteins using a variety of immunohistochemical methods. The disadvantages of this technique are that precise localization to a particular cell is difficult and it is uncertain whether the cells detected by this method are the origin or target of the cytokine or rather have nonspecifically absorbed the secreted cytokine. This question can be clarified using in situ hybridization, but current techniques are insensitive, poorly localizing, or time consuming. Biotin-labeled riboprobes were generated from cDNA fragments sandwiched between two RNA polymerase promoters (SP6 and T7 RNA polymerases) using a commercial riboprobe generation kit containing biotin-labeled UTP. The in situ hybridization technique was used to demonstrate cytokine mRNA in a range of tissues containing an inflammatory infiltrate and with a range of cytokine probes. This technique of in situ hybridization was combined with immunohistochemistry using an immunoalkaline phosphatase technique to show the powerful combination of these two techniques. The biotin-labeled riboprobes were sensitive enough to detect a range of cytokine mRNAs in a variety of tissue sections. The technique can be completed over a 24-h period and produces a stable color product that can be stored for long periods and can be quantitated using image analysis techniques. This technique was performed on paraffin-embedded tissue as well as cryosections and allowed for the detection of mRNA in archival tissue. It was also successfully combined with immunohistochemical techniques to determine simultaneously the localization of a cytokine product in particular cell lineages. A nonradioactive method for in situ hybridization using biotin-labeled riboprobes is described; it is capable of detecting mRNA products from a range of genes in a variety of tissue samples. An amplification step in the method enhances the sensitivity to a level that approaches that of radioactive methods, while maintaining the speed, safety, and simplicity of an immunoperoxidase detection system. The ability to use paraffin-embedded tissue with this method allows for improved tissue architecture and examination of archival tissue. These features should ensure greater use of in situ hybridization techniques in future research studies.

Arthritis, Rheumatoid↗

The levonorgestrel-releasing intrauterine device: a wider role than contraception.

The Levonorgestrel-releasing intrauterine device (LNG IUD) provides excellent contraception; it may reduce the rate of pelvic inflammatory disease (PID) and ectopic pregnancy compared to other 'modern' copper releasing IUDs; it can safely be used in the puerperium for breast-feeding mothers, and it significantly reduces menstrual blood loss and pain. While it was developed primarily as a contraceptive, its potential role in managing heavy and painful menstruation and the symptoms of the climacteric may eventually be just as important. Amongst developed countries New Zealand and Australia have some of the highest hysterectomy rates. By the age of 50 years 1 in 4 women in New Zealand and 1 in 5 women in Australia will have had a hysterectomy (A,B). In New Zealand 90% of these are performed for heavy menstrual bleeding and fibroids (A). The LNG IUD has been shown to be effective treatment for both these conditions and its introduction to New Zealand and Australia would offer women an additional choice beyond surgery.

Contraceptive Agents, Female↗

Granddaughters' accounts of the influence of parental mediation on relational closeness with maternal grandmothers.

This study explores granddaughters' reports of the nature and impact of parental mediation on the development of their feelings of closeness toward their maternal grandmothers. Results from close-ended questions assessing granddaughters' perceptions of parental mediation and relational closeness indicated that closeness was predicted by mediation involving: visits alone with grandmothers, the absence of criticism of grandmothers, communication indicating the grandmothers were important persons, and less influence on conversations or activities. Qualitative analysis of granddaughters' accounts of the influence of parents illustrated what they perceived to be important issues in mediation. Additionally, accounts revealed the role of other family members in the relationship mediation process.

Adolescent↗

Ki-1 skin lymphoproliferative disorders: management with radiation therapy.

Lymphomatoid papulosis and anaplastic large Ki-1 lymphoma of skin share unique clinical and pathological features. Appropriate therapy for multiple Ki-1 lymphoproliferative lesions without systemic involvement remains controversial. This paper presents results achieved with local radiation therapy. Two patients with multiple Ki-1 skin lymphoproliferative tumors were treated with local radiation using various techniques determined by the size and the depth of tumor invasion. Most lesions received 3000 cGy in 3 weeks. Complete response was achieved in all treated areas. There was virtually no morbidity. After more than 3 years, none of the treated areas developed local recurrence, and there was no evidence of internal dissemination. Ki-1 skin lymphoproliferative disorders are highly radiosensitive. When the disease is confined to the skin, and there is no evidence of spontaneous regression, or if palliation of symptoms is necessary, local radiation therapy may be an effective modality.

Humans↗

Synovial membrane inflammation and cytokine production in patients with early osteoarthritis.

OBJECTIVE: To establish the presence of inflammation in and cytokine production by synovial membranes from patients with various stages of early osteoarthritis (OA), with knee pain, normal knee radiographs, and arthroscopic evidence of chondral damage. METHODS: Synovial membrane samples were obtained from the knees of 63 patients at the time of arthroscopy for unexplained knee pain or at the time of joint replacement surgery. Evaluations of synovial membrane variables including thickness of lining layer, vascularity, and inflammatory cell infiltrate were by a blinded observer. In a subset of 20 patients, production of interleukin 1 alpha (IL-1 alpha), interleukin 1 beta (IL-1 beta), tumor necrosis factor alpha (TNF-alpha), and IL-1 receptor antagonist (IL-1ra) at the mRNA and protein levels was determined using in situ hybridization with biotin labeled ribo-probes and immunohistochemistry. RESULTS: There was evidence of thickening of the lining layer, increased vascularity, and inflammatory cell infiltration in synovial membranes from patients with all grades of OA, with the most marked changes seen in synovial tissue from patients with advanced grades of OA. Similarly, production of IL-1 alpha, IL-1 beta, and TNF-alpha was present in synovial membranes from all patients with OA, irrespective of the degree of articular cartilage damage. There was a trend to decreased levels of IL-1ra in synovial membranes from patients with OA that did not attain statistical significance. Similarly, there was a decrease in the ratio of IL-1ra to IL-1 alpha and beta with increasing grades of OA. CONCLUSION: Chronic inflammatory changes with production of proinflammatory cytokines are a feature of synovial membranes from patients with early OA, with the most severe changes seen in patients at the time of joint replacement surgery resembling those seen in rheumatoid arthritis. This low grade synovitis results in the production of cytokines that may contribute to the pathogenesis of OA.

Adolescent↗

Synovial membrane cytokine profiles in reactive arthritis secondary to intravesical bacillus Calmette-Guérin therapy.

We describe the cellular infiltrate and cytokine profile in sequential synovial membrane biopsies from a patient with acute followed by chronic synovitis after intravesical bacillus Calmette-Guérin (BCG) therapy for an in situ transitional cell carcinoma of the bladder. Histological and immunohistochemical analysis of 3 synovial biopsies were done sequentially over a 9 month period. The patient was HLA-B27 positive, but HLA-DR4 negative, and did not have the "shared epitope." Unlike other cases, this patient's arthritis did not respond initially to nonsteroidal antiinflammatory drugs and was exacerbated by corticosteroid therapy. The synovitis took a neutrophilic form, with marked synovial membrane content of interleukin 8 (IL-8) and tumor necrosis factor alpha (TNF-alpha). It subsequently developed into chronic lymphoplasmacytoid synovitis, similar to rheumatoid arthritis (RA), with decreased IL-8 but continuing IL-1 and TNF-alpha production in the synovial membrane. The synovitis resolved to a fibrotic synovium with residual thickening of the synovial lining layer and continued production of TNF-alpha. Thus, during the evolution of this arthritis, the synovial layer and continued production of TNF-alpha. Thus, during the evolution of this arthritis, the synovial membrane yielded a cellular infiltrate and cytokine content that had marked similarities with that seen in RA; however, the arthritis eventually remitted spontaneously.

Aged↗

Variability in cytokine and cell adhesion molecule staining in arthroscopic synovial biopsies: quantification using color video image analysis.

OBJECTIVE: To investigate the variability in immunostaining for cytokines and cell adhesion molecules using multiple arthroscopically directed synovial biopsies from within a rheumatoid knee joint, quantitated by color video image analysis. METHODS: Needle arthroscopic biopsies were taken from multiple sites (4-7 sites) around a knee joint in 8 patients with rheumatoid arthritis (RA). In 5 patients, immunoperoxidase staining for the cytokines tumor necrosis factor alpha (TNF-alpha), interleukin 8 (IL-8), and IL-1beta as well as the IL-1 receptor antagonist protein (IL-1ra) was performed. In 3 patients, immunoperoxidase staining for the cell adhesion molecules E-selectin (CD62E), P-selectin (CD62P), intercellular adhesion molecule 1 (ICAM-1, CD54), and platelet endothelial cell adhesion molecule (PECAM, CD31) was performed. Immunostaining was quantified using color video image analysis. RESULTS: The overall probability of paired biopsies from the same RA knee joint being significantly different from each other due to sampling variation was at most 22% for cytokine staining (usually less than 10%). There were no significant differences between intrabiopsy and interbiopsy variability for cell adhesion molecule staining of the sublining and vessels. CONCLUSION: The variability in cytokine and cell adhesion molecule staining within any single biopsy usually reflects the variability between biopsies taken from different sites in the same rheumatoid joint when the immunostaining is quantified using color video image analysis. Therefore, only a small number of synovial biopsies are required to accurately determine the cytokine and cell adhesion molecule expression in a single joint.

Aged↗

A comparison of survival of patients treated for AIDS-related central nervous system lymphoma with and without tissue diagnosis.

PURPOSE: This is a retrospective review of the treatment outcome of radiation therapy (RT) in acquired immune-deficiency syndrome (AIDS) patients with presumed primary central nervous system (CNS) non-Hodgkin's lymphoma (NHL), with and without tissue verification. METHODS AND MATERIALS: Twenty-seven patients with AIDS-related CNS NHL were treated between 1986 and 1992. They were divided into two groups. Group 1 consisted of nine patients with a positive histology for NHL. They were treated with dexamethasone (DXM) and whole brain RT. Group 2 consisted of 18 patients who, because of unique circumstances, were treated without histologic confirmation of NHL. Rapid clinical and/or radiologic response to DXM and whole-brain RT was interpreted as NHL. RESULTS: For group 1, the response rate was 87.5%, mean survival 6.1 months, and median survival 4.5 months. For group 2, the response rate was 72.2%, mean survival 5.2 months, and median survival 4.5 months. The overall response rate was 76.9%, mean survival 5.8 months, and median survival 4.5 months. CONCLUSIONS: In instances where a tissue diagnosis cannot be established, a positive response to an empiric trial of DXM and RT to 20 Gy may constitute presumptive evidence of NHL.

Antineoplastic Agents, Hormonal↗

Educating nurses to undertake clinical supervision in practice.

Alongside interest in the process of clinical supervision, there is a growing recognition of the need for education for practitioners undertaking the role of supervisor. This article describes a module accredited by the Welsh National Board and the University of Wales, Swansea, which was designed to achieve this aim and help practitioners design structures for supervision applicable to their practice settings. The structure and content of the module are described, as well as an evaluation of the first intake.

Curriculum↗