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Outlined is a protocol for the administration of emergency contraceptive pills. The indication for such treatment is unprotected intercourse within the past 72 hours. Absolute contraindications include the possibility of an existing pregnancy and a family history of stroke, heart attack, thrombophlebitis, breast or endometrial cancer, or liver tumor. Possibly excluded, depending on evaluation by a physician, are women with abnormal vaginal bleeding, active hepatitis, active gallbladder disease, high blood pressure, acute focal migraine, breastfeeding women, and those unable to understand instructions. The recommended regimen consists of six tablets of Ovral (two taken immediately, two more in 12 hours) or 12 tablets of Lo/Ovral, Nordette, or Levlen (four taken immediately, repeat dosage in 12 hours). The extra pills are to be used in cases of vomiting within three hours of pill ingestion. Women with a history of oral contraceptive-related nausea and vomiting should be provided with Compazine. Women should be informed that this method is effective in only about 92% of cases. All women who receive emergency contraception should be counseled that this is strictly a back-up method and helped to formulate a long-term birth control strategy.
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PMID:Emergency contraceptive pills (ECP) protocol. 1228 80

The intrauterine contraceptive device (IUD) is effective and reversible and has a high continuation rate. It can also be used within 7 days postcoitus. Developed separately by Richter, Grafenberg, and Ota between 1909 and 1934, the IUD gained popularity in the 1960s and 1970s with the introduction of the Margulies Spiral, the Lippes Loop, the Birnberg Bow, and the Dalkon Shield. The last proved dangerous, and the IUD became unpopular. The 4 IUDs which are available in Canada include the TCu-380S (GYNE T Slimline), the TCu-200, the NOVA-T, and the Progestasert. All are T shaped and medicated (copper or progesterone). The 1st and 3rd can be left in situ for 10 years; the 2nd, for 4 years; and the 4th, for 1 year. The NOVA-T has a copper wire with a silver core and is inserted with a unique pull-push technique. The Progestasert, which contains 38 mg of progesterone, releases 65 mcg of the hormone daily. The best candidate for IUD use is parous, but not pregnant, is in a stable monogamous relationship, and has a healthy reproductive tract and no history of ectopic pregnancy, sexually transmitted disease, pelvic inflammatory disease, undiagnosed genital bleeding, endometrial or cervical neoplasia, abnormal endometrial anatomy, compromised immune system, allergy to copper, or Wilson's Disease. The only infection related to the IUD is that associated with insertion. Such an infection is polymicrobial and involves the endogenous, cervicovaginal flora (primarily anaerobes). It is usually asymptomatic and contained by the immune system. 200 mg of Doxycycline can be given orally as a prophylactic 1 hour prior to insertion. A nonprescription, nonsteroidal, anti-inflammatory drug, also taken 1 hour before the procedure, will prevent pain and a vasovagal reaction. Paracervical anesthesia should be used. If the depth of the uterus is less than 6 cm or greater than 10 cm, another form of contraception should be used. Although little research is being done in Canada on new IUDs, the Levonorgestrel IUD from Europe and the CuFix-360 (Flexigard) offer promise. The former, which is T shaped, contains polydimethylsiloxane and levonorgestrel (52 mg, total; releases 20 mcg daily) and can be used for 7 years. The latter IUD is shapeless and consists of 6 copper sleeves strung on surgical nylon thread knotted at 1 end. The knot is inserted, using a needle, into the fundal myometrium. The truth and falsehood of several myths about IUDs are noted with supporting citations.
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PMID:The intrauterine device today. 1231 29

In the period 1989-1994, Honduran women participating in the Project Health Sector 2 have been exposed to a contraceptive mini-pill, Ovrette. The Institute of Honduran Social Security (IHSS) approved the program (in which Ovrette distribution is included) in May 1990. The program is partly funded by the Population Council, which is funded by USAID Registry with the Department of Health was not required under the Health Code since Ovrette had entered the country as a donation. In June 1993, a Commission of the Honduran Medical Association reported that the women were not given any written information on the drug. Ovrette is an oral contraceptive manufactured by Wyeth. Its active ingredient is a progestagen, Norgestrel. Contraindications for Ovrette include: non-lactating women who exhibit side-effects such as dizziness, water retention, migraine, etc.; non-lactating women with contraindications for estrogen; lactating women who reject other contraceptive drugs. The US Pharmacopeia and the US Food and Drug Administration do not authorize the drug for use by lactating women. As with other progestagens, Norgestrel passes through to the mother's milk. In 1993, the US Pharmacopeia reported that these hormones can cause harmful effects to the child, and recommended switching medications or discontinuation of lactation. In 1983, the WHO expressed concern about the possibility of injury caused by the progestagens. The possibilities included alterations to personality, behavior, anatomy of sexual organs, reproductive capacity, immunological function and development of neoplasia. Possible damages in puberty or during the reproductive age are not known since there is no study of exposed children that are older than 12 years of age.
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PMID:Honduran women received no written information on contraceptive pill. 1231 16

This article answers some questions about use of emergency contraceptive pills (ECP) in the US. It is acceptable to prescribe ECPs over the telephone. ECPs should not be given to women with severe migraine headaches with neurologic impairment. ECPs are acceptable for women who are smokers and over 35 years old, diabetics with vascular disease, women with a history of severe migraine, and women with a benign or malignant liver tumor. Women who seek ECPs over 72 hours after unprotected sexual intercourse could have ECPs, insertion of a Copper T380 IUD, or Ru-486, when available in the US. Lo-Ovral4+4 is the preferred ECP. Ovral2+2 is less often available and tends to cost more. An ECP prescription might indicate Phenergan (25 mg), 4 tablets, taken between 6 and 7 PM, and repeated in 12 hours. Another ECP prescription might indicate Lo-Ovral (21-pill pack), 4 tablets taken one half hour after anti-nausea medication, and repeated in 12 hours. If nausea is severe from the first or second dose of Lo-Ovral, an extra tablet of Phenergan may be taken. For continued contraception, the patient should be prescribed a low-dose pill and not a 50 mcg pill. The most common transition from ECP combined pills to regular oral contraception is to prescribe 4 tablets followed by 4 tablets 12 hours later, and to start a new package of pills the Sunday after menstruation begins. Nonlapsed pill taking involves taking the 4 tablets, followed by 4 tablets in 12 hours, and 1 tablet taken daily for the next 13 days (with backup contraception the first 7 days), and a lapse for 7 days. Nothing needs to be done for vomiting. Women are not likely to abuse this option. It should be widely known and appreciated that mistakes do happen, emergency contraception does work, and women should be aware of ECPs. 98% of women bleed by 21 days after ECP use. There appears to be no increased risk of birth defects among pill users who become pregnant.
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PMID:10 common questions on emergency contraception. 1234 14

We established a novel experimental model for human T-cell leukemia virus type 1 (HTLV-1)-induced tumor using NOD-SCID/gammac(null) (NOG) mice. This model is very useful for investigating the mechanism of tumorigenesis and malignant cell growth of adult T-cell leukemia (ATL)/lymphoma, which still remains unclear. Nine HTLV-1-infected cell lines were inoculated subcutaneously in the postauricular region of NOG mice. As early as 2 to 3 weeks after inoculation, seven cell lines produced a visible tumor while two transformed cell lines failed to do so. Five of seven lines produced a progressively growing large tumor with leukemic infiltration of the cells in various organs that eventually killed the animals. Leukemic cell lines formed soft tumors, whereas some transformed cell lines developed into hemorrhagic hard tumors in NOG mice. One of the leukemic cell lines, ED-40515(-), was unable to produce visible tumors in NOD-SCID mice with a common gamma-chain after 2 weeks. In vivo NF-kappaB DNA binding activity of the ED-40515(-) cell line was higher and the NF-kappaB components were changed compared to cells in vitro. Bay 11-7082, a specific and effective NF-kappaB inhibitor, prevented tumor growth at the sites of the primary region and leukemic infiltration in various organs of NOG mice. This in vivo model of ATL could provide a novel system for use in clarifying the mechanism of growth of HTLV-1-infected cells as well as for the development of new drugs against ATL.
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PMID:Rapid tumor formation of human T-cell leukemia virus type 1-infected cell lines in novel NOD-SCID/gammac(null) mice: suppression by an inhibitor against NF-kappaB. 1269 30

Multiple myeloma (MM) is a fatal lymphoid malignancy that is incurable with conventional modalities of chemotherapy. Strong and constitutive activation of nuclear factor kappa B (NF-kappaB) is a common characteristic of MM cells. In our study we successfully target NF-kappaB with a novel NF-kappaB inhibitor dehydroxymethylepoxyquinomycin (DHMEQ). DHMEQ completely abrogates constitutive NF-kappaB activity and induces apoptosis of MM cells, whereas control peripheral blood mononuclear cells (PBMC) are resistant to NF-kappaB inhibition and apoptosis by DHMEQ treatment. DHMEQ inhibition of NF-kappaB triggers activation of caspases 8 and 9, as well as G0/G1 cell cycle arrest accompanied by downregulation of antiapoptotic genes Bcl-XL and c-FLIP and cell cycle progression gene cyclins D1 and D2. DHMEQ-mediated inhibition of vascular endothelial growth factor (VEGF) production in MM cells raises the possibility that DHMEQ abrogates the autocrine VEGF loop and enhances its antitumor effects by inhibiting neovascularization in the bone marrow. Using an in vivo NOD/SCID/gammac(null) (NOG) mice model, we show that DHMEQ has a potent inhibitory effect on the growth of MM cells. Compared to other compounds having the potential to inhibit NF-kappaB, DHMEQ is a unique compound that blocks the translocation of NF-kappaB p65 into the nucleus and selectively targets NF-kappaB activated in tumor cells. Therefore, our study presents a new molecular target therapy in MM.
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PMID:A novel NF-kappaB inhibitor DHMEQ selectively targets constitutive NF-kappaB activity and induces apoptosis of multiple myeloma cells in vitro and in vivo. 1552 84

Human cells have developed innate immunity, exploiting several means to block virus infection, and viruses have evolved diverse strategies to resist these. We show here that the human immunodeficiency virus 1 (HIV-1) could neither progressively infect engrafted human leukemic T cells nor repress their growth in NOG mice. However, ED-40515(-) cells infected with HIV-1 before inoculation were found to significantly delay the onset of tumor growth and increased the survival period of NOG mice. ED-40515(-) tumor cells showed resistance to HIV-1 which was apparently correlated with the down-regulation of CD4 and CXCR4 molecules in NOG mice. Serum from three different mouse strains, including NOG, retained a suppressive effect on the CD4 molecule of ED-40515(-) cells in vitro. ED-40515(-) cells obtained from mice re-expressed CD4 and CXCR4 molecules upon in vitro culture and were again successfully infected with HIV-1. These findings indicate that HIV-1 may initially successfully delay or regress tumor growth in NOG mice, but eventually fails to do so because of the evolution of HIV-resistant cells due to a rapid down-modulation of CD4 and CXCR4. Our data also demonstrated that some unknown soluble factor(s) present in mouse serum was responsible for conferring resistance to HIV infection to human T cells.
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PMID:Mouse serum factor(s) down-modulate the CD4 and CXCR4 molecules on human T cells conferring resistance to HIV infection in NOG mice. 1565 27

Tumor xenografts in immune-deficient mice (athymic nude mice and SCID mice) are well-established animal models for the study of human cancer. Several human melanoma cell lines were reported to metastasize in the immune-deficient mice models. However, metastatic rates were extremely low in spite of large numbers of injections of cancer cells, more than 1 x 10(6) cells/mouse. The NOD/SCID/gamma(C)(null) (NOG) mouse shows multiple immunological dysfunctions, including cytokine production capability, in addition to the functional incompetence of T, B and natural killer (NK) cells. However, the immune-deficient mice, with preserved NK cell activity, might interfere with engraftment efficiency. We examined the distant metastasis of the human melanoma cell lines (A2058, A375, G361 and HMY-1, 1 x 10(4) cells/mouse) in the 6 weeks after intravenous inoculation. All four melanoma cell lines showed metastasis in the NOG mice, while no metastatic lesions were observed in the NOD/SCID mice. Metastatic lesions were noted in the liver and lung of 6/6 (100%) mice at A2058, 8/9 (89%) at A375, 2/6 (33%) at G361 and 2/8 (25%) at HMY-1. A2058 and A375 cell lines with high metastatic potentials show increased gene expression of S100A4. Western blot assay confirmed the increased protein levels of S100A4 in the A2058 and A375 cell lines. E-cadherin gene expression was conversely inhibited in these cell lines. The increased expression of S100A4 combined with inhibited E-cadherin expression resulted in high metastatic potentials of the human melanoma cell lines in vivo.
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PMID:S100A4 expression with reduced E-cadherin expression predicts distant metastasis of human malignant melanoma cell lines in the NOD/SCID/gammaCnull (NOG) mouse model. 1607 66

As there are very few reproducible animal models without conditioning available for the study of human B-cell-type Hodgkin's lymphoma (HL), we investigated the ability of HL cells to induce tumors using novel NOD/SCID/gammac(null) (NOG) mice. Four human Epstein-Barr virus-negative cell lines (KM-H2 and L428 originated from B cells, L540 and HDLM2 originated from T cells) were inoculated either subcutaneously in the postauricular region or intravenously in the tail of unmanipulated NOG mice. All cell lines successfully engrafted and produced tumors with infiltration of cells in various organs of all mice. Tumor cells had classical histomorphology as well as expression patterns of the tumor marker CD30, which is a cell surface antigen expressed on HL. Tumor progression in mice inoculated with B-cell-type, but not T-cell-type, HL cells correlated with an elevation in serum human interleukin-6 levels. Tumor cells from the mice also retained strong nuclear factor (NF)-kappaB DNA binding activity, and the induced NF-kappaB components were indistinguishable from those cultured in vitro. The reproducible growth behavior and preservation of characteristic features of both B-cell-type and T-cell-type HL in the mice suggest that this new xenotransplant model can provide a unique opportunity to understand and investigate the mechanism of pathogenesis and malignant cell growth, and to develop novel anticancer therapies.
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PMID:Hodgkin's lymphoma cells are efficiently engrafted and tumor marker CD30 is expressed with constitutive nuclear factor-kappaB activity in unconditioned NOD/SCID/gammac(null) mice. 1610 27

Natural killer (NK) cell is an important component of the innate immune system and plays a central role in host defense against tumor and virus-infected cells. This review briefly summarizes the role of murine NK cells in tumor growth and metastasis of breast cancer cells in severe combined immunodeficiency (SCID) mice. Conventional SCID and NOD-SCID strains have been used to study for xenotransplantion of human tumors. SCID mice models of cancer mimic human diseases and have provided valuable information. However, these mice strains have some residual immunity such as NK cells that somewhat limit post-transplantation growth and metastasis of human xenografts. In contrast, NOD/SCID/gammac(null) (NOG) mice without common gamma-chain inoculated with breast cancer cells were most efficient in the formation of a large tumor and metastasis. NOG mouse strain without NK activity appears to be more promising as tool for xenotransplantion of human cancer. This new xenotransplant model is relevant and can be recommended for use in clarifying the mechanism of growth of cancer cells as well as for developing new therapeutic strategies against cancer.
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PMID:Natural killer cells in breast cancer cell growth and metastasis in SCID mice. 1650 13


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