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Breastfeeding Having completed a full-term pregnancy before 30 years of age Types of Breast Cancer 1 buy anafranil 10mg overnight delivery. Ductal Carcinoma in Situ Characterized by the proliferation of malignant cells inside the milk ducts without invasion into the surrounding tissue generic 25mg anafranil visa. Infiltrating Ductal Carcinoma Is the most common histologic type of breast cancer 75mg anafranil amex. Infiltrating Lobular Carcinoma (5-10%) Infiltrating lobular carcinoma accounts for 5% to 10% of breast cancers. The tumors arise from the lobular epithelium and typically occur as an area of ill- defined thickening in the breast. Medullary Carcinoma (5%) Medullary carcinoma accounts for about 5% of breast cancers, and it tends to be diagnosed more often in women younger than 50 years. Mucinous Carcinoma (3%) Mucinous carcinoma accounts for about 3% of breast cancers and often presents in postmenopausal women 75 years and older. A mucin producer, the tumor is also slow-growing and thus the prognosis is more favorable than in many other types. Tubular Ductal Carcinoma (2%) Tubular ductal carcinoma accounts for about 2% of breast cancers. Because axillary metastases are uncommon with this histology, prognosis is usually excellent. Inflammatory Carcinoma (2%) Inflammatory carcinoma is a rare (1% to 2%) and aggressive type of breast cancer that has unique symptoms. An associated mass may or may not be present; if there is, it is often a large area of indiscrete thickening. Inflammatory carcinoma can be confused with an infection because of its presentation. Chemotherapy often plays an initial role in controlling disease progression, but radiation and surgery may also be useful. Paget Disease (1%) Paget disease of the breast accounts for 1% of diagnosed breast cancer cases. Paget disease often represents ductal carcinoma in situ of the nipple but may have an invasive component. Signs and symptoms Subjective: nontender nodule Objective: • Enlarged axillary nodes • Nipple retraction or elevation • Skin dimpling • Nipple discharge • Usually appeal in the upper outer quadrant Diagnostic tests and methods: Mammography, breast biopsy examination 218 Treatment 1. Lumpectomy: removal of the lump and partial breast tissue; indicated for early detection 2. Mastectomy • Simple mastectomy: removal of breast • Modified radical mastectomy: removal of breast, pectoralis minor muscle, and some of an adjacent lymph nodes • Radical mastectomy: removal of the breast, pectoral muscles, pectoral fascia, and axillary lymph node dissection 3. Other Surgical procedures • Oophorectomy, adrenalectomy, hypophysectomy to remove source of estrogen and the hormones that stimulate the breast tissue 4. Risk factors: age, obesity, extensive axillary disease, radiation treatment, and injury or infection to the extremity Edema resolved after development of collateral circulation. Performing prescribed exercises, elevating the arm above the heart several times a day, and gentle muscle pumping (making a fist and releasing) can help reduce the transient edema. If a trauma or break in the skin occurs, wash the area with soap and water, and apply an antibacterial ointment. Observe the area and extremity for 24 hours; if redness, swelling, or a fever occurs, call the surgeon or nurse. Metastatic breast cancer to the back Male Breast Cancer Accounts for less than 1% of all cases of breast cancer Average age at diagnosis is 67 years Risk factors: A history of mumps orchitis, Radiation exposure, Decreased testosterone levels Liver disease (compromises estrogen metabolism). Pertinent questions include the following: How is the patient responding to the diagnosis? Preoperative Nursing Interventions Providing Education and Preparation About Surgical Treatments Patients with newly diagnosed breast cancer are expected to absorb an abundance of new information during a very emotionally difficult time. The nurse plays a key role in reviewing treatment options by reinforcing information provided to the patient and answering any questions. The nurse fully prepares the patient for what to expect before, during, and after surgery. The patient should be informed that she will go home with the drain(s) and that complete instructions about drain care will be provided prior to discharge. The patient should also be reassured that appropriate analgesia and comfort measures will be provided to alleviate any postoperative discomfort. Reducing Fear and Anxiety and Improving Coping Ability The nurse must help the patient cope with the physical as well as the emotional effects of surgery. Providing the patient with realistic expectations about the healing process and expected recovery can help alleviate fears. Maintaining open communication and assuring the patient that she can contact the nurse at any time with questions or concerns can be a source of comfort. The patient should also be made aware of available resources at the treatment facility as well as in the breast cancer community such as social workers, psychiatrists, and support groups. Some women find it helpful and reassuring to talk to a breast cancer survivor who has undergone similar treatments. Promoting Decision-Making Ability The patient may be eligible for more than one therapeutic approach; she may be presented with treatment options and then asked to make a choice. This can be very frightening for some patients, and they may prefer to have someone else make the decision for them (e. The nurse can be instrumental in ensuring that the patient and family members truly understand their options.

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This enzyme deaminates adenosine (a nucleoside) to form inosine (another nucleoside) 25 mg anafranil amex. Hypoxanthine and xanthine are both purine bases discount anafranil 25mg on line, and the monophosphates are nucleotides buy 10mg anafranil with visa. Because allopurinol inhibits xanthine oxidase, the 6-mercaptopurine will not be deactivated as rapidly. Nearly ~ll somatic cells are diploid, having two copies of each type of autosome (1-;-22) and either. The two chromosomes in each diploid pair are said to be Note homologs, or homologous chromosomes. The regions that are homologous are sometimes on a chromosome referred to as pseudoautosomal regions. During meiosis-l of male spermatogenesis, the X and Y chromosomes pairin the pseudoautosomal regions, allowing the chromo- Allele-different forms of a somes to segregate int~ different cells. When a specific site on a chromosome has multiple alleles in the locus are different population, it is said to be polymorphic (many forms). Throughout human to produce disease history there have been many mutations in the ~-globin gene, and each mutation has created a new allele in the population. Some alleles cause Recessive-requires two no clinical disease, but others, like the sickle cell allele, are associated with significant disease. Note Phenotype The phenotype is generally understood as the expression of the genotype in terms of observable Major types of single-gene characteristics. Missense mutations result in the substitution of a single amino acid in the polypeptide chain (e. Nonsense mutations produce a stop codon,, • Frameshift resulting in premature termination of translation and a truncated protein. When the number of inserted or deleted bases is a multiple of three, the mutation is said to be in-frame. Mutations that cause a missing protein product or cause decreased activity of the protein are termed loss-of function. Those that produce a protein product with a new function or increased activity are termed 1 gain-of function. Recurrence risk The recurrence risk is the probability that the offspring of a couple will express a genetic disease. It is important to remember that each reproductive eventis statistically independent of all previous events. Therefore, the recur- rence risk remains the same regardless of the number of previously affected or unaffected offspring. The first affected individual to be identified in the family is termed the proband. Skipped generations are not typically seen because two Unaffected parents cannot transmit a disease-causing allele to their offspring (an exception occurs when there is reduced penetrance, discussed below). Autosomal dominant alleles are relatively rare in populations, so the typical mating pattern is a heterozygous affected individual (Aa genotype) mating with a homozygous normal individual (aa genotype), as shown in Figure I1-1-3. Note that, by convention, the dominant allele is shown in uppercase (A) and the recessive allele is shown inlowercase (a). The recurrence risk is thus 50%, and half the children, on average, will be affected with the disease. Autosomal Dominant Inheritance • Neurofibromatosis type 1 • Marfan syndrome Acute intermittent porphyria A a a aa a aa Attected offspring (Aa) are shaded. Recurrence Risk for the Mating of Affected Individual (Aa) with a Homozygous Unaffected Individual (aa) Autosomal Recessive Inheritance Important features that distinguish autosomal recessive inheritance: • Because autosomal recessive alleles are clinically expressed only in the homozygous state, the offspring must inherit one copy of the disease-causing allele from each parent. In contrast to autosomal dominant diseases, autosomal recessive diseases are typically. This mechanism, termed X inactivation, occurs in the i" chromosomes but one are blastocyst (-100 cells) during the development of female embryos. X inactivation has several important characteristics: o It is random-in some cells of the female embryo, the X chromosome inherited from Note the father is inactivated, and in others the X chromosome inherited from the mother is inactivated. Thus, as a condition in which cells • females are said to be mosaics with respect to the active X chromosome. For example, females with three X chromosomes in each cell (see Chapter 3) have two X chromosomes inacti- vated in each cell (thus, two Barr bodies can be visualized in an interphase cell). Inactivation of the X Chromosome During Embryogenesis Is a Random Process,I I I Properties of X-linked recessive inheritance! Skipped generations are commonly seen because an affected male can transmit the disease-causing mutation to a heterozygous daughter, who is unaffected but who can transmit the disease-causing allele to her sons. Male-to-male transmission is not seen in X-linked inheritance; this helps distinguish it from autosomal inheritance. Affected male-homozygous normal female: All of the daughters will be heterozygous carriers; all of the sons will be homozygous normal. Normal male-carrier female: On average, half of the sons will be affected and half of the daughters will be carriers. Affected male-homozygous normal female (X chromosome with mutation is in lower case) B. However, because X inactivation is a random process, a het- erozygous female will occasionally express an X-linked recessive mutation because; by random chance, most of the X chromosomes carrying the normal allele have been inactivated. Single-Gene Disorders X-Linked Dominant Inheritance Clinical Correlate There are relatively few diseases whose inheritance is classified as X-linked dominant. In this condition, females are differently affected than Males: 100% penetrance males, and whereas penetrance in males is 100%, that in females is approximately 60% (see margin note). Because females have two X chromosomes (and • Macro-orchidism (usually il thus two chances to inherit an X-linked disease-causing mutation) and males have only postpubertal) one, X-linked dominant diseases are seen about twice as often in females as in males. None of his sons will I be affected, but all of his daughters have the disease (assuming complete penetrance).

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The minimal transcription unit required for the expression of a therapeutic protein consists of 5′ enhancer/promoter upstream of the gene encoding for the therapeutic protein and a poly(A) signal downstream of the gene discount anafranil 10 mg fast delivery. Tissue- specific promoters are designed to interact with transcription factors or other nuclear proteins present in the desired target cells buy 75mg anafranil free shipping. The chicken skeletal a-actin promoter contains positive as-acting elements required for efficient transcriptional activity in myogenic cells cheap 25mg anafranil otc. Therefore, an a-actin promoter could direct high expression of recombinant protein in skeletal muscle. The efficiency of polyadenylation is important for gene expression, as transcripts that fail to be cleaved and polyadenylated are rapidly degraded in the nuclear compartment. Therefore, in vivo pulsatile production of certain therapeutic proteins may be beneficial for their clinical applications. This can be achieved by including gene switches in a gene expression system to turn on or off the transcription of an administered gene. A gene switch is designed to be part of a gene expression system that contains both the gene switch and a therapeutic gene. In the positive system, the target gene will be inactive until the administration of an exogenous compound or ligand. Such inducing agents or drugs include progesterone antagonists, tetracycline, ecdysone and rapamycin. This section describes the development of several lipid, peptide and polymer-based gene delivery systems. However, the encapsulation efficiency of plasmids is very low, because of the large dimension of plasmids compared to the internal diameter of the vesicles. The pH-sensitive immunoliposomes have been shown to mediate 6~8 times higher levels of transgene expression into mouse lymphoma cells, compared to non-pH-sensitive immunoliposomes. A negatively charged phospholipid such as phosphatidylserine, phosphatidic acid or phosphatidyl glycerol, in the absence or presence of cholesterol, are utilized to produce a suspension of multilamellar vesicles containing plasmids, which are then converted to small unilamellar vesicles by sonication. Cochleates have been shown to encapsulate plasmid and enhance plasmid stability and transfection efficiency. A cationic lipid consists of: • a hydrophobic lipid anchor group • a linker group • a positively charged headgroup. Lipid anchors help in forming liposomes (or micellar structures) and determine the physical properties of a lipid bilayer, such as membrane rigidity and rate of lipid exchange between lipid 341 membranes. The linker group is an important component, which determines the chemical stability and biodegradability of a cationic lipid. The head groups of cationic lipid appear to be critical for transfection and cytotoxicity of corresponding liposome formulations. The cationic amphiphiles differ markedly in structure and may be single or multiple charged as primary, secondary, tertiary and/or quaternary amines. Examples are lipospermine, cationic cholesterol, cationic detergent or lipopolysine. The relative proportions of each component and the structure of the head group influence the physicochemical properties of plasmid/lipid complexes. Many effective cationic lipids contain protonatable polyamines linked to dialkyl or cholesterol anchors. To increase the biodegradability of cationic lipids, a series of cationic lipids have been synthesized in which the ether bonds were replaced with ester bonds. Cationic lipid-based gene delivery systems lack target specificity, which results in low transfection efficiency in certain tissues due to the interference from cationic lipid-binding macromolecules either in the circulation or in the extracellular matrix. To circumvent this problem, neutral plasmid/lipospermine complexes containing a trigalactolipid have been prepared and shown to efficiently transfect hepatoma HepG2 cells bearing asialoglycoprotein receptor. Addition of 25% (mol mol−1) of the triantennary galactolipid increased the transfection efficiency by a thousand fold, compared to the lipid-based system with no targeting ligand. An efficient transfection of β-galactosidase into HeLa cells has been shown with the combination of transferrin and cationic liposome Lipofectin, whereas Lipofectin alone had low transfection efficiency. Asialofetuin is an asialoglycoprotein containing terminal galactosyl residues that have been used to target liposomes to the liver. The resulting complexes retain their ability to interact specifically with target cell receptors, leading to receptor-mediated internalization of the complex into the cells. It is known that the active sites of enzymes, receptor ligands and antibodies usually involve about 5 to 20 amino acids. One example of such a gene delivery system comprises: 343 • a galactosylated peptide that both condenses the plasmid into monodisperse nanoparticles of about 100 nm in diameter and enables specific recognition and binding to asialoglycoprotein receptors; • an amphipathic, pH-selective peptide that enables the plasmid to leave the endosomes prior to their fusion with lysosomes and entry into the cytoplasm. Two general classes of lipopeptide analogs of Tyr-Lys-Ala-Lys -n Trp-Lys peptides have been prepared by including a hydrophobic anchor. The general structures are N, N- dialkyl-Gly-Tyr-Lys-Ala-Lys -Trp-Lys and N,N -diacyl-Lys-Lys -Trp-Lys. These peptides differ from theα n n parent structures in that they self-associate to form micelles in aqueous solutions. The lytic characteristics are revealed as the carboxyl groups of the aspartyl and glutamyl side chains are protonated, which allows the peptides to assume a a-helical conformation that can be inserted into the membrane bilayer. The hydrophobic face contains only strongly apolar amino acids, while negatively charged glutamic acid residues dominate the hydrophilic face at physiological pH. At a given charge ratio of condensing peptide to plasmid, the transfection efficiency has been shown to be proportional to the concentration of the endosomolytic peptide added to the complex. The increased hydrophobicity of the complex may enhance interaction with cell membranes and facilitate cell uptake.