INTRODUCTION

Graves disease is an autoimmune disorder that leads to over activity of the thyroid gland (hyperthyroidism). An autoimmune is a condition that occurs when the immune system mistakenly attacks and destroys healthy tissue. Causes The thyroid gland is an important organ of the endocrine system. The thyroid gland is located at the front of the neck above where the collar bones meet. This gland releases the hormones thyroxin (T4) and triiodothyronine(T3), which control body metabolism. Controlling metabolism is important for regulating mood, weight, and mental and physical energy levels. When the body makes too much thyroid hormone, the condition is called hyperthyroidism. (An underactive thyroid leads to hypothyroidism.) Graves disease is the most common cause of hyperthyroidism. It is due to an abnormal immune system response that causes the thyroid gland to produce too much thyroid hormone. Graves disease is most common in women over age 20. But the disorder can occur at any age and can affect men as well. Symptoms Younger patients may have these symptoms:

Anxiety Breast enlargement in men (possible) Difficulty concentrating Double vision Eyeballs that stick out (exophthalmos) Eye irritation and tearing Fatigue Frequent bowel movements Goiter (possible) Heat intolerance Increased appetite Increased sweating Insomnia Irregular menstrual periods in women Muscle weakness Nervousness Rapid or irregular heartbeat (palpitations or arrhythmia) Restlessness and difficulty sleeping Shortness of breath with activity

Tremor Weight loss (rarely, weight gain)

Older patients may have these symptoms:

Rapid or irregular heartbeat Chest pain Memory loss Weakness and fatigue

Exams and Tests The health care provider will do a physical exam and may find that you have an increased heart rate. An exam of your neck may find that your thyroid gland is enlarged (goiter). Other tests include:

Blood tests to measure levels of TSH, T3, and free T4 Radioactive iodine uptake and scan

This disease may also affect the following test results:

Orbit CT scan or ultrasound Thyroid stimulating immunoglobulin (TSI) Thyroid peroxidase (TPO) antibody Anti-TSH receptor antibody

Treatment Treatment is aimed at controlling your overactive thyroid. Medicines called beta-blockers are often used to treat symptoms of rapid heart rate, sweating, and anxiety until the hyperthyroidism is controlled. Hyperthyroidism is treated with one or more of the following:

Ant thyroid medications Radioactive iodine Surgery

If you have radiation or surgery, you will need to take replacement thyroid hormones for the rest of your life, because these treatments destroy or remove the gland. Some of the eye problems related to Graves disease usually improve when hyperthyroidism is treated with medications, radiation, or surgery. Radioactive iodine can sometimes make eye problems worse. Eye problems are worse in people who smoke, even after the hyperthyroidism is cured.

Sometimes prednisone (a steroid medication that suppresses the immune system) is needed to reduce eye irritation and swelling. You may need to tape your eyes closed at night to prevent drying. Sunglasses and eye drops may reduce eye irritation. In rare cases, surgery or radiation therapy (different from radioactive iodine) may be needed to prevent further damage to the eye and loss of vision. Outlook (Prognosis) Graves disease often responds well to treatment. Thyroid surgery or radioactive iodine usually will cause an underactive thyroid (hypothyroidism). Without getting the correct dosage of thyroid hormone replacement, hypothyroidism can lead to:

Depression Mental and physical sluggishness Weight gain

When to Contact a Medical Professional Call your health care provider if you have symptoms of Graves disease. Also call if your eye problems or other symptoms get worse or do not improve with treatment. Go to the emergency room or call the local emergency number (such as 911) if you have symptoms of hyperthyroidism with:

Decrease in consciousness Fever Rapid, irregular heartbeat

Aplastic Anemia Aplastic anemia is a syndrome of bone marrow failure characterized by peripheral pancytopenia and marrow hypoplasia. Mild macrocytosis is observed in association with stress erythropoiesis and elevated fetal hemoglobin levels. Paul Ehrlich introduced the concept of aplastic anemia in 1888 when he studied the case of a pregnant woman who died of bone marrow failure. However, it was not until 1904 that Anatole Chauffard named this disorder aplastic anemia Staging Staging of aplastic anemia is based on the criteria of the International Aplastic Anemia Study Group, as follows:

Blood - Neutrophils less than 0.5 X 109/L; platelets less than 20 X 109/L; reticulocytes less than 1% corrected (percentage of actual hematocrit [Hct] to normal Hct) Marrow - Severe hypocellularity; Moderate hypocellularity, with hematopoietic cells representing less than 30% of residual cells

Severe aplasia is defined as including any 2 or 3 peripheral blood criteria and either marrow criterion. A further subclassification developed after the recognition that individuals with neutrophil counts lower than 0.2 X 109/L had very severe aplastic anemia (VSAA). This group is less likely than others to respond to immunosuppressive therapy. The theoretical basis for marrow failure includes primary defects in or damage to the stem cell or the marrow microenvironment. The distinction between acquired and inherited disease may present a clinical challenge, but more than 80% of cases are acquired. In acquired aplastic anemia, clinical and laboratory observations suggest that this is an autoimmune disease. On morphologic evaluation, the bone marrow is devoid of hematopoietic elements, showing largely fat cells. Flow cytometry shows that the CD34 cell population, which contains the stem cells and the early committed progenitors, is substantially reduced.[2, 4] Data from in vitro colonyculture assays suggest profound functional loss of the hematopoietic progenitors, so much so that they are unresponsive even to high levels of hematopoietic growth factors. It was hypothesized that aplastic anemia may be due to a defect at various levels such as an intrinsic defect of hematopoietic cells, external injury to hematopoietic cells, and defective stroma, which is critical for normal proliferation and functioning of hematopoietic cells. Thus, theoretically, all of these mechanisms could be responsible for aplastic anemia. This theory was the basis of many in vitro stem cell culture experiments using a cross-over design in which stem cells from patients with aplastic anemia were cultured with normal stroma and vice-versa. The conclusions from these studies led to the understanding that stem cell defect is the central mechanism in the majority of patients with aplastic anemia.[5, 6] In patients with severe aplastic anemia (SAA), stromal cells have normal function, including growth factor production. Adequate stromal function is implicit in the success of BMT in aplastic anemia because the stromal elements are frequently of host origin. The role of an immune dysfunction was suggested in 1970, when autologous recovery was documented in a patient with aplastic anemia in whom engrafting failed after BMT. Mathe proposed that the immunosuppressive regimen used for conditioning promoted the return of normal marrow function. Since then, numerous studies have shown that, in approximately 70% of patients with acquired aplastic anemia, immunosuppressive therapy improves marrow function.[3, 7, 8, 9, 10] Immunity is genetically regulated (by immune response genes), and it is also influenced by environment (eg, nutrition, aging, previous exposure).[11, 12] Although the inciting antigens that breach immune tolerance with subsequent autoimmunity are unknown, human leukocyte antigen (HLA)-DR2 is overrepresented among European and United States patients with aplastic anemia, suggesting a role for antigen recognition, and its presence is predictive of a better response to cyclosporine. Suppression of hematopoiesis is likely mediated by an expanded population of the cytotoxic T lymphocytes (CTLs) CD8 and HLA-DR+, which are detectable in the blood and bone marrow of patients with aplastic anemia. These cells produce inhibitory cytokines, such as gammainterferon and tumor necrosis factor, which can suppress progenitor cell growth. Polymorphisms

in these cytokine genes, associated with an increased immune response, are more prevalent in patients with aplastic anemia. These cytokines suppress hematopoiesis by affecting the mitotic cycle and cell killing by inducing Fas-mediated apoptosis. In addition, these cytokines induce nitric oxide synthase and nitric oxide production by marrow cells, which contributes to immunemediated cytotoxicity and the elimination of hematopoietic cells. Constitutive expression of Tbet, a transcriptional regulator that is critical to Th1 polarization, occurs in a majority of aplastic anemia patients.[7] Perforin is a cytolytic protein expressed mainly in activated cytotoxic lymphocytes and natural-killer cells. Mutations in the perforin gene are responsible for some cases of familial hemophagocytosis[13] ; mutations in SAP, a gene encoding for a small modulator protein that inhibits undefined-interferon production, underlie X-linked lymphoproliferation, a fatal illness associated with an aberrant immune response to herpesviruses and aplastic anemia. Perforin and SAP protein levels are markedly diminished in a majority of acquired aplastic anemia cases. Apart from immunological, toxin/drug-related, and infectious etiopathologies, around 10-15% of patients with apparently acquired aplastic anemia may have shortened telomeres in blood lymphocytes. This was initially presumed to reflect stressed hematopoiesis, but, subsequently, telomerase gene complex mutations have been demonstrated in such individuals as well as their healthy family members. These apparently healthy family members were subsequently tested and found to have normal or near-normal blood counts, along with hypocellular marrow fragments.[14] Congenital or inherited causes Congenital or inherited causes of aplastic anemia (20%) include the following:

Patients usually have dysmorphic features or physical stigmata; on occasion, marrow failure may be the initial presenting feature. Fanconi anemia Dyskeratosis congenita Cartilage-hair hypoplasia Pearson syndrome Amegakaryocytic thrombocytopenia (thrombocytopenia-absent radius [TAR] syndrome) Shwachman-Diamond syndrome Dubowitz syndrome Diamond-Blackfan syndrome Familial aplastic anemia Acquired causes Acquired causes of aplastic anemia (80%) include the following:

Idiopathic factors Infectious causes, such as hepatitis viruses, Epstein-Barr virus (EBV), human immunodeficiency virus (HIV), parvovirus, and mycobacteria Toxic exposure to radiation and chemicals, such as benzene Transfusional GVHD Orthotopic liver transplantation for fulminant hepatitis Pregnancy

Eosinophilic fasciitis Drugs and elements, such as chloramphenicol, phenylbutazone, and gold, may cause aplasia of the marrow. The immune mechanism does not account for the marrow failure in idiosyncratic drug reactions. In such cases, direct toxicity may occur, perhaps due to genetically determined differences in metabolic detoxification pathways. For example, the null phenotype of certain glutathione transferases is overrepresented among patients with aplastic anemia. Paroxysmal nocturnal hemoglobinuria (PNH) is caused by an acquired genetic defect limited to the stem-cell compartment affecting the PIGA gene. Mutations in the PIGA gene render cells of hematopoietic origin sensitive to increased complement lysis. Approximately 20% of patients with aplastic anemia have evidence of PNH at presentation, as detected by means of flow cytometry. Furthermore, patients whose disease responds after immunosuppressive therapy frequently recover with clonal hematopiesis and PNH. Hypertension Hypertension (HTN) affects approximately 50 million individuals in the United States and 1 billion worldwide. Unless broad and effective preventive measures are implemented, the prevalence of hypertension will continue to increase. [1] Hypertension is a major modifiable risk factor for cardiovascular disease (CVD). Current trends indicate hypertension is often undertreated and associated with poor medication and lifestyle adherence. Pharmacists play an important role then in providing patient education, identifying barriers to medication adherence, and assisting the patient in developing plans to address and improve adherence. Numerous antihypertensive agents are available and should be tailored to address specific patient characteristics. The pharmacist's knowledge of evidence-based primary literature, pharmacokinetics, and when a particular class of antihypertensive agent provides greater benefit plays an important role in the recommendation and selection of appropriate cost-effective antihypertensive agents.The following treatment guidelines are adapted from the Seventh Report of the Joint National Committee on the Diagnosis, Evaluation, and Treatment of Hypertension for Classifying and Defining Blood Pressure levels for Adults (18 years and older). Congestive heart failure occurs when the heart is not strong enough to pump blood efficiently around the body, causing fluid to collect in the lungs and body tissue, which leads to congestion. Heart failure becomes increasingly common with age. Congestive heart failure does not mean that the heart stops. It is a long-term condition that can be kept under control for many years with medication and lifestyle changes. Blood Blood supplies oxygen to the body and removes carbon dioxide. It is pumped around the body by the heart.

Lungs Lungs are a pair of organs in the chest that control breathing. They remove carbon dioxide from the blood and replace it with oxygen. Tissue Body tissue is made up of groups of cells that perform a specific job, such as protecting the body against infection, producing movement or storing fat.

Congestion Congestion is an excess of fluid in part of the body, often causing a blockage.