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By: G. Kelvin, M.B. B.CH. B.A.O., M.B.B.Ch., Ph.D.
Assistant Professor, Florida Atlantic University Charles E. Schmidt College of Medicine
Several assay methods have been developed that vary in their precision arteria music buy amlodipine no prescription, yield different ranges for non-diabetic values arterial dissection order generic amlodipine, and lack common standardization procedures pulse pressure klabunde generic amlodipine 2.5mg with visa. Clinicians must therefore become familiar with the assays used in their own laboratory and use that specific assay when evaluating changes in glycemic control in individual patients blood pressure for elderly order 5 mg amlodipine amex. Although the ambient glucose level is the dominant factor influencing glycohemoglobin, other factors may confound interpretation of the test. Some assays yield spuriously low values in patients with hemoglobinopathies such as sickle cell disease or trait and hemoglobin C or D or spuriously high values when hemoglobin F is increased. Thus for unexpectedly high or low values, factors that alter the specific test used should be excluded. In most cases, however, discrepancies between self-monitoring of blood glucose and glycohemoglobin results reflect problems with the former rather than the latter. Although glycohemoglobin provides the most accurate estimate of overall glycemic control, it is less valuable in determining what specific changes in therapy are indicated. Blood glucose measurements are essential to adjust the components of the regimen appropriately. A management plan should take into consideration the life patterns, age, work and school schedules, psychosocial needs, educational level, and motivation of the individual patient. The plan should include medications, recommendations for lifestyle changes, a meal plan, monitoring instructions (including "sick day" management), and hypoglycemia prevention and treatment strategies. Active patient participation in problem solving plus ongoing, continued support from the health care team is critical for successful management. If the goals are not met, the causes need to be identified and the plan modified accordingly. The history and physical examination should focus on early signs and symptoms of retinal, vascular, neurologic, and foot complications and reinforcement of the diet and exercise prescription. A complete ophthalmologic examination, an assessment of cardiovascular risk factors, and a timed urine collection for albumin should be obtained annually. Table 242-7 presents target glycemic guidelines for non-pregnant diabetic patients and targets for other factors that increase the potential for diabetic complications. Pancreas/Islet Transplantation Intensive insulin treatment rarely, if ever restores glucose homeostasis to levels achieved in non-diabetic individuals. The search for more effective methods of treatment thus remains a long-term goal of diabetes research. Efforts focused on transplantation of insulin-producing tissue have resulted in substantial improvement in the outcome of such pancreas transplant surgery in recent years. In major centers, most patients emerge from the perioperative period with a functioning graft, and once insulin independence is established, the majority stabilize for many years. Unfortunately, because of the need for long-term immunosuppression, pancreas transplantation is at present an option for only a select group of patients, mainly for type 1 diabetics who will require immunosuppression for renal allografts. In such individuals, successful pancreas transplantation is more effective in preventing nephropathy in the grafted kidney. Application of islet transplantation to humans with diabetes has proved exceedingly difficult, in part because of difficulty in obtaining sufficient numbers of viable human islets. Thus far, only a small percentage of type 1 diabetic patients have become insulin independent. Interestingly, islet transplantation has been much more successful in patients with chronic pancreatitis who have undergone total pancreatectomy followed by intraportal injection of their own islets. The implication is that the use of immunosuppressive drugs, chronic low-grade rejection of the foreign islet grafts, and activation of an autoimmune response account for the high incidence of failure. If correct, the future of islet transplantation therapy may depend more on manipulation of the islet or the immune system than on technical surgical advances. Prevention of Diabetes As the pathogenesis of both types of diabetes becomes better understood, the potential for prevention of these diseases is more realistic. The Diabetes Prevention Program is designed to determine whether type 2 can be prevented or delayed with early introduction of lifestyle changes or oral glucose-lowering agents (metformin) in persons with impaired glucose tolerance. Metabolic decompensation in diabetes is manifested as severe hyperglycemia with or without ketoacidosis. Although diabetic ketoacidosis is generally seen in type 1 patients and non-ketotic hyperosmolar syndrome is generally seen in type 2 patients, exceptions occur. In both conditions mortality increases with age and is usually due to an associated catastrophic illness.
Platelets contain three types of secretory granules: lysosomes blood pressure numbers what do they mean order amlodipine 5 mg visa, alpha-granules hypertension meds purchase cheapest amlodipine, and dense bodies (electron-dense organelles) fetal arrhythmia 36 weeks order 2.5mg amlodipine free shipping. In addition to release of potent vasoconstrictors from intracellular 997 Figure 184-1 Electron micrograph of an unstimulated platelet pulse pressure 41 order 5 mg amlodipine mastercard. Activated platelets expose specific receptors that bind Factor Xa and Va and in this way increase their local concentration, thus accelerating prothrombin activation. Platelets contain a membrane phospholipase C that, upon stimulation by activating agents, hydrolyzes endogenous phosphatidylinositol to form a diglyceride. The diglyceride, in turn, is converted to arachidonic acid by a diglyceride lipase. Arachidonic acid is a substrate for prostaglandin synthetase (cyclooxygenase), a reaction inhibited by aspirin and non-steroidal anti-inflammatory drugs, and is subsequently converted to prostaglandins. Von Willebrand disease prolongs the bleeding time not as a result of a platelet defect but rather because of the lack of a plasma factor important for normal platelet function. Although imperfect, the bleeding time is the only test of platelet function that correlates with susceptibility to bleeding. Even though patients with a prolonged bleeding time may be at risk for increased bleeding with surgery, not all have abnormal bleeding. The response of platelets to a variety of aggregating agents can be quantitated in platelet-rich plasma or whole blood. The aggregometer measures temporal, semiquantitative, and qualitative parameters of in vitro aggregation. This technique is of greatest value in diagnosing congenital qualitative platelet disorders. With normally functioning platelets, the following is expected: when the platelet count is 100,000 per microliter or greater, patients have no abnormal bleeding even with major surgery; with a platelet count of 50,000 to 100,000 per microliter, patients may bleed longer than normal with severe trauma; with a platelet count of 20,000 to 50,000 per microliter, bleeding occurs with minor trauma, but spontaneous bleeding is unusual; with a platelet count less than 20,000 per microliter, patients may have spontaneous bleeding; and when the platelet count is less than 10,000 per microliter, patients are at high risk for severe bleeding. Decreased Production of Platelets Hypoplasia of hematopoietic stem cells may cause thrombocytopenia (Table 184-2). Examination of the bone marrow reveals decreased numbers of megakaryocytes and either an overall decrease in cellularity or infiltration by abnormal cells. Decreased production of platelets may also be due to abnormal maturation of megakaryocytes. Deficiency of either vitamin B12 or folate can cause thrombocytopenia owing to ineffective thrombocytopoiesis (see Chapter 163). Similarly, abnormal platelet production is common in hematopoietic dysplasias (see Chapter 175). In hematopoietic dysplasia, megakaryocytes may be abnormal in appearance, such as micromegakaryocytes occasionally with a single-lobed nucleus. Table 184-2) Three types of immunologic reactions cause premature destruction of platelets: (1) development of autoantibodies against platelet-membrane antigens, (2) binding of immune complexes to platelet Fc receptors, and (3) lysis of platelets because of fixation of complement on their surface. In adults, the onset is usually more gradual, without a preceding illness and with a chronic course. The incidence of death, reported in older series to be about 5%, is likely to be significantly lower now. Adverse risk factors are severe thrombocytopenia (platelet count, <15,000), advanced age, and concomitant bleeding diatheses. Similarly, the leukocyte count and differential are normal, although these values may reflect a preceding viral illness in children. The value of assays for detecting antiplatelet antibodies on the platelet surface is unclear; most of the tests do not distinguish between autoantibodies and immune complexes that bind to the platelet Fc receptor. Furthermore, the assays do not differentiate between specific antiplatelet antibodies and non-specifically adsorbed IgG. The level of platelet-associated IgG does not correlate with the severity of thrombocytopenia. If the general clinical evaluation and blood tests do not identify a systemic cause of thrombocytopenia, the bone marrow should be examined. In adults, indications for treatment depend on the severity of bleeding and the degree of thrombocytopenia. Coagulation Factors Xa, Va, and prothrombin form a Ca2+ -dependent trimolecular complex on platelets. Asymptomatic patients with platelet counts greater than 40,000 per microliter can be observed with periodic evaluation to determine the natural fluctuations of their disease. Patients with platelet counts less than 20,000 per microliter are usually symptomatic and require treatment.
Breast cancer may recur in any site; clinically detectable metastatic disease indicates a substantial amount of body tumor burden heart attack recovery generic amlodipine 5mg amex. Responses are defined as complete (complete disappearance of all metastatic lesions irrespective of location or means of measurement) arrhythmia natural cure discount amlodipine 5mg online, partial (50% reduction in tumor mass based on comparing products of perpendicular diameters of measurable lesions before and after treatment) arterial nicking quality 10mg amlodipine, stable (less than 50% reduction or a 25% increase in measurable lesions for 3 to 4 months) hyperextension knee buy online amlodipine, and progressing (continued growth during therapy). Tumor reduction must last for at least 1 month to be considered a complete or partial response. Patients whose tumors are positive for estrogen or progesterone receptors are good candidates for endocrine therapy. Women who are older, who have a long disease-free interval (time from diagnosis to recurrence), or who have bone or soft tissue lesions are most likely to respond. Response to endocrine therapy is seen in 30 to 70% of women who are hormone receptor positive and in up to 10 to 20% who are receptor negative. The antiestrogen tamoxifen is appropriate therapy for both premenopausal and postmenopausal women. Oophorectomy can be done surgically, with external beam irradiation, or medically with luteinizing hormone-releasing hormone agonists such as goserelin or leuprolide. In postmenopausal women, newer aromatase inhibitors (letrozole and anastrozole) and progestins (megestrol and medroxyprogesterone acetate) and, in selected patients, androgens and estrogens can be used. Responses to initial hormonal therapy last an average of 12 months, and patients responding to one agent have a fair chance of responding to a second hormonal agent after failure of initial therapy. Chemotherapy is best reserved for women who have tumor progression on hormonal therapy or those who have cancers lacking hormone receptors. In general, 40 to 80% of patients have a complete or partial response to their initial chemotherapy regimen. Responses to second-line chemotherapy are frequently seen but usually last only several months. Chemotherapy using combinations of drugs has previously been shown to be superior to single-agent therapy, but new agents, especially the taxanes (paclitaxel [Taxol] and docetaxel [Taxotere]) have displayed response rates similar to those of combination regimens. High-dose chemotherapy with autologous bone marrow or stem cell transplantation is currently being studied in the research setting in patients with metastatic disease (see below). Dexamethasone in doses of 4 to 10 mg every 6 hours should be used in conjunction with irradiation. Spinal cord compression is most commonly seen in patients with bone metastases, and almost all patients have back pain. Magnetic resonance imaging is currently the imaging method of choice to establish the diagnosis. For patients with rapid loss of function or progression of symptoms while receiving radiation therapy, surgical decompression is necessary to lower the probability of paraplegia. Patients with leptomeningeal metastases frequently have headache and cranial nerve and peripheral nerve lesions. The diagnosis is best made with lumbar puncture and examination of cerebrospinal fluid for malignant cells. Gadolinium-enhanced magnetic resonance scans of the brain or spinal cord may show enhancement of the meninges in about 70% of patients with leptomeningeal spread. Intrathecal methotrexate can lead to brief remission, but the general outlook for such patients is exceedingly poor. The use of bisphosphonates can significantly 1379 reduce the complications of skeletal metastases in both premenopausal and postmenopausal patients. Pamidronate (Aredia) given intravenously every 3 or 4 weeks has been shown to be effective in this setting and can be given at the same time as endocrine therapy or chemotherapy. In addition, radioisotopes that localize in bone such as strontium-89 may be effective. External beam irradiation will result in significant palliation in patients with moderate to severe bone pain at specific metastatic sites. Hypercalcemia is a common complication of metastatic breast cancer and more likely to occur in patients with skeletal metastases. Calcitonin can also be effective in patients who need rapid reduction of their serum calcium. Also, patients with locoregional recurrence are best managed by surgical resection of chest wall lesions when feasible, followed by external beam irradiation of the involved area. Chest tube drainage and sclerotherapy are successful in about 70% of patients with persistent or recurrent malignant effusions that have not been controlled by systemic therapy. Patients with ipsilateral breast tumor recurrence after lumpectomy alone or with breast irradiation for early-stage breast cancer are usually best managed by mastectomy, although further lumpectomy may be appropriate in patients with smaller recurrences.
Adenomas are present in 75% of patients by age 30; malignant transformation is rare arterial nosebleed order amlodipine 5mg with mastercard. Rigorous therapy designed to maintain the blood glucose level above 75 mg/dL at all times may prevent or reverse adenoma formation hypertension prognosis discount amlodipine 5 mg with visa. Liver biopsy does not reveal steatosis but frequently demonstrates fibrosis arrhythmia medications buy amlodipine now, which rarely progresses to cirrhosis or portal hypertension blood pressure medication lisinopril buy 2.5 mg amlodipine with amex. Features of hepatic amyloidosis include hepatomegaly and increased serum alkaline phosphatase, each of which are found in 60% of patients with biopsy-proven liver involvement; clinical liver disease, however, is rarely encountered. A small number of patients with hepatic amyloidosis develop severe intrahepatic cholestasis with jaundice. This syndrome portends a poor prognosis, although death results from extrahepatic (primarily renal) disease. Liver biopsy is not required to confirm hepatic involvement in patients with known systemic amyloidosis. If the diagnosis is uncertain, liver biopsy may be useful and can be performed safely if clotting parameters are normal and any history of a bleeding disorder is excluded. Hepatic granulomas can be identified in approximately two thirds of patients with sarcoidosis, placing the liver behind only the lung and lymph nodes as the primary sites of 803 involvement (see Chapter 81). Liver involvement is usually recognized because of hepatomegaly or an elevated alkaline phosphatase level. A small minority of patients can develop a cholestatic syndrome characterized by pruritus and jaundice or can have hepatic failure and portal hypertension in the event the disease progresses to cirrhosis. Liver biopsy can be useful in establishing a diagnosis of sarcoidosis, because granulomas are so numerous as to be sampled even with a random needle core. Occasionally, portal granulomas can destroy intrahepatic bile ducts, mimicking primary biliary cirrhosis. The latter can be distinguished by the presence of antimitochondrial antibodies in serum. When sarcoidosis progresses to hepatic fibrosis, connective tissue deposition is more extensive than around the granulomas alone. Corticosteroids alleviate the symptoms of sarcoidosis but have not been proven to alter liver histology or the tendency toward hepatic fibrosis. Therapy should therefore be reserved for symptomatic patients in whom tuberculosis and other infectious diseases have been excluded. The most common abnormality is steatohepatitis; cholestasis and hepatic fibrosis have also been observed. Because steatohepatitis and cholestasis can both progress to hepatic fibrosis, their development is considered by many an indication to discontinue therapy. Fifty per cent of patients develop sludge after 6 weeks, and virtually 100% of patients are affected after 3 months. Stasis may be ameliorated by cholecystokinin, by pulsed infusions of amino acids, or by small enteral feedings. For the most part, pregnancy does not pose an increased risk of acute liver disease, nor does it alter the natural history of hepatic illnesses contracted during gestation. Notable exceptions are viral hepatitides caused by the herpes simplex, herpes zoster, and hepatitis E viruses. Herpes simplex hepatitis has a higher incidence in pregnant women than in the population at large. All three agents can provoke severe illness in pregnant women, with mortality rates as high as 20% in the case of hepatitis E. Transient elevations in hepatic aminotransferase levels may accompany hyperemesis gravidarum. Biochemical cholestasis, defined as an increase in circulating bile acids, can be detected in as many as 10% of normal gestations. Symptomatic cholestasis occurs in only 1 to 5% of pregnant women and is generally confined to the second and third trimesters. Most patients complain only of pruritus (pruritus gravidarum); a minority exhibit a more severe syndrome with disabling pruritus, jaundice, and steatorrhea. The latter may have an inherited predisposition toward cholestasis, with women of South American Indian and Swedish descent being at high risk.
During a normal pregnancy heart attack untreated generic amlodipine 2.5mg online, the implanted placenta replaces the endothelium and internal elastic lamina of the maternal uterine spiral arteries with fetal trophoblastic tissue arrhythmia and alcohol purchase amlodipine with mastercard. These altered arteries dilate to five times their pre-pregnant state and are no longer responsive to circulating vasoconstrictors blood pressure numbers mean generic amlodipine 10mg with amex. This trophoblastic invasion does not occur with preeclampsia heart attack romance order amlodipine in united states online, and the arteries do not dilate. This is thought to result in the secondary widespread endothelial dysfunction, with activation of platelets and the coagulation cascade. In addition, women with preeclampsia fail to develop the normal increased blood volume and reduced systemic vascular resistance of pregnancy. Women develop an imbalance of vasoactive prostaglandins, with an increase in the ratio of thromboxane A2 (vasoconstriction) to prostacyclin (vasodilation), leading to vasospasm. The rationale for low-dose acetylsalicylic acid is its inhibition of cyclooxygenase and selective reduction in thromboxane synthesis. Clinical criteria subdivide preeclampsia into severe and non-severe, based on the degree of blood pressure elevation and the presence of seizures (eclampsia) or other end-organ damage (renal dysfunction, pulmonary edema, thrombocytopenia, hepatic abnormalities, or central nervous system effects). Although delivery is the treatment of preeclampsia, a small percentage of manifestations are seen immediately post partum. Laboratory tests do not reliably predict development of preeclampsia, nor do they differentiate among the different hypertensive disorders. Transient gestational hypertension is treated with bed rest, close monitoring, and medications, when necessary. Many authorities recommend drug therapy when the blood pressure persistently exceeds 140/90 mm Hg. However, for women with pre-existing hypertension, it has not been shown to affect development of preeclampsia. The experience with antihypertensive medication in pregnancy appears in Table 253-1. The definitive treatment of preeclampsia and transient gestational hypertension is delivery. Before 34 weeks of gestation, that benefit is weighed against the fetal advantages of prolonging intrauterine development. Supplemental calcium (2 g/day) reduces the incidence of preeclampsia, without any recognized maternal or fetal adverse effects. Epidemiologic studies had suggested an inverse relationship between calcium intake and preeclampsia, which led to prospective trials of its use. Current studies suggest that low-dose acetylsalicylic acid (60 to 81 mg/day) may be preventive when at higher risk of preeclampsia, but its use is not justified for all pregnant women. Most of the 1 to 5% of women of reproductive age with hypertension have essential hypertension. Although there are fewer than 250 reported cases, pheochromocytoma during pregnancy produces significant morbidity and mortality. It reduces vascular resistance while preserving maternal cardiac output and uteroplacental perfusion. Probably safe for third trimester use, but neonatal bradycardia, respiratory distress, and hypoglycemia have been reported. Primarily used parenterally for acute management of hypertension or with methyldopa or a beta-blocker for treatment of pregnancy-associated hypertension. If used before pregnancy, it can be continued, but its use should not be initiated during pregnancy. Although it has been used safely, it is not a first-line antihypertensive agent during pregnancy. Use is contraindicated during pregnancy, because miscarriage, fetal death, malformations, and neonatal renal failure can result. Antihypertensive agents not listed may be safe during pregnancy; however, until that is known, those drugs should be switched to one of the safely used listed agents. Among women with pre-existing hypertension, the usual blood pressure decrease during the first trimester may allow gradual discontinuation of antihypertensive medications. Pharmacologic treatment can be reinstituted during the third trimester, at a threshold of 140/90 to 100 mm Hg.
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