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Associate Professor, Albany Medical College

Chronic hypertension (Chapter 55) produces characteristic retinal vascular findings that can be used to identify and assess progression of the disease medicine identification discount lamictal 25mg amex. Arterial narrowing treatment 3rd metatarsal stress fracture quality 200mg lamictal, nicking at arteriovenous crossings treatment resistant depression order lamictal with visa, nerve fiber layer infarcts 5 medications for hypertension purchase 25mg lamictal with amex, and intraretinal hemorrhages characterize hypertension. Branch retinal vein occlusion may cause macular edema and decreased visual acuity or may be asymptomatic. Photocoagulation may help to resolve macular edema but rarely improves functional outcome. Neovascularization is a rare complication, and most eyes maintain a favorable prognosis. Central retinal vein occlusion (Color Plate 18 D) is a more severe disease entity. Neovascularization of the iris or retina, occurring in up to 52% of cases, usually occurs 3 months after the initial insult. In contrast to venous occlusive disease, central retinal artery occlusion (Color Plate 18 C) is not generally associated with systemic hypertension. Emboli result most commonly from carotid stenosis (Chapter 470), but endocarditis and cardiac thromboemboli are other potential sources. Fundus examination reveals a characteristic "cherry-red spot" that reflects diffuse opacification of the infarcting macula contrasted to the hyperpigmented fovea. Branch retinal artery occlusion may go unnoticed by the patient despite a permanent visual scotoma (visual field defect). Systemic corticosteroids (prednisone, 1-2 mg/kg/day) should be initiated as soon as the diagnosis is suspected, and temporal artery biopsy should be performed within 7 days after beginning treatment. If the disease is not treated, approximately 65% of patients lose vision in the contralateral eye. Retinal involvement in polyarteritis nodosa (Chapter 293) is usually limited to the small vessels, although central retinal artery occlusion can occur. Topical corticosteroids are used to treat anterior disease, whereas systemic corticosteroids and cytotoxic agents may be required for posterior disease. Ocular Effects of Systemic Medications (Table 512-6) Patients taking systemic medications may require periodic surveillance to identify ocular toxicity. Chloroquine toxicity is thought to occur after a cumulative dose of 300 g, whereas hydroxychloroquine may cause symptoms after long-term maintenance of 750 mg/day. Any of the commonly used antituberculous medications may cause optic neuropathy, although ethambutol carries the greatest risk. Pupillary response, color vision, acuity, and visual fields are the clinical parameters used to assess optic nerve function. Cornea verticillata may be seen in patients taking amiodarone due to lysosomal accumulations within the epithelial basement membrane. Corneal whirls are usually reversible when caused by drug toxicity, and they rarely interfere with vision. Systemic corticosteroids carry the same ocular side effects as do topical corticosteroids, including glaucoma and posterior subcapsular cataract. Baloh the mechanistic understanding of vision impairment along with disturbances of pupillary and oculomotor control lies close to the heart of diagnosing neurologic disorders. To evaluate such a patient properly the examining physician must be familiar with the anatomy and physiology of the afferent visual system. The distribution of visual function across the retina takes a pattern of concentric zones increasing in sensitivity toward the center, the fovea. Axons originating from ganglion cells in the temporal retina must curve above and below the papillomacular bundle, forming dense arcuate bands. The arteries supplying the optic nerve and retina derive from branches of the ophthalmic artery. Anastomotic branches derived from the choroidal and posterior ciliary arteries, the ciliary system, supply the choroid, optic nerve head, and the outer retinal layers, including the photoreceptors. In about 10% of the population, the macula is supplied by a retinociliary artery, a branch of the ciliary system. The nasal side of the left retina and the temporal side of the right see the left side of the world, and the upper half of each retina sees the lower half of the world.

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Hyperfiltration depends medications reactions order cheap lamictal online, at least in part medications known to cause tinnitus buy generic lamictal on-line, on hyperglycemia because it is diminished by intensive treatment symptoms depression cheap 100mg lamictal amex. After several years glomerulosclerosis appears and is characterized by thickening of the glomerular capillary basement membrane and expansion of collagen matrix material within Figure 242a-10 the natural history of diabetic nephropathy and the time sequence of various medical interventions medications for osteoporosis order 50 mg lamictal free shipping. In the early years of this histologic evolution, renal function is not impaired and routine urinalysis test strips show no evidence of proteinuria. Renal biopsy specimens from these individuals generally show more pronounced expansion of mesangial volume and diffuse deposits of mesangial matrix that presumably encroach on the glomerular filtering capacity. Detection of renal disease requires sensitive assays of albumin excretion (microalbuminuria). The appearance of massive proteinuria and the nephrotic syndrome is common in this context and often heralds progression to renal insufficiency. The course is highly variable, however, particularly in type 2 diabetes, in which moderate proteinuria may persist for many years without substantive deterioration in renal function. Azotemic patients are at higher risk for acute renal failure after the injection of contrast for diagnostic studies. When such tests are necessary, special attention should be given to ensure adequate hydration before and immediately after the procedure. Erythrocyte 1282 sodium-lithium countertransport, a marker of essential hypertension that is increased in some type 1 patients with nephropathy, may be a link between a family history of hypertension and nephropathy. The risk of nephropathy is much higher in blacks, Latinos, and Native Americans with type 2 diabetes and reaches a frequency similar to that seen in type 1 diabetes (see. The appearance of hypertension increases the likelihood that microalbuminuria will progress to nephropathy. In patients with type 2 diabetes, progression of microalbuminuria to clinical proteinuria is slower and may reflect severe generalized vascular disease rather than nephropathy. Early in the course of diabetes (no microalbuminuria), primary efforts should focus on optimizing glycemic control, especially in higher-risk patients. The acceleration in generalized atherosclerosis leads to significant morbidity during dialysis or following transplantation. Survival rates for recipients of cadaver grafts remain high and are only about 10% less than those for non-diabetic graft recipients. Cardiovascular disease is the major cause of morbidity and mortality following transplantation. The preference between continuous ambulatory peritoneal dialysis and hemodialysis varies among centers. However, many diabetic patients have problems caused by the rapid shifts in blood volume that accompany hemodialysis. Mortality is substantially higher in diabetic than non-diabetic patients receiving dialysis because of the more rapid development of vascular insufficiency. Diabetic Neuropathy Symptomatic, potentially disabling neuropathy affects nearly 50% of diabetic patients. It is usually symmetrical, but may be focal and often involves the autonomic nervous system as well. The prevalence of symmetrical neuropathy is similar in type 1 and 2 diabetes, whereas focal neuropathy is more common in older type 2 patients. Hyperglycemia figures prominently; however, other factors may also be important, especially ischemia. The chronic, more insidious neuropathic disorders may be mediated by a "metabolic" process, whereas the more acute, often self-limiting neuropathies may have a vascular cause. Autonomic nerve bundles and ganglia from type 1 diabetic patients with autonomic neuropathy show monocytic infiltration, and their sera may contain complement-fixing antibodies to sympathetic ganglia, thus suggesting that autoimmune mechanisms may also contribute to this complication. This syndrome, characterized by axonal loss, is the most common manifestation of diabetic neuropathy. The process involves all somatic nerves but has a distinct predilection for distal sites. Patients complain of numbness and tingling in the extremities, especially the feet. Sometimes, distal neuropathy first expresses its presence via complications, such as foot ulceration or spreading cellulitis from a traumatic cut (see below).

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The presence of a monoclonal light chain in nephrotic urine is strongly suggestive of primary amyloidosis or light chain deposition disease top medicine purchase online lamictal. Prognosis In one series of 241 patients followed long-term after a diagnosis of benign monoclonal gammopathy medicine x ed 50mg lamictal sale. An M-protein was found in the urine in only 9 patients medications japan purchase generic lamictal on line, and bone marrow plasma cells ranged from 1 to 10% (median symptoms of anemia order discount lamictal line, 3. B, Diagnoses in 1066 cases of monoclonal gammopathy seen at the Mayo Clinic during 1996. In 11% of the patients, the M-protein level increased to more than 3 g/dL, but they did not develop symptomatic multiple myeloma, macroglobulinemia, or related disorders; their condition remained clinically "benign," although with an M-protein level that causes concern. More than half of the patients died of seemingly unrelated causes without developing multiple myeloma, macroglobulinemia, or related disorders. In seven patients, multiple myeloma was diagnosed more than 20 years after detection of the serum M-protein. The presence of more than 10% plasma cells in the bone marrow suggests multiple myeloma, but some patients with more plasma cells have remained stable for long periods. The presence of osteolytic lesions strongly suggests multiple myeloma, but metastatic carcinoma may produce lytic lesions Figure 181-4 Incidence of multiple myeloma, macroglobulinemia, amyloidosis, or lymphoproliferative disease after recognition of monoclonal protein. The presence of circulating plasma cells in the peripheral blood usually indicates active multiple myeloma. The M-protein level in the serum and urine should be serially measured, together with periodic re-evaluation of clinical and other laboratory features, to determine whether multiple myeloma or another related disorder is present. Association of Monoclonal Gammopathies with Other Diseases Monoclonal gammopathy frequently exists without other abnormalities. However, certain diseases are associated with it more often than expected by chance. M-proteins occur in the sera of some patients with chronic lymphocytic leukemia but with no recognizable effect on the clinical course. M-proteins have also been recognized in hairy cell, adult T cell, chronic myelogenous, acute promyelocytic, and acute myelomonocytic leukemias, but without a documented increased prevalence over that in the normal population. Approximately 5% of patients with sensorimotor peripheral neuropathy of unknown cause have an associated monoclonal gammopathy. Patients have been documented to have a stable serum level of M-protein and Bence Jones proteinuria for more than 15 years without developing multiple myeloma or related disorders. Exposure to radiation, benzene and other organic solvents, herbicides, and insecticides may play a role. Multiple myeloma accounts for 1% of all malignant disease and slightly more than 10% of hematologic malignancies in the United States. The median age of patients at the time of diagnosis is about 65 years; only 2% of patients are younger than 40. Biologic Aspects Multiple myeloma is a B-cell malignancy with mature plasma cell morphology. Thus, c- myc, H- ras, and p53 genes may be involved in the pathogenesis of myeloma. Cytogenetic Abnormalities Flow cytometry studies have shown aneuploidy in about 80% of patients, hyperdiploidy in 70%, and hypodiploidy in the remaining 10%. Structural changes of chromosomes 1, 11, and 14, monosomies and trisomies, and translocations have been detected, but no specific abnormality has been demonstrated. The major symptoms may result from an acute infection, renal insufficiency, hypercalcemia, or amyloidosis. Laboratory Findings A normocytic, normochromic anemia is present initially in two thirds of patients but eventually occurs in nearly every patient with multiple myeloma. IgG M-protein is found in 53%, IgA in 20%, light chain only (Bence Jones proteinemia) in 17%, IgD in 2%, and biclonal gammopathy in 1%, and 7% have no serum M-protein at diagnosis. Ninety-eight per cent of patients with multiple myeloma have an M-protein in the serum or urine at the time of diagnosis. Radiologic Findings Conventional radiographs reveal abnormalities consisting of punched-out lytic lesions.

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In humans medications available in mexico generic 100 mg lamictal fast delivery, its limiting toxicity medicine 3604 order lamictal once a day, like that of vinblastine is hematologic symptoms stomach flu buy generic lamictal on-line, and its spectrum of activity and use in combinations is under investigation symptoms before period purchase lamictal 50mg online. Etoposide is used primarily to treat metastatic testicular cancer in combination with cisplatin and bleomycin. Paclitaxel (Taxol) has been approved for use in the United States for the treatment of breast cancer and ovarian cancer and is also widely used for other epithelial tumors (head and neck, esophagus, non-small cell lung cancer) in combination therapy regimens. For example, the combination of cisplatin and paclitaxel is now first line treatment with a 10 to 20% cure rate for patients with ovarian cancer, where it improves survival compared with cisplatin and cyclophosphamide. Other toxicities include neutropenia, which is dose limiting, myalgias, and peripheral neuropathy, the latter which generally occurs only after multiple courses at conventional doses (135 to 250 mg/m2 over 24 hours). Daunorubicin (daunomycin) was the first agent in this class and is active in the treatment of acute leukemia. Daunorubicin is frequently used in combination with cytarabine in the treatment of acute myelocytic leukemia, whereas doxorubicin is incorporated into regimens for solid tumors along with cyclophosphamide, fluorouracil, etoposide, vincristine, or cisplatin. Both doxorubicin and daunorubicin must be administered intravenously by either bolus injection or prolonged infusion. For prolonged anthracycline infusions, use of a vascular access catheter is advisable. Cardiac toxicity is uncommon with cumulative bolus doses of doxorubicin of less than 550 mg/m2, above which the incidence rises progressively. In controlled studies, idarubicin in combination with cytarabine induced higher remission rates than daunorubicin and cytarabine. Liposomal preparations of doxorubicin are also being evaluated as potentially less cardiotoxic formulations. Its major uses are in combination therapy to treat carcinoma of the testis and squamous cell carcinomas of the head and neck, cervix, skin, penis, and rectum. Patients who have not received bleomycin previously should receive a test dose. Individual therapeutic doses of bleomycin are usually in the range of 5 to 10 units/m2. The incidence of pulmonary fibrosis rises at total doses above 450 units and is higher in patients with pre-existing pulmonary disease, after lung irradiation, and in the elderly. Other reactions to bleomycin include skin toxicity with blistering, desquamation, hyperkeratosis of the palms, and hyperpigmentation of creases. Mitomycin (Mutamycin, Mitocin-C, Mitomycin C) is isolated from Streptomyces caespitosus. It is usually administered intravenously but can be used for intravesical therapy of superficial bladder cancer. The major toxicity of mitomycin is delayed myelosuppression, usually appearing 4 to 6 weeks after injection. Mitomycin has a cumulative effect on bone marrow stem cells, which can lead to protracted marrow hypoplasia for 3 to 6 months after discontinuing the drug. Nausea, vomiting, and anorexia often occur at the time of administration but can usually be managed effectively with antiemetic agents. Occasionally, mitomycin can induce interstitial pneumonitis, nephrotoxicity, or hemolytic-uremic syndrome. Dactinomycin also causes significant gastrointestinal toxicity with abdominal cramps and diarrhea as well as mucositis. The drug also can cause a radiation "recall" reaction in which cutaneous erythema redevelops at a site of prior irradiation. It has some utility in adults in third-line therapy of germ cell tumors of the testis or ovary, gestational choriocarcinoma, and soft tissue sarcomas. The dose schedule used most commonly is a single infusion (200 mg/m2) every 3 weeks, although other dose schedules are being explored. The principal dose-limiting toxicities are non-hematologic, in particular diarrhea. Diarrhea may be seen within the first 24 hours of treatment, or later, occurring 4 to 8 days after treatment. Current studies are evaluating combinations of this drug with fluorouracil or raltitrexed (Tomudex), an investigational drug that targets the enzyme thymidylate synthase.

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