By T. Cobryn. University of Vermont.

Electroporation of mammalian skin: a mechan- ism to enhance transdermal drug delivery cheap 60caps lasuna free shipping. Transdermal delivery of macromolecules using skin electro- poration purchase 60caps lasuna with mastercard. The role of dermoelectroporation in the aesthetic medicine discount lasuna 60 caps without a prescription. Job’s Book of Brasilian Congress of Aesthetic Medicine 60 caps lasuna amex, Sao Paulo order lasuna 60 caps without a prescription, June 9–12, 2004. Job’s Book of International Congress of Aesthetic Medicine and Cosmetic Surgery, Lisboa, September 12–16, 2004. Job’s Book of Italian Congress of ‘‘Derma- tologists of Great Greece,’’ Vibo Valentia, Italy, October 6–9, 2004. This treatment slowly breaks down fatty deposits with subcutaneous injections of an adipocyte-dissolving for- mula. While it is in its infancy in North America, it has been practiced in Europe and South America for over 10 years. Despite the fact that lipodissolve injectors outside the United States tout its benefits based on their favorable experiences, there exists a consider- able amount of healthy skepticism in the American cosmetic medical community concern- ing this procedure. This is mainly due to the paucity of scientific literature demonstrating the histopathology, mechanism of action, and detailed measurable clinical results. This is simi- 1 lar to the situation that pioneering practitioners using Botox for cosmetic purposes found themselves in during the early 1990s. Lipodissolve injections are suitable for nonobese patients with localized fat accumu- lation, which cannot be reduced with appropriate diet or sincere efforts at exercise. Lipo- dissolve injections do not result in weight loss; lipodissolve injections modify body contours. The ideal patient has a body mass index (BMI) of less than 25. Lipodissolve is not a substitute for liposuction; it is an alternative to liposuction for smaller areas of fat accumulation in a patient who prefers a less invasive procedure. It is the author’s opi- nion that liposuction is a more cost-effective and efficient procedure than lipodissolve for larger fatty deposits. The active ingredients of the lipodissolve formula are a mixture of phosphatidylcho- line (PC), a natural substance derived from soybean lecithin, and deoxycholate (DC), a bile salt. Aventis Pharma (part of the Sanofi-Aventis Group, Paris, France), which is the third largest pharmaceutical company in the world, markets a PC/DC preparation 1 1 under the trade names Lipostabil and Essentiale in Europe (primarily Germany and 1 Italy), Russia, and South America. The Lipostabil brand contains 5% PC (50 mg/mL) 1 and 4. Lipostabil is not sold in the United States or Canada. PC is commonly known as lecithin, and the commercial preparations of purified PC are derived from soybean lecithin, rather than egg yolk. PC is composed of choline, phosphate, and two fatty acids (Fig. This is the primary consti- tuent of the bilipid cell membrane. PC is involved in the regulation of lipid metabolism (1,2), and is marketed by Aventis as an injectable intravenous infusion to lower cholesterol and triglycerides, under the name LIPODISSOLVE FOR BODY SCULPTING & 303 1 1 Lipostabil. Lipostabil is also used in the treatment of hepatitis (3–5) and cardiovascu- lar atheromatous diseases in Europe and Russia (2,6). The known ability of oral and intravenous PC to reduce systemic triglycerides and cho- lesterol eventually led to its use as a subcutaneous injection in an attempt to decrease fatty 1 deposits (Fig. The first published trial of using Lipostabil as a subcutaneous injection was in 1988 by the Italian physician Sergio Maggiori in the treatment of xanthelasma (7). Brazilian dermatologist Marcio Serra described the substantial reduction of buffalo humps in two HIV patients injected on five occasions every two weeks with 200 mg of PC. Local side effects of erythema and edema were reported to resolve over three to four days (8). Patricia Rittes reported the injection of PC into the small fat pads in the lower eyelid area at the 54th Brazilian Dermatology Congress (9).

Postmenopausal women present with breast tenderness buy cheap lasuna 60caps on-line, vaginal bleeding cheap lasuna 60 caps fast delivery, or both order 60 caps lasuna free shipping. Women with cervical and uterine cancers most commonly present with vaginal bleeding or a grossly visible cervical lesion 60caps lasuna visa. A 72-year-old woman presents with vaginal bleeding of 2 weeks’ duration buy 60caps lasuna free shipping. Her medical history is signif- icant for right breast cancer, which was surgically cured and for which she takes tamoxifen. Evaluation of this patient shows endometrial cancer. Under which of the following circumstances is chemotherapy indicated for this patient? After initial surgical intervention, the patient experiences rapidly pro- gressive, symptomatic recurrence of the cancer B. The cancer involves either ovary on initial evaluation C. The cancer involves distant sites such as lung or bone E. All of the above Key Concept/Objective: To understand the evaluation and treatment of uterine cancer For rapidly progressive, symptomatic recurrence of uterine cancer, platinum-based chemotherapy is a reasonable treatment. There is no proven survival advantage associat- ed with the use of adjuvant hormonal therapy (e. If the endometrial biopsy establishes the presence of uterine cancer, surgery for definitive resection and staging is the next most common step in management. For patients who are not optimal surgical candidates, primary radiotherapy is an option that can produce long- term survival in selected patients. Postoperative pelvic radiotherapy is considered when certain features confer an increased risk of local pelvic failure. These features include (1) deeply invasive, high-grade, early stage lesions (e. The use of tamoxifen, a drug traditionally thought of as an estrogen antagonist, is also associated with an increased uterine cancer risk. This is in part caused by the tissue-specific action of tamoxifen, which has antagonistic effects on proliferation of breast epithelium but agonistic effects on bone mineral density, lipid metabolism, and endometrial proliferation. However, the benefits of tamoxifen in the adjuvant breast cancer setting far outweigh the small risk of uterine can- cer development. A 50-year-old white woman with a history of fibrocystic breast disease and arthritis presents with abdom- inal pain of new onset. The pain is mild and suprapubic and does not radiate. A urine dipstick evaluation performed in the clinic reveals that she has a urinary tract infection. The patient, however, is concerned that she may have ovarian cancer, because her mother died of ovarian cancer at age 59. For this patient, which of the following statements is consistent with a diagnosis of ovarian cancer? Approximately 30% of women present with advanced disease B. Patients with advanced disease commonly complain of a progressive increase in abdominal girth and bloating C. The primary lymphatic drainage site of ovarian cancer is the inguinal lymph nodes D. The most common paraneoplastic syndrome associated with ovarian cancer is hypercalcemia Key Concept/Objective: To understand the common clinical features of ovarian cancer The ovary contains three distinct cell types, known as germ cells, stromal cells, and epithe- lial cells. The type of ovarian tumor that most commonly affects adult women, however, is derived from the epithelial cells that cover the ovarian surface. Epithelial ovarian can- cer occurs at a mean age of 60 years in the United States and is the most lethal of gyneco- logic tract tumors. In approximately 70% of women, the tumor has spread beyond the pelvis by the time of diagnosis and cannot be completely resected at the time of explorato- ry laparotomy. Early-onset ovarian cancer that is restricted to the pelvis usually produces no signs or symptoms. Unfortunately, approximately 70% of women present with advanced disease that has extended beyond the pelvis to involve other areas, such as the upper abdomen (stage III) and the pleural space (stage IV).

Syngeneic transplantations come from identical twins buy lasuna 60caps fast delivery; identical twins are the best possible donors of stem cells C purchase lasuna 60caps visa. In allogeneic transplantations buy 60caps lasuna visa, if two persons do not share the same HLA antigens buy lasuna 60 caps otc, B cells taken from one person will react vigorously to the mismatched HLA molecules on the surface of the cells from the other person D order 60 caps lasuna amex. When compared with allogeneic transplantation, autologous trans- plantation has the advantage of avoiding graft versus host disease (GVHD) and associated complications Key Concept/Objective: To understand the different types of hematopoietic stem cell transplantations Hematopoietic stem cell transplantation can be categorized according to the relation between the donor and the recipient and according to the anatomic source of the stem cell. Hematopoietic stem cells for transplantation may derive from bone marrow, peripheral blood, or umbilical cord blood and may be harvested from a syngeneic, allogeneic, or 5 HEMATOLOGY 27 autologous donor. Identical twins are the best possible donors of stem cells. When syn- geneic donors are used, neither graft rejection nor GVHD will develop in the recipient. Only about one in 100 patients undergoing transplantation will have an identical twin. Allogeneic transplantation, which involves a related or unrelated donor, is more compli- cated than syngeneic or autologous transplantation because of immunologic differences between donor and host. With allogeneic hematopoietic cell transplantation, in which the immune system of the patient is provided by the graft, the clinical concerns are not only with the prevention of graft rejection by host cells surviving the pretransplant preparative regimen but also with the prevention of donor cells from causing immune-mediated injury to the patient (i. Immunologic reactivity between donor and host is large- ly mediated by immunocompetent cells that react with HLAs, which are encoded by genes of the major histocompatibility complex. HLA molecules display both exogenous peptides (for example, from an infecting virus) and endogenous peptides, presenting them to T cells, an important step in the initiation of an immune response. If two persons do not share the same HLA antigens, T cells taken from one person will react vigorously to the mismatched HLA molecules on the surface of the cells from the other. These are reactions against so-called major HLA determinants. When compared with allogeneic transplanta- tion, autologous transplantation has the advantage of avoiding GVHD and associated complications; disadvantages are that the autologous cells lack the antitumor effect of an infusion of allogeneic leukocytes (the so-called graft versus tumor effect) and may contain viable tumor cells. A 20-year-old African-American patient with sickle cell disease was recently evaluated for hematopoiet- ic stem cell transplantation by his hematologist. He comes in to see you and is excited about the possi- bilities of cure but is concerned about possible complications of transplantations. Which of the following statements regarding transplant complications is true? Late toxicity (occurring weeks to months after transplantation) is usu- ally the result of the preparative regimen and can include nausea, vomiting, skin rash, mucositis, and alopecia B. Graft failure that occurs after autologous transplantation can result from marrow damage before harvesting, during ex vivo treatment, during storage, after exposure to myelotoxic agents, or as a result of infections with cytomegalovirus (CMV) or human herpesvirus type 6 (HHV-6) C. Treatment of graft failure requires the use of higher doses of myelosup- pressive agents D. Veno-occlusive disease of the liver usually occurs after the first year and only rarely occurs in the subacute setting Key Concept/Objective: To understand the complications of hematopoietic stem cell trans- plantation Pretransplant preparative regimens are associated with a substantial array of toxicities, which vary considerably depending on the specific regimen used. For example, after the standard cyclophosphamide–total body irradiation regimen, nausea, vomiting, and mild skin erythema develop immediately in almost all patients. Oral mucositis inevitably devel- ops about 5 to 7 days after transplantation and usually requires narcotic analgesia. By 10 days after transplantation, complete alopecia and profound granulocytopenia have devel- oped in most patients. Veno-occlusive disease of the liver (also referred to as sinusoidal obstruction syndrome) is a serious complication of high-dose chemoradiotherapy; it devel- ops in approximately 10% to 20% of patients. Veno-occlusive disease of the liver, charac- terized by the development of ascites, tender hepatomegaly, jaundice, and fluid retention, may occur at any time during the first month after transplantation; the peak incidence occurs at around day 16. Approximately 30% of patients who develop veno-occlusive dis- ease of the liver die as a result of the disease, with progressive hepatic failure leading to a terminal hepatorenal syndrome. Although complete and sustained engraftment is the gen- 28 BOARD REVIEW eral rule after transplantation, in some cases marrow function does not return; in other cases, after temporary engraftment, marrow function is lost. Graft failure after autologous transplantation can result from marrow damage before harvesting, during ex vivo treat- ment, during storage, or after exposure to myelotoxic agents after transplantation. Infec- tions with CMV or HHV-6 may also result in poor marrow function. Graft failure after allo- geneic transplantation may be the result of immunologically mediated graft rejection and is more common after conditioning regimens that are less immunosuppressive, in recipi- ents of T cell–depleted marrow, and in recipients of HLA-mismatched marrow.

The patient’s functional decline and tearfulness discount lasuna 60 caps free shipping, as well as occasional severe confusion with combativeness buy lasuna 60 caps with amex, are causing severe stress for both the patient and the household cheap lasuna 60 caps without prescription. The patient’s daughter asks if there are further medication options for the patient 60caps lasuna with visa. Which of the following statements regarding primary and secondary therapies for AD is true? The cholinesterase inhibitors discount 60 caps lasuna mastercard, such as donepezil, have shown promise as a cure for AD B. The cholinesterase inhibitors are the only class of agents available for the primary treatment of AD C. Treatment of depression associated with AD should be pursued as aggressively as in patients without dementia D. For treatment of anxiety and agitation in AD, short-acting benzodi- azepines and typical antipsychotics are generally recommended Key Concept/Objective: To know the appropriate primary and secondary therapies for AD The cholinesterase inhibitors donepezil, galantamine, and rivastigmine have been approved by the Food and Drug Administration for the treatment of AD. Clinical trials with each of these agents have shown that long-term use results in modest stabilization of cognitive and functional status for approximately 6 to 12 months, compared with no treat- ment. Vitamin E is often recommended for patients with AD on the basis of a study of 2 years’ duration. The glutamate modulator memantine has also been approved by the FDA for the treatment of AD. This agent is a noncompetitive receptor antagonist of N-methyl- D-aspartate. Several clinical trials have reported positive results with memantine in the treatment of moderate to severe dementia. Treatment of depression or anxiety in patients with AD should be pursued as aggressively as in patients without AD, with adherence to the best practices of geriatric pharmacology. Depression frequently coexists with AD and contributes to morbidity and loss of function. Treatment of anxiety presents somewhat more of a challenge in AD patients, because the agents commonly used in younger patients, the benzodiazepines, have distinctly unwanted side effects in AD patients. Drugs such as lorazepam and alprazolam can increase confusion in AD patients. The longer-act- ing agent clonazepam may be a better choice. Buspirone is another alternative for the treatment of anxiety in AD patients. Treatment of agitation generally requires antipsy- chotics. Quetiapine has the significant advantage of being much less likely to induce extrapyramidal signs than both newer and older agents. A 69-year-old female patient whom you have been treating for many years for hypertension and dys- lipidemia comes for a routine appointment. Both her hypertension and dyslipidemia have been difficult 11 NEUROLOGY 29 to control. She has been hospitalized on several occasions over the past few years for likely transient ischemic attacks (TIA). The National Institute of Neurological Disorders and Stroke– Association Internationale pour la Recherche et l’Enseignement en Neurosciences (NINDS-AIREN) criteria for the diagnosis of VaD are highly sensitive B. Though lacking sensitivity, the NINDS-AIREN criteria for the diagnosis of VaD are highly specific C. As described in NINDS-AIREN criteria, the onset of all cases of VaD occurs within a 3-month period following a stroke D. VaD and AD are roughly equal in prevalence Key Concept/Objective: To know the diagnostic criteria and prevalence of VaD The essence of the NINDS-AIREN criteria is that (1) the onset or worsening of dementia occurred within 3 months after a clinical stroke; (2) imaging studies show evidence of bilateral infarcts in cortical regions, basal ganglia, thalamus, or white matter; and (3) neu- rologic examination shows focal neurologic deficits. Clinical-pathologic correlation studies have shown that this definition is quite specific, meaning that patients who meet these criteria are highly likely to have VaD pathologically. However, the NINDS-AIREN criteria are very insensitive, failing to diagnose the majority of patients who prove to have VaD at autopsy. VaD may also begin insidious- ly, because there is a substantial percentage of VaD cases that appear to result from the accumulation of a series of so-called silent or covert infarcts. Patients in this group do not meet the diagnostic criterion of dementia temporally linked to stroke, but they do have brain infarcts, best visible with MRI.

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