Search

This multicenter, randomized, double-blind, placebo-controlled clinical study assessed the efficacy and safety of ezetimibe administered with lovastatin in primary hypercholesterolemia. After dietary stabilization, a 2- to 12-week washout period, and a 4-week single-blind placebo lead-in period, 548 patients with low-density lipoprotein (LDL) cholesterol > or =145 mg/dl (3.75 mmol/L) and < or =250 mg/dl (6.47 mmol/L) and triglycerides < or =350 mg/dl (3.99 mmol/L) were randomized to one of the following, administered daily for 12 weeks: ezetimibe 10 mg; lovastatin 10, 20, or 40 mg; ezetimibe 10 mg plus lovastatin 10, 20, or 40 mg; or placebo. The primary efficacy variable was percentage decrease in direct LDL cholesterol from baseline to end point for pooled ezetimibe plus lovastatin versus pooled lovastatin alone. Ezetimibe plus lovastatin significantly improved concentrations of LDL cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides compared with lovastatin alone (p <0.01). The coadministration of ezetimibe provided an incremental 14% LDL cholesterol decrease, a 5% HDL cholesterol increase, and a 10% decrease in triglycerides compared with pooled lovastatin alone. Ezetimibe plus lovastatin provided mean LDL cholesterol decreases of 33% to 45%, median triglyceride decreases of 19% to 27%, and mean HDL cholesterol increases of 8% to 9%, depending on the statin dose. The coadministration of ezetimibe 10 mg plus the starting dose of lovastatin (10 mg) provided comparable efficacy to high-dose lovastatin (40 mg) across the lipid profile (LDL cholesterol, HDL cholesterol, and triglycerides). Ezetimibe plus lovastatin was well tolerated, with a safety profile similar to both lovastatin alone and placebo. The coadministration of ezetimibe and lovastatin may offer a new treatment option in lipid management of patients with hypercholesterolemia. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to assess the efficacy and safety of ezetimibe administered with simvastatin in patients with primary hypercholesterolemia.Background: Despite the availability of statins, many patients do not achieve lipid targets. Combination therapy with lipid-lowering agents that act via a complementary pathway may allow additional patients to achieve recommended cholesterol goals.Methods: After dietary stabilization, a 2- to 12-week washout period, and a 4-week, single-blind, placebo lead-in period, patients with baseline low-density lipoprotein cholesterol (LDL-C) > or =145 mg/dl to < or =250 mg/dl and triglycerides (TG) < or =350 mg/dl were randomized to one of the following 10 groups administered daily for 12 consecutive weeks: ezetimibe 10 mg; simvastatin 10, 20, 40, or 80 mg; ezetimibe 10 mg plus simvastatin 10, 20, 40, or 80 mg; or placebo. The primary efficacy variable was percentage reduction from baseline to end point in direct LDL-C for the pooled ezetimibe plus simvastatin groups versus pooled simvastatin groups.Results: Ezetimibe plus simvastatin significantly improved LDL-C (p < 0.01), high-density lipoprotein cholesterol (HDL-C) (p = 0.03), and TG (p < 0.01) compared with simvastatin alone. Ezetimibe plus simvastatin (pooled doses) provided an incremental 13.8% LDL-C reduction, 2.4% HDL-C increase, and 7.5% TG reduction compared with pooled simvastatin alone. Coadministration of ezetimibe and simvastatin provided LDL-C reductions of 44% to 57%, TG reductions of 20% to 28%, and HDL-C increases of 8% to 11%, depending on the simvastatin dose. Ezetimibe 10 mg plus simvastatin 10 mg and simvastatin 80 mg alone each provided a 44% LDL-C reduction. The coadministration of ezetimibe with simvastatin was well tolerated, with a safety profile similar to those of simvastatin and of placebo.Conclusions: When coadministered with simvastatin, ezetimibe provided significant incremental reductions in LDL-C and TG, as well as increases in HDL-C. Coadministration of ezetimibe with simvastatin was well tolerated and comparable to statin alone. [ABSTRACT FROM AUTHOR]

Since it was first reported, the novel coronavirus disease 2019 (COVID-19) remains an unresolved puzzle for biomedical researchers in different fields. Various treatments, drugs, and interventions were explored as treatments for COVID. Nevertheless, there are no standard and effective therapeutic measures. Meanwhile, mesenchymal stem cell (MSC) therapy offers a new approach with minimal side effects. MSCs and MSC-based products possess several biological properties that potentially alleviate COVID-19 symptoms. Generally, there are three classifications of stem cell therapy: cell-based therapy, tissue engineering, and cell-free therapy. This review discusses the MSC-based and cell-free therapies for patients with COVID-19, their potential mechanisms of action, and clinical trials related to these therapies. Cell-based therapies involve the direct use and injection of MSCs into the target tissue or organ. On the other hand, cell-free therapy uses secreted products from cells as the primary material. Cell-free therapy materials can comprise cell secretomes and extracellular vesicles. Each therapeutic approach possesses different benefits and various risks. A better understanding of MSC-based and cell-free therapies is essential for supporting the development of safe and effective COVID-19 therapy.

The interaction between the membrane spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the transmembrane angiotensin-converting enzyme 2 (ACE2) receptor of the human epithelial host cell is the first step of infection, which has a critical role for viral pathogenesis of the current coronavirus disease-2019 (COVID-19) pandemic. Following the binding between S1 subunit and ACE2 receptor, different serine proteases, including TMPRSS2 and furin, trigger and participate in the fusion of the viral envelope with the host cell membrane. On the basis of the high virulence and pathogenicity of SARS-CoV-2, other receptors have been found involved for viral binding and invasiveness of host cells. This review comprehensively discusses the mechanisms underlying the binding of SARS-CoV2 to ACE2 and putative alternative receptors, and the role of potential co-receptors and proteases in the early stages of SARS-CoV-2 infection. Given the short therapeutic time window within which to act to avoid the devastating evolution of the disease, we focused on potential therapeutic treatments-selected mainly among repurposing drugs-able to counteract the invasive front of proteases and mild inflammatory conditions, in order to prevent severe infection. Using existing approved drugs has the advantage of rapidly proceeding to clinical trials, low cost and, consequently, immediate and worldwide availability.

Covid-19 has brought many difficulties in the management of infected and high-risk patients. Telemedicine platforms can really help in this situation, since they allow remotely monitoring Covid-19 patients, reducing the risk for the doctors, without decreasing the efficiency of the therapies and while alleviating patients' mental issues. In this paper, we present the entire architecture and the experience of using the Tel.Te.Covid19 telemedicine platform. Projected for the treatment of chronic diseases, it has been technologically updated for the management of Covid-19 patients with the support of a group of doctors in the territory when the pandemic arrived, introducing new sensors and functionalities (e.g., the familiar use and video calls). In Tuscany (Central Italy), during the first wave of outbreak, a model for enrolling patients was created and tested. Because of the positive results, the latter has been then adopted in the second current wave. The Tel.Te.Covid19 platform has been used by 40 among general practitioners and doctors of continuity care and about 180 symptomatic patients since March 2020. Both patients and doctors have good opinion of the platform, and no hospitalisations or deaths occurred for the monitored patients, reducing also the impact on the National Healthcare System.

An outbreak of a new coronavirus originating from Wuhan (China), responsible for a severe acute respiratory syndrome (SARS), called SARS-CoV-2, is causing a pandemic disease called CoViD-19 (Coronavirus Disease-19), although strict containment measures and restrictions on individual travel have been taken everywhere to hinder the spread of the virus. The clinical spectrum of this infection includes, in order of lesser to greater severity, asymptomatic viremia, paucisymptomatic forms, clinical conditions characterized by respiratory failure that needs mechanical ventilation and support in an intensive care unit, systemic manifestations of infection, septic shock, and multiple organ dysfunction syndromes. There is currently no vaccine to prevent CoViD-19, but the international scientific community is intensely focused on finding a vaccine that will prevent SARS-CoV-2 transmission. In the meanwhile, to prevent hospitals from risking collapse, it is crucial to stratify patients at high risk of poor lung progression, to find effective monitoring strategies, even at home, for the positive patients and/or those highly at risk of positivity of CoViD-19. Starting from the pathogenetic mechanisms involved in the development of this infection up to the clinical characteristics of the infected patients, in this review we tried to focus on the crucial points of the infection in combination with the appropriateness of the medical intervention. We aim to offer indications of therapeutic intervention that are timely and, as far as possible, effective, targeted to the individual patient in relation to age, clinical condition and comorbidities. An early diagnosis associated with an appropriate therapeutic action in the initial stages of the disease can reduce the progression of CoViD-19 towards interstitial pneumonia, thus interfering with the number of transfers to intensive care and lethality of the pandemic in progress.

Insertion of Agrobacterium rhizogenes rolB gene into plant genome affects plant development, hormone balance and defence. However, beside the current research, the overall transcriptional response and gene expression of rolB as a modulator in plant is unknown. Transformed rolB tomato plant (Solanum lycopersicum L.) cultivar Tondino has been used to investigate the differential expression profile. Tomato is a well-known model organism both at the genetic and molecular level, and one of the most important commercial food crops in the world. Through the construction and characterization of a cDNA subtracted library, we have investigated the differential gene expression between transgenic clones of rolB and control tomato and have evaluated genes specifically transcribed in transgenic rolB plants. Among the selected genes, five genes encoding for chlorophyll a/b binding protein, carbonic anhydrase, cytochrome b 6 /f complex Fe-S subunit, potassium efflux antiporter 3, and chloroplast small heat-shock protein, all involved in chloroplast function, were identified. Measurement of photosynthesis efficiency by the level of three different photosynthetic parameters (F v /F m , rETR, NPQ) showed rolB significant increase in non-photochemical quenching and a, b chlorophyll content. Our results point to highlight the role of rolB on plant fitness by improving photosynthesis., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

Background: Currently available antiarrhythmic agents for the treatment of atrial fibrillation (AF) have important limitations, leaving an unmet need for safe and effective therapy. Ranolazine is an approved antianginal agent with a favorable safety profile and electrophysiologic properties suggesting a potential role in the treatment of AF., Objective: The purpose of this study was to assess the safety and efficacy of ranolazine in the prevention of AF recurrence after successful electrical cardioversion and to ascertain the most appropriate dose of this agent., Methods: This prospective, multicenter, randomized, double-blind, placebo-control parallel group phase II dose-ranging trial randomized patients with persistent AF (7 days to 6 months) 2 hours after successful electrical cardioversion to placebo, or ranolazine 375 mg, 500 mg, or 750 mg bid. Patients were monitored daily by transtelephonic ECG. The primary end-point was the time to first AF recurrence., Results: Of 241 patients randomized, 238 took at least 1 drug dose. Ranolazine proved to be safe and tolerable. No dose of the drug significantly prolonged time to AF recurrence. AF recurred in 56.4%, 56.9%, 41.7%, and 39.7% of patients in the placebo, ranolazine 375 mg, ranolazine 500 mg, and ranolazine 750 mg groups, respectively. The reduction in overall AF recurrence in the combined 500-mg and 750-mg groups was of borderline significance compared to the placebo group (P = .053) and significant compared to 375-mg group (P = .035)., Conclusion: No dose of ranolazine significantly prolonged time to AF recurrence. However, the 500-mg and 750 mg-groups combined reduced AF recurrences, suggesting a possible role for this agent in the treatment of AF., (Copyright © 2015. Published by Elsevier Inc.)

Background: Current hypertension guidelines recommend using two antihypertensive agents when blood pressure (BP) control is not achieved with one single agent., Objective: This study was designed to assess the antihypertensive benefit of the olmesartan medoxomil 40 mg/hydrochlorothiazide (HCTZ) 12.5 mg combination versus olmesartan medoxomil 40 mg monotherapy in patients with moderate to severe hypertension., Methods: This was a randomized, double-blind, parallel-group, up-titration, multicentre, multinational, phase III study. Following a 2-week single-blind placebo run-in phase, 846 hypertensive patients with mean seated systolic BP (SeSBP) of 160-200 mmHg and mean seated diastolic BP (SeDBP) of 100-120 mmHg were randomized (1 : 2 ratio) to receive double-blind treatment with olmesartan medoxomil 40 mg or olmesartan medoxomil 40 mg/HCTZ 12.5 mg for 8 weeks (phase A). At week 8, patients not reaching BP goal (<140/90 mmHg; <130/80 mmHg in patients with diabetes mellitus) were up-titrated from olmesartan medoxomil 40 mg to olmesartan medoxomil 40 mg/HCTZ 12.5 mg or from olmesartan medoxomil 40 mg/HCTZ 12.5 mg to olmesartan medoxomil 40 mg/HCTZ 25 mg for an additional 8 weeks (phase B). Patients on goal continued their initial treatment. The primary efficacy parameter was the change in mean SeDBP during phase A., Results: Olmesartan medoxomil 40 mg/HCTZ 12.5 mg reduced mean SeDBP significantly more (-18.9 mmHg) than olmesartan medoxomil 40 mg (-15.8 mmHg) after 8 weeks of double-blind treatment (difference: -3.1 mmHg, p < 0.0001). Olmesartan medoxomil 40 mg/HCTZ 12.5 mg also reduced mean SeSBP significantly more than olmesartan medoxomil 40 mg (-5.4 mmHg, p < 0.0001). As a result, BP goal rates at week 8 were significantly higher with olmesartan medoxomil 40 mg/HCTZ 12.5 mg than with olmesartan medoxomil 40 mg (58.5% vs 44.3%; odds ratio 1.88; 95% CI 1.32, 2.54). During phase B, mean BP reductions were greater in patients up-titrated from olmesartan medoxomil 40 mg to olmesartan medoxomil 40 mg/HCTZ 12.5 mg than in those continuing on olmesartan medoxomil 40 mg (SeDBP: -9.3 mmHg vs -0.5 mmHg; SeSBP: -12.4 mmHg vs -0.5 mmHg). Similarly, mean BP reductions were greater in patients up-titrated from olmesartan medoxomil 40 mg/HCTZ 12.5 mg to olmesartan medoxomil 40 mg/HCTZ 25 mg than in those continuing on olmesartan medoxomil 40 mg/HCTZ 12.5 mg (SeDBP: -8.0 mmHg vs -0.3 mmHg; SeSBP: -12.1 mmHg vs -0.4 mmHg). In patients not on goal at week 8, addition of HCTZ 12.5 mg to olmesartan medoxomil 40 mg or up-titration from olmesartan medoxomil 40 mg/HCTZ 12.5 mg to olmesartan medoxomil 40 mg/HCTZ 25 mg brought additional patients to goal at week 16 (38.8% vs 36.9%). All treatments were well tolerated., Conclusion: The olmesartan medoxomil 40 mg/HCTZ 12.5 mg combination is superior to olmesartan medoxomil 40 mg monotherapy in reducing SeDBP and SeSBP and increasing BP goal rates after 8 weeks. Patients not on goal at week 8 with olmesartan medoxomil 40 mg or olmesartan medoxomil 40 mg/HCTZ 12.5 mg benefited from adding HCTZ 12.5 mg or up-titrating to olmesartan medoxomil 40 mg/HCTZ 25 mg, respectively, confirming that up-titration is a clinically meaningful way to improve BP control. [, Trial Registration Number: NCT00441350 (ClinicalTrials.gov Identifier)].

A 20-year-old man with mental impairment, was referred to us for evaluation of recurring idiopathic urticaria episodes, characterized by a diffuse spreading of wheals and severe itching lacking response to traditional antihistamines. Upon physical examination, he showed a persistent, generalized, reticular, red-bluish vascular skin pattern in association with diffuse arborizing telangiectasias. Such lesions were present from an early age. Laboratory and instrumental tests, performed in order to exclude any condition associated with livedo did not evidence pathological results. He was found to be positive for antinuclear autoantibodies (ANA; 1:640). Histopathologically, numerous dilated capillary vessels associated with sparse extravasated erythrocytes were observed in the upper dermis. We performed an autologous serum skin test (ASST), which resulted in a positive, suggesting an autoimmune basis of the condition. On the basis of clinical and histopathological findings, and in the absence of other clinical and laboratory data suggesting other neoplastic, immunological or systemic diseases, the diagnosis of cutis marmorata telangiectatica congenita (CMTC) associated with chronic autoimmune urticaria (CAIU) was made. CMTC is a rare congenital vascular disorder, consisting in an anomalous, persistent, red-bluish marbling of the skin, that can be associated with a wide spectrum of cutaneous and extracutaneous anomalies. In our case, neither physical examination nor instrumental investigation demonstrated any of these anomalies, with the exception of cognitive impairment. We report this case because of the rarity of a diagnosis of CMTC in an adult patient, because this condition has almost always previously been diagnosed in infancy, or it comes to observation because of the presence of associated disorders, as in our case for chronic urticaria.

Nodular scleroderma is a rare complication of systemic sclerosis; the pathogenetic implications are still unknown, although many factors are supposed to play a role in lesion development. We report the case of a young woman suffering from systemic sclerosis, who developed nodular lesions during therapeutic management with D-penicillamine and plasmapheresis. In order to better understand the essence of this disease, we examined all the possible pathogenetic mechanisms that could be implicated in nodular lesion development.

A 53-year-old man developed lichenoid lesions on the upper chest, posterior surfaces of the trunk, and abdominal region about three months before his first visit. Physical examination and laboratory findings were normal; histopathology showed vacuolar degeneration of basal keratinocytes in association with a dense lympho-histioid infiltrate arranged in a lichenoid pattern with a few melanophages and eosinophils. The fact that our patient had been irregularly taking sildenafil citratus (Viagra) led to the hypothesis of a lichenoid drug-induced eruption. Our hypothesis was confirmed by clinical resolution three weeks after discontinuation of sildenafil citratus; moreover, the patient avoided the drug for about four months, and the eruption didn't reappear. Subsequently, we performed a challenge test with the drug, and the patient developed similar lichenoid lesions. Lichenoid eruptions are rather common dermatoses that can be induced by a great number of environmental agents and are clinically but not pathogenetically well defined. We report the present case because, despite the great number of drugs that can be implicated in the development of lichenoid eruptions, the association of such dermatoses and sildenafil citratus had been described only once previously in the literature until now. Furthermore, we wish to remark on the significance of a detailed anamnestic history to make the correct differential diagnosis between lichenoid drug-induced eruptions and lichen planus. This has a great clinical importance because simple discontinuation or substitution of the drug causes lichenoid drug-induced eruption resolution.

The term "morphea" includes a wide spectrum of clinical entities, varying from localized plaques of only cosmetic importance to deep lesions resulting in considerable morbidity for the patient. In fact, although survival rates are no different from that of the general population, localized scleroderma may be associated with development of substantial disability, as occurs in deep morphea and in pediatric patients (disabling pansclerotic morphea of children). We report a case of morphea profunda affecting a young man with severe, rapidly progressive, widespread skin involvement and focus on the eventual systemic evolution of such cases. A 40-year-old man was admitted in 2002 for progressive subcutaneous indurations, preferentially involving the right side of the trunk. His health was altogether good, with the exception of a beginning chronic obstructive bronchopneumopathy. There was no family or personal history of dysmetabolic, cardiovascular, neoplastic, or cutaneous disease. Three years earlier, the patient had noted the appearance of two infiltrated, intensely red lesions on the right laterocervical and paraumbilical regions. These had been interpreted as subcutaneous lipomatosis on the basis of an ultrasound scan. The lesions had become progressively larger, while their surface had assumed a scleroatrophic appearance. Thereafter, other lesions had developed on his chest and lower limbs, mostly distributed on the right side of the body. Clinical examination revealed well demarcated, depressed sclerotic plaques with ivory-colored centers and erythematous borders ("lilac ring") localized on the neck, chest, and lower abdomen and limbs (Figure 1). They were bound to the deeper structures and arranged in a band-like linear distribution on the right side of the chest and abdomen where they extended horizontally for more than 10 cm in diameter. These lesions were totally asymptomatic. In addition, arborizing telangiectasias were evident on the neck and upper chest (Figure 2). Laboratory investigations provided normal range of erythrocyte sedimentation rat and C reactive protein levels and other inflammation markers. Antinuclear antibody, antidouble-strand DNA, antimitochondrial, anti-extractable antigens (anti-centromere, anti-Scl-70, anti-U1RNP), and anti-Borrelia burgdorferi antibodies were negative. Circulating immunocomplexes binding C1q were substantially increased. Oesophageal x-rays and lower limb electromyography were within normal limits; ventilatory function testing revealed a mild obstruction consistent with the beginning of chronic obstructive pulmonary disease. Although nailfold capillaroscopy documented nonspecific findings of connective tissue disease (mega-capillaries, segmentary dilatation and destruction), the laser-Doppler flussimetry revealed few signs of microcirculatory abnormalities, in absence of Raynaud's phenomenon. An abdominal wall ultrasonography, performed on a sclerotic plaque, documented thinning of the subcutaneous tissue, with increase of the fibrous component and lower fascia and muscle retraction. The biopsy specimen from the abdominal region included fascia and the subcutaneous tissue (previously obtained from the lower abdomen) with epidermal atrophy, a thickening and homogenization of collagen bundles in the deep dermis and hair reduction. A perivascular lympho-monocytic and plasmacellular infiltration with a dermo-epidermal distribution was present. Moreover, septal fibrosis with a perivascular lymphoplasmacellular inflammatory infiltrate was documented within the abdominal rectus muscle. The diagnosis of morphea profunda was made on the basis of clinical and histopathological findings. A therapeutic regimen based on amino benzoic potassium (Potaba; Glenwood, LLC, Glenwood, NJ), oral prednisone, and topical clobetasol was started. After several months of follow-up, the patient had obtained only moderate improvement of the clinical findings.

The term chronic autoimmune urticaria (CAIU) is used for chronic urticaria in subjects who present a whealing response to the intradermal injection of autologous serum, suggesting the presence of pathogenic antibody activities. In this study, we examined 28 chronic urticaria subjects with positive autologous serum skin test (ASST), all of whom presented autologous serum-induced lesions at different evolutive stages. Punch biopsies were taken from lesional skin of six subjects at 10', eight subjects at 30', six subjects at 60', and four subjects each at 24 and 48 h. Immunological studies focussed on infiltrating cell immunophenotype and related cytokines, chemokines and chemokine receptors, adhesion molecules. Immunohistochemical staining was performed to measure expression of CD3, CD4, CD8, tryptase, eosinophil cationic protein, myeloperoxidase, basophil granular protein, IL-4, IL-5, IL-8, CCR3 and CXCR3, ICAM-1, VCAM and ELAM. Control staining was done on unaffected skin from the patients and normal skin from four healthy donors. The main infiltrating population was represented by neutrophils, seen focally in both unaffected skin (P = 0.001) and healthy controls (P = 0.003). IFN-gamma and IL-5 were expressed focally in autologous wheals. Significant staining for IL-4 was seen at 30'. CCR3 and CXCR3 were expressed less in autologous wheals than in uninvolved skin (P < 0.0001; P = 0.002). Cellular adhesion molecules (CAMs) reached their highest expression at 30' and 60' in induced lesions, and they showed strong expression also in unaffected skin (ICAM-1: P < 0.0001). Our data show that the immunoinflammatory features of ASST-induced wheals involve a prevalent role of lymphocytes (with a mixed Th1/Th2 response), with strong neutrophil infiltration and activity and involvement of the chemokine pathway. We interpreted the finding of inflammatory cells and mediator up-regulation in uninvolved CIU skin as a sign of prolonged and widespread "urticarial status".

Background: Women are often not treated as aggressively as men to control levels of low-density lipoprotein cholesterol (LDL-C), despite evidence that women and men realize comparable cardiovascular benefit from lipid-lowering therapy. Statins are the most effective drugs currently available for treating hypercholesterolemia. Despite the impressive cholesterol-lowering capacity of statins, however, many patients on statin therapy fail to reach established target levels of LDL-C. The cholesterol absorption inhibitor, ezetimibe, blocks the intestinal absorption of dietary and biliary cholesterol, a mechanism of action complementary to that of statins, which inhibit hepatic cholesterol synthesis. Ezetimibe coadministered with statins produces significant incremental reductions in LDL-C compared with statin monotherapy., Methods: Four randomized, double-blind, placebo-controlled, balanced-parallel group trials compared the efficacy and safety of statin monotherapy (lovastatin or pravastatin 10, 20, or 40 mg; simvastatin or atorvastatin 10, 20, 40, or 80 mg) vs. ezetimibe 10 mg plus statin (as above). A gender subset analysis (women, n = 1065; men, n = 796) on data pooled across these four trials was carried out to determine whether ezetimibe plus statin for the treatment of hypercholesterolemia is equally efficacious in women and men., Results: Compared with statin monotherapy, ezetimibe plus statin demonstrated greater efficacy in reducing blood levels of LDL-C, apolipoprotein B, and triglycerides and raising high-density lipoprotein cholesterol. The beneficial effects of ezetimibe were comparable in women and men. The safety profile of subjects receiving ezetimibe plus statin was similar to that of patients receiving statin monotherapy and similar between the two sexes., Conclusions: Ezetimibe plus statin was more effective than statin alone in improving the lipid profile of patients with hypercholesterolemia and was equally efficacious in women and men. Ezetimibe plus statin was well tolerated and had a favorable safety profile in both patient subgroups. Ezetimibe coadministered with statins, a dual inhibition treatment strategy that targets both cholesterol absorption and synthesis, is an effective therapeutic option for women with hypercholesterolemia.

Background: Despite the efficacy of statins in lowering low-density lipoprotein cholesterol (LDL-C) levels, many patients who are at high risk for heart disease with hypercholesterolemia require additional LDL-C level reduction. The cholesterol absorption inhibitor, ezetimibe, has been shown to provide significant incremental reductions in LDL-C levels when co-administered with statins. This study was performed to compare the efficacy and safety of ezetimibe (10 mg) plus response-based atorvastatin titration versus response-based atorvastatin titration alone in the attainment of LDL-C goals in subjects who are at high risk for coronary heart disease (CHD) and are not at their LDL-C goal on the starting dose of atorvastatin., Methods: This was a 14-week, multicenter, randomized, double-blind, active-controlled study conducted in 113 clinical research centers in 21 countries. Participants were adults with heterozygous familial hypercholesterolemia (HeFH), CHD, or multiple (> or =2) cardiovascular risk factors, and a LDL-C level > or =130 mg/dL after a 6- to 10-week dietary stabilization and atorvastatin (10 mg/day) open-label run-in period. Eligible subjects continued to receive atorvastatin (10 mg) and were randomized to receive blinded treatment with ezetimibe (10 mg/day; n = 305) or an additional 10 mg/day of atorvastatin (n = 316). The atorvastatin dose in both groups was doubled after 4 weeks, 9 weeks, or both when the LDL-C level was not at its goal (< or =100 mg/dL), so that patients receiving combined therapy could reach 40 mg/day and patients receiving atorvastatin alone could reach 80 mg/day. The primary end point was the proportion of subjects achieving their LDL-C level goal at week 14. A secondary end point was the change in LDL-C level and other lipid parameters at 4 weeks after ezetimibe co-administration with 10 mg/day of atorvastatin versus 20 mg/day of atorvastatin monotherapy., Results: The proportion of subjects reaching their target LDL-C level goal of < or =100 mg/dL was significantly higher in the co-administration group than in the atorvastatin monotherapy group (22% vs 7%; P <.01). At 4 weeks, levels of LDL-C, triglycerides, and non-high-density lipoprotein cholesterol were reduced significantly more by combination therapy than by doubling the dose of atorvastatin (LDL-C -22.8% versus -8.6%; P <.01). The combination regimen had a safety and tolerability profile similar to that of atorvastatin alone., Conclusions: The addition of ezetimibe to the starting dose of 10 mg/day of atorvastatin followed by response-based atorvastatin dose titration to a maximum of 40 mg/day provides a more effective means for reducing LDL-C levels in patients at high risk for CHD than continued doubling of atorvastatin as high as 80 mg/day alone.

In 2002, a 38-year-old woman was referred to the department of dermatological sciences for the evaluation of erythematous-infiltrated lesions with prominent purpuric and erosive components distributed on her face, upper chest, and extensor surfaces of the limbs, which developed over a 3-month period. In 1997 the patient suffered from polyarthralgia (proximal interphalangeal,knee, wrist, and metacarpophalangeal joints) associated with morning stiffness. In 1999 she was admitted to a psychiatric unit for depression with episodes of lipothymia. In the same year, since she developed diffuse and persistent urticarial manifestations with angioedema and livedo reticularis of the limbs in association with anticardiolipin antibodies, vasculitis was proposed. Upon examination, erythematous-infiltrated and erosive lesions in association with serohemorrhagic crusts were present on the face,neck, chest, upper trunk, and extensor surfaces of the upper limbs and thighs (Figures 1-3). Telangiectasias were especially evident on the cheeks, where prominent edema conferred her face a moon-like appearance (Figure 1). Laboratory investigations disclosed microcytic anemia, elevated erythrocyte sedimentation rate, proteinuria (30 mg/dL), positive antinuclear antibodies (1:80) with diffuse fluorescence pattern, lowered complement levels (C3: 31 mg/dL, C4: 3 mg/dL), circulating immunocomplexes binding Clq, and high titers of anti-TSH receptor antibodies. Indirect immunofluorescence was negative for the detection of anti-basement membrane zone antibodies. Histological examination of the lesional skin of the shoulder documented epidermal atrophy, marked vacuolar degeneration of the basal cell layer, colloid bodies, and a perivascular lymphohistiocytic infiltration of the upper and deep dermis (Figure 4). Direct immunofluorescence performed on affected skin showed junctional granular deposition of IgG, C3,and Clq in association with perivascular C3 and Clq deposits in the upper dermis; direct immunofluorescence on sun-protected,non-lesional skin showed similar immunological deposition both at the basement membrane zone and in the perivascular dermis.Based upon the clinical, histologic, and immunopathologic findings, we proposed the diagnosis of systemic lupus erythematosus with maculopapular and erosive skin lesions. The patient was treated with methylprednisolone IV (pulse therapy, 250 mg) tapered over 10 days and later continued p.o. After a few weeks, significant improvement of cutaneous manifestations was noted.

Skin tests with autologous serum elicit an immediate wheal-and-flare response in about 30-50% of chronic idiopathic urticaria subjects, suggesting that an autoimmune mechanism might be involved in the pathogenesis of this disease. The aim of the present work, involving 68 subjects with chronic idiopathic urticaria, was to distinguish between the serum-positive and serum-negative cases and highlight the clinical differences between the two groups on the basis of the Breneman scale score. We also tried to correlate the finding of a positive response to the autologous serum skin test with other autoimmune diatheses or fully developed autoimmune disorders. Our results did not demonstrate any significant differences between the two groups with regard to mean age, sex distribution, angioedema and mucosal/cutaneous atopy. However, all subjects with positive autologous serum skin test presented more severe clinical features than serum-negative subjects. We found no differences between the two groups in the incidence of autoimmune disease.

This study assessed the effect of ezetimibe coadministered with simvastatin on high-sensitivity C-reactive protein (hs-CRP) in patients with primary hypercholesterolemia. After dietary stabilization, a 2- to 12-week washout period, and a 4-week, single-blind, placebo lead-in period, patients with baseline low-density lipoprotein cholesterol > or =145 and < or =250 mg/dl and triglycerides < or =350 mg/dl were randomized to one of these daily treatments for 12 consecutive weeks: ezetimibe 10 mg; simvastatin monotherapy (10, 20, 40, or 80 mg); ezetimibe 10 mg plus simvastatin (10, 20, 40, or 80 mg); or placebo. The primary analysis was the change in hs-CRP for the pooled ezetimibe plus simvastatin versus simvastatin monotherapy groups. Ezetimibe plus simvastatin significantly reduced median hs-CRP levels compared with simvastatin monotherapy (-34.8% vs -18.2%, p<0.01), and incremental reductions were observed at each simvastatin dose level. Combination therapy-induced significant changes in individual lipid parameters did not explain the observed decreases in hs-CRP. Thus, ezetimibe coadministered with simvastatin resulted in significant incremental decreases in hs-CRP, possibly consistent with an additional anti-inflammatory effect compared with simvastatin monotherapy.