World and Independent Cinema Essay Example | Topics and Well Written Essays - 1500 words

World and Independent Cinema - Essay Example Casino Royale reopens the sequence, creating a new timeline and chronicle sequence not meant to follow or head any earlier bond production. This enabled the movie to demonstrate an inexperienced and more valuable James and for once in the character, series of Miss Money Penny fails to appear. Additionally, forming the movie involved an intensive search for a new character to portray Bond, and critical debate surrounded Craig when he was appointed to take over from Pierce Brosnan, (Williams, 2006, p. 23). Casino Royale film documents the story of a newly selected British agent, James Bond, who in collaboration with impudent little agent of treasury, starts rogue mission to kill a terrorist bankroller in a high stakes poker game before his customers reach him first and try a global attack. The movie has some differences as compared to the mainstream (Hollywood) formula. For instance, when Pierce assumed the role of Bond J for Goldeneye, a lot was produced concerning the modernization of franchise. In fact, the only evident transformations were cosmetics, (Lindner, 2009, p. 45). Pierce Brosnan 007 is easily related to the character earlier performed by Connery S, Lazenby G, Moore R and Dalton T. With the rise of Craig Daniel to the authority to kill, martini, firearm and tux seismic shifts have taken place. The movie is not about the famous James bond of 1960s to 90s but the new era of M16s highly featured agent. The primary function of the film is to recreate the franchise. Daniel is not taking over after Brosnan; he is recreating the role. Additionally, as far as the film is concerned, little in the earlier 20 series has happened compared to the current scene. This is the origin story of Bond, and the only crucial bit of continuity is Dench Judy’s return as Mrs. M Forget. For decades now, James Bond formula has been submerged in an ocean of rip-offs and claimants, each highly over-the-top as compared to its successors. In a bid to

Organizational Communication Research Paper Example | Topics and Well Written Essays - 3000 words

Organizational Communication - Research Paper Example Effective communication in this case requires message, a sender, a recipient, codes to help in encoding the message, and a means of transmitting the message. If passed on well information contained in communication will encourage and promote good relations between people and entities. This therefore emphasizes the need for effective communication if the businesses are to prosper as well as have a good flow of information within the out of their confines. One of the characteristics of effective communication is the absence of conflict in response or reaction as has been captured perfectly by Katherine Miller (2008). When we talk of organizational communication, we essentially refer to the way in which companies, associations or groupings communicate with their employees, clientele as well as how departments interrelate with each other. It is also encompasses the relationship between a business and its environment, a process that enables the organization to relate with its surrounding in order to serve them with finesse (Carsten, & De Dreu, 2007). Literature Review: Effective communication in a very important tool in an organization, especially because of the way it helps in promoting good flow of information and hence relationship and performance of the business departments as they create a synergy for achieving the best results in terms of production. Organizational communication can either be internal or external. Internal communication is solely communication within the confines of the company while external is communication with other businesses or any other external entity. Effective communication leads to many positive effects and leads to good productivity. There are several ways that management can use communication to pass information. They include emails, meetings, face-to-face discussions, letters, video conferencing, conferences and telephone calls (Fredric, & Jablin 2007). Noteworthy, is the fact that some methods of message transfer are more effect ive and detailed than others and therefore appropriate to always evaluate the organization and weigh the most effective and cost efficient mode of communication for your business, and through which the company can achieve maximum profits. When the most appropriate mode of communication is used then message contained in it not only leads to its effective transfer but it also enhances a good relationship between various entities in the an organization and especially the top management and the workers. It also creates an enabling environment for the building of trust within the company workers (Miller, 2008). Communication as a process is a very dynamic and vibrant process when compared to other business processes. As a process communication changes with individuals and this is dependent on factors such as education, eloquence, target audience and the message being transmitted itself. It is therefore right to say that the sender of the message determines how the message will be underst ood and interpreted. If communication is efficient, it will get rid of events of conflicting messages or conflicting responses (Fredric, & Jablin, 2007). Successful communication at different levels of management is important in an organization in that it helps in building of relationships amongst these people. Communication between management and employee is also a very important aspect

IN6 Essay Example | Topics and Well Written Essays - 1250 words

IN6 - Essay Example Inspirations appear from the region of controlling configurations of ground or in-flight vehicles with purposes in air travel organize, satellite grouping, mechanical highways, movable robotics and movable sensor networks. One of the major aims is to attain a synchronized purpose while employing merely confined information. Due to their recurrent expression in multi-agent schemes, active networks have previously established considerable attention. In a determination of local connectedness of a network is brought in that below positive conditions is enough for global connectedness (Alben et al, 2002). This main focus of this paper is to see this technique in organizational management prospective. In an era when "always accessible, forever connected" has turn out to be the standard anticipation in business, benevolent employees the aptitude to access appliance and real-time data and information could be serious for a companys continued existence. Though a number of industries applications are inexorably client based, a lot of of the center business procedure applications, like that CRM, sales strength automation, and electronic mail, are network based facilities and utilities. In addition, in business situations where teamwork and information distribution are serious, it commonly creates the most intelligence to influence the corporate network as an electronic warehouse of information and possessions. In both of these statements, offering Distributed connectivity and real-time access to the mainly current information be able to be serious to member of employees effectiveness and, normally, to the fulfillment of the enterprises clientele (Deshmukh et al, 1993). This section elaborates why we need this technique for the original management? Here it is described that how this technique can provide effective project management approach and facilitate the project manager. While end-to-end direct connectivity was a necessity

World and Independent Cinema Essay Example | Topics and Well Written Essays - 1500 words

World and Independent Cinema - Essay Example Casino Royale reopens the sequence, creating a new timeline and chronicle sequence not meant to follow or head any earlier bond production. This enabled the movie to demonstrate an inexperienced and more valuable James and for once in the character, series of Miss Money Penny fails to appear. Additionally, forming the movie involved an intensive search for a new character to portray Bond, and critical debate surrounded Craig when he was appointed to take over from Pierce Brosnan, (Williams, 2006, p. 23). Casino Royale film documents the story of a newly selected British agent, James Bond, who in collaboration with impudent little agent of treasury, starts rogue mission to kill a terrorist bankroller in a high stakes poker game before his customers reach him first and try a global attack. The movie has some differences as compared to the mainstream (Hollywood) formula. For instance, when Pierce assumed the role of Bond J for Goldeneye, a lot was produced concerning the modernization of franchise. In fact, the only evident transformations were cosmetics, (Lindner, 2009, p. 45). Pierce Brosnan 007 is easily related to the character earlier performed by Connery S, Lazenby G, Moore R and Dalton T. With the rise of Craig Daniel to the authority to kill, martini, firearm and tux seismic shifts have taken place. The movie is not about the famous James bond of 1960s to 90s but the new era of M16s highly featured agent. The primary function of the film is to recreate the franchise. Daniel is not taking over after Brosnan; he is recreating the role. Additionally, as far as the film is concerned, little in the earlier 20 series has happened compared to the current scene. This is the origin story of Bond, and the only crucial bit of continuity is Dench Judy’s return as Mrs. M Forget. For decades now, James Bond formula has been submerged in an ocean of rip-offs and claimants, each highly over-the-top as compared to its successors. In a bid to

IN6 Essay Example | Topics and Well Written Essays - 1250 words

IN6 - Essay Example Inspirations appear from the region of controlling configurations of ground or in-flight vehicles with purposes in air travel organize, satellite grouping, mechanical highways, movable robotics and movable sensor networks. One of the major aims is to attain a synchronized purpose while employing merely confined information. Due to their recurrent expression in multi-agent schemes, active networks have previously established considerable attention. In a determination of local connectedness of a network is brought in that below positive conditions is enough for global connectedness (Alben et al, 2002). This main focus of this paper is to see this technique in organizational management prospective. In an era when "always accessible, forever connected" has turn out to be the standard anticipation in business, benevolent employees the aptitude to access appliance and real-time data and information could be serious for a companys continued existence. Though a number of industries applications are inexorably client based, a lot of of the center business procedure applications, like that CRM, sales strength automation, and electronic mail, are network based facilities and utilities. In addition, in business situations where teamwork and information distribution are serious, it commonly creates the most intelligence to influence the corporate network as an electronic warehouse of information and possessions. In both of these statements, offering Distributed connectivity and real-time access to the mainly current information be able to be serious to member of employees effectiveness and, normally, to the fulfillment of the enterprises clientele (Deshmukh et al, 1993). This section elaborates why we need this technique for the original management? Here it is described that how this technique can provide effective project management approach and facilitate the project manager. While end-to-end direct connectivity was a necessity

Video games are good Essay Example for Free

Video games are good Essay In this 21st generation, video games are one of the most entertaining and one of the most popular ways to enjoy time. Video games are electronic human interactive games, which can be played in different types of consoles in a variety of ways. Have you ever thought about video games being beneficial? Or not just something which helps pass time or something that is a bad addiction? Video games are so popular in today’s world that, the video game business earns billions of dollars on releasing a game or a type of console. In 2010 the play station brand hit 155 million units sales of their ever so famous console, â€Å"the play station 2,† which is also known as the â€Å"PS2. † Video games are not just an entertainment but, it has turned into something much bigger, it has turned into a business and also a living for some people. Many people state that video games are bad for us, like there is a topic posted in debate. org, where people who think video games are not of any good, and surprisingly to my benefits of my opinion 67% of the people who rated the discussion disliked it! Many people also have related violent behavior to violent games, like the tragic massacre that took place on the December 12th 2012, when 20 year old Adam Lanza fatally shot 20 children and 6 adult staffs, in Sandy Hook Elementary School. Many have said that, Violent video games was one of the main motivations for Adam’s violent act, A TV and a radio host, named Glen beck stated that the, â€Å"Sandy Hook Massacre,† was caused by video games. He also states that, â€Å"video games are a gateway drug for our kids and instead of a high, they get numbness, they get an indifferent heart and a mind that cannot tell the difference between fiction and reality. † I strongly disagree with his point; there was violence before video games. I believe the Sandy Hook murderer was a mentally ill and an unstable teenager. If video games was the case, there are a lot of children play violent video games, like the first person shooting game â€Å"Call of Duty Black Ops II,† is a violent war game and the game is really realistic and it is brutal. The game went to gross $ 1 Billion in the first 15 days of availability. With so many people playing violent games there should have more than at least 50 massacres yearly according to my calculation. I mean if a normal human being plays a violent video game for maybe even more than 12 hours a week, it wont motivate or trigger us to go kill someone, you have to have some kind of a mental illness or a violent angst, to go fling around guns in public. Video games are not harmful for someone, and many parents and critics are very judgmental about it, as many kids are not properly guided and supervised while playing video games. Video games, are surely fun but an individual should be self discipline and even the parents should be able to handle and guide their children on how much they play their video games. An article by Health Central also suggests that video games are bad. It tells the readers that it makes people un-social, obese, and also it causes them to have bad grades, aren’t these reasons all about self-disciplinary? Are video games the main cause of this? Video Games are even in fact educational, like the game Civil-war, teaches us and gives us like a first hand experience about the American civil war fought in 1861. It also gives out facts and important dates about the civil war in the loading screen. Maybe even someone who has a hard time making friends, get along with others, while playing video games or them having the same interest in video games. â€Å"A growing body of university research suggests that gaming improves creativity, perception and also decision making† (Hotz par. 1). Experts of health central said that, video games causes people to be obese, anti-social and perform bad in schools, but I believe it is the fault of those gamers who get to addictive to video game and their lack of self-discipline. Video games cannot be blamed for those reasons. If we put it like that anything we do excessively is harm to us. Playing video games is not a bad thing at all; it instead helps us pass time more entertainingly and has benefits to it as well. A research showed that people who played video games made better decisions 25% faster than those who did not play video games. A research by University of York aimed to discover if video games improver hand-eye coordination. † In order to discover this, they compared the brain activity of participants who played video games for at least 4 hours a week with the results from participants who did not play video games. The study showed that the participants who did not play video games relied mostly on a part of the brain that controls hand eye coordination. In order to complete the games, the men who were not accustomed to playing video games had to focus a large amount of mental energy on coordinating what they were seeing on the screen with the physical actions they were making on the controller. Besides hand eye co-ordination, active games like the, â€Å"Nintendo Wii has promoted where you have to do things physically which has proved to improve your physicality and give you enough exercise† (Wittman par. 5). As I mentioned before video games can be a way of living for someone nowadays, an article by Kyle Russell states that, â€Å"over 60 gamers earn more than 100,000 US dollar without counting the sponsorship deals and streaming their practice games. † Even I have experinced how drastically video games improve you reactions and hand eye cordination. When I was in middle school, we had to play indoor games during the winter as it used to be really cold outside to play soccer, which was really sad for me as I love soccer and I kind of didn’t like to play indoor game. We were made to play table-tennis, and I used to hate it as I was really not that good. Around that time was when I started playing video games and as soon as that, after two months or so, I really felt myself improving in table-tennis drastically and without practice. My reactions were really fast, I later then realized how video games had a big role in that. Video games have many benefirts, In an article by Drew Guarini posted in the Huff post says â€Å"a study by a group of Italian researchers proved that video games helps dyslexic children read better. Many may still argue that, even after all these benefits video games are not worth its cost, but if we look at the long run it might save us a lot of money, a anti video game mom, Jo Ashiline also re-considered getting a video game, she said, â€Å"This dilemma led me this Christmas to consider getting a video game system, at least a Wii that we could all play together. The kids pointed out that I spent $82 the last time we all went bowling, and with the Wii, we could bowl at home for free (Ashline, par. 7). Ultimately, it is apparent that video games are a lot more beneficial than many people think, video games have had its prejudices created by all the critics those have very invalid reasoning like how some said, Video games are the reason for mass massacre, or even maybe how video games causes bad-grades and obesity. Those reasons are not because of the video game, but because of lack of supervision and self-disciplinary. I think that Video games are a wonderful way to spend time while having many benefits to everyone. For the old folks who may think that video games are only for the younger one, you may want to re-consider. A study this year conducted by University of Iowa found out that, Playing brain-teasing game for just two hours a week may help slow the degree of mental decay associated with the natural aging process. (Guarini D, par. 10). Work Cited FYI: Video Game Statistics by the Entertainment Software Association. Critical Gaming Project. Word Press, n.d. Web. 18 Nov. 2013. Are Video Games Bad for Children? The Premier Online Debate Website. N. p. , n. d. Web. 18 Nov. 2013. Sandy hook shoting article Sandy Hook Shooter Motivated by Violent Video Games, Norway Massacre (Report). The Hollywood Reporter. N. p. , 18 Feb. 2013. Web. 19 Nov. 2013. Feraligatr, Caz. Glenn Beck: Video Games Are A Drug That Killed 28 People! Blog by CazFeraligatr IGN. IGN. N. p. , 22 Feb. 2013. Web. 20 Nov. 2013. Main Menu. Dependable Video Games. N. p. , 19 Sept. 2012. Web. 18 Nov. 2013. Video Gaming Increases Physical Activity. The Journal of Extension (JOE). Journal of Extension, n. d. Web. 20 Nov. 2013. Russel, Kyle. The Highest-Paid Professional Video Gamers In The World. Web log post. Business Insider. N. p. , n. d. Web. 20 Nov. 2013. Guarini, Drew. 9 Ways Video Games Can Actually Be Good For You. The Huffington Post. TheHuffingtonPost. com, 07 Nov. 2013. Web. 18 Nov. 2013. Work Cited Ashline, Jo. Video Games Were Invented by the Devil OC Moms: The Mom Blog : The Orange County Register. OC Moms: The Mom Blog. N. p. , 27 Dec. 2009. Web. 20 Nov. 2013.

Treatment of Rituximab in Pemphigus Vulgaris Patients

Treatment of Rituximab in Pemphigus Vulgaris Patients Part 3: Clinical Research 2 INTRODUCTION Pemphigus is the name of a group of life-threatening blistering diseases of the skin and mucous membranes. The base of treatment for this disease is corticosteroids; however, recently, new drugs, such as rituximab, have been verified for more severe forms of it. In the authors previously unpublished study, the effect of rituximab on variation in the laboratory indices of pemphigus vulgaris patients is addressed. After investigation of the files of pemphigus patients who received rituximab in Razi Hospital, Tehran, Iran from 2008 to 2013, 39 patients were entered into the study. All patients had lab sheets containing CR (creatinine), urea, ALT (alanine aminotransferase), AST (aspartate aminotransferase), Plt (platelet), Hgb (hemoglobin), and WBC (white blood cell) before and after receiving rituximab. The patients received rituximab 4 times at a dosage of 500 mg in 4 successive weeks. The lab results before receiving the first dose of rituximab were compared to the results after receiving treatment. The effect of rituximab on the variation in lab indices with the adjustment effect of age, gender, disease duration, sites of involvement, received adjoins, and the background disease were also investigated. In the initial analysis, rituximab only had a significant effect on urea reduction. In the CellCept ® (mycophenolate mofetil) receiving subgroup, the mixed consumption of rituximab led to a significant reduction in WBC. In the subgroup having background disease, rituximab had a statistically significant impact on platelet reduction. In the subgroup having no background disease, rituximab had a statistically significant effect on urea reduction. The lab indices were shown to have no significant relationship with age and disease duration. Thus, it can be predicted that disease duration and age would have no effect in the relationship between rituximab and lab indices variations. Although in stratified single-variable analysis for adjusting the effect of other variables (involvement sites and received adjoins) on the relation of rituximab and lab indices, some of these variables showed interacting effects with rituximab on the variations of lab indices. However, due to the low volume of sample and non-normal distribution of most of these variables, it was impossible to do multivariable analysis for investigation of their independent and interactive effects on variations of lab indices in an integrated manner, therefore, we can not make certain comments about their relationships. Chapter 1 Pemphigus is the name of a group of life-threatening blistering diseases that have characteristic acantholysis leading to formation of intraepithelial blisters in mucus and skin [1]. The acantholysis process is induced via attachments of flowing autoantibodies to adhesion molecules in the cells [2]. Patients with pemphigus have mucosal erosions, blisters, papules, and cutaneous erosions. The different types of pemphigus are pemphigus vulgaris, pemphigus foliaceus, immunoglobulin A (IgA) pemphigus, and paraneoplastic pemphigus. Different types of pemphigus are differentiated by clinical symptoms, related autoantigens, and histological methods. Pemphigus vulgaris has mucosal and mucocutaneous involvement. The blisters are acantholytic and suprabasal. The autoantibodies responsible for the disease are against desmoglein (DSG) 1 or both desmoglein 3 and 1. Pemphigus foliaceus only involves the skin. The blisters are acantholytic and subcorneal. The responsible autoantibodies are against desmoglein 1. IgA pemphigus has the form of grouped erythematous crusts, papules, and vesicle plucks. Blisters can be subcorneal or intraepithelial and acantholytic. The responsible autoantibodies are against desmocollin (DSC) 1 [3]. Paraneoplastic pemphigus involves vast and resistant stomatite along with different cutaneous findings. The responsible autoantibodies are against desmoplakin (DSP) or other desmosomal antigens. Pemphigus vulgaris is the most common type of pemphigus, but is still very rare. The chance of its occurrence is between 0.1 to 0.5 per 100,000 people [4]. Pemphigus often happens among adults and the average age of onset is 40 to 60 years old. It is very rare among children [5,6]. Its prevalence is almost the same in the 2 sexes [7]. Almost all the pemphigus vulgaris patients have mucosal involvement. The mouth is the most common site of involvement and is often the first site of involvement. Other mucosal membranes such as conjunctivae, nose, esophagus, vulva, vagina, cervix and anus are rarely involved [8]. As mucosal blisters are fragile and burst easily, in clinical examination it is difficult to find intact blisters, and instead the examiner tends to find mucosal erosions. Buccal and pa latal mucosa are the most common sites of blister involvement in the mouth cavity [9]. Mucosal involvement can be very painful. This pain often increases by chewing and swallowing, which can result in improper alimentation and weight reduction. Most of the patients also have cutaneous involvement appearing in the form of soft blisters in healthy skin or erythematosus. The blisters easily break, resulting in painful erosions. Pemphigus vulgaris rarely causes pruritis. Almost any part of body skin can be involved, but the palmar aspects of the foot and hands are rarely involved. The Nikolsky sign is often observed among these patients (mechanical pressure on the healthy skin results in blistering). Pemphigus is diagnosed based on the clinical, histological, immuno-pathological symptoms and laboratory findings. Even in cases where the clinical symptoms are intensively supporting pemphigus, laboratory investigation is still needed to confirm the diagnosis, as other diseases may have the same symptoms. The first line of treatment of pemphigus is systemic corticosteroids, an d addition of adjuvants may also be needed. Patients who do not respond to the first line of treatment might need additional interventions. In such patients, cyclophosphamides, rituximab, intravenous immunoglobulin (IVIG) or plasmapheresis may be helpful. Initial treatment of pemphigus vulgaris is systemic glucocorticoid, which is often applied in combination with other non-steroidal immunosuppressants such as azathioprine and mycophenolate mofetil. Pemphigus resistant to treatment is a type of pemphigus that does not respond to the aforementioned treatments. Pemphigus is a chronic disease that needs long-term treatment. A retrospective study was conducted during 1982-1993 on 40 patients [8]. On average, these patients achieved complete remission after 7.7 years; 25% had remission after 2 years; 50% after 5 years; and 75% after 10 years [8]. Most pemphigus vulgaris patients respond to initial treatments [9]. The first step, in the patients who do not respond to initial treatment, is increasing the dosage of systemic corticosteroids (1.5-2 mg/kg of prednisolone per day) or adjuvant drug. The adjuvant drug can also be changed (changing azathioprine to mycophenolate mofetil). In resistant cases, cyclophosphamides, rituximab, IVIG, and plasmapheresis could also be used. As pemphigus is an auto-immune disease caused by autoantibodies, treatments that reduce B cells are investigated [10-13]. Rituximab is a monoclonal antibody that targets CD20, located on B-lymphocytes, as its antigen. This drug has been shown to have profound effects on pemphigus treatments [13,14]. In a multicenter study conducted on 14 pemphigus vulgaris patients and 7 pemphigus foliaceus patients, both groups were resistant to systemic glucocorticoids and experienced several relapses during glucocorticoid tapering. They were then put on 1 cycle of rituximab with a weekly dosage of 275 mg/m2 for 4 weeks, and this addition proved advantageous [15]. Although, severe infections were reported in the patients under rituximab treatment, its effect on risk of infection is not clear, as other immunosuppressants were also concurrently used. Reactions during injection are among the most common side effects of rituximab. Deep vein thrombosis (DVT), pulmonary embolism, long-term hypogammaglobu linemia, and neutropenia were also common among the patients under rituximab treatment. Regarding the excellent impact of this drug on treatment of resistant pemphigus, and also on other diseases such as idiopathic thrombocytopenic purpura (ITP), vasculitis, lymphocytic leukemia, systemic lupus erythematosus (SLE), we decided to evaluate the effects of this drug on the variation of lab parameters such as white blood cell (WBC), Hemoglobin (Hg), platelet (Plt), aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, and creatinine (CR). So far, no study has been conducted on investigation of these variations due to receiving rituximab. OBJECTIVES AND HYPOTHESES Major Objective Investigation of laboratory variations after injection of rituximab in pemphigus vulgaris patients. Minor objectives of the project: Determination of rituximab impact on laboratory indices Determination of rituximab impact on laboratory indices by adjusting for the effect of age Determination of rituximab impact on laboratory indices by adjusting for the effect of gender Determination of rituximab impact on laboratory indices by adjusting for the effect of other treatment methods Determination of rituximab impact on laboratory indices by adjusting for the effect of disease duration Determination of rituximab impact on laboratory indices by adjusting for the effect of disease involved sites Determination of rituximab impact on laboratory indices by adjusting for the effect of Underlying disease Application objectives: Enhancement of health level among pemphigus vulgaris patients and paying attention to laboratory effect of patients after rituximab consumption. Research questions or hypotheses: Rituximab affects the laboratory indices Rituximab affects the laboratory indices with age effect adjustment Rituximab affects the laboratory indices with gender effect adjustment Rituximab affects the laboratory indices with disease duration effect adjustment Rituximab affects the laboratory indices with previous treatment effect adjustment Rituximab affects the laboratory indices with other disease effect adjustment Rituximab affects the laboratory indices with involved sites effect adjustment Chapter 2 Literature Review In 1997, rituximab was approved by the US Food and Drug Administration (FDA) as a treatment for non-Hodgkins lymphoma of B-cell that was resistant to chemotherapy. After that, it was applied for treatment for other diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Wegeners granulomatosis, idiopathic thrombocytopenic purpura (ITP), and Sjà ¶grens syndrome. Ten years later, its impact on the treatment of blister diseases such as pemphigus was shown [16]. In a 2006 study by Larrar et al, 2 children with autoimmune hemolytic anemia who were treated with rituximab experienced acute thrombocytopenia and neutropenia [17]. They resolved in several days, which showed that these hematologic effects are directly dependent on the toxicity of rituximab. In a study by Chairwatanatorn et al in 2003, neutropenia following application of rituximab was tested in 53 patients [18]. All patients except one were under Hodgkins lymphoma treatment. Eight cases of grade 4 neutropenia were observed after 1 to 5 months of rituximab treatment (5 patients only received rituximab and 3 patients were also under additional chemotherapy); 3 patients advanced toward sepsis. Neutropenia was not related to other diseases or treatments, and was related with reduction of neutrophil precursors, except for one of the patients whose bone marrow had hypoplasia. All cases of neutropenia occurred among the patients whose polymorphonuclear neutrophils (PMN) were normally or weakly reduced [18]. In a study by Tesfa et al in 2008, neutropenia occurred 4 or more weeks after rituximab treatment in lymphoma patients [19]. However, the mechanism of how rituximab causes neutropenia is still unknown. In a retrospective study of 113 lymphoma patients under rituximab treatment (alone or along with chemotherapy), 8 patients (7%) had neutropenia. The average onset was 88 days after receiving their last dosage of rituximab. The average time interval of neutropenia was 54 days. Four of the 8 patients underwent stem cell transplantation, 3 patients had neutropenia with fever and 2 of them needed granulocyte-colony stimulating factor (G-CSF) treatment. In the patients who had neutropenia, a cessation in maturation was observed in the promyelocytes category (the same as congenital neutropenia or Kostmann disease) [19]. A study by Otrock in 2005 addressed 2 patients who had acute thrombocytopenia after receiving rituximab [20]. One of the patients had hairy cell leukemia and the other one suffered from mantle cell lymphoma. In these patients, thrombocytopenia improved without the need of any treatment after several days. The reason for this is unknown. A study by Leo et al was conducted in 2004 for investigating the safety of rituximab [21]. In this study, the mixture of fludarabine, rituximab and cyclophosphamide was applied for treatment of follicular lymphoma. Surprisingly, severe thrombocytopenia with World Health Organization (WHO) grades 3 and 4 were observed in the patients, which resulted in the end of trial. Cytological and serological analysis was based on direct toxicity of rituximab. Chapter 3 Investigation Method 39 Therapy resistant pemphigus patients in Razi Hospital in Tehran, who had received rituximab from 2008 to 2012 were considered for inclusion in this retrospective cohort study. Data was collected before and after rituximab treatment. The variables included WBC, Hg, Plt, AST, ALT, Urea, and Cr and age, gender, involved sites, previous therapies, underlying disease, and disease duration. Test sheets associated to before and after rituximab application, containing WBC, Hg, Plt, AST, ALT, Urea and Cr were compared. Type of Study This study is a retrospective cohort study conducted on the pemphigus patients resistant to therapies who had received rituximab in 2008-2012. Studied Population Therapy-resistant pemphigus patients who were treated with rituximab in Razi Hospital, Tehran, Iran in 2008-2012. Inclusion Criteria Pemphigus patients who did not respond to the initial therapies (therapy-resistant pemphigus), and then were treated with rituximab. Exclusion Criteria Patients with no required tests before application of rituximab in their file Patients with no follow-up after receiving rituximab Patients whose first follow-up, after the last dosage of rituximab, is greater than 1 month. Sampling Method According to the available files, files of all the patients who had received rituximab from 2008 to 2012 were considered for inclusion. Data Collection The data collection tool included a checklist divided into 2 parts: one for the data before and one for the data collection after rituximab treatment. The variables included WBC, Hg, Plt, AST, ALT, Urea, and Cr and age, gender, involved sites, previous therapies, underlying disease, and disease duration. Project Implementation After studying the files of therapy-resistant pemphigus patients, the patients who had required data in their files were entered into the research. Rituximab treatment was defined as receiving 4 doses of 500 mg for 4 weeks, along with normal saline. Test sheets associated to before and after rituximab application, containing WBC, Hg, Plt, AST, ALT, Urea and Cr were compared. (The maximum time interval between the second test sheet and the last dosage of rituximab could be 1 month.) Data Analysis Finally, the finalized cases that had the inclusion criteria, were analyzed in Stata statistical software (StataCorp, Texas, USA) in terms of variations in WBC, Hg, Plt, AST, ALT, Urea and Cr after application of rituximab as the major variable and investigation of minor variables. Problems and Limitations As the base of this research was on filed files of hospital, inadequacy of data either before or after rituximab application excluded a bunch of samples from the study in a way that among 105 available files, only 39 files had the required data. Variables Major variables: quantitative measurement of white blood cells (WBC), Hemoglobin (Hgb), platelets (Plt), aspartate aminotransferase (AST), ALT, urea, and creatinine (Cr) before and after application of rituximab Minor variables: Gender Age Involved sites Previous therapies Underlying disease Disease duration The data of variables were collected according to the positive findings in the patients files (Table 1). Table 1 Patient variables. Title Variable Type Quantitative Qualitative Scientific Practical Definition Measurement Method Scale Independent Dependent Continuous Discrete Nominal Ranking WBC Number of WBC per ÃŽ ¼(mu)L of blood File reading Cell/mCl Hgb Amount of hemoglobin File reading Gr/dl Plt Number of plackets in patient blood File reading Cell/mcl AST * Amount of AST File reading IU/L ALT Amount of ALT File reading IU/L Urea Microgram of urea per deciliter of blood File reading Mg/dl Cr * Keratin amount File reading Mg/dl age * Years from birth File reading year gender * According to patient phenotype File reading Male/female Underlying disease * Existence of systemic disease File reading Having/not having Previous therapies * Received adjoin before rituximab File reading Azathioprine, IVIG Cyclophosphamide, CellCept ®, methotrexate Involved sites * Involved sites before starting rituximab File reading Upper body, lower body, face. Genitalia, sculp, mucus Disease Duration Months passed from onset to receiving rituximab File reading Month WBC white blood cell, Hgb hemoglobin, Plt platelet, AST aspartate aminotransferase, ALT alanine aminotransferase, CR creatinine, IVIG intravenous immunoglobulin Chapter 4 Results Among 105 therapy-resistant pemphigus patients who received rituximab treatment in Razi Hospital, Tehran, Iran from 2008 to 2012, only 39 patients managed to enter the study. The others were excluded due to inadequate data. Also in the included patient group, the maximum time interval between the last dosage of rituximab and follow-up was 1 month. The data of the remaining 39 patients were analyzed by Stata statistical software (StataCorp, Texas, USA) and the following results were obtained: The age of the patients ranged from 16 to 67 with a mean of 36.46 years. Their disease duration from the beginning of the disease until receiving rituximab ranged from 5 to 84 months with a mean of 39.30 months. Of the patients, 25 (64%) were men and 14 (36%) were women. It does not seem that the sex difference is related to therapy-resistant pemphigus, it is rather associated with the data collection method and exclusion of patients with incomplete files. Investigation of the involved sites showed that 25 patients (64%) had mucosal involvement, 20 patients (51.3%) had upper body involvement, 18 patients (46.2%) had lower body involvement, 19 people (48.7%) had genitalia involvement, 23 people had facial involvement, 36 people (92%) had body involvement, and in 22 patients (56.4%) the scalp was involved. The lab result variations of the mentioned patients were investigated in terms of the involved sites. The patients, before application of rituximab, were simultaneously under treatment with prednisolone and other adjoins. To summarize the unsuccessful treatments, 5 patients had cyclophosphamide, 18 of them received CellCept ® (mycophenolate mofetil), 7 people (17.9%) had intravenous immunoglobulin (IVIG), 5 patients were treated with methotrexate, and 22 patients had azathioprine. All these patients did not respond to corticosteroid and had active disease. In terms of variation in lab test results after receiving rituximab, the patients were investigated in terms of the previous adjuvants as well. Among 9 patients, 12 of them (30.8%) had systemic underlying diseases such as hypertension (HTN), diabetes mellitus (DM), Ischemic Heart Disease (IHD) and many more. The major variables were WBC, Hgb, Plt, AST, ALT, Urea and Cr before and after application of rituximab. Before Receiving Rituximab: The WBC range was 4,000-14,800 with average of 10,092. The Hgb range was 9.1-16.8 with average of 13.8. The Plt range was 100,000-683,000 with an average of 243,384. The AST range was 6-64 with average of 24.56. The ALT range was 10-143 with average of 43.92. The Urea range was 12-145 with average of 37.25. The Cr range was 0.5-1.2 with average of 0.87. After Receiving Rituximab: The WBC range was 5,400-19,000 with average of 9,964. The Hgb range was 7.4-16.7 with average of 13.42. The Plt range was 110,000-440,000 with average of 232,512. The AST range was 10-121 with average of 25.43. The ALT range was 12-144 with average of 48.46. The Urea range was 15-54 with average of 29.12. The Cr range was 0.6-1.2 with average of 0.85. The WBC had no statistically significant variations. The Hgb had no statistically significant variations. The Plt had no statistically significant variations. The AST had no statistically significant variations. The ALT had no statistically significant variations. The Urea had statistically significant variations. The Cr had no statistically significant variations. After receiving rituximab and adjusting for the effect of gender: The WBC had no statistically significant variations. The Hgb had no statistically significant variations. The Plt had no statistically significant variations. The AST had no statistically significant variations. The ALT had no statistically significant variations. The Cr had no statistically significant variations. In the case of Urea, we concluded that it depends on gender, as in men the variation was significant while in women the variations were not statistically significant. When investigating the results with adjustment of the involved sites, the following results were obtained: In patients with lower body involvement, rituximab had no significant effect on WBC, Plt, AST, ALT, Urea and Cr, but it had significant impact on Hgb reduction. In patients whose lower body was not involved, Urea significantly increased after receiving rituximab. In patients whose lower body was involved, rituximab caused a significant reduction in Cr, Urea, and Hgb. In patients whose upper body was not involved, rituximab had no significant effect on the variables. In the patients with or without facial involvement, rituximab had no significant impact on any of the variables. In patients whose genitalia region was involved, rituximab has no significant impact on any of the major variables. In patients with no genitalia involvement, rituximab resulted in significant reduction of urea. In patients with body involvement, rituximab resulted in significant reduction of urea. In patients with scalp involvement, rituximab resulted in significant reduction of urea. The adjustment of previous therapies was also addressed. As all the patients received prednisolone, the effect of adjoins (azathioprine, CellCept ®, cyclophosphamide, IVIG and methotrexate) was addressed: In patients who had received cyclophosphamide, rituximab has no statistically significant impact on the major variables. In patients who had not received cyclophosphamide, rituximab led to statistically significant reduction of urea. In patients who had received CellCept (mycophenolate mofetil), rituximab has statistically significant impact on reduction of urea and WBC. In patients who did not use IVIG adjoin, rituximab had a significant impact on reduction of urea. In patients who did not use methotrexate adjoin, rituximab had significant impact on reduction of urea. In patients who used azathioprine adjoin, rituximab had significant impact on reduction of urea. The adjustment impact of systemic underlying diseases (such as HTN, DM, IHD) was also addressed. In patients with systemic underlying disease, rituximab had significant impact on platelet reduction. In patients with no systemic underlying disease, rituximab had significant impact on urea reduction. There was no statistically significant relationship between the lab test result variations and disease duration and age (Table 1 through Table 8). TABLES Table 1 Age distribution in the studied patients Min Max Standard Deviation Average Age 16 67 13.48 36.48 Table 2 Disease duration distribution in the studies patients Min Max Standard Deviation Average Disease duration 5 84 20.28 29.30 Table 3 Absolute and relative frequency distribution of patients based on their gender Number % Men 25 64.1 Women 14 35.9 Total 39 100 Table 4 Absolute and relative frequency of involved sites at the time of rituximab injection. Frequency % Upper body 20 51.3 Lower body 18 46.2 Face 23 59 Genitalia 19 48.7 Body 36 92.3 Mucus 25 64.1 Scalp 22 56.4 Table 5 Absolute and relative frequency of received adjoins before application of rituximab Frequency % cyclophosphamide 5 12.8 CellCept ® 18 46.2 IVIG 7 17.9 methotrexate 5 12.8 azathioprine 22 56.4 IVIG intravenous immunoglobulin Table 6 Absolute and relative frequency of the patients based on having or not having underlying disease. Frequency