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Thomas T. Tsai,MD

• Cardiology Fellow
• Department of Internal Medicine
• University of Michigan
• Ann Arbor, Michigan

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The mast cell hyperplasia is probably going related to the ontogeny of the neoplastic cell populace. Mast cells are a supply of interleukin-6 that additionally serve to enhance the recruitment of Th17 cells into the infiltrate, one of the key reactive T cells of angioimmunoblastic lymphoma and the probable foundation of the neutrophilia seen in this lymphoma. The inflammatory cell infiltrate in biopsies 490 the Cutaneous Lymphoid Proliferations of angioimmunoblastic lymphoma is taken into account a sequel of a relative state of hypercytokinemia (Tripodo et al. In a gene-profiling research by De Leval and coworkers, the authors found that 90% of the genes defining the angioimmunoblastic lymphoma signature were attributed to non-neoplastic cells related to the humoral immune response, recruitment of inflammatory cells, and genes involved in vascular proliferation. The upregulation of these genes in flip results in the histology of angioimmunoblastic lymphoma. Angioimmunoblastic Lymphadenopathy/Angioimmunoblastic T Cell Lymphoma 491 Case vignettes Case vignette 1 A 32-year-old man offered with scientific options of angioimmunoblastic lymphadenopathy together with lymphadenopathy, hemolytic anemia, and optimistic Epstein�Barr virus serology. Careful inspection under oil immersion (100� objective) magnification reveals a polymorphous and pleomorphic mononuclear cell infiltrate, which obscures the vascular structure. Unlike the case illustrated in Case vignette 3, the immunoblastic cell populace is less conspicuous. A comparable phenomenon could additionally be observed in pores and skin biopsies of patients with angioimmunoblastic lymphadenopathy. There is a diffuse lymphocytic infiltrate with supervening arborizing small blood vessels noted throughout the lymph node. This case serves to emphasize that the skin findings may at instances be nonspecific and resemble a lymphomatoid hypersensitivity response. Angioimmunoblastic Lymphadenopathy/Angioimmunoblastic T Cell Lymphoma 497 Arlet P, Laroche M, Delsol G, Seigneuric G, Duffaut M, Le Tallec Y. Multiple cutaneous monoclonal B-cell proliferations as harbingers of systemic angioimmunoblastic T-cell lymphoma. Angioimmunoblastic lymphadenopathy with dysproteinemia following doxycycline administration. Skin lesions in angioimmunoblastic lymphadenopathy: histological and immunological research. Survival and clonal growth of mutating "forbidden" (immunoglobulin receptor-deficient) Epstein�Barr virus-infected B cells in angioimmunoblastic T cell lymphoma.

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Overall, totally different sorts of medications and therapies are available for the management of pulmonary infections, however in case of some pulmonary infections current therapies and therapies showed sure limitations, which are briefly discussed right here. Consequently, unnecessary and prolonged exposure to antimicrobial brokers adversely have an result on affected person outcomes, whereas inappropriate and uncontrolled use of antibiotic remedy increases chance of antibiotic resistance. According to Murdoch,12 the role of microbiological testing strategies used for the analysis and management of lower respiratory tract an infection continues to be debated. There are many limitations of microbiology laboratories to perform the traditional diagnostic checks for pulmonary infections. The tradition based mostly strategies which are presently used are slow, insensitive, could not distinguish colonization from infection and could also be influenced by previous antimicrobial used. The lack of efficacy of antibiotics and the lower in their capability to struggle pulmonary infections in susceptible patients is a matter of great concern. Nanotechnology based remedy methods and drug delivery strategies will help to ship drug molecules on the particular web site of infection. These nanoscale effects have been exploited virtually in every area of technology, and include commercial functions in energy conversion, textiles, cosmetics, electronics, water purification, lubricants, computing and much more. Moreover, many biological processes, corresponding to, immune recognition and passage across organic limitations are additionally ruled by dimension concerns. According to Buxton61 delivery of therapeutics by inhalation provides a possibility for direct transport of drug to the lung epithelium of the respiratory tract. The software and innovation of nanotechnology within the subject of medication is called "nanomedicine. The use of nanoparticles in the field of medication opens new prospects and provides new strategies for therapy of illnesses. Various forms of nanoparticles are utilized in medication to treat diseases, similar to, infectious diseases, viral, bacterial, respiratory tract illnesses, and so on. However, lately scientists may develop promising nanocarriers for treatment of diseases that affect respiratory tract.

Diseases

• Atrophoderma
• Occupational asthma - animals, insects and fungi
• Anophthalmia megalocornea cardiopathy skeletal anomalies
• Hypogonadism
• Leucinosis
• Adrenocortical carcinoma
• Hereditary type 1 neuropathy

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The reported case was an adolescent lady who introduced with isolated disease involving the pores and skin and without subsequent extracutaneous dissemination (Liu et al. One additional case was reported in a 35-year-old Chinese lady who introduced with a 2. She succumbed to her disease within eleven months of starting chemotherapy (Zhang et al. We had an extra case in a youthful male with hanging nasal and lip involvement. Light microscopic findings the infiltrates assume an effacing sample with pandermal involvement and a distinct grenz zone of papillary dermal sparing with an uninvolved epidermis. The actual definition is one of a granular lymphocytosis greater than 2000/L lasting for greater than 6 months. In one recent examine, the mean age of sufferers with persistent granular lymphocytosis was 60 years and the imply duration of disease was fifty nine months. Of curiosity was an association with recurrent bacterial an infection within the majority of these patients and the truth that over 50% of them had classic autoimmune stigmata, underlying solid visceral malignancy or other causes of immune dysfunction. While splenomegaly was frequent, different scientific stigmata, including lymphadenopathy, pores and skin involvement and sort B symptoms had been unusual (Chan et al. Frequent hematologic abnormalities included neutropenia and anemia, and in lower than half of instances, significant peripheral blood lymphocytosis. Antinuclear cytoplasmic antibodies, antinuclear antibodies, and polyclonal hypergammaglobulinemia were among the frequent serologic abnormalities. Four of eight patients had a further malignancy; none had a history of rheumatoid arthritis, lymphadenopathy or hepatosplenomegaly. However, we encountered one case where the lymphocytes assumed an virtually orderly growth sample around nerves, blood vessels, and the eccrine coil, recapitulating a reactive process. However, one would speculate that these tumors might categorical killer inhibitor receptors. Histologically the entire different scientific displays seem comparable, displaying a necrotizing angiocentric lymphomatoid vascular response. In addition, in a big percentage of cases, a larger centroblastoid morphology predominates, extra so than in cases afflicting younger sufferers. There may be a link with light sensitivity and an aberrant immune response to mosquitos.

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In three patients with S�zary syndrome-like presentations, two sufferers had an aggressive and lethal scientific course, while the opposite patient achieved remission with prednisone and chlorambucil (Pascual et al. The most typical of the T cell lymphoproliferative disorders is anaplastic giant cell lymphoma; the prognosis is variable. Patients can have an aggressive medical course, whereas others have achieved remission (Kaplan et al. In our own expertise, one affected person achieved remission while another affected person died shortly after prognosis of unrelated causes. In contrast, primary cutaneous anaplastic giant cell lymphoma not associated with strong organ transplantation has a really favorable prognosis (Bekkenk et al. Overall, while the literature precedent is restricted, it will seem that T cell lymphoproliferative illness in the setting of stable organ transplantation does comply with a more aggressive clinical course in comparison with the T cell counterpart within the nontransplanted host. Methotrexate-associated lymphoproliferative disease We have encountered a quantity of circumstances of primary cutaneous B cell lymphoma in the setting of methotrexate remedy. The commonest lymphoproliferative disease related to methotrexate therapy is diffuse massive B cell lymphoma. Partial regression and/or spontaneous decision of lymphoma after withdrawal of the immunosuppression is often reported, once more signifying a job for methotrexate in tumor formation (Theate et al. Patients with rheumatoid arthritis have additionally developed lymphoma within the setting of cyclosporine and penicillamine remedy (Kamel et al. Responses to intralesional interferon- and spontaneous remission have been reported, although nearly all of the cutaneous circumstances had more diffuse illness requiring polychemotherapy (Martin et al. Light microscopic findings In the majority of circumstances one observes a polymorphous infiltrate. There are varying numbers of Hodgkin- and Reed�Sternberg-like big cells that might be diagnostically challenging with regard to distinguishing it from Hodgkin lymphoma.

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Antimicrobial prescription is affected by acutely unwell patient populations, diagnostic uncertainty, a scarcity of appreciation for the potential harms of antimicrobials, and prescribing by clinically inexperienced physicians in training. The empirical prescription behavior of trainees could be formed by the practices of senior physicians, who rely on experience and often think about themselves exempt from evidence-based pointers. To limit inappropriate empirical prescriptions of broad-spectrum agents, interventions can embrace: the direct education supplier; selective formulary restriction; development, dissemination, and enforcement of evidence-based therapeutic tips; preprinted order sheets; and use of an audit and suggestions program. These strategies are necessary instruments which are out there to institutional antimicrobial stewardship applications to improve rational empirical antibiotic prescribing. Pharmacological treatment: the etiology of acute bronchitis is almost completely viral, so the treatment must be symptomatic, aiming to guarantee respiratory comfort and removing of secretions. The Cochrane Review from 2014 acknowledged: There is proscribed proof to assist the use of antibiotics in acute bronchitis. Antibiotics might have a modest useful effect in some patients such as frail, aged individuals with multimorbidity who might not have been included in trials to date. However, the magnitude of this profit must be considered within the broader context of potential side effects, medicalization for a self-limiting situation, increased resistance to respiratory pathogens and value of antibiotic therapy. Children with anatomic pulmonary abnormalities or neuromuscular dysfunction: Infants with neuromuscular disease or congenital anomaly that impairs the power to clear secretions from the upper airway due to ineffective cough are recognized to be in danger for a chronic hospitalization associated to lower respiratory tract infection, and therefore, could also be thought-about for prophylaxis in the course of the first yr of life. The regular microbiota is considered as containing invaluable allies in combating microbial pathogenesis by defending niches against new microbial opponents and sustaining the species range that impedes virulence. A contemporary approach could be to revise the operational definition of essentiality so that it extra precisely displays the biological reality: Which genes are essential to the pathogen in vitro under circumstances which are relevant within the host Which genes are essential to the pathogen in particular host environments, including polymicrobial communities on epithelial surfaces, where the microorganism of interest could characterize a comparatively minor planktonic inhabitants, in monomicrobial populations deep in tissues In the identical work, they identified eleven peer-reviewed, randomized scientific trials, which include a total of 2417 youngsters as much as 10 incomplete years of age. In their evaluation of these research, the reduction in new episodes of disease was a positive consequence for the utilization of probiotics in the therapy of respiratory infections in youngsters. It is noteworthy that most of these research had been carried out in developed nations with fundamental sanitation, well being care and strict, well-established, and well-organized pointers on the usage of probiotics. They concluded that the encouraging results-that is, reducing new episodes of respiratory infections-emphasize the necessity for further analysis, especially in developing countries, the place charges of respiratory infections in youngsters are greater when in comparability with the excessive per capita-income international locations recognized.

Syndromes

• In girls, the ovaries begin to increase production of estrogen and other female hormones.
• It can help your doctor decide which treatments you need next.
• Toddler formulas are offered as added nutrition for toddlers who are picky eaters. To date, they have not been shown to be better than whole milk and multivitamins. They are also expensive.
• Preschoolers are highly mobile and able to quickly get into dangerous situations. Parental supervision at this age is essential, just as it was during the earlier years.
• Poor appetite
• Good oral hygiene is important. Brush your teeth thoroughly at least twice a day and floss at least once a day.
• Breathing tube
• Thickening or lump in the breast or elsewhere
• Didanosine (Videx)

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Inherited mutations in several genes lead to alterations in the intracellular oxygen sensing pathway. The extent of these physiological changes has not been totally characterised but seems to range according to the specific genetic mutation. It is Molecular genetics of the myeloproliferative neoplasms 107 thought the associated myelofibrosis is the outcome of leakage or hypersecretion of pro-fibrotic components from bone marrow megakaryocytes. Patients normally current with bleeding or straightforward bruising, whereas others are found by the way; however, presentation with established myelofibrosis might occur. The medical utility of testing for mutations in transcriptional regulation pathways is presently not nicely defined. In addition, mutations 108 Chapter 2 in these genes have been detected in patients with apparently regular haematopoiesis. Loss of this area leads to constitutive kinase activity of the chimeric oncoprotein. An improve in bone marrow mast cells is also a standard function and occasional instances meet diagnostic criteria for systemic mastocytosis. Of observe, blastic-phase illness may be characterised by a myeloid or lymphoid phenotype and will current with leukaemia or lymphoma. Clinical manifestations 116 Chapter 2 are heterogeneous and embrace pores and skin rashes, symptoms associated to the discharge from mast cells of vaso-active mediators (hypotension/syncope, diarrhoea, flushing and anaphylaxis) and end-organ damage as a outcome of tissue infiltration (bone marrow failure, bone destruction, liver failure, splenomegaly with hypersplenism and gastrointestinal malabsorption). Organ failure is the principle source of morbidity and mortality, although a minority of sufferers develop acute leukaemia. In any given patient, nevertheless, the illness phenotype is often constant over time. The presence of mutations affecting transcriptional management pathways has been reported to predict elevated disease severity and reduced total survival;171,172 nonetheless, all research to date have included small numbers of sufferers and the medical utility of these findings stays uncertain. Leukaemic transformation is likely driven by the Molecular genetics of the myeloproliferative neoplasms 119 acquisition of additional genetic events, though the small print of these events are at present unknown. The pattern of infiltrating mast cells in the pores and skin, bone marrow and other tissues could also be difficult to distinguish morphologically from acquired neoplastic mast cell illness. Melting curve analysis has the advantage of potential sensitivity to rarer mutations affecting D816 or adjoining amino acids. Results from scientific trials, however, have been disappointing and newer molecules with improved activity are under growth.

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Combined use of the modified Hodge take a look at and carbapenemase inhibition take a look at for detection of carbapenemase producing Enterobacteriaceae and metallo-beta-lactamase producing Pseudomonas spp. Evaluation of phenotypic exams for detection of metallo-betalactamase producing Pseudomonas aeruginosa strains in China. Detection of Pseudomonas aeruginosa producing metallo-beta-lactamases in a big centralized laboratory. Evaluation of phenotypic screening checks for carbapenemase production in Pseudomonas aeruginosa from patients with cystic fibrosis. This infection is transmitted immediately with out contact, via coughing by micro-droplets of saliva (fl�gge) that transport the bacterium, which are discovered contained in the airways of people with active tuberculosis. Virulence elements of Mt are answerable for its survival inside of the human physique and in addition for most of the deleterious effects on the host. After beating the immune system, Mt replicates slowly but continuously within the lungs until the incidence of the primary signs, which marks the beginning of active tuberculosis. This proof of coevolution with the bacterium was found through studies of paleopathology in the stays of an roughly 1-year-old child found near the Mediterranean Sea. However, the increase of morbidity is bigger than the the Microbiology of Respiratory System Infections. The distal ends of the arabinogalactan are esterified with fatty acids of heavy molecular weight, termed mycolic acids, which have a size and a singular construction for mycobacteria. The illness brought on by the bacilli is set by the immune status of the host and factors of virulence within the micro organism. Upon entering the physique, Mt is in a position to survive the assault of macrophages, blocking the acidification of the phagosome (through the manufacturing of ammonia), which is crucial within the formation of the phagolysosome and the activation of the bactericidal factors launched through the merger. An alternative bacterial mechanism to avoid its destruction within the phagolysosome consists of blocking the oxidative phosphorylation course of and suppressing the manufacturing of reactive Oxygen and Nitrogen species by means of a sulfated glycolipid from the bacterial wall called sulfolipid 1. The absence of Erp in mutant strains decreases the replication of the micro organism within macrophages. For this reason, in Mt mutant strains for the gene encoding this protein, similar effects were observed as these described above. The importance of Mt progress inside phagocytes is highlighted by the enzyme fibronectin binding protein mycolytransferase and its important part in the synthesis of mycolic acid, as attenuated progress phenotypes had been noticed in human monocytes and murine macrophages when inoculated with gene faulty strains coding for this enzyme.

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Simple measures similar to hand washing, early isolation of patients suspected to have infection, limiting visitors during endemic seasons, and limiting affected person contact with symptomatic healthcare personnel or visitors are very efficient preventative measures towards these infections. In latest years there have been necessary advances within the prognosis and management of these infections. More research is needed to prevent and decrease the severity and period of immunosuppression. The field of respiratory issues in immunosuppressed sufferers is an thrilling every body indications are that the future will hold more success. Risk components and consequence beneath empirical antimicrobial remedy in a randomized multicenter research. Suppressed neutrophil operate as a threat factor for extreme infection after cytotoxic chemotherapy in sufferers with acute nonlymphocytic leukemia. Defective cytostatic activity of pulmonary alveolar macrophages in main lung cancer. Risk components for bacterial pneumonia after cytotoxic chemotherapy in advanced lung most cancers sufferers. Outbreak of Stenotrophomonas maltophilia bacteremia in allogeneic bone marrow transplant patients: role of extreme neutropenia and mucositis. Blood stream an infection after hematopoietic stem cell transplantation is associated with elevated mortality. Stenotrophomonas maltophilia: altering spectrum of a severe bacterial pathogen in sufferers with cancer. Clinical and microbiological epidemiology of Streptococcus pneumoniae bacteremia in cancer sufferers. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcareassociated pneumonia. Clinical features of Stenotrophomonas maltophilia pneumonia in immunocompromised sufferers. Extrapulmonary tuberculosis active infection misdiagnosed as cancer: Mycobacterium tuberculosis illness in patients at a Comprehensive Cancer Center (2001�2005). Risks and outcomes of invasive fungal infections in recipients of allogeneic hematopoietic stem cell transplants after nonmyeloablative conditioning. Nivoix Y, Velten M, Letscher-Bru V, Moghaddam A, Natarajan-Am� S, Fohrer C, et al.

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Role of human herpesvirus 8 interleukin-6-activated gp130 sign transducer in primary effusion lymphoma cell development and viability. The dermatopathologic manifestations of hepatitis C infection: a scientific, histological, and molecular evaluation of 35 instances. Cutaneous marginal zone lymphomas have distinctive features and embrace 2 subsets. Primary cutaneous marginal zone B-cell lymphoma with anetoderma: spontaneous involution plus de novo clonal growth. Disseminated cutaneous plasma-cytomas treated with complete pores and skin electron radiotherapy. Cytogenetic and molecular delineation of a area of chromosome 3q commonly gained in marginal zone B-cell lymphoma. Primary cutaneous B-cell lymphoma and Borrelia burgdorferi infection in patients from the Highlands of Scotland. Primary cutaneous B-cell lymphoma: a medical, histological, phenotypic and genotypic research of 21 instances. Marginal Zone Lymphoma and Other Related Post Germinal Center B Cell Lymphoproliferative Disorders of the Skin 167 Guitart J, Deonizio J, Bloom T, et al. High incidence of gastrointestinal tract issues and autoimmunity in main cutaneous marginal zone B-cell lymphomas. Primary cutaneous marginal zone B-cell lymphoma: clinical and therapeutic options in 50 instances. Cell floor phenotype, cytokines, and antibody gene expression in immortalized human B cell traces. Tumor-infiltrating T cells in primary cutaneous B-cell lympho-proliferative problems. Cutaneous manifestations of B-cell continual lymphocytic leukemia related to Borrelia burgdorferi an infection showing a marginal zone B-cell lymphoma-like infiltrate.

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In any given case of diffuse large B cell lymphoma of the pores and skin, a previous history of documented cutaneous and/or extracutaneous lymphoma together with the phenotypic profile can permit reliable classification in most cases. Both share bcl-6 positivity and in a minority of instances of follicle middle cell lymphoma, the neoplastic cells do express bcl-2. When one considers main cutaneous diffuse massive B cell lymphomas it will seem that the majority fall into the leg type versus the follicle center categories (Pham-Ledard et al. As with other forms of cutaneous lymphoma, the extent of illness influences prognosis. Patients who current with solitary or few lesions have a significantly better prognosis than those who current with a number of lesions. Five-year survival price is variable, however has been reported to be as little as 51% in the leg-type lymphoma group versus 95% for follicle middle lymphomas with a diffuse giant B cell morphology (Fernandez-Vazquez et al. The exception could be blastic marginal zone lymphoma, which is of post germinal center cell origin (Koyama et al. As with different types of major cutaneous B cell lymphoma, these tumors generally tend to recur. In one examine, only 18% of all cases of diffuse giant B cell lymphoma localized to the top and neck space recurred, whereas the lower extremity lesions manifested a recurrence fee of over 50% during a median follow-up of 72 months, probably reflecting the upper proportion of head and neck lymphomas being of the follicle center type, whereas there was most likely a disproportionate variety of lymphomas from the decrease leg that had been phenotypically in keeping with the leg type of diffuse large B cell lymphoma (Hembury et al. The values with regard to recurrences for the lower extremity cases is most likely not representative, as the numbers on this study have been low. Diffuse giant B cell lymphoma has been reported to recur as an angiotropic giant B cell lymphoma (Kamath et al. A biopsy was performed and held to be compatible with a diagnosis of primary cutaneous large cell lymphoma, leg sort. Diffuse massive cell lymphoma of the skin has emerged as a distinctive entity with a biological conduct based on the anatomic site and specific aspects of the phenotypic profile. The patient is a 70-year-old man who developed a progressively enlarging fun- gating mass on the upper again over a 4-year period. The biopsy was diagnostic of a bcl-2-negative, bcl-6-positive diffuse massive cell lymphoma consistent with a diffuse massive cell variant of main cutaneous follicle heart lymphoma. The infiltrate is either composed of a combination of small and enormous cells, with no less than 30% of the infiltrate being of large cell type, or virtually totally one comprising giant cells.

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Esiel, 29 years: Bcr-Abl effectively induces a myeloproliferative disease and manufacturing of excess interleukin-3 and granulocyte�macrophage colony-stimulating think about mice: a novel mannequin for continual myelogenous leukemia. Precursor Lesions of Cutaneous T Cell Lymphoma 113 Case vignette 5 the affected person is a 30-year-old man with indurated plaques on the face. Although neoplasia is incessantly suspected in cases of mediastinal masses, several nonneoplastic situations also affect the mediastinum and may mimic neoplasms. Cytogenetics From a pathogenetic perspective, basic Hodgkin lymphoma is quite totally different from lymphocytepredominant Hodgkin lym phoma.

Giores, 52 years: Obstruction, superior vena cava, 110�113 - diagnostic guidelines, 112 - differential diagnosis, 111�112 Obstructive atelectasis, ninety one Occlusion - brachiocephalic vein, superior vena cava obstruction vs. Therefore, it was proposed that aerosolized supply of amikacin is a promising adjunct to standard remedy for pulmonary nontuberculous mycobacterial infections. These observations are in direct distinction to those by Abel and coworkers, the place they reported an affiliation between the atopic diathesis and the development of both leukemic and nonleukemic erythrodermic T cell lymphoma (Abel et al. Unlike idiopathic lichen planus, parakeratosis, eosinophils, and plasma cells are frequently current, and deeper perivascular extension is the rule (Magro and Crowson 2000; Crowson et al.

References

• Lotspeich-Steininger CA. Anemias of abnormal nuclear development. In: Steine-Martin EA, Lotspeich- Steininger CA, Koepke CA, eds. Clinical Hematology: Principles, Procedures and Correlations, 2nd ed. Philadelphia: Lippincott, 1998; 156.
• Myles PS, Hunt JO, Holdgaard HO, et al: Clonidine and cardiac surgery: Haemodynamic and metabolic effects, myocardial ischaemia and recovery, Anaesth Intensive Care 27:137-147, 1999.
• Hillman MA, Wilke RA, Yale SH, et al. A prospective, randomized pilot trial of model-based warfarin dose initiation using CYP2C9 genotype and clinical data. Clin Med Res 2005;3:137-145.
• Scher HI, Halabi S, Tannock I, et al: Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group, J Clin Oncol 26:1148n1159, 2008.
• Mofi di R, Suttie SA, Patil PV, et al. The value of procalcitonin at predicting the severity of acute pancreatitis and development of infected pancreatic necrosis: systematic review. Surgery. 2009;146(1):72-81.
• Cavicchi M, Beau P, Crenn P, et al: Prevalence of liver disease and contributing factors in patients receiving home parenteral nutrition for permanent intestinal failure. Ann Intern Med 132:525, 2000.