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However purchase cefuroxime 250 mg mastercard medicine quiz, in niae (pneumococcus) or Haemophilus influenzae buy genuine cefuroxime treatment wax, mostly type b neonates and young infants discount cefuroxime line medications 3605, Gram-negative pneumonia is not (Hib) cheap 500mg cefuroxime free shipping treatment 4 letter word, and occasionally by Staphylococcus aureus or other strep- uncommon (Quiambao forthcoming). Just 8 to 12 of the many types of pneumococcus cause Viruses are responsible for 40 to 50 percent of infection in most cases of bacterial pneumonia, although the specific types infants and children hospitalized for pneumonia in developing may vary between adults and children and between geographic countries (Hortal and others 1990; John and others 1991; locations. Their viruses, influenza type A virus, and adenoviruses are the most role as a cause of severe disease in children under five in devel- important causes of viral pneumonia. Simoes, Thomas Cherian, Jeffrey Chow, and others In developing countries, the case-fatality rate in children 34 percent, much higher than the 5 to 10 percent for children with viral pneumonia ranges from 1. Pneumocystis jirove- mixed viral and bacterial infections from 16 to 18 percent ci and cytomegalovirus are important opportunistic infections (Ghafoor and others 1990; Shann 1986). Patient studies have confirmed the frequent association chest wall indrawing, fever in one-third of cases, and wheezing of these bacteria but added S. Inflammatory obstruction of the important pathogens (Gilks 1993; Goel and others 1999). The small airways, which leads to hyperinflation of the lungs, and first South African report on the overall burden of invasive collapse of segments of the lung occur. The first two fall within olitis include parainfluenza virus type 3 and influenza viruses. The effects of measles, diphtheria, and pertus- influenza as a cause of death in children is unknown. The limited data on virus type A may cause seasonal outbreaks, and type B may influenza in developing countries do not permit detailed cause sporadic infection. Recently, avian influenza virus has analysis of the potential benefits of that vaccine. This chapter, caused infection, disease, and death in small numbers of indi- therefore, focuses on the potential effects of Hib and pneumo- viduals, including children, in a few Asian countries. Currently three Hib conjugate vaccines are avail- oping countries (Peiris and others 2004) and could pose a able for use in infants and young children. New strains of type A viruses will vaccine in preventing invasive disease (mainly meningitis, but almost certainly arise through mutation, as occurred in the case also pneumonia),has been well documented in several studies in of the Asian and Hong Kong pandemics in the 1950s and industrialized countries (Black and others 1992; Booy and oth- 1960s. The easily measured effect is on invasive dis- negative children) (Black and others 2000; Cutts and others ease, including bacteraemic pneumonia. In Bangladesh, Brazil, Chile, incidence of all invasive pneumococcal disease in this age group andthe Gambia, Hib vaccine has been associated with a reduc- had declined by 69 percent and disease caused by the serotypes tion of 20 to 30 percent in those hospitalized with radiograph- included in the vaccine and related serotypes had declined by ically confirmed pneumonia (de Andrade and others 2004; 78 percent (Whitney and others 2003). A slight increase in rates of invasive disease caused by were inconclusive with regard to the effect of Hib vaccine on serotypes of pneumococcus not included in the vaccine was pneumonia (Gessner and others 2005). Three studies have evaluated of this vaccine show no significant efficacy (Douglas and Miles the effect of the vaccine on radiographic pneumonia (irres- 1984; Sloyer, Ploussard, and Howie 1981), studies from Finland pective of the etiological agent) and have shown a 20. Even though the vaccine resulted in a significant ride vaccine in children in developing countries are a series of reduction in culture-confirmed pneumococcal otitis, no net three trials conducted in Papua New Guinea (Douglas and reduction of ear infection was apparent among vaccinated chil- Miles 1984; Lehmann and others 1991; Riley and others 1981; dren, probably because of an increase in the rates of otitis Riley, Lehmann, and Alpers 1991). On the basis California showed that the vaccine had a protective effect of these and other studies, the investigators concluded that the against frequent ear infection and reduced the need for tympa- vaccine had an effect on severe pneumonia. Thus, a expected efficacy in these trials was attributed to the greater vaccine for ear infection may be beneficial in developing coun- contribution of the more immunogenic adult serotypes in tries with high rates of chronic otitis and conductive hearing pneumonia in Papua New Guinea (Douglas and Miles 1984; loss and should be evaluated by means of clinical trials. Although the primary outcome inthe Gambia trial 486 | Disease Control Priorities in Developing Countries | Eric A. Simoes, Thomas Cherian, Jeffrey Chow, and others was initially child mortality, it was changed to radiological others 1992). Nevertheless, the trial showed a 16 percent Byass, and others 1989; Kolstad and others 1997; Perkins and (95 percent confidence level, 3 to 38) reduction in mortality. This trial demonstrates 40 breaths per minute for children age 12 months to 5 years. Antibiotic treatment of children with rapid breathing has been shown to reduce mortality (Sazawal and Black 2003). The problem of the low specificity of the rapid breathing criterion Case Management is that some 70 to 80 percent of children who may not needthe simplification and systematization of case management for antibiotics will receive them. Children with (antibiotics administered by other than oral means) are needed audible stridor when calm and at rest or such danger signs of or when they lack confidence in mothers’ ability to cope. Children whothe Papua New Guinea study (Shann, Hart, and Thomas have a cough for more than 30 days are referred for further 1984) used chest wall indrawing as the main indicator of sever- assessment of tuberculosis and other chronic infections. Restriction of the term to lower chest wall indrawing, guidelines for detecting pneumonia based on rapid breathing defined as inward movement of the bony structures of the chest were developed in Papua New Guinea during the 1970s. In a wall with inspiration, has provided a better indicator of the study of 200 consecutive pediatric outpatients and 50 consecu- severity of pneumonia and one that can be taught to health tive admissions (Shann, Hart, and Thomas 1984), 72 percent of workers. It is more specific than intercostal indrawing, which children with audible crackles in the lungs had a respiratory frequently occurs in bronchiolitis. Chest indrawing was present in 62 percent of these approach, which could miss 25 to 40 percent of cases of pneu- cases, many with intercostal indrawing. A study in Vellore, India, found that sensitivity could chest indrawing were hospitalized, the numbers would over- be improved by lowering the threshold to 40 for children age 1 whelm pediatric inpatient facilities. Acute Respiratory Infections in Children | 487 Antimicrobial Options for Oral Treatment of Pneumonia. There is no evidence that intramuscu- the well-established finding that most childhood bacterial lar chloramphenicol succinate is more likely to produce side pneumonias are caused by S. Therefore, higher doses high sensitivity for detecting hypoxemia, a good number of than in the past—given twice a day—are now being used to hypoxemic children would still be missed using these criteria. The situation with co-trimoxazole is less clear recurring costs for replacing probes, for which reasons they are (Strauss and others 1998), and in the face of high rates of co- not available in most district or even referral hospitals in devel- trimoxazole resistance, amoxicillin may be superior for chil- oping countries. Current recommendations are for co- Intramuscular Antibiotics for Treatment of Severe trimoxazole twice a day for five days for pneumonia and intra- Pneumonia. Even though chloramphenicol is active against muscular penicillin or chloramphenicol for children with severe both S. One study additional rationale is that extremely sick children may have indicated that amoxicillin and co-trimoxazole are equally effec- sepsis or meningitis that are difficult to rule out and must be tive for nonsevere pneumonia (Catchup Study Group 2002), treated immediately. Although intravenous chloramphenicol is though amoxicillin costs twice as much as co-trimoxazole. With superior to intramuscular chloramphenicol, the procedure can respect to the duration of antibiotic treatment, studies in delay urgently needed treatment and adds to its cost. Bangladesh,India,and Indonesia indicate that three days of oral Investigators have questioned the adequacy and safety of co-trimoxazole or amoxicillin are as effective as five days of intramuscular chloramphenicol. Although early studies sug- either drug in children with nonsevere pneumonia (Agarwal gested that adult blood levels after intramuscular administra- and others 2004; Kartasasmita 2003). In a multicenter study of tion were significantly less than those achieved after intra- intramuscular penicillin versus oral amoxicillin in children with venous administration, the intramuscular route gained severe pneumonia, Addo-Yobo and others (2004) find similar wide acceptance following clinical reports that confirmed its cure rates. Local complications of intramuscular chlorampheni- needed for hypoxemia and were switched to other antibiotics if col succinate are rare, unlike the earlier intramuscular prepara- the treatment failed, this regimen is not appropriate for treating tions. Although concerns about aplastic anemia following severe pneumonia in an outpatient setting. Oxygen should countries are expected to be substantially lower when vaccines be administered at a rate of 0.

One of the more intriguing aspects of antibacdrug target order cefuroxime paypal treatment kidney cancer, we eventually might be able to search for terial therapies is that not all bacterial species respond meaningful network homologues among species in 432 | juNe 2010 | vOluMe 8 www cefuroxime 250 mg discount schedule 8 medicines. Network-based efforts could also lead to the Drug-resistant bacterial infections are becoming more cationic peptide that has development of species-specific treatments purchase cefuroxime amex treatment 2 prostate cancer, includprevalent and are a major health issue facing us today 500mg cefuroxime with amex symptoms 7 days past ovulation. The comful in the study of non-classical antibacterial agents plex effects of bactericidal antibiotics discussed in this that induce cell death. Antimicrobial peptides are short Review provide a large playing field for the developcationic peptides that are thought to kill through ment of new antibacterial compounds, as well as adjuinteractions with the membrane that result in pore vant molecules and synthetic biology constructs, that formation134,135. However, the mode of action of many could enhance the potency of current antibiotics. It antimicrobial peptides could, in fact, be more complex, will be important to translate our growing understandand cell death networks uncovered for existing antiing of antibiotic mechanisms into new clinical treatbiotics could be used as mechanistic templates to study ments and approaches so that we can effectively fight cellular responses induced by antimicrobial peptides. Gyrase inhibitors induce an oxidative damage fluoroquinolone antibiotics in Gram?negative e176 (2005). Nature 427, 72–74 activation of the superoxide stress response and 377–392 (1997). Contribution of reactive oxygen species to pathways of activation trigger antibiotic-mediated cell death. Shows that systems which facilitate membrane analogous regions of gyrA and parC in 39. Cell resistance in a bacterium with suppressed autolytic protective reaction to transpeptidase inactivation 104, 901–912 (2001). Describes the intricacies of binding between Shows for the first time that ??lactam?induced cell 82. Escherichia coli W7 and its consequences on but is necessary for interaction with rifampicin. Two bactericidal targets for penicillin in pneumococci: inhibition of the first peptide bond formation. Rifampin: mechanisms of action and autolysis-dependent and autolysis-independent killing Chem. Emergence of vancomycin tolerance in B reveals the nascent peptide exit path in the ribosome. The biological role of death and lysis in Describes the results of detailed studies that similarity to acyl-D-alanyl-D-alanine. Distinct penicillin binding proteins while the genetic code was first being deciphered. Dissociation rate of inhibition of cell wall biosynthesis by ??lactams is Escherichia coli K12. Diverse paths to bacteriostatic action of chloramphenicol against 126, 8122–8123 (2004). Streptomycin accumulation of Escherichia coli transcriptional regulation from a activities of antimicrobial cationic peptides. A predictive model for Multicomponent therapeutics for networked Discusses the role of respiration in the uptake of transcriptional control of physiology in a free living systems. Assigning numbers to the arrows: parameterizing a Drug interactions and the evolution of antibiotic 106. Uptake of 14C-streptomycin by some gene regulation network by using accurate resistance. Hydroxyurea induces hydroxyl targeting gene networks as adjuvants for antibiotic Chem. Microbiol 12, 482–489 We thank the anonymous reviewers for their helpful com114. This work was supported by the signatures to elucidate mechanisms of antibiotic 129. Endogenous nitric oxide protects bacteriathe authors declare no competing financial interests. Science 325, off?target effects that contribute to drug?induced cell 1380–1384 (2009). Genetic basis for activity Escherichia coli|Neisseria meningitidis|Pseudomonas 116. The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. All reasonable precautions have been taken by the World Health Organization to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either expressed or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall the World Health Organization be liable for damages arising from its use. It represents one of the biggest threats to global health today, and can affect any one, of any age, in any country. Antibiotic resistance occurs naturally, but misuse of antibiotics in humans and animals is accelerating the process. This survey provides a snapshot of current public awareness and common behaviours related to antibiotics in a range of countries. Both these actions can result in improper use of antibiotics, and therefore contribute to the resistance problem. Respondents in Sudan, Egypt and China were particularly likely to state that they should stop taking antibiotics when they feel better, with 62%, 55% and 53% of survey participants respectively choosing this response. The majority of respondents across the 12 countries surveyed correctly identify conditions such as bladder/urinary tract infections (72%) and skin/wound infections (72%) as treatable with antibiotics. However, the majority also incorrectly believe that viruses such as colds and flu (64%) can be treated with antibiotics. However, 57% state that there is not much that people like them can do to stop antibiotic resistance, when in fact, everyone can be part of the efforts to address this problem. The general public can help by: o preventing infections by regularly washing hands, practicing good food hygiene, avoiding close contact with sick people and keeping vaccinations up to date o only using antibiotics when prescribed by a certified health professional o always taking the full prescription o never using left-over antibiotics o never sharing antibiotics with others. The majority of respondents across the 12 countries included in the survey correctly believe that many infections are becoming increasingly resistant to treatment by antibiotics (72%). However, a majority also believe, incorrectly, that antibiotic resistance occurs when their body becomes resistant to antibiotics (76%), whereas in fact bacteria, not humans, become antibiotic resistant. These bacteria may then infect humans and the infections they cause are harder to treat than those caused by non-resistant bacteria. Further evidence of misunderstanding is suggested by the fact that 44% of respondents think that antibiotic resistance is only a problem for people who take antibiotics regularly. A total of 9,772 respondents from 12 countries completed the 14 question survey, either online or during face-to-face street interviews, depending on the appropriate methodology to gather a representative sample of adults for that country.

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This includes public areas such as lobbies; offices; corridors; elevators and stairwells; and service areas purchase generic cefuroxime symptoms 32 weeks pregnant. Areas designated as part of the hotel component are cleaned with a hotel clean regimen purchase cefuroxime with visa treatment whooping cough. Health care clean is an approach to cleaning that aims to reduce or eliminate microbial contamination 5 within the environment cheap 250 mg cefuroxime fast delivery medicine wheel colors. A health care clean should result in the elimination of generic cefuroxime 500 mg fast delivery treatment 1 degree burn, or a significant reduction in, microbial contamination of all surfaces and items within the environment, in addition to providing a visually clean environment. This requires, in addition to the performance of a hotel clean, an increased frequency and thoroughness of cleaning, as well as the use of disinfectants. The health care component of a health care facility includes all areas involved in client/patient/resident care including all client/patient/resident wards or units and including nursing stations; procedure rooms; clinic and examination rooms; diagnostic and treatment areas; and washrooms*. Areas designated as part of the health care component are cleaned with a health care clean. The health care component of the health care setting should be the priority for environmental cleaning. Areas that require a health care clean should have different cleaning protocols and additional environmental service human resources that are sufficient to allow the more intensive and frequent cleaning (and monitoring of cleaning) required for these areas. Additional cleaning practices may be required for clients/patients/residents known or suspected to be colonized or infected with a specific organism (or clients/patients/residents with a specific clinical syndrome). Additional cleaning practices are often directed towards clients/residents/patient colonized or infected with organisms that can persist for a prolonged time within the care environment, and may be relatively resistant to standard disinfectants. Health care settings should ensure that the cleaning requirements for patients requiring Additional cleaning practices are clearly communicated to environmental services. Additional cleaning practices may also be required for microorganisms that pose an extreme risk to clients/ patients/residents, staff and visitors such as Ebola Virus Disease. In addition to the above, enhanced cleaning and disinfection is often required during outbreaks of organisms when environmental contamination and subsequent transmission is known to be related to the type of organism suspected of causing the outbreak (e. Although causality has not been definitively established, numerous reports describe enhanced environmental cleaning as a 69,74,234,265 critical component of outbreak control measures for a variety of microorganisms. Policies and procedures regarding staffing in environmental services should allow for surge capacity (i. The outbreak management committee should include, among other departments, representation from environmental services who will lead the coordination of the environmental service department’s activities. Additional cleaning in an outbreak generally depends on the microorganism causing the outbreak. Components of Hotel Clean • Floors and baseboards are free of stains, visible dust, spills and streaks. Note: Frequency of health care clean is determined according to the Risk Stratification Matrix in Appendix 21: Risk Stratification Matrix to Determine Frequency of Cleaning 3. Policies and procedures should ensure that: ? Cleaning is a continuous event in the health care setting. Contamination of the environment is 63,275 increased when clients/patients/residents are coughing, sneezing or having diarrhea; have large or 275 draining wounds; have extensive dermatitis; or have other severe skin conditions. While this contamination is concentrated in the vicinity of the client/patient/resident and the areas used by the client/patient/resident (e. Staff can then transfer these microorganisms to other items and surfaces within the client/patient/resident environment, and if appropriate hand hygiene is not performed, may carry these microorganisms to other clients/patients/residents, to other client/patient/resident’s environments or to other areas of the health care environment (e. Given the potential for surfaces and items to become contaminated with microorganisms, all areas, surfaces, and items within care areas of the health care setting require cleaning on a routine basis. Thus, surfaces within the health care setting and in particular within the patient’s environment can be classified as high- and low- touch surfaces, as follows: 276,278 High-touch surfaces are those that have frequent contact with hands. The 278-282 specific surfaces that should be considered high-touch will vary between health care settings. Examples include (but are not limited to) floors, walls, ceilings, mirrors and window sills. Figure 3a and Figure 3b illustrate examples of items and sites that are high-touch and which may exhibit environmental contamination in health care settings. High-touch surfaces in care areas require more frequent cleaning and disinfection than minimal contact 244,276,280,283 surfaces. Cleaning and disinfection should be performed at least daily and more frequently if the risk of environmental contamination is higher (e. Low-touch surfaces require cleaning on a regular basis, when soiling or spills occur, and when a client/patient/resident is discharged 92 from the health care setting. For many low-touch surfaces, cleaning may occur less frequently than once per day (e. In some populations, such as bone marrow transplant or burn patients, susceptibility to infection is very high and lower levels of environmental contamination are more likely to result in clinically significant infection than in other, lower risk populations. Areas where vulnerable patients at risk for acquiring illness due to environmental microorganisms are cared for should receive more frequent environmental cleaning. In general, such areas include wards or units housing highly immunocompromised patients, and areas where patients frequently undergo invasive procedures, or both. Examples of such areas include: ? transplantation wards ? neonatal intensive care units ? burn units ? chemotherapy units ? dialysis units ? procedure and operating rooms Other care areas and patient populations are considered “less susceptible”. Routine regular cleaning and disinfection is still essential for these areas and populations but at a lower frequency than what is required for high-risk populations. Areas can be divided into those that are (likely to be) heavily, moderately or lightly contaminated, as follows: Heavy-contamination area. Areas should be considered heavily contaminated if surfaces or equipment are regularly exposed to significant amounts of blood or other body fluids (e. Areas should be considered moderately contaminated if surfaces or equipment are regularly contaminated with blood or body fluids (e. All client/resident/patient rooms and all bathrooms should be considered moderately contaminated. Areas can be considered lightly contaminated or not contaminated if surfaces are not exposed to blood or body fluids or items that have come in contact with blood or body fluids (e. Note: Regardless of the anticipated level of contamination for a given area or the frequency of routine cleaning and disinfection, if blood or body fluid spills or contamination occurs (e. When determining the appropriate frequency of cleaning and disinfection, the following principles apply: ? High-touch surfaces and items require more frequent cleaning and disinfection than low-touch surfaces and items. Using these criteria, each area or department in a health care setting can be evaluated and assigned a risk score for cleaning purposes, as illustrated in Appendix 21. As the activity or vulnerability of clients/patients/residents in an area changes, the risk score will change as well, impacting on the cleaning frequency. Noncritical medical equipment that is within the client/patient/resident’s environment and used between clients/patients/residents (e. Selection of new equipment must include considerations related to effective cleaning and disinfection (See 1. A system should be in place to clearly identify equipment which has been cleaned and disinfected. The health care setting should have written policies and procedures for the appropriate cleaning and disinfection of equipment that clearly define the frequency and level of cleaning and assign responsibility for cleaning.

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The rapid action of the tissue thromboplastins represents an extrinsic clotting pathway in contrast to the intrinsic pathway of plasma (see below) best cefuroxime 500 mg medications an 627. Although plasma does not contain a thromboplastin safe 250mg cefuroxime symptoms juvenile diabetes, there is evidence for the existence of a prothromboplastin that can be converted to thromboplastin through the mediation of platelet factors buy generic cefuroxime medications for factor 8, as well as of other factors present in normal blood cheap 250mg cefuroxime with mastercard symptoms of flu. The situation is not completely clear, partly because of the complexity of the process and partly because some of the factors have not been purified sufficiently to determine their chemical nature and relationships. The evidence is derived mainly from the description of dyscrasias in which an individual factor is present in low concentration or missing entirely from the plasma of individuals whose blood does not manifest a normal clotting time. The independent discovery of these factors by several investigators has resulted in the use of different names for the same factor. Hemophilia is hereditary and a sex-linked recessive trait; it thus occurs with significant frequency in males but is transmitted only through the female. The hemophilic clotting system apparently contains normal amounts of fibrinogen, 2+ prothrombin, Ca , etc. Three types of hemophilia are known; the blood of one type of hemophilic added to the blood of a patient with another type of hemophilia gives a clotting time much shorter than that of either specimen alone. Preparations of this globulin hasten, both in vitro and, temporarily, in vivo, the clotting of blood of individuals with hemophilia A. Thrombin formation is defective in hemophilic blood; the antihemophilic globulin is an activator of Stuart factor (see below), which is essential for the conversion of prothrombin to thrombin. Less is known concerning the factor deficient in individuals affected by hemophilia B. Bleeding symptoms are usually moderate in hemophilia C, and the inheritance 41 of the trait seems to be that of an incomplete dominant. Another factor concerned in the clotting mechanism was identified in the deficiency disease called congenital parahemophilia. The responsible factor involved in the transformation of prothrombin to thrombin is accelerator or Ac globulin (labile factor). The substance is present in plasma as an inactive pre-cursor proaccelerin (Factor V) that, during the activation of prothrombin, is transformed to accelerin. Proaccelerin may be deficient in the plasma of individuals with severe liver disease. The condition does not respond to vitamin K therapy but is corrected by administration of fresh, prothrombin-free plasma. In contrast to proaccelerin, proconvertin is a relatively stable substance and persists in stored plasma. One hypothesis 2+ suggests that proconvertin interacts with thromboplastin in the presence of Ca to form convertin, which is essential for prothrombin conversion. Another view, suggested by the name serum prothrombin conversion accelerator, is that the substance acts with thromboplastin to hasten prothrombin conversion. Proconvertin deficiency occurs in patients treated with Dicumarol or in individuals with vitamin K deficiency. Suspensions or extracts of platelets (thrombocytes) accelerate coagulation of platelet-free blood, establishing the importance of platelets in blood coagulation. The phosphatidylethanolamines and phosphatidylserines contain more than half their fatty acids as arachidonic acid. The clot-promoting activity of these phosphoglycerides is dependent on the presence of free amino groups On the serine or ethanolamine portions) and on the presence of the unsaturated fatty acids. Prevention of platelet dissolution may be accomplished by collection of blood with needles, tubing, and glassware that have been coated with silicones or other water-repellent polymers. Platelets remain intact on contact with these nonwettable, smooth surfaces, and coagulation is strongly retarded. If platelets are removed by high-speed centrifugation, human plasma kept in silicone containers will not coagulate for protracted periods even in the absence of calcium-binding agents. If platelet extracts or lysed platelets are added to plasma, clotting occurs rapidly. After injury to a blood vessel, platelets accumulate, aggregate, and fuse at the site of injury within seconds with adhesion to the exposed tissues. The mass of platelets seals the wound and acts as a nucleus around which the fibrin strands are formed. The contraction is apparently due to the presence in platelet 42 membranes of actomyosin, similar or identical in properties to that of muscle. During the dissolution of platelets, norepinephrine, serotonin, and histamine are liberated and aid in the control of blood loss by their vasoconstrictor action. Prolonged bleeding time may be due to thrombocytopenia, a deficiency of platelets. This leads to a decreased formation of active thromboplastin with deficient production of thrombin. The condition may be caused by a variety of chemical reagents including certain drugs, by ionizing radiations, by associated blood disorders, e. Mechanism of Blood Clotting Tentative mechanisms have been proposed to account for all the various factors involved in blood clotting. The evidence for the "cascade" type of sequence in the intrinsic system is incomplete, but the position of each of the factors is supported by some evidence. On the left side of each reaction is an inactive precursor and on the right an active factor, an enzyme, except in the case of fibrin. Initiation of clotting results in the successive conversion of each inactive protein to the active enzyme by the catalytic action of each newly formed enzyme. The first recognized event in the coagulation of shed blood is the activation of Hageman factor (Xli). Suggestive evidence that most, if not all, of the proteins in 2+ this scheme are enzymes is the requirement for Ca or other divalent cations in several of the conversions. Thus, present evidence suggests that many, if not all, of these enzymes are proteases. Indeed, the activation of the inactive precursors is similar to the activation of the zymogens of the proteinases, chymotrypsinogen and trypsinogen. Further, the amino acid sequence of thrombin is homologous with the sequences of the pancreatic proteinases suggesting that prothrombin, as well as possibly other zymogens in the clotting mechanism, originated by gene duplication from ancestral genes that also gave rise by gene duplication to the extensive variety of proteinase zymogens. The overlapping properties of almost all the zymogens or their active forms suggest that they all probably originated in this manner. In general, each of the inactive plasma zymogens of the cascade, the intrinsic system, is present at a higher concentration than the preceding one. Thus, when activation of Hageman factor occurs, there is an amplification of the response. The more stages in the amplification, the more effective will be the final response and the greater the possibilities for control of the process, for not only must blood loss be quickly prevented, but the process must take place only after injury and be limited to the site of injury.