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In female rats exposed to impotence quotes the sun also rises provestra 30pills on-line nicotine erectile dysfunction medications injection buy generic provestra 30 pills online, been shown to erectile dysfunction 4xorigional purchase cheap provestra be reversible on alanine aminotransferase and alkaline cessation of treatment erectile dysfunction under 30 purchase genuine provestra. Hepa to cyte vacuolation was observed more frequently in the liver of nicotine-exposed rats. Rahali 2018 To evaluate the Rats 100 28 days Given NaCl with No dose Rats sacrifice at 4 E-liquid exposure induced a significant decrease E-liquid exposure led to impact of e-liquid injection of e-liquid was lower/ wks. Sperm count in the epididymal sperma to zoa number (Table decreased epididymal with or without NaCl in containing day but and eosine 1). There viability for nicotine-free e-liquid and nicotine were also fewer viable cells in containing e-liquid rats in comparison to the the e-liquid conditions control group. Tes to sterone levels in the e-liquid-exposed rats was also lower, while inflamma to ry and oxidative states were higher. The capillary count was decreased in structures as traditional produce the same vapour humans). Serum nicotine and cotinine were higher are also abundantly apparent in to bacco smoke. No changes to p63 cells comparable with those observed those exerted by with non al staining. Behar 2017 To compare the Human 32 flavours 32 flavours & Pulmonary Tested cy to to xicity Embryonic stem cells were more sensitive than lung cells. Researchers also noted that the creamy/ buttery flavours were the understand their potential health vapours using in embryonic most cy to to xic. Exposure to Menthol 2 + nicotine led to cell-death in 90% of categories vaporised model). This could lead to and Inflamma to ry increased passage of external antigens and chemicals in to the lungs inflammation. Langmuir isocycles, reflective of the performance, which may hold value model surfactant was developed by human breathing cycle, demonstrated condensed character on smoke in harm reduction over the longer films located this group. Neutral nicotine molecules can weaken the structure surfactant monolayers under environment of the monolayer and cause destabilisation. Ce to in, diacetyl, mal to l, and coumarin did not affect cell trigger an inflamma to ry response in the oxidative flavouring, at U937) from cy to kine release and viability. Cy to to xicity: Mystery Mix (menthol flavour) was potential pulmonary to xicity and chemicals on two 1,000fiM). Otreba 2018 To examine the Human Cigarette Vapour from Human lung Used a cell viability E-cigarettes had lower cy to to xicity levels than cigarettes. Increasing “Our results not only confirm less to xicity of vapour smoke e-cigarette carcinoma assay. Used significant impact on cy to to xicity of compared with different e-cigarette vapour. Thus, the results cigarette smoke voltages of of this study are very important for as well as battery e-cigarettes the current and future legal output voltage on (3. The surfactant inhibi to ry smoke on lung significantly alter interfacial properties. Constituents: Hot cinnamon candies and menthol to bacco shared 8 constituents, with 9 and 11 unique constituents. However without nicotine, cells appeared the same as fibroblasts, raising concerns about lysosome 1mg/mL) microscopy analysis, without any liquids at all. Exposure to to bacco carcinogens (benzofipyrene and 4 brands and at concentrations tested mutation in cells. It is possible that e-cigarette use and conventional cigarette use have common antecedents, or that e-cigarette use is a direct determinant of conventional cigarette use. The evidence is consistent in observational studies and across different countries. Use of e-cigarettes with higher concentrations of nicotine is observed to have a stronger association to later conventional cigarette use. Smoking cessation • Observational studies indicate that e-cigarettes are subjectively a preferred smoking cessation method in some, but not all, populations. Conditions in the trials have limited application with most trials being short term. This section addresses part of the assigned task to ‘review all available evidence applicable to the use of e-cigarettes, personal vaporisers and nicotine on rates of smoking. Therefore, only studies published recently and not considered in these reports will be reviewed and the results will be compared to the overall findings of these previous reviews. The first assesses the evidence for e-cigarette use as a risk fac to r for the initiation of conventional cigarette smoking, the second reviews the evidence for e-cigarette use as a risk fac to r for subsequent use of illicit drugs and other harmful substances. A review of the titles found in the literature search identified 52 potential publications on the use of e-cigarettes as a possible gateway to the use of conventional cigarettes and other substances. Of the remaining 30 studies, 17 examined the relationship between e-cigarette use and conventional cigarette use, seven investigated the relationship between e-cigarette use and the use of illicit drugs and other harmful substances, and six assessed both. Of the 23 studies exploring the relationship between e-cigarette use and conventional cigarette use, eight studies were longitudinal cohort studies and 15 were cross-sectional study designs. All of the eight cohort studies we reviewed found that e-cigarette use was associated with later initiation and/or regular use of conventional cigarettes in teenagers and young adults (Kinnunen, Minkkinen et al. These studies were conducted in different populations across different countries, further confirming the robustness of the relationship. One such study, conducted by East and colleagues, involved a cohort of 923 youth in Great Britain (age range 11-18 years) who had never smoked conventional cigarettes, followed over five months. At baseline, only 21 of these never smokers had used e-cigarettes (East, Hitchman et al. Lozano and colleagues conducted a large, good quality study of 4,695 middle school students in Mexico who were followed over 20 months (Lozano, Barrien to s-Gutierrez et al. At baseline, all participants had not tried conventional cigarettes and 5% had tried e-cigarettes. This study also excluded those who had reported having tried cocaine or marijuana at baseline. The response rate was reasonable (84%), however, the retention rate at follow up was low (63%), which may have introduced bias. Prevalence of ever use of e-cigarettes with nicotine and e-cigarettes without nicotine in never cigarette smokers at baseline was 13. These associations were strongest in adolescents with a low baseline risk of smoking. This study adjusted for age, sex, educational attainment and propensity to smoke which was comprised of three fac to rs – personality (anxiety sensitivity, hopelessness, sensation seeking and impulsivity), susceptibility to peer pressure and smoking intentions. Morganstern and colleagues conducted another study in a cohort of 2,186 10th grade students in Lower Saxony and Schleswig-Holstein, Germany (Morgenstern, Nies et al. All students who were included in the analysis had never smoked conventional cigarettes at baseline, however, 14. This association was also found to be stronger among adolescents with low sensation-seeking scores and without any binge-drinking experience. The follow up period is also short and may not have captured the full effect of e-cigarette use on subsequent cigarette experimentation. Kinnunen and colleagues conducted a study of 1,988 school students aged 16 to 18 years in Helsinki, Finland (Kinnunen, Minkkinen et al. In this study, the relationship between use of e-cigarettes with and without nicotine in never cigarette smokers and daily cigarette smoking two years later was examined. At baseline, 103 participants had tried e-cigarettes with nicotine, 65 had tried e-cigarettes without nicotine and 1,820 had not tried e-cigarettes. There was an association between the use of e-cigarettes with and without nicotine and daily smoking at follow up with 8. These results should be considered carefully, however as the proportion of participants in the exposed groups are small, no confounders have been reported, and a full-peer reviewed article of the results is yet to be published. All students included in the analysis had never smoked a conventional cigarette at baseline. They also observed a higher odds of smoking initiation following use of e-cigarettes in those who were not susceptible to smoking and those who had no friends who smoked at baseline. These results should be interpreted with caution, however, as a full, peer-reviewed article of this study is yet to be published. Penzes and colleagues followed a cohort of 1,369 ninth grade students from 16 high schools in Tirgu Mures, Romania for a period of six months (Penzes, Foley et al. This study is a secondary analysis of data obtained during a randomised controlled trial investigating the effectiveness of a web-based multimedia program to prevent the initiation of smoking among adolescents.

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Regularly counsel all adults erectile dysfunction pills walgreens buy provestra 30pills without a prescription, pregnant women erectile dysfunction usmle cheap provestra, parents male erectile dysfunction pills buy genuine provestra on-line, and adolescents who smoke to erectile dysfunction treatment in qatar order provestra no prescription s to p. Include “the five As” and assess readiness to quit, using the Stages of Change Model. Assessing Readiness to Quit Sm oking: Brief Interventions M odels 5 As Model Stages of Change Model Ask about to bacco use Precontemplation—“I don’t want to quit. Recommend pneumococcal vaccine to adults 65 years and older, smokers between the ages of 16 and 64 years, and those with increased risk of pneumococcal infection. Vesicular, bronchovesicular, or bron chial breath sounds; decreased breath sounds from decreased airfow fi Note any adventitious (added) Crackles (fne and coarse) and continuous sounds. Characteristics of Breath Sounds Intensity and Pitch of Exam ple Duration Expira to ry Sound Locations Vesicular Insp > Exp Soft/low Most of the lungs Bronchovesicular Insp = Exp Medium/medium 1st and 2nd interspaces, in terscapular area Bronchial Exp > Insp Loud/high Over the manu brium Tracheal Insp = Exp Very loud/high Over the trachea Duration is indicated by the length of the line, intensity by the width of the line, and pitch by the slope of the line. While the patient is still sitting, you may inspect the breasts and examine the axillary and epitrochlear lymph nodes, and examine the temporomandibular joint and the musculoskeletal system of the upper extremities. Observe the seconds are less likely to be disabled rate, effort, and sound of breath than those taking>5 to 6 seconds. Breath sounds distant with delayed expira to ry phase and scattered expira to ry wheezes. May be associated with viral nasopharyngitis Tracheobronchitis Cough and Sputum: Dry or productive of sputum Associated Symp to ms and Setting: An acute, often viral illness, with burning retrosternal discomfort Mycoplasma and Viral Cough: Dry and hacking Pneumonias Sputum: Often mucoid Associated Symp to ms and Setting: An acute febrile illness, often with malaise, headache, and possibly dyspnea Bacterial Pneumonias Cough and Sputum: With pneumococcal infection, mucoid or purulent; may be blood streaked, diffusely pinkish, or rusty. Associated Symp to ms and Setting: An acute illness with chills, high fever, dyspnea, and chest pain; often preceded by acute upper respira to ry infection. Chronic Inflammation Postnasal Drip Cough: Chronic Sputum: Mucoid or mucopurulent Associated Symp to ms and Setting: Repeated attempts to clear the throat. Associated with chronic rhinitis, with or without sinusitis (continued) 142 Bates’ Pocket Guide to Physical Examination and His to ry Taking Table 8-3 Cough and Hemoptysis(continued) Cough, Sputum, Associated Problem Symp to ms, and Setting Chronic Bronchitis Cough: Chronic Sputum: Mucoid to purulent; may be blood-streaked or even bloody Associated Symp to ms and Setting: Often long his to ry of cigarette smoking. Bronchiectasis Cough: Chronic Sputum: Purulent, often copious and foul smelling; may be blood-streaked or bloody Associated Symp to ms and Setting: Recurrent bronchopulmonary infections common; sinusitis may coexist Pulmonary Tuberculosis Cough and Sputum: Dry, mucoid or purulent; may be blood-streaked or bloody Associated Symp to ms and Setting: Early, no symp to ms. Lung Abscess Cough and Sputum: Purulent and foul smelling; may be bloody Associated Symp to ms and Setting: A febrile illness. Often poor dental hygiene and a prior episode of impaired consciousness Asthma Cough and Sputum: Thick and mucoid, especially near end of an attack Associated Symp to ms and Setting: Episodic wheezing and dyspnea, but cough may occur alone. Often a his to ry of allergy Chapter 8 | the Thorax and Lungs 143 Table 8-3 Cough and Hemoptysis(continued) Cough, Sputum, Associated Problem Symp to ms, and Setting Gastroesophageal Cough and Sputum: Chronic, especially at Reflux night or early morning Associated Symp to ms and Setting: Wheezing, especially at night (often mistaken for asthma), early morning hoarseness, repeated attempts to clear throat. Often with his to ry of heartburn and regurgitation Neoplasm Cough: Dry to productive Cancer of the Lung Sputum: May be blood-streaked or bloody Associated Symp to ms and Setting: Usually a long his to ry of cigarette smoking Cardiovascular Disorders Left Ventricular Failure Cough: Often dry, especially on exertion or or Mitral Stenosis at night Sputum: May progress to pink and frothy, as in pulmonary edema, or to frank hemoptysis Associated Symp to ms and Setting: Dyspnea, orthopnea, paroxysmal nocturnal dyspnea Pulmonary Emboli Cough: Dry to productive Sputum: May be dark, bright red, or mixed with blood Associated Symp to ms and Setting: Dyspnea, anxiety, chest pain, fever; fac to rs that predispose to deep venous thrombosis Irritating Particles, Cough and Sputum: Variable. Traumatic Flail Chest If multiple ribs are fractured, can see paradoxical movements of the thorax. Descent of the diaphragm Expiration decreases intrathoracic pressure on inspiration. Depressed costal cartilages Thoracic Kyphoscoliosis Abnormal spinal curvatures Spinal convexity to the right Ribs (patient bending forward) widely and vertebral rotation separated deform the chest, making interpretation of lung findings dificult. It suggests left ventricular heart failure or mitral stenosis; it also may accompany obstructive pulmonary disease. Dependent edema appears in the feet and lower legs when sitting or in the sacrum when bedridden. Primary prevention, in those without evidence of cardiovascular disease, and secondary prevention, in those with known cardiovascular events. Use education and coun seling to help your patients maintain optimal levels of blood pressure, cholesterol, weight, and exercise and to reduce risk fac to rs for cardio vascular disease and stroke. Consensus Panel Guide to Com prehensive Risk Reduction for Adult Patients without Coronary or Other Ath erosclerotic Vascular Diseases. An update of the International Society on Hypertension in Blacks Consensus Statement. For Step 2, assemble risk fac to r data and calculate mul tivariable global risk assessment. Preventive Services Task Force recom mends screening all people 18 years or older for high blood pressure. In 2009, the International Diabetes Association and other societies harmonized diagnostic criteria as the presence of three or more of the five risk fac to rs listed below. Harmonizing the metabolic syndrome: a joint interim statement of the Internal Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung and Blood Institute; American Heart Association; World Heart Federation; Internal Atherosclerosis Society; and Internal Association for the Study of Obesity. Chapter 9 | the Cardiovascular System 153 Other Risk Fac to rs: Smoking, Family His to ry, and Obesity. Among adults, 13% report a family his to ry of heart attack before age 50, which roughly doubles the risk the risk of heart attack. Estimate sys to lic blood pressure this step helps you to detect an ausculta by palpation and add 30 mm Hg. Note the a wave of atrial inentvwaves intricuspid regurgitation contraction and the v wave of venous filling. Listen at the apex with thebell of the stethoscope for low-pitched extra sounds (S3, open ing snap, dias to lic rumble of mitral stenosis). Supine, with the head Listen at the 2nd right and left interspaces, along elevated 30 degrees the left sternal border, and across to the apex with the diaphragm. Listen with the bell at the right sternal border for tricuspid murmurs and sounds. Sitting, leaning Listen along the left sternal border and at the apex forward, after full for the soft decrescendo dias to lic murmur of exhalation aortic insufficiency. Palpate left and right second Pulsations of great vessels; accentuated interspaces close to sternum. Use the bell for low-pitched sounds S3, S4, murmur ofmitral stenosis at the lower left sternal border and apex. Is splitting normal in left Physiologic (inspira to ry) or pathologic 2nd and 3rd interspacesfi It is help ful to palpate the carotid upstroke while listening to any murmur—murmurs occur ring simultaneously with the upstroke are sys to lic. S2 S1 fi Location of maximal intensity Murmurs loudest at thebaseare often aortic; at theapex,they are often mitral. Listen at the apex with Left-sided S3, and dias to lic murmur of patient turned to ward left side mitral stenosis for low-pitched sounds. Gradations of M urm urs Grade Description Grade 1 Very faint, heard only after listener has “tuned in”; may not be heard in all positions Grade 2 Quiet, but heard immediately after placing the stetho scope on the chest Grade 3 Moderately loud Grade 4 Loud, with palpable thrill Grade 5 Very loud, with thrill. May be heard when the stetho scope is partly off the chest Grade 6 Very loud, with thrill. Lower pressure of blood sudden doubling of Korotkof sounds pressure cuff slowly to sys to lic indicatespulsus alternans—a sign of left ventricular heart failure. Con pressure levels: (1) where sider obstructive pulmonary disease, pericardial tamponade, or constrictive Korotkoff sounds are first heard pericarditis. High-pitched, harsh 2/6 holosys to lic murmur best heard at the apex, radiating to the axilla. S1 S2 Diminished S1 Occurs in first-degree heart block, calcified mitral valve of mitral regurgitation, and v left ventricular contractility in heart failure or coronary heart disease. S1 S2 Varying S1 S1 varies in complete heart block and any to tally irregular rhythm. S1 S2 S1 S2 Split S1 Normally heard along the lower left sternal border if audible tricuspid component. If S1 sounds split at apex, consider an S4, an aortic ejection sound, an early sys to lic click, right bundle branch block, and S1 S2 premature ventricular contractions. Chapter 9 | the Cardiovascular System 163 Variations in the Second Heart Sound— S2 Table 9-3 During Inspiration and Expiration Physiologic Splitting A2 P2 S1 S2 S1 S2 Heard in the 2nd or 3rd left interspace: the pulmonic component of S2 is usually to o faint to be heard at the apex or aortic area, where S2 is single and derived from aortic valve closure alone. Pathologic Splitting S1 S2 S1 S2 Wide splitting of S2 persists throughout respiration; arises from delayed closure of the pulmonic valve. Fixed Splitting S1 S2 S1 S2 Does not vary with respiration, as in atrial septal defect, right ventricular failure. Closure of the aortic valve is abnormally delayed, so A2 follows P2 on expiration, as in left bundle branch block. More on A2 and P2 Increased Intensity of A2, 2nd Right Interspace (where only A2 can usually be heard) occurs in systemic hypertension because of the increased ejection pressure.

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Ideally health care workers should observe patients producing the sputum specimen erectile dysfunction statistics age order provestra 30 pills, while keeping suffcient distance when the patient coughs impotence diabetes order provestra with american express. If all has been done to erectile dysfunction vyvanse cheap 30 pills provestra fast delivery get the best possible specimen erectile dysfunction drugs viagra order genuine provestra line, this specimen should be sent to the labora to ry. The labora to ry should process all sputum samples received and should not discard any sputum specimen even when they think it is mostly saliva. It was the frst molecular test that is simple and robust enough to be introduced outside sophisticated labora to ry settings. Sputum smear examination Direct (smear) microscopy is less expensive, quick, and highly specifc and provides reliable evidence of mycobacteria in the lungs. Sputum smear results are reported by the presence of stained bacilli (by Ziehl Neelsen or Auramine staining methods) observed. Chest X-ray examination Chest radiography is not a substitute for bacteriological examination. When used for screening, chest X-ray must be followed by a bacteriological examination, as chest radiography is less specifc than bacteriological tests. National Guidelines for the Management of Tuberculosis Page 16 National Guidelines for the Management of Tuberculosis Page 16 4. Pre and post-test counselling must be provided for the patient or his/her family (if the patient is very ill). The appearance becomes increasingly more atypical with advancing immune suppression. A rapid fall of temperature after a course of antibiotics makes the diagnosis likely to be pneumonia. The common causative organism in adults is Strep to coccus pneumonia which responds well to penicillin/ ampicillin or co-trimoxazole. Chest radiograph features are often normal or show a bilateral diffuse interstitial shadowing. Sarcoma Kaposi sarcoma presents with purple nodules or patches on the skin and mucous membranes. An infection beyond a bronchus blocked by a tumour may cause a lung abscess with a cavity. A solid rounded tumour may be diffcult to distinguish radiologically Lung cancer from a rounded tuberculous lesion. Palpate for an enlarged lymph node behind the inner end of the clavicle, a common place for a secondary tumour. Persistent moist, coarse ‘crackles’ may be repeatedly heard over the same area of the lung. Remember patients with severe asthma may be on long-term corticosteroid medicines. Meanwhile, efforts must be made to obtain sputum for examination, if not yet done. Label the specimen as ‘urgent’ and request the labora to ry to process and provide the report on the same day. Box 6: How to perform and interpret the Man to ux test the Man to ux test is applied as follows: Using a short fne needle and special syringe calibrated for contents of 0. Draw the ballpoint inwards to wards the induration; where it meets resistance draw a short line oblique to the radial line; do the same on the opposite side; measure the distance between the two oblique lines in millimetres; this is the exact distance of induration. National Guidelines for the Management of Tuberculosis Page 20 A false positive result is rare in the tuberculin skin test once there is agreement on the criterion for a positive result. It is for that reason that the criterion for a tuberculin test being positive is the size of the induration. With the frst tuberculin test being negative, the second test may be positive, which may be erroneously interpreted as a recent tuberculin test conversion, or recent M. This is erroneous because the second increased induration is only the result of a boosting of pre existing cellular immunity caused by the frst of the two tuberculin injections. Physicians who use the tuberculin test for moni to ring recent infection in health care settings should be particularly aware of this phenomenon. A negative test result indicates – but is not frm proof that the person is not infected by mycobacteria. These include: • Incorrect test application (subcutaneous injection instead of intradermal); inactive tuberculin, • the patient is severely immune suppressed. Similarly, environmental mycobacteria are very common in Namibia and also create a positive tuberculin test result. That is the reason for deciding on 10mm or more as the cut-off point for infection by M. It may have many different manifestations depending on the organ that is affected. Presence or absence of these signs and symp to ms should always be elicited from the patient. Specifc complaints such as pain and swelling are caused by National Guidelines for the Management of Tuberculosis Page 21 infammation of the affected organ. A needle is inserted in to the centre of the swollen lymph node, and material is aspirated in to the needle. In addition, the specimen is sent for cy to logy or his to logy if there is no obvious evidence of caseation. Tissue biopsy A biopsy from the affected organ can be obtained during a surgical procedure on patients undergoing investigation or excision of a diseased organ. The aspirate forms a web when left standing and shows a high protein content on analysis. Some tests are desirable if they can be done at start of treatment while others are indicated when a patient develops complications. Repeat labora to ry examinations are only indicated when a patient develops complications. Specifcity is increased when the lymphocyte/neutrophil ratio in the pleural fuid (of > 0. Where only smear microscopy is available, two negative smears may be considered bacteriologically negative. In the event that a patient was started on treatment as an emergency without sputum collection, sputum can still be collected when the patient’s condition has stabilised. New patients may be bacteriologically confrmed or clinically diagnosed and may have disease at any ana to mical site. They are further classifed by the outcome of their most recent course of treatment (relapse; treatment after failure; treatment after loss to follow-up or unknown last outcome) as shown in table 8. Standardised treatment means that all patients in a defned group receive the same treatment regimen, and has the following advantages over individualised prescriptions of medicines: • it minimises errors in prescription, and thus reducing the risk of development of drug resistance • it simplifes estimation of medicine requirements at all levels • it reduces costs • it ensures regular medicine supply when patients move from one area to another • treatment results can be compared. For assigning standard regimens, patients are grouped by the same patient registration groups used for recording and reporting, which differentiate new patients from those who have had prior treatment. Recommended regimens for different patient registration groups are shown in Table 9. An X-ray should be performed at baseline in all clinically diagnosed cases and all cases who are smear positive at 5 months. After this, treatment shifts to a less intensive phase of treatment the continuation phase. This is particularly important in patients at high risk of poor adherence or drug resistance 5. Defnitions of treatment outcomes the table below shows the defnition of standardised treatment outcomes. Treatment completed A patient who completed treatment but who does not have a negative sputum smear or culture result in the last month of treatment and on at least one pre vious occasion. Treatment failure A patient whose sputum smear or culture is positive at 5 months or later dur ing treatment. Died A patient who dies of any cause before starting or during the course of treatment. Treatment success the sum of those who are cured and those who completed treatment.

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This clamp was positioned at the intersection of the left and right medial lobes with the instruments base plate positioned beneath the quadrate lobe erectile dysfunction fix 30pills provestra for sale. The tines of the instrument were then clamped through the parenchyma so that the tines seated in the corresponding grooves in the base plate erectile dysfunction circumcision discount provestra express. The instrument was then opened and repositioned to erectile dysfunction for young adults order provestra with amex the left of the first injury xyzal impotence purchase provestra online from canada, so that there was an overlap to the first injury by 50%. The authors documented the liver injury by excision and inspection of the liver at the conclusion of the experiment. They noted complete penetration of the liver and one or more of the left medial lobar veins, right medial lobar vein and portal hepatic vein. Resuscitation was initiated 30 seconds post-injury with warmed ringers lactate solution. Resuscitation commenced at 392-394 260ml/min if the mean arterial pressure dropped below baseline. This model 392 represents a high volume/low pressure model as no arterial injury was noted. In this model a laparo to my and splenec to my was performed with replacement of splenic weight again with ringers lactate. Simultaneous fluid resuscitation was not administered in this model, and only after complete haemostasis was achieved. However, without active and aggressive resuscitation the dynamics change as the mean arterial pressure drops, and it may become a low pressure/high flow injury model. This injury caused a rapid drop in arterial blood pressure (up to 30mmHg) and a 75% drop in cardiac output. With the onset of hypotension, arterial spasm and the formation of clot at the injury site, the flow of arterial haemorrhage rapidly decreased in the first 3 minutes following injury. Renewal of haemorrhage typically occurred when the blood 397 397 pressure improved after resuscitation. Modifications by Alam etal allowed only 3 minutes of free bleeding prior to intervention as opposed to the prior 5 minutes. This 94 resulted in a return to higher mean arterial pressures earlier in the post-injury period. Modifications hence resulted in a low to moderate volume/low to moderate pressure 199 model. Acheson et al investigated the efficacy of 3 to pically applied haemostatic dressings 398 in a swine model of extremity arterial haemorrhage, with repeat of this model by 399 Ward et al. This model involved the arterial moni to ring of blood pressure and a jugular venous catheter for intravenous fluid administration. Animal inclusion criteria in to the study included that the animals were required to maintain a minimum of mean arterial pressure of 50mmHg after induction of anaesthesia. Initially a midline laparo to my and splenec to my was performed to exclude the discrepant hema to logic changes resulting from au to transfusion by varying sizes of the contractile porcine spleen. Ringers solution was given at 3 times the splenic weight to replace approximate volume of blood. The artery was clamped proximally and distally and a arterio to my was made in the anterior surface with a 6mm hole punch creating a highly reproducible injury. Authors to ok particular note to leave the posterior wall intact and therefore minimize the effects of artery retraction and vasospasm, which could result in spontaneous haemostasis. After 45 seconds of bleeding the test haemostat was applied followed by immediate resuscitation with pre-warmed ringers lactate at 100mls/min whenever 398 the mean arterial pressure dropped below 65mmHg. This model most accurately describes a model of high volume/high pressure due to an arterial model of injury with simultaneous rapid intravenous resuscitation in attempts to maintain the pre injury mean arterial pressure. It is clear that for a high flow/high pressure vascular injury model to maintain these characteristics it is important that the arterial injury is performed in a longituidinal direction, involves only the anterior wall of the vessel, and does not result in complete transection of the vessel. Current animal models of haemorrhage attempt to replicate the trauma situation, with wide access, and do not replicated the difficulties of major haemorrhage during minimal access endoscopic surgery. Investigation in to haemostatic techniques during a high flow/high pressure surgical scenario requires an animal model that accurately re-creates the narrow confines of the nasal cavity (chapter 8). Advanced Haemostatic Products Most current literature pertaining to advanced haemostatic agents arises from the trauma setting. Currently over 90% of combat deaths occur on the battlefields prior 395 to the injured reaching definitive casualty care. Uncontrolled haemorrhage is the 400 leading cause of death amongst this group of patients. Exsanguination most frequently occurs from to rso injuries, which are exceedingly difficult to manage with 401,402 standard techniques such as pressure dressings, to urniquets, and clamping. There is a great need for an advanced haemostatic agent effective against high flow, high pressure bleeding. This product consists of clotting proteins purified from pooled human plasma from donated blood. Mechanism of action is direct application of highly concentrated coagulation fac to rs to the site of injury causing polymerization and 199 crosslinking of fibrin. It is a 10 X 10 cm dressing consisting of two outer layers of 2 human fibrinogen (13. The haemostatic efficacy of this dressing has been evaluated in a number of experimental models involving traumatic injuries in large 392,393,403-405 animals. Kheirabadi et al compared the dry fibrin sealant dressing against a chi to san dressing and the standard gauze army field dressing in a swine aortic injury model. Results of this randomised controlled trial showed that the fibrin sealant dressing provided initial haemostasis in all pigs (n=6) and maintained haemostasis in 5 pigs (failure of one dressing at 2. Five of the 7 chi to san dressing pigs achieved initial haemostasis however prolonged haemostasis wasn’t achieved and 395 all animals exsanguinated. Pusateri et al compared the effect of nine haemostatic dressings on blood loss using a model of severe venous haemorrhage and hepatic injury in swine. Dressings studied included a dry fibrin sealant dressing, oxidized cellulose dressing, a propyl gallate dressing, a epsilon aminocaproic acid and thrombin dressing, microfibrillar collagen dressing, a fibrillar oxidated regenerated cellulose dressing, a fully acetylated poly-N-acetyl glucosamine dressing and finally a dressing containing human fibrinogen, thrombin and a equine collagen backing. Results showed that dry fibrin sealant dressing was the only effective dressing at 97 reducing post-treatment blood loss and increased the percentage of animals that achieved haemostasis when compared to gauze controls. Additionally this study also showed that the dry fibrin sealant dressing had 392 the highest adherence strength score (p<0. Finally Acheson et al investigated the effect of the dry fibrin sealant dressing against zeolite granule dressing and a chi to san dressing in a femoral arterial injury model in swine. Results showed that the zeolite granules showed no haemostatic effect and the chi to san dressing only had a temporary effect on bleeding in 1/15 swine. The dry fibrin sealant dressing achieve stable 398 haemostasis in 10 of 15 swine, preventing their deaths. Zoelite granule dressing this product is designed to rapidly absorb water, thereby concentrating red blood 199 cells, clotting fac to rs and platelets at the site of bleeding in an exothermic reaction. Zeolite granules were compared against a standard gauze dressing in a randomised controlled trial involving a swine femoral artery and vein injury model. Results showed that application of 1% Zeolite granules result in a cessation of bleeding in all 7 animals, the lowest volume of blood loss and complete survival of this group. Zeolite granule dressing use in swine showed an average increase in temperature, when applied to a wound, of up to 100 degrees celcius, which resulted in his to logical 397,398,406 changes within the artery wall, vein, nerves and muscle. His to logical changes at the wound margins included granulomas and abscesses formation in all three animals investigated long-term. Additionally one animal required euthanasia 406 due to extensive morbidity and muscle necrosis at the site of injury. Pusateri et al 98 also showed a significant reduction in the post-treatment blood loss and survival in a liver injury model when compared to gauze control, however required the use of two surgical gloves and surgical tape to protect them from the thermal effects of the 407 dressing and additionally noted extensive thermal injury to contact tissues. Poly-N-acetyl-glucosamine this is an algae-derived dressing that is distinct from chi to san in that it is fully acetylated. It is a polysaccharide produced by a fermentation process and isolated from microalgal cultures grown on culture medium. Mechanism of its haemostatic ability remains unclear but it has been suggested to result in red blood cell aggregation, platelet activation, activation of the clotting cascade and local 408-410 vasoconstriction. Use of this dressing was first shown to be superior to fibrin glue, absorbable collagen and oxidised regenerated cellulose in a splenic injury 391 model in both non-coagulopathic and coagulopathic swine. Hypothermia seems to 390 have no effect on the efficacy of Poly-N-acetyl-glucosamine. The Poly-N-acetyl glucosamine patch has also been investigated in a model of severe large venous haemorrhage and hepatic injury in swine. This more challenging injury showed that Poly-N-acetyl-glucosamine patch was ineffective in increasing survival or decreasing 392,396 blood loss.

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