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Three parts of ammonium oxalate is balanced with two parts of potassium oxalate (neither salt is suitable by itself buy viagra super active 100mg low cost, i purchase 25 mg viagra super active overnight delivery. It is more expensive than the artificial ones and has a temporary effect of 62 Hematology only 24 hours generic viagra super active 50mg amex. Heparin prevents clotting by inactivating thrombin, thus preventing conversion of fibrinogen to fibrin. It is unsatisfactory for leucocyte and platelet and leucocyte counts as it causes cell clumping and also for blood film preparation since it causes a troublesome diffuse blue background in Wright-stained smears. However, these same automated results may also point 65 Hematology to the need to examine the blood film microscopically to confirm the presence of disease suggested by the results or for early detection of disease. Of course, in a laboratory without access to such automated information, the microscopic examination of the peripheral blood film is invaluable. Examination of the blood film is an important part of the hematologic evaluation and the validity or reliability of the information obtained from blood film evaluation, the differential leucocyte count in particular depends heavily on well-made and well- stained films. While blood film preparation is a disarmingly simple straight - forward procedure, there is abundant and continuing evidence that the quality of blood films in routine hematology practice leaves much room for improvement. Adequate mixing is necessary prior to film preparation if the blood has been standing for any appreciable period of time. Preparation of blood films on glass slides has the following advantages: • Slides are not easily broken • Slides are easier to label • When large numbers of films are to be dealt with, slides will be found much easier to handle. Wedge method (Two-slide method) • A small drop of blood is placed in the center line of a slide about 1-2cm from one end. Another slide, the spreading slide placed in front of the drop of blood at an angle of 300 to the slide and then is moved back to make contact with the drop. It is essential that the slide used as a spreader have a smooth edge and should be narrower in breadth than the slide on which the film is prepared so that the edges of the film can be readily examined. If the edges of the spreader are rough, films with ragged tails will result and gross qualitative irregularity in the distribution of cells will be the rule. The bigger leucocytes (neutrophils and monocytes) will accumulate in the margins and tail while lymphocytes will predominate in the body of the film. If the drop is not too large and if the cover glasses are perfectly clean, the blood will spread out evenly and quickly in a thin layer between the two surfaces. Spinner method 70 Hematology Blood films that combine the advantages of easy handling of the wedge slide and uniform distribution of cells of the coverglass preparation may be made with special types of centrifuges known as spinners. The spinner slide produces a uniform blood film, in which all cells are separated (a monolayer) and randomly distributed. White cells can be easily identified at any spot in the film On a wedge smear there is a disproportion of monocytes at the tip of the feather edge, of neutrophils just in from the feather edge, and of both at the later edges of the film. This is of little practical significance, but it does result in slightly lower monocyte counts in wedge films. Preparation of thick blood smears Thick blood smears are widely used in the diagnosis of blood parasites particularly malaria. It gives a higher percentage of positive diagnosis in much less time since it has ten times the thickness of normal smears. Five minutes spent in examining a thick blood film is equivalent to one hour spent in traversing the whole length of a thin blood film. Method Place a small drop of blood on a clean slide and spread it with an applicator stick or the corner of another slide until small prints are just visible through the blood smear. What are the possible effects of using a blood sample that has been standing at room temperature for some time on blood cell morphology? Jenner (1880) found that the precipitate formed when eosin and methylene blue are mixed could 74 Hematology be dissolved in methyl alcohol to form a useful stain combining certain properties of both parent dye stuffs. Romanowsky (1890) found that when old (ripened and therefore "polychromed") methylene blue solution is mixed with eosin and the precipitate dissolved in methyl alcohol, a stain results that has a wider range than Jenner’s stain staining cell nuclei and platelet granules (which Jenner’s mixture failed to stain). Principle of staining Acidic dyes such as eosin unites with the basic components of the cell (cytoplasm) and hence the cytoplasm is said to be eosinophilic (acidic). Conversely, basic stains like methylene blue are attracted to and combine with the acidic parts of the cell (nucleic acid and nucleoproteins of the nucleus) and hence these structures are called basophilic. When it is planned to use an aqueous or diluted stain, the air dried smear must first be fixed by flooding for 3-5 minutes with absolute methanol. Without disturbing the slide, flood with distilled water and wash until the thinner parts of the film are pinkish red. Leishman Stain In its preparation, the methylene blue is polychromed by heating a 1 % solution with 0. With Leshman’s stain, dilution is effected with approximately two volume of distilled water to one volume of stain (the best guide is the appearance of a metallic scum). Giemsa stain Instead of empirically polychromed dyes, this stain employs various azure compounds (thionine and its methyl derivative) with eosin and methylene blue). It is commonly used in combination with Jenner or May – Grunwald stains it constitutes “panoptic staining". Staining of thick smears The stains used employ the principle of destroying the red cells and staining leucocytes and parasites.

In contrast generic 50 mg viagra super active mastercard, antibodies raised against synthetic N-terminal peptides that correspond to the hypervariable portions of M-protein serotypes 5 discount viagra super active 50 mg visa, 6 and 24 are opsonic purchase viagra super active 25mg line, but do not cross-react with human tissue (17– 19). Further studies have shown that peptide fragments of M- 106 proteins, incorporated into multivalent constructs as hybrid proteins or as individual peptides linked in tandem to unrelated carrier pro- teins, elicited opsonic and mouse-protective antibodies against mul- tiple serotypes, but did not evoke heart-reactive antibodies (20, 21). These estimates were based on sero- type distribution data from economically developed western coun- tries, and such a vaccine might need to be reconstituted, based on prevalent local strains. Current studies are directed toward utilizing commensal gram-positive bacteria as vaccine vectors (22–23). One of these is C5a peptidase, an enzyme that cleaves the human chemotactic factor, C5a, and thus interferes with the influx of polymorphonuclear neutrophils at the sites of inflammation (24). Intranasal immunization of mice with a defective form of the streptococcal C5a peptidase reduced the colo- nizing potential of several different streptococcal M-serotypes (25). A second potential vaccine target is streptococcal pyrogenic exotoxin B (SpeB), a cysteine protease that is present in virtually all group A streptococci. Mice passively or actively immunized with the cysteine protease lived longer than non-immunized animals after infection with group A streptococci (26). Epidemiological considerations Once a safe and effective streptococcal vaccine is available many practical issues would need to be addressed. Other issues, such as cost, route of administration, number and frequency of required doses, potential side-effects, stability of the material under field conditions, and dura- bility of immunity, would all influence the usefulness of any vaccine. The most promising approaches are M-protein-based, including those using multivalent type-specific vaccines, and those directed at non-type-specific, highly conserved portions of the molecule. Success in developing vaccines may be achieved in the next 5–10 years, but this success would have to contend with important questions about the safest, most economical and most efficacious way in which to employ them, as well as their cost-effectiveness in a variety of epidemilogic and socio-economic conditions. A review of past attempts and present concepts of producing streptococcal immunity in humans. Intravenous vaccination with hemolytic streptococci: its influence on the incidence of rheumatic fever in children. Persistence of type-specific antibodies in man following infection with group A streptococci. Epitopes of group A streptococcal M protein shared with antigens of articular cartilage and synovium. Rheumatic fever: a model for the pathological consequences of microbial-host mimicry. Streptococcal M protein: alpha-helical coiled-coil structure and arrangement on the cell surface. Alternate complement pathway activation by group A streptococci: role of M-protein. Inhibition of alternative complement pathway opsonization by group A streptococcal M protein. Streptococcal infections: clinical aspects, microbiology, and molecular pathogenesis. Type-specific immunogenicity of a chemically synthesized peptide fragment of type 5 streptococcal M protein. Multivalent group A streptococcal vaccine designed to optimize the immunogenicity of six tandem M protein fragments. Protection against streptococcal pharyngeal colonization with a vaccinia:M protein recombinant. Intranasal immunization with C5a peptidase prevents nasopharyngeal colonization of mice by the group A Streptococcus. Vaccination with streptococcal extracellular cysteine protease (interleukin-1 beta convertase) protects mice against challenge with heterologous group A streptococci. Acute rheumatic fever in Auckland, New Zealand: spectrum of associated group A streptococci different from expected. Adding to the burden on health systems of developing countries are the costs of outside referrals that are often required during the course of treatment. The socioeconomic costs were also borne by the parents of the patients, with 22% exhibiting absenteeism from work, and about 5% losing their jobs. As a programme design strategy, it is advisable to attempt small-scale pilot programmes before initiating large-scale national control programmes, as the lessons learnt from pilot schemes can, in addition to many other benefits, prevent the waste of scarce resources (2, 7). These studies emphasize that national prevention programmes based on secondary prophylaxis have the potential for considerable cost savings, which could be used to improve the spread and gains of a programme. Evidence has been presented from a simulation study suggested that the most cost-effective strat- egy was to treat all pharyngitis patients with penicillin (particularly those within an at-risk group), without a strict policy of waiting for the disease to be confirmed by bacterial culture (7, 11). However, this approach has not been confirmed and cannot be advocated until more thorough studies are carried out. In hospital settings where facilities are available, the “culture and treat” strategy has been shown to be cost-effective (12). Analysis of costs of acute rheumatic fever and rheumatic heart disease in Auckland. Analysis of the cost-effectiveness of pharyngitis management and acute rheumatic fever prevention. It is important to implement such programmes through the existing national infrastructure of the ministry of health and the ministry of education without building a new administrative mechanism.

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The pur- Airway Anatomy pose of the sensory fibres is to allow detection of The upper airway refers to the nasal passages purchase viagra super active 25 mg mastercard, foreign matter in the airway and to trigger the nu- oral cavity (teeth cheap viagra super active 25 mg with mastercard, tongue) order viagra super active 25 mg line, pharynx (tonsils, merous protective responses designed to prevent uvula, epiglottis) and larynx. The swallowing mechanism is an ex- ynx is the narrowest structure in the adult airway ample of such a response whereby the larynx and a common site of obstruction, the upper air- moves up and under the epiglottis to ensure that way can also become obstructed by the tongue, the bolus of food does not enter the laryngeal in- tonsils and epiglottis. The cough reflex is an attempt to clear the up- The lower airway begins below the level of the per or lower airway of foreign matter and is also larynx. The most prominent of these is the thyroid cartilage (Adam’s apple) which acts as a shield for the delicate laryngeal structures behind it. Below the larynx, at the level of the sixth cervical vertebra (C6), the cri- coid cartilage forms the only complete circumfer- ential ring in the airway. The cricothyroid muscle, an adductor muscle, is sup- This figure was plied by the external branch of the superior laryngeal nerve. The purpose of the assessment is to identify potential difficulties with airway management and to determine the most ap- propriate approach. Examples include arthritis, infection, tu- mors, trauma, morbid obesity, burns, congenital anomalies and pre- vious head and neck surgery. As well, the anesthesiologist asks about symptoms suggestive of an airway disorder: dyspnea, hoarseness, stridor, sleep apnea. Finally, it is important to elicit a history of previous difficult intubation by reviewing previous anes- thetic history and records. The physical exam is focused towards the identification of anatomi- cal features which may predict airway management difficulties. Traditional teaching main- tains that exposure of the vocal cords and glottic opening by direct laryngoscopy requires the alignment of the oral, pharyngeal and laryngeal axes (Figure 3). The “sniffing position” optimizes the alignment of these axes and optimizes the anesthesiologist’s chance of achieving a laryngeal view. An easy intubation can be anticipated if the patient is able to open his mouth widely, flex the lower cervical spine, extend the head at the atlanto-occipital joint and if the patient has enough anatomical space to allow a clear view. Class 4 corresponds well with a difficult intuba- the anesthesiologist also observes the teeth for over- tion. Classes 2 and 3 less reliably predict ease of intu- bite, poor condition and the presence of dental pros- bation. The distance from the lower border of the mandible to the thyroid notch with the neck fully ex- • Neck motion: The patient touches his chin to his tended should be at least three to four finger- chest and then looks up as far as possible. The Mallampati classification (Table 2, Figure 4) assigns a score based on the structures visualized when the patient is sitting upright, with the head in a neutral position and the tongue protruding maxi- Table 2 Mallampati Classification Soft palate, uvula, tonsillar Class 1 pillars can be seen. As well, a Airway Management short thyromental distance may indicate inadequate Airway patency and protection must be maintained at “space” into which to displace the tongue during la- all times during anesthesia. If the patient is distance and other risk factors (morbid obesity, short, deeply sedated, simple maneuvers may be required: thick neck, protuberant teeth, retrognathic chin), will jaw thrust, chin lift, oral airway (poorly tolerated if gag increase the likelihood of identifying a difficult airway. The three common airway Laboratory investigations of the airway are rarely indi- techniques are: cated. In some specific settings, cervical spine x-rays, • mask airway (airway supported manually or with chest ray, flow-volume loops, computed tomography oral airway) or magnetic resonance imaging may be required. In current practice, the use of Mask Airway: Bag mask ventilation may be used to as- a mask as a sole airway technique for anesthesia is sist or control ventilation during the initial stages of a rarely-seen although it may be used for very brief pro- resuscitation or to pre-oxygenate a patient as a prelude cedures in the pediatric patient. Figure 5 Laryngeal mask in situ When properly positioned with its cuff inflated, it sits above the larynx and seals the glottic opening (Figure 5). Like an endotracheal tube, it frees up the anes- thesiologist’s hands and allows surgical access to the head and neck area without interference. Many factors predispose a pa- Nasotracheal intubation is contraindicated in patients tient to aspiration. A cuffed endotracheal tube, al- with coagulopathy, intranasal abnormalities, sinusitis, though not 100% reliable, is the best way to protect extensive facial fractures or basal skull fractures. Some surgi- achieve intubation (oral or nasal), most often it is per- cal procedures, by their very nature, require that the formed under direct vision using a laryngoscope to ex- patient be mechanically ventilated which is most ef- pose the glottis. The patient should first be placed in the “sniff- ventilation is required when: ing position” (Figure 3) in order to align the oral, pha- 13 Movie 1. A scale represented by the “Cormack Lehane views” allows anesthesiologists to grade and document the view that was obtained on direct laryngoscopy. Grade 1 indicates that the entire vocal aperture was visualized; grade 4 indicates that not even the epiglottis was viewed. Figure 7 provides a realistic depiction of the range of what one might see when performing laryngo- scopy. It is introduced into the right side of the mouth and used to sweep the tongue to the left (Figure 6). The blade is advanced into the vallecula which is the space between the base of the tongue and the epiglottis. Keeping the wrist stiff to avoid levering the blade, the 14 Figure 6 View of upper airway on direct laryngoscopy Movie 1.

The definition of the four levels of sedation and anesthesia are: Minimal sedation (anxiolysis): A drug induced state during which patients respond normally to verbal commands discount viagra super active 25mg with mastercard. Although cognitive function and coordination may be impaired order viagra super active 25mg overnight delivery, ventilatory and cardiovascular functions are unaffected 50mg viagra super active overnight delivery. Moderate sedation: A drug induced depression of consciousness during which patients respond purposefully to verbal commands, either alone or accompanied by light tactile stimulation. Deep sedation: A drug induced depression of consciousness during which patients cannot be easily aroused but respond purposefully following repeated or painful stimulation. Patients may require assistance in maintaining a patent airway and spontaneous ventilation may be inadequate. Anesthesia: General anesthesia is a drug induced loss of consciousness during which patients are not arousable, even by painful stimulation. Patients often require assistance in maintaining a patent airway and positive pressure ventilation may be required because of depressed spontaneous ventilation or drug induced depression of neuromuscular function. Clear examples of the stages of sedation for different age groups would be very helpful in clarifying any misconceptions. There is also the assumption that there is a consistent correlation between different levels of sedation and the ability to maintain a patent airway. The updated regulations require similar standards for moderate and deep sedation as are used for patients having general anesthesia. Qualified individuals must have competency based education, training, and experience: in evaluation of patients, in performing sedation, to “rescue” the patient from the next level of sedation/anesthesia. Risks of sedation: all sedatives and narcotics have caused problems even in “recommended doses”, all areas using sedation have reported adverse events, children 1-5 yr of age are at most risk (most had no severe underlying disease), respiratory depression and obstruction are the most frequent causes of adverse events, adverse events involved – multiple drugs, drug errors or overdose, inadequate evaluation, inadequate monitoring, inadequate practitioner skills, and premature discharge. There obvious need for uniform, specialty-independent guidelines for monitoring children during sedation both inside and outside of the hospital setting. Sedation techniques: Local anesthetics play very important role in analgesia during painful procedures. Application of local anesthetics to skin and mucosal membranes as well as local and regional blocks usually easily to perform. Maximum doses ( lidocaine 5 mg/kg – 7 mg/kg with Epi, tracheal lidocaine 2 mg/kg, marcaine 2 mg/kg – 3 mg/kg with Epi, cocaine 3 mg/kg, tetracaine 1. Midazolam has amnestic effect, short duration (half-life 100 min) and easily being 29 administered; reversibility (flumazenil 0. Fentanyl is potent opioid (100 times more potent than morphine) with rapid onset, intermediate duration (30-45 min) and reversibility (naloxone 0. Nitrous oxide used alone in concentrations less than 50% is a useful mild anxiolytic, sedative agent which causes analgesia. Children frequently receive no treatment, or inadequate treatment for pain and for painful procedures. Children less than 3 years of age or critically ill children may be unable to adequately verbalize when or where they hurt. Pain management in children is often dependent on the ability of parents to recognize and assess pain and on their decision to treat pr not to treat it. Pediatric pain service should provide the pain management for acute, post- operative, terminal, neuropathic and chronic pain. These agents are administered 30 enterally: oral, or rectal route and are very useful for inflammatory, bony, or rheumatic pain. Regardless of dose, the non-opioid analgesics reach a “ceiling effect” above which pain can not be relieved by these drugs alone. Aspirin has been abandoned in pediatric practice because of its possible role in Reye’s syndrome, its effects on platelet function, and its gastric irritant properties. Rectal doses for acetaminophen being recommended by some authors are as high as 30-40 mg/kg as loading dose. Regardless of route of delivery, the daily maximum acetaminophen dose in the preterm, term, and older child is 60, 80, 90 mg/kg respectively. Factors to consider when opioids are appropriate are: pain intensity, patient age, co-existing disease, potential drug interactions, prior treatment history, physician preference, patient preference, and route of administration. All opioids are capable of treating pain regardless of its intensity if dose is adjusted appropriately and at equipotent doses most opioids have similar effects and side effects. Codeine, oxycodone (Tylox, Percocet) and hydrocodone (Vicodin, Lortab) are opioids which are frequently used to treat pain in children and adults. They are most commonly administered in the oral form, usually in combination with acetaminophen or aspirin. In equipotent doses, codeine, oxycodone, and morphine are equal as analgesics and respiratory depressants. The analgesic effects for codeine and oxycodone occur in ~ 20 min following oral intake and reach maximum at 60-120 minutes. Approximately 10% of the patients and most newborns cannot metabolize codeine into morphine so codeine has little analgesic effect in these patients.