Allergy

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The term 'allergy' was coined in 1906 by Dr. Clemens Freiherr von Pirquet, an Austrian physician, to describe any abnormal reaction of the immune system. The immune system is intended to protect the body against the noxious invaders. But in allergy, immunity has gone awry, and the system reacts to substances that are ordinarily harmless. By far the most familiar allergic reactions are respiratory - sneezing, runny nose and watery eyes caused by inhaled allergens from growing weeds, trees and grasses or moulds, house dusts, mites and animal danders. These symptoms are commonly referred as 'hay fever'. However, hay fever is a misnomer, since it is not necessarily caused by hay and a rise in body temperature is not one of its symptoms.

Hay fever is most commonly recognized as an allergic problem. Other allergic manifestations are skin eruptions from food ingestion for example hives from strawberries and eczema from chocolate, and anaphylactic shock from nuts are also commonly recognized. Allergy is sensitivity, which a susceptible individual develops to normally harmless substances. The tendency to become suceptible to various things in our environment is usually inherited. This is also referred as atopy. Hence, atopic individuals are more prone to develop an allergy. The same thing is true about children of both or one of the parents having an allergy.

A considerable percentage of the world's population reacts in various ways to inhaled particles. The severity of this reaction varies according to the degree of exposure over time and concentration of the particles present when inhaled. In the case of pollen and spores, being living entities the time of their release into the air and for a short time beyond, often cause reactions themselves when inhaled.

During the course of evolution, mankind has developed resistance to many bioallergens, but new ones often arise by mutation and also from human investigations into the nature and use of chemicals, such as pharmaceutical drugs, cosmetics, detergents pesticides and herbicides. Many of these chemicals may adhere to the outer wall of pollen and spores when airborne, as a result of the use of aerosol sprays. It is when many such aerosol sprays are inhaled together with allergenic pollens and spores, that atopic persons develop allergic reactions. Many airborne pollen grains on contact with fine mist droplets may absorb water, swell and burst, releasing large numbers of allergenic particles, which add to the allergen load of the air.

Air contains a bewildering range and variety of spores discharged from algae, mosses, liverworts, ferns and fungi in addition to pollen from dehiscing pollen sacs of gymnosperms and angiosperms. Many cryptogamic spores have been shown to be allergenic - spores of many fungi including Penicillium, Aspergillus and Alternaria. Spores of the fern Pteridium aquilinum (Bracken) are carcinogenic when inhaled in high concentration at the point of release from fertile fronds (Lacey and McCartney 1994; Caulton et al., 1995). The penetrability of allergenic particles in the pulmonary system depends on particle size. The non-living micro particles designated as 2.10 or 2.50 ppm (parts per million), together with the very small spores of moulds such as Penicillium and Aspergillus can penetrate the alveoli of the lungs thereby triggering asthmatic attacks in susceptible people. Larger allergenic spores such as the fungus Alternaria, like smaller pollen grains, may reach the bronchii and upper regions of the trachea, initiating hay fever attacks according to the season, with varying degrees of response.

Many tree and herb pollen are allergenic. The most important of these are Betula (birch) and Prosopis trees of the temperate zone and herbs such as Poaceae (grasses) as a group, Artemisia sp., Ambrosia (Ragweed) and Parthenium. Herbaceous plants such as Urtica sp. (Nettle) and Parietaria are also allergenic, but to a lesser degree than the taxa mentioned above. The degree of allergenicity, or potential allergenicity, of any pollen depends to a greater or lesser extent on the abundance of a particular plant's pollen concentration as pollen grains per cubic metre of air (m3 air) and the degree of exposure to and potential susceptibility of the person involved.

Many explanations are offered to account for the noticeable increase in the incidence of both seasonal rhinitis and asthma, especially in the ever increasing urban populations of world, such allergy susceptibility is now extending at both ends of the age range. Whatever the initial cause of these observed and recorded increases, it is obvious that the natural inborn and developed immune system is being severely weakened.

Allergic symptoms are not only seen in human beings but atopic conditions have been recorded for horses (Dixon et al, 1992) and dogs (Fraser et al, 2001) resulting from the inhalation of allergenic pollen. Evidence of weakening of the natural immune system in seals, thought to be due to the intake of toxic substances discharged into offshore waters from industrial and domestic sources, resulted in the deaths of a considerable number of these animals, causing great concern to conservationists. Whilst the airborne spora is not a likely culprit here, it may possibly be a part explanation of the weakening of immune systems in land fauna such as humans and other mammals, where allergenic spores and pollen with contaminated surfaces may play a major role in this phenomenon.

Aeroallergens can vary in intensity among populations, as with individuals, due to change in and fluctuations of local and regional weather patterns and geographical location, latitude and elevation. In addition, seasonal patterns, more clearly marked in higher latitudes, play an important part in the periodicity of asthma and 'hay fever' - hence the medical term 'seasonal rhinitis'.

Atopic reactions such as asthma and 'hay fever' are important. With asthma, the reaction may be so serious as to be life threatening. In the case of seasonal rhinitis, the economic effects are more noticeable, due to its widespread incidence in populations. Absenteeism for short periods and lower productivity are due to victims being so unwell as to be unable to concentrate and work efficiently. Hereditary factors can play a part in asthmatic conditions whereas in seasonal rhinitis, the condition can arise or decline throughout life. The interaction of heritable and environmental factors in allergenic responses are complex and not fully understood. The individual response can vary considerably.

Aeroallergens and allergenicity due to airborne allergens are a contemporary phenomenon of considerable importance to the health and economy of human society. Allergens are simply defined as substances that are capable of producing allergy. When an allergen enters the body, substances called antibodies are produced. The interaction of allergen and the antibody produce an irritation in the affected tissue. The swelling or inflammation of the nasal lining during the hay fever season is an example of this interaction.

Allergens usually enter the body by four routes, such as ingestion, inhalation, injection and by external contact with the skin. In view of the above, it is apparent that foods, dust, pollen, fungal spores, fumes and almost anything in the environment may cause allergic diseases.

The dangerous respiratory disorder, asthma, can be caused by almost anything that irritates the bronchial tissues, including tobacco smoke and can even be triggered by emotional stress. But about 40% of the time, asthma is related to allergy.

Immediate hypersensitivity in allergy patients is caused by the pollen proteins and other compounds perhaps recognizing molecules peculiar to the species. These are stored in the sexine and intine which get released through the apertures when the pollen contacts mucosal surfaces, giving rise in sensitized atopic individuals to allergic rhinitis, allergic sinusitis and bronchial asthma.

In temperate regions allergenic plants are traditionally grouped as trees, grasses and weeds which follow the generalized flowering sequence from spring to autumn. Trees and shrubs flower from late spring to midsummer, and weeds from mid-summer to autumn. However, there are some exceptions: Ricinus, Albizzia, Castanea and Tilia often flower in the summer months. Lewis has given an excellent summary of pollen allergenicity which includes pollen-producing plants of allergic significance in continental United States of America (Lewis 1984).

Hypersensitivity pneumonitis, an inflammation of the lungs producing breathlessness, wheezing, chills and fever is another allergic respiratory disease. Contaminated household humidifiers, dust and bird droppings may induce allergic manifestations. Many allergies strike the skin. Atopic dermatitis or eczema is an itchy rash that often appears on the crook of the arms or legs, but sometimes covers the entire body. It usually begins with redness and swelling and can progress to fluid - oozing blisters. Eczema, most common in children under the age of five, may often come from food. Hives or urticaria, are itchy welts caused by a variety of allergens, including food and sudden changes in temperature. Touching an animal, plant or chemical allergen can produce contact dermatitis - poison ivy and the Umbellifer, Heracleum mantegazzianum (giant Hogweed) being notable examples. In addition, the other plant and animal materials such as trichomes, fibres, insect debris, cobwebs and dust particles can also cause allergic manifestations due to their protienaceous nature (Stanley and Linskens 1974; Knox 1979).

Anaphylaxis

The direful allergic reaction is anaphylatic shock. According to Anon (1994), anaplylaxis in the allergy patient is probably one of the greatest fears of the beginner as well as the seasoned allergist.

Anaphylaxis is a systemic hypersensitivity reaction that is immunologically mediated and induced by exposure to a specific antigen in a previously sensitized individual. The word anaphylaxis, which stems from the Greek term meaning 'against protection,' was originated by Porter and Rictet in 1902 after they failed experimentally to produce prophylaxis to sea anemone toxin in dogs.

There appear to be certain features that characterize the patients most likely to suffer an anaphylactic reaction. These include: a history of atopy, a family history of anaphylaxis, multiple exposures to the same or similar antigen, and the route of administration of the antigen.

According to some allergists penicillin is the number one cause of death from anaphylaxis, with 300 cases reported per year, followed by Hymenoptera stings, which account for approximately 20 to 50 deaths per year. Body tissues suddenly swell, followed often by abdominal cramps and vomiting. Lung tissues go into spasm, the lining of the throat swells and the victim gasps for air. Finally the blood pressure plummets and death may follow unless prompt action is taken. The usual emergency first step is injection of epinephrine (adrenalin), which constricts blood vessels and raises the blood pressure. People unduly sensitive to shellfish or nuts, as well as insect stings or penicillin are especially prone to anaphylactic reactions.

Immediate medical management is directed toward reducing the exposure to the antigen, reducing the effects of the chemical mediators, and instituting the ABC's of life support-airway, breathing, and circulation, intramuscular or subcutaneous injection of epinephrine 0.3 to 0.5 cc of a 1:1000 dilution. Prefilled spring loaded epinephrine 'pens' are available and are prescribed for all patients who have had some type of anaphylactic reaction to stings. Epinephrine has effects on both alpha and beta receptors. The alpha properties increase blood pressure, decrease peripheral vasodilation, and decrease the cutaneous manifestations of the reaction. The beta effects include bronchodilation, positive inotropic and chronotropic changes on the heart, and increases in intracellular levels of cyclic adenosine monophosphate (AMP), which prevents further release of histamine and leukotrienes.

One of the rare instances where the patient experienced anaphylactic shock was in Lucknow, India. When the doctor administered a test dose of Holoptelia integrifolia antigen intradermally the patient suffered due to anaphylactic shock and had to be revived by giving emergency first aid treatment.

In response to viruses or other invaders, the immune system mounts a reaction with two kinds of white blood cells. T Lymphocytes attack the foreign substances directly. B Lymphocytes produce antibodies, which are protein molecules that attach themselves to the surface of the offender and prepare it for destruction. Once formed, antibodies or immunoglobulins continue to circulate in the blood. Two kinds turn out to be important in allergy immunoglobulin G (IgG) and immunoglobulin E (IgE).

In 1930s Drs. Mary Loveless and Robert Cooke of New York's Roosevelt Hospital, showed that IgG appeared to protect normal people from an allergic attack, just as if it were fighting an ordinary infection. When healthy volunteers were injected with ragweed (Ambrosia) extract, their IgG levels rose in response and they did not develop allergic symptoms. What the doctors could not explain however, was the fact that allergic people already had in their blood, elevated levels of IgG called the 'blocking antibody, yet for some reason did not benefit from it.

When a normal person was inoculated with serum from an allergy sufferer and then injected with an allergen, he/she exhibited inflammatory skin reaction. If he/she received the allergy injection alone no such response occurred. Thus, the difference could be accounted for only by something in the blood of the allergic patient.

In 1966, after performing countless skin tests, on themselves, the husband and wife doctor team of Kimishige and Teruko Ishizaka at the Children's Asthma Research Institute and Hospital in Denver, United States of America, isolated the guilty globulin: which they called IgE. It turns out that IgE skin-sensitizing or reaginic antibodies are involved in about 95% of allergic problems. These cells, part of the immune system, lie on all surfaces of the body where foreign particles might enter the skin, the lining of the respiratory and intestinal tracts and around the tiny veins or veinules. In response to infection, for example, mast cells release histamine and other chemical substances that enable disease-fighting antibodies and white cells to leave the blood vessels and enter the endangered tissues, but in allergy, IgE makes the mast cells run amok.

Allergy victims have 10 times as much IgE in their blood as compared to normal people. Usually the Y-shaped molecules embed themselves stem down on the mast cells. When allergens arrive they attach themselves to the arms of adjacent IgE molecules. This pulls them together and prompts the mast cells to behave inappropriately since there is no infection to fight and release their contents including histamine (Figs. 15.1a, b, c, d). At the same time, the cell membranes of the mast cells and nearby tissue cells exude arachidonic acid. This substance through the action of enzymes produces additional potent chemicals, including prostaglandins and leukotrienes. It was once thought that the histamine was the principal chemical involved in allergic reactions, causing inflammation and contraction of the smooth muscles of the respiratory tracts, but leukotrines, researchers now know, can be far more powerful. Leukotrienes (SRS-A) induce significant bronchospasms (up to 1,000 times more potently than histamine), mucus production, and increased vascular permeability. Eosinophil chemotactic factor is responsible for the many eosinophils seen in allergic reactions. Bradykinins are also potent broncho constricting agents.

While histamine constricts the central bronchial passages, the leukotrines account for the narrowing and loss of elasticity of the smaller outlying passages that can seriously impair the passage of oxygen into the blood. IgE protects whole ravages of parasitic diseases. "Perhaps best IgE producers would best survive parasites". But now this system has turned against pollen, moulds and other substances.

Certainly heredity helps determine who suffers from allergy. Generally it can be said that one is not born allergic but with a tendency to make IgE antibodies. The first things a person makes IgE antibodies to, are the first

IgE , antibodies '

IgE , antibodies '

White blood cell

Histamines

' Allergens

Histamines

Mast cell

Fig. 15.1 A. White blood cell mass produces IgE antibodies after exposure to allergens; B. Allergens bridge the area between IgE molecules pulling them together; C. The bridged IgE molecules stimulate the histamines and other chemicals; D. Up to 5,00,000 IgE molecules gather on individual mast cell.

things he/she is exposed to. That is probably why babies are prone to milk and egg allergies. But it takes time and exposure to allergens to produce symptoms. Immigrants from Europe, where ragweed (Ambrosia) is relatively scarce, may not develop hay fever for years after moving to the U.S.A.

Allergy Tests

There are several ways to test for allergies such as scratch test, prick test, inhalation (brochoprovocation) and ingestion tests, intradermal tests and RAST (radioallergosorbent test) done on a patient's blood sample.

HISTORY OF SKIN TESTING WITH POLLEN ANTIGENS

Hippocrates was perhaps the first one to describe allergic reactions in individuals. However, the first modern description of an allergic patient was published as early as 1819 by Jonathan Bostock, a physician in

London, who had clearly described a clinical symptom known today as 'asthma' and 'allergic rhinitis'. He used the term 'summer catarrh' for this clinical condition.

Wyman at Harward University, U.S.A. in 1872, clearly identified ragweed pollen as the causative agent in hay fever. Later it was Blackley, a physician from Manchester, England in 1873 who conducted a number of experiments in which he performed the first skin test with grass pollen extract to the excoriated skin of the patient's forearm and demonstrated the development of allergic reaction in the form of a weal in the allergic individuals.

Later, in 1911, Leonard Noon, an infectious disease specialist, injected allergic patients with pollen extract in an attempt to cause the patient to develop 'pollen antitoxin' to neutralize the 'toxin' that he thought was produced by the body secondary to the original pollen exposure. He developed a protocol in which various dilutions of an allergic extract were used to drop in the conjunctiva of an allergic individual. Production of erythema and inflammation of the conjuctiva determined the strength of pollen extract. French Hansel, an orolaryngologist in 1930, began experimenting with skin testing using various dilutions rather than a single test of allergenic material.

PRECAUTIONS TO BE TAKEN PRIOR TO ALLERGY TEST

In order to evaluate the allergy test accurately, certain medications such as antihistamines and tranquilizers should not be taken 48 hours before the allergy test is performed. Testing should not be done if a patient is running a fever or has an attack of asthma or hay fever. Antihistamines suppress the weal and flare response. Decongestants, cromolyn, corticosteroids, and bronchodilators do not affect skin test results, and need not be discontinued before testing.

PROCEDURE FOR SKIN TESTING OF ALLERGENS

Antigens prepared from allergens are tested on the skin of allergy patients. The following step-by-step procedure should be adopted for an accurate response.

1. Clean the injection site with an alcohol swab, moving in a circular motion. Start from the centre and move outward. Allow the alcohol to dry.

2. Carefully pick up the syringe. Pinch a two-inch fold of skin, and with one quick motion, inject the needle into the skin. The normal injection angle is between 45 degrees and 90 degrees, or straight in.

3. Release the pinched skin. While holding the barrel with one hand, pull back slightly on the plunger. Look for blood in the barrel. If there

Fig. 15.2 Steps A-E involved in the procedure for skin testing of allergens.

is blood, do not inject the allergy medication. The needle is in a vessel. Simply pull the needle out of the injection site and start again with a new syringe and a new injection site.

. If there is no blood, proceed with the injection by pushing the plunger down and inject the allergy medication.

. When finished, pull the needle from the skin and gently hold an alcohol swab on the injection site. Do not massage the area.

. Dispose of syringes properly. Make the syringe unusable by carefully breaking off the needle. Drop the unusable syringe into an empty resealable container such as a coffee can bleach bottle, or liquid detergent bottle. These steps have been shown in Figs. 15.2A to E, modified from information supplied courtesy Becton Dickinson and Company.

Fig. 15.2 Steps A-E involved in the procedure for skin testing of allergens.

Intradermal Skin Testing

Usually the upper half of the volar surface of the forearm is selected for intradermal skin testing. The surface selected is cleansed with spirit (70 % ethyl alcohol). The allergens with 1:500 dilution are used for testing. Negative control is maintained by using phosphate buffered saline diluent. 0.1 ml solution is taken in 1 ml glass tuberculine syringe fitted with 26-gauge needle. The selected skin is stretched taut and the syringe is placed at an angle of 45° to the arm, introducing the needle into the superficial layers of the skin. A small amount of allergen solution (approximately 0.02 ml) is gently injected that can raise a bleb of 1-3 mm in diameter.

The skin reactions are read after 15-20 minutes. The size of the weal is measured with a reaction gauge or by using the Shivpuri technique (1964). The pseudopodes, erythema are also noted. If a hypersensitivity (allergic) reaction is present, a positive weal will enlarge at least an additional 2 mm beyond the size of the 'negative' (5 mm) weal within 10 minutes.

The size of the skin reaction is influenced by a number of factors, including the volume and potency of allergen injected, the degree of sensitization of cutaneous mast cells (related to levels of circulating IgE specific for that allergen), and the reactivity of the skin to histamine and other mediators released from the mast cells.

Allergen exposure has the same effect on skin reactivity as the use of stronger testing antigen; that is, the production of a more intense skin reaction. Therefore, patients will usually be found to be more sensitive to skin testing carried out during the season when the allergens are at their peak, and endpoints obtained during coseasonal testing will often shift when that antigen goes out of season. These data are useful for preparation of prescription for antigen extracts for immunotherapy.

SCRATCH TESTING

Scratch testing is the original technique first described by Charles Blackley in 1873. This technique consists of making 2-mm superficial lacerations in the patient's skin followed by the application of a drop of concentrated antigen.

PRICK TESTS

The technique of the prick test was first described by Lewis and Grant in 1926. As currently performed, a single drop of antigen concentrate is placed on the skin. A sterile 26-gauge needle is passed through this drop and inserted into the skin in a superficial manner so that no bleeding is caused.

A variant of this test is the 'multitest', in which a sterile disposable applicator with eight puncture heads is used, which allows for the simultaneous testing of six antigens and a positive (histamine) and negative (glycerine) control. Grading of skin reactivity is done on a subjective 0 to 4+ basis.

Treatment of Allergy

Actually the treatment of allergy is a cooperative venture with both the patient and physician as participants. The goal of treatment is to produce an allergic balance so that the patient is freed of existing allergic illness and to avoid the development of new allergic problems. A basic part of the management of allergy is educating the patient to eliminate offending allergens whenever possible. Since certain allergens such as inhalants (air, along with airborne pollen and spores) cannot be eliminated, the reaction of the patient to these substances is controlled by desensitization. The process of desensitization is known as immunotherapy.

Desensitization is actually nothing but immunization. The desensitization is the technique of injecting small but increasing amounts of the antigens to control the allergic reaction so that the patient has little or no reaction when he is exposed to the offending substances.

The physician administers extracts of the allergen in gradually increasing doses. In time the patient acquires some protection against the allergen in his environment, much as he would after vaccination against an infection. During the treatment, IgE levels rise at first, and then drop. As they fall, levels of 'protectitive' IgG increase. Typically shots are given once or twice a week and are gradually reduced to once a month usually ending after three years. The treatment must be used judiciously as an accidental overdose can trigger an anaphylactic shock.

In about a third of patients, the shots relieve symptoms permanently, another third have recurrences in a year and the rest from 5 to 15 years after treatment. Sometimes, treating allergies can be as frustrating for the doctor as the suffering is for the patient (Seligmann et al., 1982). The basic treatments that allergists offer include injection therapy and telling people to avoid the things they are allergic to. In addition to desensitization or immunotherapy, pharmocotherapy is also equally important.

Immunotherapy

A classical case history has been given by Lewis (1984), which is reproduced below, to prove the importance of immunotherapy to allergy patients by using pollen extracts.

Case History

A 23 year old opera student complained of severe rhinitis and opthalmitis in spring and fall. The patient's symptoms began in mid-March and lasted until the end of April. He was then symptom free until mid-August when his symptoms recurred. He continued to be symptomatic until the first frost. The patient's symptoms included profuse rhinorrhea, nasal occlusion, and intense pruritus. In addition, he had severe ocular pruitus and intense lachrymation. Due to his symptoms he was considering giving up his singing career.

The patient stated that he was much better indoors than outdoors, especially in air conditioning. He was also significantly better when he went to the West Coast of U.S.A. for a vacation in late August. The patient received some benefit from antihistamines but was loath to utilize them because of excessive somnolence.

Laboratory investigations revealed an IgE of 540 IU/ml but otherwise normal.

Skin testing using a multitest apparatus revealed a 4+ reaction to giant ragweed (Ambrosia trifida) and oak (Quercus) pollen. All other skin tests were negative. Immunotherapy was instituted with ragweed and oak pollen extracts and was carried through to 2500 PNU/injection of each extract. On this regimen he had a marked reduction in both spring and fall allergy symptoms. He was able to continue to pursue his singing career.

PREPARATION OF POLLEN ANTIGENS FOR INTRADERMAL TESTING EXTRACTS

Antigens for the diagnosis of respiratory allergy are prepared from the concentrated solutions of allergenic pollen extracts, which are usually aqueous or glycerinated solutions. Normal saline is used for preparation of aqueous pollen extracts, whereas 50% glycerine saline is used for glycerinated pollen extracts. In both cases, preparations are buffered to pH 8 and phenol is added as a preservative. Precaution is taken that antigenic extracts are prepared in a dust-free sterile place, preferably using dehumidifiers, air conditioners and laminar flow.

The following steps are involved in the procedure used for preparation of antigenic pollen extracts:

1) Properly selected mature unopened flower buds are collected in large quantities followed by drying them naturally or in an oven.

2) Anthers are separated with clean sterile forceps and crushed to extract pollen. This is followed by sieving through No 100 or 300 (180 m) mesh sieves to get only pure pollen material.

3) Subjecting pollen to dehydration at 39°C for preventing microbial contamination.

4) Defatting is done by soaking the pollen in petroleum ether overnight. The process of defatting is repeated at least 3-4 times.

5) The defatted pollen are subjected to extraction using saline phosphate buffer of pH 8 for 8 to 24 or 72 hours.

6) The extracts are clarified by passing through Whatmann filtre paper No. 1.

7) Dialysis is done using dialyzing tubes for 24 hours to get rid of the irritating and colouring material.

8) The dialyzed pollen extracts are sterilized, sterility tested, standardized and are ready for use for testing in 1:500 w/v concentration.

For clear understanding, the following flow chart for the preparation of antigenic extracts from pollen can be pursued.

SIMPLIFIED FLOW CHART OF THE PREPARATION OF ALLERGENIC EXTRACTS (Courtesy Dr. Govind)

Dried, ground, 98% pure pollen sieved 0

Defatted using peroxide free diethyl ether

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Allergic To Everything

Allergic To Everything

The human body And Todays chemical infested world. Here is a news flash You are not allergic to pollen, pet dander, or whatever it is that makes your body revolt Rather, your body just can not handle that one thing, what ever it is, anymore, due to the massive barrage of toxic chemicals you and everyone else are ingesting every single day.

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  • Juliane
    Is plaint pollen grain an allergen?
    3 years ago

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