Millie Mc Reynolds Rough Draft

Millie Mc Reynolds
April 3, 2008
Rough Draft

Penicillin Allergy

Unfavorable reactions to penicillin allergy may be characterized as toxic or immunological. Toxic reactions, which are due to precise pharmacological properties of penicillin, are extremely rare, and they occur when large doses of the antibiotic are given to the patient with renal impairment. According to Stewart, “up to 70% of a given dose may be excreted in an hour and the rapidity of excretion is another reason for the lack of toxicity of penicillin”. Some immediate reactions to penicillin may be due to minor antigenic determinants. Accelerated and late allergic reactions have generally been viewed as being mediated by soluble antigen-antibody complexes. (maybe start off with something about allergies in general or allergies to medicines and the impact that has on treating patients. Also direct quotes should be avoided at all costs in formal writing.)

Penicillins are the most extensively used antibiotics for common infections and are still the treatment of choice for many infections others (Park). The frequency of penicillin allergy in the general population is unknown (Park). All forms of penicillin, including the newer semi-synthetic derivatives, are to some extent cross allergenic and possibly because of the widespread use of the penicillins, show an increase in allergic reactions to penicillin. Consider: All forms of penicillin, including the recent semi synthetic derivatives, are to some extent cross allergenic. This may be due to the widesperead use of the penicillins, which cause an increase in allergic reactions to penicillin. The first recorded allergic reaction to penicillin was in 1945, and while the first death from penicillin occured in 1946 (Stewart). (transition to new paragraph should be added)(I would maybe add in some background information on penicillin)

Females are nearly 5 times more likely than males to have a positive skin test for penicillin allergy (accoring to recent research.) . According to study findings (research) presented at the annual scientific meeting of the American College of Allergy, Asthma, and Immunology. As Brown mentions, “the findings are based on a study of 1,759 patients who participated in a skin testing protocol designed to reduce the use of broad-spectrum antibiotics and prevent antimicrobial resistance in the surgical setting". All of the subjects reported a history of penicillin allergy, but if the preoperative skin test showed no allergy, a penicillin type drug was given in the operating room. (consider revising last sentence) The researchers found that the protocol did, in fact, reduce the use of broad-spectrum antibiotics and help prevent antimicrobial resistance.

Immunological Basis of Penicillin Allergy

The different types of allergic reactions to penicillin are mediated by different antibodies. These antibodies are now considered to belong to the class of immunoglobulins; they are immunoglobulin E reword(IgE) (Stewart). There have been certain attempts to hold back the levels of IgE because of its involvement with the penicillin allergy. (what is IgE function in the immune system? why is this important?) (also, give some information on how penicillin relates to IgE, also, where does the antibodies come from and why are they present?)
As Dintzis mentions, “the administration of antigenic material to cause suppression of persistent allergic immune responses, immunotherapy, was first described in 1911 and has been widely used in clinical treatment of human allergy”. (Take a look at where you want to end your quotations) Though not all the main classes of antigen specific antibody (ies) have not been hold (held) back by these procedures. Most of the time these treatments have been a caused a to decrease onthe levels of specific IgE antibodies and an increase on the levels of the IgG antibodies (Dintzis). (What are IgG antibodies, why do you want an increase in IgG antibodies and not IgE?)

T-Cell Response and Molecular Feature of Penicillin Allergy

The peripheral blood lymphocytes of patients allergic to penicillin propagate in vitro in response to the specific β-lactam antibiotic. (I would add somewhere that penicillin is a B-lactam antibiotic) Regarding their function, this antibiotic mainly represents an appropriate mean for investigation. (I am confused by the previous sentence. I think a reword would be helpful to the reader) The bicyclic thyazolidine/β-lactam backbone is the same for all penicillins. There are many side chains that give a complete analysis of the specificity of the recognition by penicillin specific TCRs (Is this the first use of Toll-Like receptors? if so it should be written out) (Padovan). (I think its supposed to be T-cell receptors)

Penicillins constitute a large family of compounds whose common structural (structure) is a β-lactam ring condensed to a thiazolidine ring. The basic structure is formed by a thiazolidine ring attached to a Beta B-lactam ring (be consistent). The side chain determines its antibacterial, pharmacological, and to some extent, immunological characteristics. Penicillins represent a good example of an allergy stimulating drug in humans. They mainly focus on the IgE mediated hypersensitivity reactions, also the drug specific T-cell reactions that are involved in causing inflammatory response (Weltzein).

The specificity of the respective T-cell receptors is directed to the backbone and the specific side of penicillin. Which is contrast, the series of the carrier peptide contribute as holder for the haptenic determinant. ( NOt sure what that sentence means) The recognition of penicillin by a specific TCR can be predicted. And to be expected, the thyazolidine ring and the phenyl group of the side chain of the molecule may rotate and dispose in the space which will help it to be recognized. The rotation was a result from the arrangement of a big hydrophobic group contacting certain TCR sites. This change in the molecule was caused by the flexibility of the side chain of the penicillin derivative (Weltzein).

Immediate Hypersensitivity Reactions to Penicillins and other betalactams

Betalactam (BL) antibiotics are formed by a large number of chemical compounds that share a common structure and mechanism of action. Penicillins are one of the most important groups of antibiotics. Betalactam are the compounds most frequently involved in immunological drug reactions induced by specific mechanisms. Antunez stated that “since BL were first used for treating infectious diseases, they have been considered to represent the classical prototype of drug hypersensitivity”. The reason of why BL are the drugs most frequently involved in immunological reactions is because their attribution of their capacity to bind spontaneously to exogenous or endogenous proteins. All BL bind to cell or serum proteins with different kinetics, generating hapten carriers that conjugate in a concentration-dependent manner. Binding with serum proteins occurs in less than one hour whereas binding with cell proteins occurs in about eight hours (Antunez). (What is the significance to BL being able to bind so well to proteins (bacteria) and what happens once it binds to proteins that make it a great antibiotic)

Initially, rather than a still image, penicillin allergy was considered to be a moving picture where the actors were newly-released BL, different populations with different ages and variable rates of exposures, and wider treatment applications may be necessary for considering these factors (Run on sentence, revise). Of these, the most notorious finding contributing to variation in penicillin allergy is that of benzyl penicilloyl (BPO), the major determinant generated by benzyl penicillin (BP), is becoming less relevant because BP has been progressively less used and gradually replaced by a number of new BL. (Revise sentence, maybe use a period somewhere) The BPO results from the opening of the BL ring by an amino group of the protein, and this forms the major determinant that is recognized when, conjugated to poly-L-lysine (PLL), it is applied to the skin. These are composed of chemical structures that, although they share the BL ring, have sufficient differences that contribute to the nature of the epitope.

From the beginning, when BP was the only BL used, reactions were classified into three groups according to the time interval between drug intake and occurrence of symptoms which include: immediate, accelerated, or delayed (Antunez). Antunez stated that immediate reactions occur within minutes to less than one hour after hapten exposure, with typical entities being urticaria and anaphylactic shock. Delayed reactions are those occurring from 48 to 72 hours after drug intake, and involve such entities as delayed urticaria, exanthema, desquamative exanthema, Stevens-Johnson syndrome (potentially deadly skin disease), Lyell syndrome (eruption of the skin) and fixed drug eruption. These reactions have been attributed to a T cell response”. (What about accelerated symptoms?)

Among all these researches (Among all of this research that has been done, it is obvious that there needs to be more clinical and experimental research about the penicillin allergy.)that have been done is obvious that there has to be more clinical and experimental research about the penicillin allergy. Some important, as well theoretical advances have been made, but it is still difficult to understand why do some people become allergic to a given antigen while others do not?(use . instead of ?) Penicillin has been shown to induce production of antibodies and several distinct specificities and distinct immunoglobulin classes when given to humans. The causes of penicillin allergy are extremely complex. Stewart stated that “cutaneous hypersensitivity is often absent when IgG and IgM antibodies are present in relatively higher titer, and also patients with such antibodies perhaps the majority can tolerate therapeutic injections of penicillin”. It seems likely, therefore, that these can block in certain ways the attachment of penicillin antigens to skin sensitizing antigens if present. There is a fascinating irony that penicillin can be well tolerated in large doses and can also cause fatalities in the smallest doses. For this and for many other reasons like have been mention on the paper, (
It is from this and other reasons mentioned in the paper that..)
the knowledge of penicillin allergy is of fundamental importance in human medicine.

Millie- Good start on your paper. I would like to know more about the effects of penicillin and why it happens. Consider taking your paper to the writing specialist in the library to clear up some of your sentence revisions. Also, try to organize the paper so it flows a little better without having to use your headings.

Millie- I feel that biochemical structural information is predominately presented and laking in some of the immune concepts that can be presented. Maybe you did not find the information to determine why people are allergic to penicillin, but could you talk about an "normally allergic reaction" and how that effects the immune system. This would help explain to the reader what is going on inside the body cause the symptoms of penicillin allergic reactions (which i would also like to see included). Some sentences were sometimes awkward. I suggest bring in a few drafts to Dr. Robson to review, because that would be a big help. Good start!

Millie-I would suggest looking up "penicillin" and "allergies" and such on wikipedia just so you can get a good overall feel for this subject, which will hopefully lead to better organization and more areas to look into in the research you have done. More detail needs to be added on immunological responses due to penicillin.
Millie-good start to your paper. For the most part, your beginning paragraphs could use some more substance. Information seems incomplete, go into more detail. After your last topic, your paragraphs got better!

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