Although the initial synthesis developed by Sheehan was not appropriate for mass production of penicillins, one of the intermediate compounds in Sheehans synthesis was 6-aminopenicillanic acid (6-APA), the nucleus of penicillin.6-APA was discovered by researchers at the Beecham Research Laboratories (later the Beecham Group) in Surrey in 1957 (published in 1959). Attaching different groups to the 6-APA nucleus of penicillin allowed the creation of new forms of penicillins which are more versatile and better in activity. Developments from penicillin
The narrow range of treatable diseases or "spectrum of activity" of the penicillins, along with the poor activity of the orally active phenoxymethylpenicillin, led to the search for derivatives of penicillin that could treat a wider range of infections. The isolation of 6-APA, the nucleus of penicillin, allowed for the preparation of semisynthetic penicillins, with various improvements over benzylpenicillin (bioavailability, spectrum, stability, tolerance). The first major development was ampicillin in 1961. It offered a broader spectrum of activity than either of the original penicillins. Further development yielded β-lactamase-resistant penicillins, including flucloxacillin, dicloxacillin, and methicillin. These were significant for their activity against β-lactamase-producing bacterial species, but were ineffective against the methicillin-resistant Staphylococcus aureus (MRSA) strains that subsequently emerged.Another development of the line of true penicillins was the antipseudomonal penicillins, such as carbenicillin, ticarcillin, and piperacillin, useful for their activity against Gram-negative bacteria. However, the usefulness of the β-lactam ring was such that related antibiotics, including the mecillinams, the carbapenems, and, most important, the cephalosporins, still retain it at the center of their structures.
Iridocorneal endothelial (ICE) syndromes are a spectrum of diseases characterized by slowly progressive abnormalities of the corneal endothelium and features including corneal edema, iris distortion, and secondary angle-closure glaucoma. ICE syndromes are predominantly unilateral and nonhereditary. The condition occurs in predominantly middle-aged women. Signs and symptoms
Many cases are asymptomatic, however patients many have decreased vision, glare, monocular diplopia or polyopia, and noticeable iris changes. On exam patients have normal to decreased visual acuity, and a "beaten metal appearance" of the corneal endothelium, corneal edema, increased intraocular pressure, peripheral anterior synechiae, and iris changes. Mechanism
The exact mechanism is unknown, however there appears to be a component of abnormal corneal endothelium that proliferates onto the iris forming a membrane that then obstructs the trabecular meshwork, leading to iris distortion. Nodule formation can also occur when the abnormal corneal endothelium causes contractions around the iris stroma. Herpesvirus DNA has been identified in some patients following keratoplasty, suggesting the possibility that herpes simplex virus may induce the abnormal endotheliazation in the anterior chamber angle and on the surface of the iris. Variations
The Chandler variant of ICE is characterized by pathology on the inner surface of the cornea leading to abnormal endothelial pump function. Other features include possible mild iris changes, corneal edema, and normal to slight elevations in intraocular pressure.Cogan-Reese variant is characterized by multiple pigmented iris nodules. This variant is most commonly unilateral and seen in middle-aged females. Diagnosis
Treatment
Penetrating karatoplasty and endothelial keratoplasty can be used as treatments for severe cases of ICE.