This makes the sperm completely unable to penetrate the zona pellucida. The sperm in Type 2 globozoospermia has some acrosomal covering surrounded by large droplets of cytoplasmic material, suggesting secondary degenerative changes. There is also a conical nucleus. It is thought that infertility in this type of globozoospermia is due to incorrect chromatin packaging which prevents proper fertilization. Symptoms
Aside from the effect on fertility globozoospermia is symptomless. People with globozoospermia have normal physical and mental development, normal clinical features and normal hormonal profile. Genetics
Table 1: Gene mutations that have been identified in globozoospermia and the impact these mutations have on sperm function and successful fertilization. Diagnosis
The presence of round headed sperm in a semen analysis sample confirms the diagnosis of globozoospermia. The lack of acrosome can be ascertained by either morphology staining or immunofluorescence. Treatment
Until 1995, the only options for people with globozoospermia who wished to conceive were adoption or sperm donation. With the advancement of assisted reproductive techniques (ART) it is now possible for those with globozoospermia to conceive using their own sperm. The main technique used is intracytoplasmic sperm injection (ICSI) where fertilisation is achieved by a single sperm being injected into the egg. Some studies have shown it is possible for a viable embryo to be created with this technique alone, however others have found it necessary to also use calcium ionophore treatment for fertilisation to be successful. Calcium ionophore treatment is used to artificially activate the oocyte.
Phenytoin reduces the maximal activity of brain stem centers responsible for the tonic phase of generalized tonic-clonic seizures. Pharmacokinetics
Phenytoin elimination kinetics show mixed-order, non-linear elimination behaviour at therapeutic concentrations. Where phenytoin is at low concentration it is cleared by first order kinetics, and at high concentrations by zero order kinetics. A small increase in dose may lead to a large increase in drug concentration as elimination becomes saturated. The time to reach steady state is often longer than 2 weeks. History
Phenytoin (diphenylhydantoin) was first synthesized by German chemist Heinrich Biltz in 1908. Biltz sold his discovery to Parke-Davis, which did not find an immediate use for it. In 1938, outside people including H. Houston Merritt and Tracy Putnam discovered phenytoins usefulness for controlling seizures, without the sedative effects associated with phenobarbital. According to Goodman and Gilmans Pharmacological Basis of Therapeutics:

In contrast to the earlier accidental discovery of the antiseizure properties of potassium bromide and phenobarbital, phenytoin was the product of a search among nonsedative structural relatives of phenobarbital for agents capable of suppressing electroshock convulsions in laboratory animals. It was approved by the FDA in 1953 for use in seizures. Jack Dreyfus, founder of the Dreyfus Fund, became a major proponent of phenytoin as a means to control nervousness and depression when he received a prescription for Dilantin in 1966. He has claimed to have supplied large amounts of the drug to Richard Nixon throughout the late 1960s and early 1970s, although this is disputed by former White House aides and Presidential historians.