Muromonab-CD3 (trade name Orthoclone OKT3, marketed by Janssen-Cilag) is an immunosuppressant drug given to reduce acute rejection in patients with organ transplants. It is a monoclonal antibody targeted at the CD3 receptor, a membrane protein on the surface of T cells. It was the first monoclonal antibody to be approved for clinical use in humans. History
Muromonab-CD3 was approved by the U.S. Food and Drug Administration (FDA) in 1986, making it the first monoclonal antibody to be approved anywhere as a drug for humans. In the European Communities, it was the first drug to be approved under the directive 87/22/EWG, a precursor of the European Medicines Agency (EMEA) centralised approval system in the European Union. This process included an assessment by the Committee for Proprietary Medicinal Products (CPMP, now CHMP), and a subsequent approval by the national health agencies; in Germany, for example, in 1988 by the Paul Ehrlich Institute in Frankfurt. However, the manufacturer of muromonab-CD3 has voluntarily withdrawn it from the United States market in 2010 due to numerous side-effects, better-tolerated alternatives and declining usage. Indications
Muromonab-CD3 is approved for the therapy of acute, glucocorticoid-resistant rejection of allogeneic renal, heart and liver transplants. Unlike the monoclonal antibodies basiliximab and daclizumab, it is not approved for prophylaxis of transplant rejection, although a 1996 review has found it to be safe for that purpose.It has also been investigated for use in treating T-cell acute lymphoblastic leukemia. Pharmacodynamics and chemistry
T cells recognise antigens primarily via the T cell receptor (TCR).
Growth measurement parameters in children with suspected constitutional delay include a height, a weight, the rate of growth, and the calculated mid-parental height which represents the expected adult height for the child. Malnutrition or chronic disease
Diet and physical activity habits, as well as history of previous serious illnesses and medication history can provide clues as to the cause of delayed puberty. Delayed growth and puberty can be the first signs of severe chronic illnesses such as metabolic disorders including inflammatory bowel disease and hypothyroidism. Symptoms such as fatigue, pain, and abnormal stooling pattern are suggestive of an underlying chronic condition. Low BMI can lead a physician to diagnose an eating disorder, undernutrition, child abuse, or chronic gastrointestinal disorders. Primary failure of the ovaries or testes
A eunuchoid body shape where the arm span exceeds the height by more than 5 cm suggests a delay in growth plate closure secondary to hypogonadism. Turner syndrome has unique diagnostic features including a webbed neck, short stature, shield chest, and low hairline. Klinefelter syndrome presents with tall stature as well as small, firm testes. Genetic or acquired defect of the hormonal pathway of puberty
Lacking the sense of smell (anosmia) along with delayed puberty are strong clinical indications for Kallmann syndrome. Deficiencies in GnRH, the signalling hormone produced by the hypothalamus, can cause congenital malformations including cleft lip and scoliosis. The presence of neurological symptoms including headaches and visual disturbances suggest a brain disorder such as a brain tumor causing hypopituitarism.