Oskar Kobylinski (1856-1926) and the first description of Noonan syndrome in the medical literature.

While a student of University in Dorpat (now Tartu, Estonia) Oskar Kobylinski published an article reporting on his 22-year-old patient Leisar Eischikmann, who suffered from a congenital deformity of the neck. Kobylinski described this rare anomaly and called it "flüghautige Verbreitung des Halses" (wing-like extension of the neck). It was only in 1902 when the name pterygium colli was introduced, and it has been in use ever since. This malformation is part of some congenital syndromes, most prominently, Turner syndrome and, more rarely, of Noonan syndrome. As Opitz et al. pointed out, the patient described in the 1883 article from Archiv für Anthropologie is probably the first person with Noonan syndrome to have been pictured in the medical literature. The article was signed only by "O. v. Kobylinski, student of medicine." Further archival research was needed to identify this physician and provide more details about his unusual career.

A Chronology for the Identification and Disclosure of Adverse Effects of Succinylcholine.

BACKGROUND: New therapies are created to address specific problems and enjoy popularity as they enter widespread clinical use. Broader use can reveal unknown adverse effects and impact the life cycle significantly. Succinylcholine, a depolarizing neuromuscular blocker, was the product of decades of research surrounding the ancient compound, curare. It was introduced into practice in the 1950s by Burroughs Wellcome and Company (BW Co) and was welcomed due to its rapidly acting muscle relaxation effects. Global clinical use revealed adverse effects, both minor and major, in particular, hyperkalemia and malignant hyperthermia. We investigated when practitioners and the manufacturer became aware of these adverse effects, how information about these side effects was disseminated, and whether the manufacturer met the regulatory requirements of the time, specifically regarding the timely reporting of adverse effects. SOURCES: Primary literature search using online and archived documents was conducted at the Wood Library-Museum of Anesthesiology, Schaumburg, IL. We consulted documents submitted by BW Co to federal authorities, through the Freedom of Information Act (FOIA), Food and Drug Administration (FDA) reports, promotional advertisements, package inserts, published articles, and textbooks. RESULTS: Initial clinical testing in humans in 1952 found no adverse effects on cardiovascular or respiratory systems. Fasciculations and myalgia were early side effects described in case reports in 1952. Large-scale clinical trials in 1953 found abnormally long recovery times among some patients; the discovery of abnormal pseudocholinesterase enzyme activity was not fully demonstrated until the early 1960s. Bradycardia was first reported in 1957 in children, and in 1959 in adults. In 1960, animal studies reported a transient increase in plasma potassium; further experiments in 1969 clearly demonstrated succinylcholine-induced hyperkalemia in burn patients. Malignant hyperthermia was first described in 1966. Similar cases of elevated temperatures and muscle rigidity were described globally but the underlying mechanism was not elucidated until the 1990s. Standard anesthesia textbooks did not report major side effects of succinylcholine until 1960 and included newly documented side effects with each edition. BW Co's packaging contained warnings as early as the 1950s but were later updated in 1962 and beyond to reflect the newly discovered hyperkalemia and malignant hyperthermia. CONCLUSION: Particularly given the regulatory environment of the time, BW Co appropriately reported the adverse effects of succinylcholine after market entry; it updated promotional and packaging material in a timely manner to reflect newly discovered adverse effects. The toxicity, though alarming and put clinicians on alert, did not seem to heavily impact succinylcholine's use, given its various desirable properties. It is still a choice muscle relaxant used today, although there are efforts to develop superior agents to replace succinylcholine.

Hipertemia maligna: aspectos históricos / Malignant hyperthermia: historical aspects

Malignant hyperthermia is a sword of Damocles hanging upon the anesthesiologists, even in the XXIst century. Eventhough Malignant Hyperthemia’s known history does not go beyond 1960, many of its actors are forgotten or unknown for the new generations. The purpose of this article is to rescue the name of these characters and to honor their labor in a hostile enviroment when anesthesiology was a specialty still developing and the exchange of and access to information among the medical community were scarce and limited.

La hipertermia maligna es una espada de Damocles que aún cuelga sobre las cabezas de los anestesiólogos en el siglo XXI. La historia conocida de esta enfermedad no va más atrás que 1960, pese a lo cual muchos de los actores participantes en esta saga han pasado al olvido o son desconocidos para las nuevas generaciones. El propósito de esta narración es rescatar a esos personajes y resaltar su épico desempeño en una época en que el desarrollo de la anestesiología, la comunicación entre los médicos de diferentes países y sobre todo el acceso a la información, eran muy limitadas en relación a lo que vivimos hoy en día.

Malignant hyperthermia in the early days of pediatric anesthesia: an interview with anesthesiology pioneer, Dr. John F. Ryan.

Dr. John F. Ryan (1935 - ), Associate Professor of Anaesthesia at the Harvard Medical School, influenced the careers of hundreds of residents and fellows-in-training while instilling in them his core values of resilience, hard work, and integrity. His authoritative textbook, A Practice of Anesthesia for Infants and Children, remains as influential today as it did when first published decades ago. Although he had had many accomplishments, he identified his experiences caring for patients with malignant hyperthermia and characterizing the early discovery of this condition as his defining contribution to medicine. Based on a series of interviews with Dr. Ryan, this article reviews a remarkable career that coincides with the dawn of modern pediatric anesthetic practice.

Unravelling the mystery of malignant hyperthermia.

Malignant hyperthermia was an unknown condition in 1960 although there had always been occasional patients who died mysteriously under anaesthesia. The nature of the disease became apparent when a young Melbourne man presented that year with a compound fracture and a family history of deaths under anaesthesia. He survived his anaesthetic due to the combined efforts of the anaesthetist and the surgeon. His family history was then investigated by the physicians. Over the next 20 years the cause of the disease was discovered and eventually a treatment was found. This article is based around a series of interviews with many of the participants in this story.

Malignant hyperthermia. An historical vignette.

This paper reports previously unpublished accounts of the deaths in 1915 and 1919 of two members of the same family during general anaesthesia. The deaths were subsequently ascribed to a 'hereditary susceptibility' to chloroform. Contemporary evidence is presented which suggests that these deaths were among the very earliest examples of malignant hyperthermia to be described.

[Malignant hyperthermia today]. / Maligne Hyperthermie heute.

Besides offering a concise recapitulation of known facts, experiences and related viewpoints concerning malignant hyperthermia (MH), the present article offers a review of the most relevant new aspects in this field. Special emphasis is on genetics and pathogenesis of MH. The contents of the review are as follows: History; Definition of MH; Epidemiological aspects; Inheritance; Molecular genetics; Pathogenesis; Triggering agents; Awake Triggering; Sympathetic nervous system; Serotoninergic system; Involvement of other organs and cell systems; Clinical symptoms and diagnosis; MH and myopathies; Associated disorders; Treatment; Prophylaxis; Identification of susceptibility; MH testing centres in the FRG; Hot-line for MH emergencies