From ACE to ACENO: How America's Munson added Harley's British mixture to nitrous oxide.

An Ohio dentist, Corydon Munson, patented a gasometer with an attachment for vaporizing trace amounts of volatile general anesthetics or their mixtures into unoxygenated nitrous oxide. After vaporizing a variant of George Harley's ACE mixture into nitrous oxide, Munson branded his own novel anesthetic combination as ACENO.

The Reincarnation of Methoxyflurane.

Methoxyflurane was an inhaled agent commonly used for general anesthesia in the 1960s, but its clinical role gradually decreased in the 1970s because of reports of dose-dependent nephrotoxicity. In 1999 its manufacturer, Abbott Laboratories, discontinued distribution of methoxyflurane in the United States and Canada. Outside of North America, however, methoxyflurane has been reborn as an inhaled analgesic used for pain relief in the prehospital setting and for minor surgical procedures. First used in Australia and New Zealand, and subsequently in over thirty-seven other countries, low concentrations of methoxyflurane are administered with a hand-held inhaler which provides conscious sedation, so that patients can self-assess their level of pain and control the amount of inhaled agent. The Penthrox inhaler, originally developed in Australia after several other hand-held vaporizers were tried, is currently being used worldwide as a portable and disposable self-administered agent delivery system. Methoxyflurane-induced nephrotoxicity continues to be a major concern, but with cautious administration of recommended doses methoxyflurane has been established as a remarkably safe analgesic agent with minimal side effects for patients in need of rapid and potent pain relief.

Townley's Chloroform Inhaler.

While cataloguing the historical items in the Department of Anaesthesia, Addenbrooke's Hospital, Cambridge, UK, we discovered an unusual chloroform inhaler, which incorporated two air-inlet tubes in addition to its main inspiratory valve as well as a funnel on one of its lateral walls. An accompanying card stated that the device was thought to be a modification of Snow's inhaler, by James Robinson. It had been found among some old instruments in a General Practice in Huntingdon, Cambridgeshire, and had probably been acquired by an early practitioner named Dr. Newton, who qualified in 1851 and performed a lot of minor surgery in the practice. Using information published in books, medical journals, instrument catalogues, and other sources available in the public domain, we sought to confirm the identify of this inhaler and further investigate its provenance. Soon after the introduction of chloroform anesthesia in November 1847, James Robinson modified Snow's ether face-piece to produce an ingenious device for administering the vapor of chloroform. However, Robinson's inhaler did not include the air-inlet tubes, or funnels, which are an integral feature of the device found in the Addenbrooke's collection. Following further research, we formally identified our device to be of the type introduced by James Townley in 1862 for use with his "Anodyne mixture." We describe Townley's chloroform inhaler and provide an insight into the life and work of its inventor, as well as Dr. Newton and his son, who may have used the apparatus in the Cambridgeshire area.

Unusual partnerships: The Corfe-McMurdie anaesthetic inhaler of 1918 and the 2nd Australian Casualty Clearing Station.

This World War 1 ether/chloroform vaporiser-inhaler was designed by and made for Captain Anstruther John Corfe by Private Eric Aspinall McMurdie, both of the 2nd Australian Casualty Clearing Station (ACCS), Australian Army Medical Corps (AAMC). It has a plaque attached labelled 25 May 1918. It is a perfect example of the ingenuity forced by the realities of war, and is one of the unique pieces in the Harry Daly Museum at the Australian Society of Anaesthetists (ASA) headquarters in Sydney, Australia. While serving in Blendecques, France, Private McMurdie ingeniously fashioned this vaporiser from discarded items he found on the battlefield. These included Horlick's Malted Milk bottles, on which he etched measurements for ether and chloroform, and a spent brass artillery shell, which made the heating component of the inhaler. The 2nd ACCS triaged and operated on thousands of troops, and this inhaler is a reflection of the skills and innovative expertise of the staff of the 2nd ACCS which included X-rays to localise foreign bodies, and locally made splints and apparatus to treat trench foot.

The Mist Tent: An Analysis of Therapeutic Change in the History of Cystic Fibrosis Care.

Mist tent therapy for cystic fibrosis went through a rise and fall in popularity between the 1950s and 1970s, providing an opportunity to explore the nature of therapeutic change in medicine. The therapy "worked" in the context of a particularly grim life expectancy in the early 1950s and in the setting of a comprehensive therapeutic program that began in Cleveland in 1957. Although clinical studies published in the 1970s provided evidence that mist tents were ineffective or even harmful, these later studies were not necessarily more robust than earlier studies that provided evidence of mist tent efficacy, suggesting that other factors may have also contributed to mist tent abandonment. In fact, the unpalatable nature of mist tent therapy, which was described by one doctor as akin to incarceration, and studies that questioned the theoretical underpinnings of the therapy also played important roles in the eventual abandonment of mist tents.

Dispersing the Mists: An Experimental History of Medicine Study into the Quality of Volatile Inhalations.

BACKGROUND: Dr. Nelson's Improved Inhaler was first marketed with an advertisement in The Lancet in 1865. Revolutionary at the time for its ease of use and patient-friendliness, the inhaler is still in use for self-treatment by many all over the world. On the occasion of its 150th anniversary, this study reports an experimental historical medicine approach to identify evidence for the quality of vapor inhalers. METHODS: Through accessing reviews of the device's use by the contemporary medical establishment, it was established that Dr. Nelson's Inhaler enjoyed a reputation of quality and efficacy among reputable physicians generating empirical evidence of clinical performance. There was a general absence of product performance tests during this period. Therefore, modern inhalation performance testing was applied to test the aerosol delivery performance for Friars' Balsam, and its key chemical constituent, benzoic acid (BA). RESULTS: A respirable dose of 59.9 ± 9.0 µg of BA was aerosolized in a 10 minutes period from a dose of 3.3 mL Friars' Balsam (equivalent to 35.1 ± 0.2 mg of BA) in 375 mL of steaming water using the glass twin stage impinger at a flow rate of 60 L·min-1. The respirable dose from a standardized aqueous BA inhalation formulation increased from 115.9 ± 10.6 to 200.2 ± 19.9 µg by increasing the simulated inhalation period from 5 to 10 minutes. When tested with a simulated inhalation maneuver (500 mL tidal volume, 13 minutes-1 respiration rate, 1:2 inspiratory:expiratory ratio) a respirable dose of 112.8 ± 40.3 µg was produced. CONCLUSIONS: This work has highlighted the potential for aerosol drug delivery using steam inhalers that are popular with patients. Physicians should therefore be aware of the potential for lung dosing with irritants when patients self-medicate using the Nelson Inhaler with vaporizing formulations such as Friars' Balsam.

The History of Therapeutic Aerosols: A Chronological Review.

In 1956, Riker Laboratories, Inc., (now 3 M Drug Delivery Systems) introduced the first pressurized metered dose inhaler (MDI). In many respects, the introduction of the MDI marked the beginning of the modern pharmaceutical aerosol industry. The MDI was the first truly portable and convenient inhaler that effectively delivered drug to the lung and quickly gained widespread acceptance. Since 1956, the pharmaceutical aerosol industry has experienced dramatic growth. The signing of the Montreal Protocol in 1987 led to a surge in innovation that resulted in the diversification of inhaler technologies with significantly enhanced delivery efficiency, including modern MDIs, dry powder inhalers, and nebulizer systems. The innovative inhalers and drugs discovered by the pharmaceutical aerosol industry, particularly since 1956, have improved the quality of life of literally hundreds of millions of people. Yet, the delivery of therapeutic aerosols has a surprisingly rich history dating back more than 3500 years to ancient Egypt. The delivery of atropine and related compounds has been a crucial inhalation therapy throughout this period and the delivery of associated structural analogs remains an important therapy today. Over the centuries, discoveries from many cultures have advanced the delivery of therapeutic aerosols. For thousands of years, therapeutic aerosols were prepared by the patient or a physician with direct oversight of the patient using custom-made delivery systems. However, starting with the Industrial Revolution, advancements in manufacturing resulted in the bulk production of therapeutic aerosol delivery systems produced by people completely disconnected from contact with the patient. This trend continued and accelerated in the 20th century with the mass commercialization of modern pharmaceutical inhaler products. In this article, we will provide a summary of therapeutic aerosol delivery from ancient times to the present along with a look to the future. We hope that you will find this chronological summary intriguing and informative.

From closing the atmospheric ozone hole to reducing climate change. Lessons learned.

Global warming presents U.S. and transnational leaders with enormous political and policy challenges. World leadership addressed a similar worldwide environmental challenge in the 1980s and 1990s when scientists advised that accelerating emission of man-made chlorofluorocarbons was depleting the ozone layer of the earth's atmosphere. The process that led to global agreement on reducing depletion of the ozone layer holds valuable lessons, and some ironies, for scientists and policy makers seeking now to address global climate change. By understanding the international treaty process, how science informed that process, and how the physician community played a constructive role in the transition away from commercial use of ozone-depleting gases three decades ago, environmental activists can better understand the challenges, opportunities, and potential solutions under current consideration in affecting global climate change.