A comprehensive history of injection therapy for erectile dysfunction, 1982-2023.

INTRODUCTION: Although oral phosphodiesterase 5 inhibitors represent a first choice and long-term option for about half of all patients with erectile dysfunction (ED), self-injection therapy with vasoactive drugs remains a viable alternative for all those who are not reacting or cannot tolerate oral drug therapy. This current injection therapy has an interesting history beginning in 1982. OBJECTIVES: To provide a comprehensive history of self-injection therapy from the very beginnings in 1982 by contemporary witnesses and some members of the International Society for Sexual Medicine's History Committee, a complete history of injection therapy is prepared from eyewitness accounts and review of the published literature on the subject, as well as an update of the current status of self-injection therapy. METHODS: Published data on injection therapy, as a diagnostic and therapeutic tool for ED, were reviewed thoroughly by PubMed and Medline research from 1982 until June 2023. Early pioneers and witnesses added firsthand details to this historical review. Therapeutic reports of injection therapy were reviewed, and results of side effects and complications were thoroughly reviewed. RESULTS: The pioneers of the first hours were Ronal Virag (1982) for papaverine, Giles Brindley (1983) for cavernosal alpha-blockade (phentolamine and phenoxybenzamine), Adrian Zorgniotti (1985) for papaverine/phentolamine, and Ganesan Adaikan and N. Ishii (1986) for prostaglandin E1. Moxisylyte (thymoxamine) was originally marketed but later withdrawn. The most common side effect is priapism, with the greatest risk of this from papaverine, which has modified its use for therapy. Currently, prostaglandin E1 and trimixes continue to be the agents of choice for diagnostic and therapeutic use in ED. A recent agent is a mixture of a vasoactive intestinal polypeptide (aviptadil) and phentolamine. CONCLUSIONS: After 40 years, self-injection therapy represents the medication with the highest efficacy and reliability rates and remains a viable option for many couples with ED. The history of this therapy is rich.

The expansion of HIV-1 in colonial Leopoldville, 1950s: driven by STDs or STD control?

OBJECTIVES: To understand the factors that drove the exponential spread of HIV-1 in Léopoldville (Kinshasa) in the 1950s. METHODS: A review of colonial and post-colonial health service reports, medical publications, and demographic and social science research in Léopoldville. RESULTS: Sex work appeared early in the history of Léopoldville, driven by a strong gender imbalance. Throughout the colonial era, sex work was of a low-risk type, with 'free women' having a few regular clients. This sufficed for the persistence of HIV-1, but probably not for the dramatic expansion that occurred in the 1950s. During that decade, genital ulcerative diseases were uncommon and their effect on HIV-1 transmission must have been modest. Circumstantial evidence indicates that this expansion may have been related to parenteral transmission of HIV-1 in the city's sexually transmitted disease clinic, where up to 500 injections were administered daily using syringes and needles that were merely rinsed between patients. Most intravenous injections were given to treat syphilis in patients who never had any clinical evidence of this disease but only had a positive non-treponemal serology, often because of prior yaws infection. An outbreak of 'inoculation hepatitis' was reported among these patients in 1951-1952. It is only after the Congo's independence (1960) that, in a context of pauperisation, a pattern of sex work appeared in Léopoldville wherein women had sex with more than 1000 clients each year, allowing the sexual amplification of the virus. CONCLUSIONS: It is plausible that the exponential amplification of HIV-1 in Léopoldville occurred mostly parenterally in the 1950s and sexually in the 1960s.

[Injection medicines: historical notes on their use and development, with special reference to Icelandic conditions]. / Brot úr sögu stungulyfja: Med sérstöku tilliti til íslenskra adstaedna.

The first reliable syringes and hollow needles for the injections of drugs subcutaneously, intramuscularily and intravenously or for other injections came into use shortly after 1850. As far is known, morphine was the first drug to be injected subcutaneously, using a syringe and a hollow needle. Use of injection medicines, especially containing morphine or other alkaloids, became widespread among European doctors in the latter half of the 19th century. The use of injection medicines began before the existence of infectious microbes or microorganisms in general had become common knowledge, or the equilibria of electrolytes in and around living cells had been understood. Thus, injection medicines, their production and procedures of use had to pass through lengthy development lasting nearly one hundred years, in order to reach the levels of quality standards now universally accepted. It was also a definite advancement when disposable syringes and needles came into general use around 1960. Accessibility to injection medicines and their use was seemingly on a low scale in Iceland until 1930 or thereabout. The production of injection medicines in Iceland began in substance in the fourth decade of the last century. The production was generic, following official formulas, and was based in several pharmacies and a few drug companies. Only two producers offered a sizeable assortment of drugs. The production gradually became concentrated in a few firms and was finally handled by only one international, locally based, generic drugs firm, where the domestic production of injection medicines ended shortly after 2000.

A unique experiment in neurological surgery: intracerebral injection of antitoxin for tetanus.

The discipline of neurological surgery was considered primarily "hopeless" and, at best, experimental in the late 19th century. Harvey Cushing's efforts during his initial uncharted voyage through the surgery of the human cranium were rudimentary and exploratory. A direct review of his available patient records from early in his career provides the opportunity to look back at Cushing as a physician-scientist, uncovering work that demonstrates that he was at the forefront of neurosurgical intervention in avenues that have been largely overlooked. The authors present Cushing's notes pertaining to a case of tetanus. This case represents the intersection of neurosurgery and tetanus treatment in Dr. Cushing's intracerebral injection of antitoxin to treat generalized tetanus.

[On the history of injection]. / Traek af injektionens historie.

Although the effect of snake bites and poisoned arrows was known from ancient time, the development of the syringe and the needle lasted several centuries. Forms of intravenous injection and infusion are clearly documented in the 1650s. Sir Christopher Wren used a syringe made of animal bladder fixed to a goose quill to inject wine and opium into the veins of dogs. J.D. Major from Kiel and J.S. Elsholtz from Berlin probably were the first to deliberately administer intravenous injections to people in the 1660s. However, these early injections were not successful and injections did not come into fashion again until the latter part of the 1800s. Forerunners of subcutaneous administration were either the introduction of the drug under the epidermis by means of a vaccination-lancet or the application of a vesicant to remove the epidermis, after which the drug was applied to the denuded cutis. Lafargue, Lembert and Lesieur described these methods in the first half of the 1800s, and the methods continued to be of use in the second part of the century until the advent of subcutaneous injection. Alexander Wood of Edinburgh and Charles-Gabriel Pravaz from Lyon are known commonly as the inventors of the syringe for subcutaneous injection, but other pioneers such as Taylor, Washington and Rynd had already begun this form of administration. Increased use, safety and accuracy were accomplished by the progressive steps introduced by Wood, Pravaz and Luer. Thus, the syringe of Luer was fitted for aseptic heating, and a sharp needle readily perforated the skin. Sterilization by heating in an autoclave was developed by Pasteur, Chamberland and Koch, after managing aseptic conditions by the addition of preservatives such as carbolic acid. A safe method for the storage of sterile injectates was provided by Limousin's ampoule from 1886, and later by the introduction of multi-dose containers. The evolution of the syringe and its needle continues with the introduction of transdermal drug delivery by micron-scale needles and monitored drug delivery.

[Injectable dyes: more than 70 years of therapeutic usage of dyes]. / Les colorants injectables ou plus de 70 ans d'usage thérapeutique parentéral des colorants.

Synthetic dyes were first discovered at the end of the XVIIIth century (picric acid by Woulfe in 1771) and during the first part of the XIXth century: rosolic acid (Runge, 1834), mauvein (Perkin, 1856), but their development was major at the end of the XIXth century. Their therapeutic use was really starting at the beginning of the XXth century, mainly by local and oral route. It is only in the 1930's that parenteral route of administration was actually developed: methylene blue, methyl violet are some examples that were used for leprosy and filariasis, respectively. After the 2nd world war, one can observe a rapid decrease of the therapeutic use of dyes by intravenous route. Only a few dyes are still used today, such as patent blue V or fluorescein, as drugs for diagnostic use.

History, magnitude and rationality of injection use--a compilation.

Injection is a skin piercing event performed by a syringe and needle with the purpose of introducing a curative substance or vaccine into a patient. Dated back to 1657 with the first injection in animals the device is traced till 1991. The concern for proper management of injections is for occupational risk to the health worker, newer technologies to protect health workers is discussed including risk to patients and indirect risk via the environment to the community. Injection overuse is a cause of worry as it exposes the patient the risk of acquiring infections. In healthcare settings in India, most injections are unnecessary. Moreover irrational injection prescription is harmful. There also lies the misconceptions about injectable and oral medications. All professionals, in particular the doctors and nurses should become the advocates of safe injections.

Innovation, diffusion and safety of a medical technology: a review of the literature on injection practices.

The rapid uptake of the hypodermic syringe as a medical technology by physicians in Europe and America since its introduction in the middle of the 19th century has led to a level of medical and public acceptance seldom reached by other therapeutic techniques. Presently, the developed world has clear guidelines regarding injection use and safety; in contrast, developing countries are facing the brunt of risks associated with the use of this technology, which was introduced into their societies during the early 20th century. There is now a popular demand for injections, and an alarming number of unnecessary and unsafe injections are being administered. The problem of unsafe injections is not restricted to curative injections, but includes immunizations too. The association of unsafe injections and infection transmission is quite clear, and there is an urgent need to reduce the number of required injections and make them safe. An understanding of the determinants of current injection practices in the socio-cultural-economic context is necessary in order to plan relevant and effective interventions.

Treatment of vesicoureteric reflux by endoscopic injection of Teflon. 1984.

Thirteen girls with grade III-V vesicoureteric reflux were treated by endoscopic injection of Teflon paste behind the intravesical ureter. Fourteen of the 18 treated ureters showed complete absence of reflux after one injection of Teflon. Three ureters required a second injection of Teflon for successful treatment of the reflux. One ureter with grade IV reflux was converted to grade II reflux. Properly carried out, this procedure corrects reflux. It takes less than 15 minutes, may be done as a day procedure, and avoids open surgery. There have been no complications. (Reprinted with permission from Br Med J, 289: 7-9, 1984)

A history of growth hormone injection devices.

In the early 1960s, growth hormone (GH) deficiency was treated by intramuscular injection of GH extracted from human pituitary glands. Since then, there have been many advances in treatment encompassing the route of administration, the injection product and the injection device. This review considers the advances in injection device that have already taken place and how they have benefited the patient, particularly in terms of reduced pain and improved convenience. In the future, needle-free injection techniques and depot formulations of GH are likely to offer alternatives to daily subcutaneous injections.

Serial human passage of simian immunodeficiency virus by unsterile injections and the emergence of epidemic human immunodeficiency virus in Africa.

There is compelling evidence that both human immunodeficiency virus (HIV) types emerged from two dissimilar simian immunodeficiency viruses (SIVs) in separate geographical regions of Africa. Each of the two HIVs has its own simian progenitor and specific genetic precursor, and all of the primates that carry these SIVs have been in close contact with humans for thousands of years without the emergence of epidemic HIV. To date no plausible mechanism has been identified to account for the sudden emergence in the mid-20th century of these epidemic HIVs. In this study we examine the conditions needed for SIV to complete the genetic transition from individual human SIV infections to epidemic HIV in humans. The genetic distance from SIV to HIV and the mutational activity needed to achieve this degree of adaptation to human hosts is placed within a mathematical model to estimate the probabilities of SIV completing this transition within a single SIV-infected human host. We found that the emergence of even one epidemic HIV strain, following a single human exposure to SIV, was very unlikely. And the probability of four or more such transitions (i.e. HIV-1 groups M, O and HIV-2 subtypes A and B) occurring in a brief period is vanishingly small. We conclude that SIV cannot become a zoonosis, but requires adaptive mutations to become HIV. Some modern event must have aided in the transition of SIV to HIV. Our research indicates that serial passage of partially adapted SIV between humans could produce the series of cumulative mutations sufficient for the emergence of epidemic HIV strains. We examined the rapid growth of unsterile injections in Africa beginning in the 1950s as a biologically plausible event capable of greatly increasing serial human passage of SIV and generating HIV by a series of multiple genetic transitions. We conclude that increased unsterile injecting in Africa during the period 1950-1970 provided the agent for SIV human infections to emerge as epidemic HIV in the modern era.

[History of injections. Pictures from the history of otorhinolaryngology highlighted by exhibits of the German History of Medicine Museum in Ingolstadt]. / Die Geschichte der Injektionen. Bilder aus der Geschichte der Hals-Nasen-Ohren-Heilkunde, dargestellt an Instrumenten aus der Sammlung im Deutschen Medizinhistorischen Museum in Ingolstadt.

BACKGROUND: Injections are part of the arsenal of all medical disciplines. In addition to this common ground, each specialty has its own particular aspects; the historical development of these are presented here with respect to otorhinolaryngology. INTRAVENOUS INJECTIONS: The first experiments with intravenous injections were carried out in 1642 by a gentleman's hunting servant in eastern Germany. Similar experiments were done in 1656 by Christopher Wren, the astronomer, mathematician, and architect in Oxford, England, and a group of scientists around the physicist Robert Boyle. These experiments were prompted by new knowledge about blood circulation provided by William Harvey in 1628. The first books on the applications of intravenous infusions in humans were published in Germany by Major 1664 (Chirurgia Infusoria) and Elsholtz 1667 (Clysmatica Nova). Bladders of animals or enema syringes were used as instruments. Because of lethal accidents the infusions soon fell from favour. Köhler in Germany in 1776 eliminated a large bolus impacted in a patient's esophagus by an intravenous infusion of tartar emetic thus inducing violent vomiting. After this crucial experiment, foreign bodies in the esophagus were the most important indication for applying intravenous injections until Killian introduced extraction by esophagoscopy in 1990. CALIBRATED SYRINGES AFTER PRAVAZ: The French surgeon C. Pravaz in Lyon in 1853 invented a small syringe, the piston of which could be driven by a screw thus allowing exact dosage. A sharp needle with a pointed trocar could be introduced into the vessel making a dissection unnessessary. Pravaz used his syringe for obliteration of arterial aneurysms by injection of ferric sesquichlorate. Pravaz's syringe initiated the invention of a great number of various calibrated syringes made of glass or metal combined with glass. SUBCUTANEOUS INJECTION AND LOCAL ANAESTHESIA: The calibrated syringes were commonly used in the treatment of syphilis by mercurialization. In otorhinolaryngology, they had and still have their primary application in local anaesthesia, which was introduced by Carl Ludwig Schleich in Berlin in 1892. PARAFFIN-INJECTIONS: Around 1900 the injection of liquid paraffin for closing defects in subcutaneous tissues came into use (Gersuny in Vienna, Delangre in Tournai). This technique was immediately applied to rhinological indications such as a saddle nose (Stein 1901). This gave rise to the invention of special syringes and modifications of paraffin with different hardness and melting points. Around the middle of this century, paraffin was abandoned for this application because of serious complications, and new substances were introduced such like teflon, silicone and collagen. The historical development of these techniques of injections is described in details with many literature citations and figures.

Injection of morphine loco dolenti recommended as early as 1876.

The peripheral site of action of opioids was proved some 20 years ago. The concept of the peripheral action of morphine, however, appears to be over 100 years older. We report on the contents of a paper, presented on 28 April 1876 at the meeting of the Finnish Medical Association ("Finska Läkarsällskapet"), on the use of morphine and its sites of action. The author was Professor Knut Felix von Willebrand, whose details are included. Prof. v. Willebrand starts by focusing on several unwanted side effects, often seen in connection with morphine administration, and advises how they can be avoided by using the pupils of the eye as a manometer for tolerance of morphine, as suggested by Vibert. After having presented four case reports which illustrate the use of morphine in his own practice, Prof. v. Willebrand explains his conception of the sites of action of morphine. The paper gives a lively picture of the use of morphine about 125 years ago. Furthermore, it indicates that Prof. v. Willebrand believed firmly in the peripheral site of action of morphine and recommended to inject morphine loco dolenti whenever possible.