Death Rush: Poppers & AIDS

NITRITE INHALANTS: A BIBLIOGRAPHY

THE POPPERS INDUSTRY AND ITS INFLUENCE

THE APPENDICES:

APPENDIX A: Koch's Postulates:

The Case Against LAV/HTLV-III's Being the Sole,
Sufficient, or Necessary Cause of AIDS

APPENDIX B: A Toxicologic Model

APPENDIX C: Occam's Razor: The Drugs Connection

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I. POPPERS & AIDS

Don't use poppers. This is the first and the last thing to be said about them.

Poppers are a liquid mixture of isobutyl nitrite and other chemicals, packaged in small bottles under such names as “Rush”, “Ram”, “Thunderbolt”, “Locker Room”, and “Crypt Tonight” (gallows humor?). Poppers are advertised and sold to gay men, who make up virtually the entire market for the commodity. When inhaled just before orgasm, poppers seem to enhance and prolong the sensation. With regular use, they become a sexual crutch, and many gay men are incapable of having sex, even solitary masturbation, without the aid of poppers.

Poppers have become an accepted, even obligatory part of the gay male lifestyle in some cities. The odor of poppers is ubiquitous in New York City bars, backrooms and baths. At gay discos, men shuffle around on the dance floor, zombie-like, holding popper bottles under their noses.

The subject of poppers is one which arouses intense emotions. Ordinarily rational men become hysterical when it is suggested that the nitrite inhalants are harmful to the health and may play a role in causing AIDS. This is understandable. Since poppers have become necessary for them to function sexually, giving up poppers would seem, at least in the beginning, like giving up sex itself.

Normally every drug in the U.S. must undergo extensive testing before it can be sold legally. Not poppers. They are subject to no testing or quality control whatsoever. In 1981, the Stanford Medical Laboratories tested some samples of different brands of poppers, and found them to contain kerosene, hydrochloric acid, and sulfur dioxide, among other impurities.

Profits

The biggest money-maker in the gay business world is believed to be the poppers industry. Gross profits were estimated to be $50 million in 1978, and may well be double or triple that by now. (Sigell 1978)

Poppers manufacturers have impudently labelled their product a “room odorizer”, with the astounding consequence that the federal Food and Drug Administration (FDA), the California and New York Departments of Health, and other government regulatory agencies have intransigently looked the other way. What a farce! Not even an idiot would use poppers as a “room odorizer”. Everyone knows that poppers are inhaled as a drug. A large and growing body of medical research indicates that poppers are dangerous, and almost certainly implicated in causing AIDS. And yet the government agencies blithely accept the lie that poppers are only a harmless “room odorizer”.

Why have the appropriate government agencies refused to regulate poppers in any way? We don't know, but it's doubtful that they really believe the “room odorizer” marketing subterfuge. If a drug like butyl nitrite can be marketed as a “room odorizer”, then anything could be sold as anything. Heroin could be sold as a mosquito-bite remedy (“for external use only”). Live hand grenades could be sold as “paperweights”.

It is commonplace that government regulatory agencies come to be controlled by the very industries they were intended to regulate. One recalls the many recent scandals pertaining to the Environmental Protection Agency (EPA) or, a couple of decades ago, the subservience of the U.S. Department of Health to the tobacco industry. The poppers industry has a large war chest, and they know how to “influence” government agencies.

Poppers are now illegal in New York State. On June 18, Governor Cuomo signed into law Assembly Bill #890, making it illegal to possess or sell “hazardous inhalants”, including amyl and butyl nitrite, that cause intoxication.

It can be anticipated that some gay men will protest the new law as an intrusion of the state into their private lives, an infringement of their right to pursue chemical pleasures. Such protests would be misguided. Anyone who has studied the medical literature on poppers can only applaud the New York State legislature and Governor Cuomo for having done the right thing. Poppers are dangerous, and they should never have been sold legally in the first place.

Poppers as co-factor for AIDS

At present, most if not all AIDS researchers believe that an important role in causing AIDS is played by a virus named Lymphadenopathy-Associated virus (LAV) by the French scientists who isolated it in 1983. (The same virus was “rediscovered” in 1984 by an American government scientist, Robert Gallo, who called it “HTLV-III”, by which name it is known, for political reasons, in the U.S.)

The LAV virus has so far failed to satisfy Koch's postulates; therefore, its role in causing AIDS remains a matter of conjecture. The designation, “AIDS virus”, is not scientifically justified; the most one can say at present is that the LAV virus is associated with AIDS: perhaps as primary cause, perhaps as a subsidiary co-factor, or perhaps only as a harmless marker.¹

For several years, government agencies have discouraged any approaches to AIDS other than the single-infectious-agent hypothesis. Researchers who advanced drug abuse or multifactorial hypotheses tended to be ostracized and unfunded. After Robert Gallo's “discovery” of HTLV-III, it became obligatory to regard this as the primary or even sole cause of the Syndrome.

However, preliminary testing has shown that up to 80% of urban gay men have LAV antibodies, and yet only a minute percentage of them have developed AIDS. It would seem that LAV is not sufficient by itself to cause AIDS, that co-factors (like drug abuse) may be necessary for AIDS to develop.

Many AIDS researchers now believe that mere exposure to the putative virus is not sufficient to cause AIDS-that a necessary precondition may be an already weakened immune system. Attention is being focussed on possible co-factors in the lifestyles of gay men and IV drug users, the two major risk groups.

Toxic effects of amyl nitrite (the pharmaceutical predecessor of “Rush”, “Locker Room”, etc.) have been known for years. With the outbreak of the AIDS epidemic, medical researchers began to suspect that poppers may play a role in causing AIDS in gay men — either as the primary cause or in conjunction with other factors. (Durack 1981)

Few gay men, physicians, or AIDS researchers seem to be aware how extensive and powerful the evidence against poppers is. Anyone who has studied even a portion of the medical literature can only shake his head in amazement that this dubious commodity has not been banned — except in Massachusetts, Wisconsin, and, as of June 1985, New York State. (In Massachusetts, where poppers have been banned for years, only 378 cases of AIDS had been reported as of 31 March 1986. In contrast, there had been 6265 cases in New York, where poppers had been sold legally in sex shops, baths, discos, and even neighborhood smoke shops.)

The evidence against poppers has continued to accumulate. For several years, major articles in the most prestigious medical journals in the world have discussed the immunosuppressive and other harmful effects of poppers, and their possible role in causing AIDS. The question is no longer whether, but rather how much of a role poppers play in causing AIDS. Are poppers a relatively minor or a very major co-factor? So far as the effect of poppers on the health, there is no doubt that they are harmful. For some individuals, even a single episode of snorting poppers can be life-threatening.

The section that follows will summarize medical findings on poppers. However, the reader should bear in mind that this is a summary of hundreds of pages of reports and articles. Researchers concerned with the poppers connection should consult the Annotated Bibliography in Section II of this monograph.

THE SCIENTIFIC PICTURE

The evidence against poppers comes from many different types of studies, and is remarkably consistent. Whether from epidemiological, mice, or laboratory studies, the data support each other in demonstrating the harmful properties of poppers and implicating poppers in the etiology of AIDS. Despite rumors which originated with the poppers industry in 1983, there is no evidence that could reasonably be interpreted as “exonerating” poppers.

Epidemiological studies

Unfortunately, we know very little about the characteristics of people with AIDS. Most of the published epidemiological studies of gay men with AIDS were conducted several years ago, and had serious shortcomings. CDC studies, in particular, tended to be poorly designed, executed, and analyzed. We cannot assume that gay men diagnosed as having AIDS in 1986 have the same profile as the first 50-100 gay men with AIDS, who were studied in 1981-1982.

In the absence of recent, large-scale, well-conducted epidemiological studies, one may give a cautious hearing to less “scientific” evidence, such as reports from those who have known many people with AIDS. Such evidence should be evaluated critically, though it may actually be worth more than the quantitative “data” from a poorly executed survey.

Following are a few epidemiological highlights:

• 96-100% of the gay men with AIDS used poppers, usually quite heavily. These men were also heavy users of many other “recreational” drugs, including amphetamines (“speed”), cocaine, heroin, quaaludes (“ludes”), LSD, barbiturates (“downers”), and ethyl chloride. (Friedman-Kien 1982, Haverkos 1982/1985, Jaffe 1983)

• Case-control studies have implicated poppers as a statistically significant and important risk factor for the development of AIDS. (Marmor 1982, Newell 1985)

• In gay men who do not (yet) have AIDS, popper usage is correlated with immunological abnormalities similar to those found in AIDS patients. (Goedert 1982)

• Among men with swollen lymph nodes (all of whom had used poppers), heavy popper users were more likely to develop AIDS. (Mathur-Wagh 1984/1986)

• A recent study compared two groups of gay men who were antibody positive to the LAV (HTLVIII) virus: people who were clinically sick with AIDS, and people who were not sick. Usage of the nitrite inhalants proved to be one of the most important risk factors for developing AIDS, and especially, Kaposi's sarcoma. The heavier the popper usage, the greater the risk. (Moss 1985)

• Leaders of People With AIDS, who have known hundreds of PWA's, state that most of them were heavily into drugs, and all of them used poppers.

• W.J. Wallace, the manager of the Mineshaft, stated in an interview, “I really don't know anybody who's had AIDS who hasn't used drugs.”

• Finally, there is the crucial point that for 5 years AIDS, unlike a truly communicable disease, has remained compartmentalized. Gay men accounted for three-quarters of the AIDS cases 5 years ago, and account for the same proportion now in 1986. Poppers are used by gay men.

They are used by very, very few straight men, and by virtually no women at all.

Carcinogenesis

Organic nitrites like poppers combine with other substances to form deadly, cancer-causing compounds (N-nitroso compounds, nitrosamines — Jϕrgensen 1982, Newell 1984, Osterloh 1984). Danish scientists Karl Jϕrgensen and Sven-Olov Lawesson describe N-nitroso compounds as being so deadly as to have “the capacity to induce cancer after only one dose”.

Several AIDS researchers have suggested that poppers may play a role in causing the cancer, Kaposi's sarcoma, in gay male AIDS patients. KS is found in about half of the gay men with AIDS, but in a very small percentage of PWA's from the other risk groups. It is gay men who use poppers, not straight IV drug users or Haitians.

Blood cell studies (in vitro)

Several different laboratory experiments have shown that exposure of human blood cells to amyl, butyl or isobutyl nitrite causes sharp decreases in immunological function, as well as striking alterations in cell structure (“cytoplasmic protrusions with pseudopod-like extensions”, etc.). (Marmer 1982, Hersh 1983, Jacobs 1983)

One research team concluded:

“These abnormalities can help in explaining the role of amyl nitrite cellular toxicity in immunosuppressed male homosexuals.” (Marmer 1982)

Another research team stated:

“These in vitro studies strongly suggest that the inhalant nitrites may indeed be dangerous, and their use should be condemned by those physicians who treat patients who use these drugs regularly.” (Hersh 1983)

Mice studies

Powerful evidence against poppers comes from experiments on mice, which have firmly established that poppers suppress the immune system and are otherwise harmful in vivo (in a living animal).

• Five different studies found that exposure to amyl or isobutyl nitrite, either through injection or inhalation, caused immunological deficiency in mice. (Watson 1982, Neefe 1983, Lotzova 1984, Gangadharam 1985, and Ortiz 1985)

One research team concluded:

“The results of these studies indicate that immunosuppression should be added to the other reasons why isobutyl nitrite should not be used by man.” (Lotzova 1984)

One of these studies further found that the mice exposed to nitrite vapors suffered gross pathological lung damage, weight loss, and, most significantly, reversed T-cell ratios:

“Our studies do show that chronic inhalation of AN [amyl nitrite] can lead to an altered T-cell helper/suppressor ratio, the same phenomenon which occurs in AIDS victims. It does look, then, that there seems to be a link between AN inhalation and cellular immunity depression.” (Ortiz 1985)

• In a sixth study, mice exposed to low dosages of isobutyl nitrite vapors developed methemoglobinemia and thymic atrophy. (Lynch 1985) The first finding is relevant, since poppers are known to cause methemoglobinemia in humans (Horne 1979, Guss 1985) and since anemia is typically part of the AID Syndrome. (Methemoglobinemia is a form of anemia where the blood turns brown and where the oxygen supply to critical organs is reduced.) The finding of “thymic atrophy” is suggestive. Autopsies of AIDS victims show the thymus gland to be destroyed in 100% of the cases. No thymus gland, no immune system. Obviously any drug that destroys the thymus gland will play a role in causing AIDS.

• A seventh mice study could not be carried through to completion. Regardless of whether the isobutyl nitrite was ingested, inhaled, or injected, all of the mice died. (Maickel 1982)

T-cell ratios

Inhalation of amyl nitrite caused a depletion of the helper (T4) T-cells in mice (Ortiz 1985) and in humans (Gerblich 1984). Some researchers consider this condition — a reversed T-cell ratio — to be the primary immunological defect in AIDS patients.

Toxicology

Quite aside from the risk of getting AIDS, poppers are known to be hazardous to the health in many different ways. Poppers cause Heinz body cell anemia, methemoglobinemia, lung damage, serious skin burns, death or brain damage from cardiovascular collapse or stroke, dizziness, and headaches. Poppers have been used successfully to commit suicide (by drinking) and murder (victim gagged with sock soaked with poppers). (Sigell 1978, Horne 1979, Haley 1980, Dixon 1981, Romeril 1981, Guss 1985, Lynch 1985, Ortiz 1985)

AIDS: Why now?

The chronology is suggestive: Poppers became a fad among gay men beginning in 1972, just seven years before the first cases of AIDS began to be diagnosed. (Newell 1984)

* * *

It is obvious from the above that poppers are dangerous and should not be used by humans or other animals. In the context of the AIDS epidemic, when keeping one's immunological system up to par is a life or death matter, the only sane course of action is to stop using poppers immediately.

Risk-reduction guidelines

Even with considerable human resources and millions of dollars committed to finding a solution, it may very well take many years before researchers are able to describe, with scientific rigor, how AIDS is caused. In the meantime, it is imperative that intelligent guidelines for reducing the risk of getting AIDS, based on existing knowledge, be given now. Lives are at stake.

In light of what is known now, gay men should continue to follow “safe sex” guidelines. In conservative terms, this would mean either practising celibacy or limiting sex to simple body contact and mutual masturbation. The simple rule for safe sex is: “On me, not in me.”

At the same time, it is crucial for gay men to bolster their immune systems by living in a healthy way: eating nutritious food, getting enough sleep and rest, reducing stress, and getting plenty of exercise. They should avoid the use of any and all “recreational drugs” — especially including poppers.²

II. NITRITE INHALANTS:

A BIBLIOGRAPHY

Centers for Disease Control. “An Evaluation of the Immunotoxic Potential of Isobutyl Nitrite”. MMWR, pp. 457-58, 64, 9 September 1983.

This news item briefly described an experiment in which mice were exposed to isobutyl nitrite vapors, in various concentrations, for time periods ranging from 3 to 18 weeks. It asserted, “None of the animals exposed to IBN showed any evidence of immunotoxic reactions”.

The poppers industry used this little item as the basis for an advertising campaign which claimed that poppers had been “exonerated”, and that there was no connection between poppers and AIDS.

When a report on the mice study was finally published two years later, it became clear that the MMWR account had been grossly misleading. The dosages administered were too low to test the hypothesis that poppers might be immunosuppressive or otherwise harmful to men who inhaled them as “recreational” drugs. The study had selected exposures “to mimic an occupational exposure setting...rather than to conduct brief, high level exposures to imitate exposure by nitrite abusers.” (See entries under Lewis and Lynch.)

It should be noted that other mice experiments (Gangadharam, Lotzova, Maickel, Neefe, Ortiz, and Watson) have demonstrated that mice exposed to alkyl nitrites do develop immunological deficiency, as well as being harmed in other ways.

The anonymous author(s) of the MMWR piece stress that the nitrite inhalants are not harmless, for “these drugs do have toxic effects”, and they proceed to list a number of toxic effects, ranging from “dizziness” to “sudden death”. They add that “their role as a cofactor in some of the illnesses found in this syndrome has not been ruled out.”

D'Eramo, James E. “Poppers: The Writing on the Wall”. New York Native, p. 9, 4-17 June 1984.

This article reports on recent findings that tend further to implicate the nitrite inhalants as playing a role in causing AIDS.

The popular media are currently touting the LAV/HTLV-3 virus as being the only cause of AIDS. However, D'Eramo reports that one of the French scientists who discovered the virus puts forward a multifactorial model of causation:

“Dr. J.C. Chermann (a member of the Parisian Pasteur Institute team that discovered the probable viral cause of AIDS - LAV-HTLV-3) presented a model for the development of AIDS during a lecture on May 22 at Sloan-Kettering Memorial Hospital in New York City. He believes that the T-cell population must be repeatedly stimulated with foreign antigens (like LAV, sexually transmitted diseases, and drugs) for full-blown AIDS to develop. Repeated usage of poppers may play an important role in the antagonistic stimulation of the helper T-cell population. According to Dr. Chermann's model, very limited or infrequent exposures to LAV would not in themselves lead to the development of full blown AIDS.”

D'Eramo concludes:

“The untoward effects of inhaling poppers are becoming clearly recognized, especially as a co-factor in the development of AIDS.”

Dixon, D.S.; Reisch, R.F.; and Santinga, B.S. “Fatal Methemoglobinemia Resulting from Ingestion of Isobutyl Nitrite, a ‘Room Odorizer’ Widely Used for Recreational Purposes”. Journal of Forensic Sciences, pp. 587-93, July 1981.

A clinical account of a 30-year old black male who died from “acute nitrite poisoning”. He had apparently swallowed some poppers liquid. Contains a description of unsuccessful emergency procedures used, results of the autopsy, as well as a discussion of other butyl nitrite-related fatalities and the various hazards of alkyl nitrite inhalant abuse.

Durack, David T. “Opportunistic Infections and Kaposi's Sarcoma in Homosexual Men”. New England Journal of Medicine, pp. 146567, 10 December 1981.

This lead editorial poses the question of why AIDS is apparently new, since both viruses and homosexuality are at least as old as history:

“Some new factor may have distorted the host-parasite relation. So-called ‘recreational’ drugs are one possibility. They are widely used in the large cities where most of these cases have occurred, and the only patients in the series reported in this issue who were not homosexual were drug users.... Perhaps one or more of these recreational drugs is an immunosuppressive agent. The leading candidates are the nitrites, which are now commonly inhaled to intensify orgasm.... Let us postulate that the combined effects of persistent viral infection plus an adjuvant drug cause immunosuppression in some genetically predisposed men.”

Friedman-Kien, Alvin E.; Laubenstein, Linda J.; Rubenstein, Pablo; et al. “Disseminated Kaposi's Sarcoma in Homosexual Men”. Annals of Internal Medicine. pp. 693-700, June 1982.

A study of 19 men with KS. “All of the patients had used amyl or butyl nitrite inhalants.”

Gangadharam, P.R.J.; Peruman, V.K.; et al. “Immunosuppressive Action of Isobutyl Nitrite” (Presentation to the International Congress on Immunopharmacology, Florence, Italy, May 1985.) (Also press release reported in various newspapers)

Researchers at the National Jewish Center for Immunology and Respiratory Medicine in Denver found evidence confirming long-held suspicions that the “recreational” use of nitrite inhalants (poppers) greatly increases the risk of developing the Acquired Immune Deficiency Syndrome (AIDS).

Their studies involved exposing mice to RUSH\ (isobutyl nitrite) “by inhalation in a closed environment, simulating the practice of the homosexual patient”. One group of mice was exposed to RUSH\ daily; another group, every other day; and a third group, twice per week. According to the principal investigator, P.R.J. Gangadharam, PhD, after breathing isobutyl nitrite the animals became highly susceptible to disease and death caused by Mycobacterium intracellulare. This group of organisms, related to tuberculosis, is among the leading killers of people with AIDS. Mice of the same breed, who were exposed to the bacteria but not to the drug, had far lower illness and mortality rates.

The Denver scientists also linked specific, dose-related immune-system damage to isobutyl nitrite exposure:

“The animals exposed to the compound had decreased numbers of lymphocytes and macrophages, blood cells that are important in defending the body against infections.”

Dr. Gangadharam made the point that only a very small percentage of people exposed to the putative AIDS virus (LAV) become sick, and even fewer develop AIDS. “This makes is very important to investigate other possible contributing factors.”

The researchers concluded:

“We believe our findings establish that inhaling isobutyl nitrite should be considered dangerous to homosexuals and others at high risk for developing AIDS.”

Gerblich, Adi A.; Campbell, Ann E.; Schuyler, Mark R. “Changes in T-cell Lymphocyte Subpopulations After Antigenic Bronchial Provocation in Asthmatics”. New England Journal of Medicine, pp. 1349-52, May 1984.

In this study it was found that some kinds of inhaled agents caused a depletion of the helper (T4) T-cells. Some researchers consider this condition--a reversed T-cell ratio--to be the primary immune defect in AIDS patients.

In a communication to Dr. D'Eramo of the New York Native, Dr. Gerblich stated: “The same results have been found upon inhalation of amyl-nitrites.”

Goedert, James J.; Neuland, Carolyn Y.; Wallen, William C.; et al. “Amyl Nitrite May Alter T Lymphocytes in Homosexual Men”. The Lancet, pp. 412-16, 20 February 1982.

This study collected clinical, virological, and immunological data on 2 homosexual men with KS and on 15 healthy homosexual volunteers. Both men with KS had been regular amyl/butyl nitrite users. Of the men who did not have KS, 8 were regular nitrite users (1-20 times per month) and the other 7 were not (i.e., fewer than 10 doses ever).

Immunological abnormalities were found in all of the nitrite users, but in only one of the non-users. The authors conclude:

“The data suggest that nitrites may be immunosuppressive in the setting of repeated viral antigenic stimulation and may contribute to the high frequency of KS and opportunistic infections in homosexual men.”

Guss, David A.; Normann, Sven A.; and Manoguerra, Anthony S. “Clinically Significant Methemoglobinemia from Inhalation of Isobutyl Nitrite”. American Journal of Emergency Medicine, pp. 46-47, January 1985.

A case report of a 21-year old gay man who almost died from methemoglobinemia which resulted from an episode of inhaling poppers. The night before admission to the emergency room he had swallowed methaqualone (Quaalude), had inhaled cocaine, and had inhaled 'Hardware' (isobutyl nitrite) every 2-3 minutes for a period of 5-6 hours. His skin was purplish (“cyanotic”), and he had “severe headache, nausea, vomiting, chest pain, and shortness of breath.” “Arterial blood gas samples were extremely dark.... Methemoglobin was 37% of all hemoglobin.” Emergency measures were successful; the patient survived, and was found to have normal methemoglobin reductase levels.

The authors comment:

“Compared with the patient reported by Horne and associates [see Horne entry], our patient presented with severe systemic symptoms, had a methemoglobin level of more than twice that previously reported, and had normal methemoglobin reductase levels. In addition, our patient presented more than 12 hours after his last exposure to nitrites. Considering that the estimated half-life of methemoglobin is 55 minutes, this suggests peak levels of methemoglobin were probably considerably greater than those measured.”

This report is important for two reasons: First, it demonstrates that life-threatening methemoglobinemia can result from butyl nitrite inhalation, even in an individual whose body has a normal ability to reduce methemoglobin. Second, it strongly suggests the possibility of drug interaction effects, whereby the combination of butyl nitrite plus one or more other “recreational” drugs may be much more deadly than any one of these drugs by itself.

Haley, Thomas H. “Review of the Physiological Effects of Amyl, Butyl, and Isobutyl Nitrites”. Clinical Toxicology, pp. 317-29, 1980.

Contains a two-page summary of “human toxicology” re nitrites. 115 references listed. A few highlights:

“The toxic effects of amyl nitrite inhalation include rapid flushing of the face, pulsation in the head, cyanosis, confusion, vertigo, motor unrest, weakness, yellow vision, hypotension, soft thready pulse, and fainting. Accidental prolonged inhalation of amyl nitrite has resulted in death from respiratory failure.... Fatalities have occurred in workers exposed to organic nitrates after strenuous exercise 1 to 2 days after cessation of exposure. Nitrite causes a loss of tone of the vascular bed and pooling and trapping of blood in the veins of the lower extremities, resulting in marked arteriolar constriction and the induction of anoxemia in vital tissues, causing death. Hypertrophy of the left ventricle occurs in workers handling nitroglycerine, and they suffer from shortness of breath on undue exertion. The formation of methemoglobin by aliphatic nitrite interferes with oxyhemoglobin, causing anoxia of vital organs....The use of volatile nitrites to enhance sexual performance and pleasure can result in syncope and death by cardiovascular collapse.”

Haverkos, Harry W.; Pinsky, Paul F. et al. “Disease Manifestation among Homosexual Men with Acquired Immunodeficiency Syndrome (AIDS): A possible role of nitrites in Kaposi's sarcoma”. A study of the CDC AIDS Activity, Center for Infectious Diseases, 1982. Abridged version published in Sexually Transmitted Diseases, pp. 103-08, October-December 1985.

87 of the first cases of homosexual men with AIDS were classified according to disease manifestation: Kaposi's sarcoma (KS) only, Pneumocystis carinii pneumonia (PCP) only, or both KS and PCP. Each group was compared to the others as well as to controls from an earlier CDC study. (See Jaffe 1983.)

The researchers concluded that “using nitrite inhalants may be associated with the occurrence of KS in patients with AIDS.”

The Haverkos study gives us important information on the lifestyle characteristics of the homosexual men who were diagnosed as having AIDS in 1981 and early 1982. Dr. Haverkos and his colleagues found a high degree of drug abuse. Among the total 87 gay men with AIDS, the following levels of drug usage were recorded: Nitrite inhalants (poppers) - 97%, marijuana - 93%, amphetamines - 68%, cocaine - 66%, LSD - 65%, quaaludes - 59%, ethyl chloride - 48%, barbiturates - 32%, heroin - 12%, any drug intravenously - 17%.

Multiple drug usage was the rule: 58% of the subjects used five or more different “street drugs”. Furthermore, the 87 gay men with

AIDS tended to use their drugs heavily. Following are the median numbers of different days on which the various drugs were used: Marijuana - 720, nitrite inhalants - 384, amphetamines - 120, barbiturates - 96, quaaludes - 60, LSD - 36.

Hersh, Evan M.; Reuben, James M.; Bogerd, Hal; et al. “Effect of the Recreational Agent Isobutyl Nitrite on Human Blood Leukocytes and on in Vitro Interferon Production”. Cancer Research, pp. 1365-71, March 1983.

The effect of isobutyl nitrite on cellular immunological functions was studied. The experimenters found that minute quantities of isobutyl nitrite caused irreversible impairment of immunological function. They conclude:

“We speculate that these immunosuppressive effects, combined with the ability of nitrites to convert amines to nitrosamines, may be related to the development of opportunistic infections and Kaposi's sarcoma in homosexuals who use this agent.”

Dr. Hersh and his colleagues further state:

Horne III, McDonald K; Waterman, Michael R.; et al. “Methemoglobinemia from Sniffing Butyl Nitrite”. Annals of Internal Medicine, pp. 417-18, September 1979.

A man was admitted to a hospital emergency room, “complaining of a grayish complexion which developed after inhaling butyl nitrite”. He was diagnosed as having methemoglobinemia, a form of anemia where the blood turns brown, and where the oxygen supply to critical organs is reduced. Several months later, the same man reappeared, again suffering from methemoglobinemia, again after butyl nitrite inhalation.

The patient was found to be methemoglobin reductase deficient, as was his father.

An experiment was performed in which the patient and 6 non-familial subjects were asked to sniff butyl nitrite (Locker Room “room odorizer”) directly from the bottle for 12 minutes. As a result, the patient “clearly became gray”, and had high methemoglobin concentrations. The 6 normal subjects also developed methemoglobinemia, to a lesser degree. The authors conclude:

“Sniffing butyl nitrite theoretically could lead to significant methemoglobin accumulation even in normal subjects, if the nitrite exposure were intense or if inadequate time were allowed between nitrite inhalations for methemoglobin reduction. The risk of clinical methemoglobinemia would, of course, be much higher in a person whose methemoglobin clearance rate is abnormally slow and who therefore requires a longer interval between sniffs to reduce the newly formed methemoglobin.”

Jacobs, Richard F.; Marmer, Daniel J.; et al. “Cellular Immunotoxicity of Amyl Nitrite”. Journal of Toxicology- Clinical Toxicology, 20(5), pp. 421-449 (1983).

[Abstract] “Functional deficits in lymphocyte interaction following occasional or chronic exposure to inhaled nitrites may be a potential contributing but not the [primary] etiologic factor in the acquired immunodeficiency syndrome (AIDS). We evaluated the effect of amyl nitrite vapors on mononuclear cell function and demonstrated functional deficits and structural alterations in these cells. In this closed, in vitro system, exposure of cells to amyl nitrite for up to 30 minutes did not affect cell viability. The functional deficits demonstrated were: inhibition of lymphocyte erythrocyte (E) rosette formation, a suppression of lymphocyte mitogen (phytohemagglutinin) and antigen (cytomegalovirus) transformation, a block in the S, G₂ and M phases of cell cycling and diminished cell cytotoxicity to CMV infected cells. These effects on cellular function were demonstrated following 5, 0, and 15 minutes of amyl nitrite vapor exposure; some effect on all cellular functions was demonstrated at 5 minutes. The structural alterations seen on scanning and transmission electron micrographs were: reduction of filopodia, smoothing of the cell profile, cytoplasmic protrusions with pseudopod-like extensions, an increase in rough endoplasmic reticulum with swollen cisternae, alterations in size and distribution of golgi components and exocytotic vesicles in the outer membrane of the nuclear envelope. These vesicles and increased membrane proliferation suggests an effect on the membrane synthesis mechanism in these cells. These effects may be a potential factor in the alterations of phenotypic markers on T Lymphocyte populations, as well as, a potential contributing factor in the functional deficit of mononuclear cells in patients with AIDS.”

Jaffe, Harold W.; Keewhan, Choi; Thomas, Pauline A.; et al. “National Case-Control Study of Kaposi's Sarcoma and Pneumocystis carinii Pneumonia in Homosexual Men: Part 1, Epidemiologic Results”. Annals of Internal Medicine, pp. 145-51, August 1983.

In this study of the first 50 AIDS patients, 96% used nitrite inhalants (and this would be 100% if the 2 “non-users” had misunderstood the question). Moreover, the AIDS patients were extremely heavy users, with a median lifetime exposure to nitrite inhalants of 336 doses. Most of the AIDS patients were also heavy users of many other “recreational drugs”, including marijuana, cocaine, heroin, amphetamines (“speed”), barbiturates, quaaludes (“ludes”), LSD, ethyl chloride, and phencyclidine.

The control sample selected for this CDC study proved to be seriously flawed. Drawn from venereal disease clinics and private practices, many of the controls were far from healthy. Some had immunological abnormalities and swollen lymph glands, and several of them developed AIDS after the study was completed. Further, many of the controls appeared to belong to the “fast lane” segment of the gay male community, as witness such findings as that 51-60% of the controls were cocaine users, or that 21% of the private practice controls had been fist fucked.

Aside from the major sampling problems described above, the inherent bias of this study design is a bias towards unity. That is to say, the tendency would be falsely to overlook real risk factors, rather than falsely to identify risk factors that were not real. The authors of the study admit as much:

“The expected impact of these potential problems in control selection and classification would be to minimize differences between cases and controls rather than to create false differences.”

In light of the fatal flaws in sample design and selection, all analyses based upon comparison between the AIDS patients and the controls would be dismissed by most survey research professionals as “garbage in, garbage out”. The comparative data are worthless, and should be ignored. The authors of this study did draw comparative conclusions, but they were wrong to do so.

Jϕrgensen, Karl A. and Lawesson, Sven-Olov. “Amyl Nitrite and Kaposi's Sarcoma in Homosexual Men”. (letter) New England Journal of Medicine, pp. 1893-94, 30 September 1982.

The authors give the chemical formula whereby amyl or butyl nitrites can form carcinogenic N-nitroso compounds in the body — compounds so deadly as to have “the capacity to induce cancer after only one dose”.

They conclude:

“We therefore find it appropriate to suggest that amyl nitrite may cause Kaposi's sarcoma in homosexual men.”

Jϕrgensen's and Lawesson's theories are developed more fully in an article in the Danish medical journal, Ugeskr Laeger, of 13 December 1982).

Lewis, Daniel M.; Koller, Wayne; et al. “Subchronic inhalation of Isobutyl Nitrite in BALB/c Mice: II. Immunotoxicity Studies”. [See also Lynch 1985 below.] Journal of Toxicology and Environmental Health, pp. 835-47, 1985.

This is a belated report on the research conducted in 1982-83, which the CDC newsletter MMWR of 9 September 1983 had summarized as indicating no “evidence of immunotoxic reactions”. (See Centers for Disease Control 1983.) The MMWR news item was used by the poppers industry as proof that poppers had been “exonerated”. As reports on other experiments began to appear (Gangadharam 1985, Lotzova 1984, Neefe 1983, Ortiz 1985, and Watson 1982), all finding that exposure to alkyl nitrites was immunosuppressive and otherwise harmful for mice, the CDC/National Institute for Occupational Safety and Health study became “odd man out”.

Now that a report on the study has finally been published, it is clear why the government researchers failed to find “immunotoxicity”, when all of the independent researchers did find it. The dosages administered, via inhalation of vapors, were far too low. The study, in effect, evaluated the effect of nitrite vapors approximating levels to be encountered as background exposure (“room odorizer”, workers in a poppers factory), rather than those encountered when using poppers as a drug (i.e., inhaling directly from the bottle). The study is thus in the tradition of the “Poppers Bible”. (See entry under Nickerson.) At the end of their “discussion”, Lewis et al. issue a revealing disclaimer:

“The relevance of these dosages to human usage of these compounds is uncertain because persons who abuse aliphatic nitrites recreationally would have intermittent exposures of variable frequency at very high dosages with chemicals of unknown purity. Thus, this study did not attempt to model the recreational use of these drugs [emphasis added], but rather to simply evaluate the immunotoxic potential, if any, of these compounds.”

Lotzovà, Eva; Savary, Cherylyn A.; Hersh, Evan M.: et al. “Depression of Murine Natural Killer Cell Cytotoxicity by Isobutyl Nitrite”. Cancer Immunology Immunotherapy, pp. 130-134, vol. 17, 1984.

This important mice experiment demonstrated that isobutyl nitrite was NK-cell-suppressive in vivo after intravenous administration and, most importantly, also after inhalation.

In their “discussion” the authors state:

“Since in experimental animals NK cells have been implicated in the mediation of immune surveillance against tumors and resistance to various types of infections, the depression of NK-cell cytotoxicity by this agent could underlie the susceptibility of homosexual men to opportunistic infection and Kaposi's sarcoma. Furthermore, the observation that cytotoxic potential of activated NK cells was also reduced by this agent suggests that an attempt to augment NK-cell activity to promote resistance to infections and malignant disease in patients with severe immunodeficiency syndrome could fail in patients who continue to use isobutyl nitrite. Since a multifactorial depression of immunity and a certain duration of this depression probably sets the stage for successful infection of the presumed AIDS agent, the continued and prolonged use of isobutyl nitrite may play an important role in AIDS.”

They conclude:

“The results of these studies indicate that immunosuppression should be added to the other reasons why isobutyl nitrite should not be used by man.”

Lynch, Dennis W.; Moorman, William J.; et al. “Subchronic Inhalation Toxicity of Isobutyl Nitrite in BALB/c Mice: I. Systemic Toxicity”. [See also Lewis 1985 above.] Journal of Toxicology and Environmental Health, pp. 823-33, 1985.

This CDC/NIOSH study was intended to “present the toxicologic results of subchronic exposures of BALB/c mice to inhaled IBN.” (“Subchronic” apparently means something like “less than acute”.)

The salient point of their methodology is that the dosages administered were low, simulating those experienced by workers in a poppers factory³(or by a feeble-minded individual using poppers as a “room odorizer”). Lynch et al. are reasonably candid in making their disclaimer:

“Exposures were selected to mimic an occupational exposure setting in order to fill this gap in the existing literature, rather than to conduct brief, acute high-level exposures to imitate exposure by nitrite abusers.”

In light of the low dosages administered, it would not have been surprising if the mice had suffered no ill effects whatever, but this was not the case. The main toxic effects observed were mild damage to the lung tissues and the formation of methemoglobin. In addition, some of the mice developed thymic atrophy. The finding of methemoglobinemia is relevant, since poppers cause methemoglobinemia in humans (see Dixon, Guss, and Horne entries) and since anemia is typically part of the AID Syndrome. The finding of thymic atrophy is most suggestive: in autopsies of AIDS victims, the thymus gland is found to be destroyed in 100% of the cases. No thymus gland, no immune system. Obviously any drug that destroys the thymus gland will play a role in causing AIDS.

Maickel, Roger P. “Acute Toxicology of Butyl Nitrite”. Research Communications in Chemical Pathology and Pharmacology, 26:75-83, 1979.

This paper discusses laboratory techniques for analyzing the various butyl nitrites. Butyl nitrites were administered intravenously to mice, with liver damage and death resulting.

“Administration of isobutyl , n-butyl, sec-butyl or tert-butyl alcohols to mice produced similar hepatoxicity, suggesting that butyl alcohols may play a role in the hepatotoxicity observed after sBN or tBN administration.”

___ (interview). Moneysworth, January, 1982.

USERS OF DISCO DRUG DIE OF ITS DELIGHTS

CHICAGO — Butyl nitrite — a legal but potentially lethal substance used to enhance sexual pleasure and drive disco dancers to ecstatic frenzy — is creating a new type of hazard, a toxicologist warns.

“If you get enough of it in your body, the chances of saving you are zero,” Purdue University professor Roger Maickel says of the chemical marketed variously as “Rush”, “Locker Room”, “Climax”, and “Discorama”. “And you may be an unwitting victim,” he adds. “It has been reported that these compounds are sprayed out over disco floors to rev up dancers.”

Although no deaths from inhalation have been reported, Maickel says, in the last year there have been at least two reported deaths from swallowing the drug.

He says a Purdue study found butyl nitrites were fatal to mice in fairly small doses. “The blood turns brown — it can't carry oxygen,” he says. “What's interesting is that the butyl nitrites were fatal no matter how they were administered — orally, by injection or just by exposing the mice to the compound in the air.”

Government agencies have not banned butyl nitrite, he says, because they have not been marketed as drugs. “Some federal agency ought to take a stand,” Maickel asserts, “before there is a spate of deaths that could have been avoided.”

Marmer, D.J.; Jacobs, R.F.; and Steele, R.W. “In Vitro Immunotoxicity of Amyl Nitrite.” Clinical Research, p. 5, vol. 30, no. 5, 1982.

Exposing mononuclear cells to amyl nitrite vapors resulted in various cellular abnormalities. The authors conclude:

“These abnormalities can help in explaining the role of amyl nitrite cellular toxicity in immunosuppressed male homosexuals.”

Marmor, Michael; Friedman-Kien, Alvin E.; Laubenstein, Linda; et al. “Risk Factors for Kaposi's Sarcoma in Homosexual Men”. The Lancet, pp. 1083-87, 15 May 1982.

A study of 20 homosexual men with KS and 40 healthy controls. All of the men with KS had been nitrite users. Multivariate analysis indicated that use of amyl nitrite was an independent and statistically significant risk factor for KS.

In the light of their data, the authors consider a tenable hypothesis to be:

“Use of amyl nitrite may have caused Kaposi's sarcoma either by directly causing immunosuppression, thereby allowing expression of a sexually transmitted oncogenic virus; or by allowing an unknown carcinogenic agent, otherwise controlled by the immune system, to operate; or by acting as a direct or metabolically activated carcinogen.”