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There has long been an association between recreational drugs and AIDS. Surprisingly, some of the strongest associations are not with injection drugs, but with inhalant nitrites, widely marketed to and used by gay men, and with non-injection forms of cocaine, such as crack. This information is largely ignored by people who accept the infectious theory of AIDS, perhaps because this evidence does not fit that theory.
The quotes are classified as:
Nitrite InhalantsNitrite inhalants are little known outside the gay male community. They are heavily (and very cynically) marketed to this community. It is known that they are carcinogenic and immune suppressive. So how could they possibly have anything to do with an Acquired Immune Deficiency Syndrome?Joe The Popper King Miller Dead. Advance Indiana. 2010 Aug 26 http://advanceindiana.blogspot.com/2010/08/joe-popper-king-miller-dead.html Poppers are immunosuppressive. Immunosuppression may increase susceptibility to HIV and HHV-8 infection. [this website includes extensive scientific literature references on the topic of poppers (nitrite inhalants)] Wilson H. Poppers information and poppers research. poppers.cfsites.org. 2007 Dec [accessed] http://poppers.cfsites.org/ Doses of amyl nitrite, known on the street as poppers, are sold under the counter at some sex shops in Montreal and other major cities. They're ingested [probably should be inhaled] on the gay and straight party scenes, often in combination with other drugs such as ecstasy
Health Canada said it's looking into reports that poppers, sold under brand names such as Rush and Locker Room, have increased in popularity after falling out of favour in the 1990s
The combination of poppers and ecstasy, another popular party drug, could be deadly, according to a San Francisco study presented in 2001 at a Centers for Disease Control conference in Atlanta
poppers could harm people with pre-existing heart problems or a susceptibility to brain aneurysms
Poppers occupy a grey zone in Canadian law - it's illegal to sell them as aphrodisiacs, so they're marketed instead as leather cleansers, video-cassette cleaners and even incense
JustPleasure.com [in Vancouver] sells poppers for prices ranging from $10.95 to $19.95 per bottle. Carole MacFadden, director of sales and marketing, said demand for the drugs shot through the roof as soon as her firm was launched last year
MacFadden denied her company was breaking any laws by selling poppers, explaining the product doesn't appear on her website and is only sold to those who specifically request it
the drug's hallucinogenic effects impair a user's judgment, making the person more likely to take dangerous sexual risks that expose them to sexually transmitted diseases such as HIV [or perhaps directly causes AIDS diseases]. Daly B. Club scenes deadly new aphrodisiac: Amyl nitrate being inhaled from bottles. Canadian Press. 2003 Oct 5 The prevalence of reported unprotected anal intercourse (UAI) increased from 37% to 50% between 1993 & 1994 and 1996 & 1997. Almost half of all men who reported UAI in 1996 & 1997 indicated that it occurred with a partner of unknown or discordant HIV antibody status. This high-risk practice correlated with greater numbers of male sex partners, use of nitrite inhalants, sex in commercial sex environments, perceived difficulty controlling sexual risk-taking, and negative emotional reactions. Ekstrand ML et al. Gay men report high rates of unprotected anal sex with partners of unknown or discordant HIV status. AIDS. 1999 Aug 20;13:1525-33. Men were coded as high transmission risk if they reported UAI with a partner of different or unknown HIV status, as low transmission risk if they reported all UAI partners to be seroconcordant, and as no risk if they reported no UAI at all
Three variables, i.e. greater frequency of sex, any use of nitrite inhalant drugs in the previous 12 months, and difficulty avoiding sexual risks, differentiated membership in the high transmission risk group from the no transmission risk men in multivariate analyses. Ekstrand ML et al. Gay men report high rates of unprotected anal sex with partners of unknown or discordant HIV status. AIDS. 1999 Aug 20;13:1525-33. Groups of mice were exposed in an inhalation chamber to 900 ppm isobutyl nitrite ['poppers'] for 45 minutes per day for 14 days and then assayed for immune reactivity. The T-dependent antibody responses of nitrite treated mice were reduced by 50-65%
Cytotoxic T cell (CTL) induction was reduced by 40%
and the tumoricidal activity of peritoneal exudate macrophages [cells] was reduced by 40%
[in a later experiment] inhalant exposure increased the tumor incidence from 21% of control mice to 75% of inhalant exposed mice
the rate of increase in mean tumor weight was nearly 4-fold faster in nitrite exposed mice. Soderberg LSF. Increased tumor growth in mice exposed to inhaled isobutyl nitrite. Toxicology Letters. 1999 Jan 11;104(1-2):35-41. In 1995, 3,553 repeat anonymous HIV tests were performed among men who have sex with men in San Francisco
A total of 2,822 subjects met all inclusion criteria. A seroconverter was defined as a person who reported a prior HIV-negative test and whose current test was HIV positive
6 variables were significantly associated with increased HIV seroincidence in multivariate analysis: African-American ethnicity, age under 36, sex with an HIV-positive person, 10 or more sex partners, unprotected receptive anal sex, and use of the drug amyl nitrate ('poppers') during sex
Injection drug use was not associated with a significant increase in HIV seroconversion
a history of sexually transmitted disease did not appear to contribute an increased risk of seroconversion after controlling for markers of high risk sexual behavior McFarland W et al. Estimation of human immunodeficiency virus (HIV) seroincidence among repeat anonymous testers in San Francisco. Am J Epidemiol. 1997 Oct 15;146(8):662-4. http://aje.oxfordjournals.org.ezproxy.lib.ucalgary.ca/cgi/reprint/146/8/662.pdf The epidemiology of nitrite inhalant use fits well with epidemiologic AIDS-related KS [Kaposis Sarcoma] data. Nitrite inhalants are used more commonly by men who have sex with men than others; use has been declining since AIDS was reported and has roughly paralleled the reported pattern of KS cases, and use among whites is greater than among African- Americans, as is the incidence of KS. Some but not all epidemiologic studies have shown a statistical association between the development of KS among men who have sex with men with AIDS and the use of large quantities of nitrite inhalants when compared with gay men with AIDS but without KS. In addition, nitrites act on blood vessels, the site of KS, and are known to be mutagenic. Haverkos HW. Is Kaposi sarcoma caused by new herpesvirus?. Biomed Pharmacother. 1996;50(6-7):318-9. AIDS-related KS [Kaposis Sarcoma] lesions have been anecdotally reported to occur most often on the chest and face, especially the nose; those are the body areas most heavily exposed to nitrite vapors. Haverkos HW, Drotman DP. NIDA technical review: nitrite inhalants. Biomed Pharmacother. 1996;50(5):228-30. Noninfectious environmental agents, such as nitrite inhalants, also have been proposed to play a role in KS [Kaposis Sarcoma] tumorigenesis Chang Y et al. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science. 1994 Dec 16;266(5192):1865-9. [the author quotes Robert Gallo as saying] [What I found reasonable was Peter Duesberg's] concept to combine virus with certain chemicals like poppers in the monkey model, because that's KS [Kaposi's Sarcoma]. KS, there is no question, is multifactoral. KS, there is no question, is enormously augmented by HIV, but clearly it's multifactoral. We've been arguing that from the beginning. We know that. You don't just take HIV and get Kaposi's sarcoma Hoke F. Robert C. Gallo looks beyond NIH and defends the past. The Scientist. 1994 Nov 14;8(22):12. Conclusions
(1) unprotected anogenital receptive intercourse poses the highest risk for the sexual acquisition of HIV-1 infection;
(8)the association of substance [i.e. drug] use increases the likelihood of practicing anogenital receptive intercourse [they do not consider the possibility that drug use, particularly nitrite inhalants, may be the cause of disease, and receptive anal intercourse is just an associated, not causative, factor] Caceres CF, van Griensven GJP. Male homosexual transmission of HIV-1. AIDS. 1994 Aug;8(8):1051-61. 64.7% of the 187 sexual partners [of homosexual men, some with AIDS] had a history of unprotected receptive anal intercourse over the previous 5 years. Among sexual partners of HIV-1 infected men, HIV-1 seropositivity was significantly associated with a 5-year history of unprotected receptive anal intercourse, with an HIV-1-infected [partner], a history of gonorrhea or syphilis, a history of nitrite [inhalant] use, total number of unprotected receptive anal partners over the previous 5 years, nonwhite race, and lower educational level Seage GR 3rd et al. Risk of human immunodeficiency virus infection from unprotected receptive anal intercourse increases with decline in immunologic status of infected partners. Am J Epidemiol. 1993 Apr 15;137(8):899-908. http://aje.oxfordjournals.org.ezproxy.lib.ucalgary.ca/cgi/reprint/137/8/899.pdf drug use information [in Schechter et al. Lancet. 1993 Mar 13, p658] was obtained on an ever-versus-never basis, rather than being quantified. But with drugs, the dose is the poison
Indeed, Schechter's data also confirm the quantitative aspect of the drug hypothesis if one considers that antibody against HIV is a marker for drug consumption, as they do ('risk behaviours are known to correlate to HIV-1 infection
'). Since it takes about 1000 drug-promoted sexual contacts to be infected with HIV, HIV antibody-positive individuals have been exposed to the drug equivalent of 1000 contacts more than those who are HIV-negative
The T-Cell [CD4+] losses that Schechter et all attribute to HIV can also be explained by zidovudine [AZT], which is prescribed to HIV-positive, but not to HIV-negative, individuals
Thus treatment with zidovudine and a higher lifetime dose of recreational drugs in positive than in negative subjects explain the decline of T-cells in HIV-positive individuals. Duesberg P. HIV and the aetiology of AIDS. Lancet. 1993 Apr 10;341:957. We examined factors associated with the subsequent development of AIDS-related Kaposi's sarcoma in a cohort of 353 homosexual men infected with human immunodeficiency virus (HIV)
including those related to demographics, sexual behavior, illicit drug use, and medical history. We found no strong associations between any of these variables and the development of opportunistic infection, but two were related to Kaposi's sarcoma: use of nitrite inhalants and high numbers of sexual contacts during the period 1978-1982 in the AIDS epidemic centers of San Francisco, Los Angeles, and/or New York
[these] remained independently associated with risk of Kaposi's sarcoma even after multivariate adjustment for a number of classical HIV risk factors
The effect of nitrites could be due to an independent biological mechanism [i.e. another virus] or to enhancement of transmission of the cofactor [or the sole factor, with sexual transmission just a confounding factor] Archibald CP et al. Evidence for a sexually transmitted cofactor for AIDS-related Kaposi's sarcoma in a cohort of homosexual men. Epidemiology. 1992 May;3(3):203-9. Use of poppers was not significantly related to Kaposis sarcoma. Popper use was related to insertive riming: about half the men who had never used poppers or had used them less than once a month reported practising insertive rimming, whereas most (20/26) of the men who used poppers at least once a week also practised insertive rimming. Stratification of the data by insertive rimming shows that there is no trend at all in Kaposis sarcoma risk with frequency of popper use [but flaws in this analysis include self-reporting of drug use (usually under-reported), a control comparison with other people with other AIDS diseases rather than with the general population, an overall high usage of poppers (30 out of 65) compared to rare usage in the general population, and no estimate of the total lifetime exposure to poppers (just current usage). Only 6 people studied claimed never to have used poppers (less than 10%) and more than half used poppers more than once a month] Beral V et al. Risk of Kaposi's sarcoma and sexual practices associated with faecal contact in homosexual or bisexual men with AIDS. Lancet. 1992 Mar 14;339(8794):632-5. The role of nitrite [inhalants] was evaluated between 1985 and 1988 in a study of sexual transmission of the human immunodeficiency virus (HIV) among homosexual male couples in Boston, Massachusetts. Initial enrollment data suggested that a history of unprotected receptive anal intercourse and a history of nitrite use were independent risk factors for HIV infection. In addition, interaction [strong association] between nitrite use and unprotected receptive anal intercourse was observed after controlling for number of unprotected receptive anal sex partners and history of sexually transmitted diseases. Seage GR et al. The relation between nitrite inhalants, unprotected receptive anal intercourse, and the risk of human immunodeficiency virus infection. Am J Epidemiol. 1992 Jan;135(1):1-11. http://aje.oxfordjournals.org.ezproxy.lib.ucalgary.ca/cgi/reprint/135/1/1.pdf Isobutyl nitrite is a drug of abuse [poppers] popular among male homosexuals and among adolescents. In order to approximate the nitrite exposures of inhalant abusers, mice were treated with 900 ppm isobutyl nitrite in an inhalation chamber for 45 min per day for 14 days. After 14 consecutive days of exposure to isobutyl nitrite, mice weighed an average of 4% less than mice exposed to air. The spleens of nitrite-exposed mice weighed 15% less and had 24% fewer cells per spleen than those of controls. Adjusted for equal cell numbers, T cell mitogenic and allogeneic proliferative responses were significantly reduced by 33 and 47%, respectively. The frequency of T-dependent plaque forming cells (PFC) was inhibited by 63% and the total number of PFC per spleen was reduced by 72% in nitrite-exposed mice
The data suggest that habitual inhalation of isobutyl nitrite could impair immune competence and that toxicity appeared to be directed toward T cell functions. Lee SF et al. Exposure to inhaled isobutyl nitrite reduces T cell blastogenesis and antibody responsiveness. Fundamental and Applied Toxicology. 1991;17(4):821-4. Of HIV-antibody-positive men, 78.9% reported both active and passive anal intercourse, 58.8%, rectal enemas, and 53.3%, use of butyl nitrite [and note that many people lie about their sexual habits or drug use] Deininger S et al. Behavioral characteristics and laboratory parameters in homo- and bisexual men in West Berlin: an evaluation of five years of testing and counselling on AIDS. Klin Wochenschr. 1990;68:906-13. 349 homosexual or bisexual men with biopsy proven KS seen in a university hospital-based dermatology practice between 1981 and 1989 were tested for antibodies to HIV-1, and 343 were HIV-1 positive...Inhaled nitrite (poppers) use was reported by 5 [of the 6 who were HIV-1 negative]. Friedman-Kien AE et al. Kaposis Sarcoma in HIV-negative men. Lancet. 1990;335(8682):168-9. Nitrite inhalants (poppers) or other substances to which homosexual men have been preferentially exposed have been suggested as a cause of Kaposis Sarcoma. The use of poppers is highly correlated with behaviours that provide opportunities for acquiring sexually transmitted infections. Kaposis sarcoma has been associated with both sexual practices and the use of poppers
The occurrence of Kaposis sarcoma in children and elderly people with parenterally transmitted HIV and in one-tenth of AIDS patients in Africa, where poppers are not used, suggests that poppers cannot account for the pattern of occurrence of Kaposis sarcoma in AIDS patients [but then, neither can homosexual practices such as rimming and fisting, which are presumably also rare in those groups!] Beral V et al. Kaposi's sarcoma among persons with AIDS: a sexually transmitted infection?. Lancet. 1990 Jan 20;335(8682):123-8.
the areas where absorbed concentrations of volatile nitrites would be expected to be highest - the skin surround the nose and in the nasal/pulmonary mucosa - are also reported to be the areas in which KS occurs in persons with AIDS. This association logically leads to the hypothesis that there is a causal relationship between nitrites and KS, perhaps mediated by the formation of N-nitroso compounds
Nitrite inhalants are important drugs of abuse in the United States. Their association with KS and AIDS raises an important scientific question about possible synergistic reactions between viruses and chemicals in the development of cancer. It is our hope that this monograph will stimulate interest in nitrite inhalant research and attract investigators who can conduct the multidisciplinary research necessary to address the scientific questions raised at this NIDA technical review [it didnt, the virus monoculture took over and research into nitrites was killed or sidelined] Haverkos HW, Dougherty JA. Health Hazards of Nitrite Inhalants (Preface). NIDA Research Monograph. 1988;83:vii-xi. There are important reasons for considering nitrite inhalation as a factor in the development of AIDS-related KS[Kaposis Sarcoma] in young male homosexuals. These are (1) the pharmacologic properties of amyl, butyl and isobutyl nitrites, which are toxic; (2) the mutagenic, teratogenic and carcinogenic products resulting from metabolism of N-nitroso compounds; (3) the potent carcinogenicity of N-nitroso compounds in 39 different animal species; and (4) the deleterious effects of volatile nitrites on human lymphocytes both in vitro and in vivo
there are additional reasons for pursuing the connection between nitrite inhalation and development of KS. These include: (1) the timing of the production and sales of volatile nitrites for use as recreational drugs and the subsequent outbreak of the AIDS epidemic (7 to 10 years); (3) the extensive use of nitrities among male homosexuals; (3) the virtual universal history of nitrite use by young male homosexuals in whom KS has developed during the past 3 years; and (4) the age group in which KS is developing is consistent with a cohort initially exposed 7 to 10 years ago. Newell GR, Spitz MR, Wilson MB. Nitrite Inhalants: Historical Perspective. NIDA Research Monograph. 1988;83:1-14. all four butyl nitrites were found to be moderately toxic compounds in mice Maickel RP. The Fate and Toxicity of Butyl Nitrites. NIDA Research Monograph. 1988;83:15-27. Skin contact with commercial products containing butyl nitrite can produce a crusty lesion at the site. Repetitive use of the material can lead to a proliferation of these lesions around the nose and lip
Whether inhaled or swallowed, nitrites can produce anoxic states [lack of oxygen]
There is clear evidence that volatile nitrites are used as drugs of abuse
7.9% to 11.1% of high school seniors from 1979 to 1985 reported having tried these drugs
The incidence of deliberate use by homosexual men has been greater
Lowry (1980) conservatively estimated that 250 million recreational doses a year were consumed in the United States. Wood RW. The Acute Toxicity of Nitrite Inhalants. NIDA Research Monograph. 1988;83:28-38. In man, IBN [isobutyl nitrite] could initiate carcinogenesis via the formation of N-nitroso compounds or by a direct reaction with DNA, and HIV could promote KS [Kaposis Sarcoma] development, probably via its immunosuppressive action [it is not clear why HIV is brought in here, nor why immunosuppression is required for a cancer, it may be the inability to publish without giving HIV a controlling role in the development of AIDS] Mirvish SS, Ramm MD, Babcook DM. Indications from Animal and Chemical Experiments of a Carcinogenic Role for Iso-Butyl Nitrite. NIDA Research Monograph. 1988;83:39-49. The studies presented here [on mice] show that chronic inhalation of AN [amyl nitrites] can lead to a decrease in helper cells, thus alternting the T-cell H/S [Helper=CD4/Suppressor=CD8] ratio, which is the same phenomenon that occurs in AIDS victims. This suggests a link between AN inhalation and cellular immunity depression. Ortiz JS, Rivera VL. Altered T-Cell Helper/Suppressor Ratio in Mice Chronically Exposed to Amyl Nitrite. NIDA Research Monograph. 1988;83:59-73. 8 HIV-negative male volunteers gave informed consent to participate in this study
Over 4 days of the second week [after obtaining baseline immunologic data], each volunteer participated in 13 [amyl nitrite and placebo] inhalation sessions
the absolute number of blood lymphocytes decreased significantly following the inhalation protocol, then returned to baseline levels
The results showed that exposure to amyl nitrite can induce changes in immune function even after short exposure to moderate doses. Dax EM et al. Effects of Nitrites on the Immune System of Humans. NIDA Research Monograph. 1988;83:75-80. [This paper analyzed 6 studies related to nitrite use and Kaposis Sarcoma] [In Study 1, CDC, 1981-82] 84 of the 87 (97%) AIDS cases in the studies reported nitrite inhalant use
60% of KS patients and those with both diseases [KS and PCP] used nitrites more than 384 days compared with 10% of PCP patients
[Study 2, Mount Sinai School of Medicine, 1981-86] A longitudinal study of 42 homosexual men with persistent generalized lymphadenopathy
All 42 participants had used nitrites. The amount of nitrite use was statistically associated with the development of KS
[In Study 3, UCSF, 1983-86] Patients with KS were 2.2 times more likely to report greater than 4 hits per night
[this was] the variable most strongly associated with KS
[In Study 4, NCI with 245 men, 1982-]Nitrite inhalant use
was not significantly associated with AIDS, Kaposis Sarcoma or Pneumocystis pneumonia [PCP]
[In Study 5, Multicenter AIDS cohort, 1984-] No association between [reported] nitrite inhalant use and KS was reported. Significant associations for KS were found for decreased hemoglobin level [possibly caused by nitrites], decreased T-helper lymphocyte count [ditto], and increased immunoglobulin A levels
[In Study 6, CDC, including 6,700 men, 1984-]No differences in nitrite use were found between disease groups
Studies begun in 1981 and 192 asked more detailed questions about nitrites than later studies
nitrite inhalant use may be declining since the AIDS epidemic. If so, questions asked in 1985 and 1986 about nitrite use in the previous 6 months or 2 years cannot reflect accurately the amount of nitrite use at earlier times. Haverkos HW. Epidemiologic Studies-Kaposi's Sarcoma Vs. Opportunistic Infections Among Homosexual Men With AIDS. NIDA Research Monograph. 1988;83:96-105. Two other risk factors for the presence of anti-HIV [antibodies in Dutch homosexual men] were the use of cannabis and of nitrite [inhalants] van Griensven GJP et al. Risk factors and prevalence of HIV antibodies in homosexual men in The Netherlands. Am J Epidemiol. 1987 Jun;125(6):1048-57. http://aje.oxfordjournals.org.ezproxy.lib.ucalgary.ca/cgi/reprint/125/6/1048.pdf There was a moderate association with nitrite use [in gay men in San Francisco] Moss AR et al. Risk factors for AIDS and HIV seropositivity in homosexual men. Am J Epidemiol. 1987 Jun;125(6):1035-47. http://aje.oxfordjournals.org.ezproxy.lib.ucalgary.ca/cgi/reprint/125/6/1035.pdf Multivariate analysis showed that the variable most strongly associated with Kaposi's sarcoma was the use of large quantities of nitrite inhalants...This study suggests that the use of nitrite inhalants may be a cofactor in the development of Kaposi's sarcoma Haverkos HW et al. Disease manifestation among homosexual men with acquired immunodeficiency syndrome: A possible role of nitrites in Kaposi's sarcoma. Sex Transm Dis. 1985;12:203-8. Base on the results of this study and the previously reported toxicity of IBN [isobutyl nitrite], it would appear that pulmonary toxicity and methemoglobin [oxidized form of hemoglobin that cannot reversibly combine with oxygen] formation are the primary effects of subchronic inhalation Lynch DW et al. Subchronic inhalation toxicity of isobutyl nitrite in BALB/c mice, I. Systemic Toxicity. J Toxicol Env Health. 1985;15:823-33. The dosages used in this study were chosen based on some preliminary experiments we had conducted to determine the maximal tolerated dose (MTD) of IBN for mice. Those experiments indicated that 300 ppm [the maximum used in this study] was probably close to the MTD...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 Lewis DM et al. Subchronic inhalation toxicity of isobutyl nitrite in BALB/c mice, II. Immunotoxicity studies. J Toxicol Env Health. 1985;15:835-46. For marijuana, the OR [odds ratio of Kaposi's Sarcoma (KS) and/or Opportunistic Infections (OI)] increased from 2.7 to 4.3 with increasing use and for nitrites, the OR increased from 4.0 to 6.3
Of the 50 subjects who used nitrites, 86% also used marijuana. Of the 60 individuals in this study, only 10 [reported that they] never used nitrites (2 with Kaposi's Sarcoma and an Opportunistic Infection and 8 with no symptoms)
Three other drugs were significantly increased among KS/OI patients
These were methyldextro amphetamine, ethyl chloride, and opium. Newell GR et al. Risk factor analysis among men referred for possible acquired immune deficiency syndrome. Prev Med. 1985 Jan;14(1):81-91. A 21-year-old homosexual man presented
complaining of severe headache, nausea, vomiting, chest pain, and shortness of breath. The patient reported that the onset of symptoms had occurred late in the evening prior to admission. He admitted to the ingestion of methaqualone (Quaalude), inhalation of cocaine, and repeated inhalation of 'Hardware' ([brand name for] isobutyl nitrite) every 2-3 minutes for a period of 5-6 hours ending at 11:00 PM the evening before admission. Examination revealed a deeply cyanotic [blue skin due to oxygen deprivation] male in moderate distress
Arterial blood gas samples drawn with the patient breathing room air were extremely dark
Methemoglobin [hemoglobin unable to carry oxygen] was 37% of all hemoglobin [normal values are 1-2%]. The patient was given supplemental oxygen by mask and methylene blue
Approximately 45 minutes later, all symptoms had resolved, and the patient was seen to have normal, pink skin. Guss DA et al. Clinically significant methemoglobinemia from inhalation of isobutyl nitrite. Am J Emerg Med. 1985 Jan;3(1):46-7. Of eight different sex acts, seropositivity correlated only with receptive anal intercourse...and with manual stimulation of the subject's rectum
HTLV-III seropositivity was also associated with frequent nitrite inhalant use during the 12 months before phlebotomy [obtaining a blood sample]
and was inversely correlated with insertive anal intercourse [note that receptive anal intercourse is associated with higher use of nitrite inhalants] Goedert JJ et al. Determinants of retrovirus (HTLV-III) antibody and immunodeficiency conditions in homosexual men. Lancet. 1984 Sep 29;2(8405):711-6. Are poppers [nitrite inhalants] immunosuppressive? Hersh et al have demonstrated impaired lymphocyte and monocyte function with doses of nitrites that are not cytotoxic in an in vitro system. They found that these effects were irreversible after 24 hours of continuous exposure...the conversion to nitrosamines could result in increased mutagenic or carcinogenic events Mayer K. Inhalation-induced immunosuppression: sniffing out the volatile nitrite-AIDS connection [editorial]. Pharmacotherapy. 1984 Sep;4(5):235-6. Adverse effects of Nitrites [found in humans or animals, include] ...depression of the central nervous system...convulsions...increased rate and depth of repiration...reduced visual activity...increase in intraocular [within eye] pressure and formation of methemoglobin [which can result in sudden death in humans]...Fatalities have occurred in workers to exposed to strenuous exercise one to two days after cessation of exposure. Loss of vascular tone resulting in pooling of blood has also caused death. The formation of methemoglobin interferes with oxyhemoglobin, causing anoxia. Syncope and death by cardiovascular collapse have occurred...facial dermatitis...local eye irritation...depressed leukocyte function values associated with host defense...The induction of interferon was also inhibited by isobutyl nitrite treatment of fibroblast cell cultures. We showed previously that many chemicals that are carcinogenic can inhibit interferon induction...leukocytes can be permanently damaged by isobutyl nitrite...Many N-nitroso compounds have been shown to be carcinogenic in experimental animals [possibly due to the formation of nitrosamines]...In all, 290 N-nitroso compounds have been tested for carcinogenicity and 252 (87%) have shown such activity...no species is known to be resistant...Organic nitrites which include amyl, butyl, and isobutyl nitrite, can react with amines and amides (amino acids, peptides, proteins and metabolic products) to form N-nitrosamines and N-nitrosamides which are known to be teratogenic [chromosome damaging], mutagenic and carcinogenic Newell GR et al. Toxicity, Immunosuppressive Effects and Carcinogenic Potential of volatile Nitrites: Possible relationship to Kaposis Sarcoma. Pharmacotherapy. 1984 Sep;4(5):284-91. Butyl nitrite is predominantly converted to butanol, nitrite, and nitrate in acidic water and to butanol, nitrate, and methemoglobin in whole blood; however, butyl nitrite shows little initial conversion to those products in plasma. Thiol nitrosation of plasma proteins was indirectly demonstrated. Chemical nitrosation of cysteine was deduced spectrophotometrically by the interactions of butyl nitrite with cysteine and 5,5'-dithio(bis)2-nitrobenzoic acid (DTNB). Ames test mutagenicity of n-butyl nitrite was confirmed
The authors join Jorgensen and Lawesson in warning that use of alkyl nitrite may be hazardous Osterloh J, Goldfield D. Butyl nitrite transformation in vitro, chemical nitrosation reactions, and mutagenesis. Journal of Analytical Toxicology. 1984 Jul/Aug;8(4):164. Although a single-infectious-agent hypothesis would seem to explain much of the AIDS epidemic, certain epidemiologic observations remain puzzling. For example, what explains the excess of KS [Kaposis Sarcoma] cases among homosexual or bisexual men compared with other AIDS risk groups? Perhaps the route of transmission (sexual vs. nonsexual) of an AIDS agent into a susceptible host plays a role in determining clinical outcome. Or perhaps a cofactor present in the homosexual male population, such as repeated exposure to cytomegalovirus or use of inhalant sexual stimulants [e.g. nitrites], predisposes homosexual AIDS patients to develop KS. Jaffe HW, Bregman DJ, Selik RM. Acquired immune deficiency syndrome in the United States: the first 1,000 cases. J Infect Dis. 1983 Aug;148(2):339-45. We speculate that these immunosuppressive effects [measured in cell cultures], combined with the ability of nitrites to convert amines to [carcinogenic] nitrosamines, may be related to the development of opportunistic infections and Kaposis sarcoma in homosexuals who use this agent Hersh EM et al. Effect of the Recreational Agent Isobutyl Nitrite on Human Blood Leukocytes and on in Vitro Interferon Production. Cancer Res. 1983 Mar;43(3):1365-71. The carcinogenous potency of N-nitroso compounds [which can be formed within the body from volatile nitrites that are inhaled] is extraordinary. N-nitroso compounds show great organ specificity in their carcinogenic action in animal experiments...volatile nitrites, which are used as inhalants are mutagenic with or without metabolic activation in the Ames test...We therefore find it appropriate to suggest that amyl nitrite may cause Kaposis sarcoma in homosexual men Jorgensen KA, Lawesson SO. Amyl Nitrite and Kaposis Sarcoma in Homosexual Men. N Engl J Med. 1982 Sep 30;307(14):893-4. Visual observation of stained cell preparations indicated monocyte death [due to exposure to amyl nitrite] occurred more rapidly than lymphocytes. EM revealed broadening of the external foliation of the cell membrane, vesiculation of the outer membrane of the nuclear envelope and a redistribution or loss of microtubule structure in the ectoplasm Marmer DJ et al. In vitro toxicity of Amyl Nitrite [abstract]. Clin Res. 1982;30(5). Amyl nitrite was the only drug that 100% of patients [with Kaposis Sarcoma] reported ever having used, although 1 patient reported using it only once in his life
Only amyl nitrite had significantly elevated risk ratios at the [99%] probability level in the time periods 5-9 and > 10 years before disease. Marmor M et al. Risk factors for Kaposis Sarcoma in homosexual men. Lancet. 1982 May 15;1:1083-6. [we undertook] a survey of male homosexual patients attending [St. Mary's Hospital in London, UK]
250 men were interviewed
215 (86%) had inhaled nitrites within the past five years, a proportion similar to the 86.4% reported for homosexual men attending sexually transmitted disease clinics in New York, San Francisco, and Atlanta McManus TJ et al. Amyl nitrite use by homosexuals. Lancet. 1982 Feb 27;1(8270):503. The [first AIDS] patients are typically young homosexual men, most of whom live in large cities and many of whom use drugs
The leading candidates [as the cause of immunosuppression among these young men] are the nitrites, which are now commonly inhaled to intensify orgasm. Users of amyl nitrite are more likely than nonusers to have had hundreds of sexual partners and to contract venereal diseases. Preliminary data indicate that this 'liberated' subgroup may be at highest risk for immunosuppression. Durack DT. Opportunistic infections and Kaposi's sarcoma in homosexual men. N Engl J Med. 1981 Dec 10;305(24):1465-7. consider what may be the largest single money maker in the Gay world the popper industry. Within the last fifteen years the use of poppers has exploded in the Gay male world, with a spillover lately among some Lesbians
Chemically, poppers consist largely of amyl and butyl nitrites. In 1968 the Federal Drug Administration prohibited the sale of amyl nitrite except by prescription. Since then, the active ingredient in legally sold poppers (the big-name brands) has been butyl nitrite. The smaller, street-pushed varieties often continue to contain amyl nitrite. All the nitrites, however, are closely related and show similar chemical properties. Nitrites have been shown to have harmful effects. In 1977 The Journal of the American Medical Association reported that in large amounts they can cause brown blood (methemoglobinemia), a form of anemia where the blood turns brown in color and where the oxygen supply to vital organs is reduced. In 1981 The Medical Journal of Australia reported that long-term, intense nitrite-sniffing can also cause a second form of anemia, Heinz body hemolytic anemia. In January 1981, Drug Intelligence and Chemical Pharmacy reported the case of a man whose sniffing of Locker Room poppers caused severe respiratory problems (coughing, fever, spitting up blood, difficulty in breathing). Since nitrites greatly increase the heart beat while lowering blood pressure, they are dangerous for people with certain types of heart disorders (such as tachycardia), especially when such people exert themselves physically. Clinical Toxicology reported in 1980: The use of volatile nitrites to enhance sexual performance and pleasure can result in syncope (fainting) and death by cardio-vascular collapse. But the greatest medical concern is the suspicion that poppers cause cancer. It has been known for some time that when nitrites combine with amines (the latter occur naturally in the human body), the result is a class of substances known as nitrosamines. This chemical reaction is ominous because some nitrosamines have been shown to be potent causes of cancer in animals. It is precisely because nitrites form cancer-causing nitrosamines in animals that Ralph Nader has been fighting to ban even tiny amounts of nitrites as a food preservative
In 1980 it was reported by the Italian journal Bolletino Società Italiana Biologia Sperimentale that nitrites cause mutations in genes
the journal Science in 1978 referred to an MIT study that furnished, for the first time, solid evidence that nitrites are themselves carcinogens.
It there something unique about the present Gay male lifestyle that could be causing KS and PCP? An obvious suspect is poppers since (1) they have come to dominate Gay male sex life (straights use them far less), and (2) we have good medical grounds for suspecting them of being carcinogens. In addition, it usually takes cancer several years to show up after exposure to a carcinogen. The cases that are now surfacing fit in with the history of the popper fad. Evans A. Poppers: An ugly side of gay business. Pagan Press. 1981 http://paganpressbooks.com/jpl/EVANSPOP.HTM In the period October 1980-May 1981, 5 young men, all active homosexuals, were treated for biopsy-confirmed Pneumocystis carinii pneumonia at 3 different hospitals in Los Angeles, California. 2 of the patients died
2 of the 5 reported having frequent homosexual contact with various partners. All five reported using inhalant drugs [probably nitrites], and one reported parenteral [injected] drug abuse. Gottlieb MS et al. Pneumocystis pneumonia - Los Angeles. MMWR. 1981 Jun 5;30(21):250-2. http://www.cdc.gov/mmwr/preview/mmwrhtml/june_5.htm Two cases are reported of Heinz body haemolytic anaemia [breakdown of red blood cells] after the sniffing of amyl nitrite and butyl nitrite for protracted periods. Nitrites are powerful oxidizing agents which are recognized to cause haemoglobin to be oxidized to methaemoglobin Romeril KR, Concannon AJ. Heinz body haemolytic anaemia after sniffing volatile nitrites. Med J Aust. 1981 Mar 21;1:302-3. There is a considerable body of knowledge on the pharmacological and toxicologic effects of amyl nitrite but much less is available on butyl and isobutyl nitrites [which came into use when a prescription requirement for amyl nitrites was introduced]. Considering the fact that these latter compounds have been shown to produce both hypotension [low blood pressure] and methemoglobinemia [conversion of hemoglobin to the inactive form methemoglobin] by the same mechanisms as amyl nitrite, it should be possible to extrapolate the physiological data on amyl nitrite to other members of the same series [including serious cardiac, circulatory and blood abnormalities shortly after use] Haley TJ. Review of the Physiological Effects of Amyl, Butyl, and Isobutyl Nitrites. Clinical Toxicology. 1980;16(3):317-39. butyl nitrite inhalation can cause subclinical methemglobinemia [a condition in which the iron in the hemoglobin molecule is unable to carry oxygen effectively] in normal subjects Horne MK et al. Methemoglobinemia from Sniffing Butyl Nitrite. Ann Intern Med. 1979 Sep;91(3):417-8. Amyl nitrite is used widely in the male homosexual population and there are even illegal 'pushers' of this drug. It is used by the passive partner in anal intercourse to relax the anal musculature and thereby facilitate the introduction of the penis. Labataille L. Amyl nitrite employed in homosexual relations. Med Aspects Human Sexuality. 1975;9:122. |
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