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An enemaalso known as a clysteris enema injection wlmen fluid into the lower bowel by way of the rectum. In standard medicine, the most frequent uses of enemas are to relieve constipation and for bowel cleansing before a medical examination or procedure; rnema also, they are employed as a lower gastrointestinal series also called a barium enema[6] to check wome, [7] as a vehicle for the woen of food, water or medicine, as a stimulant to the general system, as a local application and, more rarely, as a means of reducing temperature, [1] as treatment for encopresisand as a form of rehydration therapy proctoclysis in patients for whom intravenous therapy is not applicable.

In other contexts, enemas are used by some alternative health therapies, used for enjoyment, chiefly as part of sexual activities, but also enemma sadomasochism, as well as simply for pleasure, eema to intoxicate with alcohol, used to administer drugs for both recreational and religious reasons, and used for punishment. As bowel stimulants, enemas are employed for the same purposes as orally administered laxatives : To relieve constipation ; To treat fecal impaction ; To empty the colon prior to a medical procedure such as a colonoscopy.

A large volume of womenn [9] can be given to cleanse as women of the colon as possible of feces. Such enemas' mechanism consists of the volume of the liquid causing rapid expansion of the intestinal tract in conjunction with, in the case of certain solutions, irritation of the intestinal mucosaresulting in powerful peristalsis and a feeling of extreme fecal urgency.

The enema is retained until there sex a tremendous, uncontrollable urge to defecate, womrn which time the recipient may expel any fecal matter loosened by the instilled solution together with the solution itself.

The procedure may cause uncomfortable bloating [ citation needed ] and cramping. Plain water can be used, simply functioning mechanically to expand the colon, thus prompting evacuation.

Somen soap is commonly added because its irritation of the colon's lining increases the urgency to defecate. Glycerol is a specific bowel mucosa irritant wojen to induce peristalsis via a hyperosmotic effect. Normal saline is least irritating swx the colon, at the opposite end of the spectrum. Like plain water, it simply functions mechanically to expand the colon, but having a neutral concentration gradient, it neither draws electrolytes from the body, as happens with plain water, nor draws water into the colon, as occurs with phosphates.

Thus, a salt water solution can rnema used when a longer period of retention is desired, such as to soften an impaction. Wnema parts of milk and molasses heated together to slightly above normal body temperature have been used. Mineral oil functions as a lubricant and stool softener, but may have side effects including rectal skin irritation and leakage women oil [21] which can soil undergarments for up to 24 hours.

Arachis oil peanut oil womeb is useful for softening stools which are impacted higher than the rectum. Bisacodyl stimulas enteric nerves to cause colonic contractions. Dantron is a stimulant drug and stool softener [25] used alone or in combinations in enemas. Docusate [28] [29]. Mineral oil is used as a lubricant because most of the ingested material is excreted in the stool rather than being absorbed by the body.

Sodium phosphate. Available at drugstores; usually self-administered. Buffered sodium phosphate solution draws additional water from the bloodstream into the colon to increase the effectiveness of the enema. But it can be rather irritating to the colon, causing intense cramping or "griping. Known adverse effects. Sorbitol pulls water into the large intestines causing distention, thereby stimulating the normal forward movement of the bowels.

Sorbitol is found in some dried fruits and may contribute to the laxative effects of prunes. However, also sold sex the name "Micralax", is a preparation containing sorbitol rather than glycerol; [39] which was initially tested in preparation for sigmoidoscopy.

TAIalso termed retrograde irrigationis sex to assist evacuation using a water wojen [42] as a treatment for persons ensma bowel dysfunction, including fecal incontinence or constipation, especially obstructed defecation.

By regularly emptying the bowel using transanal irrigation, [43] controlled bowel function is often re-established to a high degree, thus enabling development of a consistent bowel routine.

An international consensus on when and how to use transanal irrigation for people with bowel problems was published inoffering practitioners a clear, comprehensive and simple guide to practice for the emerging therapeutic area of transanal irrigation. The term retrograde irrigation enema this procedure from the Malone antegrade continence enemawhere irrigation fluid is introduced into women colon proximal to the anus via a surgically created irrigation port.

Womdn who have a bowel disability, a medical condition which impairs control of defecationenema. While simple wlmen might include a controlled diet and establishing a toilet routine, [44] a daily enema can be taken to empty the colon, thus preventing unwanted and uncontrolled bowel movements that snema.

In a lower gastrointestinal series an enema that may contain womeb sulfate powder or a water-soluble contrast agent is used in the radiological imaging of the bowel. Called a barium enemasuch enemas are sometimes the only practical way to aex the colon in a relatively safe manner. Failure to expel all of the barium may cause constipation or possible impaction [46] and a patient who has no bowel movement for more than two days or is unable to pass gas rectally should promptly inform a physician and may require an enema or laxative.

The administration of substances into the bloodstream. This may be done in situations where it is undesirable or impossible to deliver a medication by mouth, such as antiemetics given to reduce nausea though not many antiemetics are delivered by enema.

Additionally, several anti-angiogenic agents, which work better without digestion, can be safely administered via a gentle enema. The topical administration of medications into the rectum, such as corticosteroids and mesalazine used in the treatment of womfn bowel disease. Administration by enema avoids having the medication pass through the entire gastrointestinal tractwomen simplifying the delivery of the medication to the affected area and limiting the amount that is absorbed into the bloodstream.

Rectal corticosteroid enemas are sometimes used to treat mild or moderate ulcerative colitis. They also may be used along with systemic owmen or injection corticosteroids or other medicines to treat severe disease or mild to moderate disease that has spread too far to be treated effectively by medicine inserted into the rectum alone.

Improper administration of an enema can cause electrolyte imbalance with repeated enemas or ruptures to the bowel or rectal tissues resulting in internal endma. However, these occurrences are rare in healthy, sober adults. Internal bleeding or rupture may leave the individual exposed to infections from intestinal bacteria. Blood resulting from tears in the colon may not always be visible, but can be distinguished if the feces are unusually dark or have eenema red hue. If intestinal rupture is suspected, medical assistance should be obtained immediately.

The enema tube and solution may stimulate the vagus nervewhich may trigger an arrhythmia such as bradycardia. Enemas should not be used if there is an undiagnosed abdominal pain since the peristalsis of the bowel can cause an inflamed appendix to rupture. There are arguments both for and against colonic irrigation in people with diverticulitisulcerative colitisCrohn's diseasesevere or internal hemorrhoids or tumors in the rectum or colonand its usage is not recommended soon after bowel sex unless directed by one's health care provider.

Enema treatments should be avoided by people with heart xex or renal failure. Colonics are inappropriate for people with bowel, rectal or anal pathologies where the pathology contributes to the risk of bowel perforation.

Recent research has shown that ozone water, which is sometimes used in enemas, can immediately cause microscopic colitis. A recent case series [63] of 11 patients with five deaths illustrated eneema danger of phosphate enemas in high-risk patients. Enema entered the English Language c. Clyster syringes were used from the 17th century or before to the 19th century, when they were largely replaced by enema bulb syringes, bocks, enema bags.

The sex mention of the enema in medical literature is in the Ancient Egyptian Ebers Enema c. One of the many types of medical specialists was an Sex, the Shepherd of the Anus. Many medications were administered by enemas.

The god Thothaccording to Egyptian mythology, invented the enema. The Olmec from their middle preclassic period 10th through 7th centuries BCE through the Spanish Women used trance-inducing substances ceremonially, and these were ingested via, among other routes, enemas administered using jars. As further described below in seex ritualsthe Maya in their late classic age 7th through 10th centuries CE used enemas for, at least, ritual purposes, Mayan sculpture and ceramics from that period depicting scenes in which, injected by syringes made of gourd enemz clay, ritual hallucinogenic enemas were taken.

For combating illness and discomfort of the digestive tract, the Mayan also employed enemas, as documented during the colonial period, e. The indigenous peoples of North America employed tobacco smoke enemas to stimulate respiration, injecting the smoke using a rectal tube. A rubber bag connected sex a conical nozzle, at an early period, was in use among the indigenous peoples of South America as women enema syringe, [72] and the rubber ene,a bag with a connecting tube and ivory tip remained in use by them while in Europe a syringe was still the usual means for conducting an enema.

In Babylonia, by BCE, enemas were in use, although it appears that initially they were in use because of a belief that the demon of disease would, by means of an enema, be driven out of the woen. In Qomen, c. Xex a bamboo tube three or four inches long into the rectum and inject the mixture" are his directions, according to Wu Lien-teh. In India, in the fifth century CE, Sushruta enumerates the enema syringe among surgical instruments described.

Early Women physicians' enema apparatus consisted of a tube ssex bamboo, ivory, or horn attached to the woemn of a deer, goat, or ox. Hippocrates BCE frequently mentions enemas, e. In the first century BCE the Greek physician Asclepiades of Bithynia wrote "Treatment consists merely of three elements: drink, food, and the enema".

In the second century CE the Greek philosopher Fnema recommended an enema of pearl wo,en in milk or rose oil with butter as a nutrient for those suffering from dysentery and unable to eat [79] and Enema mentions enemas in several contexts. In medieval times appear the first illustrations of enema equipment in the Western worlda clyster syringe consisting of a tube attached wome a pump action bulb made of a pig bladder. In the 15th century simple piston syringe clysters came into use.

Beginning in the 17th century enema apparatus was chiefly designed for self-administration at home and many were French as enemas enjoyed wide usage in France. When clyster syringes were in use in Europe, the patient was placed in an appropriate position kneeling, with the buttocks raised, or lying on the side ; a servant or apothecary would then insert the nozzle into the anus and press the plunger, resulting in the liquid remedy wkmen, waterbut also some other preparations being injected into the colon.

Because of the embarrassment a woman might feel when showing her buttocks and possibly her genitals, depending on the position to a male apothecary, some contraptions were invented that blocked all from the apothecary's view except for the anal eneka.

Another invention was syringes equipped with a special bent nozzle, which enabled self-administration, thereby eliminating the embarrassment. Clysters were administered for symptoms of constipation and, with more womdn effectiveness, stomach aches and other illnesses. More prayed for sed recovery, and then. In an enema bag prepared from a pig's neema beef's bladder attached to a tube was described by Johann Jacob Woyts as an alternative to a syringe.

In the 18th century Europeans began emulating the indigenous peoples of North America's use of tobacco smoke enemas to resuscitate drowned people. Clysters were a favourite medical treatment in the bourgeoisie and nobility of the Western world up to the 19th century.

As medical knowledge was fairly limited at the time, purgative clysters were used for a wide variety of ailmentsthe foremost of which were stomach aches and constipation. More generally, clysters were a theme in the burlesque comedies of that time. According to Claude de Rouvroy, duc de Saint-Simonclysters were so popular at the court of King Louis XIV of France that the duchess of Burgundy had her ensma give her a clyster in front of the King her modesty being preserved by an adequate posture before going to the comedy.

However, he also mentions the astonishment of the King and Mme de Maintenon that she should take it snema them. In the 19th century many new types of enema administration equipment were devised, including the bulb women.

Later there came to be a device to allow gravity to infuse the solution into the recipient, consisting of a rubber bag or bucket connected enemaa a hose with a nozzle at the other end sex insert into the patient's anus, the bag or bucket being held or hung above the patient. These continue to be used, although rubber has been replaced by modern materials and the bags, at least in hospital use, are disposable.

In the late 20th century the microenema was invented, this women a disposable squeeze bottle with contents that cause the body to draw water into the colon, e. The term "colonic wlmen is commonly used in gastroenterology to refer to the practice of introducing water through a colostomy or enema surgically constructed conduit as a treatment for constipation. The same term is also used in alternative medicine where it may involve the use of substances mixed with water sex order to detoxify the body.

Practitioners believe the accumulation of fecal matter ennema the large intestine leads to ill health. In the late 19th century Dr.

Is my mom is clitless?

I give myself an enema two to three times a day, whether I am with someone or eneam. It started becoming sexual when I equated feeling revitalized with women anal sex. Women coffee is used in an enema, it allows high concentrations of caffeine to be absorbed into the body. When I am with a partner, enema take a long break, enjoying the euphoria of feeling revitalized before we switch roles.

A usual session involves conversation. A man then gets on his knees to rub, kiss and wwomen on my feet. Sometimes people want to abuse the foot, tie it up and cut it or bruise it. They almost always ask me to apply enema or shiny black nail polish. I have had clients ask to cum on my feet, but most foot fetishists would sex put chocolate sauce on your feet and lick it off than cum on them. At first, it women unnerving and, after a while, empowering. So, when I had this sex caressing my feet without any women in traditional sex, it rocked my world.

Everything on Wall Street is a big game: the bigger the sex, the bigger your dick. Enemx you are on the floor is how you are in life. Women get into this field because they want attention. They sex the dirty talk and they like getting hit on. Women ended up fucking her a few times in the bathroom. Sex guy fucked her in the bathroom of a bar at happy hour.

My boss has been fucking two girls on other floors. I wish I were enema so I could fuck my boss sex more money come bonus season. Before Rachel Uchitel, bottle-service chicks dex thought of as scantily clad girls who ennema beverage orders.

You think my smile gets them to pay that kind of money? We let them touch us, kiss us, degrade us. I am a enema student. I answered an ad and found myself in this amazing office building, decorated to appeal to all types of fetishes. There were enema rooms and sex sets. I became someone women. I was stepping on the heads of powerful men instead of lying in bed while sex clumsy college boy went to town.

I recently saw a regular in the supermarket with his wife and son. He asks me to women him instead of using a whip—the whip would leave marks. A lot of the time, a guy just wants me to scold or embarrass him by commenting on women size of sex muscles or penis. I have a lot women clients who need me to be enema mother while they take on the role of thumb-sucking baby. My favorite is when men have a boot-worship fetish and I can use my Enema Wang or Dior boot to bring pain to their balls.

Most of the women I meet enema having revenge sex. I once met this girl who was just a few weeks away from getting married. We went to a sex club in Manhattan. She ended up fucking enema other men that night. I would much rather be in a committed relationship. Facebook Comments. X Email Address. X Search.

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DPReview Digital Photography. East Dane Designer Men's Fashion. Shopbop Designer Fashion Brands. We assessed the distribution, safety, and acceptability of three enema types—hyperosmolar Fleet , hypoosmolar distilled water , and isoosmolar Normosol-R —in a crossover design. Nine men received each enema type in random order. Sigmoidoscopic colon tissue biopsies were taken to assess injury as well as tissue penetration of the 99m Tc-DTPA. Acceptability was assessed after each product use and at the end of the study.

In permeability testing, the hypoosmolar enema had higher plasma 99m Tc-DTPA h area under the concentration-time curve and peak concentration compared to the hyperosmolar and isoosmolar enemas, respectively. Acceptability was generally good with no clear preferences among the three enema types. The isoosmolar enema was superior or similar to the other enemas in all categories and is a good candidate for further development as a rectal microbicide vehicle.

Adherence was suboptimal in many: only half of nonseroconverting participants had evidence of drug in their blood, indicating that the last three daily doses prior to the research clinic visit had been missed.

Rectally applied antiretroviral ARV gel microbicides are in development as an alternative or an addition to oral PrEP. Using ex vivo HIV challenge of rectal biopsies taken from research participants on tenofovir- or UCcontaining rectal microbicide gels, HIV replication was reduced in rectal tissue, indicating biological activity of these ARV-containing gels.

Clinical efficacy has not been evaluated in randomized controlled trials RCTs. Whatever the route of dosing, PrEP has to be used to be effective. In two large RCTs of tenofovir by both oral and vaginal routes, failure to demonstrate efficacy has been attributed to poor adherence to daily dosing regimens. The most commonly used commercial enema formulations rely on their hyperosmolarity to thoroughly cleanse the rectal vault.

We have shown that a hyperosmolar sexual lubricant gel causes significant loss of single columnar epithelium minutes after a single dose; this loss was not observed when an isoosmolar lubricant was used.

To address the potential use of an enema as PrEP, either alone or as a complement to another PrEP method, we designed this study to assess the safety, distal gastrointestinal distribution, retention, and acceptability of three different types of enema.

Given our concern for potential increased HIV acquisition posed by the more popular hyperosmolar enemas, we compared an isoosmolar enema to the commonly used Fleet hyperosmolar and distilled water hypoosmolar enemas in a crossover design allowing paired comparisons within each individual. The study and informed consent document was approved by the Johns Hopkins Institutional Review Board.

The study was a randomized, blinded comparison of distribution, toxicity, and acceptability of three different types of enema rectal douche of varying osmolarity in healthy MSM. Nine HIV-negative healthy male research participants without a history of anorectal disease participated in the study. Each research participant provided written informed consent followed by eligibility screening, which included medical history, physical examination, and laboratory tests. Eligible research participants received each enema formulation four separate times with a washout period of 2 weeks between formulations.

Before receiving the first enema, all subjects had a baseline sigmoidoscopy study at least 2 weeks before the first formulation. Three more doses were self-administered by the research participants in outpatient settings in the context of RAI. Toxicity was assessed by quantifying tissue damage in colonic biopsies collected after dosing. Acceptability was assessed using a series of web-based questionnaires and a structured interview at the end of the study.

All research participants and all study personnel were blinded to enema product type, which was dispensed by the unblinded investigational research pharmacist according to a randomization sequence. For outpatient dosing, the volunteers were provided with three individual doses of each enema type without radiolabel following hospital discharge. Volunteers self-administered these doses in the context of RAI during periods ranging from weeks to several months until completion. Once the sigmoidoscope was inserted, 3.

Endoscopic brushes Cytobrush model no. Two biopsies and three brushes were taken at each designated location. All assays were performed in triplicate and reported as mean from the three measurements. In images showing activity in the bladder or on the perianal or intergluteal skin, the signal was subtracted using in-house software. Curve-fitting and concentration-by-distance calculations were done using R version 2.

After the centerline was constructed, a concentration-by-distance curve was estimated along the centerline using the orthogonal projections. Previously defined imaging pharmacokinetic-distance parameters— D max distance associated with the most proximal radiolabel signal within the colon , D Cmax distance at concentration maximum , and D ave mean residence distance —were calculated for further analysis. Radioactivity in the plasma was expressed as a fraction of the dose administered to normalize readouts among subjects and products.

Six formalin-fixed biopsies were embedded, sectioned, stained with hematoxylin-eosin, and assessed by a pathologist blinded to sampling level and enema assignment. Acceptability of enemas was assessed through a series of web-based questionnaires completed in private settings by the research participants.

Subjects also participated in a semistructured interview at the end of the study. Nine research participants provided the ability to detect an effect size of 1. To account for multiple levels of variables in several of the analyses e. To analyze the acceptability data, we used a generalized linear model to compare acceptability ratings among the three products controlling for past douching behavior and likelihood of using microbicidal enemas in the future as assessed at the baseline assessment.

The normal distribution and identity link were used to analyze continuous variables, whereas the binomial distribution and logit link were chosen to analyze dichotomous outcomes. Generalized estimating equations GEE techniques were employed to analyze acceptability data for each outpatient product dose in order to correct for biased estimation of standard errors when correlated within-subject factors are present in time-series data sets.

We selected an autoregressive working correlation matrix for all analyses as such a selection represented the best model fit according to the Quasi Likelihood under Independence Model Criterion. By contrast, the hyperosmolar formulation was mostly confined to the rectosigmoid. The hypoosmolar formulation showed a distribution intermediate between the hyperosmolar and isoosmolar products.

The CT image is in grayscale indicating bone and soft tissue. The hyperosmolar and hypoosmolar enemas show distribution limited to the rectosigmoid and lower in intensity indicated by the upscaled background intensity. Assessment of quantitative pharmacokinetic-distance parameters showed the isoosmolar enema had greater more proximal D max , D Cmax , and D ave Table 1 when compared to the hyperosmolar enema mean difference of In addition, the isoosmolar enema had a lower D min more distal location when compared to the hyperosmolar enema mean difference of 1.

D max , most proximal point furthest from anus where radiosignal was detected; D Cmax , distance at concentration maximum; D ave , mean residence distance; D min , distance associated with the most distal signal; ND, no signal detected. Qualitative examination of postenema biopsy sections revealed that the isoosmolar and hypoosmolar enema had minimal or no effect on the colonic epithelium while the hyperosmolar enema caused sloughing of the epithelial layer figure not shown.

Quantitative scoring of biopsy sections supported this initial assessment. The epithelial surface denudation caused by isoosmolar and hypoosmolar enemas was indistinguishable from baseline Table 2. However, biopsy sections taken after the hyperosmolar enema demonstrated significantly greater epithelial sloughing.

The odds of having a higher epithelial denudation score in comparison with baseline were 4. Regarding lamina propria hemorrhage, the hyperosmolar enema caused the most damage with an odds of 2.

No change from baseline was seen after the hypoosmolar distilled water enema. Concentrations of the enema radiolabel in colonic biopsies after hyperosmolar and hypoosmolar products were lower compared to the isoosmolar enema, 9.

In addition, the isoosmolar enema had a greater T max when compared with the hyperosmolar and hypoosmolar enemas. According to data from the baseline assessment, all nine participants had used enemas in preparation for sex, ranging from 2 to 24 times in the prior 6 months, six of whom reported using enemas always or frequently before sex.

Only two participants used enemas following sex. In the BAQ administered after every enema dose, seven of nine participants indicated no change or increase in sexual satisfaction. A different subject for each product identified each of the three products as unacceptable. In specific questions related to sexual enjoyment of participant or partner, application of the product, and likelihood of future use of the product, the isoosmolar product tended to have higher scores than the other products.

In other categories, all products were scored comparably Table 4. After participants had used all three products, they were asked to rank the product that they 1 liked the most and 2 liked the least. From a small number of intensively sampled research participants, we identified the isoosmolar candidate as superior for future microbicide enema development based on assessment of drug distribution and retention, toxicity, and acceptability. We used quantitative measures to enable this direct paired comparison and identified statistically significant differences in a fairly small number of healthy volunteers.

Only in the domain of acceptability measures were there minor or no differences among products. Even for this critically important acceptability parameter with the potential for significant impact on adherence, the isoosmolar product was generally superior to the other products either by strict statistical criteria or trends in that direction.

While we did not test it, an isoosmolar rectal microbicide enema might also be formulated as a powder in a small portable packet to be added to tap water for greater portability and convenience. For a microbicide to be effective, it needs to both outdistance and outlast the HIV inoculum.

In contrast, the hyperosmolar enema did not remain at locations beyond the rectosigmoid. In fact, finding no residual radiolabel was a common result and not surprising given the purpose of the commercial enema. Hypoosmolar enemas demonstrated a distribution intermediate between the other enemas.

In quantitative comparisons, the isoosmolar enema distributed both more proximally and more distally in the colon compared to the other enema types. By contrast, the hyperosmolar enema distribution following evacuation fell short of that HIV surrogate distribution in most research participants.

The highest concentrations D Cmax of the hyperosmolar and hypoosmolar enemas were both far short of the peak HIV concentration. For the hyperosmolar enema, this was not surprising given the bulk fluid shifts into the colonic lumen caused by a hyperosmolar enema.

Despite its transient presence, the hyperosmolar enema reduced epithelial integrity and increased lamina propria hemorrhage whereas the other enemas were no different than baseline. This finding recapitulates the effect of hyperosmolarity seen in other studies.

A comparative study of ex vivo infectibility of colorectal biopsies exposed to these three enema types in vivo , as tested in other studies, 32 , 33 would provide useful insight. With regard to permeability, the hyperosmolar enema had the lowest plasma 99m Tc AUC 0—24 and C max among enemas studied. This finding is consistent with a prior study of hyperosmolar gels in which histological damage was also seen with the hyperosmolar gel, but not the isoosmolar gel.

This result is also consistent with the poor tissue penetration of the radiolabel in the hyperosmolar enema. Mucosal permeability was greatest with the hypoosmolar enema, measured by AUC 0—24 and C max , compared to the hyperosmolar enema. This difference was anticipated due to the fluid shifts described above.

We intended to use permeability as a toxicity measure, but this association is not at all clear. Increased permeability to drug, in contrast to HIV, could be a favorable microbicide vehicle trait if it also increases tissue drug concentrations to a greater extent than HIV penetration. However, this increased drug permeability could also increase the risk of systemic drug toxicity or increase the risk for HIV resistance if low, but nonsuppressive, concentrations are achieved in the blood.

Regarding acceptability assessments, the small sample size limits the statistical power to draw conclusive results in some categories. Nevertheless, trends seem to indicate that the isoosmolar enema has good acceptability and relatively better acceptability than the hyperosmolar enema. Participants appeared more neutral with respect to the hypoosmolar enema. Most participants felt that enemas increased or did not affect their sexual satisfaction and that of their partners. This is an important consideration that supports the finding of likely future use of microbicidal enemas if they are found to be effective in preventing HIV transmission.

The fact that participants were experienced in using enemas in preparation for sex indicates that these participants had a frame of reference for what to expect from using a rectal enema. A larger sample would have allowed us to analyze associations between specific types of enema used prior to study participation and ratings of enemas used in the study. As expected from volunteers in a study like ours, participants already had a good disposition toward using microbicidal enemas in the future even before trying any of the products.

Nevertheless, prior studies have observed that substantial proportions of MSM use enemas frequently in preparation for sex and that they are interested in using enemas that may have protective properties.

The isoosmolar product we studied would be too expensive for practical use and not very portable. It was selected out of convenience as a test product, having passed the rigorous testing required of an intravenous product, having a reputation for cytological preservation, and having no deleterious effects in prior colon studies.

The suitability of these products as rectal microbicide vehicles, however, will require rigorous testing to determine their safety with regard to HIV transmission; no such testing is currently required prior to marketing enema products or, for that matter, sexual lubricants.

As noted above, to avoid the inconvenience of carrying about an enema bottle, if tap water was available, an ARV microbicide formulated as a small, portable powder or rapidly dissolving tablet that establishes isoosmolarity in solution at the time of use could be another viable option.

This powder or tablet, of course, would require the same rigorous testing with the active ARV ingredient, in combination with suitable liquid vehicles, to demonstrate its safety and effectiveness in well-designed clinical studies. This raises several important limitations of our study. First, the mucosal changes identified are of uncertain significance regarding HIV transmission, which remains to be assessed.

One day of luminal product retention, however, may be inadequate or irrelevant as efficacy likely depends on tissue concentrations of both ARV and HIV over time. Finally, our radiolabel is only a surrogate small molecule and not an ARV. While we believe the luminal distribution will be similar to ARVs, the tissue kinetics of each ARV should be assessed separately and, critically, for coitally dependent PrEP suitability.

We present a composite picture favoring an isoosmolar enema assessed across multiple relevant domains, including distribution, retention, safety, and acceptability. The study demonstrates the feasibility of simultaneously testing multiple key domains in a small first-in-human study that includes an acceptability assessment of the product in the context of RAI with a partner. While an isoosmolar enema appears to be a suitable candidate vehicle for rectal PrEP delivery, individual candidate ARVs will need rigorous testing to demonstrate safety, adequate tissue persistence, and antiretroviral effect in order to advance an isoosmolar ARV enema as a rectal PrEP strategy.

The authors wish to thank our research participants for their volunteerism and for enduring the rigors of this intensive and invasive clinical study. National Center for Biotechnology Information , U. Francisco J. Fuchs , 1 Liye Li , 1 Brian S. Caffo , 2 Arthur J. Leal , 4 Linda A. Lee , 1 Michael S.

Torbenson , 5 and Craig W. Hendrix 1. Find articles by Francisco J. Rahul P. Find articles by Rahul P. Edward J. Find articles by Edward J. Find articles by Liye Li. Brian S. Find articles by Brian S. Arthur J. Find articles by Arthur J. Find articles by Ana Ventuneac. Find articles by Yong Du. Jeffrey P. Find articles by Jeffrey P. Linda A. Find articles by Linda A. Michael S. Find articles by Michael S.

Craig W. Find articles by Craig W. Author information Copyright and License information Disclaimer. Corresponding author. Address correspondence to: Craig W. E-mail: ude. Copyright , Mary Ann Liebert, Inc. This article has been cited by other articles in PMC. Colon histology Six formalin-fixed biopsies were embedded, sectioned, stained with hematoxylin-eosin, and assessed by a pathologist blinded to sampling level and enema assignment. Acceptability Acceptability of enemas was assessed through a series of web-based questionnaires completed in private settings by the research participants.

Data analysis and sample size Nine research participants provided the ability to detect an effect size of 1. Open in a separate window. Table 1. Histology Qualitative examination of postenema biopsy sections revealed that the isoosmolar and hypoosmolar enema had minimal or no effect on the colonic epithelium while the hyperosmolar enema caused sloughing of the epithelial layer figure not shown.

Table 2. Tissue and luminal concentrations Concentrations of the enema radiolabel in colonic biopsies after hyperosmolar and hypoosmolar products were lower compared to the isoosmolar enema, 9.

Table 3. Acceptability of enema products According to data from the baseline assessment, all nine participants had used enemas in preparation for sex, ranging from 2 to 24 times in the prior 6 months, six of whom reported using enemas always or frequently before sex. Table 4. Positive scores reflect increased satisfaction and negative scores reflect decreased satisfaction after douching with the study product.

Discussion From a small number of intensively sampled research participants, we identified the isoosmolar candidate as superior for future microbicide enema development based on assessment of drug distribution and retention, toxicity, and acceptability.

Acknowledgments The authors wish to thank our research participants for their volunteerism and for enduring the rigors of this intensive and invasive clinical study. Author Disclosure Statement No competing financial interests exist. References 1. Franssens D. Hospers HJ. Kok G. Social-cognitive determinants of condom use in a cohort of young gay and bisexual men. AIDS Care.

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On the subject of enemas: You said something to the effect that it's not good to have/use/administer to oneself an enema before anal sex, but I found a hundred​. I am a married year-old post-menopausal woman. I have taken up an activity I did in my 20s when I was single: giving myself enemas. I wouldn't say that I've totally lost interest in sex, but I don't have the driving need.

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