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Biomedical subjects

Andrew R McCullough

Publications and source records attributed to Andrew R McCullough.

7 recordsLinked to original sources

Penile oxygen saturation in the flaccid and erect penis in men with and without erectile dysfunction.

It is believed that a chronic state of corporal oxygen desaturation or hypoxemia secondary to the loss of nocturnal erections is a fundamental pathophysiological cause of erectile dysfunction (ED). Limited invasive blood gas measurements in human models have shown decreased oxygen tension in vasculogenic impotence. Normative data on flaccid and erect oxygen saturation (StO(2)) levels are lacking due to the invasive nature of blood gas determinations. Our objective was to determine StO(2) in the flaccid and erect penis in men with and without ED using a tissue oximeter. This FDA-approved instrument provides instantaneous, noninvasive, painless local tissue StO(2) measurements, which highly correlate to blood gas data. The study population included 171 men (18-90 years) who presented to one andrologist. They completed the Sexual Health Inventory for Men (SHIM) based on pharmacologically unassisted erectile function and had penile StO(2) measurements taken. 64 of these men had repeat measurements after PGE-1 induced erections. There are significant differences (P<.001) in corporal and glanular StO(2) in the flaccid (right corpora, 45.23%; left corpora, 52.50%) and erect state (right corpora, 76.58; left corpora, 80.42). Men with ED (right corpora, 45.04% vs 53.58%; P=.02; and left corpora, 50.95% vs 58.78%; P=.03) have significantly lower corporal penile StO(2). Future prospective data collection can correlate penile StO(2) in specific populations, such as diabetics and RRP patients. This may help further elucidate the relationship between corporal hypoxia and the development and progression of ED and possibly its treatment and prevention.

Adolescent↗

A prospective study of the beneficial effects of dose optimization and customized instructions on patient satisfaction with sildenafil citrate (Viagra) for erectile dysfunction.

Our objective was to assess the effects of customized instructions and dose optimization on treatment satisfaction and improvement in erectile function (EF) with sildenafil citrate in men with erectile dysfunction (ED) who had not been previously treated with a phosphodiesterase-5 inhibitor. This 8-week, multicenter, open-label, flexible-dose (25, 50, or 100 mg sildenafil) study included 2 phases. During phase 1, patients took 50 mg sildenafil and followed the sildenafil sample package instructions. In phase 2, sildenafil dose could be adjusted on the basis of efficacy and tolerability, and investigators provided additional customized instructions. The primary efficacy variable was the satisfaction rate (defined as patients responding "very" or "somewhat" satisfied to the Erectile Dysfunction Inventory of Treatment Satisfaction [EDITS] Question 1). Other efficacy assessments included the International Index of Erectile Function (IIEF) and the percentage of successful sexual intercourse attempts. Of 1109 men (mean age, 54+/-13 years) treated, 867 completed the study. In phase 1, 75% of patients were very or somewhat satisfied with treatment. Mean EF domain score on the IIEF increased from 14.3 at baseline to 23.5, and 79% of sexual intercourse attempts were successful. In phase 2, 53% of patients increased their sildenafil dose to 100 mg and 2% decreased to 25 mg. Satisfaction with sildenafil increased to 86%, 91% of sexual intercourse attempts were successful, and mean IIEF EF domain score increased to 25.7. Of the 196 men who were not initially satisfied at the end of phase 1, 64% became very or somewhat satisfied with treatment by the end of phase 2. Initially high levels of efficacy and satisfaction with sildenafil were achieved when patients were provided with only the sample package instructions and the recommended 50-mg starting dose. These results were enhanced with dose optimization, individual patient counseling, and customized instructions.

Adult↗

Sexual dysfunction after radical prostatectomy.

Sexual dysfunction associated with radical retropubic prostatectomy (RRP) may start before the surgery. Men undergoing RRP frequently have some degree of sexual dysfunction. In addition to the psychological stress of the diagnosis, the biopsy may itself have a detrimental effect. After surgery, all men will experience loss of ejaculate, because the organ responsible for ejaculate has been removed. Orgasm quality is adversely affected in many men. Erectile dysfunction is immediate and recovery from it is slow. Initially, phosphodiesterase (PDE)-5 inhibitors do not work, and they take up to 18 months for their effect to be maximized. Younger men who have had bilateral nerve-sparing procedures respond the best. Combination treatment with prostaglandin E1 or high-dose PDE-5 inhibitors may provide salvage therapy when initial PDE-5 inhibitor therapy has failed.

Journal Article↗

The penis as a barometer of endothelial health.

Erectile dysfunction (ED) has only within the past 25 years been recognized as being largely organic in cause. The introduction of phosphodiesterase-5 inhibitor therapy represents a major breakthrough in the treatment of ED and has resulted in a fast-growing body of knowledge regarding the etiology of the disorder, including its close association with cardiovascular disease. ED symptoms are often an early manifestation of endothelial dysfunction and, as such, should prompt further evaluation of not only the sexual dysfunction but also cardiovascular risk. This article discusses the importance of recognizing ED as much more than a quality-of-life issue.

Journal Article↗

Achieving treatment optimization with sildenafil citrate (Viagra) in patients with erectile dysfunction.

Since its approval in 1998, sildenafil citrate (Viagra) has been shown to be efficacious in >100 clinical trials involving >8000 men with erectile dysfunction (ED). In clinical practice, however, many men do not continue long-term use of sildenafil for a variety of reasons; thus, 6 different aspects of optimizing treatment with sildenafil are described here. (1) Intercourse success rates, considered a reflection of real-world effectiveness, were assessed in 1276 patients with ED. Results indicated that the cumulative probability of achieving intercourse success with sildenafil increased with the number of attempts, reaching a plateau after approximately 8 attempts. (2) A comprehensive disease management approach that included a medical history, physical examination, educational material about ED, modifications of risk factors/lifestyle changes, and counseling resulted in successful intercourse in 74% of 111 patients taking sildenafil. (3) A survey conducted among primary care physicians revealed that almost 50% did not routinely question their patients about ED symptoms, although it is known that most patients would prefer their physician to take the initiative. (4) Overall, 55% of 137 men who were previously not successful with sildenafil became successful after reeducation and counseling, which included information on patient and partner expectations, how to properly take the drug, titration to maximum dose, and a minimum trial of 8 attempts for efficacy assessment. (5) Many men with ED have underlying comorbidities or take multiple medications that are risk factors for ED. Controlling these risk factors in 521 men from a multispecialty clinic led to an overall intercourse success rate of 82%; patients with multiple risk factors were less likely to have intercourse success than men with only 1 risk factor. (6) Finally, treatment satisfaction is a pivotal factor in maintaining long-term ED therapy. In an open-label trial, 82% of 443 subjects reported treatment satisfaction with sildenafil. In summary, these findings highlight how important it is for physicians to take a more comprehensive, proactive approach when treating men with ED, including control of risk factors, instructions on how to properly take the drug, partner involvement, and follow-up visits. Using these recommended measures, most men with ED, including those whose treatment was previously unsuccessful, can be treated successfully with sildenafil.

Coitus↗

Four-year review of sildenafil citrate.

Within 6 months of approval by the U.S. Food and Drug Administration (FDA), 5.3 million prescriptions were written for sildenafil citrate. It represented the first clearly effective and FDA-approved oral therapy for the treatment of ED. The chemical structure of sildenafil is very similar to the cyclic guanosine monophosphate molecule with which it competes, in the enzyme phosphodiesterase type-5. Sildenafil binds to the phosphodiesterase-5 enzyme, preventing the breakdown of cyclic guanosine monophosphate through competitive inhibition. The onset of action for sildenafil can be as short as 20 minutes and the duration of action may be as long as three half-lives (18 hours). Anecdotal evidence suggests that many men describe an erectogenic effect for almost 24 hours. The safety of sildenafil has been established in many pre- and postapproval studies at doses as high as eight times the maximum recommended dose. It is likely that the rare instance of myocardial infarction after taking sildenafil as directed, is due more to the activity of sexual intercourse rather than the medication itself. Efficacy have been established in patients with diabetes, parkinsonism, spinal cord injury, and those on antihypertensive (single- and multiple-therapy) agents. It has also been shown to be effective in reversing selective serotonin reuptake inhibitor-induced sexual side effects. Initial concerns about sildenafil with respect to ocular safety were based on misinterpretation of the FDA submission data. The two most common side effects are headache and flushing, both of which are short-lived and easily treated.

Journal Article↗