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Biomedical subjects

J P Heaton

Publications and source records attributed to J P Heaton.

At least 19 recordsLinked to original sources
PubMed2002

A shared care approach to the management of erectile dysfunction in the community.

Erectile dysfunction (ED) affects men of all ages and results in considerable distress and impact on quality of life for those who suffer from it. As ED is associated with a wide variety of under-lying conditions and cardiovascular co-morbidities, there is a requirement for diversity of treatment options and several factors must be considered to customise and optimise therapy. In the ideal holistic approach to management of the ED patient, both primary care and specialist physicians have an important role to play. This article reports on a sequential approach for the diagnosis and treatment of ED, with an emphasis on 'shared care'. The deliberations are based on a pan-European inter-disciplinary group that met at the Lygon Arms, UK on 22 February 2002.

Erectile Dysfunction↗
PubMed2001

Key issues from the clinical trials of apomorphine SL.

The central nervous system has the capacity to enhance the activity of dysfunctional penile tissue in men with erectile dysfunction (ED). Phase III clinical trials have been conducted using Apomorphine SL (TAP Pharmaceuticals, Deerfield, IL) as a centrally acting treatment for ED. Apomorphine SL has been administered to over 3,000 men in over 75,000 doses. In three phase III crossover double blind studies 854 patients were given a total of 8,263 tablets of apomorphine SL in 2 and 4 mg doses. The patients were between 18 and 70 years old and had multiple co-morbid conditions. Outcome measures included intercourse rates and erection rates on a per attempt basis as well as psychometric instruments and partner response evaluations. The results show that 74.1% of patients had moderate or severe grades of ED on inclusion into the studies, 31% had hypertension, 16% had documented coronary artery disease, 16% had dyslipidemia, and 16% had diabetes. Erections occurred rapidly (10-25 min). In 54.4% of attempts at 4 mg (vs 33.8% placebo, P < 0.001) erections suitable for intercourse were documented. A majority of the attempts at intercourse (50.6%, P < 0.001) were successful at 4 mg a doubling of baseline rates. Mild nausea was the most common but infrequent side effect and the rare occurrence of syncope was the most significant. No cardiac deaths were attributed. It is concluded that the clinical trials of apomorphine SL demonstrate a safe and significant rate of restoration of erectile function by means of a central mode of action. Efficacy has been shown in men with cardiovascular disease and severe grades of ED.

Adolescent↗
PubMed2001

Hormonal erectile dysfunction. Evaluation and management.

The clinical diagnosis of hypogonadism in the adult is difficult to establish on the basis of a history and physical examination and universally requires biochemical investigations. A serum testosterone determination is justified in men complaining of erectile dysfunction with or without alterations in sexual desire. Among the causes of erectile dysfunction, hypotestosteronemia rates are low. The prevalence of erectile dysfunction particularly is common at a period in life when alterations occur in male hormonal environment. The treatment of hypogonadal erectile dysfunction, regardless of age, is readily available, safe, and effective. The positive impact of treatment on the overall quality of life can be significant. The presence of erectile dysfunction in an aging man (> 55 years) does not imply the presence of hypogonadism, and, even if the two conditions are present, the indications for treatment require good clinical judgment. Persistent low testosterone levels may have significant detrimental effects in other organ systems; therefore, a timely diagnosis of androgen deficiency and appropriate treatment may have significant effects outside the narrow field of sexual performance.

Administration, Cutaneous↗
PubMed2001

Severe erectile dysfunction is a marker for hyperprolactinemia.

The need for routine prolactin (PRL) measurement in the initial evaluation of erectile dysfunction (ED) has been questioned because of the low rate of hyperprolactinemia (HP) in these men and the costs involved. In addition, it is widely thought that sexual desire problems are a good clinical marker for HP and/or low testosterone in men with ED. Within a 15-month period, 844 consecutive PRL and sexual hormone determinations were conducted in men at the Kingston General Hospital. Of these patients, 138 were comprehensively evaluated at the first visit for ED and completed the International Index of Erectile Function (IIEF). In the 138 patients, 2.2% had severe hyperprolactinemia (>35 ng/ml), within the range of 1-5% previously reported. No correlation between initial prolactin value and the sexual desire domain or the erectile function domain (EFD) of the IIEF was found for this population. However, all cases of severe HP were found to occur in men who scored less than 10 in the EFD of the IIEF. Low libido is widely accepted as a marker of HP. In this study, HP was found in patients not reporting major problems with a desire disorder. Clinically significant HP may be reliably found with routine biochemical evaluation and in this series was not detected in patients with EFD scores above 10. A routine PRL measurement is inexpensive and early detection of a serious and treatable disease may afford greater therapeutic success.

Adult↗
PubMed2001

Characterising the benefit of apomorphine SL (Uprima) as an optimised treatment for representative populations with erectile dysfunction.

The clinical profile for apomorphine sublingual (SL), a new centrally active agent for the management of the erectile dysfunction (ED) patient, is described in this article. Apomorphine SL is shown to be rapid in onset (71% of patients within 20 min) with a consistent, predictable response that is independent of severity (mild, moderate or severe), the underlying aetiology or the presence of significant co-morbidities (coronary artery disease, hypertension, etc). Importantly, there is also consistent long-term clinical benefit (>90% of attempts being successful over 18 months), for patients who respond to therapy and a benign side effect profile (<13.4% patients with adverse events). This formulation of apomorphine has a speed of onset and overall clinical profile that may offer particular advantages to the patient in terms of spontaneity and predictability of response. ED is a complex disease of varying aetiologies and severities often associated with a number of co-morbidities that require diverse solutions. Given the need for customisation of therapy to individual patient needs, the clinical profile of apomorphine SL would indicate that it will make a most welcome addition to the physician's armamentarium against ED.

Administration, Sublingual↗
PubMed2001

Intracavernosal alprostadil is effective for the treatment of erectile dysfunction in diabetic men.

The efficacy and safety of intracavernosal alprostadil was evaluated for the treatment of erectile dysfunction in men with type I or type II diabetes mellitus. This was an open-label, flexible dose-escalating study involving 336 men (77% of whom were Asian/Oriental) enrolled by 15 centres in Australia, Canada and seven countries in Asia. The effective alprostadil dose, ie the dose producing penile rigidity adequate for intercourse and lasting up to 60 min, was established by titration at the clinic prior to entry into the 6 month self-treatment home phase. All men were fully trained in the self-injection technique before entry into the home phase. Efficacy and safety were assessed using patient and partner diaries and by interview at clinic visits during the titration phase and after 1, 3 and 6 months of treatment. An effective home dose was established by titration for 94% of the 336 men (median dose 20 microg, range 2.5-60 microg). Of 278 (83%) men who entered the home phase, 277 men (247 with type II diabetes and 30 with type I diabetes) had evaluable data for alprostadil dosage and clinical response. During the home phase, a satisfactory erectile response was achieved after 99% of injections, and the median alprostadil dose remained unchanged. The initial home dose and clinical response were similar in type I and type II diabetic men. Treatment was generally well tolerated with a low incidence of penile pain (24%) In conclusion, intracavernosal alprostadil was effective and well tolerated in type I and type II diabetic men with erectile dysfunction of mixed aetiology.

Adult↗
PubMed2001

Andropause: coming of age for an old concept?

Sex hormones have a broad range of actions in regulating very diverse systems through life as well as critical reproductive and growth processes. Sex hormone biology in its satisfaction of the early demands of species survival and reproductive advantage may be leading a destructive process resulting in frailty and the less desirable aspects of aging that may, in men, be termed andropause. One important system associated directly with aging is interleukin-6, which increases as androgens decline. This may be taking place regardless of androgen receptor activity. It is currently acknowledged that androgens are the first but not the only possible treatment for andropause. There is an acute appreciation of the potentially undesirable impact of androgens on the biology of prostate cancer, as well as, possibly, the cardiovascular system. Most authors agree that careful evaluation and surveillance of the prostate must attend androgen therapy in aging men.

Aging↗
PubMed2001

Andropause--a multisystem disease.

The syndrome of androgen deficiency with aging has important biochemical and clinical manifestations. Whether this is called the andropause or by another name the patients with this condition appear to be suffering an accelerated form of aging and some will have individual or clinical reasons to receive treatment. The changes usually attributed to androgen deficiency have been recognized more recently to be due to a broader problem with a number of interlinked hormonal systems (including growth hormone, IGF-I, melatonin, leptin). Several clinical domains can be identified comprising the andropause: Substance (lean body mass, visceral fat, bone mineral density and hematopoiesis); Surface (hair and skin alterations); Central Nervous System (intellectual capacity, mood and sleep patterns); Sex (desire and erection); Prostate. Investigation is directed at the presenting complaints and measuring the serum bioavailable testosterone. Treatment is currently by testosterone replacement using one of a number of routes (parenteral, oral, transdermal). The object of treatment is improvement in the index clinical domains and biochemical normalization. Contraindications include known or suspected prostate or breast cancer.

Adult↗
PubMed2001

Antihypertensive drugs induce structural remodeling of the penile vasculature.

PURPOSE: There is a strong association between hypertension and erectile dysfunction. Studies of the treatment of hypertension have shown that some pharmacological agents are capable of inducing regression of the vascular structure during treatment. We determined whether penile vascular structure is as susceptible as other vascular beds to regression during antihypertensive drug treatment. MATERIALS AND METHODS: Adult spontaneously hypertensive rats were treated for 1 or 2 weeks with 30 mg./kg. enalapril daily, or for 2 weeks with 45 mg./kg. hydralazine daily. Structurally based vascular resistance was determined in isolated penile and skeletal muscle vascular beds perfused with Tyrode-dextran. A cumulative alpha1-adrenoceptor concentration constrictor response curve to 1 to 100 microg./ml. methoxamine was constructed and the maximum constrictor response (vasopressin, methoxamine and angiotensin II) indicating the tissue yield point (that is the average medial bulk of vascular smooth muscle) was determined. The hearts were excised and the ventricles were separated and weighed. RESULTS: Enalapril treatment progressively regressed cardiac and vascular structure during the 1 and 2-week treatment periods with a mean tissue yield point plus or minus standard deviation of -5.91% +/- 5.1% (p <0.05) and -12.1% +/- 6.0% (p <0.05), and a mean left ventricle mass of -11.8% +/- 2.2% (p <0.05) and -13.6% +/- 3.2% (p <0.05), respectively. Hydralazine treatment for 2 weeks was less effective on vascular regression with a mean yield of -7.3% +/- 2.9% (p <0.05) and it did not alter left ventricle hypertrophy compared with controls (3.7% +/- 5.0%). CONCLUSIONS: The data suggest that renin-angiotensin system inhibition may at least partially normalize penile vascular structure. The impact of these changes on erectile function must be determined.

Angiotensin II↗
PubMed2000

Andropause: a misnomer for a true clinical entity.

PURPOSE: A progressive decrease in androgen production is common in males after middle age. The resulting clinical picture has been erroneously named male menopause or andropause. A more appropriate designation is androgen decline in the aging male (ADAM). The syndrome is characterized by alterations in the physical and intellectual domains that correlate with and can be corrected by manipulation of the androgen milieu. We review the epidemiological aspects of aging and endocrinological manifestations of ADAM, and provide recommendations for treatment and monitoring of these patients. MATERIALS AND METHODS: We performed MEDLINE, Pubmed, Current Contents and Pharmaceutical Abstracts searches of relevant peer reviewed publications on andropause, male climacteric, adult hypogonadism and aging. In addition, conference proceedings were researched to provide a more complete review of the literature. Information was scrutinized and collated, and contributory data were reviewed and summarized. RESULTS: ADAM is a clinical entity characterized biochemically by a decrease not only in serum androgen, but also in other hormones, such as growth hormone, melatonin and dehydroepiandrosterone. Clinical manifestations include fatigue, depression, decreased libido, erectile dysfunction, and alterations in mood and cognition. CONCLUSIONS: The onset of ADAM is unpredictable and its manifestations are subtle and variable, which has led to a paucity of interest in its diagnosis and treatment. Urological practice commonly includes a large proportion of men older than 50 years. Therefore, it is important for urologists to recognize the manifestations of and be familiar with evaluations necessary to document ADAM as well as its treatment and monitoring.

Aged↗
PubMed2000

Central neuropharmacological agents and mechanisms in erectile dysfunction: the role of dopamine.

Central nervous system processes are fundamental to sexual function. Considerable progress has been made in our understanding of the neuroanatomical and neuropharmacological bases for erection. Based largely on rat models, there is adequate understanding presently of the general anatomical areas of the brain that relate to sexual function, including the medial amygdala, medial preoptic area, paraventricular nucleus, the periaqueductal gray, ventral tegmentum and others. There is also a burgeoning body of evidence implicating nitric oxide, dopamine, serotonin and oxytocin as critical central neurotransmitters involved in various aspects of sexual function. The role of dopamine, in particular, appears fundamental in the mediation of erectile responses in both animals and man. Additionally, clinical research with apomorphine, a D1/D2 agonist, has shown significant promise in improving erections in men with a wide range of erectile difficulties. Finally, a new classification matrix has been proposed for existing treatments for erectile dysfunction based upon the putative site and mechanism of action. Implications for the further development of neuropharmacological agents in this area are discussed.

Animals↗
PubMed2000

The prevalence and influence of significant psychiatric abnormalities in men undergoing comprehensive management of organic erectile dysfunction.

Psychiatric factors are etiologically important in a proportion of patients with erectile dysfunction. We determined the prevalence of psychopathology and the impact it has on current erectile dysfunction (ED) assessment and management. A group of 120 consecutive men with ED presenting to the Human Sexuality Clinic for the first time was prospectively investigated. All patients participated in a standardized evaluative protocol, including history, physical exam, assessment by a psychiatrist (using DSM-IV criteria), selective hormonal screen, and diagnostic intracavernosal injection. Follow-up appointments were to discuss diagnostic findings and, eventually, treatment choices. The prevalence of significant psychiatric pathology, excluding interview stress, was 33%. Only 16 of 40 cases were recognized and highlighted in the initial assessments by urological staff. There was no significant difference in the modalities of treatment choices between patients with psychiatric problems and those without. 10% of the patients had multiple organic risk factors, normal ICI, and significant psychiatric pathology. Psychopathology or emotional factors play a significant role in the etiology of ED and they are difficult to identify in a non-directed assessment. Even in the face of significant vascular risk factors, psychological abnormalities may be the primary etiology. Treating the 'phallodynamically challenged' individual without adequately addressing the possible presence of psychopathology, will account for treatment failures and have the potential for leaving untreated serious emotional problems.

Erectile Dysfunction↗
PubMed2000

The conditioned response erection (CRE)--a new approach to modelling erectile responses in the rat.

Several animal models are currently used in erectile (dys)function research; these models fail to account for the conditions involving the more spontaneous erections in humans. Recently, we observed an increase in the number of 'spontaneously' occurring erections in rats with previous exposure to apomorphine (APO), a centrally acting drug that initiates penile erections and yawns. Based on this observation, we designed a series of experiments to characterize the development of enhanced, non-apomorphine-induced erections or 'spontaneous' erectile responses to vehicle administration in rats with previous exposure to APO. We further examined the effects of castration on these conditioned erections. Naive (ie never received APO) rats were administered vehicle (1 ml/kg saline) to determine the frequency of baseline erections and yawns. An alternating series of APO (80 microg/kg s.c.) and vehicle administrations were performed over several days and subsequent erectile and yawning responses were recorded. Following 3 sets of 3 APO administrations (with vehicle administered between sets), and the 3rd vehicle administration, these rats were then surgically castrated and allowed 30 days to recover. Following this, APO was administered 3 times to determine erectile and yawning responses post-castration, followed by vehicle administration to determine the effects of castration on conditioned APO responses. The major findings were: (1) that although naive rats had a basal spontaneous erectile response (0.75 +/- 0.88; 4 of 8 rats with at least one erection), repetitive administration (up to 22 treatments) of the central initiator apomorphine significantly increased the number of erections (1.8 +/- 0.7; 7 of 8 rats with at least one erection) and yawning (2.5 +/- 2.47) responses to vehicle administration; and (2) both spontaneous yawning and erectile responses were found to be androgen dependent since castration dramatically lowered the number of erections (0.13 +/- 0.35; 1 of 8 rats with at least one erection) and yawns (0). Therefore, this method of producing erections without a pharmacological manipulation provides an additional animal model which can be used in conjunction with the APO-induced erections in characterizing the physiology and pathophysiology of erectile function in conscious rats.

Androgens↗
PubMed2000

Pre-penile arteries are dominant in the regulation of penile vascular resistance in the rat.

The amount of blood flow into the penis that will produce an erection is dependent on the sum of inflow resistance from the feeder arteries, arterioles and the intra-penile vasculature. In the present study, our objective was to determine quantitatively the contribution to inflow resistance of these different components of the rat penile vasculature. Using methods developed previously, we determined the resistance properties of the isolated perfused whole penis in situ, both in an intact system and after serial transactions of the vessels. These cuts eliminated progressively larger distal segments of the vascular bed. Perfusion pressures were recorded at different flow rates (0.5-3 ml/min/kg body weight) under conditions of maximal dilatation and maximal vasoconstriction induced by methoxamine (MXA, 40 microg/ml). Regardless of the level of vascular tone, the pudendal artery contributes approximately 70% of the total resistance of the penile vasculature. In contrast, the vasculature within the penis (tip, shaft, crus) contributes only about one quarter of the resistance. Penile arterial inflow resistance properties both at maximal vasodilation and maximal alpha1-adrenergic constriction are dominated by the extra-penile vasculature in the rat. The implications of these findings are that alterations in the pudendal-artery (eg vasodilation, vasoconstriction, stenosis) would have primary control of arterial inflow and suggest an important role for pharmacological agents which can promote a more generalized vasodilation (eg phosphodiesterase inhibitors) in contrast to selective corpus cavernosal agents.

Adrenergic alpha-Agonists↗
PubMed2000

Apomorphine: an update of clinical trial results.

Apomorphine SL (TAP Holdings, Deerfield, IL) is a centrally acting treatment for erectile dysfunction (ED) that has been undergoing phase III trials. Over 3000 men have received apomorphine SL and over 75,000 doses have been taken. In the first three phase III parallel arm cross-over double-blind studies 854 patients were given a total of 8263 tablets of apomorphine SL in 2 and 4 mg doses. The patients were between 18 and 70 y old and outcome measures included per attempt rates of intercourse and erections firm enough for intercourse as well as psychometric instruments and partner responses. The majority (74.1%) had moderate and severe grades of ED on admission to the studies, 31% had hypertension, 16% had documented coronary artery disease, 16% had dyslipidemia and 16% had diabetes. Erections occurred rapidly (10-25 min) and in 54.4% of attempts at 4 mg (vs 33.8% placebo). A majority of the attempts at intercourse (50.6%) were successful at 4 mg in patients when recorded on a per-attempt basis. The most common but infrequent and mild side effect of nausea decreases with use. The phase III trials of apomorphine SL show that there is a clinically important restoration of erectile function from this new formulation of apomorphine. It has a rapid and safe effect through action in the central nervous system. Apomorphine SL brings a new choice to the management of ED that will further benefit the millions of couples affected. International Journal of Impotence Research (2000) 12, Suppl 4, S67-S73.

Adolescent↗
PubMed2000

Infiltration of the abdominal wall with local anaesthetic after total abdominal hysterectomy has no opioid-sparing effect.

We have measured the effect of infiltration of the deep and superficial layers of the abdominal wound on morphine consumption and pain for 48 h after operation, in 40 patients undergoing total abdominal hysterectomy, in a double-blind randomized study. Patients received wound infiltration with 0.9% normal saline 40 ml or 40 ml of 0.25% bupivacaine with epinephrine 1:200,000. There were no significant differences between groups in morphine consumption, linear analogue scores for pain at rest or on movement, nausea or sedation during the first 48 h after operation. We conclude that infiltration of the deep and superficial layers of the wound of a Pfannenstiel incision with local anaesthetic solution did not confer additional analgesia in patients undergoing major gynaecological surgery.

Abdominal Muscles↗
PubMed2000

Effects of an environmental anti-androgen on erectile function in an animal penile erection model.

PURPOSE: Erectile function is testosterone dependent. For example, interference with either the levels or receptor binding of this steroid hormone may induce erectile dysfunction. Several environmental contaminants can interfere with the actions of endogenous hormones and have been termed 'endocrine disrupters.' p,p-DDE, a prominent and persistent metabolite of the insecticide DDT, has been shown to be an androgen receptor antagonist. The objective was to determine whether endocrine disrupters, as exemplified by p,p-DDE, are factors in the etiology of erectile dysfunction. MATERIALS AND METHODS: Using the established rat model of apomorphine-induced (80 microg./kg, s.c.) erections we assessed the dose-response effects of p,p-DDE in comparison to the known androgen receptor antagonist flutamide in acute (0.5 to 12 hours) and short-term (up to 8 weeks) experiments in both intact (Study 1) and castrated (Study 2) rats. As a follow up (Study 3), castrated rats treated with p,p-DDE were given increasing doses of testosterone (0.48 to 2.4 mg./kg., i.p.), eight weeks after p,p-DDE administration, to assess reversibility of p,p-DDE effect. RESULTS: A single dose of flutamide (50 mg./kg., i.p.) was found to significantly decrease apomorphine-induced erections to less than 50% over 12 hours following flutamide administration with recovery of erectile response within 48 hours. In comparison, a single dose of p,p-DDE (500 mg./kg., i.p.) decreased apomorphine-induced erections for at least two weeks (1.15+/-0.3 versus 2.5+/-1.1). Castration significantly decreased apomorphine-induced erections to approximately 0.5 erections/30 minutes. Flutamide (50 mg./kg.; i.p.) or p,p-DDE (50 mg./kg.; i.p.) did not further suppress the apomorphine erections in castrated rats. Testosterone supplementation (480 microg./kg; s.c.) in vehicle treated castrated rats recovered erectile response to pre-castrated levels, whereas p,p-DDE treated castrated rats required 4 times the dose of testosterone (2 mg./kg.; s.c.) given to vehicle treated rats to recover erections. CONCLUSIONS: The endocrine disrupter p,p-DDE can markedly interfere with erectile function and demonstrates persistence after a single dose. This supports our novel concept that environmental hormones may cause erectile dysfunction.

Androgen Antagonists↗