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Jeremy P W Heaton

Publications and source records attributed to Jeremy P W Heaton.

15 recordsLinked to original sources
PubMed2006

Pesticides and polychlorinated biphenyls as potential risk factors for erectile dysfunction.

While it is biologically plausible that environmental chemicals such as pesticides and polychlorinated biphenyls (PCBs) with suspected hormone disrupting properties may have an impact on risk of erectile dysfunction (ED), few epidemiologic studies have assessed this potential association. In a clinic-based case-control study in Kingston, Ontario, consenting subjects completed a questionnaire and donated 15 mL of blood for analysis of organochlorines and lipids by gas chromatography. Exposures were compared for 101 cases with ED and 234 comparable control subjects. For most PCB congeners and organochlorine pesticides, geometric mean levels are similar for cases and controls. Multivariate logistic regression results do not show an increased or decreased risk of ED associated with levels of most detectable environmental substances after adjustment for age, total lipids, and confounders. Levels of 2 of the ubiquitous chlorinated pesticides, oxychlordane and trans-nonachlor, which are highly correlated, appear to associate with a reduced risk of ED, but the role of chance cannot be ruled out. To our knowledge, this study is the first to investigate the possible relationship between plasma levels of organochlorines and ED risk, and results do not provide evidence of an association.

Aged↗
PubMed2006

Predictive validity of five comorbidity indices in prostate carcinoma patients treated with curative intent.

BACKGROUND: Comorbidity is important to consider in clinical research on curative prostate carcinoma because of the role of competing risks. Five chart-based comorbidity indices were assessed for their ability to predict survival. METHODS: This was a case-cohort study of prostate carcinoma patient cohort treated with curative intent in Toronto and Southeast Cancer Care Ontario regions between 1990 and 1996; the subcohort was drawn from these men, whereas cases were cohort members who died from causes other than prostate carcinoma. Comorbidity data were obtained from medical charts (269 subjects). Vital status, age, area of residence, and socioeconomic status information were available. Predictive validity was quantified by the percent variance explained (PVE) over and above age using proportional hazards modeling. RESULTS: The Chronic Disease Score (CDS) (PVE = 11.3%; 95% confidence interval [95% CI], 3.5-22.8%), Index of Coexistent Disease (ICED) (PVE = 9.0%; 95% CI, 2.9-17.9%), Cumulative Illness Rating Scale (CIRS) (PVE = 7.2%; 95% CI, 1.4-17.1%), Kaplan-Feinstein Index (PVE = 4.9%; 95% CI, 0.6-12.8%), and Charlson Index (PVE = 3.8%; 95% CI, 0.3-10.9%) each explained some outcome variability beyond age. PVE differences among indices were not statistically significant. A comorbidity identified at the time of cancer diagnosis was the cause of death in 59.2% of cases (75% for cardiac or vascular causes). CONCLUSIONS: The better-performing, more comprehensive indices (CDS, ICED, and CIRS) would be useful in measuring and controlling for comorbidity in this setting. The CDS was easiest to apply and explained the most outcome variability.

Aged↗
PubMed2006

Lower urinary tract disease: what are we trying to treat and in whom?

The diseases of the lower urinary tract are traditionally divided into abnormalities of storage and abnormalities of emptying. The targets for therapy were the organs most responsible for influencing storage and emptying. Modern understanding places the symptomatic status of the patient as the overriding criterion for treatment. It also accommodates a broader understanding of multiple and overlapping systems. Symptoms of voiding dysfunction have been clearly shown to be associated with symptoms of other genitourinary disease, for example, erectile dysfunction (ED). Treatment of voiding dysfunction has also been shown to have effects (adverse or beneficial) in these other domains. Thus, the symptoms of lower urinary tract disease (LUTD) that have to be considered now as targets relevant to these therapies include ED, ejaculatory dysfunction, sexual desire, sexual pain disorders and female sexual dysfunction. The anatomic, neural and endocrine systems that support these symptomatic functions and dysfunctions span the range from the urogenital smooth muscle to the hypothalamus, the bladder sensory output to the micturition centre and growth factors to androgens. Potentially important targets also include vascular and spinal structures, sex hormones and nitric oxide as well as the obvious genes, enzymes and receptors. The epidemiological studies prove the convergence of LUTD when viewed through the lens of the current patient-related outcomes and problem constructs. This convergence serves as a clear guidance to include wide ranging outcome instruments in all future studies with compounds being investigated for the treatment of LUTD. Out of these will come evidence of expected and unexpected collateral effects. The convergence should open the possibility to a different business model for developing therapeutic concepts. The blockbuster drug for a monolithic indication may be supplemented by agents with single or multiple pathway activity with smaller parallel targets. Using an approach based on patient reported outcomes to therapeutic targets not only widens the range of conditions, but also the patient types who can be considered as having LUTD.

Depression↗
PubMed2005

Dietary patterns and risk of prostate cancer in Ontario, Canada.

Dietary patterns reflect combinations of dietary exposures, and here we examine these in relation to prostate cancer risk. In a case-control study, 80 incident primary prostate cancer cases and 334 urology clinic controls were enrolled from 1997 through 1999 in Kingston, Ontario, Canada. Food-frequency questionnaires were completed prior to diagnosis and assessed intake in the 1-year period 2-3 years prior to enrollment. Among controls, dietary intake was used in principal components analyses to identify patterns that were then evaluated with all subjects in relation to prostate cancer risk using unconditional logistic regression, controlling for age. Four dietary patterns were identified: Healthy Living, Traditional Western, Processed and Beverages. Increased prostate cancer risk is apparent in relation to the Processed pattern, composed of processed meats, red meats, organ meats, refined grains, white bread, onions and tomatoes, vegetable oil and juice, soft drinks and bottled water. The OR for the highest tertile compared to baseline is 2.75 (95% CI 1.40-5.39), with a dose-response pattern (trend test p < 0.0035). Our results suggest that a dietary pattern including refined grain products, processed meats and red and organ meats contributes to increased prostate cancer risk. Since dietary information was collected before subjects knew their diagnosis, recall bias was avoided.

Aged↗
PubMed2005

Smoking and other lifestyle factors in relation to erectile dysfunction.

OBJECTIVE: To assess the association between erectile dysfunction (ED) and various lifestyle and medical factors, including smoking and cardiovascular disease (CVD) medications, among men attending urology clinics in Kingston, Canada. SUBJECTS AND METHODS: We conducted a case-control study of men aged 50-80 years in Kingston, Ontario who agreed to participate at visits to urology clinics during 1997-99. We compared 101 men with clinically diagnosed ED and 234 controls with various benign urological conditions. All men completed a questionnaire on lifestyle and medical factors. RESULTS: Men with ED were twice as likely to be former smokers (odds ratio 2.2, 95% confidence interval, 1.2-3.9), and cumulative smoking in pack-years suggests a dose-response pattern with the risk of ED. Having diabetes was associated with double the risk of ED, and increased alcohol intake appeared to increase the risk. CONCLUSION: There was a greater risk of ED among former smokers, and the suggestion of a dose-response relationship with cumulative smoking.

Age Distribution↗
PubMed2004

Nitric oxide-mediated regulation of hypoxia-induced B16F10 melanoma metastasis.

Tumour hypoxia is associated with resistance to therapy and with increased invasion and metastatic potential. Recent studies in our laboratory have shown that the hypoxic up-regulation of tumour cell invasiveness and chemoresistance is in part due to reduced nitric oxide (NO) signaling. Using B16F10 murine melanoma cells, we demonstrate here that the increased metastatic potential associated with exposure to hypoxia is mediated by a reduction in cGMP-dependent NO-signaling. Pre-incubation of B16F10 cells in hypoxia (1% vs. 20% O(2)) for 12 hr increased lung colonization ability by over 4-fold. This effect of hypoxia on metastasis was inhibited by co-incubation with low concentrations of the NO-mimetic drugs glyceryl trinitrate (GTN) and diethylenetriamine NO adduct (DETA/NO). In a manner similar to hypoxia, pharmacological inhibition of NO synthesis resulted in a significant increase in lung nodule formation, an effect that was prevented by co-incubation with GTN. An important NO-signaling pathway involves the activation of soluble guanylyl cyclase and the consequential generation of cGMP. Culture in the presence of a non-hydrolysable cGMP analogue (8-Br-cGMP) abrogated the hypoxia-induced lung nodule formation, suggesting that the effects of NO on metastasis are mediated via a cGMP-dependent pathway. These findings suggest that a novel mechanism whereby hypoxia regulates metastatic potential involves a downstream inhibition of cGMP-dependent NO signaling.

Animals↗
PubMed2004

Long-term penile incarceration by a metal ring resulting in urethral erosion and chronic lymphedema.

A patient presented with a metal ring around the base of his penis. The ring had been placed 3 years prior to presentation. Intra-operative findings revealed a ventral erosion with complete transection of the urethra and massive fixed lymphedema of the penile skin distal to the ring. Treatment consisted of removal of the ring with metal shears and bolt cutters. Small reduction of the edema was seen 3 months following removal, and the patient refused further treatment. The most interesting part of the outcome was the preservation of penile urethral voiding although intromission was not possible.

Aged↗
PubMed2003

Endocrine causes of impotence (nondiabetes).

The endocrine system has a major role in erections in normal men and it can also be a cause of significant morbidity. The relationship between serum testosterone measurement and erectile function is complex. Androgen treatment should certainly be considered in patients without prostate cancer but with a clinical picture that suggests a relevant contribution of hypogonadism to the ED. Other, nondiabetic, endocrine abnormalities may need to be considered in the management or the patient with ED.

Androgens↗
PubMed2002

Point: urologists should take an active role in the diagnosis and treatment of hypogonadism in the aging male.

Andropause is a problem that can be identified in some men as distinct from the changes associated with aging or chronic disease. These men have mild hypogonadism and a clinical picture that is well within the scope of urologists to identify and manage. Andropause is neither life threatening nor trivial and there are clinical guidelines published that will help to refine the understanding and definition of this condition. The character of andropause is distinct from profound hypogonadism in its relation to age, the scope and degree of contributing symptoms and the marginal reduction in testosterone. Testosterone is the established treatment for some men with andropause and the links between testosterone and cancer of the prostate create an overlap in management that places a premium on urological expertise. Obviously men with cancer of the prostate must not be given testosterone and some men may have clinical andropause and undetected cancer of the prostate. However, current understanding points to the fact that there is no additional risk from re-establishing a normal androgen environment (androgen replacement) in terms of initiating a new cancer of the prostate while testosterone will encourage growth of an established cancer. Therefore, the natural good practice of urology, and only urology, intrinsically encompasses the major issues inherent in the medical collision of cancer of the prostate and testosterone replacement. The good practice of urology includes the use of androgen replacement therapy in men who need it and have been assessed for the presence of cancer of the prostate.

Aging↗
PubMedDate not supplied

Causes of erectile dysfunction.

Erectile dysfunction (ED) arises as a result of a collision of circumstances among any of a number of factors (e.g., risk factors, causes, probable associations), each with its own primary power to affect the outcome. Furthermore, each of the components has its own timing as part of a complex effort of compensation and adjustment that often obscures the individual details. In the end, ED results from a failure of local tissues or systemic supply and control structures. The power of any individual "cause" to degrade erectile function is an important but as-yet unquantified property. The power of a small abnormality over a long or critical period (e.g., organogenesis), or many small contributions, or multiple risk factors will certainly be greater than the sum of the individual elements. Without a full quantitation of pathways and their potential influence, one can compare the importance of causative factors only in limited ways. Not surprisingly, it is the presence of a multiplicity of unidentified or poorly understood causative factors that accounts in large measure for the current inability to cure and prevent ED. There are two other important properties of a putatively causative factor for ED--reversibility and preventability--and these are strongly influenced by the time of onset and the duration of impact. Thus, a critical understanding that comes from recognizing the importance of the temporal associations of component factors is that the causes of ED in an individual may be guessed at but cannot be fully disclosed by an analysis of a "snapshot" of the disease taken at the time of diagnosis.

Erectile Dysfunction↗