Sleep disorders in pregnancy and their association with pregnancy outcomes: a prospective observational study.

PURPOSE: Sleep disturbances such as insomnia, nocturnal awakenings, restless legs syndrome, habitual snoring, and excessive daytime sleepiness are frequent during pregnancy, and these have been linked to adverse maternal and fetal outcomes. METHODS: A prospective observational study was performed in high-risk Indian pregnant women. We used modified Berlin questionnaire (MBQ), Pittsburgh sleep quality index (PSQI), International Restless Legs Syndrome Study Group 2011 criteria, and Epworth sleepiness scale to diagnose various sleep disorders, such as symptomatic OSA, poor sleep quality and insomnia, RLS, and excessive daytime sleepiness, respectively, in successive trimesters of pregnancy. Outcome variables of interest were development of gestational hypertension (GH), gestational diabetes mellitus (GDM), and cesarean delivery (CS); the Apgar scores; and low birth weight (LBW). The relationship between sleep disorders and outcomes was explored using logistic regression analysis. RESULTS: Outcome data were obtained in 209 deliveries. As compared to nonsnorers, women who reported snoring once, twice, and thrice or more had odds ratios for developing GH-4.0 (95 % CI 1.3-11.9), 1.5 (95 % CI 0.5-4.5), and 2.9 (95 % CI 1.0-8.2) and for undergoing CS-5.3 (95 % CI 1.7-16.3), 4.9 (95 % CI 1.8-13.1), and 5.1 (95 % CI 1.9-14.9), respectively. Pregnant women who were persistently positive on MBQ had increased odds for GH and CS. CONCLUSIONS: Snoring and high-risk MBQ in pregnant women are strong risk factors for GH and CS. In view of the significant morbidity and health care costs, simple screening of pregnant women with questionnaires such as MBQ may have clinical utility.

The assessment of vascular risk in men with erectile dysfunction: the role of the cardiologist and general physician.

Erectile dysfunction (ED) and cardiovascular disease (CVD) share risk factors and frequently coexist, with endothelial dysfunction believed to be the pathophysiologic link. ED is common, affecting more than 70% of men with known CVD. In addition, clinical studies have demonstrated that ED in men with no known CVD often precedes a CVD event by 2-5 years. ED severity has been correlated with increasing plaque burden in patients with coronary artery disease. ED is an independent marker of increased CVD risk including all-cause and especially CVD mortality, particularly in men aged 30-60 years. Thus, ED identifies a window of opportunity for CVD risk mitigation. We recommend that a thorough history, physical exam (including visceral adiposity), assessment of ED severity and duration and evaluation including fasting plasma glucose, lipids, resting electrocardiogram, family history, lifestyle factors, serum creatinine (estimated glomerular filtration rate) and albumin:creatinine ratio, and determination of the presence or absence of the metabolic syndrome be performed to characterise cardiovascular risk in all men with ED. Assessment of testosterone levels should also be considered and biomarkers may help to further quantify risk, even though their roles in development of CVD have not been firmly established. Finally, we recommend that a question about ED be included in assessment of CVD risk in all men and be added to CVD risk assessment guidelines.

Review of erectile dysfunction and cardiovascular risk.

Cardiovascular disease (CVD) risk assessment in men with erectile dysfunction (ED) is a critical component of evaluation of patients in the outpatient setting. A multidisciplinary approach is preferred, and multiple validated instruments have described to help gauge CVD risk. We have reviewed the relationships of ED and cardiovascular health, risk factors, pathogenesis, lifestyle modifications, and medical optimization. Moreover, we also took into consideration biomarkers for cardiovascular health and their relationship with ED and sexual dysfunction. We advocate using ED as risk for future CVD events, and review the current literature for the management of ED and CVD.

Immune response against subclinical haemonchosis in Himalayan hill goats.

Haemonchosis commonly occurs as chronic and subclinical infection in small ruminants, and understanding of immunological response against subclinical haemonchosis is of paramount importance for designing and implementing effective control strategies. The present study was designed to evaluate immunological response during subclinical haemonchosis, experimentally established in goats. Sixteen 5-6 month-old helminth naive kids were randomly allocated into one of two groups, infected and uninfected; the infected group being infected per os with 250 Haemonchus contortus larvae per kg body weight. Faecal, blood and serum samples were collected every third day up to 30 days post-infection (DPI), thereafter weekly up to 58 DPI to record changes in faecal egg count (FEC), haemoglobin (Hb), packed cell volume (PCV), peripheral eosinophil percentage and immunological parameters, such as macrophage cytokine interleukin-12 (IL-12), Th1 cytokine (IFN-γ), Th2 cytokines (IL-4, 13, 25, 33) and immunoglobulins (IgG and IgE). Pre-patent period of H. contortus in the present study was 18 days and eggs per gram (EPG) peaked on 30 DPI. The total reduction in body weight gain in the infected group was 26 g per day when compared with uninfected animals. Hb (7.35 ± 0.34 g/dL in infected animals compared with 9.76 ± 0.67 in control animals) and PCV levels (22 ± 1.54 g/dL in infected animals compared with 29.2 ± 1.27 in control animals) decreased significantly up to 44 DPI in infected group (P = 0.000). IL-4, IL-13, IL-33, IgG and IgE showed significant increase in infected animals at different periods. IFN-γ, IL-12 and IL-25 did not show any significant changes barring a steep rise of IFN-γ on 27 DPI. A positive correlation was observed between IgE and IL-4 in subclinical haemonchosis. Of particular note was that all the major cytokines, such as IFN-γ (P = 0.000), IL-4 (P = 0.000), IL-13 (P = 0.009), and both IgG (P = 0.000) and IgE (P = 0.003), were observed at the lowest concentration on 24 DPI. The effect of infection was found to be significant on cytokines with a strong interaction with time. Taken together, the data suggest that Th2 immune response is predominating in subclinical haemonchosis. The economic loss in term of body weight gain due to subclinical haemonchosis was considerable.

Genetic characterization of Theileria species infecting bovines in India.

Genetic characterization of Theileria species infecting bovines in India was attempted targeting the 18S ribosomal RNA region of the parasite. Blood samples of bovines (n = 452), suspected for haemoprotozoan infections, from 9 different states of the country were microscopically examined for Theileria species infection. Four Theileria spp. positive blood samples from each state were randomly utilized for PCR amplification of the 18S rRNA gene (approx. 1529 bp) followed by cloning and sequencing. The sequence data analysis of all the 36 isolates revealed that 33 isolates had high sequence similarity with published sequences of T. annulata, whereas 3 isolates (MF287917, MF287924 and MF287928) showed close similarity with published sequences of T. orientalis. Sequence homology within the isolates ranged between 95.8 and 100% and variation in the length of targeted region was also noticed in different isolates (1527-1538 nt). Phylogenetic tree created for T. annulata sequences revealed that a total of 24 Indian isolates formed a major clade and grouped together with isolates originating from countries like China, Spain, Turkey and USA. Remaining 09 isolates clustered in a separate group and were closely related to the TA5 isolate of T. annulata (a new genotype) originating from India and also with the isolates from East Asian countries like Japan and Malaysia. All the three T. orientalis isolates had minimal intraspecific variation (99-100% homology) amongst themselves. Further, in the phylogenetic analysis T. orientalis Indian isolates were found to cluster away from other 14 isolates of T. buffeli/sergenti/orientalis originating from different countries (Australia, China, Indonesia and Spain). However, these 3 isolates clustered together with the T. buffeli Indian isolate (EF126184). Present study confirmed the circulation of different genotypes of T. annulata in India, along with T. orientalis isolates.

Effects of sildenafil citrate (Viagra) combined with nitrate on the heart.

BACKGROUND: Sildenafil citrate (Viagra) is indicated for the treatment of erectile dysfunction. Large and sudden decreases in systemic blood pressure were reported in a substantial number of patients taking sildenafil citrate combined with nitroglycerin. We studied the effect of sildenafil citrate on the relationship between changes in systemic blood pressure and coronary blood flow. METHODS AND RESULTS: Healthy male beagles were used to assess systemic blood pressure, pulmonary arterial pressure, and flow in the left circumflex artery (in which a critical stenosis was established) and left anterior descending coronary artery. After measurement of the hemodynamic variables, 2 mg/kg sildenafil citrate was administered via a nasogastric tube. Hemodynamic changes were monitored for 1 hour. Subsequently, the acute effect of nitrate combined with sildenafil citrate was studied by the bolus injection of 0.2 mg isosorbide dinitrate before and after sildenafil citrate. Systemic blood and pulmonary arterial pressures and circumflex flow did not change during this study; however, left anterior descending coronary arterial flow increased from 16.0+/-5.8 to 24.6+/-8.7 mL/min 1 hour after administration of sildenafil citrate. The prolongation of systemic blood pressure decrease and the circumflex flow decrement induced by isosorbide dinitrate after sildenafil citrate were significantly larger and longer than those before sildenafil citrate. CONCLUSIONS: Sildenafil citrate had the effect of vasodilation in a normal coronary artery; however, a combined effect with nitrate resulted in large and protracted decreases in systemic blood pressure and coronary blood flow in vessels with critical stenosis.

Treatment of endocrinologic male sexual dysfunction.

Erectile dysfunction affects 20 million to 30 million men in the United States, and it has been reported that a significant number of impotent men (2.1% to 23%) have subnormal serum testosterone levels. A decline in serum levels of testosterone accompanies normal aging in men; however, the pathophysiological and clinical consequences of this decline are unknown. Appropriate hormonal therapy for men with hypogonadism requires an understanding of the normal physiologic regulation of the testes and the pathophysiology of underlying testicular dysfunction. This article reviews those mechanisms.

Priapism: diagnosis and management.

Recent advances in the understanding of erectile physiology have improved the prompt diagnosis and treatment of priapism. During the initial assessment, the physician must distinguish between the two basic types of priapism--low and high flow--because their associated treatment and prognosis differ. To illustrate the diverse manifestation of priapism, we describe the management of four patients with a history of priapism due to varying causes. In addition, we propose an algorithm that provides a systematic and timely approach to treatment. Resumption of erectile function after a prolonged episode of priapism has traditionally been poor but has improved. Patients must be informed that the long-term sequelae of priapism can be avoided with prompt medical or surgical treatment.

Pharmacotherapeutic advances in the treatment of erectile dysfunction.

An estimated 20 million to 30 million American men have erectile dysfunction (ED). The past 2 decades of research defining erectile physiology and investigating the pathogenesis of ED have led to the recognition of a predominantly vascular basis for organic male sexual dysfunction. These scientific advances have laid the foundation for the advent of pharmacotherapies. The Food and Drug Administration approval of intracavernosal, intraurethral, and oral pharmacotherapeutics for ED has revolutionized non-surgical management of this condition. The primary care physician is faced with the challenges of diagnosis and treatment of ED, as well as referral of patients to urologists. In this article, erectile physiology and pathophysiology are reviewed, and pharmacotherapeutics are classified and discussed by their mechanisms of action and the means of administration. A thorough understanding of these new therapeutic options is key to the accurate diagnosis and successful treatment of ED and maximal patient satisfaction and care.

Grading and staging of bladder carcinoma in transurethral resection specimens. Correlation with 105 matched cystectomy specimens.

We compared the grading and staging of transurethral resection of the bladder (TURB) and cystectomy specimens for 105 patients who underwent radical cystectomy for urothelial carcinoma between 1980 and 1984. Of 105 patients, 96% underwent cystectomy within 100 days of TURB (median interval, 10 days). Grading was performed according to the 1998 World Health Organization/International Society of Urologic Pathology grading system and staging according to the 1997 TNM classification. Histologic grade was low-grade, 13; high-grade, 92 in TURB specimens; low-grade, 17; high-grade, 88 in cystectomy specimens. Pathologic stage was Ta, 15; T1, 55; and T2, 35 in TURB specimens; Ta, 5; T1, 19; T2, 19; T3, 46; and T4, 16 in cystectomy specimens. Histologic grade at TURB was associated with pathologic stage at cystectomy (P < .001). When all advanced-stage (muscle-invasive) carcinomas (pT2 or more) were considered together, 55 patients were understaged by TURB, 4 had higher stage in TURB than in cystectomy, and 46 were the same stage as by cystectomy. Forty-three of 55 patients with stage T1 carcinoma at TURB had advanced-stage carcinoma at cystectomy, including 34 who had extravesicular extension (pT3 or more). We found pathologic understanding by TURB occurs in a significant number of patients with bladder cancer; the newly proposed grading system predicted final pathologic stage.

Erythropoietin-induced recurrent veno-occlusive priapism associated with end-stage renal disease.

This is the first report of a male hemodialysis patient experiencing recurrent dialysis-associated priapism that resolved when his concurrent erythropoietin dose was reduced from 2000 to 1500 U one time per week and held if his hemoglobin was greater than 10 g/dL. We discuss dialysis-associated priapism and the effects of erythropoietin on the coagulation cascade and male hormone levels in an effort to elucidate the etiology of priapism in this patient.

Medical and surgical advances in the radical prostatectomy patient.

Maintaining the quality of life after surgery in the radical prostatectomy patient is of paramount importance. One of the major dilemmas in surgical management of radical retropubic prostatectomy (RRP) is preservation of the neurovascular bundle and, hence, erectile function and the continence mechanism. This manuscript addresses anatomical considerations for the surgeon and discusses the following issues with regard to medical and surgical therapies: (1) incidence of erectile dysfunction solely due to complications during RRP; (2) nerve damage during RRP; (3) vascular damage during RRP; (4) current medical and surgical therapies for restoring or maintaining potency; and (5) new advances on the horizon for management of the prostatectomy patient. International Journal of Impotence Research (2000) 12, Suppl 4, S47-S52.

Pathophysiology of Peyronie's disease.

Peyronie's disease is an inflammatory condition characterized by the formation of fibrous, noncompliant nodules in the tunica albuginea which can impede tunical expansion during penile erection, leading to deformity and bending. While the cause of this disease is thought to be due to microvascular trauma and abnormal wound healing, other hypotheses include genetic predisposition. In this review the pathophysiology of Peyronie's disease is discussed as well as current hypotheses regarding its origin.

Rationale for combination therapy of intraurethral prostaglandin E(1) and sildenafil in the salvage of erectile dysfunction patients desiring noninvasive therapy.

Corpus cavernosum smooth muscle relaxation and hence penile erection are regulated in part by increases in smooth muscle synthesis of the second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). The object of this study was to determine 30-month follow-up results in motivated patients desiring noninvasive medical therapy using sildenafil citrate (Viagra) in combination with intraurethral prostaglandin E(1) (PGE(1)) (Medicated Urethral System for Erection [MUSE]). Twenty-eight patients (mean +/- s.d. age, 59 +/-7.3 y; 17 who had undergone radical prostatectomy and 11 who had a diagnosis of organic erectile dysfunction) were included in this study. Detailed history taking and physical examinations were performed and vascular risk factors noted. In these patients, treatment with either 100 mg of sildenafil citrate and/or 1000 microg of MUSE had failed. None of these patients desired intracavernosal injection. Duplex Doppler ultrasonography after redosing was carried out on all patients. Dynamic infusion corpus cavernosography/cavernosometry was obtained in 17 of 28 patients, and combination therapy was initiated using 100 mg of sildenafil citrate orally 60 min before intercourse and 500 microg of MUSE intraurethrally immediately before intercourse. Independently, either 100 mg of sildenafil citrate or 1000 microg of MUSE was not efficacious in inducing an erection sufficient for vaginal penetration in any of the 28 patients. After initiating a combination therapy, at 30 months, all 28 patients were reporting erections sufficient for vaginal penetration, with 3.6 intercourse episodes per month. None of the patients crossed over to intracavernosal therapy or penile prosthesis. During therapy, eight of 28 patients reduced the dose of sildenafil citrate to 50 mg. Combination therapy with MUSE and sildenafil may be more efficacious in the salvage of patients who desire noninvasive therapy but in whom single-treatment modalities fail. Although both cAMP- and cGMP-mediated vasodilation can lead to penile erection, combining therapies that incorporate both pathways may succeed when single therapies fail.

Percutaneous core biopsy of the penis.

To describe the efficacy of percutaneous core biopsy of penile corporal tissue, on ten impotent men, the biopsy was performed with a 19 and a 20 gauge core biopsy co-axial system using an automatic biopsy device. All biopsies were performed on an outpatient basis under local anesthesia. Adequate biopsy specimens were obtained in all. Percutaneous core biopsy of the penis is a safe procedure that is technically easy to perform.

Functional prostaglandin E (EP) receptors in human penile corpus cavernosum.

In this study, we have characterized functional EP receptors in human corpus cavernosum (HCC) tissue and in HCC smooth muscle cells (SMC). Using RNase protection assays, we determined expression of EP2, EP3I and EP3II receptor mRNA. In organ bath preparations of HCC tissue strips, PGE1 caused dose-dependent relaxation at concentrations below 300 nM. At concentrations greater than 300 nM, PGE1 caused contraction. Addition of the EP1/EP2/EP3 receptor antagonist AH6809 inhibited this contraction and facilitated further relaxation through concentrations above 1 microM of PGE1. The EP1/EP3 receptor selective agonist 17-phenyltrinor-PGE2 caused dose-dependent contraction that was partially attenuated by SC51322, an EP1 selective antagonist. In cultures of HCC SMC, PGE1 stimulated cAMP accumulation in a dose-dependent manner. Interestingly, AH6809 significantly attenuated PGE1-induced cAMP accumulation. Sulprostone, a selective EP3 receptor agonist, induced weak contractions in HCC tissue strips but augmented forskolin-induced cAMP synthesis in HCC SMC. The data in this study suggest that HCC and cultured smooth muscle cells express EP1, EP2 and EP3 receptors. These receptors mediate their responses via different biochemical pathways and are expected to have different responses in regulating smooth muscle tone. Thus, we suggest that the ultimate response in erectile tissue to various prostanoids is the integration of responses elicited by individual EP receptor subtypes to a given ligand.

Misoprostol induces relaxation of human corpus cavernosum smooth muscle: comparison to prostaglandin E1.

Prostaglandin E1 (PGE1) relaxes trabecular smooth muscle by interacting with specific G-protein coupled receptors on human corpus cavernosum smooth muscle and increasing intracellular synthesis of cAMP. Misoprostol (Cytotec), is an oral prostaglandin E analogue. The purpose of this study was to compare the functional activity of misoprostol with PGE1 in human corpus cavernosum and cultured human corpus cavernosum smooth muscle cells. Misoprostol, misoprostol free acid or PGE1 induced dose-dependent relaxations in strips of human corpus cavernosum. At concentrations greater than 10(-6) M, tissue recontraction was observed with all three agents. This was abrogated by pretreatment with the thromboxane A2 receptor antagonist SQ29,548. From these observations, we conclude that misoprostol is activated by human corpus cavernosum in situ and relaxes phenylephrine-precontrated tissue strips in vitro. This relaxation response is mediated by the increased cAMP synthesis by these agents.

Lower extremity above-knee prosthesis-associated erectile dysfunction.

Blunt pelvic and perineal trauma has been previously reported to result in site-specific veno-occlusive dysfunction and/or site-specific cavernosal artery insufficiency. We herein describe a case of erectile dysfunction in a young previously potent amputee. We postulate that the erectile dysfunction is associated with a newly described form of blunt trauma, that is, site-specific compression from a perineal weight-bearing lower extremity above-knee prosthetic device. It is hypothesized that when the force exerted by the above-knee prosthesis is directed medially towards the ischiopubic ramus, the penile crura and common penile arterial blood supply become susceptible to crush-like injury, since they are in fixed anatomic locations in the perineum sandwiched between the compressive force and the bone. Clinical evaluation of the erectile dysfunction in this patient revealed site-specific corporal veno-occlusive dysfunction and site-specific common penile arterial occlusive pathology in the precise region of the contact of the above-knee prosthesis with the perineum. Further research is needed in above-knee prosthesis design to prevent erectile dysfunction.

Preliminary report on the development and characterization of rabbit clitoral smooth muscle cell culture.

PURPOSE: Scientific model systems for physiological evaluation and investigation of pathophysiologies in clitoral function have been limited. The aim was to develop a New Zealand White rabbit clitoral corpus cavernosum smooth muscle cell culture. METHODS: Clitoral corpus cavernosum erectile tissue was harvested and placed in culture. Clitoral smooth muscle cells which migrated out from explants were grown to confluence and subcultured. Characterizations were performed by morphological and biochemical analyses. RESULTS: The cells exhibited typical morphologic characteristics of smooth muscle cells. Indirect immunofluorescence studies confirmed the presence of a-smooth muscle cell actin. Androgen and estrogen receptors were detected by specific antibodies and binding studies. The cells expressed subtypes of TGF-beta receptors. Treatment with 80 pM TGF-beta 1 24 h resulted in induction and/or increased availability of TGF-beta receptors. CONCLUSIONS: An in-vitro cell culture system using rabbit clitoral smooth muscle cells was developed. These smooth muscle cells retain their biochemical and functional integrity. This in-vitro cell culture system may facilitate studies aimed at understanding the molecular basis of female sexual function.

Expression of functional prostaglandin D (DP) receptors in human corpus cavernosum smooth muscle.

Prostaglandin D(2) (PGD(2)) binds to specific G-protein coupled receptors (DP) and induces smooth muscle relaxation by stimulating the synthesis of intracellular cAMP. In this study, we examined the role of PGD(2) and DP receptors in regulating human penile smooth muscle contractility. We determined that human corpus cavernosum tissue and smooth muscle cells in culture expressed functional DP receptor and lipocalin-like prostaglandin D synthase by reverse-transcribed polymerase chain reaction (RT-PCR). Functional PGD synthase activity was confirmed by the synthesis of PGD(2) in human corpus cavernosum smooth muscle cells upon addition of exogenous arachidonic acid. Organ bath preparations of human corpus cavernosum tissue strips, contracted with phenylephrine, relaxed in a dose-dependent fashion to either PGD(2) or the DP selective agonist BW245C. Cultures of human corpus cavernosum smooth muscle cells treated with BW245C showed a two-fold increase in cAMP synthesis. These data are consistent with the expression of functional DP receptors in human corpus cavernosum. This suggests the presence of an intact prostanoid autocrine system that may play a role in regulating penile erectile function.