sildenafil-citrate and Syndrome

There is no robust evidence that any treatment can modify the natural history of patients with heart failure and preserved left ventricular ejection fraction (HFpEF), although most agree that diuretics can control congestion and improve symptoms. HFpEF is often complicated by systemic and pulmonary hypertension, atrial fibrillation, obesity, chronic lung and kidney disease, lack of physical fitness, and old age that can complicate both diagnosis and management. Further trials should phenotype patients precisely and create better definitions of HFpEF based on biomarkers.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Digoxin; Drug Therapy, Combination; Female; Heart Failure; Humans; Male; Middle Aged; Piperazines; Prognosis; Purines; Randomized Controlled Trials as Topic; Reference Values; Risk Assessment; Sildenafil Citrate; Stroke Volume; Sulfonamides; Survival Analysis; Syndrome; Treatment Outcome; Ventricular Function, Left

Testosterone deficiency syndrome (TDS) is defined as a clinical and biochemical syndrome associated with advancing age and is characterized by typical symptoms and deficiency in serum testosterone levels. TDS is a result of the interaction of hypothalamo-pituitary and testicular factors. Now, treatment of TDS with testosterone is still controversial due to a lack of large, controlled clinical trials on efficacy. The risks of treatment with testosterone appear to be minimal, although long-term studies on the safety of testosterone therapy are lacking. The aim of the therapy is to establish a physiological concentration of serum testosterone in order to correct the androgen deficiency, relieve its symptoms and prevent long-term sequelae. All of the available products, despite their varying pharmacodynamic and pharmacokinetic profiles, are able to reach this goal. Newer testosterone patches seem not to cause severe skin irritation. Testosterone gels minimize the skin irritation while providing flexibility in dosing and a low discontinuation rate. Oral testosterone undecanoate (TU) is free of liver toxicity. Recent formulation of oral TU markedly increased shelf-live, a major drawback in the older preparation. Producing swings in testosterone levels rising rapidly to the supraphysiological range is not the case with the new injectable long-acting preparation of TU. To be able to rapidly react and stop treatment in cases where side-effects and contraindications are detected, the short-acting transdermal and oral delivery modes have certain advantages. However, there is no evidence that the use of an injectable long-acting TU in men with TDS has limitations in clinical application for this reason. The use of dehydroepiandrosterone is still controversial because of a lack of well designed long-term trials, although some recent studies suggest positive effects on various body systems. Only a few studies have been carried out to investigate the effect of hCG (human chorionic gonadotropin) in TDS with some positive results on various body systems.

Topics: Aging; Androgens; Body Composition; Drug Therapy, Combination; Hormone Replacement Therapy; Humans; Male; Muscle Strength; Osteoporosis; Phosphodiesterase Inhibitors; Piperazines; Purines; Sexual Dysfunction, Physiological; Sildenafil Citrate; Sulfones; Syndrome; Testosterone

Acute mountain sickness (AMS) is a common problem among visitors at high altitude, and may progress to life-threatening pulmonary and cerebral oedema in a minority of cases. International consensus defines AMS as a constellation of subjective, non-specific symptoms. Specifically, headache, sleep disturbance, fatigue and dizziness are given equal diagnostic weighting. Different pathophysiological mechanisms are now thought to underlie headache and sleep disturbance during acute exposure to high altitude. Hence, these symptoms may not belong together as a single syndrome. Using a novel visual analogue scale (VAS), we sought to undertake a systematic exploration of the symptomatology of AMS using an unbiased, data-driven approach originally designed for analysis of gene expression. Symptom scores were collected from 292 subjects during 1110 subject-days at altitudes between 3650 m and 5200 m on Apex expeditions to Bolivia and Kilimanjaro. Three distinct patterns of symptoms were consistently identified. Although fatigue is a ubiquitous finding, sleep disturbance and headache are each commonly reported without the other. The commonest pattern of symptoms was sleep disturbance and fatigue, with little or no headache. In subjects reporting severe headache, 40% did not report sleep disturbance. Sleep disturbance correlates poorly with other symptoms of AMS (Mean Spearman correlation 0.25). These results challenge the accepted paradigm that AMS is a single disease process and describe at least two distinct syndromes following acute ascent to high altitude. This approach to analysing symptom patterns has potential utility in other clinical syndromes.

Topics: Acute Disease; Adult; Altitude; Altitude Sickness; Antioxidants; Bolivia; Expeditions; Fatigue; Female; Headache; Humans; Male; Mountaineering; Piperazines; Purines; Severity of Illness Index; Sildenafil Citrate; Sleep Wake Disorders; Sulfones; Surveys and Questionnaires; Syndrome; Tanzania; Vasodilator Agents; Visual Analog Scale; Young Adult

Women with the primary disorder of sphincter relaxation find voiding difficult. Studies have identified neuronal nitric oxide synthase in the female urethral sphincter, and nitric oxide donors have been shown to decrease sphincter pressures. The aim of our study was to determine if sildenafil could improve sphincter relaxation and thereby increase flow rates and improve bladder emptying.. Twenty women with complete (5), partial retention or obstructed voiding (15) with a maximum flow rate (Qmax) of less than 15 ml/min with an elevated maximal urethral closure pressure (92--age cm H(2)O) and sphincter volume (>1.6 cm(3)) were included in the study. The study was a double-blind, randomised, placebo-control, crossover design, with patients taking sildenafil or placebo, and with measurement of flow rate and residual volume at baseline and after each treatment phase. Voiding diary, quality of life, and International Prostate Symptom Score (IPSS) data were also collected.. No statistical significant difference was seen in any voiding parameters and diaries when sildenafil citrate was compared with placebo. There was a significant mean decrease in IPSS of 3.64 between baseline and the sildenafil phase (p=0.0083), but not when compared with placebo. In the subgroup of women with partial retention and obstructed voiding (15/20), there was a statistically significant increase in Qmax of 4.7 ml/sec (p=0.025) between sildenafil and baseline; however this difference was not seen when compared with placebo.. This is the first study looking at sildenafil in voiding dysfunction in women. Clinical improvements with sildenafil were not significant when compared with placebo. Sildenafil was not effective as a therapeutic pharmacologic agent in this group of patients.

Topics: Adult; Cross-Over Studies; Double-Blind Method; Female; Humans; Middle Aged; Muscle Relaxation; Muscle, Smooth; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Syndrome; Urinary Retention

Topics: Animals; Carbolines; Cell Division; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Imidazoles; Isometric Contraction; Male; Middle Aged; Muscle, Smooth; Organ Culture Techniques; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Piperazines; Prospective Studies; Prostate; Prostatic Hyperplasia; Purines; Rats; Sildenafil Citrate; Stromal Cells; Sulfones; Syndrome; Tadalafil; Triazines; Urethra; Urinary Bladder; Vardenafil Dihydrochloride

To evaluate whether combination therapy with testosterone gel (T-gel) and sildenafil citrate is effective in achieving adequate potency in subjects with low-normal serum testosterone levels in whom sildenafil alone has failed.. From July 2000 to June 2001, we evaluated 90 men (aged 32 to 72 years) in whom 3 months of sildenafil therapy at the maximal recommended dose (100 mg) with at least three attempts at intercourse during the 3-month period had failed. Of these, 24 men had testosterone levels less than 400 ng/dL (range 92 to 365, mean 231.4) and were subsequently started on 1% T-gel monotherapy (AndroGel, 5 g daily). After 4 weeks of T-gel alone (week 4), sildenafil citrate (Viagra, 100 mg) was added to the treatment regimen for an additional 12 weeks (through week 16). Potency was defined as the ability to have at least one episode of satisfactory intercourse during the treatment period.. All the men had normalized serum testosterone levels after 4 weeks of T-gel monotherapy (range 424 to 596 ng/dL, mean 525). However, none of the men regained potency. At week 16, almost all (22 of 24, 92%) of the men reported improved potency with combination therapy. Improvement in erection quality was also observed.. The results of this study support the use of T-gel with sildenafil citrate in men with low-normal serum testosterone levels in whom sildenafil alone fails. It also underscores the numbers of men with low to low-normal testosterone levels who would benefit from testosterone screening when evaluated for erectile dysfunction.

Topics: Administration, Cutaneous; Administration, Oral; Adult; Aged; Androgens; Drug Therapy, Combination; Erectile Dysfunction; Humans; Male; Middle Aged; Piperazines; Prospective Studies; Purines; Sildenafil Citrate; Sulfones; Syndrome; Testosterone; Treatment Failure

To evaluate the effect of sildenafil on the response of glans penis during sexual intercourse in patients with penile prosthesis who show cold glans syndrome symptoms.. Fourteen patients who had undergone three-piece inflatable penile prosthesis implantation were evaluated. In spite of the normal functioning of the device all of them complained of a degree of dissatisfaction during SI due to a lack of engorgement in the glans penis. The patients were advised to have a dose of 100 mg VO sildenafil about 45 minutes before activating the PP and starting SI. All of them followed this scheme at least three times. They ticked questions 7, 8, 13 and 14 of the International Index of Erectile Function (IIEF) questionnaire with/without having had sildenafil.. Twelve out of thirteen patients (85.7%) indicated a more pleasant SI on sildenafil. It was related to an increase in penile glans engorgement and sensitivity. The scores obtained in the IIEF questions showed a significant increase on taking sildenafil. The partners also talked of a more comfortable SI that they related to a less painful penetration. Sildenafil-related morbidity was not found.. Sildenafil could be used to improve functional results of the penile prosthesis in those patients with CGS and seems to increase satisfaction during SI.

Topics: Body Temperature; Cold Temperature; Humans; Male; Penile Prosthesis; Penis; Piperazines; Postoperative Complications; Prospective Studies; Purines; Sildenafil Citrate; Sulfones; Syndrome; Vasodilator Agents

Preeclampsia, a hypertensive disorder of pregnancy, is detrimental to both mother and fetus. There is currently no effective treatment, but sildenafil, a phosphodiesterase-5 inhibitor, has been proposed as a potential therapy to reduce blood pressure and improve uteroplacental perfusion in preeclamptic patients. We hypothesized that sildenafil would improve the maternal syndrome and fetal outcomes in the Dahl S rat model of superimposed preeclampsia. Dahl S rats were mated, and half received sildenafil (50 mg/kg per day, via food) from day 10 through day 20 of pregnancy. The untreated Dahl S rats had a significant rise in blood pressure and a 2-fold increase in urinary protein excretion from baseline to late pregnancy; however, sildenafil-treated Dahl S rats exhibited ≈40 mm Hg drops in blood pressure with no rise in protein excretion. Sildenafil also increased creatinine clearance and reduced nephrinuria and glomerulomegaly. Sildenafil treatment reduced the uterine artery resistance index during late pregnancy in the Dahl S rat and improved fetal outcomes (survival, weight, and litter size). In addition, 19% of all pups were resorbed in untreated rats, with no incidence of resorptions observed in the treated group. Furthermore, tumor necrosis factor-α, endothelin-1, and oxidative stress, which are characteristically increased in women with preeclampsia and in experimental models of the disease, were reduced in treated rats. These data suggest that sildenafil improves the maternal syndrome of preeclampsia and blood flow to the fetoplacental unit, providing preclinical evidence to support the hypothesis that phosphodiesterase type 5 inhibition may be an important therapeutic target for the treatment of preeclampsia.

Topics: Animals; Blood Pressure; Disease Models, Animal; Female; Fetal Development; Pre-Eclampsia; Pregnancy; Pregnancy, Animal; Rats; Rats, Inbred Dahl; Sildenafil Citrate; Syndrome; Vascular Resistance; Vasodilator Agents

Patients with extensive lymphatic malformations associated with tissue overgrowth syndromes (such as Klippel-Trenaunay syndrome and CLOVES) often pose a therapeutic challenge for physicians. In recent years, it has been suggested that oral sildenafil therapy might be used to treat congenital lymphatic malformations. However, this possible new therapy has not yet been used in patients with lymphatic malformations associated with tissue overgrowth syndromes. A 30-year-old man with extensive capillary-lymphatic malformations of the right leg and thorax, and a tissue overgrowth syndrome caused by a somatic mutation in the PIK3CA gene, was treated with oral sildenafil due to symptoms of pain, dyspnea, and functional impairment. Several weeks after the start of the treatment, the patient reported softening of the lymphatic malformation and a significant improvement of his symptoms and physical condition. So far, sildenafil is still considered a last resort in the treatment of complex treatment-resistant lymphatic malformations. With this case report, we demonstrate that sildenafil could also be an alternative treatment option for lymphatic malformations in patients with syndromes belonging to the PIK3CA-related overgrowth spectrum.

Topics: Administration, Oral; Adult; Capillaries; Class I Phosphatidylinositol 3-Kinases; Genetic Predisposition to Disease; Humans; Lymphatic Abnormalities; Male; Mutation; Phenotype; Phosphatidylinositol 3-Kinases; Sildenafil Citrate; Syndrome; Treatment Outcome; Vascular Malformations

Hoarseness is a common phenomenon that can be caused by uncommon pathology. One seldom cause is Ortner's syndrome, a rare cardiovocal disease that can lead to hoarseness due to left recurrent laryngeal nerve palsy induced by mechanical compression of the nerve by cardiovascular structures. This case report describes a case of a 41-year-old woman with sudden onset of hoarseness. The patient had known pulmonary hypertension and Eisenmenger's syndrome.

Topics: Adult; Antihypertensive Agents; Cardiac Catheterization; Eisenmenger Complex; Female; Hoarseness; Humans; Hypertension, Pulmonary; Laryngoscopy; Phenylpropionates; Piperazines; Pulmonary Artery; Purines; Pyridazines; Recurrent Laryngeal Nerve; Sildenafil Citrate; Sulfonamides; Syndrome; Tomography, X-Ray Computed; Vocal Cord Paralysis

Evans syndrome is a rare cause of hemolysis in pediatric patients. The authors describe two severely affected patients who had previously been heavily treated, and who subsequently developed severe pulmonary hypertension. Both patients were successfully managed by a combination of immunosuppression and anti-pulmonary hypertension treatment. The first patient to present, case A, received an allogeneic bone marrow transplant with subsequent cure of both Evans syndrome and pulmonary hypertension and is now on a weaning dose of sildenafil. Case B is being worked up for allogeneic bone marrow transplantation. The authors speculate that the pulmonary hypertension was caused by the underlying immune dysregulation and hemolysis and that Evans syndrome joins the list of other hemolytic anemias that cause pulmonary hypertension, such as sickle cell disease, thalassemia, and paroxysmal nocturnal hemoglobinuria. However, they suggest a vasculitic process as the main cause.

Topics: Anemia, Hemolytic, Autoimmune; Bone Marrow Transplantation; Child; Child, Preschool; Female; Hemolysis; Humans; Hypertension, Pulmonary; Infant; Piperazines; Purines; Purpura, Thrombocytopenic, Idiopathic; Sildenafil Citrate; Sulfones; Syndrome; Transplantation, Homologous; Vasodilator Agents