Evaluation of the sensitivity of different doses of vasoactive drugs in diagnosing erectile dysfunction in impotent patients: a prospective case-control study.

INTRODUCTION: Erectile dysfunction (ED) is one of the most common sexual disorders worldwide affecting about 30 million men in the United States, and an estimated 100 million men worldwide. Penile duplex doppler ultrasound (PDDU) is performed using an intracavernosal injection (ICI) of a vasoactive agent to demonstrate both arterial insufficiency and veno-occlusive dysfunction. This article aims to evaluate the sensitivity of different doses of different vasoactive agents used to diagnose ED in impotent patients. MATERIAL AND METHODS: This study recruited 90 subjects with ED and 100 healthy subjects as controls. All of the subjects were assessed using the International Index of Erectile Function score (IIEF-5) while degree of erection was assessed by the Erection Hardness Score (EHS). Two penile duplex tests were done for each candidate two weeks apart. RESULTS: None of the sample population achieved a normal clinical response (EHS >2) to 10 ug PGE1. In contrast, 60 controls (60%) had a normal response (EHS >2) to 10 ug PGE1. This difference in response between the sample and control populations to 10 ug PGE1 was of high statistical significance 11 (p <0.001). In contrast, 54 (60%) out of the 90 cases had normal clinical response (EHS >2) to 0.25cc Trimix (everywhere). Interestingly, 96 controls (96%) demonstrated normal response (EHS >2) to 0.25cc Trimix. This difference in response between the sample and control populations to 0.25 cc Trimix was also of high statistical significance (p <0.001). CONCLUSIONS: Our study demonstrated a statistically significant association between the response to Trimix over PGE1 and peak systolic velocity (PSV) and end diastolic velocity (EDV). Thus, we conclude that 0.25 cc Trimix is more sensitive than 20 ug PGE1 in diagnosing ED for impotent patients and also provides a more potent response.

Longitudinal Characterization of Autoantibodies to the Thyrotropin Receptor (TRAb) During Alemtuzumab Therapy: Evidence that TRAb May Precede Thyroid Dysfunction by Many Years.

BACKGROUND: Thyroid autoimmunity, especially Graves' disease or hypothyroidism with positive autoantibodies (TRAb) to the thyrotropin receptor (TSHR), occurs in 30-40% of patients with relapsing multiple sclerosis following treatment with alemtuzumab (ALTZ). ALTZ therapy therefore provides a unique opportunity to study the evolution of TRAb prior to clinical presentation. TRAb can stimulate (TSAb), block (TBAb), or not affect ("neutral") the TSHR function, causing hyperthyroidism, hypothyroidism, or euthyroidism, respectively. METHODS: A longitudinal retrospective analysis was conducted of TRAb bioactivity over a period of nine years in 45 multiple sclerosis patients receiving ALTZ using available stored serum. Of these 45 patients, 31 developed thyroid dysfunction (TD) and 14 remained euthyroid despite being followed for a minimum of five years (NO-TD). The presence of TRAb was evaluated at standardized time points: (i) before ALTZ, (ii) latest time available following ALTZ and before TD onset, and (iii) following ALTZ during/after TD onset. Serum TRAb were detected by published in-house assays (ihTRAb): flow cytometry detecting any TSHR-binding TRAb, and luciferase bioassays detecting TSAb/TBAb bioactivity. Purified immunoglobulin G was used to verify TSAb/TBAb in selected hypothyroid cases. Standard clinical automated measurements of TRAb, antithyroid peroxidase autoantibodies (TPOAb), thyrotropin, free thyroxine, and free triiodothyronine were also collected. RESULTS: Before ALTZ, combined ihTRAb (positive with flow cytometry and/or luciferase bioassay) but not automated TRAb were present in 5/16 (31.2%) TD versus 0/14 (0%) NO-TD (p = 0.017). Detectable ihTRAb preceded TD development in 9/28 (32.1%) and by a median of 1.2 years (range 28 days-7.3 years). Combination testing of ihTRAb and TPOAb at baseline predicted 20% of subsequent cases of hyperthyroidism and 83% of hypothyroidism. CONCLUSIONS: Evidence is presented that TRAb measured with custom-made assays can be detected prior to any change in thyroid function in up to a third of cases of ALTZ-related TD. Furthermore, the presence of ihTRAb prior to ALTZ treatment was strongly predictive of subsequent TD. The findings suggest that a period of affinity maturation of TRAb may precede clinical disease onset in some cases. Combined testing of TPOAb and ihTRAb may increase the ability to predict those who will develop TD following ALTZ.

Alemtuzumab-Induced Thyroid Dysfunction Exhibits Distinctive Clinical and Immunological Features.

Context: Alemtuzumab, a highly effective treatment for multiple sclerosis (MS), predisposes to Graves disease (GD), with a reportedly indolent course. Objective: To determine the type, frequency, and course of thyroid dysfunction (TD) in a cohort of alemtuzumab-treated patients with MS in the United Kingdom. Design: Case records of alemtuzumab-treated patients who developed TD were reviewed. Results: A total of 41.1% (102 out of 248; 80 female and 22 male) of patients developed TD, principally GD (71.6%). Median onset was 17 months (range 2 to 107) following the last dose, with the majority (89%) within 3 years. Follow-up data (range 6 to 251 months) were available in 71 case subjects, of whom 52 (73.2%) developed GD: 10 of these (19.2%) had fluctuating TD. All 52 patients with GD commenced antithyroid drugs (ATDs): 3 required radioiodine (RAI) due to ATD side effects, and drug therapy is ongoing in 2; of those who completed a course, 16 are in remission, 1 developed spontaneous hypothyroidism, and 30 (64%) required definitive or long-term treatment (RAI, n = 17; thyroidectomy, n = 5; and long-term ATDs, n = 8). Three cases of thyroiditis and 16 cases of hypothyroidism were documented: 5 with antithyroid peroxidase antibody positivity only, 10 with positive TSH receptor antibody (TRAb), and 1 of uncertain etiology. Bioassay confirmed both stimulating and blocking TRAb in a subset of fluctuating GD cases. Conclusions: Contrary to published literature, we recorded frequent occurrence of GD that required definitive or prolonged ATD treatment. Furthermore, fluctuating thyroid status in GD and unexpectedly high frequency of TRAb-positive hypothyroidism suggested changing activity of TRAb in this clinical context; we have documented the existence of both blocking and stimulating TRAb in these patients.

Delayed surgical repair of penile fracture under local anesthesia.

INTRODUCTION: Penile fracture is a traumatic rupture of the tunica albuginea because of blunt injury of an erect penis. AIM: To assess the efficacy of a simple delayed surgical repair of penile fracture after a conservative treatment under local anesthesia in patients presented after 24 hours. METHODS: Twenty-four patients with penile fracture presented after 24 hours were subjected to history taking, clinical examination, urine analysis, and penile ultrasound. They underwent conservative treatment for 7-12 days, and then a surgical repair under local anesthesia was carried out. MAIN OUTCOME MEASURES: A follow-up for 6 months for sexual activity and any associated complaints in addition to local examination. RESULTS: All cases were presented with unilateral single tear, and the main cause of penile fracture was sexual intercourse. No intraoperative or postoperative complications were encountered. They regained their sexual activity 4-6 weeks after the repair. One case developed a mild penile deviation that did not interfere with sexual relation after the 6-month follow-up. CONCLUSION: Surgical repair of penile fracture after a conservative treatment is an effective method for patients with delayed presentation devoid of urethral involvement.

Penile fracture: surgical repair and late effects on erectile function.

INTRODUCTION: Penile fracture is described as a traumatic rupture of the tunica albuginea because of blunt injury of an erect penis. AIM: To assess the etiology, treatment maneuvers, and late effects of penile fractures treated by surgical repair. METHODS: Thirty-three patients diagnosed provisionally as having fractured penises. Thirty patients were managed by immediate surgical repair and three by delayed repair. MAIN OUTCOME MEASURES: International Index of Erectile Function-5 for married cases and Single-question Self-report of Erectile Dysfunction questionnaires and recording complications after 2, 3, and 6 months. RESULTS: The most common cause of fracture penis is self-inflicted acute bending (54.5%). The tear was visualized by ultrasound in 20/30 patients (66.7%) mostly on the right proximal third of the penis. All tears were unilateral with mean length 2.0 +/- 0.9 cm (range 0.5-4 cm). All patients who completed their follow-up after 6 months (N = 24) were able to achieve an adequate erection except two married cases who felt mild erectile dysfunction. Penile nodules were the most common postoperative complication (41.7%) after 6 months' follow-up. Patients treated with immediate or delayed repair had comparable complications. CONCLUSIONS: Fracture penis is not uncommon as an emergency that must be repaired either immediately or delayed. Clinical diagnosis is more predictive than ultrasound in diagnosis and determining the site of the tear. Ultrasound may be of value in patients where there is clinical doubt.