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Introduction: Although oral phosphodiesterase 5 inhibitors represent a first choice and long-term option for about half of all patients with erectile dysfunction (ED), self-injection therapy with vasoactive drugs remains a viable alternative for all those who are not reacting or cannot tolerate oral drug therapy. This current injection therapy has an interesting history beginning in 1982., Objectives: To provide a comprehensive history of self-injection therapy from the very beginnings in 1982 by contemporary witnesses and some members of the International Society for Sexual Medicine's History Committee, a complete history of injection therapy is prepared from eyewitness accounts and review of the published literature on the subject, as well as an update of the current status of self-injection therapy., Methods: Published data on injection therapy, as a diagnostic and therapeutic tool for ED, were reviewed thoroughly by PubMed and Medline research from 1982 until June 2023. Early pioneers and witnesses added firsthand details to this historical review. Therapeutic reports of injection therapy were reviewed, and results of side effects and complications were thoroughly reviewed., Results: The pioneers of the first hours were Ronal Virag (1982) for papaverine, Giles Brindley (1983) for cavernosal alpha-blockade (phentolamine and phenoxybenzamine), Adrian Zorgniotti (1985) for papaverine/phentolamine, and Ganesan Adaikan and N. Ishii (1986) for prostaglandin E1. Moxisylyte (thymoxamine) was originally marketed but later withdrawn. The most common side effect is priapism, with the greatest risk of this from papaverine, which has modified its use for therapy. Currently, prostaglandin E1 and trimixes continue to be the agents of choice for diagnostic and therapeutic use in ED. A recent agent is a mixture of a vasoactive intestinal polypeptide (aviptadil) and phentolamine., Conclusions: After 40 years, self-injection therapy represents the medication with the highest efficacy and reliability rates and remains a viable option for many couples with ED. The history of this therapy is rich., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Adrenaline auto-injectors are the first line treatment for anaphylaxis in the community setting. Both anaphylaxis and auto-injector carriage are increasing in prevalence. Adrenaline auto-injector injuries are common and most often involve the hand or digits. Such injuries carry a risk of ischemic necrosis due to profound vasoconstriction, especially if there is undying vascular pathology such as Raynaud's disease. The effects can be readily reversed with local infiltration of phentolamine. A survey was circulated to 40 clinicians working in the emergency and hand surgery departments of a major urban center. Knowledge of adrenaline duration of action and its reversal (agent, dose and location in the hospital) was assessed. All clinicians working within the two departments were eligible for participation. Only 25% of clinicians surveyed were aware of the duration of action of adrenaline. Half were aware of the correct reversal agent and only 20% knew the correct dose. Only one person was aware of phentolamine's location within the hospital. There is relatively poor clinician knowledge surrounding adrenaline reversal and a lack of easily accessible information available about dosing and drug location within the hospital. Given the time dependent nature of adrenaline auto-injector injuries Emergency Departments should consider stocking phentolamine in an emergency drugs fridge within the department along with a dosing guide. This is likely to greatly reduce time from presentation to treatment and thus the chances of digital ischemia progressing to necrosis., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: Dim light vision disturbances (DLD) comprise a wide range of symptoms affecting the quality of vision at low illumination including glare, halos, and starbursts. This exploratory study investigated 1.0% phentolamine mesylate ophthalmic solution (PMOS) as a treatment to improve vision and image quality for patients with DLD., Methods: In this placebo-controlled, randomized, double-masked clinical trial, 24 adult patients with severe DLD were randomized in a 2:1 ratio to receive either one dose of PMOS or placebo. Subjects were eligible if they reported experiencing severe night vision difficulty that was not eliminated by distance spectacle correction and scored ≥0.3 log units below the normal range of contrast sensitivity assessed under mesopic conditions with glare at ≥2 spatial frequencies. Key efficacy outcomes were change from baseline in pupil diameter, contrast sensitivity, and visual acuity. Safety measures including intraocular pressure, conjunctival hyperemia, and systemic effects were also assessed., Results: Eight subjects were randomized to placebo (63% female; mean age 47 years) and 16 were randomized to PMOS (75% female; mean age 42 years). Mean (SD) pupil diameter of PMOS-treated subjects decreased significantly - 1.3 mm (0 to - 2.8 mm) with p < 0.0001. Mean contrast sensitivity with glare in PMOS-treated subjects improved significantly post-treatment at spatial frequencies 3, 6, 12, and 18 cycles per degree (p ≤ 0.03). PMOS also demonstrated improvements in the numbers of letters read for mesopic and photopic, high- and low-contrast visual acuity (LCVA). Importantly, a statistically greater proportion of PMOS-treated eyes registered mesopic LCVA 5 letter (69% vs. 31%, p = 0.029) and 10 letter (34% vs. 6%, p = 0.04) improvement, with a trend at 15 letters (19% vs. 0%, p = 0.16). PMOS was well tolerated with the only reported side effect being a mild increase in conjunctival hyperemia., Conclusion: PMOS was well tolerated and effectively reduced pupil size with improvements in contrast sensitivity and visual acuity in adults with severe DLD. Future Phase 3 studies should be conducted to further evaluate its potential to treat DLD., Trial Registration: The trial registration number is NCT04004507 (02/07/2019). Retrospectively registered., (© 2022. The Author(s).)

Importance: Despite being the most common female sexual health complaint worldwide, current treatment options for hypoactive sexual desire disorder (HSDD) are limited in their safety and effectiveness. The hormone kisspeptin is a key endogenous activator of the reproductive hormonal axis with additional emerging roles in sexual and emotional behavior; however, its effects in women with HSDD are unknown., Objective: To test the hypothesis that kisspeptin enhances sexual and attraction brain processing in women with HSDD., Design, Setting, and Participants: This randomized clinical trial was double-masked and placebo controlled with a 2-way crossover. The trial was conducted in a university research setting in the UK from October 2020 to April 2021. Eligible participants were premenopausal women with HSDD. Functional neuroimaging, psychometric, and hormonal analyses were employed to investigate the effects of kisspeptin administration on brain processing, in response to erotic stimuli (erotic videos) and facial attraction (face images of varying attractiveness). Data were analyzed from May to December 2021., Interventions: A 75-minute intravenous infusion of kisspeptin-54 (1 nmol/kg/h) vs equivalent-rate placebo infusion., Main Outcomes and Measures: Blood oxygen level-dependent responses across the whole brain and regions of interest during kisspeptin vs placebo administration in response to erotic and facial attraction stimuli., Results: Of the 40 participants who were randomized, 32 women completed both kisspeptin and placebo visits, with a mean (SE) age of 29.2 (1.2) years. Kisspeptin administration resulted in modulations in sexual and facial attraction brain processing (deactivation of the left inferior frontal gyrus: Z max, 3.76; P = .01; activation of the right postcentral and supramarginal gyrus: Z max, 3.73; P < .001; deactivation of the right temporoparietal junction: Z max 4.08; P = .02). Furthermore, positive correlations were observed between kisspeptin-enhanced hippocampal activity in response to erotic videos, and baseline distress relating to sexual function (r = 0.469; P = .007). Kisspeptin's enhancement of posterior cingulate cortex activity in response to attractive male faces also correlated with reduced sexual aversion, providing additional functional significance (r = 0.476, P = .005). Kisspeptin was well-tolerated with no reported adverse effects., Conclusions and Relevance: These findings lay the foundations for clinical applications for kisspeptin in women with HSDD., Trial Registration: ISRCTN trial registry identifier: ISRCTN17271094.

Objective: Pediatric patients are facing greater difficulties in radial catheterization for anatomic variation and smaller diameter. This study is to investigate the efficacy of phentolamine accompanied by lidocaine subcutaneously under ultrasound guidance on radial catheterization in pediatric patients., Methods: 66 pediatric patients were enrolled and randomly divided into saline group, phentolamine group, and phentolamine+lidocaine group. Baseline characteristics and surgical types were collected. Relevant solutions were subcutaneously injected, and catheterization was subsequently conducted under ultrasound guidance. Radial artery diameter and depth were measured, the success rate of catheterization and procedure time were calculated, and the complications were evaluated with ultrasonography., Results: No significant differences were observed in age, sex, weight, American Society of Anesthesiologists' classification, systolic blood pressure, diastolic blood pressure, heart rate, hemoglobin, and surgical types among three groups. Subcutaneously, the diameter in phentolamine and phentolamine+lidocaine groups increased significantly compared with the saline group. Moreover, the diameter also increased significantly after injection compared with that before injection both in the phentolamine and phentolamine+lidocaine groups. The first-attempt success rates were significantly higher while the procedure times of cannulation were shorter in the phentolamine and phentolamine+lidocaine groups than that in the saline group. Kaplan-Meier analysis showed that the overall procedure time was shorter in the phentolamine and phentolamine+lidocaine groups than the saline group. Overall complications and vasospasm incidence were lower in the phentolamine and phentolamine+lidocaine groups than the saline group., Conclusion: Phentolamine accompanied by lidocaine subcutaneous injection under ultrasound guidance improved the first-attempt success rate and reduced the complication of radial artery catheterization in pediatric patients., Competing Interests: The authors declare that there were no competing interests., (Copyright © 2022 Erliang Kong et al.)

Wide awake local anesthetic no tourniquet (WALANT) is gaining popularity amongst hand surgeons. Digital adrenaline use has been shown to be safe in multiple studies and the misconception forbidding it is receding. Phentolamine has been shown to safely reverse the effects of adrenaline should the feared complication of digital ischemia occur. A survey was circulated to 40 specialist practitioners who regularly perform hand procedures at a major tertiary plastic and hand surgery unit. Knowledge and understanding of WALANT, onset and duration of adrenaline effects and reversal was assessed. Whilst the majority of respondents (80%) recognized digital adrenaline use as safe, only 65% were aware of the delay until adrenaline takes full effect. Similarly, only 25% of respondents were aware of the duration of effect of adrenaline. Half of respondents were aware that phentolamine is the established reversal agent for adrenaline with only 20% knowing the correct dose. Given the lack of clinician knowledge surrounding adrenaline and its reversal, we feel that to safely undertake WALANT surgery at our Unit a WALANT protocol must be implemented. Drawing on the successes in the airline industry, a variety of safety frameworks have been established to deliver targeted education for prevention and eventual management of predictable risks. We plan to develop a checklist style protocol targeting the knowledge gaps raised in the survey. This will educate and equip all practitioners working with adrenaline with the knowledge to safely manage complications should they occur. LEVEL OF EVIDENCE: Level 5 (UK Oxford Centre for Evidence based Medicine (CEBM) Levels of Evidence)., (Crown Copyright © 2022. Published by Elsevier Masson SAS. All rights reserved.)

Incomplete functional recovery after peripheral nerve injury (PNI) often results in devastating physical disabilities in human patients. Despite improved progress in surgical and non-surgical approaches, achieving complete functional recovery following PNI remains a challenge. This study demonstrates that phentolamine may hold a significant promise in treating nerve injuries and denervation induced muscle atrophy following PNI. In a sciatic nerve crush injury mouse model, we found that phentolamine treatment enhanced motor and functional recovery, protected axon myelination, and attenuated injury-induced muscle atrophy in mice at 14 days post-injury (dpi) compared to saline treatment. In the soleus of phentolamine treated animals, we observed the downregulation of phosphorylated signal transducer and activator of transcription factor 3 (p-STAT3) as well as muscle atrophy-related genes Myogenin, muscle ring finger 1 (MuRF-1), and Forkhead box O proteins (FoxO1, FoxO3). Our results show that both nerve and muscle recovery are integral components of phentolamine treatment-induced global functional recovery in mice at 14 dpi. Moreover, phentolamine treatment improved locomotor functional recovery in the mice after spinal cord crush (SCC) injury. The fact that phentolamine is an FDA approved non-selective alpha-adrenergic blocker, clinically prescribed for oral anesthesia reversal, hypertension, and erectile dysfunction makes this drug a promising candidate for repurposing in restoring behavioral recovery following PNI and SCC injuries, axonal neuropathy, and muscle wasting disorders., (© 2022. The Author(s).)

BACKGROUND Accidental finger-stick injuries have been reported with epinephrine autoinjectors, such as EpiPen and EpiPen Jr, and can result in necrosis and digital ischemia. However, long-term adverse effects are very rare. The treatment for accidental finger-stick injuries is controversial and includes intra-arterial injections of vasodilating agents, topical vasodilators, and supportive management as needed. CASE REPORT Here, we report a case of a 26-year-old pharmacist who injected herself accidentally with an EpiPen on the tip of her index finger. Warm water and nitroglycerine gel did not alleviate her symptoms. After three hours, phentolamine was injected around the necrotic area, and the skin normalized. CONCLUSIONS All health professionals should be trained in how to handle epinephrine autoinjectors safely. Phentolamine may be efficacious in treating accidental finger-stick injuries from epinephrine autoinjectors.

Objective: To explore the effect of phenolamine on the outcome and prognosis of patients with myocardial injury due to sepsis. Methods: From January 2015 to December 2017, 62 septic patients with myocardial injury were randomly divided into study group ( n= 32) and control group ( n= 30). Two groups were given conventional treatment, while the study group was treated with phentolamine. The NT-pro brain natriuretic pepitide (NT-proBNP), cardiac troponin I (cTnI), lactate dehydrogenase (LDH), creatine kinase isoenzymes (CK-MB) and tumor necrosis factor (TNF)-α, high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-1β, IL-6 were detected at 0,12, 24, 48, 72 h and 7 d after hospitalization. And left ventricular ejection fraction (LVEF), e', E and A in each time period were observed. The 28 d survival rate and length of ICU stay were observed in both groups. The data were compared with single sample t test between the two groups. Results: After 12, 24, 48, 72 h and 7 d, NT-proBNP, cTnI, LDH, CK-MB, TNF-α, hs-CRP, IL-1β, IL-6 in the study group were all significantly lower than those in the control group (all P< 0.05). The cardiac function indexes of LVEF, E/A and E/e' in the study group were all significantly improved when compared with those in the control group (all P< 0.05). The length of ICU stay and 28-day mortality in the study group were significantly lower than those in the control group ((9.8±3.6) d vs (13.0±4.1) d, t= 3.152, P= 0.004; 21.9% vs 36.7%, χ(2)=5.078, P= 0.021). Conclusion: Combined application of phentolamine can significantly improve the outcome of sepsis patients with myocardial injury and improve the survival rate.

Objective: To investigate the effect of magnesium sulfate combined with phentolamine and nifedipine for the treatment of gestational hypertension and on the levels of serum LIF and Apelin., Study Design: An experimental study., Place and Duration of Study: Obstetrics and Gynecology Clinics, The Affiliated Hospital North China University of Science and Technology, China, from September 2016 to February 2018., Methodology: One hundred and sixty patients with gestational hypertension were randomly divided into a control group and an observation group, 80 patients in each group. Control group was given magnesium sulfate alone, while observation group was added with phentolamine and nifedipine on the basis of the treatment in control group. Curative effects, pregnancy outcomes, and levels of serum LIF and Apelin were compared., Results: The total effective rate of treatment in the observation group was higher than that in the control group (p=0.005). After treatment, level of serum LIF in the observation group was higher than that in the control group (p<0.001), and level of serum Apelin in the observation group was lower than that in the control group (p<0.001). Incidence of premature birth, cesarean section and neonatal asphyxia in the observation group were all lower than those in the control group (p=0.005, p<0.001 and p=0.005, respectively), while there was no significant difference in the incidence of neonatal death between the two groups (p=0.316)., Conclusion: Magnesium sulfate combined with phentolamine and nifedipine has a better therapeutic effect on gestational hypertension, which can effectively regulate the levels of serum LIF and Apelin and improve pregnancy outcomes.

The use of low-dose epinephrine in hand surgery has made it possible to perform a wide range of surgical procedures in the office setting. Low-dose epinephrine use is safe, and its vasoconstrictive effects are reversible with phentolamine. In this report, we present late-onset finger ischemia beginning 3 hours after an ipsilateral carpal tunnel and A1 pulley release of the middle finger anesthetized with local anesthetic and low-dose epinephrine (1:100,000). Finger ischemia lasted 14 hours until rescued with phentolamine injection., (Copyright © 2017 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Background: Phentolamine mesylate (PM) is widely used to reverse local anesthesia after dental procedures. Limited knowledge is available regarding effectiveness and safety in routine dental practice., Methods: The authors conducted 2 national, prospective, noninterventional, postauthorization effectiveness studies (OraVerse Post-Authorization Efficacy Study [ORAPAES] controlled, OraVerse Non-Interventional Study [ORANIS] uncontrolled) in patients receiving a local anesthetic as part of their dental treatment. They investigated time to recovery of normal sensation and function and the frequency of adverse events (AEs). The authors used Kaplan-Meier methods to analyze times to recovery; in ORAPAES, they used hazard ratios based on Cox models using the control group as a reference., Results: In ORAPAES (n = 856), PM reduced the time to recovery of normal sensation and function with a difference in the median time of 70 and 79 minutes, respectively, with similar results observed in ORANIS (n = 445). In ORAPAES, patients in the PM group had, at any time point, a 2.77-fold higher chance of recovery to normal sensation (hazard ratio, 2.77; 95% confidence interval [CI], 2.35-3.26; P < .001) and for normal function 2.94-fold higher chance of recovery to normal sensation (95% CI, 2.49-3.47; P < .001) than in the control group. The observed incidence of AEs with PM treatment was 8.4% in ORAPAES (95% CI, 6.2-10.9) and 9.7% (95% CI, 7.1-12.7) in ORANIS. No serious AEs occurred., Conclusions: PM substantially reduced the time to recovery of normal sensation and function after local anesthesia in routine dental treatment. The results confirm the effectiveness, safety, and tolerability of PM used in patients with routine dental conditions in Germany, and that PM augments the safety of dental treatments., Practical Implications: The authors determined that PM is well suited to reverse local anesthesia after routine dental procedures., (Copyright © 2017 American Dental Association. Published by Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to evaluate, using a randomized, double-blind methodology: (1) the safety of phentolamine mesylate (Oraverse) in accelerating the recovery of soft tissue anesthesia following the injection of two percent lidocaine plus 1:100,000 epinephrine in two- to five-year-olds; and (2) efficacy in four- to five-year-olds only., Methods: One hundred fifty pediatric dental patients underwent routine dental restorative procedures with two percent lidocaine plus 1:100,000 epinephrine with doses based on body weight. Phentolamine mesylate or a sham injection (two to one ratio) was then administered. Subjects were monitored for safety and, in four- to five-year-olds, for efficacy during the two-hour evaluation period., Results: There were no significant differences in adverse events between the phentolamine and sham injections. Compared to sham, phentolamine was not associated with nerve injury, increased analgesic use, or abnormalities of the oral cavity. Phentolamine was associated with transient decreased blood pressure in some children. In four- and five-year-olds, phentolamine induced more rapid recovery of lip anesthesia by 48 minutes (P<0.0001)., Conclusions: Phentolamine was well tolerated and safe in three- to five-year-olds; in four- to five-year-olds, a statistically significant more rapid recovery of lip sensation compared to sham injections was determined.

It is widely known that the β-adrenergic receptor (AR) blocker (propranolol) inhibits human endothelial cell (EC) angiogenesis in vitro, but how the α-AR antagonist (phentolamine) affects human EC angiogenesis has not yet been studied. Here, we show for the first time that both human dermal microvascular ECs (HDMECs) and human brain microvascular ECs (HBMECs) express α-ARs. Moreover, our results indicate that phentolamine inhibits the proliferation, migration, and tubulogenesis of HDMECs and HBMECs. Finally, VEGFR-2 and Ang1/2 expression of HDMECs was suppressed by phentolamine. Together, these results indicate that phentolamine impairs several critical events of neovascularization, and α-ARs, as well as the VEGF/VEGFR-2 and Ang/Tie-2 signaling pathways, may be involved in these processes. Our results suggest a novel therapeutic strategy for the use of α-blockers in the treatment of human angiogenesis-dependent diseases.

Though uncommon, medical emergencies in the dental office are harrowing occurrences that can be the result of adverse drug reactions. Pharmacological antagonists have been developed for administration as reversal agents in emergency situations in which patients may have an untoward effect, typically caused by too much medication. Dental practitioners should be familiar with these agents to keep patients safe and help mitigate drug-induced medical emergencies. This article reviews the pharmacokinetic and pharmacodynamic principles of pharmacological antagonists; it emphasizes six specific reversal agents as they relate to the clinical practice of dentistry: naloxone, flumazenil, epinephrine, diphenhydramine, phentolamine, and atropine. Outside of emergency situations, the pharmacological antagonist phentolamine has been developed to reverse the effects of the vasoconstrictor in dental local anesthesia preparations when the effects of the agonist medication are no longer required. Such newer reversal agents are being considered for more routine use once the dental procedure is complete. This article is intended to assist dental practitioners who are familiar with pharmacological antagonists to be better able to help mitigate drug-induced medical emergencies should they occur.

Purpose: Pheochromocytomas (PHEOS) are rare catecholamine-secreting adrenal tumours requiring surgical resection. Preoperative alpha-adrenergic receptor blockade to prevent intraoperative hypertension has traditionally been achieved with phenoxybenzamine. Due to changes in the availability of phenoxybenzamine in Canada, alternate therapies are needed for patients. We report our first experience using metyrosine, a tyrosine hydroxylase inhibitor, for preoperative management in a symptomatic patient with a unilateral PHEO., Clinical Features: A 50-yr-old male was referred to our centre with a history of symptoms suggestive of a catecholamine-secreting PHEO, including tachycardia, diaphoresis, nervousness, and tremor. Computerized tomography revealed a right adrenal mass, and additional positive imaging and elevated urine epinephrine levels supported a diagnosis of PHEO. The patient was admitted to hospital five days prior to surgery, and metyrosine therapy was initiated and titrated to 4 g daily over four days. Despite adequate blood pressure (BP) control leading up to the resection, the initial BP reading in the operating room was 191/106 mmHg, but it subsequently declined and was well controlled during induction (100-110 mmHg systolic BP). Significant hypertension (up to 201/110 mmHg) developed upon tumour manipulation and resolved with phentolamine administration and surgical isolation of the tumour. The patient's BP remained stable throughout the residual part of the procedure and in the recovery room and step-down unit., Conclusion: In the case of this patient's PHEO, the use of metyrosine was unsatisfactory in achieving sufficient inhibition of catecholamine synthesis as evidenced by significant intraoperative hypertension. Metyrosine could have a role in preoperative management of these patients, but it may not be optimal as monotherapy for some patients with actively secreting tumours.

Radical prostatectomy (RP) and radiotherapy (RT) are highly effective in improving prostate cancer survival. However, both have a detrimental effect on erectile function (EF). Penile rehabilitation consists of understanding the mechanisms that cause erectile dysfunction (ED) and utilizing pharmacologic agents, devices or interventions to promote male sexual function. For the past decade, many researchers have pursued to define effective treatment modalities to improve ED after prostate cancer treatment. Despite the understanding of the mechanisms and well-established rationale for postprostate treatment penile rehabilitation, there is still no consensus regarding effective rehabilitation programs. This article reviews a contemporary series of trials that assess penile rehabilitation and explore treatment modalities that might play a role in the future. Published data and trials related to penile rehabilitation after RP and RT were reviewed and presented. Although recent trials have shown that most therapies are well-tolerated and aid in some degree on EF recovery, we currently do not have tangible evidence to recommend an irrefutable penile rehabilitation algorithm. However, advancements in research and technology will ultimately create and refine management options for penile rehabilitation.

Background: Knowing that patients desire reduced duration of local anesthesia, the authors performed a meta-analysis to evaluate the efficacy of phentolamine mesylate (PM) in reducing anesthesia duration and the occurrence of adverse effects., Types of Studies Reviewed: The authors searched studies in 4 electronic databases up to December 18, 2014. For each study, the methodological quality was assessed according to the Cochrane Collaboration's tool for assessing risk of bias. Randomized controlled trials (RCTs) that used PM met the inclusion criteria., Results: Six RCTs met the inclusion criteria and were used to carry out a meta-analysis of the effectiveness of PM and a qualitative analysis of its adverse effects. The use of PM was more effective in reversing the anesthetic effect on the lower lip and tongue than was applying a placebo. Adverse effects reported in the studies were not statistically significant, the most frequent being headache, pain during injection, and postprocedure pain., Conclusions and Practical Implications: Based on limited evidence, PM is effective in reducing the persistence of anesthesia duration on the lower lip and tongue, with infrequent adverse effects of little clinical significance., (Copyright © 2015 American Dental Association. Published by Elsevier Inc. All rights reserved.)

Introduction: Neonates with severe pulmonary valve stenosis tend to remain oxygen dependent, despite resolution of the transpulmonary gradient. Alpha 2 blockers – phentolamine – and angiotensin-converting enzyme inhibitors – captopril – were reported to improve oxygen saturation., Objective: To describe the role of phentolamine and captopril in the treatment of these patients., Methods: In a retrospective cohort study, 28 neonates with severe pulmonary valve stenosis underwent balloon valvuloplasty. Among them, 20 remained oxygen or prostaglandin dependent after intervention, and were treated with phentolamine or captopril. Oxygen saturation was monitored before and after intervention and following treatment with these medications. Mean duration of hospitalisation was recorded., Results: Mean age and weight were 25.2 days and 3.1 kg, respectively. Before balloon dilation, 18/20 (90%) neonates were on prostaglandin, whereas after the procedure only 6/18 patients required it. All 20 patients required oxygen after the procedure, and nine patients (45%) were started on phentolamine. Among them, one patient with severe infundibular stenosis did not respond favourably, and 11 patients (55%) were started on captopril. After starting phentolamine or captopril treatment, prostaglandin could be discontinued after a mean time of 15.86 hours. Within <2 days, there was an increase in mean oxygen saturation from 76.6 to 93.0%., Conclusion: Phentolamine and captopril seem to have therapeutic roles in neonates with severe pulmonary valve stenosis who remain oxygen dependent after balloon dilation. Both drugs led to vasodilation of the pulmonary and systemic vascularisation and facilitated inflow to the right ventricle. Right-to-left shunt across a patent foramen ovale or atrial septal defect decreased and saturation improved, leading to a significant reduction in the length of hospitalisation.

Background: Drug repurposing of phentolamine, an α-adrenoceptor antagonist, as an anticancer agent has been studied in human castration-resistant prostate cancer (CRPC)., Methods: Cell proliferation was examined by sulforhodamine B and CFSE staining assays. Cell cycle progression and mitochondrial membrane potential (ΔΨm) were detected by flow cytometric analysis. Protein expression was detected by Western blotting. Effect on tubulin/microtubule was determined using confocal immunofluorescence microscopic examination, microtubule assembly detection, tubulin turbidity assay, and binding assay. Several assessments were used to characterize apoptotic signaling pathways and combinatory effect., Results: Phentolamine induced anti-proliferative effect in PC-3 and DU-145, two CRPC cell lines, and P-glycoprotein (P-gp) overexpressing cells. This effect was not significantly reduced in paclitaxel-resistant cells. Rhodamine 123 efflux assay showed that phentolamine was not a P-gp substrate. Phentolamine induced mitotic arrest of the cell cycle and formation of hyperdiploid cells, followed by an increase of apoptosis. Mitotic arrest was confirmed by cyclin B1 up-regulation, Cdk1 activation, and a dramatic increase of mitotic protein phosphorylation. Both in vitro and cellular identification demonstrated that phentolamine, similar to paclitaxel, induced tubulin polymerization and formation of multiple nuclei. Besides, it did not compete with paclitaxel binding on tubulin. Phentolamine induced the phosphorylation and degradation of Bcl-2 and Bcl-xL, two anti-apoptotic Bcl-2 family members, and the loss of ΔΨm indicating the induction of mitochondrial damage. It ultimately induced the activation of caspase-9, -8, and -3 and apoptotic cell death. Moreover, combination treatment with phentolamine and paclitaxel caused a synergistic apoptosis., Conclusions: The data suggest that phentolamine is a potential anticancer agent. In contrast to a wide variety of microtubule disrupting agents, phentolamine induces microtubule assembly, leading to mitotic arrest of the cell cycle which "in turn" induces subsequent mitochondrial damage and activation of related apoptotic signaling pathways in CRPC cells. Furthermore, combination between phentolamine and paclitaxel induces a synergistic apoptotic cell death. Phentolamine has a simple chemical structure and is not a P-gp substrate. Optimization of phentolamine structure may also be a potential approach for further development., (© 2015 Wiley Periodicals, Inc.)

This study assessed the roles of chronic stress (CS) in the stimulation of the sympathetic nervous system and explored the underlying mechanisms of periodontitis. Using an animal model of periodontitis and CS, the expression of tyrosine hydroxylase (TH) and the protein levels of the α1-adrenergic receptor (α1-AR) and β2-adrenergic receptor (β2-AR) were assessed. Furthermore, human periodontal ligament fibroblasts (HPDLFs) were stimulated with lipopolysaccharide (LPS) to mimic the process of inflammation. The proliferation of the HPDLFs and the expression of α1-AR and β2-AR were assessed. The inflammatory-related cytokines interleukin (IL)-1β, IL-6 and IL-8 were detected after pretreatment with the α1/β2-AR blockers phentolamine/propranolol, both in vitro and in vivo. Results show that periodontitis under CS conditions enhanced the expression of TH, α1-AR and β2-AR. Phentolamine significantly reduced the inflammatory cytokine levels. Furthermore, we observed a marked decrease in HPDLF proliferation and the increased expression of α1-ARfollowing LPS pretreatment. Pretreatment with phentolamine dramatically ameliorated LPS-inhibited cell proliferation. In addition, the blocking of α1-ARsignaling also hindered the upregulation of the inflammatory-related cytokines IL-1β, IL-6 and IL-8. These results suggest that CS can significantly enhance the pathological progression of periodontitis by an α1-adrenergic signaling-mediated inflammatory response. We have identified a potential therapeutic target for the treatment of periodontal disease, particularly in those patients suffering from concurrent CS.

Objective: To study the effect of urapidil combined with phentolamine in the management of hypertension during extracorporeal circulation., Methods: Ninety patients undergoing aortic and mitral valve replacement were randomly divided into 3 equal groups to receive treatment with phentolamine (group A), urapidil (group B), or both (group C) during extracorporeal circulation. The mean arterial pressure (MAP) before and after drug administration, time interval of two administrations, spontaneous recovery of heart beat after aorta unclamping, ventricular arrhythmia, changes of ST-segment 1 min after the recovery of heart beat, ante-parallel cycle time, aorta clamping time, post-parallel cycle time, dopamine dose after cardiac resuscitation, and perioperative changes of plasma TNF-α and IL-6 levels were recorded., Results: There was no significant difference in MAP between the 3 groups before or after hypotensive drug administration (P>0.05). The time interval of two hypotensive drug administrations was longer in group C than in groups A and B (P<0.05). The incidence of spontaneous recovery of heart beat after aorta unclamping, incidence of ventricular arrhythmia, changes of ST-segment 1 min after the recovery of heart beat, ante-parallel cycle time, aorta clamping time, and post-parallel cycle time were all comparable between the 3 groups. The dose of dopamine administered after cardiac resuscitation was significantly larger in group B than in groups A or group C (P<0.05). The plasma levels of TNF-α and IL-6 were significantly increased after CPB and after the operation in all the groups, but were lowed in group C than in groups A and B at the end of CPB and at 2 h and 12 after the operation., Conclusions: Urapidil combined with phentolamine can control hypertension during extracorporeal circulation without causing hypotension.

There has been little data regarding the role of intracavernosal injection (ICI) treatment, its discontinuation rate and the reasons of withdrawal in patients with erectile dysfunction (ED) in the era of phosphodiesterase type 5 (PDE5) inhibitors. The aim of this study was to investigate the rate of withdrawal and its associated reasons in patients undergoing ICI therapy. Patients who were prescribed with ICI treatment two times or more were included since the introduction of sildenafil in Korea in 1999. Telephone surveys were performed to evaluate intercourse rates, withdrawal rates and their associated reasons, adverse events and the patients' satisfaction with their sex lives after the ICI treatments. Two hundred and ninety-four men were contacted by telephone. The mean age was 61.8 ± 7.9 years with a follow-up duration of 25.6 ± 32.1 months. At the last follow-up, 79.9% had discontinued the treatment. Most patients had previously failed PDE5 inhibitor treatment prior to the ICI therapy, and more than half had two or more risk factors of ED. Adequate penile rigidity after ICI therapy was restored in 60.2% of patients. The reasons for discontinuation of ICI were poor response (43.1%), inconvenience of use (18.3%), switch to other treatments (10.7%), loss of libido (6.7%), adverse events (5.5%) and return of spontaneous erection (2.8%). Pain was the most common adverse event in the withdrawal group, whereas prolonged erection was most common in the continuing group. Following ICI treatment, PDE5 inhibitors were the most common therapeutic option (63.1%). The overall satisfaction rate regarding sex life was significantly high in the treatment-continuing group. In conclusion, patients on ICI treatment had severe ED and high withdrawal rates in the era of PDE5 inhibitors. The most common reason for treatment discontinuation was poor response. Before initiating ICI treatments, sufficient counselling is necessary., (© 2013 American Society of Andrology and European Academy of Andrology.)

This study sought to identify and quantify complications with local anesthetic administration and reversal on consecutive patients seen for comprehensive dental care in a school-based, portable dental clinic, and includes data on the patients seen by the participating portable dental providers. In 923 dental visits where local anesthetic was administered, a standardized form was used to gain further information and identify any complications; this was accompanied by a questionnaire for the student's teacher, in order to quantify the student's distraction and disruption ratings following the dental visit. After statistical analysis of the 923 consecutive cases, the overall complication rate was 5.3%. All of the complications were considered to be mild or moderate, and there were no severe event reports. The complications encountered most frequently (n = 49) were associated with self-inflicted soft tissue injury. The results of this study indicate that comprehensive care with local anesthesia delivered by a school-based portable dental clinic has a low risk of complications. Whereas safe administration of dental care is achievable with or without phentolamine mesylate as a local anesthetic reversal agent, its use was determined to improve safety outcomes. Three factors appeared to directly increase the incidence of complications: the administration of an inferior alveolar nerve block, attention deficit disorder, and obesity. Teacher evaluations demonstrated that children receiving care by a portable dental team were able to reorient back to classwork and were not disruptive to classmates.

A key clinical outcome for peripheral vascular disease (PVD) in patients is a progressive decay in skeletal muscle performance and its ability to resist fatigue with elevated metabolic demand. We have demonstrated that PVD in obese Zucker rats (OZR) is partially due to increased perfusion distribution heterogeneity at successive microvascular bifurcations within skeletal muscle. As this increased heterogeneity (γ) is longitudinally present in the network, its cumulative impact is a more heterogeneous distribution of perfusion between terminal arterioles than normal, causing greater regional tissue ischemia. To minimize this negative outcome, a likely compensatory mechanism against an increased γ should be an increased temporal switching at arteriolar bifurcations to minimize downstream perfusion deficits. Using in situ cremaster muscle, we determined that temporal activity (the cumulative sum of absolute differences between successive values of γ, taken every 20 s) was lower in OZR than in control animals, and this difference was present in both proximal (1A-2A) and distal (3A-4A) arteriolar bifurcations. Although adrenoreceptor blockade (phentolamine) improved temporal activity in 1A-2A arteriolar bifurcations in OZR, this was without impact in the distal microcirculation, where only interventions against oxidant stress (Tempol) and thromboxane A(2) activity (SQ-29548) were effective. Analysis of the attractor for γ indicated that it was not only elevated in OZR but also exhibited severe reductions in range, suggesting that the ability of the microcirculation to respond to any challenge is highly restricted and may represent the major contributor to the manifestation of poor muscle performance at this age in OZR.

Objective: To re-evaluate the effects of different "cocktail therapy" to prevent from phlebitis induced by Chansu injection., Method: Patients treated with Chansu injection were divided randomLy into 4 groups with 90 per group, control group, phentolaminum group, the magnesium sulfate group-phentolaminum group, and anisodamine-phentolaminum group. Patients in the control group only received the routine nursing treatment, and patients in the various experiment group received different interventions. The comparison was made in the morbidity and the starting time of occurrence of phlebitis, the severity of pain, duration of pain., Result: The morbidity of phlebitis was 8%, 8%, 6%, respectively. The starting time of phlebitis occurrence was (22 +/- 4), (27 +/- 5), (28 +/- 7) h, respectively. The NRS of pain was (4.75 +/- 1.51), (3.27 +/- 1.02), (2.71 +/- 1.63), respectively. The duration time of pain was (4.25 +/- 1.36), (2.51 +/- 1.05), (2.19 +/- 1.13) d respectively. In control group, the morbidity of phlebitis, the starting time of occurrence of phlebitis, the severity of pain, duration of pain was 30%, (16 +/- 4) h, (6.34 +/- 1.21), (5.47 +/- 1.07) d, respectively. As compared with the control group, a significance difference was found between every group in three test groups and control group respectively (P<0.05)., Conclusion: The morbidity and the starting time of occurrence of phlebitis, the severity of pain, duration of pain was significantly reduced respectively by two different "cocktail therapy".

Bladder pheochromocytoma creates an extremely rare situation (0.06% of all bladder tumours). We came across a case with a complaint of intermittent episodes of haematuria. Cystoscopy revealed a solid, bluish submucosal growth with increased vascularity. Immediately after taking biopsy, the patient developed a sharp headache, chest heaviness and marked rise in blood pressure. The procedure was abandoned. Later, serum and urinary markers for pheochromocytoma were within normal limits. The histopathology report came out to be pheochromocytoma of the bladder. Later, partial cystectomy was carried out under general anaesthesia and histopathology confirmed the same. Thus, a surgeon/urologist should have a high index of suspicion for bladder pheochromocytoma while dealing with such cases if he comes across the characteristic symptoms of sharp headache, hypertension, palpitation, sweating, fainting or blurring of vision immediately after voiding or during the cystoscopic manipulation of tumour or cystoscopic findings of a submucosal supratrigonal vascular tumour with a bluish hue.

Metabolic syndrome (MS) is a combination of medical disorders that increase the risk of developing cardiovascular disease and diabetes. MS is associated with obesity, increased blood pressure, hyperlipidemia, and hyperglycemia. This study was designed to investigate the pharmacological profile of phentolamine, a nonselective α adrenergic receptor antagonist, in the prevention of increased blood pressure in fructose-fed rats. Phentolamine prevented the fructose-induced increase in systolic blood pressure without affecting insulin sensitivity and major metabolic parameters. The levels of plasma noradrenaline and angiotensin II, 2 proposed contributors to the development of fructose-induced elevated blood pressure, were examined. Neither noradrenaline nor angiotensin II levels were affected by phentolamine treatment. Since overproduction of nitric oxide has been shown to lead to an elevation in peroxynitrite, the role of oxidative stress, a proposed mechanism of fructose-induced elevated blood pressure and insulin resistance, was examined by measuring plasma levels of total nitrate/nitrite. Plasma nitrate/nitrite was significantly elevated in all fructose-fed animals, regardless of treatment with phentolamine. Another proposed contributor toward fructose-induced MS is an elevation in uric acid levels. In this experiment, plasma levels of uric acid were found to be increased by dietary fructose and were unaffected by phentolamine treatment.

Spinal cord stimulation (SCS) may alleviate certain forms of neuropathic pain; its mechanisms of action are, however, not fully understood. Previous studies have mainly been focused onto segmental spinal mechanisms, though there is evidence indicating a supraspinal involvement. This study aims to evaluate the relative importance of segmental and supraspinal mechanisms related to the activation of the dorsal columns (DCs). Rats were used to induce the spared nerve injury neuropathy and simultaneously subjected to chronic bilateral DC lesions at the C6-C8 level. Two pairs of miniature electrodes were implanted in each animal, with a monopolar system placed in the dorsal epidural space at a low thoracic level (below lesion) and a bipolar system placed onto the dorsal column nuclei (above lesion). Stimulation (50 Hz, 0.2 ms, 2-4V, 5 min) was applied via either type of electrodes, and tests for sensitivity to tactile and thermal stimuli were used to assess its inhibitory effects. Various receptor antagonists {bicuculline (GABA(A)), saclofen (GABA(B)), ketanserine (5HT(2)), methysergide (5HT(1-2)), phentolamine (α-adrenergic), propranolol (β-adrenergic), sulpiride (D(2)/D(3) dopamine) or saline were injected prior to the SCS. Rostral and caudal stimulations produced a comparable inhibition of neuropathic manifestations, and these effects were attenuated by about 50% after DC lesions. Pretreatment with the various receptor antagonists differentially influenced the effects of rostral and caudal stimulation. Our findings suggest that both supraspinal and segmental mechanisms are activated by SCS, and that in this model with DC lesions, rostral and caudal stimulations may activate different synaptic circuitries and transmitter systems., (Copyright © 2012 IBRO. All rights reserved.)

A 33-year-old lady accidentally injected norepinephrine into her right thumb while cleaning the first aid box where a spare Epipen for her son was kept. She presented with pain, pallor and swelling to the distal phalanx of the right thumb. After a prompt literature search and discussing the case with the National Poisons Information Service, local injection of 0.15 ml (1.5 mg) of phentolamine in 1 ml of 2% lignocaine was advised. Peripheral perfusion was restored immediately after injection and fully recovery was noted at the review clinic the following day. The presentation of this case in the accident and emergency department prompted phone calls and literature search to define the most appropriate evidence-based management for this situation. The authors conclude that local infiltration of phentolamine is the treatment of choice and this highlighted the need for local treatment protocols.

Neurogenic pulmonary edema (NPE) is a clinical syndrome characterized by the acute onset of pulmonary edema following a significant CNS insult. The cause is believed to be a surge of catecholamines that results in cardiopulmonary dysfunction. Although there are myriad case reports describing CNS events that are associated with this syndrome, few studies have identified specific treatment modalities. We present a case of NPE caused by an intracranial hemorrhage from a ruptured arteriovenous malformation. We uniquely document a rise and fall of serum catecholamine levels correlating with disease activity and a dramatic clinical response to IV phentolamine.

Epinephrine (EPI) contributes to hyperalgesia in inflammatory and stress conditions. EPI signals via adrenoceptors, which are regulated by G protein-coupled receptor kinase 2 (GRK2). We previously reported that GRK2 is decreased in nociceptors during chronic inflammation. Herein, we investigated whether GRK2 modulates EPI-induced mechanical and thermal hyperalgesia by using GRK2(+/-) mice, which express 50% of the GRK2 protein. We demonstrate for the first time that EPI-induced mechanical as well as thermal hyperalgesia is prolonged to approximately 21 days in GRK2(+/-) mice, whereas it lasts only 3 to 4 days in wild-type mice. Using cell- specific GRK2-deficient mice, we further show that a low level of GRK2 in primary sensory neurons is critical for this prolongation of EPI-induced hyperalgesia. Low GRK2 in microglia had only a small effect on EPI-induced hyperalgesia. Low GRK2 in astrocytes did not alter EPI-induced hyperalgesia. EPI-induced hyperalgesia was prolonged similarly in mice with tamoxifen-induced homozygous or heterozygous deletion of GRK2. In terms of EPI signalling pathways, the protein kinase A (PKA) inhibitor H-89 inhibited EPI-induced mechanical hyperalgesia in wild-type mice, whereas H-89 had no effect in mice with low GRK2 in sensory neurons (SNS-GRK2(+/-) mice). Conversely, intraplantar injection of the protein kinase Cε PKCε inhibitor TAT-PKC(εv1-2) inhibited hyperalgesia in sensory neuron specific (SNS)-GRK2(+/-) mice and not in wild-type mice. These results indicate that low GRK2 in primary sensory neurons switches EPI-induced signalling from a protein kinase A-dependent toward a PKCε-dependent pathway that ultimately mediates prolonged EPI-induced hyperalgesia., (Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

This study investigated the pattern of use, dentist evaluation, and patient assessment of OraVerse (OV), a solution of phentolamine mesylate formulated for intraoral submucosal injection and used for the reversal of soft anesthesia after dental procedures. Participants were provided the drug for treatment of up to 10 patients each and agreed to complete a 26-item evaluation questionnaire at the end of the clinical assessment. Data were available from 51 dentists reporting on 390 patients 4 to 90 years of age. A total of 394 dental procedures were performed: 224 (57%) in the mandible and 170 (43%) in the maxilla. Local anesthetics most frequently used were lidocaine/epinephrine (66.4%) and articaine/epinephrine (23.6%). In 81.5% of cases, OV was administered after restorative procedures. This OV dose was given as one-half, one, and two cartridges in 11.8%, 76.7%, and 10.3% of patients, respectively. An adverse reaction at the injection site was reported in 19 patients (4.9%). The median times to return to normal after injection were 60 minutes for lip sensation, 57.5 minutes for tongue sensation, and 60 minutes for oral function. Patients reported reduced duration of oral numbness (92%) and improved dental experiences (84%) after use. A total of 83% of patients said they would recommend the medication to others and 79% said they would opt for OV in the future. Dentists reported that the medication addressed an existing need (86%), met expectations (82%), was a practice differentiator (55%) and a practice builder (45%), and improved scheduling (29%). In this in-practice clinical evaluation, times to return to normal oral sensation and function after OV administration were consistent with those reported in randomized clinical studies. Both patient and dentist satisfaction rates were high.

Complex regional pain syndrome (CRPS) is a variety of painful conditions following injury which appears regionally having a distal predominance of abnormal findings. This study, evaluate the use of phentolamine for sympathetic block and regional anesthesia in treatment of CRPS related pain. In this study, 68 patients with CRPS who were referred to pain clinics of Imam Hossein and Akhtar Hospitals and Gandy Center of Surgery between 2003-2008 were evaluated. Forty three of 87 patients finally undertaken intravenous regional sympatholytic block according to therapeutic protocol. 37 patients (86%) received one block, 2 of them (4.75%) received 2 repetitions of blocks and finally repeated block for three times occurred in 4 patients (9.3%). A week after block pain relief outcomes was recorded as following; excellent in 7 patients (16.3%), good in the 32 patients (74.4%) and moderate in the 4 patients (9.3%). After a month, 8 patients (18.5%) showed excellent relief and it was good and moderate in 32 (78%) and one case (2.4%), respectively. Pain relief after three months was excellent, good and moderate in the 13 patients (31.7%), 25 patients (61%) and 3 patients (7.3%), respectively. In this study level of pain relief was significant in various intervals and it showed significant difference in relief three months after block (P=0.04). CRPS due to SMP(sympathetically maintained pain) is thought to be alleviated by phentolamine. Intravenous phentolamine infusion is potentially a new significant option for the therapy of CRPS.

Phentolamine mesylate (OraVerse), a nonselective a-adrenergic blocking drug, is the first therapeutic agent marketed for the reversal of soft-tissue anaesthesia and the associated functional deficits resulting from an intraoral submucosal injection of a local anaesthetic containing a vasoconstrictor. In clinical trials, phentolamine injected in doses of 0.2 to 0.8 mg (0.5 to 2 cartridges), as determined by patient age and volume of local anaesthetic administered, significantly hastened the return of normal soft-tissue sensation in adults and children 6 years of age and older. Median lip recovery times were reduced by 75 to 85 minutes. Functional deficits, such as drooling and difficulty in drinking, smiling, or talking--and subjects' perception of altered function or appearance--were consistently resolved by the time sensation to touch had returned to normal. Adverse effects of phentolamine injected in approved doses for reversal of local anaesthesia in patients ranging in age from 4 to 92 years were similar in incidence to those of sham injections, and no serious adverse events caused by such use were reported. The clinical use of phentolamine is viewed favorably by dentists who have administered the drug and by patients who have received it. Optimal use may require some modifications of the technique described in the package insert; cost of the agent may be influencing its widespread adoption into clinical practice. Phentolamine mesylate, in the form of OraVerse (Novalar Pharmaceuticals, San Diego, USA) represents a new therapeutic class of drugs in dentistry intended to reverse soft-tissue anaesthesia after nonsurgical dental procedures (e.g., restorative or deep scaling/root planing procedures). As shown in Figure 1, OraVerse is manufactured in 1.7 mL dental cartridges, each of which contains 0.4 mg active drug. This review describes the development of phentolamine as a dental drug, its pharmacologic characteristics, and how it may be used in clinical practice to improve patient care.

Aims: Alpha-adrenergic receptor-mediated vasoconstriction might underlie the insulin resistance seen in conditions associated with increased sympathetic tone, like chronic heart failure (CHF). Alpha-adrenergic receptor blockade by phentolamine could improve forearm blood flow (FBF) and forearm glucose uptake (FGU) in CHF patients., Methods and Results: In 8 CHF patients and in 12 healthy volunteers, FBF (plethysmography) and FGU were measured in both forearms during a 150 min hyperinsulinaemic euglycaemic clamp procedure. During the final 30 min of the clamp, phentolamine was infused into one arm (experimental arm) at a dose of 5.0 μg; min(-1) dL(-1) of forearm volume. Insulin infusion (t = 0-120 min) increased FGU in the two groups, without affecting FBF. In the CHF group, α-adrenergic receptor blockade by phentolamine (t = 120-150 min) further increased FGU in the experimental arm from 3.0 ± 0.7 to 5.0 ± 0.9 μmol min(-1) dL(-1) (P = 0.03). Forearm glucose uptake in the contralateral forearm remained unchanged. In the control group, phentolamine infusion did not increase FGU in the experimental forearm. The increase in blood flow in response to phentolamine was similar in both groups (CHF: 2.1 ± 0.3-7.5 ± 1.7 mL min(-1) dL(-1), P < 0.001; controls 1.5 ± 0.2-5.5 ± 0.8 mL min(-1) dL(-1), P < 0.001 for both, CHF vs. control, P = 0.2). Phentolamine did not affect FBF in the control arm in either group., Conclusion: Alpha-adrenergic receptor blockade improves FGU in CHF patients. As the increase in FBF is similar in controls and CHF patients, this might be explained by an improved glucose-extraction capacity in CHF patients.

Phentolamine mesylate, at dosages from 0.4 to 0.8 mg in adults and adolescents and at dosages from 0.2 to 0.4 mg in children aged 4 to 11 years, has been proven to be safe and effective for the reversal of soft tissue anesthesia (lip and tongue numbness) and the associated functional deficits resulting from a local dental anesthetic injection containing a vasoconstrictor. Its ability to block a-adrenergic receptors on blood vessels induces vasodilation and enhances the redistribution of the local anesthetic away from the injection site. The low dosages administered for dental local anesthetic reversal in all likelihood accounts for the lack of significant cardiovascular effects that are associated with the medical use of the drug for hypertensive conditions associated with catecholamine excess., (Copyright © 2010 Elsevier Inc. All rights reserved.)

This study was done to determine the effect of stress on blood glucose regulation in ICR mice. The stress was induced by the electrical foot shock-witness model. Blood glucose level was found to be increased in the electrical foot shock-induced physical stress group. Furthermore, the blood glucose levels were also elevated in the emotional stress group in both physical and emotional stress groups. The blood glucose level reached maximum 30 min after stress stimulation and returned to normal level 2 h after stress stimulation in both physical and emotional stress groups. Subsequently, we observed that intraperitoneal injection of phentolamine (an α1-adrenergic receptor antagonist), yohimbine (an α2-adrenergic receptor antagonist) or RU486 (a glucocorticoid receptor blocker) significantly inhibited blood glucose level induced by both physical and emotional stress. The results of our study suggest that physical and emotional stress increases blood glucose level via activation of adrenergic and glucocorticoid system.

PM (OraVerse) enables the dentist or dental hygienist (where permitted) to significantly decrease the duration of residual STA in patients where such numbness may prove to be potentially injurious (children, geriatric, and special needs patients), or a negative influence on their quality of life (speaking, eating, negative body image). (Note: As of August 3, 2009, dental hygienists are permitted to administer PM in the following states: Alaska, Arkansas, Hawaii, Idaho, Iowa, Louisiana, Montana, Nevada, New York, North Dakota, Oklahoma, Rhode Island, Tennessee, Utah, and Wisconsin.)

Objective: The objective of this study was to analyse the postoperative course and early outcome after the Norwood operation for patients with hypoplastic left heart syndrome. We particularly aimed to assess the impact of surgical and pharmacological modifications introduced., Methods: Of 157 patients who underwent the Norwood operation between January 1996 and December 2007, postoperative intensive care data on haemodynamics, pharmacological support and ventilation were analysed from 146 patients (six patients died intra-operatively and data were incomplete in five). The cohort was divided into three groups depending on the surgical method and type of afterload reduction. Patients of group 1 (n=39, January 1996-December 1999) were operated with deep hypothermic circulatory arrest. In patients of group 2 (n=59, January 2000-June 2003) and group 3 (n=59, July 2003-December 2007) antegrade selective cerebral perfusion was used. Patients of groups 1 and 2 received sodium nitroprusside to reduce afterload; in group 3 phentolamine was used., Results: There were no differences between the groups in terms of preoperative status and anatomy, except a higher incidence of prenatal diagnosis between groups 3 and 1. The duration and dosage of sodium nitroprusside administration were similar in groups 1 and 2. The median duration of afterload reduction was significantly longer in group 3 compared with both the other groups (72 h (range: 24-201 h) vs 48 h (range: 8-145 h) and 48 h (range: 4-173 h), respectively). The median ventilation times was shorter in group 2 compared with group 1 (61 h (range: 16-1191 h) vs 119 h (range: 26-648 h)). During the first 36 postoperative hours, the mean arterial blood pressure and coronary perfusion pressure were significantly lower in group 3 than in group 1 (50.7+/-4.8 and 28+/-3.7 mmHg vs 53.6+/-5.2 and 31.4+/-4.3 mmHg), but, in patients of group 3, the time period to consistently reach a mean arteriovenous oxygen difference below 5 ml dl(-1) was markedly shorter than in the other groups (group 3: 12h 4.90+/-1.97 ml dl(-1); group 1: 24h 4.53+/-2.25 ml dl(-1) and group 2: 24h 4.57+/-2.04 ml dl(-1)). Complication rates were similar between the groups. However, 30-day mortality decreased over the study period to an exponentially weighted moving average of 2.3%., Conclusion: Adamant afterload reduction improves systemic blood flow early after the Norwood operation and may have contributed to the reduction in early postoperative mortality achieved over 12 years., (Copyright 2009. Published by Elsevier B.V.)

Since the first description in the early 1990s, the scope of intravenous infusions tests has expanded to encompass multiple drug classes and indications. Purported advantages of these tests include elucidating mechanisms of pain, providing temporary relief of symptoms, and usefulness as prognostic tools in guiding drug therapy. In an attempt to discern the value of these tests, the authors conducted a systematic review to explore the rationale and evidence behind the following intravenous infusion tests: lidocaine, ketamine, opioid, and phentolamine. The studies evaluating all intravenous infusion tests were characterized by lack of standardization, wide variations in outcome measures, and methodological flaws. The strongest evidence found was for the intravenous lidocaine test, with the phentolamine test characterized by the least convincing data. Whereas intravenous opioid infusions are the most conceptually appealing test, their greatest utility may be in predicting poor responders to sustained-release formulations.

Introduction: Little research has been conducted about unconsummated marriage (UCM)., Aim: To report the long-term outcome of male sexual dysfunction (MSD) in UCM., Methods: From 1997 to 2008, 417 couples presented to the author with UCM. The mean UCM duration ranged from 1 hour to 8 years. The median follow-up was 78.5 months., Main Outcome Measures: Self-reported MSD in UCM based upon clinical history taking., Results: In 177 cases, UCM was due to erectile dysfunction (ED) (86), premature ejaculation (PE) (89), performance anxiety (25), vaginismus (34), hypodesire disorder (6), not knowing the coital technique (8), men who have sex with men (MSM) (2), hypogonadism (1), request by bride to delay coitus (1), and thick hymen (1) (more than one factor involved in many cases). In the remaining 240 cases, UCM was due to being under social pressure to have a quick intercourse while relatives waited behind the door to confirm and celebrate coitus by checking a handkerchief that was placed beneath the bride to become bloody by hymen perforation. Intracavernosal injection (ICI) using papaverine +/- phentholamine was used in 239 cases (57.3%); 221 (92.4%) responded. The eight cases who did not know the coital technique responded to sex education. Of the 50 men who were prescribed phosphodiesterase type 5 inhibitors, only 4 responded. Of the 26 men who received clomipramine (21) or fluoxetine (5) for PE, 2 and 1 responded, respectively. Fourteen grooms who did not respond to treatments later consummated spontaneously. No treatment was given to 94 grooms, including men with a diagnosis of psychotic disorder, men with learning difficulties, divorcing patients, and men in obligatory, loveless marriages. Ten untreated patients later consummated spontaneously. Of the 260 patients who consummated either with treatment (236) or spontaneously (24), 58 (22.3%) later presented with sexual complaints. The remaining 202 did well at a follow-up. Of the 157 couples who did not respond to treatment or did not receive treatment, 62 were either divorced or divorcing., Conclusion: We strongly advise ICI as the first-line treatment of UCM. Oral therapies of ED and PE, vacuum constriction devices (VCD), and hymenectomy are of limited value. No treatment is indicated in many cases. Most grooms do well sexually in a long-term follow-up.