Alpha-adrenergic Blocker Research Articles

Literature Review on Analytical Method Development and Validation of Alfuzosin Hydrochloride

Alfuzosin hydrochloride, an alpha-adrenergic blocker, is extensively used in the treatment of benign prostatic hyperplasia. Robust and reliable analytical methods are indispensable for quantifying alfuzosin hydrochloride in various matrices, ensuring the quality, efficacy, and safety of the drug. Recent advancements in analytical method development and validation for alfuzosin hydrochloride encompass a spectrum of techniques, including UV spectrometry, RP-HPLC, HPTLC, UPLC, and voltammetry. Optimization of chromatographic conditions, such as mobile phase composition, column selection, and detection wavelength, is crucial for achieving optimal separation and quantification of the drug. Method validation parameters, including accuracy, precision, linearity, and robustness, are assessed in accordance with ICH guidelines. These analytical methods find application in the determination of alfuzosin hydrochloride in bulk drugs, pharmaceutical formulations, and biological matrices. Stability-indicating methods are developed to evaluate drug stability under various stress conditions. The current state of analytical method development and validation for alfuzosin hydrochloride facilitates the selection of suitable analytical techniques for routine quality control and research purposes

Optimizing Treatment Strategies of Prostate Adenoma through Analytical Urodynamics

Aim: To investigate the role of urinary obstruction in determining surgical indications based on analytical urodynamics.Materials and methods. To collect observational data, a cohort of patients was selected from those receiving treatment at the Urination Pathology Centre in Vladivostok due to urinary disorders and prostate adenoma. This cohort consisted of patients aged 50 to 73 years (mean age 60.5 ± 8.2 years), with observation periods ranging from 2 to 29.3 months (mean duration 15.5 ± 13.5 months). During a two-day home uroflow monitoring session, the severity of urinary symptoms was assessed using the IPSS questionnaire prior to each monitoring event. The study utilized a domestically designed two-sensor SIGMA uroflowmeter in conjunction with LEVELEST software.Results. The study demonstrated that in patients from all three groups undergoing therapy with an alpha-1 adrenergic blocker, there was a significant reduction in clinical symptoms as measured by the IPSS questionnaire and an increase in the average effective volume of urination. However, despite these improvements, the groups exhibited differing dynamics in urinary obstruction, which ultimately determined the indications for surgical intervention.Conclusion. Home uroflow monitoring with the Sigma uroflowmeter provides an objective assessment of the lower urinary tract function in patients with bladder outlet obstruction, focusing on the urinary obstruction indicator dynamics. Repeated pharmacological testing in patients with prostate adenoma shows potential for long-term patient management, aiming to prevent detrusor failure and evaluate the efficacy of conservative therapy. Analytical urodynamic methods enable the establishment of surgical treatment indications based on uroflow monitoring outcomes.

Pharmacotherapy with alpha-1 adrenergic blockers and lipid spectrum correction in patients with urinary disorders

The study was based on treatment outcomes in a group of 130 patients aged 18–81 years. Subgroups were formed according to gender and age criteria, which included 56 men and 74 women, and were also divided into subgroups under 65 years of age and after 65. Treatment lasting continuously from 11 to 18 months was carried out in the form of combination therapy with the prescription of α1‑blockers (terazosin, doxazosin) in combination with vitamin-like drugs (levocarnitine, alpha-lipoic acid) in dosages according to the official instructions for the drug. The work involved systems for tabular assessment of the clinical symptoms of urinary disorders, as well as instrumental, laboratory, and statistical methods (Mann — Whitney test, Spearman's rank correlation coefficient).Results. Against the background of the prescribed treatment, HDL levels significantly changed from 1.3 to 1.38 mmol/L, as well as VLDL from 0.88 to 0.72 mmol/L in the general observation group. In some indicators, particularly total cholesterol, low-density lipoprotein, and triglycerides, no dynamics were noted. In the men subgroup, the indicators of both HDL and VLDL changed significantly and reliably from 1.2 to 1.29 mmol/L and, accordingly, from 0.79 to 0.65 mmol/L. In the 65-yearold subgroup, VLDL levels significantly decreased from 0.88 to 0.76 mmol/L and triglyceride levels from 1.9 to 1.65 mmol/L, respectively. In the subgroup of patients aged >65 years, there was a significant increase in HDL from 1.29 to 1.46 mmol/L.Conclusion. Long-term combination therapy over 11 months, including alpha1 inhibitors in combination with vitamin-like drugs, significantly changed the lipid spectrum. The best outcomes of pharmacotherapy were observed in the male subgroup and in patients aged >65 years.

Evaluation of Tamsulosin 0.4 mg versus 0.8 mg in Management of Patients Suffering from Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia

Abstract Introduction Lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) are common among older men. Beside watchful waiting and surgery, medical therapy includes alpha adrenergic blockers, 5 alpha reductase inhibitors, and phytotherapy. Alpha blockers are considered to be the main treatment for BPH-associated LUTS depending on the evidence that prostatic smooth muscle contraction is responsible for bladder outlet obstruction via alpha adrenergic receptor- mediated mechanism. Tamsulosin is a super selective alpha blocker. Improvement of LUTS can be assessed by maximum flow rate (Qmax), average flow rate (Qavg), post void residual (PVR) urine volume and international prostate symptom score questionnaire (IPSS). Objectives To compare the efficacy and the safety of Tamsulosin 0.4 mg/day and 0.8 mg/day in patients suffering from lower urinary tract symptoms due to benign prostatic hyperplasia. Patients and Methods A Prospective Interventional, double-blinded, controlled study was carried out on 93 patients who met the criteria and divided randomly into 2 groups; group A for Tamsulosin 0.4 mg/day and group B for Tamsulosin 0.8 mg/day. International prostate symptom score, Post void residual urine volume, and maximum flow rate of urine were assessed before and after 4 weeks of treatment. Results Both study groups showed a significant reduction in storage sub-score but only frequency was significantly reduced in group B (P < 0.001). On the other hand, Tamsulosin 0.8 mg was superior to Tamsulosin 0.4 mg regarding voiding sub score except for straining (P = 0.325). Accordingly, the total international prostate symptom score was significantly improved in group B (P < 0.001). Furthermore, maximum flow rate and post-void residual urine volume were notably improved with Tamsulosin 0.8 mg compared to Tamsulosin 0.4 mg (P < 0.001). Although the adverse events; such as headache, orthostatic hypotension, and retrograde ejaculation were more frequent, but not significant, to occur with Tamsulosin 0.8 mg, only dizziness was noted to be significant. Conclusion Tamsulosin 0.8 mg has shown better outcomes in treating patients who suffer from lower urinary tract symptoms due to benign prostatic hyperplasia than Tamsulosin 0.4 mg, and besides that, it is well tolerated.

Benign Prostate Hypertrophy: An Educational Ultrasound Images and Pharmacotherapy Mini-Review

Background: A benign increase in the size of prostate (Enlargement) can be asymptomatic, but it can cause symptoms resulting from pressure on the urethra, including frequency of urination, difficulty in starting urination, poor urine stream, dribbling after urination, and inability to pass urine. Ultrasonography has been used as early as 1971 for the diagnosis of prostatic enlargement. Patients and Methods: The case of a 53-year old diabetic and hypertensive male who had refractory psoriasis and developed benign enlargement is described and an educational ultrasound images are presented. Results: The patient was complaining of dribbling after micturition for few weeks. He was not having difficulty in starting urination nor complained of frequent micturition, and the urine stream was considered normal. The urinary bladder was normal, but with mild hazy wall outline. Pre-voiding volume was 248 ml, and post-voiding volume was 9 ml. Ultrasound of the prostate showed enlarged prostate with homogenous texture. Prostate volume was 36.6 ml (Normal: 25 ml). Therefore, Oral finasteride was started. Conclusion: Many medications have been used in the treatment of benign enlargement of the prostate during the 1960s, 1970s, and 1980s, including progestational agents, Amino acids, spironolactone, candicidin, nystatin, flutamide, bromocriptine, alpha-adrenergic blockers, Serenoa repens (Saw palmetto extracts), and mepartricin. However, the current evidence-based opinion suggests that benign enlargement of the prostate can be initially treated with medications that can reduce the volume of the prostate such as finasteride and dutasteride. Tamsulosin or alfuzosin can be added to further improve lower urinary symptoms.

Tamsulosin Versus Mirabegron in Relieving Ureteric Stent-Related Symptoms: A Prospective, Double-Blinded, Randomized Controlled Trial.

Introduction Alpha-adrenergic blockers like tamsulosin are widely used in the treatment of stent-related symptoms due to ureteric stents. Recently, mirabegron has emerged as a potential alternative. So, our study aimed to compare the effect of mirabegron and tamsulosin on ureteric stent-related morbidity. Methods In this randomized controlled study, 80 patients undergoing uncomplicated ureteroscopic lithotripsy with double J stenting for ureteric stones were enrolled. They were divided into two groups: Group A (n=40) received mirabegron (25mg) and Group B (n=40) received tamsulosin (0.4mg). Outcomes were assessed using the Ureteral Stent Symptom Questionnaire (USSQ), International Prostate Symptoms Score (IPSS), and the visual analog pain scale. The t-test and the Chi-square test were utilized to study theefficacy of the interventions across both groups. Results The USSQ urinary symptom score (25.5 vs 33.45; p < 0.001) and body pain score (16.15 vs 26.02; P < 0.001) were significantly lower in the mirabegron group. However, the general health score (17.0 vs 17.28; p = 0.62) and work performance score (7.6 vs 8.0; p = 0.28) did not show a significant difference. The storage symptom score was significantly lower in the mirabegron group (3.98 vs 5.1; p = 0.001). Furthermore, the mirabegron group reported a better quality of life score (2.18 vs 3; p < 0.001). Conclusion Mirabegron has been shown to reduce urinary symptoms associated with ureteric stents and also results in a better quality of life when compared with tamsulosin. However, large-scale, prospective, multicentric studies are further required to holistically evaluate and comprehend the beneficial effects of mirabegron on stent-related morbidity.

Alpha1-adrenergic blockers selectively antagonize the contractions induced by 6-nitrodopamine in the human vas deferens.

6-Nitrodopamine (6-ND) is released from human vas deferens and plays a modulatory role in the male ejaculation. Therapeutical use of α1-adrenoceptor antagonists is associated with ejaculatory abnormalities.To evaluate the effect of α1-adrenoceptor antagonists on the contractions induced by 6-ND, dopamine, noradrenaline, and adrenaline in the human epididymal vas deferens (HEVD).HEVD strips were suspended in glass chambers containing heated and oxygenated Krebs-Henseleit's solution. Cumulative concentration-response curves to catecholamines (10nM-300μM) were constructed in HEVD strips pre-incubated (30min) with doxazosin (0.1-1nM), tamsulosin (1-10nM), prazosin (10-100nM) and/or silodosin (0.1-10nM). The effects of these α1-adrenoceptor antagonists were also evaluated in the electric-field stimulation (EFS, 2-32Hz)-induced contractions.Doxazosin (0.1nM) caused significant reductions in 6-ND-induced HEVD contractions without affecting the contractions induced by dopamine, noradrenaline, and adrenaline. Similar results were observed with tamsulosin (1nM) and prazosin (10nM). At these concentrations, these α1-adrenoceptor antagonists largely reduced the EFS-induced contractions. Silodosin (1nM) caused concentration-dependent rightward shifts of the concentration-response curves to 6-ND but had no effect on the contractions induced by dopamine and adrenaline. Silodosin (0.1nM) only inhibited the contractions induced by noradrenaline. Silodosin at 1nM, but not at 0.1nM, caused significant reductions in the EFS-induced contractions.The results reinforce the concept that 6-ND plays a major role in the human vas deferens contractility and indicate that the ejaculation disorders caused by doxazosin, tamsulosin, prazosin and silodosin cause in man, may be due to inhibition of the contractions induced by 6-ND rather than by the classical catecholamines dopamine, noradrenaline, and adrenaline.

Diagnoses and medications associated with delayed ejaculation.

Delayed ejaculation (DE) is a disorder that can cause significant distress for sexually active men. The etiology of DE is largely idiopathic, with even less being known about clinical factors associated with the condition. We sought to use data mining techniques to examine a broad group of health conditions and pharmaceutical treatments to identify factors associated with DE. Using an insurance claims database, we evaluated all men with a diagnosis of DE and matched them to a cohort (1:1) of men with other male sexual disorders of urologic origin (ie, erectile dysfunction [ED] and Peyronie's disease [PD]). Given the low prevalence of DE, we incorporated the random forest approach for classification of DE vs controls, with a plethora of predictors and cross-validation with the least absolute shrinkage and selection operator (LASSO). We used both a high-performance generalized linear model and a multivariate logistic model. The area under the curve was reported to demonstrate classifier performance, and odds ratios were used to indicate risks of each predictor. We also evaluated for differences in the prevalence of conditions in DE by race/ethnicity. Clinical factors (ie, diagnoses and medications) associated with DE were identified. In total, 11 602 men with DE were matched to a cohort of men with PD and ED. We focused on the 20 factors with the strongest association with DE across all models. The factors demonstrating positive associations with DE compared to other disorders of male sexual dysfunction (ie, ED and PD) included male infertility, testicular dysfunction, anxiety, disorders of lipid metabolism, alpha adrenergic blocker use, anemia, antidepressant use, and psychoses such as schizophrenia or schizoaffective disorder. In addition, the prevalence of several conditions varied by race/ethnicity. For example, male infertility was present in 5% of Asian men compared to <2% of men of other races. Several medical conditions and pharmacologic treatments are associated with DE, findings that may provide insight into the etiology of DE and offer treatment options. This study is to our knowledge the first to use using data mining techniques to investigate the association between medical conditions/pharmacologic agents and the development of subsequent DE. The generalizability of our findings is limited given that all men were commercially insured. DE is associated with multiple medical conditions, a finding that may help identify the etiology for this disorder.

Isolated angioedema due to face mask and other cases of isolated angioedema.

Isolated angioedema can be divided into two groups as mast cell-mediated angioedema and bradykinin-mediated angioedema according to the known mechanisms of occurrence. However, angioedema can also occur with mechanisms whose cause is unknown. Treatment varies according to the mechanism of angioedema formation. In this prospective study, we present the causes of 80 isolated angioedema cases admitted to our clinic during the pandemic period. We would like to emphasize the causes that we found in our cases but which are rare in the literature. For example: angioedema due to allergy to nickel in the mask used during the pandemic period, T cell-mediated angioedema, alpha adrenergic receptor blocker use, and patients diagnosed with collagen tissue disease presenting with angioedema as the first clinical finding.

First-line diuretics versus other classes of antihypertensive drugs for hypertension.

First-line diuretics versus other classes of antihypertensive drugs for hypertension.

Intraoperative floppy iris syndrome: comparison of two different alpha-adrenergic blockers

Intraoperative floppy iris syndrome: comparison of two different alpha-adrenergic blockers

A case report of an atypical haemolytic uremic syndrome in pregnancy: something wicked this way comes

BackgroundAtypical Haemolytic Uremic Syndrome is an acute life-threatening condition, characterized by the clinical triad of microangiopathic hemolytic anaemia, thrombocytopenia, kidney injury. Management of pregnants affected by Atypical Haemolytic Uremic Syndrome can be a serious concern for obstetric anesthesiologist in the delivery room and in the intensive care unit.Case presentationA 35-year-old primigravida with a monochorionic diamniotic twin pregnancy, presented with an acute haemorrhage due to retained placenta after elective caesarean section and underwent surgical exploration. In the postoperative period, the patient progressively developed hypoxemic respiratory failure and, later on, anaemia, severe thrombocytopenia, and acute kidney injury. A timely diagnosis of Atypical Haemolytic Uremic Syndrome was made. Non-invasive ventilation and high-flow nasal cannula oxygen therapy sessions were initially required. Hypertensive crisis and fluid overload were aggressively treated with a combination of beta and alpha adrenergic blockers (labetalol 0,3 mg/kg/h by continuous intravenous infusion for the first 24 hours, bisoprolol 2,5 mg twice daily for the first 48 hours, doxazosin 2 mg twice daily), central sympatholytics (methyldopa 250 mg twice daily for the first 72 hours, transdermal clonidine 5 mg by the third day), diuretics (furosemide 20 mg three times daily), calcium antagonists (amlodipine 5 mg twice daily).Eculizumab 900 mg was administered via intravenous infusion once per week, attaining hematological and renal remissions. The patient also received several blood transfusion units and anti- meningococcal B, anti-pneumococcal, anti-haemophilus influenzae type B vaccination.Her clinical condition progressively improved, and she was finally discharged from intensive care unit 5 days after admission.ConclusionsThe clinical course of this report underlines how crucial it is for the obstetric anaesthesiologist to promptly identify Atypical Haemolytic Uremic Syndrome, since early initiation of eculizumab, together with supportive therapy, has a direct effect on patient outcome.

Commentary on "Integrative multiplatform molecular profiling of benign prostatic hyperplasia identifies distinct subtypes".

Commentary on "Integrative multiplatform molecular profiling of benign prostatic hyperplasia identifies distinct subtypes".

Is there any effect of long term alpha-adrenergic blocker and a single dose antibiotic usage in reducing febrile urinary tract infections after prostate biopsy?

Aim: To investigate whether the using long term alpha-adrenergic blockers before biopsy has an effect on preventing febrile urinary tract infections (FUI) secondary to biopsy in patients undergoing prostate biopsy due to elevated prostate specific antigen (PSA) .Material and Method: The data of 2558 patients who underwent transrectal ultrasonography-guided prostate biopsy (TRUS+BX) due to elevated PSA in our clinic between January 2008 and July 2021 were analyzed retrospectively. The patients were divided into two groups as those who used alpha-blockers for a minimum of three months or longer before biopsy (Group 1) and those who did not use alpha-blockers before applying to the outpatient clinic (Group 2) . Demographic data of the groups and post-biopsy FUI development rates were compared.Results: It was observed that 1340 (52.4%) of the patients were using alpha-blockers (Group 1) and 1218 (47.6%) did not (Group 2) . The median age of the patients in the pre-biopsy groups was similar [Group 1=68 (IQR=9) years and Group 2=68 (IQR=9) years, p=0.887]. There was no significant difference between the groups in terms of median prostate volume [Group1=57 (31) ml and Group 2=58 (34) ml, p=0.199]. The median PSA value was found to be significantly higher in Group 1 than in Group 2 [10.50 (5.40) ng/dl vs 10.35 (6.80) ng/dl, p=0.026]. Postvoid residual urine volume (PVR) was found to be significantly higher in Group 2 [Group 1=40 (30) ml and Group2=60 (90) ml, p&amp;lt;0.001]. Similarly, the frequency of FUI development after biopsy was found to be significantly higher in Group 2 [Group 1=17 (1.3%) and Group 2=65 (5.3%) , p&amp;lt;0.001].Conclusion: The use of alpha-adrenergic blockers for a minimum of three months or longer before prostate biopsy significantly reduces the incidence of FUI that may develop secondary to biopsy.

PS-R04-4: A CASE OF PHEOCHROMOCYTOMA IN A 17-YEAR-OLD MALE

Background: Pheochromocytoma is a rare catecholamine secreting tumor arising from the adrenal medulla and produces signs and symptoms due to excessive catecholamine secretion from the tumor. It is a rare cause of secondary hypertension and a delay in recognition and treatment can present serious consequences to the patient. Case Summary: We present a case of a 17-year-old male with a history of hypertension for 4 years with episodic headache, palpitations, and sweating. He does not have any history of serious illnesses, hospitalizations, or trauma. He was not on any medications. He has a family history of hypertension. He does not drink alcohol, smoke cigarettes, or do any illicit drugs. Upon arrival to the ER, he was conscious, coherent with BP of 170/140mmHg, PR 111bpm, RR 26cpm, and afebrile. Laboratory work-up showed proteinuria, elevated BUN and creatinine levels, hyponatremia, hypokalemia, and hypocalcemia. A 2D echocardiography showed left ventricular hypertrophy. The whole abdominal CT scan demonstrated a fairly defined hypodense mass in the left suprarenal measuring 4.8 x 6.4 x 4.7 cm. Pheochromocytoma was confirmed by biochemical tests that showed elevated plasma normetadrenaline and 24-hour urine metanephrine. The patient was initially started on an alpha-adrenergic blocker, Terazosin, and a beta-blocker, Propranolol. Blood pressure was still uncontrolled hence calcium-channel blocker, Nicardipine drip was also given to control the blood pressure. During surgery, they noted the mass to be 8x5 cm invading the superior pole to mid pole and renal hilum hence the patient underwent left open adrenalectomy with left radical nephrectomy. Immediately upon removal of the mass, the patient had a hypotensive episode, which was addressed immediately. The histopathologic finding showed no extension of the mass to the kidneys and it is consistent with pheochromocytoma. Blood pressure control without medication was achieved 13 days post-operatively. The patient is regularly monitored for the recurrence of hypertension due to the increased risk of recurrence. The patient is now living with a solitary kidney hence should also be followed up through. Conclusion: Although it is a rare condition, pheochromocytoma should be considered a differential diagnosis in young patients presenting with unexplained hypertension, headache, and palpitations. A multidisciplinary approach is the best way to achieve success in the management of a patient with pheochromocytoma.

Treatment of benign prostatic hyperplasia and abnormal ejaculation: live imaging reveals tamsulosin - but not tadalafil - induced dysfunction of prostate, seminal vesicles and epididymis.

One of the most commonly prescribed benign prostatic hyperplasia (BPH) pharmacotherapies, the alpha1-adrenergic blocker tamsulosin, is frequently discontinued, especially by younger patients due to ejaculatory disorders, often without feedback to the attending physician. Using a newly developed ex vivo system simulating sympathetic effects on the most relevant structures for the emission phase of ejaculation, that is seminal vesicles, prostate and the most distal part of the cauda epididymidis, we elucidated that tamsulosin fundamentally disturbed the obligatory noradrenaline-induced contractions in each of these structures which differed to an alternative pharmacotherapy, the PDE5 inhibitor tadalafil. Structures responsible for the emission phase of ejaculation are the seminal vesicles, the most distal part of the cauda epididymidis and the newly characterized prostate excretory ducts. The emission phase is mainly regulated by the sympathetic nervous system through alpha1-adrenergic receptor activation by noradrenaline at the targeted organs. BPH treatment with alpha1A-adrenergic antagonists such as tamsulosin is known to result in ejaculation dysfunction, often leading to discontinuation of therapy. Mechanisms of this disturbance remain unclear. We established a rodent model system to predict drug responses in tissues involved in the emission phase of ejaculation. Imitating the therapeutic situation, prostate ducts, seminal vesicles and the distal cauda epididymal duct were pre-incubated with the smooth muscle cell-relaxing BPH drugs tadalafil, a novel BPH treatment option, and tamsulosin in an ex vivo time-lapse imaging approach. Afterwards, noradrenergic responses in the relevant structures were investigated to simulate sympathetic activation. Noradrenaline-induced strong contractions ultimately lead to secretion in structures without pre-treatment. Contractions were abolished by tamsulosin in prostate ducts and seminal vesicles and significantly decreased in the epididymal duct. Such effects were not observed with tadalafil pre-treatment. Data visualized a serious dysfunction of each organ involved in emission by affecting alpha1-adrenoceptors localized at the relevant structures but not by targeting smooth muscle cell-localized PDE5 by tadalafil. Our model system reveals the mechanism of tamsulosin resulting in adverse effects during ejaculation in patients treated for BPH. These adverse effects on contractility do not apply to tadalafil treatment. This new knowledge translates directly to clinical medicine.

Does tamsulosin decrease postoperative urinary retention in spine surgery? A double-blind, randomized controlled trial.

The authors' objective was to determine whether preoperative administration of tamsulosin decreases postoperative urinary retention after spine surgery. In this randomized, double-blind, placebo-controlled clinical trial performed at a single institution between 2016 and 2019, eligible males aged 50 to 85 years were administered tamsulosin or placebo for 5 days prior to elective spine surgery. Patients were excluded if they were taking alpha adrenergic blocking drugs; were allergic to tamsulosin, lactose, or sulfa drugs; had a preexisting indwelling urinary catheter, orthostatic hypotension, history of urological surgery, or renal failure; or were scheduled for cataract surgery within 2 weeks. Screening identified 1051 eligible patients (140 declined participation, 150 did not meet the inclusion criteria, and 151 did not enroll for other reasons). A total of 610 patients were randomly assigned to receive 0.4 mg oral tamsulosin or an identical placebo capsule for 5 days preoperatively and 2 days postoperatively. A total of 497 patients were included in the final statistical analysis. The overall rate of postoperative urinary retention was 9.7%, and tamsulosin had no observed effect on reducing the rate of postoperative urinary retention as compared with placebo (9.4% vs 9.9%, p = 0.96). There were no significant differences in the reported adverse events between groups. Multivariate logistic regression was performed to model the effects of patient, surgical, and anesthetic factors on postoperative urinary retention, and the study drug remained an insignificant factor. This study did not detect an effect of perioperative tamsulosin on reducing the rate of postoperative urinary retention in male patients aged 50 to 85 years who underwent elective spine surgery. This study does not support the routine use of tamsulosin to reduce postoperative urinary retention in patients without a previous prescription. It is unknown if subpopulations exist for which prophylactic tamsulosin may reduce postoperative urinary retention.

La calcolosi delle vie urinarie in età pediatrica a tutto tondo

Overall, the incidence of paediatric urolithiasis is increasing; 50-90% of cases are due to metabolic alterations, 3-30% are associated with urinary tract infections and the remaining cases are idio-pathic. About 20-30% of children, especially boys who are younger than 2 years of age, present an anatomic urinary tract anomaly. The main symptom is abdominal pain; however, young children tend to have subtle manifestations. Abdominal ultrasound is the first-line imaging technique. Conservative treatment with fluid intake, pain relievers and alpha-adrenergic blockers are used during the acute episode, whereas a surgical treatment is indicated in selected cases. Since there is an increased rate of recurrence in comparison to adulthood, abundant hydration and changes in dietary habits have a central role in the prevention of paediatric urolithiasis. It is very important to perform a metabolic evaluation when the acute episode is resolved, as 50% of the cases present an underlying metabolic disorder. If a metabolic abnormality is diagnosed, specific preventive interventions should be undertaken. The paper presents the clinical case of an infant who during a Proteus mirabilis urinary tract infection has developed obstructive acute kidney injury due to a stone in the distal urethra. The incidence of urinary stones caused by urinary tract infection is decreasing, however this eventuality should be considered.

Effect of adrenergic receptor antagonists on clinical outcomes in metastatic renal cell carcinoma.

e16520 Background: Adrenergic receptors (ADR) have a well-established role in kidney physiology, suggesting a possible role of ADR signaling in renal cell carcinoma (RCC). Preclinical studies have shown a possible anti-tumor effect of both alpha-adrenergic blockers (AB) and beta-adrenergic blockers (BB) on renal cancer cells. However, the literature is conflicting regarding the effect on clinical outcomes. In addition, there is no comprehensive analysis of what role these medications have specifically in RCC patients with metastatic disease. In this single health system retrospective study, we evaluate the effect of AB or BB prescription on cancer-specific outcomes in patients with metastatic RCC. Methods: Clinical data was abstracted from the electronic health record and the institutional cancer registry at The Mount Sinai Health System to include patients with RCC diagnosed with metastatic disease ( de novo or relapsed) between 2016-2020. Follow up data was recorded until a data lock of 4/1/2021. Multivariate Cox regression was used to evaluate the association of AB and BB prescription on overall survival (OS) for the entire cohort and progression free survival (PFS) for patients who received any first line therapy. Multivariate logistic regression was used to evaluate association of these medications with overall response rate (ORR) of first line therapies with available data on initial response. Analyses were controlled for clinical risk factors including age at diagnosis, sex, race, treatment plan including immunotherapy, and medical history of benign prostatic hyperplasia, hypertension, or heart failure. Data was analyzed using R version 4.1.0. Results: 133 patients were identified for inclusion in the study. 61% of cases are de novo metastatic and 39% are relapsed from previously resected disease. 71% are clear cell histology, 3.8 % are papillary, and the rest are unspecified/other. 84 patients (63%) received at least a 1st line systemic therapy. AB or BB prescription alone is not associated with OS, PFS, or ORR. However, prescription of both AB and BB is associated with worse OS (HR 2.94 95% CI 1.13-7.68), worse PFS (HR 7.70 95% CI 1.80-33.0), and decreased odds of responding to 1st line therapy (OR 0.06 95% CI 0.00-0.55) on multivariate analysis. Conclusions: The data suggests that the concurrent use of both an AB and BB in patients with metastatic RCC leads to worse clinical outcomes. What remains unclear is if there is a negative synergistic effect of these medications on RCC pathophysiology or if the prescription of these medications is associated with another negative confounding clinical factor. Since these medications are commonly utilized for cardiovascular disease, multivariate analyses attempted to control for these comorbidities. Future studies may add to this data by cataloging the severity of heart failure and doses of AB and BB medications used in a RCC cohort.

Regional binding of [3H]‐MK801 to NMDA receptors in young and aged rat brain membranes

Norepinephrine (NE) and dopamine (DA) are essential neuromodulators in the central nervous system. They regulate several crucial physiological processes, including arousal/attention, focus, neuroendocrine functions, and the sleep‐wake cycle; they also play complex roles in regulating cognition and affect; therefore, dysfunctions in catecholaminergic neurotransmission are associated with various neurological consequences. Previously, we confirmed that in brain slices from aged Fischer 344 rats, there is an age‐related decrease in glutamate‐stimulated NE release in the cerebral cortex and hippocampus (Gonzales et al., 1991 &amp; Dezfuli et al., 2019) and a regionally specific decline in glutamate‐stimulated DA release, with a deficit in the striatum but not in the olfactory tubercle (Aljohani et al., 2021a). Importantly, our studies demonstrated that NMDA receptors mediate glutamate‐stimulated NE and DA release. We also have shown that the alpha‐2 adrenergic receptors agonist clonidine decreases this glutamate‐stimulated NE release in a concentration‐dependent manner; while in contrast, blockade of these receptors with phentolamine, an alpha‐1 and alpha‐2 adrenergic receptor blocker, or with idazoxan, a selective alpha‐2 receptor blocker, markedly potentiates glutamate‐stimulated NE release in cortical brain slices (Aljohani et al., 2021b). Since aging has heterogeneous effects on NMDA receptors in different brain areas, we have now begun to examine [3H]‐MK801 binding to NMDA receptors to compare changes in receptor density and responsiveness during aging in the cortex, hippocampus, striatum, and olfactory tubercle, as a possible mechanistic explanation for the changes in NE and DA release. The data from cortical membrane preparations suggest that young and old rats have similar NMDA receptor densities but may differ in their response to stimulation with glutamate/glycine.