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Veterinary and Comparative Oncology Dec 2023Adrenalectomies for canine adrenal tumours are associated with peri-operative morbidity and mortality. Objectives of this study included assessing the prognostic value...
Adrenalectomies for canine adrenal tumours are associated with peri-operative morbidity and mortality. Objectives of this study included assessing the prognostic value of tumour- or surgery-related variables in predicting peri-operative mortality and overall survival in dogs undergoing adrenalectomies for primary adrenal tumours as well as pre-treatment with phenoxybenzamine on survival to discharge with pheochromocytomas specifically. A multi-institutional retrospective cohort study was performed across nine institutions. Electronic medical record searches identified 302 dogs which met the inclusion criteria. Data collected included dog-related, tumour-related, treatment-related, surgery-related, and outcome variables. Univariate and multivariable logistic regression and cox proportional hazards models were used to identify variables associated with death prior to discharge and tumour-related survival. Overall, 87% of dogs survived to discharge with a tumour-related survival time of 3.96 years. Post-operative complications were reported in 25%. Increased surgical time (p = 0.002) and pre-surgical medical treatment other than phenoxybenzamine (p = 0.024) were significantly associated with increased peri-operative mortality while ureteronephrectomy (p = 0.021), post-operative pancreatitis (p = 0.025), and post-operative aspiration pneumonia (p < 0.001) were significantly associated with decreased overall survival. Phenoxybenzamine pretreatment had no effect on peri-operative mortality. Thirty-seven of 45 (82%) dogs with pheochromocytomas not pretreated survived to discharge, and 50 of 59 (85%) dogs with pheochromocytomas pretreated with phenoxybenzamine survived to discharge (p = 0.730). This study provides information on risk factors for death prior to discharge and tumour-related survival that may help guide clinical management and owner expectations. In addition, the study findings challenge the previously reported benefit of phenoxybenzamine for pretreatment of dogs undergoing adrenalectomies for pheochromocytomas.
Topics: Animals; Dogs; Adrenal Gland Neoplasms; Adrenalectomy; Dog Diseases; Patient Discharge; Phenoxybenzamine; Pheochromocytoma; Retrospective Studies; Risk Factors
PubMed: 37652746
DOI: 10.1111/vco.12931 -
Omics : a Journal of Integrative Biology Jul 2023Idiopathic pulmonary arterial hypertension (IPAH) is a progressive disease that affects the pulmonary arteries, resulting in increased pulmonary vascular resistance and...
Idiopathic pulmonary arterial hypertension (IPAH) is a progressive disease that affects the pulmonary arteries, resulting in increased pulmonary vascular resistance and right ventricular dysfunction, which can ultimately lead to heart failure and death. The molecular substrates of IPAH are poorly understood while diagnostics and therapeutics innovation remain as unmet needs for this debilitating disease. In this study, a network-based methodology was used to uncover the salient molecular mechanisms of IPAH to inform drug and diagnostic discovery, and personalized medicine. Expression profiling datasets associated with IPAH were obtained from the Gene Expression Omnibus database: GSE15197, GSE113439, GSE53408, and GSE67597. The comparative analysis of mRNA and miRNA expression data and the modular analysis of a transcriptome-based weighted gene coexpression network unraveled disease-specific gene and miRNA signatures. DEAD-box helicase 52 (), ESF1 nucleolar pre-RNA processing protein (), heterogeneous nuclear ribonuclearprotein A3 (), Myosin VA (), replication factor C subunit 1 (), and arginine and serine rich coiled coil 1 () were detected as the salient genes for IPAH. In addition, the salient gene-based drug repositioning analysis identified alvespimycin, tanespimycin, geldanamycin, LY294002, cephaeline, digoxigenin, lanatoside C, helveticoside, trichostatin A, phenoxybenzamine, genistein, pioglitazone, and rosiglitazone as potential drug candidates for IPAH. In conclusion, this study provides new molecular signatures in relation to IPAH and attendant potential drug candidates for further experimental and translational clinical research for patients with IPAH.
Topics: Humans; Familial Primary Pulmonary Hypertension; Hypertension, Pulmonary; Multiomics; Pulmonary Artery; MicroRNAs
PubMed: 37410515
DOI: 10.1089/omi.2023.0066 -
Sexual Medicine Reviews Apr 2024Although oral phosphodiesterase 5 inhibitors represent a first choice and long-term option for about half of all patients with erectile dysfunction (ED), self-injection...
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.
PubMed: 38644056
DOI: 10.1093/sxmrev/qeae020 -
Endocrine May 2024Preoperative medical management is critical to prevent intraoperative cardiovascular complications in patients with pheochromocytomas and paragangliomas (PPGLs). Initial... (Observational Study)
Observational Study
PURPOSE
Preoperative medical management is critical to prevent intraoperative cardiovascular complications in patients with pheochromocytomas and paragangliomas (PPGLs). Initial treatment involves α-adrenergic receptor blockers. However, while the routine use of metyrosine alongside these blockers is not strongly recommended due to a lack of evidence supporting its efficacy and associated safety concerns, there are previous studies on combination therapy with phenoxybenzamine and metyrosine. There are few reports on combination therapy with the selective α1-adrenergic receptor blocker doxazosin. Therefore, we investigated this combination treatment, which theoretically can affect perioperative outcomes in patients with PPGLs. To our knowledge, this is the first such study.
METHODS
This retrospective single-center observational study involved 51 patients who underwent surgical resection of PPGLs at Kobe University Hospital between 2014 and 2022. All patients received doxazosin at maximum doses. Fourteen patients received concomitant metyrosine, while 37 received doxazosin alone. Their perioperative outcomes were compared.
RESULTS
No severe event, such as acute coronary syndrome, was observed in either group. Intraoperatively, the doxazosin + metyrosine group exhibited a lower median minimum systolic blood pressure (56 [54-60] vs. 68 [59-74] mmHg, P = 0.03) and required lower median remifentanil (P = 0.04) and diltiazem (P = 0.02) doses than the doxazosin-alone group.
CONCLUSION
The combination of metyrosine and doxazosin as a preoperative treatment for PPGLs affects intraoperative circulatory hemodynamics, such as a reduced occurrence of blood pressure elevation during surgery. Further research is necessary to identify patients who will benefit most from this combination treatment.
Topics: Humans; Doxazosin; Female; Male; Pheochromocytoma; Middle Aged; Adrenal Gland Neoplasms; Retrospective Studies; Paraganglioma; Adult; Aged; alpha-Methyltyrosine; Adrenergic alpha-1 Receptor Antagonists; Drug Therapy, Combination; Preoperative Care; Treatment Outcome
PubMed: 38206436
DOI: 10.1007/s12020-023-03681-4 -
Journal of Medical Case Reports Mar 2024This report presents a case of cannabinoid-induced hyperemesis syndrome causing repeated violent retching in a patient with a large (8 cm) adrenal pheochromocytoma...
BACKGROUND
This report presents a case of cannabinoid-induced hyperemesis syndrome causing repeated violent retching in a patient with a large (8 cm) adrenal pheochromocytoma resulting in hypertensive urgency.
CASE PRESENTATION
A 69-year-old white male patient with a previously diagnosed pheochromocytoma presented to the emergency department with nausea and vomiting and was found to have hypertensive urgency. Computed tomography scan did not show any acute abdominal pathology and history was inconsistent with a gastrointestinal etiology. Patient had a history of daily cannabinoid use for many years and repeated self-limited hyperemesis episodes, and thus a diagnosis of cannabinoid-induced hyperemesis syndrome was made. It was concluded that the likely explanation for the hypertensive urgency was from physical compression of his adrenal tumor during the episodes of retching resulting in a catecholamine surge. The patient was given antiemetics and admitted to the intensive care unit for blood pressure management. Blood pressure was initially controlled with phentolamine and a clevidipine infusion, then transitioned to oral doxazosin and phenoxybenzamine. Hyperemesis and abdominal pain resolved after 24 hours, and his blood pressure returned to baseline. The patient was discharged with the recommendation to stop all cannabis use. On follow-up, his blood pressure remained well controlled, and he subsequently underwent adrenalectomy for tumor removal.
CONCLUSION
Hyperemesis can cause hypertensive events in patients with pheochromocytoma by increasing abdominal pressure, leading to catecholamine release.
Topics: Aged; Humans; Male; Adrenal Gland Neoplasms; Cannabinoid Hyperemesis Syndrome; Cannabinoids; Catecholamines; Hypertensive Crisis; Pheochromocytoma; Vomiting
PubMed: 38500192
DOI: 10.1186/s13256-024-04497-0 -
Analytica Chimica Acta Oct 2023A water-soluble negative sulfonic propyl ether β-CD polymer (SPE-β-CDP) to be used as chiral selector in capillary electrophoresis (CE) was polymerized. The sulfonic...
A water-soluble negative sulfonic propyl ether β-CD polymer (SPE-β-CDP) to be used as chiral selector in capillary electrophoresis (CE) was polymerized. The sulfonic substitution degree of each β-CD in SPE-β-CDP was statistically homogenized. The only one negative peak in electrophoretogram with indirect ultraviolate method proved its uniformity of electrophoretic behavior. There were 7.12 sulfonic substitution in β-CD unit and 164 μmole β-CD units in each gram of SPE-β-CDP, which corresponded a molecular weight of 7000 or more. Compared with monomer, SPE-β-CDP was lower effect on electrical current of CE, indicating a high concentration of SPE-β-CDP could be added. Its separation ability was verified by 12 chiral drugs. SPE-β-CDP also showed advantages of good water solubility, easy preparation and recovery to reduce the overall cost. However, five of 12 chiral drugs were hardly to be fully separated which was normal for any kind of chiral selector. A newly adjustable gravity mediated capillary electrophoresis (AGM-CE) technology was proposed and combined with SPE-β-CDP to enhance the chiral separation efficiencies of propranolol, salbutamol, omeprazole, ofloxacin and phenoxybenzamine which were markedly improved to 3.02, 1.17, 7.63, 4.14, and 2.81, respectively. Furthermore, its gradient mode (AGMg-CE) was also used to improve resolution through utilizing the zero mobility point, at which the effective apparent mobility of one racemate was zero. Resolutions of five chiral drugs were significantly improved, especially resolution of carvedilol changed from 0.43 to 1.0. These indicated SPE-β-CDP as chiral selector, AGM-CE and AGMg-CE as new CE technologies had a great potential in chiral separation.
Topics: Stereoisomerism; Electrophoresis, Capillary; Ethers; Water; Hydrogen-Ion Concentration
PubMed: 37827633
DOI: 10.1016/j.aca.2023.341781 -
JCEM Case Reports Mar 2024A 73-year-old man was found to have a 2-cm lipid-poor right adrenal incidentaloma on computed tomography imaging for hematuria. Twenty-four-hour urine metanephrine was...
A 73-year-old man was found to have a 2-cm lipid-poor right adrenal incidentaloma on computed tomography imaging for hematuria. Twenty-four-hour urine metanephrine was 1.1-fold elevated, then normal on repeat measurement. Paired with the second urine collection, plasma metanephrine measured by liquid chromatography tandem mass spectrometry after a 30-minute supine rest was 3.3-fold elevated. Plasma normetanephrine was 1.2-fold elevated. The 24-hour urine catecholamines and normetanephrine, measured twice, were normal. He received low-dose phenoxybenzamine and underwent successful resection of right pheochromocytoma. Postoperatively, both plasma metanephrine and normetanephrine levels normalized, using an age-appropriate upper reference limit for plasma normetanephrine. Patients who harbor small lipid-poor adrenal incidentalomas have a relatively high risk (>5%) of having pheochromocytoma, indistinguishable from adenomas or carcinomas on computed tomography scan. In such cases when 24-hour urine fractionated metanephrines are normal, plasma free metanephrines measured by liquid chromatography tandem mass spectrometry under optimal sampling conditions that are 2-fold or more elevated confirm the diagnosis of pheochromocytoma. Preoperative alpha blockade followed by surgical resection is then appropriate, rather than continued monitoring with repeat urine measurements.
PubMed: 38487512
DOI: 10.1210/jcemcr/luae035 -
Annals of the Royal College of Surgeons... Feb 2024There is wide variability in the perioperative management of phaeochromocytoma and paraganglioma (PPGL) in different centres. This study aimed to summarise the...
INTRODUCTION
There is wide variability in the perioperative management of phaeochromocytoma and paraganglioma (PPGL) in different centres. This study aimed to summarise the management of PPGLs as reported in the United Kingdom Registry for Endocrine and Thyroid Surgery (UKRETS) database and to determine current perioperative management of PPGLs by surveying UK clinicians.
METHODS
Data recorded on UKRETS from 2005 to 2021 were subjected to descriptive analyses. British Association of Endocrine and Thyroid Surgeons members were invited to participate in an open survey relating to the perioperative management of patients with PPGLs.
RESULTS
A total of 2,007 operations for PPGL from 49 participating centres were included. The median annual workload in each centre was four cases. Operations were performed predominantly laparoscopically (69%). The median length of stay (4 days) was the same in groups of surgeons stratified by volume. The survey had 29 respondents from 22 centres across the UK, and a formal protocol for perioperative management exists in 48% of the centres. Phenoxybenzamine (72%) was preferred for alpha-blockade. The practice of admitting patients for optimisation from 1 to 7 days before the day of surgery was common (62%). Central venous pressure and blood glucose monitoring were mentioned as routine intraoperative adjuncts by 72% of the responders.
CONCLUSIONS
There is significant variation in the workload and perioperative management of PPGLs in the UK. This is potentially detrimental to patient outcomes and a consensus document might be beneficial to harmonise practice across the UK.
PubMed: 38362758
DOI: 10.1308/rcsann.2023.0054 -
BMC Cardiovascular Disorders Nov 2023Population-wide, paraganglioma (PGL) is uncommon. The incidence of Takotsubo syndrome (TTS) ranges from 0.5% to 0.9% and also is an exceedingly rare manifestation of...
The simultaneous occurrence of paraganglioma, Takotsubo syndrome, and Markis type I coronary artery ectasia in the same patient is a rare, high-risk clinical syndrome: a case report.
BACKGROUND
Population-wide, paraganglioma (PGL) is uncommon. The incidence of Takotsubo syndrome (TTS) ranges from 0.5% to 0.9% and also is an exceedingly rare manifestation of PGL. Coronary artery ectasia (CAE) is also uncommon, with an incidence ranging from 1.2% to 4.9%. Herein, we present a case of PGL, TTS, and Markis type I CAE that occured in the same patient.
CASE PRESENTATION
A man in his early 40s was admitted to our hospital with a 16-hour history of abdominal colic. Computed tomography and laboratory examination led to the diagnosis of PGL, coronary angiography led to the diagnosis of Markis type I or Chinese type III CAE, and two echocardiographic examinations led to the diagnosis of TTS. When the patient was treated by phenoxybenzamine instead of surgery for the PGL, his blood pressure and glucose level gradually returned to normal. The CAE was treated by thrombolysis, antiplatelet medications, atorvastatin, and myocardial protection therapies. No symptoms of PGL, CAE, or TTS were seen during a 6-month follow-up, and the patient had an excellent quality of life. We confirmed that phenoxybenzamine was the cause of the TTS because paradoxical systolic motion of the apex, inferior wall, left ventricular anterior wall, and interventricular septum were similarly recovered when the PGL was treated by phenoxybenzamine.
CONCLUSIONS
To raise awareness of this illness and prevent misdiagnosis, we have herein presented a case of TTS that was brought on by PGL with Markis type I CAE for clinicians' reference. In addition, in clinical practice, we should consider the possibility of a concomitant coronary artery disease even if the TTS is caused by a PGL-induced catecholamine surge.
Topics: Humans; Male; Coronary Aneurysm; Coronary Angiography; Coronary Vessels; Dilatation, Pathologic; Phenoxybenzamine; Quality of Life; Risk Factors; Syndrome; Takotsubo Cardiomyopathy; Vascular Diseases; Adult
PubMed: 37924047
DOI: 10.1186/s12872-023-03577-1