-
Journal of Vascular Surgery Cases and... Dec 2023We present a case of medication-induced priapism that was refractory to conventional urologic methods and required treatment with a caverno-saphenous bypass. The patient...
We present a case of medication-induced priapism that was refractory to conventional urologic methods and required treatment with a caverno-saphenous bypass. The patient had been misusing an injectable erectile dysfunction medication consisting of alprostadil, papaverine, and phentolamine (Trimix), resulting in multiple episodes of priapism. His initial episodes of priapism were successfully treated with the traditional urologic algorithm, including phenylephrine, aspiration, and distal shunting. However, due to his continued medication misuse, these became ineffective, requiring proximal shunt surgery. Priapism requiring an extra-anatomic bypass is exceedingly rare. Following our proximal shunt surgery, he maintained partial sexual function, and his bypass remained patent.
PubMed: 38106342
DOI: 10.1016/j.jvscit.2023.101359 -
Analytical and Bioanalytical Chemistry Jan 2024The opium poppy (Papaver somniferum) is a global commercial crop that has been historically valued for both medicinal and culinary purposes. Naturally occurring opium...
Comparison of direct analysis in real-time mass spectrometry, atmospheric solids analysis probe-mass spectrometry, and ion mobility spectrometry for ensuring food safety by rapid screening of poppy seeds.
The opium poppy (Papaver somniferum) is a global commercial crop that has been historically valued for both medicinal and culinary purposes. Naturally occurring opium alkaloids including morphine, codeine, thebaine, noscapine, and papaverine are found primarily in the latex produced by the plant. If the plant is allowed to fully mature, poppy seeds that do not contain the opium alkaloids will form within the pods and may be used in the food industry. It is possible for the seeds to become contaminated with alkaloids by the latex during harvesting, posing a potential health risk for consumers. In the USA, there have been more than 600 reported adverse events including 19 fatalities that may be linked to the consumption of a contaminated poppy-containing product such as home-brewed poppy seed tea. Unwashed poppy seeds and pods may be purchased over the Internet and shipped worldwide. The Forensic Chemistry Center, US Food and Drug Administration (FDA) has evaluated several mass spectrometers (MS) capable of rapid screening to be used for high-throughput analysis of samples such as poppy seeds. These include a direct analysis in real-time (DART) ambient ionization source coupled to a single-quadrupole MS, an atmospheric solids analysis probe (ASAP) ionization source coupled to the same MS, and ion mobility spectrometers (IMS). These instruments have been used to analyze 17 poppy seed samples for the presence of alkaloids, and the results were compared to data obtained using liquid chromatography with mass spectral detection (LC-MS/MS). Results from the 17 poppy seed samples indicate that the DART-MS, ASAP-MS, and IMS devices detect many of the same alkaloids confirmed during the LC-MS/MS analyses, although both the false-positive and false-negative rates are higher, possibly due to the non-homogeneity of the samples and the lack of chromatographic separation.
Topics: Papaver; Opium; Chromatography, Liquid; Ion Mobility Spectrometry; Latex; Tandem Mass Spectrometry; Morphine; Alkaloids; Seeds
PubMed: 37999721
DOI: 10.1007/s00216-023-05042-6 -
The Journal of Sexual Medicine Dec 2023Phosphodiesterase type 5 (PDE5) inhibitor labeling states that these agents should not be used in conjunction with other erectogenic medications for fear of priapism...
BACKGROUND
Phosphodiesterase type 5 (PDE5) inhibitor labeling states that these agents should not be used in conjunction with other erectogenic medications for fear of priapism occurring.
AIM
We explored the risk of priapism and prolonged erections in men in our post-radical prostatectomy (RP) penile injection program who were using regular PDE5 inhibitor and intracavernosal injections (ICIs) as part of their rehabilitation program.
METHODS
The study cohort included men on penile injection therapy who (1) were taking tadalafil 5 mg daily or taking sildenafil 25 mg on noninjection days, (2) had an RP, (3) were using their respective PDE5 inhibitor regularly at the time of penile injection training, and (4) complied with the program instructions regarding penile injection use. Demographics, comorbidity details, PDE5 inhibitor dose and utilization, and injection dose and utilization data were collected. All patients underwent in-office injection training and used trimix (papaverine/phentolamine/prostaglandin E1) as the intracavernosal medication.
OUTCOMES
Priapism was defined as a patient self-reported penetration hardness erection ≥4 hours in duration, while prolonged erection was defined as a penetration hardness erection lasting ≥2 hours.
RESULTS
A total of 112 tadalafil users and 364 sildenafil users were compared. Mean age and duration post-RP were 62 ± 14 years and 5.2 ± 12 months, respectively, and there was no difference between tadalafil and sildenafil groups. The mean trimix dose was tadalafil 24 ± 24 units and sildenafil 31 ± 37 units (P < .05). Priapism occurred in 2 (1.7%) of 112 tadalafil users and 5 (1.4%) of 364 sildenafil users (P = .47). Excluding those men experiencing priapism on any occasion, those with any reported penetration hardness erection lasting ≥2 hours were 7 (6.3%) of 112 tadalafil users and 12 (3.3%) of 364 sildenafil users (P < .01). A total of 53% of these prolonged erections occurred within the first 6 injections at home (no difference between tadalafil and sildenafil groups).
CLINICAL IMPLICATIONS
We emphasize the need for continued monitoring and education on proper injection techniques to minimize the risk of adverse events in ICI and PDE5 inhibitor combination therapy.
STRENGTHS & LIMITATIONS
This study has a relatively large patient population with a considerable follow-up time. Additionally, the rigorous training, education, and monitoring of the participants, as well as the use of formal definitions for priapism and prolonged erections, enhances the accuracy and reliability of the results. However, there are some limitations, such as social desirability, confounding factors, and recall bias.
CONCLUSION
There is no significant difference in the incidence of priapism in an ICI program in which men combine ICI with tadalafil or sildenafil. However, tadalafil patients had a higher rate of prolonged erections, which was found to occur mostly early during the titration phase.
Topics: Male; Humans; Middle Aged; Aged; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate; Tadalafil; Erectile Dysfunction; Priapism; Reproducibility of Results; Piperazines; Purines; Penile Erection; Prostatectomy
PubMed: 37973393
DOI: 10.1093/jsxmed/qdad144 -
Pharmacoepidemiology and Drug Safety Jan 2024To explore the differences of priapism events among a diverse cohort taking erectogenic medicines (i.e., phosphodiesterase type 5 inhibitors [PDE5i] and intracavernousal...
PURPOSE
To explore the differences of priapism events among a diverse cohort taking erectogenic medicines (i.e., phosphodiesterase type 5 inhibitors [PDE5i] and intracavernousal drugs).
METHODS
We queried the World Health Organization global database of individual case safety reports (VigiBase) for records of the adverse drug reactions (ADR) with sildenafil, tadalafil, avanafil, vardenafil, papaverine, and alprostadil. Disproportionality analyses (case/non-case approach) were performed to assess the reporting odds ratio (ROR) of priapism reporting in PDE5i consumers compared to intracavernousal drug recipients.
RESULTS
From a total of 133 819 ADR events for erectogenic medications, 632 were priapism (PDE5is: n = 550, 0.41%; intracavernousal drugs: n = 82, 9.92%). Priapism disproportionality signals from intracavernousal drugs were 25 times stronger than PDE5is (ROR = 34.7; confidence interval [CI] 95%: 27.12-43.94 vs. ROR = 1.38; 95% CI: 1.24-1.54). For all PDE5i agents, the 12-17 years age group had the highest ROR (9.49, 95% CI: 3.76-19.93) followed by 2-11 years (4.31, 95% CI: 1.57-9.4). Disproportionality signals for consumers under 18 for both all PDE5is as a whole (ROR = 4.57, 95% CI: 2.48-7.73) and sildenafil (ROR = 4.89, 95% CI: 2.51-8.62) were stronger than individuals 18 or older (ROR = 1.06, 95% CI: 0.93-1.21 and ROR = 1.08, 95% CI: 0.91-1.26, respectively).
CONCLUSIONS
PDE5i use shows disproportionate priapism signals which are higher in young patients.
Topics: Male; Humans; Child, Preschool; Child; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate; Priapism; Erectile Dysfunction; Tadalafil; Drug-Related Side Effects and Adverse Reactions
PubMed: 37909414
DOI: 10.1002/pds.5721 -
Journal of Neurosurgery Feb 2024Direct cerebral revascularization is considered as one of the most technically challenging operations in neurosurgery. Technical errors are often not identified during...
OBJECTIVE
Direct cerebral revascularization is considered as one of the most technically challenging operations in neurosurgery. Technical errors are often not identified during the case, but only after the recirculation stage, making management crucial at that time of the procedure. In this study, the authors sought to describe troubleshooting of the technical errors encountered in initially failed bypass cases.
METHODS
A retrospective analysis describing a single-surgeon, single-institution experience between 2014 and 2021 was performed, based on operative reports and videos, including a 30-day follow-up period. Initially failed bypass was defined if the bypass was not patent or had a significant leak after recirculation, irrespective of the final result.
RESULTS
One hundred thirty-eight bypass cases were reviewed for complex aneurysms (n = 49), moyamoya disease (n = 59), and atherosclerosis (n = 30). Fifty-one initially failed anastomoses were identified; 43 of these were the result of a technical error. Etiologies of these failed anastomoses included a clot (n = 14), vessel kinking (n = 4), spasm (n = 5), suture-related cause (n = 5), inappropriate donor or recipient (n = 3), or lack of demand (n = 8). A major leak was attributed to an uncoagulated side branch (n = 4), vessel injury due to suture/clip placement (n = 1), or inadequate suture line coverage (n = 7). Thirty-seven (86%) of 43 cases were troubleshot successfully, as salvage maneuvers included papaverine vessel massage, donor repositioning, re-anastomosis for occlusion in select cases, local hemostatic agents, and suturing or coagulating side branches in a leak. Thirty-day follow-up revealed similar rates of patency between successfully troubleshot patients (35/37) and the rest of the cases (80/87, p = 0.6).
CONCLUSIONS
Three major patterns of a noncompatible bypass were found: a major leak, an acute occlusion, or a delayed occlusion. Based on the authors' experience, salvage strategies proved successful, showing an eventual high patency rate. The authors suggest a gradual, structured algorithm to address this stage in surgery that may contribute specifically to cerebrovascular neurosurgeons at the beginning of their careers.
Topics: Humans; Cerebral Revascularization; Retrospective Studies; Moyamoya Disease; Intracranial Aneurysm; Anastomosis, Surgical
PubMed: 37877963
DOI: 10.3171/2023.6.JNS2356 -
Heliyon Oct 2023Radial artery (RA) is a popular coronary artery bypass grafting (CABG) conduit. The challenging issue is vasospasm. A few studies are available on histopathological...
BACKGROUND AND AIMS
Radial artery (RA) is a popular coronary artery bypass grafting (CABG) conduit. The challenging issue is vasospasm. A few studies are available on histopathological differences between RA's proximal and distal ends. This study aims to compare histopathological features of the proximal and distal end of RA to find the best technique for anastomosis.
METHODS
In this matched case-control study, 80 patients were included who underwent CABG and used RA as a graft. Ten subjects were excluded. RA was harvested by open technique, and a cocktail of Papaverine, Verapamil, and Nitroglycerine was frequently applied topically. One centimeter of proximal and distal ends of the RA was evaluated considering its Histopathology. Clinical signs of RA graft vasospasm were monitored from harvesting until the post-operative period. Intima, media, and intima-media thickness (IMT) index were compared between the two cohorts.
RESULTS
Vasospasm occurred in 1.41% of patients. The mean intimal thickness in the proximal and distal ends were, respectively, 0.20 (standard deviation [SD] 0.17 mm) vs. 0.31 (SD 0.18 mm) (p < 0.001). The mean media thickness in the distal end was higher than the proximal end (0.98 [SD 0.36] vs. 1.09 [SD 0.37], p = 0.004). IMT index of the proximal and distal ends showed a statistically significant difference (0.22 [SD 0.17] vs. 0.31 [SD 0.19]) (p < 0.001).
CONCLUSION
The overall incidence rate of vasospasm in our study is comparable with other studies using the same cocktail. Proximal RA has a relatively lower medial thickness compared to the distal part, which may induce less vasospasm in CABG patients.
PubMed: 37867848
DOI: 10.1016/j.heliyon.2023.e20873 -
Clinical Toxicology (Philadelphia, Pa.) Sep 2023Poppy seed tea is used for its opioid effects and contains multiple opium alkaloids, including morphine, codeine, papaverine, and thebaine. Animal studies indicate... (Observational Study)
Observational Study
INTRODUCTION
Poppy seed tea is used for its opioid effects and contains multiple opium alkaloids, including morphine, codeine, papaverine, and thebaine. Animal studies indicate thebaine has strychnine-like properties, but there is limited literature describing human thebaine poisoning. We describe a cluster of acute thebaine poisoning in people ingesting tea made using poppy seeds with high thebaine content that entered the Australian food supply chain.
METHODS
This is an observational study of patients poisoned after drinking poppy seed tea. Cases were identified by three prospective toxicovigilance systems: the Emerging Drug Network of Australia collaboration, the New South Wales Prescription, Recreational and Illicit Substance Evaluation program, and the Emerging Drugs Network of Australia Victoria study. We report characteristics of clinical toxicity in cases with reported ingestion of poppy seed tea and analytical confirmation of thebaine exposure.
RESULTS
Forty cases presenting with multi-system toxicity following poppy seed tea ingestion were identified across seven Australian states/territories from November 2022 to January 2023. Blood testing in 23 cases confirmed high thebaine concentrations. All 23 were male (median age 35, range 16-71 years). All patients experienced muscle spasms. Rigidity was described in nine, convulsions in six, while rhabdomyolysis, acute kidney injury, and metabolic acidosis occurred in five patients. There were two cardiac arrests. The thebaine median admission blood concentration was 1.6 mg/L, with a range of 0.1-5.6 mg/L, and was the dominant opium alkaloid in all samples. Convulsions, acute kidney injury, metabolic acidosis, and cardiac arrest were associated with increasing median thebaine concentrations. Four patients were managed in the Intensive Care Unit, with two receiving continuous kidney replacement therapy (one also received intermittent haemodialysis) for kidney injury. There was one death.
CONCLUSIONS
Thebaine toxicity, like strychnine poisoning, resulted in neuromuscular excitation characterized by muscle spasm, rigidity, and convulsions. Severe toxicity, including acute kidney injury, metabolic acidosis, and cardiac arrest, appears dose-dependent.
Topics: Animals; Humans; Male; Adolescent; Young Adult; Adult; Middle Aged; Aged; Female; Thebaine; Papaver; Opium; Prospective Studies; Strychnine; Morphine; Codeine; Seeds; Seizures; Tea; Acute Kidney Injury; Acidosis; Heart Arrest; Victoria
PubMed: 37855308
DOI: 10.1080/15563650.2023.2265053 -
Cardiovascular Revascularization... Mar 2024This prospective cross-sectional study evaluated the correlation between physiological assessment (PA) and minimum lumen area (MLA) by intravascular ultrasound (IVUS)...
BACKGROUND
This prospective cross-sectional study evaluated the correlation between physiological assessment (PA) and minimum lumen area (MLA) by intravascular ultrasound (IVUS) during drug-coated balloon (DCB) treatment for femoropopliteal (FP) diseases.
METHODS
A total of 51 limbs of 44 patients undergoing endovascular treatment with DCB for de novo FP disease were examined from April 2022 to February 2023. PA was conducted at baseline, after balloon dilatation, and after DCB treatment. PA was measured before (pressure ratio; PR) and after vasodilation (peripheral flow fractional flow reserve; pFFR) with the administration of 30 mg papaverine through a guiding catheter. The correlation of PA with percent diameter stenosis (%DS) and MLA was examined, and factors correlated with higher pFFR after balloon dilatation were evaluated in a multivariate analysis.
RESULTS
At baseline, there were correlations between pressure ratio (PR) and %DS (coefficients: 0.641 [p < 0.001]) and between pFFR and %DS (0.666 [p < 0.001]). After balloon dilatation, there was no correlation between PR and %DS (coefficients: 0.33 [p = 0.27]) or between pFFR and %DS (0.41 [p = 0.71]). At baseline, PR and MLA were correlated (coefficients: 0.757 [p < 0.001]) as were pFFR and MLA (0.762 [p < 0.001]). After balloon dilatation, PR and MLA were correlated (coefficients: 0.524 [p < 0.001]) as were pFFR and MLA (0.601 [p < 0.001]). Balloon/EEM ratio, calcification >270°, and chronic total occlusion were associated with pFFR after balloon dilatation.
CONCLUSION
After balloon dilatation, PA was correlated with MLA by IVUS but not with %DS based on angiography.
Topics: Humans; Coronary Angiography; Fractional Flow Reserve, Myocardial; Prospective Studies; Cross-Sectional Studies; Treatment Outcome; Angioplasty, Balloon; Peripheral Arterial Disease; Ultrasonography, Interventional; Femoral Artery; Popliteal Artery
PubMed: 37739885
DOI: 10.1016/j.carrev.2023.09.004 -
Expert Opinion on Therapeutic Targets 2023Drugs targeting mitochondria are emerging as promising antitumor therapeutics in preclinical models. However, a few of these drugs have shown clinical toxicity.... (Review)
Review
INTRODUCTION
Drugs targeting mitochondria are emerging as promising antitumor therapeutics in preclinical models. However, a few of these drugs have shown clinical toxicity. Developing mitochondria-targeted modified natural compounds and US FDA-approved drugs with increased therapeutic index in cancer is discussed as an alternative strategy.
AREAS COVERED
Triphenylphosphonium cation (TPP)-based drugs selectively accumulate in the mitochondria of cancer cells due to their increased negative membrane potential, target the oxidative phosphorylation proteins, inhibit mitochondrial respiration, and inhibit tumor proliferation. TPP-based drugs exert minimal toxic side effects in rodents and humans. These drugs can sensitize radiation and immunotherapies.
EXPERT OPINION
TPP-based drugs targeting the tumor mitochondrial electron transport chain are a new class of oxidative phosphorylation inhibitors with varying antiproliferative and antimetastatic potencies. Some of these TPP-based agents, which are synthesized from naturally occurring molecules and FDA-approved drugs, have been tested in mice and did not show notable toxicity, including neurotoxicity, when used at doses under the maximally tolerated dose. Thus, more effort should be directed toward the clinical translation of TPP-based OXPHOS-inhibiting drugs in cancer prevention and treatment.
Topics: Humans; Mice; Animals; Mitochondria; Oxidative Phosphorylation; Neoplasms; Drug Delivery Systems; Antineoplastic Agents
PubMed: 37736880
DOI: 10.1080/14728222.2023.2261631 -
Molecular Imaging and Biology Jun 2024Tumor hypoxia contributes to aggressive phenotypes and diminished therapeutic responses to radiation therapy (RT) with hypoxic tissue being 3-fold less radiosensitive...
PURPOSE
Tumor hypoxia contributes to aggressive phenotypes and diminished therapeutic responses to radiation therapy (RT) with hypoxic tissue being 3-fold less radiosensitive than normoxic tissue. A major challenge in implementing hypoxic radiosensitizers is the lack of a high-resolution imaging modality that directly quantifies tissue-oxygen. The electron paramagnetic resonance oxygen-imager (EPROI) was used to quantify tumor oxygenation in two murine tumor models: E0771 syngeneic transplant breast cancers and primary p53/MCA soft tissue sarcomas, with the latter autochthonous model better recapitulating the tumor microenvironment in human malignancies. We hypothesized that tumor hypoxia differs between these models. We also aimed to quantify the absolute change in tumor hypoxia induced by the mitochondrial inhibitor papaverine (PPV) and its effect on RT response.
PROCEDURES
Tumor oxygenation was characterized in E0771 and primary p53/MCA sarcomas via EPROI, with the former model also being quantified indirectly via diffuse reflectance spectroscopy (DRS). After confirming PPV's effect on hypoxic fraction (via EPROI), we compared the effect of 0 versus 2 mg/kg PPV prior to 20 Gy on tumor growth delay and survival.
RESULTS
Hypoxic sarcomas were more radioresistant than normoxic sarcomas (p=0.0057, 2-way ANOVA), and high baseline hypoxic fraction was a significant (p=0.0063, Cox Regression Model) hazard in survivability regardless of treatment. Pre-treatment with PPV before RT did not radiosensitize tumors in the sarcoma or E0771 model. In the sarcoma model, EPROI successfully identified baseline hypoxic tumors. DRS quantification of total hemoglobin, saturated hemoglobin, changes in mitochondrial potential and glucose uptake showed no significant difference in E0771 tumors pre- and post-PPV.
CONCLUSION
EPROI provides 3D high-resolution pO quantification; EPR is better suited than DRS to characterize tumor hypoxia. PPV did not radiosensitize E0771 tumors nor p53/MCA sarcomas, which may be related to the complex pattern of vasculature in each tumor. Additionally, understanding model-dependent tumor hypoxia will provide a much-needed foundation for future therapeutic studies with hypoxic radiosensitizers.
Topics: Animals; Tumor Hypoxia; Electron Spin Resonance Spectroscopy; Oxygen; Cell Line, Tumor; Female; Mice; Radiation-Sensitizing Agents; Sarcoma; Radiation Tolerance; Mice, Inbred C57BL
PubMed: 37721686
DOI: 10.1007/s11307-023-01855-0