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Acta Dermatovenerologica Croatica : ADC Aug 2020Dear Editor, Cutaneous leiomyomas (CL) are rare, benign smooth muscle tumors of the skin (1). There are 3 subtypes with different origins and histopathologic features:...
Dear Editor, Cutaneous leiomyomas (CL) are rare, benign smooth muscle tumors of the skin (1). There are 3 subtypes with different origins and histopathologic features: piloleiomyoma, genital leiomyoma, and angioleiomyoma (2). Pilar leiomyoma is the most common subtype originating from arrector pili muscles of pilosebaceous unit. It presents as painful solitary or multiple papulonodules (2,3). A 30-year-old woman presented to our outpatient clinic with numerous painless, itchy papules on her gluteal region that had been present for 10 years. Dermatologic examination revealed red-brown, smooth, grouped papulonodules on bilateral gluteal regions (Figure 1). These lesions had appeared after intramuscular injections and had increased in number. Family history was unremarkable. A punch biopsy was performed with pre-diagnoses of keloid and tumoral infiltration. Histopathologic examination showed neoplastic infiltration with large bundles of spindle-like smooth muscle cells with acidophilic cytoplasm under epidermis (Figure 2). Neoplastic cells were stained by smooth muscle markers actin and caldesmon (Figure 3). Based on the clinical and histopathological findings the diagnosis of pilar leiomyoma was established. Pelvic and renal ultrasonographic examinations were normal. The patient's lesions were asymptomatic except for mild itching and she is currently in follow-up without any treatment. Pilar leiomyomas mostly manifest around the ages of 10 to 30 and are located on the trunk and extensor surfaces of the extremities. Lesions are firm, red-brown or skin-colored papulonodules with diameters varying from several mm to 2 cm (2). Differential diagnosis includes dermatofibroma, neurofibroma, smooth muscle hamartoma, neuroma, adnexal tumors, and painful papulonodular lesions such as glomus tumor (1,2). Our case clinically resembled keloid with red-brown, stiff nodules with epidermal thinning. In the literature, a patient with cutaneous pilar leiomyoma was diagnosed with eruptive keloid and treated with cryotherapy and intralesional steroid injections before histopathologic verification of pilar leiomyoma. He had multiple painless, red-purple papulonodules on the chest and arms (3). The case of a 53-year-old man with a history of multiple firm and painful lesions on the back showing segmental distribution and diagnosed with keloid-like leiomyoma was also reported (4). CL should be considered in the differential diagnosis of keloid-like lesions with atypical location and that are resistant to treatment. Cutaneous leiomyomas have different clinical presentations and many differential diagnoses, but CL can be diagnosed by histopathological examination. In all CLs, histopathologic examination shows bundles of spindle-shaped smooth muscle cells with eosinophilic cytoplasm, a cigarette-like nucleus, and a perinuclear halo. Smooth muscle markers actin and desmin are routinely positive. Histopathologic examination in our case also revealed bundles of spindle-like smooth muscle cells with large acidophilic cytoplasm; smooth muscle markers actin and caldesmon were positive. While solitary lesions are frequently sporadic cases, multiple lesions may be related to hereditary conditions such as Reed's syndrome (multiple cutaneous and uterine leiomyomatosis), hereditary leiomyomatosis, and renal cell cancer (2). These two hereditary conditions have been reported to be associated with a heterozygous germline mutation in fumarate hydratase gene (4). Our patient was considered a sporadic case due to lack of family history and uterine leiomyoma and normal renal ultrasonography. Treatment of CL depends on the number of lesions and presence of symptoms (1). Surgical excision is the gold standard in the treatment of solitary and self-limiting lesions (2). However, recurrence can be more commonly observed in patients with multiple lesions (1). Drugs targeting smooth muscle contraction such as nifedipine, nitroglycerin, and phenoxybenzamine are recommended for pain management. Methods such as cryotherapy and carbon dioxide laser ablation have been tested but their efficacy was found to be limited (1,2). In our patient, lesions were asymptomatic and few in number; we thus suggested follow-up without any treatment. CL are rare benign smooth muscle tumors of the skin. They are difficult to diagnose by clinical evaluation, but the diagnosis can be established by histopathologic examination. In patients with atypical keloid-like papulonodular lesions like our patient, pilar leiomyoma should be considered and histopathologic examination should be performed for the diagnosis.
Topics: Adult; Biopsy; Diagnosis, Differential; Female; Humans; Keloid; Leiomyoma; Male; Middle Aged; Skin Neoplasms
PubMed: 32876039
DOI: No ID Found -
Journal of Clinical Medicine Dec 2022Perioperative hemodynamic instability is one of the most common adverse events in patients undergoing adrenalectomy for pheochromocytoma. The aim of this study was to...
BACKGROUND
Perioperative hemodynamic instability is one of the most common adverse events in patients undergoing adrenalectomy for pheochromocytoma. The aim of this study was to analyze the impact of perioperative severe hemodynamic instability.
METHODS
We present a retrospective, single-center analysis in a major tertiary hospital of all consecutive patients undergoing elective adrenalectomy from 2005 to 2019 for pheochromocytoma. Severe perioperative hypertension and hypotension were evaluated, defined as changes in blood pressure larger than 30% of the preoperative patient-specific mean arterial pressure (MAP).
RESULTS
Unilateral adrenalectomy was performed in 67 patients. Intraoperative episodes of hemodynamic instability occurred in 97% of all patients ( = 65), severe hypertension occurred in 24 patients (36%), and severe hypotensive episodes occurred in 62 patients (93%). Patients with more than five severe hypotensive episodes ( = 29) received higher preoperative alpha-adrenergic blockades (phenoxybenzamine 51 ± 50 mg d vs. 29 ± 27 mg d; = 0.023) and had a longer mean ICU stay (39.6 ± 41.5 h vs. 20.6 ± 19.1 h, = 0.015).
CONCLUSION
Intraoperative hypotensive, rather than hypertensive, episodes occurred during adrenalectomy. The occurrence of more than five hypotensive episodes correlated well with a significantly longer hospital stay and ICU time.
PubMed: 36556087
DOI: 10.3390/jcm11247471 -
Pharmacology Research & Perspectives Aug 2020α1-adrenoceptor antagonists are widely used for hypertension (eg, doxazosin) and benign prostatic hypertrophy (BPH, eg, tamsulosin). Some antidepressants and...
α1-adrenoceptor antagonists are widely used for hypertension (eg, doxazosin) and benign prostatic hypertrophy (BPH, eg, tamsulosin). Some antidepressants and antipsychotics have been reported to have α1 affinity. This study examined 101 clinical drugs and laboratory compounds to build a comprehensive understanding of α1-adrenoceptor subtype affinity and selectivity. [3H]prazosin whole-cell binding was conducted in CHO cells stably expressing either the full-length human α1A, α1B, or α1D-adrenoceptor. As expected, doxazosin was a high-affinity nonselective α1-antagonist although other compounds (eg, cyclazosin, 3-MPPI, and ARC239) had higher affinities. Several highly α1A-selective antagonists were confirmed (SNAP5089 had over 1700-fold α1A selectivity). Despite all compounds demonstrating α1 affinity, only BMY7378 had α1D selectivity and no α1B-selective compounds were identified. Phenoxybenzamine (used in pheochromocytoma) and dibenamine had two-component-binding inhibition curves at all three receptors. Incubation with sodium thiosulfate abolished the high-affinity component suggesting this part is receptor mediated. Drugs used for hypertension and BPH had very similar α1A/α1B/α1D-adrenoceptor pharmacological profiles. Selective serotonin reuptake inhibitors (antidepressants) had poor α1-adrenoceptor affinity. Several tricyclic antidepressants (eg, amitriptyline) and antipsychotics (eg, chlorpromazine and risperidone) had high α1-adrenoceptor affinities, similar to, or higher than, α blockers prescribed for hypertension and BPH, whereas others had poor α1 affinity (eg, protriptyline, sulpiride, amisulpiride, and olanzapine). The addition of α blockers for the management of hypertension or BPH in people already taking tricyclic antidepressants and certain antipsychotics may not be beneficial. Awareness of the α-blocking potential of different antipsychotics may affect the choice of drug for those with delirium where additional hypotension (eg, in sepsis) may be detrimental.
Topics: Adrenergic alpha-Antagonists; Animals; Antidepressive Agents; Antipsychotic Agents; CHO Cells; Cricetulus; Humans; Receptors, Adrenergic, alpha-1
PubMed: 32608144
DOI: 10.1002/prp2.602 -
Comparative Biochemistry and... Jul 2020The role of endothelium in the electrical-field stimulation (EFS)-induced contractions of Chelonoidis carbonaria aorta was investigated. Contractions were evaluated in...
The role of endothelium in the electrical-field stimulation (EFS)-induced contractions of Chelonoidis carbonaria aorta was investigated. Contractions were evaluated in the presence and absence of L-NAME (100 μM), tetrodotoxin (1 μM), phentolamine (10 and 100 μM), phenoxybenzamine (1 and 10 μM), prazosin (100 μM), idazoxan (100 μM), atropine (10 μM), D-tubocurarine (10 μM) or indomethacin (10 μM). EFS-induced contraction was also carried out in endothelium-denuded rings. EFS-induced contraction was investigated by the sandwich assay. Concentration curves to endothelin-1 (0.1-100 nM) and U46619 (0.001-100 μM) were also constructed to calculate both Emax and EC. EFS at 16 Hz contracted Chelonoidis aorta, which was almost abolished by the endothelium removal. The addition of L-NAME increased the EFS response (2.0 ± 0.4 and 8.3 ± 1.9 mN). In L-NAME treated aortic rings, tetrodotoxin did not change the EFS-response (5.1 ± 1.8 and 4.9 ± 1.7 mN). Indomethacin, atropine and d-tubucurarine also did not affect the EFS-response. Phentolamine at 10 μM did not change the EFS-induced contraction; however, at 100 μM, reduced it (3.9 ± 1 and 1.9 ± 0.3 mN). Prazosin and idazoxan did not change EFS-induced contractions. Phenoxybenzamine at 1 μM reduced by 76% (9.6 ± 3.4 and 2.3 ± 0.8 mN) and at 10 μM by 90% the EFS response. Immunohistochemistry identified tyrosine hydroxylase in the endothelium and brain, whereas S100 protein was found only in brain. In conclusion, endothelium modulates EFS-induced contractions in Chelonoidis aortic rings and this modulation may be due to endothelium-derived catecholamines, possibly dopamine.
Topics: Animals; Aorta; Dopamine; Electric Stimulation; Endothelium; Female; Male; Muscle Contraction; Turtles
PubMed: 32289528
DOI: 10.1016/j.cbpc.2020.108763 -
Endocrinology, Diabetes & Metabolism... Mar 2022An adrenocorticotropic hormone (ACTH)-producing pheochromocytoma (PCC)/paraganglioma is the cause of ectopic Cushing's syndrome (CS) in 5.2% of cases reported in the...
SUMMARY
An adrenocorticotropic hormone (ACTH)-producing pheochromocytoma (PCC)/paraganglioma is the cause of ectopic Cushing's syndrome (CS) in 5.2% of cases reported in the literature. We present a previously healthy 43-year-old woman admitted to our hospital with cushingoid features and hypertensive urgency (blood pressure = 200/120 mmHg). Her 24-h urinary free cortisol was >4270 nmol/day (reference range (RR) = 100-380 nmol/day) with a plasma ACTH of 91.5 pmol/L (RR: 2.0-11.5 pmol/L). Twenty-four-hour urinary metanephrines were increased by 30-fold. Whole-body CT demonstrated a 3.7-cm left adrenal mass with a normal-appearing right adrenal gland. Sellar MRI showed a 5-mm sellar lesion. MIBG scan revealed intense uptake only in the left adrenal mass. She was managed pre-operatively with ketoconazole and phenoxybenzamine and underwent an uneventful left laparoscopic adrenalectomy, which resulted in biochemical resolution of her hypercortisolemia and catecholamine excess. Histology demonstrated a PCC (Grading System for Adrenal Pheochromocytoma and Paraganglioma score 5) with positive ACTH staining by immunohistochemistry. A PCC gene panel showed no mutations and there has been no evidence of recurrence at 24 months. This case highlights the difficult nature of localizing the source of CS in the setting of a co-existing PCC and sellar mass.
LEARNING POINTS
An adrenocorticotropic hormone (ACTH)-producing pheochromocytoma (PCC) is an important item to be considered in all patients presenting with ectopic Cushing's syndrome (CS). In exceptionally rare cases, patients with ectopic CS may present with multiple lesions, and a systematic approach considering all potential sources is crucial to avoid misdiagnosis. CS with a large adrenal mass but lacking contralateral adrenal atrophy should raise suspicion of an ACTH-dependent process. In patients with clinical suspicion of PCC, clinicians should be mindful of the use of steroids and beta-blockers without appropriate alpha blockade as they may precipitate an adrenergic crisis.
PubMed: 35319487
DOI: 10.1530/EDM-21-0189 -
Current Diabetes Reviews 2022Diabetes mellitus (DM) comprises differential clinical phenotypes ranging from rare monogenic to common polygenic forms, such as type 1 (T1DM), type 2 (T2DM), and...
INTRODUCTION
Diabetes mellitus (DM) comprises differential clinical phenotypes ranging from rare monogenic to common polygenic forms, such as type 1 (T1DM), type 2 (T2DM), and gestational diabetes, which are associated with cardiovascular complications. Also, the high- -risk prediabetic state is rising worldwide, suggesting the urgent need for early personalized strategies to prevent and treat a hyperglycemic state.
OBJECTIVE
We aim to discuss the advantages and challenges of Network Medicine approaches in clarifying disease-specific molecular pathways, which may open novel ways for repurposing approved drugs to reach diabetes precision medicine and personalized therapy.
CONCLUSION
The interactome or protein-protein interactions (PPIs) is a useful tool to identify subtle molecular differences between precise diabetic phenotypes and predict putative novel drugs. Despite being previously unappreciated as T2DM determinants, the growth factor receptor-bound protein 14 (GRB14), calmodulin 2 (CALM2), and protein kinase C-alpha (PRKCA) might have a relevant role in disease pathogenesis. Besides, in silico platforms have suggested that diflunisal, nabumetone, niflumic acid, and valdecoxib may be suitable for the treatment of T1DM; phenoxybenzamine and idazoxan for the treatment of T2DM by improving insulin secretion; and hydroxychloroquine reduce the risk of coronary heart disease (CHD) by counteracting inflammation. Network medicine has the potential to improve precision medicine in diabetes care and enhance personalized therapy. However, only randomized clinical trials will confirm the clinical utility of network- oriented biomarkers and drugs in the management of DM.
Topics: Biomarkers; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Phenotype; Precision Medicine
PubMed: 34951369
DOI: 10.2174/1573399818666211222164400 -
International Journal of General... 2021Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors of the head and neck. This study aimed to investigate the crucial genes and regulatory networks...
PURPOSE
Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors of the head and neck. This study aimed to investigate the crucial genes and regulatory networks involved in the carcinogenesis of NPC using a bioinformatics approach.
METHODS
Five mRNA and two miRNA expression datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and miRNAs (DEMs) between NPC and normal samples were analyzed using R software. The WebGestalt tool was used for functional enrichment analysis, and protein-protein interaction (PPI) network analysis of DEGs was performed using STRING database. Transcription factors (TFs) were predicted using TRRUST and Transcriptional Regulatory Element Database (TRED). Kinases were identified using X2Kgui. The miRNAs of DEGs were predicted using miRWalk database. A kinase-TF-mRNA-miRNA integrated network was constructed, and hub nodes were selected. The hub genes were validated using NPC datasets from the GEO and Oncomine databases. Finally, candidate small-molecule agents were predicted using CMap.
RESULTS
A total of 122 DEGs and 44 DEMs were identified. DEGs were associated with the immune response, leukocyte activation, endoplasmic reticulum stress in GO analysis, and the NF-κB signaling pathway in KEGG analysis. Four significant modules were identified using PPI network analysis. Subsequently, 26 TFs, 73 kinases, and 2499 miRNAs were predicted. The predicted miRNAs were cross-referenced with DEMs, and seven overlapping miRNAs were selected. In the kinase-TF-mRNA-miRNA integrated network, eight genes (PTGS2, FN1, MMP1, PLAU, MMP3, CD19, BMP2, and PIGR) were identified as hub genes. Hub genes were validated with consistent results, indicating the reliability of our findings. Finally, six candidate small-molecule agents (phenoxybenzamine, luteolin, thioguanosine, reserpine, blebbistatin, and camptothecin) were predicted.
CONCLUSION
We identified DEGs and an NPC regulatory network involving kinases, TFs, mRNAs, and miRNAs, which might provide promising insight into the pathogenesis, treatment, and prognosis of NPC.
PubMed: 34744455
DOI: 10.2147/IJGM.S327657 -
Journal of Feline Medicine and Surgery Dec 2021The aim of this study was to determine if male cats treated with 7 days of prazosin following relief of urethral obstruction (UO) experienced decreased rates of...
OBJECTIVES
The aim of this study was to determine if male cats treated with 7 days of prazosin following relief of urethral obstruction (UO) experienced decreased rates of recurrent urethral obstruction (rUO) within 30 days vs those treated with 7 days of placebo.
METHODS
All castrated male cats presenting for the first time with UO from May 2014 to August 2017 were eligible for enrollment. Exclusion criteria included the administration of medications or passage of a urinary catheter prior to referral, the presence of heart disease or hypertension requiring medication, prior treatment with glucocorticoids, non-steroidal anti-inflammatory medications, prazosin or phenoxybenzamine, or radiographic identification of cystoliths. Cats were treated with standardized anesthetic and analgesic protocols, standardized indwelling urinary catheter management, and were hospitalized for care. A random numbers table was generated prior to study initiation and cats were randomized to receive either prazosin (0.5 mg PO q12h for 7 days) or placebo in a blinded fashion. A 30-day follow-up with owners via telephone was performed to identify the rate of rUO. Cats that did not receive the full course of study medication were removed from the analysis. The study was unblinded at the end of data collection.
RESULTS
Eighty cats were enrolled and 65 cats completed the study; 12 were excluded because they did not receive the study medication. Sixteen of 65 cats experienced rUO (25%). Of the 16 cats experiencing rUO, five received placebo (n = 5/28 [18%]) and 11 received prazosin (n = 11/37 [30%]). Ten of the cats that experienced rUO reblocked while still hospitalized. There was no significant difference in frequency of rUO in cats treated with prazosin vs placebo ( = 0.27).
CONCLUSIONS AND RELEVANCE
Prazosin administered at 0.5 mg PO q12h did not decrease the rate of rUO in this population of obstructed male cats vs placebo. These results further support evidence suggesting that prazosin may not be beneficial in prevention of feline rUO.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cat Diseases; Cats; Male; Prazosin; Recurrence; Urethral Obstruction
PubMed: 33749375
DOI: 10.1177/1098612X211001283 -
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 Connections May 2022Patients with pheochromocytoma and paraganglioma (PPGL) are treated with α-adrenoceptor antagonists to improve peroperative hemodynamics. However, preoperative blood...
Patients with pheochromocytoma and paraganglioma (PPGL) are treated with α-adrenoceptor antagonists to improve peroperative hemodynamics. However, preoperative blood pressure targets differ between institutions. We retrospectively compared per- and postoperative hemodynamics in 30 patients with PPGL that were pretreated with phenoxybenzamine aiming at different blood pressure targets at two separate endocrine departments. All patients were subsequently undergoing laparoscopic surgery at Department of Urology, Herlev University hospital. Fourteen patients were treated targeting to symptomatic and significant orthostatic hypotension and 16 patients to a seated blood pressure below 130/80 mmHg. As a control group, we included 34 patients undergoing laparoscopic adrenalectomy for other reasons. The group titrated to orthostatic hypotension required a higher dose of phenoxybenzamine to achieve the blood pressure target. This group had less intraoperative systolic and diastolic blood pressure fluctuation (Mann-Whitney U test; P < 0.05) and less periods with heart rate above 100 b.p.m. (Mann-Whitney U test; P = 0.04) as compared to the group with a preoperative blood pressure target below 130/80 mmHg. Peroperative use of intravenous fluids were similar between the two groups, but postoperatively more intravenous fluids were administered in the group with a target of ortostatism. Overall, the control group was more hemodynamic stable as compared to either group treated for PPGL. We conclude that phenoxybenzamine pretreatment targeting ortostatic hypotension may improve peroperative hemodynamic stability but causes a higher postoperative requirement for intravenous fluids. Overall, PPGL surgery is related to greater hemodynamic instability compared to adrenalectomy for other reasons.
PubMed: 35358058
DOI: 10.1530/EC-21-0539