Simultaneous Occurrence of Germline Mutations of SDHB and TP53 in a Patient with Metastatic Pheochromocytoma

2019 ◽  
Vol 105 (4) ◽  
pp. 991-995
Author(s):  
Ewa Gniado ◽  
Colin P Carracher ◽  
Sona Sharma
Keyword(s):  
Antihypertensive Agents ◽  
Pulmonary Nodules ◽  
Germline Mutations ◽  
Simultaneous Occurrence ◽  
Channel Blockers ◽  
Progression Of Disease ◽  
Plasma Metanephrines ◽  
The Right ◽  
Aggressive Clinical Course ◽  
Tp53 Germline Mutations

Abstract Context We describe a patient with metastatic malignant pheochromocytoma who was found to have germline SDHB and TP53 mutations occurring together. Case Description A 39-year-old male presented with neck pain. Magnetic resonance imaging of the neck revealed a C3 vertebral body collapse and an underlying C3 lesion. Computed tomography (CT) of the thorax, abdomen, and pelvis showed multiple skeletal lesions, a sternal mass, bilateral pulmonary nodules, bilateral adrenal masses, and an aortocaval lymph node conglomerate. He underwent biopsy of the sternal mass, which revealed metastatic pheochromocytoma and subsequent blood work showed serum epinephrine levels of 200 pg/mL (normal 10–200 pg/mL), norepinephrine 28 241 pg/mL (normal 80–520 pg/mL), and dopamine 250 pg/mL (normal 0–20 pg/mL). Genetic testing revealed both SDHB and TP53 germline mutations. He was started on α- and β-blockers and calcium channel blockers to control hypertension and tachycardia. Two months after the diagnosis, a CT of the abdomen and pelvis showed progression of disease, with enlargement of the right adrenal mass as well as the aortocaval conglomeration. His plasma metanephrines were significantly elevated. He was started on systemic chemotherapy with cyclophosphamide, dacarbazine, and vincristine. He required several antihypertensive agents, including metyrosine, to control his blood pressure in preparation for chemotherapy. Conclusion This is the first reported case of simultaneous SDHB and TP53 germline mutations occurring in an individual with a highly aggressive clinical course of pheochromocytoma. We speculate that the simultaneous occurrence of these 2 oncogenic mutations may have led to an aggressive tumor progression.

scholarly journals Left Axis Deviation in Brugada Syndrome: Vectorcardiographic Evaluation during Ajmaline Provocation Testing Reveals Additional Depolarization Abnormalities

2021 ◽  
Vol 22 (2) ◽  
pp. 484
Author(s):  
Martijn H. van der Ree ◽  
Jeroen Vendrik ◽  
Jan A. Kors ◽  
Ahmad S. Amin ◽  
Arthur A. M. Wilde ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Brugada Syndrome ◽  
Right Ventricular Outflow Tract ◽  
Ventricular Outflow Tract ◽  
Conduction Delay ◽  
Channel Blockers ◽  
Axis Deviation ◽  
Provocation Testing ◽  
The Right

Patients with Brugada syndrome (BrS) can show a leftward deviation of the frontal QRS-axis upon provocation with sodium channel blockers. The cause of this axis change is unclear. In this study, we aimed to determine (1) the prevalence of this left axis deviation and (2) to evaluate its cause, using the insights that could be derived from vectorcardiograms. Hence, from a large cohort of patients who underwent ajmaline provocation testing (n = 1430), we selected patients in whom a type-1 BrS-ECG was evoked (n = 345). Depolarization and repolarization parameters were analyzed for reconstructed vectorcardiograms and were compared between patients with and without a >30° leftward axis shift. We found (1) that the prevalence of a left axis deviation during provocation testing was 18% and (2) that this left axis deviation was not explained by terminal conduction slowing in the right ventricular outflow tract (4th QRS-loop quartile: +17 ± 14 ms versus +13 ± 15 ms, nonsignificant) but was associated with a more proximal conduction slowing (1st QRS-loop quartile: +12[8;18] ms versus +8[4;12] ms, p < 0.001 and 3rd QRS-loop quartile: +12 ± 10 ms versus +5 ± 7 ms, p < 0.001). There was no important heterogeneity of the action potential morphology (no difference in the ventricular gradient), but a left axis deviation did result in a discordant repolarization (spatial QRS-T angle: 122[59;147]° versus 44[25;91]°, p < 0.001). Thus, although the development of the type-1 BrS-ECG is characterized by a terminal conduction delay in the right ventricle, BrS-patients with a left axis deviation upon sodium channel blocker provocation have an additional proximal conduction slowing, which is associated with a subsequent discordant repolarization. Whether this has implications for risk stratification is still undetermined.

scholarly journals Concomitant Partial Achilles Tendon Rupture and Lateral Luxation of the Superficial Digital Flexor Muscle Tendon in a Dog

VCOT Open ◽  
2021 ◽  
Vol 04 (01) ◽  
pp. e37-e40
Author(s):  
Hélène Dosseray ◽  
Claire Deroy-Bordenave
Keyword(s):  
Achilles Tendon ◽  
Achilles Tendon Rupture ◽  
Simultaneous Occurrence ◽  
Flexor Muscle ◽  
Screw Insertion ◽  
Superficial Digital Flexor Tendon ◽  
Fixation Screw ◽  
Pelvic Limb ◽  
The Right

AbstractThe aim of this study was to report a posttraumatic partial Achilles tendon (AT) rupture associated with lateral luxation of the superficial digital flexor tendon (SDFT) in a Whippet. This article is a brief communication. A Whippet was presented with posttraumatic plantigrade stance and non-load-bearing lameness of the right pelvic limb. The objective findings consisted in partial AT rupture and SDFT lateral luxation. Surgical treatment ensued: tenorrhaphy of the torn tendons and calcaneo-tibial screw insertion for tarsal immobilization, followed by suturing of the SDFT retinaculum. A casting bandage was employed for additional immobilization. Nonetheless, a bandage complication prompted the premature removal of the fixation screw and casting wrap. Complete functional recovery was achieved by the 20th postoperative week. The simultaneous occurrence of SDFT luxation and partial AT tear has not been reported in the literature before. The long-term postoperative functional outcome was highly satisfactory.

scholarly journals Pulmonary Hypertension in Acute and Chronic High Altitude Maladaptation Disorders

2021 ◽  
Vol 18 (4) ◽  
pp. 1692
Author(s):  
Akylbek Sydykov ◽  
Argen Mamazhakypov ◽  
Abdirashit Maripov ◽  
Djuro Kosanovic ◽  
Norbert Weissmann ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
High Altitude ◽  
Clinical Experience ◽  
Current Knowledge ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Treatment Options ◽  
Right Heart Failure ◽  
Channel Blockers ◽  
The Right ◽  
Extensive Clinical Experience

Alveolar hypoxia is the most prominent feature of high altitude environment with well-known consequences for the cardio-pulmonary system, including development of pulmonary hypertension. Pulmonary hypertension due to an exaggerated hypoxic pulmonary vasoconstriction contributes to high altitude pulmonary edema (HAPE), a life-threatening disorder, occurring at high altitudes in non-acclimatized healthy individuals. Despite a strong physiologic rationale for using vasodilators for prevention and treatment of HAPE, no systematic studies of their efficacy have been conducted to date. Calcium-channel blockers are currently recommended for drug prophylaxis in high-risk individuals with a clear history of recurrent HAPE based on the extensive clinical experience with nifedipine in HAPE prevention in susceptible individuals. Chronic exposure to hypoxia induces pulmonary vascular remodeling and development of pulmonary hypertension, which places an increased pressure load on the right ventricle leading to right heart failure. Further, pulmonary hypertension along with excessive erythrocytosis may complicate chronic mountain sickness, another high altitude maladaptation disorder. Importantly, other causes than hypoxia may potentially underlie and/or contribute to pulmonary hypertension at high altitude, such as chronic heart and lung diseases, thrombotic or embolic diseases. Extensive clinical experience with drugs in patients with pulmonary arterial hypertension suggests their potential for treatment of high altitude pulmonary hypertension. Small studies have demonstrated their efficacy in reducing pulmonary artery pressure in high altitude residents. However, no drugs have been approved to date for the therapy of chronic high altitude pulmonary hypertension. This work provides a literature review on the role of pulmonary hypertension in the pathogenesis of acute and chronic high altitude maladaptation disorders and summarizes current knowledge regarding potential treatment options.

Sodium Nitroprusside as a Hyperinflation Drug and Therapeutic Alternatives

2018 ◽  
Vol 31 (4) ◽  
pp. 374-381 ◽  
Author(s):  
Alex Cobb ◽  
Luciana Thornton
Keyword(s):  
Sodium Nitroprusside ◽  
Hypertensive Crisis ◽  
Antihypertensive Agents ◽  
Cost Savings ◽  
Similar Efficacy ◽  
Evidence Base ◽  
Adverse Outcomes ◽  
Channel Blockers ◽  
Acute Hypertension ◽  
Therapeutic Interchange

Sodium nitroprusside (SNP) is a generically available and rapid-acting intravenous (IV) vasodilator that has been used clinically for decades. Prior to 2013, the cost of SNP was relatively low, and SNP was an affordable option for the treatment of acute hypertension. However, from 2013 to 2017, average wholesale prices for SNP rose to as high as US$900 per vial, earning the drug its status as a “hyperinflation drug.” Hyperinflation drugs pose a significant challenge for pharmacy departments. A multidisciplinary effort involving stakeholders from many backgrounds, including pharmacists, physicians, and nurses, is key to developing an effective cost containment strategy. A therapeutic interchange, wherein a drug with similar efficacy is substituted for another, is often an appropriate strategy to address rising drug costs. Fortunately, alternative drugs with a solid evidence base exist for the management of acute hypertension. The dihydropyridine calcium channel blockers, clevidipine and nicardipine, are IV titratable antihypertensive agents with favorable pharmacokinetic and safety profiles. Various studies indicate that clevidipine and nicardipine are effective alternatives to SNP for indications including hypertensive crisis and postoperative hypertension. Some hospitals have reported significant cost savings without adverse outcomes by substituting clevidipine or nicardipine for SNP. This article is intended to serve as a review of the evidence for clevidipine and nicardipine as potential substitutes for SNP and to provide strategies to successfully implement this therapeutic interchange.

Adult Xp11.2 translocation renal cell carcinoma managed effectively with pazopanib

2021 ◽  
Vol 14 (6) ◽  
pp. e243058
Author(s):  
Cristian Solano ◽  
Shrinjaya Thapa ◽  
Mohammad Muhsin Chisti
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Stable Disease ◽  
Renal Cell ◽  
Systemic Treatment ◽  
Pulmonary Nodules ◽  
Progression Of Disease ◽  
Xp11.2 Translocation ◽  
Adrenal Nodule

Xp11.2 translocation renal cell carcinoma (TRCC) is a rare and aggressive variant of renal cell carcinoma (RCC) when presenting in adults. We report a case of a man in his early 40s who was diagnosed with stage III Xp11.2 TRCC and underwent radical nephrectomy. Seven months following the surgery, an adrenal nodule and bilateral pulmonary nodules were discovered. He underwent cryoablation of the adrenal nodule and systemic treatment with daily pazopanib. He displayed stable disease for approximately 6 years. Following this period, multiple hospitalisations interrupted daily pazopanib therapy resulting in progression of disease. His regimen was then changed to ipilimumab and nivolumab, followed by current daily therapy with axitinib. The patient now shows stable disease in his 10th year after diagnosis. This case study demonstrates the efficacy of pazopanib for metastatic Xp11.2 TRCC and warrants further investigation to supplement the guidelines regarding the use of targeted therapy for TRCC.

scholarly journals DRUG UTILIZATION BASED ADRS MONITORING OF ANTIHYPERTENSIVE AGENTS PRESCRIBED IN AL-QUWAYIYAH GENERAL HOSPITAL, SAUDI ARABIA

2018 ◽  
Vol 10 (3) ◽  
pp. 22
Author(s):  
Md Salahuddin Ansari ◽  
Faisal Al-otaibi
Keyword(s):  
Saudi Arabia ◽  
Calcium Channel ◽  
General Hospital ◽  
Drug Utilization ◽  
Calcium Channel Blockers ◽  
Antihypertensive Drugs ◽  
Antihypertensive Agents ◽  
Channel Blockers ◽  
Hypertensive Patients ◽  
Patient Interviews

Objective: To monitor drug utilization based adverse drug reactions (ADRs) of antihypertensive agents prescribed in Al-Quwayiyah general hospital, Saudi Arabia.Methods: An open, non-comparative, observational study was conducted on hypertensive patients attending the medicine outpatient department of Al-Quwayyah general hospital, Al-Quwayyah, Saudi arabia. Data were collected by conducting patient interviews. Data were captured for adverse drug reaction monitoring based on Narinjo scale and WHO format.Results: 25 ADRs were observed out of 212 hypertensive patients. Incidence was found to be higher in patients more than 40 y age, and females experienced more ADRs (n = 16, 7.54%) than males, 9 (4.62%). Combination therapy was associated with more number of ADRs (64.0%) as against monotherapy (36.0%). Calcium channel blockers were found to be the most frequently associated drugs with ADRs (n = 8), followed by diuretics (n = 6), and β-blockers (n = 5). Among individual drugs, amlodipine was found to be the commonest drug associated with ADRs (n = 8), followed by torasemide (n = 4). ADRs associated with the central nervous system was found to be the most frequent (48.0%) followed by musculoskeletal complaints (20.0%) and respiratory system disorders (16.0%).Conclusion: ADRs were experienced by taking the antihypertensive drugs prescribed in Al-Quwayyah general hospital, Saudi arabia. The findings would be useful for physicians in rational prescribing. Calcium channel blockers were found to be the most frequently associated drugs with ADRs.

scholarly journals Morphologically Identified Cutaneous Afferent DRG Neurons Express Three Different Potassium Currents in Varying Proportions

1998 ◽  
Vol 79 (4) ◽  
pp. 1814-1824 ◽  
Author(s):  
Brian Everill ◽  
Marco A. Rizzo ◽  
Jeffery D. Kocsis
Keyword(s):  
Outward Current ◽  
Potassium Currents ◽  
Entire Population ◽  
Channel Blockers ◽  
Relative Distribution ◽  
Afferent Neurons ◽  
Drg Neurons ◽  
Adult Rat ◽  
High Concentrations ◽  
The Right

Everill, Brian, Marco A. Rizzo, and Jeffery D. Kocsis. Morphologically identified cutaneous afferent DRG neurons express three different potassium currents in varying proportions. J. Neurophysiol. 79: 1814–1824, 1998. Outward K+ currents were recorded using a whole cell patch-clamp configuration, from acutely dissociated adult rat cutaneous afferent dorsal root ganglion (DRG) neurons (L4 and L5) identified by retrograde labeling with Fluoro-gold. Recordings were obtained 16–24 h after dissociation from cells between 39 and 49 mm in diameter with minimal processes. These cells represent medium-sized DRG neurons relative to the entire population, but are large cutaneous afferent neurons giving rise to myelinated axons. Voltage-activated K+ currents were recorded routinely during 300-ms depolarizing test pulses increasing in 10-mV steps from −40 to +50 mV; the currents were preceded by a 500-ms conditioning prepulse of either −120 or −40 mV. Coexpression of at least three components of K+ current was revealed. Separation of these components was achieved on the basis of sensitivities to the K+ channel blockers, 4-aminopyridine (4-AP) and dendrotoxin (DTx), and by the current responses to variation in conditioning voltage. Changing extracellular K+ concentration from 3 to 40 mM resulted in a shift to the right of the I-V curve commensurate with K+ being the principal charge carrier. Presentation of 100 mM 4-AP revealed a rapidly activating K+ current sensitive to low concentrations of 4-AP. High concentrations of 4-AP (6 mM) extinguished all inactivating current, leaving almost pure sustained current ( I K). On the basis of the relative distribution of K+ currents neurons could be separated into three distinct categories: fast inactivating current ( I A), slow inactivating current ( I D), and sustained current ( I K); only I A and I K; and slow inactivating current and I K. However, I K was always the dominant outward current component. These results indicate that considerable variation in K+ currents is present not only in the entire population of DRG neurons, as previously reported, but even within a restricted size and functional group (large cutaneous afferent neurons).

scholarly journals Update on Pulmonary Ossifications in the Differential Diagnosis of Solitary Pulmonary Nodules

2021 ◽  
Vol 10 (20) ◽  
pp. 4795
Author(s):  
Jan F. Gielis ◽  
Lawek Berzenji ◽  
Vasiliki Siozopoulou ◽  
Marloes Luijks ◽  
Paul E. Y. Van Schil
Keyword(s):  
Differential Diagnosis ◽  
Pulmonary Nodule ◽  
Solitary Pulmonary Nodule ◽  
Lower Lobe ◽  
Pulmonary Nodules ◽  
Solitary Pulmonary Nodules ◽  
Pulmonary Surgery ◽  
Pubmed Database ◽  
Post Mortem Findings ◽  
The Right

Pulmonary ossifications have often been regarded as rare, post-mortem findings without any clinical significance. We have investigated the occurrence of pulmonary ossifications in patients undergoing thoracic procedures, and how this may affect the differential diagnosis of solitary pulmonary nodules. In addition, we have performed a literature search on the occurrence and possible pathogenesis of these ossifications. From January 2008 until August 2019, we identified pulmonary ossifications in 34 patients who underwent elective pulmonary surgery. Pre-operative imaging was unable to differentiate these ossifications from solid tumors. A definitive diagnosis was made by an experienced pathologist (VS, ML). The PubMed database was researched in December 2019 with the search terms “pulmonary ossifications”; “heterotopic ossifications”; and “solitary pulmonary nodule”. In total, 27 patients were male, with a mean age of 63 ± 12 years (age 41 to 82 on diagnosis). All lesions were identified on thoracic CT and marked for resection by a multidisciplinary team. A total of 17 patients were diagnosed with malignancy concurrent with ossifications. There was a clear predilection for the right lower lobe (12 cases, 35.3%) and most ossifications had a nodular form (70.6%). We could not identify a clear association with any other pathology, either cancerous or non-cancerous in origin. Oncologic or pulmonary comorbidities did not influence patient survival. Pulmonary ossifications are not as seldom as thought and are not just a curiosity finding by pathologists. These formations may be mistaken for a malignant space-occupying lesion, both pre-and perioperatively, as they are indistinguishable in imaging. We propose these ossifications as an underestimated addition to the differential diagnosis of a solitary pulmonary nodule.

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