UNDULY ENHANCED RESPONSE TO TOLVAPTAN IN A WOMAN SHOWING SYNDROME OF INAPPROPRIATE ANTIDIURETIC HORMONE SECRETION: AN INVESTIGATION OF POSSIBLE CAUSES

Objective: To investigate possible causes of an excessive response to tolvaptan in a woman with syndrome of inappropriate antidiuretic hormone secretion (SIADH). Methods: A 32-year-old woman was admitted to our cardiologic unit 3 months after delivery for hypertension and severe hyponatremia (120 mEq/L). Two hyponatremic episodes had already been documented in her medical history. SIADH was diagnosed and treatment with tolvaptan, an arginine vasopressin (AVP) antagonist, was instituted. After the first 15-mg dose, excessive polyuria (1 L/ hour) and a rapid increase in serum sodium (13 mEq/L in 8 hours) occurred, so that therapy was stopped and restarted 2 days later at a reduced dose (5 mg). This level was effective and well tolerated. To explore the possible pharmacokinetic and pharmacodynamic mechanisms underlying the patient\u2019s hyperresponsiveness, the following tests were carried out: (1) in vivo phenotyping of CYP3A4 activity, the cytochrome responsible for tolvaptan metabolism, with two probe drugs (omeprazole and dextromethorphan); and (2) search for mutations in genes involved in AVP signaling (AVP, V2R, AQP2, OXT)

Reliability of Early Fetal Echocardiography for Congenital Heart Disease Detection: A Preliminary Experience and Outcome Analysis of 102 Fetuses to Demonstrate the Value of a Clinical Flow-Chart Designed for At-Risk Pregnancy Management

Early fetal echocardiography (EFEC) is a fetal cardiac ultrasound analysis performed between the 12th and 16th week of pregnancy (compared with the usual 18-22 weeks). In the last 10 years, the introduction of “aneuploidy sonographic markers” in screening for cardiac defects has led to a shift from late second to end of the first trimester or beginning of the second trimester of pregnancy for specialist fetal echocardiography. In this prospective study, early obstetric screening was performed between January 2014 and October 2015, using “aneuploidy sonographic markers” following SIEOG Guidelines 2014. These parameters were then collected and strategically combined in an evaluation score to select the group of pregnancies for performing EFEC, in accordance with the American Society of Echocardiography guidelines for fetal Echocardiography. All second-level examinations were performed transabdominally using a 3D convex volumetric probe with frequency range of 4-8 MHz (Accuvix – Samsung). The outcome data included transabdominal fetal echocardiography from 18 weeks to term and after birth. Overall, 99 pregnant women in the first trimester underwent EFEC (95 singleton and 4 twin pregnancies). Specifically, 30 fetuses were evaluated for extra-cardiac anomalies evidenced by obstetric screening (30%), 25 for family history of congenital heart diseases (25%), 8 for family history of genetic-linked diseases (8%), 4 for heart diseases suspected by obstetric screening (4%) and 19 by normal screening (19%). Was detected 11 (10.7%) CHD, when EFEC detected CHD, were compared to those performed later in pregnancy (18 weeks GA-term), a high degree of diagnosis correspondence was evidenced. The higher sensitivity value of EFEC vs late-FE, in comparison with the post-natal value, coupled with the high EFEC specificity shown vs both the end points, enabled us to consider it as a really reliable diagnostic technology, at least in perienced hands. The introduction of a key combination of the more sensitive obstetric and cardiologic variables should facilitate the formulation of a possible flow-chart as a guide for CHD at-risk pregnancies

Irradiation treatment of laryngeal cancer in a patient with an implantable cardioverter-defibrillator (ICD)

Background: Due to an aging population the incidence of both cardiac and tumor-related illnesses is increasing. A problem may arise if radiotherapy is necessary in close anatomic proximity to an implantable cardioverter-defibrillator (ICD). These highly precise devices may respond to ionizing radiation with a loss of function or uncontrolled stimulation, with both effects being potentially life threatening. Available guidelines recommend the dose maximum to a pacemaker to be cumulative below 2 Gy. For most patients undergoing radiation therapy of the neck or of the chest this limit is exceeded, thus making a removal of the device and an implantation of an external ICD necessary. Case Report: A patient with severe cardiac problems underwent an implantation of an ICD. However, a recurrence of a laryngeal cancer was diagnosed. The irradiation dose after resection was 60 Gy to the tumor region and 50 Gy to the lymph nodes. Irradiation peakload to the ICD was calculated to be 2.5 Gy. This dose was verified with thermoluminescence measurements. The ICD was externally deactivated during the sessions of irradiation. Device checks demonstrated no malfunction. Conclusion: Even though the dose limits of the ICD of 2 Gy were exceeded, the device demonstrated a regular function during and after radiotherapy

Heart rate variability and target organ damage in hypertensive patients

Background: We evaluated the association between linear standard Heart Rate Variability (HRV) measures and vascular, renal and cardiac target organ damage (TOD). Methods: A retrospective analysis was performed including 200 patients registered in the Regione Campania network (aged 62.4 ± 12, male 64%). HRV analysis was performed by 24-h holter ECG. Renal damage was assessed by estimated glomerular filtration rate (eGFR), vascular damage by carotid intima-media thickness (IMT), and cardiac damage by left ventricular mass index. Results: Significantly lower values of the ratio of low to high frequency power (LF/HF) were found in the patients with moderate or severe eGFR (p-value < 0.001). Similarly, depressed values of indexes of the overall autonomic modulation on heart were found in patients with plaque compared to those with a normal IMT (p-value <0.05). These associations remained significant after adjustment for other factors known to contribute to the development of target organ damage, such as age. Moreover, depressed LF/HF was found also in patients with left ventricular hypertrophy but this association was not significant after adjustment for other factors. Conclusions: Depressed HRV appeared to be associated with vascular and renal TOD, suggesting the involvement of autonomic imbalance in the TOD. However, as the mechanisms by which abnormal autonomic balance may lead to TOD, and, particularly, to renal organ damage are not clearly known, further prospective studies with longitudinal design are needed to determine the association between HRV and the development of TOD

Focal Spot, Winter 2004/2005

https://digitalcommons.wustl.edu/focal_spot_archives/1098/thumbnail.jp

Aerospace Medicine and Biology: A continuing bibliography (supplement 160)

This bibliography lists 166 reports, articles, and other documents introduced into the NASA scientific and technical information system in October 1976

GUCH POPULATION: CARDIOLOGIC AND SURGICAL DEMANDS

To evaluate the cardiologic and surgical demands of the GUCH population followed up in our Department, a retrospective analysis of 709 hospital admissions (HA) of 536 pts (mean age 34?16, range 16-79 years), carried out from 1997 to 2002, has been performed. In 293 pts the basic cardiopathy was simple (SC), in 158 of moderate complexity (MCC) and in 85 of great complexity (GCC). The reason for 169 HA was cardiac surgery and for 537 HA cardiologic issues. The overall HA/pt was 1.3 (1.1 in SC,1.3 in MCC, 2.1 in GCC). In 166 surgical pts, 171 operations were performed. First operations (n=105, 62%) were most commonly for atrial septal defect (n=50, 48%), aortic valve replacement(n=11,10%), ventricular septal defect (n=8, 8%). Reoperations (n=64, 38%) were divided among reintervention after corrective repair (n=45, 70%), further palliation (n=17, 26%), first palliation (n=2, 4%) and the most frequent were: Fontan operation (n=11, 17%), RV-PA conduit replacement (n=8, 12%), aortic valve replacement (n=6, 9%). The mean hospital stay was 19?17 days. Pleuro-pericardial effusion (n=32,18%), bleeding (n=11, 6%) and arrhythmias(n=11, 6%) were the most prevalent complications. Early mortality (n=7/171, 4%) was influenced by cyanosis (6 of 33,18% in cyanotic pts; 1 of 136, 2% in acyanotic, p<0,001) and by complexity of cardiopathy (n=6 of 43 GCC, 14%; n=1 of 72 MCC, 1%; 0 of 54 SC,0%, p<0.001) that was a risk factor also for more serious complications (20% in GCC, with respect of 9% in MCC, p<0,05 and 4% in SC, p<0.001). The principal reasons for 537 cardiologic HA in 432 pts, were: interventional procedures (n=209, 39%), diagnostic catheterisation (n=155, 29%), non invasive evaluation (n=95, 18%), arrhythmias (n=46, 10%). Closure of atrial septal discontinuity (n=167, 80%), patent ductus arteriosus (n=21, 10%), pulmonary valvuloplasty (n=8, 4%) and angioplasty of Coarctation (n=6, 3%), were more prevalent interventional procedures. In pts with GCC, heart failure and cyanosis were more commonly cause of HA than in MGC and SC (p<0.001). Despite the progress of pediatric cardiology and cardiac surgery, medical demands of GUCH remain numerous and complex throughout their lives. Therefore, it is extremely important to provide specialized surgical and cardiologic care for this complicated population

Triplet vs doublet lenalidomide-containing regimens for the treatment of elderly patients with newly diagnosed multiple myeloma

Lenalidomide-dexamethasone improved outcome in newly diagnosed elderly multiple myeloma patients. We randomly assigned 662 patients who were age \u202165 years or transplantation-ineligible to receive induction with melphalan-prednisone-lenalidomide (MPR) or cyclophosphamide-prednisone-lenalidomide (CPR) or lenalidomide plus lowdose dexamethasone (Rd). The primary end point was progression-free survival (PFS) in triplet (MPR and CPR) vs doublet (Rd) lenalidomide-containing regimens. After a median follow-up of 39 months, the medianPFSwas22 months for the triplet combinations and 21 months for the doublet (P 5 .284). The median overall survival (OS) was not reached in either arms, and the 4-year OS was 67% for the triplet and 58% for the doublet arms (P 5 .709). By considering the 3 treatment arms separately, no difference in outcome was detected among MPR, CPR, and Rd. The most common grade \u20213 toxicity was neutropenia: 64% in MPR, 29% in CPR, and 25% in Rd patients (P < .0001). Grade \u20213 nonhematologic toxicities were similar among arms and were mainly infections (6.5% to 11%), constitutional (3.5% to 9.5%), and cardiac (4.5% to 6%), with no difference among the arms. In conclusion, in the overall population, the alkylator-containing tripletsMPRandCPRwere not superior to the alkylator-free doublet Rd, which was associated with lower toxicit

Neuropsychological and Behavioral Aspects of Noonan Syndrome

Abstract: The current paper introduces concise neuropsychological assessment as an essential tool for studying the contribution of cognition and behavior in the expression of genetic syndromes, like Noonan syndrome (NS). Cognitive and behavioral findings in NS show intelligence scores across a wide range, with a mildly lowered average level. Language and motor development are often delayed, but no longer dysfunctional in adulthood. Continuing mild problems in selective and sustained attention are noted, as well as suboptimal organization skills and compromised abilities to structure complex information. These problems seem to culminate in learning difficulties, requiring attention for special needs in education. It seems that a complex of psychosocial immaturity, alexithymia and amenable traits is typical of NS patients. Consequently, psychopathology or psychological problems in leading a self-serving life may often remain underreported. This is why the authors advocate the integration of the domain of social cognition and personality in NS assessment