Hypoxia due to intrapulmonary vascular dilatation in a toddler with a congenital portacaval shunt: case report.

BACKGROUND: The term hepatopulmonary syndrome typically applies to cyanosis that results from "intrapulmonary vascular dilatation" due to advanced liver disease. Similar findings may result from a congenital portosystemic shunt without liver disease. An adverse consequence of such shunts is intrapulmonary vascular dilatation, which affects the microvascular gas exchange units for oxygen. CASE PRESENTATION: Here, we describe a toddler with chronic cyanosis, exercise intolerance, and finger clubbing due to a malformation shunt between the portal vein and the inferior vena cava. A transcatheter embolization of the shunt resulted in resolution of his findings. CONCLUSIONS: Congenital portosystemic shunts need to be considered in the differential diagnosis of cyanosis.

Psychogenic pseudosyncope: Not always a diagnosis of exclusion.

BACKGROUND: Psychogenic pseudosyncope (PPS) frequently mimics syncope. The aim of this study was to assess the prevalence and clinical features of PPS and its relationship to vasovagal syncope (VVS). METHODS: We examined retrospectively the medical records of 1,401 consecutive patients referred to a syncope unit. We identified patients who had the final diagnosis of PPS. In these patients, we retrieved the initial diagnosis made during their first visit and the subsequent tests performed leading to the final diagnosis. RESULTS: Fourteen (1.0%) patients (mean age 35 ± 14; 11 females) were diagnosed as having PPS: seven had a diagnosis of PPS alone and seven had both VVS and PPS. High frequency of attacks (53 ± 35 attacks during the previous year), prolonged loss of consciousness (minutes to > 1 hour), and a history of psychiatric disorders characterized PPS patients. Tilt test reproduced a PPS attack in the presence of normal blood pressure and heart rate in seven patients (50%), and induced VVS in another three patients who had the final diagnosis of both PPS and VVS. In two patients, one or more events occurred during the clinic visits and were directly witnessed by the clinic personnel. CONCLUSIONS: We have shown that 1% of referrals to a syncope unit have the final diagnosis of PPS and that up to 50% of cases presented with a different initial diagnosis, namely VVS. Our findings suggest that causality between syncope and psychiatric disorders is likely bidirectional. The presence of a multidisciplinary team is important to address this often unrecognized relationship.

Clinical Characteristics and Outcome of Patients with Situational Syncope Compared to Patients with Vasovagal Syncope.

BACKGROUNDS: The purpose of the study was to assess the clinical outcome of patients with situational syncope (SS) compared to patients with vasovagal syncope (VVS). METHODS: We assessed the prevalence, patients' characteristics, and outcome of consecutive patients with SS and VVS who presented to the Faint and Fall Clinic (University of Wisconsin) between January 2013 and December 2015. RESULTS: SS was found in 55/1,401 (4.0%) syncope patients with follow-up data available in 47 patients: defecation (n = 16), micturition (n = 15), cough (n = 10), swallow (n = 3), laughter (n = 1), sneeze (n = 1), and cough plus laughter (n = 1). Over the same time period, 252/1,401 patients (18%) were diagnosed with VVS with follow-up data available in 171 patients. Compared with VVS patients, SS patients were older, more likely to be male, had a higher prevalence of hypertension, had an absence of prodromes, and experienced more injuries at the time of syncope (P = 0.01 for all). During a mean follow-up duration of 15.4 ± 9.1 months, syncope recurred in 5/47 (10.6%) patients with SS and 16/171 (9.4%) patients with VVS. The recurrence rates at 1 year and 2 years were 20% (95% SE ± 13) and 40% (95% SE ± 20) for the SS group, and 23% (95% SE ± 13) and 43% (95% SE ± 20) for the VVS group (P = 0.6). No patient died. CONCLUSIONS: We have shown in a large cohort of consecutive patients with syncope that SS is a relatively infrequent form of reflex syncope with different clinical characteristics but similar recurrence rate to VVS.

Long-Term Outcome of Patients with Bifascicular Block and Unexplained Syncope Following Cardiac Pacing.

BACKGROUND: According to the ACC/AHA/HRS guidelines, cardiac pacing is reasonable in patients with bifascicular block (BF-B) and syncope when other causes have been excluded. The purpose of this study was to assess the long-term outcome of patients with BF-B and unexplained syncope following cardiac pacing. METHODS AND RESULTS: Between 2009 and 2015, we identified 43 consecutive patients (mean age of 78 ± 12 years, 64% males) who presented with syncope and BF-B and had received a pacemaker (PM). During a mean follow-up period of 31 ± 21 months, syncope recurred in seven patients (16%): 7% (95% standard error [SE] ± 3%) at 1 year and 18% (95% SE ± 7%) at 5 years. At univariable analysis, the only predictor of syncope recurrence was empiric pacing (P = 0.03). There were no syncope recurrences in the 12 patients who received a PM following a positive electrophysiological study (EPS) and the five patients with documentation of paroxysmal atrioventricular block (AVB) during cardiac monitoring (insertable loop recorder [ILR]), (EPS/ILR Group, n = 17) compared to seven of 26 (27%) patients who received empiric pacing (Empiric Group, n = 26; P = 0.02). Progression to high-degree AVB was documented during follow-up in 16 (37%) patients: nine of 17 (53%) patients in the EPS/ILR Group and seven of 26 (27%) patients in the Empiric Group (P = 0.11). There were no injuries reported during ILR monitoring. CONCLUSIONS: We have shown that syncope recurs not infrequently in patients with BF-B who received pacing for syncope. Nearly one in four patients who had empiric pacing suffered syncope recurrence compared to no recurrences in patients who received a PM following a positive EPS or documentation of transient AVB.

The pathophysiologic mechanisms associated with hypotensive susceptibility.

INTRODUCTION: Patients with vasovagal syncope (VVS) and positive tilt table test (TTT) were not found to benefit from pacing in the ISSUE-3 trial despite the presence of spontaneous asystole during monitoring. "Hypotensive susceptibility" unmasked by TTT was reported as a possible explanation. The purpose of this study was to assess the pathophysiologic mechanisms associated with hypotensive susceptibility. METHODS: 366 consecutive patients with the diagnosis of VVS who also had TTT were identified. Baroreflex gain (BRG) in addition to blood pressure (BP) and heart rate (HR) responses during the first 20 min of TTT were analyzed and compared between patients with positive TTT (n = 275, 75 %) and negative TTT (n = 91, 25 %). RESULTS: The mean BRG was similar between the groups (12.5 ± 6.3 versus 12.4 ± 6.3 ms/mmHg, p = 0.72); however, an age-dependent decrease was noted (17.6 ± 4.8, 15.0 ± 6.0, 10.6 ± 4.2, 10.3 ± 6.4 and 9.9 ± 8.5 ms/mmHg for patients <21, 21-40, 41-60, 61-80 and >80 years old, respectively; p < 0.001). In addition, we saw a main effect of age on the type of response with a greater prevalence of a vasodepressor response in older subjects (p < 0.001). During the first 20 min of TTT, BP was similar in patients with tilt-positive VVS when compared with patients with tilt-negative VVS; however, HR was significantly lower. CONCLUSION: BRG is similar in tilt-positive VVS patients when compared with tilt-negative VVS patients. An age-dependent decrease in BRG was noted with a higher prevalence of a vasodepressor response seen in older patients. The clinical significance of the blunted HR response in tilt-positive VVS remains to be determined.

Enzyme-replacement therapy in life-threatening hypophosphatasia.

BACKGROUND: Hypophosphatasia results from mutations in the gene for the tissue-nonspecific isozyme of alkaline phosphatase (TNSALP). Inorganic pyrophosphate accumulates extracellularly, leading to rickets or osteomalacia. Severely affected babies often die from respiratory insufficiency due to progressive chest deformity or have persistent bone disease. There is no approved medical therapy. ENB-0040 is a bone-targeted, recombinant human TNSALP that prevents the manifestations of hypophosphatasia in Tnsalp knockout mice. METHODS: We enrolled infants and young children with life-threatening or debilitating perinatal or infantile hypophosphatasia in a multinational, open-label study of treatment with ENB-0040. The primary objective was the healing of rickets, as assessed by means of radiographic scales. Motor and cognitive development, respiratory function, and safety were evaluated, as well as the pharmacokinetics and pharmacodynamics of ENB-0040. RESULTS: Of the 11 patients recruited, 10 completed 6 months of therapy; 9 completed 1 year. Healing of rickets at 6 months in 9 patients was accompanied by improvement in developmental milestones and pulmonary function. Elevated plasma levels of the TNSALP substrates inorganic pyrophosphate and pyridoxal 5'-phosphate diminished. Increases in serum parathyroid hormone accompanied skeletal healing, often necessitating dietary calcium supplementation. There was no evidence of hypocalcemia, ectopic calcification, or definite drug-related serious adverse events. Low titers of anti-ENB-0040 antibodies developed in four patients, with no evident clinical, biochemical, or autoimmune abnormalities at 48 weeks of treatment. CONCLUSIONS: ENB-0040, an enzyme-replacement therapy, was associated with improved findings on skeletal radiographs and improved pulmonary and physical function in infants and young children with life-threatening hypophosphatasia. (Funded by Enobia Pharma and Shriners Hospitals for Children; ClinicalTrials.gov number, NCT00744042.).

Diagnosis and treatment of late-onset Pompe disease in the Middle East and North Africa region: consensus recommendations from an expert group.

BACKGROUND: Pompe disease is a rare autosomal recessive disorder caused by a deficiency of the lysosomal enzyme alpha-glucosidase responsible for degrading glycogen. Late-onset Pompe disease has a complex multisystem phenotype characterized by a range of symptoms. METHODS: An expert panel from the Middle East and North Africa (MENA) region met to create consensus-based guidelines for the diagnosis and treatment of late-onset Pompe disease for the MENA region, where the relative prevalence of Pompe disease is thought to be high but there is a lack of awareness and diagnostic facilities. RESULTS: These guidelines set out practical recommendations and include algorithms for the diagnosis and treatment of late-onset Pompe disease. They detail the ideal diagnostic workup, indicate the patients in whom enzyme replacement therapy should be initiated, and provide guidance on appropriate patient monitoring. CONCLUSIONS: These guidelines will serve to increase awareness of the condition, optimize patient diagnosis and treatment, reduce disease burden, and improve patient outcomes.

"Vasovagal" response during ventricular fibrillation: incidence and implications.

BACKGROUND: The purpose of this study was to assess the relationship between changes in sinus node cycle length (SNCL) during ventricular fibrillation (VF) and the peripheral changes in blood pressure (BP) and sympathetic nerve activity (SNA) in human subjects. We hypothesized that patients with no SNCL shortening during VF have a vasovagal-like response with a greater decrease in BP and SNA when compared to patients with SNCL shortening. METHODS: SNCL, BP, and SNA recordings were attempted in 24 patients undergoing the implantation of a dual-chamber implantable defibrillator. Changes were measured during the first 5 seconds of VF and compared with the 5 seconds prior to VF induction. RESULTS: SNCL shortened during VF in nine patients (mean%∆SNCL = -12 ± 8%) and remained unchanged or lengthened in seven patients (mean%∆SNCL = 7 ± 7%). Eight patients had ventriculoatrial (VA) conduction prohibiting assessment of SNCL changes. In patients with SNCL shortening, the %∆MBP (mean BP) was -47 ± 6% compared to -58 ± 8% in patients with no SNCL shortening (P < 0.01). In patients with VA conduction, the %∆MBP was -54 ± 3%. SNA recordings were successfully obtained in four patients. When compared to baseline, SNA increased by 34 ± 30% in two patients with SNCL shortening, decreased by 25% in one patient with SNCL lengthening, and by 90% in the fourth patient with VA conduction. CONCLUSIONS: We have shown that patients with no SNCL shortening have a significantly greater decrease in MBP during VF when compared to patients with SNCL shortening. The underlying mechanism appears to be reflex mediated with a vasovagal-like response in patients with no SNCL shortening.

Mechanisms of sinus node cycle length changes during ventricular fibrillation.

OBJECTIVE: We have previously shown that up to one-third of patients develop no change or an increase in sinus node cycle length (SNCL) during ventricular fibrillation (VF). The purpose of the present study was to investigate the mechanism of SNCL changes during VF in a swine model. We hypothesized that changes in SNCL during VF are vagally-mediated. METHODS: In 33 anesthetized pigs DC current was used to induce VF for 10 s followed by defibrillation. SNCL changes were assessed during VF and compared to baseline. Animals that had ventriculo-atrial conduction during VF were excluded. Post-defibrillation, the pigs were randomized to receive atropine, propranolol, atropine + propranolol or placebo followed by repeat VF induction and measurement of SNCL changes. RESULTS: Ventriculo-atrial conduction was present in 14 pigs prohibiting SNCL measurements. In the remaining 19 animals, 10 demonstrated SNCL shortening (S-Group) and 9 demonstrated non-shortening (NS-Group). Atropine decreased the absolute change in SNCL from 51.2 to 26.6 ms (n = 6; p = 0.03). It attenuated the SNCL shortening previously observed in the S-Group (-99.2 ms versus -47.9 ms, p = 0.04) and reversed the SNCL prolongation initially observed in the NS-Group (27.1 ms versus -6.5 ms, p = 0.13). Similarly, atropine + propranolol decreased the absolute change in SNCL from 33.3 to 12.2 ms (n = 4; p = 0.05). No significant changes were noted with propranolol or placebo. INTERPRETATION: The SNCL changes during VF appear to be vagally-mediated. The clinical implications vis-à-vis defibrillation threshold and future device programming await future studies.

Perinatal outcome of congenital heart disease in a population with high consanguinity.

OBJECTIVE: To report the perinatal pattern and outcome of fetuses with congenital heart disease (CHD) in consanguineous marriages. METHODS: Retrospective chart review was performed for fetuses undergoing fetal echocardiography (FE) in our institution. The primary outcome was survival at 28 days after birth. RESULTS: Between 1 January 2005 and 31 December 2010, 1950 pregnant women carrying 2151 fetuses underwent a total of 2828 FEs. CHD was diagnosed in 152 fetuses (7.1%), and perinatal outcome was available in 120, among which 78 (65%) had consanguineous parents. Thirteen fetuses died in utero, while 86 (71.7%) survived. The most prevalent lesions included left heart obstruction (25.8%), conotruncal malformations (21.7%), septal defects (18.3%), and cardiomyopathy (15.8%). Correct diagnosis was achieved in 92.2% of the cases. Extracardiac malformations occurred in 48.3% of the fetuses and were associated with increased mortality regardless of the type of CHD (P<0.001, odds ratio 6.8, 95% confidence interval 2.7-17.5). CONCLUSION: Joint FE clinics detect most CHD with high accuracy. Consanguinity contributes to a higher prevalence of fetal cardiac and non-cardiac malformations. The presence of extracardiac anomalies is associated with an increase in perinatal mortality.

Standardized care pathway versus conventional approach in the management of patients presenting with faint at the University of Utah.

BACKGROUND: Despite the availability of guidelines, the evaluation of patients with faint continues to be inconsistent. The purpose of this study was to test the hypothesis that utilization of a new standardized-care pathway (Faint-Algorithm) reduces hospital admissions and improves diagnostic yield when compared to the conventional approach in the evaluation of patients with faint. METHODS: We reviewed the data of 154 consecutive patients presenting with faint to the Faint and Fall Clinic at the University of Utah (standardized group) and 100 patients previously evaluated for faint using the conventional approach (conventional group). RESULTS: Using a standardized approach, only 4% of patients were admitted when compared to 20% in the conventional group (P < 0.001). The rate of diagnosis at initial evaluation was similar between the groups; however, at 45 days, it was greater in the standardized group when compared to the conventional group (57% vs 45% in the total population, P = 0.09; 57% vs 39% in the outpatient subgroups, P = 0.02). The number of tests or consultations associated with additional charges was significantly lower in the standardized group when compared to the conventional group (1.9 ± 1.0 vs 2.6 ± 1.2, P = 0.001). CONCLUSIONS: The use of a standardized approach in the evaluation of patients with faint decreased the number of hospital admissions and increased the rate of diagnosis at 45 days. This was achieved with less utilization of costly tests and consultations.

Investigating patterns of workplace fatal fall injuries: Case study of Malaysia.

INTRODUCTION: Falling from heights can be a serious and potentially life-threatening hazard. In Malaysia, falls from heights are one of the leading causes of workplace accidents and fatalities. The Malaysian Department of Occupational Safety and Health (DOSH) reported that the year 2021 recorded an alarmingly high number of fatalities, of which the majority of the injuries were due to falls from heights. OBJECTIVE: The purpose of this study is to understand the relationship between the different variables associated with fatal falls from heights, which will help identify potential areas to work on to prevent these types of injuries. METHODS: The study analyzed 3,321 fatal falls from height accidents from 2010 to 2020 DOSH data. Data were cleaned and normalized to extract relevant information for analysis, with agreement on variables and reliability achieved through independent sampling. RESULTS: This study found that general workers were the most vulnerable category to fatal falls, with a 32% yearly average, whereas supervisors were the least vulnerable, with 4%. Roofers recorded a yearly fatal falls average of 15.5%, followed by electricians with 12%. Cramer's V results ranged from negligible, weak, and strong correlations; strong to moderate correlation between the dates of injuries and the factors used in this study, whereas the direct and root causes recorded a weak to negligible correlation with the rest of the variables. CONCLUSIONS: This study provided a better understanding of the working conditions of the Malaysian construction industry. By analyzing fall injury patterns and uncovering the factors, direct and root causes relationship with other variables, it was clear how severe the Malaysian workplace conditions were. PRACTICAL APPLICATIONS: This study will help better understand fatal fall injuries in the Malaysian construction industry and help develop prevention measures based on the uncovered patterns and associations.

Adenosinergic System and Neuroendocrine Syncope: What Is the Link?

Although very common, the precise mechanisms that explain the symptomatology of neuroendocrine syncope (NES) remain poorly understood. This disease, which can be very incapacitating, manifests itself as a drop in blood pressure secondary to vasodilation and/or extreme slowing of heart rate. As studies continue, the involvement of the adenosinergic system is becoming increasingly evident. Adenosine, which is an ATP derivative, may be involved in a large number of cases. Adenosine acts on G protein-coupled receptors with seven transmembrane domains. A1 and A2A adenosine receptor dysfunction seem to be particularly implicated since the activation leads to severe bradycardia or vasodilation, respectively, two cardinal symptoms of NES. This mini-review aims to shed light on the links between dysfunction of the adenosinergic system and NHS. In particular, signal transduction pathways through the modulation of cAMP production and ion channels in relation to effects on the cardiovascular system are addressed. A better understanding of these mechanisms could guide the pharmacological development of new therapeutic approaches.

Restoring sinus rhythm results in blood pressure reduction in patients with persistent atrial fibrillation and a history of hypertension.

INTRODUCTION: The long-term effects of atrial fibrillation (AF) on blood pressure (BP) in patients with hypertension (HTN) remain unclear. We hypothesized that restoration of normal sinus rhythm (NSR) results in a decrease in BP despite the expected increase in cardiac output. METHODS AND RESULTS: Twenty-four-hour BP measurements were obtained during AF, and on Day 1 and Day 30 post-successful cardioversion in 18 patients with AF and HTN (cardioversion group), and another 22 patients with AF and HTN with no immediate plans for cardioversion (control group). Except for the duration of AF, the clinical characteristics and use of medications were similar between the groups. In the cardioversion group, a significant decrease in diastolic blood pressure (DBP) and mean blood pressure (MBP) were noted on Day 1 post-cardioversion with no significant change in systolic blood pressure (SBP): 117/74/88 ± 13/9/9 mmHg during AF and 116/70/85 ± 13/9/10 mmHg during Day 1 post-cardioversion (P = 0.68; <0.01 and 0.04 for SBP, DBP, and MBP, respectively). In the 13 subjects who remained in NSR at Day 30, DBP and MBP decreased further on Day 30 when compared to Day 1 with no significant change in SBP: 118/76/90 ± 13/7/8 mmHg during AF; 119/72/88 ± 12/8/9 mmHg during Day 1; and 118/69/86 ± 10/8/7 mmHg during Day 30 post-cardioversion (P = 0.97; <0.001 and 0.03 for SBP, DBP, and MBP, respectively). In the control group, no significant changes in BP were noted. CONCLUSION: Restoring NSR in patients with AF and HTN resulted in a sustained decrease in DBP and MBP. To our knowledge, this is the first study to show that maintenance of NSR improves BP control in patients with AF and HTN.

Atrial bigeminy results in decreased left ventricular function: an insight into the mechanism of PVC-induced cardiomyopathy.

BACKGROUND: Premature ventricular complexes have been recently recognized as a reversible cause of cardiomyopathy. The purpose of this study was to determine if premature complexes independent of "dyssynchrony" resulted in increased left ventricular (LV) dimensions and decreased LV function. METHODS: Ten mongrel dogs underwent the implantation of a pacemaker and were randomized to a control group (n = 5) or a paced group (n = 5). In the paced group, the pacemaker was connected to two endocardial atrial leads, one inserted into the atrial port and the other one into the ventricular port with an atrioventricular delay adjusted to ensure the presence of coupled pacing simulating atrial bigeminy with conducted beats in the absence of aberrancy. Echocardiographic parameters of LV size (LV end-diastolic diameter [LV-EDD], LV end-systolic diameter [LV-ESD]), and LV ejection fraction (LVEF) were measured at baseline and after 4 weeks of monitoring (control group) or pacing (paced group). RESULTS: In the control group, LV size decreased with no significant changes in LVEF: 55% at baseline versus 70% at 4 weeks (P = 0.23). In the paced group, LV-EDD decreased with no significant change in LV-ESD. Unlike the control group, LVEF decreased significantly from 69 ± 9% at baseline to 32 ± 22% after 4 weeks of pacing (P = 0.05). CONCLUSION: We have shown that 4 weeks of coupled pacing simulating atrial bigeminy significantly reduced LV function. Our findings suggest that premature complexes independent of ventricular dyssynchrony might lead to the development of cardiomyopathy.

Atrial fibrillation: an independent risk factor for nonaccidental falls in older patients.

BACKGROUND: Nonaccidental falls are often the result of a combination of factors including cardiovascular disorders such as orthostatic hypotension and unspecified cardiac arrhythmias. The objective of this study was to determine if there is an association between atrial fibrillation (AF) and nonaccidental falls. METHODS: We reviewed the records of 442 consecutive patients >65 years old who presented to the Emergency Department at the University of Utah Medical Center with a complaint of fall. RESULTS: Two-hundred eleven patients presented with nonaccidental fall, 231 patients with accidental fall. Patients with nonaccidental fall were more likely to be older, have a history of hypertension and neurological disorders, and taking five or more medications when compared to patients with accidental fall. Despite a similar prevalence of sinus rhythm at presentation, the prevalence of a history of AF was significantly higher in patients with nonaccidental fall compared to patients with accidental fall (26% vs 15%; P = 0.003). After adjusting for clinically and statistically significant predictors with a multivariate logistic regression analysis, AF, neurological disorders, and age ≤81 years were independent predictors of nonaccidental fall. In patients ≤81 years old (median age), the risk of nonaccidental falls was 2.5 times greater in patients with a history of AF when compared to those without a history of AF (odds ratio = 2.53 [confidence interval 95% 1.3-5], P = 0.007). CONCLUSION: AF is an independent risk factor for nonaccidental falls. Our results emphasize the need to screen for AF in patients presenting with nonaccidental fall.

Very high serum ferritin levels in three newborns with Kawasaki-like illness.

Kawasaki disease (KD) is an inflammatory condition of unknown etiology that affects children, with a peak incidence in the second year of life. KD is uncommon in the first year of life and is rare in the newborn period. The present report describes three newborn infants who were admitted to hospital with fever and nearly identical clinical features of generalized inflammation. The presentations did not meet the criteria for KD; however, all three patients responded promptly and completely to intravenous immunoglobulin treatment. Specifically, the association of these presentations with very high levels of serum ferritin is reported. The authors propose that this clinical syndrome represents a variant of KD, and that serum ferritin level may be a useful marker in diagnosing KD and its variants. Additionally, the association of this clinical picture with very high serum ferritin levels raises the possibility of a link with hemophagocytic lymphohistiocytosis.

La maladie de Kawasaki (MK) est un problème inflammatoire qui touche les enfants et dont l'étiologie est inconnue. Le pic d'incidence se produit pendant la deuxième année de vie. La MK est peu courante pendant la première année de vie et rare pendant la période néonatale.Dans le présent rapport, les auteurs décrivent trois nouveau-nés fiévreux admis à leur hôpital et dont les manifestations cliniques d'inflammation généralisée étaient presque identiques. Les présentations ne respectaient pas les critères de MK. Cependant, les trois patients ont réagi rapidement et complètement au traitement à l'immunoglobuline par voie intraveineuse. Plus précisément, les auteurs rendent compte de l'association de cette présentation à de très forts taux de ferritine sérique. Ils postulent que ce syndrome clinique représente une variante de la MK et que le taux de ferritine sérique peut constituer un marqueur utile pour diagnostiquer la MK et ses variantes. De plus, l'association de ce bilan clinique à des taux de ferritine sérique très élevés soulève la possibilité d'un lien avec la lymphohistiocytose hémophagocytaire.

Safety, Pharmacokinetic, and Pharmacodynamic Study of a Sublingual Formula for the Treatment of Vasovagal Syncope.

BACKGROUND: Vasovagal syncope is a common cause of syncope which, if recurrent, can have multiple negative consequences such as injury and occupational disability. Various medications can be used to decrease the recurrence of vasovagal syncope but there are no drugs that can be used by patients to interrupt a perceived vasovagal episode. METHODS: A phase I study was performed to evaluate the tolerability and safety of a gel formulation containing capsaicin (1 mg), phenylephrine HCL (PE) and caffeine citrate (200 mg) (CPC) in normal adult volunteers. Secondary objectives were to characterize the pharmacokinetics (PK) of the CPC formulation and the highest dose of PE needed to achieve a target increase in systolic BP of at least 40 mmHg. After receiving the first dose, a second dose of the CPC mixture was administered at 2 h. Suboptimal changes in systolic blood pressure (SBP) were noted at PE doses of 0.6, 1.2, and 1.8 mg, therefore a second cohort was studied at PE doses of 10, 20, and 30 mg. Blood samples were collected in rapid sequence and were assayed for all three drugs. RESULTS: A total of 17 subjects received the drug with no serious adverse effects reported. All doses were well tolerated, although the capsaicin content usually caused expected temporary oral and gastric discomfort. One subject did not complete the study because of a vasovagal reaction that was associated with the frequent blood sampling. There was a 5-25 min lag in the appearance of measurable blood concentrations of capsaicin and phenylephrine. Most subjects had baseline caffeine concentrations from dietary use, with a gradual increase noted after 15 min consistent with GI absorption. Although the intended criterion of a 40 mmHg increase in SBP was not reached, a clinically significant increase in BP for at least 15 min was noted in the six subjects who received the highest dose of PE (30 mg), with a gradual decline over the next 2 h. CONCLUSION: The ternary mixture of capsaicin, phenylephrine, and caffeine was well tolerated when administered as two sublingual/oral doses over a 2-h period.