Procainamide. The treatment of choice for Wolff-Parkinson-White syndrome is cardioversion with direct current. Heart rate slowing drugs, commonly used in atrial fibrillation, are ineffective, and digoxin and non-dihydropyridine calcium channel blockers (e.g., verapamil, diltiazem) are contraindicated because they may increase the ventricular rate and cause ventricular fibrillation. If cardioversion is not possible, drugs that prolong the refractory period of accessory connection should be used. IV procainamide or amiodarone is preferred, but any class Ia, Ic or III antiarrhythmic drug can be used.

A 23-year-old male diagnosed with Wolff-Parkinson-White syndrome who comes to the emergency department for palpitations. The ECG shows an irregular wide QRS tachycardia, with a heart rate of 205 bpm, compatible with pre-excited atrial fibrillation. Which of the following drugs do you consider appropriate to stop the tachycardia:

Wolff-Parkinson-White syndrome: illustrative case and brief review.

The Wolff-Parkinson-White syndrome (WPWS) is a pre-excitation syndrome manifested on the 12-lead ECG by a short PR interval (less than .12 sec), a prolonged QRS interval (greater than .10 sec), and an initial slurring of the QRS complex called a delta wave. The anatomical etiology is the presence of accessory atrioventricular conduction fibers called the Kent bundle. Patients with the WPWS may present to the emergency department with a wide spectrum of symptoms, ranging from mild palpitations, to unstable tachydysrhythmias and sudden cardiac death. WPWS should be suspected in any patient presenting with a tachydysrhythmia with a rate exceeding 200/minute. Cardioversion is indicated in the unstable patient. It is impossible to predict the effect of any particular drug without prior electrophysiologic studies in a patient with WPWS. Procainamide is the safest drug for the stable WPWS patient with a tachydysrhythmia, including wide-complex and irregular rhythms. Verapamil is a useful drug in narrow-complex, regular rhythms, although complications have been reported. Atrial fibrillation may be difficult to diagnose in a very rapid tachycardia, and the use of verapamil in WPWS with atrial fibrillation is contraindicated. Electrophysiologic studies are indicated in the WPWS patient to maximize prophylactic therapy. An illustrative case as well as pathophysiology and management of WPWS are discussed.

Sodium channel blocker

Indications for Class Ia agents are supraventricular tachycardia, ventricular tachycardia, symptomatic ventricular premature beats, and prevention of ventricular fibrillation. Procainamide can be used to treat atrial fibrillation in the setting of Wolff-Parkinson-White syndrome, and to treat wide complex hemodynamically stable tachycardias. Oral procainamide is no longer being manufactured in the US, but intravenous formulations are still available. While procainamide and quinidine may be used in the conversion of atrial fibrillation to normal sinus rhythm, they should only be used in conjunction with an AV node blocking agent such as digoxin or verapamil, or a beta blocker), because procainamide and quinidine can increase the conduction through the AV node and may cause 1:1 conduction of atrial fibrillation, causing an increase in the ventricular rate. Class Ia agents include quinidine, procainamide and disopyramide. Class Ib agents

Wolff–Parkinson–White syndrome

People with atrial fibrillation and rapid ventricular response may be treated with amiodarone or procainamide to stabilize their heart rate. Procainamide and cardioversion are accepted treatments for conversion of tachycardia found with WPW. Amiodarone in atrial fibrillation with WPW, is linked to ventricular fibrillation, and thus may be worse than procainamide. AV node blockers should be avoided in atrial fibrillation and atrial flutter with WPW or history of it; this includes adenosine, diltiazem, verapamil, other calcium channel blockers, and beta blockers. They can exacerbate the syndrome by blocking the heart's normal electrical pathway (therefore favoring 1:1 atrial to ventricle conduction through the pre-excitation pathway, potentially leading to unstable ventricular arrhythmias).

Wolff-Parkinson-White syndrome presenting in atrial fibrillation.

A case of atrial fibrillation in a patient with Wolff-Parkinson-White (WPW) syndrome is presented. In this case, the patient's ECG initially was misread as ventricular tachycardia. The therapy was appropriate for the actual condition, although electrical cardioversion and defibrillation eventually were required. The treatment of WPW with atrial fibrillation in this case consisted of lidocaine and procainamide. Verapamil, propranolol, and digoxin, which normally are indicated for WPW with tachyarrhythmias, are contraindicated for WPW with atrial fibrillation.

Atrial fibrillation in the Wolff-Parkinson-White syndrome: ECG recognition and treatment in the ED.

Estimated to occur in 0.1% to 0.3% of the population, Wolff-Parkinson-White syndrome (WPW) is a condition where atrial impulses bypass the atrioventricular node and activate the ventricular myocardium directly via an accessory pathway. Clinical clues to the diagnosis include a young patient with previous episodes of palpitations, rapid heart rate, or syncope. Although several different rhythm presentations are possible, atrial fibrillation is a not infrequent dysrhythmia seen in the WPW patient. Electrocardiographic features suggestive of WPW atrial fibrillation include irregularity of the rhythm; a very rapid ventricular response; presence of a delta wave; and a wide, bizarre QRS complex. Stable patients suspected of having this condition should not receive agents that predominantly block atrioventricular conduction, but they may be treated with procainamide or ibutilide. If instability is present, electrical cardioversion is required.

Wolff-Parkinson-White syndrome and supraventricular tachycardia during infancy: management and follow-up.

The records of 90 patients with Wolff-Parkinson-White syndrome who presented with supraventricular tachycardia in the first 4 months of life were reviewed. Among these, 63% were male. Structural heart disease was present in 20%, most commonly Ebstein's anomaly. All patients presented with a regular narrow QRS tachycardia, and pre-excitation became evident only when normal sinus rhythm was established. Only one infant had atrial flutter and none had atrial fibrillation. Type A Wolff-Parkinson-White syndrome was most common (49%), with heart disease occurring in only 5% of these patients. In contrast, heart disease was identified in 45% of those with type B syndrome. Initially, normal sinus rhythm was achieved in 88% of the 66 infants treated with digoxin with no deaths. Normal sinus rhythm resumed after electrical countershock in 87% of the 15 infants so treated. Maintenance digoxin therapy was used in 85 patients. The Wolff-Parkinson-White pattern disappeared in 36% of the patients. Four infants died of cardiac causes during the mean follow-up period of 6.5 years. Two of these four infants had congenital heart disease; the third, with a normal heart initially, developed ventricular fibrillation and died from a cardiomyopathy considered related to resuscitation. The remaining infant, with a normal heart, died suddenly at 1 month of age. All were receiving digoxin. A wide QRS tachycardia later appeared in three patients, all with heart disease, one of whom died.(ABSTRACT TRUNCATED AT 250 WORDS)

Pre-excited atrial fibrillation triggered by intravenous adenosine: a commonly used drug with potentially life-threatening adverse effects.

Although serious adverse events following adenosine administration are rare, it should only be administered in an environment where continuous ECG monitoring and emergency resuscitation equipment are available. The case report describes the development of pre-excited atrial fibrillation in a 31-year-old woman with Wolff-Parkinson-White syndrome following the administration of adenosine. She had previously been fit and well and was admitted to the coronary care unit with a 2 h history of regular palpitations. A 12-lead ECG showed a narrow QRS complex tachycardia. Carotid sinus massage was unsuccessful in terminating the tachycardia and the patient subsequently received rapid boluses of intravenous adenosine. The cardiac rhythm degenerated into atrial fibrillation with ventricular pre-excitation following 12 mg adenosine.

Intravenous adenosine triphosphate during wide QRS complex tachycardia: safety, therapeutic efficacy, and diagnostic utility.

Inappropriate administration of intravenous verapamil to patients with wide QRS complex tachycardia due to ventricular tachycardia or atrial fibrillation with Wolff-Parkinson-White syndrome occurs frequently because of misdiagnosis, and may precipitate a cardiac arrest. We evaluated the safety and the diagnostic and therapeutic utility of adenosine triphosphate administered to a consecutive series of 34 patients during wide QRS complex tachycardia due to a variety of mechanisms. Patients who had a hemodynamically and electrically stable, monomorphic, wide (greater than 120 msec) QRS complex tachycardia induced during an invasive cardiac electrophysiologic test were studied. Hemodynamic stability was defined by a systolic blood pressure greater than 80 mm Hg and no clinical evidence of cerebral or myocardial ischemia. Adenosine triphosphate, 20 mg, was administered as a rapid intravenous bolus via a peripheral vein during wide QRS complex tachycardia. Five surface electrocardiogram leads, at least three intracardiac electrograms, and blood pressure were monitored. Ventricular tachycardia was present in 14 patients (mean age 50.6 +/- 19 years, cycle length 326 +/- 67 msec) and adenosine triphosphate terminated the arrhythmia in one case. Ventricular tachycardia cycle length did not change. Among 10 patients with supraventricular tachycardia with mechanisms not involving the AV node (average ventricular cycle length 346 +/- 82 msec), one case of ectopic atrial tachycardia was terminated. The ventricular rate was transiently increased in patients with Wolff-Parkinson-White syndrome and atrial fibrillation (average R-R interval 351 +/- 84 msec in control and 317 +/- 82 msec after adenosine triphosphate, p less than 0.001). Reentrant tachycardias involving the AV node (cycle length 302 +/- 52 msec) terminated in seven of 10 patients. The drug was well tolerated, and no patient developed hemodynamic compromise necessitating cardioversion as a result of adenosine triphosphate. In the setting of electrophysiology testing, adenosine triphosphate is a safe agent, even when administered inappropriately during arrhythmias for which it is relatively ineffective, such as ventricular tachycardia, and Wolff-Parkinson-White syndrome with atrial fibrillation. It is an effective agent in terminating supraventricular tachycardia involving the AV node. Tachycardia termination following adenosine triphosphate, when used as a diagnostic test to indicate obligatory participation of the AV node, had a sensitivity of 70%, specificity of 92%, and a positive predictive accuracy of 85%. Thus, adenosine triphosphate also has diagnostic utility, but should be used after the appropriate arrhythmia diagnosis has been made based on the clinical history and analysis of the 12-lead electrocardiogram.

Concealed pre-excitation causing paroxysmal reciprocating atrioventricular tachycardia in infancy.

We report 3 infants with Wolff-Parkinson-White (WPW) syndrome who presented with life-threatening paroxysmal reciprocating atrioventricular tachycardia in their first month of life. The diagnosis was confirmed by electrophysiological studies at ages 2--4 years, but the characteristic ECG of pre-excitation has not been shown in one patient and was first recorded at 2 and 3 years in the other two. In 2 patients the tachycardia proved refractory to treatment with digoxin alone but responded to the addition of propranalol or verapamil. One of these infants was converted to sinus rhythm by DC countershock, giving time to reconsider his treatment with drugs. Digoxin is a well-tried treatment acting by slowing AV conduction and interrupting the re-entry circuit. However, it may act more slowly than other agents that act on the AV node--such as intravenous verapamil. Our patients illustrate the value of long follow-up as the diagnosis of WPW syndrome could not be made in infancy. Many infants who present with paroxysmal supraventricular tachycardia in infancy may have an inapparent bypass and be examples of the WPW syndrome.

Diagnosis and Management of Common Types of Supraventricular Tachycardia.

Supraventricular tachycardia refers to rapid rhythms that originate and are sustained in atrial or atrioventricular node tissue above the bundle of His. The condition is caused by reentry phenomena or automaticity at or above the atrioventricular node, and includes atrioventricular nodal reentrant tachycardia, atrioventricular reciprocating tachycardia, and atrial tachycardia. Most persons with these tachyarrhythmias have structurally normal hearts. Sudden onset of an accelerated heart rate can cause palpitations, light-headedness, chest discomfort, anxiety, dyspnea, or fatigue. The history is important to elicit episodic symptoms because physical examination and electrocardiography findings may be normal. A Holter monitor or event recorder may be needed to confirm the diagnosis. Vagal maneuvers may terminate the arrhythmia; if this fails, adenosine is effective in the acute setting. Calcium channel blockers (diltiazem or verapamil) or beta blockers (metoprolol) can be used acutely or as long-term therapy. Class Ic antiarrhythmics (flecainide or propafenone) can be used long-term. Class Ia antiarrhythmics (quinidine, procainamide, or disopyramide) are used less often because of their modest effectiveness and adverse effects. Class III antiarrhythmics (amiodarone, sotalol, or dofetilide) are effective, but have potential adverse effects and should be administered in consultation with a cardiologist. Catheter ablation has a success rate of 95% and recurrence rate of less than 5%, and causes inadvertent heart block in less than 1% of patients. It is the preferred treatment for symptomatic patients with Wolff-Parkinson-White syndrome.

[The natural history of 270 cases of Wolff-Parkinson-White syndrome in a survey of the general population].

Among 226,464 ambulatory subjects who underwent medical check-ups over a 15-year period, 270 were found to have Wolff-Parkinson-White syndrome (1.2 case in 1,000). The syndrome was more frequent in men (181 cases, 1.4 p. 1,000) than in women (89 cases, 0.9 p. 1,000). 222 subjects were aged from 20 to 49 years (1.4 p. 1,000) and only 48 were between 50 and 80 years of age (0.7 p. 1,000). 197 subjects were re-evaluated: 119 (60.4 p. 100) complained of palpitations and 78 (39.6 p. 100) were asymptomatic. Palpitations began at all ages, even after 50 years, and usually proceeded in short attacks lasting a few seconds or minutes, with a mean recurrence rate of 5 attacks per annum (76.4 p. 100). This constant pattern sometimes was interrupted for months or years. Conversely, in a minority of cases (23.5 p. 100) an unexpected accentuation occurred which lasted for hours or days. As years went by, palpitations tented to decrease and disappear. The pre-excitation area and its degree of fusion with the normal ventricular activation had no influence on the origin and frequency of palpitations. In contrast, sustained tachycardia seemed to be more frequent in cases with lateral and posterior left pre-excitation. Among 270 subjects with pre-excitation syndrome, 7 died including 4 whose death was not due to a cardiac disease, 2 who died suddenly and 1 who succumbed to ventricular tachycardia after a road accident. None of these patients had an associated heart disease. These last 3 cases might contribute to alter the usually favourable prognosis of Wolff-Parkinson-White syndrome.

Broad complex atrial fibrillation.

The management of broad complex atrial fibrillation is complex and may be a source of morbidity and mortality if not correctly recognized and treated appropriately. We present a case series of 3 patients who were managed in our emergency department after complaints of palpitations. They presented with varying forms of rapid atrial fibrillation that had broad complexes on the 12-lead electrocardiogram. The first 2 patients were treated with calcium channel blockers for rate control, and treatment was complicated by rapid arrhythmia that required cardioversion. The final patient was correctly treated with intravenous procainamide. The diagnosis of Wolff-Parkinson-White syndrome was eventually made in all these patients. Broad complex atrial fibrillation must be treated with respect. Cases with rapid ventricular rate can decompensate from mismanagement due to poor ability to recognize the possibility of Wolff-Parkinson-White syndrome in such patients. Procainamide forms the cornerstone of treatment in hemodynamically stable rapid broad complex atrial fibrillation of unknown origin.

Diagnosis and management of arrhythmias associated with Wolff-Parkinson-White syndrome.

Because of the emergency nature of the arrhythmias associated with WPW syndrome, nurses are often called upon for diagnosis and intervention in critical settings. In such cases the nurse's understanding of mechanisms, ECG recognition, and emergency treatment guarantees the patient the best possible outcome, not only in the critical setting, but in the long term as well. The most common arrhythmias of WPW syndrome are PSVT and atrial fibrillation. In PSVT a differential diagnosis is made on the ECG between (1) CMT using the AV node anterogradely and an accessory pathway retrogradely and (2) AV nodal reentry tachycardia. Helpful clues are location of the P' wave, presence of QRS alternans, the initiating P'R interval, and presence of aberrancy. Atrial fibrillation with an accessory pathway has the morphology of VT but is differentiated because the rhythm is irregular and the rate is more than 200 beats per minute. Emergency treatment consists of blocking the accessory pathway with procainamide. Emergency treatment for both types of PSVT consists of breaking the reentry circuit at the AV node (eg, vagal maneuver, adenosine, or verapamil). Procainamide can also be used to block the retrograde fast pathway in the AV node and to terminate CMT by blocking the accessory pathway. Symptomatic patients with accessory pathways are referred for evaluation and possible radio-frequency ablation.

Usefulness of invasive and non-invasive electrophysiologic studies in the selection of antiarrhythmic drugs for the patients with paroxysmal supraventricular tachyarrhythmia.

A comparison of the effects of several antiarrhythmic agents was made in a study of 70 patients - 15 with manifest Wolff-Parkinson-White (WPW) syndrome, 17 with concealed WPW syndrome, 18 with AV nodal re-entrant tachycardia, 14 with paroxysmal atrial fibrillation and 6 with paroxysmal atrial flutter - employing intracardiac stimulation and esophageal pacing. For the termination of paroxysmal supraventricular tachycardia, intravenous administration of verapamil or aprindine was more effective than that of disopyramide or procainamide. In AV nodal re-entrant tachycardia, verapamil was the most effective for termination. In the manifest WPW syndrome, disopyramide or aprindine was indicated especially for patients with the accessory pathways of the short antegrade refractory period, because these drugs lengthened the refractory period of the accessory pathways. For the purpose of converting atrial fibrillation or flutter to the sinus rhythm, type IA drugs such as disopyramide were indicated. However, verapamil was effective for slowing down the ventricular rate in atrial fibrillation or flutter except in cases of manifest WPW syndrome. A 6-month follow-up study showed that oral administration of verapamil was also useful for putting a stop to the attacks in 24 out of 32 patients with paroxysmal supraventricular tachycardia, while oral disopyramide prevented the recurrence of atrial fibrillation in only 4 of 10 patients.

Wolff-Parkinson-White Syndrome--current views.

The Wolff-Parkinson-White (WPW) syndrome is an important clinical entity because of frequent recurrences of very rapid tachyarrhythmias. The electrocardiographic finding of the WPW syndrome often mimicks pseudo diaphragmatic (inferior) myocardial infarction which should not be misinterpreted. The most important diagnostic criterion is recognition of a delta wave; the short P-R interval or broad QRS complex may not be present in every case. The mechanism for the tachycardia is considered to be a reentry phenomenon via anomalous and normal atrioventricllar (A-V) pathways. The drug of choice for the treatment of regular supraventricular (reciprocating) tachycardia with narrow QRS complexes, which is the most common arrhythmia in the WPW syndrome, is propranolol. Digitalis is almost equally effective in this case. For tachyarrhythmias, particularly atrial fibrillation or flutter with anomalous conduction, intravenously-administered lidocaine is considered to be the drug of choice. Procainamide or quinidine is also frequently used under this circumstance with excellent therapeutic result. Many patients with the WPW syndrome require long-term maintenance drug therapy (propranolol, digitalis or quinidine in most cases). In urgent clinical situations, direct current (DC) shock should be applied immediately. In selected patients with refractory tachyarrhythmias, the use of an artificial pacemaker or surgical approach may be considered.

Wolff–Parkinson–White syndrome

Diagnosis WPW is commonly diagnosed on the basis of the electrocardiogram in an asymptomatic individual. In this case, it is manifested as a delta wave, which is a slurred upstroke in the QRS complex that is associated with a short PR interval. The short PR interval and slurring of the QRS complex are reflective of the impulse making it to the ventricles early (via the accessory pathway) without the usual delay experienced in the AV node. If a person with WPW experiences episodes of atrial fibrillation, the ECG shows a rapid polymorphic wide-complex tachycardia (without torsades de pointes). This combination of atrial fibrillation and WPW is considered dangerous, and most antiarrhythmic drugs are contraindicated.

Pharmacological Cardioversion -- Technique or Treatment -- Irregular Wide Complex or Polymorphic Tachycardia

This rhythm either has an irregular rhythm or QRS complexes that are irregular in shape. This may be from atrial fibrillation combined with Wolff-Parkinson-White syndrome or atrial fibrillation with bundle branch block, torsades de pointes and ventricular fibrillation. If the rhythm is Wolff-Parkinson-White, this condition can be worsened by the use of nodal blocking agents and a cardiology consult should be obtained for people in this rhythm. Procainamide or amiodarone may be attempted. However, this patient may need electrical cardioversion. If the rhythm is determined to be torsades de pointes, the patient should be treated with an infusion of IV magnesium, 2g to 4 g over 5 to 10 minutes.

[Dangerous arrhythmias].

The usual frequent tachyarrhythmias well known to the specialists in internal medicine, such as ventricular tachycardia and ventricular fibrillation, are not discussed in this publication; nor are the bradycardias connected with the sick sinus syndrome or with atrioventricular block of higher degrees (with one exception). In the first section a stratification of the risk after myocardial infarction is presented including the therapeutic implications. Severely reduced left ventricular function is of most negative prognostic value. After the poor results of the CAST study, which revealed a threefold greater mortality of patients with myocardial infarction and severely impaired left ventricular function under treatment with some antiarrhythmic agents of class I (Vaughan Williams), compared to patients on placebo, cardiologists have resorted to beta-blocking agents again or, in patients with severely reduced left ventricular function, to amiodarone (Cordarone), based on preliminary results of current amiodarone studies. For selected patients, implantable cardioverter-defibrillator (ICD) devices seem to have a promising future. In the second part some rare and persistent arrhythmias are mentioned that may induce heart failure in an otherwise healthy heart, such as ectopic atrial tachycardia, atrioventricular junctional tachycardia with RP > PR, His bundle tachycardia and idiopathic ventricular tachycardia (this arising only in infants). In the third section some infrequent forms of tachycardia are discussed that may be sporadically encountered in a medical office. Ventricular tachycardia of the type "torsades de pointes" is associated with on a prolonged QT or QTU time in the ECG and is mainly due to drugs (especially antiarrhythmic agents). The therapy consists in withdrawal of the drug and may include magnesium intravenously and even a temporary pacemaker. The tachycardias associated to the Wolff-Parkinson-White syndrome have gained more practical importance since it has become possible to localize the accessory pathway involved by mapping with subsequent interruption by surgery or ablation. In atrial fibrillation with an ECG pattern of delta waves at the beginning of QRS complexes, digitalis and verapamil are contraindicated since they may induce ventricular fibrillation. The Mobitz type is one, and the most rare, form of the three atrioventricular blocks of second degree. It is almost always combined with an infra-His-bundle conduction disturbance in the conducted beats, and is an immediate precursor of complete atrioventricular block. Patients with the Mobitz block usually need a pacemaker. Finally, two case reports are presented to show that superficial and incorrect diagnosis of an arrhythmia is followed by incorrect and dangerous therapy.(ABSTRACT TRUNCATED AT 400 WORDS)

[The clinical features and long-term follow-up of atrial fibrillation or atrial flutter complicating Wolff-Parkinson-White syndrome].

Twenty six patients (20 male, 6 female, aged 50 +/- 14) with recurrent episodes of atrial fibrillation or atrial flutter (Af/AF) associated with WPW syndrome were retrospectively studied and followed. During Af/AF, 17 patients showed ventricular preexcitation. Of them, 15 patients had hypotention, 8 syncope, 4 precipitating acute heart failure and 4 spontanous degenerated into ventricular fibrillation. Hypotention was found only in 2 of the 9 patients without pre-excited ventricular beats. The mean shortest prexcited R-R intervals of the former were shorter (247 +/- 47 ms) and the average ventricular rates (198 +/- 43 beat/min) were faster than those of the latter (393 +/- 80 ms & 144 +/- 22 beat/min) respectively (P < 0.01). When pre-excited Af/AF occurred, both cardioversion and antiarrhythmic agents of class I and II had marked effect in terminating the Af/AF or slowing pre-exicted ventricular responses. Digitalis and verapamil caused deterioration in the clinical condition of 6 patients (4 with hypotention, one syncope, and one ventricular fibrillation). Management of patients for WPW complicating Af/AF without pre-excited QRS was the same as for the ordinary Af/AF. Over a period of 53 +/- 44 months of follow-up, 5 died (3 of sudden death, one of heart failure, and one of noncardiac cause) in the group with preexcited Af/AF, but all of the patients without preexcited QRS during Af/AF were alive. Conclusion, clinical severity, response to the treatment, and long-term prognosis of patients of WPW with preexcited Af/AF are different from those without.

Adenosine: a clinical experience and comparison with verapamil for the termination of supraventricular tachycardias.

The efficacy and side-effects of adenosine for treatment of supraventricular arrhythmias were compared to verapamil therapy in patients presenting to the emergency room. Clinical variables and the time interval from the initiation of treatment to the termination of the supraventricular tachycardia, as well as the time from the initial effective dose of medication to the termination of supraventricular tachycardia were compared for adenosine and verapamil. Adenosine was given to a total of 44 patients, 16 patients in the electrophysiology laboratory, and 28 patients in the emergency room for evaluation and termination of their tachycardia. In the electrophysiology laboratory, 7 patients had AV node reentry, 5 had Wolff-Parkinson-White syndrome, 2 of whom had atrial flutter and fibrillation but no bypass tract reentry, 1 had concealed bypass tract reentry, 1 had Lown-Ganong-Levine syndrome, 1 had intraatrial reentry, and 1 had an automatic atrial tachycardia. Twenty-five patients received adenosine in the emergency room and 3 patients in the hospital for 31 episodes of supraventricular arrhythmias. In the emergency room, 11 patients had supraventricular tachycardia due to AV node reentry, 3 had Wolff-Parkinson-White syndrome, 6 had atrial flutter or intra-atrial re-entry, 2 had ventricular tachycardia, and 3 had sinus tachycardia. In the hospital, 2 patients had atrial flutter and one had sinus tachycardia. The group of 14 patients with supraventricular tachycardia due to Wolff-Parkinson-White syndrome or AV node reentry presenting in the emergency room were compared in a retrospective manner to the patients treated with standard verapamil therapy with respect to time from initiation of therapy to termination of supraventricular tachycardia and time from effective dose of medication to the termination of supraventricular tachycardia, as well as side-effects. There was no significant difference between the two groups with respect to clinical variables. Adenosine converted 18 of 18 episodes of supraventricular tachycardia in 14 patients 24.6 +/- 9.6 seconds from the administration of the effective dose (0.104 +/- 0.024 mg/kg) and a mean of 4.4 +/- 2.0 minutes from the initiation of therapy. Verapamil converted 29 of 32 episodes of supraventricular tachycardia in 20 patients, 10.9 +/- 7 minutes from the administration of the effective dose, and a mean of 16.8 +/- 20 minutes from the initiation of therapy using a mean of 8.4 +/- 3.4 mg of IV verapamil.(ABSTRACT TRUNCATED AT 400 WORDS)

Pre-excitation syndrome in infants and children. Effect of digoxin, verapamil, and amiodarone.

Clinical and electrocardiographic findings for 30 patients with the pre-excitation syndrome are described together with details of treatment. Nineteen (63%) were younger than 2 years, 14 of whom were under 2 months. Sixteen infants and 7 children (77%) presented with paroxysmal supraventricular tachycardia, 14 (61%) of whom had the electrocardiographic pattern of type A Wolff-Parkinson-White (WPW) syndrome. During paroxysmal bouts the QRS complex was normal in 21 patients and wide in two. Six (20%) patients had congenital heart disease often associated with WPW syndrome type B. Seventeen patients were treated with either digoxin or verapamil intravenously to stop tachyarrhythmias. Verapamil was more effective due to the immediate response and lack of adverse effects. The tachyarrhythmias resolved in all the patients and in some of them the WPW pattern resolved later indicating maturation of the conduction tissue with loss of the accessory pathways. Verapamil provides a rapid and safe form of treatment for conversion of tachyarrhythmias since it has no effect on the accessory pathways. Oral amiodarone prevents recurrent tachyarrhythmias resistant to other treatment.

Sinus tachycardia

Diagnosis Sinus tachycardia is usually apparent on an ECG, but if the heart rate is above 140 bpm the P wave may be difficult to distinguish from the previous T wave and one may confuse it with a paroxysmal supraventricular tachycardia or atrial flutter with a 2:1 block. Ways to distinguish the three are: Vagal maneuvers (such as carotid sinus massage or Valsalva's maneuver) to slow the rate and identification of P waves administer AV blockers (e.g., adenosine, verapamil) to identify atrial flutter with 2:1 block Heart sounds should also be listened to. ECG characteristics Rate: Greater than or equal to 100. Rhythm: Regular. P waves: Upright, in leads I, II and aVL, and negative in lead aVR; each P wave is followed by a QRS and T waves Inappropriate sinus tachycardia

AV nodal reentrant tachycardia

Diagnosis If the symptoms are present while the person is receiving medical care (e.g., in an emergency department), an ECG may show typical changes that confirm the diagnosis ie, QRS duration <120 ms, unless a heart block is suspected. If the palpitations are recurrent, a doctor may request a Holter monitor (portable, wearable ECG recorder). Again, this will show the diagnosis if the recorder is attached at the time of the symptoms. In rare cases, disabling but infrequent episodes of palpitations may require the insertion of a small device under the skin that continuously record heart activity (an implantable loop recorder). All these ECG-based technologies also enable the distinction between AVNRT and other abnormal fast heart rhythms such as atrial fibrillation, atrial flutter, sinus tachycardia, ventricular tachycardia and tachyarrhythmias related to Wolff-Parkinson-White syndrome, all of which may have symptoms that are similar to AVNRT.

Anti-arrhythmic surgery for atrioventricular junctional and atrioventricular re-entrant tachycardia--a report of six cases.

Since 15th March 1989, six patients with recurrent supraventricular tachycardia (SVT) had antiarrhythmic surgery performed. There were 4 males and 2 females, ages ranged from 23 to 62 years (mean 41 years). Two of these patients with the Wolff Parkinson White (WPW) syndrome also had syncope. Five of these patients had atrioventricular re-entrant tachycardia (AVRT) involving the bypass tracts. Two patients with the WPW syndrome had persistent antegrade conduction, two had intermittent conduction and the last patient had no antegrade conduction via the bypass tract. The bypass tracts were localised at the left free wall in all the five patients. Only one patient had atrioventricular junctional re-entrant tachycardia (AVJRT) of the slow-fast type. The indications for surgery for these patients include failed medical therapy, "dangerous" arrhythmias and patient's preference. All the patients had surgery performed using the endocardial dissection technique on the cardioplegic heart. There were no perioperative mortality and morbidity. All the patients were discharged within 2 weeks. To date, none of the patients had clinical recurrence of SVT and only one patient remained in atrial fibrillation and is on digoxin. In conclusion, antiarrhythmic surgery should be considered for patients with "symptomatic" palpitations as it is curative with a resumption to normal life.

Wolff-Parkinson-White Syndrome -- Treatment / Management

Pharmacological treatment of a hemodynamically stable acute tachyarrhythmia suspected to involve an accessory pathway must be based on the type of arrhythmia and accessory pathway present as certain pharmacological treatments may be detrimental or even fatal. Pathways that are not involved in the initiation and maintenance of an arrhythmia leading to AVRT will conduct an arrhythmia generated elsewhere in the heart. In the setting of an accessory pathway capable of rapid antegrade conduction, rapid atrial arrhythmias can be conducted to the ventricle inducing rapid ventricular rates that may deteriorate into ventricular fibrillation and cardiac arrest. AV nodal blockade can induce this scenario if given in the setting of a bystander accessory pathway and rapid atrial rhythm, as seen in atrial fibrillation, atrial flutter, or other atrial tachycardias. These arrhythmias will be wide complex tachycardia and may be regular or irregular, depending on the underlying arrhythmia. Without electrophysiologic study, antidromic AVRT will be difficult to diagnose definitively and should, therefore, be managed similarly with avoidance of nodal blocking agents. The pharmacologic treatment of choice for antidromic AVRT is procainamide. In the setting of preexcitation and atrial fibrillation, AV nodal blockade is contraindicated. Procainamide and ibutilide are agents of choice in atrial fibrillation with preexcitation on ECG. Amiodarone has been used in WPW pattern with atrial fibrillation, but some evidence suggests that it is less effective and has a higher risk of precipitating ventricular fibrillation. If there remains any doubt about the diagnosis of a wide complex tachycardia, it is recommended that it be managed as suspected ventricular tachycardia. [16] [18] [19] [23] [24]

Supraventricular tachycardia

Supraventricular tachycardia (SVT) is an umbrella term for fast heart rhythms arising from the upper part of the heart. This is in contrast to the other group of fast heart rhythms - ventricular tachycardia, which start within the lower chambers of the heart. There are four main types of SVT: atrial fibrillation, atrial flutter, paroxysmal supraventricular tachycardia (PSVT) and Wolff–Parkinson–White syndrome. The symptoms of SVT include palpitations, feeling of faintness, sweating, shortness of breath, and/or chest pain. These abnormal rhythms start from either the atria or atrioventricular node. They are generally due to one of two mechanisms: re-entry or increased automaticity. Diagnosis is typically by electrocardiogram (ECG), holter monitor, or event monitor. Blood tests may be done to rule out specific underlying causes such as hyperthyroidism or electrolyte abnormalities.

First_Aid_Step2

If unstable, perform synchronized electrical cardioversion starting at 100 J. If stable, control rate with diltiazem or β-blockers and anticoagulate if duration is > 48 hours. Elective cardioversion may be performed if duration is < 48 hours; otherwise, the clinician must anticoagulate or perform TEE prior to conversion. Do not give nodal blockers if there is evidence of Wolff-Parkinson-White syndrome (δ waves) on ECG. If symptomatic, give atropine and consider dopamine, epinephrine, and glucagon. If Mobitz II or third-degree heart block is present, place transcutaneous pacemaker pads, and have atropine at the bedside. A temporary transvenous pacemaker may be required for hemodynamically unstable patients. a In all cases, disruptions of CPR should be minimized. After a shock or administration of a drug, CPR should be resumed immedi ately, and fve cycles of CPR should be given before checking for a pulse or rhythm.

Rapid and low-cost method to prove the nature of no documented tachycardia in children and teenagers without pre-excitation syndrome.

Aims Symptoms in children are often difficult to interpret. The purpose of this study was to report the results of transoesophageal electrophysiological study (EPS) performed in children complaining of sudden onset tachycardia with normal non-invasive studies. Methods and results Eighty-two children and teenagers (mean age 15 +/- 3 years) presented with suspected but no documented paroxysmal supraventricular tachycardia (SVT). ECG was normal. Non-invasive studies were negative; 23 children had syncope with tachycardias. They underwent transoesophageal EPS in our out-patient clinic. The mean duration of transoesophageal EPS was 11 +/- 5 min. Electrophysiological study was negative in 25 children. AV nodal re-entrant tachycardia could be induced in 37 children, 11 of them associated with syncope. Wolff-Parkinson-White syndrome (WPW) was diagnosed in five children in which atrioventricular re-entrant tachycardia was inducible. Atrioventricular re-entrant tachycardia due to a concealed AP was induced in 14 children. Verapamil-sensitive ventricular tachycardia was induced in one patient. Factors associated with tachycardia inducibility were an older age (15.5 +/- 2 vs. 14 +/- 4 years) (P < 0.05) and the absence of syncope (81 vs. 52%) (P < 0.05). During a mean follow-up of 3 +/- 1 year, no patient with negative EPS developed documented tachycardia. In 17 children with inducible SVT, radiofrequency ablation of the re-entrant circuit was subsequently performed. Conclusion Transoesophageal EPS is a fast method for proving the nature of paroxysmal tachycardia in children and teenagers presenting with normal ECG and for demonstrating WPW syndrome not visible on standard ECG. The negative predictive value of transoesophageal EPS for the diagnosis of SVT was 100%.

First_Aid_Step2

seen after a (AVRT) node and the normal QRS. atrium through a bypass tract. Seen in Wolff-Parkinson-White syndrome. Paroxysmal atrial tachycardia Rapid ectopic pacemaker in the atrium (not sinus node). Palpitations, shortness of breath, angina, syncope, lightheadedness. Rate > 100 bpm; P wave with an unusual axis before each normal QRS. Adenosine can be used to unmask underlying atrial activity. T AB LE 2.1 -3. Ventricular Tachyarrhythmias

InternalMed_Harrison

In general, these should be managed as ventricular tachycardia until proven otherwise. If the tachycardia is regular and the patient is stable, a trial of intravenous adenosine is reasonable. Very irregular wide-complex tachycardia should be managed with cardioversion, intravenous procainamide, or ibutilide, which presumes preexcited atrial fibrillation or flutter (see above). If the diagnosis of PSVT with aberrancy is unequivocal, as may be the case in patients with prior episodes, treatment for PSVT is reasonable. In all cases, continuous ECG monitoring should be implemented, and emergency cardioversion and defibrillation should be available.

Ebstein's anomaly

Risk factors An enlargement of the aorta may occur; an increased risk of abnormality is seen in babies of women taking lithium during the first trimester of pregnancy (though some have questioned this) and in those with Wolff-Parkinson-White syndrome. Diagnosis Treatment Medication Ebstein's cardio physiology typically presents as an (antidromic) AV reentrant tachycardia with associated pre-excitation. In this setting, the preferred medication treatment agent is procainamide. Since AV-blockade may promote conduction over the accessory pathway, drugs such as beta blockers, calcium channel blockers, and digoxin are contraindicated.

Syncope (medicine)

Two major groups of arrhythmias are bradycardia and tachycardia. Bradycardia can be caused by heart blocks. Tachycardias include SVT (supraventricular tachycardia) and VT (ventricular tachycardia). SVT does not cause syncope except in Wolff-Parkinson-White syndrome. Ventricular tachycardia originate in the ventricles. VT causes syncope and can result in sudden death. Ventricular tachycardia, which describes a heart rate of over 100 beats per minute with at least three irregular heartbeats as a sequence of consecutive premature beats, can degenerate into ventricular fibrillation, which is rapidly fatal without cardiopulmonary resuscitation (CPR) and defibrillation. Long QT syndrome can cause syncope when it sets off ventricular tachycardia or torsades de pointes. The degree of QT prolongation determines the risk of syncope. Brugada syndrome also commonly presents with syncope secondary to arrhythmia.


Dehydration may be due to diarrhea of other etiologies. I have doubts about answer 3 since it does not specify which secretions are involved. We have to understand that the growth of Pseudomona aeruginosa is in the culture of bronchial secretions. Because clearly the indication to perform a sweat chlorine (to rule out FQP) are the HIPOnatremic dehydrations and not the hypernatremic ones as the answer says.

Dehydration may be due to diarrhea of other etiologies. I have doubts about answer 3 since it does not specify which secretions are involved. We have to understand that the growth of Pseudomona aeruginosa is in the culture of bronchial secretions. Because clearly the indication to perform a sweat chlorine (to rule out FQP) are the HIPOnatremic dehydrations and not the hypernatremic ones as [HIDDEN].

In a 3-month-old infant all the clinical manifestations outlined below would make it necessary to rule out cystic fibrosis, EXCEPT:

Isolation of secretions of Pseudomonas aeruginosa.

Deterioration/detention of the weight curve.

[Cystic fibrosis revealed by dehydration with hypochloronatremic alkalosis in 3 infants and a neonate].

BACKGROUND--Acute dehydration with hypochloronatremic metabolic alkalosis is a classical complication of cystic fibrosis of the pancreas. Its progressive development as a revealing manifestation of the disease is rare as is its appearance in newborns. Case n. 1.--A 13 month-old girl was admitted because of status epilepticus. She was severely dehydrated (20% weight loss) but had normal diuresis. Investigations showed metabolic alkalosis, hypochloronatremia and hypokalemia. All the manifestations disappeared within 5 days with treatment but three sweat tests were abnormal. Case n. 2.--A 7 month-old girl was admitted because she suffered from progressive loss of weight (10%); she was dehydrated and had metabolic alkalosis plus hypochloronatremia, but her diuresis was normal. Two sweat tests were abnormal. Case n. 3.--A 4.5 month-old boy was admitted because he suffered from severe (12%) weight loss. His diuresis was normal despite dehydration; metabolic alkalosis and hypochloronatremia were found. Two subsequent sweat tests were abnormal. Case n. 4.--A 3 day-old girl was admitted suffering from meconium ileus. Two initial mechanism analysis for protein were abnormal. She had a cardiorespiratory arrest on the 13th day of life, when she had lost 14% of her birth weight; investigations showed metabolic alkalosis, hyponatremia (83 mEq/l), hypochloremia (45 mEq/l); kalemia was 5.9 mEq/l. Peritoneal dialysis was needed to correct hydroelectrolytic changes. A sweat test performed on the 26th day of life was also abnormal. Investigations performed during the periods of dehydration, and repeated later, showed transient functional kidney failure. None of the four patients had any respiratory or gastrointestinal clinical manifestations of cystic fibrosis. CONCLUSION--Metabolic alkalosis with hypochloronatremia plus progressive, severe dehydration in infants whose diuresis is paradoxically normal must be followed by examination for cystic fibrosis.

Clinical profile and frequency of delta f508 mutation in Indian children with cystic fibrosis.

To document clinical profile of cystic fibrosis (CF) in Indian children and the prevalence of delta F508 mutation in these patients. Observational study. Pediatric chest clinic in an urban tertiary care center in north India. July 1995 to June 2002. Clinical features of 120 children diagnosed as CF by quantitative pilocarpine iontophoresis were recorded. A polymerase chain reaction based test for identification of delta F 508 mutation was performed on all children. Out of 3500 new cases registered in Pediatric Chest Clinic during this period 120, (3.5%) children were diagnosed as CF. Origin of parents of patients traced from almost all the States of north India. Family history suggestive of CF was present in 41 (34%) and consanguinity in 19 (61%) patients. Common clinical manifestations at the time of presentation included recurrent or persistent pneumonia in 118 (98%), failure to thrive in 108 (90%), malabsorption in 96 (80%), history of meconium ileus in 10 (8%), and rectal prolapse was present in 16 (13%). History of salt craving, salty taste on kissing and skin rashes was present in 5 patients each. 49(41%) patients were severely malnourished. Nasal polyposis was present in 5 (4%) patients. Examination of chest revealed evidence of hyperinflation in 100 (83%), kyphosis 20 (17%), crepitations 110 (92%), wheezing 40 (25%) and bronchial breathing in 20 (17%) patients. Average clinical CF scores were 51 (95%; CI 20-80). 48 (40%) patients had a CF score of LT40. Pseudomonas spp was cultured from respiratory secretions of 51 (42%), Staphylococcus spp in 18 (15%), Klebsiella spp in 8 (7%) and Hemophilus influenzae in 2 (2%) patients. Delta F508 mutation was positive in 45 chromosomes out of 240 tested. Patients originated from Pakistan had more frequency of delta F508 mutations. Cystic fibrosis does occur in Indian children; clinical features are classical. Diagnosis is often delayed and the disease is advanced in most patients at the time of diagnosis. Frequency of Delta F508 mutation is 19% i.e., less than that seen in Caucasian population. There is need to create awareness about occurrence of CF in Indian children.

Meconium ileus in newborns with cystic fibrosis - results of treatment in the group of patients operated on in the years 2000-2014.

Evaluation of diagnostic and treatment procedures in children with cystic fibrosis (CF) operated on because of meconium ileus (MI). The authors retrospectively reviewed the documentation of 10 CF newborn patients operated on in the years 2000-2014 because of MI. In prenatal ultrasound (US) examinations, suspicion of bowel abnormalities was raised in 2 cases, even though all the 10 mothers had a minimum of 3 US examinations during pregnancy. The mean gestational age of the newborns was 39.2 weeks - 36-41 weeks), their mean birth weight 3472g (2560-4550 g). Family history of CF was positive in two patients. Genetic testing was performed in all the children operated on. In all the children operated on, mutations in both alleles of the CFTR gene were found. Five patients were F508del homozygotic, 4 were heterozygotic for this mutation, one had another mutation. Sweat tests were positive in all the children. Abdominal distention was observed in 9 patients, vomiting and retention of gastric contents in 5. In 8 children meconium was not passed at all. 2 children passed a small amount of viscid meconium. Before the operation, rectal saline washouts were done in 5 newborns. Five patients were operated on during the first day of life, four on the second day and one on the third day of life. Intra-operatively a simple form of MI was diagnosed in 8 cases, a complicated form in 2 cases. In patients with the simple form of MI, a Bishop-Koop stoma was created after the evacuation of meconium. Two of these children needed a resection of some centimetres of dilated terminal ileum with doubtful viability. In newborns with the complicated form of MI, the treatment was individualized, always with stoma formation. The time of postoperative meconium evacuation through enterostomy ranged from 6 to 15 days. Enteral feeding was started on average on the 9th day postoperatively. The mean hospital stay was 22.9 days. In 8 children the stoma was taken out at the mean age of 19.4 months, in one patient the stoma closed spontaneously. No disturbances in electrolyte balance or excessive fluid loss, nor any body weight deficits connected with the stoma were observed. There were no complications during stoma closure. All the patients are alive. The time of observation ranges from 7 to 146 months (average 95 months). All the patients currently present respiratory symptoms, have pancreatic insufficiency and need pancreatic enzyme supplementation. Seven do not, however, have body weight and height deficits. All the children with weight and height deficits have abnormal liver function tests. During observation two patients had MI equivalent symptoms, which was resolved by conservative treatment. 1. In every case of intra-operative diagnosis of MI, it is necessary to perform genetic testing and sweat tests to confirm or exclude CF. 2. Mechanical intra-operative decompression of the bowel from inspissated meconium with a temporary stoma, which makes the continuation of bowel decompression possible in the postoperative period, is an effective treatment in children with MI. 3. The Bishop-Koop stoma, permitting the passage through the whole gastrointestinal tract, is a safe option. In our material, no complications of this stoma, such as stoma care problems or dyselectrolithemia were observed. 4. The decision of stoma closure in children with MI and CF should be delayed until the moment of introducing a broadened diet and should be undertaken together with a pediatrician who is a specialist in CF therapy. .

[Cystic fibrosis at a Brazilian center of excellence: clinical and laboratory characteristics of 104 patients and their association with genotype and disease severity].

To identify the clinical, laboratory and radiographic characteristics of the cystic fibrosis patients under care at Universidade Estadual de Campinas (UNICAMP) in the last decade of the twentieth century, and to investigate the association of these characteristics with genotype and severity of the disease as measured by the Shwachman score. Descriptive, retrospective and cross-sectional study of the patients assisted at UNICAMP hospital's Cystic Fibrosis Clinic from July 1990 to July 2000. One hundred and four patients were studied; 53.8% male; 93.3% Caucasian; 89.4% presented with respiratory symptoms; 59.6% presented with digestive symptoms; 5.8% had meconium ileus; 4.8% had diabetes. The mean age at onset of symptoms was 3 months, and the mean age at diagnosis was 2 years and 4 months. At diagnosis, 69.9 and 56.6% of the patients had weight and height below 10th percentile, respectively; in 10.6%, sweat chloride was < 60 mEq/l. Staphylococcus aureus was found in 80.2%, Pseudomonas aeruginosa in 76%, and Burkholderia cepacia in 5.2%. DeltaF508 homozygosis was observed in 18.75%, whereas 62.50% of the patients were DeltaF508 heterozygous. A moderate/severe Shwachman score was found in 15.7%. Eighteen patients died in that period (17.3%). The mean age at death was 7 years and 8 months; median survival after diagnosis was 18 years and 4 months. Patients who have at least one DeltaF508 mutation have more frequent alterations in fecal fat levels when compared to patients who do not have this mutation (p < 0.05). There were no differences in any parameter between DeltaF508 homozygous and heterozygous patients. The clinical and laboratory characteristics of the 104 patients studied were similar to the characteristics described for patients in other countries. Exceptions are the higher age at diagnosis and lower survival. Our results support the recommendation for early diagnosis and the need for more treatment opportunities in the population of cystic fibrosis patients.

Complications associated with symptomatic diagnosis in infants with cystic fibrosis.

To determine the complication and hospitalization rates in children with cystic fibrosis (CF) by mode of diagnosis. Newly diagnosed cases of CF were identified from the Cystic Fibrosis Foundation National Patient Registry for 2000 through 2002. Cases were categorized as symptomatic diagnosis (SYMP; n = 1760), prenatal diagnosis (PRE; n = 66), diagnosis by means of newborn screening (NBS; n = 256), or presentation with meconium ileus (MI; n = 484). Complications were defined for the calendar year of diagnosis as stunting (length <3rd percentile), wasting (weight <3rd percentile), positive Pseudomonas aeruginosa culture results, and hypoelectrolytemia or edema and hypoproteinemia. For infants (age <12 months), 70% of patients with SYMP had at least 1 complication or hospitalization, compared with 29% for patients with NBS diagnosis (P < .0001). Cross-sectional data for 2002 showed that patients with SYMP had significantly more complications compared with patients with NBS diagnosis as old as 20 years. When compared with patients with NBS diagnosis, patients with SYMP had increased mucoid P aeruginosa (P < .05) and decreased pulmonary function as assessed by means of forced expiratory volume in 1 second (P < .01). SYMP of CF is associated with increased complication rates throughout infancy, childhood, and adolescence when compared with NBS diagnosis.

Cystic fibrosis

Signs and symptoms Cystic fibrosis typically manifests early in life. Newborns and infants with cystic fibrosis tend to have frequent, large, greasy stools (a result of malabsorption) and are underweight for their age. 15–20% of newborns have their small intestine blocked by meconium, often requiring surgery to correct. Newborns occasionally have neonatal jaundice due to blockage of the bile ducts. Children with cystic fibrosis lose excessive salt in their sweat, and parents often notice salt crystallizing on the skin, or a salty taste when they kiss their child.

[Cystic fibrosis: A report of 33 pediatric Tunisian cases].

The frequency of cystic fibrosis is unknown in Tunisia, regarding the limited number of reported surveys and patients. to determine the clinical characteristics, outcome and genetic data of cystic fibrosis in Tunisian pediatric patients. Cases of cystic fibrosis managed at pediatric departments of Tunis, during 15 years (1997-2012), were reviewed. 33 children (23 males and 10 females) were enrolled. The Onset was within the first year of life in 26 patients. Revealing symptoms were the following: recurrent bronchopneumonia (28 cases), chronic diarrhea (17 cases), hepatomegaly (6 cases), malnutrition (15 cases), pseudo Bartter syndrome (3 cases), edemaanemia- hypoprotidemia (4 cases) and meconium ileus (4 cases). The diagnosis was confirmed by sweat test and genotypic data, the F508 del was the most frequent mutation (17 cases). Several complications had occurred during follow-up: chronic pseudomonas aeruginosa infection (15 cases), chronic respiratory failure (14 cases), recurrent hemoptysis (2 cases), pleural effusion (3 cases) and cirrhosis (2 cases). Ten patients died at a mean age of 7 years. One patient had pulmonary transplantation. Prenatal diagnosis was performed in 9 families. In Tunisia, cystic fibrosis is not exceptional, but its diagnosis is delayed. Our survey is characterized by more severe earliest forms, difficult and insufficient therapeutic management. A Better medical awareness and a national action plan are needed.

[Clinical characteristics and outcome of cystic fibrosis: report of 16 cases].

The aim of this report is to determine clinical characteristics and outcome of Cystic Fibrosis (CF). Cases of CF managed at Infantile Medicine A Department in Children's Hospital of Tunis during 13 years (1994-2006) were reviewed. 16 children had CF. They were 8 males and 8 females. 13 patients were consanguineous and four had similar familial cases. The mean age at diagnosis was 19 months (10 days, 13 years). 3/4 of patients were symptomatic within the first trimester of life. Revealing symptoms were: obstructive bronchopathy associated to chronic diarrhea (n=6), edema-anemia-hypotrophy-hypoproteinemia syndrome (n=3), meconium ileus (n=4), bronchiectasis (n=2) and chronic diarrhea (n=1). The diagnosis was confirmed by sweat test and genotypic data. The F508 del was the most frequent mutation (54%). Clinical outcome was characterized by the occurrence of respiratory and nutritional complications: acute respiratory failure (n=6), chronic respiratory failure (n=3), chronic pseudomonas aeruginosa infection (n=6) at a medium age of 3.8 years, recurrent haemoptysis (n=2), pleural effusion (n=2), a malnutrition (n =10) and diabetes associated to puberty delay in one patient. Seven patients died at mean age of 4.4 years (6 months, 17.3 years). Among surviving patients, six had no compromised nutritional status or lung function. Prenatal diagnosis was performed in three families. CF is characterized by earliest onset and severity of symptoms. Therapeutic insufficiency is the main cause of precocious complications and poor prognosis in our series.

Comparing the clinical evolution of cystic fibrosis screened neonatally to that of cystic fibrosis diagnosed from clinical symptoms: a 10-year retrospective study in a French region (Brittany).

Until the year 2000, systematic cystic fibrosis (CF) neonatal screening was only performed in a few regions of France. The Brittany region began in 1989, but not the neighboring region of Loire-Atlantique. The present study compares the clinical evolution of both affected populations 10 years after screening was started. Although the 77 screened and 36 nonscreened children were followed in different CF centers, they were included in similar care protocols. The clinical characteristics at diagnosis and their evolution over a 10-year period of all the children affected with CF and born between January 1, 1989 and December 31, 1998, excluding those with meconium ileus, were compared. There were no significant differences in sex ratio, gestational age, anthropometric data at birth, frequency of deltaF508 homozygotes, proportion of pancreatic-insufficient patients, and mean age between the two populations. Age at diagnosis was lower in the screened group (38 days vs. 472 days, P < 10(-7)), as was the delay in supplementation with pancreatic enzymes (1.7 months vs.15.9 months, P < 10(-7)). The proportion of children who were hospitalized at least once was higher among the nonscreened than the screened patients (86% vs. 49%, P < 10(-4)). Z-scores for weight and height were significantly better in the screened population, not only in the first years of life, but also at 5 years old for height and 8 years old for weight. The Shwachman and Brasfield scores were higher among the screened children during the whole period of follow-up. No significant differences in colonization by Pseudomonas aeruginosa nor in lung function were found. Given the homogeneity in the characteristics and the follow-up of both populations, the benefits in terms of nutrition and clinical well-being of neonatal screening appear to be clear, thus confirming the advantages of its general implementation.

Cystic fibrosis in adolescents and adults.

Forty-five patients (25 male and 20 female) over 12 years of age with cystic fibrosis have been studied clinically, radiologically and physiologically. Their mean age at the first visit was 17 years; they were followed for a mean period of 4 years and attended at least every six months. The first symptom which developed before the age of five in 42 of the 45 patients was respiratory. Thirty-two of the 45 patients had severe lung disease (Group III) at the start of the study of the seven patients died during the study. Cough and sputum were almost universal, 23 had haemoptyses and eight pneumothoraces. Staphylococcus pyogenes, Haemophilus influenzae and Pseudomonas aeruginosa were the common pathogens isolated from sputum and the increasing prevalence of the latter was again confirmed. Acquisition of the mucoid strain of pseudomonas signified poor prognosis. Established infection was never eradicated. Forty-three patients had evidence of pancreatic insufficiency; in all but one patient the symptoms were mild and five patients abandoned dietary restriction and pancreatin without ill effect. Seven patients had symptoms of partial bowel obstruction (meconium ileus equivalent) but only one required surgical relief. The liver was enlarged in seven patients and the spleen was felt in three. Three patients had diabetes mellitus. The influence of cystic fibrosis on growth and development is reported--the growth spurt is late in the majority but growth failure is not confined to those with severe lung infection or malabsorption and in these circumstances remains unexplained. Mean weight was low in relation to height and puberty was delayed in both sexes.

Pediatrics_Nelson

CF is a chronic progressive disease that can present with protein and fat malabsorption (failure to thrive, hypoalbuminemia, steatorrhea), liver disease (cholestatic jaundice), or chronic respiratory infection (Table 137-1). Many infants currently are diagnosed based on newborn screening, which has been available in all 50 states and the District of Columbia since 2010. Older children commonly present with pulmonary manifestations such as poorly controlled asthma and chronic respiratory infections. The respiratory epithelium of patients with CF exhibits marked impermeability to chloride and an excessive reabsorption of sodium. This leads to a relative dehydration of airway secretions, which results in airway obstruction and impaired mucociliary transport. This, in turn, leads to endobronchial colonization with bacteria, especially Staphylococcus aureus and Pseudomonas aeruginosa. Chronic bronchial infection results in persistent or recurrent cough that is often productive of sputum,

Cystic fibrosis

History CF is supposed to have appeared about 3,000 BC because of migration of peoples, gene mutations, and new conditions in nourishment. Although the entire clinical spectrum of CF was not recognized until the 1930s, certain aspects of CF were identified much earlier. Indeed, literature from Germany and Switzerland in the 18th century warned ("Woe to the child who tastes salty from a kiss on the brow, for he is cursed and soon must die"), recognizing the association between the salt loss in CF and illness. In the 19th century, Carl von Rokitansky described a case of fetal death with meconium peritonitis, a complication of meconium ileus associated with CF. Meconium ileus was first described in 1905 by Karl Landsteiner. In 1936, Guido Fanconi described a connection between celiac disease, cystic fibrosis of the pancreas, and bronchiectasis.

Clinical presentation of hypernatremic dehydration in exclusively breast-fed neonates.

To identify the clinical presentation of dehydration related to failure of lactation in exclusively breast-fed term infants. A prospective study was performed between January 2000 and June 2003 in Al Qassimi Hospital in the Emirate of Sharjah. Enrollment criteria included term neonates whose birth weight of > 2000 g with no underlying organic illness causing poor feeding admitted for clinical manifestations of dehydration with weight loss of > 10% during the first 2 weeks of life. The control group, a non-randomized sample included healthy full term neonates, seen in Sharjah maternal and child health care center at 4-7 days old for their routine Guthrie screening test. For each dehydrated neonate we took two neonates as controls. Mother's age, parity, length of pregnancy, any pathologic conditions, breastfeeding history and her level of knowledge of lactation was recorded. Neonatal information included mode of delivery, percentage of weight loss, clinical examination, and stool and urine output the previous day. Data was analyzed with Student 't' test and chi-square test. Out of 17208 live births, 29 neonates between the ages of 2-13 days were admitted with weight loss of between 12 and 29% (dehydrated group). 27 patients had hypernatremic dehydration with serum sodium level ranging from 150 to 195 mmol/l. Mean age of admission was 4.9 days. Reasons for admission were: signs of dehydration (55%); hyperthermia (55%); hypoglycemia (27%) and jaundice (59%). The control group included 58 healthy neonates. Their birth weight and age were comparable to those in the dehydrated group. In comparison with the control group, delivery by cesarean section (P< 0.0001), lower level of maternal breastfeeding knowledge (P=0.03), transient inadequate breast milk quantity (P=0.005) and nipple anomalies (P=0.001) was significantly more common in the dehydrated group. Fewer voidings of urine (< 6 times /day) and stool (< 3 times/day) in the previous 24 hours before admission was more frequently observed in the dehydrated group (P < 0.0001). Low level of maternal knowledge in lactation, cesarean section and failure of early postnatal follow up was associated with the neonatal dehydration. Decreased urine and stool frequency might be considered as a warning for failure of lactation.

Hyponatremic dehydration as a presentation of cystic fibrosis.

The purpose of this study is to present a case report of a child with hyponatremic dehydration diagnosed after CF and to review the cases of 13 patients with CF who had the same initial presentation in our hospital. This report reviewed the clinical records of children diagnosed with CF to ascertain the prevalence of metabolic alkalosis with electrolyte depletion as the presentation of CF. It also used sweat tests to diagnose a child with CF. The laboratory tests of a 12-month-old girl presented 3 times to the ;pediatric emergency department with vomiting and weight loss showed hyponatremia, hypochloremia, and metabolic alkalosis. The patient was subsequently diagnosed with CF by means of 2 positive sweat tests. Meanwhile, the review of the clinical records of all children diagnosed with CF from 1985 to 2004 (N = 77) showed that the prevalence of metabolic alkalosis with electrolyte depletion as the presentation of CF was 16.8%. The age of the infants ranged from 3 to 14 months. All episodes took place during summer. There are not many causes of metabolic alkalosis with hyponatremic dehydration, and one of them is CF. This report emphasizes sodium depletion as a common sign of CF presentation. This is most important in countries where the neonatal screening test for CF is not available because the disease may be asymptomatic or oligosymptomatic for several months or even years. Cystic fibrosis should be considered in differential diagnosis of any child presenting with unexplained hyponatremic dehydration.

[Dehydration and metabolic alkalosis: an unusual presentation of cystic fibrosis in an infant].

Cystic fibrosis (CF) may present during neonatal period with classic clinic symptoms related to the disease. The severity of the disease is multifactorial, one of the factors depends on the level of activity of the CFTR protein, which is related with the mutation type that affects the patient. An infant is presented who developed recurrent episodes of vomiting, anorexia, weight loss, dehydration and electrolyte abnormalities, such as metabolic alkalosis, hyponatremia, hypokalemia and hypochloremia. CF was diagnosed after the third episode showing an unusual and not very publicized presentation of the disease. Mutations !F 508 and 2789+5G-A were found. CF should be considered in patients of any age, but particularly in infants, presenting with anorexia, vomiting, failure to thrive, that are associated with recurrent episodes of hyponatremic hypochloremic, dehydration with metabolic alkalosis unexplained by other causes, even in the absence of respiratory or gastrointestinal symptoms or failure to thrive.

The use of sweat osmolality in the diagnosis of cystic fibrosis.

Sweat osmolality determination with 7-10 microliter of sweat for the establishment of the diagnosis of cystic fibrosis (CF) was evaluated in 297 probands. In 12 out of 26 infants below 2 months of age and in 3 out of 271 older probands not enough sweat could be collected at the first attempt. A final diagnosis was established before the age of 2 months in 21 out of 26 infants. In 27 CF patients sweat osmolality was 285.86 +/- 41.25 mmol/kg (mean +/- SD), the mean value - 2 SD being 203.36 mmol/kg. In 266 control subjects sweat osmolality was 107.38 +/- 29.49 mmol/kg (mean +/- SD), the mean value + 2 SD being 166.36 mmol/kg. There was no overlap between CF patients and controls in each age group. The method is simple, rapid and reliable, and improves diagnostic possibilities especially in young infants. Sweat osmolality values above 180 mmol/kg should be repeated and checked for final confirmation or exclusion of the diagnosis of cystic fibrosis.

Pediatrics_Nelson

Prolonged, direct-reacting neonatal jaundice MISCELLANEOUS Digital clubbing Failure to thrive Family history of cystic fibrosis (e.g., in sibling or cousin) Salty taste of skin (typically noted by parent on kissing affected child—from salt crystals formed after evaporation of sweat) Hyponatremic hypochloremic alkalosis in infants Nasal polyps Recurrent sinusitis Aspermia Absent vas deferens presence of known disease-causing DNA mutations are the only criteria required for diagnosis, as clinical symptoms may not be manifested early in life.

Essential fatty acid deficiency and predisposition to lung disease in cystic fibrosis.

Essential fatty acid (EFA) deficiency is a predisposing factor for pulmonary infection with Staphylococcus aureus and Pseudomonas aeruginosa, the two major pathogenic microorganisms in cystic fibrosis (CF). The goal of this study was to investigate the essential fatty acid status of CF patients from infancy to 20 years old. Plasma fatty acid profiles for phospholipid (PL) were determined for cord (n = 6), 4 months (n = 40), 16 months (n = 25), 3 y (n = 8), 5-10 y (n = 10), and 10-20 y (n = 10) aged CF patients and compared to their respective control; cord (n = 22), 1-36 months (n = 38) and adult (n = 100). Significance was established by Student's t-test (p < 0.05). The plasma PL fatty acid profile for all CF patients, except cord, revealed consistent deficiency in omega 3 and omega 6 EFAs. These deficiencies were most marked at infancy and more pronounced for patients with meconium ileus. EFA deficiency may contribute to the predisposition of CF infants to develop respiratory disease and to the excess cytotoxic activity found in bronchoalveolar lavage fluid at 2 months of age in the majority of screened infants.

Cystic fibrosis in two Chinese infants in Taiwan.

Cystic fibrosis was diagnosed in two female infants, respectively nine months old (Case 1) and six months old (Case 2). Clinical presentation of these two infants showed frequent episodes of pneumonia, dehydration and poor weight gain, despite fair intake of food since birth. Hyponatremic, hypochloremic metabolic alkalosis had been found during their previous hospitalizations. In Case 1, stool fat was positive with negative trypsin test. Both cases had abnormal findings on chest X-ray films, but the pancreas showed no remarkable cystic changes from sonography. Plastic-bag method of sweat test showed Na/Cl: 155/185 nmol/L in Case 1, Na/Cl: 127/135 nmol/L in Case 2. A family history was suggested, since each one had an elder brother who had died in early infancy with similar clinical presentations. Both patients were put on special diet therapy as well as chest physical therapy. Case 1 died suddenly at 16 months of age. Autopsy revealed mucusplugged dilated ducts with atrophy of the exocrine portion of the pancreas. DNA analysis in Case 2 showed abnormal mutation point at 1898+5 G-->T on chromosome 7.

Methods to obtain referral criteria in growth monitoring.

An important goal of growth monitoring is to identify genetic disorders, diseases or other conditions that manifest themselves through an abnormal growth. The two main conditions that can be detected by height monitoring are Turner's syndrome and growth hormone deficiency. Conditions or risk factors that can be detected by monitoring weight or body mass index include hypernatremic dehydration, celiac disease, cystic fibrosis and obesity. Monitoring infant head growth can be used to detect macrocephaly, developmental disorder and ill health in childhood. This paper describes statistical methods to obtain evidence-based referral criteria in growth monitoring. The referral criteria that we discuss are based on either anthropometric measurement(s) at a fixed age using (1) a Centile or a Standard Deviation Score, (2) a Standard Deviation corrected for parental height, (3) a Likelihood Ratio Statistic and (4) an ellipse, or on multiple measurements over time using (5) a growth rate and (6) a growth curve model. We review the potential uses of these methods, and outline their strengths and limitations.

Jane Davies

Davies leads the Strategic Research Centre for Pseudomonas Infection in Cystic Fibrosis at Imperial College London, one of few centres supported by the Cystic Fibrosis Trust. The centre looks to identify new ways to detect pseudomonas aeruginosa. Davies is part of the European CF Society Clinical Trials Network. She was involved in the design of the clinical trial, as well as validation of outcome measures. She works on the use of nasal potential difference to diagnose atypical cystic fibrosis. She was awarded a £2.8 million research grant from the Wellcome Trust to optimise the lentiviral vector for gene therapy. In 2020 she won the Senior Investigator award from the National Institute for Health Research (NIHR). Publications Davies publications include: 2011 An Atlas of Investigation and Management. Paediatric Respiratory Disease: Vol 1 Airways & Infection 2011 An Atlas of Investigation and Management. Paediatric Respiratory Disease: Vol 2 Parenchymal Disease References

Early detection of lung disease and its association with the nutritional status, genetic background and life events in patients with cystic fibrosis.

Progression of lung disease is the most prominent cause of morbidity and death in patients with cystic fibrosis (CF), but the severity of lung disease and the rate of lung function decline are highly variable. An attempt was made to define accurate estimates of disease progression in these patients early diagnosed and prospectively evaluated until 10 years of age. The primary question to ask was whether functional abnormalities detected already in infancy are associated with functional derangements later on in life, and may be useful as parameters of prognostic value. Early diagnosis of CF can best be achieved by screening of mutation by new techniques (buccal cell brushing) in infants, even when the sweat test or accurate blood sampling is not available. Moreover, in infants lung function can be assessed by infant whole-body plethysmography enabling the study of the interrelationship with delayed weight gain and growth retardation, as well as the associations with the most common disease-causing mutations. Out of a cohort of 80 infants (39 males, 41 females) with CF a follow-up study was started with 50 CF infants diagnosed during infancy (mean age 4.6 +/- 4.0 months; range 0.1-12.7 months) and prospectively evaluated at 6-month intervals during the first 2 years of life. Moreover, in 32 CF children out of this cohort, follow-up was continued until 10 years of age. Differences were encountered with respect to the different events occurring during the first years of life, especially the onset of chronic colonization with Pseudomonas aeruginosa. The association between infant lung function and specific mutations (DeltaF508 homozygotes, frameshift DeltaF508/3905insT compound heterozygotes and nonsense DeltaF508/R553X compound heterozygotes) furthermore revealed that differences in lung function within the genetic groups are mainly related to the degree of pulmonary hyperinflation. Pulmonary hyperinflation was also associated with the degree of impaired nutritional status. An association between impaired gas exchange characteristics at 10 years of age and the degree of pulmonary hyperinflation during infancy finally demonstrates that by early mutation screening, lung function testing and assessment of the nutritional status predictors of disease progression later on in life can be defined. Therefore, preventive therapeutic measures should primarily be based on such prognostic factors.

Tobramycin

Spectrum of susceptibility Tobramycin has a narrow spectrum of activity and is active against Gram-positive Staphylococcus aureus and various Gram-negative bacteria. Clinically, tobramycin is frequently used to eliminate Pseudomonas aeruginosa in cystic fibrosis patients. The following represents the minimum inhibitory concentration (MIC) susceptibility data for a few strains of Pseudomonas aeruginosa: Pseudomonas aeruginosa - <0.25 µg/mL – 92 µg/mL [ref?] Pseudomonas aeruginosa (non-mucoid) – 0.5 µg/mL - >512 µg/mL [ref?] Pseudomonas aeruginosa (ATCC 27853) – 0.5 µg/mL – 2 µg/mL The MIC for Klebsiella pneumoniae, KP-1, is 2.3±0.2 µg/mL at 25 °C [unpublished]. Contraindications Tobramycin is contraindicated in people with hypersensitivity against aminoglycoside antibiotics. The Infusion is also contraindicated in people with myasthenia gravis.

[Cystic fibrosis in adults--clinical aspects].

Nineteen patients with cystic fibrosis were seen in the I Department of Tuberculosis and Lung Diseases during 3.5 years. There were 12 (63%) female, and 7 male, aged from 16 to 35 years (mean 23.2). Most patients were diagnosed in childhood, but 4 were diagnosed in their early adulthood. The diagnosis was confirmed by positive chloride sweat test in all cases. Molecular DNA analyses were performed in 16 cases. In 9 (56%) cases two mutations in the CFTR gene were identified. In 5 cases one mutation was identified. All patients had bronchiectases confirmed by CT. Spirometry showed lung function impairment with predominantly obstructive pattern. Mean VC was 2.57l, mean FEVI was 1.66l. In 7 (37%) cases FEVI was lower then 30% of predictive value. Hypoxemia was found in 11 (58%) cases and hypercapnia in 3 (16%) cases. Sputum cultures were positive for mucoid P. aeruginosa in 12 (63%) cases, for Staph. aureus in 16 (84%) cases. Persistent colonisation with nontuberculous mycobacteria was found in 2 (10.5%) cases. Aspergillus fumigatus was identified in sputum cultures in 2 subjects who had also positive precipitation test. Diabetes mellitus was diagnosed in 2 cases. Meconium ileus equivalent was seen in 1 case. Pneumothorax was seen in 1 case. One patient died in the endstage of the illness.

Pediatrics_Nelson

Figure 35-2 Differential diagnosis of hypernatremia by mechanism. GI, Gastrointestinal; NG, nasogastric. Most children with hypernatremia are dehydrated and have the typical signs and symptoms of dehydration (see Chapter 33). Children with hypernatremic dehydration tend to have better preservation of intravascular volume owing to the shiftof water from the intracellular space to the extracellular space. Hypernatremic infants potentially become more dehydrated before seeking medical attention. Probably because of intracellular water loss, the pinched abdominal skin of a dehydrated, hypernatremic infant has a doughy feel.

Respiratory infections with Pseudomonas aeruginosa in children with cystic fibrosis: early detection by serology and assessment of risk factors.

Patients with cystic fibrosis (CF) are susceptible to lower respiratory tract infections with Pseudomonas aeruginosa and typically acquire this organism in early childhood. Once P aeruginosa infection is established, eradication may be impossible, and progressive lung disease often aggravates morbidity and mortality risks. The ability to diagnose CF by genetic testing at birth makes it possible to determine the temporal sequence of events that result in P aeruginosa-associated pulmonary infections. To evaluate the longitudinal relationship between the production of an antibody response against P aeruginosa and clinical factors associated with P aeruginosa pulmonary infections in patients with CF diagnosed in early life. Serum samples and oropharyngeal cultures (protocol cultures) were obtained at 6-month intervals from April 15, 1985, to April 15, 2000 (or for up to 180 months depending on their enrollment date) from 68 patients at 2 centers in Madison and Milwaukee, Wis, diagnosed through the Wisconsin CF Neonatal Screening Project, a longitudinal cohort study. Additional cultures were obtained at examining physicians' discretion (all cultures). Time to serum IgG, IgA, and IgM antibody titer of at least 1:256 against P aeruginosa, assessed by enzyme-linked immunosorbent assay using cell lysate, exotoxin A, and elastase as antigens; time to organism isolation from respiratory samples; time to Wisconsin Cystic Fibrosis Radiograph (WCXR) score of 5 or more. The median time to an antibody titer of at least 1:256 was 17.8, 24.2, and 70.9 months for cell lysate, exotoxin A, and elastase, respectively. The rise of anti-cell lysate and anti-exotoxin A titers to 1:256 or more occurred a mean of 11.9 (P<.001) and 5.6 (P =.04) months, respectively, before the isolation of P aeruginosa for all cultures and 18.2 (P<.001) and 11.9 (P =.006) months, respectively, before protocol cultures. There was no significant difference between the rise of anti-cell lysate and anti-exotoxin A titer and a WCXR score of 5 or more (P =.24 and.32, respectively). Treatment with long-term, non-Pseudomonas oral antibiotics and integration of CF infants with older, chronically infected patients were associated with a significantly increased risk of P aeruginosa pulmonary infection. In CF patients diagnosed through neonatal screening, P aeruginosa pulmonary infections occurred 6 to 12 months before the organism was isolated from respiratory secretions. The longitudinal monitoring of P aeruginosa antibody titers, in concert with WCXR score, should facilitate diagnosis and treatment of P aeruginosa pulmonary infections in young children with CF.

From lip to lab: salty tasting skin is the main clue that raises clinical suspicion of cystic fibrosis in young infants.

This study developed a clinical decision rule (CDR) to rule in or rule out cystic fibrosis (CF) in the first weeks of life. We combined a two-step nonconcurrent birth cohort and a cross-sectional controlled study in which observers and mothers were blinded to confirmatory sweat test results. Neonates from uncomplicated pregnancies and deliveries, with two subsequent tests for immunoreactive trypsinogen (IRT) higher than 70 ng/mL, were eligible to take part. We included 49 CF-affected and 177 CF-unaffected infants with an average age of 34 days. CF-affected infants demonstrated statistically significant differences in weight gain, stool frequency and salty tasting skin from birth. Multivariate analysis showed that the main predictors of CF were salty tasting skin (odds ratio 17.2) and weight gain of <10.5 g per day (odds ratio 4.6). Depending on the CDR score, we obtained the following results: sensitivity (42.9-61.2%), specificity (89.6-96.5%), positive (62.5-77.8%) and negative (85.6-89.1%) predictive value and positive (5.8-12.3) and negative (0.4-0.6) likelihood ratio. The CDR could provide a reliable index of clinical suspicion and timely referral for sweat testing in settings without newborn screening programmes and may also be applied to false-negative individuals where such programmes already exist.

Pseudo-Bartter's Syndrome in Patients with Cystic Fibrosis: A Case Series and Review of the Literature.

Pseudo-Bartter syndrome (PBS) is characterized by hyponatremic, hypochloremic metabolic alkalosis that mimics Bartter syndrome but with no pathology in the renal tubules. We present five patients with cystic fibrosis (CF) and PBS. Four children aged between three and five-and-one-half months with previously diagnosed CF and one aged 17 months with previously undiagnosed disease, were hospitalized during the summer season, with severe dehydration, oliguria, apathy and adynamia. Additionally, one of them had an ileostomy due to meconium ileus after birth. All children were on a diet without additional salt intake. Laboratory analysis on admission showed hyponatremia (115-133 mmol/L, mean 122.4 mmol/L), high plasma renin activity (229-500 pg/ml, mean 324 pg/ml) and metabolic alkalosis (pH 7.5-7.6, mean 7.56) in all the patients, and in four of them high blood level of aldosterone (74-560 pg/ml, mean 295.9 pg/ml), hypokalemia (2.3-2.8 mmol/L, mean 2.6 mmol/L), hypochloremia (59-71 mmol/L, mean 66 mmol/L) and low urinary sodium (5-12 mmol/L, mean 9 mmol/L). After intravenous rehydration followed by additional use of sodium and chloride in mean dosis of 1.78 mmol/kg per day, all the patients made a complete recovery. With advice for additional use of salt in the mentioned amount, the patients were discharged from the hospital. PBS is one of CF complications, especially in infants and young children in situations accompanied by increased sweating and/or other causes of additional loss of sodium and chlorine. Sometimes, as was the case with one of our patients, PBS may be the initial presentation form of the disease.

Seliciclib

Seliciclib (roscovitine or CYC202) is an experimental drug candidate in the family of pharmacological cyclin-dependent kinase (CDK) inhibitors that preferentially inhibit multiple enzyme targets including CDK2, CDK7 and CDK9, which alter the growth phase or state within the cell cycle of treated cells. Seliciclib is being developed by Cyclacel.This is a phase II, dose ranging, multicenter, randomized, double-blind, placebo-controlled study. The aim of this study is to assess the safety of increasing doses of roscovitine administered orally for 4 cycles of 4 consecutive days (treatment "on") separated by a 3 days treatment free period (treatment "off") in adult CF subjects with Cystic Fibrosis carrying 2 Cystic Fibrosis causing mutations with at least one F508del-CFTR mutation and chronically infected with Pseudomonas aeruginosa. This study involved 36 Cystic Fibrosis patients: 24 treated and 12 controls.

Recovery of birth weight z score within 2 years of diagnosis is positively associated with pulmonary status at 6 years of age in children with cystic fibrosis.

We recently reported that 60% of children newly diagnosed with cystic fibrosis who had pancreatic insufficiency responded to treatment initiation and achieved catch-up weight gain to a level comparable with their birth weight z score within 2 years of diagnosis ("responders"), whereas the remaining 40% failed to do so ("nonresponders"). The present study examined the impact of this early weight recovery on subsequent growth pattern and pulmonary status at 6 years of age. Sixty-three children with cystic fibrosis who had pancreatic insufficiency but no meconium ileus, and were enrolled in the Wisconsin Cystic Fibrosis Neonatal Screening Project, were studied. Responders were defined by a recovery of weight z score comparable with that at birth within 2 years of diagnosis. From ages 2 to 6, growth was measured by both height and BMI. Pulmonary status was evaluated by symptoms, spirometry, quantitative chest radiography, and respiratory microbiology. The majority (71%) of the responders maintained their early weight recovery through 6 years of age, whereas only 32% of the nonresponders achieved substantial growth improvement from 2 to 6 years of age. Proportionately fewer responders reported cough symptoms (10% daytime cough; 22% nighttime cough) compared with nonresponders (41% daytime cough; 45% nighttime cough) at age 6. The percentage of predicted forced expiratory volume in 1 second at age 6 was 11% higher in responders (99.5% +/- 13.9%) compared with nonresponders (88.3% +/- 18.5%). Responders had significantly better Brasfield (20.1 +/- 1.4) and Wisconsin chest radiograph (8.3 +/- 3.3) scores compared with nonresponders (Brasfield: 18.9 +/- 1.8; Wisconsin: 12.3 +/- 8.3). Respiratory microbiology results were not significantly different. Multiple regression analyses indicated that the positive association between responder and percent predicted forced expiratory volume in 1 second at 6 years of age remained statistically significant after controlling for infections with Pseudomonas aeruginosa and Staphylococcus aureus and chest radiograph scores. Growth patterns from 2 to 6 years of age were not associated with pulmonary measures at age 6. Patients with cystic fibrosis with pancreatic insufficiency who achieved early growth recovery within 2 years of diagnosis had fewer cough symptoms, higher lung function, and better chest radiograph scores at 6 years of age.

Cystic Fibrosis -- Introduction

Since ancient times, children around the world have been afflicted with cystic fibrosis that leads to shortened lifespans. In medieval Europe, these children were believed to be cursed by witches and doomed to die. The curse that became folklore pronounced, “Woe to the child who tastes salty from a kiss on the brow, for he is cursed and soon will die.” Salty skin was a sign of an impending illness without cause or cure.  Until relatively modern times, cystic fibrosis was poorly understood. In 1949, Lowe et al. postulated that cystic fibrosis must be caused by a genetic defect from the autosomal recessive pattern of inheritance of the disease. High levels of salt in the sweat of patients with cystic fibrosis suggested an abnormality in electrolyte transport from the sweat gland. Quinton postulated that sweat ducts in these patients were impermeable to chloride. Further studies led to the hypothesis that the faulty chloride channel must be situated in the apical membranes of the lung surface or glandular epithelium to explain the respiratory and systemic organ failure associated with cystic fibrosis.  Researchers now know that cystic fibrosis is an autosomal recessive disorder of exocrine gland function most commonly affecting persons of Northern European descent at a rate of 1 in 3500.  It is a chronic disease that frequently leads to chronic sinopulmonary infections and pancreatic insufficiency. The most common cause of death is end-stage lung disease. [1] [2] [3] [4]

Phage therapy

In 2007 Phase 1 and 2 clinical trials were completed at the Royal National Throat, Nose and Ear Hospital, London, for Pseudomonas aeruginosa infections (otitis). Phase 1 clinical trials were conducted at the Southwest Regional Wound Care Center of Lubbock, Texas, for a cocktail of phages against P. aeruginosa, Staphylococcus aureus and Escherichia coli developed by Intralytix. PhagoBurn, a Phase 1 and 2 trial of phage therapy against P. aeruginosa wound infection in France and Belgium in 2015–17, was terminated early due to lack of effectiveness. In July 2020, the FDA approved the first clinical trial of nebulized phage therapy in the United States. This double-blind, placebo-controlled study at Yale University will be focused on treating P. aeruginosa infections in patients with cystic fibrosis. Locus Biosciences created a cocktail of three CRISPR-modified phages. A 2019 study examined its effectiveness against E. coli in the urinary tract.