Is there a diurnal pattern in the clinical symptoms of HELLP syndrome?

OBJECTIVE: To determine if there is a diurnal pattern in the clinical symptoms of HELLP (Hemolysis, Elevated Liver enzymes, Low Platelets) syndrome. STUDY DESIGN: A retrospective study was performed in 134 pregnancies complicated by HELLP syndrome. The medical records were reviewed to describe each HELLP episode. Time of day was divided into three periods, day, evening, and night. The following parameters were categorized according to the time of day: onset of symptoms, consultation by the doctor, initial blood sampling, diagnosis and decrease of symptoms. Biochemical parameters at clinical presentation and consecutive changes within 24 h were recorded. RESULTS: In 65 pregnancies 77 HELLP episodes were well documented. Times of onset of symptoms and consultation by the doctor were significantly higher during the evening and night (p < 0.001), whereas times of diagnosis and decrease of symptoms occurred significantly more during the day (p < 0.001). In only 49.3% of the cases were diagnostic laboratory criteria met at clinical presentation. This was mainly due to platelet values in excess of 100 x 10(9)/l. Several hours later (median 8 h, range 2-23) the decrease in platelets occurred. CONCLUSIONS: A diurnal pattern exists in the clinical symptoms of HELLP syndrome that is characterized by an exacerbation during the night and recovery during the day. There is a considerable delay between the onset of symptoms and the fulfillment of diagnostic laboratory criteria.     

Computergestützte Charakterisierung von sonographischen Plazentastrukturen

Schlu?folgerungen Aus der Me?wert-Verteilung der Grauwerte im Sonogramm lassen sich Kennwerte berechnen, die eine computergestützte sonographische Reifebeurteilung der Plazenta erm?glichen. Allerdings sind die Verteilungsparameter (Median, Varianz, Schiefe, Exze?) abh?ngig von den Ger?teparametern. Zuverl?ssiger ist die Berechnung von Kennwerten, die sich auf die strukturellen Eigenschaften des Sonogramms beziehen. Bei den hier dargestellten Untersuchungen k?nnen Kennwerte für den Kontrast bzw. für die Ansammlung gleichartiger Grauwerte um einen bestimmten Punkt die sonographische Beurteilung der Plazenta optimieren. Damit erweitern sich die M?glichkeiten für die Zustandsdiagnostik der intrauterinen Lebensbedingungen.     

A paradigm shift in treatment for atrial fibrillation: from electrical to structural therapy?

See doi:10.1016/j.ehj.2003.08.014for the article to which thiseditorial refers Atrial fibrillation (AF) is associated with increased morbidityand mortality, most notably due to stroke and heart failure.Maintaining sinus rhythm in AF patients is not an easy task,and eventually it will even fail in most leading to permanentAF. Therefore, the therapeutic goal often lies in postponingpermanent AF as long as possible. Except from the surgical correctionof mitral valve disease, almost all therapeutic approaches havebeen focused on the electrical problem that is AF. The toolsto maintain sinus rhythm, however, are suboptimal, leading tofrustration at both the side of the patient and the doctor.Anti-arrhythmic drugs prevent multiple electrical wavelets byinterfering with electrical     

Effect of inhaled methanol on pituitary and testicular hormones in chamber acclimated and non-acclimated rats.

Two experiments were conducted in which the acute effects of inhaled methanol on serum hormones associated with reproductive function in the male rat were evaluated. In the first experiment, rats exposed to methanol (0, 200, 5000 and 10,000 ppm) for 6 h were killed at the end of the exposure period (6 h) or the following morning (24 h). Also, because the process of exposure itself could modify neuroendocrine function, the effect of the handling associated with placing the rat in the exposure chamber was evaluated further by dividing the exposed animals into acclimated (2 weeks of prior handling) and non-acclimated groups. At 6 h, an effect of prior handling was noted in the sham-exposed rats, with serum luteinizing hormone (LH) of the non-acclimated group being greater than that of the acclimated group. Serum LH concentrations were altered by methanol exposure, but the direction of change and the exposure level at which an effect was noted differed between the acclimated and non-acclimated rats. Methanol (5000 ppm) reduced serum LH in the non-acclimated animals, while 10,000 ppm increased LH in the acclimated rats. Follicle stimulating hormone (FSH) and testosterone were unchanged by methanol in rats killed at 6 h. Thus, this experiment did not confirm earlier reports that exposure to 200 ppm for 6 h reduced serum testosterone. At 24 h, an effect of prior handling was still present in the hormonal measures, with serum and interstitial fluid testosterone concentrations being greater in the non-acclimated rats. Also, there was a dose x handling interaction with methanol exposure inducing an increase in serum testosterone in the non-acclimated rats (up to 5000 ppm) and a decrease in the acclimated rats (up to 10,000 ppm). In the second experiment, groups of acclimated and non-acclimated rats were exposed to 0 or 5000 ppm methanol for 1, 2 and 6 h and killed immediately after removal from the chamber. Serum LH, testosterone and FSH values were not different in sham- vs methanol-exposed rats at any time point. As in experiment 1, an effect of prior handling was noted. In general, the concentrations of these hormones and serum prolactin in the non-acclimated rats were greater than those observed for acclimated rats. Methanol exposure resulted in increased prolactin concentrations under both handling conditions.(ABSTRACT TRUNCATED AT 400 WORDS)     

Acetylator genotype-dependent metabolic activation of carcinogenic N-hydroxyarylamines by S-acetyl coenzyme A-dependent enzymes of inbred hamster tissue cytosols: relationship to arylamine N-acetyltransferase

A genetic polymorphism in S-acetyl coenzyme A (AcCoA)-dependentN-acetyltransferase has been associated with a differentialrisk for certain cancers in humans. In this study, several tissuesfrom the inbred Syrian hamster with a genetically defined AcCoA-dependentN-acetyltransferase polymorphism (homozygous rapid acetylator,Bio. 87.20; homozygous slow acetylator, Bio. 82.73/H; and heterozygousacetylator, Bio. 87.20 x Bio. 82.73/H F₁), were investigatedfor the relationship of arylamine N-acetyltransferase to theAcCoA-dependent metabolic activation of carcinogenic N-hydroxy(N-OH)-arylamines to bind to DNA (O-acetyltransferase). Thelevels of both 2-aminofluorene (AF) N-acetyltransferase andN-OH-AF O-acetyltransferase activity reflected the N-acetylatorgenotype in liver, intestine, kidney and lung cytosols. A significantacetylator gene—dose response for AF N-acetyltransferaseand N-OH-AF O-acetyltransferase activities was observed in liverand lung cytosols. In contrast, acetylator genotype was notconsistently expressed for the AcCoA-dependent N-acetylationof 4-aminobiphenyl (ABP), nor for the AcCoA-dependent metabolicactivation of N-OH ABP and N-OH-3,2'-dimethyl-4-aminobiphenylin these me tissue cytosols. Two peaks of acetyltransferaseactivity were partially purified by ion exchange FPLC chromatographyfrom the hepatic cytosol of both the homozygous rapid and homozygousslow acetylator hamster. In contrast to unfractionated cytosol,the isozyme(s) eluting first clearly demonstrated levels ofAcCoA-dependent arylamine N-acetyltransferase and N-OH-arylamineO-acetyltransferase activities that were consistent with N-acetylatorgenotype (polymorphic) for all substrates tested. In contrast,the slower eluting isozyme(s) in each acetylator cytosol showedlevels of AcCoA-dependent N-and O-acetyltransferase activitiesthat did not vary with N-acetylator genotype (monomorphic).The AcCoA-dependent O-acetyltransferase activity of both themonomorphic and polymorphic peaks was paraoxon resistant. Thesestudies demonstrate acetylator genotype-dependent control ofAcCoA-dependent metabolic activation of N-OH-arylamines(O-acetylation)by polymorphic isozyme(s) similar to that for AcCoA-dependentN-acetylation of arylamines in the hamster. The polymorphicgenetic control of N-OH arylamine O-acetyltransferase may bean important risk factor for arylamine-induced cancer, in thosespecies and tissues expressing appreciable levels of O-acetyltransferaseactivity.     

Recommendations for participation in leisure-time physical activity and competitive sports of patients with arrhythmias and potentially arrhythmogenic conditions. Part II: ventricular arrhythmias, channelopathies and implantable defibrillators.

This consensus paper on behalf of the Study Group on Sports Cardiology of the European Society of Cardiology follows a previous one on guidelines for sports participation in competitive and recreational athletes with supraventricular arrhythmias and pacemakers. The question of imminent life-threatening arrhythmias is especially relevant when some form of ventricular rhythm disorder is documented, or when the patient is diagnosed to have inherited a pro-arrhythmogenic disorder. Frequent ventricular premature beats or nonsustained ventricular tachycardia may be a hallmark of underlying pathology and increased risk. Their finding should prompt a thorough cardiac evaluation, including both imaging modalities and electrophysiological techniques. This should allow distinguishing idiopathic rhythm disorders from underlying disease that carries a more ominous prognosis. Recommendations on sports participation in inherited arrhythmogenic conditions and asymptomatic gene carriers are also discussed: congenital and acquired long QT syndrome, short QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, arrhythmogenic right ventricular cardiomyopathy and other familial electrical disease of unknown origin. If an implantable cardioverter defibrillator is indicated, it is no substitute for the guidelines relating to the underlying pathology. Moreover, some particular recommendations for patients/athletes with an implantable cardioverter defibrillator are to be observed.     

Novel pore mutation in SCN5A manifests as a spectrum of phenotypes ranging from atrial flutter, conduction disease, and Brugada syndrome to sudden cardiac death

OBJECTIVES: The purpose of this study was to determine the clinical and biophysical characteristics of a novel SCN5A mutation. BACKGROUND: Brugada syndrome and isolated cardiac conduction defect have been linked to SCN5A mutations. METHODS: Eleven members of a western European family underwent electrophysiologic investigations and mutation analysis of the SCN5A gene. Wild-type and mutant SCN5A channels were expressed in HEK293 cells, and whole cell currents were studied using patch clamp procedures. RESULTS: A novel mutation, R376H, in the first pore segment of SCN5A variably causes Brugada syndrome and/or conduction disease in a single family. Biophysical analysis demonstrated a significant current reduction for the mutant, a pathophysiologic profile consistent with Brugada syndrome and isolated cardiac conduction defect. Among 11 family members, 9 were carriers of the mutation. The proband's initial presentation was a saddleback Brugada ECG, atrial flutter, and diffuse conduction disturbances. He had no inducible ventricular arrhythmias but experienced sudden cardiac death. His brother was affected by atrial flutter and had a clear conduction disorder, but he did not display baseline or evocable ECG signs of Brugada syndrome. He received an implantable cardioverter-defibrillator that delivered one appropriate shock after 1 year of follow-up. The phenotype in the family members was highly variable and ranged from noninducible and inducible asymptomatic carriers of the mutations to isolated conduction disease and to symptomatic Brugada syndrome. CONCLUSIONS: We describe the functional characterization of a novel SCN5A pore mutation, R376H, with variable clinical expression in the same family. Differentiating between electrophysiologic entities (Brugada syndrome-isolated cardiac conduction defect) is more challenging. Recognition of factors modifying the clinical presentation may be important for clinical decision making.