Abnormal two-dimensional strain echocardiography findings in children with congenital valvar aortic stenosis.

PURPOSE: Congenital valvar aortic stenosis (VAS) causes a pressure overload to the left ventricle. In the clinical setting, the severity of stenosis is graded by the pressure drop over the stenotic valve (pressure gradient). This parameter is dependent on the hemodynamic status and does not provide information regarding myocardial performance. This study was undertaken to reveal the potential of two-dimensional strain echocardiography (2DSTE) for the detection of myocardial functional changes due to congenital VAS in children. MATERIALS AND METHODS: A total of 86 patients (aged from birth to 18 years) with various degrees of isolated congenital VAS were enrolled in this study. None of the patients had undergone any form of surgical or balloon intervention. 139 healthy children served as a control group. Two-dimensional cine-loop recordings of apical 4-chamber, mid-cavity short-axis and basal short-axis views were digitally stored for off-line analysis. Longitudinal, circumferential and radial peak systolic strain and strain rate values were determined as well as the time to peak systolic strain (T2P). Two-way analysis of variance was performed to assess the relationship between VAS severity and 2DSTE parameters. RESULTS: In all patients conventional echocardiographic findings did not indicate systolic left ventricular dysfunction. All strain parameters of the control group were significantly different from those of VAS patients. There was a statistically significant, inverse relationship between global peak systolic strain parameters in all three directions and the degree of VAS (p < 0.05). Local peak systolic strain (rate) in the interventricular septum was most affected. T 2P increased significantly with VAS severity (p < 0.05). The decline in LV longitudinal systolic performance preceded that in other directions. CONCLUSION: 2DSTE detects alterations in myocardial function in children diagnosed with congenital VAS, whose conventional echocardiographic findings did not indicate ventricular systolic dysfunction.

Anomalous coronary artery from the wrong sinus in a 15-year-old boy.

Congenital coronary artery anomalies are a well-recognized risk factor for sudden cardiac death in children as well as young adults, mostly during or immediately after intense exertion on the athletic field. Because these malformations are amenable to surgical treatment, timely identification is crucial. Unfortunately, antemortem diagnosis is notoriously difficult, partly due to the absence of abnormal test results in routine investigations. We present a 15-year-old boy who collapsed during exercise due to ventricular fibrillation. Coronary abnormalities were initially not identified, but they were clearly visualized by means of an echocardiogram and confirmed by multislice computed tomography. We would like to emphasize that echocardiography is capable of accurately identifying congenital coronary anomalies when attention is paid to the correct diagnostic hallmarks.

Impaired Sertoli cell function in males diagnosed with Noonan syndrome.

In order to study male gonadal function in Noonan syndrome, clinical and laboratory data, including inhibin B, were gathered in nine pubertal males diagnosed with Noonan syndrome. Bilateral testicular maldescent was observed in four, and unilateral cryptorchidism occurred in two. Puberty was delayed in three patients. Luteinising hormone (LH) levels were normal in all patients in our series, while follicle stimulating hormone (FSH) levels were raised in seven. Inhibin B was low in six males and just above the lower limit of normal in two. Importantly, all three men with normal testicular descent displayed signs of Sertoli cell dysfunction, indicating, in contrast to earlier reports, that bilateral cryptorchidism does not seem to be the main contributing factor to impairment of testicular function in Noonan syndrome. These findings suggest different mechanisms of disturbance in male gonadal function, which is frequently associated with Sertoli dysfunction.

A visual pitfall: persistent Müllerian duct syndrome (PMDS).

Persistent Müllerian Duct Syndrome (PMDS) is a rare disorder of the anti-mullerian hormone (AMH) synthesis or receptor, which due to the visual contrast of normal masculine external genitalia and female internal genitalia can raise confusion, sometimes during surgery for cryptorchidism or hernia inguinalis. For an acute and accurate analysis of such a situation a thorough knowledge of gonadal embryology is mandatory. The diagnosis is made on finding Müllerian structures in an individual with complete virilization without signs of hypocortisolism or exposition to maternal androgens during foetal life. Karyotyping and gonadal biopsy provide additional information to confirm the diagnosis. As the risk of malignant transformation is not clear, orchidopexy is advised in patients with cryptorchidism, with lifelong palpatory follow-up. In case of urologic symptoms, surgical removal of the Müllerian remnants can be considered, with careful attention for the vulnerable ductus deferens. Despite optimal treatment the prognosis regarding fertility remain uncertain.

[Invasive pneumococcal infection in 5 newborns, 1996-2004]. / Invasieve pneumokokkeninfectie bij 5 pasgeborenen, 1996-2004.

At the Máxima Medisch Centrum in Veldhoven, The Netherlands, neonatal sepsis caused by invasive Streptococcus pneumoniae infection was diagnosed in 5 neonates between 1996 and 2004. This infection is relatively rare and its clinical features are variable, but often particularly severe and fulminant as was the case in 2 of the 5 children, one of whom died and the other was left with serious psychomotor retardation. The other 3 recovered fully. The child who died and one of the children who recovered are described in some detail. They were both prematurely born neonates, a girl and a boy, who presented almost immediately after birth with an early-onset sepsis caused by S. pneumoniae. In both cases neonatal cultures as well as maternal vaginal swabs were positive for S. pneumoniae growth. 2 different patients had other risk factors for peripartal infection. Neonatal pneumococcal infections are most likely transmitted trough the maternal vaginal tract. Maternal vaginal colonization is rare (0.11%), but associated with a high risk of transmission to the newborn. Asymptomatic neonatal colonization was not observed. In light of the likelihood of a high rate of transmission and subsequent infection, peripartal prophylactic antibiotic treatment is advised for all mothers with proven vaginal S. pneumoniae colonization. If this is not given or is not effective, then in contrast with the policy on patients with group B streptococcal colonization, prophylactic antibiotic treatment is advocated for all neonates born to colonized mothers. Amoxicillin is the preferred treatment. In areas of increasing macrolide resistance, erythromycin should only be advised in cases of penicillin allergy.

Seven cases of surgical native valve endocarditis caused by coagulase-negative staphylococci: An underappreciated disease.

BACKGROUND: Native valve endocarditis caused by coagulase-negative staphylococci is uncommon and the diagnosis is infrequently considered. The disease, however, appears to be increasing in frequency and can pursue an aggressive clinical course. We report the clinical features of 7 cases of coagulase-negative staphylococcal native valve endocarditis (CNS-NVE) seen at 1 institution with a large cardiovascular referral base over a 10-month period. All cases required valve replacement surgery. METHODS: Clinical history, echocardiograms, and microbiologic and histopathologic data were reviewed for 7 patients with surgical CNS-NVE. RESULTS: Four patients had intravenous central catheters, and 1 had recent surgery, whereas the remaining 2 had no identifiable risk factors. Presentations ranged from subacute (4 cases) to acute with complications (3 cases). Complications included congestive heart failure, stroke, and heart block. Echocardiography demonstrated valvular lesions in all 7 cases. Valve pathologic study demonstrated gram-positive cocci in all 7 cases; blood cultures grew coagulase-negative staphylococci in 6 cases and valve cultures grew Staphylococcus epidermidis in 5 cases. CONCLUSIONS: Coagulase-negative staphylococci, including S epidermidis, can cause severe native valve endocarditis requiring valve replacement. The increasing use of intravascular access devices in the community may herald an increase in the incidence of CNS-NVE. A high index of diagnostic suspicion in the appropriate clinical setting is critical for optimal management.

Platelet activating factor acetylhydrolase decreases lung reperfusion injury.

BACKGROUND: Ischemia-reperfusion injury involves free radical production, polymorphonuclear neutrophil chemotaxis/degranulation, and production of proteolytic enzymes, complement components, coagulation factors, and cytokines. Activated polymorphonuclear neutrophils, endothelial cells, and macrophages produce platelet activating factor, which further promotes these inflammatory reactions. The recently cloned plasma form of platelet activating factor-acetylhydrolase (PAF-AH) demonstrates antiinflammatory effects by degrading platelet activating factor. We evaluated the effects of PAF-AH in an isolated perfused rat lung model by adding it to the flush solutions or to the reperfusion blood. METHODS: Rat lungs were isolated, flushed with EuroCollins (EC) or University of Wisconsin (UW) solution, stored at 4 degrees C for 6 or 12 hours, and reperfused using a cross-circulating syngeneic support rat. During reperfusion, oxygenation, compliance, and capillary filtration coefficient were calculated. There were four groups in the study; group I (control) had no PAF-AH added, group II had PAF-AH added to the flush solution, group III had PAF-AH added to reperfusion blood, and group IV had PAF-AH added to both flush solution and reperfusion blood. RESULTS: After 6 hours of storage, oxygenation, compliance, and capillary filtration coefficient significantly improved for EC in group IV. For UW, oxygenation improved in group IV whereas compliance improved in groups II, III, and IV. After 12 hours of storage, compliance improved for EC in group IV and capillary filtration coefficient improved in groups III and IV. For UW, oxygenation and compliance improved in groups II and IV, whereas capillary filtration coefficient improved in group IV. CONCLUSIONS: Addition of PAF-AH to intracellular organ preservation solutions and to the blood reperfusate significantly improves postreperfusion oxygenation and compliance, and reduces lung capillary permeability.

Reductions in acetylcholine and nicotine binding in several degenerative diseases.

Alzheimer's disease, Parkinson's disease, and progressive supranuclear palsy are all characterized by loss of neurons in the basal forebrain cholinergic system and by associated reductions in cortical presynaptic cholinergic markers, such as choline acetyltransferase. In this report, we identify that a major cortical receptor alteration in these disorders is a reduction in nicotinic receptors measured using both tritiated acetylcholine and levorotatory tritiated nicotine binding.

Enhancement of [3H]DAGO1 binding to rat brain by low concentrations of monovalent cations.

The effects of mono- and di-valent cations and the nonhydrolyzable guanyl nucleotide derivative 5'-guanylimidodiphosphate (Gpp(NH)p) on the binding of the selective, high affinity mu-opiate receptor agonist, [3H]DAGO ([3H]Tyr-D-Ala-Gly-Mephe-Gly-ol), to rat brain membranes were studied in a low ionic strength 5 mM Tris-HCl buffer. Na+ and Li+ (50 mM) maximally increased [3H]DAGO binding (EC50 values for Na+, 2.9 mM and Li+, 6.2 mM) by revealing a population of low affinity binding sites. The density of high affinity [3H]DAGO binding sites was unaffected by Na+ and Li+, but was maximally increased by 50 mM K+ and Rb+ (EC50 values for K+, 8.5 mM and Rb+, 12.9 mM). Divalent cations (Ca2+, Mg2+; 50 mM) inhibited [3H]DAGO binding. Gpp(NH)p decreased the affinity of [3H]DAGO binding, an effect that was enhanced by Na+ but not by K+. The binding of the mu-agonist [3H]dihydromorphine was unaffected by 50 mM Na+ in 5 mM Tris-HCl. In 50 mM Tris-HCl, Na+ (50 mM) inhibited [3H]DAGO binding by decreasing the density of high affinity binding sites and promoting low affinity binding. The effects of Na+ in 5 mM and 50 mM Tris-HCl were also investigated on the binding of other opiate receptor agonists and antagonists. [3H]D-Ala-D-Leu-enkephalin binding was increased and inhibited. [3H]etorphine binding increased and was unchanged, and both [3H]bremazocine and [3H]naloxone binding increased by 50 mM Na+ in 5 mM and 50 mM Tris-HCl, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Huntington's disease: increased number and altered regulation of benzodiazepine receptor complexes in frontal cerebral cortex.

The properties of benzodiazepine receptors in samples of six areas of cerebral cortex from patients and controls matched with respect to age, sex, and postmortem delay have been studied by in vitro radioligand binding techniques. A statistically significant 30 to 40% increase in the number of benzodiazepine and allosterically linked GABA-A receptors is observed in the midfrontal cortex (A9/A10), but in no other cortical region examined. The degree of enhancement of [3H]diazepam binding by a given dose of GABA or pentobarbital is significantly reduced in Huntington's disease midfrontal cortex. As in the case of receptor number changes, other cortical regions examined show less prominent changes in regulation of benzodiazepine binding by GABA or pentobarbital. Direct identification of the benzodiazepine binding subunit by photoaffinity labeling with [3H]flunitrazepam reveals a single species of apparent molecular weight 51 kD in patients and controls, suggesting that gross changes in structure of the benzodiazepine binding subunit do not account for the observed alterations in benzodiazepine receptor regulation.

Local anesthetics differentiate dihydropyridine calcium antagonist binding sites in rat brain and cardiac membranes.

Local anesthetics were used to probe differences in the binding of [3H]nitrendipine to dihydropyridine calcium antagonist binding sites on rat brain and cardiac membranes. Local anesthetics inhibited [3H]nitrendipine binding to brain and cardiac membranes with the rank order of potency, dibucaine = proadifen much greater than tetracaine greater than meproadifen greater than RAC-109 (S) greater than RAC-109 (R) greater than benzocaine. Lidocaine, procaine, piperocaine and bupivacaine produced either a small potentiation or inhibition of [3H]nitrendipine binding. Dibucaine inhibited [3H]nitrendipine binding to brain membranes (IC50, 4.9 +/- 0.5 microM) by increasing the Kd, whereas in cardiac membranes (IC50, 8.5 +/- 0.9 microM) it both increased the Kd and decreased the maximum binding site capacity of [3H]nitrendipine. The potency of dibucaine to inhibit [3H]nitrendipine binding was reduced in both tissues by monovalent (Li+ greater than Na+ = K+ = Rb+; EC50, 40-50 mM) and divalent (Ca++, Mg++ and Mn++; EC50, 10-50 microM) cations. These cations reduced the effect of dibucaine on the Kd of [3H]nitrendipine in brain and on the maximum binding site capacity of [3H]nitrendipine in cardiac membranes. Inhibition of [3H]nitrendipine binding by dibucaine was best described by high (2 microM) and low (50 microM) affinity sites. The apparent affinities of these sites, but not the fractional occupancies, were similar in brain and cardiac membranes. Na+ modulated the occupancies of these sites in brain, but not in cardiac membranes, whereas Ca++ inhibited occupancy of the high affinity site in both tissues. The effects of Li+ were similar to those of Ca++. These findings indicate that brain and cardiac dihydropyridine calcium antagonist binding sites are coupled to different allosteric effectors or exist in a different membrane environment.

Escherichia coli field contamination of pecan nuts.

More pecan samples collected from grazed orchards were contaminated with Escherichia coli than were samples from nongrazed orchards. No differences in frequency of contamination between mechanically and manually harvested nuts occurred. Nutmeats from whole uncracked pecans that were soaked for 24 h in a lactose broth solution containing E. coli did not become contaminated. Twentyfour percent of the whole pecans soaked in water for 48 h to simulate standing in a rain puddle developed openings along shell suture lines which did not completely close when the nuts were redried.