Infective endocarditis in children with normal heart: Indication for surgical intervention

Although infective endocarditis is an uncommon condition, it can be fatal if not treated. The new era of infective endocarditis in children with structurally normal heart has become apparent entity. Duke criteria has been established for a long time and gives clear guidelines for diagnosis; however, surgical indication in pediatric population needs to be tailored to individual patients.     

Early outcome of tetralogy of Fallot repair in the current era of management

Background

Traditional use of trans-annular patch (TAP) to release right ventricular outflow tract (RVOT) obstruction during tetralogy of Fallot (TOF) repair may lead to a harmful pulmonary regurgitation. Different approaches have been used to release RVOT obstruction and spare the pulmonary valve (PV) function. In this study, we aim to evaluate the post-operative course of patients who had TOF repair in the current era that emphasizes on protective strategy of releasing RVOT obstruction and preserving PV function.

Methods

A retrospective study of all TOF cases repaired in our institute between March 2002 and December 2007 was conducted. Cases were classified into two groups; group I included patients that had a TAP, while group II included cases that had simple TOF repair without TAP. Group I was subdivided into two groups, group (A) which include patients who had TAP without a valve. Group (B) includes those who had TAP with a monocuspid valve (Contegra). We compared post-operative care and outcome of all groups.

Results

Eighty-three patients fulfilled the study criteria. There were 64 cases (77%) in group I, and 19 cases (23%) in group II. All children tolerated surgical repair and did well. We observed no statistically significant difference in the post-operative ICU care, complications rates and morbidity between all groups. There was no surgical mortality in all groups.

Conclusion

Children undergoing TOF repair had excellent short-term outcome with the current protective strategy aiming to spare valvular function, and conserving myocardial function. Applying a monocuspid patch technique did not show clear short-term benefits. Long term follow up is needed to evaluate future difference in different techniques.     

Treatment options for a patient experiencing pruritic rash associated with transdermal testosterone: a review of the literature.

A 22-year-old man with hypogonadotropic hypogonadism was receiving monthly intramuscular injections of testosterone replacement therapy. The patient refused to self-administer the injections because of discomfort, so the therapy was switched to testosterone patches. He experienced a pruritic, macular, erythematous rash underneath the reservoir area of two different transdermal formulations, which did not improve after pretreatment with topical corticosteroids. Eventually, he tolerated application of a testosterone gel and his serum testosterone levels returned to normal after 1 month of therapy. Commercially available and investigational testosterone products and therapeutic monitoring guidelines for androgen replacement are reviewed.     

The dopamine D3 receptor interacts with itself and the truncated D3 splice variant d3nf: D3-D3nf interaction causes mislocalization of D3 receptors

We have generated a stable cell line expressing FLAG epitope-tagged D3 dopamine receptors and used this cell line to study D3 receptor-protein interactions. To analyze protein interactions, we separately introduced into the stable cell line either D3 receptors carrying an hemagglutinin (HA) epitope tag, or an HA-tagged version of the D3 receptor splice variant D3nf. A combination of confocal laser microscopy and coimmunoprecipitation was used to assay the formation and expression pattern of D3-D3 homodimers or D3-D3nf heterodimers. When coexpressed in HEK 293 cells, FLAG- and HA-tagged D3 receptors exhibited a similar plasma membrane distribution. Using an HA epitope tag-specific antibody, we coimmunoprecipitated HA- and FLAG-tagged D3 receptors, suggesting that D3 receptors are capable of forming homodimers. Epitope-tagged D3nf polypeptides exhibited a markedly different cellular distribution than D3 receptors. When expressed in HEK 293 cells, either alone or in combination with FLAG-tagged D3 receptors, D3nf exhibited a punctate perinuclear distribution. When D3nf was introduced into the stable D3-expressing cell line, D3 receptors were no longer visualized at the plasma membrane. Instead, D3 and D3nf showed a similar, predominantly cytosolic, localization. Using the HA-specific antibody, we were able to coimmunoprecipitate D3 and D3nf polypeptides from transfected cells. These data suggest the existence of physical interaction between D3 and D3nf. This interaction appears to result in the mislocalization of D3 receptors from the plasma membrane to an intracellular compartment, a finding that could be of significance in the etiology of schizophrenia.     

Feasibility and limitations of oxcarbazepine monitoring using salivary monohydroxycarbamazepine (MHD)

The purpose of this study is to determine the feasibility of using 10-hydroxy-10,11-dihydrocarbazepine (MHD) concentration in saliva as an alternative to serum for the therapeutic monitoring of oxcarbazepine (OXC) treatment. Investigators identified subjects seen in neurology clinics at the University of Kentucky Chandler Medical Center. Patients were eligible if they agreed to participate in this study, were taking oxcarbazepine, and if a serum MHD concentration had been ordered by their physician. Unstimulated saliva specimens (0.25 mL minimum) were collected in the clinic and frozen until analysis. Blood samples were obtained by phlebotomy. Serum specimens were analyzed by a reference laboratory. Saliva MHD concentrations were determined by high-performance liquid chromatography in the Clinical Laboratory at the Cincinnati Children's Hospital Medical Center. Linear regression analysis was used to evaluate correlations. Saliva and blood specimens were collected from 28 epilepsy patients, but usable samples were obtained from only 23. The mean serum MHD concentration was 23.9 +/- 10.0 microg/mL, and the mean saliva concentration was 23.1 +/- 10.1 microg/mL. There was a significant positive correlation between the serum and saliva concentrations: saliva (y) = 0.95 serum (x) + 0.39; r = 0.941; n = 23; P < 0.001). The mean saliva:serum MHD concentration ratio was 0.96 +/- 0.15. The results of the current study indicate that the relationship between freely flowing (unstimulated) saliva and serum concentrations of MHD is sufficient for therapeutic drug monitoring. A limitation of saliva MHD monitoring is that individuals who have difficulty producing small quantities of saliva or who have viscous saliva should generally be avoided for this type of monitoring. It is also recommended to avoid saliva collection within 8 hours after OXC dosing to allow complete absorption and transformation of the parent drug.     

Increase in intranuclear nuclear factor kappaB and decrease in inhibitor kappaB in mononuclear cells after a mixed meal: evidence for a proinflammatory effect

BACKGROUND: In view of the stimulatory effect of glucose on reactive oxygen species (ROS) generation, we investigated the possibility that a mixed meal stimulates ROS generation and possibly induces concomitant proinflammatory changes. OBJECTIVE: The objective was to determine whether the intake of a 900-kcal mixed meal induces an increase in ROS generation by leukocytes and an inflammatory response at the cellular level. DESIGN: Nine normal-weight subjects were given a 900-kcal mixed meal, and 8 normal-weight subjects were given 300 mL water after an overnight fast. Blood samples were collected at 0, 1, 2, and 3 h. ROS generation by mononuclear cells and polymorphonuclear leukocytes and the expression of p47(phox) subunit were measured. Intranuclear nuclear factor kappaB (NF-kappaB) binding and the expression of inhibitor kappaBalpha (IkappaBalpha), IkappaB kinase alpha (IKKalpha), and IkappaB kinase beta (IKKbeta) were measured. Plasma concentrations of C-reactive protein (CRP) and soluble intercellular adhesion molecule were also measured. RESULTS: ROS generation by mononuclear cells and polymorphonuclear leukocytes and p47(phox) expression increased significantly. The expression of IKKalpha and IKKbeta and DNA-binding activity of NF-kappaB increased significantly, whereas IkappaBalpha expression decreased. Plasma CRP concentrations increased. The intake of 300 mL water did not induce a change in any of the above indexes. CONCLUSIONS: These data show that the intake of a mixed meal results in significant inflammatory changes characterized by a decrease in IkappaBalpha and an increase in NF-kappaB binding, plasma CRP, and the expression of IKKalpha, IKKbeta, and p47(phox) subunit. These proinflammatory changes are probably relevant to the state of chronic hypertension and obesity and to its association with atherosclerosis.     

Cell block findings from residual PreservCyt samples in unsatisfactory ThinPrep Paps: no additional benefit

Our objective was to determine whether cell blocks (CB) performed on unsatisfactory ThinPrep Pap Test residual samples rendered additional clinically significant pathologic findings not detected in the original ThinPrep Pap smears. One hundred consecutive ThinPrep Paps categorized as unsatisfactory were selected for this study. The cytologic diagnosis of unsatisfactory was based on lack of cellularity (squamous) or complete obscuring blood or inflammation. Residual PreservCyt samples from these consecutive unsatisfactory ThinPrepPaps were used to prepare a cell block, using the inverted filter technique. One hematoxylin-eosin (H&E)-stained slide was prepared and evaluated. The amount and the cellular changes were noted for all smear constituents and compared with the original slides. The average patient age was 32 +/- 11 yr. The ThinPrepPap was performed as a follow-up on a previous abnormal smear (12%), pregnancy (25%), abnormal bleeding (22%), or previous unsatisfactory ThinPrepPap (5%), or as routine screening (36%). Variable amounts of endocervical cells, endometrial cells, and metaplastic cells, as well as a variable number of squamous epithelial cells, were present in 89%, 9%, 50%, and 35% in the CB method vs. ThinPrep, respectively. Abnormal cellular changes were noted in 15% of patients (9% with LSIL, and 6% with atypia of undetermined significance); 9 patients with squamous dysplasia had a previous abnormal ThinPrep Pap. A follow-up Pap smear and/or cervical biopsy were performed in 10 of the 15 patients with abnormal cytology detected on CB method revealing: LSIL (1 patient), HSIL (1 patient), ASCUS (1 patient), and within normal limits (7 patients). The findings indicate that the preparation of a CB does not contribute significantly. Importantly, no carcinomas or HSILs were identified on CB preparations. Since a large majority of lesions identified were LSILs, a repeat Pap smear in these cases represented a more cost-effective strategy than cell block preparation, although a cell block preparation may be useful in selected cases.