Should children with infection be tested for lipid,lipoprotein and apolipoprotein?

The lipid profile is known to alter in patients with infection, but there has not been a study of the apolipoprotein levels in serum of otherwise healthy children during infection. Lipids, lipoproteins, apolipoproteins A-l and B and lipoprotein (a) were evaluated prospectively in 31 consecutive children, aged4–15 years, who were admitted to the hospital with bacterial pharyngitis. The degree of dyslipidemia associated with bacterial pharyngitis was assessed using each child as his/her own control and by comparison with 79 healthy children who had not had an infection during the past 3 months. Serum total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein A-l and apolipoprotein B levels were significantly decreased during the symptomatic phase of the disease, whereas the serum triglyceride level was slightly elevated. Serum lipoprotein (a) concentration did not change significantly. In conclusion, it is suggested that serum lipids, lipoproteins and apolipoproteins should not be assessed during infection because of the possible transient changes of these parameters during infection or inflammation.     

Bacterial endocarditis in a child presenting with acute arterial ischemic stroke: should thrombolytic therapy be absolutely contraindicated?

Thrombolysis is considered to be contraindicated in acute ischemic stroke secondary to infective endocarditis (IE). We report a 12-year-old female who presented with acute dense right hemiparesis and aphasia. Cranial magnetic resonance imaging and angiography showed multiple diffusion-restricted lesions in the left hemisphere and absence of flow in the left internal carotid artery. She was treated with intra-arterial tissue plasminogen activator within 6 hours of her presentation. Subsequently she was diagnosed with pneumococcal endocarditis and underwent debridement of vegetations and patch repair of the mitral valve. The patient did not have hemorrhagic complications following thrombolytic therapy or surgery. Pathological analysis of the mitral valve vegetations revealed mostly fibrin thrombus. Follow-up imaging showed complete recanalization of the left internal carotid artery, and the patient had a remarkable neurological recovery. This is the first case report of successful intra-arterial thrombolytic therapy in childhood IE-related stroke. We believe that thrombolytic therapy contributed to a favorable outcome in our patient and may be safe in selected patients with childhood IE-related acute ischemic stroke.     

Cyclooxygenase-1 and Cyclooxygenase-2 in the Human Optic Nerve Head

To investigate the hypothesis that eicosanoids act as cellular mediators in the optic nerve head of normals and of patients with glaucoma, we have determined the presence of the two cyclooxygenase (COX) isoforms in human tissue. Histological sections of optic nerve heads were studied by immunohistochemistry. Age matched normal donors were compared with eyes from glaucoma patients with moderate to severe nerve damage. Polyclonal antibodies to human COX-1 and COX-2 were localized with immunoperoxidase staining. Specific antibodies for vascular endothelia and microglia were also co-localized. In normal and glaucomatous eyes, COX-1 was localized exclusively to the prelaminar and lamina cribrosa regions of the optic nerve head. No staining for COX-1 was observed in the nerve fiber layer or the myelinated optic nerve. COX-1 was associated with the astrocytes of the glial columns and the cribriform plates, but not with the endothelia lining the capillaries. In glaucoma, more astrocytes appeared to be stained with antibody to COX-1 than in normals and staining was intensely perinuclear. There was no staining for COX-2 in normal tissue. A few COX-2 positive cells were found in the prelaminar, lamina cribrosa and postlaminar regions of the glaucomatous optic nerves. Positive staining for COX-2 was not associated with microglia. COX-1 is constitutively present in astrocytes that are localized exclusively to the prelaminar and lamina cribrosa regions of the human optic nerve head. Eicosanoids, synthesized by COX-1 in this tissue, may have a homeostatic and a neuroprotective role related to the axons of the retinal ganglion cells. The sparse presence of COX-2 in glaucomatous tissue probably reflects the lack of inflammation associated with glaucomatous optic neuropathy.     

Assessment of bone mineral density in the jaws and its relationship to radiomorphometric indices

Objectives

The aim of this study was to evaluate maxillary, mandibular and femoral neck bone mineral density using dual energy X-ray absorptiometry (DXA) and to determine any correlation between the bone mineral density of the jaws and panoramic radiomorphometric indices.

Methods

49 edentulous patients (18 males and 31 females) aged between 41 and 78 years (mean age 60.2 ± 11.04) were examined by panoramic radiography. Bone mineral density (BMD) of the jaws and femoral neck was measured with a DXA; bone mineral density was calculated at the anterior, premolar and molar regions of the maxilla and mandible.

Results

The mean maxillary molar BMD (0.45 g cm⁻²) was significantly greater than the maxillary anterior and premolar BMD (0.31 g cm⁻², P < 0.05). Furthermore, the mean mandibular anterior and premolar BMD (1.39 g cm⁻² and 1.28 g cm⁻², respectively) was significantly greater than the mean mandibular molar BMD (1.09 g cm⁻², P < 0.01). Although BMD in the maxillary anterior and premolar regions were correlated, BMD in all the mandibular regions were highly correlated. Maxillary and mandibular BMD were not correlated with femoral BMD. In addition, mandibular cortical index (MCI) classification, mental index (MI) or panoramic mandibular index (PMI) values were not significantly correlated with the maxillary and mandibular BMDs (P > 0.05).

Conclusions

The BMD in this study was highest in the mandibular anterior region and lowest in the maxillary anterior and premolar regions. The BMD of the jaws was not correlated with either femoral BMD or panoramic radiomorphometric indices.     

Evidence that fibrinogen γ′ directly interferes with protofibril growth: implications for fibrin structure and clot stiffness

Summary. Background: Fibrinogen contains an alternatively spliced γ‐chain (γ′), which mainly exists as a heterodimer with the common γA‐chain (γA/γ′). Fibrinogen γ′ has been reported to inhibit thrombin and modulate fibrin structure, but the underlying mechanisms are unknown. Objective: We aimed to investigate the molecular mechanism underpinning the influence of γ′ on fibrin polymerization, structure and viscoelasticity. Methods: γA/γA and γA/γ′ fibrinogens were separated using anion exchange chromatography. Cross‐linking was controlled with purified FXIIIa and a synthetic inhibitor. Fibrin polymerization was analyzed by turbidity and gel‐point time was measured using a coagulometer. We used atomic force microscopy (AFM) to image protofibril formation while final clot structure was assessed by confocal and scanning electron microscopy. Clot viscoelasticity was measured using a magnetic microrheometer. Results: γA/γ′ fibrin formed shorter oligomers by AFM than γA/γA, which in addition gelled earlier. γA/γ′ clots displayed a non‐homogenous arrangement of thin fibers compared with the uniform arrangements of thick fibers for γA/γA clots. These differences in clot structure were not due to thrombin inhibition as demonstrated in clots made with reptilase. Non‐cross‐linked γA/γA fibrin was approximately 2.7 × stiffer than γA/γ′. Cross‐linking by FXIIIa increased the stiffness of both fibrin variants; however, the difference in stiffness increased to approximately 4.6 × (γA/γA vs. γA/γ′). Conclusions: Fibrinogen γ′ is associated with the formation of mechanically weaker, non‐uniform clots composed of thin fibers. This is caused by direct disruption of protofibril formation by γ′.     

Randomized controlled trial of short-term withdrawal of i.v. immunoglobulin therapy for selected children with human immunodeficiency virus infection

BACKGROUND: The aim of the present paper was to determine whether monthly i.v. immunoglobulin (IVIG) could be safely discontinued in antiretroviral-treated human immunodeficiency virus (HIV)-infected children. METHODS: In a double-blind cross-over trial, children < or =18 years with HIV infection, well controlled on antiretroviral therapy, were randomized to alternating courses of 3 consecutive months of IVIG (400 mg/kg once a month) and 3 consecutive months of placebo for 1 year. The primary outcome was days of fever per month. Secondary outcomes were frequency of serious infections, changes in HIV viral load (VL), CD4+ counts and IgG levels. RESULTS: Fifteen children were enrolled. Using the revised pediatric HIV clinical classification system of the Centers for Disease Control and Prevention, eight were severely symptomatic (C), four were moderately symptomatic (B) and three were mildly symptomatic (A). There were no statistically significant outcome measures. The mean number of days of fever per month with IVIG versus placebo was 0.55 days versus 1.48 days (P = 0.11). The difference was 0.9 days (95% confidence interval: +2.05 to -0.25). There were no serious infections in either period. For the IVIG versus placebo periods, mean CD4 counts were 970 cells/microL versus 906 cells/microL (P = 0.12), VL 2.90 log(10) copies/mL versus 2.82 log(10) copies/mL (P = 0.70) and IgG levels were 17.41 g/L versus 16.6 g/L (P = 0.13). CONCLUSION: In antiretroviral-treated HIV-infected children short-term withdrawal of monthly IVIG was not associated with a significant increase in incidence of infections or a decline in immunologic function (CD4 count, viral load and IgG levels). These results suggest that monthly IVIG can be safely discontinued in HIV-infected children who are clinically stable and receiving combination antiretroviral therapy.     

Hereditary Complement Deficiency in Survivors of Meningococcal Disease: High Prevalence of C7/C8 Deficiency in Sephardic (Moroccan) Jews

The prevalence of complement deficiency was studied among 111survivors of sporadic menin-gococcal disease located throughthe medical records of 10 Israeli hospitals. There were 11 patientswith CH₅₀=0: one with systemic lupus erythematosus and 10 withhereditary terminal complement deficiency (four with homozygousC7 and six with C8 deficiency). There was no hereditary complementdeficiency among 39 Ashkenazi subjects as against 18 per centamong 38 Sephardi subjects and 40 per cent among 15 of Moroccanancestry (p<0.05). The age at first presentation of meningococcaldisease in complement deficient patients was 14.7+7.6, yearscompared with 8.1+10.9 in the non-deficient patients (p<0.25).None of the complement deficient patients had meningitis belowthe age of 5 years vs. 49 per cent of non-deficient subjects.Recurrent meningitis was observed in 40 vs. 4 per cent (p<0.01)and meningitis in siblings in 40 vs. 2 percent respectively(p<0.001). In addition to the 10 propositi, 11 non-propositussiblings were identified with severe complement deficiency (sixwith homozygous C7 and five with C8 deficiency). Seven of thenon-propositi had no history at all of meningitis or any otherserious systemic disease, underlining the relatively favourableprognosis of terminal complement deficiency. With increasingfamiliarity with the clinical features of this hereditary disease,it is possible now to identify on clinical grounds patientswith meningococcal disease with a high likelihood of terminalcomplement deficiency.     

Viral causes of influenza‐like illness: Insight from a study during the winters 2004–2007

Limited information is available on the viral etiology of influenza‐like illness in southern European countries, and it is still a matter of debate whether certain symptoms can be used to distinguish among the specific viruses that cause influenza‐like illness. The main objective of the present study was to identify the demographic and clinical predictors of influenza‐like illness due to specific viral agents. The study, which was observational in design, was conducted in Rome and Naples, Italy. Cases of influenza‐like illness were defined as individuals with fever >37.5°C and at least one systemic and one respiratory symptom, recruited during the winters of 2004–2005, 2005–2006, and 2006–2007. Influenza and other respiratory viruses were identified using the polymerase chain reaction (PCR), performed on throat swabs. Basic individual information was collected using a standard form. A total of 580 persons were included in the analysis. Viral pathogens were identified in fewer than 50% of the cases. Overall, 240 viral agents were detected: 22.8% were positive for influenza viruses, 10.9% for adenoviruses, 6.0% for parainfluenza viruses, and 1.7% for respiratory syncytial virus. The month of diagnosis, and muscle and joint pain were associated with influenza virus, though the positive predictive value (PPV) was low. Abdominal pain was associated with adenovirus infection. Although the PPV of symptoms for influenza virus infection was low, especially in low activity periods, these findings may help clinicians to improve their ability to perform diagnoses. J. Med. Virol. 81:2066–2071, 2009. © 2009 Wiley‐Liss, Inc.     

Electrophysiological and Clinical Comparison of Two Temporary Pacing Leads Following Cardiac Surgery

Temporary pacing leads are invaluable in diagnosis and treatment of arrhythmia after cardiac surgery. The ideal lead possesses reliable pacing and sensing capabilities throughout the postoperative period. Ease of handling and a low complication rate are essential. This study compares a new lead (Medtronic model #6492) to a temporary pacemaker lead established in clinical use (Medtronic model #6500). One lead of each type was placed in the right atrium and ventricle in 33 patients undergoing elective coronary revascularization. Pacing function was measured on the first and fourth postoperative days. Lead complications were documented. On day 1, there was no statistical difference between lead types in terms of pacing (voltage threshold, current threshold), impedance, or sensing (P wave amplitude, R wave amplitude). On day 4, both leads showed an increase in pacing threshold and a decrease in sensing ability. The only statistical difference between lead types was in atrial sensing on day 4, as measured by the P wave amplitudes (1.95 +/- 0.18 V for model 6492 vs 1.40 +/- 0.14 V for model 6500, P < 0.05). Two leads of each model failed to pace in the ventricular position and one lead in each model in the atrial position. There were no complications attributable to either pacemaker lead. We found that both lead types were reliable and functioned well. The Medtronic Model #6492 lead demonstrated better long-term sensing, although in this study the difference was not clinically significant.