The effects of grass pollen allergoid immunotherapy on clinical and immunological parameters in children with allergic rhinitis

Allergoid immunotherapy is a new form of allergen immunotherapy allowing safe administration of high allergen doses. There is limited information on the effects of allergoid immunotherapy in children with allergic rhinitis. To investigate the immunological and clinical effects of allergoid immunotherapy in children with allergic rhinitis due to grass pollen allergy. Children with allergic rhinitis were assigned to allergoid immunotherapy (n = 27) or control (n = 26, no immunotherapy) groups. Children in the immunotherapy group received seven injections of grass pollen allergoid immunotherapy before grass pollen season and continued to receive maintenance immunotherapy for 27 months. All patients were offered a pharmacotherapy regimen to be used on demand during the pollen seasons. Clinical and laboratory parameters were compared between the immunotherapy and control groups. The rhinoconjunctivitis symptom-medication score and asthma symptom score were lower in the immunotherapy group after 1 yr of maintenance immunotherapy (p < 0.01 for both). Skin test reactivity and nasal reactivity as determined by nasal provocation testing for grass pollen were significantly decreased after 1 yr of immunotherapy (p < 0.001 for both). The seasonal increase in bronchial reactivity and nasal lavage eosinophil cationic protein levels were prevented after the first year of immunotherapy (p < 0.05 for both). The seasonal increase in immunoglobulin (Ig)E decreased (p < 0.05) and grass-specific IgG, IgG(1) and IgG(4) increased significantly already at the end of the seven-injection build-up therapy (p < 0.001, for all). Interleukin (IL)-4 levels in the culture supernatants showed a steady decline from baseline at first and second year of immunotherapy (p < 0.001) but remained unchanged in the control group. Allergoid immunotherapy is an effective method in the treatment of grass pollen-induced allergic rhinitis in children and prevents the seasonal increase in bronchial hyper-reactivity. Changes in specific IgE and IgG levels and decreased IL-4 production in peripheral blood mononuclear cell culture supernatants may account for the observed clinical effects.     

Oral Valganciclovir Is Noninferior to Intravenous Ganciclovir for the Treatment of Cytomegalovirus Disease in Solid Organ Transplant Recipients

Intravenous ganciclovir is the standard treatment for cytomegalovirus disease in solid organ transplant recipients. Oral valganciclovir is a more convenient alternative. In a randomized, international trial, recipients with cytomegalovirus disease were treated with either 900 mg oral valganciclovir or 5 mg/kg i.v. ganciclovir twice daily for 21 days, followed by 900 mg daily valganciclovir for 28 days. A total of 321 patients were evaluated (valganciclovir [n = 164]; i.v. ganciclovir [n = 157]). The success rate of viremia eradication at Day 21 was 45.1% for valganciclovir and 48.4% for ganciclovir (95% CI -14.0% to +8.0%), and at Day 49; 67.1% and 70.1%, respectively (p = NS). Treatment success, as assessed by investigators, was 77.4% versus 80.3% at Day 21 and 85.4% versus 84.1% at Day 49 (p = NS). Baseline viral loads were not different between groups and decreased exponentially with similar half-lives and median time to eradication (21 vs. 19 days, p = 0.076). Side-effects and discontinuations of assigned treatment (18 of 321 patients) were comparable. Oral valganciclovir shows comparable safety and is not inferior to i.v. ganciclovir for treatment of cytomegalovirus disease in organ transplant recipients and provides a simpler treatment strategy, but care should be taken in extrapolating to organ transplant recipients not properly represented in the present study.     

Hypothalamic hamartoma with bilateral anophthalmia

Introduction Hypothalamic hamartomas are congenital malformations. Clinically, they can be asymptomatic, but they cause seizures, mental retardation and precocious puberty in many cases. Case report A 20-day-old boy with hypothalamic hamartoma and bilateral anophthalmia was presented. Except those, no other congenital anomaly was detected. Conclusion This is a rare case of hypothalamic hamartoma with bilateral anophthalmia. The mutations at SOX2 has an important role in the developing brain and eyes.     

Serum-resistant lipopolyplexes for gene delivery to liver tumour cells.

In this study, an efficient non-viral gene transfer system has been developed by employing polyethylenimine (PEI 800, 25 and 22kDa) and DOTAP and cholesterol (Chol) as lipids (lipopolyplex), at three different lipid/DNA molar ratios (2/1, 5/1 and 17/1) by using five different protocols of formulation. Condensation assays revealed that PEI of 800, 25 and 22kDa were very effective in condensing plasmid DNA, leading to a complete condensation at N/P ratios above 4. Addition of DOTAP/Chol liposomes did not further condense DNA. Increasing the molar ratio lipid/DNA in the complex resulted in higher positive values of the zeta-potential, while the particle size increased in some protocols, but not in others. High molecular weight PEI (800kDa) used in the formulation of lipopolyplexes lead to a bigger particle size, compared to that obtained with smaller PEI species, whether branched (25kDa) or linear (22kDa). These vectors were also highly effective in protecting DNA from attack by DNAse I. Transfection activity was maximal by using protocols 3 and 4 and a lipid/DNA molar ratio of 17/1. These complexes showed high efficiency in gene delivery of DNA to liver cancer cells, even in the presence of high concentration of serum (60% FBS). On the other hand, complexes formed with linear PEI (22kDa) were more effective than lipopolyplexes containing branched PEI (800 or 25kDa). The complexes resulted to be much more efficient than conventional lipoplexes (cationic lipid and DNA) and polyplexes (cationic polymer and DNA). The same behaviour was observed for complexes prepared in the presence of the therapeutic gene pCMVIL-12. Toxicity assays revealed a viability higher than 80% in all cases, independently of the protocol, molar ratio (lipid/DNA), molecular weight and type of PEI.     

Reversed-J inferior sternotomy for awake coronary bypass.

Many approaches for minimally invasive coronary bypass surgery are available and to further decrease the invasiveness, coronary artery bypass grafting has been performed under high thoracic epidural anesthesia without endotracheal intubation in the last years. Less invasive approach to coronary artery bypass graft operations is possible through combination of the high thoracic epidural anesthesia and a reversed-J sternotomy, and coronary revascularization can be accomplished without any additional technical difficulties and with a good exposure of both the left anterior descending artery and the left internal thoracic artery. This technique is less traumatic for patients and provides practical better oxygenation and shorter hospital stay.     

Angiogenesis and the blood-brain barrier in intracerebral solid and cell suspension grafts

Solid and suspension grafts of fetal central nervous system (CNS) tissue rapidly reform an intact blood-brain barrier (BBB), whereas solid grafts of peripheral nervous system (PNS) tissue fail to establish a BBB as detected by horseradish peroxide (HRP) leakage, administrated intravenously. We examined the acute changes in the BBB after grafting of fetal CNS tissue in solid and suspension form and superior cervical ganglion (SCG) and PNS tissue in the same manner. Adult rats (n = 20) received fetal (day 14–15) forebrain grafts (either solid or cell suspension) to their rostral corpus callosum bilaterally. A second group (n = 20) received SCG solid and cell suspension grafts at the same coordinates with the same technique. The animals were killed on first, third, seventh, and tenth days after grafting. Intravenous HRP (Sigma, type VI, 75 mg/5-g rat) was given 1 hour before perfusion with mixed aldehydes. Fifty-micron coronal sections were examined for the presence and location of the graft by cresyl violet and AChE staining and Mesulam's TMB method to detect HRP leakage. HRP leakage was detected in the parenchyma in all groups on the first and the third days post-transplantation indicating a disrupted BBB. No HRP reaction was seen at days 7 and 10 in groups receiving fetal forebrain tissue whether solid or cell suspension. Solid grafts of SCG consistently demonstrated HRP leakage from the first through the tenth day. However, cell suspension of SCG established a BBB by 7 days. These results suggest that within the solid grafts of CNS and PNS tissue, the permeability of the vessels is dictated by the transplanted tissue itself. When cell suspensions of the same tissue are introduced, host CNS tissue dominates as the local environment resulting in non-leaky vasculature within the graft.     

The KBG syndrome: confirmation of autosomal dominant inheritance and further delineation of the phenotype

We report on a Turkish family in which the father and his two sons were diagnosed as having the KBG syndrome. Large upper central incisors were the diagnostic finding in all three patients along with mental retardation, cryptorchidism, skeletal abnormalities, and short stature. Our report clearly confirms that the inheritance is autosomal dominant in KBG syndrome, although a high male to female ratio has been observed in published cases.