Genetic susceptibility to visceral leishmaniasis in The Sudan: linkage and association with IL4 and IFNGR1

Longitudinal studies in Sudan show ethnic differences in incidence and clinical phenotypes associated with Leishmania donovani. Immunologically, bias in type 1 vs type 2 cytokine responses is important. To determine whether polymorphisms at IL4/IL9 or IFNGR1 contribute to susceptibility, we examined 59 multicase families of visceral leishmaniasis (VL) with/without post Kala-azar dermal leishmaniasis (PKDL). Multipoint nonparametric analysis (Allegro) linked IL4/IL9 to VL per se (P=0.002). Transmission disequilibrium testing with robust variance estimates confirmed association in the presence of linkage between VL per se and IL4 (P=0.008) but not IL9. Stepwise logistic regression analysis showed both IL4RP2 and IL4RP1 markers contributed significantly to the association, suggesting a common disease-associated haplotype. In contrast, IFNGR1 was linked (P=0.031) and associated (P=0.007) to PKDL but not VL or VL per se. Hence, polymorphism in a type 2 cytokine gene influences underlying susceptibility to VL, whereas IFNGR1 is specifically related to susceptibility to PKDL.     

Paramagnetic macrocyclic complexes as contrast agents for MR imaging: proton nuclear relaxation rate enhancement in aqueous solution and in rat tissues

Paramagnetic macrocyclic chelates show promise as magnetic resonance (MR) imaging contrast agents due to stability and relaxivity comparable to those of DTPA-type chelates. For the three copper and manganese macrocyclic complexes studied in aqueous solution, T1 and T2 relaxivities ranged from 0.14 to 5.88 mM-1sec-1 at 6.25 MHz. In rats, the intravenous administration of 16 mumol/kg of Mn(cyclam) caused the liver T1 relaxation rate to double at 15 minutes after injection. T1 measurements by pulsed MR imaging and manganese analyses on excised tissue showed that both relaxation rate (1/T1) and manganese content of liver and kidney increase linearly with the dosage of Mn(cyclam). The linear relationship between 1/T1 and manganese content can be considered an "in tissue" relaxivity plot for the agent. The resulting relaxivity is 54 mM-1sec-1 in liver, compared with 3.1 mM-1sec-1 in aqueous solution. Although this work is preliminary, the implication for medical MR imaging applications is that macrocyclic contrast agents can be effective at approximately one-tenth the current typical dose used for gadolinium DTPA.     

The superior laryngeal nerve loop and its surgical implications

Summary Based upon findings from 60 cadavers (120 sides), the incidence of superior laryngeal nerve loop, connecting the cervical sympathetic chain and the superior laryngeal nerve and its branches, the external and internal laryngeal nerve, was 98.3% (118 out of 120 sides). In most cases the loop connected the sympathetic chain and the external laryngeal nerve. The external laryngeal nerve was looped, and not linear as traditionally thought. The loop could be divided into three categories, V-shaped, U-shaped and mixed, and subdivided into 5 types and 17 subtypes according to morphological variation. The loop without exception innervated not only the cricothyroid muscle, but also the thyroid gland. The loop is one of the origins of the thyroid nerve. It seems that for thyroid surgery the loop, when lower in position, should be carefully separated from the superior thyroid vessels before the latter are ligated, in order to preserve a normal nerve supply to the muscle as well as to the part of the gland that remains after surgery.

---

L'anse du nerf larynge supérieur, étude anatomique et applications chirurgicales

Résumé La fréquence d'une anse du nerf laryngé supérieur réalisant une anastomose entre la chaine sympathique cervicale et le nerf laryngé supérieur et/ou ses branches (rameau laryngé externe et ingerne), est de 98,3 % (118/120). Ce résultat s'appuie sur l'étude de 60 cadavres. Dans la plupart des cas, l'anastomose se fait entre la chaine sympathique cervicale et le rameau laryngé externe. Ce rameau laryngé externe a un trajet curviligne et non linéaire conformément aux données classiques. Il existe trois catégories d'anses : en "V", en "U" et mixte ; on peut également les subdiviser en 5 types et 17 sous-types en fonction des variations morphologiques. Cette anse innerve constamment non seulement le muscle cricothyroïdien mais aussi la glande thyroïde dont elle fournit une partie de l'innervation. Lors de la chirurgie thyroïdienne, si l'anse est en position basse, les nerfs doivent être soigneusement disséqués et séparés des vaisseaux thyroïdiens supérieurs avant ligature de ces derniers de façon à conserver l'innervation normale du muscle et de la partie restante de la glande.

     

消痔灵和强的松龙混合液治疗鼻息肉

0　引言　我科 1996 / 1998分别应用消痔灵与强的松龙混合液、消痔灵液、强的松龙液行鼻息肉内 ,鼻息肉蒂部注射治疗鼻息肉各 5 0例 ,并设对照组为鼻腔滴入及口服类固醇激素 5 0例 ,合计 2 0 0例 ,观察并对比其疗效 .1　对象和方法1.1　对象　男 12 8例 ,女 72例 ,年龄 8～ 78(平均 38)岁 ,病程 32 a～ 45 (平均 4.5 ) a.其中在本次治疗前做过一次鼻息肉摘除术后复发的 2 7例 ,做过 2次或 2次以上手术的 12例 .主要症状为鼻塞、流脓涕、头痛及嗅觉减退 .全部病例治疗前均行鼻窦 X线拍片 ,其中上颌窦炎 12 5例、筛窦炎 5 8例、蝶窦炎 2例、…     

Behavioral disturbances without amyloid deposits in mice overexpressing human amyloid precursor protein with Flemish (A692G) or Dutch (E693Q) mutation

The contribution of mutations in the amyloid precursor protein (APP) gene known as Flemish (APP/A692G) and Dutch (APP/E693Q) to the pathogenesis of Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis of the Dutch type, respectively, was studied in transgenic mice that overexpress the mutant APP in brain. These transgenic mice showed the same early behavioral disturbances and defects and increased premature death as the APP/London (APP V717I), APP/Swedish (K670N, M671L), and other APP transgenic mice described previously. Pathological changes included intense glial reaction, extensive microspongiosis in the white matter, and apoptotic neurons in select areas of the brain, while amyloid deposits were absent, even in mice over 18 months of age. This contrasts with extensive amyloid deposition in APP/London transgenic mice and less pronounced amyloid deposition in APP/Swedish transgenic mice generated identically. It demonstrated, however, that the behavioral deficiencies and the pathological changes in brain resulting from an impaired neuronal function are caused directly by APP or its proteolytic derivative(s). These accelerate or impinge on the normal process of aging and amyloid deposits per se are not essential for this phenotype.     

Integrating a population health approach into healthcare service delivery and decision making

Most regional health authorities include “improving population health and health equity” in their mission, vision, or priority statements, yet few regional health authorities or hospitals have been shown to devote the sufficient time and resources to make significant progress toward this aim. Health system leaders want to act on this priority, but many barriers and challenges conspire to limit their effectiveness. Improving population health requires both population-based and individual-level initiatives aimed at preventing disease and improving health equity. Practical examples for integrating a population health approach into the health system are presented for healthcare leaders.