Computerized tomographic analysis of orbital hypertelorism repair: spatial relationship of the globe and the bony orbit

Computerized tomographic scans provide a new means of evaluating the spatial and geometric relationships between the movement of the bony orbit and its soft tissue contents (the globe and extraocular muscles) [1, 12]. Preoperative and postoperative computerized tomographic scans were analyzed in four patients to explore these relationships. Measurement of the changes in distance between the globes correlated most closely with the change in the distance between the lateral orbital walls; resection of medial (inter-orbital) bone provides space into which the globe is translocated. The medial rectus muscle may be bowed across the medial wall osteotomy line, creating a functional shortening of the muscle; this finding may explain the esotropia that is commonly seen after this procedure [2, 3]. These observations should have a direct impact on the understanding and planning of orbital hypertelorism correction.     

Metabolism of the leukotriene receptor antagonist 5-(2-(8-phenyloctyl)phenyl)-4,6-dithianonanedioic acid (SK&F 102922) in the guinea pig. Rearrangement of the acyl glucuronide.

A primary route of inactivation of leukotrienes and their receptor antagonists (LTRA) is metabolism by omega oxidation. SK&F 102922 [5-(2-(8-phenyloctyl)phenyl)-4,6-dithianonanedioic acid] is a LTRA that was designed to be resistant to omega oxidation. Therefore, these experiments were designed to characterize the metabolic fate of [14C]SK&F 102922. Following iv administration of SK&F 102922 (5 mg/kg), 80% of injected radioactivity was excreted in bile in 1 hr. At least five metabolites and parent (18% of administered dose) were present in bile. One metabolite (M1), which accounted for less than 10% of the excreted radioactivity, was monohydroxylated. Three metabolites (M2, M3A, and M3B), which together accounted for greater than 50% of excreted radioactivity, had mass spectra consistent with acyl glucuronides. All three metabolites were alkali labile, whereas only one metabolite (M2) was susceptible to beta-glucuronidase hydrolysis. These data indicate that M3a and M3b are nonglycosidic isomers of M2 that were formed by a nonenzymic reaction involving migration of the aglycone (SK&F 102922) from C-1 to C-2, C-3, or C-4 of glucuronic acid. The 1-O-acyl-beta-glucuronide of SK&F 102922 (M2) exhibits pH dependent rearrangement, with half-lives ranging from 1 to greater than 1000 hr. Therefore, acyl glucuronidation can account for much of the metabolic fate of SK&F 102922 and, potentially, other structurally related LTRAs or endogenous leukotrienes themselves.     

Inhaled allergen-driven CD1c up-regulation and enhanced antigen uptake by activated human respiratory-tract dendritic cells in atopic asthma

Background Dendritic cells (DC) mediate inflammation in rodent models of allergic airway disease, but the role played by human respiratory‐tract DC (hRTDC) in atopic asthma remains poorly defined. Recent data suggest that CD1 antigen presentation by hRTDC may contribute to asthma pathogenesis. Objective To investigate the influence of hRTDC on the balance between atopy and allergic asthma in human subjects and to determine whether CD1 expression by hRTDC is modulated during asthmatic inflammation. Methods Sputum cells were induced from steroid‐naïve, allergen‐challenged and allergen‐naïve subjects (atopic asthmatics, atopic non‐asthmatics and non‐atopic controls). hRTDC were identified using monoclonal antibody labelling and analysis by flow cytometry. Results hRTDC stained HLA‐DR⁺ (negative for markers of other cell lineages) were predominantly myeloid and comprised ∼0.5% of viable sputum cells. Sputum cells were potent stimulators of allogeneic CD4⁺ naïve T cells and enrichment/depletion experiments correlated stimulatory potency with DC numbers. Sputum contained cells that exhibited typical dendritic morphology when analysed by electron microscopy. Myeloid hRTDC were endocytically active, but uptake of FITC‐dextran was enhanced in cells from asthmatics (P<0.001). Despite their increased endocytic capacity, asthmatic myeloid hRTDC appeared mature and expressed increased levels of maturation markers (P<0.05–P<0.001), CD1c, CD1d and langerin (P<0.05). CD1c expression by asthmatic myeloid hRTDC was enhanced upon in vivo allergen challenge (three to ninefold within 24 h; P<0.05). CD11c⁻CD123^high hRTDC were only detected in asthmatic sputum and were increased in number following allergen challenge. Conclusion Despite limited cell numbers, it proved possible to analyse human RTDC in induced sputum, providing evidence that increased antigen uptake and enhanced CD1 presentation by activated hRTDC may contribute to allergic airway disease. CD1 presentation by hRTDC in atopic asthma may therefore constitute a novel target for future intervention strategies.     

Effects of the angiotensin II type 1 receptor antagonist telmisartan on monocyte adhesion and activation in patients with essential hypertension.

Circulating monocytes from hypertensive patients show elevated secretion patterns of pro-inflammatory cytokines, an increased expression of adhesion molecules, and an increased adhesion to vascular endothelial cells. We tested the hypothesis that telmisartan, an angiotensin II type 1 (AT(1)) receptor antagonist, reduces the activation of circulating monocytes from hypertensive patients and diminishes the monocyte-endothelial cell adhesion. Monocytes of 20 hypertensive patients and 20 normotensive controls were isolated by density gradient centrifugation and Dynabeads, and the monocyte adhesion to human aortic endothelial cell monolayers was measured by adhesion assays. To characterize monocyte activation we assessed the expression of activity-related cell surface markers that are also involved in monocyte adhesion to endothelial cells, such as CD11a/b and CD54, as well as the chemokine receptors CCR1, CCR2 and CCR5 before and after telmisartan therapy using flow cytometry. Spontaneous adhesion of monocytes from hypertensive patients and the adhesion after stimulation with angiotensin II were significantly increased compared with those in normotensive controls (p<0.05). Treatment of hypertensive patients with the AT(1) receptor antagonist telmisartan significantly diminished the adhesion of circulating monocytes to human endothelial cells (p=0.02) despite the increase in the expressions of CD11b, CD54 and CCR5 after telmisartan therapy. Reducing monocyte adhesion may be a novel beneficial effect of the AT(1) receptor antagonist telmisartan helping to prevent vascular alterations in hypertension. The mechanism of action remains to be elucidated, since reduction in monocyte adhesion was not attributable to changes in adhesion molecule expression.     

Genotype prevalence and risk factors for severe clinical adenovirus infection, United States 2004-2006.

BACKGROUND: Recently, epidemiological and clinical data have revealed important changes with regard to clinical adenovirus infection, including alterations in antigenic presentation, geographical distribution, and virulence of the virus. METHODS: In an effort to better understand the epidemiology of clinical adenovirus infection in the United States, we adopted a new molecular adenovirus typing technique to study clinical adenovirus isolates collected from 22 medical facilities over a 25-month period during 2004-2006. A hexon gene sequence typing method was used to characterize 2237 clinical adenovirus-positive specimens, comparing their sequences with those of the 51 currently recognized prototype human adenovirus strains. In a blinded comparison, this method performed well and was much faster than the classic serologic typing method. RESULTS: Among civilians, the most prevalent adenovirus types were types 3 (prevalence, 34.6%), 2 (24.3%), 1 (17.7%), and 5 (5.3%). Among military trainees, the most prevalent types were types 4 (prevalence, 92.8%), 3 (2.6%), and 21 (2.4%). CONCLUSIONS: For both populations, we observed a statistically significant increasing trend of adenovirus type 21 detection over time. Among adenovirus isolates recovered from specimens from civilians, 50% were associated with hospitalization, 19.6% with a chronic disease condition, 11% with a bone marrow or solid organ transplantation, 7.4% with intensive care unit stay, and 4.2% with a cancer diagnosis. Multivariable risk factor modeling for adenovirus disease severity found that age <7 years (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.4-7.4), chronic disease (OR, 3.6; 95% CI, 2.6-5.1), recent transplantation (OR, 2.7; 95% CI, 1.3-5.2), and adenovirus type 5 (OR, 2.7; 95% CI, 1.5-4.7) or type 21 infection (OR, 7.6; 95% CI, 2.6-22.3) increased the risk of severe disease.     

General practitioners' views on the implementation of community-led maternity care in south Camden, London.

New recommendations suggesting that maternity care should be increasingly community-based have generated concern regarding the interprofessional cooperation between general practitioners and midwives. In Camden, London, this service was expanded in 1993. Although existing joint antenatal care arrangements between GPs and midwives were not expected to alter significantly, the shift of care from hospital to community midwives, and the expansion of community-led care to women with complications, was expected to have implications for the GPs. A questionnaire-based study asked GPs who provide antenatal care about their role and liaison with other professionals. Most were satisfied with the current arrangements; only a minority felt that their workload, clinical practice, or communication with obstetric teams had altered.