A connection between allergic rhinitis and allergic asthma? The "one-airway-one-disease"-hypothesis

The nose and the lungs are anatomically and physiologically divided which lead to separated strategies in diagnostic and therapy. The upper airways, from the nose and lungs may account for the traditional division in upper and lower airways. Nonetheless a link between upper and lower respiratory tracts has been repeatedly observed in the past decades making the current division in two separate entities an arbitrary dichotomy. Once allergic rhinitis and asthma are two manifestation of the atopic syndrome it is logical to expect that allergy is not a disease confined to specific target organ rather to a broad spectrum of clinical manifestations. This hypothesis has been supported from various observations: Both, allergic asthma and allergic rhinitis are characterized by a similar if not an identical inflammatory process in which mast cells and eosinophils appear to be the major effector cells, high comorbidity of both allergic manifestations as shown in epidemiologic studies. Both diseases are caused by the interaction of genetic susceptibility with environmental factors. In this review, the latest developments in epidemiology and pathophysiology with regard to nasobronchial interaction in allergic airway disease will be discussed.     

Increased matrix metalloproteinase-13 production with aging by human articular chondrocytes in response to catabolic stimuli

Chondrocyte anabolic activity has been shown to decline with aging, but catabolic activity has received little attention. In this study, the effect of aging on the chondrocyte catabolic response was determined by stimulating isolated human chondrocytes with fibronectin fragments (FN-f) or interleukin-1beta and measuring matrix metalloproteinase-13 (MMP-13) production as a catabolic response. A significant age-related increase in chondrocyte MMP-13 production was noted. FN-f stimulation of MMP-13 expression was blocked using a nuclear factor kappa-B (NFkappaB) inhibitor suggesting a role for NFkappaB in this chondrocyte catabolic response. Chondrocyte production of the NFkappaB-regulated cytokine interleukin-1beta was also found to increase with donor age in unstimulated cells. These results demonstrate a significant age-related increase in chondrocyte catabolic responsiveness which could contribute to the development of osteoarthritis in older adults.     

The sensitization of mice with a wild-type and cold-adapted variant of influenza A virus. II. Secondary cytotoxic T cell responses.

Reductions in virus titres and the generation of enhanced cytotoxic T cell (Tc) activity in the lungs of mice primed either with a wild-type, parental (H2N2) influenza virus, A/AA/6/60, or a cold-adapted variant A/AA/6/60-ca and challenged 6 weeks later with a H1N1 A/WSN virus showed that both H2N2 viruses could sensitize the mice. A comparison of graded sensitizing doses of each virus showed that inocula of 10(6) tissue culture infective doses (TCID50) of the ca-variant or 10(3) TCID50 of the wild-type virus gave similar results. The spleens and lungs of normal mice were found to contain similar levels (circa 1/10(5) cells) of precursor Tc cells and the level in the lung did not increase 2 days after intranasal (i.n.) inoculation of A/WSN virus. Two and 6 weeks after priming mice with 10(5) TCID50 of either virus, the lungs contained about a 20-fold increase in the precursor Tc cell frequency. In contrast, sensitization with a sub-lethal dose of a mouse-adapted A/WSN virus caused a 100-fold or greater increase. Sensitization of mice with the parental but not the ca-variant virus caused an increase in frequency of precursor Tc cells in the spleens of the sensitized mice and this might reflect the very low level of replication of the ca-variant virus in the mouse lung.     

Sonographic biometry of the frontal lobe in normal and growth-restricted neonates

Assessing the impact of restricted intrauterine growth on neonatal frontal lobe (FL) dimensions is important. We aimed to create a sonographic nomogram of FL dimensions in neonates at different gestational ages (GA) and evaluate the impact of small head circumference (HC) on FL dimensions. We conducted sonographic biometry of the FL at birth. We included 218 newborn infants born at GA of 24-43 wk: appropriate for GA and normal HC (n = 178), and small for GA and small HC (n = 23). Infants with a 5-min Apgar score <7, severe congenital malformations, or chromosomal abnormalities were excluded. Through a coronal ultrasound scan via the anterior fontanelle at the level where the most lateral point of the left Sylvian fissure was best demonstrated, we drew a triangle connecting the most lateral point of the Sylvian fissure, the corpus callosum, and the subcalvarian point of the interhemispheric fissure. We measured the three sides of the triangle, Sylvian-fontanellar distance, Sylvian-callosal distance, and fontanellar-callosal distance, and calculated the frontal triangular area. All four FL dimensions increased significantly between 24 and 43 wk of gestation in both appropriate for GA-normal HC and small for GA-small HC neonates, and were strongly correlated with HC and birth weight. Regression lines of GA against Sylvian-fontanellar distance, Sylvian-callosal distance, fontanellar-callosal distance, and frontal triangular area in the appropriate for GA-normal HC group differed significantly from those of the small for GA-small HC group (p < 0.05). Male neonates had significantly larger Sylvian-fontanellar and Sylvian-callosal distances than females (p < 0.01 and p < 0.015, respectively). In conclusion, FL measures increased significantly between 24 and 43 wk of gestation, and were strongly correlated with HC. We speculate that a sonographically small fetal HC implies growth restriction of the fetal FL.     

Variables associated with successful vaginal birth after one cesarean section: a proposed vaginal birth after cesarean section score

The objective of this study was to define the variables associated with vaginal birth after cesarean section (VBAC) and to develop a scoring system for the prediction of successful VBAC. We searched our computerized database for parturients with a history of one low-transverse cesarean section (CS) who were delivered during the year 2000. Variables were categorized according to the time period in which they were obtained: (1) first prenatal visit, (2) at the onset of labor, and (3) during labor. Univariate and multiple stepwise logistic regression models were fitted to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Of the 475 parturients with a history of one previous CS, 136 underwent elective CS and 339 underwent a trial of VBAC, of whom 82% were successful. Of the variables that can be obtained at the onset of labor, five were significantly associated with successful VBAC: abnormal presentation as the indication for the primary CS (OR, 7.4; 95% CI 2.8 to 19.2), a previous VBAC (OR, 7.2; 95% CI, 2.1 to 24.8), cervical dilation (OR, 2.5; 95% CI, 1.3 to 4.9), gestational age < or = 41 weeks (OR, 2.8; 95% CI, 1.1 to 7.1), and lower gestational age at the primary CS (OR, 1.2; 95% CI, 1.02 to 1.4). In the proposed VBAC score, each of the four most significant variables was assigned a score ranging between 0 and 3 based on the probability for VBAC. A score < or = 2 was associated with a success rate of 42%, a score between 3 and 6 was associated with a rate of 81%, and a score between 7 and 10 was associated with a 98% successful VBAC rate (p < 0001). The proposed VBAC score may help obstetricians when counseling their patients regarding the individual likelihood of a successful VBAC.     

De novo malignancies after intestinal and multivisceral transplantation

BACKGROUND: Maintenance immunosuppression required after organ transplantation creates a permissive environment in which cancer cells can proliferate because of lack of natural immunologic surveillance. With more than a decade of clinical experience, this report is the first to address the risk of de novo cancer after intestinal transplantation. METHODS: A total of 168 consecutive intestinal transplant recipients (86 children and 82 adults) were studied, of whom 52% were male and 91% were white. Surveillance, Epidemiology, and End Results data was used to count expected rates of de novo cancers in the general population matched for age, sex, and length of follow-up. RESULTS: With a mean follow-up of 47+/-41 months, 7 (4.2%) patients developed nonlymphoid de novo cancer, with a cumulative risk of 3% at 5 years and 28% at 10 years. Of these malignancies, one was donor-driven adenocarcinoma. With 0.58 being the expected rate of malignancy for the general population, the risk among intestinal recipients was 8.7 times higher (P =0.01). Such morbidity was significantly higher (50 times) among younger patients (<25 years), with a slight male preponderance. Induction immunosuppression was associated with early onset of de novo cancer. Patient survival after diagnosis of de novo cancer was 72% at 1 year, 57% at 2 years, and 29% at 5 years. CONCLUSION: With conventional immunosuppression, intestinal recipients are at a significantly higher risk of developing de novo cancer when compared with the general population. Thus, a novel tolerogenic immunosuppressive strategy has been recently implemented to reduce the lifelong need for immunosuppression.