Aetiology of severe demarcated enamel opacities--an evaluation based on prospective medical and social data from 17,000 children

During the 1970s dentists reported an increasing prevalence of a "new" type of enamel disturbance.The disturbance was very specific, with areas of demarcated hypomineralised enamel, and was mostly found in permanent first molars and incisors. Several studies have tried to reveal the aetiology behind the enamel disturbance but sofar no clear factors correlated have been found. The aim of the present study was to evaluate aetiological factors to severe demarcated opacities (SDO) in first permanent molars in a large cohort of children enrolled in the "All Babies in Southeast Sweden" (ABIS) project. ABIS is a prospective study of all children in five Swedish counties born between Oct 1, 1997 and Oct 1, 1999, in all about 17,000 children.They have been followed from birth with recording of a large number of factors on nutrition, diseases, medication, infections, social situation etc. With help from 89 Public Dental Service clinics in the same area preliminary examinations of the children, born between Oct 1,1997 and Oct 1,1999, reported 595 children with severe demarcated opacities (SDO) in first molars.These children and a randomly selected age matched group of 1,200 children were further invited to be examined by specialists in paediatric dentistry. At these examinations 224 severe cases were identified as well as 253 children completely without enamel disturbances among children registered in ABIS.These two groups were analysed according to any correlation between SDO and variables in the ABIS databank. The analyses showed no association between SDO and pre-, peri-, and neonatal data. However, we found a positive association between SDO and breastfeeding for more than 6 months (OR 1.9; 95% CI 1.1-3.2), late introduction of gruel (OR 1.9; 95% CI 1.1-2.9), and late introduction of infant formula (OR 1.8; 95% CI 1.2-2.9). A combination of these three variables increased the risk to develop SDO by more than five times (OR 5.1; 95% CI 1.6-15.7). No significant associations were found to other environmental, developmental, or medical factors. We conclude that nutritional conditions during first 6 months of life may influence the risk to develop severe demarcated opacities in first permanent molars.     

Cutaneous squamoproliferative lesions in kidney transplant recipients: an investigation of specific Epstein-Barr virus expression

In a previous report we demonstrated Epstein-Barr virus expression in cutaneous squamous cell carcinomas from heart transplant recipients. In a comparative study, skin lesions from renal allograft recipients were investigated for the presence of Epstein-Barr virus. Thirty cutaneous squamoproliferative lesions from 10 kidney transplant recipients were examined for Epstein-Barr virus-specific gene expression. The techniques used for detection were polymerase chain reaction, in situ hybridization and immunohistochemistry. Epstein-Barr virus DNA was not detected by polymerase chain reaction in the neoplasias, and only single Epstein-Barr virus-positive carcinoma cells were shown by in situ hybridization in three cases of infiltrative squamous cell carcinomas. Immunohistochemistry for Epstein-Barr virus latent membrane protein 1 showed a negative result in all samples. These findings differ from our earlier investigations of cutaneous squamous cell carcinomas from heart transplant recipients where Epstein-Barr virus expressions were common. This may indicate that the part Epstein-Barr virus plays in the development of post-transplant, cutaneous squamoproliferative disorders is related to type of organ transplantation and/or grade of immunosuppression.     

Determinants for a low health-related quality of life in asthmatics

People with asthma suffer from impaired health-related quality of life (HRQL), but the determinants of HRQL among asthmatics are not completely understood. The aim of this investigation was to study determinants of low HRQL in asthmatics and to study whether the determinants of HRQL differ between sexes and age groups. A cohort of three age groups in Sweden was investigated in 1990 using a questionnaire with focus on respiratory symptoms. To study quality of life, the generic instrument Gothenburg Quality of Life was used. The participants were also investigated with interviews, spirometry, and allergy testing. Asthma was diagnosed in 616 subjects. Fifty-eight per cent (n = 359) of the subjects were women; and 24% were smokers, 22% ex-smokers, and 54% were non-smokers. Women were more likely than men to report poor health-related quality of life. Respiratory symptoms severity was another independent determinant of a lower quality of life as well as airway responsiveness to irritants. Current and former smokers also reported lower quality of life. Finally, absenteeism from school and work was associated with lower quality of life. Factors such as sex, smoking habits, airway responsiveness to irritants, respiratory symptom severity, allergy, and absenteeism from school and work were associated with low HRQL in asthmatics.     

Circulating adhesion molecules in allergic and non-allergic asthma

Circulating forms of adhesion molecules (intercellular-adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin ) are related to the turnover of these molecules on the cell surface. In contrast to the other molecules, the levels of E-selectin probably exclusively reflect the activity of endothelial cells. The aim of this study was to compare levels of circulating adhesion molecules in patients with allergic (AA) and non-allergic asthma (NA) and to relate the levels of soluble adhesion molecules to methacholine responsiveness and lung function. The study comprised 19 patients with AA, 15 patients with NA and 17 healthy subjects. Soluble adhesion molecules, spirometry, methacholine responsiveness and peak flow variability was measured. The group of patients with AA had higher levels of sE-selectin than the reference group (P=0.046). Serum levels of sE-selectin correlated significantly with bronchial responsiveness (r=0.76) and peak flow variability (r=0.75) (P<0.01) in the NA but not in the AA group. All adhesion molecules in AA (P<0.05-<0.001), but only sE-selectin in NA (P<0.05), were correlated to airway conductance. sVCAM-1 was reduced by inhaled steroids (P<0.01). Our results indicate that endothelial cells are activated in asthma and that this activity has a bearing on airflow variability and bronchial responsiveness in NA.     

Mechanism of action of the oral direct thrombin inhibitor ximelagatran

Thrombin plays a central role in thrombus formation through its conversion of fibrinogen to fibrin and activation of platelets as well as amplifying its own generation by feedback activation via factors V, VIII, and XI. Consequently, thrombin represents a logical and promising target for therapeutic interventions against arterial and venous thromboembolic disorders. Ximelagatran is the first oral agent in the new class of direct thrombin inhibitors and is rapidly absorbed and bioconverted to the active moiety, melagatran, which inhibits fluid-phase and clot-bound thrombin with similar high potency. Binding to the active site of thrombin is direct and competitive and does not require the presence of co-factors. Inhibition of thrombin generation and platelet activation has been demonstrated in vitro with melagatran as well as ex vivo after oral administration of ximelagatran to healthy human volunteers. Oral ximelagatran dose dependently reduced the total thrombus area in an ex vivo flow chamber model of arterial thrombosis, reflecting the cumulative effect of inhibition of thrombin activity, thrombin generation, and platelet activation. Melagatran has also been shown to reduce thrombin-mediated inflammation in vitro. The combination of antithrombotic and anti-inflammatory activity with the practicality of oral dosing provided by ximelagatran represents an important new option for the treatment of arterial and venous thromboembolic disorders.     

Releasability of human hypereosinophilic eosinophils is related to the density of the cells

The activity of eosinophils and neutrophils with respect to the release of granule proteins was studied in 11 patients with the hypereosinophilic syndrome (HES). Granulocytes or purified eosinophils were stimulated with serum-opsonized Sephadex particles (C3b-induced release), and the released amounts of eosinophil cationic protein (ECP), eosinophils protein-X (EPX) and myeloperoxidase (MPO) were measured by means of specific radioimmunoassays (RIA). Eosinophils obtained from patients with HES released significantly more ECP ( P <0·002) and EPX ( P <0·01) after 20 min of incubation than cells from the control group. The cellular content of ECP and EPX in eosinophils obtained from the patients with HES was significantly reduced to 50% and 62%, respectively, of the content of these granule proteins of eosinophils from the control group. In separated eosinophils light-density eosinophils released more of both ECP and EPX than normal density eosinophils. There was no difference in MPO release between the patients and the control group. We conclude that the eosinophils from patients with HES have an increased propensity to release their granule proteins and the releasability seems to be related to the density of the cells.