Immunologic regulation in pregnancy

Theories to explain the failure of rejection of the fetus by the mother during pregnancy include immunologic privilege of the uterus as a graft site, lack of transplantation antigen expression on the trophoblast, weakening of maternal cellular immunity during pregnancy, and separation of maternal and fetal circulations. Evidence for and against each of these theories is discussed. Local concentration of a variety of hormones, including human chorionic gonadotropin (HCG), sex steroids, alpha-fetoprotein, and immunoglobulins, could provide a blocking mechanism to prevent maternal cellular immune attack. Possibly, progesterone, antibodies, and immune complexes are important in protecting the placenta and ultimately the fetus from rejection. Elucidation of regulatory mechanisms in pregnancy may be applicable to other problems in immunology.     

Tuberculosis,Airway Obstruction and Mortality in a Finnish Population

There is little long-term follow-up data concerning the association between past pulmonary tuberculosis (TB), airway obstruction and mortality. We aimed to analyse a national health examination survey data from 6701 adult Finns undergoing spirometry between 1978 and 1980 (follow-up through 2013). We identified TB either through a disease history or by a TB-indicative scar on a chest x-ray. We specified obstruction using the lower limit of normal (LLN) and classified severity using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 1–4. After adjusting for smoking and other confounders, past TB associated with obstruction. Compared to non-TB patients, the adjusted odds ratio (OR; 95% CI) of obstruction reached 2.21 (1.52–3.21) among patients with a scar recorded by one radiologist, 2.48 (1.63–3.78) when recorded by both radiologists and 4.59 (2.86–7.37) among patients with a disease history. Among those with neither past TB nor obstruction, with past TB only, with an obstruction only and with both, we found hazard ratios (HRs; 95% CIs) for subsequent mortality of 1.00 (reference), 1.11 (1.03–1.20), 1.62 (1.31–2.00) and 1.77 (1.45–2.16), adjusted for age, gender, smoking, body mass index (BMI), physical activity, education and general health. In conclusion, past TB strongly determines obstruction, although on its own quite weakly predicts premature death. TB and obstruction combined predict an additive mortality pattern.     

Heart transplantation in repaired transposition of the great arteries

Cardiac transplantation was carried out in a 40-year-old man with the diagnosis of repaired transposition of the great arteries and right-sided aortic arch who had end-stage cardiac failure due to myopathy of the ventricles. Because of several previous surgical repairs and the orientation of the great vessels, the operation presented some technical problems. Therefore, modifications of operative procedures were used, including recipient hypothermia, circulatory arrest, and changes in the donor heart implantation. The removal of the donor heart was modified in such a way that the graft included the aortic arch and both pulmonary arteries. With the extra length of ascending aorta and transverse arch, the innominate, left carotid, and left subclavian vessels were excised as a button, thereby leaving the distal orifice of the aorta in the superior portion of the transverse arch. For the recipient, the operation was performed using hypothermic total circulatory arrest to dissect free the huge pulmonary artery and the short right-sided aortic arch to place the clamp. Implantation of the donor heart was modified accordingly. The technical results were confirmed one and a half months later on a control digital angiogram. Thirty-five days postoperatively the patient was discharged. Six months after operation, the patient is doing better than ever before in his life. Our findings suggest that a complicated conotruncal development does not preclude cardiac transplantation.     

Oral health behavior at age of 11–12 years predicting educational plans at age of 15–16 years

Objective. The aim was to determine if oral health-related behavior at the age of 11–12 years predicts adolescents' educational plans at the age of 15–16 years when adjusting for gender and parents' occupational level. Materials and methods. The study population consisted of all fifth and sixth graders starting in the 2001–2002 school year in Pori, Finland (n = 1691); of these, 1467 returned properly filled questionnaires on behavior (toothbrushing and consumptions of xylitol products, candies, soft drinks and sports drinks) in 2001 and on educational plans in 2005. Parents' occupational levels were reported in 2001 by one of the parents of 1352 of these children. Associations between adolescents' educational plans and their behavior, gender and parents' occupation were evaluated using logistic regression model. Results. Children's oral health-related behavior at age 11–12, gender and parent's occupational level predicted their educational plans at age 15–16. Association between educational plans and behavior, especially cumulative health behavior, remained statistically significant when controlling for gender and parent's occupation: OR = 1.4 for difference of one good habit, and OR = 5.3 for difference of five good habits. Conclusions. Since difference in oral health-related behavior can be seen already in primary school, even when controlling for parents' occupational level, polarization of adolescents may begin already in primary school stage or even earlier.     

Childhood caries is still in force: A 15-year follow-up

Objective. To examine changes in caries prevalence among 3 to 15-year-old adolescents. Material and methods. Of 1582 eligible mothers, 1443 gave informed consent. Participating children and their parents were followed up continuously from 3 to 15 years of age in a pre-planned fashion and at regular intervals. Data on dental health status were obtained from 1066/1287 adolescents (82%) during regular clinical dental examinations. Results. Dentinal untreated caries (D) was seen among more than 26% of the adolescents at 15 years of age. Altogether, 4.9 carious teeth surfaces were affected in each case (mean). Close to 18% of the adolescents (186/1066) had poor dental health (DMFT was 5 or more) and 26% (271/1066) had DMFS 5 or more. Conclusions. Dental caries continues to constitute an increasing challenge in dental health care: any caries at 3, 5, 7, or 10 years of age was a predictor of poor dental health at 15 years of age.     

Selection of criteria for assessment of occlusal acceptability

There is no general agreement on criteria that could be applied to distinguish between orthodontically acceptable and non-acceptable occlusions after the completion of dental development. The aim of the present study was to analyse morphological and functional features that could be used as an index to define an acceptable occlusion in young adults. Three expert panels representing specialists in orthodontics and stomatognathic physiology participated in a modified Delphi method. Each panel responded to a questionnaire concerning the usefulness of various occlusal features, and a set of characteristics was selected on the basis of the responses; thereafter, applicability of the chosen characteristics and their cut-offs for an acceptable non-acceptable dichotomy was tested clinically. To obtain a consensus level of 100%, the last panel session was completed with a group discussion. Assessments made using the morphological criteria were compared with those made with the dental health component of the Index of Orthodontic Treatment Need. The selected morphological characteristics consisted of overjet, overbite, canine relationship, crossbite, scissors bite and midline deviation. The functional evaluation comprised assessments of discrepancy between the centric relation and the intercuspal position, working- and non-working-side contacts and protrusion contacts. The dental health component and our morphological criteria showed different sensitivity to contact point displacements, interdigitation in buccal segments and increased overbite. This study provides a set of morphological and functional indicators reflecting the current consensus opinion of Finnish professionals. Further studies are needed to analyse the reproducibility of assessment of the characteristics included.     

Extensive allelic sequence variation in the J region of the human immunoglobulin heavy chain gene locus

During the initial stages of B lymphocyte differentiation heavy chain variable (VH), diversity (DH) and joining (JH) gene segments recombine to form a functional heavy chain variable region (VDJ) gene. Evidence for genetic polymorphism of the human JH gene segments has been obtained from mature rearranged VDJ sequences. We conducted an analysis of the published rearranged JH gene sequences and found that the JH alleles present in the two published germ-line JH region sequences were rare (approx. 2%) in the rearranged sequences. As an attempt to explain this discrepancy a 2.5-kb strech of DNA containing all the six heavy chain JH region genes and the most 3' DH gene segment, DHQ52, was amplified by the polymerase chain reaction from 39 individuals and analyzed for restriction fragment length polymorphism. Five new JH region haplotypes were found and sequenced. These new haplotypes contained the coding segment alleles that were frequent in antibody genes. Surprisingly, a high number of interallelic differencies in the non-coding sequence was found between the new and the two previously published haplotypes implying that the haplotypes had been separated early in evolution. In this respect the JH locus resembles HLA loci.     

Hereditary hemochromatosis gene (HFE) mutations C282Y, H63D and S65C in patients with idiopathic dilated cardiomyopathy

BACKGROUND: Hereditary hemochromatosis (HH), a common autosomal recessive disease, leads to excessive iron accumulation in some organs, including the heart. It is therefore not surprising that cardiomyopathy is one of the most severe complications of HH. The HFE gene defects have been thought to contribute to idiopathic dilated cardiomyopathy (IDCM) in some patients, even though the results of genotype analyses have so far been contradictory. Hence we set out here to evaluate the prevalence and potential role of HFE mutations in patients with IDCM. METHODS: A total of 91 IDCM patients and 102 controls were subjected to HFE mutation analyses, in which C282Y, H63D and S65C mutations were determined for each patient. We also analyzed the impact of the C282Y and H63D mutations on the left ventricular end-diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF) and New York Heart Association (NYHA) functional classes. RESULTS: The prevalences of heterozygosity for the C282Y, H63D and S65C mutations in the IDCM patients were 13.2%, 22.0% and 2.2%, respectively. LVEDD was significantly higher (P=0.037) in those with the C282Y mutation at the end of the follow-up period than in those with no mutation. CONCLUSIONS: Our data showed no significant deviations in C282Y, H63D and S65C mutation frequencies between the IDCM patients and controls, suggesting that these mutations do not increase the risk of IDCM. Heterozygosity for the C282Y mutation may nevertheless be a modifying factor contributing to LV dilatation and remodeling.     

Apolipoprotein E ε4 allele frequency is increased in Parkinson’s disease only with co-existing Alzheimer pathology

We determined the apolipoprotein E (apoE) genotype in clinically diagnosed and neuropathologically verified cases of Parkinson’s disease (PD) (n = 45), with or without Alzheimer (AD)-type changes, and compared the apoE genotype with that in healthy age-matched controls (n = 59). The PD cases were divided into two groups according to the CERAD criteria: “O + A”, with no or only uncertain histological findings of AD, and “B + C” with histological findings suggestive or indicative of AD. DNA was isolated from frozen brain samples, and the apoE genotypes were determined using polymerase chain reaction amplification and subsequent restriction analysis by HhaI enzyme. The frequency of the apoɛ4 allele (29.4%) was significantly increased in the B + C group. The odds ratio for an apoɛ4 allele in the B + C group was 2.5 as compared to controls (95% confidence interval, 1.2–5.2). In the 0 + A group, the frequency of apoɛ4 allele (13.6%) was similar to that in controls (14.4%) and the risk of an apoɛ4 allele was not increased (odds ratio 0.94). The PD cases with an apoɛ4 allele had a greater number of cortical (P = 0.02) but not nigral Lewy bodies than those without an apoɛ4 allele (P = 0.57). The results show that neuropathologically verified PD as such is not associated with increased apoɛ4 allele frequency. Received: 15 January 1998 / Revised, accepted: 24 March 1998