Nickel penetration in allergic individuals: bioavailability versus X-ray micro-analysis detection

Development of local allergic reactions after different application times with Finn Chambers was recorded in 34 nickel-sensitive patients. Biologically significant amounts of nickel seemed to penetrate the skin within a few hours, although physical penetration was minimal. Nickel was detected only in the upper keratin cell layer with an X-ray microanalysis method.     

Contact sensitivity and atopic dermatitis: association with prognosis, a follow-up study in 801 atopic patients

The influence of contact sensitivities on the course of atopic dermatitis (AD) is not known. The objective of the study is to find the course of AD in atopic patients with and without contact sensitivities. A total of 801 atopic patients were studied and patch tested in 1983/84. A questionnaire focusing on the occurrence of dermatitis was sent to these patients 16 years later. During the follow up the number of symptom-free patients increased from 36.7% to 40.7%. In patients with positive patch-test reactions, 30.1% were symptom free in 1983/84 and 38.3% at the follow up (P= 0.001). Among those with positive patch-test reactions to fragrance mix and/or balsam of Peru, the number of symptom-free patients had increased the most: from 26.9% to 42.6% (P= 0.0095), and a similar tendency was seen among those with nickel allergy. The occurrence of dermatitis did not change among patients without contact sensitivities. Thus, the study concluded that contact allergy does not impair the prognosis of dermatitis in atopic patients.     

中老年职工工作能力与职业因素的关系研究

为探讨常见职业因素在中老年职工工作能力减退中所起的作用，以工作能力指数为工具，采用成组病例对照研究方法对１８０名工作能力减退的职工，及８５７名工作能力正常的职工，进行研究因素危险度的评价。结果显示，工作场所中的一些常见有害因素在研究的工作环境中更为普遍，经常暴露于粉尘，有害化学物质、噪声，振动，高温，潮湿等环境中的中老年职工发生工作能力减退的危险性增加；在易发生我伤事故的工作环境中工作也是一种有显     

Severe gastrointestinal complications after 1,515 adult kidney transplantations

We studied, retrospectively, the occurrence of severe gastrointestinal (GI) complications after kidney transplantation. After 1,515 consecutive adult kidney transplantations performed on 1,445 patients during 1990–1999 at our centre, 147 (10%) severe post-transplantation GI complications were found. Ten percent of the complications were fatal. The median follow-up time was 6.2 years. The main complications were gastroduodenal ulcers and colon complications. GI malignancy developed in 13 patients (0.9%). The complication rate for the first post-transplantation year was 4.8%. Delayed graft function, high age and polycystic kidney disease were risk factors. Five-year patient survival rate was significantly lower in patients with a first-year complication than in those with later or no GI complications (68% vs 88%). Graft survival with deaths censored was the same in both groups. In conclusion, severe GI complications during the first post-transplantation year remain a high risk factor also for long-term patient survival.     

Generation of reactive oxygen species by human mesothelioma cells.

Malignant mesothelioma cells contain elevated levels of manganese superoxide dismutase (MnSOD) and are highly resistant to oxidants compared to non-malignant mesothelial cells. Since the level of cellular free radicals may be important for cell survival, we hypothesized that the increase of MnSOD in the mitochondria of mesothelioma cells may alter the free radical levels of these organelles. First, MnSOD activity was compared to the activities of two constitutive mitochondrial enzymes; MnSOD activity was 20 times higher in the mesothelioma cells than in the mesothelial cells, whereas the activities of citrate synthase and cytochrome c oxidase did not differ significantly in the two cell lines. This indicates that the activity of MnSOD per mitochondrion was increased in the mesothelioma cells. Superoxide production was assayed in the isolated mitochondria of these cells using lucigenin chemiluminescence. Mitochondrial superoxide levels were significantly lower (72%) in the mesothelioma cells compared to the mesothelial cells. Oxidant production in intact cells, assayed by fluorimetry using 2',7'-dichlorodihydrofluorescein as a fluorescent probe, did not differ significantly between these cells. We conclude that mitochondrial superoxide levels are lower in mesothelioma cells compared to nonmalignant mesothelial cells, and that this difference may be explained by higher MnSOD activity in the mitochondria of these cells. Oxidant production was not different in these cells, which may be due to the previously observed increase in H2O2-scavenging mechanisms of mesothelioma cells.     

On the Etiology of Type 1 Diabetes: A New Animal Model Signifying a Decisive Role for Bacteria Eliciting an Adverse Innate Immunity Response

The cause of type 1 diabetes (T1D) remains unknown; however, a decisive role for environmental factors is recognized. The increased incidence of T1D during the last decades, as well as regional differences, is paralleled by differences in the intestinal bacterial flora. A new animal model was established to test the hypothesis that bacteria entering the pancreatic ductal system could trigger β-cell destruction and to provide new insights to the immunopathology of the disease. Obtained findings were compared with those present in two patients dying at onset of T1D. Different bacterial species, present in the human duodenum, instilled into the ductal system of the pancreas in healthy rats rapidly induced cellular infiltration, consisting of mainly neutrophil polymorphonuclear cells and monocytes/macrophages, centered around the pancreatic ducts. Also, the islets of Langerhans attracted polymorphonuclear cells, possibly via release of IL-6, IL-8, and monocyte chemotactic protein 1. Small bleedings or large dilatations of the capillaries were frequently found within the islets, and several β-cells had severe hydropic degeneration (ie, swollen cytoplasm) but with preserved nuclei. A novel rat model for the initial events in T1D is presented, revealing marked similarities with the morphologic findings obtained in patients dying at onset of T1D and signifying a decisive role for bacteria in eliciting an adverse innate immunity response. The present findings support the hypothesis that T1D is an organ-specific inflammatory disease.Our understanding of the etiology of type 1 diabetes (T1D) remains limited and originates to a large extent from two animal models: the nonobese diabetic mouse and the BioBreeding-diabetes prone rat.¹ In both models a progressive T-cell–mediated destruction of the β-cells occurs; however, the immunopathologic findings reveal limited similarities with the human disease.^2–5 In human pancreatic specimens, insulitis is discrete, affects only a few islets, and is heterogeneously distributed within the gland. In a recent meta-analysis, insulitis was reported in only 29% of patients with onset between 15 and 39 years of age and with a disease duration of <1 month.⁶ At the time of diagnosis, autoantibodies were only present in approximately 70% to 80% of affected patients.⁷ Likewise, attempts to prevent disease progression with immunosuppression^8–11 or immunointerventions^12–14 cause no or only transient preservation of β-cell function.The fact that the exocrine pancreas gets affected in patients with T1D is underappreciated, and several studies have found autoantibodies in the exocrine cells before the onset of T1D.^15–18 Mild to moderate exocrine pancreatic insufficiency is an early event in T1D,¹⁹ and a substantial reduction (32%) in pancreatic volume is already present 3 to 4 months after onset.²⁰ Also, in the classic report by Gepts,⁴ lesions of the acinar tissue were reported to occur frequently in patients with recent onset of T1D. The findings comprised mostly focal or diffuse lesions of acute pancreatitis with accumulation of leukocytes, often centered around the excretory canals.^2–5 In a more recent study of patients with long-term T1D, 40% had periductal fibrosis and 60% of cases had periductal fibrosis that extended to the interlobular pancreas.²¹ Collectively, these observations suggest that the injurious process that causes T1D affects both the exocrine and endocrine components of the pancreas and challenge the view that T1D is a β-cell–specific autoimmune disease.The low concordance rate for the development of T1D in identical twins and the current rapid increase in incidence of T1D argue against a decisive role for genetic factors. Notably, there is a close to sixfold gradient in the incidence of T1D between Russian and Finland Karelia, although the population is homogenous and the predisposing HLA genotypes are equally frequent.²² In addition, children born in Finland by immigrants from Somalia, a low incidence country for T1D, acquire the same risk for T1D as the native Finish population.²³ On the basis of these and similar observations, it is generally assumed that environmental factors may act as triggers of T1D. For decades different enteroviruses have been implicated in the pathogenesis of T1D²⁴; however, evidence of causality remains missing.Bacterial colonization of the infantile gut is influenced by environmental factors and has changed markedly in developed countries during the last decades.²⁵ Interestingly, the increased incidence of T1D²⁶ and the difference in incidence of T1D in Sweden, Italy, and Africa^26–28 are paralleled by reported frequencies of intestinal Staphylococcus aureus.^29–32 Bacteria entering the ductal system of the pancreas would be exposed to the pancreatic juice–containing substances, with marked antibacterial effects initiating release of bacterial components, such as lipopolysaccharide (LPS), lipoteichoic acid (LTA), and various toxins. Notably, these substances have been implicated in the etiology of neurogenerative diseases and neural cell death because they stimulate microglia to produce proinflammatory cytokines (IL-1b, IL-6, tumor necrosis factor-α), nitric oxide, and reactive oxygen species, causing significant cell death in neighboring neural cells.³³The present study was conducted to establish an animal model for the initial events in T1D to test the hypothesis that bacteria entering into the ductal system of the pancreas could elicit an adverse innate immunity response. Different bacterial species present transiently or continuously in the human duodenum were instilled into the ductal system of the pancreas in healthy rats. To examine the clinical relevance of the experimental model, obtained findings were compared with those present in the pancreases of two patients dying at onset of T1D.     

Small-intestinal TG2-specific plasma cells at different stages of coeliac disease

Background

In coeliac disease, ingestion of gluten induces the production of transglutaminase 2 (TG2)-targeted autoantibodies by TG2-specific plasma cells present at high frequency in the small intestinal mucosa in untreated disease. During treatment with a gluten-free diet (GFD), the number of these cells decreases considerably. It has not been previously investigated whether the cells are also present prior to development of villous atrophy, or in non-responsive patients and those with dietary lapses. We aimed to define the frequency of small bowel mucosal TG2-specific plasma cells in coeliac disease patients with varying disease activity, and to investigate whether the frequency correlates with serum and small intestinal TG2-targeting antibodies as well as mucosal morphology and the number of intraepithelial lymphocytes.

Results

Mucosal TG2-specific plasma cells were found in 79% of patients prior to development of mucosal damage, in all patients with villous atrophy, and in 63% of the patients after 1 year on GFD. In these disease stages, TG2-specific plasma cells accounted for median of 2.3, 4.3, and 0.7% of all mucosal plasma cells, respectively. After long-term treatment, the cells were present in 20% of the patients in clinical remission (median 0%) and in 60% of the patients with poor dietary adherence (median 5.8%). In patients with non-responsive coeliac disease despite strict GFD, the cells were found in only one (9%) subject; the cells accounted for 2.4% of all plasma cells. A positive correlation between the percentage of TG2-specific plasma cells and serum TG2 antibody levels (r_S?=?0.69, P?<?0.001) and the intensity of mucosal TG2-targeting IgA deposits (r_S?=?0.43, P?<?0.001) was observed.

Conclusions

Our results show that TG2-specific plasma cells are already detectable prior to villous atrophy, and that generally their frequency increases during overt disease. By contrast, on GFD, the percentage of these cells decreases. Overall, the presence of TG2-specific plasma cells in the small bowel mucosa mirrors the presence of gluten in the diet, but the frequency is not always parallel to the level of serum or intestinal TG2 antibodies. These findings increase the knowledge about the development of the TG2 plasma cell responses especially in the early phases of coeliac disease.

     

Attachment representations among substance-abusing women in transition to motherhood: implications for prenatal emotions and mother–infant interaction

We studied how attachment representations contribute to central components of transition to motherhood, prenatal emotion processing (EP) and emotional availability (EA) of mother–infant interaction, and whether there are group specific differences. Participants were 51 treatment-enrolled substance-abusing (SA) mothers and their infants and 50 non-using comparison dyads with obstetric risk. Mother’s attachment representations (AAI) and EP were assessed prenatally and EA when infants were four months. Results showed that autonomous attachment only had a buffering effect on prenatal EP among comparisons. All SA mothers showed more dysfunctional EP than comparisons and, contrary to comparisons, autonomous SA mothers reported more negative cognitive appraisals and less meta-evaluation of emotions than dismissing SA mothers. Preoccupied SA mothers showed high negative cognitive appraisals, suggesting under-regulation of emotions. Attachment representations were not associated with EA in either group; rather, SA status contributed to global risk in the relationship. Surprisingly, autonomous SA mothers showed a tendency towards intrusiveness. We propose that obstetric risk among comparisons and adverse relational experiences among almost all SA mothers might override the protective role of mother’s autonomous representations for dyadic interaction. We conclude that prenatal emotional turbulence and high interaction risk of all SA mothers calls for holistic treatment for the dyad.     

Craniofacial features in osteogenesis imperfecta: a cephalometric study

Osteogenesis imperfecta (OI) is a heterogeneous group of connective tissue diseases that mainly manifest as bone fragility and skeletal deformity. In most families it segregates as a dominant trait and results from mutations in type I collagen genes. In this study we analyzed the size and form of the bony structures in heads of 59 consecutive patients with OI types I, III, or IV (Sillence classification), using lateral radiographs. Paired controls were matched for gender and age. The purpose was to obtain baseline information of craniofacial development in OI patients that have not received bisphosphonate treatment. In OI type I we found smaller than normal linear measurements, indicating a general growth deficiency, but no remarkable craniofacial deformity. In OI types III and IV, the growth impairment was pronounced, and the craniofacial form was altered as a result of differential growth deficiency and bending of the skeletal head structures. We found strong support both for an abnormally ventral position of the sella region due to bending of the cranial base, and for a closing mandibular growth rotation. Vertical underdevelopment of the dentoalveolar structures and the condylar process were identified as the main reasons for the relative mandibular prognathism in OI. Despite of the widespread intervention with bisphosphonates, the facial growth impairment will probably remain characteristic for many OI patients, and their orthodontic treatment should be further developed.