In vitro evaluation of four methods of sealer placement.

Sealer is required during root canal obturation, although no studies have shown which method of sealer placement provides the best coverage. This study evaluated and compared four methods of sealer placement: file, lentulo spiral, ultrasonic files, and master gutta-percha cone. Forty mandibular incisors were prepared by a step-back technique. AH26 (0.04 ml) was applied to the placement device, the sealer was placed in the canal, and the canal was obturated with lateral condensation of gutta-percha. The specimens were cleared and evaluated for the presence of the sealer in the apical, middle, and coronal thirds of the canal. The results showed no statistically significant differences among the four groups. The greatest variation in sealer coverage was found in the apical level. Sealer coverage in the coronal and middle thirds was nearly identical regardless of sealer placement technique.     

Extramammary Paget's disease with diffuse involvement of the lower female genito-urinary system

Extramammary Paget's disease of the lower female genito-urinary system is an uncommon neoplasm with a high rate of recurrence. A 52-year-old white female with a history of extramammary Paget's disease, originally excised in 1985 by skinning vulvectomy and who had multiple recurrences, including two in a vaginal graft and with extension to the urethra and the uterine cervix, in 1992 underwent an anterior pelvic exenteration for control of the disease process. Standard surgical management for extramammary Paget's disease without invasion or without an underlying adenocarcinoma is simple or skinning vulvectomy. However, because the disease commonly recurs, diffuse involvement may require more extensive surgery including pelvic exenteration in extraordinary cases.     

Combined Treatment of Acute EAE in Lewis Rats with TNF-Binding Protein and Interleukin-1 Receptor Antagonist

Experimental autoimmune encephalomyelitis (EAE) is a term given to describe a collection of animal models representing the human disease multiple sclerosis (MS). Although not fully understood, the involvement of cytokines and the immune system in either EAE or human MS is well established. Past efforts have shown that inhibition of proinflammatory cytokines tumor necrosis factor (TNF-α) or interleukin-1 (IL-1) result in amelioration of acute EAE in Lewis rats. The present study examined this model for the effect of concomitant inhibition of both TNF-α and IL-1, which resulted in a modest but significant therapeutic effect that was superior to inhibition of either single agent alone with respect to four of the five variables used to follow the progression of disease in this model, i.e., clinical severity, frequency of disease, loss of body weight, and day of onset. These results are in accordance with the idea that combination treatments are likely to prove superior to single agent therapy in the treatment of autoimmune inflammatory disease.     

Polyendocrinopathy in Children, Adolescents, and Young Adults With Type 1 Diabetes: A multicenter analysis of 28,671 patients from the German/Austrian DPV-Wiss database

OBJECTIVE

To investigate diabetes-specific autoantibodies and additional autoimmune phenomena in a large cohort of young patients with type 1 diabetes.

RESEARCH DESIGN AND METHODS

Data from 28,671 patients <30 years with type 1 diabetes from 242 specialized centers in Germany and Austria were analyzed.

RESULTS

At least one β-cell antibody was present in 81.6% of patients. β-cell–Ab-negative patients were significantly younger at diabetes onset (P < 0.0001). A total of 19.6% had positive thyroid antibodies with female predominance (62%, P < 0.0001). Antibodies to tissue transglutaminase were present in 10.7%, with a significantly longer duration of diabetes (P < 0.0001). Parietal cell antibodies were found in 283 patients, associated with older age (P < 0.001), and adrenal antibodies were present in 94 patients. In 575 patients, at least three different autoimmune phenomena were present.

CONCLUSIONS

Thyroid autoimmunity and antibodies suggestive for celiac disease are the most prevalent additional immune phenomena in type 1 diabetes. Parietal/adrenal antibodies are rare.Additional autoimmune phenomena such as Hashimoto thyroiditis or celiac disease are a frequent observation in type 1 diabetes (1,2). The appearance of autoantibodies is often the first detectable sign of autoimmune diseases (3). The aim of this study was to investigate screening frequency and prevalence of autoimmune phenomena in a large cohort of children, adolescents, and young adults with type 1 diabetes.     

Feeding patterns of biting midges of the <Emphasis Type="Italic">Culicoides obsoletus</Emphasis> and <Emphasis Type="Italic">Culicoides pulicaris</Emphasis> groups on selected farms in Brandenburg,Germany

Host feeding patterns of engorged sibling species of the Culicoides obsoletus and Culicoides pulicaris groups captured during three nights on two selected farms maintaining either cattle, sheep, horses, and pigs (Seedorf, Brandenburg) or cattle, sheep, moufflons, and red and fallow deer (Paulinenaue, Brandenburg) were determined by polymerase chain reaction amplification using conserved primers and sets of species-specific primers derived from vertebrates mitochondrial cytochrome b. Out of a total of 177 blood meals analysed, 115 (65%) tested positive for a blood meal from vertebrates. 63.5% (n = 73) of the cyt b positive specimens could be further assigned down to the species level. Cattle appeared to be the most attractive hosts for Palaearctic biting midges (79.5%, n = 58) even if other large vertebrates were kept in their immediate vicinity. If pigs or horses were additionally maintained on a farm, they were likewise attacked by biting midges but at a distinctly smaller rate than cattle (pigs 13.7%, horses 2.7%). In this study, game animals appear to be less attractive than cattle since only a few engorged midges had taken a blood meal from red deer (4.1%). None of the blood meals analysed tested positive for sheep. Preliminary results reveal that biting midges of the C. pulicaris and C. obsoletus groups can feed on a range of vertebrate hosts but with a distinct preference for cattle even if other livestock are maintained in adjacent areas.     

Modulatory effects of neuropsychopharmaca on intracellular pH of hippocampal neurones in vitro

Background and purpose:

The intracellular pH (pHi) of neurones is tightly regulated by, for example, membrane-bound acid-exchangers and loaders. Nevertheless, excessive bioelectric activity lowers steady-state pHi. In turn, even a moderate acidification can inhibit neuronal activity, a process believed to be part of a negative feedback loop controlling neuronal excitation. As moclobemide, an antidepressant, and also some antiepileptic drugs can reduce neuronal pHi in hippocampus slices in vitro, we screened a panel of currently used neuropsychopharmaca for comparable effects.

Experimental approach:

BCECF-AM loaded hippocampal slices were superfused with 16 different neuroleptics, antidepressants and antiepileptics under bicarbonate-buffered conditions. Changes in steady-state pHi of CA3 neurones were measured fluorometrically.

Key results:

The antipsychotics haloperidol, clozapine, ziprasidone, and the antidepressants amitriptyline, doxepin, trimipramine, citalopram, mirtazapine, as well as the anticonvulsive drug tiagabine reversibly reduced the steady-state pHi by up to 0.35 pH-units in concentrations of 5–50 µM. In contrast, venlafaxine, the anticonvulsants carbamazepine, clonazepam, gabapentin, lamotrigine, zonisamide, and the mood stabilizer lithium had no effect on neuronal pHi.

Conclusion and implications:

These data substantiate the view that clinically relevant concentrations of neuroleptics and antidepressants can mediate changes in neuronal pHi, which may contribute to their pharmacological mode of action. Effects on pHi should be taken into account when therapeutic or even harmful effects of these drugs are evaluated.     

Comparative study on the maxillary symmetry in preoperatively treated children with cleft lip and cleft palate]

Comparative studies on the palatal symmetry in healthy new-born babies and in new-born babies with cheilognathopalatoschisis revealed cleft palates with a high degree of asymmetry. Therefore, it is reasonable to measure the treatment results achieved in cleft patients against the degree of palatal symmetry attained. This evaluation was performed in 30 subjects with unilateral complete cleft and in 20 individuals with bilateral complete cleft.     

The SRCR/SID region of DMBT1 defines a complex multi-allele system representing the major basis for its variability in cancer

Deleted in malignant brain tumors 1 (DMBT1) at 10q25.3-q26.1 has been proposed as a candidate tumor-suppressor gene for brain and epithelial cancer. DMBT1 encodes a multifunctional mucin-like protein presumably involved in epithelial differentiation and protection. The gene consists of highly homologous and repeating exon and intron sequences. This specifically applies to the region coding for the repetitive scavenger receptor cysteine-rich (SRCR) domains and SRCR-interspersed domains (SIDs) that constitutes the major part of the gene. This particular structure may previously have interfered with the delineation of DMBT1 alterations in cancer. Uncovering these, however, is of mechanistic importance. By a combined approach, we conducted a detailed mutational analysis, starting from a panel of 51 tumors, including 46 tumor cell lines and five primary tumors. Alterations in the repetitive region were present in 22/31 (71%) tumors that were investigated in detail. Six tumors showed presumably de novo mutations, among these three with point mutations in combination with a loss of heterozygosity. However, none of the alterations unambiguously would be predicted to lead to an inactivation of DMBT1. We define seven distinct DMBT1 alleles based on variable numbers of tandem repeats (VNTRs). At least 11 tumors exclusively harbored these VNTRs. The data suggest that the SRCR/SID region defines a complex multi-allele system that has escaped previous analyses and that represents the major basis for the variability of DMBT1 in cancer. DMBT1 thus compares to mucins rather than to conventional tumor suppressors.