Congenital goitrous primary hypothyroidism in two German families caused by novel thyroid peroxidase (TPO) gene mutations.

Congenital hypothyroidism occurs with a prevalence of approximately 1:3 500. Defects in thyroid hormone synthesis which lead to goitrous hypothyroidism account for 10-15% of these cases. Several genetic defects have been characterized and mutations in the thyroid peroxidase (TPO) gene are the most common cause for dyshormonogenesis.So far, more than 80 mutations in the TPO gene have been described, resulting in a variable decrease in TPO bioactivity. Clinically TPO defects manifest with congenital primary goitrous hypothyroidism.We here present 2 children with congenital primary hypothyroidism, who were identified to have compound heterozygous TPO mutations. They both shared the same novel mutation in the TPO gene (C756R) in exon 13. One case presented with an apparently dominant inheritance of thyroid dyshormonogenesis.

Detectability of residual Epiphany and gutta-percha after root canal retreatment using a dental operating microscope and radiographs--an ex vivo study.

AIM: To compare the detectability of residual Epiphany and gutta-percha after root canal retreatment using a dental operating microscope and radiographic examination with the residual area measured after rendering the roots transparent. METHODOLOGY: Sixty extracted single-rooted maxillary central incisor teeth were enlarged to apical size 40. Thirty canals were filled using vertically compacted Epiphany, the remainder were filled with vertically compacted gutta-percha and AH Plus sealer. After re-instrumentation to apical size 50, radiographs of the roots were taken in buccolingual and mesiodistal direction. Residual filling material was categorized by three observers using the radiographs and a dental operating microscope. The area of remaining material that was made visible by radiographs was measured with the aid of a computer image analysis programme. After clearing the roots, areas of residual filling material on the root canal wall were measured using a microscope. RESULTS: Computer image analysis of the radiographs showed significantly smaller areas of remaining gutta-percha and Epiphany compared with the analysis of the transparent teeth that revealed only one absolutely clean root (Epiphany). Especially in the gutta-percha group, the scores determined by the observers using radiographic examination gave an over-optimistic impression of cleanliness compared with the scores determined by the visualization through the microscope. CONCLUSION: Especially for remaining gutta-percha, the operating microscopes provided better detection of residual root filling material in retreated maxillary incisor teeth.

Effectiveness of hand and rotary instrumentation for removing a new synthetic polymer-based root canal obturation material (Epiphany) during retreatment.

AIM: To evaluate the effectiveness of hand and rotary instrumentation for removal of vertically compacted Epiphany and gutta-percha during retreatment. METHODOLOGY: Sixty extracted single-rooted maxillary central incisors were enlarged to size 40 using FlexMaster instruments. The teeth were randomly divided into four groups of 15 specimens each. The canals of two groups were obturated using vertically compacted Epiphany. The others were filled with vertically compacted gutta-percha and AH Plus sealer. One Epiphany group and one gutta-percha group was reinstrumented with Gates Glidden burs and Hedström files. In the other two groups, obturation material was removed using Gates Glidden burs and RaCe rotary instruments. After clearing the roots, the area of remaining obturation material on the root canal wall was measured using a computer image analysis program. Statistical analysis was performed using Repeated Measures Analysis of Variance and anova. RESULTS: Retreatment of specimens obturated with gutta-percha showed significantly more remaining obturation material than specimens filled with Epiphany (P < 0.05). No difference was found between the removal with Hedström files and with RaCe instruments (P > 0.05). Regarding the mean time of retreatment and time required for reaching the working length, Hedström files were significantly faster than RaCe instruments (P < 0.05). The times did not depend on the kind of obturation material (P > 0.05). CONCLUSIONS: Vertically compacted Epiphany in combination with Epiphany Root Canal Sealant was removed more effectively than gutta-percha and AH Plus sealer. Hedström files were more rapid than RaCe rotary instruments.

Transcriptional dysregulation in skeletal malformation syndromes.

Normal skeletal development requires coordinated temporal and spatial gene expression patterns that specify the functions of various cell types. Transcription factors by definition coordinate this process and are themselves subject to hierarchical levels of regulation. Together they determine the context-dependent function of each transcription factor. Hence, loss-of-function and gain-of-function mutations within specific transcription factors cause dysregulation of broad transcriptional networks. Consequences are usually dominantly inherited skeletal malformation syndromes that can be broadly viewed as consequences of defects of cellular differentiation, proliferation, and survival versus defects in pattern formation. The study of human phenotypes and mutations can lead to hypotheses about targets within the respective transcriptional network. These targets can then be confirmed by combining mouse genetic and in vitro studies. Although this has been successful in a small group of skeletal dysplasias, the majority of transcriptional networks during skeletogenesis remain to be elucidated.

Twenty-four hour ambulatory blood pressure profile of a new slow-release formulation of diltiazem in mild to moderate hypertension.

Twelve patients with a mild to moderate essential hypertension were included in a double-blind, balanced, randomized placebo-controlled cross-over study to assess the efficacy and duration of action of a new slow-release formulation of diltiazem (300 mg) given once daily for 3 weeks. All office blood pressure measurements were done 24 hours after drug intake. In order to improve the accuracy of the trial, 24-hours non-invasive ambulatory blood pressure monitoring (Spacelabs 90207 system) were performed as well. Diltiazem significantly lowered supine and standing systolic and diastolic office blood pressure (by 16.9/12.7 mmHg and by 17.3/13.8 mmHg, respectively), without changing office heart rate. Diltiazem also significantly lowered ambulatory blood pressure measured over 24 hours, as well as ambulatory heart rate. The blood pressure lowering effect was most pronounced during the daytime period and did not reach statistical significance during the sleeping hours. The treatment was well tolerated, and there were no significant side effects. The results confirm the antihypertensive efficacy of diltiazem LP 300 mg once daily during the daytime and during the early morning blood pressure rise, without inducing nocturnal hypotension.

Peripheral blood T lymphocytes subpopulations in HLA-B7 related rheumatic diseases: ankylosing spondylitis and reactive synovitis.

The etiology of B lymphocyte hyperactivity in ankylosing spondylitis (AS) and in reactive synovitis is unknown and data available on the cellular immune system are controversial. We therefore evaluated peripheral blood T cell populations in AS patients and patients with reactive synovitis (RS) using monoclonal antibodies, previously shown to react with all T cells (OKT3), the inducer-helper T cell subset (OKT4) and the suppressor-cytotoxic T cell subset (OKT8). Results were compared with a normal control group and a group of rheumatoid arthritis (RA) patients. In AS an increase of OKT4+ cells was found, but the total number of T helper-inducer cells in peripheral blood was not different from the normal group and the group of patients with RS. Contrary to the results found in RA, where the helper-inducer/suppressor-cytotoxic ratio (OKT4+/OKT8+) was significantly increased, the immunoregulatory ratio in AS and in RS was normal suggesting another mechanism leading to B cell hyperactivity than in RA.

Immunoregulatory changes in autoimmune disease.

Peripheral blood T cell subpopulations were determined in patients with various rheumatic diseases [rheumatoid arthritis (RA); ankylosing spondylitis (AS); reactive synovitis (RS)]. No significant variation in OKT3+ cells was found among these groups. In RA, an increased percentage of OKT4+ was found in relation to the control group. For the other groups no difference was observed. In RA, a decreased percentage of OKT8+ cells was observed. Thus, the immunologic imbalance found in RA was not encountered in AS and RS although these disease--as well as the other pathologic disorders--are characterized by serum hypergammaglobulinemia. Furthermore, the decreased number of T suppressor cells found in peripheral blood of patients with active RA was not observed in their synovial fluid. Therefore we propose a failure of localization mechanism of T suppressor-cytotoxic lymphocytes in the synovial membrane of RA. Single doses of prednisolone produced a temporary decrease in peripheral blood total lymphocytes, T cells, T helper-inducer cells, and a less marked decrease in T suppressor-cytotoxic cells, in effect, a normalization of the immune balance, characterized by a decreased T helper/T suppressor ratio. In a similar fashion, patients receiving long-term levamisole exhibited a decrease in total lymphocytes, T lymphocytes, T helper cells, and T suppressor cells 6 and 24 hr after drug intake with a subsequent normalization of the OKT4+/OKT8+ ratio.

Evaluation of T cell subsets with monoclonal antibodies in synovial fluid in rheumatoid arthritis.

Monoclonal antibodies that react with all T cells (OKT3), the inducer-helper T cell subset (OKT4), and the suppressor-cytotoxic T cell subset (OKT8) have been used to evaluate T cell and T cell subpopulations in synovial fluid (SF) from patients with rheumatoid arthritis (RA). We found that the immunoregulatory ratio of SF lymphocytes ranged from normal values to extremely low values indicating normal to excess numbers of OKT8+ cells. The rheumatoid synovium in patients with RA is characterized by the presence of lymphoid aggregates in which HLA-DR+ interdigitating cells form close contacts with a large number of OKT4+ T cells, while the OKT8+ T cells are sparse. It may be that the localizing mechanisms for OKT8+ suppressor cells in lymphoid aggregates are deficient in RA and the cells are thus permitted to pass into synovial exudates, resulting in an increase of OKT8+ cells in the SF.

The effect of low doses of prednisolone on the traffic of T helper-inducer cells in rheumatoid arthritis.

The effects of a single dose of 5 and 10 mg of prednisolone on the kinetics of lymphocytes and T lymphocyte subsets were investigated in patients suffering from active rheumatoid arthritis. Six hours after intake of 10 mg of the drug a significant drop in total lymphocyte count, total T-cell numbers and T-helper cell numbers was recorded. The values returned to baseline values within 24 hours. Intake of 5 mg of prednisolone depressed total T-cell count and more particularly the absolute numbers of T-helper cells. No statistically significant changes occurred in T suppressor-cytotoxic cell traffics. The influence on the kinetics of T-helper cells was responsible for a significant decrease of helper/suppressor ratios in the intravascular compartment.

[Perforations of the oesophagus (author's transl)]. / Osophagusperforationen.

The different reasons for perforations of the oesophagus are listed with their preferential locations. A survey is given on the necessary x-ray diagnostics including computed tomography according to the clinical signs. Examples of the characteristic x-ray findings and follow-up are demonstrated with their relation to the surgical possibilities.

[Posttraumatic osteolysis of the distal clavicula end (author's transl)]. / Posttraumatische Osteolyse des distalen Klavikulaendes.

Posttraumatic osteolysis of bone is rare. Its etiology is unknown. A case of posttraumatic osteolysis of the distal clavicle end is reported. Differentialdiagnostical and ethiological relations are discussed. The literature of posttraumatic osteolysis especially of distal clavicle osteolysis is reported.

Determination of T lymphocyte subpopulations by monoclonal antibodies in rheumatoid arthritis. Influence of immunomodulating agents.

The pathogenesis of rheumatoid arthritis is unknown, but clear abnormalities of the immune system are well documented in this disease. We therefore evaluated T cell subpopulations in patients with rheumatoid arthritis using monoclonal antibodies previously shown to react with all T cells (OKT3), with inducer/helper T cells (OKT4) and with suppressor/cytotoxic T cells (OKT8). These investigations disclosed evidence of a significant decrease in the number of OKT8+ cells/mm3 and a high inducer-helper/suppressor-cytotoxic (OKT4+/OKT8+) ratio in active rheumatoid arthritis. A modest number of patients with active arthritis were treated wit levamisole or with synthetic thymopoietin 32-36 (thymopoietin pentapeptide or TP-5). These individuals responded with ratio decreases to more normal levels. Our data support the hypothesis that monoclonal T cell antibodies may offer an important tool for the further evaluation of patients with rheumatoid arthritis and their individual response to treatment.

[Double pylorus through antrobulbar fistula formation (author's transl)]. / Doppelpylorus durch antro-bulbäre Fistelbildung.

Three patients are presented with double pylori due to antrobulbary fistulas after penetration of ulcers through the prepyloric mucosa or the pyloric ring. Two cases were diagnosed radiographically; in one of them the diagnosis was confirmed by gastroscopy and verified by subsequent operation. The third case was revealed at autopsy. The etiology and pathogenesis of fistulas within the gastrointestinal tract are discussed with regard to the current literature.

[Duplicature of the duodenum (author's transl)]. / Duplikatur des Duodenums.

A case of duodenal duplication in an adult is presented with endoscopic, radiographic and operative findings. Successful therapy consisted in retromesocolic duodenal-duplication-jejunostomy. The literature concerning congenital duplications of the small intestine-especially duodenal duplications-is reviewed.