Primary hyperparathyroidism, C-cell hyperplasia and papillary thyroid carcinoma in a patient with RET germline polymorphism S836S

BACKGROUND: In most examined populations the RET germline polymorphism S836S is found in about 3.6% of the normal population but in about 9% of patients suffering from sporadic C-cell hyperplasia or medullary thyroid carcinoma. The polymorphism S836S is thought to be involved in the development of sporadic medullary thyroid carcinoma. CASE PRESENTATION: We report a 48-year-old woman suffering from primary hyperparathyroidism (parathormone 121-166 pg/ml, normal <72), bilateral diffuse and nodular C-cell hyperplasia (calcitonin after pentagastrin administration 156 pg/ml, normal <4.6), and papillary thyroid carcinoma. Two commercial analyses of RET did not reveal any germline mutation within the known hot spots. However, sequencing revealed the presence of the RET polymorphism S836S. Following total thyroidectomy and removal of two hyperplastic parathyroid glands parathormone decreased to 51 pg/ml and calcitonin was no longer detected. CONCLUSIONS: The pathogenetic importance of the RET polymorphism S836S is still obscure. However, according to the published overrepresentation of the RET polymorphism S836S in patients suffering from apparent sporadic medullary thyroid carcinoma, it is conceivable that it also plays a role in multiglandular endocrine disease.     

Isolated and combined effects of prolonged exposures to noise and whole-body vibration on hearing,vision and strain

Summary This study was carried out in order: (1) to examine the effects of isolated and combined prolonged exposures to noise and whole-body vibration on hearing, vision and subjectively experienced strain, and (2) to check the combined effects with repeated exposures. Six male subjects were exposed twice to noise (N) at 92 dBA, whole-body vibration (V) in the Z-axis at 4 Hz and 1.0 ms^–2 rms, and noise and vibration (NV) for 90 min with each condition. Temporary threshold shifts of hearing (TTS) and their integrals (ITTS) were measured at 4, 6, 10, and 12 kHz. Visual acuity was examined by means of a very sensitive test. Cross-modality matching (CMM) of the handgrip force was used to judge the subjectively experienced strain. NV induced a clear tendency of higher TTS and ITTS than N, with several significant differences most pronounced at 10 kHz. With repeated exposures, the effect of NV decreased, while the reactions to N and V remained unchanged. The individual reactions to NV differed. The influence of the duration of exposures on vision depended on the condition; N caused time-dependent changes, whereas V did not. CMM-data increased with the duration of the exposure during V and NV. N was generally judged to be more straining than V; NV caused higher strain than V during the first 30 min of exposure only. Correlations between different effects suggest certain links between them. Additionally, less motivation — daily obtained by a questionnaire — often correlated with higher ITTS during N and NV. The results also illustrate the combined effects on the individual susceptibility, repetition of exposure, the kind of response, and, possibly, the actual psychic state.Abbreviations CMM cross-modality matching - MVC maximum voluntary contraction force - N exposure condition: noise level 92dBA, no whole-body vibration - NV exposure condition: combined exposure to noise with a level of 92 dBA and wholebody vibration with 4 Hz, 1 ms^–2 rms - V exposure condition: whole-body vibration with 4 Hz, 1 ms^–2 rms - TTS temporary threshold shift - ITTS integral of temporary threshold shift - WBV whole-body vibration in the common sense This work was done in the Temporary International Research Team on Combined Effects of Noise and Vibration of the Council of Mutual Economic Assistance of the Socialist Countries. The authors gratefully acknowledge the help and assistance of L.-M. Brumm, Y. Bening, M. Godau, G. Weber, and R. Vizcaino.     

Bilateral subclavian steal syndrome: Treatment with percutaneous transluminal angioplasty and stent placement

A 66-year-old man presented with bilateral subclavian steal syndrome (SSS) due to proximal subclavian artery occlusions. He was treated by percutaneous transluminal balloon angioplasty (PTA) and stent implantation in the left subclavian artery and by PTA alone in the right subclavian artery. We could demonstrate that interventional treatment of symptomatic bilateral SSS is possible. If PTA alone is insufficient, stent implantation should be considered.     

Septicaemia among neonates with tetanus.

In a study of 149 cases of neonatal tetanus (NNT) admitted into the University of Calabar Teaching Hospital, 49 (33 per cent) were also found to have septicaemia. The dominant organisms were coliforms and Staphylococcus aureus. A comparison of the clinical features of the septicaemic and non-septicaemic neonates showed umbilical cord infection to be an indicator of septicaemia. There was no significant difference in the case fatality rates of the two groups of patients and the overall case fatality was low (37 per cent). This is attributable to early diagnosis and treatment of the septicaemia cases. It is suggested that paediatricians should have a high index of suspicion of septicaemia among cases of NNT as a means of reducing case fatality.     

Morphometric analysis of murine skin wound healing: Standardization of experimental procedures and impact of an advanced multitissue array technique

Morphometric data based on skin wounding offer important information for the characterization of the phenotype of transgenic mouse models. The goal of this study was the comparison of technical procedures concerning wounding, processing, and evaluation of samples in different mouse strains. The multitissue array technique was used to estimate its adaptability for standardized analysis in wound healing. Skin wounds between days 1 and 14 after wounding were analyzed. The influence of mouse strain (C57BI/6 vs. FVB/N mice), sex, size of the punch biopsies, and preparation of the tissue sections was investigated on 94 mice. The parameters distance between the migration tongues (deltaMT) and surface not covered by epithelium were evaluated to describe the reepithelialization, and the distance between the adnexa was chosen to measure wound contraction. In addition, the techniques to measure the area of granulation tissue (GT) were evaluated. The data illustrate the requirement of standardized conditions for skin wound-healing experiments and demonstrate that histological preparation in serial sections is mandatory to detect slight differences in wound contraction. For the analysis of cellular composition in GT, multitissue arrays are useful tools in wound-healing studies.     

A multicenter clinical trial of gadolite oral suspension as a contrast agent for MRI

The purpose of this study was to assess the effectiveness and safety of Gadolite Oral Suspension as a gastrointestinal (GI) contrast agent for MRI in a phase II and two phase III multicenter clinical trials. Gadolite was administered to 306 patients with known or suspected abdominal and/or pelvic disease. MRI with T1- and T2-weighted sequences was performed before and after ingestion. Efficacy was evaluated by having two masked readers rate the certainty of their MR diagnosis (0 = uncertain, 1 = probable, 2 = definite) on randomly presented pre- and post-Gadolite Oral Suspension enhanced images. Principal investigators also evaluated the images and established the final diagnosis. Vital signs, clinical chemistries, and adverse events were documented. Blood and urine samples were analyzed for gadolinium content to determine whether Gadolite Oral Suspension was absorbed systemically. Certainty in MR diagnosis increased significantly (P < .001) for both blinded readers between pre- and post-Gadolite images (.49–1.18 for reader 1; .46–1.53 for reader 2). Sensitivity, specificity, and accuracy also increased for both masked readers. No gadolinium was detected in blood or urine samples. There were no serious adverse events and no apparent drug-related trends in mean vital signs or laboratory values. Gadolite is a highly effective, safe, and well tolerated contrast agent for clinical use with MRI.     

Enhancement of immunogenicity of Jeg3 cells by ectopic expression of HLA-A*0201 and CD80

PROBLEM: The choriocarcinoma cell line Jeg3 suppresses immunity in vitro by secretion of soluble factors like leukemia inhibitory factor suppressing leukocyte activation. The cells lack expression of classical human leukocyte antigen (HLA)-A and -B alleles but express some HLA-C, and non-classical HLA-G and -E. Upon binding to killing inhibitory receptor on natural killer (NK) cells, HLA-G prevents activation of cytolytic activity. We investigated whether Jeg3 cells are capable of immune stimulation after complementation with classical HLA and T cell costimulatory signal CD80. METHOD OF STUDY: Jeg3 cells were transduced to express HLA-A*0201 and/or CD80. Parental Jeg3 or transfectants Jeg3-A2, Jeg3-CD80 or Jeg3-CD80-A2 were used to stimulate allogeneic resting and activated peripheral blood lymphocytes (PBL). The different cell lines were loaded with a HLA-A2-restricted Epstein-Barr virus (EBV) recall antigen peptide epitope and antigen presenting ability was examined. T cell lines specific for Jeg3 and transfectants were generated from HLA-A2 matched and nonmatched donors and compared for expansion, phenotypes and cytolytic activity. RESULTS: While all Jeg3 cell lines induced only marginal proliferation of resting T cells, phytohemagglutinin (PHA)-activated T cells were stimulated by CD80 or CD80-A2 expressing Jeg3. Only the transfectant Jeg3-CD80-A2 was capable of specific T cell stimulation by EBV recall antigen presentation. T cell lines of HLA-A2 non-matched donors stimulated with the Jeg3 transfectants showed significant expansion only when HLA-A2 and the costimulus CD80 were present. T cells from HLA-A2 positive donors did not expand significantly or differentially. No NK cells grew under any condition. In Jeg3-CD80-A2 stimulated T cells lines CD8+ cells expanded preferentially. These T cells exerted cytolytic activity toward all Jeg3 cell lines. CONCLUSION: Our data suggest that, in spite of immunosuppressive mechanisms, proliferative and cytolytic T cell responses are induced by Jeg3 cells when classical HLA- and/or costimulatory signals are present on the cells.