Karin Hengst

Teaching ultrasound in a curricular course according to certified EFSUMB standards during undergraduate medical education: a prospective study

BackgroundAs a non-invasive and readily available diagnostic tool, ultrasound is one of the most important imaging techniques in medicine. Ultrasound is usually trained during residency preferable according to German Society of Ultrasound in Medicine (DEGUM) standards. Our curriculum calls for undergraduate training in ultrasound of medical students in their 4th year of undergraduate education. An explorative pilot study evaluated the acceptance of this teaching method, and compared it to other practical activities in medical education at Muenster University.Methods240 medical students in their 4th year of undergraduate medical education participated in the training and completed a pre- and post-questionnaire for self-assessment of technical knowledge, self-assurance of the procedure, and motivation in performing ultrasound using a Likert scale. Moreover, students were asked about their interest in pursuing a career in internal medicine. To compare this training to other educational activities a standardized online evaluation tool was used. A direct observation of procedural skills assessment (DOPS) for the first time applied on ultrasound aimed to independently assess the success of our teaching method.ResultsThere was a significant increase in technical knowledge and self-assurance (p < 0.001) of the students’ self-assessments. The clinical relevance and self-motivation of the teaching were evaluated positively. The students’ DOPS results demonstrated proficiency in the understanding of anatomic structures shown in ultrasonographic images, including terminology, machine settings, and transducer frequencies.ConclusionsTraining ultrasound according to certified DEGUM standards was successful and should be offered in undergraduate medical education. The evaluation of the course affirmed the necessity, quality and clinical relevance of the course with a top ranking score of hands-on training courses within the educational activities of the Medical Faculty of Muenster.

Characterization of the RET protooncogene transmembrane domain mutation S649L associated with nonaggressive medullary thyroid carcinoma

CONTEXT For rare and novel RET mutations associated with hereditary medullary thyroid carcinoma (MTC), clinical and functional studies are needed to classify the RET mutation into one of the three clinical risk groups. OBJECTIVE We analyzed proliferative properties and clinical implications associated with the RET protooncogene transmembrane domain mutation S649L. DESIGN The transforming potential and mitogenic properties of S649L mutation were investigated clinically and by evaluating kinase activity, cell proliferation, and colony formation. PATIENTS Fifteen individuals from five kindreds were identified as carriers of a RET protooncogene mutation in exon 11 codon 649 (TCG(Ser)-->TTG(Leu)). In two out of five index patients, a second RET mutation (C634W or V804L) was detected. RESULTS Eight gene carriers were operated on. Histology revealed MTC and C-cell hyperplasia in three index and three screening patients respectively. In all other gene carriers (aged 41-64 years), calcitonin levels were in the normal range, and pentagastrin-stimulated calcitonin levels were <100 pg/ml. Therefore, thyroidectomy had not yet been performed. In one index patient carrying the S649L mutation, hyperparathyroidism was confirmed histologically. RET S649L-expressing NIH3T3 cells exhibited a clear increase of phosphotyrosine and proliferation rate when compared with parental NIH3T3 cells but a significantly lower kinase activity and cell growth rate when compared with RET C634R-expressing cells. When compared with RET C634R, the S649L mutant showed moderate transforming potential with small-sized colonies. CONCLUSIONS Our clinical and in vitro findings indicate that the transmembrane RET S649L mutation is associated with late-onset non-aggressive disease. Recommendations for prophylactic thyroidectomy should be individualized depending on stimulated calcitonin levels.

The impact of repetitive transcranial magnetic stimulation on pituitary hormone levels and cortisol in healthy subjects

BACKGROUND Repetitive transcranial magnetic stimulation (rTMS) is a new therapeutic tool in the treatment of affective disorders but only few studies on its safety exist. We aimed to determine the impact of rTMS on (neuro)endocrinological serum levels by a placebo-controlled cross-over study. METHODS 23 healthy subjects were stimulated by rTMS in a typical paradigm used in the treatment of depression (coil placed over left dorsolateral prefrontal cortex, 10 and 20 Hz stimulation). Placebo, infrathreshold, and suprathreshold stimulation were applied in random order. The serum levels of cortisol, prolactin, FSH, and TSH were measured before and after stimulation. RESULTS After infrathreshold stimulation, cortisol and TSH serum levels decreased mildly but significantly. All other stimulations had no significant impact on hormone levels. In female, but not in male, subjects placebo stimulation yielded a significant increase of prolactin. CONCLUSIONS rTMS as applied for the treatment of depression leads to only very mild and safe changes of hormones. These changes, in particular the decrease of cortisol levels, might explain in part the efficacy of rTMS.

Thyroid echogenicity in manic-depressive patients receiving lithium therapy

BACKGROUND Lithium is known to induce subclinical or overt hypothyroidism and changes of thyroid volume in manic-depressive patients. Little is known about alterations of thyroid echogenicity due to drug-induced dysfunction. METHODS Twenty manic-depressive patients receiving lithium therapy for at least 6 months and 20 euthyroid volunteers without any antidepressive medication as control group, matched in age and gender, were investigated by laboratory measurements and thyroid ultrasonography including standardized grey scale analyses in representative regions of interest (ROI). RESULTS Thyroid function was normal in all patients (mean FT4 1.1+/-0.2 ng/dl, mean TSH 1.6+/-0.9 micro U/ml) and controls (mean FT4 1.5+/-0.4 ng/dl, TSH 1.1+/-0.3 micro U/ml). Except for two patients, no thyroid autoantibody levels could been detected. Thyroid volumetry revealed significant higher mean values for the lithium treated patients (16.9+/-11.9 ml) compared with the controls (11.4+/-4.5 ml, P<0.05) with a considerable number of goiters (six patients vs. one control). Thyroid echogenicities in both groups were similar (patients 23.9+/-3.7 grey scales, Grauwerteinheiten = GWE, controls 24.2+/-1.3 GWE) and did not depend on the size of the organs. CONCLUSION Lithium treatment contributes to increased thyroid volumes, probably due to inhibition of thyroid function and TSH upregulation, but not to changes of thyroid echo levels in patients with still euthyroid function. Further echogenicity studies on patients with lithium-induced overt hypothyroidism and autoimmune activity will be of special interest.

Surgical Strategy in a Kindred with a Rare RET Protooncogene Mutation of Variable Penetrance with Regard to Multiple Endocrine Neoplasia

Prophylactic thyroidectomy is recommended for carriers of RET protooncogene mutations owing to their nearly complete penetrance for medullary thyroid carcinoma (MTC). However, this guideline is challenged by mutations exhibiting variable penetrance of C-cell pathology. A 38-year-old woman presented with pathologic basal and pentagastrin-stimulated calcitonin levels. Genetic analysis revealed a heterozygous RET protooncogene germline mutation in codon 791 (exon 13) (TATTyr?TTTPhe), followed by thyroidectomy and systematic central lymph node dissection. Histology showed C-cell hyperplasia (CCH) only. Three additional carriers were identified among family members. The 71-year-old father refused surgery despite pathologic calcitonin levels. The index patient’s 37-year-old sister had normal basal and stimulated calcitonin levels, and her 6-year-old son had a 10-fold rise of calcitonin after pentagastrin stimulation. Both patients underwent the same operation as the index patient. The sister had 25 hyperplastic C-cells, but the her son had extensive CCH without MTC. The eldest uncle of the index patient had died of metastatic MTC at the age of 52 with unknown carrier status. Despite variable penetrance, each carrier of a RET protooncogene germline mutation should undergo thyroidectomy, even if basal and stimulated calcitonin levels are normal because at present no test can exclude or predict the age of development of MTC. Moreover, pathologic calcitonin levels cannot differentiate between CCH and MTC. Central lymph node dissection is recommended, as lymph node metastases occur early, significantly worsening the prognosis.

Nicotinamide treatment ameliorates the course of experimental colitis mediated by enhanced neutrophil-specific antibacterial clearance

SCOPE In previous studies, we could show that the B vitamin nicotinamide (NAM) enhanced antimicrobial activity of neutrophils. Here, we assessed the effects of NAM in two models of experimental colitis. METHODS AND RESULTS Colitis was induced in C57BL/6 mice either by oral infection with Citrobacter rodentium or by DSS (dextran sodium sulphate) administration, and animals were systemically treated with NAM. Ex vivo bacterial clearance was assessed in murine and human whole blood, as well as isolated human neutrophils. In C. rodentium-induced colitis, NAM treatment resulted in markedly decreased systemic bacterial invasion, histological damage and increased fecal clearance of C. rodentium by up to 600-fold. In contrast, NAM had no effect when administered to neutrophil-depleted mice. Ex vivo stimulation of isolated human neutrophils, as well as murine and human whole blood with NAM led to increased clearance of C. rodentium and enhanced expression of antimicrobial peptides in neutrophils. Moreover, NAM treatment significantly ameliorated the course of DSS colitis, as assessed by body weight, histological damage and myeloperoxidase activity. CONCLUSION Pharmacological application of NAM mediates beneficial effects in bacterial and chemically induced colitis. Future studies are needed to explore the clinical potential of NAM in the context of intestinal bacterial infections and human inflammatory bowel disease (IBD).

MicroRNA-320a Strengthens Intestinal Barrier Function and Follows the Course of Experimental Colitis.

Background:Inflammatory bowel disease is a chronic-remittent disorder with the risk of disabling complications due to uncontrolled inflammation. Accurate biomarkers are needed to noninvasively monitor the disease course to tailor therapy. We evaluated the potential of the specific microRNA (miR)-320a to monitor disease activity in experimental colitis or patients with Crohns disease and investigated its functional role in intestinal epithelial barrier formation. Methods:The impact of miR-320a on intestinal barrier function was tested in vitro in T84 epithelial cells by transepithelial resistance measurement and quantitative real-time polymerase chain reaction analysis on inflammatory and microbial stimulation. Experimental colitis was studied in dextran sodium sulfate colitis, T-cell transfer colitis, and IL-10-/- mice. Disease course was monitored by body weight measurement, colonoscopy, and histological examination. MiR-320a expression during inflammation was assessed in T84 cells, murine blood, and colonic tissue and in peripheral blood from patients with Crohns disease with active or quiescent disease. Results:MiR-320a transfection of T84 cells reinforced barrier integrity reflected by increased transepithelial resistance (P < 0.01) and inhibited barrier-destructive enteropathogenic Escherichia coli effects resulting in increased tight junction protein JAM-A expression (P = 0.02) and decrease of barrier integrity–destabilizing miR-320a target PPP2R5B (P < 0.001). Tumor necrosis factor-&agr; and interleukin-1&bgr; stimulation increased a miR-320a epxression in T84 cells. MiR-320a level was increased in blood samples from colitic mice and patients with Crohns disease showing a strong correlation with disease activity (r2 = 0.67). Conclusions:MiR-320a strengthens intestinal barrier function in vitro and has the potential to monitor disease activity of colitic mice. Future studies are needed to further evaluate the potential of miR-320a in patients with inflammatory bowel disease.

Successful treatment of oral Crohn's disease by anti-TNF-alpha dose escalation - a case report

BackgroundCrohn’s Disease (CD) is typically characterized by abdominal symptoms, however, besides gastrointestinal symptoms, CD patients may suffer from extraintestinal manifestations which are far less common and medical treatment can be challenging.Case presentationWe report about a 34-year-old Crohn’s Disease (CD) patient in clinical remission under adalimumab therapy who presented in the clinic for Cranio-Maxillo Surgery due to severe pain in the mandibular area. Ulcerative lesions of the buccal-side mucosa of the right mandible were detected. To rule out malignancy, a biopsy was obtained and revealed ulcerative stomatitis with noncaseating granulomas consistent with oral CD. Shortening the adalimumab administration interval to weekly injections resulted in a complete healing of the oral CD lesions without residual inflammation.ConclusionThe case presented here demonstrates that gastroenterologists should evaluate and consider oral CD lesions as a possible marker of disease activity in patients despite having quiescent intestinal CD.