Medullary Carcinoma of the Thyroid Gland

Medullary thyroid carcinoma (MTC) is an uncommon thyroid tumor that has attracted a great deal of interest because of its frequent presentation as a familial tumor and its primary involvement in the type II multiple endocrine neoplasia (MEN) syndromes MEN-IIA and MEN-IIB and familial medullary thyroid carcinoma (FMTC). The MTC tumor cells secrete the polypeptide hormone calcitonin, which serves as an excellent tumor marker, useful for defining the presence of disease, preoperatively or following thyroidectomy. The discovery that mutations in the RET proto-oncogene are associated with MEN-II syndromes was highly significant in that it demonstrated a clear correlation between genotype and phenotype; and most importantly it provided a mechanism whereby family members at risk could be identified by direct DNA analysis. Virtually all patients with MEN-IIA, MEN-IIB, and FMTC develop MTC; therefore there is a clear rationale for performing thyroidectomy as soon as a RET mutation has been identified. Because MTC appears to be much more aggressive in patients with MEN-IIB, thyroidectomy is performed during the first year of life in this setting, whereas in patients with MEN-IIA, where the tumor appears to be more indolent, the procedure can be safety delayed until age 5 years. Reoperative neck exploration in patients with evidence of persistent or recurrent MTC has been effective in a significant number of patients, although the success of the operation requires careful patient selection and preoperative assessment. MTC, as expressed in the MEN-II syndromes, is an excellent model to evaluate the usefulness of interventional therapy in patients demonstrated to have a genetic predisposition for cancer.     

Initiating the inflammatory phase of incisional healing prior to tissue injury

BACKGROUND: The time required for incisional healing accounts for the majority of postoperative pain and convalescence. Impaired healing prolongs the process further. If a method for accelerating acute incisional wound healing could be developed, patients would benefit from decreased wound failure and an earlier return to their premorbid condition. MATERIALS AND METHODS: In a rat dermal model, cytokine or vehicle infiltration prior to incision was performed using a single dose or four daily doses preincision. Planned incision sites were primed with the proinflammatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) or platelet-derived growth factor BB (PDGF-BB) in an effort to activate the inflammatory phase of healing prior to wounding. At the time of incision closure, one half of the incisions were treated with transforming growth factor beta(2) (TGF-beta(2)). Incisional sites were biopsied and stained with hematoxylin and eosin and immunohistochemistry for inflammatory cells and fibroblast populations and breaking strength was measured. RESULTS: Priming skin with GM-CSF or PDGF-BB mimicked the early inflammatory phase of wound healing. Macrophage staining (EB1) and fibroblast staining (vimentin) were significantly increased prior to incision. Inflammatory priming as well as priming coupled with TGF-beta(2) at the time of the incision closure synergistically improved breaking strength. CONCLUSION: This study demonstrates that sequential therapy consisting of priming of tissue with an inflammatory cytokine followed by application of a proliferative cytokine at the time of incision closure nearly doubles the breaking strength of an acute wound. By manipulating the inflammatory and early proliferative phases of wound healing with tissue growth factors, it may be possible to accelerate acute wound repair and shift the wound healing trajectory to the left.     

Characterization of supercritical fluid extracts of St. John's wort (Hypericum perforatum L.) by HPLC-MS and GC-MS.

Supercritical fluid extracts (carbon dioxide without modifiers) of St. John's Wort (Hypericum perforatum L., Clusiaceae) were analyzed by GC-MS, HPLC-DAD and HPLC-DAD-MS. Besides the dominating phloroglucinols hyperforin (36.5 +/- 1.1%) and adhyperforin (4.6 +/- 0.1%), the extracts mainly contained alkanes (predominantly nonacosane), fatty acids and wax esters. The apolar components tended to accumulate in a waxy phase resting a top of the hyperforin-enriched phase. No components of higher polarity like naphthodianthrones were found. A set of hyperforin oxidation products was detected and tentatively assigned using HPLC-MS.     

Twin pregnancies in Cardiff and Vale of Glamorgan over four decades: natural twinning is on the increase

Objective

To assess trends in twinning over four decades using a population-based registry.

Design

Ecological study to conduct trend analysis of twin pregnancies in a geographically defined area over 40 years.

Setting

All pregnancies in the Cardiff and Vale of Glamorgan area of South Wales from 1965 to 2004, as recorded in the Cardiff Birth Survey (CBS) database.

Methods

Trends of the incidence of all twin pregnancies (≥18 weeks of gestation) were calculated in 5-year increments, beginning with 1965–1969 and ending in 2000–2004. Natural twinning rates could only be calculated for the terminal five time periods (i.e., 1980–1984, 1985–1989, 1990–1994, 1995–1999, and 2000–2004), when information regarding non-spontaneous (iatrogenic) twinning was first collected in the database. All results were adjusted for maternal age.

Results

The total twinning rate was 13.1 per 1000 pregnancies in the 1st time period (1965–1969). Subsequently, there was a gradual reduction in twinning, reaching a nadir of 10.3 per 1000 for the time period 1980–1985 (Z = 3.15, P value < 0.001). This was followed by a gradual increase in twinning, reaching a maximum of 15.7 per 1000 for both 1995–1999 and 2000–2004 (Z = −5.18, P value < 0.0001). After exclusion of the cases of iatrogenic pregnancies, the natural twinning rate showed a continuous and gradual increase from 10 per 1000 spontaneous pregnancies in 1980–1984 to 13.3 per 1000 in 2000–2004 (Z = −5.08, P value < 0.0001).

Conclusion

The data showed a gradual, continuous increase in natural twinning rates over the last two decades. Such an increase cannot be attributed to the rise in maternal age alone.     

Progressive noninfectious anterior vertebral fusion in a girl with axial mesodermal dysplasia spectrum

We report a 7-year-old-girl who presented with the clinical criteria of the axial mesodermal dysplasia spectrum. Her parents were first cousins. Her facial dysmorphism was compatible with Goldenhar syndrome and in addition, she had anterior noninfectious vertebral fusions of the cervical and the thoracolumbar vertebrae, a congenital dermal sinus and a hypoplastic sacrum. The urogenital and the anal-recto regions were normal. To the best of our knowledge, this is the first clinical report of a child with axial mesodermal dysplasia in association with progressive noninfectious anterior vertebral fusion.     

Zur Physiologie der Muskelendplatte und zur Pathogenese

Zusammenfassung An Hand experimenteller Untersuchungen über die Funktion der motorischen Endplatte und unter Verwendung neuerer ausländischer Literatur wird versucht, den Vorgang der Erregungsübertragung vom motorischen Nerven auf die Muskelfaser darzustellen, soweit dieses für die Pathogenese von neurologischen Krankheitsbildern von Interesse erscheint. Störungen der Erregungsübertragung können in einer Erschwerung bzw. Blockade der Übertragung oder in einer wiederholten Erregungsbildung auf Einzelreiz (Eigenrhythmik) bestehen. Für die erste Gruppe sind die Myasthenia gravis und wahrscheinlich die paroxysmale Lähmung Beispiele, für die zweite Gruppe die Myotonie und wahrscheinlich die Tetanusinfektion.Aus der Kenntnis des für die neuromuskuläre Übertragung bedeutungsvollen Acetylcholinstoffwechsels (Bildung und Spaltung durch Cholinesterase) ergeben sich Hinweise für die Therapie. Insbesondere ergeben sich Parallelen zwischen der KCl-Wirkung im Tierexperiment und der therapeutischen Anwendung des KCl bei Erkrankungen im Bereich des Motoneurons.Auf neuere Curarepräparate und ihre Anwendung in der Klinik wird hingewiesen.Herrn Prof.Frey zum 70. Geburtstag gewidmet.