Familial adenomatous polyposis (Gardner's syndrome) and thyroid carcinoma

Summary The case history of a 24-year-old woman with Gardner's syndrome [familial adenomatous polyposis (FAP)] and papillary thyroid carcinoma is presented, representing the 37th report of this association. Although FAP is transmitted as an autosomal dominant trait with similar penetrance in both sexes, thyroid carcinoma has been found almost exclusively in women (94.3%). The majority have been papillary carcinomas (88.5%), which have become apparent during the third decade (average 23.6, range 16–40 years). Most (55.5%) thyroid carcinomas have been discovered 1–17 years after FAP was identified, although some have been found before (29.6%), or at the same time (14.8%) FAP was diagnosed. Multicentric papillary carcinomas have been reported in 64% (14 of 22) of FAP patients, a frequency at least twofold greater than usual. Although papillary carcinoma found before age 30 (as it was in most patients with FAP) typically has an excellent prognosis, one patient with FAP developed distant metastases from thyroid carcinoma and a 28-year-old woman's death was attributed to papillary carcinoma. The high frequency of multicentric papillary thyroid carcinoma in young patients with FAP and the potential for metastases and death due to thyroid carcinoma warrant aggressive diagnostic screening at regular intervals with neck palpation, ultrasonography, and if necessary, fineneedle aspiration biopsy. When thyroid carcinoma is found, total or near-total thyroidectomy should be considered because of the tumor's high likelihood of being multifocal. Since almost 30% of the thyroid carcinomas associated with FAP have been diagnosed 4–12 years before polyposis was identified, young patients presenting with thyroid carcinoma should be questioned regarding bowel function and a family history of gastrointestinal disease, and consideration should be given to periodic testing for fecal occult blood.The views expressed herein are those of the authors and do not necessarily reflect those of the Army or the Department of Defense.     

Use of parenteral nutrition in treatment of advanced regional enteritis

Eight patients with advanced regional enteritis characterized by multiple areas of involvement, previous surgery (5 of 8), and failure on medical therapy (6 of 8) were placed on total parenteral nutrition for a period of 30 days. In eight of nine courses administered, definite improvement marked by weight gain, diminished pain, decreased diarrhea, and increased serum albumin was found. However, clinical remission was transient in seven of eight successful courses, indicating that parenteral nutrition is not a definitive form of therapy. However, the results suggest that parenteral nutrition may be useful in patients with regional enteritis to a) restore nutrition, b) induce remission, and c) prepare a debilitated patient for surgery. Additional experience is required to determine the efficacy of parenteral nutrition for therapy of fistulae caused by regional enteritis.     

The colitis of Behcet's disease: A separate entity?

Summary An additional case of Behcet's disease with colonic involvement has been presented. This association is rare, as only 13 prior cases with adequate data were available for comparison. Controversy exists as to whether these cases represented true involvement of the colon by Behcet's disease, coincidental inflammatory bowel disease and Behcet's disease, or merely autoimmune phenomena associated with inflammatory bowel disease. Unusual colonoscopic lesions noted in our patient and other features enumerated in the text suggested to us that at least some of these cases represented primary Behcet's disease involving the colon.     

Gastric blood flow

Summary In summary, the vascular bed of the stomach is an area of great potential importance to both gastric and vascular physiologists. There are available many technics for its investigation. Simultaneous study of both hemodynamic and secretory phenomena can be conducted on the stomach. In the next few years information concerning the circulation of the stomach may help elucidate problems in the physiology and pathology of gastric secretion. Hightower observed recently: The topic of visceral circulation, particularly as it pertains to the digestive tract, has not been commented upon in recent...Reviews of Physiology. This subject has become increasingly important in the past few years and is an area with which physiologists interested in the digestive system will become more and more concerned.³³     

Administration of pegylated recombinant human megakaryocyte growth and development factor to humans stimulates the production of functional platelets that show no evidence of in vivo activation

This report describes the effect of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on platelet production and platelet function in humans. Subjects with advanced solid tumors received PEG-rHuMGDF daily for up to 10 days. There was no increase in circulating platelet count at doses of 0.03 or 0.1 microgram/kg/d by day 12 of study. At doses of 0.3 and 1.0 microgram/kg/d there was a threefold median increase (maximum 10-fold) in platelet count by day 16. The platelets produced in vivo in response to PEG-rHuMGDF showed unchanged aggregation and adenosine triphosphate (ATP)-release responses in in vitro assays. Tests included aggregation and release of ATP in response to adenosine diphosphate (ADP) (10, 5, 2.5, and 1.25 mumol/L), collagen (2 micrograms/mL), thrombin-receptor agonist peptide (TRAP, 10 mumol/L) and ristocetin (1.5 mg/mL). Administration of aspirin to an individual with platelet count of 1,771 x 10(3)/L resulted in the typical aspirin-induced ablation of the normal aggregation and ATP-release response to stimulation with arachidonic acid (0.5 mg/mL), collagen, and ADP (2.5 and 1.25 mumol/L). There was no change in the expression of the platelet-surface activation marker CD62P (P-selectin) nor induction of the fibrinogen binding site on glycoprotein IIb/IIIa as reported by the monoclonal antibody, D3GP3. An elevation of reticulated platelets was evident after 3 days of treatment with PEG-rHuMGDF and preceded the increase in circulating platelet count by 5 to 8 days; this reflected the production of new platelets in response to PEG-rHuMGDF. At later time points, the mean platelet volume (MPV) decreased in a manner inversely proportional to the platelet count. Levels of plasma glycocalicin, a measure of platelet turnover, rose 3 days after the initial increase in the peripheral platelet count. The level of plasma glycocalicin was proportional to the total platelet mass, suggesting that platelets generated in response to PEG-rHuMGDF were not more actively destroyed. Thus, the administration of PEG-rHuMGDF, to humans, increased the circulating platelet count and resulted in fully functional platelets, which showed no detectable increase in reactivity nor alteration in activation status.     

Identification of a proline-binding motif regulating CD2-triggered T lymphocyte activation

An intracellular protein termed CD2 binding protein 2 (CD2BP2), which binds to a site containing two PPPGHR segments within the cytoplasmic region of CD2, was identified. Mutagenesis and NMR analysis demonstrated that the CD2 binding region of CD2BP2 includes a 17-aa motif (GPY[orF]xxxxM[orV]xxWxxx GYF), also found in several yeast and Caenorhabditis elegans proteins of unknown function. In Jurkat T cells, over-expression of the isolated CD2BP2 domain binding to CD2 enhances the production of interleukin 2 on crosslinking of CD2 but not the T cell receptor. Hence, a proline-binding module distinct from SH3 and WW domains regulates protein–protein interactions.