A non-acromegalic case of multiple endocrine neoplasia type 1 accompanied by a growth hormone-releasing hormone-producing pancreatic tumor.

Cases of acromegaly due to GHRHproducing pancreatic endocrine tumors have been reported. Here we present a case of a 31-yr-old nonacromegalic man with hyperparathyroidism and elevated serum IGF-I with normal serum GH levels. Serum GH was not suppressed below 1 ng/ml by the glucose tolerance test and increased in response to TR H and GHRH administration. Magnetic resonance imaging (MRI) revealed pituitary hyperplasia and an abdominal computed tomography (CT ) scan showed a tumor in the pancreatic tail. Plasma concentration of GHRH was elevated. Based on these clinical data, multiple endocrine neoplasia (MEN) type 1 was suspected. Three enlarged parathyroid glands were removed and a distal pancreatectomy was performed. Pathological examination of the parathyroid glands and pancreatic tumor showed nodular hyperplasia and a well-differentiated endocrine tumor, respectively, both compatible with MEN features. Immunohistochemistry revealed positive immunoreactivity for GHRH, SS , insulin, glucagon, chromogranin A, and pancreatic polypeptide in the pancreatic tumor. After pancreatic surgery, elevated levels of GHRH and IGF-I were normalized and pituitary hyperplasia definitely decreased in size. In cases of pituitary hyperplasia with elevated IGF-I, ectopic GHRH syndrome must be considered even if physical features of acromegaly are absent. It is also important to measure plasma GHRH concentrations in order to give a diagnosis.

Novel germline RET proto-oncogene mutations associated with medullary thyroid carcinoma (MTC): mutation analysis in Japanese patients with MTC.

Germ-like and somatic mutations in the RET proto-oncogene are associated with inherited and sporadic medullary thyroid carcinoma (MTC). The majority of patients with multiple endocrine neoplasia type 2A (MEN2A) and familial medullary thyroid carcinoma (FMTC) carry germ-line point mutations that result in the substitution of one of five cysteine residues. We investigated exons 10, 11, 13, 14 and 16 of the RET proto-oncogene in 33 unrelated Japanese patients with MTC. Eleven of the 33 cases (33%) were found to have germ-line mutations. Three previously unreported mutations in exon 10 and 11 were identified: one in codon 620, (TGC-->GGC), resulting in a cysteine to glycine substitution, and two in codon 630, (TGC-->TCC) and (TGC-->TAC), resulting in cysteine to serine and cysteine to tyrosine changes, respectively. The new mutations were present in the germ-line DNA of four unrelated patients for whom a family history of MTC had not been documented. Because the new RET alleles described here involve cysteine residues in a region of protein previously associated with FMTC and MEN2A, it is very likely that they represent mutations that predispose to the development of MTC.

[Morphological characteristics of human mast cells in normal and pathological thyroid glands. Functional aspect of human mast cells in comparison with rat mast cells].

We examined the distribution and population density of human mast cells in thyroid glands. The results were compared with those of Sprague-Dawley (SD) rats because they thyroid function of SD rats is known to be under the control of bioactive amines discharged from mast cells. Normal thyroid tissues were obtained either form autopsy or from a normal portion of the tissue distant from nodular lesions. Thyroid tissues were surgically removed from cases of Graves' disease and other tumorous lesions such as follicular adenoma, follicular carcinoma, papillary carcinoma and medullary carcinoma. The tissues were fixed with buffered formaldehyde or Carnoy fluid and embedded in paraffin. Mast cells were stained with toluidine blue and naphthol ASD chloroacetate esterase (esterase). Immunoperoxidase reactions to antihuman tryptase and chymase monoclonal antibodies were then observed. The mast cells were also observed by electron microscopy. The histamine content of the thyroid tissues was estimated by the high-performance liquid chromatography method. The mast cells in SD rat thyroid glands were scattered in perifollicular connective tissues which were comprised of capillaries, fibroblasts, nerve fibers and occasional fine deposits of collagen fibrils. Their cytoplasmic granules appeared to be distinct, electron dense and amorphous. In contrast, the mast cells in normal human thyroid glands were scattered exclusively over relatively thick interstitial spaces like the interlobular and subcapsular connective tissues. These mesenchymal tissues were composed of bundles of collagen fibrils, fibroblasts, histiocytes and thin cytoplasmic processes of unknown origin. In pathologic thyroid tissues, the mast cells were distributed in a similar pattern over the connective tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Miniature membrane oxygenator for use in neonatal ECMO.

A new miniature membrane oxygenator (Kuraray KMO, size, 0.3 m2, with a priming volume of 47 ml, compliance of less than 0.1 ml/100 mmHg, and pressure loss of 45 mmHg) with improved gas transfer and mechanical durability was developed and tested. The membrane material is a hollow fiber double layer polyolefin. The testing procedures determined by the AAMI were followed, and the results showed improved O2 and CO2 transfer (70 ml/min and 55 ml/min, respectively). Hemolysis was within acceptable limits, and plasma leakage was undetectable after 7 days of perfusion. Clinical study demonstrated satisfactory performance.

Binding of heparin onto ethylene-vinyl alcohol copolymer membrane.

Heparin was ionically bound onto the surface of an ethylene-vinyl alcohol copolymer (EVAL) membrane which was derivatized by aminoacetalization to produce cationic surface charges. The amount of bound heparin was proportional to the ion exchange capacity of the aminoacetalized membrane and the maximal amount obtained in this experiment was 96 Unit/cm2 (0.59 mg/cm2). Plasma recalcification times were measured for the heparinized membrane thus obtained. Recalcification times increased proportionally with the amount of heparin bound on the membrane, while original EVAL membranes and the non-heparinized aminoacetalized membrane did not show increases in recalcification times. This means that the heparinized EVAL membrane has a more nonthrombogenic property due to the release of heparin. The apparent amount of heparin released from the membrane into plasma was estimated from plasma recalcification times. The release rate was 0.30-0.33 Unit/cm2/h (1.8 X 10(-3)-2.0 X 10(-3) mg/cm2/h) for the membranes whose surface was considered to be saturated with heparin. The release amount was about 0.6% compared to the adsorbed heparin in the case of the 96 Unit/cm2-heparinized membrane incubated in plasma for 60 min.