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Objectives: The objective of the study was to evaluate the safety and efficacy of high-concentration intranasal desmopressin (HCIN-DDAVP) 1.5 mg/mL, in patients weighing ≤50 kg with mild hemophilia A or mild type 1 von Willebrand disease (VWD). Study design: This was a single-center, nonrandomized, open-label, single-dose trial of HCIN-DDAVP. Nine boys with hemophilia A, 8 girls with mild VWD, and 8 boys with mild VWD were evaluated. HCIN-DDAVP responses were compared with historic IV-DDAVP responses in 13 of the patients. Results: HCIN-DDAVP administration resulted in statistically significant mean increases in factor VIII procoagulant activity, ristocetin cofactor, and von Willebrand factor antigen levels in each of the 3 study groups. Mean (± 1 SD) increase in factor VIII procoagulant activity was 25.7 ± 11.9 U/dL in mild hemophilia A. Ristocetin cofactor increased 108.5 ± 53.8 U/dL in girls and 95.8 ± 36.0 U/dL in boys with mild VWD. Intravenous desmopressin acetate responses were comparable to HCIN-DDAVP responses in patients who received both preparations. Adverse events were mild and resolved without intervention. Conclusion: We conclude that administration of 150 μg of high concentration intranasal desmopressin is safe and effective in patients weighing ≤50 kg with mild hemophilia A or mild type 1 VWD. (J Pediatr 2002;140:595-9)

In this paper, we present a systematic way of proving the existence of periodic solutions to a dynamical system using numerical techniques. In particular, we consider an n-dimensional ordinary differential equation, periodic in time, and state necessary conditions to prove the existence of both stable and unstable periodic solutions with the use of ordinary differential equation solvers (implemented by computer) and a knowledge of their error bounds. The method used is based on a simple shooting method and is an alternative to the Kantorovich theorem.A particularly difficult problem is considered in which the Lipschitz constant is large along unstable solutions. This leads to a modified scheme incorporating a multipoint shooting method to prove the existence of periodic solutions.The multipoint shooting method is then applied to a model in epidemiology to estimate a region of existence of an unstable periodic solution.

At least five morphological types of endocrine cells can be identified by electron microscopy in the rat stomach, most of which can decarboxylate 5-hydroxytryptophan to serotonin. To identify which o f these cells can synthesize 5-hydroxytryptamine from l-tryptophan, the physiological precursor of 5-hydroxytryptamine biosynthesis, pieces of rat stomach were incubated in organ culture with l-[ 3 H]tryptophan, with and without inhibitors, and were processed for light microscopic and electron microscopic radioautography. l-[ 3 H]tryptophan labeled all EC cells heavily, but labeled other endocrine cells-ECL, A-like, G, and D-only lightly. The labeling of EC cells was markedly reduced when 5-hydroxytryptamine synthesis was inhibited by either p-chlorophenylalanine or carbidopa, but was not appreciably reduced when protein synthesis was inhibited with cycloheximide. The labeling of Alike, G, and D cells by l-[ 3 H]tryptophan was similar to that produced by l-[ 3 H]leucine and was almost abolished by cycloheximide. The labeling of ECL cells by l-[ 3 H]tryptophan was shown by grain counts to be greater than the labeling of A-like and parietal cells, to persist after incubations with cycloheximide, but to be inhibited by p-chlorophenylalanine or carbidopa. Amine-fluorescence studies also indicated that ECL cells could synthesize some 5-hydroxytryptamine, and biochemical studies showed that the oxyntic mucosa could synthesize 5-hydroxytryptamine. Incubations of mucosa with 5-[ 3 H]hydroxytryptamine usually produced little or no labeling of endocrine cells. Thus, this study demonstrates that all EC cells can readily synthesize 5-hydroxytryptamine from tryptophan and therefore, as previously suggested from topographical and cytochemical studies, probably represent the argentaffin cells of light microscopy. This study also suggests that ECL cells can also synthesize and store some 5-hydroxytryptamine, but presumably not enough normally to be detected by conventional argentaffin, chromaffin, or amine-fluorescent techniques, which usually demonstrate few reactive cells in oxyntic glands, were ECL cells abound.

Rat fundic mucosa contains numerous APUD endocrine cells that can take up 5-hydroxytryptophan (5-HTP) and decarboxylate it to 5-hydroxytryptamine (serotonin), detectable by its formaldehyde-induced yellow fluorescence. To identify these cells by electron microscopy, pieces of rat gastric mucosa were incubated with DL-5-HTP. Some specimens were fixed in 4% formaldehyde-0.5% glutaraldehyde, while others were frozen, freeze-dried, and exposed to paraformaldehyde vapors. Thick sections of the Epon-embedded specimens were examined and photographed by fluorescence microscopy, and fluorescing and nonfluorescing cells were identified by electron microscopy in serial thin sections. Control specimens, not incubated with 5-HTP, revealed fluorescence of only the mast cells and EC cells, which were abundant in the pylorus, but rare in fundic mucosa. Specimens incubated with 5-HTP also exhibited numerous yellow fluorescent endocrine cells in fundic mucosa, which cells were found to be the ECL cells; the A-like cells did not fluoresce. In pyloric mucosa, many G and D (D1) cells also exhibited weak or moderate fluorescence after 5-HTP incubation. Thus, this study supports the contention of previous radioautographic studies that the ECL, but not the A-like, cells are the APUD endocrine cells of rat fundic mucosa, that G and D cells also possess some APUD activity, and that EC cells represent the enterochromaffin cells, which normally synthesize and store demonstrable quantities of serotonin.

Rat gastric oxyntic glands contain argyrophil "enterochromaffin-like" endocrine cells that synthesize and store histamine and also have APUD ability—they can take up exogenous l-5-hydroxytryptophan (5-HTP), can decarboxylate it to 5-hydroxytryptamine (5-HT, serotonin) by the enzyme DOPA-decarboxylase, and can store the amine. Previous cytochemical studies suggested that these cells correspond to both the ECL and A-like cells, the two predominant endocrine cells identified by electron microscopy (EM) in rat oxyntic glands. In a recent study, however, we demonstrated that the ECL but not the A-like cell exhibited APUD ability when rat gastric mucosa was incubated with H3-5-HTP and studied by EM radioautography. The purpose of the present study was to identify by EM radioautography the histamine-synthesizing endocrine cells in the rat stomach. Pieces of rat (male Sprague-Dawley) gastric mucosa were incubated in organ culture with l-H3-histidine (50 μCi, 1.8 × 10 −5 M) with and without inhibitors and were processed for LM and EM radioautography. H3-histidine labeled the ECL cells heavily but the A-like and other endocrine cells only lightly. The labeling of ECL cells was only modestly reduced by cycloheximide, an inhibitor of protein synthesis, whereas the labeling of A-like and other endocrine cells was almost abolished. In contrast, the labeling of ECL cells was markedly reduced by 4-bromo-3-hydroxybenzyloxyamine (NSD-1055), an inhibitor of histidine decarboxylase and DOPA decarboxylase, but was not appreciably affected by carbidopa, an inhibitor of only the DOPA decarboxylase. Incubations with H3-histamine (50 μCi, 0.9 × 10 −5 M) failed to label endocrine cells. Thus, this study demonstrates that the ECL but not the A-like cell is the histamine-synthesizing endocrine cell of the rat stomach.

The oxyntic glands of rat and mouse stomachs contain argyrophil "enterochromaffin-like" endocrine cells that synthesize and store histamine and also have APUD ability—they can take up exogenous L-5-hydroxytryptophan (5-HTP), can decarboxylate it to 5-hydroxytryptamine (5-HT, serotonin) by the enzyme DOPA decarboxylase, and can store the amine. Previous cytochemical studies have suggested that these cells correspond to both the ECL and A-like cells, the two predominant endocrine cells identified by electron microscopy in rat and mouse oxyntic glands. The purpose of this study was to identify by EM radioautography the APUD and thereby the enterochromaffin-like cells in the oxyntic glands of these rodents. Pieces of rat and mouse gastric mucosa were incubated in organ culture with H3-5-HTP, H3-5-HTP and carbidopa (an inhibitor of DOPA decarboxylase), and H3-5-HT and were processed for LM and EM radioautography. Additional pieces of rat gastric mucosa were incubated with 5-HTP, freeze-dried, and processed by the Falck-Hillarp technique to permit the detection of 5-HT by fluorescence microscopy. After H3-5-HTP incubations, the EeL cells of both the rat and mouse oxyntic glands were labeled by EM radioautography, but the A-like cells of only the mouse were so labeled. Since this labeling was inhibited by carbidopa and since exogenous H3-5-HT failed to label endocrine cells, the labeling must have resulted from the uptake of exogenous H3-5-HTP and its intracellular conversion to H3-5-HT. The failure of some rat oxyntic endocrine cells to form and store 5-HT from exogenous 5-HTP was also demonstrated by the Falck-Hillarp technique and by LM radioautography. Thus, this study demonstrates that only the ECL and not the A-like cell of rat oxyntic glands is an APUD and therefore enterochromaffin-like cell, and that despite their morphologic similarities, the A-like cells of the rat and mouse have metabolic differences.

The rat stomach was shown some years ago to contain numerous endocrine cells with APUD abilitycells that could take up the amino acids l-5-hydroxytryptophan (5-HTP) or l-dihydroxyphenylolanine (l-DOPA) and could decarboxylase them to their respective amines, 5-hydroxytryptamine (5-HT, serotonin) and dopamine, by means of the enzyme DOPA-decarboxylase. In a recent study, most of the APUD endocrine cells in the rat oxyntic mucosa were shown by electron microscopic radioautography to be the enterochromaffinlike cells, while the A-like cells were shown to lack APUD ability. To identify the APUD cells in the pyloric mucosa, pieces of rat pylorus were incubated in organ culture with 3 H-5-HTP and were processed for light microscopic and electron microscopic radioautography. Additional specimens were incubated with 3 H-5-HTP and carbidopa, an inhibitor of DOPA-decarboxylase, used to block the decarboxylation of 3 H-5-HTP to 3 H-5-HT, or with 3 H-5-HT, used to determine where exogenous 3 H-5-HT localizes in the pyloric mucosa. The 3 H-5-HTP labeled all three types of endocrine cells identified within the pyloric glands-the G, enterochromaffin, and D cells. As this labeling was inhibited by carbidopa, and as exogenous 3 H-5-HT labeled these cells only lightly, the labeling must have resulted from the uptake and intracellular conversion of the 3 H-5-HTP to 3 H-5-HT. Thus despite their morphologic differences, all rat pyloric endocrine cells possess APUD ability, a property shared by many, but not all, of the peptide-and amine-producing endocrine cells located throughout the body.