Gastrointestinal manifestations in patients with gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS): a systematic review with analysis of individual patient data.

BACKGROUND AND AIM: Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is an autosomal dominant syndrome characterized by fundic gland polyps (FGP) as well as an increased risk of gastric cancer. The syndrome has been recognized as a clinical entity for less than a decade. A clinical suspicion may be complex and can vary from incidental findings of FGPs at gastroscopy to obstructive symptoms with dyspepsia and vomiting. The diagnosis is established by genetic detection of a pathogenic variant in the promotor 1B region of the APC gene. As of yet there are no established clinical criteria for the diagnosis. To increase knowledge of the condition and to discuss possible genetic testing and surveillance strategies, we performed a systematic review of all reported patients with GAPPS. METHODS: This review was organized according to PRISMA guidelines. The search, which was conducted on September 7th, 2023, was applied to MEDLINE and restricted to only humans and papers in the English language. Only the studies on patients/families with GAPPS verified by identification of a pathogenic variant in the APC promoter 1B were included. RESULTS: Twelve publications with a total of 113 patients were identified. In all instances the diagnosis was genetically verified with reports of four different variants within the APC promotor 1B region. Eighty-eight patients (90.1%) had gastric polyps, of these seven patients had low-grade dysplasia and five patients had both low- and high-grade dysplasia. Thirty-seven patients (45.7%) underwent gastrectomy. There were no reports of duodenal polyps (0%). Gastric cancer was found in 31 patients (30.1%) with a median age of 48 years (range 19-75). Twenty-six patients died (23.2%) of which 19 had developed gastric cancer (73.1%). One patient was diagnosed with metastatic colorectal cancer (2.2%) and died at 73 years of age. Nineteen patients had colorectal manifestations with < 20 polyps (41.3%). CONCLUSION: Patients with a pathogenic variant in the APC promoter 1B region have an increased risk of gastric polyposis and early-onset gastric cancer. However, there is considerable variation in clinical expression and penetrance, which makes decisions on surveillance and the timing of prophylactic gastrectomy challenging.

Two-dimensional fusion imaging of planar bone scintigraphy and radiographs in patients with clinical scaphoid fracture: an imaging study.

BACKGROUND: Although magnetic resonance imaging (MRI) is now considered the gold standard in second-line imaging of patients with suspected scaphoid fracture and negative radiographs, bone scintigraphy can be used in patients with pacemakers, metallic implants, or other contraindications to MRI. Bone scintigraphy is highly sensitive for the detection of fractures, but exact localization of scintigraphic lesions may be difficult and can negatively affect diagnostic accuracy. PURPOSE: To investigate the influence of image fusion of planar bone scintigraphy and radiographs on image interpretation in patients with suspected scaphoid fracture. MATERIAL AND METHODS: In 24 consecutive patients with suspected scaphoid fracture, a standard planar bone scintigraphy of both hands was supplemented with fusion imaging of the injured wrist. Standard and fusion images were evaluated independently by three experienced nuclear medicine physicians. In addition to the diagnosis, the degree of diagnostic confidence was scored in each case. RESULTS: The addition of fusion images changed the interpretation of each of the three observers in seven, four, and two cases, respectively, reducing the number of positive interpretations of two of the observers from 11 and nine cases to six and seven cases, respectively. The degree of diagnostic confidence increased significantly in two observers, and interobserver agreement increased in all three pairs of observers from 0.83, 0.57, and 0.73 to 0.89, 0.8, and 0.9, respectively. CONCLUSION: Image fusion of planar bone scintigrams and radiographs has a significant influence on image interpretation and increases both diagnostic confidence and interobserver agreement.

Genetic diversity of the attachment (H) protein gene of current field isolates of canine distemper virus.

To characterize the variability of recent field isolates of canine distemper virus (CDV) from different hosts and geographical areas, we conducted nucleotide sequence analysis of the gene encoding the haemagglutinin (H), the attachment protein of this virus. Pronounced differences between field isolates were revealed in comparison to the Convac and Onderstepoort vaccine strains. The diversity of CDV appeared to exceed that determined for measles virus. Phylogenetic analysis also separated the field isolates of CDV from the vaccine strains and provided evidence for the existence of different contemporary genotypes of CDV. Isolates from a Greenlandic sledge dog and a Siberian seal formed a distinct lineage. The remaining isolates formed a group. This group contained two European isolates from mink and ferret, a single lineage comprising three European dog isolates, and another separate lineage of North American isolates from dog, javelina, raccoon and captive leopards.

Comparative analysis of the attachment protein gene (H) of dolphin morbillivirus.

DMV, dolphin morbillivirus, a paramyxovirus of uncertain origin recently emerged in Mediterranean dolphins. This study presents the complete nucleotide sequence of the hemagglutinin (H) gene including the gene boundaries. The single open reading frame of the DMV H gene encodes a protein of 604 residues which exhibits overall sequence characteristics similar to the H genes of other morbilliviruses. When compared to its closest homologues, measles virus (MV) and rinderpest virus (RPV), DMV has, respectively, 44 and 46% of amino acid residues in identical positions. The primary sequence of the DMV H protein is markedly less conserved than that of the fusion protein. The comparative data at the genomic level correspond with cross-neutralization studies with different morbilliviruses. Retrospective serogical studies dating back to 1983 indicate DMV-like infections in whales of the eastern Atlantic. The presented data support and extend previous studies suggesting that this novel morbillivirus is one of the phylogenetically oldest morbilliviruses known to circulate today. The relationship of DMV and established morbilliviruses to the newly emerged candidate morbillivirus infecting horse and man is discussed.

Secretion of pancreastatins from the porcine digestive tract.

Pancreastatin, a 49-amino acid peptide with a COOH-terminal glycine amide, was originally isolated from porcine pancreas, but pancreastatin immunoreactivity has been found in several neuroendocrine tissues. There are strong indications that pancreastatin is derived from chromogranin A, since the amino acid sequence 240-288 in porcine chromogranin A corresponds to pancreastatin flanked by typical signals for proteolytic processing. We have studied the effect of electric stimulation of the nervous supply to perfused porcine pancreas, antrum, nonantral stomach, and small intestine on the release of immunoreactive pancreastatin, and we characterized the molecular nature of the secreted immunoreactivity by using a radioimmunoassay specific for the COOH-terminal glycine amide of porcine pancreastatin in combination with chromatography. In all tissues nerve stimulation significantly increased the release of immunoreactive pancreastatin. The secreted immunoreactive pancreastatin was heterogeneous, consisting of pancreastatin itself, a COOH-terminal pancreastatin fragment, and NH2-terminally extended pancreastatin forms. Pancreastatin predominated in the perfusate from pancreas and antrum, whereas mainly NH2-terminally extended molecular forms were secreted from the antrectomized stomach and small intestine. The different molecular forms of pancreastatin were secreted from the perfused organs in the same molar ratio as they occur in extracts of the corresponding tissues. Thus, pancreastatin and other chromogranin A-derived peptides in organ-specific proportions regularly accompany the secretion of the peptide hormones from the gastrointestinal tissues on appropriate stimulation.

Secretion of pancreastatins from isolated, perfused, porcine adrenal glands.

Pancreastatin is a 49 amino acid peptide with a C-terminal glycine amide originally isolated from porcine pancreas. There are strong indications that pancreastatin is derived from chromogranin A, since the amino acid sequence 240-288 in porcine chromogranin A contains pancreastatin flanked by typical signals for proteolytic processing. Several molecular forms of immunoreactive pancreastatin have been reported to be present in porcine adrenal medulla, but no information on the secretion of the peptides is available. We studied stimuli for the release of immunoreactive pancreastatin from adrenal glands as well as the molecular nature of the released immunoreactivity using isolated, perfused, porcine adrenal glands with intact splanchnic nerve supply and a radioimmunoassay specific for the C-terminal glycine amide of porcine pancreastatin in combination with chromatography. Stimulation of the splanchnic nerves greatly enhanced the release of immunoreactive pancreastatin by a mechanism that seems to involve cholinergic nicotinic transmission. The pancreastatin immunoreactivity was due to large amounts of a N-terminally extended pancreastatin form, possibly corresponding to the chromogranin A(1-288) fragment and small amounts of pancreastatin and a C-terminal pancreastatin fragment. Adrenal extracts also contained unprocessed chromogranin A. We conclude that in the porcine adrenals at least 25% of chromogranin A is processed to smaller molecular forms with the pancreastatin sequence forming their C-terminus. These forms appear to be released in parallel with the catecholamines.

Characterization of immunoreactive pancreastatin in porcine tissues.

Pancreastatin is a 49 amino acid peptide with a C-terminal glycine amide originally isolated from porcine pancreas. There are strong indications that pancreastatin is derived from chromogranin A, since the amino acid sequence 240-288 in porcine chromogranin A contains pancreastatin flanked by typical signals for proteolytic processing. In the present study the distribution and molecular nature of immunoreactive pancreastatin were examined in selected porcine tissues. For this purpose a radioimmunoassay specific for the C-terminal sequence of porcine pancreastatin, that did not cross-react with porcine chromogranin A was used in combination with gel permeation chromatography and reverse-phase high-pressure liquid chromatography (HPLC). We demonstrated the presence of pancreastatin, a C-terminal pancreastatin fragment and N-terminally extended molecular forms in the examined tissues. Pancreastatin predominated in the pancreas and stomach antrum, while N-terminally extended molecular forms were mainly present in the stomach body, jejunum and adrenal gland. The specific distribution pattern of the molecular forms probably reflects a tissue-specific processing of chromogranin A.

Binding of C-reactive protein to Aspergillus fumigatus fractions.

Calcium-dependent binding of C-reactive protein (CRP) to Aspergillus fumigatus was determined by enzyme-linked immunosorbent assay. A homogenate of young hyphae was fractionated by hydrophobic interaction chromatography followed by gel filtration. High CRP-binding activity was found in a fraction of mol. wt c. 500,000 which was characterised by strong binding to the hydrophobic column. Three fractions of less conspicuous CRP-binding activity were identified (c. 500 000, 150 000 and 150 000-50 000 mol. wt respectively). In these four fractions, phosphorylcholine was detected by an anti-phosphorylcholine mouse hybridoma antibody. Some CRP-binding activity in fractions with low affinity for the hydrophobic column did not correspond closely with the presence of phosphorylcholine. It is suggested that C-reactive substance in A. fumigatus is heterogeneous. The C-reactive substances did not correspond with fractions containing major antigens (470 000 and 250 000 mol. wt respectively) which elicit a strong immune response in man.