Genetic predisposition to clinical manifestations in familial adenomatous polyposis with special reference to duodenal lesions

OBJECTIVES: In familial adenomatous polyposis (FAP), genetic predisposition for duodenal adenomatosis has not been investigated precisely. The aim of this study was to investigate the correlation between adenomatous polyposis coli (APC) gene mutation and duodenal adenomatosis in FAP. METHODS: APC gene mutation was determined by means of a protein truncation test in 34 patients from 25 families with FAP. The prevalence and grade of duodenal adenomatosis were compared among the proximal mutation group (exons 1-9), the distal mutation group (exons 10-15), and the undetermined groups. The correlation between the course of duodenal adenomatosis and APC gene mutation was retrospectively investigated in 19 patients. RESULTS: The prevalence of duodenal adenomatosis was lower in the proximal mutation group (44%) than in the distal mutation (100%) and undetermined (83%) groups. In patients with positive duodenal adenomatosis, the endoscopic grade did not differ among the groups. The endoscopic grade increased in two of the four patients with the proximal mutation group (50%), in three of 10 patients with the distal mutation group (30%), and in two of five patients (40%) with the undetermined group. CONCLUSIONS: Truncating APC gene mutation proximal to exon 9 may contribute to the less frequent development of duodenal adenomatosis in FAP, but severity and progression of duodenal adenomatosis do not seem to be determined by APC gene mutation alone.     

Serrated adenoma in familial adenomatous polyposis: relation to germline APC gene mutation

BACKGROUND: Serrated adenoma is a precursor of colorectal cancer. AIM: To clarify possible genotype-phenotype correlations of serrated adenomas in familial adenomatous polyposis (FAP). Patients: Eleven patients from eight families with FAP. METHODS: We performed total colonoscopy with multiple biopsies in patients. Neoplasia with a serrated glandular structure was regarded as a serrated adenoma. In each patient, germline mutations of the APC gene were determined. Colonic phenotype was compared with germline mutations of the APC gene. RESULTS: Serrated adenomas were found in three patients. These patients had macroscopic polyps <100 in number. Pedigrees with serrated adenomas had the truncating germline APC mutation at codon 161, 332, or 1556 while in the other pedigrees mutations were found between codons 554 and 1324. CONCLUSIONS: In FAP, serrated adenoma may be a phenotype characteristic of the attenuated form.     

Pregnancy-associated cytotoxic lymphoma: a report of 4 cases

The clinicopathological and biological significance of Hodgkin's disease and non-Hodgkin's lymphoma, which are infrequently encountered in women of childbearing age, remains to be clarified. We recently reviewed 4 cases of non-Hodgkin's lymphoma of the T/natural killer (T/NK)-cell phenotype, all of which were associated with pregnancy and characterized by the expression of the cytotoxic granule-associated proteins T-cell intracellular antigen-1 and/or granzyme B. The 4 cases selected had presented between November 1993 and May 1999. The criteria for selection were that the onset of clinical manifestations occurred during pregnancy or within 6 months after delivery. The patients comprised 1 patient with p80/anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL), 1 with p80/ALK-negative ALCL, and 2 with peripheral T/NK-cell lymphomas of unspecified type. The diseases followed aggressive clinical courses: 3 patients died within 6.5 months after diagnosis, and only 1 was still alive with the disease 17 months after diagnosis. The diseases appeared to progress rapidly after delivery. Maternal immunity and hormonal changes during pregnancy may be closely related to the biological behavior of these unusual tumors.This study is, to the best of our knowledge, the first to address pregnancy-associated cytotoxic lymphoma.     

Changes in Helicobacter pylori status in patients with rheumatoid arthritis under non-steroidal anti-inflammatory drugs

BACKGROUND: The role of Helicobacter pylori infection in rheumatoid arthritis (RA) patients during treatment with non-steroidal anti-inflammatory drugs (NSAID) is still unclear. METHODS: By means of endoscopy and biopsy, gastroduodenal lesions and H. pylori status were repeatedly examined in 88 RA patients at intervals ranging from 26 to 49 months. Histology and culture were applied to determine H. pylori status. Serial changes in gastroduodenal lesions and histologic score for mucosal atrophy were compared among groups classified by initial and second H. pylori status. RESULTS: There were 28 patients with continuously positive H. pylori infection (CP group), 33 patients with continuously negative H. pylori infection (CN group), 7 patients in whom H. pylori status became negative (PN group), and 20 patients in whom H. pylori status could not be determined (UD group). Age, duration and species of NSAID, disease activity of RA, gastroprotective drugs applied and the prevalence of gastroduodenal mucosal lesions were not different among the groups at either the initial or the second examination. In the PN group, the score for mucosal atrophy at the second examination was significantly lower than at the initial examination, whereas no difference was found for the CP, CN and UD groups. Overall, histologic score for mucosal atrophy was higher in H. pylori-positive patients than in H. pylori-negative patients at both initial and second examination. CONCLUSIONS: In RA patients using NSAIDs, H. pylori infection may not affect the course of gastroduodenal lesions and activity of RA, but the infection contributes to mucosal atrophy.     

Impact of Triggering Events on Outcomes of Acute Heart Failure

Background

The onset of acute heart failure is known to be associated with increased physical activity and other specific behaviors that can trigger hemodynamic deterioration. This analysis aimed to describe the distribution of triggers in patients hospitalized for acute heart failure, and investigate their effects on in-hospital outcomes.

Plasma level of homocysteine is correlated to extracranial carotid-artery atherosclerosis in non-hypertensive Japanese

BACKGROUND: Results of some epidemiologic studies in Western countries have clarified that hyperhomocysteinemia is a plausible risk factor for atherosclerotic vascular disease, but its role in Japanese communities is not known. DESIGN: A community-based cross-sectional design. METHODS: We performed a cross-sectional study of 474 elderly men aged 60-74 years in two Japanese rural communities (Noichi in southwestern Japan and Ikawa in northeastern Japan). We examined the association between plasma concentrations of homocysteine and the maximum intima-media thickness (assessed by ultrasonography). RESULTS: The prevalence of thickening was 10.7% for the lowest tertile of homocysteine level and 21.1% for the highest tertile. For the subjects without hypertension, the odds ratio for having carotid intima-media thickening was 5.8; it was significantly higher for the highest tertile of homocysteine level than it was for the lowest after adjusting for age, hypercholesterolemia, hypoalphalipoproteinemia, diabetes, and smoking by using a multiple logistic regression model. However, its correlation was not evident for those with hypertension. CONCLUSIONS: High levels of plasma homocysteine are correlated to extracranial carotid artery atherosclerosis in elderly men without hypertension in Japanese rural communities.     

Case of pseudohypoparathyroidism type 1b diagnosed as having hypocalcemia

The patient (age 46; female) had hypocalcemia without characteristic physical findings of Albright hereditary osteodystrophy in July, 1998. She had no evidence of tetany. Her blood test revealed elevated serum concentration of parathyroid hormone (PTH) in spite of hypocalcemia and hyperphosphatemia. Her Ellsworth-Howard test presented decreased excretion of both phosphate and cAMP in urine after PTH injection compared with normal range of response, indicating end-organ resistance to the actions of PTH. Finally, Ellsworth-Howard test, together with lack of clinical manifestations, resulted in diagnosis of pseudohypoparathyroidism type 1b.     

Hyperthyroid Graves' disease after hemithyroidectomy for papillary carcinoma: report of three cases

Here we report three cases of hyperthyroid Graves' disease that occurred after partial thyroidectomy for papillary carcinoma. In Case 1, the patient first developed hyperthyroidism 2 years after resection of left thyroid lobe, was treated for 2 years with antithyroid drug which was then discontinued, and relapsed with periodic paralysis after 8 years of remission. In Case 2, a hyperfunctioning remnant thyroid was noted 22 years after right hemithyroidectomy. In Case 3, where thyrotoxic symptoms became evident 7 weeks after right hemithyroidectomy, autoantibodies to thyroglobulin and thyroid microsome were positive in preoperative serum, in line with a report by others detecting these antibodies in 2 out of 3 such cases examined. Later bioassay revealed activity of thyroid stimulating antibodies in that serum, with further increase in titer in the sample taken at the clinical manifestation. Hence in Case 3, surgical stress may have altered immunological homeostasis, promoting a preclinical Graves' disease to full-blown hyperthyroidism.