A novel mutation in the last exon of ATRX in a patient with α-thalassemia myelodysplastic syndrome

Abstract:  We describe a patient with acquired alpha-thalassemia myelodysplastic syndrome (ATMDS). A previously healthy 66-year-old man presented with hemoglobin of 9.3 g/dL, mean corpuscular volume 59 fL, and a bone marrow aspirate with increased erythroid precursors and hypolobulated megakaryocytes. Hemoglobin H inclusions were seen in most red cells after 1% brilliant cresyl blue supravital stain of the peripheral blood. At the molecular level, we identified of a novel mutation in the most 3' exon of the ATRX gene ( C GA→ T GA substitution in codon 2407) resulting in a premature termination codon (p.R2407X). This case provides further evidence for a link between ATRX mutations and ATMDS, and suggests a possible role for the conserved Q-box element in ATRX function.     

NASOGALLBLADDER DRAINAGE FOR MIRIZZI’S SYNDROME

The authors experienced a case of Mirizzi’s syndrome successfully treated with endoscopic nasogallbladder drainage (ENGBD). The patient was a 63‐year‐old man. He was admitted with abdominal pain and jaundice. Laboratory data indicated leukocytosis and elevation of serum bilirubin level. Abdominal ultrasound showed marked swelling of gallbladder and debris in the gallbladder, therefore, the authors strongly suspected Mirizzi’s syndrome. He had past history of acute myocardial infarction and treated with anticoagulation therapy. Then, the authors couldn’t perform surgical removal or percutaneous transhepatic drainage, and tried endoscopic transpapillary drainage. Endoscopic retrograde cholangiopancreatography revealed smooth stricture in the superior portion of common bile duct and occlusion of the cystic duct, and ENGBD was then performed. After ENGBD, his complaints, laboratory data, swelling of gallbladder and stricture of common bile duct were all remarkably improved.     

PEUTZ‐JEGHERS SYNDROME ASSOCIATED WITH RENAL AND GASTRIC CANCER THAT DEMONSTRATED AN STK11 MISSENSE MUTATION

A 75‐year‐old male was admitted to the gastroenterology unit of Nagoya City University Hospital due to epigastralgia after surgical treatment for right renal cancer. Endoscopy revealed advanced type 1 gastric cancer in the corpus of the stomach and multiple polypoid lesions in the stomach and duodenum. X‐ray examination of the small intestine using barium showed multiple polyps in the upper jejunum. Faint pigmentation on the palm was also detected. Peutz‐Jeghers syndrome (PJS) was diagnosed, despite a lack of family history. Total gastrectomy, resection of part of the upper jejunum and intraoperative endoscopic polypectomy of duodenal polyps was performed. This is the second reported case of PJS associated with renal cancer. We also detected a missense mutation in the tumor suppressor gene STK11 that, when mutated, is causative for PJS.     

Hormonal profiles and follicular growth in cycles with imminent ovarian hyperstimulation

Ovarian hyperstimulation syndrome is a common and serious complication of human menopausal gonadotrophin/human chorionic gonadotrophin treatment. We evaluated the changes in the pituitary and ovarian hormone profiles and ultrasonographic follicular regression in 12 patients in whom human menopausal gonadotrophin was discontinued due to 'imminent' ovarian hyperstimulation. Following discontinuation, three distinct periods were observed: (i) days 1-2, the levels of oestradiol, testosterone and prolactin, and the total number of follicles continued to rise; (ii) days 3-6, the levels of oestradiol, testosterone and prolactin declined sharply and the total number of follicles was reduced significantly, while the large and medium sized follicles continued to increase. Levels of follicle-stimulating hormone and luteinizing hormone gradually declined to reach their lowest levels by days 5-6 and then increased. (iii) Thereafter the number of follicles and steroid output declined to early follicular phase levels. We conclude that discontinuation of human menopausal gonadotrophin and withholding human chorionic gonadotrophin in cycles with laboratory signs of 'imminent' ovarian hyperstimulation syndrome, allows regression of the ovarian ultrasonographic finding and prevents the development of clinical symptoms. However, if rescue of the cycle is attempted, human chorionic gonadotrophin should be given during the first 4 days after discontinuation of stimulation.     

Cabergoline compared to levodopa in the treatment of patients with severe restless legs syndrome: results from a multi-center, randomized, active controlled trial.

We report the first large-scale double-blind, randomly assigned study to compare two active dopaminergic therapies for Restless Legs Syndrome (RLS), the dopamine agonist cabergoline (CAB) and levodopa/benserazide (levodopa). Patients with idiopathic RLS were treated with fixed daily doses of 2 or 3 mg CAB or 200 or 300 mg levodopa for 30 weeks. Efficacy was assessed by changes in the IRLS (International RLS Severity Scale) and by time to discontinuation of treatment due to loss of efficacy or augmentation. 361 of 418 screened patients (age 58 +/- 12 years, 71% females) were randomly assigned and treated (CAB: n = 178; levodopa: n = 183) in 51 centers of four European countries. Baseline IRLS total score was 25.7 +/- 6.8. The baseline-adjusted mean change from baseline to week 6 in IRLS sum score was d = -16.1 in the CAB group and d = -9.5 in the levodopa group (d = -6.6, P < 0.0001). More patients in the levodopa group (24.0%) than in the CAB group (11.9%, P = 0.0029, log-rank test) discontinued because of loss of efficacy (14.2% vs. 7.9%, P = 0.0290) or augmentation (9.8% vs. 4.0%, P = 0.0412). Adverse events (AEs) occurred in 83.1% of the CAB group and in 77.6% of the levodopa group. In both groups, most frequent AEs were gastrointestinal symptoms (CAB: 55.6%, levodopa: 30.6%, P < 0.0001). This first large-scale active controlled study in RLS showed superior efficacy of cabergoline versus levodopa after a 30-week long-term therapy. Tolerability was found more favorable with levodopa than with cabergoline.     

Factors predicting mortality in midlife adults with and without Down syndrome living with family

Background Little is known about the mortality of individuals with Down syndrome who have lived at home with their families throughout their lives. The current study evaluates the predictors, causes and patterns of mortality among co‐residing individuals in midlife with Down syndrome as compared with co‐residing individuals with ID owing to other causes. Method This paper examines mortality in 169 individuals with and 292 individuals without Down syndrome from 1988 to 2007. Dates and causes of death were obtained from maternal report, the Social Security Death Index and the National Death Index. Risk factors predicting mortality, including demographic variables, transition variables, and initial and change measures of health, functional abilities and behaviour problems, were obtained from maternal report. Results Having Down syndrome is a risk factor of mortality, net of other risk factors including older age, poorer functional abilities, worsening behaviour problems, residential relocation and parental death. The causes of death among individuals with and without Down syndrome who are in midlife and co‐residing with their families are similar, and are most commonly due to cardiovascular or respiratory problems. Conclusions The findings indicate that midlife adults with Down syndrome who co‐reside with their families generally exhibit similar causes of mortality as do midlife adults with intellectual disability owing to other causes, but show an elevated risk of mortality in midlife net of other variables, such as age and changes in functional abilities and behaviour problems.     

Hydrops Fetalis Caused by Fetal Kasabach-Merritt Syndrome

There have been only 2 previous reports of nonimmunologic hydrops fetalis (NIHF) caused by fetal Kasabach-Merritt syndrome, both of which were pathological studies. This is the first clinical case report of NIHF due to fetal Kasabach-Merritt syndrome that was prenatally diagnosed by sonography, computerized tomography, and percutaneous umbilical blood sampling.     

Bullous systemic lupus erythematosus with antiphospholipid syndrome

We report the case of a 44-year-old male with a 10-year history of manifestations of the rare form of bullous systemic lupus erythematosus (SLE) with coexisting antiphospholipid syndrome (APS) that remained undiagnosed until thrombotic-embolic episodes appeared and high titres of anticardiolipin (ACL) antibodies were detected. The patient fulfilled the criteria for SLE and the atypical cutaneous manifestations together with histopathological changes and a favourable response to sulphones were the grounds for the diagnosis of the bullous variety of SLE. Treatment with prednisolone, acenocoumarol and dapsone resulted in marked clinical improvement, reduction in antinuclear antibodies (ANAs) and normalization of ACL antibody titres.     

Sural nerve biopsies in Guillain-Barre syndrome: axonal degeneration and macrophage-associated demyelination and absence of cytomegalovirus genome.

T-cell infiltration was detected by immunohistochemistry in only 2 of 10 sural nerve biopsies from patients with Guillain-Barré syndrome (GBS). The number of endoneurial macrophages, identified by the monoclonal antibody MAC 387, was increased, compared with the number in 10 cases of axonal neuropathy. Macrophage-associated demyelination was identified in 7 and axonal degeneration in 8 cases. Cytomegalovirus (CMV) genome was not detected with the polymerase chain reaction.