Decreased insulin requirement in relation to GFR in nephropathic Type 1 and insulin-treated Type 2 diabetic patients.

AIMS: In the presence of impaired renal function, patients require less insulin mainly because insulin clearance is prolonged. The aim of this study was to evaluate the insulin requirement related to glomerular filtration rate (GFR) in nephropathic Type 1 and Type 2 diabetic patients. METHODS: In a retrospective study we compared insulin requirement in 20 nephropathic Type 1 diabetic patients and 20 insulin-treated Type 2 diabetic patients from the onset of overt nephropathy until the final stage of renal disease. All patients had proteinuria > 0.5 g/24 h and creatinine clearance >/= 80 ml/min per 1.73 m2 at baseline. Creatinine clearance, urinary protein excretion, glycated haemoglobin and the required insulin doses were determined 3- to 6-monthly, basal C-peptide was measured at the beginning and the end of the observation period. The required insulin doses were evaluated at creatinine clearance rates of 80, 60, 40, 20 and 10 ml/min per 1.73 m2 (or at the initiation of dialysis treatment). RESULTS: The insulin requirement of patients with Type 1 diabetes was reduced from 0.72 +/- 0.16 IU/kg per day at a creatinine clearance rate of 80 ml/min, to 0.45 +/- 0.13 IU/kg per day at a creatinine clearance rate of 10 ml/min (decrement of 38%, P < 0.001). The insulin dose required by Type 2 diabetic patients was reduced from 0.68 +/- 0.28 IU/kg per day at a creatinine clearance rate of 80 ml/min to 0.33 +/- 0.19 IU/kg per day at a clearance rate of 10 ml/min (decrement 51%, P < 0.001). The fall in GFR, urinary protein excretion and glycated haemoglobin levels was similar in the two groups. In patients with Type 2 diabetes, C-peptide levels at the beginning and the end of renal function impairment were 2.2 (0.4-7.3) vs. 2.7 (0.1-4.9) ng/ml (NS). The reduction in insulin requirement was approximately the same in patients with an initial C-peptide level < 1.0 and in those >/= 1.0 ng/ml (decrement 57% vs. 46%). CONCLUSIONS: The reduction in insulin requirement in renal insufficiency is similar in Type 1 and insulin-treated Type 2 diabetic patients. In subjects with Type 2 diabetes, the residual insulin secretion has no impact on the reduction in insulin requirement dependent on the GFR.     

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.     

Pediatric lupus versus adult lupus role of the laboratory

Systemic lupus erythematosus (SLE) is the archetypical immunologic disease. Approximately 20% of patients present in the first two decades of life. This article highlights some of the differences between pediatric and adult onset lupus.Children are defined as different from adults on the basis of age. Lupus presents with different gender ratios based on hormonal or pubertal status with more significant skewing toward female patients in the childbearing years. Female patients in the childbearing years appear to have a higher relative risk for mortality. Despite this, children have greater disease severity at onset based on the number of patients who present with significant organ inflammation, the amount of corticosteroids required and the abnormalities in lupus serologies including autoantibodies and low complements. Children present frequently with congenital and acquired complement defects. Children have an increased risk of infections that can be confused with lupus. They have a higher risk of serious pneumococcal infection and may have less protection from vaccinations received at the time of disease onset.The clinical immunology laboratory is critical in the diagnosis and treatment of pediatric SLE. The rapid analysis and transfer of laboratory results can be life saving for the child with suspected new onset lupus. The laboratory is also helpful in determining disease activity through analysis of immunologic trends over time in pediatric lupus patients. This is especially important in the noncompliant adolescent patient who has a correlation between disease activity and lupus serologic tests. Finally, the clinical immunology laboratory is an important tool for better understanding of the immunologic phenomena associated with lupus and of disease pathophysiology.     

Severe hemorrhagic radiation proctitis advancing to gradual cessation with hyperbaric oxygen

Summary We report a case of a male patient suffering from a severe hemorrhagic radiation proctitis which gradually ceased with hyperbaric oxygen. We discuss the mechanisms of chronic radiation injury and the effect of the hyperbaric oxygen. This therapy is proposed as an alternative to surgical intervention for this abnormality.     

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.     

Genetic abnormalities and CNS tumors: report of two cases of ependymoma associated with Klinefelter’s Syndrome (KS)

Objects Genetic syndromes associated with ependymoma are uncommon, with the exception of NF2. We describe two cases of ependymoma presenting with Klinefelter’s Syndrome (KS) as co-morbid condition. Materials and methods The first patient was diagnosed for KS during pregnancy; he also presented a thyroid agenesis and a deficit of methyltetrahydrofolate reductase (MTHFR); at 30 months of age he was operated on for a grade II ependymoma of IV ventricle; after a multiple-stage surgery, he underwent oral chemotherapy and stereotactic radiotherapy, but after 15 months he presented a local recurrence and died. The second patient was diagnosed for KS at the age of 16 months; at 10 years of age, due to back pain, he underwent an MRI, which showed a cauda equine tumor. He underwent surgery and radiotherapy. Histology was of mixopapillary ependymoma. Conclusion In a review of literature, various neoplasms have been described in association with KS. To our knowledge, these are the first two cases reported of ependymoma associated to KS. A retrospective study of 44 monoinstitutional ependymoma cases demonstrated association with genetic syndromes in 22%.     

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.