The <Emphasis Type="Italic">TP53</Emphasis> mutational spectrum and frequency of <Emphasis Type="Italic">CHEK2*1100delC</Emphasis> in Li–Fraumeni-like kindreds

Li–Fraumeni syndrome (LFS) is a dominantly inherited cancer predisposition syndrome characterized by a wide spectrum of neoplasms occurring at young age. Germline mutations in the TP53 tumor suppressor gene have been identified in approximately 71 of LFS patients and 22 of Li–Fraumeni-like (LFL) patients. Mutations within the cell cycle checkpoint gene CHEK2 have also been reported in some patients with LFS, LFL, and phenotypically suggestive of LFS (PS-LFS) not carrying a TP53 mutation. In this study, we show that 7 of the 23 patients with LFS/LFL tested positive for deleterious mutations in p53. Fifteen of the remaining sixteen were not found to carry the CHEK2* 1100delCmutation. These results indicate that CHEK2*1100delC is not a common cause of LFS, LFL, or PS-LFS in North American kindreds not carrying a TP53 mutation. Of note, two patients were found to carry p53* R72P, which is of unknown clinical significance. Lack of segregation of this allele in one of these kindreds provides strong evidence that the R72P allele is not disease-causing. While mutations in p53 account for a proportion of patients with LFS/LFL, future studies are needed to determine if other genes are responsible for LFS/LFL families not carrying germline p53 mutations.     

Adiponectin level is reduced and inversely correlated with the degree of proteinuria in type 2 diabetic patients

AIMS: Adiponectin seems to be an important modulator for metabolic and vascular diseases. We aimed to measure plasma adiponectin levels in type 2 diabetic patients and investigate any association with the severity of proteinuria. METHODS: 80 patients (mean age, 46.9 +/- 5.1 years; body mass index (BMI), 25.8 +/- 1.98 kg/m2) and 47 healthy volunteers (mean age, 46.1 +/- 5.5 years; BMI 26.74 +/- 2.23 kg/m2) were included. Plasma adiponectin concentration, insulin levels, homeostasis model assessment (HOMA) indices, calculated glomerular filtration rate (GFR), high sensitive C reactive protein (hsCRP) and biochemistry panel were determined in all subjects. The association between adiponectin concentration and proteinuria was evaluated. Additionally, the relationship between adiponectin and hsCRP and calculated GFR were also investigated. RESULTS: Adiponectin levels in patients were significantly lower than those of controls (n = 80; 8.76 +/- 4.50 microg/ml for patients, n = 47; 24.27 +/- 5.59 microg/ml for controls, p < 0.001). Plasma adiponectin levels in patients with proteinuria were significantly lower than those without proteinuria (n = 43; 6.81 +/- 2.82 microg/ml for proteinuria, n = 37; 11.98 +/- 3.32 microg/ml for no proteinuria, p < 0.001). There was a significant negative correlation between plasma adiponectin concentrations and the degree of proteinuria (r = -0.433, p < 0.001). There were also significant negative correlations between adiponectin concentrations and insulin levels as well as HOMA index in the patient group (r = -0.322, p = 0.004; r = -0.301, p = 0.032). Additionally there was a significant negative correlation between adiponectin and hsCRP levels in the patient group (r = -0.872, p < 0.001). CONCLUSION: The results show that adiponectin is lower in patients with type 2 diabetes and the levels are negatively correlated with the severity of proteinuria.     

A peripheric neuromodulation technique for curing detrusor overactivity: Stoller afferent neurostimulation

OBJECTIVE: To perform Stoller afferent neurostimulation (SANS) with and without a low-dose anticholinergic (oxybutynin hydrochloride) in patients with detrusor overactivity and compare the results obtained with the two therapeutic approaches. MATERIAL AND METHODS: A total of 43 patients with symptoms of detrusor overactivity (frequency, urgency, urge incontinence) underwent urodynamic studies (UDS). Those in whom UDS revealed phasic detrusor overactivity were evaluated using a quality of life questionnaire and voiding diaries. Patients were randomized into two groups: Group 1 received SANS alone; Group 2 received SANS combined with a low-dose anticholinergic (5 mg of oral oxybutynin hydrochloride). Both groups were re-evaluated following 8 weeks of therapy. RESULTS: There were 21 patients in Group 1 and 22 in Group 2. The treatment response rate was 61.6% and 83.2% in Groups 1 and 2, respectively. In both groups, the best symptomatic improvements were obtained in patients with urge incontinence. The percentage decreases in the mean number of symptoms of frequency and urgency were 36.7% and 46.1%, respectively in Group 1 and 44.2% and 61.1%, respectively in Group 2. However, there were no statistically significant differences in the effects on frequency and urgency between the two groups. The anticholinergic drug was well tolerated by all patients in Group 2. One patient reported local tenderness, and a small hematoma developed in another following SANS therapy. CONCLUSION: SANS is an easy and inexpensive therapeutic method with low morbidity in patients with an overactive bladder. Combination with a low-dose anticholinergic increases the success rate without causing any significant side-effects.     

Necrotizing fasciitis in a child: a rare complication of idiopathic nephrotic syndrome

In nephrotic syndrome there is an increased tendency for bacterial infections due to immunological changes secondary to proteinuria, treatment (including steroids), and other as yet unknown causes. However, necrotizing fasciitis (NF) is an uncommon complication of the disease and has rarely been reported in nephrotic children. We report a 14-month-old boy with nephrotic syndrome who developed sepsis and NF as a complication. He was treated successfully with intensive medical and surgical treatment.     

Thrombin activatable fibrinolysis inhibitor in Behçet's disease

INTRODUCTION: Thrombin activatable fibrinolysis inhibitor (TAFI) is a procarboxypeptidase downregulating plasmin formation, thereby causing a tendency for thrombosis development. Since, Beh?et's disease (BD) is a systemic vasculitis, which is commonly complicated by arterial and venous thrombosis, we aimed to find out plasma TAFI levels in BD, compared with healthy controls. We also searched whether plasma TAFI levels were significantly different between Beh?et's subgroups with and without thrombosis. MATERIALS AND METHODS: In this study, 105 BD patients (M/F: 64/41; mean age 36+/-1 years), followed up by Ege University Rheumatology Department were enrolled. The exclusion criteria were hemophilia, hyperlipidemia, diabetes mellitus, hepatic diseases renal failure, antiphospholipid positivity, oral contraceptive use and pregnancy. Age-and sex-matched healthy controls (n=53) were also included. Plasma TAFI levels were measured by ELISA. Since TAFI is also an acute-phase reactant, we also measured other inflammatory markers such as C-reactive protein (CRP). RESULTS: Plasma TAFI levels were significantly higher in Beh?et's patients (91.1+/-7.4 ng/ml) compared with healthy controls (14.3+/-4.5 ng/ml) (P<0.001), but there were no significant difference between the subgroups with and without thrombosis. In BD, there was no correlation between plasma TAFI levels and CRP. CONCLUSIONS: Regardless of manifest thrombosis, plasma TAFI levels in BD were significantly higher than in healthy controls. High TAFI levels might possibly contribute to the thrombotic tendency in BD. Future studies investigating TAFI gene polymorphism and functional activity are clearly needed, to clarify the exact role of TAFI in Beh?et's thrombosis.     

Acute pulmonary edema in a newborn with infracardiac type total anomalous pulmonary venous return and surgical repair

Total anomalous pulmonary venous return (TAPVR) is a rare congenital pathology. Early diagnosis and urgent surgery are life-saving, especially in newborns with pulmonary venous obstruction, which is most commonly seen with infracardiac type. A three-day-old baby boy presented to another clinic with tachypnea and cyanosis. Initial work-up aimed at ruling out persistant pulmonary hypertension, respiratory distress syndrome and pneumonia. Acute pulmonary edema then developed, and on echocardiography obstructive type infracardiac TAPVR was suspected. Cardiac catheterization was done for definitive diagnosis. Urgent surgery was undertaken and pulmonary veins were anastomozed to left atrium with posterior approach. Patient was extubated at 10th day and discharged after three weeks. During one-year follow-up the patient was free of symptoms. Infracardiac type TAPVR is a rare pathology in which early diagnosis and urgent surgery with special postoperative case are mandatory for survival.     

Oxidative stress and antioxidant status in elderly diabetes mellitus and glucose intolerance patients

Increased oxidative stress and impaired anti-oxidant defense have been suggested as contributory factors for initiation and progression of complications in diabetes mellitus. Aging itself has been shown to be along with increased oxidative stress and lower anti-oxidant defense. We aimed at investigating oxidative stress and anti-oxidant enzymes in 61 elderly subjects. Fifteen healthy individuals (group 1, mean age 72.2 +/- 5.13), 13 glucose intolerant patients (group 2, mean age 71.7 +/- 4.9), 19 patients with type 2 diabetes mellitus (T2DM) without any complication (group 3, mean age 70.0 +/- 6.0), and 14 patients with T2DM with at least one complication (group 4, mean age 69.8 +/- 4.7) were included in the study. Whilst plasma levels for malondialdehyde (MDAP) and erythrocyte malondialdehyde (MDAE) were measured as markers of oxidative stress, activity of erythrocyte superoxide dismutase (SOD), glutathion peroxidase (GSH-Px), and catalase (CAT) were taken as markers of oxidative defense system. MDAP level was significantly elevated in group 4 (P = 0.001). MDAE was elevated in patients with T2DM, particularly in group 4, however, the difference between the groups was of borderline significance (P = 0.07). Whilst CAT was elevated in groups 3 and 4 compared to control subjects (P = 0.025 and 0.002, respectively), no difference was found for SOD between the groups. GSH-Px activity was found to be increased in groups 2, 3 and 4, it did not reach statistical significance (P = 0.106). There were significant correlations between CAT and MDAE (P < 0.0001, r = 0.056) and MDAP (P = 0.016, r = 0.306). These results suggest that there was an increased oxidative stress in elderly diabetics, however, this is not due to reduced erythrocyte antioxidant defense potential but, rather, increased free radical production possibly due to hyperglycemia.     

The value of scintigraphy in the evaluation of oropharyngeal dysphagia

Healthy adults can swallow boluses of 20 ml water in a single swallow. Individuals with impaired swallowing, however, may be unable to do so, instead requiring two or more swallows; this phenomenon is called piecemeal deglutition. The term dysphagia limit refers to the volume at which piecemeal deglutition occurs. The aim of our study was to investigate the potential value of scintigraphic evaluation of piecemeal deglutition and dysphagia limit in patients with dysphagia, based on correlation with the results of submental electromyography (SM-EMG) and laryngeal sensor monitoring (LS). The study population comprised 24 patients with dysphagia secondary to neurological disorders and ten normal adults, who formed a control group. In the scintigraphic evaluation, subjects underwent four separate dynamic studies using 5, 10, 15 and 20 ml of water containing 0.5 mCi technetium-99m labelled sulphur colloid, and time-activity curves (TACs) were created for each study. Static thoracic images were also recorded in order to detect airway aspiration Observation of two or more peaks on TACs within the 10-s acquisition period was considered a sign of piecemeal deglutition. If piecemeal deglutition occurred at or below 20 ml, this volume was regarded as the dysphagia limit. Piecemeal deglutition was not found in any normal subjects; by contrast, it was observed in 14 of the 24 (58%) patients on scintigraphy and in 17 (71%) patients on EMG and LS. In three patients, signs of the airway aspiration were observed on static thoracic images. Scintigraphic and electrophysiological findings were in agreement in 19 patients (79%), and the correlation between scintigraphy and the electrophysiological methods for the evaluation of dysphagia was statistically significant (r=0.57, P=0.003). The novel finding of this study is the demonstration of piecemeal deglutition and dysphagia limit on scintigraphic studies in patients with neurogenic dysphagia. Based on this finding we consider that scintigraphic evaluations of piecemeal deglutition and dysphagia limit could be of value especially in centres which do not have electrophysiological test facilities. The technique should be added to the list of standard scintigraphic methods for the evaluation of patients with oropharyngeal dysphagia.