Microarray based comparative genomic hybridisation (array-CGH) detects submicroscopic chromosomal deletions and duplications in patients with learning disability/mental retardation and dysmorphic features

The underlying causes of learning disability and dysmorphic features in many patients remain unidentified despite extensive investigation. Routine karyotype analysis is not sensitive enough to detect subtle chromosome rearrangements (less than 5 Mb). The presence of subtle DNA copy number changes was investigated by array-CGH in 50 patients with learning disability and dysmorphism, employing a DNA microarray constructed from large insert clones spaced at approximately 1 Mb intervals across the genome. Twelve copy number abnormalities were identified in 12 patients (24% of the total): seven deletions (six apparently de novo and one inherited from a phenotypically normal parent) and five duplications (one de novo and four inherited from phenotypically normal parents). Altered segments ranged in size from those involving a single clone to regions as large as 14 Mb. No recurrent deletion or duplication was identified within this cohort of patients. On the basis of these results, we anticipate that array-CGH will become a routine method of genome-wide screening for imbalanced rearrangements in children with learning disability.     

1p36 deletion syndrome: Review and mapping with further characterization of the phenotype,a new cohort of 86 patients

Chromosome 1p36 deletion syndrome (1p36DS) is one of the most common terminal deletion syndromes (incidence between 1/5000 and 1/10,000 live births in the American population), due to a heterozygous deletion of part of the short arm of chromosome 1. The 1p36DS is characterized by typical craniofacial features, developmental delay/intellectual disability, hypotonia, epilepsy, cardiomyopathy/congenital heart defect, brain abnormalities, hearing loss, eyes/vision problem, and short stature. The aim of our study was to (1) evaluate the incidence of the 1p36DS in the French population compared to 22q11.2 deletion syndrome and trisomy 21; (2) review the postnatal phenotype related to microarray data, compared to previously publish prenatal data. Thanks to a collaboration with the ACLF (Association des Cytogénéticiens de Langue Française), we have collected data of 86 patients constituting, to the best of our knowledge, the second-largest cohort of 1p36DS patients in the literature. We estimated an average of at least 10 cases per year in France. 1p36DS seems to be much less frequent than 22q11.2 deletion syndrome and trisomy 21. Patients presented mainly dysmorphism, microcephaly, developmental delay/intellectual disability, hypotonia, epilepsy, brain malformations, behavioral disorders, cardiomyopathy, or cardiovascular malformations and, pre and/or postnatal growth retardation. Cardiac abnormalities, brain malformations, and epilepsy were more frequent in distal deletions, whereas microcephaly was more common in proximal deletions. Mapping and genotype–phenotype correlation allowed us to identify four critical regions responsible for intellectual disability. This study highlights some phenotypic variability, according to the deletion position, and helps to refine the phenotype of 1p36DS, allowing improved management and follow-up of patients.     

The spectrum of circadian blood pressure changes in type I diabetic patients

BACKGROUND: The objective of the present study was to characterize the spectrum of circadian blood pressure changes in type I diabetes at different stages of nephropathy by using two monitorings in each patient in order to avoid intra-individual variability. PATIENTS AND METHODS: A total of 80 type I diabetic subjects and the same number of age, sex and awake mean blood pressure (BP)-matched controls were included. According to urinary albumin excretion, there were 57 normoalbuminurics, 15 persistent microalbuminurics and eight proteinurics. Two 24 h ambulatory blood pressure monitorings were performed at the same urinary albumin excretion stage in absence of antihypertensive treatment for each diabetic subject and for their respective control. Blood pressure and heart rate averages during 24 h, awake, sleep, and day: night ratio were calculated. RESULTS: Seven of the eight proteinuric subjects were hypertensives, whereas hypertension was absent in the normoalbuminuric and microalbuminuric groups. The intraindividual reproducibility in diabetics showed repeatability coefficients for the 24 h systolic and diastolic pressure of 33 and 42%, respectively. This reproducibility for the day: night ratio was generally worse, 57% for systolic and 59% for diastolic. A progressive increment in the mean ambulatory BP was observed across the three groups of diabetics and the differences in BP observed were most evident during the night-time period. Though no differences in the 24 h circadian pattern were present between the normoalbuminurics and their controls, nocturnal differences were observed, not only in microalbuminurics for systolic BP (P < 0.05), but also in proteinurics for both systolic BP (P < 0.01) as well as diastolic BP (P < 0.05). No differences were observed in heart rate among the diabetic groups. The non-dipping pattern in the two monitorings was observed in 80, 58, 18 and 10% of the proteinurics, microalbuminurics, normoalbuminurics and control groups, respectively. CONCLUSIONS: Persistent abnormal circadian variability seems to be an early and frequent characteristic of type I diabetics with an increased urinary albumin excretion. Although present in some normalbuminuric subjects, the frequency of this abnormality increases as the incipient nephropathy progresses. By the time proteinuria is established, nearly all subjects present the abnormal pattern.     

Ambulatory blood pressure monitoring during antihypertensive treatment: the case of non-responder patients

OBJECTIVE: To analyse the discrepancies between casual and ambulatory blood pressure in hypertensive patients during treatment. PATIENTS AND METHODS: Patients were gathered intio two groups according to casual diastolic blood pressure (DBP) and antihypertensive treatment: group A (responders) with casual DBP < 90 mmHg administered one or more antihypertensive drugs and group B (non-responders) with DBP >/= 95 mmHg taking two or more antihypertensive drugs, maintained during three consecutive visits at 2-week intervals. For all of them casual blood pressure measurements, 24 h ambulatory blood pressure monitoring and assessment of end-organ damage were performed. RESULTS: The difference between casual blood pressure and average 24 h ambulatory blood pressure were significantly higher for group B than those observed for group A (26 versus 7 mmHg systolic, 16 versus 5 mmHg diastolic). Thirty per cent of the patients in group B and 16% in group A had casual blood pressure more than 20 mmHg higher than awake ambulatory blood pressure, whereas 8% in group B and 20% in group A had higher values for ambulatory than for casual blood pressure. In group A 8% of patients had awake DBP higher than 95 mmHg and 8% had awake DBP 85-95 mmHg. Patients of group A with awake DBP >/= 85 mmHg were younger than those with awake DBP < 85 mmHg (41.4+/-8.8 and 52.1+/-13.4 years, respectively). In patients of group B, there was less end-organ damage in the patients with awake DBP < 85 mmHg than there was in patients with awake DBP >/= 95 mmHg (World Health Organization grade I/II-III, 6/10 and 3/20, respectively). CONCLUSION: The differences between casual and ambulatory blood pressures were higher in the 'non-responder' patients. In group A the small percentage of patients who had persistently higher ambulatory blood pressure were younger. In group B one-quarter of the patients had 'normal' ambulatory blood pressure and less end-organ damage. Ambulatory blood pressure monitoring will be useful for better assessment of hypertension control in a subset of hypertensive patients.     

Diagnosis of high blood pressure in children by means of ambulatory blood pressure monitoring

Conclusions In conclusion, ambulatory BP monitoring has become a useful tool for the proper assessment of hypertension and should be performed as part of the initial evaluation in older children with persistent mild hypertension. The accurate diagnosis of whether or not hypertension is present in children may both prevent unnecessary diagnostic evaluation as well as allow early intervention so as to prevent the development of persistent hypertension and its sequelae.     

A comparison of surgical devices for grade II and III hemorrhoidal disease. Results from the LigaLongo Trial comparing transanal Doppler-guided hemorrhoidal artery ligation with mucopexy and circular stapled hemorrhoidopexy

Purpose

Little is presently known on the impact of device type for Doppler-guided hemorrhoidal artery ligation/mucopexy (DGHAL) or circular stapled hemorrhoidopexy (CSH) when a surgical treatment is considered for hemorrhoidal disease (HD). In this study, we aimed to compare the outcome in terms of adverse events and recurrence rate, of patients included in the multicenter LigaLongo RCT (ClinicalTrials.gov NCT01240772) according to the type of devices used.

Methods

In the DGHAL arm (N?=?193), the procedure was done with transanal hemorrhoidal dearterialization (THD)? (THD, Correggio, Italy) (104 patients) and with HAL-RAR? (Agency for Medical Innovations (AMI) GmbH, Feldkirch, Austria) (89 patients). In the CSH arm (N?=?184), procedure for prolapse and hemorrhoids (PPH)-03? (Ethicon Endo-Surgery, Cincinnati OH) and hemorrhoidopexy and prolapse (HEM)? (Covidien, Inc.) staplers were used in respectively 106 and 78 cases. Surgery-related morbidity at 90 postoperative days (POD) based on the Clavien-Dindo procedure-related complication score and clinical outcome in terms of recurrence and reoperation rate at 12 postoperative months (POM) was collected.

Results

Three hundred and seventy-seven patients were randomized according to HD grade. In the DGHAL arm, the number of ligations and mucopexies was higher in the AMI group (p?<?0.0001); at 90 POD, the overall morbidity was similar between the two groups. In the CSH arm, donut sizes were similar; at 90 POD, the PPH group had a higher risk of postoperative grade 1 morbidity (anal urgency or incontinence) compared to the HEM group (p?=?0.003). At 12 POM, no statistical difference was found between the two groups of each arm in terms of grade III recurrence or reoperation.

Conclusion

Postoperative morbidity and outcome at 1 year were similar regardless of the type of devices used. These findings suggest that device type has little impact on HD treatment results.

Trial registration

clinicaltrials.gov—Identifier NCT01240772