Re-examination of factors associated with expansion of CGG repeats using a single nucleotide polymorphism in FMR1

In at least 98% of fragile X syndrome cases, the disease results from expansion of the CGG repeat in the 5' end of FMR1. The use of microsatellite markers in the FMR1 region has revealed a disparity of risk between haplotypes for CGG repeat expansion. Although instability appears to depend on both the haplotype and the AGG interspersion pattern of the repeat, these factors alone do not completely describe the molecular basis for the linkage disequilibrium between normal and fragile X chromosomes, in part due to instability of the marker loci themselves. In an effort to better understand the mechanism of dynamic mutagenesis, we have searched for and discovered a single nucleotide polymorphism in intron 1 of FMR1 and characterized this marker, called ATL1, in 564 normal and 152 fragile X chromosomes. The G allele of this marker is found in 40% of normal chromosomes, in contrast to 83% of fragile X chromosomes. Not only is the G allele exclusively linked to haplotypes over-represented in fragile X syndrome, but G allele chromosomes also appear to transition to instability at a higher rate on haplotypes negatively associated with risk of expansion. The two alleles of ATL1 also reveal a highly significant linkage disequilibrium between unstable chromosomes and the 5' end of the CGG repeat itself, specifically the position of the first AGG interruption. The data expand the number of haplotypes associated with FMR1 and specifically allow discrimination, by ATL1 alleles, of single haplotypes with differing predispositions to expansion. Such haplotypes should prove useful in further defining the mechanism of dynamic mutagenesis.      

Epidemiological Studies on Echinococcosis and Characterization of Human and Livestock Hydatid Cysts in Mauritania

Background

Echinococcosis/hydatidosis is considered endemic in Mauritania. The aim of this study is to present an epidemiological study on the echinococcosis in man and animals in the Nouakchott region.

Methods

The internal organs from livestock carcasses were inspected for research of hydatid cysts. The hydatid fluid was examined for research of the protoscoleces. Dogs were necropsied for the collect of Echinococcus granulosus.

Results

In the Nouakchott Hospital, 24 surgical operation of human hydatid cysts have been performed, out of which 50% were localised in the lung, 33% in the liver and 17% elsewhere. Then, the incidence rate would be of 1.2% per 100 000 inhabitants in Mauritania. In the dog, the prevalence rate is 14%. The average number of E. granulosus on the whole dogs is 172 and 1227 on the positive dogs. Concerning the livestock, hydatid cysts found in 30.1% of the dromedary, 5.5% of the cattle and 6.5 of the sheep. The fertility rate of hydatid cysts in humans (75%) and camels (76%) was significantly higher than that of sheep (24%) and cattle (23%) (P<0.0001). Hydatid infestation is characterized globally by the dominance of pulmonary localizations in humans (50%) and camels (72.7%) and in the liver in sheep (76.1%) and cattle (82.3%).

Conclusion

The differences between prevalence rates, the fertility of hydatid cysts and diversity sites localization observed in humans and camels of one hand and the sheep and cattle on the other hand, depends possibly the strain(s) diversity of E. granulosus.     

Delayed Presentation of Lateral Femoral Circumflex Artery Injury Post Cannulated Hip Screw Surgery –A Case Report

An elderly patient underwent cannulated hip screw surgery for a subcapital neck of femur fracture.Nine days post surgery, she was noted to have collapsed with a falling haemoglobin level. Computed tomography revealed a large haematoma to the thigh. Further angiography showed active bleeding from one of the branches of the lateral femoral circumflex artery (LFCA),which we postulate was caused by the sharp tip of a version guidewire used during fracture fixation surgery. Iatrogenic injury during hip fracture fixation is a rare event,particularly to the circumflex branches of the profunda femoris artery (PFA), and may occur from hard wire use intraoperatively or from the fracture itself. The LFCA branches laterally from the PFA, runs anterior to the femoral neck,where we suspect it was injured in our case.Whilst a version wire is a useful radiological guide intra-operatively,manually clearing a passage for its insertion into the femoral head/neck junction and using the blunt end is recommended. A combination of acute swelling in the operated region and falling haemoglobin post surgery should alert the clinician to possible vascular injury.Compared to duplex ultrasonography,CT angiography remains the gold standard in its specificity and sensitivity for diagnosing arterial injuries.With early recognition and prompt radiological intervention, this rare complication of fracture fixation surgery can be treated without the need for further surgery.     

Autonomic neuropathy tests correlate with left ventricular mass and cardiac diastolic function in normotensive patients with type 2 diabetes mellitus and without left ventricular hypertrophy

BACKGROUND:

Hypertensive diabetic patients, when compared with essential hypertensive patients, have a higher left ventricular mass index (LVMI) and an impaired cardiac diastolic function (CDF). Autonomic neuropathy (AN) could contribute to this finding.

OBJECTIVE:

To evaluate the relationship between AN tests, and LVMI and CDF in normotensive patients with type 2 diabetes mellitus (DM2) and without AN symptoms or left ventricular hypertrophy.

METHODS:

In 21 normotensive patients with DM2 (group 1) and 16 control subjects (group 2), LVMI and CDF were evaluated using atrial deceleration time, isovolumic relaxation time, E wave, A wave and E/A wave ratio. AN tests performed included a deep breathing test, Valsalva manoeuvre and lying-to-standing test.

RESULTS:

Groups did not differ in clinical and echocardiographic characteristics. None of the patients in either group presented with left ventricular hypertrophy. In group 1, there were correlations between the deep breathing test and LVMI (r=−0.6; P<0.01) and between the deep breathing test and E/A wave ratio (r=0.4; P<0.05). No correlations were found in the control group.

CONCLUSION:

In DM2 patients, AN tests correlated with LVMI and CDF before left ventricular hypertrophy, hypertension, impaired CDF and diabetic AN symptoms were present. The present study suggests that AN tests could be regularly performed in DM2 patients. Any abnormalities in tests should be followed by a cardiac evaluation.     

How large is the lung recruitability in early acute respiratory distress syndrome: a prospective case series of patients monitored by computed tomography

Introduction  

The benefits of higher positive end expiratory pressure (PEEP) in patients with acute respiratory distress syndrome (ARDS) have been modest, but few studies have fully tested the "open-lung hypothesis". This hypothesis states that most of the collapsed lung tissue observed in ARDS can be reversed at an acceptable clinical cost, potentially resulting in better lung protection, but requiring more intensive maneuvers. The short-/middle-term efficacy of a maximum recruitment strategy (MRS) was recently described in a small physiological study. The present study extends those results, describing a case-series of non-selected patients with early, severe ARDS submitted to MRS and followed until hospital discharge or death.     

Bioactivity-guided identification and cell signaling technology to delineate the immunomodulatory effects of Panax ginseng on human promonocytic U937 cells

Background  

Ginseng is believed to have beneficial effects against human diseases, and its active components, ginsenosides, may play critical roles in its diverse physiological actions. However, the mechanisms underlying ginseng's effects remain to be investigated. We hypothesize some biological effects of ginseng are due to its anti-inflammatory effects.     

The pathophysiology and clinical relevance of platelet heterogeneity

Recent studies on platelet heterogeneity support the hypothesis that platelet production is regulated to maintain a constant functional platelet mass. In concept this form of regulation is analogous to the manner by which RBC production is controlled to maintain the oxygen- carrying capacity of blood. The platelet mass appears to correlate more closely with platelet function than the platelet count alone, since several factors in addition to the platelet count have been shown to influence the platelets' hemostatic function. These factors include platelet size, density, age, and previous hemostatic interactions. Application of these concepts to clinical problems has provided important insights into platelet physiology and reactivity. Failure to account for differences in platelet heterogeneity among individuals may introduce significant errors in the interpretation of data from laboratory and clinical investigations. However, despite advances, a number of practical issues remain to be resolved before measurements of platelet heterogeneity become accepted as routine clinical tests and are used in the diagnosis of pathologic states.