Interaction between two glaucoma genes, optineurin and myocilin

Myocilin (MYOC) and optineurin (OPTN) are two genes linked to glaucoma, a major blinding disease. To investigate the possible molecular interactions between MYOC and OPTN genes, we over-expressed MYOC and examined its effect on the level of endogenous OPTN in human trabecular meshwork (TM) cells and vice versa. We noted that over-expressing MYOC did not affect the OPTN level, whereas OPTN over-expression induced an up-regulation of the endogenous MYOC. This induction was also observed in other ocular and non-ocular cell types including PC12 cells. The endogenous levels of both OPTN and MYOC genes were in addition found increased when PC12 cells underwent differentiation upon treatment with nerve growth factor (NGF). Over-expression of OPTN resulted in prolonged turnover rate of MYOC mRNA but had little effect on the promoter activity of the MYOC gene. The over-expressed OPTN was localized in the cytoplasm, not translocated into the nucleus. These results indicate that interaction exists between OPTN and MYOC genes. Regulation of MYOC expression by OPTN is achieved primarily through control of the mRNA stability.     

Delayed gastric emptying rates and impaired antral motility in children fulfilling Rome III criteria for functional abdominal pain

Background Gastric sensorymotor dysfunctions have been implicated in the pathophysiology of some functional gastrointestinal disorders, such as functional dyspepsia and irritable bowel syndrome. Therefore, we hypothesized that abnormal gastric emptying and impaired antral motility are possible underlying mechanisms of symptoms in children with functional abdominal pain (FAP). Methods Hundred and two children [37 (36.3%) males, 4–14 years, mean 7.8 years, SD 2.7 years] fulfilling Rome III criteria for FAP were recruited for this study. An age and sex compatible group of healthy children (n = 20) were selected as controls [8 (40%) males, 4–14 years, mean 8.4 years, SD 3.0 years]. Liquid gastric emptying rate (GER) and antral motility parameters (amplitude of antral contractions, frequency of antral contractions and antral motility index) were assessed using a previously reported ultrasound method. Key Results Average GER (42.1% vs 66.2% in controls), amplitude of antral contractions (56.5% vs 89%), frequency of contractions per 3 min (8.5 vs 9.3), and antral motility index (4.9 vs 8.3) were significantly lower in patients with FAP compared with controls (P < 0.01). Fasting antral area was higher in patients (1.4 vs 0.6, P < 0.0001). GER negatively correlated with the scores obtained for severity of abdominal pain (r = ?0.29, P = 0.004). Conclusions & Inferences Gastric emptying rate and antral motility parameters were significantly impaired in patients with FAP and GER negatively correlated with symptom severity. These findings highlight the possible role of gastrointestinal motility abnormalities in the pathophysiology of childhood FAP.     

Is fresh frozen plasma effective for thrombocytopenia in adults with dengue fever? A prospective randomised double blind controlled study

RATIONALE: Thrombocytopenia is a common problem which causes concern and complications in dengue fever. If proven effective, intravenous fresh frozen plasma is a simple and widely available therapeutic option to manage thrombocytopenia. OBJECTIVE: To test the efficacy of fresh frozen plasma (FFP) on thrombocytopenia in patients with dengue fever. DESIGN: 109 serologically confirmed dengue patients with platelet counts <40 000/mm3 were randomised into two groups. Group A (treatment) comprised 53 patients and group B (control) 56 patients. Group A received an intravenous infusion of 3 units (600 ml) of FFP over 90 minutes. Group B received an intravenous infusion of an equal volume of isotonic saline over the same period. The primary outcome measure was the difference between pre- and post-interventional platelet counts at 12, 24 and 48 hours. RESULTS: Following Intervention, the mean platelet count was significantly higher in Group Athan in Group B at 12 hours (p=0.04; t-test). The mean platelet counts continued to be higher in Group A than in Group B at 24 and 48 hours post-intervention, but the differences were not statistically significant. CONCLUSIONS: In dengue patients with thrombocytopenia, infusion of 600 ml FFP may contribute to a significant increase in platelet count in the first 12 hours, but not thereafter.     

Cerebral microembolism and ischemic changes associated with carotid endarterectomy

Purpose: The purpose of this study is to characterize microembolic signals (MS) that occur during the various phases of carotid endarterectomy (CEA) and to consider their relationship to postoperative changes on magnetic resonance imaging (MRI). Methods: This was a retrospective study of 76 patients who underwent 78 carotid endarterectomies at a referral center. Perioperative transcranial Doppler monitoring and MRI were performed before and after CEA. The types of MS that occurred during phases of surgery were analyzed and compared with MRI changes. Results: We observed a clinical stroke in one patient (1.3%) and ipsilateral small areas of silent ischemic change on seven postoperative MRI studies (9.0%). In 95% of CEAs, MS were detected. Only those MS observed in the recovery room that occurred at a rate of more than five per 15 minutes were associated with postoperative MRI ischemic changes (p < 0.0001). Conclusions: Ischemic changes on MRI after CEA are related to postoperative MS. (J Vasc Surg 1998;27:1024-31.)