Is the search for right-to-left shunt still worthwhile?

OBJECTIVES: Patent foramen ovale (PFO) is a common disembryogenic defect with well-attested prevalence but dubious etiopathogenetic linkage with cryptogenic stroke and different clinical conditions. Transcranial color-coded Doppler (TCCD) assures high accuracy in diagnosing right-to-left shunt (RLS) and its functional aspects. Aim of the study was to evaluate RLS prevalence and degree in subjects submitted to TCCD for conditions theoretically associated or caused by paradoxical embolism to the brain. METHODS: PFO assessment, performed in 10 major diagnostic categories and a control group, followed a standardized protocol with a 10 or 20 microbubbles (MB) cutoff to identify any or only large RLS, respectively. RESULTS: Among 2113 patients, a significant larger RLS prevalence was found in stroke (53.3%), TIA (45.7%) and migraine with aura (39.7%) when compared with non-migraineurs controls (25.5%). RLS degree was significantly higher in stroke and TIA patients: The ROC curve from MB load data helped to identify new cutoff values for both normal breathing (42 MB) and Valsalva (139 MB) tests. From logistic regression, a family history for PFO, ASA, and male gender appeared independent predictors of a RLS. By contrast, RLS seemed independent of white matter abnormalities presence on brain neuroimaging or stroke mimics. CONCLUSIONS: In addition to recently defined criteria, genetically determined inheritable traits and epidemiologic characteristics (male gender) should be taken into account when assessing PFO and related cerebrovascular risk profile. A newly defined threshold in TCCD MB count is suggested to discriminate shunts related to stroke and TIA from innocent ones.

The contribution of germline rearrangements to the spectrum of BRCA2 mutations.

BACKGROUND: Few germline BRCA2 rearrangements have been described compared with the large number of germline rearrangements reported in the BRCA1 gene. However, some BRCA2 rearrangements have been reported in families that included at least one case of male breast cancer. OBJECTIVE: To estimate the contribution of large genomic rearrangements to the spectrum of BRCA2 defects. METHODS: Quantitative multiplex PCR of short fluorescent fragments (QMPSF) was used to screen the BRCA2 gene for germline rearrangements in highly selected families. QMPSF was previously used to detect heterozygous deletions/duplications in many genes including BRCA1 and BRCA2. RESULTS: We selected a subgroup of 194 high risk families with four or more breast cancers with an average age at diagnosis of < or = 50 years, who were recruited through 14 genetic counselling centres in France and one centre in Switzerland. BRCA2 mutations were detected in 18.6% (36 index cases) and BRCA1 mutations in 12.4% (24 index cases) of these families. Of the 134 BRCA1/2 negative index cases in this subgroup, 120 were screened for large rearrangements of BRCA2 using QMPSF. Novel and distinct BRCA2 deletions were detected in three families and their boundaries were determined. We found that genomic rearrangements represent 7.7% (95% confidence interval 0% to 16%) of the BRCA2 mutation spectrum. CONCLUSION: The molecular diagnosis of breast cancer predisposition should include screening for BRCA2 rearrangements, at least in families with a high probability of BRCA2 defects.

Does transcatheter closure of patent foramen ovale really "shut the door?" A prospective study with transcranial Doppler.

BACKGROUND AND PURPOSE: Transcatheter closure of patent foramen ovale (PFO) is increasingly being performed and monitored with transthoracic or transesophageal echocardiography, whereas contrast-enhanced transcranial Doppler (ce-TCD), which probably represents the most suitable tool to quantify right-to-left shunt (RLS) in the brain vessels, has been systematically overlooked. Our goal is to prospectively assess efficacy and safety of PFO transcatheter closure using ce-TCD. METHODS: A total of 140 consecutive patients (mean age, 46+/-13 years; male/female ratio, 63/77) with PFO-related large RLS and no other recognized cause of focal cerebral ischemia underwent transcatheter closure. TCD was done preoperatively and 1 month after the procedure in all patients, after 3 months in 120, after 6 months in 112, and after 1 year in 104 patients. RESULTS: Implantation was successful in all patients. During Valsalva strain, a large shunt was still detectable in 31 of 140 (22%), 15 of 120 (13%), 9 of 112 (8%), and 9 of 104 (9%) patients at the 1-, 3-, 6-, and 12-month visits, respectively. Periprocedural and postprocedural complications included atrial fibrillation in 8% and scintillating scotomata in 6% of patients. During the 1-year follow-up period, only 1 transient ischemic attack was recorded in a patient with paroxysmal atrial fibrillation and complete PFO closure. CONCLUSIONS: Transcatheter PFO closure in patients with cryptogenic stroke and large RLS may be less successful than reported previously. TCD appears the ideal tool to follow up the closure process and to identify early, during follow-up, those patients who will be left with a significant shunt. Atrial fibrillation is more common than believed previously and may underlie the occurrence of further cerebrovascular events despite complete PFO closure. Irritative visual phenomena may occur as a consequence of nickel toxicity.

Comparison of enoxaparin and unfractionated heparin on thrombin generation in acute coronary syndromes without ST-segment elevation.

Recent clinical trials have demonstrated a better ability of low-molecular-weight heparin, compared to unfractionated heparin, in reducing ischemic cardiac events in patients with acute coronary syndromes without ST-segment elevation. No data are available concerning the in-vivo comparison of enoxaparin and unfractionated heparin on thrombin generation in patients with unstable angina or non-Q-wave myocardial infarction. We measured the plasma levels of prothrombin fragment 1+2 (a marker of prothrombin activation) and thrombin/antithrombin complex (a marker of thrombin generation) in 45 patients with non ST-elevation acute coronary syndromes who were randomized to receive enoxaparin, 3000 IU anti-Xa as an i. v. bolus, followed by 70 IU anti-Xa/Kg every 8 h for 3 days (23 pts. Group 1) or a bolus of 100 IU/kg of unfractionated heparin followed by infusion for 3 days titrated to maintain the aPTT between 70 and 90 s (22 pts, Group 2). Plasma levels of prothrombin fragment 1+2 reduced significantly at 3rd h of treatment in both groups (-42% in Group 1 and -45% in Group 2), reached the lowest plasma concentration at the 24th h and exhibited a slight increase at the 72nd h; no differences were observed between the two groups at any time points. Plasma thrombin/antithrombin complex levels had a similar behaviour: reduced markedly in both groups at the 3rd h (-52% in Group 1 and -46% in Group 2), remained lower during the first two days and slightly rose at 72nd h. No differences between the two groups in plasma levels of this marker were apparent during drug infusion. In Group 1 the aPTT did not show significant changes: in Group 2 the mean value of aPTT doubled the basal value at any time point of determination. Both enoxaparin and unfractionated heparin produced a marked and similar reduction of thrombin generation. Other unknown mechanisms might explain the different clinical effects of the two heparins.

Amplatzer Muscular VSD Occluder for catheter closure of a 20 mm hypertensive patent ductus arteriosus. A case report and literature review.

The treatment of very large patent ductus arteriosus (PDA) was thought to be solely surgical. There is not enough experience in transcatheter closure of large hypertensive PDA. In this report, successful catheter closure of a large and hypertensive ductus using the Amplatzer Muscular VSD Occluder and a literature review are presented.

Silent brain embolism during transcatheter closure of patent foramen ovale: a transcranial Doppler study.

The aim of this report is to quantify the amount of spontaneous microembolism detected in brain vessels by transcranial Doppler (TCD) during transcatheter closure of right-to-left shunt (RLS). We examined 29 patients who had had a stroke or a transient ischaemic attack (17 females and 12 males; mean age 45+/-15 years). They all underwent TCD monitoring during the procedure and microembolic signals (MES) were recorded. Detection of MES was distributed as follows: during femoral catheterisation in 8 patients (25%), during atrial catheterisation in 5 patients (17%), during transeptal crossing in 14 patients (48%), during left disc opening in 28 patients (96%) and during right disc opening in 7 patients (24%). The highest rates of MES were observed during left disc opening and less during transeptal crossing with an average count of 31 (range 3-135) and 3 (range 1-18) respectively. Brain embolism occurs throughout the procedure after femoral catheterisation for PFO closure. Our results indicate that the majority of MES reached the brain during the opening of the left disc in the left atrium: 28/29 patients exhibited MES with an average of 31 (3-135), thus supporting the notion that gas embolism accounted for the findings.

Migraine: traditional or "innovative" treatment? A preliminary case-control study.

The aim of this preliminary case-control study was to compare, in patients with migraine and PFO, transcatheter closure of PFO vs. medical treatments. Twelve patients were treated with antimigraine drugs and twelve underwent percutaneous transcatheter closure. All patients were followed-up for 12 months. Our preliminary results seem to confirm that, compared to medical treatment, PFO closure is by far more effective in reducing both frequency, duration and intensity of migraine attacks. Furthermore, the occurrence of prodromal aura is almost abolished.

Bovine cumulus-corona cells in maturing oocytes. A scanning electron microscopic study.

The ultrastructural features of cumulus-corona cells surrounding maturing oocytes in bovine were studied by means of scanning electron microscope in order to provide a detailed description of their surface changes during oocyte maturation. Cumulus corona cell complexes of immature oocytes showed a compact aspect with narrow intercellular spaces. The spaces around mature oocytes enlarged because they were progressively filled with abundant microfibrillar extracellular matrix. In cumulus corona cells complexes of immature oocytes very numerous long and filiform microvilli were observed, whereas the cumulus corona cell surface surrounding mature oocytes showed occasional large cytoplasmic protrusions along with scanty microvilli and numerous blebs.