Diagnostic value of a negative single complete compression ultrasound of the lower limbs to exclude the diagnosis of deep venous thrombosis in pregnant or postpartum women: a retrospective hospital-based study

OBJECTIVE: We aimed at determining whether a negative single complete compression ultrasonography (CUS) of the lower limbs veins is a safe and accurate diagnostic method to rule out the diagnosis of deep venous thrombosis in pregnant and early postpartum women. DESIGN: Hospital-based retrospective study. SETTING: The gynaecology and vascular ultrasound units of three general hospitals in western France. PATIENTS: We identified from the hospitals databases all pregnant or up to three months postpartum women who underwent CUS for a suspicion of deep venous thrombosis between January 2002 and December 2004. METHODS: Questionnaires were sent to all women with a negative CUS. Their medical records were also checked. MAIN OUTCOME MEASURES: We assessed the three-month thromboembolic risk and its 95% percent confidence interval in women left untreated on the basis of a negative single complete CUS of the lower limbs. RESULTS: During the study period, 162 pregnant or postpartum women underwent CUS for a suspicion of deep venous thrombosis. It was positive in 44 (27%). The 118 women who had a negative CUS were sent the questionnaire. Information about the three-month follow-up was found for 107 patients (91%). None of them experienced a thromboembolic event during follow-up: 0.0% (95% CI: 0.0-3.6). CONCLUSIONS: Single complete CUS of lower limbs veins appears to be a safe method to rule out the diagnosis of deep venous thrombosis in pregnant or early postpartum women. This has to be confirmed by a prospective management study with a formal follow-up.     

Parkinson's disease, chronic hydrocarbon exposure and striatal neuronal damage: a 1-H MRS study

Several patients with Parkinson' s disease (PD) reveal an history of chronic exposure to hydrocarbon-solvents. Chronic exposure to hydrocarbon-solvents has been proposed as a risk factor for more severe forms of PD with earlier onset of symptoms and reduced response to dopaminergic therapy. A direct correlation between disease severity and exposure degree has been previously shown. Seven exposed PD patients (two with low degree exposure and five with high degree exposure), 10 unexposed PD patients matched for sex, age and Hoehn and Yahr scale (=3 in the "on" phase), and 10 unexposed PD patients matched for sex, age and l-dopa daily intake instead of disease severity (Hoehn and Yahr scale=3.5 in the "on" phase) were studied. Twenty normal subjects without previous exposure to hydrocarbon-solvents and matched for age and sex with HPD patients were studied for comparison. The purpose of the study was to assess neuronal degeneration in the striatum of exposed vs unexposed PD patients. The authors investigated whether neuronal damage/loss was detectable in the lentiform nucleus measuring N-acetylaspartate (NAA) levels by 1-H MRS. Multiple single voxel MRS water-suppressed spectra were obtained also from the white matter and the occipital lobe. NAA was normal in the lentiform nucleus of patients with low exposure as well as in patients with no exposure whereas it was decreased in PD patients with high degree exposure. White matter and occipital lobe NAA content was normal both in exposed and unexposed PD patients. Clinical expression is more severe in PD patients with previous high degree solvent exposure because of the associated post-synaptic damage of the nigro-striatal pathway.     

The Fetus with Ganglionic Eminence Abnormality: Head Size and Extracranial Sonographic Findings Predict Genetic Diagnoses and Postnatal Outcomes

BACKGROUND AND PURPOSE:Ganglionic eminence abnormalities on fetal MR imaging are associated with cerebral malformations. Their presumed genetic basis and associated postnatal outcomes remain largely unknown. We aimed to elucidate these through a multicenter study.MATERIALS AND METHODS:Between January 2010 and June 2020, seven hospitals in 2 countries performing fetal MR imaging examinations identified fetal MR imaging studies demonstrating ganglionic eminence enlargement, cavitation, or both. Cases with no genetic diagnosis, no whole exome sequencing, or no outcome of a liveborn child were excluded. Head size was classified as large (fronto-occipital diameter > 95th centile), small (fronto-occipital diameter <5th centile), or normal.RESULTS:Twenty-two fetuses with ganglionic eminence abnormalities were identified. Of 8 with large heads, 2 were diagnosed with MTOR mutations; 1 with PIK3CA mutation–producing megalencephaly, polymicrogyria, polydactyly, hydrocephalus (MPPH) syndrome; 3 with TSC mutations; 1 with megalencephaly capillary malformation syndrome; and 1 with hemimegalencephaly. Cardiac rhabdomyoma was present prenatally in all cases of TSC; mutation postaxial polydactyly accompanied megalencephaly capillary malformation and MPPH. Of 12 fetuses with small heads, 7 had TUBA1A mutations, 1 had a TUBB3 mutation, 2 had cobblestone lissencephaly postnatally with no genetic diagnosis, 1 had a PDHA1 mutation, and 1 had a fetal akinesia dyskinesia sequence with no pathogenic mutation on trio whole exome sequencing. One of the fetuses with a normal head size had an OPHN1 mutation with postnatal febrile seizures, and the other had peri-Sylvian polymicrogyria, seizures, and severe developmental delay but no explanatory mutation on whole exome sequencing.CONCLUSIONS:Fetal head size and extracranial prenatal sonographic findings can refine the phenotype and facilitate genetic diagnosis when ganglionic eminence abnormality is diagnosed with MR imaging.

The human ganglionic eminence (GE) is a focal thickening in the proliferative neuroepithelium lining the ventricles of the telencephalic lobes, situated inferolateral to the frontal horns of the lateral ventricles, and persists throughout nearly all of fetal life, longer than other proliferative areas.^1,2 It is thickest at 20 weeks, decreases in size by approximately 50% between 26 and 28 weeks'' gestation, and involutes by 34–36 weeks'' gestation; this period of rapid involution of the GE through fibrinolysis has been theorized as a contributing factor to the selective vulnerability of preterm neonates to hemorrhage in this region.² Most cortical GABAergic interneurons are generated in the GE, and they migrate to the cortex by first tangential and then radial migration. The GE also contributes to a population of thalamic neurons and is responsible for forming most of the basal ganglia. Furthermore, the GE represents an intermediate target for thalamocortical and corticothalamic axons and is a source of oligodendrocyte precursors.^1-3Abnormal persistence, enlargement, and cavitation of GEs on fetal MR imaging have been associated with markedly reduced fetal head size and underdevelopment of sulcation (microlissencephaly),⁴ as well as a range of other brain malformations, including mild partial callosal agenesis, vermis hypoplasia and rotation, cerebellar hypoplasia, ventriculomegaly, enlarged subarachnoid spaces, and molar tooth malformation.⁵Although the normal GE is demonstrable with sonography using an endovaginal 3D technique between 9 and 13 weeks'' gestation,⁶ the pathologic GE has been identified at or after the midtrimester only recently in isolated case reports,^7,8 without postnatal outcome or genetic diagnosis. Coexistence of GE abnormalities with other brain malformations of the corpus callosum, cerebellum, or microcephaly may be the impetus for fetal MR imaging in which the GE abnormality is first recognized.A very recent report⁹ on a large cohort of fetuses with GE alterations at MR imaging highlighted the more frequently associated brain anomalies. However, the authors themselves stressed that a scarcity of knowledge on the genetic substrate of such GE anomalies is the major drawback for the correct characterization and understanding of the pathophysiology. We have also noted an association of fetal GE abnormalities with extremely large and small head sizes.Better understanding of the intracranial and extracranial associations of this abnormality, its genetic causes, and postnatal outcomes for liveborn children is pivotal for the following reasons:

1. Genetic diagnosis requires accurate fetal phenotyping; lack thereof is one of the greatest barriers to the use of prenatal whole genome and exome sequencing.^10,11
2. Given the current lack of wide availability of fetal exome and genome sequencing during pregnancy, an understanding of the causes of GE abnormalities would facilitate prenatal counseling and decision-making within a clinically realistic timeframe.

We hypothesized that a multi-institutional study of prenatal sonographic findings, genetic analyses, and postnatal outcomes of fetuses with prenatal MR imaging showing an abnormality of the GE would enable us to do the following:

1. Establish the genetic abnormalities most often associated with GE abnormalities
2. Narrow the range of differential diagnoses for a given fetus by categorization based on cranial biometry and specific extracranial structural abnormalities
3. Develop a less biased picture of the relative likelihood of various genetic causes for the GE abnormalities by involving multiple subspecialist fetal MRI centers in case identification.

     

Anti-(apolipoprotein A-1) IgGs are associated with high levels of oxidized low-density lipoprotein in acute coronary syndrome

ApoA-1 (apolipoprotein A-1) is the main component of HDL (high-density lipoprotein) and stabilizes PON-1 (paraoxonase-1), which prevents lipid peroxidation and oxLDL (oxidized low-density lipoprotein) formation. Autoantibodies against apoA-1 [anti-(apoA-1) IgG] have been found in antiphospholipid syndrome and systemic lupus erythematosous, two diseases with an increased risk of thrombotic events, as well as in ACS (acute coronary syndrome). OxLDL levels are also elevated in these diseases. Whether anti-(apoA-1) IgGs exist in other prothrombotic conditions, such as APE (acute pulmonary embolism) and stroke, has not been studied and their potential association with oxLDL and PON-1 activity is not known. In the present study, we determined prospectively the prevalence of anti-(apoA-1) IgG in patients with ACS (n=127), APE (n=58) and stroke (n=34), and, when present, we tested their association with oxLDL levels. The prevalance of anti-(apoA-1) IgG was 11% in the ACS group, 2% in the control group and 0% in the APE and stroke groups. The ACS group had significantly higher median anti-(apoA-1) IgG titres than the other groups of patients. Patients with ACS positive for anti-(apoA-1) IgG had significantly higher median oxLDL values than those who tested negative (226.5 compared with 47.7 units/l; P<0.00001) and controls. The Spearman ranked test revealed a significant correlation between anti-(apoA-1) IgG titres and serum oxLDL levels (r=0.28, P<0.05). No association was found between PON-1 activity and oxLDL or anti-(apoA-1) IgG levels. In conclusion, anti-(apoA-1) IgG levels are positive in ACS, but not in stroke or APE. In ACS, their presence is associated with higher levels of oxLDL and is directly proportional to the serum concentration of oxLDL. These results emphasize the role of humoral autoimmunity as a mediator of inflammation and coronary atherogenesis.     

Correlation between cardiac biomarkers and right ventricular enlargement on chest CT in non massive pulmonary embolism

BACKGROUND: Troponin I (cTnI), myoglobin, heart-type fatty acid binding protein (H-FABP), and natriuretic peptides (BNP, NTproBNP) were all reported to be elevated in patients with pulmonary embolism (PE). METHODS: To assess the correlation between the aforementioned markers and helical computed tomography (hCT) right ventricular dysfunction (RVD) in non massive PE, we performed this prospective pilot study on 50 patients. RESULTS: Patients with RVD had significant higher natriuretic peptides prevalence than cardiomyocytes damage-related markers (48% vs 20%, P=0.006). Significant prevalence differences were observed only for natriuretic peptides when patients with RVD and those without were compared (74% vs 33% for NT-pro BNP, P=0.005 and 65% vs 22% for BNP, P=0.003). Patients with RVD had significant higher biomarkers median plasmatic values than those without (BNP: 170 vs 36 pg/ml, P=0.0027; NT-proBNP: 1369 vs 170.7 pg/ml, P=0.0024; cTnI: 0.032 vs 0 ng/ml, P=0.0034; H-FABP: 4.32 vs 2.23 ng/ml, P=0.0032; myoglobin: 36.7 vs 28.2 ng/ml, P=0.03). Significant correlations were only obtained between RV/LV index and plasmatic natriuretic peptides (NT-proBNP: r=0.36, P=0.009; BNP r=0.28; P=0.047). CONCLUSIONS: Natriuretic peptides prevalence elevation and median values are significantly higher when RVD is present and significantly correlate with hCT RVD.     

Early prenatal MR imaging diagnosis of polymicrogyria

The case of a 24-week-old fetus that showed features suggestive of focal cortical developmental anomaly at prenatal MR imaging is presented. The anomaly was confirmed to be polymicrogyria by 34-week prenatal and the 3-day postnatal MR imaging studies. The report demonstrates that the development of polymicrogyria can be assessed throughout different stages by prenatal MR imaging. In the case reported, the additional presence of periventricular heterotopia strongly suggests that a neuronal migration alteration coexisted with a postmigrational disorder.     

Comparative effect of nimesulide and ibuprofen on the urinary levels of collagen type II C-telopeptide degradation products and on the serum levels of hyaluronan and matrix metalloproteinases-3 and -13 in patients with flare-up of osteoarthritis

BACKGROUND AND AIM: Because in vitro studies have shown that nimesulide not only preferentially inhibits COX-2 but also reduces the action/release of pro-inflammatory cytokines, down-regulates the synthesis and/or activity of collagenase(s), and releases reactive oxygen species and other toxic substances from neutrophils, this study investigated whether nimesulide and ibuprofen could affect levels of biochemical markers of joint inflammation and collagen catabolism in patients with flare-up of knee or hip osteoarthritis. METHODS: Ninety patients were included in this randomised, prospective, single- blind study. They received either nimesulide (n = 45) or ibuprofen (n = 45) for a 4-week treatment period. The following parameters were analysed by ELISA: urinary levels of C-terminal cross-linking telopeptide of type II collagen (CTX-II), a marker of type II collagen breakdown; serum levels of hyaluronan (HA), a marker of synovial inflammation and hyperplasia; and circulating levels of stromelysin-1 (matrix metalloproteinase-3 [MMP-3]), collagenase-1 (MMP-1) and collagenase-3 (MMP-13). Statistical analysis used was ANOVA. RESULTS: At the end of the treatment period, nimesulide but not ibuprofen markedly reduced the urinary levels of CTX-II (p < 0.001) and the serum levels of HA (p < 0.05), two markers known to prognosticate poor outcome of the osteoarthritis disease process. Nimesulide also reduced the serum levels of both MMP-3 (p < 0.05) and MMP-13 (p < 0.001). Furthermore, in the nimesulide group, the decrease in levels of CTX-II correlated significantly with the decrease in levels of HA and MMP-13. CONCLUSION: Although nonsteroidal anti-inflammatory drugs are effective in improving pain and disability in OA patients, to date it has been unclear to what extent these drugs could affect joint metabolism and hence joint structure. Patients with flare-up of their osteoarthritis disease process exhibit enhanced levels of markers of joint inflammation and cartilage collagen breakdown, which were markedly decreased by nimesulide but not by ibuprofen.     

Epilepsy and quality of life in adults: a review of instruments

The aim of this report is to describe the state of the art of quality of life (QoL) instruments used for adults with epilepsy and to help those in the field to identify, select, and use the instruments most suitable for their purposes. We searched Medline and the Cochrane Database for articles in English, German, French, Spanish, Portuguese and Italian published by the end of 2002. Electronic retrieval was completed by hand-search. The final list included 203 articles reporting 205 studies. There were 62 validation studies and 143 clinical studies, including 7 population studies, 45 "pure" observational, 37 observational with aspects of validation and 54 experimental (38 randomized clinical trials and 16 non-randomized or non-controlled trials). Twenty-four generic and 21 specific QoL instruments were used. Eight were used in more than 10 studies, while 21 were used only once; 7/24 generic and 19/21 specific questionnaires were validated for epilepsy. The different domains considered in the 26 questionnaires specifically validated for epilepsy are listed. We classified questionnaires according to three aspects: validation, diffusion of use, and specificity of domains. Questionnaires covering all three aspects (WPSI, ESI-55, QOLIE-89, QOLIE-31, QOLIE-10, Liverpool Batteries) should be preferred when planning a QoL study in epilepsy. However, those covering only two aspects (SF-36, SEALS, EPSES, EOS, PESOS, QOLAS) could also be useful in selected situations or may become a first-choice instrument in the future, after more widespread use or complete validation. All the other instruments should at present be considered only for second choice.