A prognostic index relating 24-hour ambulatory blood pressure to cardiac events in ischemic cardiomyopathy following defibrillator implantation

Background: We assessed the role of left ventricular ejection fraction and of ambulatory blood pressure monitoring (ABPM) to predict cardiac death and heart failure in patients with defibrillator fulfilling MADIT II criteria. ABPM variables assessed included: mean 24 hours diastolic and systolic blood pressure, mean 24 hours heart rate, and pulse pressure.
Methods: We studied 105 consecutive patients (age 67 ± 11), all with a defibrillator and ejection fraction ≤ 30%).
Results: At 1-year follow-up, there were 29 events (25%), three cardiac deaths, and 26 hospitalizations for heart failure. Age, creatinine, mean 24 hours diastolic blood pressure, and mean 24 hours systolic blood pressure (but not ejection fraction) were associated with events. A prognostic index (PI) was built by age and ABPM variables, according to the formula (120 – age) + (mean 24 hours diastolic blood pressure + mean 24 hours systolic blood pressure). Receiver operating characteristic curves showed the best cutoff for PI = 220 (sensitivity 81%, specificity 71%, positive predictive value 56%, negative predictive value 88%). Cox regression analysis confirmed the significant association between lower PI (< 220) and clinical events (HR 4.8, 95% CI 1.8–12.3, P = 0.0001 for PI). Overall, 12% of patients with high PI values (≥ 220 n = 71) had clinical events at 12-month follow-up, compared with 61% of patients with low PI (< 220 n = 34) (P < 0.0001).
Conclusion: The PI built by mean 24 hours diastolic and systolic blood pressure and age could be a simple method to stratify risk of cardiac death and acute heart failure in MADIT II patients, in whom ejection fraction, uniformly depressed, is not predictive.     

Assessment of environmental stress in Parablennius sanguinolentus (Pallas, 1814) of the Sicilian Ionian coast

The blenny Parablennius sanguinolentus was selected as a useful bioindicator of environmental pollution. Chemical parameters in water and sediments from three different sampling sites along the Sicilian Ionian coast were determined and metal concentrations in fish muscle were measured. DNA fragmentation and oxidation in erythrocytes and hepatocytes was determined by the Comet assay and HSP70 expression levels were evaluated in the liver. The results show an increased level of chromium in sediments and high polycyclic aromatic hydrocarbon (PAH) concentrations in water at one site. The bioaccumulation of metals in muscle tissue shows high concentrations of lead in some samples. A high percentage of DNA damage in blood and liver cells, as well as high hepatic levels of HSP70, were found in all the sites. The results demonstrate the usefulness of an integrated chemical and biological approach for the determination of environmental stress.     

Benign adult familial myoclonic epilepsy (BAFME): evidence of an extended founder haplotype on chromosome 2p11.1-q12.2 in five Italian families

Benign adult familial myoclonic epilepsy (BAFME or FAME) is an autosomal dominant condition, characterized by shivering-like tremors of cortical origin, myoclonus, and epilepsy. Linkage to chromosomes 2p11.1-q12.2 and 8q23.1-q24.11 has been reported in Japanese and Italian families, respectively. We aimed to determine whether a common founder haplotype was shared by five BAFME families from southern Italy and attempted preliminary genotype-phenotype correlation analyses. Five Italian BAFME families were identified. One family has not been previously reported. DNA from 53 affected individuals was genotyped with highly polymorphic microsatellite markers spanning chromosomes 2p11.1-q12.2 and 8q23.1-q24.11. Multipoint linkage analysis was performed using LINKMAP 5.1 software assuming an autosomal dominant trait with 0.99 penetrance and frequency of 0.001. Significant linkage was found on chromosome 2p11.1-q12.2 and a maximum cumulative lod score of 18.5 was found for markers D2S2161 and D2S388. The haplotype "5332" of adjacent markers D2S388, D2S2216, D2S113, and D2S2175 segregates with the disease in all families indicating that the same mutation inherited from a common ancestor segregates in these families. Preliminary genotype-phenotype showed that patients carrying the disease haplotype show minor clinical differences, suggesting that expressivity of the founder mutation is not markedly influenced by other factors. The identification of causative mutations in BAFME requires an extensive and collaborative screening effort.     

Circadian activity rhythm abnormalities in ill and recovered bipolar I disorder patients

OBJECTIVES: Most physiological indicators of bipolar disorder (BPD) reflect current acute illness, and rarely have proved to be state-independent. Activity rhythms are highly abnormal in acute phases of BPD; we compared circadian activity rhythms in BPD I patients during ill and recovered states to those of normal controls to test the hypothesis that some abnormalities may persist. METHODS: We compared 36 adult DSM-IV BPD I patients during acute mania or mixed states, and during full and sustained clinical recovery, to 32 healthy controls of similar age and sex distribution, using wrist-worn, piezoelectric actigraphic monitoring for 72 h and computed cosinor analysis of circadian activity rhythms. RESULTS: We verified expected major differences between manic or mixed-state BPD I patients and matched normal controls, including phase advances averaging 2.1 h in ill BPD I patients and 1.8 h in recovered patients. Moreover, recovered BPD patients differed highly significantly from controls in several measures, including acrophase advance, higher percentage of nocturnal sleep, and lower average daily activity (mesor). Actigraphic measures among recovered BPD patients were independent of ratings of mania (on the Young Mania Rating Scale), depression (on the Hamilton Depression Rating Scale), or rating-scale scored subjective distress, as well as the type and dose of concurrent psychotropic medication. CONCLUSIONS: These findings suggest that abnormal activity rhythms, including sustained phase advances, may represent enduring (trait) characteristics of BPD patients even during clinical recovery. If verified, such indices may be useful in supporting diagnoses and as an objective phenotype for genetic or other biological studies.     

Sequencing of substance use and affective morbidity in 166 first-episode bipolar I disorder patients

Objectives:  Since bipolar disorder (BPD) patients have high rates of comorbid substance abuse, and the temporal relationships involved are unclear, we evaluated the sequencing of specific substance use and affective morbidity.
Methods:  Prospective follow-up (4.7 years) of 166 first-episode DSM-IV type I BPD patients with reliable, standardized assessments provided data for longitudinal analysis of temporal distribution of alcohol and cannabis use versus manic or depressive episodes or symptoms, using generalized estimating equation regression modeling.
Results:  By quarters, cannabis use selectively and strongly preceded and coincided with mania/hypomania, and alcohol use preceded or coincided with depression, whereas substance use was unassociated with mood states in preceding quarters.
Conclusions:  These preliminary findings suggest potentially predictive temporal associations, in which the abuse of cannabis or alcohol anticipated or corresponded with, but did not follow, affective morbidity, including selective association of cannabis with mania and alcohol with depression.     

Imaging of amyloid beta in Alzheimer's disease with 18F-BAY94-9172, a novel PET tracer: proof of mechanism

BACKGROUND: Amyloid-beta (Abeta) plaque formation is a hallmark of Alzheimer's disease (AD) and precedes the onset of dementia. Abeta imaging should allow earlier diagnosis, but clinical application is hindered by the short decay half-life of current Abeta-specific ligands. (18)F-BAY94-9172 is an Abeta ligand that, due to the half-life of (18)F, is suitable for clinical use. We thus studied the effectiveness of this ligand in identifying patients with AD. METHODS: 15 patients with mild AD, 15 healthy elderly controls, and five individuals with frontotemporal lobar degeneration (FTLD) were studied. (18)F-BAY94-9172 binding was quantified by use of the standardised uptake value ratio (SUVR), which was calculated for the neocortex by use of the cerebellum as reference region. SUVR images were visually rated as normal or AD. FINDINGS: (18)F-BAY94-9172 binding matched the reported post-mortem distribution of Abeta plaques. All AD patients showed widespread neocortical binding, which was greater in the precuneus/posterior cingulate and frontal cortex than in the lateral temporal and parietal cortex. There was relative sparing of sensorimotor, occipital, and medial temporal cortex. Healthy controls and FTLD patients showed only white-matter binding, although three controls and one FTLD patient had mild uptake in frontal and precuneus cortex. At 90-120 min after injection, higher neocortical SUVR was observed in AD patients (2.0 [SD 0.3]) than in healthy controls (1.3 [SD 0.2]; p<0.0001) or FTLD patients (1.2 [SD 0.2]; p=0.009). Visual interpretation was 100% sensitive and 90% specific for detection of AD. INTERPRETATION: (18)F-BAY94-9172 PET discriminates between AD and FTLD or healthy controls and might facilitate integration of Abeta imaging into clinical practice.     

Different content of chitin-like polysaccharides in multiple sclerosis and Alzheimer's disease brains

Chitin is an insoluble N-acetyl-glucosamine polymer coating fungi cell wall and several human parasites. It is hydrolysed by chitotriosidase (Chit); however, as chitin is absent in humans, the significance of human Chit activity is unknown. The level of plasma Chit activity positively correlates with Alzheimer's disease (AD) and multiple sclerosis (MS). A recent study revealed the presence of potentially detrimental chitin-like substances in AD brain by Calcofluor histochemistry, whilst its search in MS brains has never been described to date. Through a comparative immunohistochemical analysis we confirm the presence of abundant chitin-like deposition in AD brains but fail to demonstrate it in MS brains. Interestingly, co-localization of beta-amyloid, Calcofluor and the nuclear marker DAPI was observed. Therefore, Chit production in MS patients is induced by mechanisms other than those operating in AD. Microglia-derived Chit activity in MS may counterbalance the naturally occurring glucosamine aggregation, protecting the brain from the chitin-like substance deposition.