Stability of hippocampal subfield volumes after trauma and relationship to development of PTSD symptoms.

BACKGROUND: The hippocampus plays a central role in post-traumatic stress disorder (PTSD) pathogenesis, and the majority of neuroimaging research on PTSD has studied the hippocampus in its entirety. Although extensive literature demonstrates changes in hippocampal volume are associated with PTSD, fewer studies have probed the relationship between symptoms and the hippocampus' functionally and structurally distinct subfields. We utilized data from a longitudinal study examining post-trauma outcomes to determine whether hippocampal subfield volumes change post-trauma and whether specific subfields are significantly associated with, or prospectively related to, PTSD symptom severity. As a secondary aim, we leveraged our unique study design sample to also investigate reliability of hippocampal subfield volumes using both cross-sectional and longitudinal pipelines available in FreeSurfer v6.0. METHODS: Two-hundred and fifteen traumatically injured individuals were recruited from an urban Emergency Department. Two-weeks post-injury, participants underwent two consecutive days of neuroimaging (time 1: T1, and time 2: T2) with magnetic resonance imaging (MRI) and completed self-report assessments. Six-months later (time 3: T3), participants underwent an additional scan and were administered a structured interview assessing PTSD symptoms. First, we calculated reliability of hippocampal measurements at T1 and T2 (automatically segmented with FreeSurfer v6.0). We then examined the prospective (T1 subfields) and cross-sectional (T3 subfields) relationship between volumes and PTSD. Finally, we tested whether change in subfield volumes between T1 and T3 explained PTSD symptom variability. RESULTS: After controlling for sex, age, and total brain volume, none of the subfield volumes (T1) were prospectively related to T3 PTSD symptoms nor were subfield volumes (T3) associated with current PTSD symptoms (T3). Tl - T2 reliability of all hippocampal subfields ranged from good to excellent (intraclass correlation coefficient (ICC) values > 0.83), with poorer reliability in the hippocampal fissure. CONCLUSION: Our study was a novel examination of the prospective relationship between hippocampal subfield volumes in relation to PTSD in a large trauma-exposed urban sample. There was no significant relationship between subfield volumes and PTSD symptoms, however, we confirmed FreeSurfer v6.0 hippocampal subfield segmentation is reliable when applied to a traumatically-injured sample, using both cross-sectional and longitudinal analysis pipelines. Although hippocampal subfield volumes may be an important marker of individual variability in PTSD, findings are likely conditional on the timing of the measurements (e.g. acute or chronic post-trauma periods) and analysis strategy (e.g. cross-sectional or prospective).

Duplication of isodicentric chromosome 13, idic(13)(p11.2), leading to pentasomy 13q in acute myeloid leukemia without maturation.

Isodicentric chromosome 13, idic(13)(p11.2), is a very rare chromosomal aberration in acute myeloid leukemia (AML). We describe here a novel case of AML without maturation, where the leukemic cells harbored double idic(13)(p11.2) and a normal chromosome 13 resulting in pentasomy 13q. Analyses were done on aspirated bone marrow cells from diagnosis. We utilized G-banding analysis, 24-color karyotyping and additional FISH analyses with various locus-specific probes to characterize the chromosomal complement. Oligonucleotide-based 180K aCGH analysis was done to search for submicroscopic imbalances. The karyotype was 47,XY,idic(13)(p11.2)x2[23]/46,XY[2]. Pantelomeric FISH analysis indicated critically short telomeres. Oligo-based aCGH analysis confirmed high copy gain of chromosome 13q and did not disclose other genomic imbalances. Reviewing the literature, this may be the second case of pentasomy 13q, since idic(13)(p11.2), when analyzed by conventional cytogenetics, is indistinguishable from i(13)(q10). Both cases were associated with immature AML and a poor outcome. We propose that idic(13)(p11.2) is a new recurrent abnormality in AML without maturation and suggest that pentasomy 13q is an early event in pathogenesis of AML through amplification of genes located on 13q.

Epicardial versus transvenous left ventricular lead placement in patients receiving cardiac resynchronization therapy: results from a randomized prospective study.

BACKGROUND: The aim of this prospective study was to determine the differences in left ventricular (LV) lead positioning for cardiac resynchronization therapy (CRT): comparing a percutaneous transvenous approach via the coronary sinus versus epimyocardial placement via a left lateral mini-thoracotomy. METHODS: Eighty consecutive patients with symptomatic left ventricular dysfunction and an indication for CRT were randomized to receive either a transvenous (n = 40) or epicardial (n = 40) LV-lead placement. Postoperative follow-up included assessment of NYHA functional class, ECG and echocardiography. RESULTS: The transvenous group had a shorter ICU stay (0.66 vs. 3.8 days) and shorter ventilation times (0.34 vs. 3.2 h). The epicardial group had less exposure to radiation (7.4 vs. 23 min) and required less use of contrast medium (3.24 vs. 61 ml). At 6 months follow-up, no major differences in LV-lead parameters (threshold, sensing, and impedance) were observed. CONCLUSION: Both epicardial and transvenous LV-lead placement for CRT therapy are safe and effective. The transvenous approach is less invasive and should be considered the standard procedure for patients without renal insufficiency. However, in a case of difficult coronary venous anatomy with the inability to position the lead as desired, epicardial LV-lead placement remains an alternative option.

Antioestrogen inhibits myelination in brains of juvenile Zebra finches.

The effects of the antioestrogen Keoxifene on the ontogenetic process of myelination, on the differentiation of neurones of telencephalic song motor centres, on cerebellar structures and on behaviour were studied in male Zebra finches. Brain differentiation was studied by using computer aided analysis of silver impregnated brain sections and by measuring soma sizes of neurones after Nissl staining. An antioestrogen induced inhibition of myelination could be detected in the song motor centre robust nucleus of the archistriatum (RA) and in the cerebellum, whereas the region magnocellular nucleus of the anterior neostriatum (MAN) showed no difference between treated birds and controls.

Kinetics of DNA synthesis in feeding-dependent and independent hepatocyte populations of rats after partial hepatectomy.

The effects of food consumption on the kinetics of hepatic DNA synthesis after partial hepatectomy (PH) have been studied in rats. Short-term (4-24 hr) fasting before or after PH resulted in depression and/or delay of DNA synthesis on days 1, 2 and 3 of regeneration. This depression was found in hepatocytes and, to a lesser extent, in littoral cells. Re-feeding resulted in an increase of DNA synthesis within 3-8 hr. The results suggest that two different hepatocyte subpopulations exist in regenerating rat liver: one which proceeds to DNA synthesis without apparent exogenous signals, and another one which needs, in addition to the specific mitogenic action of PH, food intake as a secondary permissive signal in order to initiate DNA synthesis. In the latter population food consumption appears to be required at two different stages: (1) in G0 or the early pre-replicative phase (PRP); (2) in the late PRP 3-8 hr before initiation of DNA synthesis. In the latter stage dietary protein is needed, but no so in the former. The dependence on feeding in the late PRP increases relatively with time after PH. No evidence was found to suggest a different distribution of the two cell populations throughout the liver acinus. The findings support the hypothesis that the known effects of the light-dark rhythm on the timing of DNA synthesis after PH are mediated by the natural feeding rhythm of rats fed ad libitum. In addition they offer a means for improving the synchrony of hepatocyte proliferation in regenerating rat liver.

Adaptive responses of rat liver to the gestagen and anti-androgen cyproterone acetate and other inducers. II. Induction of growth.

Treatment of female Wistar rats with cyproterone acetate (CPA) leads to considerable enlargement of the liver. The organ content of water, dry mass, protein, RNA, and DNA increased in parallel with the enlargement; only lipid accumulation showed a slight excess. The changes were maximal after treatment for 3 days and increased in a dose-dependent manner, the threshold dose being 5--10 mg CPA/kg DNA synthesis was strongly enhanced after a lag phase of 12--14 h; a maximal rate of synthesis was attained after 18--24 h. The number of parenchymal cells involved in DNA synthesis and mitosis were increased up to 20-fold. Sinusoidal cells participated only slightly in the growth process, and their number decreased relative to the number of parenchymal cells. These results indicate that CPA induces (presumably adaptive) liver growth essentially by parenchymal hyperplasia; of the model inducers used for comparison only pregenolone-16 alpha-carbonitrile (PCN) produced a similarly strong hyperplastic response while liver enlargement elicited by a alpha-hexachlorocyclohexane (alpha-HCH), phenobarbital (PB) and 3-methylcholanthrene (3-MC) was partly or exclusively due to hypertrophy. Liver growth was also observed in male rats treated with CPA, but was less pronounced in this sex. After discontinuation of treatment, liver enlargement and the increase of DNA regressed partially within 1--3 weeks; this regression seemed to be due to sequestration of old cells which were not involved in replication after CPA treatment. The relationship between induction of liver growth by CPA and hepatoma formation in rats is discussed.