Altered resting state complexity in schizophrenia

The complexity of the human brain's activity and connectivity varies over temporal scales and is altered in disease states such as schizophrenia. Using a multi-level analysis of spontaneous low-frequency fMRI data stretching from the activity of individual brain regions to the coordinated connectivity pattern of the whole brain, we investigate the role of brain signal complexity in schizophrenia. Specifically, we quantitatively characterize the univariate wavelet entropy of regional activity, the bivariate pairwise functional connectivity between regions, and the multivariate network organization of connectivity patterns. Our results indicate that univariate measures of complexity are less sensitive to disease state than higher level bivariate and multivariate measures. While wavelet entropy is unaffected by disease state, the magnitude of pairwise functional connectivity is significantly decreased in schizophrenia and the variance is increased. Furthermore, by considering the network structure as a function of correlation strength, we find that network organization specifically of weak connections is strongly correlated with attention, memory, and negative symptom scores and displays potential as a clinical biomarker, providing up to 75% classification accuracy and 85% sensitivity. We also develop a general statistical framework for the testing of group differences in network properties, which is broadly applicable to studies where changes in network organization are crucial to the understanding of brain function.     

The significance of resin-embedded bone marrow histology for the detection of rare cells in the bone marrow

Different methods for identification of cell types in resin sections of undecalcified bone marrow cores are described and discussed. These newer immuno-histo-cyto-chemical technics are usefull for the visualization of cell types and may provide a valuable tool for the detection of rare cells in marrow sections.     

A case of acute humoral rejection in liver transplantation: successful treatment with plasmapheresis and mycophenolate mofetil

We present a case of a 23-year-old female who underwent orthotopic liver transplantation (OLTx) for biliary atresia, 22 years after a failed Kasai operation. Unusually, her postoperative course was complicated by severe acute humoral rejection. In this case report, we discuss her management as well as the role of plasmapheresis in treating allograft dysfunction secondary to acute humoral rejection in liver transplant patients.     

Double-Blind Study of Alprazolam, Diazepam, Clonidine, and Placebo in the Alcohol Withdrawal Syndrome: Preliminary Findings

Both a reduction in the inhibitory effects of GABA (disinhibition) and activation of the sympathetic nervous system are manifested during the alcohol withdrawal syndrome. This study was designed to explore the relative efficacy of medications that differentially affects these two biological systems: the benzodiazepines, which attenuate GABAergic disinhibition, and the α₂-adrenergic receptor agonists, which decrease sympathetic activation. The benzodiazepine diazepam ( n = 6), the α₂-receptor agonist clonidine ( n = 7), the benzodiazepine alprazolam (that is also purported to have α₂-receptor agonist properties) ( n = 6), and placebo ( n = 6) were evaluated in their effectiveness in decreasing signs and symptoms of alcohol withdrawal. Drug-free, alcohol-dependent patients were administered 1 of the 4 medications in a double-blind design until symptoms of withdrawal, as measured by the Clinical Instrument Withdrawal Assessment for Alcohol-Revised, were successfully treated. Alprazolam was significantly more efficacious than both clonidine and placebo in decreasing withdrawal symptoms. Diazepam was more effective than clonidine and placebo on some measures of withdrawal. Clonidine decreased systolic blood pressure significantly more than the other two active drugs and placebo, but was no more effective than placebo in decreasing other symptoms of withdrawal. Alprazolam did not significantly decrease blood pressure compared with diazepam or placebo. Despite the small sample size, these preliminary findings suggest that the efficacy of alprazolam in the treatment of alcohol withdrawal is related to its effect at the benzodiazepine receptor and not its α₂-receptor agonist properties.     

Quantitative magnetic resonance imaging in the calcaneus and femur of women with varying degrees of osteopenia and vertebral deformity status.

Quantitative magnetic resonance imaging (QMRI) allows measurement of two parameters that are related to the integrity of the trabecular bone: R2*, the rate constant of the free induction signal, and trabecular bone volume fraction (BVF), the counterpart of apparent density. In this work, R2* and BVF were measured in 68 women (mean age, 58.2 +/- 9.5 years) of varying spinal bone mineral density (BMD) T scores (mean, -1.37 +/- 1.54) and vertebral fracture status on a commercial 1.5 T whole-body imager using customized image acquisition and processing techniques. Twenty-five of the patients had vertebral fractures, characterized by the total cumulative deformity burden exceeding 200%. R2* was measured in the calcaneus and proximal femur and BVF could be measured in the calcaneus only. On a pixel-by-pixel basis, calcaneal R2* and BVF within each subject were highly positively correlated (r2 = 0.61 +/- 0.11) but the correlation of region-of-interest (ROI) means for different calcaneal sites among patients was weaker (r2 = 0.34; p < 0.0001). The strongest discriminator of vertebral deformity was R2* of the calcaneus, which was lower in the fracture group, consistent with lower trabecular density. Among the calcaneal sites examined, the subtalar region, a location characterized by dense nearly horizontal trabeculae that transmit the stresses imparted by body weight from the tibia to the heel, best discriminated the two groups (p = 0.0001), with 77% diagnostic accuracy as determined from the area under the receiver operating characteristic (ROC) curve (compared with 66% for vertebral BMD). The cavum calcanei, an anterior site of low trabecular density, and the tuber calcanei (the location ordinarily used for ultrasound measurements) also had significantly reduced R2* in the fracture group (p < 0.005 and p = 0.01, respectively). The R2av*, computed as the average of all pixels in the calcaneus, was a strong discriminator as well (p < 0.005). On the other hand, calcaneal BVF was only marginally discriminating (p = 0.05). Among the BMD sites examined, the lumbar spine (average L1-L4) was significant (p = 0.005, 66% diagnostic accuracy), as was the femoral neck (p = 0.01). The data suggest the calcaneus to be suited as a surrogate site to assess vertebral osteoporosis and that R2* is sensitive to alterations in bone quality not captured by density.     

Intensive and sequential combination chemotherapy for aggressive malignant lymphomas (protocol LNH-80)

Ninety-seven patients with aggressive malignant lymphoma (ML) were treated with an intensive and sequential chemotherapy (protocol LNH-80). There were 42 patients with intermediate grade ML, 53 patients with high-grade ML, and two patients with true histiocytic ML. Most of the patients were in advanced stage: 21 stage III and 61 stage IV. The LNH-80 protocol schedule comprised three phases: (1) induction with three courses of an intensified CHOP-Bleo (cyclophosphamide, doxorubicin, vindesine, methylprednisolone, and bleomycin); (2) consolidation with cytarabine, followed by high-dose methotrexate and folinic acid rescue, then asparaginase; and (3) final intensification with two courses of CVAP-Bleo (cyclophosphamide, teniposide, cytarabine, methylprednisolone, and bleomycin). CNS prophylaxis included one injection of methotrexate during each induction course and the drugs of the consolidation phase. In cases of initial CNS localization, cranial radiotherapy was added. Eighty-four patients (87%) went into complete remission (CR), 18 (21%) of whom relapsed, usually during the phase of treatment or within 6 months of completing chemotherapy. Sixty-three patients are alive with an overall median follow-up of 24 months. The median survival time and the median disease-free survival have not been reached, and the survival curve seems to have plateaued at above 60%. There was no statistical difference between intermediate-grade ML (CR 90%, relapse 18%) and high-grade ML (CR 84%, relapse 24%). The toxicity of this treatment is mainly encountered during the induction phase: almost all patients had short-term neutropenia, less than 0.500 g/L in 57, with a documented infection in 25. Overall treatment-related mortality was 6%, with four patients dying during the induction phase.     

Location of Talar Osteochondral Defects in Chronic Lateral Ankle Instability in an Asian Population

Osteochondral defect of the talus is traditionally described to involve the anterolateral and posteromedial portion of the talar dome in patients with chronic lateral ankle instability. Recent studies challenged this notion with advances in preoperative imaging and arthroscopy. Since Asian patients are more prone to ligamentous laxity, we postulate that the morphology and severity of osteochondral defects may be different in this population. Intraoperative records of 272 patients undergoing modified Broström-Gould procedure were reviewed for arthroscopic evidence of osteochondral defects. We characterized the morphology according to an anatomical 9-grid classification. Talar osteochondral defects were seen in 52 (19.1%) patients with a double lesion present in 1 patient. Medial-sided lesions account for nearly 3-quarters (n = 38, 73.1%) of all lesions and tend to be larger (79.4 ± 55.7 mm² vs 51.0 ± 28.6 mm², p =.08). There was no osteochondral defect seen in the central zones. There was no significant gender or age differences between patients with medial and lateral lesions. The most commonly performed procedure was microfracture. Osteochondral defects are commonly encountered in our Asian patients undergoing surgery for chronic lateral ankle instability. Contrary to published data, medial lesions are prevalent with no central lesions seen.