Compartmental volumetry of the superior temporal gyrus reveals sex differences in schizophrenia--a post-mortem study

Brain imaging studies have shown superior temporal gyrus (STG) volume loss and abnormal patterns of asymmetry in schizophrenia; however, these are not consistent findings. Post-mortem volumetry of three different STG regions (defined by external landmarks) was used to compare 17 schizophrenics to 20 age- and sex-matched controls. Total STG volumes did not differ. A significant gray-matter volume reduction in schizophrenics was observed in the middle compartment (reaching from the mamillary body to the lateral geniculate body). This may have been related to reduced length of this region, particularly in schizophrenic females. These results reflect the problematic issue of defining boundaries of macroscopic brain structures.     

An assessment of the osteoinductive potential of commercial demineralized freeze-dried bone in the murine thigh muscle implantation model

Early studies have demonstrated that implantation of laboratory preparations of demineralized freeze dried bone (DFDB) into the thigh muscle of mice induces ectopic osteoinduction. However, with the development of commercial preparations of DFDB for clinical use, concerns have been raised as to the osteoinductive properties of such preparations. The aim of this study was to investigate the osteoinductive potential of some commercial preparations of DFDB compared to a newly developed product which incorporates DFDB into a collagen sponge. Commercial preparations of DFDB or the DFDB/collagen sponge were inserted into the thigh muscles of 60 adult Swiss CD-1 mice. At the completion of each experimental period (7, 14, 30, 90 and 180 days), the animals were sacrificed, and the hindquarters of the mice were radiographed. The area where each graft had been placed was then excised, processed for light microscopy, and stained with hematoxylin and eosin or von Kossa's stain. Histological analysis of the DFDB/collagen sponges demonstrated significant remineralization which increased with time. Remineralization of the DFDB/collagen sponges was verified by radiographs which showed a significant increase in radiopacity over time. There was no radiographic evidence of mineralized tissue formation or remineralization in any of the commercial DFDB samples studied. At all time points studied, histological analyses failed to show evidence of bone formation for any of the preparations. The results suggest that commercially available DFDB is not osteoinductive in the murine model and question the use of such materials in clinical periodontics. The results found for the DFDB/collagen sponge indicate a different mechanism of activity from DFDB as evidenced by its rapid remineralization. The role this remineralization process has in osteoinduction is unknown and requires further study.     

The radiographic and imaging characteristics of porous tantalum implants within the human cervical spine

STUDY DESIGN: Seven cadaveric cervical spines were implanted with a porous tantalum spacer and a titanium alloy spacer, and their radiographic and imaging characteristics were evaluated. OBJECTIVE: To determine the radiographic characteristics of porous tantalum and titanium implants used as spacers in the cervical spine. SUMMARY OF BACKGROUND DATA: Anterior decompressive surgery of the disc space or the vertebral body creates a defect that frequently is repaired with autologous bone grafts to promote spinal fusion. Donor site morbidity, insufficient donor material, and additional surgical time have spurred the development of biomaterials to replace or supplement existing spinal reconstruction techniques. Although the promotion of a solid bony fusion is critical, the implanted biomaterial should be compatible with modern imaging techniques, should allow visualization of the spinal canal and neural foramina, and should permit radiographic assessment of bony ingrowth. METHODS: Cadaveric spines containing the implants were imaged with plain radiography, computerized tomography, and magnetic resonance imaging. The image distortion produced by the implants was determined qualitatively and quantitatively. RESULTS: The tantalum and titanium spacers were opaque on plain radiographic films. On computed tomographic scans, more streak artifact was associated with the tantalum implants than with the titanium. On magnetic resonance imaging, the porous tantalum implant demonstrated less artifact than did the titanium spacer on T1- and T2-weighted spin echo and on T2*-weighted gradient-echo magnetic resonance images. Overall, the tantalum implant produced less artifact on magnetic resonance imaging than did the titanium spacer and therefore allowed for better visualization of the surrounding bony and neural structures. CONCLUSION: The material properties of titanium and porous tantalum cervical interbody implants contribute to their differential appearance in different imaging methods. The titanium implant appears to image best with computed tomography, whereas the porous tantalum implant produces less artifact than does the titanium implant on several magnetic resonance imaging sequences.     

Hypertonicity regulates the function of human neutrophils by modulating chemoattractant receptor signaling and activating mitogen-activated protein kinase p38

Excessive neutrophil activation causes posttraumatic complications, which may be reduced with hypertonic saline (HS) resuscitation. We tested if this is because of modulated neutrophil function by HS. Clinically relevant hypertonicity (10-25 mM) suppressed degranulation and superoxide formation in response to fMLP and blocked the activation of the mitogen activated protein kinases (MAPK) ERK1/2 and p38, but did not affect Ca2+ mobilization. HS did not suppress oxidative burst in response to phorbol myristate acetate (PMA). This indicates that HS suppresses neutrophil function by intercepting signal pathways upstream of or apart from PKC. HS activated p38 by itself and enhanced degranulation in response to PKC activation. This enhancement was reduced by inhibition of p38 with SB203580, suggesting that p38 up-regulation participates in HS-induced enhancements of degranulation. HS had similar effects on the degranulation of cells that were previously stimulated with fMLP, but had no effect on its own, suggesting that HS enhancement of degranulation requires another signal. We conclude that depending on other stimuli, HS can suppress neutrophil activation by intercepting multiple receptor signals or augment degranulation by enhancing p38 signaling. In patients HS resuscitation may reduce posttraumatic complications by preventing neutrophil activation via chemotactic factors released during reperfusion.     

Hepatic export of glutathione and uptake of constituent amino acids, glutamate and cysteine, in broilers in vivo

This study was conducted to document the glutathione (GSH) cycle (interorgan circulation of GSH) in broilers in vivo. Two experiments were conducted on 36 anesthetized male broilers (n = 6 per treatment) implanted with cannulae in the carotid artery, hepatic portal, and hepatic veins. Plasma GSH, glutamate, cysteine, cystine, and cysteinylglycine levels in each vessel were monitored following a bolus injection [Experiment (Exp.) 1] or 30 min continuous infusion (Exp. 2) of GSH, or a gamma-glutamyltranspeptidase inhibitor (AT125) into the hepatic portal vein. Controls received saline alone. The GSH and AT125 treatments were used to determine the effect of increasing the prehepatic GSH load and of inhibiting systemic GSH degradation, respectively, on the GSH cycle. Hepatic export of GSH was clearly evident in all three treatment groups in both experiments (Exp.). The GSH and AT125 treatments raised amino acid levels in some or all of the vessels, whereas cysteinylglycine was elevated by AT125 and depressed by the GSH treatment compared to Controls. Hepatic uptake of glutamate, cysteine, and/or cystine was observed in Controls and GSH-treated birds, but not in birds given AT125 (Exp. 2). Neither hepatic export nor uptake of cysteinylglycine was observed in any treatment group. The results clearly demonstrate the ability of the avian liver to export GSH into the general circulation despite alterations that might arise from changes in extra-hepatic ability to utilize GSH or its constituent amino acids.     

Inhibition of neutral endopeptidase causes vasoconstriction of human resistance vessels in vivo

BACKGROUND: Neutral endopeptidase (NEP) degrades vasoactive peptides, including the natriuretic peptides, angiotensin II, and endothelin-1. Systemic inhibition of NEP does not consistently lower blood pressure, even though it increases natriuretic peptide concentrations and causes natriuresis and diuresis. We therefore investigated the direct effects of local inhibition of NEP on forearm resistance vessel tone. METHODS AND RESULTS: Four separate studies were performed, each with 90-minute drug infusions. In the first study, 10 healthy subjects received a brachial artery infusion of the NEP inhibitor candoxatrilat (125 nmol/min), which caused a slowly progressive forearm vasoconstriction (12+/-2%; P=0.001). In a second two-phase study, 6 healthy subjects received, 4 hours after enalapril (20 mg) or placebo, an intra-arterial infusion of the NEP inhibitor thiorphan (30 nmol/min). Thiorphan caused similar degrees of local forearm vasoconstriction (P=0.6) after pretreatment with both placebo (13+/-1%, P=0.006) and enalapril (17+/-6%, P=0.05). In a third three-phase study, 8 healthy subjects received intra-arterial thiorphan (30 nmol/min), the endothelin ETA antagonist BQ-123 (100 nmol/min), and both combined. Thiorphan caused local forearm vasoconstriction (13+/-1%, P=0.0001); BQ-123 caused local vasodilatation (33+/-3%, P=0.0001). Combined thiorphan and BQ-123 caused vasodilatation (32+/-1%, P=0.0001) similar to BQ-123 alone (P=0.98). In a fourth study, 6 hypertensive patients (blood pressure >160/100 mm Hg) received intra-arterial thiorphan (30 nmol/min). Thiorphan caused a slowly progressive forearm vasoconstriction (10+/-2%, P=0.0001). CONCLUSIONS: Inhibition of local NEP causes vasoconstriction in forearm resistance vessels of both healthy volunteers and patients with hypertension. The lack of effect of ACE inhibition on the vasoconstriction produced by thiorphan and its absence during concomitant ETA receptor blockade suggest that it is mediated by endothelin-1 and not angiotensin II. These findings may help to explain the failure of systemic NEP inhibition to lower blood pressure.     

The role of fine-needle aspiration biopsy in the initial diagnosis of pediatric bone and soft tissue tumors: an institutional experience

A 13-year-old girl developed atonic seizure at 2 years of age. At the age of 10 years, gelastic seizures were noted. Magnetic resonance imaging (MRI) revealed a hypothalamic mass protruding down into the basal cistern and up into the third ventricle. An interictal electroencephalogram (EEG) showed paroxysmal spike and wave complex discharges. Since the seizures failed to respond to medical therapy, it was decided to try to control them by removing the mass. The operation was carried out through an interhemispheric trans-lamina terminalis approach. The lesion was so similar to normal brain tissue that the resection had to be limited enough to avoid complications. Histological examination of the mass showed a hamartoma. Postoperative MRI showed residual mass, but no seizure has been noted since the operation. The EEG recorded one year after the operation showed no spike and wave complex discharge, although she was still on anticonvulsant drugs. The authors propose that surgical therapy should be considered as a treatment for intractable gelastic epilepsy with hypothalamic hamartoma and that the first operation should be conservative enough to avoid complications, because it can bring about good results even if it is only a partial resection.     

Lysosomal sequestration of free and esterified cholesterol from oxidized low density lipoprotein in macrophages of different species

Macrophage foam cells of atherosclerotic lesions store lipid in lysosomes and cytoplasmic inclusions. Oxidized low density lipoprotein (oxLDL) has been proposed to be the atherogenic particle responsible for the free and esterified cholesterol stores in macrophages. Currently, however, there is a paucity of data showing that oxLDL can induce much cholesterol accumulation in cells. The present studies compare the ability of mildly oxLDL (TBARS = 5 to 10 nmols/mg LDL protein) with acetylated LDL to induce free cholesterol (FC) and esterified cholesterol (EC) accumulation in pigeon, THP-1, and mouse macrophages. Mildly oxLDL stimulated high levels of loading comparable to acLDL where the cellular cholesterol concentrations ranged from 160 to 420 microg/mg cell protein with EC accounting for 52-80% of the cholesterol. Pigeon and THP-1 macrophages stored most (60-90%) of oxLDL cholesterol (both FC and EC) in lysosomes, and the bulk (64-88%) of acLDL cholesterol in cytoplasmic inclusions. Consistent with lysosomal accumulation, cholesterol esterification was 75% less in THP-1 macrophages enriched with oxLDL cholesterol compared with acLDL. Furthermore, addition of an acyl-CoA:cholesterol acyltransferase inhibitor did not significantly affect either cholesterol loading or the percent distribution of FC and EC in THP-1 and pigeon cells incubated with oxLDL. Surprisingly, mouse macrophages stored most of oxLDL (71%) and acLDL (83%) cholesterol within cytoplasmic inclusions. Also, in mouse macrophages, esterification paralleled cholesterol loading, and was 3-fold more in oxLDL treated cells compared with acLDL treated cells. Inhibition of ACAT led to a 62% and 90% reduction in the %EC in oxLDL and acLDL treated mouse macrophages, respectively. The results demonstrate that mildly oxidized low density lipoprotein (oxLDL) stimulates macrophage foam cell formation and lipid engorgement of lysosomes. However, the fate of oxLDL cholesterol markedly differs in macrophages of different species.     

Modelling ordinal responses from co-twin control studies

The co-twin control design has been widely used in studying the effects of environmental factors on the development of diseases. For binary outcomes that arise from co-twin control studies, the conditional likelihood method is commonly used. This approach, however, does not readily extend to ordinal response data because the standard conditional likelihood does not exist for cumulative logit or proportional odds models. In this paper, we investigate the applicability of the random-effects and GEE approaches in analysing ordinal response data from co-twin control studies. Using both approaches, we re-analyse data from a co-twin control study of the impact of military services during the Vietnam era on post-traumatic stress disorders (PTSD). The ordinal models have considerably increased power in detecting the effects of exposure when compared to the analyses using a dichotomized response. We discuss the interpretation of the estimates from GEE and random-effect models in the context of the twin data.