An analysis of ideal and actual time to surgery after traumatic spinal cord injury in Canada.

STUDY DESIGN: Retrospective analysis of a prospective registry and surgeon survey. OBJECTIVES: To identify surgeon opinion on ideal practice regarding the timing of decompression/stabilization for spinal cord injury and actual practice. Discrepancies in surgical timing and barriers to ideal timing of surgery were explored. SETTING: Canada. METHODS: Patients from the Rick Hansen Spinal Cord Registry (RHSCIR, 2004-2014) were reviewed to determine actual timing of surgical management. Following data collection, a survey was distributed to Canadian surgeons, asking for perceived to be the optimal and actual timings of surgery. Discrepancies between actual data and surgeon survey responses were then compared using χ2 tests and logistic regression. RESULTS: The majority of injury patterns identified in the registry were treated operatively. ASIA Impairment Scale (AIS) C/D injuries were treated surgically less frequently in the RHSCIR data and surgeon survey (odds ratio (OR)= 0.39 and 0.26). Significant disparities between what surgeons identified as ideal, actual current practice and RHSCIR data were demonstrated. A great majority of surgeons (93.0%) believed surgery under 24 h was ideal for cervical AIS A/B injuries and 91.0% for thoracic AIS A/B/C/D injuries. Definitive surgical management within 24 h was actually accomplished in 39.0% of cervical and 45.0% of thoracic cases. CONCLUSION: Ideal surgical timing for traumatic spinal cord injury (tSCI) within 24 h of injury was identified, but not accomplished. Discrepancies between the opinions on the optimal and actual timing of surgery in tSCI patients suggest the need for strategies for knowledge translation and reduction of administrative barriers to early surgery.

Low birth weight is associated with adiposity, impaired skeletal muscle energetics and weight loss resistance in mice.

BACKGROUND: In utero undernutrition is associated with obesity and insulin resistance, although its effects on skeletal muscle remain poorly defined. Therefore, in the current study we explored the effects of in utero food restriction on muscle energy metabolism in mice. METHODS: We used an experimental mouse model system of maternal undernutrition during late pregnancy to examine offspring from undernourished dams (U) and control offspring from ad libitum-fed dams (C). Weight loss of 10-week-old offspring on a 4-week 40% calorie-restricted diet was also followed. Experimental approaches included bioenergetic analyses in isolated mitochondria, intact (permeabilized) muscle and at the whole body level. RESULTS: U have increased adiposity and decreased glucose tolerance compared to C. Strikingly, when U are put on a 40% calorie-restricted diet they lose half as much weight as calorie-restricted controls. Mitochondria from muscle overall from U had decreased coupled (state 3) and uncoupled (state 4) respiration and increased maximal respiration compared to C. Mitochondrial yield was lower in U than C. In permeabilized fiber preparations from mixed fiber-type muscle, U had decreased mitochondrial content and decreased adenylate-free leak respiration, fatty acid oxidative capacity and state 3 respiratory capacity through complex I. Fiber maximal oxidative phosphorylation capacity did not differ between U and C but was decreased with calorie restriction. CONCLUSIONS: Our results reveal that in utero undernutrition alters metabolic physiology through a profound effect on skeletal muscle energetics and blunts response to a hypocaloric diet in adulthood. We propose that mitochondrial dysfunction links undernutrition in utero with metabolic disease in adulthood.

Reduced plasma peroxyl radical trapping capacity and increased susceptibility of LDL to oxidation in poorly controlled IDDM.

Oxidation of low-density lipoproteins (LDLs) has been postulated to play an important role in atherogenesis. Because oxidant stress may be increased and antioxidant defenses reduced in diabetes, the susceptibility of LDL to oxidative modification and total peroxyl radical trapping potential (TRAP) of plasma were evaluated in subjects with poorly controlled insulin-dependent diabetes mellitus (IDDM). The lag phase of conjugated diene formation after initiation of LDL oxidation by the addition of copper was shorter in diabetic subjects than in normal control subjects (126 +/- 11 vs. 165 +/- 15 min [means +/- SE], P < 0.05). This could not be attributed to the presence of oxidation-susceptible, small, dense LDL particles in the diabetic subjects, whose lipoprotein particle distribution did not differ from the control subjects. However, the total TRAP of plasma, a measure of antioxidant defense, was reduced (626 +/- 34 vs. 877 +/- 41 microM, P < 0.0001) in diabetes. Of the plasma antioxidants measured, only uric acid and vitamin A were decreased in diabetes (P < 0.01), and both levels correlated with TRAP (r = 0.75, P < 0.001; r = 0.54, P < 0.001, respectively). The correlation between uric acid levels and TRAP persisted when the diabetes and control groups were analyzed separately. The reduced TRAP of plasma and the increased susceptibility of LDL to oxidative modification observed is consistent with a role for lipoprotein oxidation in the pathogenesis of atherosclerosis in IDDM.

A novel method for simultaneous anterograde and retrograde labeling of spinal cord motor tracts in the same animal.

Examination of repaired spinal cord tracts has usually required separate groups of animals for anterograde and retrograde tracing owing to the incompatibility of techniques such as tissue fixation. However, anterograde and retrograde labeling of different animals subjected to the same repair may not allow accurate examination of that repair strategy because widely variable results can occur in animals subjected to the same strategy. We have developed a reliable method of labeling spinal cord motor tracts bidirectionally in the same animal using DiI, a lipophilic dye, to anterogradely label the corticospinal tract and Fluoro-Gold (FG) to retrogradely label cortical and brainstem neurons of several spinal cord motor tracts in normal and injured adult rats. Other tracer combinations (lipophilic dyes or fluorescent dextrans) were also investigated but were less effective. We also developed methods to minimize autofluorescence with the DiI/FG technique, and found that the DiI/FG technique is compatible with decalcification and immunohistochemistry for several markers relevant for studies of spinal cord regeneration. Thus, the use of anterograde DiI and retrograde FG is a novel technique for bidirectional labeling of the motor tracts of the adult spinal cord with fluorescent tracers and should be useful for demonstrating neurite regeneration in studies of spinal cord repair.(J Histochem Cytochem 49:1111-1122, 2001)

Postcraniotomy gas-containing brain abscess: a neurosurgical emergency. Case report.

BACKGROUND: Gas-containing brain abscesses are very rare, and the majority are caused by Clostridium perfringens. We report a case of gas-containing brain abscess that required urgent surgery after a craniotomy for a brain tumor. METHODS AND RESULTS: The patient was a 53-year-old male who presented with a cerebral neoplasm. A temporal lobectomy was performed and the diagnosis of low grade glioma was confirmed. Although the surgery was uneventful the postoperative course was complicated; the patient became agitated and febrile and deteriorated to a deep coma. A computed tomography scan demonstrated gas in the temporal fossa at the lobectomy site, producing mass effect. Urgent surgical debridement and drainage was performed and C. perfringens and mixed flora were found. Antibiotics were started and the patient's condition markedly improved. He was awake and alert, followed commands adequately and was extubated; however, after a week he suffered massive gastrointestinal bleeding and died. CONCLUSIONS: Early recognition of a gas-containing brain abscess is of great interest to immediately start the appropriate treatment. Urgent surgical debridement and broad spectrum chemotherapy are major components in the management of this entity.

Pseudotumoral chagasic meningoencephalitis as the first manifestation of acquired immunodeficiency syndrome.

BACKGROUND: Patients with AIDS frequently show secondary involvement of the brain by different infectious agents, and Chagas' disease is now recognized as a potential opportunistic infection. To our knowledge, pseudotumoral chagasic meningoencephalitis has not been previously reported as the first manifestation of AIDS. METHODS AND RESULTS: A 30-year-old Argentinian man without any risk factor for HIV infection was admitted to the hospital with an acute onset of drowsiness. A computed tomography scan showed a hypodense parietal tumor-like lesion. Open brain biopsy revealed hemorrhagic necrosis and numerous amastigotes of Trypanosoma cruzi. Nifurtimox was started, but the patient died. CONCLUSIONS: Chagas' disease can reactivate in patients with AIDS and present as a brain mass that is indistinguishable from other infectious or neoplasic processes. Our report demonstrates this entity as the first manifestation of AIDS.

Statistical determination of the optimal sample size of secondary effluent BOD5 and SS.

A statistical technique is presented for determining the optimal sample size required to estimate the true geometric mean with an allowable error at a desired level of confidence. Attention is focused on its application in the monitoring of secondary effluent BOD5 and SS. It is concluded that continuous monitoring of effluent BOD5 or SS throughout the year may generate much more data than are required for practical purposes. This statistical method may be used by operators or regulatory agencies to formulate cost-effective monitoring schemes. Records of the sample size data of secondary effluent BOD5 and SS across Canada are also discussed.

Isolation and characterization of cDNA clones corresponding to transcripts from the BamHI H and F regions of the Epstein-Barr virus genome.

The Epstein-Barr virus (EBV) mutant P3HR1 is incapable of immortalizing B lymphocytes because of a 6.8-kilobase deletion in the BamHI W, Y, and H regions of the viral genome (M. Rabson, L. Gradoville, L. Heston, and G. Miller, J. Virol. 44:834-844, 1982). To characterize transcripts that are encoded in this region, poly(A)+ RNA from the EBV-transformed lymphoblastoid cell line JY was isolated, and this RNA was used to generate a cDNA library in lambda gt10. By screening 500,000 recombinant bacteriophages with the BamHI H fragment, we isolated 10 cDNA clones and characterized them in detail. One group of six cDNA clones was derived from a 2.9-kilobase early transcript encoded by the IR2 repeat element and showed restriction site polymorphism for the enzyme SmaI. The second group consisted of four cDNA clones, all of which contained the BamHI-H right reading frame (BHRF1), and used the polyadenylation signal at base pair 662 in the BamHI F fragment. Computer analysis of the hydrophobicity of the BHRF1 protein revealed that it is likely to be a membrane protein. Northern blotting experiments with RNA from an EBV producer line, B95-8, and a tightly latent lymphoblastoid B-cell line, IB4, revealed that BHRF1 is contained in at least two different mRNA species which can be detected during the latent cycle of EBV. These data and the recent characterization of a spliced transcript (containing five exons in common with other known latent messages [M. Bodescot and M. Perricaudet, Nucleic Acids Res. 14:7103-7113, 1986]) suggest that alternative splicing is used to generate transcripts containing BHRF1, as for the EBV nuclear antigen 1 transcripts. Furthermore, the observation that a potential oncogene activated in human follicular lymphomas is homologous to the BHRF1-encoded polypeptide (M. L. Cleary, S.D. Smith, and J. Sklar, Cell 47:19-28, 1986) suggests a possible role for this putative viral protein in EBV-induced growth transformation of B lymphocytes.

ApoE enhances lipid uptake by macrophages in lipoprotein lipase deficiency during pregnancy.

A woman with primary lipoprotein lipase (LPL) deficiency developed marked hypertriglyceridemia, pancreatitis, eruptive xanthomas, and unusual palmar xanthomas during pregnancy. Hypotheses to account for the palmar xanthomas were that oxidative modification of triglyceride (TG)-rich lipoproteins occurred due to increased plasma residence time, or that their apolipoprotein E (apoE) content was abnormally elevated. Indices of oxidation of her TG-rich lipoproteins did not support the hypothesis that oxidative changes were a causative factor for her xanthomata. However, degradation of her TG-rich lipoproteins by macrophages was markedly increased (1844 ng/mg protein) during pregnancy as compared to hypertriglyceridemic (with normal LPL) and normotriglyceridemic controls (352 and 126 ng/mg protein, respectively). Post pregnancy the degradation of the subject's TG-rich lipoproteins fell to 289 ng/mg protein. Compositional analysis showed significant enrichment of the particles with apoE (0.97 mass ratio of apoE:apoB during pregnancy, in contrast to 0.38 for normolipidemic controls), and was correlated with the rate of degradation of the TG-rich lipoproteins. Thus, the increased uptake of the TG-rich lipoproteins by macrophages appears to be the result of an unusual enrichment of these lipoproteins with apoE.

Low serum testosterone level as a predictor of increased visceral fat in Japanese-American men.

OBJECTIVE: To examine the association between baseline testosterone levels and changes in visceral adiposity in Japanese-American men. DESIGN: Prospective observational study. SUBJECTS: Second-generation Japanese-American males enrolled in a community-based population study. MEASUREMENTS: At baseline, 110 men received a 75g oral glucose tolerance test (OGTT), and an assessment of body mass index (BMI); visceral adiposity measured as intra-abdominal fat area (IAF) using computed tomography (CT); fasting insulin and C-peptide levels; and total testosterone levels. IAF was re-measured after 7.5 y. Subcutaneous fat areas were also measured by CT in the abdomen, thorax and thigh. The total fat (TF) was calculated as the sum of IAF and total subcutaneous fat areas (SCF). RESULTS: After 7.5y, IAF increased by a mean of 8.0 cm2 (95% CI: 0.8, 15.3). Baseline total testosterone was significantly correlated with change in IAF (r= -0.26, P= 0.006), but not to any appreciable degree with change in BMI, TF, or SCF. In a linear regression model with change in IAF as the dependent variable, baseline testosterone was significantly related to this outcome while adjusting for baseline IAF, SCF, BMI, age, diabetes mellitus status (OGTT by the WHO diagnostic criteria) and fasting C-peptide (regression coefficient for baseline testosterone [nmol/l] = -107.13, P = 0.003). CONCLUSIONS: In this Japanese-American male cohort, lower baseline total testosterone independently predicts an increase in IAF. This would suggest that by predisposing to an increase in visceral adiposity, low levels of testosterone may increase the risk of type 2 diabetes mellitus.