Compressive and shear force generated in the lumbar spine of female rowers

Rowers have and accrue greater lumbar spine bone mineral density (BMD) associated with mechanical loading produced during rowing. The aim of this study was to estimate the mechanical loading generated at the lumbar spine (LS) that is apparently providing an osteogenic benefit. The cohort comprised 14 female rowers (average age: 19.7yrs; height: 170.9 cm, weight: 59.5 kg) and 14 female matched controls (average age: 20.9 m yrs; height: 167.5 cm; weight: 58.1 kg). BMD was assessed using the Hologic QDR 2000+ bone densitometer, indicating higher lumbar spine BMD in the rowers compared to the control subjects (1,069 +/- 0.1 vs. 1,027 +/- 0.1 g/cm2). No significant difference existed for BMD at any other site. All rowers performed a six-minute simulated race on a Concept II rowing ergometer. Mechanical loading generated at the lumbar spine during this task was assessed using a two-dimensional model of the spine, enabling the calculation of the compressive and shear forces at L4/L5. The shear force was the joint reaction force perpendicular to the spine at the L4/L5 joint. Peak compressive and shear force at the lumbar spine of the rowers were 2,694 +/- 609 (N) and 660 +/- 117 (N), respectively. Peak compressive force at the LS relative to body weight was 4.6 times body weight. The literature would suggest that forces of this magnitude, generated at the LS during maximal rowing, may be contributing to the site specific higher LS BMD found in the rowers.     

Early DAT is distinguished from aging by high-dimensional mapping of the hippocampus. Dementia of the Alzheimer type

OBJECTIVE: To determine the feasibility of using high-dimensional brain mapping (HDBM) to assess the structure of the hippocampus in older human subjects, and to compare measurements of hippocampal volume and shape in subjects with early dementia of the Alzheimer type (DAT) and in healthy elderly and younger control subjects. BACKGROUND: HDBM represents the typical structures of the brain via the construction of templates and addresses their variability by probabilistic transformations applied to the templates. Local application of the transformations throughout the brain (i.e., high dimensionality) makes HDBM especially valuable for defining subtle deformities in brain structures such as the hippocampus. METHODS: MR scans were obtained in 18 subjects with very mild DAT, 18 healthy elderly subjects, and 15 healthy younger subjects. HDBM was used to obtain estimates of left and right hippocampal volume and eigenvectors that represented the principal dimensions of hippocampal shape differences among the subject groups. RESULTS: Hippocampal volume loss and shape deformities observed in subjects with DAT distinguished them from both elderly and younger control subjects. The pattern of hippocampal deformities in subjects with DAT was largely symmetric and suggested damage to the CA1 hippocampal subfield. Hippocampal shape changes were also observed in healthy elderly subjects, which distinguished them from healthy younger subjects. These shape changes occurred in a pattern distinct from the pattern seen in DAT and were not associated with substantial volume loss. CONCLUSIONS: Assessments of hippocampal volume and shape derived from HDBM may be useful in distinguishing early DAT from healthy aging.     

MR spectroscopy study of dichloroacetate treatment after ischemic stroke

In a double-blind, placebo-controlled study, we used 1H MR spectroscopy to assess the effect of a single infusion of sodium dichloroacetate on lesion lactate 1 to 5 days after ischemic stroke. Apparent trends toward a reduction in lactate/N-acetyl compound ratios were seen at the higher drug doses employed, and in patients treated in the first 2 days following infarction. Use of spectroscopic measures as endpoints is feasible in acute stroke clinical trials.     

Misleading results with the 14-3-3 assay for the diagnosis of Creutzfeldt-Jakob disease

The definitive diagnosis of Creutzfeldt-Jakob disease (CJD) requires brain tissue analysis. A positive assay for the 14-3-3 protein in CSF has been suggested to be highly sensitive and specific in patients with CJD. The authors describe three patients for whom CSF 14-3-3 assays were falsely positive or falsely negative. Caution against overreliance on this putative biomarker is suggested in the diagnosis of CJD.     

Differentiation of atypical parkinsonian syndromes with routine MRI

OBJECTIVE: To evaluate the use of routine MRI in differentiating between patients with progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal degeneration (CBD) and control subjects. METHODS: Two neuroradiologists rated blindly and independently axial T2-weighted and proton density MR images of 54 patients with MSA, 35 patients with PSP, 5 patients with CBD, and 44 control subjects. RESULTS: More than 70% of patients with PSP and more than 80% of patients with cerebellar predominant MSA could be classified correctly with 0.5-T or 1.5-T scans, and no patient in these groups was misclassified. In the remaining patients an unequivocal differentiation could not be made. However, only approximately 50% of patients with parkinsonism-predominant MSA could be classified correctly, and 19% of them (all of whom had had 0.5-T scans) were misclassified. CONCLUSIONS: Characteristic findings on routine MRI, either 1.5 T or 0.5 T, can contribute to the identification of MSA and PSP. However, in a minority of patients no unequivocal diagnosis can be made using MRI findings alone.     

Cytoreductive surgery and perioperative intraperitoneal chemotherapy for peritoneal carcinomatosis from colorectal carcinoma: non-mucinous tumour associated with an improved survival

AIMS: Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy has been reported as a treatment option for patients with peritoneal carcinomatosis from colorectal carcinoma. METHODS: Thirty patients with colorectal peritoneal carcinomatosis underwent cytoreductive surgery and perioperative intraperitoneal chemotherapy. All appendiceal cancers were excluded. All patients were followed until January 2006 or death. Univariate analysis was performed to evaluate significant prognostic factors for overall survival, defined from the time of surgery. RESULTS: There were 13 male patients. The mean age at the time of surgery was 54years. There was no hospital mortality. The mean duration of hospital stay was 27days. The overall median survival was 29months, with 1- and 2-year survival of 72% and 64%, respectively. Twenty-one patients had complete cytoreduction and their 1- and 2-year survival rates were 85% and 71%, respectively. Univariate analysis demonstrated that patients with non-mucinous colorectal adenocarcinoma, Peritoneal Cancer Index (PCI) < or =13, and complete cytoreduction were associated with an improved survival. CONCLUSIONS: This study reported on 30 patients who underwent cytoreductive surgery and perioperative intraperitoneal chemotherapy for colorectal peritoneal carcinomatosis. Patients with mucinous tumour had relatively more extensive intraperitoneal disease. Non-mucinous colorectal adenocarcinoma, PCI < or =13, and complete cytoreduction were associated with an improved survival.     

Albendazole: a potent inhibitor of vascular endothelial growth factor and malignant ascites formation in OVCAR-3 tumor-bearing nude mice.

PURPOSE: Angiogenesis and vessel hyperpermeability are the two factors leading to the formation of ascites. Vascular endothelial growth factor (VEGF) plays a pivotal role in malignant ascites formation. We have recently shown that albendazole inhibits peritoneal growth of human colorectal cancer cells (HT-29). The present study was designed to find out if albendazole can suppress ascites formation in ascites-producing peritoneal carcinomatosis. EXPERIMENTAL DESIGN: Female nude mice bearing peritoneal tumors of human ovarian cancer cells (OVCAR-3) were treated with albendazole. Following i.p. inoculation and ascites development, mice were given i.p. albendazole (150 mg/kg) or the vehicle x 3 weekly for 4 weeks. RESULTS: Whereas vehicle-treated mice developed overt ascites requiring repeated aspiration, ascites formation in the albendazole-treated mice was markedly suppressed. As a result of this, 7 of 10 mice from the control group had to be euthanized before the course of treatment was over. Suppressed ascites production and reduced tumor vascularity observed was a result of dramatic reduction in tumor VEGF production as revealed by profoundly lower VEGF ascites fluid and plasma levels. In vitro, incubation of SKOV-3 cells with various concentrations of albendazole led to significant dose-dependent inhibition of VEGF secretion. Examination of floating tumor cells collected from the peritoneal wash revealed profound down-regulation of VEGF mRNA in albendazole-treated mice. CONCLUSIONS: These findings suggest for the first time that in nude mice bearing OVCAR-3 peritoneal tumors, by inhibiting VEGF production, albendazole abolishes tumor angiogenesis and ascites formation.     

Preclinical characterization of AEG35156/GEM 640, a second-generation antisense oligonucleotide targeting X-linked inhibitor of apoptosis.

PURPOSE: Cancer cells can use X-linked inhibitor of apoptosis (XIAP) to evade apoptotic cues, including chemotherapy. The antitumor potential of AEG35156, a novel second-generation antisense oligonucleotide directed toward XIAP, was assessed in human cancer models when given as a single agent and in combination with clinically relevant chemotherapeutics. EXPERIMENTAL DESIGN: AEG35156 was characterized for its ability to cause dose-dependent reductions of XIAP mRNA and protein in vitro and in vivo, to sensitize cancer cell lines to death stimuli, and to exhibit antitumor activity in multiple human cancer xenograft models as a single agent or in combination with chemotherapy. RESULTS: AEG35156 reduced XIAP mRNA levels with an EC50 of 8 to 32 nmol/L and decreased XIAP protein levels by >80%. Loss of XIAP protein correlated with increased sensitization to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in Panc-1 pancreatic carcinoma cells. AEG35156 exhibited potent antitumor activity relative to control oligonucleotides in three human cancer xenograft models (prostate, colon, and lung) and was capable of inducing complete tumor regression when combined with taxanes. Antitumor effects of AEG35156 correlated with suppression of tumor XIAP levels. CONCLUSIONS: AEG35156 reduces XIAP levels and sensitizes tumors to chemotherapy. AEG35156 is presently under clinical assessment in multiple phase I trials in cancer patients as a single agent and in combination with docetaxel in solid tumors or cytarabine/idarubicin in leukemia.     

Magnetic resonance imaging of growth plate injuries: the efficacy and indications for surgical procedures

In 23 patients with growth plate injuries, magnetic resonance imaging (MRI) studies were performed a total of 31 times to evaluate the physis which showed plain radiographic evidence of possible damage. Fourteen patients clinically showed growth arrest, and 10 patients required a Langenskiold operation. In 3 patients who underwent this operation, subsequent premature total fusion of the physis adversely affected the postoperative results. We propose that the merging shape of the arrest line with calcification of the provisional zone of the metaphysis shown by MRI indicates poor viability of the physis. MRI provided useful information on the appearance of the growth plate and changes in the metaphysis, both of which affected the prognosis and the results of the surgical procedures.