Mechanical loading affects the energy metabolism of intervertebral disc cells

Research has shown that mechanical loading affects matrix biosynthesis of intervertebral disc (IVD) cells; however, the pathway(s) to this effect is currently unknown. Cellular matrix biosynthesis is an energy demanding process. The objective of this study was to investigate the effects of static and dynamic compressive loading on energy metabolism of IVD cells. Porcine annulus fibrosus (AF) and nucleus pulposus (NP) cells seeded in 2% agarose were used in this experiment. Experimental groups included 15% static compression and 0.1 and 1 Hz dynamic compression at 15% strain magnitude for 4 h. ATP, lactate, glucose, and nitric oxide (NO) contents in culture media, and ATP content in cell–agarose construct were measured using biochemical assays. While the total ATP content of AF cells was promoted by static and dynamic loading, only 1 Hz dynamic loading increased total ATP content of NP cells. Increases in lactate production and glucose consumption of AF cells suggest that ATP production via glycolysis is promoted by dynamic compression. ATP release and NO production of AF and NP cells were significantly increased by dynamic loading. Thus, this study clearly illustrates that static and dynamic compressive loading affect IVD cell energy production while cellular responses to mechanical loading were both cell type and compression type dependent. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:1634–1641, 2011     

Experience with high-dose gadolinium MR imaging in the evaluation of brain metastases.

PURPOSE: To assess the effectiveness and safety of higher doses of gadoteridol in the MR evaluation of patients with brain metastases. MATERIALS AND METHODS: Thirty-one patients with a clinical suspicion of brain metastases were studied prospectively with gadoteridol, a new, nonionic, low-osmolality contrast agent. Each patient received an initial injection of 0.1 mmol/kg and an additional dose of 0.2 mmol/kg 30 minutes later. Images were obtained before, immediately after, and 10 and 20 minutes after the initial dose. Images also were acquired immediately after the additional dose of gadoteridol. RESULTS: No adverse effects were attributed to the injection of gadoteridol. Four patients' examinations were excluded from analysis because of machine malfunction (two patients) and excessive motion artifact (two patients). Four patients had no detectable metastases. After the additional dose of gadoteridol, there was a marked qualitative improvement in lesion conspicuity and detection. The conspicuity of 80 of 81 lesions was increased in the high-dose studies, and 46 new lesions were detected in 19 of 27 patients. Quantitative image analysis demonstrated a significant increase in normalized mean lesion contrast between the initial-dose and high-dose studies (35 lesions identified in 13 patients, P less than .0001). The additional information gained by high-dose examinations contributed to a potential modification of the treatment in 10 of 27 patients. High-dose examinations increased flow-related artifact in the posterior fossa in 12 of 27 patients. CONCLUSION: Based on our preliminary results, high-dose gadolinium-enhanced MR examinations may have advantages over 0.1 mmol/kg examinations in detecting early and/or small metastases. This may be significant in the management of patients with cerebral metastases.     

Genotype-directed, dose-finding study of irinotecan in cancer patients with UGT1A1*28 and/or UGT1A1*6 polymorphisms

Irinotecan-induced severe neutropenia is associated with homozygosity for the UGT1A1*28 or UGT1A1*6 alleles. In this study, we determined the maximum-tolerated dose (MTD) of irinotecan in patients with UGT1A1 polymorphisms. Patients who had received chemotherapy other than irinotecan for metastatic gastrointestinal cancer were enrolled. Patients were divided into three groups according to UGT1A1 genotypes: wild-type (*1/*1); heterozygous (*28/*1, *6/*1); or homozygous (*28/*28, *6/*6, *28/*6). Irinotecan was given every 2 weeks for two cycles. The wild-type group received a fixed dose of irinotecan (150 mg/m(2)) to serve as a reference. The MTD was guided from 75 to 150 mg/m(2) by the continual reassessment method in the heterozygous and homozygous groups. Dose-limiting toxicity (DLT) and pharmacokinetics were evaluated during cycle 1. Of 82 patients enrolled, DLT was assessable in 79 patients (wild-type, 40; heterozygous, 20; and homozygous, 19). Dose-limiting toxicity occurred in one patient in the wild-type group, none in the heterozygous group, and six patients (grade 4 neutropenia) in the homozygous group. In the homozygous group, the MTD was 150 mg/m(2) and the probability of DLT was 37.4%. The second cycle was delayed because of neutropenia in 56.3% of the patients given the MTD. The AUC(0-24 h) of SN-38 was significantly greater (P < 0.001) and more widely distributed in the homozygous group. Patients homozygous for the UGT1A1*28 or UGT1A1*6 allele can receive irinotecan in a starting dose of 150 mg/m(2), but many required dose reductions or delayed treatment in subsequent cycles. UMIN Clinical Trial Registration number: UMIN000000618.     

Acute exacerbations and respiratory failure in chronic obstructive pulmonary disease

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) describe the phenomenon of sudden worsening in airway function and respiratory symptoms in patients with COPD. These exacerbations can range from self-limited diseases to episodes of florid respiratory failure requiring mechanical ventilation. The average patient with COPD experiences two such episodes annually, and they account for significant consumption of health care resources. Although bacterial infections are the most common causes of AECOPD, viral infections and environmental stresses are also implicated. AECOPD episodes can be triggered or complicated by other comorbidities, such as heart disease, other lung diseases (e.g., pulmonary emboli, aspiration, pneumothorax), or systemic processes. Pharmacologic management includes bronchodilators, corticosteroids, and antibiotics in most patients. Oxygen, physical therapy, mucolytics, and airway clearance devices may be useful in selected patients. In hypercapneic respiratory failure, noninvasive positive pressure ventilation may allow time for other therapies to work and thus avoid endotracheal intubation. If the patient requires invasive mechanical ventilation, the focus should be on avoiding ventilator-induced lung injury and minimizing intrinsic positive end-expiratory pressure. These may require limiting ventilation and "permissive hypercapnia." Although mild episodes of AECOPD are generally reversible, more severe forms of respiratory failure are associated with a substantial mortality and a prolonged period of disability in survivors.     

Magnetic resonance imaging of the brain in schizophrenia. The pathophysiologic significance of structural abnormalities

In a second large series of schizophrenic patients studied with magnetic resonance imaging at the University of Iowa, Iowa City, earlier findings of decreased frontal, cerebral, and cranial size were not replicated. In this second series, control subjects were selected to be educationally equivalent to the schizophrenic patients, a modification in design that may partially account for the failure to replicate. By means of coronal images, ventricular volume was compared in patients and controls and found to differ to a highly significant degree, with the frontal horns being possibly slightly more enlarged than the rest of the ventricular system. A prominent sex effect was also observed, with most of the increased ventricular size occurring in the male patients. Within the male patients, the thalamus was also observed to be significantly smaller, a finding that could be consistent with periventricular injury. Patients with prominent negative symptoms had significantly larger ventricular size than did those with the mixed or positive subtypes. Because of its superior resolution, magnetic resonance imaging appears to offer a more sensitive index of ventricular enlargement than that provided by computed tomography.     

Association study of novel human serotonin 5-HT(1B) polymorphisms with alcohol dependence in Taiwanese Han.

BACKGROUND: Abnormal serotonergic pathways are implicated in numerous neuropsychiatric disorders, such as depression, anxiety, migraine, substance abuse, and alcoholism. The human serotonin receptor 1B, encoded by the HTR1B gene, is a presynaptic serotonin autoreceptor that plays a role in regulating serotonin synthesis and release. Because the linkage of antisocial alcoholism to the HTR1B gene was recently reported in two populations, it was of interest to identify genetic variants at the HTR1B locus and study their association with alcoholism in the Taiwanese Han population. METHODS: We sequenced DNA from Taiwanese Han to screen for genetic variation in the coding, promoter, and partial 3' untranslated regions of the HTR1B locus of 158 alcohol-dependent cases with withdrawal symptoms and 149 control subjects, who either never drank or drank only occasionally and in low quantities. RESULTS: Seven variants were identified. Positive associations were found between variant A-161T and alcohol dependence at both the allelic and genotypic level. In addition, an expression study showed that the A-161T variant affected reporter gene activity. CONCLUSIONS: Our results support an association between HTR1B and alcohol dependence. The HTR1B A-161T polymorphism may be valuable both as a functional and as an anonymous genetic marker for HTR1B.     

Abnormalities of the foot in patients with diabetes mellitus: findings on MR imaging

The MR appearances of foot problems in patients with diabetes mellitus are illustrated. MR has been found to be effective in the diagnosis of osteomyelitis, the most common indication for imaging the feet of diabetic patients. MR has the ability to image numerous pathologic processes, especially subtle soft-tissue changes, that are not detectable with other imaging methods.     

Extrusion of eye socket magnetic implant after MR imaging: potential hazard to patient with eye prosthesis.

Metallic implants or prostheses can be potentially hazardous during magnetic resonance (MR) imaging because of movement or dislodgment of the foreign object. Magnetic eye implants have been reported to exhibit strong movement when placed in water and exposed to a field of 1.5 T. The authors report a case of orbital implant extrusion possibly caused by the movement of a magnetic orbital implant during MR imaging at 0.5 T.