Promising one- to six-year results with the Motec wrist arthroplasty in patients with post-traumatic osteoarthritis.

The Motec cementless modular metal-on-metal ball-and-socket wrist arthroplasty was implanted in 16 wrists with scaphoid nonunion advanced collapse (SNAC; grades 3 or 4) and 14 wrists with scapholunate advanced collapse (SLAC) in 30 patients (20 men) with severe (grades 3 or 4) post-traumatic osteoarthritis of the wrist. The mean age of the patients was 52 years (31 to 71). All prostheses integrated well radiologically. At a mean follow-up of 3.2 years (1.1 to 6.1) no luxation or implant breakage occurred. Two wrists were converted to an arthrodesis for persistent pain. Loosening occurred in one further wrist at five years post-operatively. The remainder demonstrated close bone-implant contact. The clinical results were good, with markedly decreased Disabilities of the Arm Shoulder and Hand (DASH) and pain scores, and increased movement and grip strength. No patient used analgesics and most had returned to work. Good short-term function was achieved using this wrist arthroplasty in a high-demand group of patients with post-traumatic osteoarthritis.

Mitochondrial-related gene expression changes are sensitive to agonal-pH state: implications for brain disorders.

Mitochondrial defects in gene expression have been implicated in the pathophysiology of bipolar disorder and schizophrenia. We have now contrasted control brains with low pH versus high pH and showed that 28% of genes in mitochondrial-related pathways meet criteria for differential expression. A majority of genes in the mitochondrial, chaperone and proteasome pathways of nuclear DNA-encoded gene expression were decreased with decreased brain pH, whereas a majority of genes in the apoptotic and reactive oxygen stress pathways showed an increased gene expression with a decreased brain pH. There was a significant increase in mitochondrial DNA copy number and mitochondrial DNA gene expression with increased agonal duration. To minimize effects of agonal-pH state on mood disorder comparisons, two classic approaches were used, removing all subjects with low pH and agonal factors from analysis, or grouping low and high pH as a separate variable. Three groups of potential candidate genes emerged that may be mood disorder related: (a) genes that showed no sensitivity to pH but were differentially expressed in bipolar disorder or major depressive disorder; (b) genes that were altered by agonal-pH in one direction but altered in mood disorder in the opposite direction to agonal-pH and (c) genes with agonal-pH sensitivity that displayed the same direction of changes in mood disorder. Genes from these categories such as NR4A1 and HSPA2 were confirmed with Q-PCR. The interpretation of postmortem brain studies involving broad mitochondrial gene expression and related pathway alterations must be monitored against the strong effect of agonal-pH state. Genes with the least sensitivity to agonal-pH could present a starting point for candidate gene search in neuropsychiatric disorders.

A comparison of normalization methods for high density oligonucleotide array data based on variance and bias.

MOTIVATION: When running experiments that involve multiple high density oligonucleotide arrays, it is important to remove sources of variation between arrays of non-biological origin. Normalization is a process for reducing this variation. It is common to see non-linear relations between arrays and the standard normalization provided by Affymetrix does not perform well in these situations. RESULTS: We present three methods of performing normalization at the probe intensity level. These methods are called complete data methods because they make use of data from all arrays in an experiment to form the normalizing relation. These algorithms are compared to two methods that make use of a baseline array: a one number scaling based algorithm and a method that uses a non-linear normalizing relation by comparing the variability and bias of an expression measure. Two publicly available datasets are used to carry out the comparisons. The simplest and quickest complete data method is found to perform favorably. AVAILABILITY: Software implementing all three of the complete data normalization methods is available as part of the R package Affy, which is a part of the Bioconductor project http://www.bioconductor.org. SUPPLEMENTARY INFORMATION: Additional figures may be found at http://www.stat.berkeley.edu/~bolstad/normalize/index.html

Reliability of goniometric measurements and visual estimates of hip ROM in patients with osteoarthrosis.

BACKGROUND AND PURPOSE: Range of motion (ROM) measurements have been included in several hip scores evaluating the results after hip surgery. The clinical procedures of performing these measurements vary and disagreement exists about the accuracy of visual estimatess compared to goniometer measurements. The purpose of this study was to study the reliability of goniometric measurements and visual estimates of hip ROM in patients with osteoarthrosis. METHOD: Hip ROM measurements (abduction, adduction, extension, flexion and internal/external rotation) were recorded by four different teams on the same day and were repeated one week later. Teams 1, 2 and 3 consisted of physiotherapists using standardized goniometric measurements. Team 4 involved an experienced orthopaedic surgeon making the assessments from visual estimates only. Twenty-five patients (6 M, 19 F; mean age 68.5 years, range 46-76 years) with osteoarthrosis of the hip, verified both clinically and radiologically, participated in the study. RESULTS: With the exception of abduction (p = 0.03), there were no significant differences between the measurements recorded on the first and the second occasions for the same teams. The coefficient of variance was 5.5% for flexion (lowest) and 26.1% for extension (highest). Reproducibility was best for flexion. There was also high reliability when all the arcs of motion were summed up (abuction + adduction + extension + flexion + internal/external rotation). With the exception of internal rotation, there were highly significant differences between the teams when two people performed the measurements compared to the values measured by a single individual. Concordance, expressed as the standardized agreement index, between visual estimates made by one individual (the orthopaedic surgeon) and goniometric measurements made by two experienced physiotherapists, were 0.77-0.83 which indicates good agreement. CONCLUSION: The reproducibility of hip ROM measurements was highest for flexion. There was also high reliability when all the six arcs of motion were summed up. Concordance between visual estimates and goniometric measurements indicates good agreement.

Assessment of left ventricular wall motion and delineation of the endocardial border after intravenous injection of Infoson during dobutamine stress echocardiography.

OBJECTIVES: To investigate whether intravenous injection of Infoson facilitates the assessment of left ventricular wall motion and definition of endocardial border and thereby reduces inter- and intra-observer variability during dobutamine stress echocardiography. BACKGROUND: Clear detection of the endocardial border is essential during dobutamine stress echocardiography. Although several contrast agents have been tested for their efficacy in enhancing definition of left ventricular endocardium, their usefulness during dobutamine stress echocardiography has not been evaluated. METHODS: Thirty coronary artery disease patients underwent dobutamine stress echocardiography. Infoson was injected at 0.2 ml/kg in both apical four- and two-chamber views. Detection of the left ventricular endocardial borders was scored from 0 (undetectable) to 10 (best) and expressed as a percentage of image quality at rest and peak stress by two independent observers. Regional wall motion was also evaluated and the total wall motion score index calculated each time. RESULTS: Delineation of the left ventricular endocardium improved from 76 +/- 4% to 84 +/- 2% at rest (P < 0.01) and from 75 +/- 4% to 89 +/- 1% at peak stress (P < 0.01) after administration of Infoson. The greatest improvement was seen in the basal and middle regions of the lateral and anterior walls. Inter- and intra-observer variability was reduced after administration of Infoson. At rest, the probability of concordance between two observers increased from 0.86 (0.82-0.89) to 0.91 (0.88-0.94) (P < 0.05) and at peak stress from 0.86 (0.82-0.9) to 0.90 (0.86-0.92) after administration of Infoson (P < 0.05). The probability of concordance between on- and off-line assessment by one observer also increased from 0.84 (0.8-0.88) to 0.90 (0.86-0.93) (P < 0.01) at rest and from 0.90 to 0.92 (NS) at peak stress. Overall, a change in wall motion score index occurred in 16 of 30 (53%) patients after administration of Infoson, thus improving the accuracy of the stress test compared with coronary angiography. The wall motion score index was overestimated in 11 of 16 (37%) patients without Infoson while the detection of new wall motion abnormalities increased in 5 of 16 (17%) (P < 0.01). CONCLUSIONS: Intravenous administration of Infoson facilitates the assessment of wall motion, particularly of the basal lateral and anterior walls where endocardial border drop-out frequently occurs during dobutamine stress echocardiography; it thus reduces the inter- and intra-observer variability.

Sexual victimization, generalized perception of control, and posttraumatic stress disorder symptom severity.

We examined the relations among various characteristics of sexual victimization, posttraumatic stress disorder (PTSD) symptom severity, and generalized perception of control. Our main focus lay in testing three predictions derived from the animal model of PTSD articulated by Foa, Zinbarg, and Olasov-Rothbaum (1992) based on the effects of uncontrollable and/or unpredictable aversive events. A sample of 117 female undergraduates participated and completed self-report measures of past experience with child sexual abuse, adult sexual victimization, PTSD symptom severity, and locus of control. The results showed that child sexual abuse experienced on multiple occasions was associated with diminished generalized perception of control and that diminished generalized perception of control is associated with greater PTSD symptom severity following adult sexual victimization when experienced on a single occasion or involving force. These results provide partial support for the uncontrollability/unpredictability model of PTSD. Further research is necessary, however, to firmly establish the direction of causality involved in these associations.

Intra-arterial digital subtraction angiography with isotonic dimeric (iodixanol) and monomeric (iohexol) nonionic contrast media: radiographic, clinical and neurophysiological evaluation.

Monomeric (iohexol 300 mg I/ml) and dimeric (iodixanol 270 mg I/ml) nonionic contrast media were compared in a double-blind, randomised, parallel group trial. Safety and efficacy of the media in intra-arterial cerebral digital subtraction angiography were evaluated by assessing adverse events, discomfort, EEG, heart rate and quality of radiodiagnostic information. Seventy-six patients underwent selective injection of the carotid and/or vertebral arteries. Both contrast media were well tolerated. No serious adverse events occurred. No effects on heart rate and EEG were evident. The arteriograms were of high quality and overall diagnostic information was optimal in 94% of the examinations. No clinically important differences between the two contrast media were found.

Main results of the first comparative clinical studies on Visipaque.

The results are reviewed from 18 European clinical vascular studies in 1950 patients where iodixanol (Visipaque) - a new isotonic, dimeric, nonionic contrast medium (CM) - is compared to other CM. Visipaque gave better patient comfort, i.e., less pain and heat sensation after vascular injections than the comparative CM. Adverse events reported after Visipaque were otherwise similar to nonionic CM but lower than after ioxaglate (Hexabrix) and other ionic CM. Human renal safety of Visipaque has been extensively studied. Only small changes in glomerular filtration rate and serum creatinine were measured with the monomeric nonionic CM as well as with Visipaque. The excretion of marker enzymes for renal tubular cell function was generally lowest for Visipaque. Thus Visipaque was highly tolerable in the kidneys. To study cardiac safety, electrophysiological and hemodynamic changes were recorded. Visipaque had generally no electrophysiological or hemodynamic effects, or less pronounced effects compared to the other CM. Radiograms revealed that Visipaque 320 mg I/ml yielded the same attenuation as 350 to 370 mg I/ml of the other CM and, similarly, 270 mg I/ml of Visipaque gave as good visualization as 300 mg I/ml of comparative CM.

Iodixanol in cardioangiography. A double-blind parallel comparison between iodixanol 320 mg I/ml and ioxaglate 320 mg I/ml.

Iodixanol (Visipaque) 320 mg I/ml, a non-ionic, dimeric, isotonic contrast medium, was compared to ioxaglate (Hexabrix) 320 mg I/ml in cardioangiography. One hundred and two patients with normal renal function were included in the study. The objectives were to evaluate safety, tolerability, radiographic efficacy and effects on renal function. Adverse events, discomfort, vital signs, clinical chemistry parameters, diagnostic information and radiographic density were recorded. Both contrast media had minor effects on the renal function parameters monitored. The patients who received iodixanol experienced fewer adverse events, significantly less discomfort and had a lower increase in heart rate than did the patients in the ioxaglate group. The radiographic efficacy was good in both groups. Iodixanol 320 mg I/ml is safe and effective for use in cardioangiography.

Iodixanol in femoral arteriography. A randomized, double-blind, phase III, parallel study with iodixanol 270 mg I/ml and iohexol 300 mg I/ml.

Two contrast media, iodixanol (Visipaque, Nycomed) 270 mg I/ml and iohexol (Omnipaque, Nycomed) 300 mg I/ml, were compared in femoral arteriography, in 147 patients. Both contrast media were diagnostically effective for use in femoral arteriography, without any significant difference. Pain was reported in connection with injection of iohexol by 36% of the patients, after injection of iodixanol none reported pain. Seventy-two percent of the patients in the iodixanol group reported a sensation of warmth in connection with contrast injection versus 90% in the iohexol group. The average intensity of the warmth was greater with iohexol than with iodixanol. Fourteen percent of patients in the iodixanol group and 1% in the iohexol group reported one or more subjective adverse events.

Iodixanol and ioxaglate in cardioangiography: a double-blind randomized phase III study.

A new non-ionic, dimeric contrast medium iodixanol (Nycomed AS, Norway) has a very low osmolality and is isotonic with blood. It has been compared with ioxaglate (Hexabrix, Laboratoire Guerbet, France) in a double-blind, randomized, parallel trial. The aims of the trial were to evaluate and compare the safety (vital signs, adverse events, discomfort and clinical-chemical parameters in blood and urine) and radiographic efficacy (diagnostic information and radiographic density) of iodixanol 320 mg I/ml vs ioxaglate (Hexabrix 320 mg I/ml) in coronary angiography and left ventriculography. Seventy-six patients referred for cardioangiography, two patients were withdrawn, 36 receiving iodixanol and 38 ioxaglate were included in the trial. Six patients (16%) in the iodixanol group and 16 (42%) patients in the ioxaglate group reported adverse events (P = 0.02). One serious adverse event occurred in the iodixanol group where a patient experienced transient cortical blindness and transitory global amnesia, but the patient recovered completely the day after the examination. Twenty-six patients reported injection-associated sensation of warmth in the iodixanol group versus 34 in the ioxaglate group (P = 0.06). Following contrast injection there were no differences between the groups regarding vital signs (ECG, heart rate, left ventricular pressures). Both contrast media were well tolerated by the kidneys, and on average only minor effects on clinical-chemical parameters in blood and urine were observed in the two groups. The radiographic efficacy was good in both groups.

Iodixanol in abdominal digital subtraction angiography. A randomized, double-blind, parallel trial with iodixanol and iohexol.

The safety, tolerability and efficacy of iodixanol 270 mg I/ml were compared to those of iohexol 300 mg I/ml in a double-blind, randomized, parallel abdominal intra-arterial DSA phase III trial. Fifty-nine patients were included in the trial; 39 patients received iodixanol and 20 received iohexol. The mean volume of iodixanol administered was 235.8 ml (0.93 g I/kg b.w.) while the mean volume of iohexol was 254.7 ml (1.10 g I/kg b.w.). No differences in diagnostic information and radiographic density were apparent in spite of the difference in the concentration of iodine. No serious adverse events occurred. Four patients (10%) in the iodixanol group and 2 (10%) in the iohexol group experienced adverse events. Eight percent of the injections of iodixanol promoted discomfort, compared to 12% of the injections of iohexol. An increase in S-urea and S-creatinine was seen with both agents the first day after injection, but appeared to be less pronounced with iodixanol than with iohexol. Other serum tests revealed no changes of clinical importance. Both iodixanol and iohexol were found to be effective, safe and well tolerated contrast media for abdominal intra-arterial DSA.