Mitochondrial DNA deletions/rearrangements in parkinson disease and related neurodegenerative disorders

Inhibition of mitochondrial respiratory chain function may contribute to dopaminergic neurodegeneration in the substantia nigra (SN) of patients with Parkinson disease (PD). Since large-scale structural changes (e.g. deletions and rearrangements in mitochondrial DNA [mtDNA]) have been associated with mitochondrial dysfunction, we tested the hypothesis that increased total mtDNA deletions/rearrangements are associated with neurodegeneration in PD. This study employed a well-established technique, long-extension polymerase chain reaction (LX-PCR), to detect the multiple mtDNA deletions/rearrangements in the SN of patients with PD, multiple system atrophy (MSA), dementia with Lewy bodies (DLB), Alzheimer disease (AD), and age-matched controls. We also compared the total mtDNA deletions/rearrangements in different brain regions of PD patients. The results demonstrated that both the number and variety of mtDNA deletions/rearrangements were selectively increased in the SN of PD patients compared to patients with other movement disorders as well as patients with AD and age-matched controls. In addition, increased mtDNA deletions/rearrangements were observed in other brain regions in PD patients, indicating that mitochondrial dysfunction is not just limited to the SN of PD patients. These data suggest that accumulation of total mtDNA deletions/rearrangements is a relatively specific characteristic of PD and may be one of the contributing factors leading to mitochondrial dysfunction and neurodegeneration in PD.     

Prediction of peak oxygen uptake in men using pulmonary and hemodynamic variables during exercise

PURPOSE: Many attempts have been made to predict peak VO2 from data obtained at rest or submaximal exercise. Predictive submaximal tests using the heart rate (HR) response have limited accuracy. Some tests incorporate submaximal gas exchange data, but a predictive test without gas exchange measurements would be of benefit. Addition of stroke volume and pulmonary function (PF) measurements might increase the predictability of a submaximal exercise test. METHODS: In this study, an incremental exercise test (10 W x min(-1)) was performed in 30 healthy men of various habitual activity levels. Step-wise multiple regression analysis was used to isolate the most important predictor variables of peak VO2 from a set of measurements of PF: lung volumes, diffusion capacity, airway resistance, and maximum inspiratory and expiratory pressures; gas exchange; minute ventilation (V(E)), tidal volume (V(T)), respiratory exchange ratio (RER = carbon dioxide output divided by VO2); and hemodynamics (HR, stroke index (SI) = stroke volume/body surface area, and mean arterial pressure). These measurements were made at rest and during submaximal exercise. RESULTS: Using the set of PF variables (expressed as percentages of predicted), FEV1 explained 30% of the variance of peak VO2. No other PF variables were predictive. After addition of resting hemodynamic data, SI was included in the prediction equation, raising the predictability to 40%. At the 60-W exercise level, 48% of the variance in peak VO2 could be explained by SI and FEV1. At 150 W, the prediction increased to 81%. At this level VCO2/O2 (RER) also entered the prediction equation of peak VO2: 6.44 x FEV1(%) + 13.0 x SI - 1921 x RER + 2380 (SE = 142 mL x min(-1) x m(-2), P < 0.0001). Leaving out the gas exchange variable RER, maximally 64% of the variance in peak VO2 could be explained. CONCLUSION: In conclusion, inclusion of pulmonary function and hemodynamic measurements could improve the prediction accuracy of a submaximal exercise test. The submaximal exercise test should be performed until a level of 150 W is reached. Noninvasive stroke volume measurements by means of EIC have additional value to measurement of HR alone. Finally, measurement of gas exchange significantly improves the predictability of peak VO2.     

Multispectral analysis of magnetic resonance images

Magnetic resonance (MR) imaging systems produce spatial distribution estimates of proton density, relaxation time, and flow, in a two dimensional matrix form that is analogous to that of the image data obtained from multispectral imaging satellites. Advanced NASA satellite image processing offers sophisticated multispectral analysis of MR images. Spin echo and inversion recovery pulse sequence images were entered in a digital format compatible with satellite images and accurately registered pixel by pixel. Signatures of each tissue class were automatically determined using both supervised and unsupervised classification. Overall tissue classification was obtained in the form of a theme map. In MR images of the brain, for example, the classes included CSF, gray matter, white matter, subcutaneous fat, muscle, and bone. These methods provide an efficient means of identifying subtle relationships in a multi-image MR study.     

Excretory urography with iohexol: evaluation in children

A multicenter clinical study was conducted using iohexol, a second-generation nonionic contrast medium, for excretory urography performed in 130 children. Doses of iohexol (300 mg iodine/ml) ranged between 150 and 660 mgI/kg (0.5 and 2.2 ml/kg). Iohexol was tolerated well, and no significant adverse reactions occurred. Sixty-five iohexol urograms were evaluated to determine the minimum dose for adequate visualization of the kidneys and collecting systems. A dose greater than 300 mgI/kg (1.0 ml/kg) always resulted in a urogram of diagnostic quality, while visualization was insufficient for diagnosis in 10% of studies done with doses of 150-300 mgI/kg (0.5-1.0 ml/kg). Another 65 iohexol urograms were compared in a blinded manner with a similar number of studies performed using iothalamate meglumine at comparable iodine concentration and dose. Visualization of calyces and pelvoinfundibular structures achieved with iohexol was rated better with statistical significance, but there was no difference in visualization of the renal parenchyma or ureters. Use of iohexol in excretory urography may be advantageous in children who are at greatest risk for an adverse reaction to contrast media or in those most likely to benefit from use of a low osmolality contrast agent.