Lactate metabolism during exercise in patients with mitochondrial myopathy

Patients with mitochondrial DNA mutations often have elevated plasma lactate at rest and during exercise, but it is unknown whether the high lactate levels are caused by a high production, an impaired oxidation or a combination. We studied lactate kinetics in 10 patients with mtDNA mutations and 10 matched healthy control subjects at rest and during cycle exercise with a combination of femoral arterio-venous differences of lactate, and lactate tracer dilution methodology. During exercise, lactate concentration and production rates were several-fold higher in patients, but despite mitochondrial dysfunction, lactate was oxidized in muscle to the same extent as in healthy control subjects. This surprisingly high ability to burn lactate in working muscle with defective mitochondria, probably relates to the variability of oxidative capacity among muscle fibers. The data suggests that lactate is not solely an indicator of impaired oxidative capacity, but an important fuel for oxidative metabolism, even in muscle with severely impaired mitochondrial function.     

Development and Validation of a Highly Accurate Quantitative Real-Time PCR Assay for Diagnosis of Bacterial Vaginosis

Bacterial vaginosis (BV) is the most common gynecological infection in the United States. Diagnosis based on Amsel''s criteria can be challenging and can be aided by laboratory-based testing. A standard method for diagnosis in research studies is enumeration of bacterial morphotypes of a Gram-stained vaginal smear (i.e., Nugent scoring). However, this technique is subjective, requires specialized training, and is not widely available. Therefore, a highly accurate molecular assay for the diagnosis of BV would be of great utility. We analyzed 385 vaginal specimens collected prospectively from subjects who were evaluated for BV by clinical signs and Nugent scoring. We analyzed quantitative real-time PCR (qPCR) assays on DNA extracted from these specimens to quantify nine organisms associated with vaginal health or disease: Gardnerella vaginalis, Atopobium vaginae, BV-associated bacteria 2 (BVAB2, an uncultured member of the order Clostridiales), Megasphaera phylotype 1 or 2, Lactobacillus iners, Lactobacillus crispatus, Lactobacillus gasseri, and Lactobacillus jensenii. We generated a logistic regression model that identified G. vaginalis, A. vaginae, and Megasphaera phylotypes 1 and 2 as the organisms for which quantification provided the most accurate diagnosis of symptomatic BV, as defined by Amsel''s criteria and Nugent scoring, with 92% sensitivity, 95% specificity, 94% positive predictive value, and 94% negative predictive value. The inclusion of Lactobacillus spp. did not contribute sufficiently to the quantitative model for symptomatic BV detection. This molecular assay is a highly accurate laboratory tool to assist in the diagnosis of symptomatic BV.     

NEED FOR FACIAL REANIMATION AFTER OPERATIONS FOR VESTIBULAR SCHWANNOMA: PATIENTS PERSPECTIVE

A total of 779 patients operated on for vestibular schwannoma mostly by the translabyrinthine approach in Denmark during the period 1976-2000 answered a questionnaire about various postoperative consequences. In this paper we describe the patients' facial function evaluated by professionals one year postoperatively and self-evaluated by each patient according to the House-Brackmann scale at the time of the questionnaire. The patients' self-evaluation was more pessimistic than that of the professionals with 26% reporting House-Brackmann grade IV-VI, compared with 20%. One hundred and seventeen (15%) of 779 patients considered their facial palsy to be a big problem and 125 patients (16%) were interested in surgical treatment for the sequelae of facial palsy. Seventy-eight (10%) had already had some kind of operation, usually the VII-XII coaptation. Thirty-three of 61 patients who had already been operated on for facial palsy were interested in further surgical treatment. One hundred and ninety-five patients (25%) had some kind of operation on the eye, mostly (88%) a tarsorrhaphy. Reanimation procedures such as a palpebral gold weight or a spring, apparently still have a small place in Denmark. In conclusion, there seem to be a considerable and unmet need for surgical reanimation of facial function in patients with facial palsy after operations for vestibular schwannoma in Denmark.     

Comparative Effectiveness of Computed Tomography- Versus Ultrasound-Guided Percutaneous Radiofrequency Ablation Among Medicare Patients 65 Years of Age or Older With Hepatocellular Carcinoma

Background

For patients with hepatocellular carcinoma (HCC) not eligible for surgical resection, radiofrequency ablation (RFA) is a promising technique that reduces the risk of disease progression.

Quantitative assessment of global cerebral metabolic rate of oxygen (CMRO2) in neonates using MRI

The cerebral metabolic rate of oxygen (CMRO₂) is the rate of oxygen consumption by the brain, and is thought to be a direct index of energy homeostasis and brain health. However, in vivo measurement of CMRO₂ is challenging, in particular for the neonatal population, in whom conventional radiotracer methods are not applicable because of safety concerns. In this study, we propose a method to quantify global CMRO₂ in neonates based on arteriovenous differences in oxygen content, and employ separate measurements of oxygenation and cerebral blood flow (CBF) parameters. Specifically, arterial and venous oxygenation levels were determined with pulse oximetry and the novel T₂ relaxation under spin tagging (TRUST) MRI, respectively. Global CBF was measured with phase contrast (PC) flow velocity MRI. The proposed method was implemented on a standard 3‐T MRI scanner without the need for any exogenous tracers, and the total scan duration was less than 5 min. We demonstrated the feasibility of this method in 12 healthy neonates within an age range of 35–42 gestational weeks. CMRO₂ values were successfully obtained from 10 neonates. It was found that the average CMRO₂ in this age range was 38.3 ± 17.7 µmol/100 g/min and was positively correlated with age (p = 0.007; slope, 5.2 µmol/100 g/min per week), although the highest CMRO₂ value in this age range was still less than half of the adult level. Test–retest studies showed a coefficient of variation of 5.8 ± 2.2% between repeated CMRO₂ measurements. In addition, given the highly variable blood flow velocity within this age range, it is recommended that the TRUST labeling thickness and position should be determined on a subject‐by‐subject basis, and an automatic algorithm was developed for this purpose. Although this method provides a global CMRO₂ measure only, the clinical significance of an energy consumption marker and the convenience of this technique may make it a useful tool in the functional assessment of the neonatal population. Copyright © 2014 John Wiley & Sons, Ltd.