Substrate utilization and kinetics of surfactant metabolism in evolving bronchopulmonary dysplasia

OBJECTIVES: To use stable isotopically labeled precursors of pulmonary surfactant phospholipids to measure precursor utilization and surfactant turnover in premature infants who required mechanical ventilation at birth, 2 weeks, and >4 weeks of age. STUDY DESIGN: Infants of < or =28 weeks' gestation received simultaneous 24-hour intravenous infusions of [1,2,3,4-13C4] palmitate and [1-13C1] acetate at birth, 2 weeks, and > or =4 weeks of life. Disaturated phospholipids were extracted from sequential tracheal aspirate samples obtained over a period of 2 weeks. Fractional catabolic rate (a measure of total turnover) and the fractional synthetic rates from plasma palmitate and de novo synthesis (acetate) were measured. RESULTS: The fractional catabolic rate increased from 25.3% +/- 7.0% per day at birth to 53.8% +/- 14.4% per day at 4 weeks (P=.001). The combined contribution from plasma palmitate and de novo synthesis to total synthesis increased from 44.2% +/- 19.8% at birth to 85.2% +/- 32.8% at 4 weeks (P=.03). CONCLUSIONS: Total surfactant turnover increased in premature infants with evolving bronchopulmonary dysplasia. The increasing contributions from acetate and plasma palmitate suggest a decrease in surfactant phospholipid recycling.     

Effect of HELP-LDL-apheresis on serum concentrations of human lipoprotein(a): kinetic analysis of the post-treatment return to baseline levels

In addition to LDL, Lp(a) can be quantitatively eliminated from plasma in an extracorporeal LDL-apheresis procedure based on precipitation with heparin at pH 5.12. The rates of return of post-apheresis Lp(a) and LDL-cholesterol concentrations to baseline levels were investigated in six individuals with familial hypercholesterolaemia (one homozygote, five heterozygote) and one normolipaemic individual. The first-order disappearance constants (kappa) were derived for LDL and Lp(a) according to Apstein et al. The kappa values for LDL in the homozygous FH and the normolipaemic individual were 0.082 and 0.43 respectively while the heterozygous FH patients had kappa values intermediate between the two (median 0.231; range 0.116-0.261). The first-order disappearance constants of Lp(a) did not correlate with those of LDL. The homozygous FH and normolipaemic individuals had Lp(a) kappa values of 0.158 and 0.199 respectively; the corresponding values in the heterozygous FH patients were: median 0.142; range 0.045-0.179.     

Enabling Task-Specific Volitional Motor Functions via Spinal Cord Neuromodulation in a Human With Paraplegia

We report a case of chronic traumatic paraplegia in which epidural electrical stimulation (EES) of the lumbosacral spinal cord enabled (1) volitional control of task-specific muscle activity, (2) volitional control of rhythmic muscle activity to produce steplike movements while side-lying, (3) independent standing, and (4) while in a vertical position with body weight partially supported, voluntary control of steplike movements and rhythmic muscle activity. This is the first time that the application of EES enabled all of these tasks in the same patient within the first 2 weeks (8 stimulation sessions total) of EES therapy.     

彩色多普勒血流会聚法定量诊断二尖瓣狭窄的研究

本研究应用Ｍ型彩色多普勒血流会聚法、二维彩色多普勒血流会聚法测量２１例以二尖瓣狭窄为主的风心病患者二尖瓣狭窄瓣口面积，并分别与二维超声直接测面积法及多普勒超声压力减半时间法所测二尖瓣口面积相比较。结果表明，Ｍ型彩色多普勒血流会聚法与二维彩色多普勒血流会聚法在检测二尖瓣狭窄瓣口面积方面基本可靠，但两者的准确性无显著差异。本文初步分析了Ｍ型彩色多普勒血流会聚法及二维彩色多普载血流会聚法测量二尖瓣狭窄瓣口面积的优缺点及临床价值。     

Persistently low lymphocyte counts after FCR therapy for chronic lymphocytic leukemia are associated with longer overall survival

Decreased absolute lymphocyte counts (ALCs) following frontline therapy for chronic lymphocytic leukemia may be associated with disease control, even in patients without evidence of minimal residual disease. We studied the prognostic significance of ALCs during the first year following treatment with fludarabine, cyclophosphamide, and rituximab (FCR). We evaluated 99 patients who achieved a partial response without lymphocytosis (<4.0 × 10³cells/μL) or better after FCR. Absolute lymphocyte counts were recorded at 3‐, 6‐, 9‐, and 12‐month posttreatment and correlated with overall survival (OS) and event‐free survival (EFS). For each time point, analyses were limited to patients without lymphocytosis, so as to avoid possible biases from undocumented disease progressions. Lymphopenia (ALC < 1.0 × 10³cells/μL) at 3 m after FCR (69% of patients n = 68), was associated with a longer OS (5y OS 91% vs 64%, P = .001), as were ALC ≤ 2 × 10³ cells/μL at 6 m (5y OS 85% vs 48%, P = .004) and ALC ≤ 1.8 × 10³ cells/μL at 9 m (5y OS 93% vs 54%, P = .009). A normal‐range ALC (≤4 × 10³ cells/μL) at 12 m was also associated with a 91% 5y OS. Higher ALCs (but without lymphocytosis) were associated with shorter EFS (median EFS 27 months for ALC > 1.8 vs not reached for ALC ≤ 0.7 at 9 months, P < .0001). In conclusion, lower ALC levels in the first few months following frontline FCR therapy were associated with longer OS and EFS. Possible explanations may be that lower ALCs reflect deeper clonal suppression or protracted T_reg depletion. Absolute lymphocyte count levels may be a cheap and widely available prognostic marker, though the added value for clinical practice is the minimal residual disease era needs to be explored.     

Low‐dose fludarabine and cyclophosphamide combined with standard dose rituximab (LD‐FCR) is an effective and safe regimen for elderly untreated patients with chronic lymphocytic leukemia: The Israeli CLL study group experience

Chronic lymphocytic leukemia (CLL) is a disease of elderly patients. The fludarabine, cyclophosphamide, and rituximab (FCR) regimen is considered the treatment of choice for young fit patients with CLL; however, this combination is toxic for older patients. At the time this study was first planned and initiated, there was no standard chemo‐immunotherapy regimen regarded as standard therapy for the less fit elderly patient with CLL. Here, we conducted a single‐arm, phase II trial to examine the efficacy and safety of lower‐dose fludarabine and cyclophosphamide combined with a standard dose of rituximab (LD‐FCR) in elderly patients with previously untreated CLL. Forty patients received LD‐FCR and were included in the efficacy analysis. Two patients treated with FC alone were only included in the safety analysis. The median age was 72.7 years (range, 65.0 to 85.0). The overall response and complete response rates were 67.5% and 42.5%, respectively. Median progression‐free survival (PFS) was 35.5 months (95% CI, 29.27‐41.67). Two patients (4.8%) died during the study period. Hematological toxicities and infections were the most common complications encountered; grade 3 to 4 treatment‐related neutropenia occurred in 20 (47.6%) patients. During the entire study follow‐up, 26 patients (61.9%) had all grades of infection including six (14.3%) with neutropenic fever and eight (19%) with grade 3 to 4 non‐neutropenic infections. In conclusion, LD‐FCR is an effective and relatively safe regimen for previously untreated patients with CLL. It has the advantage of being both “time and cost limited” and, even in the era of novel agents, can still be considered when planning treatment for elderly patients without high‐risk biomarkers. However, recent results in fit elderly patients using the combination of bendamustine and rituximab which have achieved longer PFS with good safety profile must be taken into consideration in this regard.     

Simple index of functional connectivity at rest in Multiple Sclerosis fatigue

Objective

To investigate the EEG-derived functional connectivity at rest (FCR) patterns of fatigued Multiple Sclerosis (MS) patients in order to find good parameters for a future EEG-Neurofeedback intervention to reduce their fatigue symptoms.

Sensory processing during kinesthetic aftereffect following illusory hand movement elicited by tendon vibration

We investigated how the human sensory-motor system elicits a somatosensory aftereffect. Tendon vibration of a limb excites the muscle spindle afferents that contribute to eliciting illusory movements of the limb. After the cessation of vibration, a transient sensation in which the vibrated limb returns towards its original position (kinesthetic aftereffect) is often experienced, even in the absence of the afferent inputs recruited by the vibration. We vibrated the tendon of either the right wrist extensor or flexor muscle that elicited an illusory flexion or extension movement, which was followed by its corresponding extension or flexion aftereffect. First, we psychophysically investigated how the preceding illusory movement affects the aftereffect. Second, we examined the cortico-spinal excitability during the aftereffect to evaluate its changes from the time during the illusion. We measured the amplitude of the motor-evoked potential that is evoked by a single-pulse transcranial magnetic stimulation to the hand section of the contralateral motor cortex (M1). All 19 subjects experienced the aftereffect, and the amount of aftereffect was approximately 70% of the preceding illusion. During the illusion, the cortico-spinal excitability increased more in non-vibrated than in vibrated muscle, so as to reflect the illusory directions. During the aftereffect, the excitability was significantly reduced only in the non-vibrated muscle, with no change in the vibrated muscle, which, in turn, caused an opposite pattern in the unbalanced excitability between the two muscles, and the degree of unbalanced excitability was correlated with the sensation of aftereffect. The kinesthetic aftereffect seems to be elicited by a sensory process that is determined by the preceding illusory movements. Motor-cortical processing of the unbalanced sensory information from the stimulated and non-stimulated muscles may contribute to the elicitation of kinesthetic aftereffect.