Does thoracic bioimpedance accurately determine cardiac output in COPD patients during maximal or intermittent exercise?

STUDY OBJECTIVES: The monitoring of cardiac output (CO) during exercise rehabilitation in patients with COPD, often including strenuous exercise, is advisable. Invasive methods (thermodilution, Fick method) are accurate, but for clinical routine use noninvasive CO estimation is required. We have shown that impedance cardiography (Physio Flow; Manatec Biomedical; Macheren, France) is reliable in COPD patients at rest and during a recumbent, light-intensity exercise. The aim of our study was to evaluate the validity of this noninvasive device in COPD patients during a maximal incremental exercise test (IET) and also during a strenuous intermittent work exercise test (IWET). DESIGN: Prospective comparative study of the impedance cardiograph vs the direct Fick method applied to oxygen. PATIENTS: Eight patients with moderate-to-severe COPD (59 +/- 6 years old; FEV(1), 38 +/- 15% predicted; residual volume, 194 +/- 64% predicted) [mean +/- SD].Measurements and main results: Forty-nine simultaneous measurements of CO by means of the direct Fick method (COfick) and CO measured by the impedance cardiograph (COpf) were obtained during the IET, and 108 measurements were made during the IWET. The correlation coefficients between the two measurements were r = 0.85 and r = 0.71 for the IET and the IWET, respectively. COpf was higher than COfick. The difference between the two methods was 3.2 +/- 2.9 L/min during the IET and 2.5 +/- 2.1 L/min during the IWET. Expressed as a percentage of the mean of the two measurements, this corresponded to 31 +/- 21% and 25 +/- 20%, respectively. CONCLUSIONS: The relatively high number of values differing by > 20% precludes the use of impedance cardiography in clinical routine in such a difficult setting (hyperinflated patients and intense exercise).     

Chondrocalcinosis secondary to hypomagnesemia in Gitelman's syndrome

Chondrocalcinosis can be associated with hyperparathyroidism, hemochromatosis, hypophosphatasia, and hypomagnesemia. Gitelman syndrome (GS), an inherited disorder due to loss of function mutations of the gene encoding the distal convoluted tubule Na-Cl cotransporter (NCCT), is characterized by hypokalemia metabolic alkalosis, hypomagnesemia, and hypocalciuria. A 53-year-old man, with history of recurrent joint effusions and pains affecting knees and wrists, had transient episodes of muscle pain, weakness, cramping, and fatigue over a one-year period. Laboratory tests showed hypokalemia, metabolic alkalosis, hypocalciuria, and hypomagnesemia related to genetically proven GS. Radiographs of affected joints revealed calcium pyrophosphate dihydrate deposition. This observation points out the necessity to look for Mg depletion (and especially GS) in the biological investigation of chondrocalcinosis. Additionally, the association between GS (NCCT inactivation) and high bone mineral density provides a new insight into the possible role of thiazides in osteoporosis management.     

Bone metabolism in adolescent boys with anorexia nervosa

BACKGROUND: Anorexia nervosa (AN) is a condition of severe undernutrition associated with low bone mineral density (BMD) in adolescent females with this disorder. Although primarily a disease in females, AN is increasingly being recognized in males. However, there are few or no data regarding BMD, bone turnover markers or their predictors in adolescent AN boys. HYPOTHESES: We hypothesized that BMD would be low in adolescent boys with AN compared with controls associated with a decrease in bone turnover markers, and that the gonadal steroids, testosterone and estradiol, and levels of IGF-I and the appetite regulatory hormones leptin, ghrelin, and peptide YY would predict BMD and bone turnover markers. METHODS: We assessed BMD using dual-energy x-ray absorptiometry and measured fasting testosterone, estradiol, IGF-I, leptin, ghrelin, and peptide YY and a bone formation (aminoterminal propeptide of type 1 procollagen) and bone resorption (N-telopeptide of type 1 collagen) marker in 17 AN boys and 17 controls 12-19 yr old. RESULTS: Boys with AN had lower BMD and corresponding Z-scores at the spine, hip, femoral neck, trochanter, intertrochanteric region, and whole body, compared with controls. Height-adjusted measures (lumbar bone mineral apparent density and whole body bone mineral content/height) were also lower. Bone formation and resorption markers were reduced in AN, indicating decreased bone turnover. Testosterone and lean mass predicted BMD. IGF-I was an important predictor of bone turnover markers. CONCLUSION: AN boys have low BMD at multiple sites associated with decreased bone turnover markers at a time when bone mass accrual is critical for attainment of peak bone mass.     

Differential effects of antihypertensive agents on electrocardiographic voltage: results from the Appropriate Blood Pressure Control in Diabetes (ABCD) trial

Background

Serial decline in electrocardiographic voltage in patients with increased left ventricular mass has been associated with a lower risk of cardiovascular events.

Methods

We studied 468 patients with diabetes mellitus and hypertension in the Appropriate Blood Pressure Control in Diabetes (ABCD) trial. Patients were randomized in a stratified design to receive initial treatment with either enalapril or nisoldipine and to either intensive or moderate treatment goals. We measured an electrocardiographic index for increased left ventricular mass, the adjusted Cornell voltage, serially by treatment group. The association between changes in electrocardiographic voltage and cardiovascular events was defined with Cox proportional hazards analysis.

Results

In 5 years of follow-up, the decline in adjusted Cornell voltage was significantly greater for patients treated with enalapril than for patients treated with nisoldipine (repeated measures analysis of variance P = .002). In the Cox proportional hazards model, treatment assignment (enalapril vs nisoldipine) was the strongest predictor of cardiovascular events, but the presence of coronary disease at baseline, the duration of diabetes mellitus, and change in voltage were also independent predictors of cardiovascular events.

Conclusions

In the ABCD study, enalapril treatment was associated with a lower risk of myocardial infarction. The reduction in left ventricular mass as reflected by diminished electrocardiographic voltage may explain some, but not all, of the effect of enalapril in this study.     

Hidden Genetic Variation in LCA9‐Associated Congenital Blindness Explained by 5′UTR Mutations and Copy‐Number Variations of NMNAT1

Leber congenital amaurosis (LCA) is a severe autosomal‐recessive retinal dystrophy leading to congenital blindness. A recently identified LCA gene is NMNAT1, located in the LCA9 locus. Although most mutations in blindness genes are coding variations, there is accumulating evidence for hidden noncoding defects or structural variations (SVs). The starting point of this study was an LCA9‐associated consanguineous family in which no coding mutations were found in the LCA9 region. Exploring the untranslated regions of NMNAT1 revealed a novel homozygous 5′UTR variant, c.‐70A>T. Moreover, an adjacent 5′UTR variant, c.‐69C>T, was identified in a second consanguineous family displaying a similar phenotype. Both 5′UTR variants resulted in decreased NMNAT1 mRNA abundance in patients’ lymphocytes, and caused decreased luciferase activity in human retinal pigment epithelial RPE‐1 cells. Second, we unraveled pseudohomozygosity of a coding NMNAT1 mutation in two unrelated LCA patients by the identification of two distinct heterozygous partial NMNAT1 deletions. Molecular characterization of the breakpoint junctions revealed a complex Alu‐rich genomic architecture. Our study uncovered hidden genetic variation in NMNAT1‐associated LCA and emphasized a shift from coding to noncoding regulatory mutations and repeat‐mediated SVs in the molecular pathogenesis of heterogeneous recessive disorders such as hereditary blindness.     

Acromiohumeral Distance During Neuromuscular Electrical Stimulation of the Lower Trapezius and Serratus Anterior Muscles in Healthy Participants

Context

Compromise to the acromiohumeral distance has been reported in participants with subacromial impingement syndrome compared with healthy participants. In clinical practice, patients with subacromial shoulder impingement are given strengthening programs targeting the lower trapezius (LT) and serratus anterior (SA) muscles to increase scapular posterior tilt and upward rotation. We are the first to use neuromuscular electrical stimulation to stimulate these muscle groups and evaluate how the muscle contraction affects the acromiohumeral distance.

Objective

To investigate if electrical muscle stimulation of the LT and SA muscles, both separately and simultaneously, increases the acromiohumeral distance and to identify which muscle-group contraction or combination most influences the acromiohumeral distance.

Design

Controlled laboratory study.

Setting

Human performance laboratory.

Patients or Other Participants

Twenty participants (10 men and 10 women, age = 26.9 ± 8.0 years, body mass index = 23.8) were screened.

Intervention(s)

Neuromuscular electrical stimulation of the LT and SA.

Main Outcome Measure(s)

Ultrasound measurement of the acromiohumeral distance.

Results

Acromiohumeral distance increased during contraction via neuromuscular electrical stimulation of the LT muscle (t₁₉ = −3.89, P = .004), SA muscle (t₁₉ = −7.67, P = .001), and combined LT and SA muscles (t₁₉ = −5.09, P = .001). We observed no differences in the increased acromiohumeral distance among the 3 procedures (F_2,57 = 3.109, P = .08).

Conclusions

Our results supported the hypothesis that the muscle force couple around the scapula is important in rehabilitation and scapular control and influences acromiohumeral distance.Key Words: subacromial impingement syndrome, real-time ultrasound, rehabilitation

Key Points

• Acromiohumeral distance increased during neuromuscular electrical stimulation of the lower trapezius muscle, serratus anterior muscle, and combined lower trapezius and serratus anterior muscles.
• The increase in acromiohumeral distance was not different among the 3 neuromuscular electrical-stimulation procedures.
• The muscle force couple around the scapula is important in rehabilitation and scapular control and influences acromiohumeral distance.

Optimal upper limb function depends on the ability to statically and dynamically position the shoulder girdle in an optimal coordinated fashion.^1,2 Suboptimal motor control is considered a risk factor for developing shoulder subacromial impingement syndrome.^3–14 Alterations in scapular motion have been linked to a decrease in serratus anterior (SA) muscle activity, an increase in upper trapezius muscle activity, and an imbalance of forces between the upper and lower parts of the trapezius muscle.¹⁵ This may adversely affect scapular positioning, resulting in reduced scapular upward rotation, increased anterior scapular tilt, and scapular winging.^4,9,16 In turn, scapular upward rotation and posterior tilt are considered vital for elevating the acromion and, hence, widening the subacromial space, thereby preventing impingement of the subacromial tissues.^17,18 Atalar et al¹⁹ suggested that reduced scapular mobility led to a decrease in acromiohumeral distance (AHD) during upper extremity abduction. Therefore, when developing rehabilitation strategies for patients with subacromial impingement syndrome, correcting neuromuscular control of the SA and trapezius muscles is important.^20,21Overall, researchers^22,23 have supported the theory that altered activity in the scapular rotator muscles is present in patients with subacromial impingement syndrome and have highlighted the role of scapular rotator muscle training as an essential component of shoulder rehabilitation. A clinical practice strategy, supported by research data, recommends that patients who have subacromial shoulder impingement and present with primary movement dysfunction of the scapula should be given strengthening programs targeting the lower trapezius (LT) and SA muscles.^24,25 The LT muscle is reported to increase posterior scapular tilt, and the SA muscle is believed to increase upward rotation of the scapula.² In turn, posterior scapular tilt and upward scapular rotation are associated with increased AHD.^17,18Authors^9,23,26–29 of electromyographic (EMG) studies have tested muscle activity in participants with subacromial impingement syndrome and in healthy persons. In patients with subacromial impingement syndrome, when the upper extremity was at rest and during flexion and abduction, the EMG signal amplitude of the upper trapezius muscle increased, whereas the EMG signal amplitude of the LT and SA muscles decreased.^30,31 These researchers have considered the immediate changes in the surface EMG activity of the scapular rotator muscles. However, to our knowledge, we are the first to use neuromuscular electrical stimulation (NMES) to stimulate the muscle groups of the LT and SA and evaluate the effect of muscle contraction in these muscles on the AHD. Neuromuscular electrical stimulation is used for various medical applications and is a common intervention during rehabilitation to improve function and motor control,³² prevent and treat shoulder pain,³³ increase range of motion,³⁴ and facilitate changes in muscle action and performance.³⁵ Therefore, the purpose of our study was to investigate whether stimulation of the LT and the SA muscles (separately and simultaneously) with NMES would increase the AHD and to investigate which muscle-group contraction or combination most influenced the AHD.