Telehealth mitigates COPD disease progression compared to standard of care: a randomized controlled crossover trial.

BACKGROUND: We showed excellent adherence and satisfaction with our telehealth care (TC) approach for COPD. Here, the results of a consecutive randomized controlled trial are presented. METHODS: Patients were randomly assigned to TC or standard care (SC). During TC, patients answered six daily questions online, and focused on the early recognition of exacerbations, in addition to SC. RESULTS: The mean increase in COPD assessment test (CAT) was 1.8 vs. 3.6 points/year in the TC and SC groups, respectively (P = 0.0015). Satisfaction with care (VAS) at baseline was 8.2; at the end of SC, 8.5 (P = 0.062); and after TC, 8.8 (P < 0.001). We detected significantly more moderate exacerbations during TC. CONCLUSION: Whilst receiving TC, the slope of the CAT increase - an indicator of the naturally progressive course of COPD - was reduced by 50%. Satisfaction with care increased with TC. The higher number of detected moderate exacerbations probably indicates a higher diagnostic sensitivity than without TC.

Physical activity and the frequency of acute exacerbations in patients with chronic obstructive pulmonary disease.

PURPOSE: Acute exacerbations (AE) in patients with COPD are associated with a decline in lung function, increased risk of hospitalization, and mortality. In this cross-sectional study we tested whether the level of objectively measured daily physical activity and exercise capacity are associated with the number of COPD exacerbations. METHODS: In 210 patients with COPD (67 % men; mean (SD) age: 63 (8) years) enrolled in The Obstructive Pulmonary Disease Outcomes Cohort of Switzerland (TOPDOCS) physical activity (PA) (steps per day, physical activity level, (PAL)), exercise capacity (6-min walking distance, (6MWD)), comorbidities, lung function, and medication were assessed. Differences between COPD patients with frequent (≥2 year) and infrequent (0-1 year) exacerbations were assessed. Univariate and multivariate analyses were performed to investigate whether the level of objectively measured daily physical activity and exercise capacity are associated with the number of COPD exacerbations. RESULTS: Patients with frequent AE had a significantly lower FEV1 and 6MWD compared to patients with infrequent AE. In univariate analysis, the number of exacerbations was inversely associated with FEV1, 6MWD, BMI, and smoking status while there was a positive association with RV/TLC and combined inhaled medication. However, there was no significant association with PAL and steps per day. In multivariate analysis, FEV1 and the use of combined inhaled medication were independently associated with the number of AE, after correction for covariates. CONCLUSIONS: The findings of this study imply that FEV1, independent of inhaled medication, is significantly associated with COPD exacerbations. Neither physical activity nor exercise capacity was independently associated with COPD exacerbations.

[Breathlessness: different causes and qualities of dyspnea]. / Wenn das Atmen Mühe macht: Ursachen und Typen der Atemnot.

Dyspnea is the unpleasant awareness of breathing while healthy persons will hardly sense their own breath at rest. Dyspnea is comparable to pain because both caution the organism that will activate protective mechanisms to avoid further damage. Dyspnea results from central nervous processing of respiratory feed back signals. Feed back from respiratory muscles, the chest wall, the airways and the lung reach the brain while partial pressure of oxygen and carbon dioxide is continuously monitored and arterial blood gases are permanently stabilized. Sensation of breathlessness depends on its origin. Main qualities of dyspnea include air hunger during hypercapnia, laboured breathing during increased minute ventilation and chest tightness in asthma. During chronic dyspnea, respiratory control aims for a new breathing pattern that will ease breathlessness. Since respiratory control includes both autonomic regulation and cortical modulation of breathing, voluntarily guided respiration can be employed to influence other autonomic regulated systems and pain perception.

Disability and survival in Duchenne muscular dystrophy.

BACKGROUND: Duchenne muscular dystrophy (DMD) leads to progressive impairment of muscle function, respiratory failure and premature death. Longitudinal data on the course of physical disability and respiratory function are sparse. OBJECTIVES: To assess prospectively physical impairment and disability, respiratory function and survival in patients with DMD over several years to describe the course of the disease with current care. METHODS: In 43 patients with DMD, aged 5-35 years, yearly assessments of physical disability by the Duchenne muscular dystrophy physical Impairment and Dependence on care (DID) score, ranging from 9 (no disability) to 80 (complete dependence), and forced vital capacity (FVC), were obtained over a mean time interval of 5.4 (SD 2.1) years. RESULTS: DID scores were correlated with age according to a hyperbolic function (f = 85.3 x age/(10.05+age), R = 0.62, p<0.0001). FVC declined exponentially with age (f = 139.1 x exp(-0.08 x age), R = 0.52, p<0.0001). Mean age at which patients lost their ambulation was 9.4 (SD 2.4) years and they became dependent on an electric wheelchair at 14.6 (4.0) years. Age at the beginning of assisted ventilation was 19.8 (3.9) years, Three patients died during the observation period. The estimated probability of survival to age 30 years was 85% (median survival was 35 years). CONCLUSIONS: Our detailed observations of the progression of physical disability, dependence on care and respiratory impairment in patients with DMD from childhood to adult life is valuable for predicting the clinical course with current medical care. Compared with historical data, survival has improved considerably.

Periodic whole body acceleration: a novel therapy for cardiovascular disease.

BACKGROUND: Periodic whole body acceleration in the spinal axis (pGz) applied by a motion platform is a novel treatment modality that induced endothelial nitric oxide release into the circulation of animals, healthy subjects and patients with inflammatory diseases during single treatment sessions in previous studies. We hypothesized that patients with advanced arteriosclerotic diseases who are not candidates for a surgical intervention would clinically benefit from repeated pGz treatments over several weeks through improvement of endothelial function. PATIENTS AND METHODS: 11 patients, 5 men (37 to 71 y) with stable ischemic heart disease, LVEF < 35%, NYHA stage > II, and 6 patients (51 to 83 y, 1 woman) with intermittent leg claudication, Fontaine stage II, were enrolled after optimization of pharmacological therapy. PGz was applied for 40 min, 5 days/week during 5 weeks. Quality of life (SF-36 questionnaire), exercise performance, and endothelial function were assessed at baseline, during the treatment period, and 4 weeks after discontinuation of pGz. RESULTS: PGz was well tolerated. In heart failure paitents, pGz therapy improved quality of life, increased 6 min walking distance by a mean +/- SE of 105 +/- 24 m, and improved postischemic skin hyperemia (p < .05 in all instances). In 4 of 6 patients with intermittent claudication, quality of life, treadmill walking distance and post-ischemic skin hyperemia improved with pGz therapy (p < .05). Four weeks after discontinuation of pGz, most therapeutic effects had vanished in both patient groups. CONCLUSIONS: In patients with severe heart failure and with leg claudication who remain symptomatic despite maximal medical therapy and who were not candidates for surgery, periodic acceleration applied over several weeks improved quality of life and exercise capacity. The clinical benefits appear to be mediated through improved endothelial function.

Transient short free running circadian rhythm in a case of aneurysm near the suprachiasmatic nuclei.

A free running circadian rest-activity cycle is rare in sighted individuals living in a normal environment. Even more rare is a periodicity shorter than 24 hours, as observed in actigraphic recordings in a female patient during convalescence after a whiplash injury in a car accident. The documented free running period was 22.5 hours for 19 days. During the subsequent weeks re-entrainment occurred following re-establishment by a social zeitgeber, with a slightly early circadian phase of nocturnal melatonin onset relative to a late sleep period. Magnetic resonance imaging and cerebral angiography showed an aneurysm at the bifurcation of the right internal carotid artery, close to the circadian pacemaker structure (the suprachiasmatic nuclei), which was later occluded.

Bronchoscopic radioisotope injection for sentinel lymph-node mapping in potentially resectable non-small-cell lung cancer.

OBJECTIVE: Prospective study to evaluate the feasibility of a preoperative bronchoscopic radioisotope application, followed by conventional sentinel lymph-node (SLN) identification and to investigate the occurrence and distribution of micrometastases in relation to SLN activity. METHODS: Twenty patients with a mean age of 63 years and proven clinical stage T1-3 N0-1 non-small-cell lung cancer (NSCLC) were included. A dosage of 80MBq radiolabeled technetium-99m nanocolloid was endoscopically administrated on intubated patients in the operation theatre. At thoracotomy, scintigraphic readings of both the primary tumor and hilar and mediastinal lymph-node stations were obtained with a hand-held gamma-counter. Patients underwent lung resection and mediastinal lymphadenectomy. Radiolabeled nodes were also examined separately on back-table. SLNs were defined as the hottest nodes or nodes with at least one-tenth of the radioactivity of the hottest nodes. SLNs pathologic assessment included standard examination using hematoxylin and eosin staining on step sections and immunohistochemistry (ICH) for cytokeratins. RESULTS: Identification of SLNs was possible in 19/20 (95%) patients after bronchoscopic radioisotope application. In 7/19 (37%) patients, a unique SLN was identified, whereas in 12/19 (63%) patients, nodes from two different stations could be classified as SLNs. Metastatic nodal disease was found in 9/19 (47%) patients. ICH revealed micrometastases in 2/12 (17%) patients, initially classified nodal negative. Pathologic negative SLNs were a predictor for absence of metastatic nodal disease after mediastinal lymphadenectomy. No complication related to the procedure was observed. CONCLUSION: Our preliminary results suggest that preoperative bronchoscopic radioisotope injection for SLN identification is a safe and simple method, improving accuracy of SLN detection in comparison to intraoperative technique. The absence of metastases in the SLNs seems to predict a negative nodal status accurately.

Occlusion of experimentally created fusiform aneurysms with porous metallic stents.

BACKGROUND AND PURPOSE: Carotid fusiform aneurysms are most commonly treated with occlusion of the parent vessel. The purpose of our study was to assess the effectiveness of self-expanding, cobalt-alloy stents in the ablation of experimental fusiform aneurysms with preservation of the parent vessel in a carotid artery model. METHODS: Porous metallic stents were placed endovascularly along the lengths of experimentally created fusiform aneurysms in the carotid arteries of dogs; aneurysms were also created in the animals' opposite carotid arteries to serve as controls. RESULTS: Before stent placement, angiography of the carotid arteries showed large fusiform aneurysms along the lengths of the common carotid arteries and complex patterns of flow. Immediately after stent placement there was disruption of the usual flow patterns within the lumens of the fusiform aneurysms. The lumen between the wall of the aneurysm and stented carotid showed stasis of contrast material and blood. Near-complete ablation of all aneurysms was observed 8 weeks after stent placement. The stented carotid arteries remained widely patent; control aneurysms and carotid arteries were patent and unchanged. Histopathologic analysis revealed fibrotic reactive scar tissue filling the space between the stent wires and outer wall of the fusiform aneurysm. CONCLUSION: Changing blood flow dynamics within an aneurysm can promote thrombus formation. The stent promotes stasis and thrombus within the residual lumen between the stent wall and the outer wall of the aneurysm because its woven wire mesh interferes with usual blood flow patterns, which then promotes formation of thrombus and fibrosis within the residual aneurysmal lumen.

Ventilatory mechanics and gas exchange during exercise before and after lung volume reduction surgery.

Many patients with emphysema are able to meet ventilatory demands during resting conditions, but they show severe limitations during exercise. To examine the effect of lung volume reduction (LVR) surgery on exercise performance and the mechanism of possible improvement, we measured ventilatory mechanics (pulmonary resistance [RL], work of breathing [WOB], dynamic intrinsic positive end-expiratory pressure [PEEPi,dyn], peak expiratory flow rate [PEFR]), breathing pattern, oxygen uptake (V O2), and carbon dioxide removal (V CO2) at rest and during cycle ergometry in eight patients before and 3 mo after LVR surgery. Ventilatory mechanics were evaluated assessing esophageal pressure and air flow. Three months after LVR surgery, the tolerated workload was doubled when compared with the preoperative value (p < 0.0005), associated with a reduction of RL (p < 0.05), PEEPi,dyn (p < 0.005), and WOB (p < 0. 005) at comparable workloads. Maximal ventilatory capacity and maximal tidal volume (VT) increased significantly (p < 0.01). Maximal V O2 increased from 474 +/- 23 to 601 +/- 16 ml/min (p < 0. 005) and maximal V CO2 from 401 +/- 13 to 558 +/- 21 ml/min (p < 0. 005), though no significant difference at comparable workloads could be observed. In conclusion, emphysema surgery leads to an improvement of ventilatory mechanics at rest and during exercise. Higher maximal VT and minute ventilation were observed, resulting in improvement of maximal V O2 and V CO2 and exercise capacity.

Effect of resistive loading on variational activity of breathing.

To examine the effect of resistive loading on variational activity of breathing, we studied 18 healthy subjects breathing at rest and with inspiratory resistive loads of 3 and 6 cm H2O/L/s, applied randomly for 1 h each. Compared with resting breathing, a resistive load of 3 cm H2O/L/s decreased the total variational activity of expiratory time (TE) and minute ventilation (V I), whereas a load of 6 cm H2O/L/s increased the total variational activity of inspiratory time (TI). Compared with the load of 3 cm H2O/L/s, the load of 6 cm H2O/L/s increased total variational activity of tidal volume (VT), TI, TE, and V I. Partitioning of the total variational activity revealed that these alterations were due to changes in the random uncorrelated fraction. Compared with rest, both the resistive loads of 3 and 6 cm H2O/L/s increased the number of breath lags displaying significant serial correlations ("short-term memory") of TI. Compared with rest, the load of 3 cm H2O/L/s increased the autocorrelation coefficient at a lag of one breath for VT and the load of 6 cm H2O/L/s increased the correlated fraction of variational activity of VT. Thus, three measures of correlated behavior-autocorrelation coefficient at a lag of 1 breath, "short-term memory," and the correlated fraction of total variational activity- increased with loading. In conclusion, resistive loading changed total variational activity according to the size of the load: the random fraction decreased with the smaller load but increased with the larger load; in contrast, correlated behavior increased with both loads. The different behaviors of random and correlated variability with loading may reflect different physiologic influences on respiratory control.

Effect of elastic loading on variational activity of breathing.

To examine the effect of elastic loading on variational activity of breathing, we studied 11 healthy subjects breathing at rest and with inspiratory elastic loads of 9 and 18 cm H2O/L, applied randomly for 1 h each. Compared with rest, a load of 18 cm H2O/L decreased gross variability, quantitated as standard deviation, of tidal volume (VT) and expiratory time (TE) (p < 0.01 in both instances) but increased that of inspiratory time (TI) (p < 0.03). The autocorrelation coefficients at a lag of 1 breath for each breath component were not altered by elastic loading, although the number of breath lags with significant serial correlations for TE tended to increase with a load of 18 cm H2O/L (p = 0.08). A load of 18 cm H2O/L decreased only the fraction of variational activity of VT and TE due to uncorrelated, random behavior (white noise), while it increased that fraction for TI (p < 0.05 in each instance); the correlated and oscillatory fractions did not change. Uncorrelated random behavior constituted > 87% of the variance of each breath component, correlated behavior represented 3 to 11%, and oscillatory behavior represented < 1.5% during both rest and loaded breathing. Elastic loading changed the gross variability of each primary breath component by altering the random fraction of variational activity; it had no significant effect on the structured, correlated fraction. We speculate that the observed changes in variational activity may reflect an attempt by the controller to compensate for the increased load while simultaneously minimizing load-induced dyspnea.

[Rhabdomyolysis in patients treated with simvastatin and cyclosporin: role of the hepatic cytochrome P450 enzyme system activity]. / Rhabdomyolyse bei mit Simvastatin und Ciclosporin behandelten Patienten: Rolle der Aktivität des Cytochrom-P450-Enzymsystems der Leber.

We describe two patients treated with a combination of cyclosporin and simvastatin who had to be hospitalized due to rhabdomyolysis. As suggested by reduced cyclosporin clearance, both patients had impaired activity of the hepatic cytochrome P450 enzyme system, which may have contributed to the development of rhabdomyolysis. After cessation of treatment with simvastatin and intensive hydration, both patients recovered within one week. While rhabdomyolysis has been described in several patients receiving the combination lovastatin/cyclosporin, so far only one case has been reported in patients treated with simvastatin/cyclosporin. Our cases therefore suggest that this complication may be more frequent than previously suspected. In patients treated with cyclosporin, HMG-CoA reductase inhibitors should be used cautiously, and concomitant administration of drugs inhibiting the hepatic cytochrome P450 enzyme system should be avoided.

Primary picosecond molecular events in the photoreaction of the BR5.12 artificial bacteriorhodopsin pigment.

The picosecond dynamics of the photoreaction of an artificial bacteriorhodopsin (BR) pigment containing a retinal in which a five-membered ring spans the C-12 to C-14 positions of the polyene chain (BR5.12) is examined by using time-resolved absorption and fluorescence and resonance Raman spectroscopy. The ring within the retinal chromophore of BR5.12 blocks the C-13 = C-14 isomerization proposed to be a primary step in the energy storage/transduction mechanism in the BR photocycle. Relative to the native BR pigment (BR-570), the absorption spectrum of BR5.12 is red-shifted by 8 nm. The fluorescence spectrum of BR5.12 closely resembles that of BR-570 although the relative fluorescence yield is higher (approximately 10-fold). Picosecond transient absorption (4-ps pulses, 568-662 nm) measurements reveal an intermediate absorbing to the red side of BR5.12. Kinetic fits show that the red-absorbing intermediate appears within < 3 ps and decays with a time constant of 17 +/- 1 ps to form only BR5.12. No emission in the 650- to 900-nm region can be attributed to the red-absorbing species. Since rotation around C-12 - C-13 and isomerization around C-13 = C-14 are prevented in BR5.12, these results demonstrate that motion in these regions of the retinal is (i) necessary to form the K-like intermediate observed in the native BR-570 photocycle and (ii) not necessary to form a red-absorbing intermediate that has spectral and kinetic properties analogous to those of J-625 in the native BR photocycle. Discussions of the excited and ground electronic state assignments for the intermediate observed in the BR5.12 photoreaction are presented.

Picosecond time-resolved absorption and fluorescence dynamics in the artificial bacteriorhodopsin pigment BR6.11.

The picosecond molecular dynamics in an artificial bacteriorhodopsin (BR) pigment containing a structurally modified all-trans retinal chromphore with a six-membered ring bridging the C11=C12-C13 positions (BR6.11) are measured by picosecond transient absorption and picosecond time-resolved fluorescence spectroscopy. Time-dependent intensity and spectral changes in absorption in the 570-650-nm region are monitored for delays as long as 5 ns after the 7-ps, 573-nm excitation of BR6.11. Two intermediates, J6.11 and K6.11/1, both with enhanced absorption to the red (> 600 nm) of the BR6.11 spectrum are observed within approximately 50 ps. The J6.11 intermediate decays with a time constant of 12 +/- 3 ps to form K6.11/1. The K6.11/1 intermediate decays with an approximately 100-ps time constant to form a third intermediate, K6.11/2, which is observed through diminished 650-nm absorption (relative to that of K6.11/1). No other transient absorption changes are found during the remainder of the initial 5-ns period of the BR6.11 photoreaction. Fluorescence in the 650-900-nm region is observed from BR6.11, K6.11/1, and K6.11/2, but no emission assignable to J6.11 is found. The BR6.11 fluroescence spectrum has a approximately 725-nm maximum which is blue-shifted by approximately 15 nm relative to that of native BR-570 and is 4.2 +/- 1.5 times larger in intensity (same sample optical density). No differences in the profile of the fluorescence spectra of BR6.11 and the intermediates K6.11/1 and K6.11/2 are observed. Following ground-state depletion of the BR6.11 population, the time-resolved fluroescence intensity monitored at 725 nm increases with two time constants, 12 +/- 3 and approximately 100 ps, both of which correlate well with changes in the picosecond transient absorption data. The resonance Raman spectrum of ground-state BR6.11, measured with low-energy, 560-nm excitation, is significantly different from the spectrum of native BR-570, thus confirming that the picosecond transient absorption and picosecond time resolved fluorescence data are assignable to BR6.11 and its photoreaction alone and not to BR-570 reformed during there constitution process (<5% of the BR6.11 sample could be attributed to native BR-570).The J6.11 and K6.11 absorption and fluorescence data presented here are generally analogous to those measured for native J-625 and K-590, respectively, and therefore, the primary events in the BR6.11 photoreaction can be correlated with those in the native BR photocycle. The BR6.11 photoreaction, however, exhibits important differences including slower formation rates for J and K intermediates as well as the presence of a second K intermediate. These results demonstrate that the restricted motion in the C11=C12-C13 region of retinal found in BR6.11 does not greatly change the overall photoreaction mechanism,but does alter the rates at which processes occur.

Time-resolved absorption and fluorescence from the bacteriorhodopsin photocycle in the nanosecond time regime.

Picosecond transient absorption (PTA) in the 568-660-nm region is measured over the initial 80 ns of the bacteriorhodopsin photocycle. After photocycle initiation with 573-nm excitation (7-ps pulsewidth), these PTA data reflect the formation during the initial 40 ps of two long-recognized intermediates with red-shifted (relative to that of BR-570) absorption bands, namely J-625 and K-590. PTA signals at 568, 628, and 652 nm are unchanged for the remainder of the 80-ns photocycle interval measured, demonstrating that no other intermediates, including the proposed KL, are observable by absorption changes. Picosecond time-resolved fluorescence (PTRF), measured at 740 nm, is initiated by 7 ps excitation of the species present at various time delays after the photocycle begins. PTRF signals change rapidly over the initial 40 ps, reflecting, first, the depletion of the ground state BR-570 population and, subsequently, the formation of K-590. The PTRF signal then decreases monotonically with a time constant of 5.5 +/- 0.5 ns from its maximum near a 50-ps delay until it reaches a minimum at a delay of approximately 13 ns. For time delays between 13 and 80 ns, the PTRF signal remains unchanged and slightly higher than that measured from BR-570 alone. The rapid decrease in PTRF signals over the same photocycle interval in which the PTA signals remain unchanged suggests that the retinal-protein interactions involving electronically excited K-590 (K*) are being significantly altered.

[Effect of halving the dosage of atenolol in essential hypertension]. / Effekt einer Dosishalbierung von Atenolol bei essentieller Hypertonie.

In the present study the effect of halving the dose of atenolol in 41 essential hypertensives was analyzed. Prereduction dosage of atenolol was 100 mg in 26 and 50 mg in 15 patients. In 16 cases the beta-blocker was administered as monotherapy and in the remaining patients atenolol was combined with a calcium antagonist and/or a diuretic. Dosage of these drugs was constant throughout the whole study. During an observation period of 12 weeks after halving atenolol from a mean dose of 82 mg to 41 mg, no significant changes in systolic and diastolic blood pressure or in response rate (defined as a diastolic blood pressure of 95 mm Hg or less) were observed. In view of our results and those of other authors, it is recommended that in patients with mild hypertension whose blood pressure has been kept below 140/85 mm Hg by treatment for at least one year, betablockers may be reduced in a step-wise fashion.

Detection of N-myc gene amplification in bone marrow specimen of stage IV neuroblastoma patients.

N-myc gene amplification is an unfavorable prognostic factor in neuroblastoma; therefore, its detection might have therapeutical consequences. Because of the reliability of noninvasive diagnostic methods such as X-ray examination and measurement of vanilymandelic acid and the lack of technical unavailability at most institutions, the determination of the N-myc status of neuroblastoma often is not done. In our investigation of 14 neuroblastoma patients, we could demonstrate N-myc gene amplification in the bone marrow of 5 patients with neuroblastoma stage IV disease and in bone marrow infiltration without enrichment of neuroblastoma cells. Otherwise, no information about the tumor content of N-myc gene copies at the time of initial diagnosis could be obtained. At the subsequent resection, the N-myc gene amplification was confirmed by the additional Southern blot analysis and in situ hybridization of tumor tissue. Furthermore, the N-myc status of bone marrow was analyzed during the stages of chemotherapy in three cases.

[N-myc status of neuroblastoma from bone marrow cells]. / Untersuchung des N-myc Status beim Neuroblastom aus Knochenmarkzellen.

The analysis of the N-myc gene in bone marrow specimens at the time of initial diagnosis and as well at the time of relapse from patients with Neuroblastoma stage IV and bone marrow infiltration could give some informations about the N-myc status of these patients. In stage IV neuroblastoma patients with bone marrow infiltration an estimation of the N-myc gene amplification should be attempted, if otherwise no information about the tumor content of the N-myc gene could be gathered. In our investigation we could demonstrate a Southern-blot-analysis of 27 bone marrow specimens with respect to the N-myc gene status which correlated qualitatively well to the N-myc amplification detected later on in the corresponding tumor tissue. In six cases the tumor infiltrated bone marrow showed a clear amplification of the N-myc gene. Because of the contamination by non malignant cells in bone marrow there was a quantitative difference in the calculated N-myc gene copies between the examined bone marrow specimens and corresponding tumor tissue.