In vitro effects of bethanechol on specimens of intestinal smooth muscle obtained from the duodenum and jejunum of healthy dairy cows

OBJECTIVE: To describe the in vitro effects of bethanechol on contractility of smooth muscle preparations from the small intestines of healthy cows and define the muscarinic receptor subtypes involved in mediating contraction. SAMPLE POPULATION: Tissue samples from the duodenum and jejunum collected immediately after slaughter of 40 healthy cows. PROCEDURES: Cumulative concentration-response curves were determined for the muscarinic receptor agonist bethanechol with or without prior incubation with subtype-specific receptor antagonists in an organ bath. Effects of bethanechol and antagonists and the influence of intestinal location on basal tone, maximal amplitude (A(max)), and area under the curve (AUC) were evaluated. RESULTS: Bethanechol induced a significant, concentration-dependent increase in all preparations and variables. The effect of bethanechol was more pronounced in jejunal than in duodenal samples and in circular than in longitudinal preparations. Significant inhibition of the effects of bethanechol was observed after prior incubation with muscarinic receptor subtype M(3) antagonists (more commonly for basal tone than for A(max) and AUC). The M(2) receptor antagonists partly inhibited the response to bethanechol, especially for basal tone. The M(3) receptor antagonists were generally more potent than the M(2) receptor antagonists. In a protection experiment, an M(3) receptor antagonist was less potent than when used in combination with an M(2) receptor antagonist. Receptor antagonists for M(1) and M(4) did not affect contractility variables. CONCLUSIONS AND CLINICAL RELEVANCE: Bethanechol acting on muscarinic receptor sub-types M(2) and M(3) may be of clinical use as a prokinetic drug for motility disorders of the duodenum and jejunum in dairy cows.

[Calcium and blood pressure]

The regulation of blood pressure is complex with several organs being involved. Intracellular calcium plays a crucial role in the regulation of cardiovascular functions: An increased influx of calcium into the vascular smooth muscle cells leads to an augmental muscular tone and therefore to an increased vascular resistance and rise in blood pressure. Parathormone plays a permissive role since it regulates the calcium-influx into the cells and thus increases the vasoconstrictive effect. There is a positive correlation between parathormone and blood pressure, present in primary as well as secondary hyperparathyroidism. Moreover, patients with essential hypertension have high parathormone levels already before hypertension is diagnosed. A calcium-rich diet (> 1000 mg calcium daily) slightly decreases blood pressure. This positive effect is due to parathormone suppression with a subsequently decreased calcium content in the vascular smooth muscle cells. A calcium-rich diet inhibits lipogenesis in the fat tissue; thus additionally improving the cardiovascular risk profile.

The significance of the sympathetic nervous system in the pathophysiology of periodic leg movements in sleep

STUDY OBJECTIVES: Periodic leg movements in sleep (PLMS) are frequently accompanied by arousals and autonomic activation, but the pathophysiologic significance of these manifestations is unclear. DESIGN: Changes in heart rate variability (HRV), HRV spectra, and electroencephalogram (EEG) spectra associated with idiopathic PLMS were compared with changes associated with isolated leg movements and respiratory-related leg movements during sleep. Furthermore, correlations between electromyographic activity, HRV changes, and EEG changes were assessed. SETTING: Sleep laboratory. PATIENTS: Whole-night polysomnographic studies of 24 subjects fulfilling the criteria of either periodic leg movements disorder (n = 8), obstructive sleep apnea syndrome (n = 7), or normal polysomnography (n = 9) were used. MEASUREMENTS AND RESULTS: Spectral HRV changes started before all EEG changes and up to 6 seconds before the onset of all types of leg movements. An initial weak autonomic activation was followed by a sympathetic activation, an increase of EEG delta activity, and finally a progression to increased higher-frequency EEG rhythms. After movement onset, HRV indicated a vagal activation, and, the EEG, a decrease in spindle activity. Sympathetic activation, as measured by HRV spectra, was greater for PLMS than for all other movement types. In EEG, gamma synchronization began 1 to 2 seconds earlier for isolated leg movements and respiratory-related leg movements than for PLMS. Significant correlations were found between autonomic activations and electromyographic activity, as well as between autonomic activations and EEG delta activity, but not between higher-frequency EEG rhythms and EMG activity or HRV changes. CONCLUSIONS: These results suggest a primary role of the sympathetic nervous system in the generation of PLMS.

Lung aeration during sleep

BACKGROUND: During sleep, ventilation and functional residual capacity (FRC) decrease slightly. This study addresses regional lung aeration during wakefulness and sleep. METHODS: Ten healthy subjects underwent spirometry awake and with polysomnography, including pulse oximetry, and also CT when awake and during sleep. Lung aeration in different lung regions was analyzed. Another three subjects were studied awake to develop a protocol for dynamic CT scanning during breathing. RESULTS: Aeration in the dorsal, dependent lung region decreased from a mean of 1.14 +/- 0.34 mL (+/- SD) of gas per gram of lung tissue during wakefulness to 1.04 +/- 0.29 mL/g during non-rapid eye movement (NREM) sleep (- 9%) [p = 0.034]. In contrast, aeration increased in the most ventral, nondependent lung region, from 3.52 +/- 0.77 to 3.73 +/- 0.83 mL/g (+ 6%) [p = 0.007]. In one subject studied during rapid eye movement (REM) sleep, aeration decreased from 0.84 to 0.65 mL/g (- 23%). The fall in dorsal lung aeration during sleep correlated to awake FRC (R(2) = 0.60; p = 0.008). Airway closure, measured awake, occurred near and sometimes above the FRC level. Ventilation tended to be larger in dependent, dorsal lung regions, both awake and during sleep (upper region vs lower region, 3.8% vs 4.9% awake, p = 0.16, and 4.5% vs 5.5% asleep, p = 0.09, respectively). CONCLUSIONS: Aeration is reduced in dependent lung regions and increased in ventral regions during NREM and REM sleep. Ventilation was more uniformly distributed between upper and lower lung regions than has previously been reported in awake, upright subjects. Reduced respiratory muscle tone and airway closure are likely causative factors.

A Novel Implantable Hearing System with Direct Acoustic Cochlear Stimulation

A new implantable hearing system, the direct acoustic cochlear stimulator (DACS) is presented. This system is based on the principle of a power-driven stapes prosthesis and intended for the treatment of severe mixed hearing loss due to advanced otosclerosis. It consists of an implantable electromagnetic transducer, which transfers acoustic energy directly to the inner ear, and an audio processor worn externally behind the implanted ear. The device is implanted using a specially developed retromeatal microsurgical approach. After removal of the stapes, a conventional stapes prosthesis is attached to the transducer and placed in the oval window to allow direct acoustical coupling to the perilymph of the inner ear. In order to restore the natural sound transmission of the ossicular chain, a second stapes prosthesis is placed in parallel to the first one into the oval window and attached to the patient's own incus, as in a conventional stapedectomy. Four patients were implanted with an investigational DACS device. The hearing threshold of the implanted ears before implantation ranged from 78 to 101 dB (air conduction, pure tone average, 0.5-4 kHz) with air-bone gaps of 33-44 dB in the same frequency range. Postoperatively, substantial improvements in sound field thresholds, speech intelligibility as well as in the subjective assessment of everyday situations were found in all patients. Two years after the implantations, monosyllabic word recognition scores in quiet at 75 dB improved by 45-100 percent points when using the DACS. Furthermore, hearing thresholds were already improved by the second stapes prosthesis alone by 14-28 dB (pure tone average 0.5-4 kHz, DACS switched off). No device-related serious medical complications occurred and all patients have continued to use their device on a daily basis for over 2 years. Copyright (c) 2008 S. Karger AG, Basel.

Intraindividual comparison of human radial and internal thoracic arteries in vitro and the effect of preoperative calcium blocker therapy

The patency rate of radial artery (RA) conduits is considerably lower than that of internal thoracic artery (ITA) grafts and the evidence suggests that this is due to a clinically suspected higher incidence of vasospasm. The aim of this study was, therefore, to compare intraindividually the pharmacological reactivity of RA with that of ITA. Both RA and ITA were taken from the same patients and investigated in parallel. Changes in tone were monitored isometrically on ring preparations from both arteries in organ baths with modified Krebs-Henseleit solution containing 1.25 mm calcium chloride at 1 g passive preload. In intraindividual comparisons maximal receptor-mediated contractile responses to noradrenaline and endothelin-1 and endothelium-dependent acetylcholine-induced relaxant responses revealed no differences between both arteries. By contrast, depolarization-induced contractions to potassium chloride (KCl) appeared to be significantly higher in RA than in ITA. Further analysis, however, revealed that this difference was due to preoperative calcium entry blocker (Ca(2+)eB) therapy. Compared with control tissues, maximal responses to KCl were significantly attenuated in the ITA but unchanged in RA when arteries were obtained from patients with preoperative Ca(2+)eB therapy. The present results suggested that functional responses to pharmacological stimuli of both RA and ITA were quite similar. Preoperative Ca(2+)eB therapy, however, attenuated markedly responses to KCl of the ITA leaving those of RA unchanged. These results, demonstrating a lower sensitivity to Ca(2+)eB of RA, therefore suggested that in addition to Ca(2+)eB other classes of drug may be more effective at reducing the propensity of RA conduits to vasospasm.

Impact of freezing/thawing procedures on the post-thaw viability of cryopreserved human saphenous vein conduits

BACKGROUND: Cryopreserved human blood vessels are important tools in reconstructive surgery. However, patency of frozen/thawed conduits depends largely on the freezing/thawing procedures employed. METHODS: Changes in tone were recorded on rings from human saphenous vein (SV) and used to quantify the degree of cryoinjury after different periods of exposure at room temperature to the cryomedium (Krebs-Henseleit solution containing 1.8M dimethyl sulfoxide and 0.1M sucrose) and after different cooling speeds and thawing rates following storage at -196 degrees C. RESULTS: Without freezing, exposure of SV to the cryomedium for up to 240 min did not modify contractile responses to noradrenaline (NA). Pre-freezing exposure to the cryomedium for 10-120 min attenuated significantly post-thaw maximal contractile responses to NA, endothelin-1 (ET-1) and potassium chloride (KCl) by 30-44%. Exposure for 240 min attenuated post-thaw contractile responses to all tested agents markedly by 62-67%. Optimal post-thaw contractile activity was obtained with SV frozen at about -1.2 degrees C/min and thawed slowly at about 15 degrees C/min. In these SV maximal contractile responses to NA, ET-1 and KCl amounted to 66%, 70% and 60% of that produced by unfrozen controls. Following cryostorage of veins for up to 10 years the responsiveness of vascular smooth muscle to NA was well maintained. CONCLUSION: Cryopreservation allows long-term banking of viable human SV with only minor loss in contractility.

The immediate and sustained effects of volume challenge on regional blood flows in pigs

BACKGROUND: The postoperative assessment of volume status is not straightforward because of concomitant changes in intravascular volume and vascular tone. Hypovolemia and blood flow redistribution may compromise the perfusion of the intraabdominal organs. We investigated the effects of a volume challenge in different intra- and extraabdominal vascular beds. METHODS: Twelve pigs were studied 6 h after major intraabdominal surgery under general anesthesia when clinically normovolemic. Volume challenges consisted of 200 mL rapidly infused 6% hydroxyethyl starch. Systemic (continuous thermodilution) and regional (ultrasound Doppler) flows in carotid, renal, celiac trunk, hepatic, and superior mesenteric arteries and the portal vein were continuously measured. The acute and sustained effects of the challenge were compared with baseline. RESULTS: Volume challenge produced a sustained increase of 22% +/- 15% in cardiac output (P < 0.001). Blood flow increased by 10% +/- 9% in the renal artery, by 22% +/- 15% in the carotid artery, by 26% +/- 15% in the superior mesenteric artery, and by 31% +/- 20% in the portal vein (all P < 0.001). Blood flow increases in the celiac trunk (8% +/- 13%) and the hepatic artery (7% +/- 19%) were not significant. Increases in regional blood flow occurred early and were sustained. Mean arterial and central venous blood pressures increased early and decreased later (all P < 0.05). CONCLUSIONS: A volume challenge in clinically euvolemic postoperative animals was associated with a sustained increase in blood flow to all vascular beds, although the increase in the celiac trunk and the hepatic artery was very modest and did not reach statistical significance. Whether improved postoperative organ perfusion is accompanied by a lower complication rate should be evaluated in further studies.

[The treatment of orthostatic hypotension with metoclopramide]

The dopamine receptor antagonist metoclopramide (paspertin, primpéran, gastrosil, meclopran, gastro-timelets), used as monotherapy or in combination with an inhibitor of the cyclooxygenase enzyme, affords good results in orthostatic hypotension due to insufficiency of the sympathetic nervous system. The mechanism of action in these cases is unclear but is assumed to be elevation of vascular tone in the splanchnic vessels. A case is discussed which documents the effectiveness of metoclopramide therapy in orthostatic hypotension, even in absence of signs of autonomic dysfunction.

Transdermal nitroglycerin in patients with subarachnoid hemorrhage

Delayed ischemic neurological deficit (DIND) following cerebral vasospasm remains a cause for high morbidity and mortality in patients with subarachnoid hemorrhage (SAH). There is experimental and clinical evidence of positive effects of nitric oxide (NO) donors on cerebral vasospasm. We therefore analysed the effect of transdermal nitroglycerin in patients with SAH measuring transcranial Doppler velocities (TCD), cerebral blood flow (CBF) and DIND. Nitroglycerin was used in a target dose of 14 microg/kg/h. TCD assessment was performed daily. CBF measurements were done using the perfusion CT-technique. Blood pressure, volume intake and vasopressor administration, were registered. Nine patients were randomly assigned either to the nitroglycerin group (N-group) and eight patients in the control group (C-group). Mean TCD values in the extracranial portion of the internal carotid artery (ICA) were lower in the N-group (p<0.005). Mean TCD in the middle cerebral arteries (MCA) showed no difference. The Lindegaard ratio was higher in the N-group (p<0.04). CBF in the N-group was higher than in the C-group (p<0.03). Even though nitroglycerin reduces blood pressure and lowers ICA TCD-values and increases the Lindegaard ratio, a higher CBF was measured in the N-group. Thus, nitroglycerin influences the cerebral vascular tone and increases CBF. SAH therapy with nitroglycerin is possible without increasing the risk of DIND. The exact timing of onset, duration and reduction of nitroglycerin administration in respect to the appearance of vasospasm may have a strong impact on the success of such a therapy.

Pulse contour analysis: a valid assessment of central arterial stiffness in children?

In adults the contour analysis of peripheral pressure waves in the upper limb reflects central aortic stiffness. Here, we wanted to demonstrate the appropriateness of pulse contour analysis to assess large artery stiffness in children. Digital volume pulse analysis, with the computation of the stiffness index and pulse wave velocity between carotid and femoral artery, were simultaneously determined in 79 healthy children between 8 years and 15 years (mean age 11.4 years, 32 girls). The stiffness index of 42 healthy adults (mean age 45.6 years, 26 women) served as control. Pulse wave velocity between carotid and femoral artery was directly correlated with systolic pressure and mean blood pressure, as well as with pulse pressure. The results from the stiffness index of children revealed the expected values extrapolated from the linear regression of adulthood stiffness index vs. age. Childhood stiffness index positively correlated with pulse wave velocity (r(2) = 0.07, P = 0.02) but not with blood pressure parameters. The exclusion of individuals with an increased vascular tone, as indicated by a reflexion index > 90%, improved the correlation between stiffness index and pulse wave velocity (r(2) = 0.13, P = 0.001). Our data indicate that digital volume pulse-based analysis has limitations if compared with pulse wave velocity to measure arterial stiffness, mostly in patients with a high vascular tone.

Effects of verum acupuncture compared to placebo acupuncture on quantitative EEG and heart rate variability in healthy volunteers

OBJECTIVES: The aim of this single-blind randomized crossover study was to evaluate specific effects of manual acupuncture on central and vegetative nervous system activity measured by quantitative electroencephalography (qEEG) and heart rate variability (HRV). DESIGN: Twenty (20) healthy volunteers (mean: 25.2 +/- 3.6 years) were monitored simultaneously using a qEEG system and a 12-channel electrocardiogram recorder during verum acupuncture (VA) at acupuncture point Large Intestine 4 (Hegu) (LI4) or placebo acupuncture (PA) at a sham point. RESULTS: In the EEG conduction of the occipital area, needle stimulation in VA increased alpha1-frequency significantly, and the ratio alpha1/theta was shifted to the benefit of alpha1 over all electrodes. The HRV parameters showed a significant increase of the low frequency/high frequency (HF) ratio during the first minute of stimulation in VA, indicating an initial increase of sympathetic activation. However, an increase of HF power in the minute after stimulation followed by a decrease in heart rate suggests delayed vagal activation. De qi (a sensation that is typical of acupuncture needling) occurred in 16 subjects during VA and in 9 volunteers during PA (80% versus 45%). CONCLUSIONS: Manual stimulation on LI4 seems to lead to specific changes in alpha EEG-frequency and in HRV parameters. A linear relationship between the HRV parameters and the alpha EEG band might point to a specific modulation of cerebral function by vegetative effects during acupuncture.

Subverting the subject position : toward a new discourse about students as writers and engineering students as technical communicators

There is ample evidence of a longstanding and pervasive discourse positioning students, and engineering students in particular, as “bad writers.” This is a discourse perpetuated within the academy, the workplace, and society at large. But what are the effects of this discourse? Are students aware faculty harbor the belief students can’t write? Is student writing or confidence in their writing influenced by the negative tone of the discourse? This dissertation attempts to demonstrate that a discourse disparaging student writing exists among faculty, across disciplines, but particularly within the engineering disciplines, as well as to identify the reach of that discourse through the deployment of two attitudinal surveys—one for students, across disciplines, at Michigan Technological University and one for faculty, across disciplines at universities and colleges both within the United States and internationally. This project seeks to contribute to a more accurate and productive discourse about engineering students, and more broadly, all students, as writers—one that focuses on competencies rather than incompetence, one that encourages faculty to find new ways to characterize students as writers, and encourages faculty to recognize the limits of the utility of practitioner lore.

Skill Acquisition and the Influence of Attentional Focus and Practice

Attentional focus and practice schedules are important components in learning a new skill. For attention this includes focusing inward or outward, for practice this includes interference between tasks. Little is known about how the two interact. Four groups; blocked/extraneous (BE); blocked/skill-focused (BS); random/extraneous (RE); and random/skill-focused (RS), practiced 100 trials of golf putting and 64 trials of a key-pressing task in addition to responding to a random tone distracting attention towards or away from skill movement. Participants performed immediate and delayed retention tests. Results demonstrated the BE group had decreased RTE scores compared to the BS group. Immediate retention demonstrated superior scores for blocked practice. Delayed retention demonstrated superior CEVE scores for extraneous focus. For golf putting, both attention conditions with blocked practice learned faster compared to random groups. Posttest scores demonstrated the random and skill focused group to improve in all putting conditions.

Consensus statement of the European Heart Rhythm Association: updated recommendations for driving by patients with implantable cardioverter defibrillators

Patients with an implantable cardioverter defibrillator (ICD) have an ongoing risk of sudden incapacitation that might cause harm to others while driving a car. Driving restrictions vary across different countries in Europe. The most recent recommendations for driving of ICD patients in Europe were published in 1997 and focused mainly on patients implanted for secondary prevention. In recent years there has been a vast increase in the number of patients with an ICD and in the percentage of patients implanted for primary prevention. The EHRA task force on ICD and driving was formed to reassess the risk of driving for ICD patients based on the literature available. The recommendations are summarized in the following table and are further explained in the document. [table: see text] Driving restrictions are perceived as difficult for patients and their families, and have an immediate consequence for their lifestyle. To increase the adherence to the driving restrictions, adequate discharge of education and follow-up of patients and family are pivotal. The task force members hope this document may serve as an instrument for European and national regulatory authorities to formulate uniform driving regulations.