Clinical efficacy of reduction in house-dust mite exposure in specially designed, mechanically ventilated "healthy" homes

In temperate climates, energy-conserving measures may increase indoor humidity, enhancing house-dust mite (HDM) growth. Movement of families to "healthy" homes with mechanical ventilation systems reduced HDM exposure. The effect on asthma control of moving to the "healthy" homes was studied in 14 asthmatic patients allergic to HDM. Base-line evaluations of lung function, asthma symptoms, and medication requirements were made before moving and again after 5 and 15 months' residence. A control group of 11 mite-sensitive asthmatic patients who did not move were examined contemporaneously with the study group at base line and at the first follow-up investigation. After 5 months, the residents of the "healthy" homes improved in forced expiratory volume in 1 s (FEV₁), medicine score, and serum IgE. These changes were significantly different from control group measurements. After 15 months, statistically significant improvements from base line were found in FEV₁, average daily peak expiratory flow values, medicine score, symptom score, and serum IgE. Insignificant trends toward improvement were seen in provocation concentration of histamine and blood eosinophils. A significant relation was found between reduction in medicine score and fall in HDM exposure. The present study shows that a specific HDM-avoidance procedure can result in an overall, clinical improvement in HDM-sensitive asthmatic patients.     

Heterogeniety in regulation of glomerular function

The aim was to study differences in filtration driving forces and glomerular filtration rates between superficial and deep nephrons when urine flow rate was altered at the macula densa region. In young rats stop-flow pressures and single nephron glomerular filtration rates (SNGFR) were measured in the superficial proximal tubules and in the loops of Henle in the papilla. SNGFR was also measured with a modified Hanssen technique. The stop-flow pressures of superficial nephrons amounted to 30.9±0.8 mmHg (mean ± SE) and those of juxtamedullary nephrons to 52.2±1.6 mmHg. In the stop-flow condition the net driving filtration forces were calculated to be about 19 mmHg and 50 mmHg for the superficial and deep glomeruli, respectively. In free flow conditions both net driving forces were calculated to be 19 mmHg. The micropuncture technique gave a SNGFR value for superficial nephrons of 29.6±2.9 and for deep nephrons of 84.1±8.5 nl±min^-1 g^-1 kidney weight (KW). With a modified Hanssen technique the corresponding values were 25.8±3.3 and 27.7±2.9 nl. min^-1.g^-1KW. The tubuloglomerular feedback mechanism is considered to have a powerful regulatory influence on the glomerular filtration rate of deep nephrons.     

The juxtaglomerular apparatus in malignant hypertension of man

Summary Investigation of the behaviour of the renal Juxtaglomerular apparatus in 19 patients with malignant hypertension has shown that in kidneys fixed immediately after operation the Juxtaglomerular granulation index is twice as high as in autopsy kidneys. The formation of renin by the epitheloid cells begins with the appearance of osmiophilic substances in the region of the endoplasmic reticulum. The first stages of granule formation are small rhomboid particles in the Golgi cisternes, which aggregate to form bigger round or polymorphic granules in the Golgi area.In pathological conditions the substances synthesized may be set free and become active locally as a result of fibrinoid necrosis of the vascular wall. The rate of production is increased firstly by forcing rhe production of active agents in the preexistent epitheloid cells, secondly by transformation of the so-called bivalent cells and finally, by cell division.In accelerated hypertension the production of renin also takes place in nephrons whose glomeruli, tubules and macula densa, are damaged. There is a correlation between blood pressure elevation and the Juxtaglomerular granulation index.

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Zusammenfassung Untersuchungen über das Verhalten des juxtaglomerulären Zellkomplexes der Niere bei 19 Patienten mit maligner Hypertonie haben folgendes ergeben: In operativ gewonnenen und sofort fixierten Nieren ist der juxtaglomeruläre Granulationsindex doppelt so hoch wie in Nieren aus dem Sektionsgut. Die Reninbildung der epitheloiden Zellen beginnt mit dem Auftreten osmiophiler Substanzen im Bereich des endoplasmatischen Reticulums. Kleine rhomboide Gebilde in Golgizisternen sind Vorstufen von reifen Sekretgranula, die sich im Golgifeld zu größeren runden oder vielgestaltigen Sekrettropfen zusammenlagern.Unter pathologischen Bedingungen können infolge fibrinoider Gefäß- wandnekrosen Sekretsubstanzen lokal frei und lokal wirksam werden. Vermehrte Arbeitsleistung erfolgt zunächst durch Forcierung der Sekretproduktion in den präexistenten epitheloiden Zellen, sodann durch Transformierung sogenannter bivalenter Zellen und schließlich durch Zellneubildungen.Reninproduktion findet bei akzelerierter Hypertonie auch in solchen Nephronen statt, deren Glomerula und Tubuli samt Macula densa strukturell geschädigt sind. Es besteht eine Korrelation zwischen Höhe des Blutdruckes und Höhe des Granulationsindex.

     

Voluntary Heart Rate Control During Static Muscular Effort

To test the hypothesis that voluntary heart rate (HR) control is possible with simultaneous muscular effort, 8 male subjects were trained in feedback assisted bidirectional HR control, and also practiced hand grip exercises requiring different levels of effort for 3 consecutive daily sessions. In a fourth session subjects were required to increase and decrease HR while simultaneously performing muscle contractions of 0%, 10%, 30% and 50% of maximum voluntary contractions. Substantial and reliable variations in HR were produced by instructions and by muscular effort during the first 3 sessions; and in the fourth session bidirectional HR control continued even with the relatively elevated baselines induced by muscular effort. Concomitant chin EMG levels did not vary with degree of muscular effort nor with instructions to increase or decrease HR, but increased over the course of any type of trial. Discussion suggests the use of artificially elevated baselines as a strategy for studying HR deceleration and concludes that the present study provides strong evidence of subjects' abilities to voluntarily control HR during muscular effort. This conclusion lends support to the notion that biofeedback therapies may be of clinical utility in real life by modulating the eliciting effects of stressors.     

Blood lactate in trained cyclists during cycle ergometry at critical power

Summary The purposes of this investigation were to determine the validity of critical power (CP) as a measure of the work rate that can be maintained for a very long time without fatigue and to determine whether this corresponded with the maximal lactate steady-state (la_ss,max). Eight highly trained endurance cyclists (maximal oxygen uptake 74.1 ml · kg^–1 · min^–1, SD 5.3) completed four cycle ergometer tests to exhaustion at predetermined work rates (360, 425, 480 and 520 W). From these four co-ordinates of work and time to fatigue the regression of work limit on time limit was calculated for each individual (CP). The cyclists were then asked to exercise at their CP for 30 min. If CP could not be maintained, the resistance was reduced minimally to allow the subject to complete the test and maintain a blood lactate plateau. Capillary blood was sampled at 0, 5, 10, 20 and 30 min into exercise for the analysis of lactate. Six of the eight cyclists were unable to maintain CP for 30 min without fatigue. In these subjects, the mean power attained was 6.4% below that estimated by CP. Mean blood lactates (n = 8) reached a steady-state (8.9 mmol · l^–1, SD 1.6) during the last 20 min of exercise indicating that CP slightly overestimated la_{ss, max}. Individual blood lactates during the last 20 min of exercise were more closely related to the y-intercept of the CP curve (r=0.78, P<0.05) than either CP (0.34, NS) or mean power output (r=0.42, NS). The present investigation has shown that highly trained endurance cyclists can tolerate previously unreported levels of blood lactate during 30 min of exercise at or near their CP. Blood lactates during continuous exercise are higher than at the same work rate during an incremental test. The CP provides a simple and inexpensive means of assessing the exercise intensity which can be maintained continuously, while avoiding the methodological difficulties associated with ventilatory and lactate thresholds.     

The use of successive blood-pressure measurements to estimate blood-pressure variability

Multiple daily, self-determined blood-pressure measurements were obtained from 254 hypertensive patients for 1 month. In an effort to establish a practical and reliable technique for estimating blood-pressure variability, standard deviations from three (at one time of day) or nine (throughout the day) successive self-determinations were compared with a reference value, taken to be the standard deviation for the entire month (252 determinations per subject). Neither the standard deviation of three measures taken on one occasion nor that of nine measures taken throughout the day correlated well with the reference value (average R₃=.21 for SBP, .20 for DBP; average R₉=.39 for SBP, .38 for DBP). However, when a sample consisting of 12 measures (taken three at a time, at the same time of day, weekly for 4 weeks) was used, the average correlation rose to .60 for SBP and .54 for DBP. Thus, it appears that 12 samples taken in this way provide a reliable estimate of the standard deviation for an entire month, and it is suggested that this sampling technique also would enhance the reliability of conclusions drawn from assessments of the prognostic value of blood-pressure variability.     

Cerebellar involvement in the coordination control of the oculo-manual tracking system: effects of cerebellar dentate nucleus lesion

Summary When the hand of the observer is used as a visual target, oculomotor performance evaluated in terms of tracking accuracy, delay and maximal ocular velocity is higher than when the subject tracks a visual target presented on a screen. The coordination control exerted by the motor system of the arm on the oculomotor system has two sources: the transfer of kinaesthetic information originating in the arm which increases the mutual coupling between the arm and the eyes and information from the arm movement efferent copy which synchronizes the motor activities of both subsystems (Gauthier et al. 1988; Gauthier and Mussa-Ivaldi 1988). We investigated the involvement of the cerebellum in coordination control during a visuo-oculo-manual tracking task. Experiments were conducted on baboons trained to track visual targets with the eyes and/or the hand. The role of the cerebellum was determined by comparing tracking performance defined in terms of delay, accuracy (position or velocity tracking errors) and maximal velocity, before and after lesioning the cerebellar dentate nucleus. Results showed that in the intact animal, ocular tracking was more saccadic when the monkey followed an external target than when it moved the target with its hand. After lesioning, eye-alone tracking of a visual target as well as eye-and-hand-tracking with the hand contralateral to the lesion was little if at all affected. Conversely, ocular tracking of the hand ipsilateral to the lesion side became more saccadic and the correlation between eye and hand movement decreased considerably while the delay between target and eyes increased. In normal animals, the delay between the eyes and the hand was close to zero, and maximal smooth pursuit velocity was around 100 degrees per second with close to unity gain; in eye-alone tracking the delay and maximal smooth pursuit velocity were 200 ms and 50 deg per second, respectively. After lesioning, delay and maximum velocity were respecttively around 210 ms and 40 deg per second, that is close to the values measured in eye-alone tracking. Thus, after dentate lesioning, the oculomotor system was unable to use information from the motor system of the arm to enhance its performance. We conclude that the cerebellum is involved in the coordination control between the oculomotor and manual motor systems in visuo-oculo-manual tracking tasks.     

Reach to grasp: the natural response to perturbation of object size

This study assessed the reach to grasp movement and its adaptive response to a perturbation of object size. In blocked trials, subjects (n = 12) were instructed to reach 35 cm to grasp and lift a small- (0.7 cm) or large-diameter (8 cm) cylinder. Under an unconstrained condition (condition 1), no instructions as to the type of grasp to adopt were given. Subjects thus naturally used a precision grip (PG) for the small cylinder and whole hand prehension (WHP) for the large cylinder. Under condition 2, subjects were instructed to utilize a PG for grasps of both the large and small cylinders. For condition 3, the instruction was to use WHP irrespective of object size. Kinematic organization was determined with analysis of the recordings of active markers placed on the wrist, thumb, and three fingers. For condition 1 the results showed a temporal arrangement of both components (transport and manipulation) which differed from that of conditions 2 and 3. In perturbed trials, illumination shifted from the small to large cylinder or vice versa. With condition 1, subjects automatically switched from one grasp to another with no or little increase of movement duration. This was generally achieved by an earlier temporal setting of peak wrist deceleration. For conditions 2 and 3, where a change of aperture was required, movement duration was prolonged without adaptation of earlier transport component parameters. It is concluded that the adaptive responses to a change of distal patterning also affect the organization of the proximal component. Assessment of grasps constrained by instructions may lead to interpretations of central control of the reach to grasp movement which differ from those obtained by assessing more natural prehensile patterns.     

Brain stimulation-induced changes of phonation in the squirrel monkey

Summary In 11 squirrel monkeys (Saimiri sciureus), the brain stem was systematically explored with electrical brain stimulation for sites affecting the acoustic structure of ongoing vocalization. Vocalization was elicited by electrical stimulation of different brain structures. A severe deterioration of the acoustical structure of vocalization was obtained during stimulation of the caudoventral part of the periaqueductal grey, lateral parabrachial area, corticobulbar tract, nucl. ambiguus and surrounding reticular formation, facial nucleus, hypoglossal nucleus, solitary tract nucleus and along the fibres crossing the midline at the level of the hypoglossal nucleus. It is suggested that these structures are part of, or at least have direct access to, the motor coordination mechanism of phonation. Complete inhibition of phonation was obtained from the raphe and raphe-near reticular formation.Abbreviations Ab nucl ambiguus - APt area praetectalis - BC brachium conjunctivum - BP brachium pontis - Cb cerebellum - CC corpus callosum - Cd nucl. caudatus - Cf nucl. cuneiformis - Cel nucl. centralis lateralis - Cl claustrum - CM centrum medianum - Cn nucl. cuneatus - Co nucl. cochlearis - CoI colliculus inferior - CoS colliculus superior - CP commissura posterior - CPf cortex piriformis - CRf corpus restiforme - CSL nucl. centralis superior lateralis thalami - CT corpus trapezoideum - DBC decussatio brachii conjunctivi - DG nucl. dorsalis tegmenti (Gudden) - DLM decussatio lemnisci medialis - DPy decussatio pyramidum - DR nucl. dorsalis raphae - DV nucl. dorsalis n. vagi - DIV decussatio n. trochlearis - EP epiphysis - FC funiculus cuneatus - FL funiculus lateralis - FLM fasciculus longitudinalis medialis - FRM formatio reticularis myelencephali - FRP formatio reticularis pontis - FRPc formatio reticularis pontis caudalis - FRPo formatio reticularis pontis oralis - FRTM formatio reticularis mesencephali - FV funiculus ventralis - G nucl. gracilis - GC substantia grisea centralis (periaqueductal grey) - GL nucl. geniculatus lateralis - GM nucl. geniculatus medialis - GP globus pallidus - GPM griseum periventriculare mesencephali - GPo griseum pontis - Hip hippocampus - HL nucl. habenularis lateralis - H habenula - IP nucl. interpeduncularis - LC locus coeruleus - LD nucl. lateralis dorsalis thalami - Lim nucl. limitans - LLd nucl. lemnisci lateralis, pars dorsalis - LLv nucl. lemnisci lateralis, pars ventrali - LM lemniscus medialis - LP nucl. lateralis posterior thalami - MD nucl. medialis dorsalis thalami - MV nucl. motorius n. trigemini - NCS nucl. centralis superior - NCT nucl. trapezoidalis - NMV nucl. mesencephalicus n. trigemini - NR nucl. ruber - NSV nucl. spinalisn. trigemini - NTS nucl. tractus solitarii - NIII nucl. oculomotorius - NIV nucl. trochlearis - NVI nucl. abducens - NVII nucl. facialis - NXII nucl. hypoglossus - OI oliva inferior - OS oliva superior - P nucl. posterior thalami - PbL nucl. parabrachialis lateralis - PbM nucl. parabrachialis medialis - PC depedunculus cerebri - Pd nucl. peripeduncularis - Pg nucl. parabigeminalis - Pp nucl. praepositus - PuI nucl. pulvinaris inferior - PuL nucl. pulvinaris lateralis - PuM nucl. pulvinaris medialis - PuO nucl. pulvinaris oralis - Py tractus pyramidalis - Pv nucl. principalis n. trigemini - R Ab nucl. retroambiguus - RL nucl. reticularis lateralis - RTP nucl. reticularis tegmenti pontis - Sf nucl. subfascicularis - SGD substantia grisea dorsalis - SGV substantia grisea ventralis - SN substantia nigra - ST stria terminalis - St subthalamus - TRM tractus retroflexus (Meynert) - TSc tractus spinocerebellaris - Ves nucl. vestibularis - VL nucl. ventralis lateralis - VPI nucl. ventralis posterior inferior - VPL nucl. ventralis posterior lateralis - VPM nucl. ventralis posterior medialis - VR nucl. ventralis raphae - Zi zona incerta - II tractus opticus - VII n. facialis     

Effects of angiotensin-converting enzyme inhibition on arterial,venous and capillary functions in cat skeletal muscle in vivo

The aim of the present study was to analyse quantitatively, on a cat gastrocnemius muscle preparation in vivo, the effects of local angiotensin-converting enzyme (ACE) inhibition by enalaprilat on total regional vascular resistance (tone) and its distribution to the large-bore arterial resistance vessels (>25 μm), the small arterioles (<25 μm) and the veins. Associated effects on capillary pressure and fluid exchange were also studied. Close-arterial infusion of enalaprilat (0.05–0.20 mg kg muscle tissue min^-1) elicited a moderate dilator response in all three consecutive sections of the muscle vascular bed, an increase in capillary pressure and transcapillary fluid filtration. This dilation could be abolished by the selective bradykinin B₂-receptor antagonist Hoe 140 (2 mg kg^-1 min^-1, i.a.), indicating that the dilator mechanism of ACE inhibition was an increased local concentration of bradykinin, and hardly at all a decreased concentration of angiotensin (AT) II. The generalized dilator response to ACE inhibition along the vascular bed suggested a relatively uniform distribution of ACE from artery to vein and this was further supported by the finding that a close-arterial infusion of AT I (0.04–0.32 μg kg^-1 min^-1), which was vasoactive only after conversion to AT II by local ACE, elicited a generalized constrictor response in all three vascular sections. In contrast, infused AT II (0.01–0.16 μg kg^-1 min^-1) constricted almost selectively the large-bore arterial vessels. The specific angiotensin AT₁-receptor antagonist losartan (2 mg kg^-1 min^-1, i.a.) abolished the constrictor response to AT II but did not affect vascular tone under control conditions, indicating that AT II is not involved in the initiation of basal vascular tone in muscle. These results, taken together, indicate that under basal conditions vascular ACE contributes to the local control of vascular tone in skeletal muscle by degrading the endogenous dilator bradykinin, and not by converting AT I into vasoconstrictor AT II.