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[Treatment of a severe temporary heart arrhythmia by transvenous pacing in a neonate (author's transl)].

Report of the treatment of a neonate with bradycardia (cardiac dysrhythmia) with an external transvenous pacemaker. At the age of 19 days the child developed repeated and critical dysrhythmias which made intubation and artificial respiration necessary. Conservative therapy attempts were without success. A stimulation-catheter was inserted through the internal jugularis vein and an external Demand-pacemaker connected to it. The stimulation-catheter was disconnected after 12 days with the complete cessation of the initial frequent bradycardia episodes. The cause of the cardiac dysrhythmia could not be clearly found. Tachycardia-bradycardia syndrome and Phase-IV block are being discussed.

Bradycardia↗

Vagal expiratory afferent discharges during spontaneous breathing.

Expiratory discharges in cervical afferent vagal fibres during spontaneous respiration were observed in anesthetized animals (17 rabbits, 4 cats and 2 monkeys). The percentages of such units among the total observed fibres was 11% in rabbits, 5% in monkeys, 2% in cats. All the experiments were done after section of the recurrent laryngeal nerve and the abdominal branches of the vagus nerve. Changing the intraesophageal pressure from +15 mm Hg to -25 mm Hg by injection or suction of air into or out of the esophagus, of which the abdominal end had been ligated, did not affect the expiratory discharges significantly suggesting that the receptors were not in the esophagus. Injection of air into the lungs to elevate the intratracheal pressure to 5 mm, 10 mm or 15 mm Hg could not excite such receptors. Collapse of the lungs caused by artificial pneumothorax produced continuous discharges in such fibres. Inflation of collapsed lungs by an artificial respiration pump stopped the sustained discharges immediately. The average conduction velocity of the afferent fibres was 25.5 m/s. It seems that this is a type of slowly adapting, low threshold pulmonary receptor with medium sized afferent fibres. The adequate stimulus of such receptors is deflation of the lungs. The possible advantage of participation of such receptors, in addition to the pulmonary stretch (inflation) receptors, in regulation of normal respiration is discussed in the light of the concept of 'paired receptors'.

Animals↗

Effect of carbonic anhydrase inhibitors and acidosis in choroid plexus epithelial cell sodium and potassium.

To elucidate the mechanism by which carbonic anhydrase inhibitors block fluid production by the choroid plexus (CP), Na-K transport by the rat choroidal epithelium was investigated by measuring acetazolamide- and benzolamide-induced changes in cell [K] and [Na]. Although plasma and cerebrospinal fluid [K] and [Na] were not significantly altered after 1 hr of drug treatment, both acetazolamide (20 mg/kg) and benzolamide (40 mg/kg) decreased in vivo CP cell [Na] by 11 to 18 mmol/kg of cell H2O and substantially increased cell [K] by 25 to 35 mmol. Compensatory artificial respiration to control blood pH blocked the drug-induced effects of cell electrolytes. Furthermore, acetazolamide (5 x 10(-5) and 5 x 10(-4) M) did not significantly alter cell [Na] or [K] in in vitro incubations of CP, although cell [K] tended to decrease in a drug concentration-dependent manner. Thus, carbonic anhydrase inhibitors have no direct effect on the gradient for Na or K between choroid cell fluid and surrounding extracellular fluid. It is proposed that the carbonic anhydrase inhibitors reduced Na entry into the choroid epithelium across the basolateral membrane concurrent with a decrease in the rate of the apical membrane Na-K pump. To investigate whether the drug-induced extracellular acidosis changed cell electrolyte levels directly or indirectly, in vitro CP tissue incubations were performed in which the pH of the artificial cerebrospinal fluid was varied from 7.24 to 7.44. CP cell [K] increased by 20 mmol/kg of H2O and cell [Na] fell by 10 when bathing medium pH was lowered from 7.39 to 7.24. We postulate that the lowered blood pH directly stimulates K uptake and Na efflux from the CP cell, although an indirect effect of acidosis, either through an alteration of levels of circulatory hormones or of autonomic input to the CP, cannot be excluded.

Acetazolamide↗

Cardiovascular and respiratory responses to electrical and chemical stimulation of the hippocampus in anesthetized and awake rats.

Electrical (30-60-s trains of 0.25-ms pulses at 25 Hz, currents 10-150 microA) and chemical (microinjections of 0.1-0.5 microliters of a 1.0 M glutamate solution) stimulation of the hippocampal formation in the anesthetized and the awake rat evokes marked decreases in heart rate, blood pressure and slower, deeper, more regular respirations. Artificial ventilation (2 ml/breath; 100 breaths/min) has no effect on the cardiovascular responses, indicating that these effects are not secondary to respiratory changes. Administration of methyl atropine (0.4 mg/kg) eliminates the bradycardia response and attenuates or obliterates the blood pressure response but does not alter the respiratory response. This suggests that the cardiovascular responses are mediated partially by the vagus nerve and partially by sympathetic influences. Ablation of the medial frontal cortex, a visceral motor region which projects directly to the nucleus of the solitary tract and which receives a heavy direct projection from the CA1 and subicular cell fields of the ventral hippocampus, markedly attenuates or eliminates the cardiovascular and respiratory responses to stimulation of the ventral but not the dorsal hippocampus. The possibility that the medial frontal cortex may be a relay by which the hippocampus influences cardiovascular responses, including those observed during stress, is discussed.

Animals↗

Pharmacologic modification of subretinal fluid absorption in the rabbit eye.

We studied in the rabbit the effects of pharmacologic agents on the absorption of Hanks' solution from the subretinal space of experimental nonrhegmatogenous detachments. Intravenous acetazolamide had no effect at a clinical dose (15 mg/kg) but increased the rate of fluid absorption significantly at high doses (50 mg/kg). Acetazolamide causes systemic pH to fall, while PCO2 and PO2 increase; however, duplicating some of these effects by artificial respiration or breathing 95% O2 plus 5% CO2 did not alter the rate of fluid absorption. Adding cyclic AMP and related agents to the vitreous and subretinal space slowed down fluid absorption by 25%, whereas cyclic GMP analogues increased the rate of absorption by 33%.

Absorption↗

Effects of pentobaribtal and ketamine on brain stem auditory potentials. Latency and amplitude intensity functions after intraperitoneal administration.

Latency and amplitude intensity functions of two short latency (less than 5 ms) components (I and IV) of the brain stem auditory potentials were recorded from scalp electrodes in 18 paralyzed, hooded rats breathing with the assistance of artificial respirators. Averaged responses were obtained in three groups of rats before and 30 minutes after intraperitoneal injections of saline, ketamine hydrochloride (Ketalar), and pentobarbital sodium. Although both ketamine and pentobarbital significantly decreased heart rate and altered the gross EEG, they did not significantly change the latency or amplitude intensity functions of the two evoked-potential components.

Acoustic Stimulation↗

Smooth muscle electromyography of the urinary bladder.

To elucidate smooth muscle activity of the urinary bladder, we utilized an optimized animal model and a specially developed, computer-aided data acquisition and analysis system for bioelectrical signals. Twenty-five Wistar rats were pharmacologically paralyzed and artificially respirated. The urinary bladder was exposed by a suprapubic midabdominal incision, and both ureters were ligated to prevent physiological filling of the bladder. The bladder was initially emptied by slight manual pressure and was then filled via a transurethral catheter in 0.1-ml steps to a maximum of 0.45 ml with physiological saline. A custom-made, gold-plated needle electrode was tangentially guided by a micromanipulator to the smooth muscle of the bladder dome, and the recordings commenced. Furthermore, smooth muscle EMG recordings of the bladder were performed after pharmaco-stimulation of the detrusor with carbachol. Initial results demonstrate that, with the animal model presented here, it is possible to record reproducible and almost artifact-free smooth muscle activity from the urinary bladder. All experiments displayed a stochastic distribution of similar electrical events, increasing in appearance and amplitude with increased bladder volume and after pharmacostimulation with carbachol. Two-dimensional power spectrum analysis revealed a main signal frequency below 1 Hz.

Animals↗

Life-threatening dystonia-dyskinesias in a child: successful treatment with bilateral pallidal stimulation.

We report a 13-year-old boy who developed severe, refractory dystonia-dyskinesias as an abrupt worsening of a previously nonprogressive movement disorder. The movements became continuous, requiring artificial respiration and continuous sedation in the intensive-care unit. Various drugs and drug combinations failed to achieve control. The child was then treated successfully with bilateral pallidal (GPi) stimulation as shown in the videotape. Four months later and without medication, the boy regained autonomous gait and audible speech; his neurologic condition continues to improve.

Adolescent↗

Neurophysiological investigation of effects of the D-1 agonist SKF 38393 on tonic activity of substantia nigra dopamine neurons.

The effects of the D-1 agonist SKF 38393 on tonic activity of rat substantia nigra pars compacta dopamine neurons were studied using extracellular, single-unit recording techniques. Unlike nonselective D-1/D-2 dopamine agonists or the D-2 agonist quinpirole, SKF 38393 did not inhibit dopamine neuronal activity when applied iontophoretically or when administered intravenously in doses up to 20 mg/kg to chloral hydrate-anesthetized rats. Moreover, pretreatment with SKF 38393 did not alter the inhibitory response of these neurons to apomorphine or the D-2 agonist quinpirole. However, in locally anesthetized, gallamine-treated, artificially respired rats, dopamine cell activity was significantly altered by i.v. administration of SKF 38393; firing rate increases and decreases were observed. Administration of the inactive enantiomer of SKF 38393, S-SKF 38393, did not induce similar changes in parallel experiments. These results support the idea that unlike D-2 autoreceptor stimulation, D-1 receptor stimulation does not exert a direct local effect on dopamine neurons in the substantia nigra pars compacta and suggest that D-1 receptor stimulation at sites postsynaptic to the dopamine cells may indirectly affect the activity of some dopamine neurons through long-loop feedback mechanisms.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Functional MRI at 4.7 tesla of the rat brain during electric stimulation of forepaw, hindpaw, or tail in single- and multislice experiments.

Stimulation of peripheral nerves activates corresponding regions in sensorimotor cortex. We have applied functional magnetic resonance imaging (fMRI) techniques to monitor activated brain regions by means of measuring changes of blood oxygenation level-dependent contrast during electric stimulation of the forepaw, hindpaw, or tail in rats. During alpha-chloralose anesthesia, artificial respiration, and complete muscle relaxation, stimulations were delivered at 3 Hz via subcutaneous bipolar electrodes with 500-microseconds-current pulses of 0.2-2.0 mA. Single- or multislice gradient echo images were collected during recording sessions consisting of five alternating rest and stimulation periods. Stimulation of the right and left forepaws and hindpaws repeatedly led to robust activation of the contralateral sensorimotor cortex. There was a significant correlation (P < 0.05) between current pulse strength and amount of activation of the sensory cortex during forepaw stimulation. The center of the main cortical representation of the forepaw was situated 3.4 mm lateral to the midline and 5 mm posterior to the rhinal fissure. The main representation of the hindpaw was 2.0 mm lateral to the midline and 6 mm posterior to the rhinal fissure. Tail stimulation gave rise to a strikingly extended bilateral cortical activation, localized along the midline in medial parietal and frontal cortex 4 and 5 mm posterior to the rhinal fissure. In conclusion, the experiments provide evidence that peripheral nerve stimulation induces a fMRI signal in the respective division of the somatosensory cortex in a stimulus-related manner. The marked cortical activation elicited by tail stimulation underlines the key importance of the tail.

Afferent Pathways↗

The hydrogen gas clearance method for liver blood flow examination: inhalation or local application of hydrogen?

The combined method of hydrogen inhalation and local hydrogen production enable the determination of hepatic blood flow (HBF) and local hepatic blood flow (LHBF). LHBF was registered within a small superficial tissue volume of 0.5 mm in diameter by means of a multi-wire electrode having 200 microns producing and 100 microns measuring wires arranged within less than 300 microns distance between the measuring wires. The feeding current for hydrogen production was 1 microA, the potential less than 10 V. The clearance in response to inhalation was registered by means of the same measuring electrodes within the same tissue volume. Spontaneously breathing rats (Wistar-Frömter strain, 180-230 g bw, N = 19, ketamin-xylazine anesthesia, artificial respiration) showed the following flow values: HBF +/- SD = 0.50 +/- 0.26 ml/g.min, n = 48 registrations; LHBF +/- SD = 4.66 +/- 2.13 ml/g.min, n = 43. The validity of the combined method is demonstrated in the LHBF/HBF graph which summarizes the data of hemorrhagic and control animals, m = 0.1 and yo = 0.001. The correlation coefficient of r = 0.685 shows a reasonable correlation of the combined data despite the wide scattering of the individual values.

Animals↗

A comparative analysis of THAM (Tris-buffer) in traumatic brain oedema.

The effect of THAM on brain oedema parameters was initially investigated in animals with cold brain lesions; THAM was then used in head injury patients, ICP, SAP and CPP were analyzed. In the experiments with rats after freezing lesion, THAM was compared to equivalent doses of Na-bicarbonate. The animals were artificially respirated and sacrificed 6 h after trauma. THAM did significantly reduce water (wet-dry weight technique) and sodium contents in both hemispheres, whereas bicarbonate was ineffective. The potassium contents were even preserved at almost normal levels. In 80 patients receiving alternatively THAM (18-36 g/100-200 ml/1-2h), mannitol (20%, 125-250 ml/20-40 min) or sorbitol (40%, 70-140 ml/20-40 min), the ICP rapidly decreased following THAM infusion. The maximal fall in ICP (33%) was equal to that with mannitol and sorbitol. The slope of ICP decrease was equal with THAM and Mannitol but steeper with sorbitol. With THAM, however, the effect on ICP lasts longer than with osmotherapy. The EEG improved more rapidly after THAM. As shown by blood plasma values, the action of THAM is not based on osmotic effects. The increases in pH and especially in base excess suggest an intracerebral buffering. The encouraging results with THAM require a randomized clinical trial after severe head injury which is presently prepared.

Adolescent↗

Ultrastructure of Reissner's membrane in the rabbit.

The ultrastructure of Reissner's membrane in the rabbit is described following vascular perfusion-fixation of live, anesthetized and artificially respirated healthy animals. A new and improved technique of fixation is employed that includes a pressure feedback controlled peristaltic pump and an oxygen-carrying fixative. In ultrathin sections capillaries were observed between the two cell layers comprising Reissner's membrane. The mesothelial cells facing the scala vestibuli were connected by junctional complexes and neither pores nor discontinuities were observed in the cell layer. In the epithelial cells a well-developed tubulocisternal endoplasmic reticulum (TER) was noted. Computerized three-dimensional reconstruction documented the continuity of this TER, from prominent disc-shaped subsurface cisterns lining the luminal cell membrane to smaller subsurface cisterns lining the abluminal and lateral cell membranes, forming a transcellular canalicular pathway. The possible function of the TER in Reissner's membrane is discussed with reference to endolymph/perilymph homeostasis.

Animals↗

Loss of information concerning hair displacement and other somatic stimuli in the first somatic sensory cortex of unanesthetized Macaca mulatta monkeys following dorsal funiculus transections.

Metal microelectrodes were used to record extracellular potentials from single cells in the four cytoarchitectural areas 3a, 3b, 1 and 2 of the representation of the lower body of the postcentral gyrus of Macaca mulatta monkeys. The animals were paralyzed and artificially respirated while remaining awake. Non-noxious natural stimuli were employed to determine response characteristics, like the submodality, of cells. After recording from a series of normal animals, spinal cord lesions of the dorsal funiculus, were surgically performed at cervical or high thoracic spinal levels. The animals were allowed to recover, and the above-mentioned cell characterization procedures were performed. After the recording, animals were humanely sacrificed and histological reconstructions of the penetrations and the spinal lesions were made. In the postcentral gyrus of normal animals, cells in cytoarchitectural areas 3b and 1 responded predominantly to cutaneous stimuli while cells in areas 3a and 2 responded predominantly to deep stimuli. Responses to displacement of hairs were only recorded in the predominantly cutaneous areas. In these areas in animals with dorsal funiculus transections at cervical or high thoracic spinal cord levels, many fewer cells responded to somatosensory stimulation than in the same areas in normal animals. There were no longer any responses to hair displacement stimuli. In this lower body region, responses to cutaneous stimuli and responses to some deep stimuli were reduced. Cortical areas 3b and 1, that normally showed responses predominantly to cutaneous stimuli, had an increased percentage of responses to deep stimuli. Cells that did not respond to our somatic stimuli but that had a spontaneous firing pattern were found in the first somatic sensory cortex (SI). We conclude that at rostral spinal levels, the dorsal funiculus contains all of the information about hair displacement stimuli of the lower body that projects to the first somatic sensory cortex as well as much information from cutaneous receptors and some from deep receptors on the body surface. Temporal information as well as precise receptive field demarkation is also supplied to SI cells by the dorsal funiculus.

Animals↗

Motor neuron disease with multi-system involvement presenting as tetraparesis, ophthalmoplegia and sensori-autonomic dysfunction.

We carried out a postmortem examination on two Japanese patients, 64- and 80-year-old men whose survival was prolonged with an artificial respirator. They had no family history of neuropsychiatric disorders and were suspected, clinically, as having a motor neuron disease that differed from amyotrophic lateral sclerosis (ALS). As well as upper and lower motor neuron impairment, they showed a variety of symptoms, such as sensory disturbances, hypohidrosis, impotence, ophthalmoparesis and/or atonic neurogenic bladder, and their protein content in cerebrospinal fluid was elevated markedly. Pathological examination revealed the following extensive nervous system involvement: (1) the upper and lower voluntary motor systems, including the IIIrd, IVth and VIth cranial nerve nuclei: (2) the reticular formation and its major afferent pathways; (3) the vestibulospinal and tectospinal systems; (4) the spinocerebellar system and the exteroceptive somatic afferent pathways; (5) the dentatorubral and pallidoluysian systems; and (6) the substantia nigra, locus ceruleus and intermediolateral and Onufrowicz's nuclei. Neither Bunina bodies, Lewy body-like hyaline inclusions nor ubiquitin immunoreactive skein-like structures were observed. The distribution of the lesions was quite different from that in patients with ALS and the other known related diseases. Recently, seven autopsied cases with clinical and histopathological similarities to our patients have been reported in Japan. Our conclusion is that our two and these seven patients should be classified as having a new motor neuron disease entity, which can be is differentiated from ALS.

Aged↗

Accidental intrathecal vincristine administration. Report of a case.

A case is described of accidental intrathecal administration of vincristine, with detailed clinical observations over a 17-day period. The clinical picture resembled that seen with toxicity from intravenously administered vincristine, but was rapidly progressive and resulted in death. The onset was characterised by opisthotonos, followed by ascending paralysis and finally bulbar and cerebral involvement. The specific changes in the brain at autopsy were masked by those due to prolonged artificial respiration prior to death. The accidental drug administration occurred owing to procedural errors, which can be avoided by strict attention to rules.

Brain↗

Three-dimensional organization of a transcellular tubulocisternal endoplasmic reticulum in epithelial cells of Reissner's membrane in the guinea-pig.

The ultrastructure of the epithelial cells of Reissner's membrane (membrana vestibularis) in the guinea-pig is described following vascular perfusion with glutaraldehyde of live, anaesthetised and artificially respirated animals. Postfixation in a solution containing OsO4 and potassium ferricyanide revealed a well-developed tubulocisternal endoplasmic reticulum, not previously described, the continuity of which has been mapped by serial sectioning and reconstruction. Large disc-shaped subsurface cisternae lining the cell membrane, but separated from it by a space approximately 10 nm wide, are in continuity with the smooth endoplasmic reticulum, forming an elaborated transcellular canalicular pathway. This structure is compared to that found in solute-transporting epithelia, e.g., renal proximal tubule, gall bladder, small intestine and choroid plexus. The fixation method used in the present study is compared to other techniques used for preservation of Reissner's membrane. Each epithelial cell of Reissner's membrane is endowed with one kinocilium, one to four multivesicular bodies, and a number of intercalated bodies. The functional significance of the canalicular pathway is discussed.

Animals↗