Irregular Respiration Research Articles

Joubert syndrome associated with unilateral ptosis and leber congenital amaurosis

Two siblings are described with clinical features of Joubert syndrome associated with unilateral ptosis, severe visual disturbances with normal appearing fundi, and an occipital meningocele; one child also had polydactyly. Neither child manifested responses to electroretinography and one did not manifest visual evoked potentials. The siblings were considered to have characteristics of Leber congenital amaurosis and Joubert syndrome as well as unilateral ptosis. The presence of these findings in siblings suggests a genetic basis for their disease. Careful investigations should be conducted on infants with dysplasia of the cerebellar vermis, including tests for respiratory irregularities, retinal abnormalities, and renal abnormalities to further clarify the interrelationships of these conditions.

Verapamil-induced behavioral, autonomic and motor effects in cats

The effects of verapamil, a calcium antagonist, injected into the cerebral ventricles on behavior, autonomic and motor activity of unanesthetized cats have been investigated. Verapamil evoked emotional behavior (miaowing and aalertness), autonomic responses (mydriasis, tachypnoea, dyspnoea, defecation, micturition, licking and panting) and motor phenomena (ataxia, muscular weakness and adynamia). These effects lasted from a few minutes to several hours. The most consistent phenomena were miaowing, alertness, mydriasis and respiratory irregularities. The possible mechanism of action of verapamil on behavior, autonomic and motor activity may be an action on voltage-operated calcium channels in the brain.

Mutual Relations between the Local Shift of the Brain Stem, Change in Brain Stem Function, and Transtentorial Herniation during the Process of the Gradual Expansion of an Intracerebral Balloon

A local shift of the brain stem and transtentorial herniation are studied in the state of increased intracranial pressure (ICP) induced by a supratentorial mass lesion. Analysis of ICP dynamics is based on the correlations between an increased ICP and the local shifts of the brain. Simultaneous measurement of brain shifting, ICP, systemic blood pressure, respiration, cerebral blood flow (CBF), electroencephalogram, and the size of pupils were carried out using 18 mongrel dogs and 5 monkeys. In the initial phase of mass expansion, tentorial herniation was observed on the balloon side, and the midbrain shifted to the ventral and contralateral side with a gradual increase in ICP. The pons and the ponto-medullary junction were also dislocated to ventral direction. With further mass expansion, tentorial herniation was also observed on the contralateral side, and the midbrain altered its displacement to dorsal and to the balloon side, while the pons and the ponto-medullary junction continued to shift ventrally. At the steepest rise in ICP, dorsal shift of the midbrain reached a maximum, while irregular respiration, hypotension, and a decrease in CBF were observed, and the midbrain turned its shift to ventral direction again. In conclusion, an acute deterioration of the brain stem was induced by the adverse shift of the brain stem between the midbrain and the pons during an acute increased ICP.

Improvement of bioavailability of poorly absorbed drugs. III. Oral acute toxicity and local irritation of medium chain glyceride.

Oral acute toxicity of medium chain glyceride (MCG) was studied in mice and rats. In mice and rats, clinical signs such as irregular respiration, laxity of movement, staggering gait and loss of righting reflex appeared after single oral administration of MCG at a relatively large dose. The LD50 values determined in male and female mice were 26.9 and 28.5 ml/kg, and in male and female rats were 27.4 and 26.7 ml/kg, respectively. In order to evaluate the biological safety of MCG suppository of cefmetazole sodium (CMZ), its local irritation on the mucous membrane was studied. Primary eye irritation of MCG suppository of CMZ was studied in rabbits. Although mild irritation was seen in conjunctivae, no remarkable changes were observed in cornea and iris. Furthermore, primary effect of MCG suppository of CMZ on the rectal mucous membrane was studied macro- and microscopically. It was observed that remarkable histological changes of rectal mucous membrane by MCG suppository of CMZ were not observed in all animals used.

Acute toxicity of vanadium compounds in rats and mice

Sodium metavanadate (NaVO 3) and vanadyl sulphate pentahydrate (VOSO 4 · 5H 2O) were administered to rats and mice. The following LD 50 (14-day) were determined: NaVO 3, 98.0 mg/kg (rats) and 74.6 mg/kg (mice) when given orally, and 18.4 mg/kg (rats) and 35.9 mg/kg (mice) when given i.p.; VOSO 4 · 5H 2O, 448.0 mg/kg (rats) and 467.2 mg/kg (mice) when given orally, and 74.1 mg/kg (rats) and 113.0 mg/kg (mice) when given i.p. The majority of deaths occurred during the first 24 h. The clinical and physical signs appearing after the intoxication include irregular respiration, diarrhea, ataxia and paralysis of the hind legs. These signs disappeared for the most part after 48 h, which suggests a quick elimination of vanadium.

Hypothermic effect of 2,4-dinitrophenol infused ICV in the cat

The effects on body temperature and behavior of 2,4-dinitrophenol injected into the cerebral ventricles of the cat was investigated in these experiments. Infused in a volume of 0.1–0.2 ml, 2,4-dinitrophenol produced a dose-dependent fall in body temperature, the duration of which was also dose-dependent. Apart from hypothermia, 2,4-dinitrophenol evoked mydriasis, respiratory irregularities, urination, vomiting, ataxia, muscular weakness, sedation and occasional clonic-tonic convulsions. Of all the autonomic effects, the most consistent was the effect on thermoregulation. The possible mechanisms of action in the brain of 2,4-dinitrophenol on the thermoregulatory mechanisms are discussed.

Joubert's syndrome with retinal dysplasia: neonatal tachypnoea as the clue to a genetic brain-eye malformation.

Five children with features of Joubert's syndrome and Leber's amaurosis are described. The presenting symptoms were panting tachypnoea in the newborn, prolonged apnoeic attacks in the neonatal period (in both of identical twins), global developmental delay, and failure to develop vision. Three children had multiple hemifacial spasms, such as have been seen in Joubert's syndrome, and the same three had cystic dysplasia of the kidneys. Necropsy confirmed the retinal and renal pathology, together with agenesis of the vermis and brainstem dysgenesis in the identical twins. It is concluded that a gene for Leber's amaurosis may commonly manifest itself as the specific hind brain malformation underlying Joubert's syndrome. In infants with respiratory irregularities (especially rapid panting), hemifacial spasms, or developmental delay, absence of the cerebellar vermis should be specifically sought by ultrasound and computed tomography, and the electroretinogram measured, whether or not impaired vision is clinically evident.

Correlation between ventilation and brain blood flow during sleep.

The relationships between brain blood flow (BBF) and ventilation (VI) were studied during sleep in 13 goats. Unilateral BBF was continuously measured with an electromagnetic flow probe; total and regional BBF were assessed by the radioactive microsphere technique in four animals. Interacting changes in VI and BBF occurred during both slow wave (SWS) and rapid eye movement (REM) sleep. During SWS, significant decreases in VI and increases in arterial PCO2 occurred compared to wakefulness. BBF during SWS correlated linearly with arterial CO2 tension (PaCO2); nd the relationship was similar to that for awake goats breathing CO2. During REM sleep, VI was significantly less than both the awake (W) and SWS states due principally to a decrease in tidal volume. BBF during REM sleep was significantly and substantially increased compared with both the W and SWS states; this increase was shared by all brain areas. The increase in BBF during REM sleep was greater than that predicted from changes in PaCO2. In five goats provided with chronic sagittal sinus fistulae, arteriovenous oxygen difference was measured in separate studies and found to be significantly lower during REM sleep compared with W; brain O2 consumption was similar in magnitude in the REM and W states. Thus, the high BBF of REM sleep was also unexplained by an increase of brain metabolic activity. We conclude that, during SWS, increases in BBF are explained by hypoventilation and hypercapnia. In contrast, during REM sleep, BBF is substantially in excess of that expected from PaCO2 or brain metabolism. It is postulated that this excess of BBF during REM sleep could reduce the central chemoreceptor pH relative to that present in SWS. The combination of reduction of sensitivity to CO2 and lower tissue PCO2 during REM sleep makes it likely that the output of the central chemoreceptors during this state is less than that during SWS and wakefulness. This may contribute to the low tidal volume and respiratory irregularities of this sleep period.

Sleep structure and nocturnal disordered breathing in familial dysautonomia

In 13 patients with familial dysautonomia sleep recordings were obtained to investigate the possibility that autonomic nervous system dysfunction plays a role in disordered breathing during sleep. Sleep structure in some of our patients was abnormal, showing decreased amount of REM sleep and increased REM latencies. All patients showed breathing disorders in sleep. The average number of apneic spells was 73.4 per night; 77% of the patients had more than 50 apneic spells per night. Abnormal breathing patterns were not uniform and were independent of patients' primary complaints. Typically, even severe respiratory irregularities were not associated with the usual cardiac response, indicating that our patients had “cardiac dysautonomia”.

Effect of naloxone on the hypotensive action of clonidine in the conscious, normotensive goat.

The possible involvement of opioid receptors in the effects of clonidine was studied in conscious, normotensive goats. Clonidine was infused intravenously followed by an intravenous injection of naloxone. Blood pressure was recorded through an intraarterial catheter. All doses of clonidine (0.2-7 micrograms/kg) significantly lowered blood pressure and decreased heart rate. Hypotension after 0.2-0.7 micrograms/kg of clonidine was significantly reduced by naloxone (1 mg/kg), while naloxone did not antagonize hypotension induced by the larger doses of clonidine. The bradycardiac effect of 0.7-2 micrograms/kg of clonidine was reduced by naloxone while that of 0.2 and 7 micrograms/kg was not. Clonidine also induced sedation and respiratory irregularity, but these changes were not modified by naloxone. Opioid mechanisms possibly participate in the hypotensive action of clonidine, but less in the normotensive animal than in spontaneously hypertensive animals.

Inhalation toxicity of adiponitrile in rats

Adiponitrile, a chemical intermediate used in the manufacture of hexamethylenediamine, has moderate acute toxicity both orally and dermally. The acute inhalation toxicity was determined by exposing groups of young adult male ChR-CD rats for single 4-hr periods. The LC50 was 1.71 mg/liter. Male rats were exposed to either 0 (control), 0.03, 0.1, or 0.3 mg vaporized adiponitrile/liter for ten 6-hr periods (5 exposure days, 2 rest days, 5 exposure days). Clinical signs during exposure included irregular respiration and mild salivation. Rats exposed to 0.3 mg/liter showed weight loss during the first 5 exposures followed by a normal rate of weight gain. After 10 exposures, rats in this group had the following clinical pathologic changes: increased blood glucose, urea nitrogen, creatinine, and urine glucose; decreased erythrocyte count, hemoglobin, leukocyte count, relative number of eosinophils, and urine osmolality. Rats exposed to 0.1 mg/liter had increased urea nitrogen and lymphocytes and decreased numbers of neutrophils and eosinophils. No changes in clinical pathology parameters were seen in rats exposed to 0.03 mg/liter. Rats from all groups had normal values 14 days following the last exposure. Pathologic examination failed to reveal any compound-related changes.

Effects of clonidine infusion and withdrawal on blood pressure and behaviour in the rat. A preliminary study.

Clonidine (10 micrograms/kg/hr) was administered continuously to normotensive rats for 5 days using osmotic minipumps. This treatment attenuated the episodic fluctuations in blood pressure normally observed during rapid eye movement (REM) sleep. However, 18-24 hr after withdrawal of clonidine, pronounced fluctuations in blood pressure superimposed upon tonic increases in pressure as well as muscular twitching and irregular respiration were seen during sleep. These responses were abolished by an injection of clonidine or phentolamine. The results demonstrate that after withdrawal of clonidine administration, an increased lability of blood pressure occurs during sleep and probably results from an increased frequency and duration of REM sleep.

冠動脈内アラキドン酸（ＡＡ）注入による心筋虚血の発生とその予防

A Wedge-Pressure catheter was inserted to 1cm above aortic valve in ascending aorta through left common carotid artery of 36 rabbits. 1.5mg/kg of sodium arachidonate (AA) was injected into the proximal portion of ascending aorta after inflation of balloon which obstructed the ascending aorta. The inflation remained for 5 seconds, the solution was perfused into coronary arteries. 14 rabbits among the 36 rabbits were not pretreated before injection of AA, each 11 rabbits were pretreated intravenously with 10mg/kg of OKY-1580 and OKY-046 (specific inhibitors on TXA2 synthetase) respectively 3 minutes before AA injection. ECG, respiratory movement and blood pressure were recorded. Before, 3 and 60 minutes after AA, 5ml of heparinized blood was collected, added with indomethacin (10μM in final concentration) and centrifuged to collect PPP for measurement of TXB2 and 6-keto-PGF1α using radioimmunoassay (RIA). In control, 5 out of 14 cases died because of apnea. Blood pressure decreased in 5 or 6 seconds after AA, irregular respiration and arrhythmia in some 10 seconds, ST deviation in 20 seconds, apnea appeared in 30 seconds. Arrhythmia and marked ST depression appeared in all cases. Apnea was seen in 10 cases. In OKY groups, arrhythmia, ST depression and apnea were prevented significantly. In control, TXB2 values were 1.2±0.2ng/ml (mean±SE) before, 10.2±3.3 minutes after, and 1.3±0.2 60 minutes after. In OKY-046, 1580 groups, those 3 minutes after were 0.8±0.1, 1.1±0.2 respectively showing complete inhibition of TXB2. In control, 6-keto-PGF1α values were 2.1±0.4ng/ml before, 133.1±40.0 3 minutes after and 2.5±0.8 60 minutes after. In OKY-046, 1580 groups, those 3 minutes after were 41.4±7.5, 74.4±13.0 respectively also showing significant difference with that of control group. ST deviation on ECG had good correlation with the value of TXB2 (r=0.765, p<0.005), but no relation with the value of 6-keto-PGF1α. Histological findings of heart were not so severe as expected, but showed more remarkable ischemic changes in control than OKY groups. These findings clearly show that intracoronary injection of AA causes myocardial ischemic changes through TXA2, because OKY protected cardiopulmonary changes, but also suggest the important role of PGI2.

The impact of autonomic nervous system dysfunction on breathing during sleep.

Ten patients with autonomic nervous system dysfunction (familial dysautonomia, juvenile diabetes, or Shy-Drager syndrome) were studied to assess the impact of their impairment on breathing during sleep. Several types of breathing dysfunction during sleep were identified independent of the patients' primary complaints. Obstructive sleep apnea syndrome was the most common; central sleep apnea and disturbances of te respiratory oscillator also were seen. Esophageal reflux was found to be the cause of some sleep-related problems. The observed respiratory irregularities were not associated with the usual cardiac response; a "decoupling" of heart rate from the respiratory cycle was noted during sleep in these patients.

Cot death among children of nurses. Observations of breathing patterns.

Research into cot death has recently been focused on a search for pre-existing chronic abnormalities rather than on the immediate events before death. Because nurses are trained observers, 30 nurses who had lost children by cot death were questioned. In particular, they were asked about any respiratory symptoms which had been present in the absence of respiratory tract infection. Some (37%) of the nurse mothers had noted unusual respiratory events (wheezing, apnoea, irregular respiration, or cyanosis) in their children during the early months of life. Only 6% on non-nurse mothers who similarly had lost children recalled respiratory difficulties. None of the 60 nurse mothers with healthy infants gave a history of respiratory difficulties in the absence of infection. The importance of taking a careful history from any parent who loses a child by cot death is stressed.

Central respiratory and circulatory effects of Gymnodinium breve toxin in anaesthetized cats.

1 In cats anaesthetized with pentobarbitone, observations were made on respiration, spontaneous and evoked diaphragmatic electromyograms, blood pressure, heart rate, indirectly-induced contractions of the anterior tibialis muscle and nictitating membrane, and electrical excitability of the inspiratory centre in the medulla oblongata.2Gymnodinium breve toxin (GBTX) was administered intravenously, intra-arterially to the brain, and intracerebroventricularly. Physiological effects were recorded while alveolar P(CO) (2) was controlled at a constant level except when changes in gas tension were made in order to measure CO(2)-ventilatory responsiveness.3 Adequate doses of GBTX given intravenously by bolus injection elicited a non-tachyphylactic reflex response triad of apnoea, hypotension and bradycardia mediated by the vagus nerves independently of arterial baroreceptor and chemoreceptor innervation.4 After vagotomy, additional amounts of GBTX (i.v.) resulted in apneustic breathing, hypertension and tachycardia. The cardiovascular effects were abolished by ganglionic blockade with hexamethonium.5 Smaller doses of GBTX were required intra-arterially and intracerebroventricularly than by the intravenous route of injection to produce respiratory irregularity and cardiovascular hyperactivity.6 Evoked motor responses, electrical excitability of the medulla oblongata and CO(2)-ventilatory responsiveness were largely spared even though GBTX caused marked disturbances in respiratory rhythmicity and cardiovascular functions.7 It is concluded that GBTX acts reflexly on vagally innervated receptors to evoke a Bezold-Jarisch effect but that the toxin further acts centrally to cause irregular breathholding and hypertension with tachycardia, leading ultimately to respiratory and circulatory failure.

Posterior Fossa Subdural Hemorrhage in the Newborn

Posterior fossa subdural hematoma formation in the newborn is an infrequently reported event. It is characterized by a complicated delivery, usually at term, followed by developing lethargy and irritability within the first few days of life. Respiratory irregularities, tense anterior fontanelle, and increasing head circumference ensue, accompanied by a falling hemoglobin and blood-stained cerebrospinal fluid. Various cranial nerves may also be involved. Previously reported cases have been marked by diagnostic delays that affected the subsequent outcome of some of the patients. Computed tomography (CT) allows for earlier confirmation of the diagnosis, especially where coronal views are employed. Three cases are reported here to illustrate the above features.

A case of suspected congenital rubella encephalopathy

A case of suspected congenital rubella syndrome was reported. The patient, a 3-month-old female, was admitted because of irregular respiration. She was diagnosed as suspected congenital encephalodysplasia by CT-scan. Her condition deteriorated and she died 11 days after admission. From postmortem findings it was speculated that neuropathological findings were caused by rubella virus infection in uterus and the injury on delivery.

Experimental head injury in monkeys using rotational acceleration impact (author's transl)

Investigations of head injury using monkeys were performed to elucidate the effect of linear as well as rotational acceleration impact to produce brain contusion and concussion. The results of investigations using pure linear acceleration impact, which had already been reported, showed that concussion occurred in all monkeys, but that no visible lesion except subarachnoid hemorrhage was found, even though negative pressure of under minus 1 atmosphere was recorded in the contralateral side of the impact. In this paper, the result of investigation using a newly designed and constructed impactor system to deliver rotational acceleration impact is reported. The impactor system was accelerated by compressed air, 1.5-3.5 kg/cm2 in pressure, and velocity of the impact shaft was 20.2-36.4 m/sec. Under light anesthesia with ketamine hydrochloride, the impact was delivered to the occipital area of 18 monkeys, weighing 5.9 to 10.5 kg, through a restraint mask which was made of iron frame and plaster of Paris for each animal in order to obtain a broad impact area and to avoid fracture. Averaged frontal angular acceleration ranged from 29, 000 to 281, 000 rad/sec2 and its duration was 0.64-4.0 msec. Averaged frontal acceleration was 480-1, 080 G's and its duration was 1.26-4.50 msec. Skull fractures were found in 6 monkeys. Four of them had comminuted and depressed fractures that became fatal within 10 minutes after impact due to laceration of the medulla oblongata and/or of the main intracranial vessels. The remaining two had only multiple linear fractures without depression and these animals recovered from initial concussion. Among the 12 monkeys without any fracture, 11 recovered from the initial concussion within 10 minutes after the impact. One monkey died in the state of concussion. There was noted correlation between the severity of concussion and changes in systemic blood pressure immediately after the impact, which is classified into three groups (Fig. 3). Among the 12 monkeys without fracture, 7 had cortical hemorrhage and contusion at the para-sagittal area, tip or base of the frontal and temporal lobe (viz. contre coup injury), or the brain stem and the upper cervical cord. Coup injury in the occipital lobe did not result in this series with the exception of the comminuted depressed fracture group. Intramedullary hemorrhage in the upper cervical cord was found in 5 monkeys; 2 with and 3 without fracture. Four among these 5 survived apnea followed by irregular respiration for several seconds after the impact. As reported previously, pure linear acceleration impact did not produce any visible brain lesion. On the other hand, rotational acceleration impact caused brain damages. It was, therefore, supposed that rotational acceleration impact was a greater cause for producing blunt brain injury than translational impact. Furthermore, it was suggested that the contusion threshold of the brain was close to the concussion threshold.

Unilateral inferior temporal lobectomy with hippocampectomy for relief of incisural herniation.

1. The syndrome of incisural hippocampal herniation, accompanied by unilateral and then bilateral fixed pupils, deepening coma, respiratory irregularity (Cheyne-Stokes), contralateral hemiplegia, ipsilateral decerebrate posturing rising blood pressure, and finally renal shutdown, indicates a terminal state that requires immediate relief. 2. Accepted methods of relief by brain shrinkage, dexamethasone, subtemporal decompression, anterior temporal lobectomy, cutting of the tentorium, and even massive uncapping of the skull, have failed in the author's experience to reverse the process when once established. 3. Presentation is made of a rapid and relatively simple inferior horizontal temporal lobectomy, including the hippocampal gyrus, so as to relieve peduncle compression, blockage of cerebrospinal fluid circulation, midbrain haemorrhage, and infarction in the posterior cerebral artery distribution area. 4. Reports are given of 15 cases out of 30 cases in which operation proved lifesaving, with restoration of normal function in 13. 5. Those patients who died did so in an average of five days, and generally showed either no herniation or continuing evidence of tumour or internal bleeding. 6. Very young patients particularly have an excellent chance of survival, which is seven times better than that of adults in having good to excellent results without operation.