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Respiratory changes in parasternal intercostal length.

In an attempt to understand the role of the parasternal intercostals in respiration, we measured the changes in length of these muscles during a variety of static and dynamic respiratory maneuvers. Studies were performed on 39 intercostal spaces from 10 anesthetized dogs, and changes in parasternal intercostal length were assessed with pairs of piezoelectric crystals (sonomicrometry). During static maneuvers (passive inflation-deflation, isovolume maneuvers, changes in body position), the parasternal intercostals shortened whenever the rib cage inflated, and they lengthened whenever the rib cage contracted. The changes in parasternal intercostal length, however, were much smaller than the changes in diaphragmatic length, averaging 9.2% of the resting length during inflation from residual volume to total lung capacity and 1.3% during tilting from supine to upright. During quiet breathing the parasternal intercostals always shortened during inspiration and lengthened during expiration. In the intact animals the inspiratory parasternal shortening was close to that seen for the same increase in lung volume during passive inflation and averaged 3.5%. After bilateral phrenicotomy, however, the parasternal intercostal shortening during inspiration markedly increased, whereas tidal volume diminished. These results indicate that 1) the parasternal intercostals in the dog are real agonists (as opposed to fixators) and actively contribute to expand the rib cage and the lung during quiet inspiration, 2) the relationship between lung volume and parasternal length is not unique but depends on the relative contribution of the various inspiratory muscles to tidal volume, and 3) the physiological range of operating length of the parasternal intercostals is considerably smaller than that of the diaphragm.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Use of the inferior epigastric artery for coronary bypass.

Between December 1988 and April 1991, 74 free inferior epigastric arteries were used in 73 patients for coronary artery bypass grafts. In addition, 72 of the patients received a left internal mammary artery for single or sequential grafting to the left anterior descending system and 62 a right internal mammary artery to the circumflex or the right coronary artery. Twenty-seven patients had no saphenous vein available, and two had no suitable internal mammary artery; in an attempt to make a complete arterial revascularization, we chose the inferior epigastric artery as an alternative conduit in 24 young patients and in 10 reoperations; bilateral internal mammary artery dissection was avoided in four patients with impaired lung function and in six patients with selected two-vessel disease to spare one internal mammary artery. The technique for harvesting the inferior epigastric artery is described. Fifty-three inferior epigastric artery grafts were anastomosed to the distal right coronary artery or to its branches, 18 to the distal obtuse marginals of the circumflex artery (three as sequential grafts and one as a natural Y graft), and three to the left anterior descending system. The mean number of distal anastomoses is 3.60 per patient. Seventy proximal anastomoses of the inferior epigastric artery were made to the aorta and four to one internal mammary artery. There were four early deaths and one nonfatal myocardial infarction. Four abdominal wound hematomas needed surgical drainage. Sixty-one patients underwent angiographic study on postoperative day 10:59 of 61 inferior epigastric artery grafts (63 of 65 inferior epigastric artery distal anatomoses) and 111 of 111 internal mammary artery grafts (155 of 156 internal mammary artery distal anastomoses) were patent. Clinical follow-up of all the survivors (100% follow-up) could be obtained with a mean period of 9 months (1 to 28 months). There was no late cardiac death, no infarction, and all the patients were free of angina. Nineteen patients underwent a 6-month postoperative angiographic study. Seventeen of 19 inferior epigastric artery grafts were patent and 16 of 19 were intact; 34 of 34 internal mammary artery grafts (46 of 47 internal mammary artery distal anastomoses) were patent and intact. In conclusion, free inferior epigastric artery grafts can reach the diaphragmatic ischemic areas of the heart. The early patency rate and the clinical results are encouraging but only long-term evolution and evaluation can determine the true efficacy of the inferior epigastric artery graft as a reliable conduit for coronary artery bypass graft operations.

Abdominal Muscles↗

Effects of single breath lung inflation on the pattern of subsequent breaths.

In rabbits, on release of lung inflations 0.4 to 3.3 times control VT and lasting 1 to 30 sec, VT, peak diaphragmatic activity (Ep) and inspiratory duration (Ti) increased, whereas expiratory duration (Te) decreased relative to pre-inflation values. Similar changes occurred between pre- and postinflation occluded breaths. These changes lasted from a few breaths up to 30 sec, and were positively correlated with magnitude and duration of inflations. Postinflation changes of pulmonary stretch receptor activity were relatively small and limited to 1-3 breaths. At chemical drive close to control: (a) postinflation VT vs Ti relationship moved to the right without changing its slope, Ti occluded eventually exceeding Ti after vagotomy; (b) the Te vs Ti relationship moved downwards, its slope being decreased and eventually abolished; (c) the average rate of rise of E was decreased. An increase of VT, Ep and Ti, and a decrease Te also occurred on release of stimulation of the central ends of the cut vagi producing apnea at FRC in mono- and bilateral vagotomized rabbits. Postinflation effects were mainly of central origin and tentatively explained as rebound phenomena within the respiratory center.

Animals↗

Dual chamber cardiac pacing in children: Single chamber pacing dual chamber sensing cardiac pacemaker or dual chamber pacing and sensing cardiac pacemaker?

BACKGROUND: Dual chamber pacemakers (single chamber pacing dual chamber sensing cardiac pacemaker (VDD) and dual chamber pacing and sensing cardiac pacemaker (DDD)) are being used frequently in children and adolescents. The aim of this study was to verify the safety and performance of the VDD and DDD pacing systems, and to evaluate the differences between two pacing modes with regard to atrial sensing and tracking functions. METHODS: In this study, we evaluated 14 patients with VDD pacing and 15 patients with DDD pacing between 1994 and 2000. In the patient group with VDD pacing, all had congenital or acquired atrioventricular (AV) block. In the patient group with DDD pacing, 11 had congenital or acquired AV block, three had sinus node dysfunction with AV conduction disturbance and one had idiopathic hypertrophic subaortic stenosis. Twenty-eight devices were implanted in the subpectoral area using the transvenous route. After implantation the atrial tracking capabilities of the pacing systems were analyzed by telemetry, Holter monitoring, and treadmill exercise testing. RESULTS: The mean age of patients in the VDD pacing group was younger. The percentage of congenital heart disease was higher in the DDD pacing group. There was no significant difference regarding fluoroscopy time during implantation and follow-up time between the two groups. During implantation, in the VDD pacing group the mean sensed atrial signal was 3.1 +/- 1.3 mV and this decreased to 1.37 +/- 0.68 mV (P < 0.05) during follow-up. This pattern was also observed in DDD group (3 +/- 2 mV vs 1.9 +/- 1.5 mV, P < 0.05). Although the P wave measurement at implantation did not differ between the two groups, it was significantly higher in the DDD pacing group at the last control. Three patients with VDD pacing were reprogrammed to VVI or single chamber pacing and sensing, rate adaptive cardiac pacemaker because of complete loss of AV synchrony. There was no atrial sensing problem in the DDD pacing group. During the follow-up, one patient with VDD pacing developed diaphragmatic stimulation and required lead revision. In one patient with DDD pacing, venous thrombosis occurred in the right subclavian vein and was treated with thrombolytic therapy. During treadmill exercise testing, in one patient with VDD and one patient with DDD pacing temporary failure of atrial sensing occurred. At 24 h Holter monitoring, intermittent loss of atrial sensing was documented in two patients with VDD pacing. CONCLUSIONS: Dual chamber pacing in children with DDD or VDD pacemakers is a suitable method for bradycardia treatment. Atrial sensing problems may occur in VDD pacemakers. Therefore, DDD pacing mode should be preferred whenever suitable for the patient to maintain the AV synchrony.

Adolescent↗

Inspiratory muscle activity during rebreathing in intact and vagotomized rabbits.

The relation between relative peak 'integrated' diaphragmatic (Adi) and cranial (u) or caudal (1) inspiratory intercostal activity (Aic) was assessed in intact and vagotomized rabbits during rebreathing. During unloaded rebreathing Aic increased markedly more than Adi, and Aicu more than Aicl, independently of intact vagi. Vagal signals facilitated inspiratory intercostals, since vagotomy or vagal blocks increased Adi more than Aic without changing diaphragm activity time course, and delta Aic/delta Adi in the same range of Adi values was greater before than after vagotomy. Reflexes from the chest wall were not involved since phrenic block after vagotomy modified rib cage motion without changing Aic, independently of chemical drive. Possibly chemical and vagal dependent changes in fusimotor activity contribution to VT, as the latter increases. Obstruction at FRC shifted postvagotomy Aic vs. Adi relationship upwards, suggesting reflex facilitation of intercostals by chest wall receptors. The strength of this reflex was largely independent of intact vagi, since pre- and postvagotomy Aic vs. Adi relations coincided, and of chemical drive, since postvagotomy delta Aic/delta Adi for obstructed and unimpeded rebreathing were similar.

Airway Obstruction↗

[Effect of dialysates on ultrastructure of mouse peritoneal mesothelium].

OBJECTIVE: To observe the effect of various peritoneal dialysates on the ultrastructure of the peritoneal mesothelium. METHODS: Continuous ambulatory peritoneal dialysis mice model was made by injecting domestic lactate, acetate, and American Baxter dialysates intraperitoneally. The diaphragmatic peritoneum of the mice was taken at 10th day and 21th day respectively after injection. RESULTS: After 10 day experiment, the mesothelial ultrastructure of Baxter group was normal, but some pathological changes occurred in the peritoneal mesothelium of both domestic lactate and acetate groups. And the injury of the peritoneal mesothelium was progressing with times, e.g. adhesion and exfoliation of the microvilli, shrinkage of the mesothelial cells and even fibrous adhesion. The extent of effects on the mesothelial cells varied in three groups, the least is Baxter group. After 21 day experiments, the diameters of the stomata were (6.96 +/- 2.46) microns and (6.98 +/- 2.16) microns in both domestic lactate and acetate dialysates groups respectively, which were much greater than those in physiological condition (1.47 +/- 0.88) microns (P < 0.01). The distribution density of the lymphatic stomata were significantly increased in acetate and lactate dialysate groups compared with the control group (P < 0.01). But little effects on the lymphatic stomata were showed after using Baxter dialysate. After discontinuing experiment for 10 days, the impairment of the peritoneal mesothelium recovered in Baxter group and improved to varying degrees in both domestic dialysate groups. The lymphatic stomata were still abnormal in both domestic dialysate groups. CONCLUSIONS: Our findings indicate that lactate and acetate dialysates are more like to elicit peritoneal fibrosis and the increase of distribution density and the enlargement of the lymphatic stomata can significantly enhance their absorption effects and increase their reabsorption quantity of dialysate from the peritoneal cavity during peritoneal dialysis. These changes of the lymphatic stomata and their lymphatic reabsorption are thought to be associated with deterioration of peritoneal function, and to cause ultrafiltration failure in the patients on long-term continuous ambulatory peritoneal dialysis (CAPD) therapy.

Acetates↗

Effect of paraesophageal hernia on sphincter function and its implication on surgical therapy.

Fifteen patients with a paraesophageal hernia were studied with 24 hour esophageal pH monitoring and esophageal manometry to clarify the physiologic aspects of the cardia and resolve controversies over the type of surgical repair. The results were compared with those obtained in 34 randomly selected patients with a sliding hernia and 18 normal control subjects. Sixty percent of the patients with a paraesophageal hernia had an incompetent cardia on 24 hour pH studies which was associated with a lower esophageal sphincter of normal pressure, short overall length, and a small segment exposed to abdominal pressure. In comparison, 70 percent of patients with a sliding hernia had an incompetent cardia which was associated with a lower esophageal sphincter of low pressure, normal overall length, and a short segment exposed to abdominal pressure. With either type of hernia, symptoms were not helpful in determining the competency of the cardia. When urgent surgery is necessary, repair should include an antireflux procedure. If facilities and time permit, more specific evaluation of the cardia can be performed, and if competent, the repair should be limited to reduction of the stomach and closure of the defect.

Adult↗

Optimal pressure support level for beginning weaning in patients with COPD: measurement of diaphragmatic activity with step-by-step decreasing pressure support level.

PURPOSE: The study objective was to determine an "optimal" individual pressure support (PS) level for beginning weaning with PS ventilation in patients with chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: Eleven COPD patients intubated and ventilated for acute respiratory failure and judged ready for weaning were studied. The technique consisted of lowering the PS level from a point that was characteristic for each patient and measurable under controlled mechanical ventilation, after setting the ventilator as recommended for COPD patients judged ready for weaning, that is, peak inflation pressure (PIP). This determination was based mainly on exploring the diaphragm with an electromyographic technique by defining the optimal PS level as the lowest PS level associated with no EMG evidence of diaphragmatic stress. Diaphragmatic electromyographic activity (diEMG) was recorded by a bipolar esophageal electrode (Disa-Denmark), and the high-frequency electrical component/low-frequency ratio (H/L) was calculated. The reference H/L was determined during a few spontaneous ventilatory cycles. Muscle stress was defined as a greater than 20% reduction in H/L compared with the reference value. RESULTS: Optimal PS levels ranged from 4 to 24 cm H2O with a mean of 14+/-6 cm H2O. Two patients with optimal PS level at 4 cm H2O did not require weaning and were quickly extubated. For the nine other patients, optimal PS levels were found to be 70% of PIP; in none was it necessary during weaning to use PS levels higher than individual optimal PS levels. CONCLUSIONS: Optimal PS level established with diEMG monitoring seems to be a useful index for beginning weaning in the PS ventilation mode in COPD patients. The hypothesis of beginning weaning with a PS level equal to 70% of PIP needs to be tested.

Aged↗

Activation of human respiratory muscles during different voluntary manoeuvres.

1. This study used three techniques (bilateral phrenic nerve stimulation, motor cortex stimulation and quantitative electromyography) to assess the degree of activation of the diaphragm, intercostal-accessory muscles and abdominal muscles during postural tasks and respiratory manoeuvres. They included maximal inspiratory and expulsive efforts. 2. Bilateral phrenic nerve stimuli at supramaximal levels produced an average change in transdiaphragmatic pressure (Pdi) of 28 cmH2O during relaxation. During maximal inspiratory or expulsive efforts, all subjects were able to activate the diaphragm fully at functional residual capacity as judged by the failure of stimuli delivered during the voluntary efforts to increase Pdi. Peak voluntary Pdi was about 30% less for inspiratory than expulsive manoeuvres. 3. By contrast, transcranial activation of motor cortical output to the diaphragm and abdominal muscles produced an increment in abdominal pressure of 25 +/- 7 cmH2O during maximal voluntary expulsive efforts. Given the lack of response to phrenic nerve stimulation at similar voluntary pressures, this suggests that abdominal muscles, and not the diaphragm, fail to generate their full contractile force during maximal voluntary expulsive manoeuvres. 4. Motor cortical stimulation during weak inspiratory efforts produced a small reduction in oesophageal pressure (i.e. increase in net inspiratory force) of 7-14 cmH2O. This response could not be extinguished during maximal voluntary inspiratory efforts in two of three subjects. This occurred despite the cortical co-activation of 'antagonist' muscles in the chest wall and abdomen, and passive transmission of pressure from the abdominal to thoracic compartments. 5. Integrated electromyographic activity (EMG) recorded from abdominal muscles (rectus abdominis, external oblique) was greater during trunk flexion than during maximal expulsive efforts. Similarly, integrated EMG of the intercostal-accessory muscles (sternomastoid, scalenes, parasternal intercostals) was greater during tasks requiring head and/or neck flexion than during the maximal inspiratory efforts. 6. These data show that the diaphragm can be fully activated by the central nervous system during voluntary respiratory tasks but that other agonist 'respiratory' muscles need not be activated fully. Given the complex actions of 'inseries' respiratory muscles revealed here, it is argued that differences in the transdiaphragmatic pressure during various postural and respiratory tasks do not necessarily imply variation in the level of diaphragmatic neural drive.

Diaphragm↗

Conditions leading to pediatric cardiology consultation in a tertiary academic hospital.

OBJECTIVE: To determine the basis for cardiac consultations for pediatric patients in an academic hospital setting. METHODS: The activities of the cardiology consultation service were tabulated for 12 months, from July 2001 to June 2002. Patients were identified from 4 sources, ie, a monthly log of patient encounters maintained by the consultation service, encounter forms submitted to the billing office, consultation notes maintained in a central file, and a departmental list of echocardiography studies. Patients who required clearance for noncardiac surgical procedures were generally evaluated in the cardiology clinic and not by the consultation service. Patient data were obtained from consultation and echocardiography reports and from hospital computer-based records for discharge summaries for inpatient admissions, emergency department encounter summaries, and laboratory reports. For each patient, consultations were tabulated as separate encounters if they occurred on different days in the emergency department, during separate admissions, or for different clinical concerns during a single admission. RESULTS: A total of 2071 consultations were performed for 1724 patients. The age at the time of consultation was 6.6 +/- 9.3 years (median: 1.2 years; range: 1 day to 60.6 years). A total of 1507 patients (87.4%) had a single consultation; 217 patients (12.6%) had multiple encounters, ranging from 2 to 9, accounting for 564 consultations (27.2%). Clinical concerns included murmurs (18.5%), cardiac function (12.7%), arrhythmias (12.7%), intercurrent illnesses among cardiac patients (11.3%), cyanosis (6.3%), syndromes (5.7%), chest pain (5.2%), syncope/dizziness (4.5%), subacute endocarditis (4.4%), follow-up evaluations of fetal diagnoses (4.3%), Kawasaki disease (3.4%), cor pulmonale (3%), recent cardiac surgery or catheterization (1.6%), cerebrovascular accidents (1.2%), and miscellaneous conditions. Four diagnoses accounted for 91% of murmur evaluations, ie, patent ductus arteriosus, ventricular septal defects, innocent murmurs, and pulmonary branch murmur of infancy. The most common murmur diagnosis in the neonatal intensive care unit was patent ductus arteriosus (68%), in the well-child nursery was ventricular septal defect (64%), and on the medical ward was innocent murmur (62%). The most common basis for evaluation of function was oncologic disease. Among patients evaluated for function, there were 3 new diagnoses of structural congenital heart disease, all involving neonates with aortic arch obstruction. Approximately two-thirds of arrhythmias were supraventricular in origin. The most common arrhythmias requiring treatment were supraventricular tachycardia and atrial flutter/fibrillation, the latter occurring mainly among older patients with structural heart disease. Diagnoses made with fetal echocardiography accounted for 14.3% of newborn consultations and included 83% of patients with cyanotic cardiac disease. Three syndromes accounted for 57% of consultations for this indication, ie, VACTERL association (vertebral anomalies, anal atresia, congenital heart disease, tracheoesophageal fistula, renal abnormality, and limb anomalies), trisomy 21, and infant of diabetic mother. Chest pain and syncope/dizziness were frequently evaluated in the emergency department and, in this setting, accounted for 13 and 10% of all evaluations and 19 and 25% of evaluations for new patients, respectively. For patients evaluated for chest pain, the most common basis was musculoskeletal/costochondritic (42%) or idiopathic (22%). There was a cardiac or pericardial basis in 11% of cases; these patients either had known heart disease associated with this complication or systemic symptoms, abnormal cardiac auscultatory findings, and electrocardiographic features of pericarditis. Syncope/dizziness most commonly had a vasovagal (50.5%) or orthostatic (24.7%) basis. There was a cardiac basis in 5.4% of cases; these patients were more likely to have symptoms associated with exercise. Although endocarditis was a frequent clinical concern (91 patients), only 3 cases were identified, involving 2 patients with structural heart disease and 1 neonate with an indwelling intracardiac catheter. Two other patients had central venous lines, intravascular thrombus, and fungemia. Kawasaki disease was the most common acquired condition leading to consultation. Cor pulmonale was most commonly screened among patients with congenital diaphragmatic hernia, chronic lung disease of prematurity, pneumonitis, reactive airway disease, or cystic fibrosis. Patients with recent cardiac surgery or cardiac catheterization typically had postpericardiotomy syndrome or complications associated with vascular access. Approximately 20% of cases of cerebrovascular accidents had a cardiac basis. CONCLUSIONS: Although a variety of conditions were assessed, some were encountered more frequently. Future educational curricula developed for cardiac training of pediatric residents should appropriately emphasize conditions necessitating consultation.

Academic Medical Centers↗

Endoscopic and manometric study of the cardia in post-gastrectomy patients.

This study was undertaken to clarify the incidence of hiatus hernia and the functional changes in the cardia of post-gastrectomy patients. One hundred and four post-gastrectomy patients and 399 non-gastrectomy patients were selected for endoscopic study, and the diagnosis of hiatus hernia was made by observing the shape of the cardia inside the stomach. A manometric study was also done on 12 patients with gastric carcinoma and 14 patients with gallstones. Hiatus hernia was observed in 37.5 per cent of the post-gastrectomy patients, this incidence being significantly higher than the 19.3 per cent of the non-gastrectomy patients (p less than 0.01). In the latter group alone the incidence of hernia steadily increased with advancing age. In the post-gastrectomy patients, reflux esophagitis and heartburn were observed in 20.2 per cent and 27.9 per cent, respectively. These incidences tended to be higher in the patients with hernia but there were no significant differences. The manometric study revealed that lower esophageal sphincter pressure was significantly decreased after gastrectomy, but not after cholecystectomy.

Aged↗

Control of breathing in normal subjects and in patients with chronic airflow obstruction.

In order to assess ventilatory control in patients with chronic airflow obstruction (CAO), the present study was carried out in nine patients with chronic obstructive pulmonary disease (COPD), eight asthmatics and nine normal subjects. We analysed the components of the respiratory control system at three levels: neural, assessed by diaphragmatic electromyography (EMGd), muscular, assessed by mouth occlusion pressure (P0.1), and ventilatory, assessed by mean inspiratory flow (VT/TI). EMGd was recorded by surface electrodes. During a CO2 rebreathing test, patients showed a normal or greater EMGd response slope (EMGdS), while for a given degree of EMGdS, P0.1 response slope (P0.1S) was found to be significantly reduced; in contrast, for a given degree of P0.1S, VT/TI response slope (VT/TIS) was found to be significantly reduced in COPD patients only. These data show that, compared to normal subjects, patients with CAO have a normal or increased neural component of the respiratory activity (EMGdS) and a relatively lower neuromuscular coupling (P0.1S/EMGdS). Probably due to different parenchymal and airway involvement, musculoventilatory transfer (VT/TIS/P0.1S) was found to be reduced in COPD patients but not in asthmatics. A complementary study, showing a good agreement between surface and oesophageal EMGd seems to confirm that surface EMGd is a useful and promising tool for clinical investigation.

Asthma↗

[Tako-tsubo syndrome associated with a long course of the left anterior descending coronary artery along the apical diaphragmatic surface of the left ventricle].

INTRODUCTION AND OBJECTIVES: Tako-tsubo-like transient left ventricular apical ballooning has been described in Japan, but few cases have been reported in Western countries. We report one of the first series outside Japan, which provides new information on the coronary anatomy of this disorder. PATIENTS AND METHODS: From January 1998 to February 2003 we observed 11 patients with a clinical suspicion of acute myocardial infarction, normal coronary arteries, and transient tako-tsubo-like systolic left ventricular apical ballooning. We compared the coronary artery anatomy in these 11 patients with that in 44 controls matched for age and sex: 22 with normal coronary arteries and 22 with acute myocardial infarction related with an obstructive thrombus in the left anterior descending coronary artery. RESULTS: As in Japanese patients, tako-tsubo syndrome in Caucasian patients frequently occurs in women in their seventh or eighth decades of life, and is usually preceded by emotional or physical stress. The left anterior descending in our patients with tako-tsubo syndrome was longer overall, and its recurrent diaphragmatic segment was longer, than in controls. To compare these groups we designed a measure termed recurrent segment index (left anterior descending recurrent segment length/total left anterior descending length x 100). In tako-tsubo syndrome this index was 22.3 (1.5)%, vs 10.9 (6.7)% in normal controls (P<.001), and 11.3 (7.7)% in acute myocardial infarction patients (P<.001). Patients with acute myocardial infarction and a high recurrent segment index (> or =16%) had ventriculographic findings of systolic apical ballooning identical to those in patients with tako-tsubo syndrome. CONCLUSIONS: All our patients with tako-tsubo syndrome had a left anterior descending with a long recurrent segment. The identical ventriculographic findings in patients with tako-tsubo syndrome and those with acute myocardial infarction with a long recurrent segment may be due to a common etiology.

Adult↗

Phrenic nerve conduction in infancy and early childhood.

Diaphragmatic action potentials (DAPs) were mapped on the thorax bilaterally in 16 neurologically normal infants and 8 boys aged 1 to 4 years during artificial ventilation after thoracic surgery. Transcutaneous stimulation was used to activate the phrenic nerve at the supraclavicular fossa at the end of an artificial inspiration. The DAPs were of positive polarity and were recorded on the ipsilateral anterolateral chest wall over the sixth to the eighth intercostal spaces, with a maximal peak at the seventh intercostal space. The DAP latencies gradually decreased from 6 to 8 ms at birth to about 5 ms at the age of 1 year, despite an increase of conduction distance. Statistical analyses revealed that DAP amplitude did not correlate with age. The latencies and amplitudes of the DAPs displayed little interside variation. The results are valuable not only as a reference for the diagnosis of patients with phrenic nerve palsy, but also as an indicator of the normal development of the phrenic nerve.

Action Potentials↗

The bulbar respiratory centre in the rabbit. II. Responses of respiratory neurons to intermittent electrical bulbar stimulation during in- or expiration.

In anesthetized rabbits, spirogram and diaphragmatic activity were examined during electrical stimulation of the bulbar lateral reticular formation. The activity of bulbar respiratory neurons was recorded contra- or ipsilaterally to the stimulation site. One volley of repetitive stimuli per breath was delivered during either inspiration of expiration. 1. Each volley of about 120 ms duration at 100 pulses per second, delivered early in inspiration, caused an immediate and transient inhibition of the diaphragmatic activity. An inspiratory rebound comprising lengthening of inspiration and increase in tidal volume occurred. a) "Inspiratory" and "expiratory-inspiratory" phase-spanning neurons exhibited inhibition during the volley. The burst discharge was lengthened and the spike density increased after stimulus. The same was true of some "inspiratory-expiratory" phase-spanning units. b) The discharge of most of the "inspiratory-expiratory neurons was not inhibited. "Expiratory" units were excited. In both types of cells activation occurred which outlasted the volley. 2. When applied during expiration, the volley caused a short inspiratory twitch. a) "Inspiratory" and "expiratory-inspiratory" neurons exhibited a short post-stimulus firing and the spike density was increased. In some units of the latter type, however, the burst discharge was shortened. b) Most of the "expiratory" and "inspiratory-expiratory" neurons were not inhibited by the volley. Cells of the former type often produced post-stimulus after-discharge; the burst discharge of units belonging to the latter type was shortened. The effects of expiratory stimuli upon neuronal activity, however, were less consistent than those elicited by inspiratory volleys. 3. During spontaneous irregularities of single inspirations (short interruptions), EI and I neurons exhibited comparable burst pattern changes. The changes in pattern of IE and E units were also comparable and differed distinctly from the behaviour of the EI and I cells. No major differences in behaviour were observed between neurons which were inhibited during lung inflation (alpha units) and those which were activated during inflation (beta cells). The findings are in accord with the effects observed during electrical bulbar stimulation, suggesting that EI and I units are inspiratory-activating cells, whereas IE and E neurons may have an inspiratory-inhibitory function. 4. The conclusion is drawn that the effects of bulbar stimulation on the respiratory movements are the result of manipulation on intrinsic rhythmogenesis.

Animals↗

Severe infantile neuropathy with diaphragmatic weakness and its relationship to SMARD1.

A group of 13 patients with early onset diaphragmatic palsy in association with a progressive neuropathy is presented. All eight of those tested were found to have mutations in the same gene encoding the immunoglobulin mu-binding protein 2 (IGHMBP2) in patients with spinal muscular atrophy (SMA) with respiratory distress type 1. Six out of these eight patients had either homozygous or compound heterozygous mutations, and two had only a single heterozygous mutation. Detailed analysis of the clinical picture and the neurophysiological and histopathological findings indicated that these patients shared similar characteristics, which were further developed as a set of diagnostic criteria. Some of the most striking of these were early onset of respiratory compromise, a markedly low birth weight, very slow motor nerve conduction velocities and a general decrease in the size of myelinated fibres on sural nerve biopsy. Extensive histological examination of the spinal cord in one patient failed to find any evidence of an SMA. Four out of the five not tested genetically were positive for all diagnostic criteria. None of the cases of early onset neuropathies or spinal muscular atrophies with early respiratory failure reviewed in the literature shares the exact characteristics, but many do have very close similarities. Their classification varies, but the discovery of mutations in IGHMBP2 in cases that are variously classified as SMA plus or severe infantile neuropathy with respiratory distress points to a need for the search for this genetic defect to be widened to include both groups. The fact that we identified other, similar cases of neuropathy and early respiratory failure with and without IGHMBP2 mutations suggests genetic as well as clinical heterogeneity in these infants. It is possible that infants that do not have mutations in the IGHMBP2 gene will be found to have mutations in a similar functioning gene.

Axons↗

Diaphragm strength in patients with recent hemidiaphragm paralysis.

Eleven patients with unilateral diaphragm paralysis of recent onset were studied to investigate the effect of the paralysis on inspiratory muscle function. Nine of the patients had noticed a decrease in exercise tolerance, which was not explained by any other pathological condition. Hemidiaphragm dysfunction was confirmed by the demonstration of a greatly reduced or absent transdiaphragmatic pressure on stimulation of the phrenic nerve in the neck, by means of surface bipolar electrodes (unilateral twitch Pdi), compared with normal values on the contralateral side. Transdiaphragmatic pressure was 44.6% (9.4%) predicted during a maximal sniff and 30.3% (16.8%) predicted during a maximal static inspiration against a closed airway, confirming diaphragm weakness. Maximum static inspiratory mouth pressures were also low (61.7% (12.7%) predicted), consistent with a reduction in inspiratory muscle capacity. Phrenic nerve conduction time was prolonged on the affected side in nine patients, consistent with phrenic nerve dysfunction, whereas on the unaffected side it was normal. It is concluded that recent hemidiaphragm paralysis causes a reduction in transdiaphragmatic pressure that is associated with a reduction in maximum inspiratory mouth pressure. Phrenic nerve stimulation is a useful technique with which to confirm and quantify hemidiaphragm dysfunction. Measurement of phrenic nerve conduction time provides useful information about the underlying pathology.

Diaphragm↗

Apical cell membranes are shed into urine from injured podocytes: a novel phenomenon of podocyte injury.

Previously it was shown that urine from patients with nephritis contains podocytes and their fragments (podocalyxin [PCX]-positive granular structures [PPGS]), reflecting the degree of podocyte injury. The present study was designed to trace PPGS to their origin. Urine samples and renal biopsy specimens from 53 children with nephrotic syndrome and nephritis were examined immunohistochemically. Immunofluorescence studies of kidney sections using an anti-PCX antibody demonstrated that PPGS originated from the glomerulus and flowed into the tubular lumen. Electron microscopic examination revealed that PPGS originated from microvillous or vesicle-like structures on injured podocytes in the glomerulus. For examining the origin of the PPGS, apical, slit-diaphragmatic, and basal portions of the podocytes were specifically stained, revealing that PPGS are composed primarily of apical podocyte membranes. Several newly developed antibodies that are reactive with various segments of the PCX molecule were used to analyze more detailed membrane structures, and it was found that PPGS contained intact PCX molecules, indicating that cell membrane structures are excreted in urine. The quantification of PCX content and podocyte numbers revealed that urinary sediment PCX (u-sed-PCX) content per urinary podocyte was much higher than PCX content per podocyte from isolated glomeruli of normal controls, suggesting that u-sed-PCX are derived from sources other than just the cell debris of detached podocytes. Analysis of the correlation between u-sed-PCX and renal histology revealed that the presence of PPGS reflects acute glomerular injury. In conclusion, podocyte apical cell membranes are shed into the urine from injured podocytes, indicating a previously unrecognized manifestation of podocyte injury.

Adolescent↗