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PubMed2002

Respiratory sensation and ventilatory mechanics during induced bronchoconstriction in spontaneously breathing low cervical quadriplegia.

Intensity of dyspnea during induced bronchoconstriction in asthma is strongly related to the reduction in inspiratory capacity (IC) as a result of dynamic hyperinflation. To determine the role of rib cage and intercostal muscle afferents in symptom perception during bronchoconstriction, we measured the relationship between dyspnea intensity and IC during induced bronchoconstriction in six subjects with complete C4-C7 quadriplegia who did not require assisted ventilation. Spirometry, lung volumes, breathing pattern, esophageal pressure (Pes), and dyspnea intensity (Borg Scale) were measured during high-dose methacholine bronchoprovocation up to 256 mg/ml or a maximum change (Delta) in FEV(1) of 50%. Contemporaneous control data from subjects with asthma (n = 12) who had completed the same protocol were used for comparison. At maximum response in quadriplegia, FEV(1) decreased by 1.42 +/- 0.18 L (62 +/- 4%predicted) (mean +/- SEM), and IC decreased by 0.89 +/- 0.12 L (30 +/- 4%predicted). Dyspnea at maximum response was rated "moderate" to "severe": Borg 3.6 +/- 0.3. The predominant qualitative respiratory sensations were inspiratory difficulty and unsatisfied inspiration. The best correlate of dyspnea (Borg) was DeltaIC(%predicted) (p < 0.0005), whereas changes in FEV(1), Pes-derived measurements and breathing pattern did not contribute further to the strength of this relationship. Dyspnea intensity, quality, and changes in spirometry and lung volumes at maximum response were similar to those reported previously in asthma. The relationship between dyspnea intensity and DeltaIC(%predicted) was linear and consistent across groups. We conclude that the quality and intensity of dyspnea during methacholine-induced bronchoconstriction and dynamic hyperinflation was not altered by extensive chest wall deafferentation.

Adult↗
PubMed1978

Renin-angiotensin system inhibition in conscious dogs during acute hypoxemia. Effects on systemic hemodynamics, regional blood flows, and tissue metabolism.

The role of the renin-angiotensin system in mediating the circulatory and metabolic responses to hypoxia was studied in three groups of conscious dogs that were infused continuously with normal saline, teprotide (10 mug/kg per min), and saralasin (1 mug/kg per min), respectively. Hypoxia was produced by switching from breathing room air to 5 or 8% oxygen-nitrogen mixture. Plasma renin activity increased from 2.3+/-0.4 to 4.9+/-0.8 ng/ml per h during 8% oxygen breathing, and from 2.8+/-0.4 to 8.4+/-1.8 ng/ml per h during 5% oxygen breathing. As expected, cardiac output, heart rate, mean aortic blood pressure, and left ventricular dP/dt and dP/dt/P increased during both 5 and 8% oxygen breathing in the saline-treated dogs; greater increases occurred during the more severe hypoxia. Teprotide and saralasin infusion diminished the hemodynamic responses to 5% oxygen breathing, but did not affect the responses to 8% oxygen breathing significantly. In addition, the increased blood flows to the myocardium, kidneys, adrenals, brain, intercostal muscle, and diaphragm that usually occur during 5% oxygen breathing were reduced by both agents. These agents also reduced the increases in plasma norepinephrine concentration during 5% oxygen breathing, but had no effects on tissue aerobic or anaerobic metabolism. In dogs pretreated with propranolol and phentolamine, administration of teprotide (0.5 mg/kg) during 5% oxygen breathing reduced mean aortic blood pressure and total peripheral vascular resistance, and increased cardiac output and heart rate, but did not affect left ventricular dP/dt, dP/dt/P, and end-diastolic pressure. Simultaneously, renal and myocardial blood flows increased and myocardial oxygen extraction decreased, while myocardial oxygen consumption did not change significantly. These results suggest that the renin-angiotensin system plays an important role in the hemodynamic responses to severe hypoxia. It appears that angiotensin not only exerts a direct vasoconstrictor action, especially upon the coronary and renal circulations, but also potentiates the cardiovascular effects of sympathetic stimulation that occur during severe hypoxia.

Angiotensins↗
PubMed2006

Progress in applying the Three Rs to the potency testing of Botulinum toxin type A.

Botulinum toxin type A (BTA) is being increasingly used for a range of therapeutic purposes and also for cosmetic reasons. For many years, the potency of BTA has been measured by using an LD50 assay in mice. This assay is a cause for concern due to its unpleasant nature and extreme severity, and the requirement for high numbers of mice to be used. Alternatives to this potency assay are presently reviewed with particular reference to the work at the National Institute for Biological Standards and Control (NIBSC), and to recent work by the UK manufacturer of the substance. An in vivo local paralysis assay with considerably less severity has been developed and is in use at the NIBSC. Alternative, ex vivo functional assays in use include the measurement of BTA-induced paralysis of neurally-stimulated rodent diaphragm or rat intercostal muscle. The latter method has the advantage of allowing more preparations to be derived from one animal. However, these ex vivo methods have not yet been fully validated and accepted by regulatory agencies as potency assays. Endopeptidase assays, although not measuring muscle paralysis directly, may provide a very useful consistency test for batch release and may replace the routine use of the LD50 test for that purpose. These assays measure the cleavage of the SNAP-25 protein (the final stage of BTA action), and have been validated for batch release by the National Control Laboratory (NIBSC), and are in regular use there. ELISA assays, used alongside the endopeptidase assay, also provide useful confirmatory information on the amounts of functional (and non-functional) BTA present. The UK manufacturer is further validating its endopeptidase assay, an ex vivo muscle assay and an ELISA. It is anticipated that their work will lead to a change in the product license, hopefully within the next two years, and will form a critical milestone towards the end of the LD50 potency test.

Acetylcholine↗
PubMed1997

The lesions of experimental equine morbillivirus disease in cats and guinea pigs.

Nine cats and four guinea pigs became affected with severe disease during experiments on the infectivity of equine morbillivirus, a newly recognized cause of respiratory disease in horses and humans. Four of the cats were challenged by subcutaneous inoculation, two by intranasal installation, two by oral dosage, and one by direct contact with a cat previously infected by subcutaneous inoculation. All four guinea pigs were inoculated subcutaneously. Gross pathology seen in all affected cats was characterized by hydrothorax and dark, heavy, wet, congested and/or hemorrhagic lungs with froth sometimes found in the respiratory passages. Pulmonary lymph nodes were enlarged and edematous. Six cats also had congested ceca with accompanying edema of mesenteric lymph nodes. Histologically, the lesions in the lungs of the cats were those of severe interstitial pneumonia characterized by serofibrinous alveolar edema, alveolar macrophages, intra-alveolar hemorrhage, thrombosis of small veins, alveolar wall necrosis, and syncytial cells. Clearly defined vascular lesions included intramural hemorrhage, edema, and necrosis and syncytial cells in the endothelium of pulmonary arteries and veins, 20-80 microm in diameter. Vascular lesions accompanied by parenchymal degeneration were also seen in the gastrointestinal and lymphoid organs. Syncytial cells were also visible in the lymphoid tissues of lymph nodes, spleen, and Peyer's patches. At necropsy, all guinea pigs were cyanosed and had congestion and edema in the gastrointestinal tract. Histologically, there was widespread vascular disease in arteries and veins, 20-80 microm in diameter, in many organs such as the lungs, kidneys, spleens, lymph nodes, gastrointestinal tracts, and skeletal and intercostal muscles, but there was no severe pulmonary edema as seen in horses and cats. Sections of tissues of the cats and guinea pigs, examined by indirect immunocytochemical stains, confirmed that the vascular damage was associated with the presence of equine morbillivirus antigen. The syncytia in small blood vessels in the lungs and other organs of both cats and guinea pigs were similar to those seen in horses, and their presence was interpreted as an important characteristic of the disease consistent with a reaction to a morbillivirus.

Animals↗
PubMed2003

The gene for HMSN2C maps to 12q23-24: a region of neuromuscular disorders.

BACKGROUND: Hereditary motor and sensory neuropathy type 2C (HMSN2C, Charcot-Marie-Tooth 2C [CMT2C]) is an autosomal dominant motor and sensory neuropathy involving limb, diaphragm, vocal cord, and intercostal muscles. OBJECTIVE: To identify the chromosome localization for this disorder in one large American family of English and Scottish ethnicity. METHODS: Variable clinical severity led the authors to combine several approaches to accurately identify affected patients. Genome-wide two-point linkage analysis, high-definition mapping, and multipoint and recombinant haplotype analyses were performed. Mutation analysis of the triplet repeat region of ataxin-2 was also carried out. RESULTS: The initial genome-wide scan identified a region at 12q24, and fine mapping provided a maximal lod score of 4.73 (D12S1645 and D12S1583 at theta = 0.01 and 0, respectively). With multipoint analysis, a higher lod score of 5.17 was obtained and localized to the same region at 119.0 cM. Haplotype analysis narrowed the region to approximately 5.0 cM between D12S1646,D12S1330 and D12S105,D12S1339 (12q23.3-24.21). Ataxin-2, the gene responsible for spinocerebellar ataxia type 2 (SCA2), localizes to this region, but no triplet repeat expansion or point mutations within the repeat were found. CONCLUSIONS: The gene for HMSN2C maps to 12q23-24. This region is associated with SCA2, scapuloperoneal spinal muscular atrophy, and congenital distal spinal muscular atrophy. Further studies are needed to demonstrate the specific gene alteration and its relationship with nearby genes.

Age of Onset↗
PubMed1976

Guanidine and germine in Eaton-Lambert syndrome.

A 43-year-old man with Eaton-Lambert syndrome developed chronic interstitial nephritis after 4 years of guanidine hydrochloride therapy. The diagnosis of Eaton-Lambert syndrome was confirmed by clinical neurophysiologic studies and by intracellular electrode studies of end-plate potentials from an intercostal muscle biopsy. Because guanidine had toxic effects in this patient, an alternative form of therapy was tried. Germine-3-acetate (500 mg per day orally) resulted in clinical and electric improvement of the myasthenic syndrome. However, the sensory side effects of numbness of the limbs and unpleasant taste were sufficiently annoying that germine was discontinued.

Adult↗
PubMed1977

Ultrastructural localization of the acetylcholine receptor in myasthenia gravis and in its experimental autoimmune model.

Peroxidase-conjugated alpha-bungarotoxin (P-BGT) was used for the ultrastructural localization of the acetylcholine receptor in end-plates in external intercostal muscles of four patients with myasthenia gravis, in forelimb digit extensor muscles of rats with advanced chronic experimental autoimmune myasthenia gravis, and in suitable human and rat controls. In control end-plates, the previously reported localization of acetylcholine receptor on the terminal expansions of the postsynaptic folds and, in traces, on the presynaptic membrane was confirmed. By contrast, in myasthenia gravis some postsynaptic regions bound no P-BGT; in other regions, the folds displayed only faint traces of the reaction product, or only some segments of the postsynaptic membrane showed the reaction product; finally, in some regions there was no apparent decrease in reaction product. In general, those postsynaptic regions showing the greatest decrease in P-BGT binding were also the simplest or showed the most degenerative changes, and the presynaptic staining was decreased in proportion to the decrease in the adjacent postsynaptic P-BGT binding. In the experimental animals, the abnormalities in the amount and distribution of the acetylcholine receptor were essentially like those in the more severely affected patients. Morphometric estimates of the postsynaptic acetylcholine receptor surface correlated well with the patients' clinical status and linearly with the miniature end-plate potential amplitude.

Action Potentials↗
PubMed1993

Thoracic epidural anesthesia causes rib cage distortion in anesthetized, spontaneously breathing dogs.

The effects of thoracic epidural anesthesia on the performance of the parasternal intercostal muscles were investigated by measuring electromyographic activity and length changes of the parasternals (EMG activities and length, respectively, of the parasternals) in seven pentobarbital anesthetized, spontaneously breathing dogs. Epidural injection of 0.1 mL/kg of 2% lidocaine decreased tidal volume and minute ventilation during unstimulated breathing. These changes were accompanied by complete abolishment of EMG activities of the parasternals and passive elongation of the parasternals during inspiration. At equivalent end-tidal PCO2 values (70 and 80 mm Hg) during CO2 rebreathing, tidal volume and minute ventilation were lower after epidural block compared to the corresponding values before the block. Thoracic epidural anesthesia impaired contraction of the parasternals and conceivably other respiratory muscles in the rib cage as well and could induce a distortion of the rib cage. The authors conclude that respiratory muscles in the rib cage contribute considerably to the maintenance of ventilation in anesthetized dogs.

Anesthesia, Epidural↗
PubMed1994

Respiratory rhythm in the isolated central nervous system of newborn opossum.

1. Respiratory activity was recorded from spinal ventral roots in the isolated intact central nervous system (CNS) of newborn opossum, Monodelphis domestica. These signals occurred in synchrony with movements of the ribs and the electromyogram (EMG) recorded from the intercostal muscles during inspiration. Rhythmical activity could be recorded for more than 6 h in acute preparations. 2. The rhythm-generating region was shown to be located in the lower brain stem by perfusing different CNS regions with medium containing 20 mmoll-1 Mg2+, which blocks synaptic transmission reversibly in the opossum CNS. The conclusion that respiration was generated by neurones in the lower brain stem was further confirmed by selective ablation of part of the CNS. 3. Recordings were made from 128 neurones in the respiratory region of the lower brain stem with activity related to the respiratory rhythm. They consisted of two inspiratory groups and two expiratory groups. In the groups of inspiratory units, recordings were made from 69 early inspiratory and 38 inspiratory units. In the groups of expiratory units, recordings were made from 17 post-inspiratory and 4 expiratory units. The sites of 22 respiratory neurones were marked in 4-day-old animals by injecting Pontamine Sky Blue. These neurones were distributed from 175 microns anterior to 525 microns posterior to the obex, from 225 to 450 microns lateral to the midline and from 175 to 425 microns deep to the ventral surface of the brain stem. 4. The respiratory rhythm recorded in the isolated CNS was influenced by pH and neurotransmitters. The respiratory rate decreased by about 26% at high pH (7.7) and increased by about 33% at low pH (7.1). Bath application of noradrenaline (30-100 mumol l-1) decreased the respiratory rate and increased the amplitude of the rhythmic bursts significantly. All these effects were reversible. 5. The results presented here indicate that the isolated intact CNS of newborn opossum offers advantages for exploring mechanisms responsible for generating the respiratory rhythm.

Animals↗
PubMed1990

Nasal 'pressure' receptors.

This study was performed to identify, recording from single fibers of the ethmoidal nerve, nasal receptors which respond to changes in the upper airway pressure during nasal occlusion. In 15 anaesthetized rats breathing through the nose, three consecutive nasal occlusions were performed while recording the afferent activity of ethmoidal nerve fibers, the EMG activity of an external intercostal muscle, temperature in the nose and upper airway pressure. Twenty-two afferent fibers were activated during the three inspiratory efforts with occlusions applied at end-expiration, when the upper airway was subjected to negative pressure (-1.93, -2.16 and -2.22 kPa at the 1st, 2nd and 3rd effort, respectively). The number of impulses was 24, 22 and 20 (n = 22) at the 1st, 2nd and 3rd effort, respectively. The pressure threshold were measured as -0.73, -0.87 and -0.96 kPa (n = 22) in each effort. Three fibers were also stimulated by positive pressure during occlusions performed at end-inspiration. In 5 rats breathing through a tracheostomy, maintained negative (-0.1-3.7 kPa) and positive (0.8-3.0 kPa) pressures were applied to the isolated upper airway. All the 12 fibers tested were activated by the maintained negative pressure, whereas three of them were also activated by the maintained positive pressure. However, none of fibers tested were stimulated by tracheal occlusions. These results indicate that the ethmoidal branch of the trigeminal nerve contains fibers connected to nasal 'pressure' receptors, mostly 'negative pressure' receptors, that may play a role in the maintenance of upper airway patency.

Air Pressure↗
PubMed1998

Congenital bronchoesophageal fistula in an adult.

We present a rare case of a congenital bronchoesophageal fistula in a 54-year-old woman with a history of poor feeding tolerance since infancy and repeated pulmonary infections. She initially presented with epigastric and right upper quadrant abdominal pain. Her workup included a barium esophagogram that revealed a fistula between her midesophagus and a left lower lobe segmental bronchus. The fistula was divided, a left lower lobe superior segmentectomy was performed, and an intercostal muscle was placed over the esophageal closure. The patient noted an immediate decrease of postprandial coughing. Congenital respiratory esophageal fistulas that are not associated with esophageal atresia may persist into adulthood before they become clinically apparent. The diagnosis should be considered in certain individuals with suggestive symptomatology and unexplained respiratory pathology.

Bronchial Fistula↗
PubMed2000

MRI and CT in the differential diagnosis of pleural disease.

STUDY OBJECTIVE: To explore the role of MRI in the differential diagnosis of pleural disease. PATIENTS: Forty-two patients with pleural disease were included. METHOD: Retrospective study. All patients were examined with both CT and MRI. The morphologic features of pleural lesions and magnetic resonance signal intensity on T1-weighted, T2-weighted, and contrast-enhanced T1-weighted images were evaluated. RESULTS: Mediastinal pleural involvement, circumferential pleural thickening, nodularity, irregularity of pleural contour, and infiltration of the chest wall and/or diaphragm were most suggestive of a malignant cause both on CT and MRI. Pleural calcification on CT was suggestive of a benign cause. Contrary to what has been previously reported in the literature, neither on CT nor on MRI, pleural thickness >1 cm revealed significant difference between malignant and benign pleural disease (p>0.05, chi(2) test). High signal intensity in relation to intercostal muscles on T2-weighted and/or contrast-enhanced T1-weighted images was significantly suggestive for a malignant disease. Using morphologic features in combination with the signal intensity features, MRI had a sensitivity of 100% and a specificity of 93% in the detection of pleural malignancy. CONCLUSION: When signal intensity and morphologic features are assessed, MRI is more useful and therefore superior to CT in differentiation of malignant from benign pleural disease.

Adult↗
PubMed1976

Esophagopleural fistula after pneumonectomy.

Rupture of the esophagus into the space left after pneumonectomy is a rare and often fatal complication. Esophagopleural fistulas occurred in three patients following pneumonectomy. After previous methods failed, two patients were successfully treated by using a one-stage procedure which included (1) suture closure of the fistula, (2) buttressing the repair with a viable, pedicled, two-rib intercostal-muscle flap, and (3) performing an extensive thoracoplasty with a continuous drip infusion of neomycin. Such a procedure offers the maximum opportunity for successful treatment of this catastrophic lesion.

Esophageal Fistula↗
PubMed1989

Effect of sternotomy and coronary bypass surgery on postoperative pulmonary mechanics. Comparison of internal mammary and saphenous vein bypass grafts.

Coronary artery bypass grafting (CABG) is commonly performed via a median sternotomy with a reversed saphenous vein (SV) and/or an internal mammary artery (IMA) graft. Sternotomy and IMA harvesting may adversely affect postoperative respiratory function (PFTs) as disruption of the sternun may impair chest wall stability, and the decrease in intercostal muscle blood supply after removal of the IMA may reduce the force of respiration. We compared preoperative and six- to eight-week postoperative PFTs in patients undergoing CABG. The results were independent of age, sex, number of grafts, aortic cross clamp time, duration of bypass run, and postbypass fluid gradient. It was concluded that sternotomy caused a decrease in postoperative PFTs and that IMA harvesting may be accompanied by greater impairment in PFTs than when SV grafts alone were used.

Aged↗
PubMed2001

Iatrogenic esophagobronchial fistula arising in irradiated Barrett's esophagus.

A 47-yr-old male underwent a right upper lobectomy for stage IIB bronchoalveolar carcinoma followed by 4600 Gy of irradiation. One year later a fistula formed from an ulcerated region of Barrett's esophagus into the left main bronchus. Bronchotomy repair with onlay patch intercostal muscle flap and esophageal repair with serratus anterior muscle flap plus postoperative esophageal stent placement for stricture resulted in good functional results.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed2005

Emergency endovascular repair of an aortoesophageal fistula caused by a foreign body.

PURPOSE: To report stent-graft treatment of an aortoesophageal fistula caused by a foreign body. CASE REPORT: A 32-year-old man was admitted with massive upper gastrointestinal bleeding 10 days after swallowing a fish bone. Computed tomography demonstrated a fistula from the proximal descending thoracic aorta to the mid esophagus. The bleeding was initially controlled by inflating a Sengstaken-Blakemore tube. A 28-mm x 16-cm Talent stent-graft was delivered transfemorally to repair the aortic defect; the esophageal injury was repaired primarily using a pedicled intercostal muscle flap via a right thoracotomy. Chest radiography at 12 months showed no migration of the stent-graft. Blood parameters of infection were normal; the patient remains well 18 months after stent-graft implantation. CONCLUSIONS: This case illustrates stent-graft treatment of a life-threatening hemorrhage from an aortoesophageal fistula.

Adult↗
PubMed1992

Structure and distribution of the lymphatic vessels in the parietal pleura of the monkey as studied by enzyme-histochemistry and by light and electron microscopy.

The entire distribution of lymphatics in whole mount preparations of the Japanese monkey was studied using the enzyme-histochemical technique reported by KATO et al. (1990, 1991). In this staining, the lymphatic endothelium was colored dark brown by its positive 5'-nucleotidase activity, while most blood vessels (especially arterioles) were colored blue due to their positive alkaline phosphatase reaction. The whole mount preparations of the pleura treated enzyme-histochemically clearly indicated the distribution, branching patterns and running courses of lymphatic vessels. They revealed numerous short blind-ending knobs which represented the initial portions of lymphatics. These knobs were seen near the surface of the parietal pleura along its entire extent. In the costal and diaphragmatic pleura, the lymphatics ran parallel to the intercostal muscle fibers, but perpendicular to the tendinous and muscular fibers of the diaphragm; they formed ladders, independent of the courses of blood vessels. In the mediastinal pleura, lymphatic vessels showed a tree-like branching accompanying blood vessels. Under the light microscope, toluidine-blue stained semithin sections revealed the initial part of lymphatics as a small irregularly outlined cavity (7-10 microns in diameter) surrounded by a dense connective tissue. This lymphatic dilation was sometimes located close to a thin mesothelial layer. Such a structure suggesting a "stoma" was seen near the attachment of the muscular diaphragm to the sternum and along the borders of the ribs. Transmission electron microscopy revealed an occasional interruption in the mesothelium. This stoma continued to a submesothelial cavity whose base comprised an attenuated endothelium of an extended lymphatic vessel.

5'-Nucleotidase↗
PubMedDate not supplied

Congenital myasthenia gravis in Smooth-Haired Miniature Dachshund dogs.

Three 8-week-old Miniature Smooth Haired Dachshund littermates were diagnosed with myasthenia gravis based on clinical signs, results of electrophysiological testing, and response to the short-acting anticholinesterase drug, edrophonium chloride. Congenital myasthenia gravis was confirmed by the demonstration of decreased acetylcholine-receptor density in external intercostal muscle in the absence of demonstrable serum antiacetylcholine receptor antibody or antibodies complexed to acetylcholine receptors in muscle biopsy samples. Unlike most previously reported cases of congenital myasthenia gravis that are relentlessly progressive, clinical signs resolved spontaneously by 6 months of age.

Aging↗