To study the mechanisms and kinetics underlying the development of increased airway responsiveness (AR) after allergic sensitization, animal models have been invaluable. Using barometric whole-body plethysmography and increases in enhanced pause (Penh) as an index of airway obstruction, we measured responses to inhaled methacholine in conscious, unrestrained mice after sensitization and airway challenge with ovalbumin (OVA). Sensitized and challenged animals had significantly increased AR to aerosolized methacholine compared with control animals. AR measured as Penh was associated with increased IgE production and eosinophil lung infiltration. In a separate approach we confirmed the involvement of the lower airways in the response to aerosolized methacholine using tracheotomized mice. Increases in Penh values after methacholine challenge were also correlated with increased intrapleural pressure, measured via an esophageal tube. Lastly, mice demonstrating AR using a noninvasive technique also demonstrated ...

Noninvasive Measurement of Airway Responsiveness in Allergic Mice Using Barometric Plethysmography

Hirschsprung disease (HSCR, aganglionic megacolon) represents the main genetic cause of functional intestinal obstruction with an incidence of 1/5000 live births. This developmental disorder is a neurocristopathy and is characterised by the absence of the enteric ganglia along a variable length of the intestine. In the last decades, the development of surgical approaches has importantly decreased mortality and morbidity which allowed the emergence of familial cases. Isolated HSCR appears to be a non-Mendelian malformation with low, sex-dependent penetrance, and variable expression according to the length of the aganglionic segment. While all Mendelian modes of inheritance have been described in syndromic HSCR, isolated HSCR stands as a model for genetic disorders with complex patterns of inheritance. The tyrosine kinase receptor RET is the major gene with both rare coding sequence mutations and/or a frequent variant located in an enhancer element predisposing to the disease. Hitherto, 10 genes and five loci have been found to be involved in HSCR development.

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Hirschsprung disease, associated syndromes and genetics: a review

• A carbon dioxide hypersensitivity theory of panic has been posited. We hypothesize more broadly that a physiologic misinterpretation by a suffocation monitor misfires an evolved suffocation alarm system. This produces sudden respiratory distress followed swiftly by a brief hyperventilation, panic, and the urge to flee. Carbon dioxide hypersensitivity is seen as due to the deranged suffocation alarm monitor. If other indicators of potential suffocation provoke panic, this theoretical extension is supported. We broadly pursue this theory by examining Ondine's curse as the physiologic and pharmacologic converse of panic disorder, splitting panic in terms of symptomatology and challenge studies, reevaluating the role of hyperventilation, and reinterpreting the contagiousness of sighing and yawning, as well as mass hysteria. Further, the phenomena of panic during relaxation and sleep, late luteal phase dysphoric disorder, pregnancy, childbirth, pulmonary disease, separation anxiety, and treatment are used to test and illuminate the suffocation false alarm theory.

False suffocation alarms, spontaneous panics, and related conditions. An integrative hypothesis.

The long QT syndromes: a critical review, new clinical observations and a unifying hypothesis.

Purpose: To present an overview of the applicability of heart rate variability measurements in medicine. Data Sources: During a 4-year period all new papers concerning heart rate variability were c...

Heart Rate Variability

Congenital failure of automatic control of ventilation, gastrointestinal motility and heart rate.

A theoretical analysis of the barometric method for measurement of tidal volume

The barometric method is unique in permitting measurement of tidal volume in a totally noninvasive manner. Its application and accuracy have been limited by several complex problems. These include control of inspired gas composition, base-line stability, and asymmetry of processes occurring during inspiration and expiration. A new method is described that addresses these problems and facilitates long-term measurements. New calculations, which avoid previous errors that caused the method to systematically underestimate tidal volume, are illustrated.

Practical implementation of the barometric method for measurement of tidal volume

Heart rate and heart rate variability during sleep in aborted sudden infant death syndrome

Noninvasive studies of ventilation and ventilatory pattern were performed serially in 15 normal infants in the first 4 mo of life during REM and quiet sleep with the barometric method. We measured ...

M. A. Epstein

Papers

Congenital failure of automatic control of ventilation, gastrointestinal motility and heart rate.

A theoretical analysis of the barometric method for measurement of tidal volume

Practical implementation of the barometric method for measurement of tidal volume

Heart rate and heart rate variability during sleep in aborted sudden infant death syndrome

Maturation of ventilation and ventilatory pattern in normal sleeping infants