Exploring the role of the Kölliker-Fuse nucleus in breathing variability by mathematical modelling.

The Kölliker-Fuse nucleus (KF), which is part of the parabrachial complex, participates in the generation of eupnoea under resting conditions and the control of active abdominal expiration when increased ventilation is required. Moreover, dysfunctions in KF neuronal activity are believed to play a role in the emergence of respiratory abnormalities seen in Rett syndrome (RTT), a progressive neurodevelopmental disorder associated with an irregular breathing pattern and frequent apnoeas. Relatively little is known, however, about the intrinsic dynamics of neurons within the KF and how their synaptic connections affect breathing pattern control and contribute to breathing irregularities. In this study, we use a reduced computational model to consider several dynamical regimes of KF activity paired with different input sources to determine which combinations are compatible with known experimental observations. We further build on these findings to identify possible interactions between the KF and other components of the respiratory neural circuitry. Specifically, we present two models that both simulate eupnoeic as well as RTT-like breathing phenotypes. Using nullcline analysis, we identify the types of inhibitory inputs to the KF leading to RTT-like respiratory patterns and suggest possible KF local circuit organizations. When the identified properties are present, the two models also exhibit quantal acceleration of late-expiratory activity, a hallmark of active expiration featuring forced exhalation, with increasing inhibition to KF, as reported experimentally. Hence, these models instantiate plausible hypotheses about possible KF dynamics and forms of local network interactions, thus providing a general framework as well as specific predictions for future experimental testing. KEY POINTS: The Kölliker-Fuse nucleus (KF), a part of the parabrachial complex, is involved in regulating normal breathing and controlling active abdominal expiration during increased ventilation. Dysfunction in KF neuronal activity is thought to contribute to respiratory abnormalities seen in Rett syndrome (RTT). This study utilizes computational modelling to explore different dynamical regimes of KF activity and their compatibility with experimental observations. By analysing different model configurations, the study identifies inhibitory inputs to the KF that lead to RTT-like respiratory patterns and proposes potential KF local circuit organizations. Two models are presented that simulate both normal breathing and RTT-like breathing patterns. These models provide testable hypotheses and specific predictions for future experimental investigations, offering a general framework for understanding KF dynamics and potential network interactions.

Assessing normal pulse wave velocity in the proximal pulmonary arteries using transit time: a feasibility, repeatability, and observer reproducibility study by cardiovascular magnetic resonance.

PURPOSE: To calculate pulse wave velocity (PWV) in the proximal pulmonary arteries (PAs) by cardiovascular magnetic resonance (CMR) using the transit-time method, and address respiratory variation, repeatability, and observer reproducibility. MATERIALS AND METHODS: A 1.9-msec interleaved phase velocity sequence was repeated three times consecutively in 10 normal subjects. Pulse wave (PW) arrival times (ATs) were determined for the main and branch PAs. The PWV was calculated by dividing the path length traveled by the difference in ATs. Respiratory variation was considered by comparing acquisitions with and without respiratory gating. RESULTS: For navigated data the mean PWVs for the left PA (LPA) and right PA (RPA) were 2.09 +/- 0.64 m/second and 2.33 +/- 0.44 m/second, respectively. For non-navigated data the mean PWVs for the LPA and RPA were 2.14 +/- 0.41 m/second and 2.31 +/- 0.49 m/second, respectively. No statistically significant difference was found between respiratory non-navigated data and navigated data. Repeated on-table measurements were consistent (LPA non-navigated P = 0.95, RPA non-navigated P = 0.91, LPA navigated P = 0.96, RPA navigated P = 0.51). The coefficients of variation (CVs) were 12.2% and 12.5% for intra- and interobserver assessments, respectively. CONCLUSION: One can measure PWV in the proximal PAs using transit-time in a reproducible manner without respiratory gating.

Hospice home care centre - abstract

The Hospice concept provides great comfort to the terminally ill. However, the original in-patient type of Hospice is expensive; hence it is not possible to provide its benefits to the very poor in the Third World. In recent times, the move has been to have patients remain in the comfort of family surroundings. The Hospice Home Care Centre was planned to investigate what form of care would be most practical and appropriate to the needs of very poor patients in the area around Eastern Kingston. Since April 1987, 179 patients have been referred to the Centre. Among female patients (n=137), cervical (44 percent) and breast (29 percent) cancers predominate, while in male patients (n=42), lung (24 percent), prostate (11 percent) and stomach (11 percent) cancers are more common. The length of time for which patients are looked after averages just over 2« months (AU)

Observations on idiopathic scoliosis aetiology and natural history in Jamaica - abstract

In 1953, the Orthopaedic Department at the University of the West Indies opened. Over the next five years, careful records were kept of the diagnosis of every patient seen in the Clinics. Amongst the findings was the observation that the idiopathic form of scoliosis appeared to be uncommon. There was a strong impression that the incidence of scoliosis was altering. From the second half of 1956, records of every patient with scoliosis from whatever cause have been kept. Only cases of severity great enough to attend an Orthopaedic Clinic and found to have a curve measuring over 10 degrees have been included. These records show that scoliosis has been an unusual condition from at least 1920 when our earliest case was reported as having developed. The condition continued to be unusal up to 1963. Then the whole position began to change. The records of the dates of presentation of new cases showed that there was a sudden increase after 1960 so that these patients became a major clinical problem. The increase in frequency rose rapidly till 1982. Then began a downturn in the number of cases which have continued. This has been in spite of a continuing annual population increase of 1.5 per cent and a steady 50 per cent of the population remaining under 15 years of age. Over the thirty-two years of this study, the general pattern of idiopathic scoliosis seen elsewhere has been found. In addition to the idiopathic group, there were almost 10 per cent due to some obvious cause. The infantile and juvenile types were seen only seldom. It was found that the idiopathic scoliosis patient was consistently above the average height for her age group and that the normal growth spurt appeared earlier in the idiopathic group than in other children. Thus, in Jamaica, there has been almost an epidemic of idiopathic scoliosis which started around 1963 and began to fall off after 1982. The increase in both the heights of these patients and their metacarpal indices suggests that something may have stimulated growth (AU)

The Natural history of idiopathic scoliosis in Jamaica - abstract

This study analyses 877 cases, 691 female and 186 male patients. Eighty-one of these cases were of the secondary form of scoliosis and the diagnosis of these is presented. The age of onset of the 796 idoipathic cases showed only 0.3 percent of the infantile type and 2.5 percent of the juvenile type. Both of these figures are less than in most other reported series. The study was begun in 1956 and records every case seen at the University's Orthopaedic Clinic which deals with scoliosis in Jamaica and several of the other Caribbean islands. The last two years, after 1966, have been excluded because many patients had had the condition for several years before they presented to hospital which would falsify any observations concerning the year of onset. The types of curve and their frequency are presented. Special attention was paid to the year of onset of the idiopathic variety which showed a remarkable increase after 1968. This observation has led to suggestions concerning the aetiology of idiopathic scoliosis which have been correlated with:- a). The idiopathic type was found to be particularly common in patients from the three higher income groups in the community; b). The average heights of both male and female idiopathic scoliosis patients are over 2 cm greater than for normal children of similar age; c). The metacarpal indices similarly are greater than those found in normal children of similar age; d). The growth spurt starts earlier in patients with idiopathic scoliosis. These findings, together with the increased frequency up to 1983 and the subsequent decline in frequency which is continuing, suggest that social factors are of importance in the aetiology of the condition (AU)