Short term effect of oxygen on renal haemodynamics in patients with hypoxaemic chronic obstructive airways disease.

BACKGROUND: Oxygen therapy is effective in the prevention and treatment of oedematous exacerbations of cor pulmonale. As renal blood flow is reduced in cor pulmonale a study was designed to investigate whether one of the beneficial effects of oxygen was to increase renal blood flow. The effect of oxygen therapy on renal haemodynamics measured noninvasively was examined in patients with chronic obstructive airways disease and previous episodes of oedema. METHODS: Renal blood flow waveforms were recorded in a single vessel by colour flow Doppler ultrasound in nine hypoxaemic patients (PaO2) (arterial oxygen tension < 8 kPa while they were breathing air) with chronic obstructive airways disease and previous oedema and eight age matched normoxaemic volunteers (arterial oxygen saturation (SaO2) 97% or more when breathing air) while they were breathing air and oxygen. SaO2 and transcutaneous PaO2 (TcPO2) and PaCO2 (TcPCO2) were monitored. Five renal velocity profile recordings were made from the same segmental vessel with the patient breathing room air for one hour followed by oxygen titrated to achieve an oxygen saturation of 95% or more without a rise in TcPCO2 for 15 minutes. Control subjects breathed 35% oxygen. RESULTS: No significant change in the pulsatility index (a measure of distal vascular resistance) or mean height of the waveform (Tamx, a measure of renal blood flow) occurred in the control subjects while they were breathing air or oxygen. The pulsatility index of the patients with chronic obstructive airways disease was significantly greater than that in the control subjects breathing air (1.44 (SD 0.28) v 1.03 (0.14). Breathing oxygen was associated with an increase in TcPO2 in the patients (from 6.9 (1.9) to 11.5 (0.7) kPa), a fall in pulsatility index (from 1.44 (0.28) to 1.26 (0.14) and an increase in Tamx (from 0.187 (0.055) to 0.234 (0.087) m/s). CONCLUSIONS: The results suggest that renal vascular resistance is increased in patients with chronic obstructive airways disease and hypoxaemia and that short term oxygen therapy reduces renal vascular resistance and increases blood flow. Some of the benefits of oxygen therapy in cor pulmonale may be due to improvements in renal haemodynamics.     

Evaluation of a hand-held spirometer, the Respiradyne, for the measurement of forced expiratory volume in the first second (FEV1), forced vital capacity (FVC) and peak expiratory flow rate (PEFR)

A hand-held spirometer, the Respiradyne (R), was evaluated for the measurement of forced expiratory volume in the first second (FEV1), forced vital capacity (FVC) and peak expiratory flow rate (PEFR) by comparing it with a Vitalograph spirometer (V) and a Wright's peak flow meter (W) in 70 subjects (normals and patients). The results showed close agreement for FEV1; r = 0.99, R = 0.961V + 0.03 X 10(-5) and FVC; r = 0.99, R = 1.003V-0.044. Results for PEFR using the Respiradyne were generally higher than with the peak flow meter; r = 0.98, R = 1.151W-17.576. The Respiradyne is portable and simple to operate and may be suited to use in a variety of non-laboratory situations.     

A clinically relevant modification to existing inhaler therapy.

A modified formulation of inhaled salbutamol and a new inhaler device were studied in a group of 11 moderate-to-severe asthmatic patients. Changes in airway calibre (FEV1, Vmax30) were measured before and after inhalation of the new formulation, and compared with changes following inhalation of conventional salbutamol. A standard Rotahaler was used as a reference for the new inhaler. The study was conducted as a two-part randomized, double-blind cross-over trial. We found a significantly greater bronchodilatation of the larger airways using the modified drug in the Rotahaler. The new inhaler did not show any superiority over the Rotahaler, contrary to expectations from in vitro work. A slightly shorter model may better reflect the in vitro results. The study has implications for inhalation therapy in general.     

Maximum relaxation rate of the diaphragm during weaning from mechanical ventilation.

BACKGROUND--The maximum relaxation rate (MRR; percentage fall in pressure/10 ms) of oesophageal (POES) and transdiaphragmatic (PDI) pressure slows under conditions of loaded breathing, and has been measured previously in normal subjects. MRR has not been measured in intubated patients weaning from mechanical ventilation. METHODS--Five postoperative patients who were expected to wean and nine patients who had previously failed were studied. POES and PDI MRR, peak oesophageal pressure during spontaneous breathing, maximum oesophageal pressure, and the inspiratory duty cycle were measured at rest during mechanical ventilation, in the first two minutes of spontaneous breathing, and after reventilation in those patients who failed, or before extubation in those patients who succeeded. RESULTS--At rest POES MRR in intubated patients had a range of 5.6-11 and PDI MRR 6.9-10.0, with a coefficient of variation of 9.9% and 7.3% respectively. POES and PDI MRR were similar before and after extubation in five postoperative patients, and POES MRR was reflected by endotracheal MRR measured at the airway. In five patients who failed to wean POES and PDI MRR slowed by 47% and 44%, and fully recovered after 10 minutes reventilation. In four patients who were successfully weaned MRR was unchanged during spontaneous breathing. At the time when MRR decreased, the respiratory muscles were heavily loaded in relation to their strength. CONCLUSIONS--Weaning failure occurs when the applied load exceeds the capacity of the respiratory muscles, and this is associated with a slowing of respiratory muscle MRR.     

Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability

X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene. Disease-associated alleles (37-66 CAGs) change in length when transmitted from parents to offspring, with a significantly greater tendency to shift size when inherited paternally. As transgenic mice carrying human AR cDNAs with 45 and 66 CAG repeats do not display repeat instability, we attempted to model trinucleotide repeat instability by generating transgenic mice with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions in their genomic context. Studies of independent lines of AR YAC transgenic mice with CAG 45 alleles reveal intergenerational instability at an overall rate of approximately 10%. We also find that the 45 CAG repeat tracts are significantly more unstable with maternal transmission and as the transmitting mother ages. Of all the CAG/CTG repeat transgenic mice produced to date the AR YAC CAG 45 mice are unstable with the smallest trinucleotide repeat mutations, suggesting that the length threshold for repeat instability in the mouse may be lowered by including the appropriate flanking human DNA sequences. By sequence-tagged site content analysis and long range mapping we determined that one unstable transgenic line has integrated an approximately 70 kb segment of the AR locus due to fragmentation of the AR YAC. Identification of the cis - acting elements that permit CAG tract instability and the trans -acting factors that modulate repeat instability in the AR YAC CAG 45 mice may provide insights into the molecular basis of trinucleotide repeat instability in humans.