Ventilatory and arousal responses to added inspiratory resistance during sleep

Airway resistance increases during sleep. We have determined the ventilatory and arousal responses to the addition of inspiratory resistance of 4, 7, or 10 cmH2O/L/s during sleep in 10 normal men who slept wearing valved face masks. Insufficient ventilatory response data were obtained during rapid eye movement (REM) sleep to allow adequate analysis. The immediate responses to loading were decreases in tidal volume (VT), breathing frequency (f), and minute ventilation (VE), with no difference between wakefulness and Stage 2 and Stage 3/4 sleep in the effects of loading on VT and VE, but f fell more during wakefulness than during sleep (p less than 0.05) because of a greater lengthening of inspired time (TI) (p less than 0.05). During the first 10 breaths, occlusion pressure (P0.1) increased similarly in all EEG stages. Averaging responses during the 2-min periods when resistances were applied, the only variable to differ between EEG stages was TI, which increased more in wakefulness than in Stage 2 or Stage 3/4 sleep (p less than 0.01). Arousal within 2 min of application of resistance occurred less frequently from Stage 3/4 sleep than from Stage 2 or REM sleep (p less than 0.02). The study demonstrates that sleep modifies the changes in respiratory timing produced by resistive loading without having a major effect on ventilation or P0.1 responses. The low frequency of arousal from Stage 3/4 sleep with loading may explain why asthmatics rarely awaken from this stage with wheeze.     

Patterns of hematopoietic chimerism following bone marrow transplantation for childhood acute lymphoblastic leukemia from volunteer unrelated donors

Hematopoietic chimerism was analyzed in serial bone marrow samples taken from 28 children following T-cell depleted unrelated donor bone marrow transplants (UD BMT) for acute lymphoblastic leukemia (ALL). Chimeric status was determined by polymerase chain reaction (PCR) of simple tandem repeat (STR) sequences (maximal sensitivity, 0.1%). At least two serial samples were examined in 23 patients. Of these, two had evidence of complete donor engraftment at all times and eight showed stable low level mixed chimerism (MC) (<1% recipient hematopoiesis). All 10 of these patients remain in remission with a minimum follow-up of 24 months. By contrast, 13 patients demonstrated a progressive return of recipient hematopoiesis. Five of these relapsed (4 to 9 months post BMT), one died of cytomegalovirus pneumonitis and seven remain in remission with a minimum follow-up of 24 months. Five children were excluded from serial analysis as two serial samples were not collected before either relapse (3) or graft rejection (2). We conclude that as with sibling transplants, ex vivo T depleted UD BMT in children with ALL is associated with a high incidence of MC. Stable donor engraftment and low level MC always correlated with continued remission. However, detection of a progressive return of recipient cells did not universally correlate with relapse, but highlighted those patients at greatest risk. Serial chimerism analysis by PCR of STRs provides a rapid and simple screening technique for the detection of relapse and the identification of patients with progressive MC who might benefit from detailed molecular analysis for minimal residual disease following matched volunteer UD BMT for childhood ALL.     

The effects of a three-month exercise programme on neuropsychological function in elderly institutionalized women: a randomized controlled trial

This randomized controlled trial examined the effect of a 3-month exercise programme on neuropsychological function in a population of very elderly institutionalized women. Baseline neuropsychological testing was performed, and following 3 months of exercise or control intervention, subjects were retested 3-7 days after the completion of the study period. Apart from the Word Fluency Test, there was no significant improvement in any of the neuropsychological test scores. This study may not have shown any significant improvement in neuropsychological function because our exercise programme was too light to improve aerobic fitness, or because neuropsychological tests were repeated 3-7 days after exercise was completed and any acute effects of exercise may have disappeared by that time.     

Effects of noradrenaline and isoproterenol on cardiopulmonary function in a canine model of acute pulmonary hypertension

The authors investigated acute cardiopulmonary effects of noradrenaline and isoproterenol infusion in a canine model of increased pulmonary vascular resistance (PVR) and decreased cardiac output (CO). In six anesthetized, ventilated dogs, autologous blood clots were injected over approximately two hours to increase right ventricular (RV) afterload and decrease CO. After CO had decreased 40 percent dogs were treated with noradrenaline or isoproterenol in alternate sequence. Both drugs increased stroke volume but only isoproterenol affected CO. Flow increased from 1.3 to 3.0 L X min-1 (p less than .01) with isoproterenol infusion. Corresponding to the increase in CO, RV filling pressure and PVR decreased, from 9 to 5 mm Hg, and from 36 to 16 mm Hg X L-1 X min (p less than .01) respectively. When a moderate decrease in CO complicates an acute increase in PVR, isoproterenol may be an excellent drug to treat the decrease in flow.     

Breathing pattern and eye movement density during REM sleep in humans

Changes in the density of eye movement during rapid eye movement (REM) sleep are associated with changes in ventilation and ventilatory response in animals. Recent data in patients with chronic obstructive pulmonary disease suggest that periods of frequent eye movements may be associated with hypoxemia during REM sleep. We have therefore investigated the association between eye movements and ventilation and ventilatory pattern in 10 normal men. Expired ventilation was measured using a pneumotachograph attached to a valved face mask with a dead space of 50 ml and incorporating a peripheral CO2 leak detector. Ventilation was reduced (p less than 0.02) in all stages of sleep compared with that during wakefulness, with no difference between the level of ventilation in each sleep stage (awake, 7.18 +/- 0.43 SEM; Stage 2, 6.47 +/- 0.43; Stage 3/4, 6.45 +/- 0.52; REM sleep, 6.55 +/- 0.47 L/min). During REM sleep, eye movements (EMs) were associated with rapid shallow breathing. Dividing REM into 20-s epochs with or without EMs, EMs were associated with a raised breathing frequency (no EMs, 14.4 +/- 0.4 breaths/min; EMs, 15.8 +/- 0.5 breaths/min; p = 0.01), reduced tidal volume (0.49 +/- 0.03 L; 0.41 +/- 0.03 L; p less than 0.01), and reduced minute ventilation (6.87 +/- 0.45 L; 6.27 +/- 0.51 L; p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of shared care on blood pressure in patients with chronic kidney disease: a cluster randomised controlled trial

Background

Chronic kidney disease (CKD) is highly prevalent in patients with diabetes or hypertension in primary care. A shared care model could improve quality of care in these patients

Aim

To assess the effect of a shared care model in managing patients with CKD who also have diabetes or hypertension.

Design and setting

A cluster randomised controlled trial in nine general practices in The Netherlands.

Method

Five practices were allocated to the shared care model and four practices to usual care for 1 year. Primary outcome was the achievement of blood pressure targets (130/80 mmHg) and lowering of blood pressure in patients with diabetes mellitus or hypertension and an estimated glomerular filtration rate (eGFR)<60ml/min/1.73m².

Results

Data of 90 intervention and 74 control patients could be analysed. Blood pressure in the intervention group decreased with 8.1 (95% CI = 4.8 to 11.3)/1.1 (95% CI = −1.0 to 3.2) compared to −0.2 (95% CI = −3.8 to 3.3)/−0.5 (95% CI = −2.9 to 1.8) in the control group. Use of lipid-lowering drugs, angiotensin-system inhibitors and vitamin D was higher in the intervention group than in the control group (73% versus 51%, 81% versus 64%, and 15% versus 1%, respectively, [P = 0.004, P = 0.01, and P = 0.002]).

Conclusion

A shared care model between GP, nurse practitioner and nephrologist is beneficial in reducing systolic blood pressure in patients with CKD in primary care.     

Sleep problems,internalizing and externalizing symptoms,and domains of health-related quality of life: bidirectional associations from early childhood to early adolescence

Study ObjectivesTo examine longitudinal, bidirectional associations among behavioral sleep problems, internalizing and externalizing symptoms, and domains of health-related quality of life (HRQoL) from early childhood to adolescence in a population sample of Australian children.MethodData were drawn from the Longitudinal Study of Australian Children, a national prospective cohort study with 4983 children participating in the Kindergarten cohort. Data were collected when children were aged 4–5, 6–7, 8–9, 10–11, and 12–13 years. At each study wave, the primary parent (97% mothers) reported on behavioral child sleep problems, internalizing and externalizing symptoms, and HRQoL domains (psychosocial and physical). Cross-lagged structural equation models were used to evaluate bidirectional associations.ResultsAt nearly every age, behavioral sleep problems were associated with worse subsequent psychosocial and physical HRQoL. Despite bidirectional associations between mental health and HRQoL at many waves, HRQoL domains more strongly predicted later internalizing symptoms, while externalizing symptoms more strongly predicted later HRQoL. Many of the bidirectional associations among sleep, mental health, and HRQoL were found earlier in childhood.ConclusionsBehavioral sleep problems may forecast later HRQoL psychosocial and physical impairments. Attending to both sleep problems and HRQoL could prevent the progression of internalizing conditions, while a focus on externalizing concerns could prevent the worsening of these symptoms, sleep problems, and HRQoL, particularly during the transition to school.     

Optimizing the management of patients with spinal myeloma disease

Myeloma is one of the most common malignancies that results in osteolytic lesions of the spine. Complications, including pathological fractures of the vertebrae and spinal cord compression, may cause severe pain, deformity and neurological sequelae. They may also have significant consequences for quality of life and prognosis for patients. For patients with known or newly diagnosed myeloma presenting with persistent back or radicular pain/weakness, early diagnosis of spinal myeloma disease is therefore essential to treat and prevent further deterioration. Magnetic resonance imaging is the initial imaging modality of choice for the evaluation of spinal disease. Treatment of the underlying malignancy with systemic chemotherapy together with supportive bisphosphonate treatment reduces further vertebral damage. Additional interventions such as cement augmentation, radiotherapy, or surgery are often necessary to prevent, treat and control spinal complications. However, optimal management is dependent on the individual nature of the spinal involvement and requires careful assessment and appropriate intervention throughout. This article reviews the treatment and management options for spinal myeloma disease and highlights the value of defined pathways to enable the proper management of patients affected by it.