Integration of the Duke Activity Status Index into preoperative risk evaluation: a multicentre prospective cohort study.

BACKGROUND: The Duke Activity Status Index (DASI) questionnaire might help incorporate self-reported functional capacity into preoperative risk assessment. Nonetheless, prognostically important thresholds in DASI scores remain unclear. We conducted a nested cohort analysis of the Measurement of Exercise Tolerance before Surgery (METS) study to characterise the association of preoperative DASI scores with postoperative death or complications. METHODS: The analysis included 1546 participants (≥40 yr of age) at an elevated cardiac risk who had inpatient noncardiac surgery. The primary outcome was 30-day death or myocardial injury. The secondary outcomes were 30-day death or myocardial infarction, in-hospital moderate-to-severe complications, and 1 yr death or new disability. Multivariable logistic regression modelling was used to characterise the adjusted association of preoperative DASI scores with outcomes. RESULTS: The DASI score had non-linear associations with outcomes. Self-reported functional capacity better than a DASI score of 34 was associated with reduced odds of 30-day death or myocardial injury (odds ratio: 0.97 per 1 point increase above 34; 95% confidence interval [CI]: 0.96-0.99) and 1 yr death or new disability (odds ratio: 0.96 per 1 point increase above 34; 95% CI: 0.92-0.99). Self-reported functional capacity worse than a DASI score of 34 was associated with increased odds of 30-day death or myocardial infarction (odds ratio: 1.05 per 1 point decrease below 34; 95% CI: 1.00-1.09), and moderate-to-severe complications (odds ratio: 1.03 per 1 point decrease below 34; 95% CI: 1.01-1.05). CONCLUSIONS: A DASI score of 34 represents a threshold for identifying patients at risk for myocardial injury, myocardial infarction, moderate-to-severe complications, and new disability.

Provoked models of asthma: what have we learnt?

Asthma is a chronic inflammatory disease of the airways characterized by physiological abnormalities of variable airflow obstruction and airway hyperresponsiveness (AHR) to a wide variety of physical and inhaled chemical stimuli and the presence of symptoms. AHR is measured by challenging the airways with a variety of agonists and naturally occurring stimuli, which results in constriction of the airway smooth muscle, leading to airway narrowing and airflow limitation. There are two distinct mechanisms by which the airways can narrow to a constrictor stimulus and these are defined by the pathways they take to induce AHR. Direct stimuli are pharmacological agents administered exogenously (such as histamine or methacholine) that act 'directly' on specific receptors on the bronchial smooth muscle to cause constriction. The other mechanism by which the airway can narrow is via the inhalation of indirect stimuli, which include natural stimuli, such as allergen or exercise, and pharmacological agents such as adenosine monophosphate and hyper-osmotic agents (e.g. hypertonic saline or dry powder mannitol). These stimuli induce airway narrowing 'indirectly' by causing the endogenous release of mediators of bronchoconstriction from airway inflammatory cells. Provoked models of asthma have been extremely valuable in understanding the pathobiology of asthma, in aiding diagnosis, in helping to clarify the mechanisms of actions of effective drugs and in the development of new entities to treat asthma. Some provoked models are valuable clinically, particularly those that measure direct AHR, while others, particularly allergen challenge, have been used in animal models and in humans to study the mechanisms of allergen-induced airway inflammation and the associated physiological changes, as well in the development of new drugs for asthma. An emerging role for measurements of AHR is in the evaluation of the optimal treatment for patients with asthma.

Relationship between airway responsiveness to mannitol and to methacholine and markers of airway inflammation, peak flow variability and quality of life in asthma patients.

BACKGROUND: Airway hyperresponsiveness (AHR) to stimuli that cause bronchial smooth muscle (BSM) contraction indirectly through the release of endogenous mediators is thought to reflect airway inflammation more closely compared with AHR measured by stimuli that act directly on BSM. METHODS: Fifty-three adult non-smoking asthmatics (28 females, 18-56 years) who were not taking inhaled steroids were challenged with mannitol (up to 635 mg) and methacholine (up to 8 mumol). Induced sputum eosinophils, exhaled nitric oxide (eNO), peak flow variation and clinical severity of asthma according to the Global Initiative for Asthma guidelines were measured in addition to the health-related quality-of-life score using the Juniper asthma quality-of-life questionnaire. FINDINGS: Both AHR to mannitol as well as to methacholine was associated with elevated markers of airway inflammation: in 83% of asthma patients with AHR to mannitol, and in 88% of asthma patients with AHR to methacholine, the eNO level was >20 p.p.b. Sputum% eosinophils >1% was measured in 70% of asthma patients with AHR to mannitol and in 77% of asthma patients with AHR to methacholine. In asthma patients without AHR, 15% had an eNO level >20 p.p.b., but none had sputum% eosinophils >1%. AHR to mannitol was more closely associated with the percentage of sputum eosinophils (PD(15) to mannitol vs. sputum% eosinophils: r: -0.52, P<0.05), compared with AHR to methacholine (PD(20) to methacholine vs. sputum% eosinophils: r: -0.28, NS). Furthermore, there was a stronger correlation between AHR to mannitol and the level of eNO [PD(15) to mannitol vs. eNO (p.p.b.): r: -0.63, P<0.001], compared with AHR to methacholine [PD(20) to methacholine vs. eNO (p.p.b.): r: -0.43, P<0.05]. INTERPRETATION: In asthma patients not being treated with steroids, AHR to mannitol and to methacholine indicated the presence of airway inflammation. AHR to mannitol reflected the degree of airway inflammation more closely when compared with methacholine.

Haemodynamic effects of angiotensin converting enzyme inhibition after cardiopulmonary bypass in dogs.

Recent studies have suggested a possible causative relationship between elevated plasma levels of Angiotensin II (AII) and the vasoconstriction associated with conventional cardiopulmonary bypass. The haemodynamic effects of SQ14225, a specific angiotensin converting enzyme inhibitor, have been studied in a group of five dogs submitted to a 60 min period of cardiopulmonary bypass (CPB). A 20 min infusion of SQ14225 in a dose of 2 microgram .kg-1 .h-1 was administered to each dog 2 h after the end of the period of CPB. Measurements of peripheral vascular resistance index (PVRI), cardiac index (CI) and plasma levels of Angiotensin II were obtained at the start and end of the infusion period. The results in the five blocked dogs were compared with a control series of ten unblocked dogs submitted to an identical cardiopulmonary bypass regine. In the blocked dogs, PVRI fell significantly during infusion of SQ14225 from 38.27 units to 21.70 units (P <0.01). There was a simultaneous significant increase in cardiac index from 3.00 to 3.98 litre.m2 .min-1 (P <0.01). Plasma Angiotensin 11 levels fell in the blocked dogs from 57 to 11.5 pg.cm-2 during the infusion period (normal levels <15 pg.cm-3). In the control unblocked dogs, there was no corresponding fall in PVRI, no rise in cardiac index, and no fall in elevated plasma AII levels. The difference between the groups were statistically highly significant (P <0.005). These results indicate that reduction in elevated plasma AII levels after CPB using converting enzyme inhibitor SQ14225 is associated with a significant fall in peripheral vascular resistance and a significant rise in cardiac index. In addition, the study confirms the causative relationship between elevated plasma levels of Angiotensin II and the increased vasoconstriction associated with non-pulsatile CPB.

Role of angiotensin II in the development of peripheral vasoconstriction during cardiopulmonary bypass.

The possible relationship between angiotensin II -- the end product of the renin-angiotensin system, and the increase in peripheral vasoconstriction associated with cardiopulmonary bypass, has been investigated in 12 patients undergoing elective open-heart surgical procedures. Plasma angiotensin II (AII) levels were measured by radio-immunoassay at the start and the end of the period of cardiopulmonary bypass. Measurements of peripheral vascular resistance index were made at the times of AII sampling. Plasma AII levels rose during CPB from 78.0 to 231.3 pg.cm-3 (normal values less than 35 pg.cm-3). Peripheral vascular resistance index also rose during perfusion from 20.87 to 27.83 units. The rise in plasma AII levels and in peripheral vascular resistance index were correlated for each of the 12 patients. A highly significant correlation was obtained (r = 0.91; P less than 0.001). These results confirm the presence of parallel rises in plasma angiotensin II levels and in peripheral vasoconstriction during conventional non-pulsatile cardiopulmonary bypass, and suggest that increased plasma AII levels may be principal causative factor in the increased vasoconstriction associated with open-heart surgical procedures.

Transfer of patients receiving advanced mechanical circulatory support.

OBJECTIVE: Improving results with ventricular assist devices have led to their wider clinical application. Centers can stabilize, support, and wean or transfer patients to regional transplant centers. METHODS: Prospectively collected data were reviewed to evaluate the clinical results of patients transferred to our institution while receiving advanced mechanical circulatory support. RESULTS: Since 1993, 16 patients were accepted while receiving support with either extracorporeal membrane oxygenation or a ventricular assist device. The 10 male and 6 female patients ranged in age from 9 to 60 years (mean, 42.1 years). Thirteen had had cardiac surgical procedures, two had acute myocardial infarctions, and one had myocarditis. The distance transported ranged from 0.2 to 309 miles (mean, 132 miles). Twelve patients were transferred by ground, and 4 were transported by air. Seven patients were originally supported with extracorporeal membrane oxygenation, 6 with centrifugal pumps, and 3 with ABIOMED ventricular assist devices (ABIOMED, Inc, Danvers, Mass). Two patients had clinical complications during transfer, and one had a cerebrovascular accident, recovered, was weaned, and survived. A second patient had hemodynamic deterioration. There were no technical complications associated with transport. Six patients were left on the original support device; 3 of the 6 were weaned and survived, and 3 died during support. The 10 remaining patients were switched to other ventricular assist devices: 9 patients to Thoratec devices (Thoratec Laboratories, Pleasanton, Calif) and 1 patient to a Novacor device (Baxter Healthcare Corp, Novacor Division, Oakland, Calif). Six of the 10 patients underwent transplantation and survived. Four patients died while being supported by the devices. Nine patients were discharged, with 1 late death at 29 months. Eight patients are alive 4 to 65 months after discharge. CONCLUSIONS: These data suggest that patients receiving advanced support can be moved between clinical centers with acceptable risks. Because 33% of the survivors were weaned, transplantation is not required for survival.

Effects of cardiopulmonary bypass on gut blood flow, oxygen utilization, and intramucosal pH.

Studies documenting rises in endotoxin after cardiopulmonary bypass (CPB) have postulated gut mucosal hypoperfusion. We have investigated alterations in jejunal blood flow by laser Doppler flow measurement, intramucosal pH (pHi) by tonometry, and oxygen utilization in a canine model of hypothermic CPB (n = 11 dogs). After 10 minutes of hypothermic CPB, despite no major reduction in superior mesenteric artery flow, mucosal laser Doppler flow decreased to -38.2% +/- 9.3% of levels obtained before bypass (p = 0.008) and serosal laser Doppler flow, to -47.3% +/- 11.4% (p = 0.006). During the hypothermic phase, mesenteric oxygen consumption fell from 0.18 +/- 0.01 to 0.098 +/- 0.01 mL.min-1.kg-1 (p = 0.005), and mesenteric oxygen delivery fell from 1.97 +/- 0.39 to 1.14 +/- 0.12 mL.min-1.kg-1 (p = 0.05). There was no change in jejunal pHi. During the rewarming phase, there was a substantial increase in mucosal laser Doppler flow, peaking at +69.8% +/- 15.2% (p = 0.03), whereas serosal laser Doppler flow returned to values seen prior to CPB (-16.4% +/- 21.5%; p = 0.25). These changes coincided with a surge in oxygen consumption (0.33 +/- 0.042 mL.min-1.kg-1; p = 0.009), while mesenteric oxygen delivery remained depressed at 1.09 +/- 0.12 mL.min-1.kg-1 (p = 0.04). Jejunal pHi fell from a value of 7.36 +/- 0.04 before CPB to 7.12 +/- 0.07 (p = 0.02), thus indicating mucosal hypoxia. During the rewarming phase of hypothermic CPB, there is a disparity between mesenteric oxygen consumption and oxygen delivery with villus tip ischemia; these findings may explain the pathophysiology of endotoxemia during CPB.

Genetically engineered serine protease inhibitor for hemostasis after cardiac operations.

BACKGROUND: The serine protease inhibitor aprotinin has been widely reported for its beneficial action in limiting blood loss after cardiopulmonary bypass (CPB). A potent human serine protease inhibitor known as protease nexin II or amyloid precursor protein has been recently isolated. A recombinant protein known as recombinant Kunitz protease inhibitor (rKPI; Scios Nova, Mountain View, CA) with sequence homology to the protease nexin II-amyloid precursor protein molecule has been manufactured. METHODS: Recombinant Kunitz protease inhibitor was assessed in an ovine model of CPB as a hemostatic agent after CPB. Sheep (n = 22) underwent CPB for 90 minutes. Two thoracic drains were sited and drain losses collected for a period of 3 hours after CPB. Wounds were subjectively assessed before closure for "dryness" using a visual analogue scale. Sheep were randomized to control (n = 8), aprotinin (n = 8), and rKPI (n = 6) groups. RESULTS: Control animals had a drain loss of 409.4 +/- 39.4 mL/3 h, compared with 131.3 +/- 20.3 mL/3 h for the aprotinin group and 163.7 +/- 34.3 mL/3 h for the rKPI group (p = 0.16). Hemoglobin loss was 11.6 +/- 3.6, 6.02 +/- 2.1, and 4.6 +/- 1.2 g/3 h for the control, rKPI, and aprotinin groups respectively (p = 0.25). The subjective analysis of the wounds at the end of CPB found aprotinin (1.25 +/- 0.16; p < 0.05) and rKPI (1.17 +/- 0.17; p < 0.05) animals to score significantly lower than control animals (2.63 +/- 0.42). CONCLUSIONS: On the basis of these in vivo findings, genetic modification may yield a more efficacious serine protease inhibitor with the inherent advantages of using a human-based protein.

Risk analysis in patients bridged to transplantation.

BACKGROUND: Efforts to predict mortality in bridge to cardiac transplant patients have concentrated on preventricular assist device (VAD) status. To more fully identify factors influencing survival to transplant, we reviewed the preoperative and postoperative VAD courses of 105 bridge to transplant patients. METHODS: Sixty-four parameters (34 pre-VAD, 30 post-VAD), including hemodynamics, complications, and evaluations of major organ function were examined and analyzed. RESULTS: Thirty-three patients (31%) died on VADs and 72 were transplanted. There were two posttransplant operative deaths (3%). By univariate analysis 23 of 64 factors were significant. These 23 factors were entered into a stepwise logistic regression analysis to identify predictors of survival to transplant. Four factors, including pre-VAD intubation (p < 0.005), cardiopulmonary bypass (CPB) time during VAD insertion (p < 0.0001), mean pulmonary artery pressure (first postoperative day after VAD) (p < 0.0002), and highest post-VAD creatinine (p < 0.01) were independent predictors of transplantation. CONCLUSIONS: Other than the need for intubation, pre-VAD variables were of little value in predicting survival to transplant. Problems during VAD insertion (long CPB time) and post-VAD renal insufficiency were independent predictors. Severe complications that developed during the interval of VAD support, including cerebrovascular accident, bleeding and infection, were surprisingly not predictors for transplantation.

Evidence for two distinct nonlinear components in the human pattern ERG.

We obtained the electroretinogram (PERG) in three observers to a 4.6 c/deg grating pattern with a sinusoidal luminance profile which was modulated in time simultaneously with two sinusoidal temporal frequencies (f1 and f2), or at a single frequency (either f1 or f2). Input temporal frequency ranged from 2.4 to 7.5 Hz. A pattern modulated in the counterphase mode with a single frequency produces a response containing only even harmonics of that frequency. However, when the pattern is counterphase modulated with both f1 and f2, the PERG contains second order response frequencies corresponding to intermodulation components (sums and differences) between the two fundamental frequencies. Such frequencies do not exist in the stimulus--they can only be generated by nonlinear neural interactions. Our results provide evidence for at least two nonsaturating nonlinear response mechanisms in the human retina.

Inhaled mannitol identifies methacholine-responsive children with active asthma.

Inhaled mannitol has been developed for bronchial challenge testing in adults. This study determined if mannitol could identify children with active asthma and responsive to methacholine, and whether mannitol challenge was faster to complete than methacholine challenge. Twenty-five children (aged 6-13 years) responsive to methacholine and 10 nonasthmatic children unresponsive to methacholine were studied. The methacholine challenge (Cockcroft protocol) was followed by a mannitol challenge on separate days. Twenty-one asthmatic children were positive to mannitol. Three taking inhaled corticosteroids with borderline methacholine responsiveness did not respond to mannitol, and one could not complete the mannitol challenge due to cough. The geometric mean (GM) and 95% confidence interval (CI) for PD(15) for mannitol was 39 mg (19, 78), and PC(20) for methacholine was 0.6 mg/mL (0.35-1.02) (r(p) = 0.75, p < 0.001, n = 21). Responses to mannitol were repeatable: GM PD(15) for the first challenge was 29 mg (CI: 17,50), and for the second challenge, 33 mg (CI: 20, 55) (P = 0.44, n = 9). Mannitol was faster to administer than methacholine (median (range)) 14 min (5-32) vs. 29 min (19-49), respectively (P < 0.001). Time to recover to baseline FEV(1) spontaneously and after bronchodilator administration was similar for both challenges. There were no significant falls in arterial oxygen saturations. During mannitol challenge, the mean (SD) fall in FEV(1) in nonasthmatic children was 3.1% (2.9). We conclude that mannitol identifies children with airway hyperresponsiveness and is faster to perform than the methacholine challenge.

Laboratory protocol for exercise asthma to evaluate salbutamol given by two devices.

PURPOSE: As new delivery devices and formulations are being introduced for drugs given by inhalation, there is a need to evaluate their equivalence with old preparations. One way to do this is to investigate their equivalence in protecting from exercise-induced asthma (EIA). METHODS: We used a protocol for EIA to compare the protective effect of salbutamol delivered by the pressurised metered dose inhaler (pMDI) and the new Diskus dry powder device. Twenty-seven asthmatic subjects with moderately severe EIA completed an exercise test on four separate days at two study centers. Exercise was performed by cycling for 8 min while inhaling dry air (0% RH, 20-24 degrees C). The target workload in W was predicted as (53.76 x predicted FEV1) - 11.07 and 95% of this target was achieved at 4 min of exercise. This target was chosen in order to achieve ventilation between 50 and 60% of predicted maximum in the last 4 min. RESULTS: There was no significant difference in the workload, ventilation, or heart rate achieved on the study days. The severity of EIA was measured as the % fall in FEV1. EIA severity was similar on the placebo and control day and the coefficient of variation was 19.4%. The mean +/- SD % fall on the control, placebo, salbutamol by Diskus, and pMDI were 42.0% +/- 15, 39.4% +/-17.6, 13.4% +/- 13.2, and 8.5% +/- 13.8, respectively. Salbutamol significantly inhibited the % fall in FEV1 after exercise, and there was no difference between the preparations. CONCLUSION: The protocol described here is suitable for evaluating equivalence of salbutamol preparations in protecting against EIA and could be used to evaluate the protective effect of other medications.

The United Kingdom Heart Valve Registry.

The United Kingdom Heart Valve Registry project began in 1986 following discussions between the Department of Health (DOH) and the Society of Cardiothoracic Surgeons of the United Kingdom and Ireland. The intention was to establish a computerized database for valve replacement operations carried out in the UK Health Service cardiac units. This paper describes the experience gained over the first five years of this project. Around 30,000 patients were entered in the registry between 1986 and 1990. All Uk Health Service cardiac surgical units contribute their data, which is processed by the central Registry Office. The accuracy of the mortality data is ensured by tracking the registered patients through the Office of Population Census and Surveys (OPCS). The pattern of valve replacement surgery over the period 1986-90 revealed several interesting trends. Although the number of procedures remained static at around 5,000 valve transplants per year, the number of aortic replacements increased and the number of mitrals decreased. The use of prosthetic valves increased from 54% in 1986 to over 70% in 1990. The mean age of the patients increased from 58.31 years in 1986 to 60.97 years in 1990, with over 22% of the valve replacement operations in 1990 being performed on patients over 70 years of age. The five year survival rate for patients over 70 years at the time of the valve implant is significantly lower than for patients under 70 years (p < 0.005).

Survival and cause of death after mitral valve replacement in patients aged 80 years and over: collective results from the UK heart valve registry.

OBJECTIVE: Over the last decade there has been an increasing number of patients aged 80 years and over undergoing heart valve replacement. However, literature on the outcome of mitral valve replacement (MVR) in this age group is still limited. METHODS: We conducted the present study by analysing data extracted from the UK Heart Valve Registry. From January 1986 to December 1994, 86 patients underwent isolated MVR and 10 underwent combined MVR with aortic valve replacement (AVR) and were reported to the Registry. RESULTS: The 30 day mortality was 10.4% (9/86) in the MVR group and 10% (1/10) in the MVR and AVR group. The actuarial survival was 79.8, 64.1 and 40.7% at 1, 3 and 5 years, respectively, in the MVR group. Of the 10 early (30 day) deaths, 8 were due to cardiac reasons and 19 of the 28 late deaths were due to non-cardiac reasons. A total of 55 (57.2%) patients received a bioprosthetic valve implant and 41 (42.8%) patients received a mechanical valve implant. There was no difference in survival between the two groups. CONCLUSIONS: The above results suggest that MVR in octogenarians produces a satisfactory early postoperative outcome and moderate medium-term benefit. There is no difference in survival between patients receiving bioprosthetic and patients receiving mechanical valve implants.

Eye movement indices of mental workload.

Four investigations were carried out to assess the feasibility of using eye movement measures as indices of mental workload. In the first experiment, saccadic extent was measured during free viewing while subjects performed low, moderate and high complexity, auditory tone counting as the workload tasks. The range of saccadic extent decreased significantly as tone counting complexity (workload) was increased. In the second experiment the range of spontaneous saccades was measured under three levels of counting complexity with a visual task that did not require fixation or tracking. The results indicated that the extent of saccadic eye movements was significantly restricted as counting complexity increased. In the third experiment, the effects of practice were examined and decreased saccadic range under high tone counting complexity was observed even when significant increases in performance occurred with practice. Finally, in experiment 4, the first experiment was repeated with additional optokinetic stimulation and the saccadic range was again observed to decrease with tone counting complexity. The results indicated that the extent of spontaneous and elicited eye movements was significantly restricted as counting complexity increased. We conclude that this measure may provide a valuable index of mental workload.

The effect of methylprednisolone pre-treatment on brain damage in dogs during cardiopulmonary bypass. A double blind study.

Brain damage remains a significant cause of post-operative morbidity following open-heart surgical procedures. Though cerebral ischaemia and micro-embolic damage are considered the main causative factors, further understanding of this particular clinical problem has been hampered by the lack of an acceptably sensitive experimental model. Recent development of a biochemical marker model using cerebrospinal fluid levels of creatine kinase enzyme and its B brain specific isoenzyme have been used in the present study designed to investigate the effect of corticosteroid pre-treatment of dogs submitted to 60 minutes of normothermic cardiopulmonary bypass. Identical vials containing methylprednisolone 30 mg/kg body weight or placebo were administered intravenously to the dog before the period of bypass was begun. The cisterna magna was cannulated in order to obtain appropriate cerebrospinal fluid samples. The results indicate a rise in the enzyme and isoenzyme levels in cerebrospinal fluid during the period of perfusion for both total creatine kinase enzyme and its B isoenzyme. Analysis of the results following completion of the study indicated that the levels of enzyme and isoenzyme rise in the steroid treated group were always lower than the levels obtained in the group receiving placebo. Though this difference was consistent it did not achieve statistical significance. Analysis of the distribution of the rise in enzyme levels in the individual dogs in the two groups suggested, however, that the group of dogs receiving methylprednisolone were possibly protected from excessive degrees of enzyme release indicating a possible protective effect of steroid pre-treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of aerosols for bronchial provocation testing in the laboratory: where we have been and where we are going.

Bronchial provocation testing with pharmacological agents that act directly on airway smooth muscle has important limitations. These include the inability to identify exercise-induced asthma (EIA), to differentiate the airway hyperresponsiveness (AHR) of airway remodelling from the AHR of active inflammation and to differentiate between doses of steroids. Recent studies show that tests that act indirectly to narrow airways are more sensitive than pharmacological agents for identifying airway inflammation and response to treatment. Adenosine monophosphate (AMP) is an indirect challenge that acts on mast cells to cause release of mediators. Hypertonic saline is another and, since its development in the 1980s, has become widely used in Australia. Hypertonic (4.5%) saline is used to identify those with active asthma, those with EIA and those who wish to enter certain occupations or sports (e.g., diving). The recent development, again in Australia, of a test that uses dry powder mannitol has promise for use in the laboratory, the office, or for testing in the field. AHR to mannitol identifies people with EIA and is an estimate of its severity. The mannitol response is modified by drugs used to prevent EIA, implying that similar mediators are involved. A mannitol test can be used to monitor response to steroids and is more sensitive than histamine for identifying persistent airway hyperresponsiveness in asthmatics well controlled on steroids. These findings suggest that indirect challenges give more useful clinical information about currently active asthma and the response to treatment than direct challenge and they will become more widely used.

Transfer of perceptual-motor training and the space adaptation syndrome.

Perceptual cue conflict may be the basis for the symptoms which are experienced by space travelers in microgravity conditions. Recovery has been suggested to take place after perceptual modification or reinterpretation. To elucidate this process, 10 subjects who repeatedly experienced a visual/vestibular conflict (Purkinje) over trials and days, were then tested in a similar but not identical perceptual situation (pseudo-Coriolis) to determine whether any savings in perceptual adaptation had occurred as compared to an unpracticed control group (N = 10). The practiced subjects experienced lessening dizziness and ataxia within and over sessions. Their response to the new perceptual situation was markedly less than the control group (p less than 0.001). Assessment of "adaptability," in addition to the provocative vestibular tests now in use, may improve prediction of susceptibility to the space adaptation syndrome. An adaptability trait may exist in humans which, properly measured, could be used to predict who would adapt more readily to visual/vestibular conflict and perhaps to environmental stressors in general.