1: Respir Physiol Neurobiol. 2004 Jul 20;141(2):191-9. Protocol to measure acute cerebrovascular and ventilatory responses to isocapnic hypoxia in humans. Kolb JC, Ainslie PN, Ide K, Poulin MJ. Faculty of Kinesiology, University of Calgary, Calgary, Alta., T2N 4N1, Canada. This study describes a protocol to determine acute cerebrovascular and ventilatory (AHVR) responses to hypoxia. Thirteen subjects undertook a protocol twice, 5 days apart. The protocol started with 8 min of eucapnic euoxia (end-tidal P(CO2) (PET(CO2)= 1.5 Torr) above rest; end-tidal P(O2) (PET(O2)) = 88 Torr) followed by six descending 90 s hypoxic steps (PET(O2) = 75.2, 64.0, 57.0, 52.0, 48.2, 45.0 Torr). Then, PET(O2) was elevated to 300 Torr for 10 min while PET(O2) remained at eucapnia (5 min) then raised by 7.5 Torr (5 min). Peak blood flow velocity in the middle cerebral artery (MCA) and regional cerebral oxygen saturation (Sr(O2)) were measured with transcranial Doppler ultrasound and near-infrared spectroscopy, respectively, and indices of acute hypoxic sensitivity were calculated (AHR(CBF) and AHRSr(O2)). Values for AHR(CBF), AHRSr(O2) and AHVR were 0.43 cm s(-1) % desaturation(-1), 0.80% % desaturation(-1) and 1.24l min(-1) % desaturation(-1), respectively. Coefficients of variation for AHR(CBF), AHRSr(O2) and AHVR were small (range = 8.0-15.2%). This protocol appears suitable to quantify cerebrovascular and ventilatory responses to acute isocapnic hypoxia. Publication Types: Clinical Trial Validation Studies PMID: 15239969 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 2: Can J Physiol Pharmacol. 2002 Aug;80(8):796-803. Effects of modafinil on heat thermoregulatory responses in humans at rest. Launay JC, Besnard Y, Guinet A, Bessard G, Raphel C, Savourey G. Departement des Facteurs Humains, Centre de Recherches du Service de Sante des Armees, La Tronche, France. jclaunay@crssa.net The effects of modafinil on heat thermoregulatory responses were studied in 10 male subjects submitted to a sweating test after taking 200 mg of modafinil or placebo. Sweating tests were performed in a hot climatic chamber (45 degrees C, relative humidity <15%, wind speed = 0.8 m x s(-1), duration 1.5 h). Body temperatures (rectal (Tre) and 10 skin temperatures (Tsk)), sweat rate, and metabolic heat production (M) were studied as well as heart rate (HR). Results showed that modafinil induced at the end of the sweating test higher body temperatures increases (0.50 +/- 0.04 versus 0.24 +/- 0.05 degrees C (P < 0.01) for deltaTre and 3.64 +/- 0.16 versus 3.32 +/- 0.16 degrees C (P < 0.05) for deltaTsk (mean skin temperature)) and a decrease in sweating rate throughout the heat exposure (P < 0.05) without change in M, leading to a higher body heat storage (P < 0.05). AHR was also increased, especially at the end of the sweating test (17.95 +/- 1.49 versus 12.52 +/- 1.24 beats/min (P < 0.01)). In conclusion, modafinil induced a slight hyperthermic effect during passive dry heat exposure related to a lower sweat rate, probably by its action on the central nervous system, and this could impair heat tolerance. Publication Types: Clinical Trial Controlled Clinical Trial PMID: 12269790 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 3: J Pathol. 2001 Oct;195(3):312-20. Molecular classification of breast cancer patients by gene expression profiling. Ahr A, Holtrich U, Solbach C, Scharl A, Strebhardt K, Karn T, Kaufmann M. Department of Obstetrics and Gynecology, J.W. Goethe-University, Theodor-Stern-Kai 7, D-60590 Frankfurt, Germany. ahr@em.uni-frankfurt.de For many tumors, pathological subclasses exist which have to be further defined by genetic markers to improve therapy and follow-up strategies. In this study, cDNA array analyses of breast cancers have been performed to classify tumors into categories based on expression patterns. Comparing purified normal ductal epithelial cells and corresponding tumour tissues, the expression of only a small fraction of genes was found to be significantly changed. A subset of genes repeatedly found to be differentially expressed in breast cancers was subsequently employed to perform a classification of 82 normal and malignant breast specimens by cluster analysis. This analysis identifies a subgroup of transcriptionally related tumours, designated class A, which can be further subdivided into A1 and A2. Correlation with classical clinicopathological parameters revealed that subgroup A1 was characterized by a high number of node-positive tumours (14 of 16). In this subgroup there was a disproportionate number of patients who had already developed distant metastases at the time of diagnosis (25% in this subgroup, compared with 5% among the rest of the samples). Taken together, the use of these differentially expressed marker genes in conjunction with sample clustering algorithms provides a novel molecular classification of breast cancer specimens, which facilitates the identification of patients with a higher risk of recurrence. Copyright 2001 John Wiley & Sons, Ltd. PMID: 11673828 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 4: Med Sci Sports Exerc. 2000 Jan;32(1):162-6. Resting heart rate definition and its effect on apparent levels of physical activity in young children. Logan N, Reilly JJ, Grant S, Paton JY. Department of Human Nutrition, Centre for Exercise Science and Medicine, University of Glasgow, Scotland. PURPOSE: Heart rate monitoring is widely used to measure physical activity in children, but it may be dependent on the definition of resting heart rate used and the protocol used to measure or derive resting heart rate (RHR). The aim of this study was to determine the effect of RHR definition on activity levels assessed by PAHR-25 (% time at >25% of RHR), PAHR-50 (% time at >50% of RHR), and activity heart rate (AHR; mean HR minus RHR). METHODS: Minute-to-minute heart rates were measured over 3 d in 20 healthy preschool children aged 3-4 yr. Resting heart rate was measured for 5 min after a 10-min rest and was also derived from the following different but commonly used protocols: 1) mean of lowest heart rate plus all heart rates within three beats; 2) mean of lowest 5; 3) lowest 10; 4) lowest 50. This gave five different definitions of RHR. Differences in RHR and in the derived indices of activity among definitions were tested for agreement using a Bland-Altman analysis, and by rank order correlation. RESULTS: Differences in RHR among all definitions were statistically significant. These resulted in significant differences in apparent physical activity levels: PAHR-25 varied 10-50% depending on the protocol used to define RHR; PAHR-50 varied by 16-65% as a function of the protocol used to define RHR. However, the different definitions of RHR had no significant influence on physical activity level when children were rank ordered. CONCLUSION: Choice of method for defining RHR has a profound effect on the apparent level of activity of children. This does not alter the relative assessment of activity by rank order. A consensus definition of RHR is desirable if comparisons of activity levels between samples or populations are to be made and if the adequacy of physical activity levels is to be assessed using heart rate. PMID: 10647544 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 5: Nucl Med Commun. 1998 Sep;19(9):859-66. Assessment of 99Tcm-tetrofosmin lung uptake: a modified method to avoid the contribution from high chest wall activity. Heiba SI, Ziada G, Higazy E, Saleh M, Elgazzar AH. Department of Nuclear Medicine, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait. Evaluation of lung uptake during routine 99Tcm-tetrofosmin myocardial SPET (single photon emission tomography) studies may be hindered by substantial chest muscle uptake, particularly post-exercise. This study investigated this proposal and analysed the various components of chest activity that may add to the real lung uptake. Exercise SPET studies were performed on normal subjects using 99Tcm-tetrofosmin and compared with the results of 99Tcm-sestamibi and 201Tl studies. The chest to heart count ratio (CHR) was calculated from the anterior SPET projection and further subclassified into lung, anterior chest and posterior chest to heart ratios (LHR, AHR, PHR) from the left anterior oblique (LAO) projection. On post-exercise images, the 99Tcm-tetrofosmin CHR was significantly higher than that of 201Tl and 99Tcm-sestamibi. Both the 99Tcm-tetrofosmin AHR and PHR were higher than those of 201Tl and 99Tcm-sestamibi. However, the LHR was similar for all three radiopharmaceuticals. In contrast, the rest 99Tcm-tetrofosmin images differed little from the 201Tl and 99Tcm-sestamibi ones. Thus, 99Tcm-tetrofosmin lung uptake post-exercise should be interpreted with caution, as chest muscle uptake is higher than normal. A more accurate evaluation of 99Tcm-tetrofosmin lung uptake is achieved from the LAO projection, where the contribution from chest muscle counts is much less than in the routinely used anterior projection. PMID: 10581592 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 6: J Physiol. 1994 May 15;477 ( Pt 1):169-75. Increased hypoxic ventilatory sensitivity during exercise in man: are neural afferents necessary? Pandit JJ, Bergstrom E, Frankel HL, Robbins PA. University Laboratory of Physiology, Oxford. 1. The acute ventilatory response to 3 min periods of hypoxia (AHR) was examined in nine patients with clinically complete spinal cord transection (T4-T7) during (a) rest and (b) electrically induced leg exercise (EEL). 2. EEL was produced by surface electrode stimulation of the quadriceps muscles so as to cause the legs to extend at the knee against gravity. End-tidal PCO2 was held constant 1-2 mmHg above resting values throughout both protocols. 3. On exercise, the average increase in metabolic CO2 production (VCO2 +/- S.E.M.) was 41 +/- 5 ml min-1. Venous lactate levels did not rise with exercise. 4. Baseline euoxic ventilation did not increase significantly with EEL, but there was a consistent and highly significant increase in the ventilatory response to hypoxia during EEL (mean delta AHR +/- S.E.M. of 1.6 +/- 0.21 min-1). 5. We conclude that an increase in hypoxic sensitivity during exercise can occur in the absence of volitional control of exercise and in the absence of afferent neural input from the limbs. PMID: 8071884 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 7: J Sports Med Phys Fitness. 1989 Dec;29(4):358-64. Comparison of ventilatory and heart rate responses to hypoxia at rest and during light exercise in high school judo athletes. Ohyabu Y, Takahashi T, Ogura K, Masuda T, Takahashi K, Sato N, Honda Y. Ventilatory and heart rate responses to hypoxia at rest and during light exercise (30W) were compared in 21 high school judo athletes. The results of ventilatory and heart rate responses to hypoxia were analyzed by the hyperbolic equations, VE = VO + AVE/(PETO2-CVE) and HR = HRO + AHR/(PETO2-CHR), respectively, where VE and HR are the observed ventilation and heart rate, VO and HRO the horizontal asymptote in ventilation and heart rate for infinite endtidal PO2 (PETO2), AVE and AHR the slope constants indicating the magnitude of hypoxic sensitivity, and CVE and CHR the vertical asymptote in PETO2 for infinite ventilation and heart rate. AVE was further recalculated after VE was normalized for a 70 kg body mass, using an allometric coefficient, and was defined as AVEN. The absolute magnitudes of hypoxic response in ventilation and heart rate at PETO2 40 mmHg were also determined as delta V40 = AVE/(40-CVE) and delta HR40 = AHR/(40-CHR), respectively. (1) The enhanced hypoxic ventilatory chemosensitivity previously found in heavy-weight judo athletes at rest was confirmed. However this characteristic disappeared with exercise. (2) It was also confirmed that there was no significant correlation between hypoxic heart rate sensitivity and body weight at rest. With exercise, this was found also to be the case. (3) On the other hand, when the hypoxic responses at rest were compared to those of the exercise studies, significant positive correlations were illustrated in both ventilatory and heart rate responsiveness. These results demonstrated that although ventilatory and heart rate responses did not quantitatively exhibit parallel change, the two activities did demonstrate a certain synergism between rest and exercise. PMID: 2628634 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 8: Eur J Appl Physiol Occup Physiol. 1984;52(4):451-6. Ventilatory and heart rate responses to hypoxia in well-trained judo athletes. Ohyabu Y, Yoshida A, Hayashi F, Nishibayashi Y, Sakakibara Y, Sato N, Honda Y. Twenty-four active judo athletes were examined by an isocapnic progressive hypoxia test. The results of ventilatory and heart rate responses to hypoxia were analyzed by the hyperbolic equations, VE = VO + AVE/(PETO2 - CVE) and HR = HRO + AHR/(PETO2 - CHR), respectively, where VE and HR are observed ventilation and heart rate, VO and HRO the horizontal asymptote in ventilation and heart rate for infinite end-tidal PO2 (PETO2), AVE and AHR the slope constant indicating the magnitude of hypoxic sensitivity, and CVE and CHR the vertical asymptote in PETO2 for infinite ventilation and heart rate. AVE was further re-calculated after VE was normalized for a 70 kg body mass, using an allometric coefficient, and was defined as AVEN. 1) AVE and AVEN significantly increased with increasing body weight (BW) as has been reported previously, but no such correlation was found between AHR and BW. 2) VO2 at rest was found to be positively correlated with AVE and AVEN but not with AHR. 3) The relationship between AVE and AHR was not significant. Thus, the characteristic feature seen in hypoxic ventilatory activity was not accompanied by a similar trend in heart rate response. PMID: 6540675 [PubMed - indexed for MEDLINE] ---------------------------------------------------------------