Persons with chronic fatigue syndrome (CFS) often complain of an inability to maintain activity levels and experience a variety of orthostatic symptoms such as dizziness, trembling, nausea, postural hypotension with bradycardia or tachycardia, sweating, palpitations, paleness, and syncope. Orthostatic intolerance (OI) may be defined as an inability to maintain systolic blood pressure (SBP) within 20 mmHg of resting level upon moving from a supine to upright posture. The primary objective of this study is to determine whether men and women with CFS are more susceptible to OI during a 3-stage head-up tilt (HUT) than non CFS, sedentary subjects matched by age, sex, and ethnicity. The secondary objective is to examine whether possible underlying mechanisms may be predictively associated with OI susceptibility in CFS. Possible causes of OI include autonomic nervous system (ANS) dysfunction and altered hematological profile. Thus, specific aims included within this objective are: 1) to determine whether there are differences in resting cardiovascular function {i.e., blood pressure [BP], heart rate [HR], stroke volume [SV], cardiac output [CO], total peripheral resistance [TPR], and contractility [i.e., ejection fraction (EF), fractional shortening (FS), and the velocity of circumferential shortening corrected by HR (VCFc)]}, ANS function {i.e., beta1-, beta2-, and alpha-receptor sensitivities, baroreceptor sensitivity [BRS], and vagal function [i.e., respiratory sinus arrhythmia (RSA), RSA envelope (RSAE), high frequency (HF) spectral component, and HR range]}, and hematological profile [i.e., red blood cell volume (RBCV), plasma volume (PBV), and total blood volume (TBV)] between CFS and non-CFS groups; and 2) to determine whether cardiovascular, ANS, and hematological measures differentially predicted OI during HUT. The results indicate that OI susceptibility does not occur with greater prevalence in persons with CFS than non-CFS sedentary persons. However, power analyses revealed that with a much larger sample size group differences in OI susceptibility would be found. The CFS group was distinguished from the control group only by differences in blood volume measures. There appears to be no substantive group differences in a range of cardiovascular and ANS measures; moreover, none of these measures, including the blood volume measures, accounted for differences in OI susceptibility. Compensatory mechanisms may be present in CFS for the diminished blood volume that could explain the lack of group differences in OI susceptibility. In addition, future research may find some clues relevant to CFS pathophysiology in the assessment of hemodynamic responses during orthostatic challenge in the present subjects.

Σκοπός της μελέτης ήταν η διερεύνηση της σχέσης ανάμεσα στο μεταβολισμό του σιδήρου και το σακχαρώδη διαβήτη τύπου 2. Έτσι ο στόχος της παρούσης μελέτης ήταν διπλός. α) Να καθορισθεί η συχνότητα των μεταλλάξεων C282Y και H63D στον Ελληνικό πληθυσμό και να συγκριθεί με αυτήν άλλων χωρών και ταυτοχρόνως, να ελεγχθεί αν η συχνότητα των ανωτέρω μεταλλαγών είναι διαφορετική στους διαβητικούς τύπου 2 σε σχέση με το γενικό πληθυσμό και να γίνει συσχέτιση ανάμεσα στην ύπαρξη η όχι των μεταλλάξεων αυτών και σε δείκτες μεταβολισμού του σιδήρου όπως η φερριτίνη, ο σίδηρος, ο κορεσμός τρανσφερίνης. β) Να ελεγχθεί αν στους διαβητικούς τύπου 2, η συχνότητα της κληρονομικής αιμοχρωμάτωσης (ομοζυγώτες), όπως αυτή μπορεί να καθορισθεί με βάση το γονότυπο του γονιδίου HFE είναι αυξημένη σε σχέση με το γενικό πληθυσμό. Υλικό και μέθοδοι Αρχικά δείγμα 100 διαβητικών τύπου 2 και 100 ατόμων από το γενικό πληθυσμό ελέγθησαν για τις μεταλλάξεις του γονιδίου HFE C282Y και H63D με τη μέθοδο της PCR και RFLP. Στη συνέχεια μελετήθηκαν 500 διαβητικοί τύπου 2 και 423 μάρτυρες. Στα άτομα αυτά εκτιμήθηκε το φορτίο του οργανισμού σε σίδηρο (Σίδηρος ορού, ολική δεσμευτική ικανότητα σε σίδηρο, φερριτίνη) και καθορίστηκε ο γονότυπος αναφορικά με τις μεταλλάξεις C282Y και H63D με τη μέθοδο της PCR και RFLP. Αποτελέσματα- Συμπεράσματα 1. Η συχνότητα του αλληλομόρφου C282Y στον Ελληνικό πληθυσμό(0,0075) είναι χαμηλότερη των ατόμων Βορειοευρωπαικής καταγωγής και πλησιάζει αυτή ατόμων από περιοχές της νότιας Ευρώπης. Η συχνότητα του αλληλομόρφου H63D (0,115) είναι παρόμοια με αλλους πληθυσμούς. 2. Δεν ανευρέθη διαφορά στη συχνότητα των μεταλλάξεων C282Y και H63D ανάμεσα στην ομάδα των διαβητικών τύπου 2 και στο γενικό πληθυσμό. 3. Η παρουσία οποιασδήποτε από τις παραπάνω μεταλλάξεις στην ετερόζυγη μορφή συνεισφέρει στην αύξηση του φορτίου του οργανισμού σε σίδηρο. Αυτό βρέθηκε και στις δύο ομάδες. 4. Οι διαβητικοί τύπου 2 παρουσιάζουν μεγαλύτερο κορεσμό τρανσφερρίνης αίματος και υψηλότερα επίπεδα φερριτίνης συγκρινόμενοι με το γενικό πληθυσμό. Οι ανωτέρω δείκτες θα μπορούσαν να αντιπροσωπεύουν αυξημένο φορτίο του οργανισμού σε σίδηρο. 5. Λόγω της χαμηλής συχνότητας του αλληλομόρφου C282Y δεν κατέστη δυνατή η ανίχνευση ομοζυγωτών C282Y/ C282Y. / Several authors have suggested a positive association between diabetes type 2 and the C282Y and H63D mutations of the hereditary hemochromatosis gene but others have disputed it. There are also papers reporting an increased iron load in diabetes type 2 and possible associations with the pathogenesis of the disease. We performed therefore a study in 100 type 2 diabetics and 100 age and sex matched controls to assess the role of the C282Y and H63D mutations in the HFE gene as a risk factor for type 2 diabetes mellitus in Greece. We also evaluated the iron load in 500 diabetes type 2 patients and 423 age and sex matched controls. We did not find any differences in the allele frequencies of the above mutations between patients with diabetes type 2 and the controls. The allele frequencies are estimated to be 0.0075 for the C282Y and 0.115 for the H63D mutation. Subjects with at least one mutation (C282Y or H63D) had higher transferrin saturation compared to those with no such mutations. This seems to apply to both diabetics (49± 8,6 vs 44,5± 5,4, p<0,01) and control group (49,3± 7,3 vs 42,6± 3,3 p<0,01). Patients with diabetes type 2 have higher transferrin saturation compared to the general population. These differences were found among men (n=250, mean± SD 31,8+11 vs n=73, mean± SD 29,5+8, p=0,05) as well as among women (n=250, mean± SD 28.5+10 vs n=350, mean± SD 25.5+9.6, p=0.001). The present study is in concord with previous work reporting that type 2 diabetes patients have higher ferritin levels compared to controls.

Through the recruitment of immunologic mechanisms, allogeneic hematopoeitic cell transplantation (HCT) has been establiched as a curative treatment for various hematologic diseases. The most convenient source to obtain hematopoietic progenitor cells are peripheral blood stem cells (PBSCs) which are harvested from the donor via leukapheresis after mobilization with granulocyte-colony stimulating factors. With the introduction of reduced intensity condition (RIC), the curative potential of allogeneic HCT became accessible to older and/or frail patients otherwise ineligible for HCT. However, new challenges arise as the increasing age of patients is inevitably accompanied by a comparable increase in the age of donors. Safety considerations of collecting PBSCs might attain new dimensions. Data to potential risks in elderly donors are lacking. Moreover, the impact of donor’s age on the feasibility of PBSCs collection and on the quality of the harvest in terms of stem cells (CD34+) and natural killer (NK)-cells has not been studied. It is also unknown whether PBSCs obtained from donors above 50 years would negatively influence engraftment or the incidence of graft-versus-host disease (GVHD) in the recipient. These questions were explored in a retrospective study including 167 recipients of an allogeneic HCT (52.7% after RIC) from a matched related sibling. Median donors’ age was 47 years [67 (40%) donors were > 50 years including 34 donors > 60 years]. Safety of mobilization and leukapheresis was age independent. Adequate PBSCs were collected from all donors though a higher CD34+-cell count was seen in donors < 50 years (p<0.0005), whereas harvests from donors > 60 years contained a higher NK-cell count (p=0.003). Engraftment in the recipient occurred after a median of 12 days and was not affected by an advanced donor age. Similarly, a higher incidence of GVHD was not seen in recipients of harvests from older donors. For the first time, we show that donor’s age, even beyond 60 years, does not preclude successful collection of PBSCs from siblings, does not jeopardize the short-term safety of the donor, and is not associated with deleterious sequels for the recipient in terms of engraftment or GVHD. As NK-cells have been implicated in the suppression of GVHD, and the mediation of a graft versus leukemia effect, the impact of the higher number of NK-cells in harvests from elderly donors on relapse of hematologic malignancies in the recipient warrants further studies.

Hemoglobin Zurich is a hemoglobin anomaly that results when one amino acid (histidine) is substituted by arginine at position 63 in the beta chain of hemoglobin molecules [β 63 His—Arg]. When Hemoglobin Zurich individuals are exposed to sulfonamide medication, their hemoglobins denature and subsequently form Heinz bodies which attach to the surface of the plasma membrane. Four Hemoglobin Zurich family members were the subjects of the current study. They included a splenectomized female subject, non-splenectomized female and male subjects, and a non-splenectomized female member without Hemoglobin Zurich as the control. The results collaborate that splenectomy increases the number of erythrocytes containing Heinz bodies in peripheral blood. The menstrual cycle apparently has no statistical affect on the increased ratio of Heinz body-containing erythrocytes to normal erythrocytes.

Malaria has exerted a major selective pressure for red blood cell (RBC) polymorphisms that confer protection to severe disease. There is a predominance of blood type O in malaria endemic regions, and several lines of evidence suggest that the outcome of Plasmodium falciparum infection may be influenced by ABO blood type antigens. Based on observations that enhanced phagocytosis of infected polymorphic RBCs is associated with protection to malaria in other red cell disorders, we hypothesized that infected type O RBCs may be more efficiently cleared by the innate immune system than infected type A and B RBCs. The present work demonstrates human macrophages in vitro and murine monocytes in vivo phagocytosed P. falciparum infected O RBCs more avidly than infected A and B RBCs independent of macrophage donor blood type. This difference in clearance may confer relative resistance to severe malaria in individuals with blood type O.

Malaria has exerted a major selective pressure for red blood cell (RBC) polymorphisms that confer protection to severe disease. There is a predominance of blood type O in malaria endemic regions, and several lines of evidence suggest that the outcome of Plasmodium falciparum infection may be influenced by ABO blood type antigens. Based on observations that enhanced phagocytosis of infected polymorphic RBCs is associated with protection to malaria in other red cell disorders, we hypothesized that infected type O RBCs may be more efficiently cleared by the innate immune system than infected type A and B RBCs. The present work demonstrates human macrophages in vitro and murine monocytes in vivo phagocytosed P. falciparum infected O RBCs more avidly than infected A and B RBCs independent of macrophage donor blood type. This difference in clearance may confer relative resistance to severe malaria in individuals with blood type O.

Strong evidence exists to support the use of a continuous (>8hr/day) hypoxic stimulus (either geographical altitude or simulated hypoxia) for enhancing the physical performance of endurance athletes. However, evidence supporting the use of acutely intermittent hypoxia (<1hr/day) for enhancing performance is less clear. The purpose of this study was to determine the effect of acutely intermittent hypoxic exposure on physiological and physical performance measures in team sport athletes. Using a single-blind controlled design, 14 trained basketball players (HYP = 7, CON = 7) were subjected to 15 days of intermittent hypoxia or normoxia. Each exposure was 37 minutes in duration (four cycles of 7min on, 3min off) and achieved using a nitrogen dilution device (Airo Ltd, Auckland, NZ). Prescribed peripheral oxygen saturation levels (SpO2) were maintained using an automatic biofeedback system and were progressively decreased from 86-89% on Day 1 to 75-78% on Day 15. A range of physiological measures and performance tests were conducted seven and two days before, and ten days after the intervention. The tests were: an incremental treadmill test to establish peak oxygen consumption ( peak) and running economy (RE), Yo-Yo Intermittent Recovery Test (YYIRT), and the Repeated High-Intensity Endurance Test (RHIET). Whole-blood samples were taken to assess a range of haematological measures. At 10 days post-intervention the HYP group, relative to the CON group, exhibited the following percent changes (±90% confidence limits, CL), and effect sizes (ES; ±90% CL); YYIRT running speedpeak (4.8; ± 1.6%, ES: 1.0 ± 0.4; benefit almost certain), RHIET total sprint time (-3.5; ± 1.6%; ES: -0.4 ± 0.2; benefit very likely), RHIET slowest sprint time (-5.0; ± 2.4%; ES: -0.5 ± 0.2; benefit very likely), soluble transferrin receptor (9.2; ± 10.1%; ES: 0.3 ± 0.3; benefit possible) running economy (11km.hr-1) (-9.0; ± 9.7%; ES: -0.7 ± 0.7; benefit likely, probable), and running economy (13km.hr-1) (-8.2; ± 6.9%; ES: -0.7 ± 0.5; benefit likely, probable). Changes to running economy (9km.hr-1), peak, maximum heart rate and lactate and all other blood measures were unclear. In conclusion, acutely intermittent hypoxia resulted in worthwhile changes in physical performance of trained basketball players in tests relevant to competition. However, the lack of clear change in physiological and haematological measures makes it difficult to determine the underlying mechanism for such enhancement.

Strong evidence exists to support the use of a continuous (>8hr/day) hypoxic stimulus (either geographical altitude or simulated hypoxia) for enhancing the physical performance of endurance athletes. However, evidence supporting the use of acutely intermittent hypoxia (<1hr/day) for enhancing performance is less clear. The purpose of this study was to determine the effect of acutely intermittent hypoxic exposure on physiological and physical performance measures in team sport athletes. Using a single-blind controlled design, 14 trained basketball players (HYP = 7, CON = 7) were subjected to 15 days of intermittent hypoxia or normoxia. Each exposure was 37 minutes in duration (four cycles of 7min on, 3min off) and achieved using a nitrogen dilution device (Airo Ltd, Auckland, NZ). Prescribed peripheral oxygen saturation levels (SpO2) were maintained using an automatic biofeedback system and were progressively decreased from 86-89% on Day 1 to 75-78% on Day 15. A range of physiological measures and performance tests were conducted seven and two days before, and ten days after the intervention. The tests were: an incremental treadmill test to establish peak oxygen consumption ( peak) and running economy (RE), Yo-Yo Intermittent Recovery Test (YYIRT), and the Repeated High-Intensity Endurance Test (RHIET). Whole-blood samples were taken to assess a range of haematological measures. At 10 days post-intervention the HYP group, relative to the CON group, exhibited the following percent changes (±90% confidence limits, CL), and effect sizes (ES; ±90% CL); YYIRT running speedpeak (4.8; ± 1.6%, ES: 1.0 ± 0.4; benefit almost certain), RHIET total sprint time (-3.5; ± 1.6%; ES: -0.4 ± 0.2; benefit very likely), RHIET slowest sprint time (-5.0; ± 2.4%; ES: -0.5 ± 0.2; benefit very likely), soluble transferrin receptor (9.2; ± 10.1%; ES: 0.3 ± 0.3; benefit possible) running economy (11km.hr-1) (-9.0; ± 9.7%; ES: -0.7 ± 0.7; benefit likely, probable), and running economy (13km.hr-1) (-8.2; ± 6.9%; ES: -0.7 ± 0.5; benefit likely, probable). Changes to running economy (9km.hr-1), peak, maximum heart rate and lactate and all other blood measures were unclear. In conclusion, acutely intermittent hypoxia resulted in worthwhile changes in physical performance of trained basketball players in tests relevant to competition. However, the lack of clear change in physiological and haematological measures makes it difficult to determine the underlying mechanism for such enhancement.

Thesis (Ph.D.)--Aberdeen University, 2008. / Title from web page (viewed on Feb. 26, 2009). Includes bibliographical references.

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