-
[show abstract]
[hide abstract]
ABSTRACT: MYD88 is a cytoplasmic adaptor protein involved in the antiviral response of blastic plasmacytoid dendritic cells.(1) A heterozygous mutation of exon 5 (c.794T>C) in MYD88 gene has been recently identified in diffuse large B-cell lymphomas (DLBCL) with activated B-cell-like phenotype,(2) primary cutaneous DLBCL,(3) primary central nervous system DLBCL,(4) as well as in a minority of cases of splenic marginal zone lymphoma(5) and chronic lymphocytic leukemia.(6) The corresponding single amino acid substitution (L265P) affects the Toll/IL-1 receptor (TIR) domain of MYD88, and favours tumour cell survival through IRAK1 (interleukin-1 receptor associated kinase)/IRAK4, and NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling.
British Journal of Dermatology 09/2012; · 3.67 Impact Factor
-
J Peveling-Oberhag,
G Crisman,
A Schmidt,
C Döring,
M Lucioni, L Arcaini,
S Rattotti,
S Hartmann,
A Piiper,
W-P Hofmann,
M Paulli,
R Küppers,
S Zeuzem,
M-L Hansmann
[show abstract]
[hide abstract]
ABSTRACT: The precise molecular pathogenesis of splenic marginal zone lymphoma (SMZL) is still unknown. Clinical and epidemiological data suggest that chronic hepatitis C virus (HCV) infection may have an etiological role in a subset of cases.We performed a large-scale microRNA (miRNA) expression profiling analysis of 381 miRNAs by quantitative reverse transcription PCR (Q-RT-PCR) of 26 microdissected splenic tissue samples (7 HCV(+) SMZL; 8 HCV(-) SMZL and 11 non-neoplastic splenic controls). Single assay Q-RT-PCR and miRNA in situ hybridization (miRNA-ISH) were used to confirm the results in an independent cohort. Unsupervised hierarchical clustering of miRNA expression profiles demonstrated a distinct signature of SMZL compared with the normal splenic marginal zone. Supervised analysis revealed differentially expressed miRNAs, including miRNAs with previously recognized tumor suppressive or oncogenic potential. Five miRNAs were found significantly overexpressed in SMZL, including miR-21, miR-155 and miR-146a, whereas seven miRNAs showed significantly reduced expression, including miR-139, miR-345, miR-125a and miR-126. Furthermore, we identified miR-26b, a miRNA known to have tumor suppressive properties, as significantly downregulated in SMZL arising in HCV-positive patients (P=0.0016). In conclusion, there is a characteristic dysregulation of miRNA expression in SMZL with a possible implication in its molecular tumorigenesis.
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 02/2012; 26(7):1654-62. · 8.30 Impact Factor
-
M Varettoni,
A Tedeschi, L Arcaini,
C Pascutto,
E Vismara,
E Orlandi,
F Ricci,
A Corso,
A Greco,
S Mangiacavalli,
M Lazzarino,
E Morra
[show abstract]
[hide abstract]
ABSTRACT: An increased incidence of second cancers has been reported in lymphoproliferative disorders.
We assessed the frequency, characteristics and predictive factors of second cancers in 230 patients with Waldenström macroglobulinemia (WM) and compared the incidence of second cancers in WM with that of an age- and sex-matched control population.
Twenty-two patients (10%) developed solid cancers and 10 (4%) second hematologic malignancies. In a competing risk model, the cumulative incidence of solid cancers was 12% at 10 years and 17% at 15 years while the incidence of hematologic malignancies was 6% and 8%, respectively. The overall risk of second cancer in WM was 1.69 times higher than expected (P = 0.002). WM patients were at increased risk for diffuse large B-cell lymphoma [standardized incidence ratio (SIR) 9.24, P < 0.0001], myelodisplastic syndrome/acute myeloid leukemia (SIR 8.4, P < 0.0001), brain cancer (SIR 8.05, P = 0.0004). The risk of a second hematologic malignancy was fourfold higher in patients previously treated, though not reaching statistical significance (P = 0.19).
WM patients are at higher risk of second cancers as compared with the general population. The sample size does not allow firm conclusions about the effect of therapy on the development of second cancers.
Annals of Oncology 04/2011; 23(2):411-5. · 6.43 Impact Factor
-
F Passamonti,
E Rumi,
D Pietra,
C Elena,
E Boveri, L Arcaini,
E Roncoroni,
C Astori,
M Merli,
S Boggi,
C Pascutto,
M Lazzarino,
M Cazzola
[show abstract]
[hide abstract]
ABSTRACT: We studied the relationship between JAK2 (V617F) mutant allele burden and clinical phenotype, disease progression and survival in patients with polycythemia vera (PV). The percentage of granulocyte mutant alleles was evaluated using a quantitative real-time polymerase chain reaction-based allelic discrimination assay. Of the 338 patients enrolled in this prospective study, 320 (94.7%) carried the JAK2 (V617F) mutation. Direct relationships were found between mutant allele burden and hemoglobin concentration (P=0.001), white blood cell count (P=0.001), spleen size (P=0.001) and age-adjusted bone marrow cellularity (P=0.002), while an inverse relationship was found with platelet count (P<0.001). During the study period, eight patients progressed to post-PV myelofibrosis (MF) (all carrying >50% mutant alleles), while 10 patients developed acute myeloid leukemia (AML). The mutant allele burden was significantly related to the risk of developing myelofibrosis (P=0.029) and retained its significant effect also in multivariable analysis (P=0.03). By contrast, the risk of developing AML as well as that of thrombosis was not significantly related to mutant allele burden. Leukocytosis did not affect thrombosis, MF, leukemia or survival. In conclusion, a JAK2 (V617F) allele burden >50% represents a risk factor for progression to MF in PV.
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 09/2010; 24(9):1574-9. · 8.30 Impact Factor
-
P Noris,
C Klersy,
M Zecca, L Arcaini,
A Pecci,
F Melazzini,
V Terulla,
V Bozzi,
C Ambaglio,
F Passamonti,
F Locatelli,
C L Balduini
[show abstract]
[hide abstract]
ABSTRACT: Distinguishing inherited thrombocytopenias from immune thrombocytopenia (ITP) can be difficult, and patients are therefore at risk of misdiagnosis and inappropriate treatments. Although it is known that the most common inherited forms of thrombocytopenia are characterized by increased platelet size, the diagnostic power of this feature has never been investigated.
The aim of this study was to test the hypothesis that platelet size can be used to differentiate ITP from inherited macrothrombocytopenias. Patients/methods: We measured mean platelet volume (MPV) and mean platelet diameter (MPD), within 2 h of blood sampling, in 35 patients with inherited macrothrombocytopenias [15 MYH9-related disease (MYH9-RD), three biallelic and 17 monoallelic Bernard-Soulier syndrome (BSS)], and 56 with ITP. Using receiving operating characteristic analysis, we searched for the best cut-off values to differentiate between these conditions.
As expected, platelets were larger in inherited macrothrombocytopenias than in ITP. An MPD larger than 3.3 mum differentiated MYH9-RD and BSS from ITP with 0.89 sensitivity and 0.88 specificity, and an MPV larger than 12.4 fL had 0.83 sensitivity and 0.89 specificity. Combining MPD with MPV increased sensitivity and specificity to 0.97 and 0.89, respectively.
Platelet size evaluation by both an appropriate cell counter and blood film examination is useful for differentiating inherited macrothrombocytopenias from ITP.
Journal of Thrombosis and Haemostasis 10/2009; 7(12):2131-6. · 5.73 Impact Factor
-
Bone marrow transplantation 10/2009; 45(4):798-800. · 3.00 Impact Factor
-
M Paulli, L Arcaini,
M Lucioni,
E Boveri,
D Capello,
F Passamonti,
M Merli,
S Rattotti,
D Rossi,
R Riboni,
E Berti,
U Magrini,
R Bruno,
G Gaidano,
M Lazzarino
[show abstract]
[hide abstract]
ABSTRACT: Hepatitis C virus (HCV) infection has been linked to lymphoproliferative disorders. Marginal zone B-cell lymphoma (MZL) represents one of the most frequent lymphoma subtypes associated with HCV infection. We describe an unusual subset of HCV-associated MZL characterized by subcutaneous presentation. Materials and methods: A series of 12 HCV-positive patients presenting with subcutaneous nodules that revealed lymphoma infiltration at biopsy. Molecular analysis of immunoglobulin heavy chain (IGH) gene rearrangement and FISH investigations for t(11;18)(q21;q21) and t(14;18)(q32;q21) were carried out in nine patients.
The 12 patients (median age 69.5 years), all with positive HCV serology, presented with single or multiple subcutaneous nodules resembling lipomas. Histologically the lesions showed lymphoid infiltrates, consistent with extranodal MZL of mucosa-associated lymphoid tissue (MALT). Functional IGH gene rearrangements were identified in nine tested patients, with somatic mutations in 82%, indicating a histogenesis from germinal center-experienced B cells. The t(11;18) was found in two of nine cases. Staging did not show any other lymphoma localization. In two patients, a response was achieved with antiviral treatment. Extracutaneous spread to MALT sites occurred in a case.
Our observations expand the spectrum of HCV-associated lymphomas to include a subset of extranodal MZL characterized by a novel primary 'lipoma-like' subcutaneous presentation and indolent clinical course.
Annals of Oncology 10/2009; 21(6):1189-95. · 6.43 Impact Factor
-
E Rumi,
F Passamonti,
L Pagano,
M Ammirabile, L Arcaini,
C Elena,
A Flagiello,
R Tedesco,
C Vercellati,
A P Marcello,
D Pietra,
R Moratti,
M Cazzola,
M Lazzarino
[show abstract]
[hide abstract]
ABSTRACT: High oxygen-affinity haemoglobin variants and 2,3-diphosphoglycerate (2,3-DPG) deficiency are inherited diseases generating low tissue oxygen tension and erythropoietin-driven erythrocytosis, that characterizes the clinical phenotype of patients. Level of blood p50 (the oxygen tension at which haemoglobin is 50% saturated) is used to recognize these conditions.
To define the clinical utility of blood p50 measurement in the diagnosis of isolated erythrocytosis.
Venous blood p50 measurement was included in the diagnostic work-up of 102 consecutive patients with isolated erythrocytosis besides blood cell count, arterial oxygen saturation, serum erythropoietin measurement and screening for JAK2 mutations.
Haematological Outpatient Section at University Hospital.
Seven patients had relative erythrocytosis. Among 95 patients with absolute erythrocytosis, 4 (4.2%) had decreased p50 level. The extended study of family members revealed a familial inheritance. Two families had haemoglobin variants already described as Haemoglobin Malmö and Haemoglobin San Diego. In one family, the proband had a new high oxygen-affinity haemoglobin variant (Haemoglobin Safi) resulting from the transversion C-->A at codon 81 of the alpha2-globin gene. In the last family, a deficiency of 2,3-DPG was found. Within the 91 patients with normal p50 values, 46 (51%) had secondary erythrocytosis, 13 (14%) polycythemia vera and 32 (35%) idiopathic erythrocytosis.
This study suggests that the investigation of blood p50 level may be useful to define diagnosis in patients with isolated erythrocytosis.
Journal of Internal Medicine 10/2008; 265(2):266-74. · 5.48 Impact Factor
-
E Boveri, L Arcaini,
M Merli,
F Passamonti,
S Rizzi,
L Vanelli,
E Rumi,
S Rattotti,
M Lucioni,
C Picone,
A Castello,
C Pascutto,
U Magrini,
M Lazzarino,
M Paulli
[show abstract]
[hide abstract]
ABSTRACT: Among marginal zone lymphomas (MZLs), bone marrow (BM) involvement features are well established in the splenic marginal zone lymphoma (SMZL); few data are available for extranodal marginal zone lymphoma (EMZL) and nodal marginal zone lymphoma (NMZL).
Incidence and patterns of histologic BM involvement are studied in 120 MZL patients (48 SMZL, 59 EMZL, 13 NMZL) at onset and during follow-up; relationships between clinical features, BM histology and flow cytometry (FC) are analyzed.
At diagnosis, BM involvement occurs in 90% SMZL, 22% EMZL and 54% NMZL (P<0.0001); at reevaluation, incidence raises to 96% in SMZL and 34% in EMZL. Concordance between histology and FC is found in 87% of cases; most discordant cases have positive histology but negative FC. SMZL and EMZL show a nodular BM infiltration; the interstitial pattern is frequent in NMZL (P<0.0001); sinusoidal localization is typical of SMZL, frequent in NMZL and occasional in EMZL (P=0.0001). Stage, leukemic disease, B symptoms, more than one extranodal involved site, splenomegaly, elevated beta2-microglobulin, serum monoclonal component, International Prognostic Index (IPI) and age-adjusted IPI are directly related to BM infiltration.
The different prevalence of BM involvement in MZL subtypes reflects their heterogeneous dissemination modalities; histology seems more sensible than FC to detect BM infiltration; development of BM involvement during follow-up is typical of EMZL.
Annals of Oncology 09/2008; 20(1):129-36. · 6.43 Impact Factor
-
L Arcaini,
F Montanari,
E P Alessandrino,
A Tucci,
E Brusamolino,
L Gargantini,
R Cairoli,
P Bernasconi,
F Passamonti,
M Bonfichi,
V Zoli,
C Bottelli,
S Calatroni,
D Troletti,
M Merli,
C Pascutto,
I Majolino,
G Rossi,
E Morra,
M Lazzarino
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the clinical outcome of patients with relapsed or refractory follicular lymphoma treated with immunochemotherapy, in vivo purging and high-dose therapy with autotransplant.
Sixty-four patients were enrolled in the trial. Primary end point was progression-free survival (PFS). Secondary end points were the in vivo purging effect on stem-cell harvest and the impact of molecular response on the outcome.
At enrollment, 59% of patients were PCR+ for bcl-2 rearrangement in bone marrow (PCR-informative). After the immunochemotherapy, before mobilization, 97% obtained complete response or partial response and 87% of patients informative for bcl-2 were molecularly negative. Sixty-one patients proceeded to in vivo purging and peripheral blood stem cell (PBSC) mobilization with rituximab and high-dose AraC. The median number of CD34+ cells collected was 16.6 x 10(6)/kg. Of 33 PCR-informative patients, the harvests resulted in PCR- in all. Fifty-eight patients received high-dose therapy and autotransplant of in vivo purged PBSC. After a median follow-up of 3.5 years, 41 patients are in complete remission. Five-year PFS is 59%.
This study demonstrates that patients with advanced relapsed or refractory follicular lymphoma treated with immunochemotherapy, in vivo purging and autotransplant may obtain long-lasting PFS. In bcl-2-positive patients, in vivo purging allows the harvest of lymphoma-free PBSC. Absence of the bcl-2 rearrangement after autotransplant is associated with persistent clinical remission.
Annals of Oncology 08/2008; 19(7):1331-5. · 6.43 Impact Factor
-
L Arcaini,
S Burcheri,
A Rossi,
M Paulli,
R Bruno,
F Passamonti,
E Brusamolino,
A Molteni,
A Pulsoni,
M C Cox, [......],
A Fabbri,
M Frezzato,
M T Voso,
F Zaja,
F Montanari,
M Merli,
C Pascutto,
E Morra,
S Cortelazzo,
M Lazzarino
[show abstract]
[hide abstract]
ABSTRACT: Hepatitis C virus (HCV) infection is frequently associated with B-cell non-Hodgkin's lymphomas. We investigated the prevalence of HCV infection in nongastric marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT) in order to define the relationship between the viral infection and the presenting features, treatment, and outcome.
We retrospectively studied 172 patients with a histological diagnosis of marginal zone B-cell lymphoma of MALT, except for stomach, and with available HCV serology, among a series of 208 patients.
HCV infection was documented in 60 patients (35%). Most HCV-positive patients (97%) showed a single MALT organ involvement. HCV-positive patients showed a more frequent involvement of skin (35%), salivary glands (25%), and orbit (15%). The majority of stage IV HCV-positive patients (71%) had a single MALT site with bone marrow involvement. The overall response rate was similar in HCV-positive (93%) and HCV-negative patients (87%). Overall survival (OS) and event-free survival (EFS) did not differ according to HCV infection. In multivariate analysis, advanced disease (stage III-IV) was associated with a poorer OS (P = 0.0001), irrespective of HCV serostatus.
This study shows that nongastric marginal zone lymphomas are characterized by a high prevalence of HCV infection. Patients with involvement of a single MALT site have the highest prevalence of HCV. HCV-positive nongastric lymphomas of MALT show an indolent course similar to HCV-negative patients and seem an ideal target for exploiting the antilymphoma activity of antiviral treatments.
Annals of Oncology 03/2007; 18(2):346-50. · 6.43 Impact Factor
-
C Visco, L Arcaini,
E Brusamolino,
S Burcheri,
A Ambrosetti,
M Merli,
E Bonoldi,
M Chilosi,
A Viglio,
M Lazzarino,
G Pizzolo,
F Rodeghiero
[show abstract]
[hide abstract]
ABSTRACT: Diffuse large B-cell lymphoma (DLBCL) has been correlated to hepatitis C virus (HCV) infection in few series, but characteristics and outcome of these patients remain undefined.
We analyzed 156 previously untreated consecutive HCV-positive patients with DLBCL observed between 1994 and 2004 in three major institutions from northern Italy.
Median age at presentation was 63 years and 8% of patients had DLBCL transformed from low-grade lymphomas. Spleen was the most frequently involved extranodal site, followed by liver and stomach. Treatment was delivered with cure-intent in 132 patients, while the remaining 24 patients received monochemotherapy or radiotherapy alone due to old age or seriously impaired hepatic function. Only five patients (4%) had to discontinue chemotherapy due to severe liver function impairment. The addition of rituximab did not seem to affect patients' tolerance to treatment. Five-year overall survival of the entire cohort was 72%, while 5-year progression-free survival (PFS) of the 132 patients treated with cure-intent was 51%. Hepatitis B virus co-infection, advanced Ann Arbor stage and nodal origin of the tumor resulted the strongest adverse prognostic factors.
Patients with HCV-positive DLBCL share distinctive clinical features. Future studies should prospectively evaluate the association between HCV and aggressive lymphomas.
Annals of Oncology 10/2006; 17(9):1434-40. · 6.43 Impact Factor
-
Leukemia 06/2005; 19(5):888-9. · 9.56 Impact Factor
-
L Arcaini,
E Orlandi,
E P Alessandrino,
I Iacona,
E Brusamolino,
M Bonfichi,
P Bernasconi,
S Calatroni,
A Tenore,
F Montanari,
D Troletti,
C Pascutto,
M Regazzi,
M Lazzarino
[show abstract]
[hide abstract]
ABSTRACT: We studied a model of in vivo purging with Rituximab and high-dose (HD) cytarabine in 14 patients with relapsed/refractory follicular lymphoma and two with refractory mantle cell lymphoma enrolled in a program of HD chemotherapy and autotransplant. After two courses of debulking immunochemotherapy with Rituximab, Vincristine and Cyclophosphamide, we used a combination of Rituximab, HD cytarabine and granulocyte colony-stimulating factor for peripheral blood stem cells (PBSC) mobilization. The median number of CD34+ cells collected was 14.69 x 10(6)/kg (range 5.74-73.2). Monitoring of peripheral CD19+ and CD20+ B cells prior to and throughout the purging period showed that a treatment with Rituximab, Vincristine and Cyclophosphamide results in a profound depletion of B cells in peripheral blood. B-cell depletion persists during mobilization with Rituximab and HD cytarabine allowing a collection of PBSC free of B cells (median CD19+ and CD20+ cells counts 0%). Of nine patients PCR positive for bcl-2 or bcl-1 in blood and marrow at the start of immunochemotherapy, all showed PCR-negative PBSC. In conclusion, in patients with indolent lymphoma, the concurrent administration of Rituximab and HD cytarabine is a safe and efficient method to obtain in vivo purged PBSC. Immunochemotherapy prior to mobilization produces B-cell depletion and seems to be a useful preparative step.
Bone Marrow Transplantation 08/2004; 34(2):175-9. · 3.75 Impact Factor
-
M Lazzarino, L Arcaini,
P Bernasconi,
E P Alessandrino,
L Gargantini,
R Cairoli,
E Orlandi,
C Astori,
E Brusamolino,
G Pagnucco,
A A Colombo,
S Calatroni,
I Iacona,
M B Regazzi,
E Morra
[show abstract]
[hide abstract]
ABSTRACT: Options for relapsed/refractory indolent lymphoma include chemotherapy, immunotherapy and high-dose therapy with autologous support. The best combination of these approaches, however, is not defined. We treated 10 patients with relapsed/refractory follicular (n = 7) or mantle cell lymphoma (n = 3) using chemotherapy, immunotherapy, high-dose therapy and autotransplant in a sequence of four phases, each designed to play a specific role in tumour eradication. After the debulking with VACOP-B (doxorubicin, cyclophosphamide, etoposide, vincristine, prednisone, bleomycin) (phase 1), 9/10 patients responded but none achieved a molecular response. After the immuno-chemotherapy phase, which combined Rituximab with vincristine and cyclophosphamide, seven patients were in complete response (CR) and three in good partial response (PR), and all those with a molecular marker of disease showed a disappearance of the signal from marrow and blood. Phase 3, which coupled high-dose cytarabine with Rituximab, was effective in mobilizing an adequate number of progenitor cells that were polymerase chain reaction negative in all informative cases. Phase 4 consisted of high-dose therapy with autologous support followed by two doses of Rituximab. Autograft was performed in nine patients. The haematopoietic recovery was as expected. This sequence of chemotherapy, immuno-chemotherapy, stem cell mobilization with in vivo purging and autotransplant, organized in four blocks of treatment, was simple to administer and devoid of toxic effects. It permits rapid attainment of clinical and molecular response and enables the harvest of lymphoma-free peripheral blood progenitor cells even in heavily pretreated patients with relapsed or refractory disease.
British Journal of Haematology 02/2002; 116(1):229-35. · 4.94 Impact Factor
-
Haematologica 11/2001; 86(10):E24. · 6.42 Impact Factor
-
A Corso, L Arcaini,
S Mangiacavalli,
C Astori,
E Orlandi,
A Lorenzi,
F Passamonti,
C Klersy,
C Pascutto,
A Canevari-Sciorati,
M Lazzarino
[show abstract]
[hide abstract]
ABSTRACT: Skeletal involvement is typical of multiple myeloma (MM) and its occurrence increases with the progression of the disease. We performed a study to evaluate the clinical importance of osteocalcin (bone gla-protein, BGP) and bone alkaline phosphatase (b-AP) as indices of osteoblastic activity, and deoxypyridoline (DPD) as a marker of bone resorption.
Fifty-two MM patients, 39 patients with monoclonal gammopathy of undetermined significance (MGUS), and 30 normal controls entered the study. Of the 52 MM patients, 10 showed lytic lesions at standard X-rays and 42 did not; 21 were untreated and 31 had been treated with chemotherapy (combined with bisphophonates in 15). Of these last, 12 had progressive disease and 19 were in plateau phase.
DPD levels were higher in MM patients than in patients with MGUS or healthy controls (p = 0.0001 and p = 0.0008, respectively). No statistical differences were seen between patients with MGUS and healthy controls. BGP serum levels were significantly lower in MM patients than in MGUS patients (p = 0.001) or healthy controls (p = 0.001). b-AP was significantly higher in MGUS patients than in MM patients (p = 0.04). Biochemical parameters were analyzed in a continuous fashion and after dichotomization into low and high values with respect to normal ones. Abnormal high values of DPD showed statistically significant correlations with presence of osteolysis (p = 0.008), advanced stage (p = 0.03) and abnormal beta2-microglobulin (beta2M) values (p = 0.03), while DPD as a continuous variable correlated significantly only with the presence of osteolysis (p = 0.02). In contrast, neither BGP nor b-AP showed statistical correlations with the presence of lytic lesions, or with other clinical or laboratory parameters. In 15 patients followed with serial controls, modifications of DPD levels reflected bone disease status well. Of the 42 patients without radiologic evidence of skeletal lesions, 15 had abnormal DPD values. Spinal magnetic resonance imaging (MRI) showed initial lytic lesions in 10 of them.
Biochemical markers of bone metabolism are useful in evaluating and monitoring skeletal involvement in MM patients. They may help clinicians to identify: 1) from among patients without radiologic evidence of lytic lesions, those who deserve more accurate radiologic examinations (namely MRI); 2) from among asymptomatic patients, and in association with spinal MRI, those patients at higher risk of progression who might benefit from early treatment.
Haematologica 05/2001; 86(4):394-8. · 6.42 Impact Factor
-
A Schneider,
R E Greene,
C Keyl,
G Bandinelli,
C Passino,
G Spadacini,
M Bonfichi, L Arcaini,
L Malcovati,
A Boiardi,
P Feil,
L Bernardi
[show abstract]
[hide abstract]
ABSTRACT: Regulation of the vascular system may limit physical performance and contribute to adaptation to high altitude. We evaluated vascular function in 10 Himalayan high-altitude natives and 10 recently acclimatized sea-level natives at an altitude of 5,050 m.
We registered electrocardiogram, blood flow velocity in the common femoral artery, and blood pressure in the radial artery using non-invasive methods under baseline conditions, and during maximal vasodilation after 2 min leg occlusion. Vascular mechanics were characterized by estimating pulse wave velocity and input impedance.
Pulse wave velocity and parameters of input impedance did not differ between groups under baseline conditions. In the post-ischemic period, the ratio between maximal hyperemic and baseline blood flow velocity was significantly higher in the high-altitude than in the sea-level natives (5.7 +/- 2.5 versus 3.8 +/- 1.2, P < 0.05). The leg vascular resistance decreased in the post-occlusive period without differences between groups. Characteristic impedance decreased in the post-ischemic period by about one third of the baseline level without differences between groups. The post-ischemic decrease of input impedance modulus was more marked in the high-altitude than in the sea-level natives at low frequencies (28 +/- 12 versus 6.4 +/- 20% at 2 Hz, P < 0.01).
Our results demonstrate a superior ability to increase blood flow velocity as a response to muscular ischemia in high-altitude natives compared to sea-level natives. This phenomenon may be associated with a more effective coupling between blood pressure and blood flow which is probably caused by differences in conduit vessel function.
Journal of Hypertension 02/2001; 19(2):213-22. · 4.02 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This study was performed to investigate the influence of breathing control on the autonomic cardiac regulation at high altitude in adapted and non-adapted awake subjects. We recorded electrocardiogram and pulse oximetry in 14 short-term acclimatized lowlanders and 14 Himalayan Sherpas during resting conditions at an altitude of 5,050 m. Spectrum analysis was performed on synchronized 15 min periods of R-R intervals and the oxygen saturation of arterial blood (SaO2). Despite mean SaO2 being similar in lowlanders and Himalayan Sherpas [78.5 (SD 7.0)% compared to 79.4 (SD5.8)%, respectively], fluctuations in SaO2 were significantly increased in lowlanders compared to Sherpas, thus indicating an unstable regulation of respiration control in lowlanders. Regression analysis demonstrated a significant relationship between spectrum power of SaO2 and the relative power of R-R intervals in the frequency band between 0.01 and 0.08 Hz in lowlanders, but not in Sherpas. Our results demonstrate differences in respiratory and autonomic cardiac control between non-adapted lowlanders and Himalayan high-altitude residents and indicate that unstable breathing control during chronic hypobaric hypoxia is significantly correlated with the autonomic cardiocirculatory regulation.
Arbeitsphysiologie 01/2001; 83(6):481-6. · 2.15 Impact Factor
-
M Bonfichi,
A Balduini, L Arcaini,
A Lorenzi,
C Marseglia,
L Malcovati,
L Bernardi,
C Passino,
G Spandacini,
P Feil,
C Keyl,
A Schneider,
A Boiardi,
G Bandinelli,
R E Greene,
C Bernasconi
British Journal of Haematology 07/2000; 109(4):895-6. · 4.94 Impact Factor
