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Biomedical subjects

K Ault

Publications and source records attributed to K Ault.

At least 19 recordsLinked to original sources
PubMed2001

Predictors of Chlamydia trachomatis infection among women attending rural Midwest family planning clinics.

OBJECTIVE: To determine predictors of Chlamydia trachomatis infection among women 14-24 years of age attending family planning clinics throughout a rural Midwestern state. METHODS: The study population included 16,756 women between the ages of 14 and 24 years attending family planning clinics for annual examinations throughout the state of Iowa in 1997. All women under 25 years of age having annual exams were tested for C. trachomatis during the visit. At the time of exam, both behavioral and demographic data were collected on all women participating in the study. RESULTS: The majority of women in the study (96%) reported no symptoms of chlamydia. Only 2.5% of all women had a positive test result. In the multivariate model, the odds ratios were significantly increased among the youngest age (14-17 years; OR = 2.2), those with mucopurulent cervicitis (OR = 3.4), cervical friability (OR = 2.2), symptomatic for infection (OR = 1.8), risk history (OR = 1.6), and black race (OR = 1.2) and predictive of a C. trachomatis infection. CONCLUSIONS: Risk factors predictive of C. trachomatis infection among younger aged women attending family planning clinics in a Midwest rural population are consistent with predictors of infection among women attending family planning clinics across the United States. The overall findings suggest the importance of developing screening guidelines as a means of lowering chlamydia rates. This may be a particularly difficult task in light of the low rate of symptoms that would lead a woman to seek medical care, even in younger age women who are at higher risk. In addition, screening guidelines would be more difficult to implement in a rural setting.

Adolescent↗
PubMed2001

Incidence of post transplant myelodysplasia/acute leukemia in non-Hodgkin's lymphoma patients compared with Hodgkin's disease patients undergoing autologous transplantation following cyclophosphamide, carmustine, and etoposide (CBV).

Secondary malignancies, particularly myelodysplasia (MDS), are serious events following high dose therapy with autologous stem cell support. We observed a higher frequency of secondary malignancies in patients with Hodgkin's disease (HD) than in patients with non-Hodgkin's lymphoma (NHL) undergoing high dose therapy with the same non-TBI conditioning regimen. Three hundred patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) were treated with cyclophosphamide, carmustine and etoposide and autologous stem cell support from 1986 through 1994. Median follow up of survivors is 3.9 years. Five-year survival is 51% for HD and 48% for NHL. Eleven patients developed second malignancies (9/150 treated for HD vs. 2/150 treated for NHL) a median of 2.4 years from transplantation and 5.2 years from initial diagnosis. Six patients had myelodysplasia or acute leukemia (MDS/AML) and 5 had lymphomas or solid tumors. Actuarial risk of MDS/AML at five years for patients transplanted for non-Hodgkin's lymphoma is 3% (95% CI 0.6-9.6%). HD patients had significantly different pretreatment characteristics than patients with NHL. A Cox model showed that greater number of prior relapses and prior radiation therapy were significant risk factors for the development of MDS/AML. These data suggest that CBV is associated with a lower risk of secondary MDS/AML than TBI containing regimens and that much of the risk is associated with the pre-transplantation therapy. The use of autotransplantation early in the course of therapy for relapsed lymphoma might prevent some cases of MDS/AML.

Acute Disease↗
PubMed2001

Fox (forkhead) genes are involved in the dorso-ventral patterning of the Xenopus mesoderm.

Fox (forkhead/winged helix) genes encode a family of transcription factors that are involved in embryonic pattern formation, regulation of tissue specific gene expression and tumorigenesis. Several of them are transcribed during Xenopus embryogenesis and are important for the patterning of ectoderm, mesoderm and endoderm. We have isolated three forkhead genes that are activated during gastrulation and play an important role in the dorso-ventral patterning of the mesoderm. XFKH1 (FoxA4b), the first vertebrate forkhead gene to be implicated in embryonic pattern formation, is expressed in the Spemann-Mangold organizer region and later in the embryonic notochord. XFKH7, the Xenopus orthologue of the murine Mfh1(Foxc2), is expressed in the presomitic mesoderm, but not in the notochord or lateral plate mesoderm. Finally, XFD-13'(FoxF1b)1 is expressed in the lateral plate mesoderm, but not in the notochord or presomitic mesoderm. Expression pattern and functional experiments indicate that these three forkhead genes are involved in the dorso-ventral patterning of the mesoderm.

Amino Acid Sequence↗
PubMed2000

Molecular basis for differing antineurogenic effects of GATA-1a and GATA-1b in Xenopus.

The erythroid transcription factor GATA-1 in Xenopus has been cloned as a pair of presumably duplicated genes designated as xGATA-1a and xGATA-1b. Although both xGATA-1a and xGATA-1b are able to stimulate erythropoiesis, only xGATA-1b is capable of inhibiting neurogenesis in Xenopus embryos. Chimeras of these two genes were constructed by permuting coding and untranslated regions (UTR) on both ends of these two xGATA-1, and their neurogenesis-inhibitory effects were studied. These results reveal that (1) sequence variations between the coding regions alone do not account for the neurogenesis effect; (2) 3' UTR of xGATA-1a causes the loss of the neurogenesis inhibition of xGATA-1b; (3) 3' UTR of xGATA-1b is essential to inhibit neurogenesis. In addition, the presence of either UTR does not affect the stability of the mRNA in vitro. These observations suggest the influence of 3' UTR in xGATA-1 on the inhibition of neurogenesis.

3' Untranslated Regions↗
PubMed1999

Deficient platelet-derived nitric oxide and enhanced hemostasis in mice lacking the NOSIII gene.

Endothelial nitric oxide synthase (eNOS) has been identified in human platelets. Although platelet-derived nitric oxide (NO) has been shown to inhibit platelet recruitment in vitro, its role in the regulation of the hemostatic response in vivo has not been characterized. To define the role of platelet-derived NO in vivo, we studied mice that lacked a functional eNOS gene (NOSIII). Surface P-selectin expression in platelets from eNOS-deficient mice was not significantly altered; however, bleeding times were markedly decreased in eNOS-deficient versus wild-type mice (77.2+/-3 versus 133.4+/-3 seconds, P<0.00005). To determine the contribution of endothelium- versus platelet-derived NO to the bleeding time, isolated platelets from either eNOS-deficient or wild-type mice were transfused into a thrombocytopenic eNOS-deficient mouse and the bleeding time was measured. The bleeding times in mice transfused with eNOS-deficient platelets were significantly decreased compared with mice transfused with wild-type platelets (Deltableeding time, -24.6+/-9.1 and -3.4+/-5.3 seconds, respectively; P<0.04). Platelet recruitment was studied by measuring serotonin release from a second recruitable population of platelets that were added to stimulated platelets at the peak of NO production. There was 40.3+/-3.7% and 52. 0+/-2.1% serotonin release for platelets added to wild-type or eNOS-deficient platelets, respectively (P<0.05). In summary, mice that lacked eNOS had markedly decreased bleeding times even after endothelial NO production was controlled. These data suggest that the lack of platelet-derived NO alters in vivo hemostatic response by increasing platelet recruitment. Thus, these data support a role for platelet-derived NO production in the regulation of hemostasis.

Animals↗
PubMed1999

Consequences of GATA-1 deficiency in megakaryocytes and platelets.

In the absence of the hematopoietic transcription factor GATA-1, mice develop thrombocytopenia and an increased number of megakaryocytes characterized by marked ultrastructural abnormalities. These observations establish a critical role for GATA-1 in megakaryopoiesis and raise the question as to how GATA-1 influences megakaryocyte maturation and platelet production. To begin to address this, we have performed a more detailed examination of the megakaryocytes and platelets produced in mice that lack GATA-1 in this lineage. Our analysis demonstrates that compared with their normal counterparts, GATA-1-deficient primary megakaryocytes exhibit significant hyperproliferation in liquid culture, suggesting that the megakaryocytosis seen in animals is nonreactive. Morphologically, these mutant megakaryocytes are small and show evidence of retarded nuclear and cytoplasmic development. A significant proportion of these cells do not undergo endomitosis and express markedly lower levels of mRNA of all megakaryocyte-associated genes tested, including GPIbalpha, GPIbbeta, platelet factor 4 (PF4), c-mpl, and p45 NF-E2. These results are consistent with regulation of a program of megakaryocytic differentiation by GATA-1. Bleeding times are significantly prolonged in mutant animals. GATA-1-deficient platelets show abnormal ultrastructure, reminiscent of the megakaryocytes from which they are derived, and exhibit modest but selective defects in platelet activation in response to thrombin or to the combination of adenosine diphosphate (ADP) and epinephrine. Our findings indicate that GATA-1 serves multiple functions in megakaryocyte development, influencing both cellular growth and maturation.

Animals↗
PubMed1999

Cocaine effects on immunocompetent cells: an observation of in vitro cocaine exposure.

This study investigated in vitro effects of cocaine on the function of T and B lymphocytes, natural killer cells and macrophages in a mouse model. In mature C57BL/6J mice (60-90 day-old), splenocytes were cultured with cocaine at different concentrations ranging from 4 to 64 microg/ml for 24 h. The exposure to cocaine in vitro was found to affect (1) T cell function, with reduced responses to stimulation of Con-A, PHA and Interleukin 2, and decreased production of gamma-IFN; (2) B cell function, with reduced response to LPS; (3) natural killer cell function, with attenuated killing capacity; (4) monocyte-macrophage function, with decreased ability to inhibit the growth of tumor cells. The results of the study indicated a direct cocaine effect on four major immune competent cells, and the generally suppressive effects of in vitro cocaine exposure may be related to its in vivo action on the immune system.

Animals↗
PubMed1998

Randomized trial of an oral platelet glycoprotein IIb/IIIa antagonist, sibrafiban, in patients after an acute coronary syndrome: results of the TIMI 12 trial. Thrombolysis in Myocardial Infarction.

BACKGROUND: Inhibitors of the platelet glycoprotein IIb/IIIa receptor given intravenously have been shown to be effective in reducing ischemic complications after coronary angioplasty and in unstable angina, making this a promising new class of agents for the treatment and prevention of ischemic events in patients with acute coronary syndromes. Sibrafiban (Ro 48-3657) is an oral, peptidomimetic, selective antagonist of the glycoprotein IIb/IIIa receptor. METHODS AND RESULTS: The Thrombolysis in Myocardial Infarction (TIMI) 12 trial was a phase II, double-blind, dose-ranging trial designed to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of sibrafiban in 329 patients after acute coronary syndromes. In the PK/PD cohort of TIMI 12, 106 patients were randomized to receive one of seven dosing regimens of sibrafiban, ranging from 5 mg daily to 10 mg twice daily for 28 days. In the safety cohort, 223 patients were randomized to one of four dose regimens of sibrafiban (ranging from 5 mg twice daily to 15 mg once daily) or aspirin for 28 days. High levels of platelet inhibition were achieved: mean peak values ranged from 47% to 97% inhibition of 20 micromol/L ADP-induced platelet aggregation on day 28 across the seven doses. Twice-daily dosing provided more sustained platelet inhibition (mean inhibition, 36% to 86% on day 28), whereas platelet inhibition returned to baseline levels by 24 hours with once-daily dosing. Major hemorrhage occurred in 1.5% of patients treated with sibrafiban and in 1.9% of patients treated with aspirin. Protocol-defined "minor" bleeding, usually mucocutaneous, occurred in 0% to 32% of patients in the various sibrafiban groups and in none of the patients treated with aspirin. Minor bleeding was related to total daily dose (P=.002), once- versus twice-daily dosing (P<.0001), renal function (P<.0001), and presentation with unstable angina (P<.01). CONCLUSIONS: The oral glycoprotein IIb/IIIa antagonist sibrafiban achieved effective, long-term platelet inhibition with a clear dose-response but at the expense of a relatively high incidence of minor bleeding. Oral IIb/IIIa inhibition deserves further study as a new treatment strategy in patients after acute coronary syndromes.

Acute Disease↗
PubMed1998

Interactive effects of cocaine and gender on thymocytes: a study of in vivo repeated cocaine exposure.

This study used a mouse model including both sexes to assess the impact of repeat cocaine exposure on the differentiation and function of T cell in thymus. Cocaine hydrochloride in 0.9% saline, 5 mg or 40 mg/kg, was administrated by i.p. injection to C57BL/6 mice for 10 days. Thymocytes were obtained 24 h after the 10th injection. Repeat in vivo cocaine exposure inhibited the proliferation of T lymphocytes in response to Con-A and Con-A plus anti-CD28. The proliferation induced by IL-2 in the Con-A stimulated T blasts was attenuated in cocaine treated mice. These effects were seen at a lower cocaine dose in female mice. The total number of thymocytes was reduced. Although the percentage of mature thymocytes (CD4+ CD8- and CD4- CD8+ cells) was not altered, the absolute cell numbers were attenuated. Both percentage and absolute cell number of immature thymocytes (CD4+ CD8+) decreased and the pre-mature (CD4- CD8-) cells increased. CD28 and CD25 expression were attenuated in Con-A stimulated thymocytes of mice treated with cocaine at 40 mg/kg. Interleukin 2 production was not significantly altered, however, gamma-IFN production was decreased by cocaine exposure at 40 mg/kg. In conclusion, cocaine exerts inhibitory effects on the function of mature thymocytes, and on the differentiation of thymocytes. A gender difference in response to cocaine was noted in that female mice were more sensitive to lower dose of cocaine exposure.

Animals↗
PubMed1998

Elevated plasma glycocalicin levels and decreased ristocetin-induced platelet agglutination in hemodialysis patients.

A bleeding diathesis caused by platelet dysfunction is a major cause of morbidity and mortality in patients with uremia. Platelet adhesion to vascular subendothelium is defective in uremia and depends on the interactions of the platelet glycoprotein (GP) Ib/IX complex with the vascular wall. We measured levels of platelet surface GPIb, platelet surface GPIX, plasma glycocalicin (a product of enzymatic cleavage of GPIb), and ristocetin-induced platelet agglutination (RIPA) in patients undergoing chronic hemodialysis compared with patients undergoing peritoneal dialysis and healthy controls. Patients undergoing chronic maintenance hemodialysis have higher levels of platelet surface expression of GPIb (187+/-10 fluorescent units; P < 0.001) than either healthy controls (120+/-4 fluorescent units; P < 0.001) or patients undergoing peritoneal dialysis (127+/-5 fluorescent units; P < 0.001). Similar changes were observed in platelet surface GPIX. Plasma glycocalicin levels were elevated in chronic hemodialysis patients (71+/-5 nmol/L) compared with healthy controls (36+/-3 nmol/L; P < 0.001). Plasma glycocalicin levels also increased progressively throughout the hemodialysis procedure. The slope of RIPA was significantly lower in chronic hemodialysis patients (46+/-3) than in either healthy controls (67+/-4; P < 0.05) or peritoneal dialysis patients (62+/-2; P < 0.05). In conclusion, patients undergoing chronic maintenance hemodialysis have increased plasma glycocalicin levels and decreased RIPA, which may contribute to diminished platelet adhesion to vascular subendothelium and increased bleeding associated with uremia.

Blood Platelets↗
PubMed1997

Loss of heterozygosity in human ovarian cancer on chromosome 19q.

Abnormalities in the function of oncogenes and tumor suppressor genes have been associated with many human malignancies. The recognition of sites of loss of heterozygosity (LOH) has led to the identification of such genes. We previously reported that abnormalities of mRNA expression of ERCC1 and ERCC2 may be characteristic of epithelial ovarian carcinoma and brain tumors. This led to an investigation of chromosome 19q13.2-q13.4 which contains these DNA repair genes. A 7-Mb region was analyzed using six microsatellite repeats. Loss of heterozygosity has been identified in 53% (8/15) of cases at marker D19S246 which lies in a 2-Mb segment between HRC and KLK1. The genetic material both centromeric and telomeric to the region of loss was conserved. This area is telomeric to three DNA repair genes where LIG1 is 1-Mb centromeric and ERCC1 and ERCC2 are 3.5- and 4.0-Mb centromeric, respectively. These findings represent the first report of a biologically significant rate of LOH on chromosome 19q13.2-q13.4 in human ovarian carcinoma.

Adolescent↗
PubMed1997

Increased reticulated platelets in dialysis patients.

The purpose of this study was to measure the percent reticulated platelets and platelet counts in patients on chronic hemodialysis, peritoneal dialysis and normal volunteers. The relationship between the percent reticulated platelets and the platelet count can then be used to determine the rate of platelet turnover. Platelet rich plasma was obtained, platelets were fixed and incubated with thiazole orange and analyzed for the percent reticulated platelets by flow cytometry. Normal controls had a mean of 2.77 +/- 0.17% reticulated platelets while peritoneal dialysis patients had a mean percent reticulated platelets of 6.92 +/- 0.68 (P < 0.00001). Chronic hemodialysis patients had a mean percent reticulated platelets of 8.21 +/- 0.36 (P < 0.00001 vs. normal controls and P = 0.05 vs. peritoneal dialysis patients). Platelet counts did not differ significantly among the three groups. The identity of reticulated platelets was confirmed in experiments measuring platelet specific glycoproteins, experiments using RNase, and in mixing experiments with normal and uremic platelets and plasma. We conclude that dialysis patients have a marked increase in circulating reticulated platelets compared to normal controls, indicating accelerated platelet turnover. Increased platelet activation and turnover may contribute to the qualitative platelet dysfunction observed in dialysis patients.

Blood Platelet Disorders↗
PubMed1997

Identification and characterization of three new promoter/operators from Corynebacterium diphtheriae that are regulated by the diphtheria toxin repressor (DtxR) and iron.

DtxR is a dimeric, sequence-specific, DNA-binding protein that functions as an iron-dependent, negative global regulator in Corynebacterium diphtheriae. Under high-iron conditions, DtxR represses the synthesis of diphtheria toxin, corynebacterial siderophore, and other components of the high-affinity iron uptake system. Three DtxR-regulated promoter/operators designated tox, IRP1, and IRP2 were reported previously. In this study, we identified and characterized three additional DtxR-regulated promoter/operators from C. diphtheriae designated IRP3, IRP4, and IRP5. When beta-galactosidase was expressed from these three new promoter/ operators in Escherichia coli containing dtxR+ on pDSK29, enzyme levels were 5- to 30-fold lower during high-iron growth than during low-iron growth. In gel shift assays, the mobility of DNA fragments containing each promoter/operator decreased in the presence of purified DtxR and Co2+. In footprinting assays, DtxR protected 36-, 35-, and 30-bp regions of IRP3, IRP4, and IRP5, respectively, from cleavage by DNase I. In the 19-bp core of each promoter/operator, 12 or 13 bp matched the consensus for the DtxR-binding site. The putative polypeptides encoded by the open reading frames (ORFs) downstream from IRP3 and IRP4 were homologous, respectively, to several bacterial transcriptional regulators and to the deduced polypeptide encoded by an ORF located between the E. coli genes for primosomal replication protein N and adenine phosphoribosyltransferase. The putative polypeptide encoded by the ORF downstream from IRP5 was not homologous to any sequence in the protein database at the National Center for Biotechnology Information. When the ORFs downstream from IRP3 and IRP4 were expressed under the control of the phage T7 promoter in E. coli, polypeptide products of the predicted sizes were detected in small amounts by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

Amino Acid Sequence↗
PubMed1997

High-dose cyclophosphamide, carmustine, and etoposide with autologous transplantation in Hodgkin's disease: a prognostic model for treatment outcomes.

PURPOSE: To identify clinical factors predictive of treatment outcome after high-dose chemotherapy (HDC) for Hodgkin's disease and to develop a prognostic model for progression-free and overall survival. PATIENTS AND METHODS: 102 patients with relapsed or refractory Hodgkin's disease were treated with high-dose cyclophosphamide, carmustine, and etoposide and autologous marrow and/or peripheral blood progenitor cell support. Median follow-up of survivors is 4.1 years (1.8-7.5 years). Factors potentially important for treatment outcome were examined in univariate analysis, and Cox regression with forward selection was performed. A prognostic model was developed. RESULTS: Poorer progression-free and overall survival were associated with nodular sclerosis histology, abnormal performance status, progressive disease at HDC, more than one extranodal site of disease, and shorter time from initial diagnosis to HDC. These factors and the presence of B symptoms at relapse also predicted for decreased overall survival. Progressive disease immediately prior to HDC, more than one extranodal disease site, and abnormal performance status retained significance for both progression-free and overall survival in multivariate analysis. Progression-free and overall survival are 42% (95% confidence interval, CI, 34 to 53) and 65% (95% CI 54 to 73) at three years. A model based on number of risk factors present divides patients into low, intermediate, and high risk groups with three-year actuarial survival of 82%, 56%, and 19% respectively. Treatment outcome for patients treated with HDC at first chemotherapy relapse was not significantly different from that of the group overall (p > 0.3). CONCLUSIONS: Asymptomatic patients with Hodgkin's disease involving at most one extranodal site whose disease is controlled by conventional dose chemotherapy or radiation therapy at the time of HDC have good outcomes after this therapy. Presence of increasing numbers of risk factors are associated with poorer outcomes. Results of HDC compare favorably to those of standard dose salvage therapy. These data can be used to estimate likely outcomes in patients undergoing HDC for Hodgkin's disease, to identify potential candidates for innovative therapies, and to evaluate strategies for the optimal use of HDC in Hodgkin's disease.

Adult↗
PubMed1996

Clozapine-induced myotoxicity in patients with chronic psychotic disorders.

Muscle dysfunction related to clozapine treatment is largely unrecognized. We evaluated weekly creatine kinase (CK) levels in 37 consecutive clozapine-treated outpatients with chronic psychotic disorders. Those with CK elevations underwent clinical neurologic evaluation, electromyography (EMG), and nerve conduction studies. Patients with probable myopathy had a quadriceps muscle biopsy. Twenty control patients had a single CK level determination. Twenty-nine of 37 clozapine-treated patients had CK elevations. Three patients had extreme CK elevations (> 20,000 IU/L), without myoglobinuria. Mean CK levels were significantly greater in clozapine patients (194 IU/L) than in control patients (142.3, p = 0.033). Of 18 clozapine-treated patients evaluated clinically, 6 had mild proximal weakness. EMG in 13 patients was myopathic in 5, normal in 5, and neurogenic in 3. Muscle biopsy in 5 patients showed rare regenerating myofibers and mild acute denervation (1), mild type II fiber atrophy (1), minimal acute denervation (1), and normal muscle (2). In conclusion, clozapine therapy may be associated with CK elevations and, rarely, mild myopathy.

Chronic Disease↗
PubMed1995

Dynamic Nature of Thrombin Generation, Fibrin Formation, and Platelet Activation in Unstable Angina and Non-Q-Wave Myocardial Infarction.

Thrombin and platelets are directly involved in arterial thrombosis, typically occurring at sites of atherosclerotic plaque rupture among patients with acute coronary syndromes. Understanding the dynamic nature of pathologic thrombosis has important clinical implications. Methods: Fibrinopeptide A (FPA), thrombin-antithrombin complexes (TAT), and prothrombin activation fragment 1.2 (F1.2), plasma markers of fibrin formation (thrombin activity) and thrombin generation, and platelet activation, determined by the recognition of a surface-expressed platelet alpha-granule protein, P-selectin, using flow cytometry, were measured in 36 consecutive patients with unstable angina and non-Q-wave myocardial infarction participating in the Thrombolysis In Myocardial Ischemia (TIMI) III B trial. Results: Thrombin generation (TAT 12.1 +/- 17.8 ng/ml vs. 3.4 +/- 1.0 ng/ml; F1.2 0.19 +/- 0.14 nmol/l vs. 0.12 +/- 0.8 nmol/l), fibrin formation (FPA 15.8 +/- 23.5 ng/ml vs. 7.5 +/- 2.3 ng/ml), and platelet activation) 10.6 +/- 2.4% vs. 2.5 +/- 2.0%) were increased significantly in patients compared with healthy, age-matched controls (p < 0.01). Fibrin formation, represented by plasma FPA levels, did not correlate with the percentage of activated platelets (r = -.10, p = 0.69). Thrombin generation and platelet activation also did not correlate. A statistically insignificant trend between TAT and platelet activation was observed (r =.42, p = 0.07); however, even with TAT levels in excess of 20 ng/ml (nearly sixfold greater than normal healthy controls) platelet activation was increased by only 1.7-fold. Conclusions: Thrombin generation, fibrin formation, and platelet activation are increased modestly among patients with unstable angina and non-Q-wave myocardial infarction. Despite the involvement of platelets and coagulation proteins in arterial thrombotic processes, their relative contributions may vary, providing a pathophysiologic basis for the dynamic expression of di sease and response to treatment observed commonly in clinical practice.

Journal Article↗
PubMed1995

Spontaneous platelet activation and aggregation during obstructive sleep apnea and its response to therapy with nasal continuous positive airway pressure. A preliminary investigation.

STUDY OBJECTIVE: To determine whether alterations of platelet reactivity occur during obstructive sleep apnea (OSA) and, if so, whether therapy with nasal-continuous positive airway pressure (N-CPAP) alters this reactivity. DESIGN: Patients with suspected moderate to severe OSA had blood drawn for spontaneous platelet aggregation (sAGG) and activation (sACT) measurements at hourly intervals during diagnostic polysomnography (PSG) and, in those with confirmed OSA, on a separate night during which N-CPAP was applied. SETTING: Tertiary care center sleep laboratory. PATIENTS: Six patients with OSA had matched blood samples drawn on both diagnostic and N-CPAP treatment nights. Five patients without confirmed OSA served as controls. INTERVENTIONS: N-CPAP was applied to those patients with OSA and pressures adjusted with goals of eliminating apneas; N-CPAP was then maintained through the night. MEASUREMENTS AND RESULTS: sACT and sAGG were measured using flow cytometric determination of P-selectin expression using a monoclonal antibody. Platelet aggregation was assessed by measuring the proportion of platelets larger than resting platelets by light scatter techniques. Mean values for sACT and sAGG were higher on the diagnostic night compared with treatment night (p = 0.001 and p = 0.003, analysis of variance, respectively). The mean baseline supine sACT compared with completion supine sACT for both diagnostic and N-CPAP nights also revealed significant differences (mean = 16.6 +/- 3.5% vs 36.9 +/- 7.5%, p = 0.04; and 11.9 +/- 3% vs 39.5 +/- 9.1%, p = 0.04). Platelet activation during sleep in five subjects without OSA resembles that found in patients with OSA during N-CPAP. CONCLUSIONS: Increased platelet sACT and sAGG occur during sleep in patients with OSA. This effect is greatly reduced by N-CPAP.

Adult↗