Does non-invasive ambulatory blood pressure monitoring disturb sleep?

OBJECTIVE: To assess the effects of non-invasive ambulatory blood pressure monitoring upon sleep in healthy men. METHODS: Spontaneous variations in the quality of sleep were assessed by taking polygraph recordings in 44 healthy men aged 17-69 years. Subjects were allowed one night to become accustomed to the laboratory environment, and then their sleep was recorded for 4 consecutive nights. On day 4 blood pressure was measured every 10 min for 24 h. RESULTS: The blood pressure recording procedure caused a small but significant decrease in the amount of slow-wave sleep and an increase in the duration of nocturnal awakenings. As a result, sleep efficiency was decreased. The number of nocturnal awakenings was not affected by the blood pressure measurements. The effects of ambulatory blood pressure monitoring were qualitatively similar in young and older volunteers. CONCLUSION: Non-invasive ambulatory blood pressure monitoring induces modest sleep disturbances which are unlikely to artifactually distort the physiological 24-h blood pressure profile.     

Detection of circulating human platelet fragments by using monoclonal antibodies against platelet glycoprotein IIb-IIIa complex

A radioimmunoassay (RIA) for the detection of platelets and platelet fragments was developed. A sandwich of two monoclonal antibodies directed against the platelet-specific glycoprotein complex IIb-IIIa (GP IIb-IIIa) was used in this assay. A discontinuous 7.5-20% (v/v) albumin gradient was applied to separate platelets and their fragments of various sizes. In platelet suspensions fractionated in this way, we observed that particles smaller than normal platelets still carried the GP IIb-IIIa antigens. This procedure enabled us to detect platelet-derived particles in platelet-rich plasma from thrombocytopenic patients.     

A monoclonal antibody to the human platelet glycoprotein IIb/IIIa complex induces platelet activation

The platelet glycoprotein (GP) IIb/IIIa complex functions as the receptor for fibrinogen on activated platelets. The effects of two anti-GPIIb/IIIa monoclonal antibodies on platelet function were studied. These antibodies, 6C9 and C17, recognized different epitopes, which were exclusively present on the undissociated GPIIb/IIIa complex. Whereas C17 inhibited the binding of fibrinogen to platelets and platelet aggregation induced by adenosine diphosphate (ADP) or collagen, 6C9 caused irreversible aggregation of platelets, both in the presence and absence of extracellular fibrinogen. When incubated with unstirred (non-aggregating) platelets, 6C9 induced release of alpha and dense granule-constituents as well as binding of 125I-fibrinogen to platelets. The latter was evidently mediated in part by platelet-derived ADP, since it was inhibited to a large extent by apyrase, the ADP-hydrolyzing enzyme. F(ab')2 fragments of 6C9 did not induce platelet-release reactions but caused (slow) aggregation of platelets in the presence of extracellular fibrinogen. These results indicate that binding of an antibody to a specific site on the platelet GPIIb/IIIa complex may cause fibrinogen-mediated aggregation. The Fc part of the platelet-bound antibody appears to be involved in the induction of platelet release.     

Prevalence of thrombocytopenia in HIV-infected and non-HIV infected drug users and homosexual men

We studied the prevalence and risk factors for thrombocytopenia among 299 drug users and 461 homosexual men. The prevalence of thrombocytopenia was 3.3% in HIV-negative homosexual men, 8.7% in HIV-negative drug users, 16.4% in HIV-positive homosexual men, and 36.9% in HIV-positive drug users. With multivariate logistic regression HIV-seropositivity (odds ratio 3.3), a history of injecting drugs (OR 3.9), an increased number of lymphocytes (OR 0.44), an increased number of neutrophils (OR 0.53) and a larger mean platelet volume (OR 2.8) were independently and significantly associated with thrombocytopenia. The results obtained with linear regression analysis were consistent with the results of the logistic regression. The higher prevalence of thrombocytopenia among drug users was related to a history of intravenous drug use but not to recent injecting. The mechanisms causing thrombocytopenia among HIV-positives and HIV-negatives seem to be related, but HIV-infection seems to enhance thrombocytopenia in an independent way.     

Frequent ongoing T-cell receptor rearrangements in childhood B- precursor acute lymphoblastic leukemia: implications for monitoring minimal residual disease

Crosslineage T-cell receptor delta (TCR delta) rearrangements are widely used as tumor markers for the follow up of minimal residual disease in childhood B-precursor acute lymphoblastic leukemia (ALL) by polymerase chain reaction (PCR). The major drawback of this approach is the risk of false-negative results due to clonal evolution. We investigated the stability of V delta 2D delta 3 rearrangements in a group of 56 childhood B-precursor ALL patients by PCR and Southern blot analysis. At the PCR level, V delta 2D delta 3-to-J alpha rearranged subclones (one pathway for secondary TCR delta recombination) were demonstrated in 85.2% of V delta 2D delta 3-positive patients tested, which showed that small subclones are present in the large majority of patients despite apparently monoclonal TCR delta Southern blot patterns. Sequence analysis of V delta 2D delta 3J alpha rearrangements showed a biased J alpha gene usage, with HAPO5 and J alpha F in 26 of 32 and 6 of 32 clones, respectively. Comparison of V delta 2D delta 3 rearrangement status between diagnosis and first relapse showed differences in seven of eight patients studied. In contrast, from first relapse onward, no clonal changes were observed in six patients studied. To investigate the occurrence of crosslineage TCR delta rearrangements in normal B and T cells, fluorescence-activated cell sorter-sorted peripheral blood CD19+/CD3- and CD19-/CD3+ cell populations from three healthy donors were analyzed. V delta 2D delta 3 rearrangements were detected at low frequencies in both B and T cells, which suggests that V delta 2-to-D delta 3 joining also occurs during normal B-cell differentiation. A model for crosslineage TCR delta rearrangements in B-precursor ALL is deduced that explains the observed clonal changes between diagnosis and relapse and is compatible with multistep leukemogenesis of B-precursor ALL.     

Platelet-Associated IgG in Thrombocytopenia: A Comparison of Two Techniques

The results obtained in the analysis of 130 thrombocytopenic patients with a radioimmunoassay (RIA) for platelet-associated IgG (PA-IgG) and the platelet suspension immunofluorescence test (PIFT) were compared. The RIA was positive in 33 of 41 (82.9%) patients with idiopathic thrombocytopenia (ITP) and in 51 of 79 (64.4%) patients with secondary thrombocytopenia (STP). The PIFT was positive in 37 of the 41 (90.2%) ITP patients and in 57 of the 79 (72.2%) STP patients. Sensitivity and specificity for the diagnosis of ITP of both tests were comparable: 82.9 and 40.9% for the PA-IgG(RIA) and 90.2 and 36.7% for the PIFT. A significant positive correlation was observed between the mean amount of PA-IgG measured and the height of PIFT scores with anti-IgG. Of 38 discrepancies between PA-IgG(RIA) and PIFT with anti-IgG, 15 were due to borderline results, 17 were associated with abnormal platelet-size distribution and 20 were associated with occurrence of IgM antibodies. These results suggest influences of platelet fragments and/or aggregates on accurate measurement of PA-IgG. Both fragments and aggregates escape from accurate platelet counting, while their contribution to the total IgG content remains. Therefore, a falsely elevated PA-IgG (RIA) may be measured.     

Autoimmune haemolytic anaemias. V. Studies on the resistance against complement haemolysis of the red cells of patients with chronic cold agglutinin disease

Experiments are described the results of which sustain the hypothesis that resistance against complement haemolysis, which is a characteristic of the red cells of patients with chronic cold agglutinin disease, is due to the following mechanism: when red cells react with cold auto-agglutinins in vivo, they are either haemolysed immediately, or, due to an unknown factor, escape direct haemolysis. In the latter case β₁E and β₁A disappear from the cell membrane. To the sites where these proteins have been attached once, no new β₁E or β₁A molecules can be bound. Full complement activation thus becomes impossible.     

Knowledge about asthma and COPD: associations with sick leave, health complaints, functional limitations, adaptation, and perceived control

We sought to investigate associations between knowledge about the disease and sick leave, health complaints, functional limitations, adaptation and perceived control. Patients with asthma (n = 101) and COPD (n = 64) underwent lung function tests and completed questionnaires. In addition, all were asked the question: ‘what is the diagnosis of your disease?’, with the response categories: ‘asthma’ and ‘COPD (chronic bronchitis or emphysema)’. Thirty-five percent of the asthma patients and 30% of the COPD patients did not know their correct diagnosis. Sick leave was not associated with knowledge about the disease in asthma and COPD. In asthma, much knowledge about management of the disease was associated with better adaptation (P = 0.01) and less perceived control over health by external factors (P = 0.02). Knowing the correct diagnosis was associated with less control over health by powerful others (P = 0.02). For COPD, more knowledge about management of the disease was associated with better adaptation (P = 0.02) and less control over health by internal factors (P = 0.01). Knowing the correct diagnosis was associated with less control over dyspnea at work (P = 0.01).     

Neutrophil cytoplasmic antibodies (p-ANCA) in ulcerative colitis.

AIMS--To study ulcerative colitis associated neutrophil cytoplasmic antibodies (p-ANCA) in respect of class and subclass distribution, antigen specificity, and (sub)cellular localisation of the antigen(s) to which these antibodies are directed. METHODS--p-ANCA positivity was determined using the standard indirect immunofluorescence test (IIFT). The immunoglobulin (Ig) subclass distribution of p-ANCA was investigated using monoclonal antibodies directed against IgG1, IgG2, IgG3, and IgG4. Intracellular antigen localisation studies were performed on (fractionated) neutrophils using antigen-specific antibodies. RESULTS--In contrast to vasculitis associated ANCA, ulcerative colitis p-ANCA are mainly of IgG1 and IgG3 subclass and lack IgG4. Ulcerative colitis p-ANCA are myeloid specific. IIFT data indicate that the related antigen(s) seem(s) to be located not in the cytosol, but in the granules (most likely the azurophil granules) of the neutrophil. CONCLUSIONS--p-ANCA in ulcerative colitis have a different immunoglobulin subclass distribution than the ANCA of systemic necrotising vasculitis and necrotising and crescentic glomerulonephritis. This may point to differences in immune regulation between these diseases. Both cathepsin G and lactoferrin are recognised by a subpopulation of ulcerative colitis p-ANCA. In our series, eight out of 36 (22%) of ulcerative colitis associated p-ANCA react with lactoferrin and seven (19.5%) other sera with cathepsin G. None of them recognised both antigens. The main target antigen(s) of ulcerative colitis p-ANCA still remain(s) to be identified.