Fibrinogen and high molecular weight fibrinogen during and after normal pregnancy

INTRODUCTION: Pregnancy has recently been described as a generalized intravascular inflammatory response to the conceptus. Total fibrinogen concentrations increase during pregnancy. The percentage high molecular weight fibrinogen (HMW-Fg) of the concentration total fibrinogen is known to increase during acute-phase conditions like inflammation. Therefore, we investigated whether the percentage high molecular weight fibrinogen increases during normal pregnancy. MATERIALS AND METHODS: Eighteen healthy nulliparous women with uncomplicated pregnancies with normal course and outcome participated in this study. Five blood samples were drawn from every woman in the gestational age periods 9 to 16, 17 to 24, 25 to 33 and 34 to 42 weeks and at 12 to 20 weeks after delivery. Total fibrinogen concentrations were determined according to Clauss and the percentage high molecular weight fibrinogen was assessed by SDS-electrophoresis and densitometry after isolation of fibrinogen by precipitation. One-way analysis of variance (ANOVA) was used to evaluate differences between gestational age periods and correlation coefficients were calculated by Pearson's method. RESULTS: Total fibrinogen concentrations increased with advancing gestational age and decreased after delivery. The percentage high molecular weight fibrinogen of the total fibrinogen remained unaltered during and after pregnancy. CONCLUSIONS: During normal pregnancy, there is an increase of total fibrinogen concentrations with advancing gestational age, without a rise in percentage high molecular weight fibrinogen. After delivery, the total fibrinogen returns to baseline concentrations.     

Inflammatory mediators for the diagnosis and treatment of sepsis in early infancy

Interleukin-6 (IL-6), interleukin-8 (IL-8), and procalcitonin (PCT) are important parameters in the diagnosis of sepsis and for differentiating between viral and bacterial infection in children. We compared the value of IL-6, IL-8, and PCT with C-reactive protein (CRP) in the diagnosis and treatment of late-onset sepsis among infants admitted to the neonatal intensive care unit (group I) and febrile infants admitted to general hospitals from home (group II). Group I was divided into subgroups Ia, positive blood culture (all Gram-positive cocci); Ib, negative blood culture; and Ic, controls. Group II was divided into subgroups IIa, systemic enterovirus infection, and IIb, no enterovirus infection. Enterovirus was identified by real-time (RT) polymerase chain reaction (PCR) and/or by culture in blood and cerebrospinal fluid (CSF). The positive predictive values of IL-6, IL-8, and PCT (78%, 72%, and 83%, respectively) were better than that of CRP (63%) in the diagnosis of neonatal sepsis. After 48 h of antibiotic treatment, IL-6 and IL-8 levels significantly decreased and PCT stabilized in clinically recovered patients, suggesting that these markers may be useful in distinguishing patients in which antibiotic treatment may be discontinued. Among infants of subgroup IIa, 80%-90% had normal values of IL-6, IL-8, and PCT, whereas CRP was increased in 40%. In conclusion, IL-6, IL-8, and PCT are better parameters than CRP in the diagnosis and follow-up of neonatal sepsis due to coagulase-negative staphylococci (CoNS) and in the exclusion of bacterial infection among those with enteroviral infection among febrile infants presenting from home.     

Neurological complications caused by desmopressin in adults with nocturia

Desmopressin is occasionally used to reduce the frequency of nocturnal toilet visits. We describe an 86-year-old woman with nocturnal incontinence due to a urinary tract infection, and a 49-year-old man with frequent toilet visits in the night, known to consume excessive amounts of alcohol. They were admitted to hospital with neurological symptoms due to severe hyponatraemia, 114 and 102 mmol/l respectively, while using desmopressin. After the desmopressin had been discontinued and the fluid balance restored, they recovered completely. Hyponatraemia is inherent to the mechanism of action of desmopressin. Desmopressin should be prescribed only on sound indication, and risk factors for developing severe hyponatraemia should always be taken into consideration. Proper instruction and follow-up are important to prevent severe complications.     

In vivo blockade of tumor necrosis factor-alpha in patients with rheumatoid arthritis: longterm effects after repeated infusion of chimeric monoclonal antibody cA2

OBJECTIVE: To investigate the longterm consequences of tumor necrosis factor-alpha (TNF-alpha) blockade in patients with rheumatoid arthritis (RA), to compare changes after repeated infusion of cA2 monoclonal antibody with those occurring after the initial treatment, and to investigate significant correlations of cellular or serological changes to the duration of clinical benefit for each patient. METHODS: A clinical trial testing TNF-alpha monoclonal antibody cA2 in treatment of RA showed this therapeutic agent is highly effective. A dosage of 1 mg/kg or 10 mg/kg cA2, given in a single infusion, was compared to placebo. After clinical relapse all patients were (re)treated with 3 or 10 mg/kg cA2. In parallel to this clinical study, we investigated cellular and molecular changes induced by in vivo blockade of TNF-alpha. RESULTS: After an initial transient increase, T lymphocyte counts were not significantly different from starting values throughout the observation period. Monocyte counts as well as serum interleukin 6 (IL-6) and soluble intercellular adhesion molecule 1 (sICAM-1) concentrations remained decreased for several weeks after infusion. After a repeated infusion, increases in numbers of T cells and decreases in monocytes and IL-6 and sICAM-1 concentrations were evident again. Changes in cell counts, however, were smaller, especially in the group initially treated with the low dose (1 mg/kg), despite a higher retreatment dosage of 3 or 10 mg/kg cA2. Similarly, in this group decrease of IL-6 and sICAM-1 concentrations was less pronounced, was delayed to Day 7 after infusion, and lasted for a shorter period than seen after initial treatment. CONCLUSION: We conclude that in vivo TNF-alpha blockade leads to prolonged cellular and serological changes. This effect appears to be less pronounced after repeated infusion of cA2 compared to the initial treatment, mainly in the low dose group.     

Paraoxonase genotype and carotid intima-media thickness in children with familial hypercholesterolemia.

BACKGROUND: Paraoxonase (PON) 1 is a high-density lipoprotein-associated enzyme that may protect against cardiovascular disease. METHOD: We have studied the contribution of PON-1 and PON-2 single nucleotide polymorphisms (SNP; L55M, Q192R and T-107C, S311C) to the intima-media thickness of the common carotid artery in a population of children with classic familial hypercholesterolaemia. RESULTS: The L-variant of the L55M SNP was associated with increased common carotid artery intima-media thickness when compared with the M-variant (P value for trend 0.03). No significant relationship was observed between the other SNP and common carotid artery intima-media thickness. CONCLUSIONS: Our findings suggest that variation at the PON-1 locus contributes to early atherosclerosis in children with familial hypercholesterolaemia.     

Changes in metabolites and tissue water status after focal ischemia in cat brain assessed with localized proton MR spectroscopy

Localized proton spectroscopy was used to monitor changes in metabolism and the biophysical status of tissue water in cat brain induced by occlusion of the middle cerebral artery. Changes in the intensity of N-acetyl-aspartate (NAA), total creatine (tCr), and lactate (Lac) signals in localized volumes of interest in the ischemic hemisphere were quantified relative to the preischemic signal. Changes in the apparent diffusion coefficient (ADC), T₁- and T₂-relaxation times of water in those volumes were also quantified. Lactate was shown to increase rapidly in the first 0.5?2.0 h of ischemia and stabilized afterwards. The ADC of water started to decrease from 0.64 × 10^?9 m2/s to 0.54 × 10^?9 m2/s in the first minutes following occlusion, as was shown in two cases where ADC was measured with high temporal resolution, and stabilized after approximately 3 h at 0.38 × 10^?9 m2/s (n = 6). NAA and tCr decreased by 35% (P< 0.0001) and 30% (P< 0.005), respectively, in the first 8 h of ischemia in comparison with the preischemic control levels. T₁ and T₂ gradually increased with 0.3 s (P< 0.0001) and 5.2 ms (P< 0.0001), respectively, during the same time span.     

Extranuclear detection of histones and nucleosomes in activated human lymphoblasts as an early event in apoptosis

OBJECTIVE: To evaluate the presence of histones and nucleosomes in cell lysates of freshly isolated peripheral blood mononuclear cells (PBMC), fully activated lymphoblasts, or lymphoblasts after induction of apoptosis. METHODS: Each histone class (H1, H2A, H2B, H3, and H4) was detected by western blot analysis with specific antibodies. Annexin V/propidium iodide (PI) staining was performed for each treatment to distinguish viable, early, and late apoptotic, and necrotic cells. DNA degradation was evaluated by PI staining in a hypotonic buffer. RESULTS: All five histones were detected in cell lysates of activated lymphoblasts in higher concentrations than in lysates of PBMC. An additional significant increase of H2A, H2B, H3, H4, and complete nucleosomes in cell lysates of lymphoblasts was found during interleukin (IL)2 deprivation for 8 or 24 hours. The content of these histones or nucleosomes in cell lysates decreased after delayed IL2 readdition. H1 content in cell lysates was not affected by IL2 deprivation or addition. Quantities of H2A, H2B, H3, and H4 in cell lysates correlated significantly with signs of early apoptosis. UV-B light exposure or etoposide treatment of lymphoblasts resulted in a distinct increase for each histone class in cell lysates compared with standard curves. No bands for post-translationally modified histones were detected in cell lysates in contrast with signals in nuclear preparations. CONCLUSION: Extranuclear accumulation of histones and nucleosomes is an early event of apoptosis in human lymphoblasts. Dysregulation of early apoptosis might support the induction of autoimmunity against nuclear components.     

Financial disclosures of authors involved in spine research: an underestimated source of bias

Background

Reporting financial disclosures has become standard practice in both journal publications and during oral forum at scientific meetings. Despite this, the effect of reporting a financial disclosure of any member of an authorgroup, on the tone of the conclusion of an article has gained little attention. This study was performed to determine what effect reporting a financial disclosure has on the conclusion of an article.

Methods

A literature search for all articles on interspinous devices and cervical disc prostheses, published from January 1st, 2008 until December 1st, 2010 was performed. Financial disclosures were reported, as were funding by commercially active parties. The tone of the conclusions was graded as positive, neutral or negative.

Results

The odds ratio (OR) for a positive conclusion in cases where a financial disclosure was reported was 16.5 (95% CI: 4.7–58.1). Effect modification occurs with the presence of funding by a commercially active party. In cases where a financial disclosure was reported and funding was available for the study, the OR was 1.0 (95% CI: 0.08–12.6), whilst the OR was 33.3 (95%CI: 4.2–262.3) if funding was not provided. This discrepancy is mainly due to the large number of articles with a neutral/negative conclusion if the authors failed to report any financial disclosure and were not funded by a commercially active party.

Conclusions

Reporting a financial disclosure is a potential source of bias. Authors with disclosed financial relationships less often publish articles with a neutral/negative conclusion. This source of bias should certainly be taken into account during the critical appraisal of articles, particularly when the quality of the literature is being assessed.