Weak D in the Tunisian population

BackgroundMore than 90 weak D types have been discovered to date. As there are no published data on the frequencies of weak D types in the Tunisian population, the aim of this study was to determine the composition of weak D alleles in our population.ResultsAmong the D+ donor cohort, weak D type 4 was the most prevalent allele (n=33, 1.2%) followed by weak D type 2 (n=6, 0.17%), weak D type 1 (n=4, 0.11%), and weak D type 5 (n=1, 0.28%) and weak D type 11 (n=1, 0.28%). RHD sequencing identified a weak D type 4.0 allele in all 19 samples tested. Among the D− pool, comprising 223 samples, we detected one sample with weak D type 4.0 associated with a C+c+E−e+ phenotype which had been missed by routine serological methods.DiscussionWeak D type 4.0 appears to be the most prevalent weak D in our population. However, all samples must be sequenced in order to determine the exact subtype of weak D type 4, since weak D type 4.2 has considerable clinical importance, being associated with anti-D alloimmunisation. One case of weak D type 4 associated with dCe in trans had been missed by serology, so quality control of serological tests should be developed in our country.     

Chronic lymphocytic leukemia revealed by a branulomatous zosteriform eruption

A 70-year-old woman presented with an atypical erythematopapular zosteriform eruption of 3 weeks' duration. The patient had no history of previous vesicular eruption. She developed a painful burning sensation on the neck. Clinical examination revealed a cluster of small erythematous firm papules and plaques in a zosteriform distribution on the left ear, face, neck, and shoulder (Figure 1A). The lesions were unilateral and did not cross the midline. Multiple cervical and axillary lymph nodes were palpable. Laboratory tests revealed an increase in white blood cells of 25,000/mm3, with 17,910/mm3 lymphocytes and a normal range of hemoglobin, platelets, creatinine, and liver enzymes. Erythrocyte sedimentation rate was 87 mm. Blood smear results showed small, morphologically mature lymphocyte cells. In immune phenotyping, lymphocyte cells co-express CD5 and B-cell-surface antigens CD19 and CD23, as well as a restriction of kappa immunoglobulin light chains. The cells were CD22-, CD79b-, CD38-, CD10-, CD25- and FMC7-. Computed thoracoabominal tomography revealed cervical, mediastinal, abdominal, and pelvic adenopathy confirming the diagnosis of B-cell chronic lymphocytic leukemia (B-CLL) stage B. Histology of a skin biopsy from a papule showed a dense nodular granulomatous infiltrate in the dermis (Figure 2A). The infiltrate contained epithelioid and giant cells surrounded by lymphocytes and plasma cells. Small monomorphic lymphocytes without mitotic figures predominated (Figure 2B). The epidermis was irregularly thickened. Immunohistology revealed a polymorphous infiltrate with a phenotype of reactive T lymphocytes (CD3, CD5 positive) (Figure 2C), B lymphocytes (CD20 positive) (Figure 2D). Epithelioid and giant cells were positive for CD68 (Figure 2E). A latent herpes zoster infection with granulomatous reaction at the site ofzoster lesions was highly suspected as the patient reported a unilateral burning sensation without a history of vesicular zosteriform eruption. She received treatment with intravenous acyclovir 10 mg/kg every 8 hours. The papular lesions resolved markedly (60%) on macular plaques at the end of the treatment. Following topical treatment with corticosteroids, the lesions healed completely within 4 weeks (Figure 1B). Concerning leukemia, our patient was monitored without therapy by the hematologist.     

Acid-base status is an important factor for inflammation,but don’t forget CO2!

Zampieri and colleagues used sophisticated statistical methods to create a picture of acid-base pattern and inflammation relationship in a clinical context. The observed independent relationship between acidosis and albumin concentration and inflammatory pattern opens up a new area for research. It has become clear that, in addition to the characterization of mediators, receptors, and cellular phenotypes, the inflammatory response has to be interpreted in light of acid-base status, albumin concentration, and probably also carbon dioxide level.Until now, the interplay between acid-base status and inflammation has received little attention, especially in a clinical context. The article by Zampieri and colleagues [1] in a previous issue of Critical Care is a pioneering study analyzing the relationship between acidosis variables, inflammatory mediators, and end-organ failures (acute kidney injury and shock). Since the metabolic and inflammatory reactions are simultaneous, the demonstration of interplay that is more than a simultaneous modification remains a difficult challenge. Because of this, the authors used three different statistical methods to separate the confounding factors. First, they developed a generalized linear model using the measured mediator as a dependent variable and components of acid-base status as variables. Second, they performed a multivariate adaptive regression with splines in order to evaluate the association of selected cytokines and acid-base components. Third, they performed a principal component analysis using Simplified Acute Physiology Score 3 as a way of quantifying illness severity in order to assess the independent association of acid-base variables and cytokine levels. The authors found that, in 87 prospective unselected patients, the level of strong anion gap (SIG) was positively associated with TNFα and IL-6, IL-8, and IL-10. A negative association was found between albumin level and TNFα and IL-6, IL-7, IL-8, and IL-10 and IFNγ. The conclusion drawn from these results opens up a new route for research to understand the mechanisms that link acid-base variables, albumin level, and immunological activation.Such a topic is important and clinically relevant since plasma and interstitial fluid constitute the microenvironment for immune and tissue cells. Acid-base and albumin characteristics may then interfere with the cell response to different signals such as endotoxin. In addition, both fluid resuscitation and capillary leak may largely influence the composition of the cell microenvironment, especially when a crystalloid such as saline or a balanced crystalloid such as Ringer’s lactate is used. The role of surrounding cell pH could be seen as a result of metabolic acidosis and carbon dioxide (CO₂) level, an aspect that was not investigated in the study [2,3]. Given the picture presented in this article, some approaches might be tested to clarify the mechanisms involved in immune modifications induced by acid-base changes. First, immune cells should be drawn from septic patients that have been incubated in the septic plasma or drawn after replacement of septic plasma by healthy plasma; both acid-base conditions or albumin concentration can then be modified to test their impact on immune cells phenotype. This might help to clarify how the pH, the SIG, and albumin concentration change the immune cell phenotypes. Second, similar experiments with healthy cells incubated in plasma from acutely injured patients could be performed to demonstrate the role of physicochemical plasma patterns. Mediators and cell functions then could be evaluated in different acid-base conditions. Until now, few data on alkalosis have been reported in terms of immunity, and the essential information comes from acidosis situations. One author of the study was part of a group [4] that showed that metabolic acidosis induced by hydrochloric acid and lactic acidosis added to culture media of RAW 264.7 cells have opposite effects: hydrochloric acid at a pH of 7 seems essentially pro-inflammatory (nitric oxide level, IL-6/IL-10 ratio, NF-κB DNA binding), whereas lactic acidosis is essentially anti-inflammatory. A group with the same author, using a rat model, confirmed these results in terms of systemic cytokines [5]. In that study, the authors found a positive relationship between SIG and IL-6, IL-8, and IL-10 and TNFα, which was independent of illness severity. Even though albumin was not administered in the presented cohort, it can be discussed in light of immune effects. The authors observed a negative correlation between albumin level and IL-6, IL-8, IL-10, monocyte chemoattractant protein-1 and IFNγ. In addition to its complex effects, albumin was shown to be immunosuppressive for peripheral blood monocytes (IFNγ and TNFα) and also for T lymphocyte clone [6], which confirmed the presented results. Except for specific indications, albumin is not recommended for use in fluid resuscitation, especially after the recent negative results of a randomized clinical trial [7]. Third, the role of hypo- or hypercarbia has to be investigated since elevated CO₂ was shown to modulate mammalian inflammatory and innate immune responses in vitro and in vivo [3], independently of extra- and intra-cellular pH. During a sterile insult of inflammation stimulation, hypercapnia may be of benefit but would be deleterious in the setting of infection due to host immunosuppression. The underlying mechanism implicates the NF-κB signaling pathway as an important hub of CO₂ sensitivity [3,8]. This, in combination with the ability of elevated CO₂ to enhance bacterial and fungal virulence and survival, suggests that hypercapnia may predispose humans to infections or worsen outcomes [3]. Understanding the involved molecular signaling pathways will be of great importance in the identification of new approaches to control infection and inflammation in the clinical setting.     

Factors leading to work absenteeism in Tunisian ankylosing spondylitis patients

Background

The work productivity loss due to ankylosing spondylitis (AS) has a notable socioeconomic impact.

Embryonic exposure to dimethoate and/or deltamethrin impairs sexual development and programs reproductive success in adult male offspring mice

Pesticides can be toxic to desirable plants and animals, including humans. The aim of this study was to investigate the reproductive effects of low doses of pesticides on male offspring of exposed pregnant mice. Three groups of five female mice were treated daily by oral gavage with dimethoate (5 mg kg(-1) per day), deltamethrin (5 mg kg(-1) per day) and their mixture at 5 mg kg(-1) per day from day 3 to day 21 of pregnancy. Fertility, sexual behaviour and a number of reproductive endpoints, such as organ weights, sperm evaluations and testicular histology, were examined on four adult male offspring of exposed pregnant mice. When compared with control, a dose of deltamethrin 5 mg kg j(-1) causes a decrease in the absolute and relative weight of the testes of exposed mice and it affects their fertility by reducing the density, mobility and vitality of sperm and increasing the number of abnormal forms of these cells (P ≤ 0.01). The same results were obtained in mice exposed to a dose of 5 mg kg j(-1) combination of dimethoate and deltamethrin. This study demonstrated that deltamethrin and combination of dimethoate and deltamethrin caused a decrease in the absolute and relative weight of the testes, which affected the sperm parameters of male offspring of exposed mice to a low dose of these pesticides during pregnancy.