As the availability and quality of imaging techniques improve, doctors are identifying more patients with no history of transient ischaemic attack or stroke in whom imaging shows brain infarcts. Until recently, little was known about the relevance of these lesions. In this systematic review, we give an overview of the frequency, causes, and consequences of MRI-defined silent brain infarcts, which are detected in 20% of healthy elderly people and up to 50% of patients in selected series. Most infarcts are lacunes, of which hypertensive small-vessel disease is thought to be the main cause. Although silent infarcts, by definition, lack clinically overt stroke-like symptoms, they are associated with subtle deficits in physical and cognitive function that commonly go unnoticed. Moreover, the presence of silent infarcts more than doubles the risk of subsequent stroke and dementia. Future studies will have to show whether screening and treating high-risk patients can effectively reduce the risk of further infarcts, stroke, and dementia.

https://www.thelancet.com/pdfs/journals/laneur/PIIS1474-4422(07)70170-9.pdf

Silent brain infarcts: a systematic review

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular 'reactive oxygen species' (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation.

/pdf/iron-behaving-badly-inappropriate-iron-chelation-as-a-major-229l082exr.pdf

Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

https://www.cell.com/cell-metabolism/pdf/S1550-4131(13)00055-7.pdf

Iron and diabetes risk.

All asthmatics have exercise-induced asthma (EIA). In periods where the asthma spontaneously deteriorate, there will be more exercise-induced asthma. About 3/4 of the asthmatics will have a positive exercise test on the first challenge. Exercise is not the best test to obtain the diagnosis of asthma, as other tests, e.g. inhalation of histamine, is more sensitive and specific. The best pretreatment of EIA is inhaled beta 2-agonists. Inhaled, nebulized SCG seem to offer better protection against EIA than inhalation of SCG as a powder and is most effective in children. EIA should today primarily be used in studies concerning the pathogenesis of asthma and in the evaluation of medication against asthma.

[Exercise-induced asthma].

Although overt stroke is a common complication of sickle cell disease (SCD), its incidence is very low in Kuwaiti patients. On the other hand, the prevalence of silent brain infarcts, which is reported to be about 17–20% in American patients, has not been documented in adult Kuwaiti patients. This is a 1-year study of consecutive, asymptomatic SCD patients seen in the hematology clinic of Mubarak Al-Kabeer Hospital. Patients with a past history of seizure or any other neurological abnormality were excluded. The patients’ charts were reviewed for frequency of hospitalizations, any documented complications, and steady-state CBC. MRI was done with a 1.5-Tesla unit with super-conducting magnet. T1- and T2-weighted sagittal and axial sections and proton-density axial images were obtained in 5-mm-thick sections. Thirty-five patients were studied, made up of 25 SS and 10 S 0 Thal, aged between 17 and 44 years, with a mean age of 26.9 ± 9.3 years. MRI findings consistent with infarcts were found in 7 (20.0%) patients—6 SS and 1 S 0 thal— with a mean age of 31.8 ± 8.2 years, which was significantly higher (P < 0.05) than the mean age of the unaffected group (25.1 – 9.0 years). There were also no differences in the mean Hb, Hb F, or any other hematological parameter in the two groups. Among the affected 6 SS, 2 had co-existent -thal trait. It is interesting that, while silent infarcts are prevalent in young American patients, it is in the older age group that they occur in Kuwaiti patients. Further studies are needed to investigate the factors modulating this

https://onlinelibrary.wiley.com/doi/pdf/10.1002/ajh.10376

Silent brain infarcts in adult Kuwaiti sickle cell disease patients.

Background and aim Studies suggest that iron plays a significant role in the development of diabetes and its complications. This study evaluates the associations of iron metabolism parameters with the metabolic syndrome (MS), control and complications in female patients with type 2 diabetes mellitus (T2DM). Methods and results Ferritin, soluble Transferrin Receptor (sTfR), sTfR/Log ferritin ratio (sTfR-F index), iron, full blood count and high-sensitivity C-reactive protein (hs-CRP) were determined in 110 female patients with T2DM. Steady state beta cell function (%B), insulin sensitivity (%S) and insulin resistance were assessed with homeostasis model. Patients were divided into tertiles of ferritin and sTfR-F index and according to the presence or absence of the MS and diabetic complications. Patients within the lowest tertile of the sTfR-F index had significantly higher fasting insulin, percent B, low-density lipoprotein cholesterol and Apolipoprotein B than those in the highest tertile. Ferritin showed significant correlations with insulin, percent B and inverse correlations with adiponectin and percent S. The sTfR-F index was significantly correlated with insulin, percent B and lipid parameters. Correcting for hs-CRP abolished the correlations with ferritin but not the sTfR-F index. Higher indices of body iron were significantly associated with diabetes complications but no associations were found with MS, glucose or glycemic control. Multiple regression analysis with confounding variables showed ferritin and the sTfR-F index were not independently associated with diabetes complications. Conclusions Association of ferritin with metabolic derangements and complications in diabetes is partly dependent on association with inflammation. Iron status, estimated with the sTfR-F index, is associated with metabolic derangements and complications but the associations are dependent on other risk factors. Prospective studies that use the sTfR-F index as a marker of iron status are required to confirm the role of iron in the etiopathogenesis of T2DM and its complications.

Body iron stores in relation to the metabolic syndrome, glycemic control and complications in female patients with type 2 diabetes

While sickle cell disease (SCD) is generally mild in most Kuwaitis, because of their elevated fetal Hb levels, avascular necrosis of the femoral head (AVNFH) appears to be a common complication. It wa

Avascular Necrosis of the Femoral Head in Adult Kuwaiti Sickle Cell Disease Patients

Background: Proteinuria is a common manifestation of renal disease which is a significant cause of morbidity in patients with sickle cell disease (SCD). Objective: To evaluate and compare cystatin C, β 2 -microglobulin, and creatinine as markers of renal disease in relation to the degree of proteinuria and other complications of SCD. Methods: 24 h urine collections were used for estimation of urine protein and creatinine clearance in 59 patients with SCD. Results were correlated with plasma cystatin C, β 2 -microglobulin, creatinine, glomerular filtration rate (GFR; derived from plasma creatinine by Cockcroft-Gault, MDRD formulae, and calculated cystatin C clearance), and clinical and haematological variables. Results: Comparing the different methods of GFR, the proportion of patients with hyperfiltration (GFR >140 ml/min) were 30.5% (MDRD), 44.1% (Cockcroft-Gault), and 10.2 % (calculated cystatin C clearance). Cystatin C was the most consistent marker of hyperfiltration. The endogenous markers of GFR showed an increasing trend with increasing proteinuria, but haematological variables were not correlated with cystatin C, β 2 -microglobulin, or plasma creatinine. Urine protein excretion was correlated with age ( r  = 0.33) and significant proteinuria was present in 13.6% of patients. Patients with proteinuria had lower haemoglobin concentration (p = 0.027) than those without proteinuria but HbF was not related to the degree of proteinuria or to markers of GFR. Conclusions: Markers of GFR show variable ability to identify hyperfiltration in patients with SCD, but cystatin C is the best endogenous marker. Proteinuria is associated with age, haemoglobin, and abnormalities of GFR. Routine screening is recommended to allow for early detection and intervention.

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Comparison of renal function markers in Kuwaiti patients with sickle cell disease.

BACKGROUND Recent reports have shown elevated concentrations of serum cystatin C (CC) in patients with solid tumours. The aim of our study was to investigate whether patients with proliferative haematological disorders have increased serum concentrations of CC compared with normal subjects. METHODS Full blood count, serum CC, beta2-microglobulin (beta2M) and serum creatinine were determined in 27 apparently healthy subjects and 35 patients with proliferative haematological disorders. Creatinine clearance was calculated using the Cockroft-Gault formula. RESULTS CC and beta2M showed a significant correlation with each other (r=0.96, P<0.0001). Serum beta2M (P=0.001) and the serum beta2M:CC ratio (P=0.001) were significantly higher in the patients with normal renal function than in controls, but serum CC was not significantly different (P=0.08). CC did not show a significant correlation with blood count parameters. DISCUSSION Compared with beta2M and the beta2M:CC ratio, serum CC is not influenced by cell proliferation in haematological disorders.

http://acb.sagepub.com/content/39/3/308.full.pdf

Rajaa Marouf

Papers

Silent brain infarcts in adult Kuwaiti sickle cell disease patients.

Body iron stores in relation to the metabolic syndrome, glycemic control and complications in female patients with type 2 diabetes

Avascular Necrosis of the Femoral Head in Adult Kuwaiti Sickle Cell Disease Patients

Comparison of renal function markers in Kuwaiti patients with sickle cell disease.

Serum concentration of cystatin C is not affected by cellular proliferation in patients with proliferative haematological disorders.