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

Retinopathy of prematurity

ContextSickle cell disease is characterized by a state of nitric oxide resistance
and limited bioavailability of L-arginine, the substrate for
nitric oxide synthesis. We hypothesized that increased arginase activity and
dysregulated arginine metabolism contribute to endothelial dysfunction, pulmonary
hypertension, and patient outcomes.ObjectiveTo explore the role of arginase in sickle cell disease pathogenesis,
pulmonary hypertension, and mortality.DesignPlasma amino acid levels, plasma and erythrocyte arginase activities,
and pulmonary hypertension status as measured by Doppler echocardiogram were
prospectively obtained in outpatients with sickle cell disease. Patients were
followed up for survival up to 49 months.SettingUrban tertiary care center and community clinics in the United States
between February 2001 and March 2005.ParticipantsTwo hundred twenty-eight patients with sickle cell disease, aged 18
to 74 years, and 36 control participants.Main Outcome MeasuresPlasma amino acid levels, plasma and erythrocyte arginase activities,
diagnosis of pulmonary hypertension, and mortality.ResultsPlasma arginase activity was significantly elevated in patients with
sickle cell disease, with highest activity found in patients with secondary
pulmonary hypertension. Arginase activity correlated with the arginine-ornithine
ratio, and lower ratios were associated with greater severity of pulmonary
hypertension and with mortality in this population (risk ratio, 2.5; 95% confidence
interval [CI], 1.2-5.2; P = .006). Global
arginine bioavailability, characterized by the ratio of arginine to ornithine
plus citrulline, was also strongly associated with mortality (risk ratio,
3.6; 95% CI, 1.5-8.3; P<.001). Increased plasma
arginase activity was correlated with increased intravascular hemolytic rate
and, to a lesser extent, with markers of inflammation and soluble adhesion
molecule levels.ConclusionsThese data support a novel mechanism of disease in which hemolysis contributes
to reduced nitric oxide bioavailability and endothelial dysfunction via release
of erythrocyte arginase, which limits arginine bioavailability, and release
of erythrocyte hemoglobin, which scavenges nitric oxide. The ratios of arginine
to ornithine and arginine to ornithine plus citrulline are independently associated
with pulmonary hypertension and increased mortality in patients with sickle
cell disease.

https://jamanetwork.com/journals/jama/articlepdf/201168/JOC50051.pdf

Dysregulated arginine metabolism, hemolysis-associated pulmonary hypertension, and mortality in sickle cell disease.

Vitamin D testing and the use of vitamin D supplements have increased substantially in recent years. Currently, the role of vitamin D supplementation, and the optimal vitamin D dose and status, is a subject of debate, because large interventional studies have been unable to show a clear benefit (in mostly vitamin D replete populations). This may be attributed to limitations in trial design, as most studies did not meet the basic requirements of a nutrient intervention study, including vitamin D-replete populations, too small sample sizes, and inconsistent intervention methods regarding dose and metabolites. Vitamin D deficiency (serum 25-hydroxyvitamin D [25(OH)D]  50 nmol/L or 20 ng/ml is, therefore, the primary treatment goal, although some data suggest a benefit for a higher threshold. Severe vitamin D deficiency with a 25(OH)D concentration below <30 nmol/L (or 12 ng/ml) dramatically increases the risk of excess mortality, infections, and many other diseases, and should be avoided whenever possible. The data on a benefit for mortality and prevention of infections, at least in severely deficient individuals, appear convincing. Vitamin D is clearly not a panacea, and is most likely efficient only in deficiency. Given its rare side effects and its relatively wide safety margin, it may be an important, inexpensive, and safe adjuvant therapy for many diseases, but future large and well-designed studies should evaluate this further. A worldwide public health intervention that includes vitamin D supplementation in certain risk groups, and systematic vitamin D food fortification to avoid severe vitamin D deficiency, would appear to be important. In this narrative review, the current international literature on vitamin D deficiency, its relevance, and therapeutic options is discussed.

/pdf/vitamin-d-deficiency-2-0-an-update-on-the-current-status-d2khfi6tk7.pdf

Vitamin D deficiency 2.0: an update on the current status worldwide.

Single nucleotide polymorphism (SNP) is the simplest form of DNA variation among individuals. These simple changes can be of transition or transversion type and they occur throughout the genome at a frequency of about one in 1,000 bp. They may be responsible for the diversity among individuals, genome evolution, the most common familial traits such as curly hair, interindividual differences in drug response, and complex and common diseases such as diabetes, obesity, hypertension, and psychiatric disorders. SNPs may change the encoded amino acids (nonsynonymous) or can be silent (synonymous) or simply occur in the noncoding regions. They may influence promoter activity (gene expression), messenger RNA (mRNA) conformation (stability), and subcellular localization of mRNAs and/or proteins and hence may produce disease. Therefore, identification of numerous variations in genes and analysis of their effects may lead to a better understanding of their impact on gene function and health of an individual. This improved knowledge may provide a starting point for the development of new, useful SNP markers for medical testing and a safer individualized medication to treat the most common devastating disorders. This will revolutionize the medical field in the future. To illustrate the effect of SNPs on gene function and phenotype, this minireview focuses on evidences revealing the impact of SNPs on the development and progression of three human eye disorders (Norrie disease, familial exudative vitreoretinopathy, and retinopathy of prematurity) that have overlapping clinical manifestations.

SNPs: Impact on Gene Function and Phenotype

Using amplification, allele-specific oligonucleotide (ASO) hybridization and DNA sequencing we have documented the molecular basis of 64 α- and 123 β-thalassemia (thai) chromosomes, and the haplotypes

Molecular Characterization of α-Thalassemia Determinants, β-Thalassemia Alleles, and βs Haplotypes among Kuwaiti Arabs

Avascular necrosis (AVN) of the hip is a common cause of morbidity in sickle cell disease (SCD). Its prevalence increases with age and predisposing factors include coexistent α-thalassemia trait, freq

Avascular necrosis of the hip in children with sickle cell disease and high Hb F: magnetic resonance imaging findings and influence of alpha-thalassemia trait.

Admission records of children with sickle cell anemia (SS), in the two main teaching hospitals in Kuwait, were reviewed for a 1-year period The haplotypes of 92 βs chromosomes (from 39 SS,

Morbidity, βs Haplotype and α-Globin Gene Patterns among Sickle Cell Anemia Patients in Kuwait

Background: Recent studies have demonstrated an association of the T allele of a promoter polymorphism [C590T] of interleukin-4 (IL-4) gene with asthma/atopy in the US and Japanese

Interleukin-4 gene promoter polymorphism [C590T] and asthma in Kuwaiti Arabs.

The course and severity of systemic lupus erythematosus (SLE) in children is generally similar to the adult form with potential serious organ system involvement, there are, however, factors that influence the prevalence and clinical behavior of the disease. Our objective was to analyse the organ system involvement and immunological findings in Kuwaiti children with SLE in relation to gender and age of onset and compare these findings to that in published reports. Organ system involvement and serologic profiles were analysed in 35 children with SLE. The major organ systems studied were: renal, hematological, cardiac, pulmonary, hepatic and the central nervous system. The prevalence of ANA, anti-dsDNA, anti-Sm, SSA, SSB and anti-cardiolipin antibodies were studied in addition to complement C3 and C4 levels. The results showed that a high percentage of children had hematological involvement (34%); thrombocytopenia (23%) and hemolytic anemia (20%). Renal involvement was proven by biopsy in only 10 children (29%). Neuropsychiatric manifestations were seen in five (14%) of patients. Males had a tendency for major organ involvement relative to females. All patients had positive ANA tests. All males had positive anti-dsDNA tests compared to 86% of female patients. The most significant finding in this study is the high frequency of hematological manifestations and the relatively low incidence of renal disease and neuropsychiatric abnormalities in Kuwaiti children with SLE.

Mohammad Z. Haider

Papers

Molecular Characterization of α-Thalassemia Determinants, β-Thalassemia Alleles, and βs Haplotypes among Kuwaiti Arabs

Avascular necrosis of the hip in children with sickle cell disease and high Hb F: magnetic resonance imaging findings and influence of alpha-thalassemia trait.

Morbidity, βs Haplotype and α-Globin Gene Patterns among Sickle Cell Anemia Patients in Kuwait

Interleukin-4 gene promoter polymorphism [C590T] and asthma in Kuwaiti Arabs.

Systemic lupus erythematosus in Kuwaiti children: organ system involvement and serological findings.