Complications Associated with Sickle Cell Trait: A Brief Narrative Review

Sickle cell trait occurs in approximately 300 million people worldwide, with the highest prevalence of approximately 30% to 40% in sub-Saharan Africa. Long considered a benign carrier state with relative protection against severe malaria, sickle cell trait occasionally can be associated with significant morbidity and mortality. Sickle cell trait is exclusively associated with rare but often fatal renal medullary cancer. Current cumulative evidence is convincing for associations with hematuria, renal papillary necrosis, hyposthenuria, splenic infarction, exertional rhabdomyolysis, and exercise-related sudden death. Sickle cell trait is probably associated with complicated hyphema, venous thromboembolic events, fetal loss, neonatal deaths, and preeclampsia, and possibly associated with acute chest syndrome, asymptomatic bacteriuria, and anemia in pregnancy. There is insufficient evidence to suggest an independent association with retinopathy, cholelithiasis, priapism, leg ulcers, liver necrosis, avascular necrosis of the femoral head, and stroke. Despite these associations, the average life span of individuals with sickle cell trait is similar to that of the general population. Nonetheless, given the large number of people with sickle cell trait, it is important that physicians be aware of these associations.     

Discovering the genetics underlying foetal haemoglobin production in adults

Sickle cell disease (SCD) and β thalassaemia, caused by lesions that affect the HBB (β globin gene), form the most common human genetic disorders world-wide, and represent a major public health problem. Inter-individual variation in foetal haemoglobin (HbF) expression is a known and heritable disease modifier; high HbF levels are correlated with reduced morbidity and mortality in both diseases. This review traces our progress in the understanding of the persistence of HbF in adults as a quantitative trait and the genetic approaches used in teasing out the loci contributing to its variability in normal populations and in patients with haemoglobinopathies. Three major loci – Xmn1- HBG2 single nucleotide polymorphism, HBS1L-MYB intergenic region on chromosome 6q, and BCL11A – contribute 20–50% of the trait variance in patients with sickle cell anaemia and healthy European Caucasians. It is likely that the remaining trait variance is due to numerous other loci, many contributing modest effects. Identification of the three major loci has not yet been translated into new therapeutic approaches for HbF reactivation but an immediate application would be an improved prediction of one's ability to produce HbF, which in turn, may improve prediction of disease severity.     

Alexithymia and depression: A 1-year follow-up study in outpatients with major depression

Objective: To examine the changes in alexithymic features and depressive and other psychological distress symptoms during a 1-year follow-up among patients with major depression. Methods: The study population comprised 120 outpatients suffering from major depression. Diagnosis was made with Structured Clinical Interview (SCID-I) for DSM-III-R. The severity of depression was evaluated with the 17-item Hamilton Rating Scale for Depression (HAM-D), and self-reported depression with the Beck Depression Inventory (BDI-21). Alexithymic features were assessed with the Twenty-Item Toronto Alexithymia Scale (TAS-20). Self-reported psychological distress symptoms were evaluated with the Brief Symptom Inventory (BSI). Results: Measures of depression and distress were significantly lower at the follow-up than at the baseline, while the total TAS-20 scores did not change significantly during the follow-up. A closer examination revealed that various TAS-20 factors behaved differently. Changes in Factors 1 and 2 were associated with changes in mood, whereas those in Factor 3 were not. Additionally, recovery from depression was associated with decrease in alexithymic features. Conclusion: Difficulties in identifying and in describing feelings are associated with changes in mood, while externally oriented thinking is not.     

Assessment of State and Trait Anxiety in Subjects with Anxiety and Depressive Disorders

The State-Trait Anxiety Inventory (STAI) is one of the most widely used scales for the evaluation of anxiety in medical and, to a lesser extent, psychiatric patients. Although there is a relatively large amount of STAI data about anxiety for individuals with a variety of psychiatric disorders, the results of many anxiety studies include only state or trait and many studies have been influenced by comorbidity and by variations in diagnostic criteria used. We studied state and trait anxiety and compared the revised form of the STAI (Form Y) with the original (Form X) to evaluate the anticipated improvement in the measure. In addition, we compared the STAI results with those of another self-report measure (the Symptom Checklist–90 anxiety and depression scales) and also with interviewer-rated measures of anxiety (Hamilton Rating Scale for Anxiety) and depression (Hamilton Rating Scale for Depression). Results indicate that the STAI does not clearly differentiate anxiety disorders from depressive disorders and support the use of multiple tests and of both self-report and interviewer ratings in the evaluation of anxiety and depression in psychiatric patients.     

Age-related differences in spontaneous trait judgments from facial appearance

We tested whether there are age-related declines in detecting cues to trustworthiness, a skill that has been demonstrated to be rapid and automatic in younger adults. Young (M_age = 21.2 years) and older (M_age = 70.15 years) adults made criminal appearance judgments to unfamiliar faces, which were presented at a duration of 100, 500 or 1,000 ms. Participants’ response times and judgment confidence were recorded. Older were poorer than young adults at judging trustworthiness at 100 ms, and were slower overall in making their judgments. Further, the cues (i.e. perceptions of anger, trustworthiness and happiness) underlying criminality judgments were the same across age groups. Judgment confidence increased with increasing exposure duration for both age groups, while older adults were less confident in their judgments overall than their young counterparts. The implications are discussed.     

Chromosomes 18 and X are quantitative trait loci for nephrotic-range proteinuria in rats

Numerous cellular and molecular perturbations have been studied to elucidate the pathogenic mechanisms underlying nephrotic-range proteinuria, which may in turn shed light on disease-specific mechanisms. We have analyzed the publicly available data from the PhysGen partial panel of consomic rats to determine whether there are quantitative trait loci that associate with nephrotic-range proteinuria. As of this writing, consomic rat strains subjected to the renal protocol have been bred by the Program for Genomic Applications for 15 of the 22 rat chromosomes for both genders, predominantly with the Brown–Norway (BN) and Dahl salt-sensitive (SS) strains as parents. We defined chromosomes of interest as consomic SS-xBN strains whose phenotype measurements differed significantly from SS but not BN strains, stratified by gender. We filtered and clustered differentially expressed genes by function in renal tissue from relevant strains. Proteinuria was significantly higher in male SS vs. male SS-18BN, and it was significantly higher in male SS vs. female SS. Functional clustering of differentially expressed genes yielded two specific functional clusters: apoptosis (p=0.022) and angiogenesis (p=0.046). Gene expression profiles demonstrated differential expression of apoptotic and angiogenic genes. However, TUNEL stains of renal tissue showed no significant difference in the number of apoptotic nuclei. We conclude that chromosomes 18 and X are quantitative trait loci for nephrotic-range proteinuria in rats.     

多巴胺D4受体基因与精神分裂症质量性状和数量性状的关联分析

目的探讨多巴胺D4受体(DRD4)基因第3外显子48 bp可变重复序列(VNTR)多态性与精神分裂症疾病表型的质量性状和数量性状的关系.方法应用聚合酶链反应(PCR)、变性聚丙烯酰胺凝胶电泳结合银染技术检测162例精神分裂症患者(患者组)及162名正常人(对照组)的DRD4基因48 bp VNTR多态性;利用阳性与阴性症状量表(PANSS)来评定精神分裂症疾病表型的数量性状.用χ2检验和单因素方差分析(one way-ANOVA)分析DRD4基因与精神分裂症疾病表型的质量性状和数量性状的关系.结果 (1)患者组与对照组间DRD4基因的基因型及等位基因的频率分布的差异无统计学意义 (P＞0.05).按性别比较,3/5基因型在女性患者(47%)中的频率明显高于男性患者(29%)和女性对照者(32%),差异有统计学意义(P<0.05).(2)患者组DRD4基因3种基因型间PANSS总分及其分量表分差异无统计学意义(P＞0.05);但患者组长片段基因型"思维障碍"的因子分明显高于中片段基因型者,差异有统计学意义(P<0.05);女性患者长片段基因型者概念紊乱条目分明显高于中片段基因型者(P=0.01)和短片段基因型者,差异有统计学意义(P<0.05).结论 (1)DRD4基因48 bp VNTR与精神分裂症疾病表型的质量性状和数量性状可能无关联;(2)DRD4基因48 bp VNTR与精神分裂症疾病表型中的"思维障碍"和"概念紊乱"的数量性状可能存在关联,长片段基因型患者的症状可能较严重.     

Scoring alternatives for FIM in neurological disorders applying Rasch analysis

OBJECTIVE: The Functional Independence Measure (FIM) is an internationally widely used outcome measure. The aim of this study was to evaluate the structural properties of FIM using the Rasch model, with regard to scoring within rehabilitation centres in Scandinavia. MATERIALS AND METHODS: FIM data from 1660 patients with stroke, traumatic brain injury and spinal cord injury were analysed. The best models with respect to person separation were determined, together with person reliability, item separation, disordered categories, distance of more than 1.4 logits between categories and item fit to the model. RESULTS: Analysis showed disordering using seven categories in all three diagnoses. After collapsing of categories a four-category scale was the best solution. CONCLUSIONS: Decreasing the categories from seven to four may be one way of dealing with problems of disordered thresholds. Further studies are also needed in order to try the suggested scale in clinical settings and to compare it with the original FIM scale.     

Bisalbuminemia in chronic kidney disease

Hereditary and acquired bisalbuminemia, in which the serum contains an albumin variant differing from albumin A by single amino-acid substitutions, have been reported in different races or ethnic groups and in association with various pathologic states. The importance of this rare condition in the pathophysiology of established diseases is uncertain. We evaluated a 68-year-old woman with chronic kidney disease who presented with worsened serum creatinine concentration despite lack of dietary or medical changes. Serum protein electrophoresis was performed with an automated rapid electrophoresis system. Bisalbuminemia was noted as an incidental finding on serum protein electrophoresis. The serum creatinine level stabilized with dietary protein restriction and a -blocking agent/diuretic combination for blood pressure control. Although the possibility that some physiologic or pharmacologic substances may not bind to abnormal albumin variants as well as they bind to normal albumin should not be discounted, the finding of bisalbuminemia did not influence the diagnosis, management, course, or prognosis of chronic kidney disease. The role of persistent bisalbuminemia in renal disease is uncertain.