Rearrangements of the RAR-α gene in acute promyelocytic leukaemia:

We have used genomic probes which specifically recognize DNA rearrangements of the RAR-alpha locus on chromosome 17q21 in patients with acute promyelocytic leukaemia (APL) and acute myeloid leukaemia (AML) subtypes. Molecular data were examined in comparison with morphological and immunophenotypic characterization at diagnosis in 20 hypergranular FAB M3 cases, five microgranular APL (M3v), 51 non-M3 AML and 12 myeloid CML blast crises. Rearrangements of the RAR-alpha locus were only detected in 23/25 APL cases and in none of the other FAB subtypes analysed. Surface marker characterization showed a consistent immunophenotypic profile--HLADR negative, CD9 and CD13/33 positive--in all M3 and M3v cases. Neither HLADR negativity nor CD9 positivity were associated with RAR-alpha rearrangements in non M3 AML. Our data indicate that RAR-alpha gene rearrangements are relevant diagnostic features of both M3 and M3v, and may prove useful molecular marker for follow-up analysis in APL patients.     

Aspects of the clinical management of hereditary thrombophilia: a personal perspective

There is a paucity of evidence-based medicine regarding the clinical management of patients with inherited thrombophilia, and randomized controlled multinational clinical trials of anticoagulant prophylaxis, particularly of secondary prophylaxis, in this population are urgently required. For acute episodes of venous thromboembolism, no data suggest that patients with thrombophilia should be treated differently to those without thrombophilia. Based on the results of a retrospective study, it is recommended that all thrombophilic individuals receive short-term thromboprophylaxis with unfractionated heparin or low-molecular-weight heparin when they are to be exposed to circumstantial risk factors (e.g. surgery, prolonged immobilization, pregnancy and puerperium). In the absence of specifically designed clinical trials, secondary prophylaxis should be based on common sense and clinical experience. From this standpoint, it is recommended that low-risk patients be treated with oral anticoagulants for 6 months, whereas high-risk patients should receive lifelong anticoagulant therapy. Which treatment strategy to adopt for intermediate-risk patients is more controversial -- prolongation of oral anticoagulant therapy to at least 12 months is suggested.     

Prospective study of hepatitis after factor VIII concentrate exposed to hot vapour

A factor VIII concentrate prepared from large plasma pools and then exposed to hot vapour to inactivate blood-borne viruses was evaluated in 28 factor-VIII deficient patients (14 vaccinated against the hepatitis B virus, HBV) who had not been treated with any blood product and hence were highly susceptible to the development of post-transfusion hepatitis. Tests for aminotransferases and HBV markers were made every 2 weeks in the first 4 months and at 5, 6 and 12 months. Twenty-four patients were considered not to have developed hepatitis, either because they had no elevations of aminotransferases or did not become seropositive for HBV markers. The four remaining unvaccinated patients (three treated with the same batch and the fourth with a different one) developed HBV infection 8-24 weeks after the first concentrate infusion. Hence, this method of viral inactivation did not afford complete protection from hepatitis B.     

Polymorphisms in the CD14 gene associated with pulmonary function in farmers

RATIONALE AND OBJECTIVES: Farmers experience airway obstruction, which may be attributable in part to endotoxin inhalation. CD14 is a receptor for endotoxin. MATERIALS AND METHODS: Based on our findings of increased circulating CD14 associated with the CD14/-159 T allele, we hypothesized that carriers of this allele would have decreased lung function among endotoxin-exposed individuals. CD14/-159TT farmers (n = 19) had significantly lower lung function as measured by FEV1 (p = 0.028) and mean forced expiratory flow during the middle half of the FVC (FEF25-75) (p = 0.05) compared with farmers with the C allele (n = 78). Also, farmers with the CD14/-1619GG genotype (n =11) were associated with lower lung function (FEV1, p = 0.008; FEF25-75, p = 0.009) compared with farmers with the A allele (n = 86). RESULTS: No association between CD14/-550 and lung function was observed (FEV1, p = 0.32; FEF25-75, p = 0.11). Increased prevalence of wheezing was reported in farmers homozygous for CD14/-159T (p = 0.013) or CD14/-1619G (p = 0.019) compared with farmers with the CC or AA genotype, respectively. No association was found between TLR4/Asp299Gly and lung function or wheeze. CONCLUSION: We conclude that the CD14/-159 or CD14/-1619 loci may play a role in modulating lung function and wheeze among agricultural workers.     

Eating disorders in patients with type 1 diabetes: a meta-analysis

A meta-analysis of controlled studies on prevalence of eating disorders in Type 1 diabetes was performed in order to assess differences between diabetic and non-diabetic female subjects. All controlled studies using the Diagnostic and Statistical Manual of Mental Disorders Third Edition Revised (DSM Ill-R) or the DSM Fourth Edition (DSM IV) criteria for interview-based diagnosis were included in the analysis. The total sample was composed of 748 and 1587 female subjects with and without diabetes, respectively. The prevalence of anorexia nervosa (AN) in Type 1 diabetic subjects was not significantly different from that of controls (0.27 vs 0.06%), while that of bulimia nervosa and of the two conditions combined was significantly higher in diabetic patients (1.73 vs 0.69%, and 2.00 vs 0.75%, respectively; both p < 0.05). Type 1 diabetes is associated with a higher prevalence of bulimia nervosa in females.     

von Willebrand disease "Vicenza" with larger-than-normal (supranormal) von Willebrand factor multimers

When normal volunteers or patients with type I von Willebrand disease (VWD) are given desmopressin (DDAVP), a set of larger-than-normal (supranormal) von Willebrand factor (VWF) multimers, similar to those present in VWF-containing cells such as platelets megakaryocytes and endothelial cells, appear transiently in postinfusion plasma. In two kindreds with mild lifelong bleeding symptoms transmitted as an autosomal dominant trait, all ten symptomatic members (but none of the five asymptomatic members) had a supranormal multimeric structure for plasma VWF, apparently identical to that seen for postdesmopressin normal plasma. Plasma factor VIII coagulant activity (VIII:C), VWF antigen (VWF:Ag), ristocetin-induced platelet agglutination, and ristocetin cofactor (RiCof) activity were low. Platelet VWF:Ag and RiCof levels (tested for three patients only) were normal. Bleeding times were normal or slightly prolonged. The patients' platelet multimeric structure was the same as that for normal platelets. After desmopressin infusion the plasma VWF multimeric structure remained supranormal as for preinfusion plasma, with VIII:C VWF:Ag and RiCof increasing markedly over baseline values and disappearing at a normal rate. Examination of the VWF subunit composition from three of these patients indicated that proteolytic processing of their VWF did not differ from normal. This study describes the first variant of VWD with a supranormal multimeric structure.     

Differences in functional connectivity in major depression versus bipolar II depression

Background

Objective methods of differentiating unipolar versus bipolar depression would enhance our ability to treat these disorders by providing more accurate diagnoses. One first step towards developing diagnostic methodology is determining whether brain function as assessed by functional MRI (fMRI) and functional connectivity analyses might differentiate the two disorders.

Methods

Fourteen subjects with bipolar II depression and 26 subjects with recurrent unipolar depression were studied using fMRI and functional connectivity analyses.

Results

The first key finding of this study was that functional connectivity of the right posterior cingulate cortex differentiates bipolar II and unipolar depression. Additionally, results suggest that functional connectivity of this region is associated with suicidal ideation and depression severity in unipolar but not bipolar II depression.

Limitations

The primary limitation is the relatively small sample size, particularly for the correlational analyses.

Conclusions

The functional connectivity of right posterior cingulate cortex may differential unipolar from bipolar II depression. Further, connectivity of this region may be associated with depression severity and suicide risk in unipolar but not bipolar depression.     

Thalamic atrophy in patients with pure hereditary spastic paraplegia type 4

Journal of Neurology - SPG4 is an autosomal dominant pure form of hereditary spastic paraplegia (HSP) caused by mutations in the SPAST gene. HSP is considered an upper motor neuron disorder...     

Chemotherapy and peripheral neuropathy

Neurological Sciences - Chemotherapy-induced peripheral neurotoxicity (CIPN) is a major dose-limiting side effect of many anti-cancer agents, including taxanes, platinums, vinca alkaloids,...