First living‐related liver transplant to cure factor VII deficiency

Congenital factor VII deficiency is an autosomal recessive serious disorder of blood coagulation with wide genotypic and phenotypic variations. The clinical presentation can vary from asymptomatic patients to patients with major bleedings in severe deficiency (factor VII <1%). Investigations show prolonged PT and low factor VII. Treatment modalities include FFP and repeated recombinant factor VII infusions. We hereby report the first successful LRLT for factor VII deficiency in an infant, the first‐ever youngest baby reported worldwide. A six‐month‐old male child presented with easy bruisability, ecchymotic patches, hematuria, and convulsions. CT of the head showed subdural hemorrhage, which was treated conservatively. He had markedly increased PT (120 s) with normal platelets, and aPTT with factor VII level <1%. Despite the treatment by rFVIIa administration weekly, which was very expensive, he still had repeated life‐threatening bleeding episodes. LRLT was performed with mother as the donor, whose factor VII level was 57%. A factor VII infusion plan for pre‐, intra‐ and postoperative periods was formulated and TEG followed. Postoperatively, his factor VII started increasing from third day and was 38% on 24th day with PT <14 s. He had uneventful intraoperative and postoperative courses. LT is a safe and definite cure for factor VII deficiency.     

Increase in gamma/delta T cell receptor bearing lymphocytes in normal small bowel mucosa in latent coeliac disease.

A jejunal biopsy specimen from an asymptomatic 35 year old man was studied because of a low serum titre of reticulin antibody and the finding of coeliac disease in his son. In this specimen villous structure was quite normal as was the total number of intraepithelial lymphocytes, but the number of gamma/delta T cell receptor bearing lymphocytes was 10 times higher than the mean in control subjects. Two years later a further biopsy specimen was obtained because of clinical symptoms and an increased titre of reticulin antibody. This specimen showed villous atrophy with crypt hyperplasia and increased infiltration of intraepithelial lymphocytes compatible with coeliac disease. A control biopsy specimen taken during gluten free diet showed normalisation of the villous architecture. Latent coeliac disease may be characterised by an increase in gamma/delta positive cells similar to that seen in established coeliac disease.     

The Contribution of Anxiety Sensitivity to Obsessive–Compulsive and Anxiety Symptoms in a Naturalistic Treatment Setting

Anxiety sensitivity (AS), a fear of arousal-related sensations, is prevalent in a number of disorders. We examined the relationship between internalizing symptoms and the anxiety sensitivity components of physical, social, and cognitive concerns in a sample of 165 patients seeking treatment in a clinic specializing in cognitive behavioral therapy for anxiety-related disorders. Social anxiety symptoms were associated with greater social concerns. Cognitive concerns were characteristic of both depression and generalized anxiety symptoms, suggesting these two classes of symptoms may share AS symptomatology. Physical concerns were specifically related to panic symptoms. Although obsessive–compulsive symptoms were related to cognitive concerns using univariate regression, these symptoms were not strongly related to any of the anxiety sensitivity components when the correlation between disorders was taken into account. Thus, within the internalizing symptoms studied here, the anxiety sensitivity domains were most relevant to panic, social anxiety, generalized anxiety, and depressive symptoms and less related to obsessive–compulsive symptoms.     

Resistance to activated protein C due to a factor V gene mutation The most common inherited risk factor of thrombosis

The protein C anticoagulant pathway is of major importance in maintaining vascular patency. Resistance to the key enzyme of this system, activated protein C (APC), is a recently discovered congenital defect of the protein C system. This genetic defect is present in 20% to 60% of venous thrombosis patients, making it by far the most common known pathogenetic risk factor of thrombosis. APC resistance is due to a single point mutation in the factor V gene (G to A at nucleotide position 1691) that predicts the replacement of arginine(506) by glutamine. This is associated with the loss of one of three APC cleavage sites in factor Va, one of the substrates for APC, and hypercoagulability. The identification of APC resistance as an additional genetic risk factor in a large proportion of symptomatic protein C- and protein S-deficient families has provided evidence that thrombosis is a polygenetic disease. Thus, several genetic defects act in concert with environmental factors in the pathogenesis of venous thromboembolism.     

Rise in morning saliva cortisol is associated with abdominal obesity in men: a preliminary report

An abnormal regulation of the hypothalamic-pituitary-adrenal (HPA) axis is associated with risk factors for cardiovascular disease and Type 2 diabetes mellitus. The objective of this study was to examine if morning saliva cortisols show similar associations. Twenty-eight men, all 53 yr of age, delivered during an ordinary working day saliva cortisol samples immediately upon awakening and 15 min thereafter as well as at different times during the day, including after a standardized lunch. Dexamethasone (0.5 mg) suppression of cortisol was also measured. The rise of morning cortisol values was positively associated with body mass index (r: 0.45, p=0.016), waist/hip ratio (r: 0.54, p=0.003), abdominal sagittal diameter (r: 0.54, p=0.003), glucose (r: 0.54, p=0.003), insulin (r: 0.57, p=0.002) and triglycerides (r: 0.46, p=0.014). The morning rise also correlated positively with the elevation of cortisol following lunch (r: 0.45, p=0.043) but not with other cortisol measurements or dexamethasone suppression. Elevation of cortisol immediately after awakening has previously been found to provide a simple indicator of HPA axis regulation, as suggested also by the results of this study, and an elevated rise has been reported after exposure to frequent or chronic perceived stress. The rise of cortisol immediately after awakening might be an indicator of an increased risk of developing serious, prevalent diseases via the metabolic syndrome.     

Modulation of anti-idiotypic immune response by immunization with the autologous M-component protein in multiple myeloma patients

Multiple myeloma is characterized by a proliferation of clonal B lymphocytes and plasma cells. The idiotypic structure of clonal immunoglobulin (Ig) expressed on the tumour B-cell surface can be regarded as a tumour-specific antigen and, as such, a potential target for anti-idiotypic T and B cells in an immune regulation of the tumour-cell clone. Active immunization using the autologous monoclonal Ig as a 'vaccine' was shown to induce tumour-specific immunity in murine B-cell tumours and in human B-cell lymphoma. With the aim to induce or amplify an anti-idiotypic response in multiple myeloma, five stage I–III patients were repeatedly immunized with the autologous monoclonal IgG. Induction of idiotype-specific cellular immunity was analysed in vitro by an enzyme-linked immunospot assay (interferon-γ and interleukin-4 secreting cells). B cells secreting anti-idiotypic IgM antibodies were also analysed. An anti-idiotypic T-cell response was amplified 1.9–5-fold in three of the five patients during immunization. The number of B cells secreting anti-idiotypic antibodies also increased in these three patients. In two of the patients induction of idiotype-specific immunity was associated with a gradual decrease of blood CD19⁺ B cells. The induced T-cell response was eliminated during repeated immunization. Further studies are warranted to optimize the immunization schedule in order to achieve a long-lasting T-cell immunity against idiotypic determinants on the tumour clone. A role for immunity in controlling the tumour clone remains to be established.     

Correction to: Role of complement and potential of complement inhibitors in myasthenia gravis and neuromyelitis optica spectrum disorders: a brief review

Journal of Neurology - The original version of this article unfortunately contained a mistake. Fifth sentence of the fourth paragraph in the section “Non-nAChR autoantibody targets in...