Determination of the breakpoint and molecular diagnosis of a common alpha-thalassaemia-1 deletion in the Indian population

The previously described South African type alpha-thalassaemia-1 mutation was identified in Indian HbH patients using a polymerase chain reaction (PCR) strategy. A multiplex PCR assay was devised to detect heterozygotes and homozygotes. This alpha-thalassaemia-1 mutation was found to be the commonest determinant causing HbH disease in this population. In one family this mutation was found in combination with a novel splice donor mutation alpha2 IVS I-1 (G-->A). Characterization of the breakpoint junction sequence revealed, in addition to a 23 kb deletion, that there was an addition of approximately 160 bp bridging the breakpoints. Similar to other deletions in the alpha-globin gene cluster, there is an Alu repeat-mediated mechanism for the origin of the deletion.     

Comparative efficacy and safety of the Ambu® AuraOnce™ laryngeal mask airway during general anaesthesia in adults: a systematic review and meta‐analysis

Previous comparisons between the Ambu^® AuraOnce^? and other laryngeal mask airways have revealed different results across various clinical studies. We aimed to perform a systematic review with meta‐analysis on the efficacy and safety of the AuraOnce compared with other laryngeal mask airways for airway maintenance in adults undergoing general anaesthesia. Our search of PubMed, PubMed Central, Scopus and the Central Register of Clinical Trials of the Cochrane Collaboration yielded nine randomised controlled trials eligible for inclusion. Comparator laryngeal mask airways were the LMA Unique^? (four trials), the LMA Classic^® (five trials) and the Portex^® Soft Seal^® (three trials). The AuraOnce provided an oropharyngeal leak pressure higher than the LMA Unique (304 participants, mean (95% CI) difference 3.1 (1.6–4.7) cmH₂O, p < 0.0001) and equivalent to the LMA Classic. The Soft Seal provided a higher leak pressure than the AuraOnce (229 participants, mean (95% CI) difference 3.5 (0.4–6.7) cmH₂O, p = 0.03). Insertion was significantly faster with the AuraOnce than the LMA Unique (304 participants, mean (95% CI) difference 5.4 (2.1–8.71) s, p = 0.001) and Soft Seal (229 participants, mean (95% CI) difference 9.5 (3.0–15.9) s, p = 0.004), but similar to the LMA Classic. The first‐insertion success rate of the AuraOnce was equivalent to the LMA Unique, LMA Classic and Soft Seal. We found a higher likelihood of bloodstaining on the cuff with the Soft Seal and a higher incidence of sore throat with the LMA Classic. We conclude that the AuraOnce is an effective alternative to the LMA Classic and LMA Unique, and easier to insert than all three other devices studied.     

Correlating clinical manifestations with factor levels in rare bleeding disorders: a report from Southern India

Data on the clinical manifestations of patients with clotting factor defects other than Haemophilia A, B and von Willebrand disease are limited because of their rarity. Due to their autosomal recessive nature of inheritance, these diseases are more common in areas where there is higher prevalence of consanguinity. There is no previous large series reported from southern India where consanguinity is common. Our aim was to analyze clinical manifestations of patients with rare bleeding disorders and correlate their bleeding symptoms with corresponding factor level. Data were collected in a standardized format from our centre over three decades on 281 patients who were diagnosed with rare bleeding disorders (fibrinogen, prothrombin, factor V (FV), FVII, FX, FXI, FXIII and combined FV or FVIII deficiency). Patients with liver dysfunction or those on medications which can affect factor level were excluded. All patients with <50% factor levels were included in this analysis. Patients were analysed for their salient clinical manifestations and it was correlated with their factor levels. The data shows that FXIII deficiency is the commonest and FXI deficiency is the rarest in Southern India. There was no significant difference in bleeding symptoms among those who were < or >1% factor coagulant activities among all disorders, except for few symptoms in FVII and FX deficiency. An international collaborative study is essential to find out the best way of classifying severity in patients with rare bleeding disorders.     

Reversal of Tumor Immune Inhibition Using a Chimeric Cytokine Receptor

The success of adoptively transferred tumor-directed T cells requires them to survive and expand in vivo. Most tumors, however, employ immune evasion mechanisms, including the production of inhibitory cytokines that limit in vivo T-cell persistence and effector function. To protect tumor-directed T cells from such negative influences, we generated a chimeric cytokine receptor in which the interleukin (IL) 4 receptor exodomain was fused to the IL7 receptor endodomain. We thereby inverted the effects of tumor-derived IL4 so that the proliferation and activation of tumor directed cytotoxic T cells was enhanced rather than inhibited in the tumor microenvironment, resulting in superior antitumor activity. These transgenic T cells were only activated in the tumor environment since triggering required exposure to both tumor antigen (signal 1) and tumor-derived IL4 (signal 2). This selectivity supports future clinical adaptation.     

Anaesthetic management of emergency caesarean section in a patient with seizures and likely raised intracranial pressure due to tuberculous meningitis

We report the anaesthetic management of a term pregnant woman with active tuberculous meningitis, who had experienced seizures, had signs of raised intracranial pressure and required emergency caesarean section. Peripartum anaesthetic management of a patient with tuberculous meningitis is a rare event.     

Qualitative and quantitative radio-anatomical variation of the posterior clinoid process

This study was conducted to investigate the radiological anatomy of the posterior clinoid process (PCP) to highlight preoperative awareness of its variations and its relationships to other skull base landmarks. The PCPs of 36, three-dimensional computed tomographic cadaveric heads were evaluated by studying the gross anatomy of the PCP and by measuring the distances between the PCP and other skull base anatomical landmarks relevant to transnasal or transcranial skull base approaches. PCP variations were found in five specimens (14%): in two the dorsum sellae was absent, in one the PCP and the anterior clinoid process (ACP) were connected unilaterally and in two bilaterally. The mean distance between the right/left PCP and the crista galli was 45.14 ± 4.0 standard deviation (SD_/46.24 ± 4.5 SD, respectively, while the distance to the middle point of the basion at the level of the foramen magnum was 40.41 ± 5.1 SD/41.0 ± 5.2 SD, respectively. The mean distance between the PCP and the ACP was 12.03 ± 3.18 SD on the right side and 12.11 ± 2.77 SD on the left. The data provided highlights the importance of careful preoperative evaluation of the PCP and of its relationships to other commonly encountered skull base landmarks. This information may give an idea of the exposure achievable through different transcranial and transnasal approaches. This is especially relevant when neuronavigation is not available.     

An endoscopic,cadaveric analysis of the roof of the fourth ventricle

We performed endoscopic dissections of the roof of the fourth ventricle in eight fresh human cadaveric heads to characterize the endoscopic anatomy of the roof of the fourth ventricle and the anatomical configuration of the structures forming its roof. We also made three-dimensional (3D) silicone casts of the fourth ventricle in seven formalin-fixed specimens to evaluate the 3D configuration of the structures that create the roof of the fourth ventricle. The roof of the fourth ventricle can be divided into three zones. The upper zone is formed by the superior cerebellar peduncle and superior medullary velum and is associated with the lingula. The middle zone is formed by the inferior cerebellar peduncles and inferior medullary velum and is associated with the nodule in the midline and with the peduncle of the flocculus. The lower zone is formed by the tela choroidea and is associated with the tonsils. The 3D shape of the roof the fourth ventricle resembles that of a rhomboid-based pyramid; the edges of the base represent the borders of the ventricle, and the apex is the cerebellar fastigium. The lateral recess is shaped like a triangular-based pyramid, with its base connected to the cavity of the fourth ventricle and its tip opening into the lateral cerebellomedullary cistern through the foramen of Luschka. Our results may help in the endoscopic exploration of and microsurgical approaches to the fourth ventricle through its roof.