Development of mycosis fungoides after bone marrow transplantation for chronic myeloid leukaemia: transmission from an allogeneic donor.

We report on a patient who developed donor-derived cutaneous T-cell lymphoma (CTCL) 4 years after successful treatment of chronic myeloid leukaemia with an allogeneic bone marrow transplant. The patient developed an eczematous rash unresponsive to topical therapy and immunosuppression. When CTCL was diagnosed in the recipient, his sibling donor had been attending his local dermatology unit with a maculosquamous rash, which proved subsequently to be mycosis fungoides. An identical pattern of donor and recipient clonality assessment and T-cell receptor gene sequencing indicated that the CTCL was probably transmitted in the bone marrow harvest. This suggests that CTCL cells circulate in the marrow at an early subclinical stage in this disease. This is the second case of donor-derived CTCL reported to date.

Anaesthetists' risk assessment of placebo nerve block studies using the SHAM (Serious Harm and Morbidity) scale.

The SHAM (Serious Harm and Morbidity) scale was developed to categorise the severity of potential complications of placebo control interventions in the context of local anaesthesia research. A convenience sample of 43 anaesthetists used the SHAM scale to grade ten published randomised controlled trials investigating local anaesthesia nerve blocks. The Fleiss κ statistic assessed agreement between these anaesthetists and probability of random agreement (Pr(e)) when using the SHAM scale; a κ > 0 shows concordance between assessors above random agreement. Overall κ was 0.50 (95% CI 0.49-0.51, p < 0.001), Pr(e) = 0.21. There was moderate agreement between assessors in determining whether studies were low-risk (SHAM score 0-2) or high-risk (SHAM score 3-4) (κ 0.60 (95% CI 0.58-0.62), Pr(e) = 0.51). Compared with anaesthetists given clinical examples of interventions when applying the SHAM score, anaesthetists who were not given examples showed significantly less inter-individual agreement (κ 0.76 (95% CI 0.72-0.81), Pr(e) = 0.5 vs 0.45 (95% CI 0.41-0.49), Pr(e) = 0.52, p < 0.0001). These results suggest that the SHAM score can be successfully used to grade the severity of potential complications of placebo-controlled interventions in local anaesthesia research and represent a first step towards the score's validation.

Break on through: The role of innate immunity and barrier defence in atopic dermatitis and psoriasis.

The human skin can be affected by a multitude of diseases including inflammatory conditions such as atopic dermatitis and psoriasis. Here, we describe how skin barrier integrity and immunity become dysregulated during these two most common inflammatory skin conditions. We summarise recent advances made in the field of the skin innate immune system and its interaction with adaptive immunity. We review gene variants associated with atopic dermatitis and psoriasis that affect innate immune mechanisms and skin barrier integrity. Finally, we discuss how current and future therapies may affect innate immune responses and skin barrier integrity in a generalized or more targeted approach in order to ameliorate disease in patients.

Use of invasive placebos in research on local anaesthetic interventions.

Placebos play a vital role in clinical research, but their invasive use in the context of local anaesthetic blocks is controversial. We assessed whether recently published randomised controlled trials of local anaesthetic blocks risked harming control group patients in contravention of the Declaration of Helsinki. We developed the 'SHAM' (Serious Harm and Morbidity) scale to assess risk: grade 0 = no risk (no intervention); grade 1 = minimal risk (for example, skin allergy to dressing); grade 2 = minor risk (for example, subcutaneous haematoma, infection); grade 3 = moderate risk (with or without placebo injection) (for example, neuropraxia); and grade 4 = major risk (such as blindness, pneumothorax, or liver laceration). Placebo interventions of the 59 included trials were given a SHAM grade. Nine hundred and nineteen patients in 31 studies, including six studies with 183 children, received an invasive placebo assessed as SHAM grade ≥ 3. A high level of agreement (78%, κ = 0.80, p < 0.001) for SHAM grades 0-4 increased to 100% following discussion between assessors. More than half of the randomised controlled study designs subjected patients in control groups to risks of serious or irreversible harm. A debate on whether it is justifiable to expose control group patients to risks of serious harm is overdue.

Somatostatin-28 and pro-ocytocin/neurophysin convertases: basic pair selective endoproteases involved in pro-hormone processing in the rat brain cortex and bovine corpus luteum.

Two neuropeptide precursor processing enzyme systems were characterized in the rat brain cortex and bovine neurohypophysis and corpus luteum. The first one combines the action of a 90 kDa endoprotease which cleaves somatostatin-28 before the Arg-Lys doublet and that of an aminopeptidase B-like enzyme. The second system associates the action of a 58 kDa endoprotease cleaving pro-ocytocin/neurophysin (1-20) after the Lys-Arg dibasic moiety and a carboxypeptidase B-like activity. Both systems appear to be located in membrane-limited secretory vesicles of the producing organs, and to exhibit the properties of metallo-enzymes sensitive to divalent cation chelators. In contrast, they do not show the characteristics of serine-proteases and of trypsin-like enzymes. Studies with substrate analogs selectively modified at the basic doublet indicated that the integrity of both basic amino acids is essential but that conformational parameters, probably governed by the amino acid sequences flanking the basic doublet, play an important role. These data will be discussed in relation to a hypothesis on the predicted preferred secondary structure of these restriction loci.

Lighting a lamp for persons who are visually challenged.

This paper is an outgrowth of an investigation to (1) identify persons with diabetes mellitus who manifest varying degrees of self-destructive behavior, (2) compile a list of dangerously negative self-management practices observed in the person who is visually challenged, (3) outline a comprehensive diabetes skills update designed to restore self-esteem, and (4) suggest to the rehabilitation worker and the diabetes educator ways to enhance instruction. The paper lists behaviors that may cause deadly harm to persons visually challenged by diabetes mellitus, requiring careful observation by the diabetes educator. A case report shows that numerous teaching opportunities arise from analyzing self-care skills that are lost due to vision pathology.

Cochlear implantation in children with large vestibular aqueduct syndrome and a review of the syndrome.

OBJECTIVE: Children with Large Vestibular Aqueduct Syndrome (LVAS) frequently develop speech and language skills prior to deterioration of their hearing. Operations designed to halt the progression of hearing loss have largely failed so the question of Cochlear Implantation in these children has arisen. It had been suggested that there would be technical difficulties in implanting these patients and, therefore, there had been an initial reluctance to proceed to implantation. The aim of the present paper is to assess surgical and functional outcomes in implanted children with LVAS and review the related literature. MATERIAL AND METHODS: From the 170 children assessed by MRI in the Nottingham Paediatric Cochlear Implant Programme, seven (4%) were identified as having LVAS. Four of these children were implanted and had at least 12 months follow up. Two of the children are on the waiting list for implantation and one child was not implanted because of absence of the cochlear nerve. Operative findings, complications and outcome measures were recorded. The auditory skills of the children were assessed before implantation and 1 year following implantation. A literature search was done to identify other series with experience in implanting children with LVAS. RESULTS: Full insertion of the electrode array was achieved in all our cases. After cochleostomy two patients experienced a mild CSF leak that was easily controlled by the muscle graft. On the first day post-operation two patients were nauseous and one had an episode of vomiting, however, all were discharged within 24 h of surgery. Initial outcome measures at 12 months post-implantation were encouraging showing significant progress in children's auditory skills. CONCLUSIONS: The results of the present study and the review of the literature suggest that LVAS is not a contraindication to implantation as initial concerns about severe perilymph leaks and surgical complications have proved to be unfounded. The post-operative progress of these children in listening skills also suggest that these children are suitable for cochlear implantation

Facial paralysis in Wegener's granulomatosis of the middle ear.

A case of Wegener's granulomatosis, which presented as chronic otitis media with facial nerve palsy, is described. Early diagnosis is vital if unnecessary surgical exploration is to be avoided. A false negative cANCA may delay the diagnosis, especially in cases of locoregional disease, and a policy of repeated titres should be adopted, if clinical suspicion is high.

Anaesthesia-related haemodynamic complications in Williams syndrome patients: a review of one institution's experience.

Williams syndrome is a genetic disorder associated with cardiac pathology, including supravalvular aortic stenosis and coronary artery stenosis. Sudden cardiac death has been reported in the perioperative period and attributed to cardiovascular pathology. In this retrospective audit, case note and anaesthetic records were reviewed for all confirmed Williams syndrome patients who had received an anaesthetic in our institution between July 1974 and November 2009. There were a total of 108 anaesthetics administered in 29 patients. Twelve of the anaesthetics (11.1%) were associated with cardiac complications including cardiac arrest in two cases (1.85%). Of the two cardiac arrests, one patient died within the first 24 hours postanaesthetic and the other patient survived, giving an overall mortality of 0.9% (3.4%). We conclude that Williams syndrome confers a significant anaesthetic risk, which should be recognised and considered by clinicians planning procedures requiring general anaesthesia.

A survey of aseptic precautions and needle type for paediatric caudal block in Australia and New Zealand.

This cross-sectional survey was designed to evaluate the current practice of anaesthetists in Australia and New Zealand with regard to aseptic technique and needle type during the performance of single-shot caudal blocks. Professional bodies suggest that full aseptic precautions be taken during the administration of caudal or epidural blocks. It has been suggested that using an intravenous cannula or a styletted needle may obviate the occurrence of epidermoid tumours. A total of 202 members of the Society for Paediatric Anaesthesia in New Zealand and Australia were invited to participate in this internet-based survey. Eighty-four responses were received. Most respondents used some form of antiseptic handwash (81%), wore sterile gloves (85.7%), used antiseptic skin preparation (100%) and draped the site (57.1%). When performing caudal blocks, 43.1% used unstyletted needles, 27.2% used styletted spinal needles and 29.6% used intravenous cannulas. However, 11.9% did not wash hands, 10.7% did not wear gloves and 42.9% did not drape the site. Three respondents reported neither handwashing, wearing gloves or draping, instead only using an alcohol swab for skin preparation. The majority of respondents in our region appear to use some level of aseptic precautions, albeit to a variable degree. Published recommendations may either be perceived as overly cautious or as ambiguous in that they do not specify caudal practice as distinct from other epidural blocks. There is a need for clearer professional guidance to support a minimum level of aseptic precaution for single-shot caudal epidural blocks.

Anaesthesia for excision of an intraoral mass in a neonate: use of a laryngeal mask during removal of congenital epulis.

Congenital epulis is a rare intraoral tumour of the newborn arising from gingival mucosa, most commonly from the alveolar ridge. It may interfere with normal feeding or potentially compromise respiration. We describe the anaesthetic management of one such case of a female infant born with a single epulis, approximately 3 cm in diameter, protruding from her mouth. The lesion was removed one day after delivery, under general anaesthesia using a laryngeal mask airway to control the infant's airway. The rationale for this management plan and alternatives to this strategy are discussed.

Descending necrotising mediastinitis: a safe treatment algorithm.

Descending necrotising mediastinitis can complicate oropharyngeal infection and has a high associated mortality. We present three cases treated in our department and propose a treatment algorithm based on our experience and literature review. The primary oropharyngeal infection was peritonsillar abscess in two cases and odontogenic abscess in one. Two patients underwent cervicotomy and later thoracotomy. The third underwent cervicotomy with transcervical mediastinal drainage and later required pericardial drainage via a subxiphoid incision. All recovered fully and were discharged within 6 weeks. To enable successful treatment, diagnosis needs to be prompt and surgical drainage adequate. Thoracic management of the chest is essential.

Nasal polyposis and facial pain.

A cohort of 973 patients with symptoms of rhinosinusitis and/or facial pain was followed up for a mean of 2 years 2 months and, within this, was a group of 220 with nasal polyps. Only 39 (18%) had pain or pressure as a symptom. Out of the 220 with nasal polyps, 190 had polyps without any purulent secretions and, of these, only 5 (2.6%) had pain attributable to their paranasal sinus disease. Ten out of the 15 with pain and polyps without pus were found to have pain as a result of neurological or medical cause after endoscopic sinus surgery and a trial of medical nasal treatment and, where necessary, drugs to treat neurological conditions. Thirty patients (13.6%) had nasal polyposis and purulent secretions, and, within this subgroup, 24 (79%) had pain as well. Of the 24 with pain and purulent secretions, 19 (80%) responded to treatment for their paranasal sinus disease, a far higher proportion than with nasal polyps without pus. In conclusion, in patients who have nasal polyps without purulent secretions, be cautious about attributing any symptoms of facial pain or pressure as being due to their paranasal sinuses as it is more probable that it is coincidental and the result of a neurological cause.

Sedation for paediatric stereotactic radiosurgery: the dexmedetomidine experience.

Dexmedetomidine is a potent alpha2 adrenergic agonist, with sedative and analgesic properties which may make it a suitable sedative agent for procedures on paediatric patients. A six-year-old boy required sedation for stereotactic radiosurgical ablation of an arteriovenous malformation on two occasions. Sedation with dexmedetomidine was planned, with increased dosage used on the second occasion. On both occasions dexmedetomidine was inadequate as a sole agent and required supplementation with other agents.

An endopeptidase associated with bovine neurohypophysis secretory granules cleaves pro-ocytocin/neurophysin peptide at paired basic residues.

The octacosapeptide sequence [Tyr18] pro-ocytocin/neurophysin (1-18)NH2 [pro-OT/Np(1-18)NH2] was synthesized and used as substrate to detect endoprotease(s) possibly involved in the processing of this precursor in bovine hypothalamo-neurohypophyseal tract. An endopeptidase (58 Kda) was detected in Lysates made from highly purified neurosecretory granules. This protease which cleaves the peptide bond on the carboxyl side of the Lys-Arg doublet, and no single basic residue, generates both OT-Gly10-Lys11-Arg12+Ala13-Val-Leu-Asp-Leu-Tyr18 (NH2) from the octacosapeptide substrate. In addition, a carboxypeptidase B-like activity converting OT-Gly10-Lys11-Arg12 into OT-Gly10 was detected in the same granule Lysates. It is hypothesized that a combination of these endoprotease and carboxypeptidase B-like activities together with the amidating enzyme of secretory granules might participate in the cleavage and processing of pro-OT/Np in vivo.

Enzymes processing somatostatin precursors: an Arg-Lys esteropeptidase from the rat brain cortex converting somatostatin-28 into somatostatin-14.

The post-translational proteolytic conversion of somatostatin-14 precursors was studied to characterize the enzyme system responsible for the production of the tetradecapeptide either from its 15-kDa precursor protein or from its COOH-terminal fragment, somatostatin-28. A synthetic undecapeptide Pro-Arg-Glu-Arg-Lys-Ala-Gly-Ala-Lys-Asn-Tyr(NH2), homologous to the amino acid sequence of the octacosapeptide at the putative Arg-Lys cleavage locus, was used as substrate, after 125I labeling on the COOH-terminal tyrosine residue. A 90-kDa proteolytic activity was detected in rat brain cortex extracts after molecular sieve fractionation followed by ion exchange chromatography. The protease released the peptide 125I-Ala-Gly-Ala-Lys-Asn-Tyr(NH2) from the synthetic undecapeptide substrate and converted somatostatin-28 into somatostatin-14 under similar conditions (pH 7.0). Under these experimental conditions, the product tetradecapeptide was not further degraded by the enzyme. In contrast, the purified 15-kDa hypothalamic precursor remained unaffected when exposed to the proteolytic enzyme under identical conditions. It is concluded that this Arg-Lys esteropeptidase from the brain cortex may be involved in the in vivo processing of the somatostatin-28 fragment of prosomatostatin into somatostatin-14, the former species being an obligatory intermediate in a two-step proteolytic mechanism leading to somatostatin-14.

Characterization of the 80,000 molecular weight form of neurophysin isolated from bovine neurohypophysis.

Partially purified immunoreactive species extracted from bovine posterior pituitary have been labeled with 125I and analyzed by immunoprecipitation with antineurophysin antibodies followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Under denaturing, but nonreducing conditions, a band of Mr = 80,000 was observed. This band corresponded to immunoreactive species detected by radioimmunoassay after chromatography of unlabeled material on a Sepharose CL-4B gel filtration column run in the presence of 6 M guanidine hydrochloride. Under nondenaturing conditions, this species behaved like molecules with an apparent Mr of 140,000 to 160,000. Electrophoretic analysis of the immunoprecipitated material showed that it contained an immunoreactive, single polypeptide chain of Mr = 80,000. Another immunoreactive species of similar molecular weight was also detected, apparently derived from the first one by peptide bond cleavage yielding two fragments of Mr = 68,000 and 10,000, respectively, held together by disulfide bridges. The Mr = 68,000 fragment had lost immunoprecipitability, although its peptide map was largely homologous to that or Mr = 80,000 polypeptide. The 10,000 piece was shown by radioimmunoassay and peptide analysis to be homologous to neurophysin.