Enteral nutrition and bone marrow transplantation.

This retrospective study evaluated the efficacy of enteral nutrition for pediatric patients undergoing the challenging treatment of allogeneic bone marrow transplantation. During the period from January 1999 to May 2000, 15 patients were transplant recipients. On admission to the hospital, 87% of patients were above the 50th percentile for weight for age. Nasogastric tubes were inserted while platelet counts remained greater than 50 x 10(9) mL/L. A specialized elemental formula for pediatric patients was commenced. These feeds were administered continuously and were titrated until caloric requirement or tolerance level had been achieved. During hospitalization for bone marrow transplantation, enteral nutrition was the major form of nutritional support for all patients. Enteral feeds continued even during maximal gut toxicity and were supported with antiemetics and analgesia. There were insignificant weight fluctuations during hospitalization, with 80% of children above the 50th percentile weight for age being discharged. Enteral nutrition via a nasogastric tube was effective in the provision of nutrition during bone marrow transplantation and continues to have an important role in this unit.     

Cortical plasticity in the first year after cochlear implantation

This study aimed to investigate changes in auditory and visual cortical activity over the first year following cochlear implantation using (18)F-fluorodeoxyglucose positron emission tomography. Subjects underwent scanning prior to the initial implant activation (control), after one to two months of implant use (early activation) and after one year of implant use (late activation). All subjects had activation of the auditory cortices. Group analysis using Statistical Parametric Mapping package SPM99 showed these became more focused over the first year of implant use. There was no evidence of left hemispheric dominance at any stage post implantation.Visual cortical activations were highly variable between patients and did not increase significantly between early and late activations. Taken together, our results lead us to suggest that the neural processes that occur during the first year of auditory rehabilitation following cochlear implantation vary between individuals to a greater extent than previously reported.     

Positron emission tomography of murine liver metastases and the effects of treatment by combretastatin A-4

. There are major potential advantages in non-invasive measurement of preclinical tumour biology and therapeutic response in clinically relevant, internal body sites, notably the ability to follow outcome in individual animals rather than averaging results from groups. We have exploited positron emission tomography (PET) to determine the feasibility of detecting liver metastases in B6D2F₁ mice using fluorine-18 fluorodeoxyglucose ([¹⁸F]FDG) both before and after treatment by the novel cytotoxic agent, combretastatin A-4. The normal distribution of [¹⁸F]FDG in the absence of disease was characterised, with the clear delineation of the brain, the heart and the urinary bladder in all studies. In untreated mice with liver metastases, a strong correlation (r ² = 0.98) was found between the quantitative estimates of [¹⁸F]FDG uptake obtained by analysis of PET images, and those obtained from ex vivo assay of liver plus metastases excised immediately after imaging. In this first series, the effective limit of resolution was in livers containing a number of small metastases (range 8–14) with a single volume equivalent of approximately 200 mm³. PET image analysis was concordant with histological measurements in showing that single intraperitoneal doses of combretastatin A-4 resulted in an average 30% volume destruction of metastatic mass by 24 h following administration. Received 1 August and in revised form 26 October 1998     

Haploinsufficiency of desmoplakin causes a striate subtype of palmoplantar keratoderma [published erratum appears in Hum Mol Genet 1999 May;8(5):943]

Desmosomes are highly organized intercellular adhesive junctions that are particularly prominent in epidermis and other tissues experiencing mechanical stress. Desmoplakin, a constitutive component of the desmosomal plaque, is the most abundant protein present in such junctions and plays a critical role in linking the intermediate filament network to the plasma membrane in these tissues. Here we report the first mutation in the gene encoding desmoplakin. The identified mutation, resulting in a null allele and haploinsufficiency, was observed in genomic DNA from a kindred with the dominantly inherited skin disorder, striate palmoplantar keratoderma. Affected individuals had a linear pattern of skin thickening on the fingers and palms and circumscribed areas of skin thickening on the soles. Affected skin demonstrated loosening of intercellular connections, disruption of desmosome-keratin intermediate filament interactions and a proportion of rudimentary desmosomal structures. The disorder mapped to chromosome 6p21 with a maximum lod score of 10.67. The mutation was a heterozygous C-->T transition in exon 4 of the desmoplakin gene and predicted a premature termination codon in the N-terminal region of the peptide. This is the first reported mutation of desmo-plakin and also the first inherited skin disorder in which haploinsufficiency of a structural component has been implicated. It identifies dosage of desmoplakin as critical in maintaining epidermal integrity.      

Extravasation of phenytoin in the hand

A case of subcutaneous phenytoin extravasation in the hand is reported. Treatment consisting of compressive dressing, elevation, and splinting was successful in restoring hand function.     

Foreign epitopes in immunodominant regions of hepatitis B core particles are highly immunogenic and conformationally restricted.

The presentation of heterologous amino acid sequences on the surface of hepatitis B core antigen (HBcAg) particles has been studied using a defined linear neutralization site from human rhinovirus (HRV). Previous work has shown that fusion particles, in which the HRV peptide sequence is linked to the amino terminus of the HBcAg protein, induce excellent immune responses in experimental animals. Using predictive models of HBcAg particulate structure and the approximate location of the major immunogenic regions we have designed and constructed bacterial expression vectors which direct synthesis of chimeric particles in which heterologous sequences are presented within an immunodominant area on the particle. Immunological responses to the heterologous peptide sequence are improved by at least tenfold when compared with amino terminal fusions of the same peptide sequence to HBcAg. Moreover, the restriction placed on the heterologous peptide by its linkage at both ends within the HBcAg protein results in a more constrained structure. In the case of the rhinovirus peptide sequence this results in an antigenic conformation more closely resembling that on the native virus particle. Such a system lends itself well as a general approach to the induction of high titre antibodies against defined epitopes.     

Antigen processing and presentation of human rhinovirus to CD4 T cells is facilitated by binding to cellular receptors for virus

Human rhinovirus serotypes (HRV) fall into two distinct groups, major and minor, by virtue of their cell receptor-binding ability. In this study minor receptor-binding group viruses are demonstrated to bind directly to cells of the murine immune system, including lymphoid dendritic cells which act as antigen-presenting cells, although they do not produce a productive infection in murine cells. This binding is specific and can be blocked by other serotypes of minor-group HRV Pre-treatment of HRV 1A, a minor-group virus, with HRV 1A-specific antibodies inhibited the cellular proliferation of murine virus primed T helper cells, whereas antibody treatment of HRV 15, a non-binding major serotype, gave no inhibition. The cell binding ability of minor-group HRV played a role in the overall immunogenicity of this virus group, which was shown to be enhanced compared to the immunogenicity of major-group viruses in mice.     

Orthopaedic assessment unit: a service model for the delivery of orthopaedic trauma care in a major trauma centre during the global pandemic (COVID-19)

IntroductionWe describe a new service model, the Orthopaedic Assessment Unit (OAU), designed to provide care for trauma patients during the COVID-19 pandemic. Patients without COVID-19 symptoms and isolated musculoskeletal injuries were redirected to the OAU.MethodsWe prospectively reviewed patients throughput during the peak of the global pandemic (7 May 2020 to 7 June 2020) and compared with our historic service provision (7 May 2019 to 7 June 2019). The Mann–Whitney and Fisher Exact tests were used to test the statistical significance of data.ResultsA total of 1,147 patients were seen, with peak attendances between 11am and 2pm; 96% of all referrals were seen within 4h. The majority of patients were seen by orthopaedic registrars (52%) and nurse practitioners (44%). The majority of patients suffered from sprains and strains (39%), followed by fractures (22%) and wounds (20%); 73% of patients were discharged on the same day, 15% given follow up, 8% underwent surgery and 3% were admitted but did not undergo surgery. Our volume of trauma admissions and theatre cases decreased by 22% and 17%, respectively (p=0.058; 0.139). There was a significant reduction of virtual fracture clinic referrals after reconfiguration of services (p<0.001).ConclusionsRapid implementation of a specialist OAU during a pandemic can provide early definitive trauma care while exceeding national waiting time standards. The fall in trauma attendances was lower than anticipated. The retention of orthopaedic staff in the department to staff the unit and maintain a high standard of care is imperative.