The orthopaedic aspects of mycetoma.

This article presents an overview of mycetoma and offers guidelines for orthopaedic surgeons who may be involved in the care of patients with this condition.

SEPN1-related myopathies: clinical course in a large cohort of patients.

OBJECTIVE: To assess the clinical course and genotype-phenotype correlations in patients with selenoprotein-related myopathy (SEPN1-RM) due to selenoprotein N1 gene (SEPN1) mutations for a retrospective cross-sectional study. METHODS: Forty-one patients aged 1-60 years were included. Clinical data including scoliosis, respiratory function, and growth measurements were collected by case note review. RESULTS: Mean age at onset was 2.7 years, ranging from birth to the second decade of life. All but 2 remained independently ambulant: one lost ambulation at age 5 years and another in his late 50s. The mean age of starting nocturnal noninvasive ventilation (NIV) was 13.9 years. One child required full-time NIV at the age of 1 year while in 2 cases NIV was started at 33 years. Two patients died from respiratory failure at the age of 10 and 22 years, respectively. The mean age at scoliosis onset was 10 years, in most cases preceded by rigidity of the spine. Fourteen patients had successful spinal surgery (mean age 13.9 years). Twenty-one were underweight; however, overt feeding difficulties were not a feature. CONCLUSIONS: This study describes the largest population affected by SEPN1-RM reported so far. Our findings show that the spectrum of severity is wider than previously reported. Respiratory insufficiency generally develops by 14 years but may occur as early as in infancy or not until the fourth decade. Motor abilities remain essentially static over time even in patients with early presentation. Most adult patients remain ambulant and fully employed.

Shenton's line.

This paper considers the history of Shenton's line.

A pilot randomised controlled trial of a home-based exercise programme aimed at improving endurance and function in adults with neuromuscular disorders.

AIM: To investigate the feasibility and effect of a home-based exercise programme on walking endurance, muscle strength, fatigue and function in people with neuromuscular disorders (NMDs). METHODS: 20 adults with NMDs recruited to a control (n = 11) or exercise (n = 9) group were assessed by blinded assessors at baseline and at week 8. Walking and strengthening exercises were given to the exercise group in an 8-week home exercise programme. A 2-min walk distance was the main outcome measurement; isometric muscle strength, fatigue and function were secondary measurements. RESULTS: 2-min walk distances were not found to change in either group (p>0.05; control: mean 14.50 (SD 22.06) m; exercise: mean 2.88 (SD 20.08) m), and no difference was observed in the change scores between groups (p>0.05). Leg muscle strength increased in the exercise group (p<0.05) but not in the control group (p>0.05). Significance was reached between the groups with respect to the difference in change in muscle strength scores in the right quadriceps (p<0.05; control: mean -2.82 (SD 4.87) kg; exercise: mean -7.08 (SD 2.82) kg). No change was observed in fatigue or function scores (p<0.05). CONCLUSIONS: A home-based approach aimed at improving endurance in adults with NMDs is feasible and further investigation on a larger sample is warranted.

Application of Maximum Entropy reconstruction to PISEMA spectra.

Maximum Entropy reconstruction is applied to two-dimensional PISEMA spectra of stationary samples of peptide crystals and proteins in magnetically aligned virus particles and membrane bilayers. Improvements in signal-to-noise ratios were observed with minimal distortion of the spectra when Maximum Entropy reconstruction was applied to non-linearly sampled data in the indirect dimension. Maximum Entropy reconstruction was also applied in the direct dimension by selecting sub-sets of data from the free induction decays. Because the noise is uncorrelated in the spectra obtained by Maximum Entropy reconstruction of data with different non-linear sampling schedules, it is possible to improve the signal-to-noise ratios by co-addition of multiple spectra derived from one experimental data set. The combined application of Maximum Entropy to data in the indirect and direct dimensions has the potential to lead to substantial reductions in the total amount of experimental time required for acquisition of data in multidimensional NMR experiments.

Rotational osteotomies for congenital radioulnar synostosis.

In five children, six forearms with a fixed pronation deformity secondary to congenital radioulnar synostosis were treated by a derotation osteotomy of the distal radius and the midshaft of the ulna. There were three boys and two girls with a mean age of 4.9 years (3.5 to 8.25) who were followed up for a mean of 29 months (18 to 43). The position of the forearm was improved from a mean pronation deformity of 68 degrees (40 degrees to 80 degrees ) to a pre-planned position of 10 degrees of supination in all cases. Bony union was achieved by 6.3 weeks with no loss of correction. There was one major complication involving a distal radial osteotomy which required exploration for a possible compartment syndrome.

NMR experiments on aligned samples of membrane proteins.

NMR methods can be used to determine the structures of membrane proteins. Lipids can be chosen so that protein-containing micelles, bicelles, or bilayers are available as samples. All three types of samples can be aligned weakly or strongly, depending on their rotational correlation time. Solution NMR methods can be used with weakly aligned micelle and small bicelle samples. Solid-state NMR methods can be used with mechanically aligned bilayer and magnetically aligned bicelle samples.

Biosynthesis and purification of a hydrophobic peptide from transmembrane domains of G-protein-coupled CB2 receptor.

A major challenge for the structural study of the seven-transmembrane G-protein-coupled receptors is to obtain a sufficient amount of purified protein at the milligram level, which is required for either nuclear magnetic resonance (NMR) spectroscopy or X-ray crystallography. In order to develop a high-yield and cost-effective method, and also to obtain preliminary structural information for the computer modeling of the three-dimensional receptor structural model, a highly hydrophobic peptide from human cannabinoid subtype 2 receptor CB2(65-101), was chosen to develop high-yield membrane protein expression and purification methods. The peptide included the second transmembrane helix with the associated loop regions of the CB2 receptor. It was over-expressed in Escherichia coli, with a modified TrpDelta LE1413 (TrpLE) leading fusion sequence and a nine-histidine tag, and was then separated and purified from the tag in a preparative scale. An experimental protocol for the chemical cleavage of membrane protein fragment was developed using cyanogen bromide to remove the TrpLE tag from the hydrophobic fusion protein. In addition, protein uniformly labeled with isotopic 15N was obtained by expression in 15N-enriched minimum media. The developed and optimized preparation scheme of expression, cleavage, and purification provided a sufficient amount of peptide for NMR structure analysis and other biophysical studies that will be reported elsewhere. The process of fusion protein cleavage following purification was monitored by high-performance liquid chromatography (HPLC) and mass spectrometry (MS), and the final sample was validated by MS and circular dichroism experiments.

Linear sebaceous naevus syndrome and resistant rickets.

The association between vitamin-D-resistant rickets and linear sebaceous naevus syndrome is extremely rare. Only eight cases have been described in the English literature and in none were the skeletal aspects addressed. We present three new cases and describe the musculoskeletal features. The details and outcome of surgery for correction of the deformities are discussed. The disturbances of metabolism of vitamin D and the effects of pharmacological treatment are also described.

Improving primary orthopaedic and trauma care in Nepal.

PURPOSE: To evaluate the efficacy of training programmes for the village health practitioners aimed at improving primary orthopaedic and trauma care in our rural setting. MATERIALS & METHODS: Six year prospective study of training workshops in local health institutions was carried out using locally available manpower and materials. RESULTS: After 6 years the evaluation of this programme shows a significantly improved (p < 0.05) knowledge base and working skills after completion of training workshop. SUMMARY: To avoid unnecessary complications, effective primary health care provided by an appropriately trained person should be available at the peripheral level. This training programme seems successful in achieving this goal and hence needs adoption for wider use in Nepal.

A new surgical technique for keratoglobus-tectonic lamellar keratoplasty followed by secondary penetrating keratoplasty.

PURPOSE: To develop a technique that achieves satisfactory visual rehabilitation in keratoglobus, without the problems of re-epithelialization failure and with minimal risk of graft rejection. METHODS: A patient with bilateral keratoglobus and visual acuities of light perception in the right eye and 6/60 in the left underwent a tectonic lamellar keratoplasty to the right eye. The cornea was first trephined to the depth of the anterior stroma within the limbus. A lamellar dissection technique then was used to tunnel into sclera under the limbus to preserve stem cells. The host corneal epithelium was completely débrided, and a donor corneoscleral button, denuded of its endothelium, was laid on top. A paracentesis was made, and aqueous was aspirated until the anterior chamber had collapsed enough to take up a more physiologic shape. The donor corneoscleral graft was sutured into the prefashioned scleral bed with long, interrupted sutures. Once in situ, the donor graft was débrided of epithelium, and the host limbus was sutured on to it, covering its scleral component. Six months later, a penetrating keratoplasty was performed. The same procedure was performed on the left eye 2 years later. RESULTS: The right eye maintained a best-corrected visual acuity of 6/60 for 16 months after the penetrating graft until the graft decompensated, leaving a final acuity of counting fingers. The left eye maintained a best-corrected visual acuity of 6/18. CONCLUSION: Tectonic lamellar keratoplasty to preserve the host limbus, followed by secondary penetrating keratoplasty, is a realistic alternative to other procedures for the surgical management of keratoglobus.

The mouse Na+-K+-ATPase gamma-subunit gene (Fxyd2) encodes three developmentally regulated transcripts.

The Na(+)-K(+)-ATPase is understood to function as a hetero-oligomer of alpha- and beta-subunits, but a third subunit, gamma, has been proposed to influence the enzyme's catalytic function. Recently, two variants of the gamma-subunit have been described in kidney, raising the possibility of multiple gamma-subunits with diverse functions. We now report the cloning and sequencing of the mouse gamma-subunit gene (Fxyd2). Analysis of the structure of the gene shows that it encodes three mRNAs that have distinct NH(2)-terminal (extracellular) encoding sequences but common transmembrane and COOH-terminal-encoding sequences resulting from differential splicing and, probably, alternate promoter usage. The three mRNAs have tissue-specific expression patterns. The existence of three different extracellular domains of the gamma-variants and how they may interact with the sodium pump to alter its cation transport properties must now be taken into account for future understanding of the modulation of the Na(+)-K(+)-ATPase by its gamma-subunit.

Menjugate (Chiron).

Chiron has developed and launched Menjugate, a vaccine for the treatment for meningococcus C infections caused by the pathogen Neisseria meningitidis [177064]. In August 1999, Chiron filed with the UK MCA for a license to market Menjugate. The licence was granted in March 2000 [339082], [344773], [357897] and as of April 2000, a vaccination program was underway in the UK [362152]. Menjugate is indicated for children of 12 months and older, but Chiron was expecting approval in the US for infants younger than 12 months by the end of 2000. The company will also pursue mutual recognition in Europe [376204]. In August 2000, Chiron received marketing clearance for Menjugate from the Irish Medicines Board as a conjugate against meningococcal C disease [378353]. The vaccine employs CRM-conjugate technology, whereby a diphtheria toxoid is used as a carrier protein for the meningitis C-specific antigens. The vaccine is being developed for its potential to provide protection against meningitis in both adults and infants. In July 2000, Chiron entered into a comarketing and co-promotion agreement with Aventis Pasteur under which Aventis will assist Chiron in marketing and sales efforts for Menjugate in the UK [374760].

Tetracel (American Home Products).

American Home Products (AHP) is developing Tetracel as a vaccine for children (aged 12 to 18 months) against diphtheria, tetanus, pertussis and Haemophilus influenzae type B (Hib) [275146]. The components are contained in AHP's two currently marketed vaccines. ACEL-Immune contains diphtheria and tetanus toxoids with acellular pertussis vaccine adsorbed, and HibTITER contains the Haemophilus influenzae B conjugate vaccine (diphtheria CRM197 protein conjugate) [239655]. As of January 2000, Lehman Brothers predicted Tetracel to be approved in the US during 2000 [354434].

A novel microencapsulated peptide vaccine against hepatitis B.

A 48 amino acid synthetic peptide (S121/48) representing residues 121-167 of the major envelope protein of hepatitis B virus (HBsAg) was successfully encapsulated into polylactide co-glycolide microspheres. A single immunization of the microspheres in BALB/c (H-2d) mice resulted in the production of high-titre anti-HBs antibodies (IgG1-type). The response was long lasting and was superior to that obtained using the same peptide adjuvanted with Freund's complete adjuvant. A T-cell memory response was detected 10 weeks after a booster immunization (approximately 35 weeks after initial immunization) as measured by in-vitro re-stimulation of splenocytes. This study illustrates the feasibility of a single dose vaccine for hepatitis B and is, to our knowledge, the first demonstration of a synthetic peptide immunogen inducing anti-native protein antibodies of comparable titre to those obtained with conventional vaccines for hepatitis B. The suitability of a synthetic peptide vaccine for hepatitis B is discussed.