Mutations in the fukutin-related protein gene (FKRP) identify limb girdle muscular dystrophy 2I as a milder allelic variant of congenital muscular dystrophy MDC1C.

The limb girdle and congenital muscular dystrophies (LGMD and CMD) are characterized by skeletal muscle weakness and dystrophic muscle changes. The onset of symptoms in CMD is within the first few months of life, whereas in LGMD they can occur in late childhood, adolescence or adult life. We have recently demonstrated that the fukutin-related protein gene (FKRP) is mutated in a severe form of CMD (MDC1C), characterized by the inability to walk, leg muscle hypertrophy and a secondary deficiency of laminin alpha2 and alpha-dystroglycan. Both MDC1C and LGMD2I map to an identical region on chromosome 19q13.3. To investigate whether these are allelic disorders, we undertook mutation analysis of FKRP in 25 potential LGMD2I families, including some with a severe and early onset phenotype. Mutations were identified in individuals from 17 families. A variable reduction of alpha-dystroglycan expression was observed in the skeletal muscle biopsy of all individuals studied. In addition, several cases showed a deficiency of laminin alpha2 either by immunocytochemistry or western blotting. Unexpectedly, affected individuals from 15 families had an identical C826A (Leu276Ileu) mutation, including five that were homozygous for this change. Linkage analysis identified at least two possible haplotypes in linkage disequilibrium with this mutation. Patients with the C826A change had the clinically less severe LGMD2I phenotype, suggesting that this is a less disruptive FKRP mutation than those found in MDC1C. The spectrum of LGMD2I phenotypes ranged from infants with an early presentation and a Duchenne-like disease course including cardiomyopathy, to milder phenotypes compatible with a favourable long-term outcome.

Occurrence of pulmonary thromboembolism immediately after arthroplasty.

INTRODUCTION: Respiratory complications are common after arthroplasty, with pulmonary thromboembolic disease (PTE) and fat emboli being the most serious. A scintigraphic study was designed to assess the occurrence of both diseases. A prospective tomographic study of perfusion was performed within 24 h of arthroplasty. Details of the detection of fat embolism will be presented elsewhere. METHODS: Patients with previous PTE were excluded. Tomographic lung studies were acquired after 99mTc-macroaggregated albumin injection. Pre- and post-operative arterial blood gases (ABGs) and relevant chest radiography/computed tomography scans were obtained. ABGs were analysed as the difference in alveolar-arterial oxygen gradients, pre- and post-operatively (DA-a). RESULTS: Forty patients were studied (16F, 24M) with a mean age of 71 years (range 36-88 years). Of these, 16 were hip and 24 knee arthroplasties. PTE was detected in 25 of 38 (66%) patients evaluated. The value of DA-a was significantly different between patients with PTE and without PTE (P>0.05). Administration of prophylactic pre-operative low molecular weight heparin makes no difference to the early onset of PTE. CONCLUSION: There is a high incidence of PTE immediately after arthroplasty.

SPET of a computerised model of diffuse lung disease.

Emphysema is a common and debilitating disease that is the commonest cause of end-stage respiratory failure. Treatment is either by lung transplantation or by lung volume reduction surgery (LVRS) that improves the biomechanics of respiration. Patient selection for LVRS hinges on the demonstration of heterogeneous disease, predominantly involving the upper lobes, as a good surgical outcome is most likely in these patients. We used a virtual model of lung scintigraphy to compare planar with tomographic scintigraphy for the detection of diffuse lung disease. Lesions of the magnitude of the lung acinus, as well as larger and smaller lesions, were distributed throughout the lungs in volumes from 2% to 50%. Single-photon emission tomography does not add incremental value to planar images for the detection of diffuse lung disease.

Importance of positioning and technical factors in anatomic localization of sporting injuries in scintigraphic imaging.

Sports medicine is becoming increasingly important as more people take up exercise for health and well-being. It is adding to the spectrum of acute and chronic injuries that have traditionally been seen in elite or professional athletes. Because of its high sensitivity and lesion contrast, bone scintigraphy has traditionally played a key role in the detection of such injuries. This role has been reduced in recent times by the increased use of magnetic resonance imaging (MRI), which has functional capability, high-contrast resolution, and high-spatial resolution. Bone scintigraphy has the capability of detecting early cortical ligament avulsion and enthesopathic disease before the onset of edema or changes in bone marrow that are detected by MRI. If this capability is added to more precise anatomic localization of lesions, we may see a resurgence in its use in sports medicine. A number of techniques are presented in this article, encompassing positioning, special views, and tomographic reconstructions, that can significantly improve the accuracy of localization of scintigraphic abnormalities with reference to anatomic models or sources of cross-sectional anatomy.

High-dose intra-arterial cisplatin and concurrent hyperfractionated radiation therapy in patients with locally advanced primary squamous cell carcinoma of the head and neck: report of a phase II study.

BACKGROUND: This phase II study evaluates the tolerability and efficacy of concurrent hyperfractionated radiation therapy (HFX-RT) and high-dose intra-arterial (IA) cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). METHODS: Between December 1995 and November 1997, 20 patients with locally advanced T4/T3 SCCHN were treated with HFX-RT (76.8-79.2 Gy at 1.2 Gy bid over 6-7 weeks) and high-dose IA cisplatin (150 mg/m(2) given at the start of RT boost treatment [start of week 6]). Seventeen patients (85%) had T4 disease, and 14 (70%) had N2/ N3 disease. RESULTS: Grade 3-5 acute toxicity was limited to one grade 4 (5%) and 14 grade 3 (70%) mucosal events. No grade 3/4 hematologic toxicity was observed. Median weight loss during therapy was 9% (range, 2%-16%). Eighteen patients had complete response (90%) at the primary site; 14 were confirmed pathologically. Among 17 patients with positive neck disease, 16 (94%) achieved complete response in the neck, including 12 of 13 patients with N2/N3 disease who underwent planned neck dissection. Active follow-up ranges from 12 to 32 months (median, 20 months) with 11 patients alive without disease, 5 dead of disease, and 4 dead of intercurrent disease. Eighteen patients (90%) remained disease free at the primary site, and the locoregional control rate is 80%. CONCLUSIONS: High-dose IA cisplatin and concurrent HFX-RT as used in this study is feasible and warrants further investigation. The high complete response rate and low grade 4 toxicity in this highly unfavorable subset of patients appears better than previously reported chemoradiation regimens for more favorable patients.

Single-photon emission tomography of a computerised model of pulmonary embolism.

Planar pulmonary scintigraphy is currently the standard investigation for the diagnosis of pulmonary embolism. There are a number of problems with the technique, particularly in patients with an intermediate scan report under the PIOPED criteria. The technique is also under threat from the increasing use of spiral CT angiography. A putative improvement may be gained by use of tomography. The incremental value of tomography over planar studies was therefore evaluated in a virtual model of pulmonary scintigraphy. A model of the segmental anatomy of the lungs was developed from computed tomography, cadaveric human lungs and available anatomical texts. Counts were generated within the phantom by Monte Carlo simulation of photon emission. Eighteen single segmental lesions were interspersed with 47 subsegmental defects and displayed on an Icon reporting station. These were presented in the transaxial, sagittal and coronal planes to four experienced reporters to obtain assessment of defect size. Planar studies of the same defects were displayed to the same observers in the standard eight views with a normal study for comparison. With planar studies, the accuracy of estimation of defect size was 51% compared with 97% using tomographic studies. Defects in the medial basal segment of the right lower lobe were not identified in planar studies but were easily seen by all observers in the tomographic study. It is concluded that there is marked improvement in the accuracy of determination of defect size for tomographic studies over the planar equivalents. This is especially important in the lung bases, the most common reported site of pulmonary emboli. Tomography permits visualisation of defects in the medial basal segment of the right lung, which are not seen in planar studies.