Leukocyte adhesion deficiency II patients with a dual defect of the GDP-fucose transporter

Leukocyte adhesion deficiency II (LAD II) is a rare congenital disease caused by defective fucosylation leading to immuno-deficiency and psychomotor retardation. We have previously identified the genetic defect of LAD II in a patient whose Golgi GDP-fucose transporter (GFTP) bears a single amino acid exchange that renders this protein nonfunctional but correctly localized to the Golgi. We now report a novel dual defect by which a truncated GFTP causes the disease in a new LAD II patient. We show that the truncation renders this GFTP unable to localize to the Golgi, the compartment where it is required. Furthermore, the missing part of the GFTP can be dissected into 2 regions, one that is needed for Golgi localization and one that is additionally required for the function of the GFTP. We investigated the subcellular localization of all known defective GFTPs allowing us to divide all genetically analyzed LAD II patients into 2 groups, one in which single amino acid exchanges in the GFTP impair its function but not its subcellular localization, and another group with a dual defect in function and Golgi expression of the GFTP due to the absence of 2 important molecular regions.     

Sclerosing injections to treat midportion Achilles tendinosis: a randomised controlled study evaluating two different concentrations of Polidocanol

Two to three ultrasound (US) and colour Doppler (CD)-guided injections of the sclerosing substance Polidocanol (5 mg/ml) have been demonstrated to give good clinical results in patients with chronic midportion Achilles tendinopathy. This study aimed to investigate if a higher concentration of Polidocanol (10 mg/ml) would lead to a less number of treatments, and lower volumes, needed for good clinical results. Fifty-two consecutive Achilles tendons (48 patients, mean age 49.6 years) with chronic painful midportion Achilles tendinopathy, were randomised to treatment with Polidocanol 5 mg/ml (group A) or 10 mg/ml (group B). The patients and treating physician were blinded to the concentration of Polidocanol injected. All patients had structural tendon changes and neovascularisation in the Achilles midportion. Treatment was US + CD-guided injections targeting the region with neovascularisation (outside ventral tendon). A maximum of three treatments (6-8 weeks in between) were given before evaluation. Patients not satisfied after three treatments were given additional treatment with Polidocanol 10 mg/ml, up to five treatments. For evaluation, the patients recorded the severity of Achilles tendon pain during activity on a visual analogue scale (VAS), before and after treatment. Patient satisfaction with treatment was also assessed. At follow-up (mean 14 months) after three treatments, 18/26 patients in group A and 19/26 patients in group B were satisfied with the treatment and had a significantly reduced level of tendon pain (P < 0.05). After completion of the study, additional treatments with Polidocanol 10 mg/ml in the not satisfied patients resulted in 26/26 satisfied patients in both groups A and B. In summary, we found no significant differences in the number of satisfied patients, number of injections or volumes given, between patients treated with 5 or 10 mg/ml Polidocanol.     

Chronic hepatitis: role of diffusion-weighted imaging and diffusion tensor imaging for the diagnosis of liver fibrosis and inflammation

PURPOSE: To determine the diagnostic performance of liver apparent diffusion coefficient (ADC) measured with conventional diffusion-weighted imaging (CDI) and diffusion tensor imaging (DTI) for the diagnosis of liver fibrosis and inflammation. MATERIALS AND METHODS: Breathhold single-shot echo-planar imaging CDI and DTI with b-values of 0 and 500 second/mm(2) was performed in 31 patients with chronic liver disease and 13 normal volunteers. Liver biopsy was performed in all patients with liver disease with a median delay of two days from MRI. Fibrosis and inflammation were scored on a 5-point scale (0-4). Liver ADCs obtained with CDI and DTI were compared between patients stratified by fibrosis stage and inflammation grade. Receiver operating characteristic (ROC) curve analyses were conducted to evaluate the utility of the ADC measures for prediction of fibrosis and inflammation. RESULTS: Patients with liver fibrosis and inflammation had significantly lower liver ADC than subjects without fibrosis or inflammation with CDI and DTI. For prediction of fibrosis stage > or = 1 and stage > or = 2, area under the ROC curve (AUC) of 0.848 and 0.783, sensitivity of 88.5% to 73.7%, and specificity of 73.3% to 72.7% were obtained, for ADC < or =1.40 x 10(-3) mm(2)/second and < or =1.30 x 10(-3) mm(2)/second (using CDI), respectively. For prediction of inflammation grade > or = 1, AUC of 0.825, sensitivity of 75.0%, and specificity of 78.6% were obtained using ADC < or = 1.30 x 10(-3) mm(2)/second (using CDI). CDI performed better than DTI for diagnosis of fibrosis and inflammation. CONCLUSION: Liver ADC can be used to predict liver fibrosis and inflammation with acceptable sensitivity and specificity.     

Conspicuity of zones of ablation after radiofrequency ablation in porcine livers: comparison of an extracellular and an SPIO contrast agent

PURPOSE: To compare conspicuity of zones of ablation on nonenhanced, gadopentetate dimeglumine-(Gd-DTPA) and ferucarbotran-(SPIO)-enhanced magnetic resonance (MR) images. MATERIALS AND METHODS: In all, 33 radiofrequency ablations (RFA) were performed in 17 healthy porcine livers at 1.5T MR imaging 1 day and 2 and 4 weeks after RFA: T2-weighted (w) ultra turbo spin echo (UTSE), proton density (PD)-w UTSE, T1-w gradient echo (GRE) pre- and 5 minutes postcontrast administration, dynamic T1-w GRE during Gd-DTPA (Magnevist) or SPIO (Resovist) administration, T2-w UTSE, and PD-w UTSE sequences 10 minutes after SPIO administration. Regions of interest (ROIs) for contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR) were drawn in consensus by two radiologists. RESULTS: PD-w SPIO-enhanced images (23.5 +/- 5.5) showed higher liver-to-lesion CNR than T1-w GRE Gd-DTPA-enhanced images (13.5 +/- 6.1) 1 day after RFA (P < or = 0.05). At all other timepoints, liver-to-lesion CNR of PD-w and T2-w SPIO-enhanced images did not differ significantly from T1-w GRE Gd-DTPA-enhanced images (P > or = 0.05). Nonenhanced T2-w images revealed lower liver-to-lesion CNR (7.0 +/- 7.5/6.5 +/- 5.9/6.8 +/- 5.0, 1 day/2 weeks/4 weeks, respectively) than T2-w SPIO-enhanced (17.4 +/- 4.8/15.3 +/- 4.5/14.2 +/- 5.7), PD-w SPIO-enhanced (23.5 +/- 5.5/16.9 +/- 3.6, 1 day/2 weeks), and T1-w Gd-DTPA-enhanced (15.3 +/- 3.6/12.7 +/- 3.5, 2/4 weeks) images (P < or = 0.05). Liver-to-lesion CNR of SPIO-enhanced dynamic T1-w GRE images after 30, 80, 150, and 240 seconds did not change significantly over time (P > or = 0.05). CONCLUSION: One day after RFA lesion conspicuity on PD-w ferucarbotran-enhanced images is better than on T1-w GRE Gd-DTPA-enhanced images. At all other timepoints, ferucarbotran is not superior to gadolinium. Ferucarbotran- and gadolinium-enhanced images improve lesion conspicuity compared with nonenhanced T2-w images at all timepoints.     

Free-breathing 3D steady-state free precession coronary magnetic resonance angiography: comparison of diaphragm and cardiac fat navigators

PURPOSE: To compare the performance of the conventional diaphragm navigator (DNAV) and the recently developed cardiac fat navigator (FatNAV) in suppressing respiration-induced cardiac motion in free-breathing 3D balanced steady-state free precession coronary MRA (SSFP CMRA). MATERIALS AND METHODS: In 16 healthy volunteers the right coronary artery (RCA) was imaged at 1.5T using a navigator-gated 3D SSFP CMRA sequence. DNAV and FatNAV gating were performed in random order. Image quality difference was scored by three experienced readers blinded to the gating technique. Blood signal-to-noise ratio (SNR), blood-to-myocardium contrast-to-noise ratio (CNR), and navigator efficiency were calculated. RESULTS: Diagnostically interpretable CMRA was obtained successfully in all 16 subjects with FatNAV gating (0% failure rate) and only 14 subjects with DNAV gating (12% failure rate). Compared to DNAV gating, FatNAV gating provided similar SNR and CNR, better image quality (P < 0.01), and 28% improvement in navigator efficiency (P = 0.002). CONCLUSION: FatNAV gating provides more effective motion suppression and better image quality than DNAV gating for free-breathing 3D SSFP CMRA of the RCA in healthy subjects.     

Methylprednisolone and interleukin-10 reduce gray matter damage in the contused Fischer rat thoracic spinal cord but do not improve functional outcome

The effects of two antiinflammatory and neuroprotective agents, methylprednisolone (MP) and interleukin-10 (IL-10), singly and in combination on tissue damage, axonal preservation and functional recovery were studied in the contused adult Fischer rat thoracic spinal cord 12 weeks after injury. MP (30 mg/kg at 5 min, and 2 and 4 h after injury) was administered intravenously and IL-10 (15 or 30 microg/kg at 30 min after injury), intraperitoneally. MP, IL-10, or the combination significantly reduced the volume of damaged tissue (including cavities) compared to control animals. The loss of spinal tissue (cavities) was reduced after treatment with MP alone or combined with IL-10, but not with IL-10 alone. The reduction in tissue damage was confined to spinal gray matter; at the level of the lesion epicenter, the thickness of the lateral white matter columns was similar in all groups. Retrograde tracing using fast blue revealed that the number of spared propriospinal and supraspinal projections was similar in all groups at 12 weeks after the contusion. The open-field BBB-test showed no significant difference in hindlimb locomotion between groups. Our results demonstrate that all tested antiinflammatory treatments significantly increase the volume of spared spinal gray matter 3 months after a moderate contusion of the Fischer rat thoracic spinal cord, but none of the treatments improved axonal preservation or functional recovery.     

Distal femur resection with endoprosthetic reconstruction: a long-term followup study

The distal femur is a common site for primary and metastatic bone tumors and therefore, it is a frequent site in which limb-sparing surgery is done. Between 1980 and 1998, the authors treated 110 consecutive patients who had distal femur resection and endoprosthetic reconstruction. There were 61 males and 49 females who ranged in age from 10 to 80 years. Diagnoses included 99 malignant tumors of bone, nine benign-aggressive lesions, and two nonneoplastic conditions that had caused massive bone loss and articular surface destruction. Reconstruction was done with 73 modular prostheses, 27 custom-made prostheses, and 10 expandable prostheses. Twenty-six gastrocnemius flaps were used for soft tissue reconstruction. All patients were followed up for a minimum of 2 years. Function was estimated to be good or excellent in 94 patients (85.4%), moderate in nine patients (8.2%), and poor in seven patients (6.4%). Complications included six deep wound infections (5.4%), six aseptic loosenings (5.4%), six prosthetic polyethylene component failures (5.4%), and local recurrence in five of 93 patients (5.4%) who had a primary bone sarcoma. The limb salvage rate was 96%. Distal femur endoprosthetic reconstruction is a safe and reliable technique of functional limb sparing that provides good function and local tumor control in most patients.     

Missed and mismanaged injuries of the spinal cord

OBJECTIVE: The purpose of this study was to determine the incidence of missed and mismanaged injuries of the spinal cord, to identify factors contributing to a failure to recognize such injuries, and to assess the consequences of such failures. METHODS: Missed and mismanaged injuries were defined using previously validated statements. All medical records and radiographs of patients with acute traumatic spinal cord injury admitted to the Regional Spinal Cord Injury Unit in Sheffield, United Kingdom, over a period of 10 years from 1989 were evaluated. Patients with no neurologic deficits were excluded from the study. RESULTS: Of the 569 patients, the diagnosis of spinal cord injury was missed in 52 instances (9.1%). The patients were mismanaged in 34 instances, and the treatment offered to 30 was considered negligent. In 26 of 52 (50%), mismanagement resulted in neurologic deterioration. The study identified several factors that contributed to a failure to recognize a spinal cord injury. These include ambience and circumstances surrounding the injury, inadequate neurologic assessment, associated injuries, and radiographic errors. CONCLUSION: Despite a greater awareness of the potential for spinal injury after road traffic accidents, failure to recognize a spinal cord injury in the acute care setting appears to be increasing. Injuries are seldom missed because of an isolated cause, but rather because of a combination of several factors. Increased vigilance on the part of the primary care physicians and careful documentation may reduce allegations of medical negligence.     

The Vienna functional electrical stimulation system for restoration of walking functions in spastic paraplegia

An eight-channel stimulation system, currently intended for stimulation of lower extremities, was developed and is introduced. The major development goals were easy handling, modularity to make the system easily adaptable for other functional electrical stimulation (FES) applications, and a wide stimulation parameter range for application-specific parameter optimization. For paraplegic stepping, the system worn by the patient consists of 2 four-channel stimulation modules, a central unit holding the battery and circuitry for power management and communication control, a wireless remote control unit, and a palmtop computer as the main control and input device. A software package for Microsoft Windows supports the design and optimization of stimulation sequences in the rehabilitation center. First tests with patients familiar with FES showed smoother movements during stepping and acceptable good handling. In combination with the PC software, the required stimulation sequences could be created in a very short time.