Biological activity of two botulinum toxin type A complexes (Dysport® and Botox®) in volunteers

Despite extensive clinical experience and published data regarding botulinum toxin, questions remain about the clinical substitution of one botulinum toxin formulation for another. In the case of Dysport and Botox, dose-equivalence ratios ranging from 1:1 to 6:1 (Dysport:Botox) have been advocated. This dose-ranging, electroneurographic study investigated the dose equivalence, diffusion characteristics (spread) and safety of these two type-A toxins in 79 volunteers. Dysport and Botox caused significant and similar reductions in compound muscle action potential (CMAP) amplitude in the target muscle (extensor digitorum brevis, EDB) 2 weeks after injection, with effects persisting to the 12-week timepoint. For both products, the reduction in amplitude was increased with increasing doses and with increasing concentration. The effects of toxin on neighbouring muscles were much smaller and of a shorter duration than those on the target muscle, implying a modest spread of toxin. Unlike the target muscle, the effects were greater with the higher volume, suggesting this volume led to greater diffusion from the EDB. No adverse events were reported. Statistical modelling with CMAP amplitude data from the target muscle gave a bioequivalence of 1.57 units of Dysport:1 unit of Botox (95 % CI: 0.77-3.20 units). The data indicate that a dose-equivalence ratio of 3:1 was within the statistical error limits, but ratios over 3:1 are too high.     

Clinical implications of identifying non-B subtypes of human immunodeficiency virus type 1 infection.

Although human immunodeficiency virus type 1 (HIV-1) infection in the United States has predominantly involved subtype B, increasing global travel is leading to wider dissemination of genetically heterogeneous subtypes. While physicians depend on HIV-1 viral load measurements to guide antiretroviral therapy, commonly used molecular assays may underestimate the viral load of patients with non-B subtypes. Nine patients with non-B subtypes of HIV-1 were identified by physicians who suspected a non-B subtype on the basis of a low or undetectable HIV-1 viral load, by the Amplicor HIV-1 Monitor test, version 1.0, in conjunction with either a declining CD4 cell count or history of travel outside the United States. Use of version 1.5 of the Amplicor HIV-1 Monitor test detected a median HIV-1 viral load that was 2.0 log(10) RNA copies/mL higher than was determined with version 1.0. Clinical management was altered in all cases after diagnosis of a non-B-subtype infection. These cases demonstrate that it is critical for physicians to suspect and diagnose non-B subtypes of HIV-1 so that an assay with reliable subtype performance can be used to guide antiretroviral therapy.     

Fixation method does not affect restoration of rotation center in hip replacements: A single-site retrospective study

ABSTRACT: BACKGROUND: Aseptic loosening is one of the greatest problems in hip replacement surgery. The rotation center of the hip is believed to influence the longevity of fixation. The aim of this study was to compare the influence of cemented and cementless cup fixation techniques on the position of the center of rotation because cemented cup fixation requires the removal of more bone for solid fixation than the cementless technique. METHODS: We retrospectively compared pre- and post-operative positions of the hip rotation center in 25 and 68 patients who underwent artificial hip replacements in our department in 2007 using cemented or cementless cup fixation, respectively, with digital radiographic image analysis. RESULTS: The mean horizontal and vertical distances between the rotation center and the acetabular teardrop were compared in radiographic images taken pre- and post-operatively. The mean horizontal difference was 2.63 mm (range: -11.00 mm to 10.46 mm, standard deviation 4.23 mm) for patients who underwent cementless fixation, and 2.84 mm (range: -10.87 to 5.30 mm, standard deviation 4.59 mm) for patients who underwent cemented fixation. The mean vertical difference was 0.60 mm (range: -20.15 mm to 10.00 mm, standard deviation 3.93 mm) and 0.41 mm (range: -9.26 mm to 6.54 mm, standard deviation 3.58 mm) for the cementless and cemented fixation groups, respectively. The two fixation techniques had no significant difference on the position of the hip rotation center in the 93 patients in this study. CONCLUSIONS: The hip rotation center was similarly restored using either the cemented or cementless fixation techniques in this patient cohort, indicating that the fixation technique itself does not interfere with the position of the center of rotation. To completely answer this question further studies with more patients are needed.     

Time Course and Role of Morphine Dose and Concentration in Intrathecal Granuloma Formation in Dogs: A Combined Magnetic Resonance Imaging and Histopathology Investigation

Background: Intrathecal morphine infusion leads to intrathecal granulomas. In dogs, the authors examined time course of granuloma formation and the role of concentration in granuloma development.

Methods: Dogs were prepared with lumbar intrathecal catheters and vest-mounted pumps. To define the time course of granuloma formation, serial magnetic resonance imaging was performed in animals receiving 10 or 31 days of morphine infusion (12.5 mg/ml at 40 [mu]l/h). At these times, morphine was removed from the infusate, and further magnetic resonance images were acquired over 14-35 additional days. To assess dose versus concentration, dogs received 28-day infusions of vehicle, 12 mg morphine/day as 12.5 mg/ml at 40 [mu]l/h, or 1.5 mg/ml at 334 [mu]l/h (12 mg/day) for 28 days. Additional dogs received 3 mg/day as 12.5 mg/ml at 10 [mu]l/h.

Results: Serial magnetic resonance images in dogs receiving morphine (12.5 mg/ml at 40 [mu]l/h) revealed pericatheter-enhancing tissues as early as 3 days with a prominent signal by 10 days. Removal of morphine reduced the mass volume within 7 days. At a fixed infusion rate, the incidence of granuloma formation with the continuous intrathecal infusion of morphine ranged from 0 in vehicle-treated dogs to 100% in dogs treated with 12.5 mg/ml at 40 [mu]l/h (12 mg/day). Infusion of 12 mg/day at 1.5 mg/ml (334 [mu]l/h) resulted in granuloma in one of four animals. The authors found that infusion of morphine in different concentrations at a fixed rate resulted in a dose-dependent increase in concentration, with the granuloma-producing, dose-yielding lumbar cerebrospinal fluid morphine concentrations around 40 [mu]g/ml.     

Photo-cross-linkable poly(p-phenylene)s. Synthesis,Langmuir-Blodgett multilayer film properties and pattern formation

We describe the synthesis of a soluble poly(p-phenylene) (PPP) derivative with hydroxy-functionalities in the side chain by copolycondensation. This allows the introduction of further functionalities by polymer analogous reactions. Esterification with cinnamoyl chloride leads to a photo-reactive material that can be processed by the Langmuir-Blodgett (LB)-technique to form ultrathin, highly anisotropic films. Photo-irradiation of these films leads to the formation of cross-links which lock in the long range ordered structure of the layered films which then becomes stable to temperatures of more than 160°C. Cross-linking is achieved by direct irradiation into the absorption band of the photo-reactive units or by use of sensitizers, which gives rise to more efficient reaction conditions with fewer side-reactions. Since the cross-linked film is insoluble in all solvents, the photo-reactive material serves as photo-resist. Irradiation through a mask followed by dissolution of the non-cross-linked film can be used for microlithography at micron scale resolution.