Dual‐action ambroxol in treatment of chronic pain in Gaucher Disease

A significant number of patients with Gaucher disease (GD) suffer from chronic or acute pain that reduces their quality of life. A mutation in lysosomal enzyme β‐glucosidase (GCase) leads to an accumulation of glucocerebroside in the macrophage‐lineage cells, causing the development of clinical symptoms. Novel studies have revealed that ambroxol (trans‐4‐(2‐amino‐3,5‐dibromobenzylamino)‐cyclohexanol), the well‐known mucolytic drug, acts as a chaperone for the mutant, misfolded enzyme. In addition, as has recently been shown, ambroxol is a Na_v1.8 channel blocker in Aβ, Aδ and unmyelinated C fibres, and therefore reduces the transmission of sensory stimuli from the primary afferent neurons to the dorsal spinal cord. In this way, it can act analgetically. Thus, in addition to broncholytic properties, ambroxol combines two other important functions: it enhances enzyme replacement therapy (ERT) and pain management in patients with GD. We present a 38‐year‐old female patient with type 3 GD who had reported permanent bone pain in the lumbar‐sacral part of the spine for over a year without any pathology evidenced in the undertaken, recommended diagnostic tests. The pain was partly controlled with standard analgesics, that is, paracetamol and tramadol. Ambroxol was introduced at a dose of 150mg/d without a noticeable effect. However, when the dose was increased up to 450mg/d, the intensity of pain diminished and subsided within the following months. Two of three attempts to reduce the dose of ambroxol resulted in a pain relapse within a week, which subsided after resetting the previous, higher dose. This observation of the effects of ambroxol in a GD patient is worth considering for other GD patients with chronic pain.     

A study of respiratory effects from exposure to 2 ppm formaldehyde in healthy subjects

Formaldehyde (FA) is a common indoor air pollutant with irritative properties. It has been suggested that FA may produce physiologic alterations of the respiratory system. To study such responses, 15 nonsmoking, healthy subjects were exposed in a double blind, random manner to 0 and 2 ppm FA for 40 min in an environmental chamber. In addition, the same exposures were repeated on a separate day with the subjects performing moderate exercise (450 kpm/min) for 10 min. Exposures were carried out under controlled environmental conditions (temperature = 23 degrees C, relative humidity = 50%). Pulmonary function was measured before, during, and after exposures using partial and maximal flow-volume curves and airway resistance. Symptom diaries were given to the subjects; upper and lower airway symptoms were recorded for up to 24 hr following exposures. No significant bronchoconstriction was noted in this group. In 3 subjects, sequential measurements of peak flow over a 24-hr period following FA exposure failed to reveal any delayed airway response. On a separate day, 6 healthy subjects failed to demonstrate changes from their baseline responsiveness to methacholine after exposure to 2 ppm FA. Respiratory symptoms were, in general, confined to the upper airways and were mild to moderate in severity. We conclude that short exposures to 2 ppm FA do not result in acute or subacute changes in lung function among healthy individuals either at rest or with exercise. Subjective complaints following such exposures are confined to irritative phenomena of the upper airways.     

Clinical application of diffusion tensor imaging and fiber tractography in the management of brainstem cavernous malformations: a systematic review

This study aimed to systematically review the literature to determine the clinical utility and perspectives of diffusion tensor imaging (DTI) in the management of patients with brainstem cavernous malformations (BSCMs). PubMed, Embase, and Cochrane were searched for English-language articles published until May 10, 2021. Clinical studies and case series describing DTI-based evaluation of patients with BSCMs were included. Fourteen articles were included. Preoperative DTI enabled to adjust the surgical approach and choose a brainstem safe entry zone in deep-seated BSCMs. Preoperatively lower fractional anisotropy (FA) of the corticospinal tract (CST) correlated with the severity of CST injury and motor deficits. Postoperatively increased FA and decreased apparent diffusion coefficient (ADC) corresponded with the normalization of the perilesional CST, indicating motor improvement. The positive (PPV) and negative predictive value (NPV) of qualitative DTI ranged from 20 to 75% and from 66.6 to 100%, respectively. The presence of preoperative and postoperative motor deficits was associated with a higher preoperative resting motor threshold (RMT) and lower FA. A higher preoperative CST score was indicative of a lower preoperative and follow-up Medical Research Council (MRC) grade. DTI facilitated the determination of a surgical trajectory with minimized risk of WMTs’ damage. Preoperative FA and RMT might indicate the severity of preoperative and postoperative motor deficits. Preoperative CST score can reliably reflect patients’ preoperative and follow-up motor status. Due to high NPV, normal CST morphology might predict intact neurological outcomes. Contrarily, sparse and relatively low PPV limits the reliable prediction of neurological deficits.

     

Rapid fecal calprotectin testing to assess for endoscopic disease activity in inflammatory bowel disease: A diagnostic cohort study

Results:One hundred and twenty-six patients, of whom 52% were females, were included in the final analysis with a mean age of 44.4 ± 16.7 years. Comparing FC to endoscopic findings, the following results were calculated: A cutoff point of 100 μg/g showed Sn = 83%, Sp = 67%, PPV = 65%, and NPV = 85%; and 200 μg/g showed Sn = 66%, Sp = 82%, PPV = 73%, and NPV = 77%. Based on ROC curve, the best FC cutoff point to predict endoscopic disease activity was 140 μg/g. Using this reference, FC levels strongly correlated with colorectal, ileocolonic, and ileal disease and predicted endoscopic activity.Conclusions:FC is an accurate test when used as an initial screening tool for patients suspected of having active IBD. Given its noninvasive nature, it may prove to reduce the need for colonoscopy and be an added tool in the management of IBD.     

Abdominal obesity modifies long-term associations between periodontitis and markers of systemic inflammation

Objective

Periodontitis is considered to promote atherosclerosis and cardiovascular diseases through increased low-grade systemic inflammation. However, there is no information on the long-term impact of periodontitis on systemic inflammation from cohort studies. Thus, this study aims to assess the impact of periodontitis on systemic inflammation (fibrinogen and white blood cells (WBC)) in a population-based longitudinal survey in north-eastern Germany.

Methods

The study sample comprised 2622 subjects from the Study of Health in Pomerania with complete 5- and 11-year follow-ups. Periodontitis was assessed by probing depth and clinical attachment level. Multilevel regression analyses were applied to evaluate associations between periodontitis measures and i) fibrinogen/WBC count using 11-year follow-up data and ii) respective z-scores of fibrinogen/WBC count using 5- and 11-year follow-up data. We adjusted for common cardiovascular risk factors and stratified analyses by abdominal obesity (P for interaction <0.10).

Results

In lean subjects, beta-coefficients of mean probing depth were B = 0.13 (0.08–0.019; P < 0.001) for fibrinogen and B = 0.50 (0.37–0.64; P < 0.001) for WBC count using 11-year follow-up data only. For lean subjects, models using z-scores confirmed that increased mean probing depths were associated with increased fibrinogen z-scores (B = 0.14 (0.09–0.18; P < 0.001)) and increased WBC z-scores (B = 0.16 (0.11–0.20; P < 0.001)). Consistent results were found for mean clinical attachment levels. For abdominally obese subjects, relations between periodontitis measures and levels of inflammation markers were less pronounced or non-significant.

Conclusion

Modified by abdominal obesity, periodontitis affected systemic inflammation in a significant dose-dependent manner. Results contribute to the discussion on how periodontitis is linked to atherosclerosis and cardiovascular diseases.     

Effect of Si addition on Ca- and P-impregnated implant surfaces with nanometer-scale roughness: an experimental study in dogs

Objectives: To investigate the effect of Si addition on a nanometer‐scale roughness Ca and P implant surfaces in a canine tibia model by biomechanical and histomorphometric evaluations. Material and methods: The implant surfaces comprised a resorbable media CaP microblasted (control) and a CaP resorbable media+silica‐boost microblasted (experimental) surfaces. Surfaces were characterized by scanning electron microscopy (SEM), X‐ray photoelectron spectroscopy (XPS), and optical interferometry (IFM) down to the nanometric level. The animal model involved the bilateral placement of control (n=24) and experimental surface (n=24) implants along the proximal tibiae of six dogs, remaining in vivo for 2 or 4 weeks. After euthanization, half of the specimens were torqued‐to‐interface failure, and the other half was subjected to histomorphologic and bone‐to‐implant contact (BIC) evaluation. Torque and BIC statistical evaluation was performed by the Friedman test at 95% level of significance, and comparisons between groups was performed by the Dunn test. Results: IFM and SEM observations depicted comparable roughness parameters for both implant surfaces on the micrometer and nanometer scales. XPS analysis revealed similar chemical composition, except for the addition of Si on the experimental group. Torque‐to‐interface failure and BIC mean values showed no significant differences (P=0.25 and 0.51, respectively) at both 2‐ and 4‐week evaluation points for experimental and control groups. Early bone healing histomorphologic events were similar between groups. Conclusions: The experimental surface resulted in not significantly different biomechanical fixation and BIC relative to control. Both surfaces were biocompatible and osseoconductive. To cite this article:
Coelho PG, Granato R, Marin C, Jimbo R, Lin S, Witek L, Suzuki M, Bonfante EA. Effect of Si addition on Ca‐ and P‐impregnated implant surfaces with nanometer‐scale roughness: an experimental study in dogs. Clin. Oral Impl. Res. 23 , 2012; 373–378.
doi: 10.1111/j.1600‐0501.2010.02150.x