Update on the use of dapsone in dermatology

Dapsone (4,4'-diaminodiphenylsulfone) is the only remaining sulfone used in anthropoid therapeutics and is commercially available as an oral formulation, an inhaled preparation, and a 5% or 7.5% cream. Dapsone has antimicrobial effects stemming from its sulfonamide-like ability to inhibit the synthesis of dihydrofolic acid. It also has anti-inflammatory properties such as inhibiting the production of reactive oxygen species, reducing the effect of eosinophil peroxidase on mast cells and down-regulating neutrophil-mediated inflammatory responses. This allows for its use in the treatment of a wide variety of inflammatory and infectious skin conditions. Currently in dermatology, the US Food and Drug Administration (FDA)-approved indications for dapsone are leprosy, dermatitis herpetiformis, and acne vulgaris. However, it proved itself as an adjunctive therapeutic agent to many other skin disorders. In this review, we discuss existing evidence on the mechanisms of action of dapsone, its FDA-approved indications, off-label uses, and side effects.     

The spatial cerebral damage caused by larger infarct and β-amyloid toxicity is driven by the anatomical/functional connectivity

Large cerebral infarctions are major predictors of death and severe disability from stroke. Conversely, data concerning these types of infarctions and the affected adjacent brain circuits are scarce. It remains to be determined if the co-morbid concurrence of large infarct and β-amyloid (Aβ) toxicity can precipitate the early development of dementia. Here, we described a dose-dependent effect of a unilateral striatal injection of vasoconstrictive endothelin-1 (ET-1) along with Aβ toxicity on CNS pathogenesis; driven by the anatomical and functional networks within a brain circuit. After 21 days of treatment, a high dose (60 pmol) of ET-1 (E60) alone caused the greatest increase in neuroinflammation, mainly in the ipsilateral striatum and distant regions with synaptic links to the striatal lesion such as white matter (subcortical white matter, corpus callosum, internal capsule, anterior commissure), gray matter (globus pallidus, thalamus), and cortices (cingulate, motor, somatosensory, entorhinal). The combined E60 + Aβ treatment also extended perturbation in the contralateral hemisphere of these rats, such as increased deposition of amyloid precursor protein fragments associated with the appearance of degenerating cells and the leakage of laminin from the basement membrane across a compromised blood–brain barrier. However, the cerebral damage induced by the 6 pmol ET-1 (E6), Aβ and E6 + Aβ rats was not detrimental enough to injure the complete network. The appreciation of the causal interactions among distinct anatomical units in the brain after ischemia and Aβ toxicity will help in the design of effective and alternative therapeutics that may disassociate the synergistic or additive association between the infarcts and Aβ toxicity.     

Effectiveness of a microabrasion technique using 16% HCL with manual application on fluorotic teeth: A series of studies

BACKGROUND Dental fluorosis is caused by excessive fluoride ingestion during tooth formation.As a consequence,there is a higher porosity on the enamel surface,which causes an opaque look.AIM The aim of this study was to identify a dental intervention to improve the smile in patients with tooth fluorosis.Additional aims were to relate the stain size on fluorotic teeth with the effectiveness of stain removal,enamel loss and procedure time using a manual microabrasion technique with 16%hydrochloric acid(HCL).METHODS An experimental study was carried out on 84 fluorotic teeth in 57 adolescent patients,33 females and 24 males,with moderate to severe fluorosis.The means,standard deviations and percentages were analyzed using nonparametric statistics and ArchiCAD 15 software was used for the variables including stain size and effectiveness of stain removal.RESULTS The average enamel loss was 234μm and was significantly related to the procedure time categorized as 1-4 min and 4.01-6 min,resulting in a P>0.000.The microabrasion technique using 16%HCL was effective in 90.6%of patients and was applied manually on superficial stains in moderate and severe fluorosis.Procedure time was less than 6 min and enamel loss was within the acceptable range.CONCLUSION Microabrasion is a first-line treatment;however,the clinician should measure the average enamel loss to ensure that it is within the approximate range of 250μm in order to avoid restorative treatment.     

Cleido cranial dysplasia: report of a family

A family case of Cleidocranial Dysplasia is presented. A mother and two adolescent girls were examined. In all three cases, a radiological series was performed over the entire body. Generalized dysplasia in bones, prolonged retention of primary teeth, and delayed eruption of permanent, as well as supernumerary teeth was diagnosed. The citogenetic study with GTG band showed normal 46, XX. Bilateral audiometry in the mother demonstrated a mild to moderate hypoacustic condition. Radiological findings are presented and the importance of early diagnosis is discussed.     

Creating a synergy effect: A cluster randomized controlled trial testing the effect of a tailored multimedia intervention on patient outcomes

Objective

Improving adherence is a challenge and multiple barriers are likely to explain non-adherence. These barriers differ per patient and over course of the regimen. Hence, personalized interventions tailored to the specific barriers are needed. In a theoretical and evidence-based Tailored Multimedia Intervention, technology (online preparatory assessment, text messaging) was used as an add-on to a tailored counseling session (learned during a communication skills training), with the expectation of synergistic effects.

Improving ACE inhibitor use in patients hospitalized with systolic heart failure: a cluster randomized controlled trial of clinical practice guideline development and use

Rationale, aims and objectives The efficacy of angiotensin‐converting enzyme (ACE) inhibitors in treating heart failure is well established, but there is concern that these agents are underutilized. This study aimed to evaluate the effect of developing and implementing Clinical Practice Guidelines (CPGs) on the quality of care given to patients receiving ACE inhibitors for systolic heart failure. Methods Twenty cardiology units in Lorraine (France) were randomized to an experimental (n = 10) or a control group (n = 10). In each experimental unit, doctors were involved in drafting and implementing CPGs; those at control units were not. Practice surveys were conducted in all units before and after the intervention; 723 patients with heart failure and less than 75 years old were included. The main outcome was compliance with the CPGs. Results Before intervention, clinicians in both groups were already compliant with CPGs relating to indications and contra‐indications, adverse effects management, concomitant therapy and monitoring of biologic factors. After intervention, adherence to others CPGs was generally better in the experimental group. Compliance with the CPG relating to ACE inhibitor dose on discharge was higher in the experimental group (P = 0.003). Compliance with CPGs relating to increasing ACE inhibitors doses (P < 0.0001) and the contents of the discharge letter (P = 0.02) improved in all units between the two periods. Conclusions These results suggest that doctors involved in drafting and implementing CPGs are more likely to comply with them.     

Clinical and immunological effects of a 6 week immunotherapy cycle with murabutide in HIV-1 patients with unsuccessful long-term antiretroviral treatment

In an effort to evaluate the potential of non-specific immunotherapy in restoring global immunity, we have examined the clinical tolerance and biological effects of a 6 week administration of the immunomodulator, murabutide, in chronically infected HIV-1 patients. Forty-two subjects, presenting weak immune reconstitution and ineffective virus suppression following long-term highly active antiretroviral therapy (HAART), were randomized to receive, or not, murabutide 7 mg/day on five consecutive days/week. Clinical and immunological parameters were monitored before and after the immunotherapy period. Administration of murabutide was generally well tolerated, although some grade III adverse events, reversible on treatment cessation, were observed. Interestingly, in comparison with pre-inclusion levels, at 1 week after the immunotherapy cycle, only murabutide recipients presented a significant increase in CD4 cells, platelet counts, and in the percentage of patients with undetectable viral loads (<50 copies/mL). Statistical significance between the two groups was only evident with the latter parameter. Some of these clinical changes were maintained even up to 12 weeks after murabutide administration, and were accompanied by an increased ability to mount cellular responses to active immunization with a recall antigen, and by a significant increase in the percentage of patients presenting positive lymphoproliferative responses to the viral antigen gp160. These results warrant further evaluation of extended periods or cycles of murabutide immunotherapy as adjunct to HAART.     

Upper limb function and activity in people with facioscapulohumeral muscular dystrophy: a web-based survey

Purpose To investigate the upper extremity (UE) at the level of impairments and related activity limitations and participation restrictions in people with facioscapulohumeral muscular dystrophy (FSHD). Methods The study was conducted using web-based questionnaires that were distributed amongst people with FSHD in the Netherlands. Eighty-eight respondents started the survey, and 71 completed it. The questionnaires covered the following dimensions: Function, Activity and Participation of the International Classification of Functioning Disability and Health. Results More than 40% of the respondents experienced pain in one arm or both the arms. Increased pain and stiffness scores and longer disease duration were associated with increased limitation scores. For basic activities, lifting the arm above shoulder-level was most frequently reported as most limited, coherent with the clinical picture of FSHD. Among the respondents, 50% indicated restrictions at school, 78% indicated restrictions at work and more than 80% indicated restrictions whilst participating in sports, hobbies, household activities and romantic relationships. Conclusions This study has shown that alongside the well-known problem of lifting the arms above shoulder-level, UE activities below shoulder height during vocational and occupational activities are also problematic in patients with FSHD. Alongside disease duration, pain and stiffness are associated with UE activity limitations.

• Implications for Rehabilitation

• Attention is needed for pain and experienced stiffness in the upper extremity as it is frequently present in patients with FSHD.

• Rehabilitation professionals need to be aware that patients with FSHD not only experience problems with activities above shoulder height, but also with activities below shoulder height.

• At least 50% of the patients with FSHD experience restrictions in participation as a result of limitations in their UE.