CLDN1 Arg81His founder variant causes ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis (ILVASC) syndrome in Moroccan Jews.

Neonatal ichthyosis and sclerosing cholangitis syndrome (NISCH), also known as ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis (ILVASC), is an extremely rare disease of autosomal recessive inheritance, resulting from loss of function of the tight junction protein claudin-1. Its clinical presentation is highly variable, and is characterized by liver and ectodermal involvement. Although most ILVASC cases described to date were attributed to homozygous truncating variants in CLDN1, a single missense variant CLDN1 p.Arg81His, associated with isolated skin ichthyosis phenotype, has been recently reported in a family of Moroccan Jewish descent. We now describe seven patients with ILVASC, originating from four non consanguineous families of North African Jewish ancestry (including one previously reported family), harboring CLDN1 p.Arg81His variant, and broaden the phenotypic spectrum attributed to this variant to include teeth, hair, and liver/bile duct involvement, characteristic of ILVASC. Furthermore, we provide additional evidence for pathogenicity of the CLDN1 p.Arg81His variant by transmission electron microscopy of the affected skin, revealing distorted tight junction architecture, and show through haplotype analysis in the vicinity of the CLDN1 gene, that this variant represents a founder variant in Jews of Moroccan descent with an estimated carrier frequency of 1:220.

The anatomical pattern of ductal arborization in parotid glands using cone-beam computerized sialography.

Cone-Beam Computed Tomography-Sialography (Sialo-CBCT) is used to demonstrate salivary ductal structure. This study aimed to conduct a volumetric analysis of the anatomical morphology of Normal-Appearing Glands (NAGs) in parotid sialo-CBCT. Our retrospective study included 14 parotid sialo-CBCT scans interpreted as NAGs in 11 patients with salivary gland impairment. The main duct length and width, as well as number and width of secondary and tertiary ducts were manually evaluated. We found that the main parotid duct showed an average width of 1.39 mm, 1.15 mm, and 0.98 mm, for the proximal, middle and distal thirds, respectively. The arborization pattern showed approximately 20% more tertiary (average number 11.1 ± 2.7) than secondary ducts (average number 9.0 ± 2.4) and approximately 8% narrower tertiary ducts (average width 0.65 ± 0.11 mm) compared to the secondary ducts (average width 0.77 ± 0.14 mm). Our anatomical analysis of NAGs in parotid sialo-CBCT demonstrated progressive narrowing of the main duct and increasing arborization and decreasing lumen size starting from the primary to the tertiary ducts. This is the most updated study regarding the anatomy of the parotid glands as demonstrated in sialo-CBCT. Our results may provide clinicians with the basic information for understanding aberration from normal morphology, as seen in salivary gland pathologies as well facilitate planning of treatment strategies, such as minimally invasive sialo-endoscopies, commonly practiced today.

Trigeminal Neuropathy After Mandibular Fractures: Epidemiology and Neurophysiologic Diagnosis.

OBJECTIVES: To study the trigeminal nerve neuropathy prevalence after mandibular fractures and follow nerve recovery and to examine associations with clinical features. SUBJECTS: The files of 304 patients treated for 424 mandibular fractures in Hadassah Medical Center between 2001 and 2008 were analyzed. Twenty-five patients with paresthesia were examined by electro-diagnostic conduction test (quantitative sensory testing). RESULTS: The most common fracture sites were the symphysis (28.5%) and condyle (21.4%). A strong correlation between fracture severity and treatment modality was found. Nerve damage occurred in 13.4% of nondisplaced fractures and in 65.3% of >5 mm displaced fractures. Patients who were treated by open reduction internal fixation demonstrated the biggest difference in quantitative sensory testing values between the affected and nonaffected sides. C nerve fibers were the most damaged and least regenerated. There was correlation between damage perception and objective test results. CONCLUSIONS: There is a correlation between fracture type and displacement severity on neurologic deficit and prognosis. The objective neurosensory damage was manifested by higher nerve excitation threshold on the injured side. Patients should be informed on the prognosis of neurologic deficit according to fracture type.

Comparison of the efficacy of a novel sustained release clotrimazole varnish and clotrimazole troches for the treatment of oral candidiasis.

OBJECTIVES: Candida albicans is a common fungal infection and is commensal in 40-65 % of healthy adults. The development and pharmacokinetics of a novel sustained release clotrimazole varnish (Clot-SRV) for topical oral use have been reported. The aim of this study was to compare the efficacy of this varnish with clotrimazole troche treatment of oral candidiasis. MATERIALS AND METHODS: Of the 12 patients with denture stomatitis treated for 14 days, six used Clot-SRV (study group) and six clotrimazole troches (control). The patients were instructed to use Clot-SRV (50 mg of clotrimazole) once a day, and the control group was instructed to use five troches of 10 mg clotrimazole/day. Microbiological samples were obtained from saliva, buccal mucosa, palate, and denture. The degree of erythema was recorded at three time points, and subjective opinions noted using a questionnaire. RESULTS: At the end of the study, the control group had relatively more cases of erythema on all examined surfaces; patients who applied the Clot-SRV had significantly lower levels of candida on the denture surfaces and in saliva, and had better compliance to the medication. CONCLUSIONS: The novel clotrimazole sustained release varnish may be an important part of a new protocol for oral candidiasis, with improved clinical outcomes.

Detection of mandibular condyle pesudocysts in panoramic radiographs: Digital and film-based radiology.

OBJECTIVE: To determine the detection rate of mandibular condyle pseudocyst in both digital panoramic radiographs and film-based panoramic radiographs. METHOD AND MATERIALS: All film-based and digital panoramic radiographs of patients treated at our institute during a 4-month period were analyzed by two experienced practitioners. Diagnosis of a condylar pseudocyst was based on the following criteria: appearance of cyst-like radiolucency, partially or completely circumscribed by radiopaque border, located at the anterior aspect of mandibular condyle. RESULTS: 825 radiographs (415 film-based, 410 digital) were included in the study. In 342 (41.5%) radiographs at least one condylar pseudocyst was observed, with no differences between radiograph type, 173 (42.2%) in digital and 169 (40.7%) in film-based radiographs (P = .36). Condylar pseudocyst detection rate was positively associated with older age (P < .001), whereas gender had no influence (P = .93). CONCLUSION: An equally high detection rate of condylar pseudocyst was found in digital and film-based panoramic radiographs.

Levels of sirolimus in saliva and blood following oral topical sustained-release varnish delivery system application.

PURPOSE: Sirolimus (rapamycin) is a mammalian target of rapamycin pathway blocker. The efficacy of sirolimus is currently studied for its antiproliferative properties in various malignancies and particularly in squamous cell carcinoma and other oral disorders. Topical application at the oral cavity can augment sirolimus availability at the site of action by increasing sirolimus levels in saliva and hence efficacy, along with improved safety (low levels in the blood to avoid side effects) and compliance. Our purpose was to evaluate the release profile and safety of a topical sirolimus sustained-release varnish drug delivery system. SUBJECTS AND METHODS: Sirolimus sustained-release varnish drug delivery system containing a total of 0.5 mg of the drug was applied to nine healthy male volunteers. Saliva and blood levels were determined utilizing mass spectrometry and chemiluminescent microparticle immunoassay, respectively. The prolonged release profile and safety were evaluated for the oral topical delivery system. RESULTS: After the application of the drug delivery system, a sustained-release profile was observed in the oral cavity. We have measured moderate sirolimus levels for up to 12 h. The safety was confirmed, and systemic sirolimus blood levels were negligible. CONCLUSIONS: After an application of sirolimus sustained-release varnish drug delivery system, prolonged drug levels can be achieved in the saliva. The oral topical sirolimus concentrations were potentially therapeutic along with minimal systemic exposure. These results broaden the potential clinical use of sustained-release oral topical rapalogs.