Novel REST Truncation Mutations Causing Hereditary Gingival Fibromatosis.

Hereditary gingival fibromatosis (HGF) is a rare genetic disorder featured by nonsyndromic pathological overgrowth of gingiva. The excessive gingival tissues can cause dental, masticatory, and phonetic problems, which impose severe functional and esthetic burdens on affected individuals. Due to its high recurrent rate, patients with HGF have to undergo repeated surgical procedures of gingival resection, from childhood to adulthood, which significantly compromises their quality of life. Unraveling the genetic etiology and molecular pathogenesis of HGF not only gains insight into gingival physiology and homeostasis but also opens avenues for developing potential therapeutic strategies for this disorder. Recently, mutations in REST (OMIM *600571), encoding a transcription repressor, were reported to cause HGF (GINGF5; OMIM #617626) in 3 Turkish families. However, the functions of REST in gingival homeostasis and pathogenesis of REST-associated HGF remain largely unknown. In this study, we characterized 2 HGF families and identified 2 novel REST mutations, c.2449C>T (p.Arg817*) and c.2771_2793dup (p.Glu932Lysfs*3). All 5 mutations reported to date are nonsenses or frameshifts in the last exon of REST and would presumably truncate the protein. In vitro reporter gene assays demonstrated a partial or complete loss of repressor activity for these truncated RESTs. When coexpressed with the full-length protein, the truncated RESTs impaired the repressive ability of wild-type REST, suggesting a dominant negative effect. Immunofluorescent studies showed nuclear localization of overexpressed wild-type and truncated RESTs in vitro, indicating preservation of the nuclear localization signal in shortened proteins. Immunohistochemistry demonstrated a comparable pattern of ubiquitous REST expression in both epithelium and lamina propria of normal and HGF gingival tissues despite a reduced reactivity in HGF gingiva. Results of this study confirm the pathogenicity of REST truncation mutations occurring in the last exon causing HGF and suggest the pathosis is caused by an antimorphic (dominant negative) disease mechanism.

Modulation of symptomatic palatal tremor by magnetic stimulation of the motor cortex.

OBJECTIVES: Magnetic stimulation of the motor cortex can be used to determine the involvement of the cortex in rhythmic movement disorders. Symptomatic palatal tremor (SPT) is thought to come from a pacemaker that is relatively resistant to internal and external stimulation. In this study, we investigated the effect of magnetic stimulation of motor cortex on SPT. METHODS: Five male patients, aged 67-79 years, with SPT after brain stem infarction or hemorrhage, all had a synchronous mouth angle twitch with the palatal movement. Electromyographic activity was recorded with a monopolar needle electrode from orbicularis oris. In experiment 1, transcranial magnetic stimulation (TMS) was delivered at 200% motor threshold (MT) to reset SPT. In experiment 2, the effect of TMS intensities was studied at 80-240% MT in two SPT patients. To determine the influence of the TMS, we used the resetting index (RI). RESULTS: TMS reset the tremor in all 5 SPT patients at 200% MT with RIs of 0.86-0.96. The latency of the tremor reappearance after TMS was longer than the pre-stimulus tremor interval, and the intervals between the subsequent tremor bursts were also prolonged. The degree of tremor resetting was closely correlated with the magnetic stimulus intensity and the latency of the tremor reappearance after TMS. CONCLUSIONS: Stimulation of the motor cortex may modulate the generator of SPT.

Pilot evaluation of a nurse-administered carepath for successful colonoscopy for persons with spinal cord injury.

Due to ongoing improvements in medical care, the life expectancy of persons with spinal cord injury (SCI) continues to improve and approach that of the able-bodied population. As the SCI population ages, cancer would be expected to increase as a cause of death. When a patient presents with occult fecal blood and anemia, colonscopy to the cecum is often pursued. It has been our experience that 80 percent of patients are found to have inadequate bowel preps resulting in suboptimal colonoscopy when the prep is attempted at home. Because of this, we developed a nurse-administered carepath necessitating a 48-hour admission for bowel prep and colonoscopy. The bowel prep consists of magnesium citrate, polyethylene glycol-electrolyte solution, and sodium phosphate/biphosphate enemas. Throughout hospitalization, the patient receives a clear liquid diet. Eighteen patients have been placed on the carepath. At the time of colonoscopy, all 18 were noted to have received an acceptable bowel prep allowing vizualization to the cecum. A description of the carepath and its benefits is presented.

Periodontal attachment loss associated with proximal tooth restorations.

This study documents that periodontal attachment loss is greater adjacent to restored tooth surfaces than adjacent to unrestored tooth surfaces. This finding emphasizes the importance of the prevention of caries and poor restorations.