Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017168 (gastroesophageal reflux disease)
 11,783 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phonomicrosurgical treatment of premalignant vocal fold epithelium and microinvasive cancer combines principles of surgical oncology with advanced laryngoscopic microsurgical-techniques. This treatment is guided by mucosal-wave theory of voice production and strives not only to cure the disease but also to achieve optimal vocal function. Surgical techniques developed during the past two centuries have improved methods for vocal fold visualization, tissue retrieval, and tissue evaluation. Examination of the evolution of these surgical techniques reveals the incomplete convergence of laryngoscopic surgical theory with both the concept of premalignancy and the anatomical-physiological principles of voice production. This historical review, which helps to explain the lack of consensus about current treatment options, led to a series of four investigations. They were conducted with the aim of developing a laryngoscopic (phonomicrosurgical) management approach for improving the treatment of premalignant and microinvasive vocal fold epithelium. In the first of four investigations, 42 patients (each of whom had a significant smoking history) underwent microlaryngoscopic biopsy of 52 vocal fold lesions. These lesions, which were suspicious for atypia or malignancy and were confined to the musculomembranous vocal fold, were mapped according to surface involvement and depth of penetration. Review of the maps revealed that 27 of the 52 lesions involved only the superior/ventricular surface. For these patients, the entire layered vocal fold structure could potentially be preserved on the medial/vocalizing surface. Twenty-five of the 52 lesions involved both the superior/ventricular surface and the medial/vocalizing surface. No lesion involved only the medial surface. These data suggest that (in smokers) geographic localization of keratotic and erythroplastic lesions on the superior/ventricular surface of the musculomembranous vocal fold are likely to contain atypia. This characteristic facilitates the appropriate selection of patients for biopsy and may spare individuals, who have lesions resulting from hyperfunctional dysphonia and/or gastroesophageal reflux, from unnecessary biopsy. These two disorders typically result in pathology on the medial and/or posterior glottal surfaces. In order to determine whether a directed biopsy or an excisional biopsy approach is preferable for obtaining an accurate diagnosis, all specimens underwent whole-mount sectioning for three-dimensional histopathological analysis. Keratosis was noted: without atypia in 14; with atypia in 27; and with carcinoma in 11. The severity of the atypia usually varied throughout each specimen. The surface appearance of the lesion was not a reliable prognosticator of the severity of dysplasia either between patients or in different areas of the same lesion; therefore, excisional biopsy and whole-mount, multiple-section histopathological analysis were necessary for obtaining an accurate diagnosis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Premalignant epithelium and microinvasive cancer of the vocal fold: the evolution of phonomicrosurgical management. 788 66

Many phenotypic manifestations have been reported in cardiofaciocutaneous (CFC) syndrome, but none, to date, are pathognomonic or obligatory. Previous histopathological studies reported findings in skin and hair; no autopsy studies have been published. We report the clinical and autopsy findings of a 7-year-old boy with severe CFC syndrome and malnutrition of psychosocial origin. Manifestations of CFC, reported previously, included macrocephaly and macrosomia at birth; short stature; hypotonia; global developmental delays; dry, sparse thin curly hair; sparse eyebrows and eyelashes; dilated cerebral ventricles; high cranial vault; bitemporal constriction; supraorbital ridge hypoplasia; hypertelorism; ptosis; exophthalmos; depressed nasal bridge; anteverted nostrils; low-set, posteriorly-rotated, large, thick ears; decayed, dysplastic teeth; strabismus; hyperelastic skin; wrinkled palms; keratosis pilaris atrophicans faciei; ulerythema ophryogenes; hyperkeratosis; gastroesophageal reflux; and tracheobronchomalacia. Additional findings, not previously reported, include islet cell hyperplasia, lymphoid depletion, thymic atrophy and congenital hypertrophy of peripheral nerves with onion bulb formations. Although the islet cell hyperplasia, lymphoid depletion, and thymic atrophy are nonspecific findings that may be associated with either CFC or malnutrition, the onion bulb hypertrophy is specific for a demyelinating-remyelinating neuropathy. These findings implicate congenital peripheral neuropathy in the pathogenesis of the developmental delays, feeding difficulties, respiratory difficulties, ptosis and short stature in this case. Additional studies of other cases of CFC are needed.
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PMID:Cardiofaciocutaneous syndrome (CFC) with congenital peripheral neuropathy and nonorganic malnutrition: an autopsy study. 1600 34

Germline mutations in BRAF are a major cause of cardio-facio-cutaneous (CFC) syndrome, which is characterized by heart defects, characteristic craniofacial dysmorphology and dermatologic abnormalities. Patients with CFC syndrome also commonly show gastrointestinal dysfunction, including feeding and swallowing difficulties and gastroesophageal reflux. We have previously found that knock-in mice expressing a Braf Q241R mutation exhibit CFC syndrome-related phenotypes, such as growth retardation, craniofacial dysmorphisms, congenital heart defects and learning deficits. However, it remains unclear whether BrafQ241R/+ mice exhibit gastrointestinal dysfunction. Here, we report that BrafQ241R/+ mice have neonatal feeding difficulties and esophageal dilation. The esophagus tissues from BrafQ241R/+ mice displayed incomplete replacement of smooth muscle with skeletal muscle and decreased contraction. Furthermore, the BrafQ241R/+ mice showed hyperkeratosis and a thickened muscle layer in the forestomach. Treatment with MEK inhibitors ameliorated the growth retardation, esophageal dilation, hyperkeratosis and thickened muscle layer in the forestomach in BrafQ241R/+ mice. The esophageal dilation with aberrant skeletal-smooth muscle boundary in BrafQ241R/+ mice were recovered after treatment with the histone H3K27 demethylase inhibitor GSK-J4. Our results provide clues to elucidate the pathogenesis and possible treatment of gastrointestinal dysfunction and failure to thrive in patients with CFC syndrome.
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PMID:Activated Braf induces esophageal dilation and gastric epithelial hyperplasia in mice. 2897 66