Animal Models of Barrett's Esophagus and Esophageal Adenocarcinoma–Past,Present, and Future

Esophageal adenocarcinoma is the fastest rising cancer in the United States. It develops from long‐standing gastroesophageal reflux disease which affects >20% of the general population. It carries a very poor prognosis with 5‐year survival <20%. The disease is known to sequentially progress from reflux esophagitis to a metaplastic precursor, Barrett''s esophagus and then onto dysplasia and esophageal adenocarcinoma. However, only few patients with reflux develop Barrett''s esophagus and only a minority of these turn malignant. The reason for this heterogeneity in clinical progression is unknown. To improve patient management, molecular changes which facilitate disease progression must be identified. Animal models can provide a comprehensive functional and anatomic platform for such a study. Rats and mice have been the most widely studied but disease homology with humans has been questioned. No animal model naturally simulates the inflammation to adenocarcinoma progression as in humans, with all models requiring surgical bypass or destruction of existing antireflux mechanisms. Valuable properties of individual models could be utilized to holistically evaluate disease progression. In this review paper, we critically examined the current animal models of Barrett''s esophagus, their differences and homologies with human disease and how they have shaped our current understanding of Barrett''s carcinogenesis.     

Preexisting posterior capsule defect progressing to white mature cataract.

We present two children discovered to have a total cataract in one eye with a posterior subcapsular cataract in the other eye. Sequential photography documented rapid progression of the posterior subcapsular cataract to a preexisting posterior capsule defect and subsequently to a white, mature cataract. We propose that early intervention be considered in cases with any posterior subcapsular changes (no matter how subtle) and history of total cataract in the fellow eye, especially in any situation where loss of follow-up is likely to occur. In the event surgery is not advised, parents should be warned about possible cataract progression and the importance of regular follow-up examinations.     

Ulcer of the tongue as a presenting feature of pulmonary tuberculosis

Oral tuberculosis is very rare and when present they are usually secondary to pulmonary tuberculosis. Tuberculous lesions of the tongue have become so infrequent that they are virtually a forgotten disease entity and may pose a diagnostic problem. The case reported in this paper emphasizes the importance of including tuberculosis in the differential diagnosis of any chronic oral ulcer. The low number of oral infections by M. tuberculosis could be due to underreporting.     

Divergent dislocation of the elbow in a child (a case report).

A rare case of simultaneous disruption of superior radio-ulnar joint and posterior dislocation of the same elbow in a 6 year old boy is presented. It was possible to achieve the stable reduction by means of closed manipulation, restoring normal function in 6 weeks time. The possible mode of injury is discussed. There are only 4 cases reported of such a divergent elbow dislocation in modern literature.     

Anosognosia in mild cognitive impairment: Relationship to activation of cortical midline structures involved in self-appraisal.

Awareness of cognitive dysfunction shown by individuals with Mild Cognitive Impairment (MCI), a condition conferring risk for Alzheimer's disease (AD), is variable. Anosognosia, or unawareness of loss of function, is beginning to be recognized as an important clinical symptom of MCI. However, little is known about the brain substrates underlying this symptom. We hypothesized that MCI participants' activation of cortical midline structures (CMS) during self-appraisal would covary with level of insight into cognitive difficulties (indexed by a discrepancy score between patient and informant ratings of cognitive decline in each MCI participant). To address this hypothesis, we first compared 16 MCI participants and 16 age-matched controls, examining brain regions showing conjoint or differential BOLD response during self-appraisal. Second, we used regression to investigate the relationship between awareness of deficit in MCI and BOLD activity during self-appraisal, controlling for extent of memory impairment. Between-group comparisons indicated that MCI participants show subtly attenuated CMS activity during self-appraisal. Regression analysis revealed a highly significant relationship between BOLD response during self-appraisal and self-awareness of deficit in MCI. This finding highlights the level of anosognosia in MCI as an important predictor of response to self-appraisal in cortical midline structures, brain regions vulnerable to changes in early AD.     

Secondary intraocular lens implantation for pediatric aphakia.

PURPOSE: We sought to report the outcome of secondary intraocular lens (IOL) implantation in children. METHODS: This was a retrospective case review. RESULTS: A total of 77 eyes were identified. An average age at secondary implantation was 7.8 +/- 5.0 years, whereas the average age at primary cataract surgery was 1.5 +/- 2.6 years. Average follow-up was 2.7 +/- 1.9 years. Thirty eyes received a hydrophobic acrylic IOL implantation whereas 47 eyes received a PMMA IOL. The sites of fixation for implanted IOLs were as follows: anterior-chamber (n = 6), sulcus (n = 42), in-the-bag (n = 14), optic-capture (n = 6), piggyback (n = 4), and sutured (n = 5). Complications included clinically significant decentration, 4 (5.2%); visual axis opacification, 4 (5.2%); dislocation of the IOL, 2 (2.6%); and pupillary capture requiring repositioning of IOL, 1 (1.3%). Clinically significant decentration requiring surgical intervention was noted only in eyes with sulcus-fixated foldable IOLs (28.6%; 4/14). None of the 29 eyes with sulcus-fixated PMMA IOL implantation developed decentration. All the decentrations were in an inferior direction and occurred in eyes of male patients (P = 0.03). Eyes with an axial length of >23 mm were 4 times more likely to develop decentration if implanted with a sulcus-fixated foldable IOL when compared with eyes measuring <23 mm (P = 0.03). Postoperative geometric mean visual acuity was significantly better than preoperative visual acuity (P < 0.001). CONCLUSION: Secondary IOL implantation can be safely achieved in pediatric eyes. In-the-bag fixation of foldable IOLs is associated with a low rate of complications. Foldable lenses appear to have a higher rate of decentration than PMMA lenses when placed in the sulcus in eyes of myopic male patients.     

Heterogeneity of serum peptides with immunoactivity detected by a radioimmunoassay for proinsulin-like growth factor-II E domain: description of a free E domain peptide in serum.

We have reported that normal human sera contain immunoactivity (IA) detected by a RIA directed against the first 21 amino acids of the E domain of proinsulin-like growth factor-II (pro-IGF-II). Marked elevations of E-21 IA were found in the serum of patients with nonislet cell hypoglycemia (NICTH) and patients with renal failure receiving chronic hemodialysis. In this paper we describe some of the properties of the E-21 IA of normal and abnormal sera. The E-21 IA eluted from a calibrated acid Sephadex G-50 column as two major peaks. In normal serum the first major peak had a mol wt (Mr) between 14,000-15,000, and the second peak had a Mr between 5,000-6,000. When E-21 IA from serum of a patient with NICTH was similarly studied, most of the IA was present as a Mr 11,000 peak and only a small amount was present as a 5,000-6,000 Mr peak. In contrast, most of the E-21 IA present in the sera of patients on hemodialysis was present in the smaller molecular form, which eluted from a reverse phase column as a single component. This small Mr peak lacked determinants for the IGF-II monoclonal antibody (Amano), for pooled serum IGF-binding proteins, and for the IGF-I receptors on human placental membranes. We suggest that the 15- and 11-kilodalton peaks represent the glycated and unglycated forms of pro-IGF-II (E-21) reported by others. The glycated form appears to predominate in normal serum, whereas the nonglycated form predominates in the serum of patients with NICTH and renal failure. The 5,000-6,000 Mr E-21 IA probably represents a fragment of the free E domain of pro-IGF-II. Its size is consistent with cleavage of the free E domain between Arg46 and Arg47. The accumulation of this E-21 IA in renal failure is evidence that the kidney has a major role in the clearance of this fragment, which is not accomplished by the membranes used in hemodialysis.