Surgical management of corneal plaques in vernal keratoconjunctivitis: a clinicopathologic study

PURPOSE: To describe the surgical management and histopathologic and immunohistochemical findings in corneal plaques of shield ulcers in vernal keratoconjunctivitis. PATIENTS AND METHODS: Three children (ages 4, 7.5, and 9) presented with corneal plaques unresponsive to conservative systemic and topical medical treatment. Plaques were scraped under general anesthesia, and soft bandage contact lenses were placed. The excised tissue was evaluated by histopathology and immunohistochemistry. RESULTS: During surgery, plaques were found to extend beyond the ulcer margins. Histopathology revealed granular, deeply-eosinophilic, laminar material, firmly attached to the Bowman layer in all cases. Immunohistochemistry confirmed this to be eosinophil-derived major basic protein (MBP). After surgical removal, complete epithelization was evident within 1-4 weeks in all cases. CONCLUSIONS: Corneal plaque is a rare complication of vernal keratoconjunctivitis. These plaques usually do not resolve with standard conservative measures. Failure to epithelialize may be a result of the plaque material extending below the edges of adjacent epithelium. We suggest that MBP plaques precipitate on the denuded stromal bed, thereby playing a pathogenic role in nonhealing shield ulcers.     

Evaluating the risk of tuberous sclerosis in cases with prenatal diagnosis of cardiac rhabdomyoma

OBJECTIVE: To evaluate the prenatal parameters that increase the risk of tuberous sclerosis in prenatal management of fetal cardiac tumors suspected as rhabdomyoma. METHODS: The study was a retrospective survey of 18 documented cases in which cardiac rhabdomyoma was suspected during pregnancy. The following parameters were evaluated as possible risk factors associated with tuberous sclerosis: tumor size, isolated or multiple, and family history of tuberous sclerosis. RESULTS: Eighteen documented cases in which cardiac rhabdomyoma was found during pregnancy were evaluated. Of these cases, seven (39%) had proven tuberous sclerosis and 11 were found to be non-associated tuberous sclerosis tumors. When combining the present data with previous series, cases with diagnosis of tuberous sclerosis had equal mean tumor size to those with normal outcome. Family history of tuberous sclerosis in the presence of cardiac rhabdomyoma almost invariably ended with tuberous sclerosis (86%). All other cases with diagnosis of tuberous sclerosis and no family history had all multiple cardiac tumors. CONCLUSION: The present data suggest that 39% of in utero suspected cardiac rhabdomyoma would have tuberous sclerosis. Family history and multifocality remain the strongest predictors of tuberous sclerosis, whereas size of the cardiac tumor can not reliably be used to predict tuberous sclerosis in prenatal counseling.     

Neurexin mediates the assembly of presynaptic terminals

Neurexins are a large family of proteins that act as neuronal cell-surface receptors. The function and localization of the various neurexins, however, have not yet been clarified. Beta-neurexins are candidate receptors for neuroligin-1, a postsynaptic membrane protein that can trigger synapse formation at axon contacts. Here we report that neurexins are concentrated at synapses and that purified neuroligin is sufficient to cluster neurexin and to induce presynaptic differentiation. Oligomerization of neuroligin is required for its function, and we find that beta-neurexin clustering is sufficient to trigger the recruitment of synaptic vesicles through interactions that require the cytoplasmic domain of neurexin. We propose a two-step model in which postsynaptic neuroligin multimers initially cluster axonal neurexins. In response to this clustering, neurexins nucleate the assembly of a cytoplasmic scaffold to which the exocytotic apparatus is recruited.     

Responsiveness to rapid atrial pacing of the specialized atrioventricular conduction system in children

Summary Responsiveness to rapid atrial pacing of the specialized atrioventricular (A-V) conduction system was studied in 25 patients aged 2 months to 18 years. Atrial pacing via a catheter placed at the right atrial superior vena cava junction was initiated at rates slightly greater than the sinus rate and gradually increased to rates as high as 600 stimuli per minute. His bundle electrograms were obtained in most patients. When the atrial pacing rate (x-axis) was plotted against the corresponding ventricular rate (y-axis), the curve was M-shaped. The initial ascending limb occurred during 1:1 A-V conduction with rates as high as 270 stimuli per minute. The first descending limb resulted from Wenckebach type A-V block occurring at rates of 160 to 300 stimuli per minute. The second ascending limb corresponded to periods of 2:1 A-V block observed at rates of 200 to 536 stimuli per minute, and the final descending limb was related to higher degrees of block at both the pacing site and the A-V node. The second descending limb was seen with pacing rates of 296 to 600 stimuli per minute. The rates required to produce Wenckebach type A-V block in this group of children were higher than those reported in adults. One patient with spontaneous first-degree A-V block developed 2:1 A-V block at a pacing rate of only 150 stimuli per minute.This technique for studying the response to rapid atrial pacing of the specialized A-V conduction system characterises its functional capacity. The technique can be applied rapidly and safely in selected patients.     

Five years of fecal microbiota transplantation——an update of the Israeli experience

AIM To evaluate and describe the efficacy of fecal microbiota transplantation(FMT) for Clostridium difficile infection(CDI) in a national Israeli cohort.METHODS All patients who received FMT for recurrent(recurrence within 8 wk of the previous treatment) or refractory CDI from 2013 through 2017 in all the five medical centers in Israel currently performing FMT were included. Stool donors were screened according to the Israeli Ministry of Health guidelines. Clinical and laboratory data of patients were collected from patients' medical files, and they included indications for FMT, risk factors for CDI and disease severity. Primary outcome was FMT success(at least 2 mo free of CDI-related diarrhea post-FMT). Secondary outcomes included initial response to FMT(cessation of diarrhea within 7 d) and recurrence at 6 mo.RESULTS There were 111 FMTs for CDI, with a median age of 70 years [interquartile range(IQR): 53-82], and 42%(47) males. Fifty patients(45%) were treated via the lower gastrointestinal(LGI, represented only by colonoscopy) route, 37(33%) via capsules, and 24(22%) via the upper gastrointestinal(UGI) route. The overall success rate was 87.4%(97 patients), with no significant difference between routes of administration(P = 0.338). In the univariant analysis, FMT success correlated with milder disease(P = 0.01), ambulatory setting(P 0.05) and lower Charlson comorbidity score(P 0.05). In the multivariant analysis, only severe CDI [odd ratio(OR) = 0.14, P 0.05] and inpatient FMT(OR = 0.19, P 0.05) were each independently inversely related to FMT success. There were 35(32%) patients younger than 60 years of age, and 14(40%) of them had a background of inflammatory bowel disease.CONCLUSION FMT is a safe and effective treatment for CDI, with capsules emerging as a successful and well-tolerated route. Severe CDI is less likely to respond to FMT.     

Oral Insulin: The Rationale for This Approach and Current Developments

Insulin remains the most effective and durable hypoglycemic agent for the treatment of diabetes. The addition of an effective oral insulin dosage form to the antidiabetes armamentarium may have significant benefits in terms of fostering compliance and adherence among patients, as well as physiologic advantages due to the fact that such a dosage form replicates the natural route of insulin secretion and absorption through the portal vein and targets the liver directly. Several companies have developed technological platforms that protect polypeptides and proteins from enzymatic hydrolysis, enable their transport across the epithelial lining, and promote their absorption from the gastrointestinal tract. A review of the potential physiological rationale and advantages, as well as of current pertinent technologies used specifically with insulin, is herewith provided.     

Large Congenital Melanotic Nevi in an Extremity with Neurocutaneous Melanocytosis

Abstract:   A 14-day-old boy presented with a large congenital melanocytic nevus over his left thigh with approximately 17 satellite nevi distributed over the rest of his skin surface. Six weeks later, he developed generalized tonic–clonic seizures and additional satellite nevi became apparent ( n  > 20). A subsequent brain magnetic resonance imaging demonstrated right temporal T1 hyperintense signal abnormality. At 4 months of age the patient underwent a lumbar puncture that was normal without evidence of melanocytes or tumor. Nevertheless, a few days later he underwent resection of his right medial temporal lesion which demonstrated melanocytosis in the temporal lobe as well as melanocytosis in subependymal areas in other parts of the brain and ventricles, confirming the suspected diagnosis of neurocutaneous melanocytosis. Our case supports previous studies that conclude that the number of satellite nevi is a greater predictor of neurocutaneous melanocytosis than is the location of large congenital melanocytic nevus. In our case, cerebrospinal fluid studies were not reliable even in the face of florid neurocutaneous melanocytosis involving the leptomeninges and ventricles.