Bilateral Crystalline Corneal Deposits as First Clinical Manifestation of Monoclonal Gammopathy: A Case Report

Aims: To report the clinical and diagnostic findings of a patient with bilateral corneal deposits caused by an underlying monoclonal gammopathy. Methods: Slit-lamp biomicroscopy, confocal microscopy and additional serological tests were performed on a 35-year-old man presenting with bilateral crystalline corneal deposits. Results: The patient was diagnosed as having monoclonal gammopathy based on elevated levels of serum immunoglobulin G. Confocal microscopy showed highly reflective (protein) deposits throughout the entire cornea, with the highest density in the epithelium and anterior stromal keratocytes. Conclusions: Monoclonal gammopathy, a potential sign of a life-threatening disease, can lead to dense, bilateral corneal deposits. As such changes can occur long before ocular or systemic discomforts appear, an early diagnosis is crucial. Ophthalmologists should be aware of corneal deposits as potential warning signs of monoclonal gammopathy

The fate of heterotopically grafted neural precursor cells in the normal and dystrophic adult mouse retina

PURPOSE. To study the integration and differentiation of heterotopically transplanted neural precursor cells in the retina of adult mouse mutants displaying apoptotic degeneration of photoreceptor cells. METHODS. Neural precursor cells were isolated from the spinal cord of transgenic mouse embryos ubiquitously expressing enhanced green fluorescent protein. Cells were expanded in vitro and transplanted into the retina of adult wild-type and age-matched ␤2/␤1 knock-in mice. ␤2/␤1 knock-in mutants display apoptotic death of photoreceptor cells and were generated by placing the cDNA of the ␤1 subunit into the gene of the ␤2 subunit of Na,K-ATPase. The integration and differentiation of grafted cells in recipient retinas was studied 1 or 6 months after transplantation. RESULTS. Mutant retinas contained more donor-derived cells than wild-type hosts. Moreover, in mutants, donor cells integrated into deeper retinal layers. In both genotypes, grafted cells differentiated into astrocytes and oligodendrocytes. Only a few ganglion cell axons were myelinated by donor-derived oligodendrocytes 1 month after transplantation, whereas extensive myelination of the nerve fiber layer was observed 6 months after transplantation. Unequivocal evidence for differentiation of grafted cells into neurons was not obtained. CONCLUSIONS. Heterotopically transplanted neural precursor cells are capable of integrating, surviving, and differentiating into neural cell types in normal and dystrophic retinas of adult mice. The particular environment of a pathologically altered retina facilitates integration of transplanted precursor cells. In principle, neural precursors may thus be useful to substitute for or replace dysfunctional or degenerated cell types. Results of the present study also indicate that replacement of retinal cell types is likely to require more appropriate donor cells, such as retinal precursor cells. (Invest Ophthalmol Vis Sci. 2001;42:3311-3319) I nherited retinal dystrophies are a heterogeneous group of disorders characterized by progressive retinal degeneration. Effective therapeutic treatments of retinal dystrophies in humans are currently not available. However, animal experiments have shown beneficial effects of various therapeutic strategies, including gene therapy to substitute for the pathogenic gene, application of growth factors to minimize cell degeneration, or transplantation of committed cell types to replace dysfunctional or degenerated cells. 10 -12 Neural precursors have been isolated from the developing and adult brain and can be massively expanded in vitro, providing, in principle, unlimited amounts of cell material for transplantation (different from primary retinal cells). When transplanted into the developing or adult brain, they have been demonstrated to integrate extensively into the recipient tissue, to survive for extended periods, and to eventually differentiate into those cell types that are affected in the host. 22 These cells were expanded in vitro in the presence of mitogens and subsequently transplanted into the retina of adult wild-type mice and mouse mutants displaying apoptotic degeneration of photoreceptor cells. As a mutant host, we used ␤2/␤1 knock-in mice. 23 ␤1 and ␤2 are subunits of Na,K-ATPase, a heterodimeric ion pump additionally consisting of a catalytic ␣-subunit. 23,24 ␤-subunits play a pivotal role for the formation of functional Na,K-ATPases as exemplified, for instance, by the severe phenotype of ␤2-deficient mice. 25 Such mice display a variety of severe defects in the central nervous system (CNS), including massive apoptotic degeneration of photoreceptor cells, and die at the end of the third postnatal week. 23 To obtain information about the fate of heterotopically transplanted neural precursor cells in the normal and dystrophic mouse retina, we isolated such cells from the spinal cord of EGFP transgenic mice and transplanted them into the retinas of adult wild-type mice and ␤2/␤1 knock-in mutants. Heterotopically transplanted neural precursor cells integrated into the mutant retina without disrupting the histoarchitecture of the host tissue. Quantitative investigations revealed that donorderived cells were more numerous and more widely distributed in mutant retinas than in retinas of age-matched wild-type From th

The effects of iron fortification on the gut microbiota in African children: a randomized controlled trial in Cote d'Ivoire.

BACKGROUND: Iron is essential for the growth and virulence of many pathogenic enterobacteria, whereas beneficial barrier bacteria, such as lactobacilli, do not require iron. Thus, increasing colonic iron could select gut microbiota for humans that are unfavorable to the host. OBJECTIVE: The objective was to determine the effect of iron fortification on gut microbiota and gut inflammation in African children. DESIGN: In a 6-mo, randomized, double-blind, controlled trial, 6-14-y-old Ivorian children (n = 139) received iron-fortified biscuits, which contained 20 mg Fe/d, 4 times/wk as electrolytic iron or nonfortifoed biscuits. We measured changes in hemoglobin concentrations, inflammation, iron status, helminths, diarrhea, fecal calprotectin concentrations, and microbiota diversity and composition (n = 60) and the prevalence of selected enteropathogens. RESULTS: At baseline, there were greater numbers of fecal enterobacteria than of lactobacilli and bifidobacteria (P < 0.02). Iron fortification was ineffective; there were no differences in iron status, anemia, or hookworm prevalence at 6 mo. The fecal microbiota was modified by iron fortification as shown by a significant increase in profile dissimilarity (P < 0.0001) in the iron group as compared with the control group. There was a significant increase in the number of enterobacteria (P < 0.005) and a decrease in lactobacilli (P < 0.0001) in the iron group after 6 mo. In the iron group, there was an increase in the mean fecal calprotectin concentration (P < 0.01), which is a marker of gut inflammation, that correlated with the increase in fecal enterobacteria (P < 0.05). CONCLUSIONS: Anemic African children carry an unfavorable ratio of fecal enterobacteria to bifidobacteria and lactobacilli, which is increased by iron fortification. Thus, iron fortification in this population produces a potentially more pathogenic gut microbiota profile, and this profile is associated with increased gut inflammation. This trial was registered at controlled-trials.com as ISRCTN21782274

Effects of the timing of initial feeding on growth and survival of spotted mandarin fish Siniperca scherzeri larvae

The effects of delayed first feeding on growth and survival of spotted mandarin fish Siniperca scherzeri larvae were examined under controlled conditions. Morphometric characters [yolk-sac volume, oil globule volume, head depth ( H D ), body depth ( B D ), eye diameter ( E D ), musculature height ( M H ), mouth diameter ( M D ) and total length ( L T )], body mass ( M ), specific growth rate ( S GR ) and survival were evaluated under different first-feeding time (2, 3, 4 and 5 days after hatching). Larvae began to feed exogenously at 2 days after hatching (DAH) and the point of no return ( P NR ) occurred between 5 and 6 DAH at 23° C, range ±1·0° C. The yolk volume of larvae first-fed at 2 days had a significant difference compared with that of larvae first-fed at 3, 4 and 5 days on 3 and 4 DAH. The larvae first-fed at 2 days achieved comparatively better growth performance than that of 3, 4 and 5 days. On 5 DAH, all morphometric characters had significant differences between 2 and 5 days and 2 and 4 days initial feeding, respectively. Total mortality was recorded on 9 DAH for the larvae first-fed at 5 days. On 12 DAH, significant differences were observed between 2 and 4 days and 3 and 4 days initial feeding for all morphometric characters. From 16 DAH to the end of experiment, all growth variables of the larvae first-fed at 2 days were significantly higher than those in other treatments. The S GR (2–9 DAH) first-fed at 2 and 3 days were significantly higher than 4 and 5 day treatments, and the S GR (9–16 DAH) first-fed at 2 days was significantly higher than 3 and 4 day treatments. There was no significant difference, however, of S GR (16–28 DAH) among treatments. Survival rate was significantly higher at 2 days initial feeding (27·42%) when compared with 3 (15·96%) and 4 days (7·92%) initial feeding at the end of experiment. The present study suggests that the first feeding of S. scherzeri larvae should be initiated at 2 days after hatching for achieving good growth and survival.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78713/1/j.1095-8649.2009.02328.x.pd

Corneal Biomechanical Changes after Crosslinking for Progressive Keratoconus with the Corneal Visualization Scheimpflug Technology

Purpose. To evaluate the effect of corneal crosslinking in progressive keratoconus by applying in vivo corneal visualization Scheimpflug technology. Design. Longitudinal retrospective study. Subjects and Controls. Seventeen eyes of patients treated with corneal crosslinking for progressive keratoconus. Methods. Corneal visualization Scheimpflug technology analyses (research software version 6.07r08) of subjects with progressive keratoconus before and 3 months after corneal crosslinking (CXL) were reviewed retrospectively. t-test (for normal distribution) and Wilcoxon matched-pairs test (if not normally distributed) were used to test for statistically significant differences between pre- and post-CXL analyses. Results. We demonstrated statistically significant differences for the intraocular pressure (median: +3 mmHg, P =0.004), the central corneal pachymetry (pachy; mean: −35 µm, P<0.001), the timespan between the air impulse release and the first applanation of the cornea (A1time; median: +0.12 ms, P<0.05), and the timespan between the air impulse release and the second applanation of the cornea (A2time; median: −37 ms, P<0.05). Conclusions. With the A1time and the A2time, we identified two parameters that demonstrated a statistically significant improvement of the biomechanical properties of the cornea after CXL. Despite the known initial decrease of the pachymetry after CXL, none of the analyzed parameters indicated a progression of the keratoconus

A single-dose comparison of the acute effects between the new somatostatin analog SOM230 and octreotide in acromegalic patients

Treatment with the somatostatin receptor (sst) subtype 2 predominant analogs octreotide and lanreotide induces clinical and biochemical cure in approximately 65% of acromegalic patients. GH-secreting pituitary adenomas, which are not controlled, also express sst(5). We compared the acute effects of octreotide and SOM230, a new somatostatin analog with high affinity for sst(1,2,3,5) on hormone release in acromegalic patients. In a single-dose, proof-of-concept study, 100 microg octreotide and 100 and 250 microg SOM230 were given s.c. to 12 patients with active acromegaly. Doses of 100 and 250 microg SOM230 dose-dependently suppressed GH levels from 2-8 h after administration (-38 +/- 7.7 vs. -61 +/- 6.7%, respectively; P < 0.01). A comparable suppression of GH levels by octreotide and 250 microg SOM230 was observed in eight patients (-65 +/- 7 vs. -72 +/- 7%, respectively). In three patients, the acute GH-lowering effect of 250 microg SOM230 was significantly superior to that of octreotide (-70 +/- 2 vs. -17 +/- 15%, respectively; P < 0.01). In one patient, the GH-lowering effect of octreotide was better than that of SOM230. Tolerability for SOM230 was good. Glucose levels were initially slightly elevated after octreotide and SOM230, compared with control day, whereas insulin levels were only significantly suppressed by octreotide. We conclude that SOM230 is an effective GH-lowering drug in acromegalic patients with the potential to increase the number of patients controlled during long-term medical treatment

The multi-ligand somatostatin analogue SOM230 inhibits ACTH secretion by cultured human corticotroph adenomas via somatostatin receptor type 5.

Objective: Currently, there is no effective medical treatment for patients with pituitary-dependent Cushing’s disease. A novel somatostatin (SS) analogue, named SOM230, with high binding affinity to SS receptor subtypes sst1, sst2, sst3 and sst5 was recently introduced. We compared the in vitro effects of the sst2-preferring SS analogue octreotide (OCT) and the multi-ligand SOM230 on ACTH release by human and mouse corticotroph tumour cells. Methods: By quantitative RT-PCR the sst subtype expression level was determined in human corticotroph adenomas. In vitro, the inhibitory effect of OCT and SOM230 on ACTH release by dispersed human corticotroph adenoma cells and mouse AtT20 corticotroph adenoma cells was determined. In addition, the influence of dexamethasone on the responsiveness to OCT and SOM230 was studied. Results: Corticotroph adenomas expressed predominantly sst5 mRNA (six out of six adenomas), whereas sst2 mRNA expression was detected at significantly lower levels. In a 72 h incubation with 10 nmol/l SOM230, ACTH release was inhibited in three out of five cultures (range –30 to –40%). Ten nmol/l OCT slightly inhibited ACTH release in only one of five cultures (– 28%). In AtT20 cells, expressing sst2, sst3 and sst5, SOM230 inhibited ACTH secretion with high potency (IC50 0.2 nmol/l). Dexamethasone (10 nmol/l) pre-treatment did not influence the sensitivity of the cells to the inhibitory effect of SOM230, suggesting that sst5 is relatively resistant to negative control by glucocorticoids. Conclusions: The selective expression of sst5 receptors in corticotroph adenomas and the preferential inhibition of ACTH release by human corticotroph adenoma cells by SOM230 in vitro, suggest that SOM230 may have potential in the treatment of patients with pituitary-dependent Cushing’s disease