Effects of 0.5% apraclonidine on optic nerve head and peripapillary retinal blood flow

AIMS: To examine the effects of 0.5% apraclonidine on optic nerve head (ONH) and peripapillary retinal blood flow by scanning laser Doppler flowmetry (SLDF). METHODS: ONH and peripapillary retinal blood flow of 17 healthy subjects were measured by SLDF before and 1 hour and 3 hours after unilateral administration of 0.5% apraclonidine. The fellow eyes were treated with balanced salt solution and the examiners were masked as to which eye was treated with apraclonidine. On each occasion, three scans were obtained and haemodynamic variables (volume, flow, and velocity) were analysed at eight locations, four in the neural rim and four in the peripapillary retina, avoiding ophthalmoscopically visible vessels. The statistical significance of changes from the baseline value of variables and the differences in the measured quantities between apraclonidine treated eyes and fellow eyes at each time point were evaluated using Wilcoxon signed rank test. RESULTS: The intraocular pressure was reduced significantly in apraclonidine treated eyes by 15.0% (p = 0.001) at 1 hour and 30.0% (p = 0.000) at 3 hours after administration. In the volume, flow, or velocity of ONH and peripapillary retinal blood flow, there were no significant changes from the baseline values at 1 hour and 3 hours after apraclonidine administration in either apraclonidine treated eyes (p > 0.4) or fellow eyes (p > 0.2). Also, no significant differences were found in the measured quantities between apraclonidine treated eyes and fellow eyes at each time point (p > 0.1). CONCLUSION: A single dose of topical apraclonidine 0.5% in healthy subjects does not have adverse effects on the ONH and peripapillary retinal blood flow.     

Solid-solution structure and the weakly first-order displacive transformation in Fe-Pd alloys

The solid-solution structure of an Fe-31 at. pct Pd single crystal quenched from 1173 K was measured by combined X-ray diffraction (XRD) and atom-probe microanalysis, with analysis of diffuse X-ray scattering supplemented by computer simulation. Detailed comparison of composition-fluctuation amplitudes on the size scale of 50 atoms shows good agreement between diffraction and atom-probe results, revealing a nonrandom solution structure with a broadened composition distribution, consistent with the existence of a miscibility gap in the system. Also consistent with the L1₀-FePd ordering present in the Fe-Pd system, the diffuse scattering indicates some short-range order in the higher Pd regions. Computer simulation of the diffuse scattering indicates Fe atom displacements in 〈100〉 directions in Fe-rich regions forming microdomains oriented along {110} planes, consistent with previous electron microscopy observations of fine structures above the nominal transformation temperature. Combining the measured composition distribution with a magnetics-based model of the composition dependence of the parent-phase instability temperature predicts a spreading of the weakly first-order cubic-tetragonal phase transformation, whereby tetragonal domains are locally stabilized at temperatures 300 K above the temperature where macroscopic plate products first appear. Composition fluctuations can thus introduce a significant component of continuous character to a weakly first-order displacive transformation.     

Transgene expression of bcl-xL permits anti-immunoglobulin (Ig)-induced proliferation in xid B cells

Mutations in the tyrosine kinase, Btk, result in a mild immunodeficiency in mice (xid). While B lymphocytes from xid mice do not proliferate to anti-immunoglobulin (Ig), we show here induction of the complete complement of cell cycle regulatory molecules, though the level of induction is about half that detected in normal B cells. Cell cycle analysis reveals that anti-Ig stimulated xid B cells enter S phase, but fail to complete the cell cycle, exhibiting a high rate of apoptosis. This correlated with a decreased ability to induce the anti-apoptosis regulatory protein, Bcl-xL. Ectopic expression of Bcl-xL in xid B cells permitted anti-Ig induced cell cycle progression demonstrating dual requirements for induction of anti-apoptotic proteins plus cell cycle regulatory proteins during antigen receptor mediated proliferation. Furthermore, our results link one of the immunodeficient traits caused by mutant Btk with the failure to properly regulate Bcl-xL.     

Nitrogen oxide in the treatment of oxygenation failure in neonates

Oxygenation problems are common in very sick infants, and involve a high risk of mortality or residual morbidity. We describe two infants with severe oxygenation difficulties. In one baby these were caused by meconium aspiration, while in the second, premature (1,500 g birth weight) infant Escherichia coli septicemia had precipitated persistent pulmonary hypertension. Inhaled nitric oxide led to immediate improvement in oxygenation, and the one infant was weaned off mechanical ventilatory support after four days, the other after ten days. There were no discernible side effects in either baby. Nitric oxide treatment should be considered for infants with life-threatening oxygenation problems who do not respond adequately to conventional management.     

Lipomatous glioneurocytoma of the posterior fossa with divergent differentiation: case report

OBJECTIVE AND IMPORTANCE: We report a case of a posterior fossa neuroepithelial tumor with unusual clinical presentation, magnetic resonance imaging appearance, and morphological features. CLINICAL PRESENTATION: This 66-year-old man presented with a history of gait ataxia, dizziness, and tinnitus and was found to have a large tumor in the posterior fossa and cerebellopontine angle. INTERVENTION: Gross total excision of the tumor was accomplished. Histologically, the most unique features were macrovesicular accumulations of lipid, giving the tumor (at least focally) an appearance virtually identical to that of mature adipose tissue. Evidence of biphasic neuronal and glial differentiation was noted by immunohistochemistry and electron microscopy. CONCLUSION: A literature review is presented. Diagnostically, this neoplasm seems to fit in a unique group of rarely described, lipomatous neuroectodermal tumors that show divergent neuronal and glial differentiation.     

Anti-C1q receptor/calreticulin autoantibodies in patients with systemic lupus erythematosus (SLE)

We report a case of acute glomerulonephritis associated with acute Q fever. An abattoir worker with a nonspecific febrile illness and pneumonia and abnormal liver function test results developed hematuria, proteinuria, and acute renal failure that resolved with appropriate antimicrobial therapy. Renal biopsy demonstrated diffuse proliferative and exudative glomerulonephritis. Serological tests confirmed recent infection with Coxiella burnetii, with a fourfold rise in the titer of phase II antibody, positive phase II IgM antibody, and negative phase I antibody. Other known causes of glomerulonephritis were excluded. Most reports of renal complications of C. burnetii infection describe glomerulonephritis associated with endocarditis due to chronic Q fever. Renal involvement in patients with acute C. burnetii infection has been rarely described. Glomerulonephritis should be recognized as a complication of acute C. burnetii infection and endocarditis due to chronic Q fever.     

XV454, a novel nonpeptide small-molecule platelet GIIb/IIIa antagonist with comparable platelet alpha(IIb)beta3-binding kinetics to c7E3

XV454 demonstrated high potency (IC50 = 14-25 nM) in inhibiting human platelet aggregation induced by adenosine diphosphate (ADP, 10 microM), thrombin receptor agonist peptide (TRAP) (10 microM), or collagen (20 microg/ml). XV454 exhibited a high degree of selectivity for platelet alpha(IIb)beta3 in comparison with c7E3, which is a nonspecific antagonist for both alpha(IIb)beta3 and alpha(v)beta3. Both XV454 and c7E3 bind with high affinity to either activated (A) or unactivated (U) human, baboon, or canine platelets. XV454 binds with a relatively higher affinity [Kd = 0.5 nM (A), 0.6 nM (U)] as compared with c7E3 [Kd = 9.1 nM (A), 9.2 (U) nM]. XV454 demonstrated a tight association with human, baboon, and, to a lesser extent, with canine platelets (t(1/2) of dissociation = 110 +/- 6, 80 +/- 10, and 23 +/- 2 min, respectively). Both c7E3 and XV454 associate tightly with a slower dissociation rate with unactivated human platelets: t(1/2) of 42 and 116 min, respectively. In non-human primates, oral (0.1 mg/kg, p.o.) and intravenous (0.05 mg/kg, i.v. bolus administration of XV454 methyl ester pro-drug resulted a long-lasting maximal antiplatelet efficacy for < or = 72 h with significant but reversible prolongation of bleeding time and without effects on platelet count, clinical chemistry, or hemodynamic profile. In conclusion, XV454 represents a potent antiplatelet agent in inhibiting platelet aggregation along with a high affinity and relatively slow dissociation rate from human platelet GPIIb/IIIa receptors that allow a long-lasting antiplatelet efficacy after single i.v. or oral administration.