Optic nerve injury after sudden traumatic rotation of the eye. A case report

Optic nerve injury is regularly accompanied by signs of local facial or ocular injury, fractures or unconsciousness. The energy of the blow is thought to be delivered to the optic nerve directly by stretching and tearing and by shock wave forces and secondarily as sequelae of contusion. A case is described in which optic nerve injury is caused by a sudden traumatic duction of the eyeball, with all signs of local or systemic contusion missing. During observation the primarily healthy optic nerve head developed subtotal optic atrophy. This case strengthens the belief that the optic nerve is particularly vulnerable to stretching, tearing and torsion.     

A phase Ib,open‐label,single arm study to assess the safety,pharmacokinetics, and impact on humoral sensitization of SANGUINATE infusion in patients with end‐stage renal disease

The endeavor to study desensitization in kidney transplantation has not been matched by an effort to investigate strategies to prevent sensitization. In this study (NCT02437422), we investigated the safety, impact on sensitization, and pharmacokinetics of SANGUINATE (SG), a hemoglobin‐based oxygen carrier, as a potential alternative to packed red blood cells (PRBC) in transplant candidates with end‐stage renal disease (ESRD). Ten ESRD subjects meeting inclusion/exclusion (I/E) criteria were planned to receive three weekly infusions of SG (320 mg/kg). The study was stopped after five subjects were enrolled, and their data were analyzed after completing a follow‐up period of 90 days. Two subjects had elevated troponin I levels in setting of SG infusion, one of which was interpreted as a non‐ST elevation myocardial infarction. All other adverse events were transient. SG pharmacokinetic analysis showed mean (SD) C_max, T_max, AUC, and half‐life of 4.39 (0.69) mg/mL, 2.42 (0.91) hours, 171.86 (52.35) mg h/mL, and 40.60 (11.96) hours, respectively. None of the subjects developed new anti‐HLA antibodies following SG infusion and throughout the study period. In conclusion, SG is a potential alternative to PRBCs in ESRD patients considered for kidney transplantation as it was not associated with humoral sensitization. Larger studies in highly sensitized patients are required to further evaluate for potential safety signals.     

In vivo and in vitro binding of C4 molecules on red cells: a correlation of numbers of molecules and agglutination

The fourth component of human complement (C4) is one that is essential to the antibody-mediated classical activation pathway. C4d, present on all normal and most patient red cells (RBCs), may be detected by the human antisera anti-Rodgers (Rg) and -Chido (Ch). A study has been made of the Rg/Ch antigens on normal and patient RBCs in an attempt to understand the mechanism by which C4 is bound to normal RBCs in the absence of RBC antibodies (Abs). Because RBCs from C1q-deficient patients express Rg/Ch, it seems that C1q is not essential for C4 binding. Treatment of normal RBCs with proteolytic enzymes, including trypsin, eliminated positive reactions with anti-Rg/Ch even though the C4d fragment is considered to be resistant to cleavage by trypsin. By correlating agglutination reactions with numbers of bound C4d and C3d molecules, it is evident that both C4d and C3d were affected by trypsin treatment and that anti-Rg/Ch were not capable of agglutinating RBCs with less than 50 molecules of bound C4d. It is concluded that trypsin-sensitive and -insensitive RBC membrane structures may both act as acceptors for C4. RBCs with null phenotypes of the major blood group systems all expressed Rg/Ch antigens, so none of the structures that carry these antigens act preferentially as acceptors for C4.     

Studies on the mechanism of bacterial resistance to complement-mediated killing. II. C8 and C9 release C5b67 from the surface of salmonella minnesota S218 because the terminal complex does not insert into the bacterial outer membrane

The mechanism for consumption of terminal complement components and release of bound components from the surface of serum-resistant salmonella minnesota S218 was studied. Consumption of C8 and C9 by S218 occurred through interaction with C5b67 on the bacterial surface because C8 and C9 were consumed when added to S218 organisms previously incubated in C8-deficient serum and washed to remove all C5b67 on the bacterial surface because C8 and C9 were consumed when added to S218 organisms previously incubated in C8- deficient serum and washed to remove al but cell bound C5b67. Rapid release of (125)I C5 and (125)I C7 from the membrane of S218 was dependent on binding of C8 because (125)I C5 and (125)I C7 deposition in C8D serum was stable and was twofold higher in C8D than in PNHA, and addition of purified C8 or C8 and C9 to S218 previously incubated in C8D serum caused rapid release of (125)I C5 and (125)I C7 from the organism. Analysis by sucrose density gradient ultracentrifugation of the fluid phase from the reaction of S218 and 10 percent PNHS revealed a peak consistent with SC5b-9, in which the C9:C7 ratio was 3.3:1, but the NaDOC extracted bound C5b-9 complex sedimented as a broad peak with C9:C7 of less than 1.2:1. Progressive elution of C5b67 and C5b-9 from S218 but not serum-sensitive S. minnesota Re595 was observed with incubation in buffers of increasing ionic strength. Greater than 90 percent of the bound counts of (125)I C5 or (125)I C9 were released from S218 by incubation in 0.1 percent trypsin, but only 57 percent of (125)I C9 were released by treatment of Re595 with trypsin. These results are consistent with the concept that C5b-9 forms on the surface of the serum-sensitive S. minnesota S218 in normal human serum, but the formed complex is released and is not bactericidal for S218 because it fails to insert into hydrophobic outer membrane domains.     

Complement activation by artificial blood substitute Fluosol: in vitro and in vivo studies

A perfluorocarbon blood substitute, Fluosol, is undergoing clinical trials as an adjunct to chemotherapy. The adverse effects associated with its administration have been postulated to result from complement activation. When gel electrophoresis and Western blotting of Fluosol are used after its incubation with serum, activated C3 and factors Bb and H are bound to the Fluosol particles in a time-dependent fashion, which suggests that complement activation with Fluosol, as does that with zymosan, occurs on the surface of the particles. Paradoxically, it is found, both by the measurement of Fluosol-bound C3d and by fluid-phase C5a, that lower concentrations of Fluosol cause greater amounts of complement activation, which suggests a complex interaction of activators and inhibitors that changes as the available surface area is decreased. Studies performed with bystander red cell-bound C3d demonstrated in vivo complement activation occurring in six patients receiving Fluosol as an adjunct to chemotherapy for colon cancer. In two patients, there was a marked increase in red cell-bound C3d after Fluosol infusion; these two patients also developed adverse reactions during Fluosol infusion. These studies suggest that the Fluosol surface plays a major role in the initiation and regulation of complement activation that is seen during Fluosol infusion.     

Comparison of eight commercial on-site screening devices for drugs-of-abuse testing

Eight commercially available on-site drugs-of-abuse testing devices for detecting cannabinoids (THC-COOH), opiates (OPI), cocaine (COC), amphetamines (AMP), metamphetamines (MET) and benzodiazepines (BZO) were evaluated. The used urine specimens suspected of being drug positive were all confirmed by gas chromatographic/mass spectrometry (GC/MS). For AMP and MET, sensitivities varied between 83 and 95% and specificities between 98 and 100%. Correspondingly, sensitivities between 88 and 98% and specificities between 95 and 100% were observed for THC-COOH. For BZO, sensitivities varied between 91 and 97% and specificities between 97 and 100%. Only a few confirmed positive samples were available for OPI and COC, the sensitivities being between 83 and 100% and 100%, respectively. On-site devices did not always find extremely high drug concentrations. False-negative results were found with AMP in particular. Pholcodine, commonly used as medicine, was observed to give false-positive results with most of the devices and was not, however, included in given cross-reactivity tables. It was found that the devices differed markedly with respect to interpretation of test results and to ease of test performance, leading to the suggestion that different criteria for selecting on-site devices for either emergency laboratories in hospitals or for police stations and prisons should be used. Since the overall specificity of any of the devices was not 100% and false positives were identified, we found it important to confirm any positive screening test result.