Clinical Immunophenotype at Disease Onset in Previously Healthy Patients With Cryptococcal Meningitis.

Cryptococcal meningitis (CM) is a global disease with significant morbidity and mortality. Although low peripheral blood cluster of differentiation 4 (CD4) cell counts are found to be related to a high burden of cryptococcus in HIV-infected patients, little is known about possible immune defects in previously healthy patients (PHPs). We performed a retrospective study of 41 CM patients treated from January 2005 to December 2014 who did not have HIV-infection. There were 33 PHPs and 8 not previously healthy patients (non-PHPs). We analyzed clinical test data pertaining to peripheral blood T cells, antibodies, inflammation markers, and cerebral spinal fluid (CSF) completed during the disease onset phase and 5 years following diagnosis. PHPs had significantly higher counts of cluster of differentiation 3 (CD3), cluster of differentiation 4 (CD4), and cluster of differentiation 45 (CD45) cells, and lower percentages of CD8 cells than non-PHPs (P < 0.05). Measurements of inflammatory markers and immunoglobulin in blood were comparable except for lower immunoglobulin A (IgA) levels in non-PHPs (P = 0.0410). Examination of CSF revealed lower white blood cell (WBC) counts in non-PHPs. Five-year mortality in PHPs was higher than in non-PHPs (22.0% vs 12.5%) but this was not statistically significant (P > 0.05). Multivariate analysis revealed that higher immunoglobulin G (IgG) levels in serum during disease onset may be an independent predictor of mortality (P = 0.015). In conclusion, PHPs demonstrate an immunophenotype that is distinct from that of non-PHPs, leading to an improved understanding of the immunology of cryptococcal meningitis.

[Establishment of animal model of chronic optic nerve injury and pathological changes thereof: experiment with cats].

OBJECTIVE: To establish an animal model of chronic optic nerve injury which is suitable for experimental research. METHODS: Dil, a tracer, was injected through the bone windows into the brain of 48 cats so as to mark the retinal ganglion cells (RGCs). Two weeks later the 48 cats were randomly divided into 6 equal groups. The normal group did not receive any other treatment. Other 8 cats underwent sham operation. Imitating the clinical pterional approach, a balloon was implanted into the place under the optic nerve and chiasm in the other 32 cats, then the volume of the balloons were increased by injecting contrast agent at different times to cause the optic nerve and chiasm compressed chronically for 1, 2, 4, or 6 weeks. Flash-visual evoked potential (F-VEP) was measured before operation and at the corresponding observation times in different groups. By the end of the experiment the cats were killed with the specimens of retina and optic nerve taken out to undergo light microscopy and electron microscopy to observe the pathological changes. Eight eyes were taken out from each group to calculate the number of RCGs 1, 2, 4, and 8 weeks after operation respectively. RESULTS: Microscopy showed retina showed profound morphological changes 8 weeks after compression; Demyelination of optic nerve began to occur 2 weeks after compression and progressed later. Axonal degeneration was found 4 week after compression and became more significant 8 weeks later. Under electron microscopy, pathological changes of retina was found 4 weeks and more prominent 8 weeks after compression; Slight demyelination and disorganized of cytoskeleton in the optic nerve were shown 2 weeks after compression, and became more profound later; Myelin regeneration was found 8 weeks after compression. The number of RGCs was reduced significantly by 37% (293/465) since 8 weeks after compression. F-VEP recording showed an extension of latency and depression of amplitude 4 weeks after compression, and the changes were more significant 8 weeks later. CONCLUSION: An animal model of chronic optic nerve injury by compression has been established which is stable and well repeatable. The pathological changes of compressed optic nerve are aggravated gradually as the compression lasts and the volume increases. Degeneration of RGCs occurs secondarily and obviously later than the axonal degeneration.