Analysis of optokinetic and eye tracking data on normal subjects

This study was undertaken to determine the incidence of abnormal eye tracking patterns in normal subjects and to compare the optokinetic (OPK) response of normal subjects using a nystagmographic gonioscope (Nystagmotrac) and Coats's type of OPK drum. Eye movement was recorded by means of an electronystagmographic (ENG) recorder, and the speed of the slow component was computed for the OPK response. The eye tracking test showed a high rate of abnormality among our subjects. Optokinetic testing revealed highly symmetrical responses for all subjects.     

Pseudotumor cerebri and hypothyroidism

A 38-year-old obese woman with concurrent hypothyroidism and pseudotumor cerebri was monitored with serial thyroid function tests and CSF pressure determinations during levothyroxine sodium replacement therapy. Following normalization of the patient's thyroid status, assessed by both clinical and chemical indexes (serum thyroxine level, 1.5 to 11.0 micrograms/dL; serum thyrotropin level, 128 to 1.5 micro units/mL), intracranial hypertension persisted for more than four months. After weight loss, acetazolamide therapy, and intermittent CSF drainage failed to produce remission, glucocorticoid therapy was associated with prompt, sustained resolution of the pseudotumor cerebri. Contrary to previous reports, this patient's clinical course suggests that thyroid hormone deficiency and pseudotumor cerebri are not causally related.     

Dendritic cells in the cerebrospinal fluid and peripheral nerves in Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy

The role of antigen-presenting cells (APC) involved in induction of T and B cell mediated autoaggressive immunity in Guillain-Barre syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is poorly understood. We studied the numbers and phenotype of dendritic cells (DC) in blood and cerebrospinal fluid (CSF) over the course of GBS and CIDP before and after immunomodulatory treatment. Four out of seven GBS patients examined prior to treatment with high-dose intravenous immunoglobulins (IvIg) had elevated numbers of CD123(+) plasmacytoid DC in the CSF, while both GBS and CIDP patients examined prior to treatment had elevated numbers of CD11c(+) myeloid DC in the CSF, as compared to patients with noninflammatory neurological diseases (OND). The percentages of blood DC expressing the cell surface marker CD1a, co-stimulatory molecules CD80 and CD86, adhesion molecule CD54, and chemokine receptors CCR1, CCR2, CCR5, and CXCR4 were not affected in GBS or CIDP. The immunohistochemistry of sural nerve biopsies revealed CD11c(+)CD83(-)CD14(-)CD16(-) immature myeloid DC at low numbers, mostly in the perineurium, without difference between CIDP patients and controls. In contrast, the numbers of CD11c(+)CD14(+)/CD16(+) macrophages were higher within the endoneurium in CIDP patients compared with the controls. The recruitment of DC to CSF in GBS and CIDP may be important in capturing antigens released from inflamed spinal nerve roots into CSF and in transferring these antigens from CSF to local lymph nodes, where naive T and B cells may be activated.     

Dendritic cells activate autologous T cells and induce IL-4 and IL-10 production in myasthenia gravis

Dendritic cells (DC), as initiators and orchestrators of immune responses, control both naive and primed T cell responses. Depending on their maturation stage, DC promote immunity or tolerance. Here we investigated (1) the phenotype and cytokine secretion patterns of IL-10-modulated immature DC (IL-10-DC) and lipopolysaccharide (LPS)-driven mature DC (LPS-DC) in comparison with unmodulated immature DC (imDC) and (2) the effects of IL-10-DC, and of LPS-DC, vs. imDC on autologous T cell responses in patients with myasthenia gravis (MG) compared with healthy controls (HC). All three types of DC derived from MG significantly increased the levels of CD4+CD25+ T cells and of their subfraction expressing CD69, when compared to DC derived from HC. IL-10-DC induced production of IL-10 and IL-4 by T cells from MG patients, but only IL-10 production from HC. LPS-DC activated autologous T cells as reflected by augmented CD25, CD69 and CTLA-4 expression on CD4+ T cells, without differences between MG and HC. This was associated with increased production of both Th1 (IFN-gamma) and Th2 (IL-10 and IL-4) cytokines by T cells. These results indicate that DC-induced activation of autologous T cells is more pronounced in MG than in HC. In addition, DC-induced T cell responses in MG vs. HC are more Th2-prone.     

Virologic and immunologic response,clinical progression,and highly active antiretroviral therapy adherence

A growing body of evidence suggests that a high degree of adherence is required to achieve and maintain a successful virologic response both in the short and long term. This holds true despite the definition of adherence or how it is measured. Reported differences in the degree of adherence required are likely due to differences in study design, difficulty measuring patient adherence, patient population studied, and the antiretroviral regimen studied. Virologic suppression and immunologic response often go hand in hand, but the impact of adherence on change in CD4 count tends to be delayed and, therefore, less apparent than the impact on HIV viral load. Degree of adherence has also been shown to be associated with AIDS-related morbidity, mortality, and hospitalizations.