Mechanisms of intra-dialyser granulocyte activation: a sequential dialyser elution study

INTRODUCTION: During haemodialysis (HD), an early and transient white blood cell (WBC) reduction is noted in the peripheral blood, which has been attributed mainly to the sequestration of polymorphonuclear cells (PMN) in the pulmonary vasculature. However, WBC also adhere to the dialyser, as demonstrated before in an elution study performed after HD. In the present study, we investigated if intradialyser WBC sequestration contributes to the WBC nadir in the blood shortly after the start of HD and whether or not different mechanisms underlie PMN adherence in dialyser and lung. In addition, PMN degranulation was analysed not only in peripheral blood but also in dialyser eluates (DE). SUBJECTS AND METHODS: Dialysers were eluted after 7 1/2 (DE-7 1/2) and 180 (DE-180) min of HD in eight patients. Blood samples were taken before HD (t0), and at t7 1/2 and t180. Besides WBC count and differentiation, PMN adhesion (CD11b and CD62L) and degranulation markers (CD63 and CD66b) were assessed by flow cytometry. RESULTS: In the blood, a WBC fall was noted at t7 1/2 (from 5.8 to 4.8 x 10(9)/l; absolute about 5 x 10(9) cells). DE contained 3.0 x 10(6) cells at t7 1/2, and 57.2 x 10(6) at t180 (P = 0.015). As for CD11b, at t7 1/2 both in the blood and DE an increased expression was observed, as compared to t0 (P = 0.01); CD11b expression in DE-7 1/2 was higher than in DE- 180 (P = 0.025). In contrast, CD62L showed downregulation only in DE both at t7 1/2 (mean fluorescence intensity (MFI) PB 4172 and DE-7 1/2 2353, P = 0.01), and at t180 (MFI 794, P = 0.03 versus DE-7 1/2), when compared to blood at t0. As for degranulation markers, an increase was observed in blood at t7 1/2 (MFI CD63 from 357 to 506, P = 0.02; CD66b from 507 to 794, P = 0.001), in comparison with t0. Eluted PMN at t7 1/2 showed a higher expression of CD63 than PMN in blood at t7 1/2 and DE-180 (MFI in DE-7 1/2 1280 and blood 506, P = 0.003). The expression of CD66b was increased in DE-7 1/2 (MFI 1803 versus blood 794, P = 0.01), and even more in DE-180 (MFI 2763, P = 0.002), when compared to blood. CONCLUSIONS: From these data it is concluded first, that intradialyser PMN sequestration does not contribute markedly to the WBC nadir in the circulation. Second, intradialyser PMN trapping appears to result primarily from non-adhesion-molecule-mediated factors, as indicated by an increased expression of CD11b at t7 1/2 on eluted PMN associated with low cell numbers in DE, and normalized CD11b expression at t180 associated with considerably higher cell numbers in DE. Third, HD-induced degranulation seems to be a complex phenomenon. After a rapid transient onset, characterized by an early upregulation of CD63 and CD66b on PMN leaving the dialyser, degranulation continues within the device as indicated by an additional rise in the expression of CD66b on PMN in DE-180.      

Psychiatric profiles and patterns of cerebral blood flow in focal epilepsy: interactions between depression, obsessionality, and perfusion related to the laterality of the epilepsy.

OBJECTIVES: In a study of patients with focal epilepsy the hypothesis was explored that different measurements of psychopathology are related to specific distributions of cerebral perfusion. METHODS: Forty patients had SPECT performed with (99m)Tc-HMPAO. In addition, patients received a psychiatric evaluation with the following psychiatric questionnaires: the Beck depression inventory, the Leyton obsessionality inventory, the Bear-Fedio questionnaire, and the social stress and support interview. Patients were analysed in two groups according to the laterality of the epilepsy. Nine patients were excluded based on poor quality scans (n = 1), unlateralised epilepsy (n = 4), and left or ambidextrous handedness (n = 4). RESULTS: There were no overall differences between the left and right epilepsy groups on measures of psychopathology. Associations were found between scores on some of the rating scales and regional cerebral blood flow. Specifically, for patients with left sided epilepsy, higher scores on the Beck depression inventory were associated with lower contralateral temporal and bilateral frontal perfusion, and higher occipital perfusion. For patients with right sided epilepsy higher scores on the Leyton obsessionality inventory were associated with increased perfusion in ipsilateral temporal, thalamic, and basal ganglia regions and bilateral frontal regions. CONCLUSION: The results do not support the notion that lateralised epileptogenic lesions are associated with different levels of depression, obsessionality, or personality traits. They support the view that certain psychopathological symptom patterns are related to specific regional dysfunctions depending on the laterality of a hemispheric lesion.     

Wallerian degeneration: evaluation with MR imaging

Twenty-three patients who underwent routine magnetic resonance (MR) imaging of the brain were found to have signal or structural abnormalities corresponding to white matter tracts. Images were evaluated for anatomic and MR signal characteristics of the involved tract, associated primary lesions, and, when possible, changes in MR signal and anatomic structures with time. Images from 20 patients demonstrated a thin band of abnormal signal contiguous with the primary lesion and conforming to the known anatomic pathway of a white matter tract. Cerebral infarction was the most common associated primary disorder (n = 17). Neoplasms (n = 2), demyelinating (n = 1) and posthemorrhagic (n = 2) conditions, and an idiopathic movement disorder (n = 1) were associated with white matter tract signal abnormalities that were indistinguishable from those seen with infarction. Signal abnormality corresponding to the corticospinal tract was the type most commonly seen. No change in signal characteristics was seen with time (six cases) or following contrast material administration (two cases). The authors conclude that MR imaging provides a sensitive method of evaluating wallerian degeneration in the living human brain.     

Epiretinal membranes in sickle cell disease.

Epiretinal membranes at the macula were seen in 4% of the eyes of 355 patients with homozygous sickle cell (SS) disease and sickle cell haemoglobin-C (SC) disease under the age of 60 years. The presence of proliferative sickle retinopathy (PSR), the extent of involvement of PSR, and vitreous haemorrhage all constitute risk factors for the formation of epiretinal membranes. The occlusion of PSR lesions by treatment appears to reduce the risk of epiretinal membranes being formed.     

Effects of whole-body rotation on masseteric motoneuron excitability

Vestibular stimulation is a popular clinical treatment for enhancing the excitability of spinal motoneurons innervating trunk and limb muscles, but whether vestibular stimulation can also influence trigeminal motoneurons is not known. We determined whether or not vestibular stimulation evoked by rotation of a seated subject would modify the excitability of masseteric motoneurons. The amplitude and frequency of occurrence of masseteric compound action potentials evoked by standard chin taps provided measures for assessing masseteric motoneuron excitability. Eleven healthy adults with no orofacial or otologic disorders served as subjects. Each sat in a motorized dental chair with his head stabilized by a halo head-piece so that chair rotation caused labyrinthine excitation. The frequency (3/s) of chin taps and their impact force were maintained constant by microcomputer control. After each tap, a 16-ms sample of EMG recorded from surface electrodes over the right masseter was digitized and stored for subsequent visual inspection. Only compound action potentials meeting rigorous criteria in terms of latency, amplitude, duration, and waveform were accepted as responses. The mean frequencies of occurrence and the mean amplitudes of the responses showed wide variability. Histogram displays of every response for each subject, however, revealed enhanced output from the masseteric motoneuron pool during the decleration and postrotation phases. In subjects not immediately retested this enhancement was persistent but decayed during the next 5 min. In five subjects the experiment was repeated after 1 min. The changes in response variables during phases 3 and 4 were significantly less than on the first trial, suggesting habituation. These results provide quantitative evidence that the dynamic input from vestibular ampullary receptors in response to rotation enhances masseteric motoneuron output.