Neopterin in AIDS,other immunodeficiencies,and bacterial and viral infections

Summary An increase in total urinary neopterin was observed in 12 of 13 patients with acquired immunodeficiency syndrome (AIDS), seven of 13 patients with lymphadenopathy, one of six healthy homosexual males, seven of ten adult patients with staphylococcal pneumonia, 11 of 12 children with viral infections, four of seven children with bacterial infections, and 12 of 13 children with various immune defects. Extremely high values of total urinary neopterin and monapterin were observed in severely ill patients with AIDS and those with familial hemophagocytic lymphohistiocytosis. Neopterin excretion was normal in two AIDS patients with Kaposi's sarcoma, but without opportunistic infections at that time. On reexamination of one of these patients later on, elevated neopterin values were noted. Parallel increases in neopterin and monapterin were found, whereas biopterin was usually normal. The increase in total neopterin was mainly due to 7,8-dihydroneopterin and was accompanied by an increase in 3-hydroxysepiapterin. Increased neopterin in urine is assumed to reflect the increase in GTP pool and GTP cyclohydrolase I activity as observed in stimulated monocytes. Thus, neopterin, as a measure of the activation of the nonspecific cellular immune system, may be used diagnostically to detect allograft rejection after transplantations and to follow-up HTLV-III positive patients.

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Neopterin bei AIDS, anderen Immundefekten, Bakteriellen und viralen Infektionen

Abbreviations AIDS acquired immunodeficiency syndrome - ARC AIDS related complex - BH₄ tetrahydrobiopterin - GTP guanosine triphosphate Supported by the Swiss National Science Foundation, project 3.266-0.82 and 3.601-0.84     

Optical coherence tomography reflects clinically relevant gray matter damage in patients with multiple sclerosis

Journal of Neurology - Retinal degeneration leading to optical coherence tomography (OCT) changes is frequent in patients with multiple sclerosis (PwMS). To investigate associations among OCT...     

Attenuation of Blood Flow Pulsatility along the Atlas Slope: A Physiologic Property of the Distal Vertebral Artery?

BACKGROUND AND PURPOSE:Physiologic and pathologic arterial tortuosity may attenuate blood flow pulsatility. The aim of this prospective study was to assess a potential effect of the curved V3 segment (Atlas slope) of the vertebral artery on arterial flow pulsatility. The pulsatility index and resistance index were used to assess blood flow pulsatility.MATERIALS AND METHODS:Twenty-one healthy volunteers (17 men, 4 women; mean age, 32 years) were examined with a 3T MR imaging system. Blood velocities were measured at 2 locations below (I and II) and at 1 location above the V3 segment (III) of the vertebral artery by using a high-resolution 2D-phase-contrast sequence with multidirectional velocity-encoding.RESULTS:Pulsatility and resistance indices decreased along all measurement locations from proximal to distal. The pulsatility index decreased significantly from location II to III and from I to II. However, the decrease was more pronounced along the Atlas slope than in the straight-vessel section below. The decrease of the resistance index was highly significant along the Atlas slope (location II to III). The decrease from location I to II was small and not significant.CONCLUSIONS:The pronounced decrease in pulsatility and resistance indices along the interindividually uniformly bent V3 segment compared with a straight segment of the vertebral artery indicates a physiologic attenuating effect of the Atlas slope on arterial flow pulsatility. A similar effect has been described for the carotid siphon. A physiologic reduction of pulsatility in brain-supplying arteries would be in accordance with several recent publications reporting a correlation of increased arterial flow pulsatility with leukoencephalopathy and lacunar stroke.

The flow waveform in an arterial vessel is affected by many factors. Main influencing parameters are inflow determinants (cardiac function), outflow determinants (downstream tissue), and resistance presented by the vessel wall.^1–4Due to the different functions of large and small arteries, arterial flow waveforms undergo changes along the vascular tree. The large conduit arteries have an elastic wall to minimize longitudinal impedance.⁵ In contrast, the distal arteries that regulate the demand for blood of the downstream tissue have a more muscular wall to effectively change lumen size.The elasticity of the large arteries has a buffering function, which decreases pressure and flow pulsatility by taking up energy during systole and releasing it during diastole (Windkessel effect), thus delivering blood in a more continuous stream to peripheral vascular beds.⁶ Due to increased wall stiffness, waveform changes occur with normal aging but also in pathologies that affect vascular compliance.⁷ Recent studies with large patient cohorts indicate that the brain is vulnerable to increased arterial pulsatility, reflected by a higher number of white matter hyperintensities and a greater incidence of lacunar strokes.^8–10The most important techniques for noninvasive flow measurements and therefore flow wave characterization are Doppler sonography and phase-contrast (PC) MR imaging. Both techniques are important clinical tools. Doppler sonography has the advantage of a widely available method with very high spatial and temporal resolution; however, it is user-dependent and restricted to sonography-accessible vessel locations.¹¹ Phase-contrast MR imaging, in turn, has the advantage of providing blood flow measurements independent of the user without anatomic restrictions, however, with lower spatial and temporal resolution.^12–14Regarding PC-MR imaging, a 2D-PC sequence with unidirectional velocity-encoding is routinely applied. This sequence is fast and robust; however, due to its unidirectional vessel encoding, it may underestimate flow velocities due to placement errors.¹⁵ Newer techniques such as 4D-PC-MR imaging and 2D-PC-MR imaging with multidirectional velocity-encoding have been shown superior to 2D-PC-MR imaging with unidirectional velocity-encoding in curved vessel sections.^16–19The aim of the present study was to evaluate blood flow characteristics along the curved vessel section of the distal vertebral artery, extending from the transverse foramen C2 to the dura mater cranial to the Atlas vertebra (Atlas slope), to evaluate the effect of a tortuous vessel geometry on blood flow pulsatility. For blood flow and velocity measurements, a 2D-PC sequence with multidirectional velocity-encoding has been applied.     

Failure of recombinant human granulocyte-macrophage colony-stimulating factor therapy in aplastic anemia patients with very severe neutropenia

Four patients with very severe aplastic anemia refractory to antilymphocyte globulin were administered recombinant human granulocyte- macrophage--colony stimulating factor (GM-CSF). One patient with minimal residual myelopoiesis responded transiently to two separate courses of GM-CSF at 4 and 8 micrograms/kg/d administered intravenously and another course at 4 micrograms/kg/d administered subcutaneously. Septicemia and bilateral pneumonia that had been resistant to conventional therapy resolved. Three patients with no evidence of residual myelopoiesis did not respond to GM-CSF. In one patient, the dose was increased to 32 micrograms/kg/d with no effect on hematopoiesis. Immediate side effects were minimal at GM-CSF doses up to 16 micrograms/kg/d. GM-CSF may, however, have been involved in the pathophysiology of thrombosis of the inferior vena cava in the patient administered 32 micrograms/kg/d. We conclude that GM-CSF does not induce hematopoiesis in long-standing, severe, treatment-resistant aplastic anemia with complete myelopoietic failure. However, in patients with minimal residual myelopoiesis, GM-CSF could be a promising adjuvant therapy for severe infection.