The detection of intrathecal synthesis of anti-herpes simplex IgG antibodies: comparison between an antigen-mediated immunoblotting technique and antibody index calculations. European Union Concerted Action on Virus Meningitis and Encephalitis

The detection of intrathecal antibody synthesis was compared by the calculation of antibody indices (AI) derived from ELISA techniques with the detection of virus-specific oligoclonal IgGs by an antigen-mediated capillary blot technique. Twenty-seven paired serum and cerebrospinal fluid (CSF) samples were examined from 15 immunocompetent patients with herpes simplex virus encephalitis (HSE) diagnosed by PCR on early CSF samples. These techniques were also applied to paired samples from 20 multiple sclerosis (MS) patients, 10 patients with other inflammatory neurological diseases and 10 patients with non inflammatory neurological disorders. There was a good correlation between the results obtained by AI and those obtained by immunoblotting, especially in HSE (2 discordant results out of 27). Discrepancies were more frequent (25%) in MS patients where a "polyspecific" reaction characterized by low affinity antibodies is known to occur. Some of the discrepancies could, in part, be due to serological cross-reaction with varicella zoster virus.     

Anterior opercular syndrome, caused by herpes simplex encephalitis

Bilateral frontal and parietal opercular lesions cause a syndrome characterized by paralysis of the masticatory, facial, pharyngeal, and tongue muscles (the anterior opercular syndrome). The anterior opercular syndrome can occur in patients with herpes simplex encephalitis (HSE), but in most of these patients the diagnosis of HSE was not confirmed. We describe the anterior opercular syndrome in four patients with HSE. In two of these patients, the anterior opercular syndrome dominated the clinical picture, but in the other two patients it was overshadowed by other manifestations of HSE. The diagnosis of HSE was confirmed by detection of herpes simplex virus (HSV) DNA in the CSF (two patients), culture of the HSV from a brain biopsy (one patient), and elevated HSV antibody titers in the CSF (one patient). Our patients made a partial recovery. Acute onset of weakness of masticatory, facial, pharyngeal, and glossal muscles, accompanied by fever, headache, and partial motor seizures of the face should suggest HSE.     

Intrathecal release of pro- and anti-inflammatory cytokines during stroke

A growing body of evidence points out the potential role of inflammatory mechanisms in the pathophysiology of ischaemic brain damage. We have recently demonstrated that stroke patients display an intrathecal production of proinflammatory cytokines, such as IL-1beta and IL-6 already within the first 24 h after the beginning of symptoms (Tarkowski et al., 1995). The aim of the present study was to investigate patterns of local inflammatory responses as a consequence of acute stroke. Thirty stroke patients were studied prospectively on days 0-3, 7-9, 21-26 and after day 90 with clinical evaluations, radiological assessments and analysis of cerebrospinal fluid (CSF) cytokine levels. In addition, 15 healthy control CSF samples were used. Significantly increased CSF levels of IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-10 were observed early during the stroke with a peak on day 2 for the proinflammatory cytokines IL-8 and GM-CSF, and on day 3 for the immunoregulatory cytokine IL-10. Patients with a brain infarct predominantly located in the white matter showed significantly higher levels of IL-8 in CSF than patients with an infarct mainly located in the grey matter. Also, high levels of intrathecal tumour necrosis factor-alpha (TNF-alpha) were associated with the presence of white matter disease. Our study demonstrates an intrathecal production of proinflammatory and immunoregulatory cytokines in patients with stroke, supporting the notion of localized immune response to the acute brain lesion. A better understanding of the inflammatory response in stroke may lead to new treatment strategies.     

Elevated serum and CSF levels of soluble CD30 during clinical remission in multiple sclerosis

OBJECTIVE: To ascertain the presence of the Th2 response in MS patients by evaluating the level of soluble (s) CD30 across the clinical spectrum of MS and during relapse and remission. BACKGROUND: MS is considered a T-cell-mediated disorder with the immune attack dominated by a Thl cytokine response. Elevated levels of sCD30 have been associated with CD4+ cells that secrete Th2-type cytokines. METHODS: Levels of sCD30 were determined in the serum and CSF of patients with primary progressive MS, secondary progressive MS, relapsing-remitting MS (RRMS), both in relapse and remission, and in patients with other inflammatory neurologic disease (IND) and noninflammatory neurologic disease (NIND). None of the patients were on immunomodulatory treatment. RESULTS: Higher serum levels of sCD30 were detected in all MS subgroups and IND patients compared with NIND patients. RRMS patients in remission had significantly higher levels than those in relapse (median, 45.7 U/mL versus 18.3 U/mL; p = 0.04). Significantly higher CSF levels were also found in all groups, except those with RRMS in relapse compared with NIND patients. Again, RRMS patients in remission had higher CSF sCD30 levels compared with those in relapse (median, 4.0 U/mL versus 3.0 U/mL; p = 0.08). CONCLUSIONS: Serum and CSF levels of sCD30 are increased in MS, particularly during remission. The results provide additional evidence for the presence of a Th2 response and indicate that sCD30 may be of value as a marker of lesion resolution.     

Exchangeability of Qsr1p, a large ribosomal subunit protein required for subunit joining, suggests a novel translational regulatory mechanism

The incidence of herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) in herpes simplex encephalitis (HSE) was investigated using cerebrospinal fluid (CSF) samples from sixty-four cases of HSE. A polymerase chain reaction (PCR) employing primers flanking a region of the HSV thymidine kinase gene common to both HSV-1 and HSV-2 was used to detect HSV in the CSF. HSV-1 and HSV-2 were differentiated by digestion with restriction enzymes. Two enzymes were employed; Aval which cleaved only the HSV-2 gene product and Avall which cleaved only the HSV-1 gene product. Sixty-three cases of HSE were found to be due to HSV-1; one case due to HSV-2. These data confirm previous observations that HSV-2 is a rare cause of post-neonatal herpes encephalitis but indicates that a PCR procedure capable of detection of both viruses is essential for efficient diagnosis of HSE.     

Heart transplantation in infants and children with situs inversus

Chemokines (chemoattractant cytokines) attract and activate specific leukocyte subsets. With regard to their expression by brain parenchymal cells, they may represent the key molecules that control leukocyte entry into the subarachnoid space. In order to evaluate the contribution of chemokines in vivo, we determined the levels of MCP-1, MIP-1alpha, RANTES, IL-8, as well as of the sIL-2R in three patients with proven herpes simplex encephalitis type 1 (HSE-1). CSF samples were drawn by a subarachnoid catheter system throughout the time course of hospitalisation. Results were compared to chemokine levels in serum drawn in parallel. The clinical status was documented by the Modified Barthel Index and correlated with chemokine levels in the CSF. The results were compared with the chemokine levels in the CSF of 17 control patients with normal CSF routine parameters. High chemokine levels were detectable in the CSF of all HSE-patients. MCP-1 peak levels were found at the time of admission, while maximal IL-8 levels occurred 4 to 8 h later. The levels of MIP-1alpha and RANTES were lower than those of MCP-1 with a maximum at the time of admission. In all patients the levels of the sIL-2R increased later in the time course, at 14 to 20 h after admission. When the levels of MCP-1 were compared with the clinical status by Modified Barthel Index, we found a high reciprocal correlation (r=-0.82). Routine CSF parameters, such as leukocytes, albumin and immunoglobulins did not correlate with the clinical status. Chemokine levels in serum were found to be close to the detection limits of the ELISA systems. Our data suggest that chemokines play an important role in the pathogenesis of HSE. They may be useful parameters to monitor the stage and severity of the disease. The late increase of sIL2-R levels may indicate the beginning of the reconstitution phase.     

Interleukin-6 and development of vasospasm after subarachnoid haemorrhage

The authors characterized the role of interleukins in the cerebrospinal fluid (CSF) in the development of vasospasm after subarachnoid haemorrhage (SAH), particularly interleukin-6 (IL-6). Concentrations of interleukin-1 beta (IL-1 beta), IL-6, and interleukin-8 (IL-8) were measured serially in CSF of 24 patients and in serum of 9 patients with SAH and correlated clinically. Additionally, the effects of the same cytokines on the cerebral arteries of dogs were analyzed on angiograms after intracisternal injection. Changes in levels of eicosanoids, angiogenic factors, and soluble cell adhesion molecules were investigated in the CSF of injected dogs. CSF concentrations of IL-6 and IL-8 were elevated significantly above control levels from the acute stage of SAH until the chronic stage. Patients with symptomatic vasospasm had significantly higher levels of IL-6 as well as IL-8 in CSF on days 5 and 7. Intracisternal injection of IL-6 induced long-lasting vasoconstriction in five out of eight dogs, while IL-8 did not. The diameter of canine basilar artery after IL-6 was reduced 29 +/- 5% from pretreatment diameter at 8 hours. Prostaglandins E2 and I2 were elevated in CSF for the first 4.5 hour of this IL-6-induced vasospasm. Neither angiogenic factors such as platelet-derived growth factor-AB and vascular endothelial growth factor nor soluble cell adhesion molecules were significantly elevated in CSF. IL-6, which increases to very high concentrations in CSF after SAH, may be important in inducing vasospasm, as IL-6 produced long-lasting vasoconstriction in the canine cerebral artery, which may be partly related to activation of the prostaglandin cascade.     

Cognitive effects of topiramate, gabapentin, and lamotrigine in healthy young adults

BACKGROUND AND PURPOSE: The neuronal death that accompanies an ischemic stroke has previously been attributed to a necrotic process. However, numerous studies in experimental models of ischemia have recently indicated that programmed cell death, also called apoptosis, may contribute to neuronal death. The aim of the present study was to investigate the intrathecal levels of proteins regulating apoptosis in acute stroke and to relate these levels to brain damage and to production of proinflammatory and anti-inflammatory cytokines. METHODS: Thirty stroke patients were studied prospectively on days 0 to 4, 7 to 9, 21 to 26, and after day 90 with clinical evaluation, radiological assessment, and analysis of cerebrospinal fluid (CSF) levels of soluble (s) Fas/APO-1 and sbcl-2, 2 proteins that regulate apoptosis. In addition, analysis of the intrathecal levels of cytokines interleukin (IL)-1beta, IL-6, IL-8, IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha was performed. Nineteen CSF samples from healthy subjects were used for control purposes. The patients were examined with MRI 1 to 3 months after stroke onset for measurement of infarct volume RESULTS: Significantly decreased CSF levels of sFas/APO-1 were observed during the entire observation period, with a maximal decrease on day 21 after the onset of stroke. The intrathecal levels of sFas/APO-1 were significantly negatively correlated with the volume of brain infarct and with the neurological deficit 3 weeks and 3 months after the onset of the stroke. In addition, the intrathecal levels of sFas/APO-1 were significantly correlated with the levels of IL-1beta, IL-6, IL-10, and GM-CSF 3 weeks after the onset of the disease. The intrathecal levels of sbcl-2 were significantly decreased during the first 3 days after stroke onset and at the same time were positively correlated with the levels of IL-6 and tumor necrosis factor-alpha. CONCLUSIONS: Our study demonstrates decreased intrathecal levels of proteins with antiapoptotic properties, suggesting that patients with acute stroke display a propensity toward apoptosis. Control of factors regulating apoptosis may lead to decreased delayed brain damage in stroke.     

Total aortic arch reconstruction for multiple great vessel occlusive disease

The immune system involvement in psoriasis has been documented by the presence of activated T-cells both in peripheral blood and in psoriatic skin lesions and by the intervention of cytokines in the inflammatory process. On this basis, we have undertaken a study in order to examine, in addition to activation markers such as CD25 and CD54 (ICAM-1) on peripheral blood mononuclear cells (PBMNCs) surface, serum levels of soluble interleukin (IL)-2 receptor (sIL-2R), soluble ICAM-1 (sICAM-1), soluble CD4 (sCD4), soluble CD8 (sCD8), beta 2-microglobulin and fibronectin (FN) in psoriatic patients analyzed both in acute and remission phase obtained by topical therapy alone. Our results show that PBMNCs expressing IL-2 receptor (CD25) were increased both in percentage and absolute number in respect to controls, and were not modified after remission. On the contrary, the significantly higher number of CD54+ lymphocytes evaluated in acute psoriasis, showed a reduction during the remission phase, even if the values persisted higher than controls. Serum levels of sIL-2R, sICAM-1, sCD4, sCD8 and beta 2-microglobulin were significantly higher than controls both in acute and remission phase; only FN levels were found to be lower, in patients evaluated both in acute psoriasis and after therapy, in respect to normal donors. On the whole, these results seem to indicate the persistence of both cellular and soluble activation markers even in psoriasis remission phase; in this light, we can suppose that topical therapy alone is not able to efficiently down-regulate activation mechanisms involved in the pathogenesis of the disease.     

Econazole, miconazole and SK & F 96365 inhibit depolarization-induced and receptor-operated contraction of guinea-pig isolated trachea in vitro

Recently, there have been some reports that schizophrenia is accompanied by an immune-inflammatory response, characterized by increased secretion of interleukin-6 (IL-6), soluble IL-2 receptor (sIL-2) and lower plasma levels of CC16 (Clara cell protein), an endogenous anti-cytokine. It was shown that clozapine, an atypical antipsychotic drug, may increase the plasma levels of sIL-2R and pro-inflammatory cytokines. This study was carried out in order to examine serum IL-6, IL-6R, CC16, IL-1R antagonist (IL-1RA), transferrin receptor (TfR) and sCD8 antigen, both before and after treatment with clozapine in schizophrenic subjects versus normal controls. Schizophrenic patients showed significantly higher plasma IL-6R and IL-1RA and lower plasma CC16 than normal controls. Treatment with clozapine significantly increased plasma sCD8, IL-6, CC16 and IL-1RA concentrations. The clozapine-induced increments in plasma IL-6 and CC16 appeared during the first 2 weeks of treatment, whereas the increases in plasma sCD8 and IL-1RA appeared after 5 weeks. Clozapine appears to have complex in vivo immunomodulatory effects.     

Early diagnosis of herpes simplex virus encephalitis by single photon emission computed tomography (SPECT) in patients with normal MRI

Since treatment of herpes simplex virus encephalitis (HSVE) is most effective when started early, a sensitive and specific method for early diagnosis would be of great benefit. MRI and CT are commonly used for this purpose. In this study, we presented two patients who had serologically confirmed HSVE and had normal CT and MRI, but were diagnosed as having HSVE by means of SPECT in the early stage. Case 1 was a 56-year-old man who suddenly developed alexia. On admission, physical and neurological examination were unremarkable except for alexia, agraphia, acalculia, and left-right disorientation. Brain CT, MRI, and cerebral angiography were all normal. However, SPECT showed hyperaccumulation of 99m Tc-HM-PAO in the right temporal-occipital area. On the 5th hospital day, he became comatose. CSF study revealed marked pleocytosis. Even then, MRI including Gd-enhanced study was normal while SPECT continued to show hyperaccumulation. Detection of herpes simplex virus DNA in CSF by polymerase chain reaction was negative. Anti-HSV antibody titer in CSF and serum confirmed intrathecal production of the antibody on the 14th hospital day. Abnormal accumulation of tracer in SPECT returned to normal on the 31st day when he was alert but still had a mild Gerstman syndrome. Case 2 was a 61-year-old man with disturbance of consciousness, mental dysfunction, and generalized convulsion. He was diagnosed as having HSVE by means of CSF pleocytosis, detection of HSV DNA in CSF by polymerase chain reaction, and presence of anti-HSV antibody in the CSF. CT and MRI again revealed no abnormality while SPECT clearly showed hyperaccumulation in the left temporal lobe in an early stage. Hyperaccumulation of lipophilic tracer on SPECT study, especially in the temporal lobes, has been reported in the early stage of HSVE by previous investigators. Unlike MRI or enhanced CT, the increased tracer accumulation in SPECT does not reflect disruption of the blood-brain-barrier or inflammatory edema, but reflects hyperperfusion or some other HSVE related abnormality which is currently unknown. From these observations, we suggest that local hyperperfusion occurs before local inflammation, and that SPECT is the most useful scanning method for early diagnosis of HSVE when this disease is clinically suspected.     

The false-positive rate of thoracic outlet syndrome shoulder maneuvers in healthy subjects

Cytokines are considered as mediators of immune and inflammatory responses. Cisternal CSF levels of interleukin (IL)-6, IL-8, monocyte chemoattractant protein-1 (MCP-1) and of the soluble adhesion molecule E-selectin were evaluated in patients operated on for intracranial aneurysms. Cisternal CSF samples were obtained at surgery in 41 selected patients (31 with diagnosis of subarachnoid hemorrhage (SAH) and 10 control patients operated on for incidental unruptured aneurysms); 14 patients were operated within 72 h after SAH (early surgery) and 17 were operated after day 10 after the hemorrhage (delayed surgery). The CSF levels of cytokines were evaluated using radioimmunoassay and their concentrations were related to the timing of surgery, the amount of cisternal subarachnoid blood clots and the onset of clinical and angiographical evidence of arterial vasospasm. Mean cisternal CSF levels of IL-6, IL-8 and AMCP-1 are significantly higher in samples obtained from patients early operated after SAH, while levels of E-selectin were below the threshold value of the method in all 41 cases. In the early operated group 7 patients presented symptomatic vasospasm: levels of IL-8 and MCP-1 were not significantly different were compared to those of uncomplicated cases; on the other hand, significantly higher levels of IL-6 were shown in the subgroup of patients operated within 72 h after SAH and developing vasospasm. Among the patients undergoing delayed surgery 5 presented symptomatic vasospasm, but no significant difference was shown in cisternal CSF levels of cytokines measured. The results of the present study show that in patients with unruptured aneurysms cytokines are present in cisternal CSF in scarce quantities and that in subarachnoid spaces after SAH there is an impressive increase of IL-6, IL-8 and MCP-1. Moreover, the higher cisternal CSF levels of IL-6 found in the early stage after SAH might have a predictive value regarding the occurrence of symptomatic vasospasm.     

Interleukin-1 beta differentially affects interleukin-6 and soluble interleukin-6 receptor in the blood and central nervous system of the monkey

Two studies were conducted to investigate whether behavioral and physiological responses induced by administration of interleukin-1 beta (IL-1 beta) were also associated with changes in interleukin-6 (IL-6) and soluble IL-6 receptor levels (sIL-6R). Following intravenous injection of rhIL-1 beta, blood and cerebrospinal fluid (CSF) samples were collected from juvenile rhesus monkeys. Marked increases in IL-6 levels were evident at 1 h in both blood and intrathecal compartments. IL-1 beta also induced significant elevations in the release of ACTH and cortisol into the blood stream, and following high doses, the monkeys evinced signs of sickness behavior. The second study characterized the IL-beta dose-response relationship showing that these physiological changes were most evident at doses between 0.5 microgram and 1.0 microgram IL-1/kg body weight. Soluble IL-6 receptor concentration was also increased, but only in plasma. There was no detectable sIL-6R in CSF. The large release of IL-6 into CSF suggests that some behavioral symptoms may be due to intrinsic changes in central nervous system activity concomitant with the alterations in peripheral physiology.     

Laboratory diagnosis of subacute and acute encephalitis probably of viral origin: seven years of experience

The results obtained in the laboratory diagnosis of 609 cases of acute or subacute encephalitis, studied during a period of time of even years, is briefly presented. Diagnostic methods included virus isolation from stools and cerebrospinal fluid (CSF); specific serology in serum; detection of intrathecal production of IgG antibody; and, in the last two years, detection of viral genome sequences in CSF by the polymerase chain reaction. Significant results were obtained in 196 cases (32.2%) and the alfa-herpesviruses were responsible for a major part of them (77.5%). Furthermore, 18 cases were likely to respond to dual infection by both herpes simplex and varicella-zoster viruses. Epstein-Barr virus and Human herpesvirus 6 were found in CSF from three immunocompetent patients. Besides the current vaccination program, measles virus is still responsible for an important part (22/196, 11.2%) of cases of viral encephalitis.     

Elevated serum levels of soluble CD30 in patients with atopic dermatitis (AD)

The immunopathology of AD is still unclear, but evidence for an immune response polarized towards Th2 activity has been provided. The CD30 molecule belongs to the tumour necrosis factor (TNF) receptor family and is expressed on activated T cells with a sustained expression in Th2 cells. This molecule also exists in a soluble form (sCD30). Elevated serum levels of sCD30 have been found in patients with Hodgkin's disease, chronic hepatitis B infection and HIV infection. Studies were undertaken to compare the serum levels of sCD30 in patients with AD (n=49) and healthy non-atopic controls (n=94). The presence of sCD30 was analysed with ELISA. A significantly higher concentration of sCD30 was noted in AD patients, median sCD30 level 29 U/ml (range 1-708 U/ml), compared with healthy non-atopic controls (P<0.001), where the median level was 11 U/ml with a range of 1-1042 U/ml. No correlation was found between sCD30 levels and total serum IgE, or between the AD patients' SCORAD values and concentration of sCD30. sCD30 levels were also analysed in 20 AD patients, which during ketoconazole treatment had improved their clinical scores and reduced their serum IgE and eosinophil cationic protein levels. However, no significant decrease in sCD30 levels was noted after treatment. The results show that patients with AD have elevated levels of sCD30, but without correlation to total serum IgE or disease activity.     

Herpes simplex virus type 2 induced retinal necrosis in BALB/c mice

We injected herpes simplex virus type 2 of MS- or G-strain into the anterior chamber of BALB/c mice. In the contralateral eye inflammatory cell infiltration began in the ciliary body; focal retinitis, detected by day 8, led to total destruction of the retina by day 10. Contralateral disease was observed in 75% of mice inoculated with 8 x 10(3) pfu herpes simplex virus type 2, but in only 20% of mice receiving 80 pfu herpes simplex virus type 2. Still this low concentration, however, produced a suppressed delayed-type hypersensitivity response. Anti-herpes simplex virus type 2 antibody, first detected on day 8, reached high titers on day 10; by then, most of the mice had died of encephalitis. The G-strain of herpes simplex virus type 2 was more neurotoxic than the MS-strain, but produced the same incidence of contralateral retinitis. Herpes simplex virus type 2 products contralateral necrotizing retinitis comparable to that produced by herpes simplex virus type 1. These findings, like those of other authors, suggest a role for herpes simplex virus type 2 in some cases of acute retinal necrosis in humans.     

Protective role of the virus-specific immune response for development of severe neurologic signs in simian immunodeficiency virus-infected macaques

The pathogenesis of human immunodeficiency virus-associated motor and cognitive disorders is poorly understood. In this context both a protective and a harmful role of the immune system has been discussed. This question was addressed in the present study by correlating the occurrence of neurologic disease in simian immunodeficiency virus (SIV)-infected macaques with disease progression and the humoral and cellular intrathecal antiviral immune response. Overt neurologic signs consisting of ataxia and apathy were observed at a much higher frequency in rapid progressor animals (6 of 12) than in slow progressors (1 of 7). Whereas slow progressors mounted a strong antiviral antibody (Ab) response as evidenced by enzyme-linked immunosorbent and immunospot assays, neither virus-specific Ab titers nor Ab-secreting cells could be found in the cerebrospinal fluid (CSF) or brain parenchyma of rapid progressors. Similarly, increased infiltration of CD8(+) T cells and cytotoxic T lymphocytes specific for viral antigens were detected only in the CSF of slow progressors. The finding that neurologic signs develop frequently in SIV-infected macaques in the absence of an antiviral immune response demonstrates that the immune system does not contribute to the development of motor disorders in these animals. Moreover, the lower incidence of neurologic symptoms in slow progressors with a strong intrathecal immune response suggests a protective role of the virus-specific immunity in immunodeficiency virus-induced central nervous system disease.     

Serum levels of soluble CD23, but not soluble CD25, predict disease progression in early stage B-cell chronic lymphocytic leukemia

Serum levels of the soluble forms of CD23 (sCD23) and CD25 (sCD25) were prospectively analyzed with respect to their prognostic relevance in early stage B-cell chronic lymphocytic leukemia (B-CLL). SCD23 and sCD25 levels were determined in 105 patients with newly diagnosed B-CLL (Binet stage A). In 93 of the patients, these levels were correlated with other already established indicators for risk of disease progression, including the histologic pattern of bone marrow infiltration, lymphocyte doubling time (LDT), and the serum level of thymidine kinase (TK). High serum levels of both sCD23 and of sCD25 were associated with a diffuse bone marrow infiltration, a LDT < or = 12 months, and elevated (>5 U/L) serum TK, respectively. Moreover, examination of the clinical course of 76 untreated patients showed that high levels of sCD23, but not of sCD25, at initial diagnosis were linked with disease progression. Furthermore, in a stepwise Cox regression model, high levels of sCD23 and a short LDT were shown to be strong predictors of progressive disease within the first year of disease presentation. Therefore, it appears to be justified to incorporate sCD23 levels into the risk profile of early stage B-CLL and to take them into account for stratification in risk-adapted treatment strategies.     

An economic analysis of teleconsultation in otorhinolaryngology

Meningococcal sepsis is a good model to study the dynamic response of cytokines and other soluble factors in vivo in the early stages of the disease. Levels of soluble CD14, interleukin-6 (IL-6), IL-6 receptor (IL-6R), and C-reactive protein (CRP) have been measured in plasma from 26 children with septic shock (nine of whom had disseminated intravascular coagulation) and from ten control children. All samples were collected at the onset, before treatment, and, when possible, 24 and 48 hours later. At admission, patients had significantly higher levels of IL-6 (p < 0.001) and CRP (p < 0.001), and lower levels of IL-6R (p < 0.005) than normal controls. After 24 hours, there was a significant increase of sCD24 (p < 0.05) and CRP (p < 0.001). Although IL-6 showed a progressive decline since the onset, its levels were always higher than controls. There was an inverse correlation between IL-6 and both IL-6R (p < 0.001) and CRP (p < 0.001), probably due to the later increase of CRP. Nevertheless, sCD14 did not correlate with IL-6 levels. We have confirmed the finding of IL-6 as a sensitive and reliable inflammatory marker in septic shock. Moreover, the ratio IL-6/IL-6R may have a prognostic value, given a putative role of IL-6R in modulating the effects of IL-6 in meningococcal sepsis.