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Biomedical subjects

E J Thompson

Publications and source records attributed to E J Thompson.

At least 109 records · Page 6Linked to original sources

High cerebrospinal fluid and serum levels of tumor necrosis factor-alpha in asymptomatic HIV-1 seropositive individuals. Correlation with interleukin-2 and soluble IL-2 receptor.

The relationship between tumour necrosis factor-alpha (TNF-alpha) and the interleukin-2 (ILL-2) system in HIV-1 infection is important in understanding the dynamics of early immune response before the development of acquired immunodeficiency syndrome. Levels of TNF-alpha, IL-2 and soluble IL-2 receptor (sIL-2R) in serum and cerebrospinal fluid (CSF) samples from 31 asymptomatic HIV-1 seropositive individuals were measured. High levels of TNF-alpha were detected in CSF of 17 (55%) and serum of 22 (71%) subjects, 15 (88%) of whom had elevated CSF IL-2 levels and 16 (94%) had high sIL-2R levels. Moreover, CSF levels of TNF-alpha significantly correlated with CSF levels of IL-2 and sIL-2R. TNF-alpha, IL-2 and sIL-2R seem to be released within the intrathecal compartment early in the course of HIV-1 infection. In view of the known cytotoxic effects of TNF-alpha, an early release may contribute to subsequent development of neurological complications.

Cerebrospinal Fluid Proteins↗

Cerebrospinal fluid ferritin in brain necrosis: evidence for local synthesis.

Ferritin was measured in cerebrospinal fluid (CSF) and serum of an unselected neurological population. An increase in CSF ferritin was found to be associated with pathological processes in which there was either necrosis or haemorrhage involving the brain. There was no correlation between the CSF and serum concentrations of ferritin in the reference population. Neither was there any correlation between CSF ferritin and CSF albumin in the reference population. After subarachnoid haemorrhage, intrathecal production of ferritin was found to occur since in some patients the concentration of ferritin in CSF was higher than that of homologous serum. Even in the reference population the concentration of ferritin found in the CSF was much higher than could be explained by passive transfer across the blood-CSF barrier. Therefore local synthesis of ferritin by brain cells occurs even under normal circumstances.

Albumins↗

An unexpected pathway for the metabolic degradation of 1,3-dialkyl-3-acyltriazenes.

In the presence of NADPH, rat liver microsomes catalyzed the degradation of a series of 1,3-dialkyl-3-acyltriazenes, and the extent of the reaction was correlated with compound lipophilicity. In the case of two methylcarbamoyltriazenes, 1-(2-chloroethyl)-3-benzyl-3- (methylcarbamoyl)triazene (CBzM) and 1-(2-chloroethyl)-3-methyl-3-(methylcarbamoyl)triazene (CMM), microsomal metabolites were isolated. Identification of the CBzM metabolites as 1-(2-chloroethyl)-3-benzyl-3-(hydroxymethylcarbamoyl)triazene and 1-(2-chloroethyl-3-benzyl-3-carbamoyltriazine, and the CMM metabolite as 1-(2-chloroethyl)-3-methyl-3-(hydroxymethylcarbamoyl)triazene indicated that the first metabolic step involves hydroxylation of the methylcarbamoyl substituent. Detailed studies of the metabolism of CBzM indicated that the Km for the reaction was 84 microM, and that metabolism was more efficient if microsomes were prepared from male than from female rats. During prolonged incubation, the metabolites of CBzM were also degraded. The degradation of CBzM and its metabolites was inhibited by SKF-525A and metyrapone, suggesting the involvement of a cytochrome P450 isozyme, and supporting the hypothesis that the process is oxidative rather than hydrolytic in both cases. Metabolic oxidation represents an alternative pathway to chemical or enzymatic hydrolysis for the in vivo decomposition of (methylcarbamoyl)triazenes. This mechanism may ultimately explain the antitumor efficacy and low acute toxicity of selected compounds.

Alkylating Agents↗

Elevated serum levels of tumor necrosis factor-alpha in Guillain-Barré syndrome.

Activated T lymphocytes and macrophages play a putative role in the the pathogenesis of Guillain-Barré syndrome. Both cell types secrete tumor necrosis factor-alpha, a cytokine that has well-recognized toxic effects on myelin, Schwann cells, and endothelial cells. We determined serum and cerebrospinal fluid concentrations of tumor necrosis factor alpha in 26 patients with Guillain-Barré syndrome, 27 patients with other polyneuropathies, 30 patients with neurological diseases of the central nervous system, and 14 healthy control subjects. Markedly increased serum levels were detected in 14 patients (54%) with Guillain-Barré syndrome and to a significantly lesser extent, in patients with other polyneuropathies (26%) and in neurological control subjects (23%). Tumor necrosis factor-alpha was not detected in the cerebrospinal fluid of patients with Guillain-Barré syndrome or other polyneuropathies. Increased serum concentrations in patients with Guillain-Barré syndrome correlated directly with disease severity and these concentrations returned to normal in parallel with clinical recovery. These findings emphasize the complexity of the immune response in patients with Guillain-Barré syndrome and suggest that tumor necrosis factor-alpha may be important in the pathogenesis of peripheral demyelination in this disorder.

Adolescent↗

In vivo relationship of interleukin-2 and soluble IL-2 receptor to blood-brain barrier impairment in patients with active multiple sclerosis.

Interleukin (IL)-2 has well-recognized effects on cerebral endothelial cells and, therefore, may mediate disruption of the blood-brain barrier in patients with multiple sclerosis (MS). To evaluate the in vivo relationship of the IL-2 system to blood-brain barrier impairment in MS, levels of IL-2 and soluble IL-2 receptors (sIL-2R) in cerebrospinal fluid (CSF) and serum samples from 50 patients with active MS and 49 controls were correlated with values of the CSF to serum albumin ratio. Intrathecal levels of IL-2 and sIL-2R were significantly higher in MS compared with the control groups and correlated with albumin ratios in MS patients. Intrathecal levels of IL-2 and sIL-2R also correlated with the degree of barrier damage in these patients. It is suggested that intrathecal levels of IL-2 and sIL-2R are related to barrier impairment in MS and may be important in understanding some of the pathological changes of this condition.

Adult↗

Intrathecal synthesis of interleukin-2 and soluble IL-2 receptor in asymptomatic HIV-1 seropositive individuals. Correlation with local production of specific IgM and IgG antibodies.

The relationship between the interleukin-2 (IL-2) system and the humoral response against human immunodeficiency virus type-I (HIV-1) is important in understanding the immune reaction before the development of AIDS. Levels of IL-2 and soluble IL-2 receptor (sIL-2R) in serum and cerebrospinal fluid (CSF) samples from 31 asymptomatic HIV-1 seropositive individuals were measured and correlated with levels of anti-1 IgG and IgM antibodies. High IL-2 levels were detected in the CSF of 20 (65%) subjects, 18 (90%) of whom had evidence of intrathecal synthesis of HIV-1-specific IgM antibodies. Similarly, IgG antibodies were detected in 10 subjects who had elevated IL-2 levels in the CSF. Moreover, intrathecal levels of IL-2 and sIL-2R correlated with intrathecal synthesis of both IgG and IgM antibodies. Local release of IL-2 seems to play an important role in the initiation of the antibody response against HIV-1 in early stages of infection and may be utilised in devising effective therapeutic strategies.

Adolescent↗

Lymphocytic meningitis following insertion of a porcine dermis dural graft.

We describe a case of lymphocytic meningitis following insertion of a porcine dermis implant to repair an operative dural defect. Histology of the excised implant revealed local abscess formation with a granulomatous reaction. Oligoclonal Immunoglobulin G, part of which could be removed by absorbtion with the porcine dermis, was present in the patient's cerebrospinal fluid, and, to a less marked degree, in his serum. The cerebrospinal fluid glucose was markedly depressed. An unusual hypersensitivity reaction to the porcine implant was considered the most likely explanation for this meningitic illness. The patient went on to make a full recovery following excision of the implant.

Adult↗

Increased levels of circulating ICAM-1 in serum and cerebrospinal fluid of patients with active multiple sclerosis. Correlation with TNF-alpha and blood-brain barrier damage.

The mechanism for the initiation of blood-brain barrier damage and intrathecal inflammation in multiple sclerosis (MS) is poorly understood. We have recently reported that levels of tumor necrosis factor-alpha (TNF-alpha) correlate with blood-brain barrier damage in patients with active MS. Stimulation of endothelial cells by TNF-alpha induces the expression of intercellular adhesion molecule-1 (ICAM-1), which is an important early marker of immune activation and response. We report herein for the first time the detection of high levels of free circulating ICAM-1 in serum and cerebrospinal fluid of patients with active MS. Levels of circulating ICAM-1 in these patients correlated with CSF pleocytosis, TNF-alpha levels and blood-brain barrier damage. These findings have important implications for the understanding and investigation of the intrathecal inflammatory response in active MS.

Adult↗

Atypical gunshot wound caused by cylinder index error.

Atypical gunshot wounds are caused by a diverse set of parameters relating to weapons and ammunition. Documentation of cases where atypical gunshot wounds can be explained facilitates future interpretation of wounds in unusual cases. We report an atypical gunshot wound produced by a double-action Colt .38-caliber special handgun with a cylinder index error. Cylinder index error is caused by a misalignment between the cylinder chamber and barrel forcing cone. When properly functioning, the cylinder chamber and barrel forcing cone are held in alignment by the union of the ratchet and latch pin. In this case, misalignment was caused by wear of the ratchet and latch pin, which allowed play in the cylinder. With the weapon turned on its side, and the swing arm down, the cylinder chamber overlaps the barrel forcing cone. When fired, the index error caused lead fragments to shear off the bullet and expel laterally out the cylinder gap between the cylinder chamber and barrel forcing cone, creating fragment entrance wounds several centimeters distant from the site of contact entry.

Aged↗

Correlation of interleukin-2 and soluble interleukin-2 receptor with clinical activity of multiple sclerosis.

Concentrations of interleukin-2 (IL-2) and soluble IL-2 receptor (sIL-2R) in serum and CSF samples were measured in 63 patients with multiple sclerosis (MS) to evaluate their usefulness as markers of disease activity. CSF concentrations of IL-2 and sIL-2R were significantly higher in MS relapse compared with MS patients in remission or with control subjects. These concentrations correlated with the clinical score by which disease severity was assessed, with the number of relapses per year, and with the total disease duration. Furthermore, there was evidence of intrathecal release of IL-2 and sIL-2R in clinically active MS. The results extend the notion that an activated cellular immune state parallels the evolution of the pathological process in MS and suggest that measurement of IL-2 and sIL-2R concentrations may provide an objective marker of disease activity in patients with MS.

Adult↗

Patterns of blood-brain barrier impairment and clinical features in multiple sclerosis.

Seventy four patients with clinically definite multiple sclerosis were studied by using polyacrylamide gel electrophoresis of cerebrospinal fluid to assess blood-brain barrier function. Blood-brain barrier impairment was associated with recent clinical relapses of multiple sclerosis and worsened across a spectrum from the relapsing-remitting type of multiple sclerosis to secondary and primary progressive disease. The association between blood-brain barrier impairment and primary progressive disease is particularly interesting in the light of recent evidence that focal gadolinium enhancement on MRI is relatively unusual in patients with this disease.

Adult↗

Hairy leukaemic cell influx into the cerebrospinal fluid secondary to encephalomyelitis.

A case report of a 53 year old male with hairy cell leukaemia is presented in whom encephalomyelitis caused by toxoplasmosis resulted in an influx of hairy cells into the cerebrospinal fluid following disruption of the blood-brain barrier. These cells subsequently disappeared as the barrier reformed. It is suggested that the presence of hairy cells in the cerebrospinal fluid is a secondary self-limiting phenomenon.

Central Nervous System↗

Transesophageal echocardiography: a new window on the heart and great vessels.

TEE adds an exciting new dimension to the field of echocardiography. It has expanded the physician's ability to clearly examine cardiac structures and bloodflow; in many instances it has been the means by which rapid and lifesaving diagnoses have been made. The nurse collaborates with the physician during TEE by ensuring adequate preparation, remaining at the patient's bedside to assist with and monitor the effects of probe insertion and ensuring close observation and postprocedural follow up. The complication rate for TEE is negligible. Possibilities include routine pediatric use, biplane imaging and incorporation with exercise stress testing.

Echocardiography↗

Determination of interleukin-2 in cerebrospinal fluid by a sensitive enzyme-linked immunosorbent assay.

A sensitive technique was developed for the quantitative detection of intrathecal production of interleukin-2 (IL-2). Concentrations of IL-2 in paired cerebrospinal fluid (CSF) and serum samples were measured by an enzyme-linked immunosorbent assay using a monoclonal antibody and an affinity purified polyclonal antibody. The assay produced a linear response with respect to IL-2 concentration, and could readily detect levels of IL-2 as low as 1.5 international units/ml. Concentrations of IL-2 in CSF and serum samples were standardised by calculating their ratio to albumin concentration in order to correct for passive transudation of IL-2 across blood-CSF barriers. CSF IL-2/albumin ratios higher than concomitant serum ratios were considered indicative of intrathecal IL-2 production. The technique provides a sensitive, specific, and reproducible method for the determination of in vivo synthesis of IL-2 within the central nervous system.

Enzyme-Linked Immunosorbent Assay↗

Fluids of the brain and the pathogenesis of MS.

The plaques of multiple sclerosis are generally thought to spread outwards from central veins. We propose that periventricular plaques in the cerebral hemispheres, and superficial plaques in the brain stem and spinal cord, point to the importance of demyelinating factors in the cerebrospinal fluid.

Body Fluids↗

Distribution of cerebrospinal fluid oligoclonal IgM bands in neurological diseases: a comparison between agarose electrophoresis and isoelectric focusing.

Isoelectric focusing (IEF) and agarose gel electrophoresis were used to detect oligoclonal IgM bands in cerebrospinal fluid and serum samples from 850 patients with diverse neurological diseases. Oligoclonal IgM bands in cerebrospinal fluid were mainly detected in patients with infectious and inflammatory disorders of the nervous system. Both IEF and agarose electrophoresis revealed similar frequencies of oligoclonal IgM bands. Bands detected by IEF were mainly seen in the anodal range. Despite higher resolving capacity, IEF was less specific than agarose gel electrophoresis. It is concluded that oligoclonal IgM bands have important diagnostic significance and that agarose gel electrophoresis is more suitable for their detection in routine clinical work and use in differential diagnosis.

Blood Protein Electrophoresis↗