- Email: [email protected]
INTERFERON AND MYALGIC ENCEPHALOMYELITIS
471
tiny inoculum, part of which must have been washed out with soap and water. In experiments in rabbits, 4 x 10’ parasites were required to cause a mild, occasional parasitaemia in 14 days. Our case suggests that T gambiense has a high affinity for human tissues. Department of Haematology, College of Medical Sciences, University of Calabar, Calabar, Nigeria
A. O. EMERIBE
INTERFERON AND MYALGIC ENCEPHALOMYELITIS
SIR,- Lymphokines including interferon may be the mediators of the fatigue in myalgic encephalomyelitis or postinfection fatigue syndrome (PIFS), perhaps after secondary release to a low grade persistent intracellular infection.1,2 McDonald et al,3noting the neuropsychiatric symptoms and fatigue commonly reported in patients who receive recombinant alpha-interferon, were reminded of the clinical features of the postviral syndromes. Studies of the interferon system in patients with this disorder have been equivocal. Circulating interferon was not found in a small sample of patients thought to have such a syndrome secondary to chronic Epstein-Barr virus infection.’ However, increased levels of 2’-5’-oligo-adenylate synthetase, a cellular enzyme specifically induced by interferon, have been demonstrated in such patients.4,5 We examined the sera of patients with PIFS and control subjects for circulating gammainterferon (IFN-&ggr;) and also measured the serum levels of neopterin, an intermediate in the synthetic pathway of biopterin and a reliable marker of IFN-y activity.6 These mediators were chosen because IFN-y is the major cytokine released by T cells after viral or other intracellular infection; neopterin is preferentially induced by IFN-y rather than by other cytokines.6 52 consecutive patients (35 females) who fulfilled 6ur diagnostic criteria for PIFS2 entered the study. All had been persistently symptomatic for at least 6 months (range 6-180). 20 healthy adults (11 females) were the controls. Serum IFN-y levels were measured with a solid-phase radioimmunoassay (Centocor, USA), and neopterin levels were measured by radioimmunoassay with a double-antibody technique (Henning, Berlin). IFN-y was undetectable in the serum of 39 of the patients (75%) and in 8 of the controls (40%). Low levels of interferon were found in the remaining samples (below 1-2 U/ml). There was no significant difference between patients and controls. Mean serum neopterin values in the patients were similar to those of the controls: 10-2 (8-6) nmol/1. The results indicate that subjects with PIFS do not have an increased serum IFN-y level. This does not exclude the possibility of a local increase of IFN-y or other lymphokines at specific sites in the central nervous system in such patients. IFN-y has a short serum half-life and may therefore become undetectable in serum samples despite ongoing or local interferon activity in vivo. Furthermore in patients with PIFS a local cell-mediated (T cell) immune response to intracellular pathogens in muscle and/or neural cells may elicit local interferon activity without producing a detectable change in serum interferon or neopterin levels. Measurement of these and other mediators in cerebrospinal fluid or other sites in the central nervous system of patients with PIFS may shed light on the pathogenesis of this disorder. 8
0 (SD 4-1) vs
Department of Immunology, University of New South Wales, Prince Henry Hospital, Sydney, Australia
ANDREW LLOYD DAVID ABI HANNA DENIS WAKEFIELD
1. Wakefield D, Lloyd A. Pathophysiology of myalgic encephalitis. Lancet 1987; ii: 918-19 2 Lloyd AR, Wakefield D, Dwyer J. The post-infection fatigue syndrome Fact or fiction? Aust NZ J Med (in press). 3. McDonald EM, Mann AH, Thomas HC. Interferons and mediators of psychiatric morbidity. an investigation in a trial of recombinant &agr;-interferon in hepatitis-B carriers Lancet 1987; ii: 1175-78. 4 Straus S, Tosato G, Armstrong G, et al. Persisting illness and fatigue m adults with evidence of Epstein-Barr virus infection. Ann Intern Med 1985; 102: 7-16 5 Morag A, Tobi M, Ravid Z, Revel M, Schattner A. Increased (2’-5’-oligo-A synthetase activity m patients with prolonged illness associated with serological evidence of persistent Epstein-Barr virus infection. Lancet 1982, i 744. 6 Huber C, Batchelor JR, Fuchs D, et al. Immune response-associated production of neopterin. J Exp Med 1984; 160: 310-16.
CAPTOPRIL IN PATIENTS WITH ILEUS
SIR,-Dr Flynn and colleagues report (Jan 23, p 173) the use of intravenous captopril in patients with postoperative ileus. The sublingual route might have been appropriate in this situation. We have given 25 mg captopril sublingually to eight salt-replete, supine healthy male volunteers. All reported complete dissolution of the tablet within 10 min. In venous blood sampled 55 min after the dose plasma renin activity rose from 0-99 (SEM 0-17) to 6-91 (2-10)
indicating angiotensin-converting-enzyme ng/ml/h (p<0001), inhibition. Sublingual captopril may be a simple and effective administration. Department of Pharmacology
pharmacologically
and Clinical Pharmacology, Ninewells Hospital, Dundee DD1 9SY
alternative
to
intravenous
JOHN J. MCMURRAY ALLAN D. STRUTHERS
"BLIND" LABORATORY ANALYSIS
SIR,-In studies reported in The Lancet specimens have often been collected from groups of patients and controls and sent to a laboratory for tests. The results may show that, for instance, markers of a certain virus infection are significantly more common in patients than in controls, and it is inferred that the virus is the cause of the patients’ disease. What is frequently not revealed is whether the laboratory workers knew which specimens came from patients and which from controls and, if they did not, how this was concealed from them. Many virological tests depend on appearances in tissue culture and microscopy, and the extent to which investigations are pursued often depends on an early subjective decision about these appearances. Admittedly, it is possible to read tests objectively by machines such as ELISA readers, but even then choices such as how often to repeat a test have to be made. Whatever the investigation, therefore, it is preferable that patient and control specimens be mixed and coded so that the laboratory deals with them "blind". Researchers who fail to do "blind" laboratory analysis weaken the impact and validity of their findings unnecessarily. Virus Reference Laboratory, Central Public Health Laboratory, London NW9 5HT
PHILIP P. MORTIMER
TRACING OF LABORATORY CONTAMINATION: QUALITY CONTROL APPROACH
SIR,-Beaumont1 found blood on various surfaces in the suggested that the contamination resulted from a breakdown in good work-practices. Most probably this was after indiscriminate touching of surfaces with contaminated gloves. We have found widespread contamination with serum and failure of basic hygiene practices after the introduction of simulated patients’ samples containing tracers into a routine clinical chemistry laboratory. The samples were horse serum containing spores of Bacillus subtilis variety globigii (NCTC 10073, Microbial Technology Laboratory, Porton Down, Wiltshire), 108 colony-forming units per ml, and 0-1% ’Uvitex NFW’, a liquid optical brightener (Hughes and Hughes, Romford, Essex). Fluorescence from the brightener was detected under ultraviolet light and affected surfaces were swabbed, plated onto nutrient agar, and then incubated
necropsy room and
aerobically at 37°C for published elsewhere.
16 h. More details of the
technique will be
Fluorescence with tracer spores was detected on gloves, equipment, and bench surfaces that had been used to handle the test sera.
In
some
instances, the smeared pattern of fluorescence,
together with a positive culture, suggested inadequate attempts to deal with a spill. In the laboratory that was studied, samples from patients infected with hepatitis B virus and human immunodeficiency virus are occasionally handled. This double-tracer technique can be used to make staff more aware of the potential infection hazards posed by contaminated surfaces. Moreover, the photographs of areas where both tracers are detected will help to reinforce the impact of training
tiny inoculum, part of which must have been washed out with soap and water. In experiments in rabbits, 4 x 10’ parasites were required to cause a mild, occasional parasitaemia in 14 days. Our case suggests that T gambiense has a high affinity for human tissues. Department of Haematology, College of Medical Sciences, University of Calabar, Calabar, Nigeria
A. O. EMERIBE
INTERFERON AND MYALGIC ENCEPHALOMYELITIS
SIR,- Lymphokines including interferon may be the mediators of the fatigue in myalgic encephalomyelitis or postinfection fatigue syndrome (PIFS), perhaps after secondary release to a low grade persistent intracellular infection.1,2 McDonald et al,3noting the neuropsychiatric symptoms and fatigue commonly reported in patients who receive recombinant alpha-interferon, were reminded of the clinical features of the postviral syndromes. Studies of the interferon system in patients with this disorder have been equivocal. Circulating interferon was not found in a small sample of patients thought to have such a syndrome secondary to chronic Epstein-Barr virus infection.’ However, increased levels of 2’-5’-oligo-adenylate synthetase, a cellular enzyme specifically induced by interferon, have been demonstrated in such patients.4,5 We examined the sera of patients with PIFS and control subjects for circulating gammainterferon (IFN-&ggr;) and also measured the serum levels of neopterin, an intermediate in the synthetic pathway of biopterin and a reliable marker of IFN-y activity.6 These mediators were chosen because IFN-y is the major cytokine released by T cells after viral or other intracellular infection; neopterin is preferentially induced by IFN-y rather than by other cytokines.6 52 consecutive patients (35 females) who fulfilled 6ur diagnostic criteria for PIFS2 entered the study. All had been persistently symptomatic for at least 6 months (range 6-180). 20 healthy adults (11 females) were the controls. Serum IFN-y levels were measured with a solid-phase radioimmunoassay (Centocor, USA), and neopterin levels were measured by radioimmunoassay with a double-antibody technique (Henning, Berlin). IFN-y was undetectable in the serum of 39 of the patients (75%) and in 8 of the controls (40%). Low levels of interferon were found in the remaining samples (below 1-2 U/ml). There was no significant difference between patients and controls. Mean serum neopterin values in the patients were similar to those of the controls: 10-2 (8-6) nmol/1. The results indicate that subjects with PIFS do not have an increased serum IFN-y level. This does not exclude the possibility of a local increase of IFN-y or other lymphokines at specific sites in the central nervous system in such patients. IFN-y has a short serum half-life and may therefore become undetectable in serum samples despite ongoing or local interferon activity in vivo. Furthermore in patients with PIFS a local cell-mediated (T cell) immune response to intracellular pathogens in muscle and/or neural cells may elicit local interferon activity without producing a detectable change in serum interferon or neopterin levels. Measurement of these and other mediators in cerebrospinal fluid or other sites in the central nervous system of patients with PIFS may shed light on the pathogenesis of this disorder. 8
0 (SD 4-1) vs
Department of Immunology, University of New South Wales, Prince Henry Hospital, Sydney, Australia
ANDREW LLOYD DAVID ABI HANNA DENIS WAKEFIELD
1. Wakefield D, Lloyd A. Pathophysiology of myalgic encephalitis. Lancet 1987; ii: 918-19 2 Lloyd AR, Wakefield D, Dwyer J. The post-infection fatigue syndrome Fact or fiction? Aust NZ J Med (in press). 3. McDonald EM, Mann AH, Thomas HC. Interferons and mediators of psychiatric morbidity. an investigation in a trial of recombinant &agr;-interferon in hepatitis-B carriers Lancet 1987; ii: 1175-78. 4 Straus S, Tosato G, Armstrong G, et al. Persisting illness and fatigue m adults with evidence of Epstein-Barr virus infection. Ann Intern Med 1985; 102: 7-16 5 Morag A, Tobi M, Ravid Z, Revel M, Schattner A. Increased (2’-5’-oligo-A synthetase activity m patients with prolonged illness associated with serological evidence of persistent Epstein-Barr virus infection. Lancet 1982, i 744. 6 Huber C, Batchelor JR, Fuchs D, et al. Immune response-associated production of neopterin. J Exp Med 1984; 160: 310-16.
CAPTOPRIL IN PATIENTS WITH ILEUS
SIR,-Dr Flynn and colleagues report (Jan 23, p 173) the use of intravenous captopril in patients with postoperative ileus. The sublingual route might have been appropriate in this situation. We have given 25 mg captopril sublingually to eight salt-replete, supine healthy male volunteers. All reported complete dissolution of the tablet within 10 min. In venous blood sampled 55 min after the dose plasma renin activity rose from 0-99 (SEM 0-17) to 6-91 (2-10)
indicating angiotensin-converting-enzyme ng/ml/h (p<0001), inhibition. Sublingual captopril may be a simple and effective administration. Department of Pharmacology
pharmacologically
and Clinical Pharmacology, Ninewells Hospital, Dundee DD1 9SY
alternative
to
intravenous
JOHN J. MCMURRAY ALLAN D. STRUTHERS
"BLIND" LABORATORY ANALYSIS
SIR,-In studies reported in The Lancet specimens have often been collected from groups of patients and controls and sent to a laboratory for tests. The results may show that, for instance, markers of a certain virus infection are significantly more common in patients than in controls, and it is inferred that the virus is the cause of the patients’ disease. What is frequently not revealed is whether the laboratory workers knew which specimens came from patients and which from controls and, if they did not, how this was concealed from them. Many virological tests depend on appearances in tissue culture and microscopy, and the extent to which investigations are pursued often depends on an early subjective decision about these appearances. Admittedly, it is possible to read tests objectively by machines such as ELISA readers, but even then choices such as how often to repeat a test have to be made. Whatever the investigation, therefore, it is preferable that patient and control specimens be mixed and coded so that the laboratory deals with them "blind". Researchers who fail to do "blind" laboratory analysis weaken the impact and validity of their findings unnecessarily. Virus Reference Laboratory, Central Public Health Laboratory, London NW9 5HT
PHILIP P. MORTIMER
TRACING OF LABORATORY CONTAMINATION: QUALITY CONTROL APPROACH
SIR,-Beaumont1 found blood on various surfaces in the suggested that the contamination resulted from a breakdown in good work-practices. Most probably this was after indiscriminate touching of surfaces with contaminated gloves. We have found widespread contamination with serum and failure of basic hygiene practices after the introduction of simulated patients’ samples containing tracers into a routine clinical chemistry laboratory. The samples were horse serum containing spores of Bacillus subtilis variety globigii (NCTC 10073, Microbial Technology Laboratory, Porton Down, Wiltshire), 108 colony-forming units per ml, and 0-1% ’Uvitex NFW’, a liquid optical brightener (Hughes and Hughes, Romford, Essex). Fluorescence from the brightener was detected under ultraviolet light and affected surfaces were swabbed, plated onto nutrient agar, and then incubated
necropsy room and
aerobically at 37°C for published elsewhere.
16 h. More details of the
technique will be
Fluorescence with tracer spores was detected on gloves, equipment, and bench surfaces that had been used to handle the test sera.
In
some
instances, the smeared pattern of fluorescence,
together with a positive culture, suggested inadequate attempts to deal with a spill. In the laboratory that was studied, samples from patients infected with hepatitis B virus and human immunodeficiency virus are occasionally handled. This double-tracer technique can be used to make staff more aware of the potential infection hazards posed by contaminated surfaces. Moreover, the photographs of areas where both tracers are detected will help to reinforce the impact of training