242

IMMUNOGLOBULIN CONCENTRATIONS AND LYMPHOCYTE PHENOTYPES IN TWO PATIENTS WITH CHRONIC FATIGUE SYNDROME

*Normal ranges (from Edwards AJ, e2 al.

ClinExpImmunoII984; 58:420-27): IgG =7 2-16-2 g/l,IgGI= =3 3 2-10 g/1, T4 = mean 456 (SD 157/t),T8 =272 (124/1), and B 86 (42/)it).
comment (Nov 28, p 1273), would refer him to three psychopharmacology textbooks edited byAmerican, Austrian, British, and German authors (to reflect the international homogeneity of views on this topic) that clearly state the indications for benzodiazepines.1-3 A treatment of proven efficacy should not be withheld from patients with acute or chronic anxiety states. One persons opinion should not result in the removal of benzodiazepines when scientific evidence points in the opposite direction. It is the doctors responsibility to weigh carefully the benefits and risks when considering whether to prescribe a benzodiazepine for a patient.

The finding of IgGl deficiency in these patients is novel, as lone deficiency of this subclass is rare and affected patients appear to have common variable hypogammaglobulinaemia. In a large study of IgG subclass deficiencies, Soderstrom et aP found only 16% of these patients had pure IgGI deficiency and of these, 9% had depressed T4/T8 ratios, although 54% had abnormal response to the mitogenic lectins phytohaemagglutinin and concanavalin A. Most patients were examined because of recurrent bacterial a infections. The origin of the defect described here may be either. failure of T-cell help or excess subclass-specific suppression. The transitory nature of the defect in case 1 argues against permanent deletion of IgGl-secreting B-cells. If an infectious agent is responsible for the symptoms and objective abnormalities described in these case reports, then what is it? EBV, CMV, and HIV are unlikely candidates. Krueger et al4 described a patient with fatigue and high titres of antibody to HHV6, though the prevalence of this antibody within the normal community has yet to be established. Only one of our cases had strongly positive indirect immunofluorescence to HHV6 antigen and we failed to recover the virus from either patient. Further scrutiny of cases with chronic fatigue may reveal a range of subtle immunological abnormalities, of which altered expression of latent EBV infection is only one. As yet there is no clue to whether a single agent or a single host defect can account for cases such as these.
We thank Dr Crawford (Royal Postgraduate Medical School) for EBV serology, Dr R. Tedder (Middlesex Hospital Medical School) for HHV6 serology, Prof A. Milford Ward (Royal Hallamshire Hospital, Sheffield) for assaying immunoglobulin subclasses, and Ruth Beattie for reverse transcriptase assays.
Sections of Communicable Diseases and Immunological Medicine, Northwick Park Hospital and Clinical Research Centre, Harrow HA1 3UJ

Sandlers standard

Department of Psychiatry Research, Hillside Hospital, Long Island Jewish Medical Center, Glen Oaks, New York 11004, USA
1.

W. WOLFGANG FLEISCHHACKER

Rickels K, Schweizer EE. Current pharmacotherapy of anxiety and panic. In: Meltzer H, ed. Psychopharmacology: the third generation of progress. New York: Raven
Press, 1987: 1193-205.

2.

Poldinger W, Wider I. Psychopharmakotherapie bei Angstsyndromen, phobischen Syndromen und Zwangssyndromen. In: Langer G, Heimann H, eds Psychopharmaka. Vienna: Springer, 1983. 447-67. 3. Rickels K, Downing W, Winokur A. Antianxiety drugs: Clinical use m psychiatry. In. Iversen LL, Iversen SD, Snyder SH, eds. Handbook of psychopharmacology XIII: Biology of mood and antianxiety drugs. New York. Plenum, 1978: 395-430

VITAMIN

B12 AND SEAWEED

ROBERT READ GAVIN SPICKETT JENNIFER HARVEY ANDREW J. EDWARDS H. ELLIOTT LARSON

1.

Jones JF, Straus SE. Chronic Epstein-Barr virus infection. Annu Rev Med 1987; 38:
195-209

2. DuBois RE. Gammaglobulin therapy for chronic mononucleosis syndrome. AIDS Res 1986; 2: S191-95. 3. Soderstrom T, Soderstrom R, Avanzini A, et al. Immunoglobulin G subclass deficiencies. Int Archs Allergy Appl Immunol 1987; 82: 476-80. 4. Krueger GRF, Koch B, Ablashi DV Persistent fatigue and depression in patient with antibody to human B-lymphotropic virus. Lancet 1987; ii: 36

BENZODIAZEPINES IN ANXIETY

SiR,—Your correspondents remarks (Nov 7, p 1080; Dec 12, p 1406) on benzodiazepines may reflect personal opinion, but statements such as "there is no use for these drugs in the treatment of anxiety" are not justified. Several well-controlled trials prove that benzodiazepines have a place in the treatment of various types of anxiety disorders.We can all see the possible hazards of prescribing these drugs but personal opinions should not be elevated to the status of generalisations without scientific back-up. Dr Carney and his colleagues contradict themselves, finding "no place for benzodiazepines in the treatment of anxiety" yet one sentence later conceding that "they may be used in states of acute psychiatric disturbance". An acute anxiety state is an acute psychiatric disturbance, as any doctor working in an emergency service would know. As for Professor Cohens questions about the sort of patients who should receive benzodiazepines I, strongly reinforcing Dr

SiR,—We need to know if non-animal foods such as seaweed, algae, and fermented soya products can contribute to human vitamin B12 needsl,2 because vegetarian and macrobiotic life styles are gaining popularity. Little is known about the vitamin B12 content of (and bioavailability from) these food products.3,4 As part of a study on macrobiotically fed Dutch children we analysed about forty plant foods for vitamin B12 by an in-house radioassay based on the method of Lau et aP with pure intrinsic factor (Sigma) as binder and cyanocobalamin as standard. The between-assay coefficient of variation was 5-8% based on a twentyfold analysis of pooled milk samples (8-5 ± 0-5 )J.g per 100 g). Samples were extracted by autoclaving (120°C) for 10 min in 0-1 mol/1 sodium acetate buffer pH 4-6, containing freshly added 0 005% potassium cyanide. Products rich in vitamin B2 were also measured by microbiological assay (Difco). Neither in fermented soya products (tempeh, shoyu, tamari, rice miso, barley miso, tofu) nor in other fermented products (amesake rice, umeboshi prunes) did we find measurable vitamin B12 (all below 0-02 I1g per 100 g). Small amounts (0-02-0-5 I1g per 100 g) were found in barley malt syrup, sourdough bread, parsley, and shitake. Some algae were rich in vitamin B12 (table). For some products conflicting results between the two assays were obtained, as reported by Herbert et al. The higher value for spirulina with the Lactobacillus leichmanni assay may be due to corrinoid-like EI2 analogues giving a growth response in the microbiological assay but with no affinity for binding to intrinsic factor. The lower microbiological assay levels found for kombu, wakame, and kelp are more difficult to explain but indicate that intrinsic factor may have some affinity for corrinoids that are non-responsive to L leichmanni. Interesting is the high vitamin B12 content of nori, with good agreement between the two assays. This high level was confirmed in other samples of this product from different sources in the USA and Japan (table).
Is the vitamin B12 in nori available to the human body? Preliminary findings in vitamin-B12-deficient macrobiotically fed

243
VITAMIN

B12

CONTENT OF SOME ALGAE MEASURED BY RADIOASSAY AND MICROBIOLOGICAL ASSAY

WN

Westbrae Natural. ND

=not

determined.

children (plasma vitamin B12 below 130 pmol/1) suggests that it is not. The inclusion of nori and/or spirulina in these childrens diets resulted in a further deterioration in mean cell volume despite increasing plasma vitamin B12 levels. These results stress the importance of more research on the specificity of the assay methods and on the bioavailability of vitamin Bi2 in non-animal products.
TNO-CIVO Toxicology
and Nutrition Institute, 3700AJ Zeist, Netherlands

H.

VAN DEN

BERG

Department of Human Nutrition, Agricultural University,

Wageningen
1 Immerman AM. Vitamin B12 status

P. C. DAGNELIE W. A. VAN STAVEREN

on a vegetarian diet. World Rev Nutr Diet 1981; 37: 38-54. 2. Long A. Vitamin B12 for vegans. Br Med J 1977; ii: 192 3. Djurtofft R, Nielsen JP. Increase in some B-vitamins, including B12, during fermentation of tempeh, produced from cowpeas and or soy beans. J Plant Foods 1983; 5: 135-41. 4. Herbert V. Recommended dietary intakes (RDI) of vitamin B12 in humans. Am J Clin Nutr 1987; 45: 671-78. 5. Lau KS, Gottlieb C, Wasserman LR, Herbert V. Measurement of serum vitamin B12 level using radioisotope dilution and coated charcoal Blood 1965, 26: 202-14. 6. Herbert V, Drivas G Spirulina and vitamin B12. JAMA 1982; 248: 3096-971.

Published work on acute leukaemia in pregnancy is difficult to interpret because it spans many years, during which treatment options have changed.l Retrospective data can be misleading and biased. Case-reports suggest that, where disease is uncontrolled, there is considerably more risk to the mother should she deliver, than where remission can be induced first. Unfortunately, this is not always possible, as the above case demonstrates; furthermore the risks of termination increase the longer it is delayed. Should the fetus die in utero, there is the added possibility of a coagulopathy. Termination should not therefore be discounted in early pregnancy and, with appropriate platelet support, a termination may be far less life-threatening than allowing the pregnancy to continue in the presence of active leukaemia. Each case needs to be assessed on its merits.
Selly Oak Hospital, Birmingham B29 6JD

J. A. MURRAY H. GEE

1. Catanzarite VA, Ferguson JE. Acute leukemia and pregnancy a review of management and outcome, 1972-1982 Obstet Gynecol Survey 1984; 39: 663-78

INTRAVASCULAR COAGULATION AND MYCOPLASMA PNEUMONIAE INFECTION

ACUTE LEUKAEMIA DURING PREGNANCY

SiR,—Dr Mulder and Dr Spierings (Nov 14,

case

1152) report

SiR,—We agree with Dr Volkenandt and colleagues (Dec 26, p 1521) that a successful pregnancy may be possible in patients being treated for acute leukaemia but we question their statement that termination is inadvisable in early pregnancy and should be considered only when the mother is in complete remission. They state that childbirth in a state of granulocytopenia and thrombocytopenia may be disastrous for the mother, but by avoiding termination they would be exposing some patients to this very risk. Nor is there any guarantee that haematological remission is going to be achieved with chemotherapy, as illustrated by the following case. In May, 1985, a 27-year-old woman was admitted with a haemoglobin of 4-7 g/dl, a white cell count of 22 x 109/1 (20% blasts), and a platelet count of 18 x 10*/1. Acute myeloblastic leukaemia was diagnosed and she was found to be 16-18 weeks pregnant. Termination of pregnancy, by intra-amniotic prostaglandin with antibiotic cover, was uneventful. Chemotherapy with daunorubicin, cytarabine, and thioguanine was started but the patient failed to enter remission. Although her first course of treatment was well tolerated she became septicaemic after the second course, when she had a prolonged episode of granulocytopenia and thrombocytopenia. A fungal septicaemia developed and she spent 3 months in hospital during which time she received 42 units of blood and 129 units of platelets. She received further chemotherapy but never entered remission and died 12 months after presentation. Volkenandt et al do not give us details of the platelet count in their first three cases, and the fourth case, with severe thrombocytopenia,
associated with an intrauterine death. The course of the first is unusual, with disease persisting after treatment during pregnancy. Did this patient require regular blood product support?
was case

of Mycoplasma pneumoniae infection complicated by stroke due to intravascular coagulation. Although this clotting abnormality has been reported during M pneumoniae infection," the pathogenetic mechanism is obscure. We have shown that lipoglycans from mycoplasmas (Acheloplasma and Ureaplasma spp), like lipopolysaccharides of gram-negative bacterial can induce the production of procoagulant activity, similar to that of tissue factor, by human mononuclear cells in vitro.6 We have since found that a strain of M pneumoniae (10119, National Collection of Typed Cultures, Colindale, London) activates the production of procoagulant (tissue-factor-like) activity by human leucocytes in vitro (unpublished). Because this activity is a potent trigger of blood coagulation (tissue-factor), our results suggest a mechanism for the clotting abnormalities that complicate severe M pneumoniae infections.
Institute of Medical Microbiology,

University of Bari, I-70124 Ban, Italy

1. Nilsson

GIUSEPPE MIRAGLIOTTA

DONATO FUMAROLA

acute

IM, Rausing A, Denneberg T, Christensson P. Intravascular coagulation and renal failure in a child with Mycoplasma infection Acta Med Scand 1971, 189:

359-65. 2. De Vos M, Van Nimmen L, Baele G. Disseminated intravascular coagulation during a fatal Mycoplasma pneumoniae infection. Acta Haematol ( Basel) 1974; 52: 120-25. 3. Pickins S, Catterall JR. Disseminated intravascular coagulation and myocarditis associated with Mycoplasma pneumoniae infection. Br Med J 1978; i: 1526 4. Mulder LJMM, Spierings ELH. Stroke in a young adult with Mycoplasma pneumoniae infection complicated by intravascular coagulation Neurology 1987; 37: 1430-31. 5 Lemer RG, Goldstein R, Cummings G Stimulation of human leukocyte procoagulant thromboplastic acivity by endotoxin Proc Soc Exp Biol Med 138: 145-48 6 Miragliotta G, Barone G, Monna RA, Fumarola D, Smith PF Induction of procoagulant activity in human leukocytes with lipoglycans from Mycoplasmas.

J Clin Microbiol 1987, 25: 1295-97