969

Enterovirus infection was tested by complement fixation assay with

picomavirus antigen (Virion Institute), an antigenic preparationfrom coxsackievirus (Bl to B6 and A9 types) and echovirus (4, 6,9-14,24, and 30 types) groups. After defibrination and removal ofcomplement, plasma samples were read, with 50% haemolysisjudged visually as positive. The positivity threshold was 1/10 serumdilution. In the PPCM group, 27/38 (71-05%) samples werepositive while in the controls 27/37 (72-97%) samples were positive.O’Connell and Sanderson and their colleagues1.2 showed, by

endomyocardial biopsy, subacute or chronic myocarditis lesions inPPCM. Coxsackievirus and echovirus are common agents of

presumed viral myocarditis.4 Our results indicate the highfrequency of coxsackievirus and echovirus infection among womenin Niger, but do not show a higher prevalence among cases ofPPCM. A study of the course of antibody titres over time is

required.

Department of Internal Medicine,Faculté des Sciences de la Santé,Niamey, Niger;Medicine Internal Service,Hôpital National,Niamey;and Immunology Laboratory,

Faculté de Médecine Pitié-Salpêtrière,75013 Pans, France

A. CÉNAC*Y. GAULTIERA. DEVILLECHABROLLER. MOULIAS

*Present address: 99 rue Mathieu Donnart, 29200 Brest, France.

1 O’Connell JB, Costanzo-Nordin MR, Subramanian R, et al. Peripartumcardiomyopathy clinical, hemodynamic, histologic and prognostic characteristics.J Am Coll Cardiol 1986; 8: 52-56.

2 Sanderson JE, Olsen EGJ, Gatei D. Peripartum heart disease: an endomyocardialbiopsy study. Br Heart J 1986; 56: 285-91.

3 Cénac A, Gaultier Y, Soumana I, Touré IA, Develoux M La myocardiopathiepost-partum: evaluations clinique et échographique de la résponse au traitement:trente cas observes en région soudanosahélienne. Presse Méd 1988, 17: 940-44.

4. Wenger NK, Abelmann WH, Roberts WC. Myocardite. In: Hurst JW, ed. Le coeur.Pans: Masson. 1985; 1211-31.

INTRAVENOUS GAMMAGLOBULIN,ANTIPHOSPHOLIPID ANTIBODIES, AND

THROMBOCYTOPENIA

SIR,-Dr Carreras and colleagues (Aug 13, p 393) reportsuccessful gammaglobulin treatment of a woman with lupusanticoagulant and recurrent fetal loss. Another condition in whichthis therapy can be of benefit is before an operation in patients withantiphospholipid antibodies (ie, lupus anticoagulant [LAC] andanticardiolipin), which are associated with an increased risk ofthrombotic complications.1A 42-year-old man was referred to us because of

thrombocytopenia and prolonged activated partial thromboplastintime (APTT) before an operation for a discal hernia. Physicalexamination, routine blood biochemistry, and urine analysis werenormal. Blood counts showed: haemoglobin 13-7 g/dl, red cell count4 81 x 10/1, reticulocytes 0-9%, white cell count 5-08 x 109(1 withnormal differential count, and thrombocytopenia (platelets45 x 109/1). Bone marrow, including megakaryocytes, was normal.Coagulation studies showed that prolongation of APTT was due toLAC since: (1) APTT was not corrected in a 1:1 mixture withnormal plasma (patient 36-5 s, normal 28-2 s, mixture 34-9 s); (2)kaolin clotting time (KCT)Z was prolonged and not corrected bymixture (patient 117 s, normal 64 s, mixture 98 s); and (3) diluteRussell viper venom test (RVVT)3 was positive (patient 38 s,normal 28-7 s). IgG anticardiolipin antibodies, assayed by ELISA,4were increased (30 U, normal below 10). A direct Coombs test waspositive. Serology for sytemic lupus erythematosus was negative.The patient was considered at increased postoperative risk for

bleeding because of thrombocytopenia, and for thrombosis becauseof antiphospholipid antibodies. Therefore we decided to administerintravenous gammaglobulin (Sandoz) 0-4 g/kg daily for 5 days.After this treatment, LAC activity disappeared (APTT 27-6 s,KCT 72 s) and platelets increased to 150 x 109/1. However,anticardiolipin antibodies remained unchanged. The patient wasoperated on under routine calcium heparin prophylaxis and no

haemorrhagic or thrombotic complications occurred. After 2

months LAC activity (APTT 30-2 s, KCT 102-5 s) and

thrombocytopenia (75 x 10/1) reappeared.Following this observation, we used the same schedule to treat

two other patients who had antiphospholipid antibodies andthrombocytopenia; a 28-year-old woman with systemic lupuserythematosus and history of recurrent abortion and

thrombophlebitis, and a 45-year-old man with epilepsy andprevious thrombophlebitis. However, neither showed any

significant modification of LAC activity, serum level of

anticardiolipin antibodies, or platelet count.The mechanism of action of high-dose intravenous

gammaglobulin in the treatment of immune disorders is poorlyunderstood. Many effects of intravenous gammaglobulin on thefunction of the immune system have been identified, includinginterference with the binding of immune particles to macrophageFc receptors, decreased Fc-receptor-mediated phagocytosis,enhancement of suppressor T-cell function, depression of naturalkiller-cell activity, and lowering of autoantibody titres by anidiotype-anti-idiotype reaction.To test whether the transient inhibition of LAC seen in our first

patients was due to an idiotype-anti-idiotype effect, the followingin-vitro experiment was done.s Patients and control plasmas wereincubated (2 h at 37°C and overnight at 4°C) with saline orincreasing concentrations of gammaglobulin (from O’l 1 to 40 mg/mlfinal concentration) and KCT and RVVT were measured. Noshortening of coagulation times (ie, no inhibition of LAC activityafter incubation with gammaglobulin) was seen in the patient’splasma.Thus our observations indicate that: (1) intravenous

gammaglobulin can reduce LAC activity and increase plateletnumber in some but not all patients with antiphospholipidantibodies; (2) this effect can be clinically worthwhile before anoperation, as well as in the treatment of LAC-associated recurrentabortion; and (3) the inhibitory effect on LAC activity was observedin vivo but not in vitro, suggesting a cell-mediated immunemechanism rather than an idiotype-anti-idiotype interaction. 6

Division of Haematology,Ospedali Riuniti,24100 Bergamo, Italy

TIZIANO BARBUIGUIDO FINAZZIANNA FALANGASERGIO CORTELAZZO

1. Vermylen J, Blockmans D, Spitz B, Deckmyn H. Thrombosis and immune disorders.Clin Haematol 1986; 15: 393-412.

2. Exner T, Rickard A, Kronenberg H. A sensitive test demonstrating lupusanticoagulant and its behavioural pattern. Br J Haematol 1978; 40: 143-51.

3. Thiagarajan P, Pengo V, Shapiro SS. The use of the dilute Russell viper venom timefor the diagnosis of lupus anticoagulant Blood 1986; 68: 869-74.

4. Loizou S, Mc Crea JD, Rudge AC, Reynolds R, Bolyle CC, Harris EN. Measurementof anti-cardiolipin antibodies by an enzyme-linked immunosorbent assay

(ELISA): standardization and quantitation of results Clin Exp Immunol 1985; 62:738-45

5. Sultan Y, Kazathkine M, Maisonneuve P, Nydegger U. Anti-idiotypic suppression ofautoantibodies to factor VIII (antihaemophilic factor) by high dose intravenousgammaglobulin. Lancet 1984 ii: 765-68.

6 Gris JC, Schved JF, Tousch D, Hereil S, Feugeras O Anti-idiotypic antibodiesagainst anti-phospholipid autoantibodies which suppress lupus-like anticoagulantactivity. Nouv Rev Fr Hematol 1988, 30: 143-47.

CLINICAL SPECTRUM OF NEUROLEPTICMALIGNANT SYNDROME

SIR,-Severe parkinsonism, hyperthermia, and autonomic

dysfunction in a patient on a neuroleptic drug suggests neurolepticmalignant syndrome (NMS).1 Failure to recognise and promptlytreat the condition by neuroleptic withdrawal and

dopaminomimetic agents, with or without the muscle relaxantdantrolene, can lead to myonecrosis and acute myoglobinuric renalfailure. 20-30% of cases are fatal. The development of NMS inpatients receiving dopamine antagonists1 or dopamine depletingagents2 and in parkinsonian patients on levodopa "drug holidays"3‘suggests that central dopamine deficiency is responsible. Theextrapyramidal effects and hyperpyrexia point to involvement ofthe terminal fields of dopamine neurons in the striatum andhypothalamus. We report a patient with early NMS, before the

970

onset of hyperthermia, who responded to levodopa and

bromocriptine.A 26-year-old inpatient with schizophrenia was put on

chlorpromazine at doses steadily increasing to 1000 mg daily over 6weeks, but with only a moderate response. He remained psychotic,and on Dec 10,1987, intramuscular pipothiazine (200 mg monthly)was started, with oral procyclidine (10 mg daily). His mental stateimproved but on March 7, after three pipothiazine injections,pronounced parkinsonian effects were noted. This complicationworsened despite a doubling of the dose of procyclidine, which wasstopped after a further 3 days in case it was producing an allergicreaction. On March 12 his temperature was 372°C and there was asustained sinus tachycardia (120/min). The tachycardia persistedand his blood pressure ranged between 115-180 mm Hg systolicand 75-100 mm Hg diastolic. On transfer to the neurology unit onMarch 15, he had a temperature of 37’1°C; there was pronounceddiaphoresis and a sinus tachycardia, but he was normotensive. Hedisplayed profound hypokinesia and bradykinesia, cogwheelrigidity, and a resting tremor. He could shuffle only a few stepsbefore postural instability caused him to fall. An infection screenwas negative and his creatinine phosphokinase (CPK) was 1144IU/1 (normal 10-170).He was immediately put on levodopa 100 mg/benserazide 10 mg

(’Sinemet-110’) four times daily, the doses being increased to 200mg/75 mg after 2 days when it was clear that his mental state had notdeteriorated. Over the following week, the autonomic disturbanceand mild fever settled and the parkinsonian syndrome graduallyimproved. Bromocriptine 2-5 mg twice daily was added 8 days afterlevodopa had been started but did not seem to accelerate the rate ofimprovement and was discontinued 14 days later because of emesis.After 6 weeks of treatment, all parkinsonian features had

disappeared and levodopa was successfully withdrawn over theensuing 3 weeks.NMS was confirmed by the raised serum CPK activity. Support

for this diagnosis comes from the response to phenothiazinewithdrawal and dopaminomimetic therapy. The features are notconsistent with an extrapyramidal drug reaction, catatonia,malignant hyperthermia, heatstroke, or central anticholinergicsyndrome. This was an early case of NMS in which, had treatmentbeen delayed, hyperpyrexia would have developed-providing alesson for psychiatrist and neurologist alike. Any patient receivingneuroleptic medication who has a severe extrapyramidal reactionshould be closely observed for autonomic dysfunction and low-grade fever; the CPK should be measured early in the course of suchan illness. More prompt treatment with neuroleptic withdrawal andlevodopa, with or without bromocriptine, may obviate the need forintravenous dantrolene and might also reduce the risk of fataloutcome.

_ __ _

Departments of Neurologyand Psychiatry,

Crumpsall Hospital,Manchester M8 6RB

C. E. CLARKED. SHANDG. M. YUILLM. H. P. GREEN

1. Guzé BH, Baxter LR. Neuroleptic malignant syndrome. N Engl J Med 1985; 313:163-66

2. Burke RE, Fahn S, Mayeux R, Weinberg H, Louis K, Willner JH. Neurolepticmalignant syndrome caused by dopamine-depleting drugs in a patient withHuntington disease. Neurology 1981; 31: 1022-26.

3. Friedman JH, Feinberg SS, Feldman RG A neuroleptic malignant-like syndromedue to L-dopa withdrawal. Ann Neurol 1984; 16: 126-27

4. Sechi G, Tanda F, Mutani R. Fatal hyperpyrexia after withdrawal of L-dopaNeurology 1984; 34: 249-51.

MICROALBUMINURIA AND POSTURE

SIR,-Dr Yudkin and colleagues (Sept 3, p 530) report thatmicroalbuminuria is a predictor of vascular disease in non-diabeticsubjects. They do not describe how they collected the urine samples(ie, period of urine collection, position of subject). There is nogeneral agreement about the collection of urine and clinic staff haveused different procedures to estimate urinary albumin excretionrate (AER). Collection of urine over 24 hours or longer may beinconvenient and is often not practical for screening or monitoringprogrammes for microalbuminuria in a general clinic.1,2 DaytimeAER, the albumin concentration of the first morning urinespecimen, or the albumin/creatinine ratio of random daytime urine

EFFECT OF UPRIGHT POSTURE ON URINARY ALBUMIN EXCRETION

RATE (AER) AND ALBUMIN/CREATININE RATIO IN 17 DIABETICPATIENTS WITHOUT CLINICAL PROTEINURIA*

i i

*Data are shown as median (range). tp=0 017, tp=0 011, upright Msupme.

specimens are often used as indicators of early diabetic kidneydisease. Posture (supine or upright), time of day, and exercise allaffect urinary albumin excretion. The effect of physical activity canbe reduced by avoiding strenuous exercise early in the day.However, little is known about how much AER is affected bypostural change.We assessed the effect of posture on AER and the albumin!

creatinine ratio in 7 men and 10 women (aged 45-65 years) whowere ’Albustix’-negative and had diabetes. Informed consent wasobtained. Subjects with infection of the urinary tract were excluded.Following 60 minutes of rest in the supine position, 2 h urinesamples were collected from each subject for supine resting orupright (static) positions, in random order. Urinary albuminwas measured by radioimmunoassay3 and creatinine by spectro-photometry. Subjects were divided into 2 groups according to anAER when supine of less than 20 ng/min or 20 Ilg/min or over.Statistical analysis was done with Wilcoxon’s signed-rank test orSpearman rank correlation coefficient. The table shows the resultsfor the 2 groups.The AER and albumin/creatinine ratio was significantly higher

for the upright position than for the supine position in the groupwith an AER of 20 pg/min or over, whereas the values wereunchanged in those with an AER of under 20 ug/min. Of the 8subjects with a supine AER of under 20 Ilg/min the AER increasedabove 20 ng/min with the upright position in 2 (37-5 and 22 9pg/min, respectively), and the albumin/creatinine ratio exceeded2-0 mg/mmoP in 3 and 2-6 mg/mmol4 in 1. When the cut-off is anAER of 20 ug/min with the patient upright, 2 of 10

microalbuminuric subjects were normoalbuminuric when supine.Upright-posture-induced changes in the AER and the albuminlcreatinine ratio varied from 10 to 486% and from 10 to 413%,respectively, and the values correlated significantly (r=09191,p < 0-001).

If the optimum cut-off value for screening for microalbuminuriais an AER of 20 or 30 Ilg/min or over4 or an albumin/creatinine ratioof over 2-6 mg/mmol,4 the risk of overestimation or

underestimation, caused by the subject’s posture, would probablybe low. Nevertheless, a standardised position would be desirable,particularly for follow-up studies, since in individuals the changesin both AER and albumin/creatinine ratio attributable to the

upright posture were inconsistent and variable. Use of the

albumin/creatinine ratio might not help to minimise or reduce theeffect of postural change.

Departments of Metabolic Diseases and Nutrition,University of Dusseldorf,4000 Dusseldorf, FRG

Third Department of Internal Medicine,Hirosaki University School of Medicine,Hirosaki 036, Japan

TSUNEHARU BABA

SHUYA MURABAYASHITSUKIKO TOMIYAMAKAZUO TAKEBE

1. Gatling W, Knight C, Mullee A, Hill RD. Microalbuminuria in diabetes, a populanonstudy of the prevalence and an assessment of three screening tests Diabetic Med1988; 5: 343-47.

2. Hitchison AS, Paterson KR. Collecting urine for microalbumin assay Diabetic Med1988, 5: 527-32.

3. Miles DW, Mogensen CE, Gundersen HJG. Radioimmunoassay for urine albuminusing a single antibody. Scand J Clin Lab Invest 1979; 26: 5-11

4. Cohen DL, Close CF, Viberti GC. The variability of overnight urinary albuminexcretion in insulin-dependent diabetic and normal subjects. Diabetic Med 1987; 4:437-40.