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Associated with this haplotype was a high frequency ofpositive skin prick tests to mixed grass pollens or the housedust mite (Dermatophagoides pteronyssinus) and higher levelsof both total IgE and IgE specifically directed against grasspollen. The association with HLA-B 12, short time to relapsein HLA-B12 positive patients treated with cyclo-phosphamide, and a high incidence of atopy in SRNS werefurther confirmed by the same group of workers.7 Mostrecently, Meadow et al., in clinical and immunologicalstudies, observed a relation between SRNS and standardatopic disorders although not for HLA-B12, nor betweenatopy and tendency to relapse.8,9 These clinical observationsare unfortunately not supported by evidence of reaginicantibody activity. Total serum IgE levels are known to beraised in a quarter of children with SRNS independent ofstate of relapse or remission. 10, 11 The report by Meadow et al.of a fall in IgE in 4 out of 9 children, from grossly raised tonormal serum levels independent of clinical state, confirmsprevious observations. Furthermore, early reports that IgE isdetectable in the glomeruli have not been substantiated.9,12-15Immediate or type-I hypersensitivity reactions are of

considerable theoretical and practical importance. If they arepart of the pathogenesis of SRNS, there is the possibility of acure. Desensitisation to the specific allergen implicated hasmet with only limited success, restricted to individual casereports in patients with nephrotic syndrome. 16,17Furthermore, the beneficial effect from pollen desensitisationis inconclusive, and only in carefully selected asthmatics havecontrolled trials of desensitisation to house dust and housedust mite resulted in clinical improvement. 18,19 Thetreatment is painful and has side-effects. Equallydisappointing has been the investigation of hypersensitivityto food products. Contrary to previous reports, Meadow et al.found that allergen avoidance made no appreciable-differenceto the frequency of relapse in children with SRNS.Attempts to block the release of biochemical mediators,

produced perhaps by interaction of reaginic antibody andmast cells, distal to the kidney and thus responsible forincrease in glomerular permeability, have also been

disappointing to date. Disodium cromoglycate andabsorbable analogues are ineffective in preventingrelapse.8,20,21

7 Trompeter RS, Barratt TM, Kay R, Turner MW, Soothill JF. HLA atopy andcyclophosphamide in steroid-responsive childhood nephrotic syndrome. Kidney Int1980; 17: 113-17.

8. Meadow SR, Sarsfield JK. Steroid-responsive nephrotic syndrome and allergy. Clinicalstudies. Arch Dis Childh 1981; 56: 509-16.

9. Meadow SR, Sarsfield JK, Scott DG, Rajah SM. Steroid-responsive nephroticsyndrome and allergy: immunological studies. Arch Dis Childh 1981; 56: 517-24.

10. Groshong T, Mendelson L, Mendoza S, Bazaralm M, Hamburger R, Tune B. SerumIgE m patients with minimal-change nephrotic syndrome. J Pediat 1973; 83:767-71.

11. Lagrue G, Wirquin E, Moretti JP, Hirbec G, Lagrue R, Galle P. Etude des IgE seriquedans les nephrophathies glomerulaires. J Urol Nephrol 1974; 80: 795-801.

12. Gerber MA, Paronetto F. IgE in glomeruli of patients and nephrotic syndrome. Lancet1971; i: 1097-99.

13. Lewis EJ, Kallen RS, Rowe DS. Glomerular localisation of lgE in lipoid nephrosis.Lancet 1973; i: 1395.

14. Roy LP, Westberg NG, Michael AF. Nephrotic syndrome-no evidence for role of IgE.Clin Exp Immunol 1973; 13: 553-59.

15 Robertson MR, Potter EV, Roberts ML, Patterson R. Immunoglobulin E in renaldisease. Nephron 1976; 16: 535-42.

16. Williamson DAS. Nephrotic syndrome associated with inhaled antigens. Lancet 1970;i: 778.

17. Richards W, Olsen D, Church JA. Improvement of idiopathic nephrotic syndromefollowing allergy therapy. Ann Allergy 1977; 39: 332-34.

18. Aas K. Hyposensitisation in house dust allergy asthma. Acta Paediatr Scand 1971, 60:264-68.

19. Warner JO, Price JF, Soothill JF, Hey EN. Controlled trial of hyposensitisation toDermatophagoides pteronyssinus in children with asthma. Lancet 1978; ii: 912-15.

20 Trompeter RS, Thomson PD, Barratt TM, Soothill JF. Controlled trial of disodiumcromoglycate in prevention of relapse of steroid responsive nephrotic syndrome ofchildhood. Arch Dis Childh 1978; 53: 430-32.

21. Bluett NH, Chantler C, Hughes DT. Failure of doxantrazole in steroid responsivenephrotic syndrome. Lancet 1977; i: 809.

Atopy implies a tendency of the individual to synthesiseIgE antibody after contact with one or more environmentalallergens. The causative allergens, when known, are usuallywidespread in the environment, so host variables, in partgenetically determined, must underlie the state of atopy.Although there has been little success so far in demonstratinga simple cause and effect relation between atopy, tissue type,and vulnerability to SRNS, the hypothesis remains

challenging. Further research must address the questionwhether the HLA antigen, or indeed the predisposition toatopy, is related to the characteristic determining relapserather than to the syndrome itself.

HOT FLUSHES

ONE of the fruits of the French Revolution was the dis-

covery of ménespausie (cessation of menses) as a clinicalsyndrome. Thenceforth, belief in the "critical time"

("climacteric"), offered a convenient explanation for all

megrims and miasms coinciding with the "change of life". iWood2 has lately analysed twenty symptoms commonly attri-buted to the menopause and found only one specificsymptom-hot flushes. Menopausal hot flushes were

probably first described (in the dowager Lady Rieden) inGermany by Heister in 1712.3Hot flushes begin shortly after ovarian failure, whether it is

primary, due to menopause or castration,4 or secondary, dueto pituitary insufficiency. 5 They are precipitated byemotional upset, hot drinks and meals, a warm room or bed,and alcohol. The classic description by Glaevecke4 can hardlybe bettered: "The hot flush starts with a kind of aura, with adiscomfort in the lower abdomen or epigastrium, often with achill, followed quickly by an intense hot feeling ascendingtowards the head. The affected skin, mainly the face, becomesred. This is accompanied by anxiety and unease in theprecordium. After a short interval, a variable amount of sweatbreaks out. A feeling of exhaustion ends the attack."The cause of hot flushes (or flashes, as some Americans call

them) is unknown. Although ovarian extracts (and later,oestrogens) have been regarded as specific treatment since thebeginning of the century,6 blood oestrogen levels are notdirectly related to hot flushes’ and the oestrogen dogma hasbeen severely shaken by Mulley and Mitchell,8 whose papercaused a lot of blushing and cold sweat in some readers sincethe issue is still emotional and apt to raise the temperature.

Lately, various endocrine epiphenomena have been

reported with hot flushes-for instance, rising blood levels ofluteinising hormone;9-11 dehydroepiandrosterone, andro-

1. Wilbush J. What’s in a name? Some linguistic aspects of the climacteric. Maturitas1981; 3: 1-9.

2. Wood C. Menopausal myths. Med J Aust 1979; i: 496-99.3. Campbell H. Flushing and morbid blushing. London: HK Lewis, 1890.4. Glaevecke. Körperliche und geistige Veränderungen im weiblichen Körper nach

künstlichem Verluste der Ovarien einerseits und des Uterus andererseits Arch

Gynaekol (Berlin) 1889; 35: 1-88.5. Meldrum DR, Erlik Y, Lu JKH, Judd HL Objectively recorded hot flushes in patients

with pituitary insufficiency. J Clin Endocr Metab 1981; 52: 684-87.6. Novak E. Disturbances of the menopause. In: Curtis AH, ed. Obstetrics and

gynecology, vol. 3. Philadelphia: Saunders, 1933: 157.7. Hutton JD, Jacobs HS, Murray MAF, James VHT. Relation between plasma oestrone

and ostradiol and climacteric symptoms Lancet 1978; i: 678-81.8. Mulley G, Mitchell JRA. Menopausal flushing: Does oestrogen therapy make sense?

Lancet 1976; i: 1397-99.9. Casper RF, Yen SSC, Wilkes MM. Menopausal flushes: A neuroendocrine link with

pulsatile luteinizing hormone secretion. Science 1979; 205: 823-25.10. Meldrum DR, Tataryn IV, Frumar AM, Erlik Y, Lu JKH, Judd HL. Gonadotropins,

estrogens, and adrenal steroids during the menopausal hot flash. J Clin EndocrMetab 1980; 50: 685-89.

11. Ravnikar V, Elkind-Hirsch K, Schiff I. The association between LHRH, LH, andvasomotor flushes. Proceedings of the 62nd Annual Meeting of the AmericanEndocrine Societv, 1981 160 (abstr. no. 310).

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stenedione, cortisol, and progesterone; 10 neurotensinand adrenaline;l2 and luteinising-hormone releasing factor. 11 lThe most consistent change (though disputedl2) is theincrease in blood luteinising hormone but, unfortunately,this and many other changes do not precede but follow theonset of the hot flush.1O The latest theory of hot flushespostulates an involvement of endogenous opioids, sincenaloxone reduced the number of hot flushes.13 This theoryhas serious flaws. Firstly, it is based on a wrong analogy-comparison of alcohol-precipitated flushing in chlorpro-pamide users (which is said to be alleviated by naloxone14)with menopausal hot flushes. Chlorpropamide flush is notaccompanied by sweating, and people who have experiencedboth types regard them as different.15 Alcohol-

chlorpropamide flushing is a disulfiram-like reactionassociated with raised blood acetaldehydel6 and may have agenetic basis.15 Secondly, without objective detection of hotflushes-for example, by plethysmography I 7 and bymeasurement of skin temperature and conductance5, 18—evaluation of any therapy is inconclusive. Moreover, theplacebo effect in hot flushes is pronounced6,8 and in one studymore than 75% of women with severe hot flushes were"cured" by the laboratory environment only.l’ Thirdly, theeffect of naloxone has been inconsistent and is based on obser-vation in six women only; one of these became worse afternaloxone, one became better on placebo, and one or two hadno change. 13,19Menopausal women are commonly oversensitive to heat,

feeling warm when other members of their family do not,dressing more lightly than before the menopause, and

becoming uncomfortable or exhausted in hot weather. 3,17They may complain of hot waves passing over the whole bodyand some are plagued by profuse sweating at night,necessitating several changes of night clothes. Tataryn et al.17observed that, during hot flushes, the finger temperature rosewhile the core temperature actually fell, presumably owing toa sudden downward setting of the central thermostat in thehypothalamus. Since heat sensitivity arises even in

menopausal women who do not have hot flushes,17 perhapsmore attention should be paid to dysfunction of

thermoregulation in the menopause.

EPILEPSY AND VIOLENCE

EXPERTS on epilepsy from four countries have reported astudy in which 5400 epileptic patients were screened to findcases with aggressive phenomena during seizures. 1

12. Kronenberg F, Carraway R, Côté LJ, Linkie DM, Crawshaw LI, Downey JA. Changesin thermoregulation, immunreactive neurotensin, catecholamines and LH duringmenopausal hot flashes. Proceedings of the 62nd Annual Meeting of the AmericanEndocrine Society, 1981: 141 (abstr. no. 236)

13. Lightman SL, Jacobs HS, Maguire AK, McGarrick G, Jeffcoate SL. Climactericflushing: Clinical and endocrine response to infusion of naloxone. Br J ObstetGynaecol 1981; 88: 919-24.

14. Leslie RDG, Pyke DA, Stubbs WA. Sensitivity to enkephalin as a cause of non-insulindependent diabetes. Lancet 1979; i: 341-43.

15. Leslie RDG, Pyke DA. Chlorpropamide-alcohol flushing: a dominantly inherited traitassociated with diabetes. Br Med J 1978; ii: 1519-21.

16. Jerntorp P, Almér L-O, Melander A. Is the blood chlorpropamide concentrationcritical in chlorpropamide alcohol flush? Lancet 1981; i: 165-66.

17. Ginsburg J, Swinhoe J, O’Reilly B. Cardiovascular responses during the menopausalhot flush. Br J Obstet Gynaecol 1981; 88: 925-30.

18. Tataryn IV, Lomax P, Meldrum DR, Bajorek JG, Chesarek W, Judd HL. Objectivetechniques for the assessment of postmenopausal hot flashes. Obstet Gynecol 1980;57: 340-44.

19. Lightman SL, Jacobs HS. Naloxone: non-steroidal treatment for postmenopausalflushing? Lancet 1979; ii· 1071.

1. Delgado-Escueta AV, Mattson RH, King L et al. The nature of aggression duringepileptic seizures. N Engl J Med 1981, 305: 711-16.

Eventually 19 were found, but even this small number wasreduced to 13 because of diagnostic disagreements. Video-tapes were then made of the patients’ seizures and the tapeswere rated by the panel of epileptologists. Good agreementwas obtained among the panel and they rated 7 patients asexhibiting significant aggression during their seizures. Theaggression varied from shouting of insults and spitting tokarate chops and smashing of property, 5 of the 7 patientsbeing rated as showing an angry mood during the seizure. Inother words, this study has neatly confirmed the clinical viewthat aggressive phenomena, including quite destructive acts,can arise during epileptic seizures but that such aggression israre. An interesting aspect of this study is that it included 2cases in which the patient became aggressive when restrained3 or 4 minutes after the seizure was over-a phase whenpatients are known to be irritable and during which tragediescan happen.2 Unfortunately it is not clear whether patientswere routinely provoked by touching or moving during thepost-ictal phase and whether aggression beginning later (sayan hour after the seizure) was included. The research seems tohave been stimulated by an increasing number of cases in theUnited States in which "epilepsy" is used as a defence againsta murder charge. As the international group points out, thereare in fact very few published reports of homicidal behaviourduring the phases of altered consciousness of epilepticseizures. In the United Kingdom Gunn and Fenton3described 2 cases, and Gunn2 another.Part of the American medicolegal problem seems to be that

the bogey of the "epileptic equivalent" lives on. That is to saythere is still a readiness to attribute impulsive violence, in anindividual with a minor or non-specific electroencephalo-graphic abnormality, to epilepsy, with the speculation thatthe only manifestation of epilepsy in the individual concernedis an occasional outburst of impulsive violence. This is ofcourse a circular argument. The only tenable clinical positionin the present state of knowledge is to insist that epilepsyshould be diagnosed only when there is definite evidence ofaltered consciousness or stereotyped motor or sensoryphenomena-preferably coinciding with laboratory evidenceof electrical dysrhythmia in the brain. If other behaviour,such as a criminal assault, is to be attributed to epilepsy thenthe assault itself should meet established criteria for epilepsyand, best of all, arise in an individual in whom epilepsy can bediagnosed confidently from phenomena other than theincident in question. Post-ictal irritability, confusion, andoccasionally psychosis may also lead to assaultative

behaviour, but again the evidence for the epilepsy and the,alleged ictus preceding the assault should be rigorous.Some workers are impatient with this conservative

approach to the relation between epilepsy and violence. Markand Ervin4 talk of episodic dyscontrol; Pincus,5 in a signededitorial commenting on the paper from the internationalgroup, is worried by the small number of cases amassed afterso extensive a search, wonders if the entry criteria to the studywere too strict, and raises the possibility that epileptics have atendency to violence between seizures. What motivates theenthusiasm for associating violence and epilepsy? Theanswer is complex but important factors are the legalconsequences of successfully pleading epilepsy as a deter-minant of violence, and therapeutics. In the U.S.A. someStates still have capital punishment and a successful plea of

2. Gunn J. Epileptic homicide: a case report. Br J Psychiatry 1978; 132: 510-13.3. Gunn J, Fenton G. Epilepsy, automatism, and crime. Lancet 1971, i: 1173-764. Mark VH, Ervin FR. Violence and the brain. New York: Harper and Row, 19705. Pincus J. Violence and epilepsy. N Engl J Med 1981; 305: 696-98