Protection of low-density lipoprotein from oxidation by 3,4-dihydroxyphenylethanol

under such circumstances?’ If needed psychiatric provided, what will happen to the untreated prisoner?’ Alternatively, if treatment is given, albeit involuntarily, to restore competence for execution, unsettled constitutional, in addition to ethical, issues may be raised. The main mission of psychiatrists, and physicians generally, is to serve as healers, rather than as cogs in the machine of the state.’ The issue of treating patients incompetent for execution places psychiatrists in a seeming lose-lose situation: it is difficult to abstain from treating the needy patient, yet the eventual result of successful treatment is death. There remains a salient need for guidelines that may better enable psychiatrists to navigate through the choppy, unsettled waters of participation in capital be

given

care

is

not

punishment. Leo Uzych Canterbury Drive, Wallingford,

103

PA 19086, USA

1

Council on Ethical and Judicial Affairs. Physician participation in capital punishment. JAMA 1993; 270: 365-68.

2 3

Editorial. Doctors and death row. Lancet 1993; 341: 209-10. Heilbrun K, Radelet ML, Dvoskin J. The debate on treating individuals incompetent for execution. Am J Psychiatry 1992; 149: 596-605. Skolnick AA. Health professionals oppose rules mandating participation in executions. JAMA 1993; 269: 721-23. Board of Trustees. Position statement on medical participation in capital punishment. Am J Psychiatry 1980; 137: 1487.

4 5

SiR-Your editorial on US physicians and the death penalty touched very briefly on psychiatrists. For the sake of good order it should be noted that the World Psychiatric Association (WPA) at its general assembly in Athens, Greece, October, 1989, unanimously adopted a resolution proposed by its largest member association, the American Psychiatric Association, which obliged all the WPA members to refrain-on ethical grounds-from participation in the execution of death penalty. The task to be avoided was to declare a person as being "fit" for execution (whatsoever this might mean). Hopefully, this agreement between the roughly 70 member associations all over the world will help to enlighten psychiatrists still "seeking clarification". Fini

Schulsinger

Institute of Preventive Medicine, 1399

Malnutrition in

Copenhagen K,

displaced

Denmark

persons in Zaire

SiR-Since September, 1992, ethnic conflicts in the Shaba province of Zaire have forced hundreds of thousands of people of Kasaian origin to flee back to their home province. Most of them had lived in Shaba for several decades. In Kasai province, they found asylum either in rural settings, small towns, or in peri-urban areas. Relief organisations set up transit camps at arrival, but no aid was provided for resettlement. Therefore, displaced people had to rely mainly on the resident population for support. There was some risk that sharing had greatly depleted food stocks and that malnutrition and mortality figures had increased. To assess the situation, a nutrition and mortality survey was done in the villages around Kabinda town (eastern Kasai province, population 150 000) from Jan 11-20, 1994. With a two-stage cluster sampling method, we randomly selected 935 children aged 6-59 months in 30 clusters; 132 (14%) were displaced persons. A case of malnutrition was defined as a child with a weight-for-height index less than -2 Z score, or with bilateral foot oedema. Prevalence of malnutrition was 25% among displaced children and 6-2%

1296

among resident children

(relative risk [RR] 40; 95% CI

2-7-6-0). each head of that had occurred household on number and cause of deaths in the family in the past 6 months. Of 4146 people surveyed (638 households), 768 (19%) were displaced people, of whom 53% were sharing a resident’s household. The reported 6 month mortality rate was 76 per 1000 for the displaced group and 15 per 1000 for the resident group (RR 51; 95% CI 3-6-7-4). Measles was the leading cause of death among residents (25-5% of all deaths), whereas protein-energy-malnutrition was the leading cause of death among displaced persons (54-1% of total death). In similar conditions, malnutrition accounted for 40% of the total deaths among Dinkas in southern Sudan in April, 1993,’ and for 41-6% of total deaths in Somalia in 1992.2 The data from Kasai reveal higher malnutrition and mortality rates in the displaced group than in the resident population. These figures may soon worsen since most displaced populations are not living in camps, but are regarded as already resettled in rural areas. If one wants to avoid community conflict in this sensitive area of Zaire, international aid should be directed to displaced persons wishing to settle in Kasai as well as to residents. Particular attention should be paid to those who are relocated in periurban areas where housing, sanitary, and nutritional conditions are poor and where no aid is being given. Access to some of the displaced populations is difficult, and awareness of international agencies should be raised to avoid emergence of a new "terra incognita". Finally, a plan of action to aid populations who wish to resettle in Kasai should be designed and implemented rapidly.

Mortality

was

investigated by interviewing

Marie Laurence Lambert, Vincent Brown, Florence Isabelle Voiret

Villagi,

Epicentre, 75011 Paris, France; and Médecins Sans Frontières, Zaire 1

2

Quillet C. A nutritional and mortality survey, Wayjock and Liethnom counties, Southern Sudan, April, 1993. Report for Médecins Sans Frontières, 1993. Manoncourt S, Doppler B, Enten F, Elmi Nur A, Osman A, Vial P. Public health consequences of the civil war in Somalia, April, 1992. Lancet 1992; 340: 176-77.

Protection of low-density lipoprotein from oxidation by 3,4-dihydroxyphenylethanol SiR-There is increasing evidence that oxidative modification of low-density lipoprotein (LDL) is important in the pathogenesis of atherosclerosis.’ Several studies show that antioxidants such as probucol and butylated hydroxytoluene can inhibit development of atherosclerotic lesions in Watanabe and cholesterol-fed rabbits.’ Furthermore, dietary supplementation with vitamin E, a lipophilic vitamin with antioxidant properties, is associated with a reduced risk of coronary artery disease in human beings.2 In addition, the presence of phenolic components of red wine with antioxidant properties is proposed as an explanation for the French paradox (the compatibility of a high-fat diet with a low incidence of coronary

atherosclerosis).3 Olive oil

component of the Mediterranean diet, is rich in acid known to lower plasma LDL cholesterol and to reduce susceptibility of LDL to oxidative modification compared with diets rich in polyunsaturated fats.’ Oleic acid, however, may not be the only component of olive oil protecting LDL from oxidation; in fact, olive oil contains a number of antioxidants. We studied the effect of

oleate,

a

a

fatty

3,4-dihydroxyphenylethanol (DPE), from olive oil,

on

a

compound purified

the in-vitro oxidative modification of LDL.

also evaluated. LDL was incubated at the final concentration of 50 ng apo B/mL phosphate-buffered saline with Cu2+ 20 jumoI/L at 25°C. The oxidative modification of LDL was evaluated by monitoring conjugated diene formation at 234 nm. Lag time of oxidation was almost doubled in the presence of DPE (from 27 to 53 min, maximum diene production was not affected p<001), (bottom figure). Together these data suggest that DPE can retard oxidation of LDL probably by two mechanisms: by directly protecting LDL from oxidation, and by interfering with cell-mediated LDL oxidation. Further studies are underway to verify whether dietary enrichment with DPE as well as other antioxidants from olive oil could act as antiatherosclerotic compounds by preventing LDL oxidation. This work was supported, in part, by the Progetto Finalizzato Invecchiamento (publication 943406). We thank Maddalena Marazzini for editorial assistance.

Paola

1

Paola Roma, Claudio Galli, Alberico L Catapano Pharmacological Sciences, University of Milan, 20133 Milan, Italy

Grignaffini,

Institute of

Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL. cholesterol: modifications of low density lipoprotein that increase its atherogenicity. N Engl J Med 1989; 320: 915. Stampfer MJ, Hennekens CH, Manson JE, Colditz GA, Rosner B, Willett WC. Vitamin E consumption and the risk of coronary disease

Beyond

2

3

4

Time (min)

Figure: Effect of DPE on biological (top) and chemical (bottom) oxidation of LDL For top figure, 500 L of thiobarbituric acid 0.67% and 500 uL of trichloroacetic acid 20% were added to 250 uL of minimal essential culture medium. Samples were heated at 100°C for 1 h before reading absorbance at 532 nm. Data are expressed as % of control (LDL incubated in same conditions without DPE). For bottom figure, LDL was preincubated with or without DPE (4 mmol/L) for 1 h at 37°C; unbound drug was removed by gel filtration and LDL diluted to the final concentration of 50 ug apo B/mL in phosphatebuffered saline containing Cu2+ 5 )jmoi/L. Time-dependent formation of conjugated dienes was evaluated as index of oxidation. Data are means of triplicate determinations that did not differ by more than 5%.

Biological oxidation of LDL was caried out under sterile conditions by incubating LDL (0-1 mg apo B/mL) with EAhy-926 cells (a permanent cell line with the characteristics of human endothelial cells) and Cu’ 5 4mol/L for 24 h in the presence of various concentrations of DPE (range 0-5-10 )JLmol/L). Peroxidation of LDL lipids was evaluated by monitoring the formation of thiobarbituricsubstances.5 Under these acid-reactive experimental conditions DPE 5 irnoI/L fully inhibited LDL oxidation (top figure). To verify whether DPE acts on lipoproteins, on cells, or both, we separately preincubated LDL (1 h) and cells (18 h) with different concentrations of DPE. LDL and cells not preincubated were used as a control. Unbound DPE was removed from LDL by gel filtration and from cells by washing with phosphate-buffered saline. Fresh medium was then added and biological oxidation of LDL evaluated at different times. Pretreatment of either LDL or cells with DPE reduced the extent of oxidation. In both instances, however, the concentration of DPE required to reduce oxidation was higher than the concentration shown to be effective in the co-incubation system (4 mmol/L and 50 umol/L, respectively, vs 5 Ilmol/L) suggesting that the DPE can act in both LDL and cells (data not shown). Chemical (non cell-mediated) oxidation of LDL was

5

in women. N Engl J Med 1993; 20: 328. Frankel NE, Kanner J, German JB, Parks E, Kinsella JE. Inhibition of oxidation of human low-density lipoprotein by phenolic substances in red wine. Lancet 1993; 341: 454-57. Reaven P, Parthasarathy S, Grasse BJ, Miller E, Steinberg D, Witzum J. Effects of oleate-rich and linoleate-rich diets on the susceptibility of low density lipoprotein to oxidative modification in mildly hypercholesterolemic subjects. J Clin Invest 1993; 91: 668. Negre-Salvayre A, Paillous N, Dousset N, Bascoul J, Salvayre R. Wavelength dependence of photoinduced peroxidation and cytotoxicity of LDL. Photochem Photobiol 1992; 55: 197.

Neonatal detection of

aspartylglycosaminuria

SiR-Recent advances in the treatment of Gaucher’s disease’ and murine mucopolysaccharidosis VIP have boosted hopes of successful treatment of lysosomal storage diseases. In many of them, the affected infants appear normal at birth and clinical symptoms may develop over several years. This symptomless period provides the opportunity for therapeutic approaches. Aspartylglycosaminuria (AGU) is a common lysosomal storage disease with a high prevalence in Finland, where it is the third most frequent genetic cause of mental retardation.3 We believe that a specific treatment for AGU will be developed and so we have investigated whether the disease can be diagnosed neonatally by a glycosylasparaginase assay of serum samples. Umbilical cord serum specimens are already collected from all newborn babies in Finland because of a national screening programme for congenital hypothyroidism. We have applied the fluorometric glycosylasparaginase assay4 to umbilical cord serum samples by use of a 96-well microplate and microplate fluorometer. The mean glycosylasparaginase activity in 6564 umbilical serum samples was 13-7 (SD 42; range 4-3-64) mU/L. In one sample from an apparently normal full-term baby girl no glycosylasparaginase activity (<0-1 1 mU/L) could be detected. She was found to have a high urinary excretion of aspartylglucosamine and the diagnosis of the Finnish-type AGU was confirmed by DNA analysis. This report of the diagnosis of AGU in a newborn infant with no known family history of AGU encourages the use of fluorometric glycosylasparaginase assay in neonatal of the disease. Children with AGU have been 5-5 screening 1297