Continuous subcutaneous apomorphine as replacement for levodopa in severe parkinsonian patients after surgery

859

PATIENTS’ DETAILS AND LABORATORY FINDINGS

evidence of HIV-1 transmission. These results are discordant with those for patient 6 in Ariyoshi’s report. It is noteworthy that of these 12 cases, 10 had CD4 counts higher than 500/ul, and of these 6 had CD4 count over 700/µl. We and others have shown that high plasma and cell viral loads are closely correlated with lower CD4 counts.1,2 Moreover, results of the European Collaborative Study are in accord with our observations: in 78 mothers whose CD4 counts were greater than 700/µl, 73 did not transmit HIV to their infants.3 Therefore, Ariyoshi’s findings should be regarded as rare.

Other factors

Means

(SD) shown

concentrations did not differ between the two groups. Therefore we conclude that the difference can be ascribed to structural features of LDL. The relation between the lag time and various variables was tested. The variables were included in a forward and backward stepwise multiple regression analysis with the lag time as the dependent variable. Only LDL size affected lag time, with small LDL being more resistant to oxidation (r=—138 [SD 3-8 p < 0-002). When LDL size was taken into account, LDL oxidation lag time was even more significantly inversely correlated with the severity of coronary atherosclerosis (r = — 18-0 [4’6], p < 0,001). To assess the relation between graft atherosclerosis and the susceptibility of LDL to oxidation, an index was calculated. For each patient the number of grafts with more than 50% stenosis was divided by the total number of inserted grafts. For patients having a higher LDL index, we measured a shorter LDL oxidation lag time (Spearman rank correlation coefficient r= -040, p=0’04), indicating that graft atherosclerosis is also related to an enhanced sensitivity of LDL to oxidation. Our data suggest that oxidative modification of LDL is related to the development and/or progression of atherosclerosis in both grafts and coronary arteries. Division of Biopharmaceutics, Centre for Biopharmaceutical Sciences

YOLANDA B. DE RIJKE

Sylvius Laboratory, University of Leiden,

CARLA J.M. VOGELEZANG THEO J.C. VAN BERKEL

2300 RA Leiden, Netherlands, Gaubius Laboratory, IVVO-TNO, Leiden, and Department of Cardiology, University Hospital of Leiden

HANS M. G. PRINCEN HARRIETTE F. VERWEY ARNOUD VAN DER LAARSE ALBERT V. G. BRUSCHKE

1.

2.

Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL. Beyond cholesterol: modifications of low-density lipoprotein that increase its atherogenicity N Engl J Med 1989; 320: 915-24. Princen HMG, van Poppel G, Vogelezang C, Buytenhek R, Kok FJ Supplementation with vitamin E but not &bgr;-carotene in vivo protects low density lipoprotein from lipid peroxidation in vitro: effect of cigarette smoking A rterioscler osis Thromb 1992; 15: 554-62.

Viral load and mother-to-infant HIV transmission SIR,-Dr Ariyoshi and colleagues (Aug 15, p 435) report the contribution of maternal viral load to HIV-1 transmission. In 6 cases they showed no association between maternal plasma and cell viral load and outcome of transmission to the child. In 2 cases, mothers had virus in the plasma and no transmission occurred; in 1 case the mother had no detectable viraemia and HIV status of the infant was positive. We quantified plasma and cell virus load in 20 women, at least three times during pregnancy, with the French ANRS consensus technique,’ and investigated HIV status of newborn babies with conventional techniques (cocultures and

PCR). As did Ariyoshi et al, we showed that high plasma and cell virus loads do not inevitably lead to mother-to-infant transmission. We found evidence of HIV infection in 2 newborn babies from 3 mothers with virus detectable in the plasma and in 5 newborn babies from 8 mothers with cell load of greater than 100 TCID50 per 106 peripheral blood mononuclear cells (PBMC). However, 12 cases with no detectable viral plasma load and low level of viral cell load (< 100 TCIDso per 106 PBMC), none showed

are

probably involved in the contamination of the

infant, such as emergence of maternal virulent fast-replicating HIV variants (either syncytium or non-syncytium inducing)selective transmission of maternal variants,5 or co-infection with other mibrobial agents.6 Although high levels of maternal viral load were clearly not always associated with transmission to infant, there is some evidence that a high level of maternal viraemia is associated with high risk of transmission. Indeed, very low levels or absence of maternal viraemia are associated with lower risk of transmission. We think that these factors should be considered by the mother when the outcome of the pregnancy is discussed.

Laboratoire of Virology, and Service of Paediatrics and Gynaecology/Obstetrics, Centre Hospitalier Universitaire 31059 Toulouse, France

PUEL J. IZOPET D. LHERITIER L. BRIANT M. GUYADER J. TRICOIRE A. BERREBI

J. Purpan,

1. Rouzioux 2

3.

4.

5

6

C, Puel J, Agut H, Brun-Vezinet F, et al. Comparative assessment of quantitative HIV viremia assays AIDS 1992; 6: 373-77 Coombs RW, Collier AC, Allain JP, Nikora B, Leuther M, Gjerset GF, Corey L. Plasma viremia in human immunodeficiency virus infecton. N Engl J Med 1989, 321: 1626-931. European Collaborative Study Risk factors for mother-to-child transmission of HIV 1. Lancet 1992, 339: 1007-12 Gruters RA, Terpstra FG, de Goede REY, et al. Immunological and virological markers in individuals progressing from seroconversion to AIDS AIDS 1991; 5: 837-44 Wolinsky SM, Wike CM, Korber BTM, et al Selective transmission of human immunodeficiency virus type-1 variants from mother to infants Science 1992, 255: 1134-37. Holmes W. Vertical transmission of HIV Lancet 1991; 337: 793-94

Continuous subcutaneous apomorphine replacement for levodopa in severe parkinsonian patients after surgery

as

in advanced Parkinson’s disease is issue after surgery because of confusion, swallowing difficulties, or gastrointestinal complications.’ This may lead to critical neurological deterioration and infectious complications. We report one man and three women (age 46-78, duration of disease 7-18 years) in whom continuous subcutaneous apormorphine infusion2,3 effectively replaced oral antiparkinsonian therapy for 4-15 days. The first patient had severe constipation complicated by an adynamic bowel syndrome with four episodes of sigmoid volvulus’ within 2 years. The first two episodes were reduced by sigmoidoscopy, but the third necessitated a sigmoidectomy, followed by severe motor disability, chest infection, and cutaneous complications after levodopa withdrawal. A subtotal colectomy was done during the fourth episode, but without complication because subcutaneous apomorphine infusion, with a Graseby MS 26 portable minipump2,3 at 4-6 mg per h, was given instead of oral levodopa from the 4th preoperative to the 8th postoperative day. The second patient had a total hysterectomy plus radiation therapy for a uterine carcinoma. She developed radiation-induced ileitis and intestinal occlusion that required gastric aspiration and parenteral nutrition. Interruption of levodopa was complicated by severe motor deterioration, pneumonia, and weight loss. Subcutaneous apomorphine (3-7 mg per h) with a Vial SE 200B non-portable pump was started on the 7th day; oral therapy could be resumed onlv after the 3rd week. Intestinal occlusion recurred six times over the next 2 years but any complication was prevented by apomorphine infusion for about a week. The third and fourth patients underwent surgery after hip fracture. Oral antiparkinsonian treatment was interrupted

SIR,-Levodopa withdrawal

an

860

because of confusion. When first seen 5 days post-surgery, both had severe parkinsonian signs with major swallowing difficulties. Subcutaneous apomorphine with a nonportable pump was started at 2 mg per h, gradually increased to 4-5 mg per h, and maintained for about 4 days, when oral medication could be resumed. Parenteral treatment in surgical parkinsonian patients was first attempted with intravenous levodopa infusion.’ However, a large volume of fluid is required, there may be some loss of effectiveness after a few days, and severe peripheral side-effects occur (vomiting, postural hypotension) if intravenous levodopa cannot be given with an oral decarboxylase inhibitor. 5,6 Alternatively, if psychiatric disturbances have limited the parenteral use of lisuride,7 subcutaneous apomorphine has been effective and safe in on-off fluctuating parkinsonian patients.2,3 Subcutaneous apomorphine can be started at low dose and gradually increased. Nausea and vomiting with continuous apomorphine infusion are rare in these severe parkinsonian patients who have taken oral dopaminergic

postoperatively

At 0, 30, 60, 90, 120, and 150 min, at corresponding blood glucoses of 4-7,3-6,4-2,4-4, 2-4, and 3’4 mmol/1, GH was 0,1,0-7,0-5,98, and 4-2 ng/l, respectively. Treatment with synthetic GH at 1 IU/kg per week for 6 months was successful (figure). Linear growth catch-up occurred again, growth velocity increased from 69 to 8-6 cm per year, and the patient’s height (121 cm) is now between below 1 SD of the mean for age and median.

agonists routinely. Continuous subcutaneous apomorphine is simple to administer, well tolerated, effective at 4-6 mg/h, and useful in severe parkinsonian patients who require short-term parenteral treatment after surgery or in other acute situations when neither the oral route nor nasogastric feeding tubes can be used. Department of Neurology, Hôpital de l’Antiquaille, Lyon 05, France, 4

Léon Delhomme,

rue

Paris,

E. BROUSSOLLE M. H. MARION P. POLLAK

and Department of Clinical and Biological Neurosciences, Grenoble

L, Quigley EMM, Pfeiffer RF. Gastrointestinal dysfunction in Parkinson’s disease: frequency and pathophysiology. Neurology 1992; 42: 726-32. 2. Stibe CMH, Kempster PA, Lees AJ, Stern G. Subcutaneous apomorphine in parkinsonian on-off oscillations. Lancet 1988, i: 403-06. 3. Pollak P, Champay AS, Hommel M, Perret JE, Benabid AL Subcutaneous apomorphine in Parkinson’s disease. J Neurol Neurosurg Psychiatry 1989; 52: 544 4 Kupsky WJ, Grimes MM, Sweeting J, Bertsch R, Cote LJ. Parkinson’s disease and megacolon concentric hyaline inclusions (Lewy bodies) in entenc ganglion cells. Neurology 1987; 37: 1253-55. 5. Rosin AJ, Devereux D, Eng N, Calne DB Parkinsonism with "on-off" phenomena: intravenous treatment with levodopa after major abdominal surgery. Arch Neurol 1979; 36: 32-34. 6. Marion MH, Stocchi F, Quinn NP, Jenner P, Marsden CD. Repeated levodopa infusions in fluctuating Parkinson’s disease: clinical and pharmacokinetic data Clin Neuropharmacol 1986; 2: 165-81 7 Critchley P, Perez F, Quinn N, Coleman R, Parkes D, Marsden CD. Psychosis and the lisuride pump Lancet 1986; ii: 349. 1. Edward

Bartter’s syndrome with impairment of growth hormone secretion SIR,-Serious growth retardation during infancy and childhood is regularly observed in Bartter’s syndrome. The underlying mechanism of dwarfism is unclear, although in bovine corpus luteal cell cultures, a prostaglandin dose-dependent inhibiting action against an insulin-like growth factor II receptor has been demonstrated.2 We report an Italian boy aged 5 years and 10 months who

These data do not accord with reports that show striking bone-age improvement with indomethacin,3-5 or normalor even increased1.7 plasma GH in Bartter’s syndrome. Thus we postulate an independent, partial GH secretion impairment. Division of Paediatrics,

was

admitted because of vomiting. He was weak, anorexic, craved salt, and had severe dwarfism, with a statural age of 4 years and 3 months, weight equivalent of 2 years and 9 months, and bone age of 4 years. Hypokalaemia (2-2 mmol/1), hyperreninaemia (> 25 pg/l per h), hyperaldosteronism (1 nmol/1), normal blood pressure (90/50 mm Hg), and excessive urinary losses of sodium (138 mmol per 24 h), chloride (146 mmol per 24 h), potassium (36 mmol per 24 h), and magnesium (3-48 mg/kg per 24 h) were consistent with Bartter’s syndrome. Treatment with indomethacin was effective. At 50 mg daily (ie, 3 mg/kg per day) serum potassium exceeded 3 mmol/1, and he improved clinically with linear growth catch-up. His height reached just below 1 SD of the mean for age (figure). After 16 months of indomethacin, bone age was 5 years (chronological age 7 years and 4 months), which was even more delayed compared with that at diagnosis. We investigated the growth hormone (GH) response to arginine-insulin stimulation.

however,

Height and weight in boy with Bartter’s syndrome. K + = potassium citrate 18 mmol per day, Ind=indomethacin, GH=recombmant somatotropin, 1 IU/kg per week for 6 months, and KCI = 16 mmol per day. M = mean and DS = standard deviation.

Ospedale Civile Maggiore, 37123 Verona, Italy

LUIGI A. BOER GIUSEPPE ZOPPI

Simopoulos AP, Bartter FC Growth characteristics and factors influencing growth in Bartter’s syndrome J Pediatr 1972; 81: 56-65 2. McArdle CA, Holtorf AP. Oxytocin and progesterone release from bovine factor I, insulin, and prostaglandins. Endocrinology 1989; 124: 1278-86. 3. Floret D, David M, Roux A, Hage GN, Teyssier G. Syndrome de Bartter: effets a long 1.

term de l’indométacine sur la croissance. Nouv Presse Med 1979; 8: 17-21. 4. Patnarca PL, Siani A, Branchi M, Buratti P Sindrome di Bartter follow-up di 5 anri

di un bambino trattato con inhibitori della sintesi delle prostaglandine Riv Ital Ped (IJP) 1990; 16: 99-105. 5. Villa MP, Zappulla F, Salardi S, Balsamo A, Vecchi F, Pirazzoli P, Bernardi F, Cicognani A, Cacciari di sindrome di Bartter. Min Ped 1980; 32: 1259-68 6. Calvani M, Lalli F, Brinciotti R, Mattioli P, Miotti AM. Sindrome di Bartter con iperreninemia persistente associata a sindrome feto-alcoolica Min Ped 1984; 36: 1161-68. 7 Simopoulos AP Growth characteristics in patients with Bartter syndrome. Nephron 1979; 23: 130-35. 8. Zoppi G, Bressan F, Bariani A Studio trasversale della crescita dei bambini e degli adolescenti veronesi. Acta Paediatr Lat 1988, 41: 235-52.