490

Evidence from research and mortality and morbidity rates suggests clearly that community-based care and non-intervention management of childbirth in low-risk women is the safest form of care. Moreover, women regard these as the most acceptable forms of care, according to the select committee report. Developing community-based care would "... help engender the belief that pregnancy for most women is a normal event... provide the ability for obstetricians to concentrate on abnormal pregnancies and give continuity of care, which may improve pregnancy outcomes". (Rider ACE, during a lecture at Surrey University, May, 1992). Professionals involved in childbirth should start thinking of what is best for women and their babies, and stop trying to retain control over a process which, after all, belongs only to those affected by

it-pregnant women. Obstetric

Hospital, University College Hospital,

MARIA-JOSE CONTI

London WC1 E 2AU, UK

IM, Parsons RJ, Lawrence GF, Arora SS. An assessment of continuous fetal heart rate monitoring in labour. Am J Obstet Gynecol 1978; 131: 526-32. 2. Wood C, Rain P, Oats J, Farrel E, Beischer N, Anderson I. A controlled trial of fetal heart rate monitoring in a low risk obstetric population. Am J Obstet Gynecol 1981; 141: 527-34. 3. MacDonald D, Grant A, Sheridan-Pereira M, Boylan P, Chalmers I. The Dublin randomized controlled trial of intrapartum fetal heart rate monitoring. Am J Obstet Gynecol 1985; 152: 524-39. 4. MacArthur C, Lewis M, Knox EG. Health after childbirth. London: HM Stationery 1. Kelso

Office, 1991. 5. Van Allen D, Eskes M, Treffers PE.

Midwifery in the Netherlands: the Wormerveer study; selection, mode of delivery, perinatal mortality and infant morbidity. Br J Obstet Gynaecol 1989; 96: 656-62. 6. European Community. Midwives Directive 80/155/EEC article 4.

Vincristine for thrombotic

thrombocytopenic

purpura

SIR,- Thrombotic thrombocytopenic purpura (TTP) is and characterised by consumption thrombocytopenia, fragmentation haemolytic anaemia, renal impairment, neurological deficit, and pyrexia, although not every patient has all these features. Treatment with fresh frozen plasma (FFP) has reduced the mortality from 80% to less than 20%,1-3 but such therapy is not always successful, may be difficult to administer in patients with renal failure, and carries the risk of transmitting viral infections. We report a 52-year-old man with TTP refractory to intensive FFP therapy (at least 4daily for 18 days). After 18 days vincristine was administered: 5 days later the platelet count improved, but fell after a further 6 days. A further bolus of vincristine led to a second response, again at 5 days and followed by clinical improvement. The patient received weekly maintenance vincristine for 3 weeks and rare

remains well 2 years later.4 This reproducible result encouraged us to introduce vincristine for other patients with TTP, and we have now treated 5 patients aged 20-72. All had severe TTP with platelets under 50 x 109/1 (range 4-46), haemoglobin under 12 g/dl (5-5-11-7), and

neurological dysfunction (3 encephalopathy, 1 hemiplegia, 1 seizure); 3 patients required renal dialysis for at least 10 days and 3 had fever. Vincristineinduced disease remission in every patient, all of whom

are

well

at

least 6 months later with

no

residual

neurological or renal impairment. Each patient responded with a rise in platelet count at around 5 days after treatment (figure). Vincristine has been little used for the treatment of TTP; indeed in two reports, only 2 out of 210 patients received this drug.2,3 Anecdotal reports of vincristine’s efficacy’-6 have been treated sceptically because the drug has usually been used with FFP or other therapies. 1-3 Although FFP had been given to 3 of our 5 patients, such treatment had failed in the index case and only small quantities were given to the other 2 cases. Steroids had been given to our index patient and 1 other, but in both for less than 5 days. Therefore neither FFP nor steroids had an important role in achieving remission of TTP in at least 3 of our patients. In contrast, the consistent time from the start of vincristine to the rise in platelet count is compelling evidence that this drug was effective. Furthermore, the fact that improvement in the platelet count predicted clinical improvement in every case confirms the belief that abnormal platelet aggregation is central to the pathophysiology of TTP.

Vincristine therapy for TTP (six treatments in 5 patients):

Drug administered

on

day 0.

First-line treatment for TTP is FFP, preferably by plasmapheresis,2 but we propose that vincristine should also be given at the time of diagnosis. We start with a 2 mg bolus followed by two further injections on alternate days, with assessment of any benefit after 5 days. If the platelet count responds, we continue

vincristine 1 mg every week for

at

least 3 weeks and monitor the

platelet count for evidence of relapse. Vincristine therapy for TTP should be assessed against historical controls, rather than denying patients entered into prospective studies the benefit of this treatment.

Departments of Haematology and Medicine, Royal Shrewsbury Hospital, Shrewsbury SY3 8QR, UK

N. T. J. O’CONNOR M. J. O’SHEA L. F. HILL

Kennedy SS, Zacharski LR, Beck JR. Thrombotic thrombocytopenic purpura. analysis of 48 unselected cases. Semin Thromb Hemost 1980; 6: 341-49. 2. Rock GA, Shumak KH, Buskard NA, et al. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura N Engl J Med 1991; 325: 393-97. 3. Bell WR, Brame HG, Ness PM, Kiekler TS. Improved survival in thrombotic thrombocytopenic purpura: hemolytic uraemic syndrome. N Engl J Med 1991; 1

325: 398-403.

4. O’Connor NTJ, Bruce-Jones P, Hill LF. Vincristine therapy for thrombotic thrombocytopenic purpura. Am J Hematol 1992; 39: 234-36. 5. Gutterman LA, Stevenson TD. Treatment of thrombotic thrombocytopenic purpura with vincristine. JAMA 1982; 247: 1433-36. 6. Welborn JL, Emrick P, Acevedo M. Rapid improvement of thrombotic thrombocytopenic purpura with vincristine and plasmapheresis. Am J Hematol

1990; 35: 18-21.

Screening

for

cystic fibrosis carriers

SIR,-A July 25 editorial on carrier screening for cystic fibrosis (CF) compares two strategies-one preconceptional and based in primary care and one aimed at women attending the antenatal clinic. The difficulties that studies of both these strategies have revealed cause you to caution against nationwide adoption of such screening. We agree: neither approach has the merit of cascade screening, starting off with individuals with CF. Carrier screening for any recessive genetic disease requires an adequate level of background knowledge in the population who are offered screening and of self-motivation in wishing to be screened. Cascade testing, starting with individuals with a family history and their spouses, then offering to test the relatives of all those who are positive, allows one to reach a knowledgeable group at increased risk and who are interested in being tested. We have found cascade testing very popular and successful

491

among the relatives of people with CF. An important benefit of concentrating on this group is the capacity to relieve anxiety in those who test negative. While Moira Mennie and her co-workers (July 25, p 214) admit that their antenatally based programme caused anxiety in some of those screened, testing for carriers in those with a family history (even in pregnancy), relieves anxiety if one compares this group to that in the days before such tests were available. Ideally one would always like to test before conception but there are relatives who first show interest when confronted by a pregnancy. We have been steadily increasing testing of relatives of those with CF m our population and have been actively inviting families to contact relatives with the offer of testing. Effective cascade testing depends on accurate genotyping of individuals with CF and we have a very large cohort of tested individuals,! having to date tested 591 affected people from separate families and having identified twenty different mutations in them (accounting for 92% of CF genes). Thus, we are then able to test in relatives for the relevant mutations, no matter how rare these may be in the general population. While relatives of a parent who carries a rare mutation are identified in our application of cascade screening, they would be missed in general population based screening. Our tests of partners, with no family history of CF, cover the four commonest mutations (F508, G551D, G542X, 621 +1G-T) which cover 86% of mutations in our

populations.1.2 Parents apart, we have tested 397 relatives, establishing 194 to be carriers and 203 to be negative. We have tested 208 of their spouses with no family history of CF and have detected 7 carriers. 5 carrier couples have been identified and counselled and in all of these pregnancies have been undertaken with prenatal diagnosis. 2 unaffected carrier children have been born after prenatal tests and the birth of 2 further predicted carriers is awaited. 1 child with CF, as predicted, has been born. This couple had presented for testing well into the pregnancy; CF in the fetus was predicted at 17 weeks. By testing a fraction of the numbers screened by the Edinburgh (July 25, p 214) and London (p 217) groups we have identified more carriers and more carrier couples than either. Cascade screening provides the opportunity of population screening directed at the group most likely to be interested in being tested and at highest risk. General medical history taking, especially in a family-planning setting or antenatal clinic, should include an inquiry about a family history of CF and the offer of carrier testing to those who reply positively. Those without a family history who inquire about CF testing should also be offered tests. We plan more vigorous cascade screening for CF in our population accompanied by education and counselling, especially for those more distantly related to the individual with CF. This will ensure that a greater and greater proportion of those at highest risk and who are interested in knowing their carrier status will be in a position to exercise informed reproductive options. A reduction in the incidence of CF is achievable by an active programme of cascade screening and fewer of the drawbacks of unfocused screening would be encountered. Regional Genetic Service, Royal Manchester Children’s Hospital, University of Manchester, Manchester M27 1 HA, UK 1 2

MAURICE SUPER MARTIN J. SCHWARZ GERALDINE MALONE

Super M, Schwarz MJ Mutations of the cystic fibrosis gene within the population of the Northwest of England. Eur J Pediatr 1992; 151: 108-11. Super M. The gene defect in cystic fibrosis and clinical application of the knowledge. J RSoc Med 1992; 85: 6-8

Transmission of Pseudomonas cepacia among cystic fibrosis patients SIR,-As you outline in your June 6 editorial cross-infection by Pseudomonas cepacia among patients with cystic fibrosis (CF) is a cause of widespread concern. However, there is no uniformity of opinion on the mode of transmission1,2 and, in particular, whether person-to-person contact is important. We report the transmission of Pseudomonas cepacia between 6 children attending the Cardiff CF unit, 2 of whom died. A chain of cross-infection during hospital admissions, derived from the index case, seems to have been responsible for the subsequent cases.

Transmission of Pseudomonas cepacia admission in children with cystic fibrosis. Vertical

double

arrows

indicate

during

concurrent

hospital admission.

O.P.=outpatient was found to be colonised in after a four-week visit to a Canadian September, 1987, shortly holiday camp for people with CF. At this time, in Cardiff, patients were admitted either to the open ward or to a cubicle, dependent on availability of beds. In July, 1988, a second case (B) was recognised, after admission at the same time as patient A. In April, 1990, a third patient (C) was identified in whom dates of admission had overlapped with that of patient A. CF sibs of patients B and C also became colonised (patients D and E); it is noteworthy that the colonisation of sibs B and D took place 22 months apart, whereas only 2 months separated this event in sibs C and E. All patients had the same bacteriocin type (J. R. W. Govan, personal communication), providing further evidence for person-to-person transmission. After recognition of these new cases in 1990 (maximum prevalence of P cepacia 5/85 patients [5’9%]) management changes were instituted so that all patients were admitted only to cubicles, and hand washing and plastic aprons were required for all staff treating patients with such infection who attended a separate outpatient clinic. However, complete separation of the children colonised with P cepacia (from those not colonised) was hard to achieve on the ward. In May, 1992, a sixth patient (F) who had been admitted at the same time as patients (C) and (E), proved to have P cepacia. Patients A and B died at 15-8 and 12-3 years, respectively. Both survived more than 3 years after colonisation with P cepacia but had substantial lung disease before this event. All patients were colonised with P aeruginosa before acquiring P cepacia. We are now barrier-nursing all our patients with CF who need to be admitted, irrespective of microbiology fmdings. This barrier nursing cannot be complete, in view of the lack of toilet facilities in the cubicles, but further guidelines have been laid down for all aspects of care and we are seeking to acquire suitable isolation cubicles. We are very concerned about the emotional and psychological effects of barrier-nursing and the curtailment of long friendships. Nevertheless, many parents and even some patients are worried about the possibility of cross-infection and have accepted the new measures well. Relatives are encouraged to take the children out of hospital at least once during the day, and many courses of intravenous antibiotics are given at home. Until more is known about P cepacia we intend to continue this practice.

The index

case

(A in the figure)

Department of Child Health, Cystic Fibrosis Unit, University Hospital of Wales, Cardiff CF4 4XW, UK

L. MILLAR-JONES A. PAULL Z. SAUNDERS M. C. GOODCHILD

1. LiPuma JJ, Dasen SE, Nielson DW, Stem RC, Stull TL. Person-to-person transmission of Pseudomonas cepacia between patients with cystic fibrosis. Lancet 1990; 336: 1094-95 2. Simmonds EJ, Conway SP, Ghoneim ATM, Ross H, Littlewood JM. Pseudomonas cepacia. a new pathogen in patients with cystic fibrosis referred to a large centre in the United Kingdom. Arch Dis Child 1990; 65: 874-77.

Screening for cystic fibrosis carriers.

490 Evidence from research and mortality and morbidity rates suggests clearly that community-based care and non-intervention management of childbirth...
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