Doctors' experience and traumatic lumbar punctures

POMB/ACE protocol can be confirmed and shown to be due to the platinum-containing arm of POMB this would provide an attractive alternative to etoposide-containing protocols in patients with low-volume stage II nonseminomatous testis cancer. Methotrexate crosses the blood-testis barrier, is not effect associated with tAML and has little on the spermatogenesis/’" Although alkylating agent in POMB/ACE (cyclophosphamide) could also have contributed to the lower incidence of contralateral tumours, this agent is associated with tAML, long-term oligospermia or azoospermia, and germinal aplasia. Most patients with testis cancer are of reproductive age, and the influence of therapy on gonadal function and fertility is of concern. The possibility of reducing the incidence of tumour in the contralateral testis other than by radiation is an attractive option and needs exploring in a randomised trial. Chris Boshoff, Gordon Rustin, Richard Ed Newlands, Lydia Holden, Jo Ong

Begent,

Tim Oliver,

Department of Medical Oncology, Royal London Hospital, London E1 2AD, UK; Department of Medical Oncology, Charing Cross Hospital, London; and Academic Department of Oncology, Royal Free Hospital, London

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Horwich A, Norman A, Fisher C, et al. Primary chemotherapy for stage II nonseminomatous germ cell tumours of the testis. J Urol 1994; 151: 72-78. Boshoff C, Begent RHJ, Oliver RTD, et al. Secondary cancers following etoposide containing therapy m germ cell cancer. Proc ASCO 1994: abstr 767. Osterlind A, Berthelsen JG, Abildgaard N, et al. Risk of bilateral testicular germ cell cancer in Denmark: 1960-1984. J Natl Cancer Inst

1991; 83: 1391-95. Shamberger RC, Rosenberg SA, Seipp CA,

et al. Effects of high dose ovarian and testicular functions in patients undergoing postoperative adjuvant treatment of oseteosarcoma. Cancer Treat Rep 1981; 65: 739-46. Rustin GJS, Rustin F, Dent J, et al. No increase risk in second tumours after cytotoxic chemotherapy for gestational trophoblastic tumors. N Engl J Med 1983; 308: 473-76.

methotrexate and vincristine

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on

Lack of association between mitochondrial gene mutation np 3243 and type 1 diabetes mellitus and autoimmune thyroid diseases SIR-An A-to-G mutation at np 3243 of the mitochondrial genome has been reported to be associated with diabetes mellitus.’ Oka and colleagues2 reported that this mutation existed in 3 of 27 patients with insulin-dependent diabetes mellitus (IDDM) with a gradual onset.3 The prevalence of this mutation in 11% of these patients is over ten times higher than that in randomly collected noninsulin-dependent diabetes mellitus (NIDDM)/ which raises the possibility that this mutation may produce autoimmunity leading to type 1 diabetes mellitus. We screened IDDM patients for the presence of this mutation. All patients had juvenile onset type 1 diabetes. Of 116 unrelated patients (50 from the UK, mean age at diagnosis 11-3 [SD 67] years, 27 male; and 66 Japanese, 6-4 [3-6], 22 male), no individual was found to have the mutation. Autoimmunity also leads to hypothyroidism or hyperthyroidism, which are often associated with IDDM. We believe these autoimmune thyroid diseases (AITDs) are important for screening because patients with MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes), in which this mutation was originally identified, often have AITDs. Screening of 149 patients with thyroid diseases for this mutation was negative. In total, 260 patients with autoimmune diseases were screened, but we 1086

find this mutation in any of our patients. Although exclude the possibility that the mutation exists with much lower prevalence in autoimmune diseases than in NIDDM, we conclude that the A-to-G mutation at np 3243 is not a principal cause of autoimmunity in these diseases.

could

we

not

cannot

Masato Odawara,

Kayoko Sasaki, Shigeo Nagafuchi, Ayako Tanae, Kamejiro Yamashita Institute of Clinical Medicine, University of Tsukuba, National Children’s Hospital, Tokyo, Japan

Tsukuba-city, 305, Japan; and

den Ouweland JMW, Lemkes HHPJ, Ruitenbeek K, et al. Mutation in mitochondrial tRNALEU(UUR) gene in a large pedigree with maternally transmitted type 2 diabetes mellitus and deafness. Nature Genet 1992; 1: 368-71. 2 Oka Y, Katagiri H, Yazaki Y, Murase T, Kobayashi T. Mitochondrial gene mutation in islet-cell-antibody-positive patients who were initially non-insulin-dependent diabetics. Lancet 1993; 342: 527-28. 3 Kobayashi T, Itoh T, Kosaka K, et al. Time course of islet cell antibodies and &bgr;-cell function in non-insulin-dependent stage of type 1 diabetes. Diabetes 1987; 36: 510-17. 4 Kadowaki T, Kadowaki H, Mori Y, et al. A subtype of diabetes mellitus associated with a mutation of mitochondrial DNA. N Engl J Med 1994; 330: 962-68. 1

van

Doctors’

experience and traumatic lumbar punctures SIR-Ethical questions have been raised about lumbar puncture by novices.1,2 The principle of informed consent suggests that a patient is entitled to know if the procedure is being performed by a novice. That assumes a higher risk associated with inexperience but there are no data addressing this assumption. In one report 20% of lumbar punctures were apparently traumatic.3 A traumatic procedure can confound diagnosis because red blood cells (RBC) so introduced may lead to a false-positive diagnosis of central-nervous-system (CNS) haemorrhage (or truly endogenous red cells may be falsely attributed to trauma, leading to a false negative diagnosis); similarly, introduced white cells could lead to a false positive diagnosis of CNS inflammation while endogenous white cells may be falsely attributed to a traumatic lumbar puncture. Given that the likely source of bleeding is the radicular vessels on freely floating nerve roots,4 it is unclear whether supervision or experience will alter the incidence of traumatic lumbar puncture. But are traumatic punctures more common when done by less experienced doctors? We assessed all cerebrospinal fluid samples in a large university hospital one month before the July 1 house-officer turnover date and one month afterwards. We assumed: (1) that trainees did most of the lumbar punctures; (2) that with the influx of interns, there was less experience overall after July 1; and (3) that the incidence of traumatic procedures for experienced practitioners was 5-10% (depending on whether cut-off was 4375 or 1000 RBC/µL, see below). After square-root transformation at test was used to compare RBC counts. Two methods of classifying a procedure as traumatic or non-traumatic were used, a cut-off of >4375 RBCs/µL being used to correct for errors in white-cell-count-dependent diagnoses and a cut-off of >1000 RBC/µL to correct for errors in red-cell-countdependent diagnoses. We did Fisher’s exact tests on data with these two cut-offs. In June and July 1993, 211 samples were analysed from 195 lumbar punctures on 131 patients. 15 had duplicate cell counts done, and these were averaged. There was no significant difference in the mean RBC count between the two months but the statistical power for this analysis was inadequate because the SDs were huge (table). However, for

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addressed.

negative

Gram-positive’bacteria, especially coagulasestaphylococci, streptococci, and enterococci,

for about a quarter of the strains isolated from and they are relatively insensitive to such as norfloxacin and ciprofloxacin.2,3 A reduction in the susceptibility to ciprofloxacin of blood culture isolates of coagulase-negative staphylococci from patients with haematological malignancy given long-term fluoroquinolone prophylaxis has been observed.Also, a cautionary example of the failure of fluoroquinolone to prevent biliary-stent-associated infection has been reported.’ Ciprofloxacin had been given to prevent further relapses of septicaemia caused by Klebsiella oxytoca. The patient died after episodes of septicaemia caused by ciprofloxacinresistant Enterococcus faecalis and Pseudomonas aeruginosa, and Ps aeruginosa aeruginosa and Candida spp resistant to ciprofloxacin were isolated from the biliary stent at necropsy. The emergence of bacterial resistance could be avoided if it could be shown that the improvement in biliary stent function observed by Barrioz and colleagues can be achieved by non-antibiotic drugs. account

biliary sludge, fluoroquinalones Table: Mean RBC counts and frequency of traumatic procedures for lumbar punctures done in June and July, 1993

the cut-off of 4375/uL the study would have been powerful enough to have detected a change of 15% from June to July (a=0’05, &bgr;=0.9); and for the 1000/µL cut-off the study would have been almost as powerful (&bgr;=0.79, a=0-05). the differences between June and July were not significant for either cut-off. We found no relation between the frequency of traumatic lumbar puncture and the presumed experience of the doctor, suggesting that inexperience with this procedure does not adversely affect patient care. The patient’s permission for a trainee to do a lumbar puncture would still have to be sought but it might not be necessary to warn about an increased risk of trauma if the operator was inexperienced. This retrospective study has potential flaws. We may not have had enough data to reveal a true difference. July may be too early-ie, the new doctors may not start doing significant numbers of lumbar punctures until later in the year. The learning curve may last more than a year-ie, the doctors in June were still inexperienced. We also assumed rates of 5-10% for traumatic lumbar punctures done by experienced doctors, and that may have been wrong.

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Mark H Wilcox Clinical

Microbiology and Public Cambridge CB2 2QW, UK

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Charles Williams, Norman Fost Brown

University, Providence, Rhode Island, USA; and University of Wisconsin, Madison, WI 53792, USA

Preventing biliary stent occlusion SIR-Barrioz and colleagues (Aug 27, p 581) report the successful use of a combination of ursodeoxycholic acid and norfloxacin to prevent the occlusion of biliary stents inserted to relieve obstructive jaundice. They do not consider in detail whether either agent alone was responsible for the observed benefit. Although ursodeoxycholic acid may act by displacing hydrophobic bile acids in bile, it also has immunomodulatory activity. Barrioz et al refer to work by Smit and co-workers,’ but do not clearly state that this group found that either aspirin or tetracycline inhibited the accumulation of biliary sludge in stents. Treatment with the individual drugs was associated with significant reductions in bilirubin and protein content, respectively, but combination therapy was not used. Tetracycline is much less active than norfloxacin against the gram-negative enteric bacteria which predominate in biliary sludged Hence, there is a precedent for drugs with different modes of action each to affect biliary sludge formation.

Furthermore, Barrioz et al make no mention of infective complications in the 37 patients in whom trial entry was considered. The possibility that resistant bacteria will be selected for by the long-term administration of antibiotic is

Laboratory, Addenbrooke’s Hospital,

Smit JM, Out MMJ, Groen AK, et al. A placebo controlled study of the efficacy of aspirin and doxycyline in preventing the clogging of biliary endoprosthesis. Gastrointest Endosc 1989; 35: 485-89. Speer AG, Cotton PB, Rode J, et al. Biliary stent blockage with bacterial biofilm. Ann Intern Med 1988; 108: 546-53. Phillips I, King A, Shannon K. In vitro properties of the quinolones. In: Anriole VT, ed. The quinolones. San Diego: Academic Press, 1988: 83-117.

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1 Botkin J. Informed consent and the lumbar puncture. Am J Dis Child 1989; 143: 899-904. 2 Williams CT, Fost N. Ethical considerations surrounding first time procedures: a study and analysis of patient attitudes toward spinal taps by students. Kennedy Inst Ethics J 1992; 2: 217-31. 3 Marton KI, Vender MI. The lumbar puncture: patterns of use in clinical practice. Med Decision Making 1981; 1: 331-44. 4 Breuer AC, Tyler HR, Marzewski DJ, Rosenthal DS. Radicular vessels are the most probable source of needle induced blood in lumbar puncture: significance for the thrombocytopenic cancer patient. Cancer 1982; 49: 2168-72.

Health

Spencer RC. Ciprofloxacin and coagulasenegative staphylococci. J Antimicrob Chemother 1991; 27: 685-87. Wilcox MH, Rice P, spencer RC. Biliary stent associated infection. J Hosp Infect 1991; 18: 82-84. Wilcox MH, Finch RG,

SIR-Barrioz and colleagues’ observation is potentially important for endoscopists involved in the management of patients with biliary obstruction. Unfortunately, we do not believe that the case is proven. First, rates of stent occlusion vary widely; some occlude after many months whereas others, apparently well sited in similar patients, block after only a few weeks. Accordingly, only studies that include a large number of matched patients are valid, and a trial of 20 patients (10 in each group) should be regarded as

questionable. Second, we

are struck by the very short duration of stent in the patency conservatively treated patients. Certainly, the of duration patency of the first (median 6 weeks) and all stents (median 7 weeks) in Barrioz and colleagues’ conservatively treated group is considerably lower than that reported in publications for 10-12 F straight plastic stents. The Dutch study to which they refer’ had a median stent patency of 18 weeks for first stents. Even longer durations of patency have been reported by British2 (median 24 weeks) and Japanese3 (median 25 weeks) workers. Our experience has been similar and most patients died with the first stent in situ. Frakes and co-workers5 reported occlusion rates of 4% and 11% at 12 and 24 weeks, respectively, after insertion. However, in the French trial, 90% (9/10) of stents had occluded by 16 weeks. Second and subsequently inserted stents inevitably have a shorter duration of patency,2,4 yet this was not seen in the Barrioz trial for the conservatively treated group, undoubtedly because the patency of the first stent was so short. Third, since there is no evidence that endoscopic stenting prolongs survival in malignant obstructive jaundice, the striking difference in survival between actively (median 67

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