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Alzheimer’s disease in patients with atypical forms of Down’ssyndrome are important in establishing the role and site of geneloci on chromosome 21 that predispose to Alzheimer’s disease.

V P Prasher

Department of Psychiatry, University of Birmingham, Queen Elizabeth PsychiatricHospital, Birmingham B15 2QZ, UK

1 Oliver C, Holland AJ. Down’s syndrome and Alzheimer’s disease:review. Psych Med 1986; 16: 307-22.

2 Mann DMA. Alzheimer’s disease and Down’s syndrome.Histopathology 1988; 13: 125-37.

3 Wisniewski KE, Wisniewski HM, Wen GY. Occurrence ofneuropathological changes and dementia of Alzheimer’s disease inDown’s syndrome. Ann Neurol 1985; 17: 278-82.

4 Rowe IF, Ridler MAC, Gibberd FB. Presenile dementia associatedwith mosaic trisomy 21 in a patient with Down syndrome child. Lancet1989; ii: 229.

5 Whalley LJ. The dementia of Down’s syndrome and its relevance toaetiological studies of Alzheimer’s disease. Ann N Y Acad Sci 1982;396: 39-53.

6 Sylvester PE. The anterior commissure in Down’s syndrome. J MentDefic Res 1986; 13: 19-26.

7 Goate AM, Haynes AR, Owen MJ, et al. Predisposing locus forAlzheimer’s disease on chromosome 21. Lancet 1989; i: 352-55.

Late diagnosis of chronic salicylateintoxication

SiR-Aspirin is metabolised rapidly to the more persistentsalicylic acid, which has low therapeutic index and saturablemetabolism. Taking slightly larger than therapeutic doses overseveral days can lead to a disproportionate rise in plasma drugconcentrations and to chronic salicylate intoxication. We

report two patients who were treated in surgical wards and thenfor several days in the intensive care unit before such chronicintoxication was recognised.A 44-year-old man was admitted for cystoscopy because of

haematuria, dysuria, and frequency of 3 weeks’ duration. Hishistory included severe chronic anxiety and analgesicnephropathy, although he denied recent use of analgesics. Hewas drowsy with a respiratory rate of 28 per min. Serumbicarbonate was 8 mmol/L (normal 24-30), and the anion gapwas 15 mmol/L (2-12). The next day, the patient developedprogressive respiratory failure without fever, cough, sputum,or chest pain. Blood gases on room air revealed pH 7-22, PaOz38 mm Hg, and PaC02 22 mm Hg. Other abnormal

investigations were: chest radiograph which showed diffusealveolar shadowing; serum creatinine 0.31 mmol/L (normal<011); white cell count 18-5 x 109/L; lactate dehydrogenase(LDH) 1092 U/L (120-250); aspartate aminotransferase (AST)70 U/L (0-40); and prothrombin time 26 s (control 13). Thepatient was transferred to intensive care where mechanicalventilation was started for the provisional diagnosis of atypicalpneumonia. High-dose intravenous erythromycin and

gentamicin were administered. A transbronchial lung biopsydone 3 days after admission showed diffuse alveolar damageconsistent with adult respiratory distress syndrome (ARDS).In view of the mixture of findings, salicylate overdose wassuspected and was confirmed by retrospective analysis ofadmission serum (445 mg/L, 2-47 mmol/L). The patientrecovered after 6 more days in intensive care and 6 on the ward.A 42-year-old woman was admitted to a surgical ward with

abdominal pain and vomiting. She had a long history ofanalgesic and diazepam abuse, and epilepsy for which she tookphenytoin and carbamazepine. In the past, recurrent episodesof acute abdominal pain had led to three laparotomies and thediagnosis of adhesions. Examination was normal apart frommild epigastric tenderness and a respiratory rate of 24 per min.Serum bicarbonate was 19 mmol/L and the anion gap was 17.

Creatinine, amylase, and radiographs of the abdomen and chestwere normal. Treatment consisted of intravenous fluids,nasogastric suction, and opioids. Over the next 2 days, thepatient became drowsy and increasingly dyspnoeic. The chestradiograph showed diffuse alveolar shadowing. Abnormallaboratory results were: arterial blood gases on room air, pH719, PaOz 40 mm Hg, PaCOz 52 mm Hg; LDH 771 U/L; andprothrombin time 26 s. Laparotomy revealed no reason for theepigastric pain or deterioration. The patient was transferred tointensive care for mechanical ventilation and a transbronchial

lung biopsy, which revealed diffuse alveolar damage consistentwith ARDS. No pathogens were found in the lung on culture orhistology. In view of the history and clinical laboratoryfindings, chronic salicylate poisoning was diagnosed, andconfirmed in retrospective admission serum (365 mg/L, 2-03mmol/L). The concentrations at 23, 47, 61, and 72 h of,respectively, 365,176,75, and 8 mg/L, demonstrated continuedabsorption over the first 24 h in hospital and zero-orderelimination kinetics. The patient recovered over 15 days inintensive care and 6 on the ward.On admission or soon after, these patients demonstrated the

cardinal clinical and laboratory features that should lead to thediagnosis of chronic salicylate intoxication,1 includingabdominal pain, tachypnoea, encephalopathy, acid-fastdisturbances (especially respiratory alkalosis and metabolicacidosis), coagulopathy, and ARDS. Nevertheless, the

diagnosis was missed, which compromises the prognosis.’ Inour two patients failure to make the diagnosis led to numerousunwarranted interventions, including transbronchial lungbiopsy in both and laparotomy in one.

Susan M Pond, John G Armstrong, Alan HendersonDivision of Medicine, University of Queensland, Princess Alexandra Hospital, Brisbane,Queensland, Australia 4102

1 Anderson RJ, Potts DE, Gabow PA, Rumack BH, Schrier RW.Unrecognised adult salicylate intoxication. Ann Intern Med 1976; 85:745-48.

Screening for chlamydia infection

SiR-We strongly support Blackwell and colleagues’ statement(July 24, p 206) that screening for chlamydia infection beforetermination of pregnancy is both essential practice and costeffective. Our departments have collaborated to offer screeningfor sexually transmitted diseases to all women attending fortermination of pregnancy and have shown a significantlyincreased prevalence of chlamydia in this population.However, our experience in this project leads us to take issuewith some of Blackwell and co-workers’ comments.Treatment given only to those women with proven infection

is preferable to universal prophylaxis. Prophylaxis is necessaryonly if chlamydia swabs are taken at operation since Blackwellet al show that without prophylaxis 63% of women with apositive test will have developed pelvic infection before theycan be contacted. In our practice women are screened at theirinitial clinic appointment and those with infection are

identified and treated preoperatively to prevent pelvicinfection and to avoid the need to give universal prophylaxiswith its inherent side-effects. None of the 9-5% of women withchlamydia in our study developed postoperative complicationswhen treated in this way. Blackwell et al do not state the dose of

oxytetracycline that they use as prophylaxis but the dose hasimplications for cost-analysis as well as toxicity and

compliance.The use of genitourinary medicine (GUM) staff at the initial

gynaecology visit reduces the number of clinic attendancesnecessary because many conditions can be diagnosedimmediately by microscopy; in the Swansea system recall was

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necessary, leading to an inevitable recall failure rate-forinstance all those identified with Trichomonas vaginalisinfection. 11-5% of women in Blackwell’s study who hadchlamydial infection later proved to have genital warts whenthey were examined at the GUM clinic. In our study 3-2% of allwomen seeking termination of pregnancy had genital wartsdiagnosed yet none had been identified in the gynaecologyclinic. Combining the expertise of gynaecology and GUMtrained staff clearly improves diagnostic acumen, continuity oftreatment, follow-up, and compliance, all of which are

enhanced by good collaboration. Screening at a clinic fortermination of pregnancy provides a safety-net systemwhereby those women who fail to re-attend for treatment afterpositive results can be treated on admission to the gynaecologyday ward.Other sexual health gains include opportunistic cervical

cytology tests. In our study 476;0 of women had a clearindication for cytological testing. Furthermore, the chance toimprove women’s access to information about family planningand sexual health was enhanced by the use of health advisersand written information. We were also able to offer tests for

hepatitis B, syphilis, and HIV, as well as emotional support andcounselling when necessary. None of these benefits can begained simply by taking swabs from women under generalanaesthesia.Such a coordinated approach to sexual health care follows

the guidelines laid down by the UK government.1 We believethere should be a concerted effort to make screening for genitaltract infection standard practice in women attending for

termination of pregnancy. The evidence is mounting thatfailure to do so is negligent.

Nicola Smith, Simon Barton, Sheila Purkayastha, J RichardSmith

Departments of Genitourinary Medicine and Obstetrics and Gynaecology, Chelsea andWestminster Hospital, London SW10 9NH, UK

1 Department of Health. The health of the nation. London: HMStationery Office, 1992.

SIR&mdash;Before Blackwell and colleagues’ report, several

investigators assumed that the facts that some women seekingtermination of pregnancy might harbour chlamydial infectionand that some women (not necessarily the same women) mightdevelop pelvic infection after termination were sufficient

justification for screening, rather than the use of acceptedcriteria for screening. 1 I have previously outlined a

mathematical model suggesting that at a prevalence of 10%there was no clear justification for generalised screening.2,3

Blackwell and colleagues show that about two-thirds ofwomen who were chlamydia positive went on to develop pelvicinfection; this figure is higher than those of other studies, inwhich frequency of chlamydia infection was up to 28%. Weare not told how many of the chlamydia-negative womendeveloped pelvic inflammatory disease (PID).

Findings of other studies suggest that the percentage mightbe as high as 10%.2 It cannot be assumed that previoustreatment of chlamydial infection will prevent PID. Both thesefactors need to be taken into account in any economic appraisal.

Finally, Blackwell et al do not apply any sensitivity analysis.Such analysis is the economic equivalent of confidenceintervals. If the prevalence of chlamydia were slightly differentfrom the 8% they find, or the risk of PID in such women wereslightly more or less than 63 %, what difference would this havemade to their cost analysis? Since the financial advantagecalculated is small ([11,20- 4.64 = 6.54 per case), where thetotal cost per case is likely to be measured in hundreds ofpounds, small variations in these two values may cancel outsuch a small saving. Estimates of costs in Blackwell’s unit may

be inappropriate to other units. I therefore caution a more

qualified acceptance of the Swansea group’s findings andadvice.

Malcolm Griffiths

Department of Obstetrics and Gynaecology, Royal Berkshire Hospital, Reading,Berkshire RG1 5AN, UK

1 Sackett DL, Holland WW. Controversy in the detection of disease.Lancet 1975; ii: 357-59.

2 Griffiths M. Predictions of the effectiveness of a policy of screening forChlamydia trachomatis in women requesting termination of pregnancy.Br J Fam Plan 1991; 17: 44-45.

3 Griffiths M. Potential endocervical pathogens before termination ofpregnancy. BMJ 1992; 305: 179.

Authors’ reply

SiR-We agree with Smith and colleagues that, ideally,treatment for any infection should only be given to patientswho are actually infected. Since undetected chlamydialinfection has such a high morbidity in patients attending fortermination of pregnancy, preoperative screening should behighly sensitive if universal prophylaxis is to be abandoned infavour of treatment of only those patients in whom chlamydia isdetected. In our study the chlamydia detection rate variedwidely between doctors but some doctors had done too fewterminations for the statistical significance of chlamydiaisolation rates to be assessed.

We are auditing results of 2000 terminations to see if there isvariation between doctors in swabbing techniques. Concernabout such variation, plus the fact that we noted a suddendecrease in chlamydia detection after a change in junior staff,suggested that detection of chlamydia in all infected patientswas not reliable, which led us to introduce prophylaxis for allpatients. In addition, our patients are referred for terminationof pregnancy from eight sites in West Glamorgan and a centraltermination of pregnancy clinic is not practical. We also feelthat the delay between taking swabs and getting the results maylead to an unjustifiable delay of surgery.We used 500 mg oxytetracycline four times daily for ten days

for uncomplicated chlamydial infection. We now use thisregimen as prophylaxis. Treatment toxicity and complianceassessment is being addressed in a long-term follow-up study.We agree with the need for close links between

gynaecologists and genitourinary physicians. In Swansea alljunior doctors receive basic training in the presentation,diagnosis, and management of common genital tract infectionsin the department of genitourinary medicine, which facilitatesinter-departmental referral of appropriate cases. AlthoughGUM and gynaecology clinics might be practical in a Londonteaching hospital, in many district general hospitals, such asours, in which the consultant genitourinary physicians do nothave full-time junior staff and cover several clinics up to 80miles away, the introduction of such combined clinics is not

possible.We considered the points that Griffiths raises before we

introduced prophylaxis for chlamydial infection and anaerobicvaginosis for all patients. Analysis of our data showed thatwomen with chlamydia infection before termination of

pregnancy were at very high risk of developing pelvic infection.If we include data from our pilot study, we have information on500 women out of a total yearly study population of 1500. Wetherefore felt that our data were reliable and that for ethical and

medico-legal reasons we had to take preventive action.

However, although we were aware of the mathematical modelsuggested by Griffiths, we felt that long-term clinical audit wasthe gold standard for assessing the costeffectiveness of ourmanagement changes.

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We have now done terminations on over 2000 women

managed according to our new regimen and the benefits interms of reduced patient morbidity in those with pre-operativechlamydia infection have been profound. These results will bepublished shortly. We point out that Griffiths’ analysis offinancial savings does not take into account savings fromreduction in long-term morbidity, especially with respect tosub-fertility, the treatment of which is expensive and

distressing for the patients.The main aim of our study was to improve patient care.

Before prophylaxis was introduced, many miserable sick

women willingly attended the GUM clinic or gynaecologyoutpatient departments for treatment of pain. Now,paradoxically, somewhat less appreciative but vigorouslyhealthy women reluctantly return for follow-up tests andcontact tracing: this is arguably the most valid saving derivedfrom our management changes.

A L Blackwell, P D Thomas, K Wareham, S J EmerySingleton Hospital, Sketty, Swansea SA2 8QA, UK

Lyme borreliosis imported from Africa

SiR-Infection with Lyme borreliosis has been reported fromthe USA, Europe, Australia, Asia, and North Africa,1 andLyme disease is now the most common vector-borne disease inthe USA.2 Serological testing for Lyme borreliosis is difficultand there is no consensus on positive and negative cut-offs.3Thus doctors may have to rely on clinical diagnosis.During 1992, 22 patients were seen in our practice in whom

Lyme disease was diagnosed clinically and serologically. In 8the disease appeared to have been contracted in Ireland

whereas in the others exposure overseas had a major role. Inthese patients, presenting features were diverse but the

underlying symptom was waves of abnormal lethargy. We haveserological confirmation of Lyme borreliosis in patientsreturning from Nigeria, Angola, Kenya, Tanzania, and

Zambia. In most of these cases, the patients had a history oftick-bite and 4 gave good descriptions of annular erythema, thecutaneous manifestation closely associated with Lyme disease.Our patients responded well to oral doxycycline, or in somecases high-dose intravenous ceftriaxone.These cases are among the first series of serologically

confirmed Lyme disease from tropical Africa, and we

recommend that doctors seeing patients returning from thisregion with significant lethargy should consider the possibilityof imported Lyme disease.

’

Graham Fry, Vincent KennyDepartment of International Health and Tropical Medicine, Royal College of Surgeonsin Ireland, Dublin 2, Ireland.

1 Wilson ME. A world guide to infection. Oxford: Oxford UniversityPress, 1991.

2 Schantz PM. Parasitic zoonoses in perspective. Int J Parasitol 1991;2: 21.

3 Callister SM, Case KL, Scheel RF. Diagnostic testing for Lymedisease. Labmedia VII, 1990.

Is there an increase of bone density inchildren?

SiR-Studies of bone density in children and adolescents withsingle (SPA) or dual photon absorptiometry (DXA) haveshown a linear increase with age in bone-mass accumulation upto an age of 15-18 years, with some acceleration duringpuberty.1-3 Bone mineral content (BMC) and bone mineraldensity (BMD) determined with these methods are said to be

Figure: Comparison of total bone density and trabecularbone density between 8 healthy children and the normalrange of adults ( x 250)

closely related not only to age but also to weight and height.4However, when SPA and DXA are used in growing children, ithad to be taken into consideration that the increase in photonabsorption might be due not only to an increase in bone densitybut also to an increase in bone size. Kroger et al4 have

developed a hypothetical model of vertebral column andfemoral neck in order to obtain apparent volumetric BMD withDXA measurements. When BMD values were thus correctedfor bone size, BMD and age no longer showed any significantcorrelation and apparent volumetric density did not changeduring childhood and adolescence. These data accord withresults of our pilot study analysing total bone density andtrabecular bone density by quantitative computed tomography(QCT) at the distal radius. (CT Bone Scanner SCT 900, StratecElectronic, Birkenfeld, Germany) in 8 healthy children

(48-11-3 years old). The figure shows all values were withinthe normal ranges for adults. Our finding is in line with studiesof human skeletons showing that the percentage of ash weightand the density of dry, fat-free osseous skeletons remain stablefrom early childhood until old age.5 This finding is also

supported by looking at biological changes in bone duringgrowth-ie, increases in total bone length, cortical thickness,and in the biomechanical organisation of the trabecularstructure. These processes will change bone size, dimension,and structure rather than bone density.Thus, data on bone density measured by photon absorption

methods have to be interpreted very carefully in children andadolescents. In our view, the increase of photon absorption ingrowing bones is mainly due to the increase of bone size and notto an increase in density. Further studies should examinewhether photon absorption methods can be improved by