Inflammatory bowel disease presenting as travellers' diarrhoea

241

conception, as Rosevear et al suggest, and an indirect effect by modifying steroid genesis, as shown by Barbiery et all These on

workers found that nicotine and anabasine (not arabinase, as in Rosevear’s report) inhibit human granulosa cell aromatase via a highly specific mechanism. An indirect cause of early abortion may be corpus luteum insufficiency, as suggested by Bodis et alwho found that 10-’-10-° mol/L of nicotine in serum-free medium resulted in an increased secretion of oestradiol and a decrease in progesterone in a dose-dependent manner in human granulosa cell culture. These results are important for smoking women, demonstrating that women should cease smoking before

conception. University of Oklahoma, Health Science Center, Oklahoma City, Oklahoma 73104, USA

PETER M. GOCZE ZOLTAN PORPACZY

1. Pattinson HA, Taylor PJ, Pattinson MH. The effect of cigarette

smoking on ovarian

function and early pregnancy outcome of in vitro fertilization treatment. Fertil Steril 1992; 55: 780-83. 2. Barbieri RL, McShane PM, Ryan KJ. Constituents of cigarette smoke inhibit human granulosa cell aromatase. Fertil Steril 1986; 46: 232-36. 3. Bodis J, Hanf V, Torok A, Tinneberg H-R. Smoking and corpus luteum function.

Fertil Steril 1992; 57: 703.

StR,—Rosevear and colleagues’ data on the association between cigarette smoking and fertilisation rates during IVF conflict with the findings of other workers. Elenbogen et all found evidence of a lower fertilisation rate in smokers, but others2-4 did not. Indeed, Hughes et aJ5 found a higher fertilisation rate among smokers, and suggest that their lower transfer rate might have been due to the association of smoking with other personal characteristics that impede IVF. Thus the effect of smoking on IVF remains uncertain. In discussing possible mechanisms for their findings, Rosevear et d leave the impression that smoking women have lower endogenous oestrogen concentrations in serum. This is not so; in both premenopausal and postmenopausal women serum oestradiol and oestrone concentrations are similar in smokers and nonsmokersP,6-8 The manner in which smoking exerts antioestrogenic effects is not clear. Cancer Epidemiology Unit,

Uppsala Universitet, S-751 85 Uppsala, Sweden

INGEMAR PERSSON

S, Mashiach S, et al. The effect of smoking on the outcome of in-vitro fertilization-embryo transfer. Hum Reprod 1991; 6: 242-44. 2. Pattinson HA, Taylor PJ, Pattinson MH. The effect of cigarette smoking on ovarian function and early pregnancy outcome of in-vitro fertilization treatment. Fertil Steril 1991, 55: 780-83. 3. Trapp M, Kemeter P, Feichtinger W. Smoking and in-vitro fertilization. Human Reprod 1986, 6: 357-58. 4. Harrison KL, Breen TM, Hennessey JF. The effect of patient smoking habit on the outcome of IVF and GIFT treatment. Aust NZ J Obstet Gynaecol 1990; 30: 340-43. 5. Hughes EG, YoungLai EV, Ward SM. Cigarette smoking and outcomes of in-vitro fertilization and embryo transfer: a prospective cohort study. Hum Reprod 1992; 7: 358-61. 6. Baron JA, La Vecchia C, Levi F. The antiestrogenic effect of cigarette smoking in women. Am J Obstet Gynecol 1990; 162: 502-14. 7. Barrett-Connor E. Smoking and endogenous sex hormones in men and women. In: Wald N, Baron J, eds. Smoking and hormone-related disorders. Oxford: Oxford

University Press, 1990: 183-96.

8. Key TJA, Pike MC, Baron JA, et al. Cigarette smoking and steroid hormones in J Steroid Biochem Molec Biol 1991; 39:

was

in

severe

Dryburn Hospital, Durham DH1 5TW, UK

DAVID LAIRD

St Benedict’s Hospice, Sunderland

TIM LOVEL

1. Owen H, Reekie RM, Clements JA, Watson R, Nimmo WS. Analgesia from morphine and ketamine. Anaesthesia 1987; 42: 1051-56. 2. Kanamaru T, Saeki S, Katsumata N, Mizuno K, Ogawa S, Suzuki H. Ketamine infusion for control of pain in patients with advanced cancer. Masui 1990; 39: 1368-71.

Inflammatory bowel disease presenting as JOHN A. BARON

1. Elenbogen A, Lipitz

women.

pain despite 10 400 mg of oral with morphine daily, together tricyclic antidepressants and steroids. Within 24 h of starting an infusion of ketamine at a rate of 0mg/kg per h she was free of severe pain and said she was comfortable. The morphine was reduced to 1000 mg daily. She remained on ketamine infusion for 48 days and had improved mobility and restful sleep. The rate of the infusion was maintained between 0 25-0mg/kg per h by means of a Graseby syringe driver with boosts of subcutaneous ketamine before dressing changes. She died peacefully 48 days after starting ketamine infusion. There was no rise in liver enzymes or mental disturbance attributable to ketamine. The nursing staff were impressed with the ease of control of the infusion to anticipate pain due to dressing changes, which had previously necessitated supplementation with Entonox. Ketamine (2-(0-chlorophenyl)-2-methylamino cyclohexamine) has been in general clinical use as an anaesthetic agent since 1970. At anaesthetic levels of infusion it produces so-called dissociate anaesthesia. Its potent analgesia is thought to be due to a selective depressant effect on the medial thalamic nuclei and suppression of spinal cord activity through N-methyl-D-aspartate mechanisms. Owen et all found ketamine to be useful in providing postoperative analgesia and Kanamaru et aP showed that ketamine was beneficial in 12 patients whose pain did not respond to conventional techniques. An infusion rate of 01-0mg/kg per h seems to provide analgesia without the dysphoria that can accompany the use of ketamine for anaesthetic purposes. We have treated a further six similar patients with equally satisfactory results. admission she

529-34.

Paradoxical pain SiR,-Dr Morley and colleagues (Oct 24, p 1045) describe the induction of paradoxical pain or overwhelming pain syndrome by high-dose morphine, and supply valuable pharmacological data for

their patient. They also propose that methadone instead of

morphine or diamorphine might be effective because its metabolism differs from that of these drugs. We report the efficacy of a subcutaneous infusion of ketamine in a patient with pain partly resistant to opioids. A 49-year-old woman with a 3-year history of breast carcinoma was admitted for pain relief to the Hartlepool Hospice. Her pain was constant, severe, and burning, affecting the upper half of her torso and her left arm to the elbow. Its site corresponded with the cutaneous involvement of her adenocarcinoma of breast. On

travellers’ diarrhoea SiR,—Gastrointestinal infections are common among travellers abroad. Although small intestinal infections outnumber infections in the colon, colitis caused by Shigella sp and Entamoeba histolytica is well recognised as a travellers’ disease. In addition, Salmonella sp, Campylobacter jejuni, Aeromonas hydrophila, and Plesiomonas shigelloides can cause colitis. Inflammatory bowel disease (IBD) (ie, ulcerative colitis and Crohn’s disease) is a chronic relapsing disease of unknown cause. There are reports in which ulcerative colitis has started in relation to an acute infection with salmonella,’ Cjejaari, or A hydrophila.3 In a study of 105 patients with a sigmoidoscopically verified first attack of colitis, 24 fell ill during travel to the Mediterranean (18), Asia (5), and UK (1). 60 patients were diagnosed as having IBD based on relapse (47) or insidious/subacute onset and development of crypt distortion or basal plasmacytosis (13).4 Out of these, 10 had a history of travel. The patients were assessed clinically, sigmoidoscopically, and microbiologically. Detailed description of the microbiological procedures will be reported elsewhere. In brief, faeces and rectal biopsy specimens were cultured. Isolated Escherichia coli strains were analysed for toxins, adhesins, and enteroinvasivity.5 Tissue culture cells were used to detect Clostridiwn difficile toxin B and Chlamydia trachoma tis, and enzyme-linked immunosorbent assay and electron microscopy to detect rotavirus and enteric viruses. Wet smears were prepared for

parasitic pathogens. Among the patients with IBD, 1 had C difficile toxin B in faeces although no antibiotics had been given. Otherwise no pathogens were detected. Pathogens were detected in all patients with infectious colitis (table). Patients with IBD (7/10) had signs of crypt distortion and basal plasmacytosis, by contrast with patients who had infectious colitis. In the IBD patients the onset was acute in 3, subacute in 3, and insidious in 4. Initially IBD patients had less frequent bowel

movement

than those with infectious colitis

242

CLINICAL DETAILS OF PATIENTS WITH INFECTIOUS COLITIS AND IBD

*1 patient with IBD had C difficile toxin

in

faeces but normal temperature, tin faeces.

(table). With the exception of patients with E histolytica and C difficile, patients with infectious colitis had a high temperature and were admitted earlier than those with IBD. Blood was commonly detected in the faeces of patients with IBD, salmonella, or shigella. There was no difference in age distribution, vomiting, abdominal pain, or increased C-reactive protein between patients with IBD or infectious colitis (table). That the first attack of IBD occurred in relation to travel is not a new finding, although the frequency was higher than expected. What is worrying is that 9 of 10 patients with IBD attended an infectious disease clinic. With a recent history of travel, it is reasonable that diagnosis is aimed at identifying an infectious cause. In 2 patients the delay may have contributed to making colectomy necessary. A subacute/insidious onset of disease and less than five bowel movements per day should alert the attending physician to IBD. An acute onset points in the direction of infection but with negative microbiological findings the clinician should consider IBD. Rectal biopsies should be done in all patients presenting with colitis since crypt distortion and basal plasmacytosis are often found in IBD, and will hence be a guide in the treatment of patients with a first attack of colitis.6 Department of Gastroenterology, Danderyd University Hospital, Danderyd, Sweden

GUDRUN SCHUMACHER BO KOLLBERG

Department of Medical Microbiology, University of Lund, S-223 62 Lund, Sweden

ÅSA LJUNGH

1. Dronfield MW, Fletcher J, Langman MJS. Coincident salmonella infections and ulcerative colitis: problems of recognition and mangement. BMJ 1974; i: 99-100. 2. Taylor-Robinson S, Miles R, Whitehead A, Dickinson RJ. Salmonella infection and ulcerative colitis. Lancet 1989; i: 1145. 3. Willoughby JMT, Rahman AFMS, Gregory MM. Chronic colitis after Aeromonas infection. Gut 1989; 30: 686-90. 4. Schumacher G, Sandstedt B, Möllby R, Kollberg B. Clinical and histologic features differentiating non-relapsing colitis from first attacks of inflammatory bowel

disease. Scand J Gastroenterol 1991; 26: 151-61. 5. Wiström J, Gentry LO, Palmgren A-C, et al. Ecological effects of short-term ciprofloxacin treatment of travellers’ diarrhoea. J Antimicrob Chemother 1992; 30: 693-706. 6. Surawicz CM. Diagnosing colitis: biopsy is best. Gastroenterology 1987; 92: 538-40.

Brain

biopsy for intracranial

mass

lesions

in AIDS your Nov 7 editorial on brain biopsy for intracranial lesions in AIDS you say that primary prophylaxis for toxoplasma encephalitis might be effective; however, there are no reliable data on how effective it would be. As seen in Pneumocystis carinii pneumonia prophylaxis, some failures might be expected. Furthermore, primary prophylaxis for toxoplasma encephalitis is not widely accepted. Toxoplasma encephalitis is the most common cause of intracranial mass lesions in AIDS worldwide and, by contrast with progressive multifocal leucoencephalopathy or central nervous system lymphoma, it is potentially treatable. Whether an AIDS patient with intracranial mass lesions should be treated

SIR,-In

mass

empirically with antitoxoplasma drugs will depend on several individual and geographical characteristics. The number of CD4 cells per tL, the presence of previous positive serological rests for Toxoplasma gondii, and the number of lesions on computed tomography or, preferably, magnetic resonance imaging (a single lesion is suggestive of central nervous system lymphoma) should all be considered. The potential of new, less invasive diagnostic techniques, such as the polymerase chain reaction for detection of T gondii in cerebrospinal fluid,l seems promising. The patient’s clinical status will determine whether biopsy would establish a definite diagnosis if non-invasive procedures had failed to do so. The prevalence of toxoplasmosis in the general population in a particular region should also be taken into account. Finally, routine necropsy in AIDS patients would establish the aetiology of intracranial mass lesions in an individual and the prevalence of various causes in a specific AIDS population, as well as its relation to immunity status or other epidemiological factors. Brain biopsy, although generally safe, is an invasive procedure that may produce inconclusive results if the specimen does not contain the type of tissue necessary for a diagnosis findings can be misleading if several disorders coexist in a patient. In some cases of intracranial mass lesions diagnosed by biopsy as toxoplasma encephalitis, necropsy has revealed toxoplasma encephalitis coexisting with various other diseases, such as lymphoma,

Mycobacterium tuberculosis, cytomegalovirus,

or

Mycobacteriwn

avium-intracellulare.3 Clinical data for intracranial mass lesions in AIDS patients show that emphasis on biopsy in the early 1980s has shifted to empirical antitoxoplasma therapy.’ Although brain biopsy should not be used indiscriminately in AIDS patients with intracranial mass lesions, the more defmed the indications for brain biopsy are, the more useful this diagnostic procedure will be. Hospital de la Santa Creu i Sant Pau, 08025 Barcelona, Spain; Hospital Clínic i Provincial, Barcelona; and Facultad de Medicina, Valladolid

ESTEBAN MARTINEZ ANGELES MARCOS ELENA MARTINEZ-CHAMORRO CARMEN MARTINEZ-CHAMORRO PERE DOMINGO

Farga MA, Alcaraz MJ, Querol JM, et al. Diagnóstico de toxoplasmosis cerebral en pacientes con sindrome de inmunodeficiencia adquirida mediante PCR. Enf Infec Microbiol Clin 1992; 10 (suppl 2): 56. 2. Wong B, Gold JWM, Brown AE, et al. Central nervous system toxoplasmosis in homosexual men and parenteral drug abusers. Ann Intern Med 1984; 100: 36-42. 3. Bishburg E, Eng RHK, Slkim J, Perez G, Johnson E. Brain lesions in patients with acquired immunodeficiency syndrome. Arch Intern Med 1989; 149: 941-43. 4. Renold C, Sugar A, Chave JP, et al. Toxoplasma encephalitis in patients with the acquired immunodeficiency syndrome. Medicine 1992; 71: 224-39. 1.

SIR,-We agree with your sentiment that although brain biopsy is a low-risk procedure it is not a no-risk procedure. This risk may be further compounded in patients with a coagulation disorder-eg, thrombocytopenia or haemophilia. The only imaging techniques considered were magnetic resonance imaging (MRI) and computed tomography (CT), with no mention of positron emission tomography (PET) which may be of use in the selection of patients for biopsy. Although this method is not widely available in the UK it is much used in the USA and continental Europe. Hoffinan et al’ have demonstrated a potential role of 18F-fluorodeoxy-glucose (18FDG) in the assessment of space-occupying lesions in the brains of patients with AIDS. Lesions with a high 18FDG uptake were more likely to have a malignant process and should therefore be biopsied if that is considered the correct course of action in an individual, whereas those with a low uptake were more likely to have an opportunistic infection and could therefore be continued on presumptive antitoxoplasma treatment. Although these data are few they do indicate a further non-invasive means to select patients for a therapeutic strategy. We have investigated a patient with severe haemophilia and AIDS who presented with a lower right quandrantanopia. The patient was allergic to sulphonamides. The MRI scan showed multiple lesions; the T2 image clearly showed a large lesion in the occipital area involving both white and grey matter (figure, upper) and the 18FDG showed a single area of low uptake in this region