1121

plus

toxin became infected after

a

large dose of live gastric

helicobacters. This result indicates that intervention

against H pylori is a real

possibility. Much needs to be done to define further the best protocol and to identify less potentially toxic adjuvants, such as cholera toxoid rather than toxin.7 Formulation of equivalent safe vaccines of H pylori would make possible the immunisation of children in countries such as China and Columbia and so prevent the establishment of long-term inflammation, and its possible consequences.

MINHU CHEN ADRIAN LEE STUART HAZELL

School of Microbiology and Immunology, University of New South Wales, Kensington, NSW 2033, Australia

1. Forman D, Newell DG, Fullerton F, et al. Association between infection with Helicobacter pylori and risk of gastric cancer: evidence from a prospective investigation. Br Med J 1991; 302: 1302-05. 2. Sharma AW, Mayrhofer G. A comparative study of infections with rodent isolates of Giardia duodenalis in inbred strains of rats and mice. Parasite Immunol 1988; 10: 169-79. 3. Czinn SJ, Nedrud JG. Oral immunization against Helicobacter pylori. Infect Immun 1991; 59: 2359-63. 4. Lee A, Hazell SL, O’Rourke J, Kouprach S. Isolation of a spiral-shaped bacterium from the cat stomach. Infect Immun 1988; 56: 2843-50. 5. Lee A, Fox JG, Otto G, Murphy J. A small animal model of human Helicobacter pylori active chronic gastritis. Gastroenterology 1990; 99: 1315-23. 6. Dick-Hegedus E, Lee A. Use of mouse model to examine anti-Helicobacter pylori 1991; 26: 909-15. agents. Scand Gastroenterol J 7 Liang X, Lamm ME, Nedrud JG. Cholera toxin as a mucosal adjuvant: glutaraldehyde treatment dissociates adjuvanticity from toxicity. J Immunol 1989; 143: 484-90.

respiratory quality-of-life questionnaires that are applicable to patients with COPD.2.3 Although the frequency of this urgency has not been investigated formally we have been finding a frequency of about 50% in outpatients. We decided to try and find out what burden this excretion urgency places on patients. A symptom may be medically interesting but of little consequence to quality of life if it is not distressing. 55 COPD outpatients were sent a questionnaire asking the degree of "bother" caused by five problems commonly found in COPD patients. The paired comparison method (in which problems are shown in pairs and the patient is asked which causes the most bother) was used. Of the 25 patients who returned completed questionnaires, all reported "being unable to do things because you get too breathless" and 14 reported "Having to go to the toilet when you get breathless". Of those who experienced excretion urgency, 6 rated it as causing more bother than being unable to do things and 8 rated being unable to do things as more bother than excretion urgency. These findings show that when COPD patients experience excretion urgency, this can sometimes have a substantial effect on quality of life. 1 patient told us that urgency was reduced after a change in therapy led to less breathessness. One possibility was that the excretion urgency was iatrogenic, associated with theophylline; however, we found no association between this drug and excretion urgency. Department of Psychology, Polytechnic South West, Plymouth PL4 8AA, UK

M. E. HYLAND

Department of Thoracic Medicine,

Helicobacter pylori infection with age SIR,-Dr Mendall and colleagues (April 11, p 896) give an important insight into the epidemiology of Helicobacter pylori infection as determined by serology. However, they repeat the received wisdom that Hpylori infection increases progressively with age. This is not necessarily true if direct tests are done, since serology may merely represent past infection. We studied 462 patients, not on antibiotics or ulcer-healing therapy, who had normal upper digestive endoscopy. A gastric antral forceps biopsy was taken for urea gel/indicator testing (CLO-test). There was no sex difference. Though a progressive rise in infection age:

rates was

noted up

to

age

Age (yr)

70, there was a fall after that Proportion positive 4/17 (24%) 20/63 (32 % ) 25/67 (37%) 28/78 (36 % ) 24/50 (48%J

14-19 20-29 30-39 40-49 50-59 60-69 70-79 80-92 All

43/67(64%) 30/84 ( 36 %J 11/36 (31 %J

185/462 (40%) Various explanations might account for this finding, but it does suggest that older people return to the lower infection rates seen under age 30. Certainly the relation between H pylori infection and age is not simply a progressive one. Bishop Auckland General Hospital, Bishop Auckland DL14 6AD, UK

M. C. BATESON

Excretion urgency in chronic obstructive pulmonary disease

SIR,-During

research into the

quality of life of patients with

chronic obstructive pulmonary disease (COPD), we held four focus groups where patients talked to each other about how their

respiratory disorder affected their lives. It emerged that some patients experience excretion urgency associated with the sensation of increased breathlessness. Some repeatedly feel the urge to urinate or to defaecate, or both. The feeling of urgency does not appear to be related to the amount of excretion which subsequently takes place. Such difficulties are not reported in previous accounts of quality of life deficit in COPD patients,l nor does this topic feature in general

King’s College School and Dentistry,

of Medicine

J. BOTT

London SE5

McSweeny AJ, Labuhn KT. Chronic obstructive pulmonary disease. In: Spilker B, ed. Quality of life assessments in clinical trials. New York: Raven, 1990: 391-417. 2. Guyatt GH, Berman LB, Townsend M, Pugsley SO, Chambers LW. A measure of quality of life for clinical trials in chronic lung disease. Thorax 1987; 42: 773-78. 3. Jones PW, Quirk FH, Basveystock CM, Littlejohns P. A self-complete measure for chronic airflow limitation—the St George’s respiratory questionnaire. Am Rev Respir Dis (in press). 1.

Intramuscular medroxyprogesterone acetate for sexual aggression in elderly men SIR,-Sexual aggression in male dementia patients responds poorly to behavioural management or to psychotropic drugs. Anti-androgens have few side-effects (rise in blood pressure, mild pedal oedema) and they reduce sexual drive and sexually aggressive acts in cognitively intact and brain-damaged hypersexual men of all ages.l-4 Treatment thus far reported in old men has been with daily or weekly dosing. In the two cases described here, inappropriate sexual aggression was eliminated with small doses of intramuscular medroxyprogesterone acetate (MPA) every two weeks. A 72-year-old man’s hypersexuality began with molestation of his 12-year-old stepdaughter 25 years earlier. For many years, he had frequent contact with prostitutes, and in the most recent 2 years had begun fondling women of all ages, had exposed himself to children, and openly masturbated anally. He had been discharged from military service at age 25 with 10% psychiatric disability and had been admitted to hospital and treated with electroconvulsive therapy two or three times because of violence, auditory hallucinations, and grandiose delusions. He became unable to work vehicle accident which resulted in loss of a ruptured spleen. His aberrant sexual behaviour increased after his head injury. Insidious onset of cognitive impairment began at age 70. Evaluation at age 71 established organic mental disorder. A computed tomographic brain scan revealed only mild cerebral atrophy. A small dose of thioridazine produced severe extrapyramidal effects. MPA 100 mg every 2 weeks was started on Oct 15, 1991. On Oct 28, his testosterone level had dropped from 2-9 ng/ml to 1 ’7 ng/ml and his sexual behaviour had improved in that he no longer made inappropriate sexual comments to staff and patients. However, the patient continued inappropriate behaviours such as inserting objects (shampoo bottles, soap) into his rectum. The MPA dose was at

age

62, after

a motor

consciousness, multiple fractures, and

1122

increased to 150 mg and after 2 more weeks his inappropriate sexual behaviour ceased. An 84-year-old man was noted to be hypersexual after admission to a nursing-home. He made sexual advances to female residents. He frequently attempted to fondle female staff, and when they refused fondling or interrupted his fondling of other residents, he became physically and verbally aggressive. The insidious development of cognitive impairment began at age 72. Alzheimer’s disease was diagnosed at age 74, on the basis of clinical examination and neuropsychological testing. He had no previous psychiatric history, but had undergone repair of an abdominal aortic aneurysm, had a history of hypothyroidism and was taking glyburide 2-5 mg daily for adult-onset diabetes. Small doses of thioridazine produced severe sedation and lethargy. MPA 200 mg was given. His hypersexual behaviour abated within 2 weeks. He was continued on MPA 200 mg every other week and his thioridazine (25 mg four times a day) was gradually discontinued over the next 3 weeks. Departments of Psychiatry

MYRON F. WEINER MARGO DENKE KATHRYN WILLIAMS ROBERT GUZMAN

and Internal Medicine, University of Texas, Southwestern Medical Center, Dallas, Texas 75235, USA 1.

Cooper AJ. Progestogens in the Psychiatry 1986; 31: 73-79.

treatment

of male

sex

offenders:

a

review.

Can J

LA, Bland WP, Ruskin P, et al. Antiandrogen treatment of aberrant sexual activity. Am JPsychiatry 1987; 144: 1511. 3. Cooper AJ. Medroxyprogesterone acetate (MPA) treatment of sexual acting out in men suffering from dementia. J Clin Psychiatry 1987; 48: 368-70. 4. Cooper AJ. Medroxyprogesterone acetate as a treatment for sexual acting out in organic brain syndrome. Am J Psychiatry 1988; 145: 1179.

These

observations

have

considerable

potential clinical

importance. Since polyomavirus infection

may precede CMV infection and since both viruses may take 10-14 days to isolate, the presence of typical features of viral cystitis should make one vigilant for the possibility of coincident CMV infection. This is important now that it has been shown that the early treatment of symptom-free patients with positive CMV surveillance cultures significantly improves survival in the first 100 days after BM T. 1,3 Polyomavirus infection may be a marker of early CMV disease.

DAVID I. MARKS KATE WARD MRC/LRF Leukaemia Unit,

Department of Haematology, Hammersmith Hospital, London W12 ONN, UK

JILL HOWS A. JOHN BARRETT JOHN M. GOLDMAN

1. Goodrich JM, Mon M, Gleaves CA, et al. Early treatment with ganciclovir to prevent cytomegalovirus disease after allogeneic bone marrow transplantation. N EnglJ Med 1991; 325: 1601-07. 2. Apperley JF, Rice SJ, Bishop JA, et al. Late-onset hemorrhagic cystitis associated with urinary excretion of polyomaviruses after bone marrow transplantation. Transplantation 1987; 43: 108-12. 3. Schmidt GM, Horak DA, Niland JC, et al. A randomized, controlled trial of prophylactic ganciclovir for cytomegalovirus pulmonary infection in recipients of allogeneic bone marrow transplants: the City of Hope-Stanford-Syntex CMV Study Group. N EnglJ Med 1991; 324: 1005-11.

2. Ross

Viral

(polyomavirus) cystitis heralding cytomegalovirus infection

SIR,-Cytomegalovirus (CMV) infection

are

often

seen

and

polyomavirus (BK) allogeneic bone-marrow in especially profoundly

after

transplantation (BMT),i immunosuppressed patients. In both, the infection seems to be due to reactivation of latent virus. There is no specific treatment for polyomavirus infection but early treatment of CMV infection seems to improve survival.’1 We describe here six patients with both infections after BMT for chronic myeloid leukaemia (table). In all cases the donor and/or recipient had been positive for CMV IgG pre-BMT. All six were receiving cyclophosphamide as part of their pre-transplant conditioning. All had graft-versus-host disease and were treated with high-dose intravenous methylprednisolone (1 g/m2), and two received monoclonal antibody against interleukin-2 receptor. Although the mean times to diagnosis of CMV infection and polyomavirus were similar, in four cases the polyomavirus was isolated before CMV was diagnosed (range 4-10 days, mean 6 days). Five patients had CMV isolated from multiple sites and all were treated with ganciclovir and CMV hyperimmune globulin;’ in two, CMV pneumonitis developed. Two patients with polyomavirus had no urinary symptoms, two had mild symptoms, and two required diamorphine for symptomatic control of severe nocturnal frequency. The mean duration of urinary symptoms was 2 weeks. These patients had other viral infections. One patient had adenovirus isolated from a gastric biopsy specimen and another had herpes simplex virus type I detected in throat gargle fluid. CLINICAL AND VIROLOGICAL DATA

BAL = bronchoalveolar lavage

Hyperhomocysteinaemia and recurrent or abruptio placentae

spontaneous abortion

SIR,-Hibbard (1964) was the first to report an association between spontaneous abortion and abruptio placentae and a maternal folate deficiency due to a defective folate metabolism.’ However, studies on this subject are conflicting. Homocysteine remethylation to methionine is dependent on both folate and vitamin B12’ Enzyme deficiencies involved in homocysteine remethylation and folate and vitamin B12 metabolism (and malnutrition and malabsorption of those vitamins) results in hyperhomocysteinaemia.2-4 Classic homocysteinuria is an autosomal recessively inherited metabolic disorder due to a deficiency of pyridoxine-dependent cystathionine synthase.4,5 This enzyme converts homocysteine into cystathionine, and its deficiency results in excess storage of homocysteine. Untreated homozygous women with classic homocysteinuria experience fetal loss rates of almost 50%,’ and increased perinatal mortality in obligate heterozygotes has also been reported.6 We hypothesised that even moderate hyperhomocysteinaemia might be a risk factor for recurrent spontaneous abortion and abruptio placentae, so we decided to measure homocysteine concentrations in non-pregnant women with a history of recurrent spontaneous abortion or abruptio placentae but no known risk factors for such events. Recurrent abortion was defined as two more more successive miscarriages (up to 16 weeks from the beginning of the last menstrual period) with confirmation by pregnancy test, ultrasound scan, or histopathological examination. Blood concentrations of vitamins relevant to homocysteine metabolism were also studied. On the 21 st day of the ovulatory cycle we did a standardised oral methionine loading test in 24 such women (mean age 31-8 [SD 4-8]), 14 had recurrent spontaneous abortion and 10 had a history of abruptio placentae. The controls were 15 normal women (mean age 31-4 [4’7]),7,8 All women had normal liver and kidney function. 6 patients in the study group had concentrations of total homocysteine 6 h after methionine loading more than 2 SD above the mean for controls (table). Their fasting homocysteine values were also increased, albeit not significantly. Cystathionine synthase activity was measured in cultured fibroblasts of all methionine intolerant patients, using a previously reported method with slight modificationand it ranged from 1 -8 to 18nmol/h per mg protein (normal 2-3-18 2), thus excluding heterozygosity for homocysteinuria in these patients. The mean fasting values of folate and especially vitamin B12 in serum were lower in the hyperhomocysteinaemic women, but not significantly in comparison with controls. A possible cause for hyperhomocysteinaemia in these 6 women may be diminished homocysteine remethylation, induced by, for