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
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
