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DEXAMETHASONE SUPPRESSION TESTS IN DEPRESSION AND RESPONSE TO TREATMENT
92 DEXAMETHASONE SUPPRESSION TESTS IN DEPRESSION AND RESPONSE TO TREATMENT
COMPARISON OF CELL CULTURES WITH MOLECULAR HYBRIDISATION IN DETECTION OF PERSISTENT ADENOVIRUS INFECTION IN TONSILLAR TISSUE
SIR,-Dr Gold and his colleagues (May 31, p. 1190) report that, after successful electroconvulsive treatment, five of six depressed patients were no longer hypersecretors of cortisol on the dexamethasone suppression test (DST). Unfortunately, we told whether any of the patients rapidly relapsed after their last treatment, so that findings neither confirm nor refute my suggestion (Feb. 16, p. 376) that the DST is a useful predictor of safe withdrawal of antidepressant therapy. Since my original report, two additional patients whose depressions remitted following tricyclic antidepressant therapy have been found to be hypersecretors of cortisol when the 1 mg 34 h DST was done after they had been depression-free for one month while continuing antidepressants. Both patients relapsed rapidly when the antidepressants were stopped. The patients, from this and my original report, who showed an abnormal DST one month following clinical remission relapsed 2, 3, 5, 6, and 8 weeks following discontinuation of treatment. The five patients whose DST reverted to normal following treatment have now been drug-free for over 7 months. None have relapsed. I strongly urge physicians to have both clinical and neuroendocrine evidence of remission before discontinuing antidepres-
are not
santtherapy. New York Psychopharmacologic Institute, New York, N Y. 10028, U.S.A.
IVAN K. GOLDBERG
For solution hybridisation, reaction mixtures contained 5 mg/ml sheared tonsil or E. coli (control) DNA, 37 ng/ml 3H-labelled adenovirus type 5 DNA (specific activity, 2. 7x 106 CpM/tig), 5 mmol/1 EDTA, 25 mmol/l "hepes", 1-5 mola NaCl and 50% formamide. 10 ul aliquots were heat denatured, incubated at 43°C to a maximum equivalent Cot of 1.7 xl 05 and the proportion of reassociated adenovirus DNA, determined by hydroxylapatite chromatography, plotted against tonsil DNA concentration x time (Cot, relative to 0-12 mol/1
NaCP). For in-situ hybridisation, 30-50x 103 cpm 3H-labelled adenovirus type 5 DNA (specific activity, l-7xx 106 cpm/(JLg) was hybridised to fixed impression smears of tonsil tissue and hybridisation detected by auto-
radiography.’I ALLOPURINOL IN DUCHENNE DYSTROPHY
SIR,-I wish to protest against the publication (June 21, p. 1358) of that letter by Dr Castro-Gago and others on the use of allopurinol in Duchenne muscular dystrophy. The experience reported was vague, the trial was uncontrolled, and the "improvement" in the youngest boys seems compatible with the well-known spurious improvement which often occurs before the age of 6. At a time when there is distressing controversy over the use of this drug (New Scientist, June 12, p. 229) precisely because of the inadequacy of the original trials, and when publicity is raising unfounded hopes in hundreds of familes affected by the disease, it is tragic that The Lancet should add to the confusion. Surely when the idea of a possible new therapy for an "incurable" disease is launched journals should insist that subsequent publications, even letters, are scientifically irreproachable. Regional Neurological Centre, Newcastle General Hospital, Newcastle Upon Tyne NE4 6BE
nucleic acid sequences in tonsil tissue by in situ and solution hybridisation and also, for comparison, attempted recovery of infectious virus from primary tonsil cell cultures.2 Ten experiments are summarised in the table and suggest that results with the two methods of hybridisation may not always agree. One possible explanation is that if the virus genome is present in only a small number of cells it might be detectable by in situ hybridisation if sufficient cells are screened but not by solution
hybridisation. Herpes simplex virus can reach the brain after inoculation at a peripheral site,3 and, in man, latent herpes infections can be detected in sensory ganglia.’ It is reasonable to suspect that this virus may persist in brain tissue. Virology Department, Withington Hospital, Manchester M20 8LR
SIR,-Dr Middleton and colleagues (May 10, p. 1038) report failure to detect herpes simplex virus DNA sequences in brain tissue from demented elderly patients. Few such specihave yet been tested by the complex techniques of molecular hybridisation and it may be misleading to compare negative results in five specimens tested by solution hybridisation with positive results in three of five specimens tested by in-situ
mens
LARGE-BOWEL CANCER IN MARRIED COUPLES IN SWEDEN
S:R,—The assumption by Dr Jensen and associates (May 31, p. 1161) that spouses have similar diets is not unreasonable, but there is little evidence to support this hypothesis. We have measured the nutrient intakes of the individual members of 82 Cambridge families concurrently over 7 days (unpublished). The calculation of nutrient intakes was based on food
hybridisation.I We are examining
2. Rowe
tem.
3.
the adenovirus/human tonsil model sysLatent adenovirus infections in human tonsillar tissue are well recognised and such tissue is readily available following tonsillectomy. We have compared the detection of adenovirus Seqeira LW, Jennings LC, Carrasco LH, Lord MA, Curry A, Sutton RNP. Detection of herpes simplex viral genome in brain tissue. Lancet 1979, ii: 609-12.
R. N. P. SUTTON
D. GARDNER-MEDWIN
DETECTION OF VIRUS GENOME IN HUMAN TISSUES
1.
M. A. LORD R. F. ITZHAKI
WP, Huebner RJ, Gilmore LK, Parrot RH, Ward TG. Isolation of a
cytopathic agent from human adenoids undergoing spontaneous degeneration in tissue culture. Proc Soc Exp Biol Med 1953; 84: 570-73. Knotts FB, Cook ML, Stevens JG. Latent herpes simplex virus in the central nervous system of rabbits and mice. J Exp Med 1973; 138: 740-44.
4. Warren
KG, Devlin M, Gilden DH, Wroblewska Z, Brown SM, Subak-
Sharpe J, Koprowski H. Isolation of herpes simplex virus from human trigeminal ganglia including ganglia from one patient with multiple sclerosis. Lancet 1977; ii: 637-39. RJ, Graham DE, Neufeld BR. Analysis of repeating DNA sequences by reassociation. Methods Enzymol 1974, 29: 363-418.
5. Britten
COMPARISON OF CELL CULTURES WITH MOLECULAR HYBRIDISATION IN DETECTION OF PERSISTENT ADENOVIRUS INFECTION IN TONSILLAR TISSUE
SIR,-Dr Gold and his colleagues (May 31, p. 1190) report that, after successful electroconvulsive treatment, five of six depressed patients were no longer hypersecretors of cortisol on the dexamethasone suppression test (DST). Unfortunately, we told whether any of the patients rapidly relapsed after their last treatment, so that findings neither confirm nor refute my suggestion (Feb. 16, p. 376) that the DST is a useful predictor of safe withdrawal of antidepressant therapy. Since my original report, two additional patients whose depressions remitted following tricyclic antidepressant therapy have been found to be hypersecretors of cortisol when the 1 mg 34 h DST was done after they had been depression-free for one month while continuing antidepressants. Both patients relapsed rapidly when the antidepressants were stopped. The patients, from this and my original report, who showed an abnormal DST one month following clinical remission relapsed 2, 3, 5, 6, and 8 weeks following discontinuation of treatment. The five patients whose DST reverted to normal following treatment have now been drug-free for over 7 months. None have relapsed. I strongly urge physicians to have both clinical and neuroendocrine evidence of remission before discontinuing antidepres-
are not
santtherapy. New York Psychopharmacologic Institute, New York, N Y. 10028, U.S.A.
IVAN K. GOLDBERG
For solution hybridisation, reaction mixtures contained 5 mg/ml sheared tonsil or E. coli (control) DNA, 37 ng/ml 3H-labelled adenovirus type 5 DNA (specific activity, 2. 7x 106 CpM/tig), 5 mmol/1 EDTA, 25 mmol/l "hepes", 1-5 mola NaCl and 50% formamide. 10 ul aliquots were heat denatured, incubated at 43°C to a maximum equivalent Cot of 1.7 xl 05 and the proportion of reassociated adenovirus DNA, determined by hydroxylapatite chromatography, plotted against tonsil DNA concentration x time (Cot, relative to 0-12 mol/1
NaCP). For in-situ hybridisation, 30-50x 103 cpm 3H-labelled adenovirus type 5 DNA (specific activity, l-7xx 106 cpm/(JLg) was hybridised to fixed impression smears of tonsil tissue and hybridisation detected by auto-
radiography.’I ALLOPURINOL IN DUCHENNE DYSTROPHY
SIR,-I wish to protest against the publication (June 21, p. 1358) of that letter by Dr Castro-Gago and others on the use of allopurinol in Duchenne muscular dystrophy. The experience reported was vague, the trial was uncontrolled, and the "improvement" in the youngest boys seems compatible with the well-known spurious improvement which often occurs before the age of 6. At a time when there is distressing controversy over the use of this drug (New Scientist, June 12, p. 229) precisely because of the inadequacy of the original trials, and when publicity is raising unfounded hopes in hundreds of familes affected by the disease, it is tragic that The Lancet should add to the confusion. Surely when the idea of a possible new therapy for an "incurable" disease is launched journals should insist that subsequent publications, even letters, are scientifically irreproachable. Regional Neurological Centre, Newcastle General Hospital, Newcastle Upon Tyne NE4 6BE
nucleic acid sequences in tonsil tissue by in situ and solution hybridisation and also, for comparison, attempted recovery of infectious virus from primary tonsil cell cultures.2 Ten experiments are summarised in the table and suggest that results with the two methods of hybridisation may not always agree. One possible explanation is that if the virus genome is present in only a small number of cells it might be detectable by in situ hybridisation if sufficient cells are screened but not by solution
hybridisation. Herpes simplex virus can reach the brain after inoculation at a peripheral site,3 and, in man, latent herpes infections can be detected in sensory ganglia.’ It is reasonable to suspect that this virus may persist in brain tissue. Virology Department, Withington Hospital, Manchester M20 8LR
SIR,-Dr Middleton and colleagues (May 10, p. 1038) report failure to detect herpes simplex virus DNA sequences in brain tissue from demented elderly patients. Few such specihave yet been tested by the complex techniques of molecular hybridisation and it may be misleading to compare negative results in five specimens tested by solution hybridisation with positive results in three of five specimens tested by in-situ
mens
LARGE-BOWEL CANCER IN MARRIED COUPLES IN SWEDEN
S:R,—The assumption by Dr Jensen and associates (May 31, p. 1161) that spouses have similar diets is not unreasonable, but there is little evidence to support this hypothesis. We have measured the nutrient intakes of the individual members of 82 Cambridge families concurrently over 7 days (unpublished). The calculation of nutrient intakes was based on food
hybridisation.I We are examining
2. Rowe
tem.
3.
the adenovirus/human tonsil model sysLatent adenovirus infections in human tonsillar tissue are well recognised and such tissue is readily available following tonsillectomy. We have compared the detection of adenovirus Seqeira LW, Jennings LC, Carrasco LH, Lord MA, Curry A, Sutton RNP. Detection of herpes simplex viral genome in brain tissue. Lancet 1979, ii: 609-12.
R. N. P. SUTTON
D. GARDNER-MEDWIN
DETECTION OF VIRUS GENOME IN HUMAN TISSUES
1.
M. A. LORD R. F. ITZHAKI
WP, Huebner RJ, Gilmore LK, Parrot RH, Ward TG. Isolation of a
cytopathic agent from human adenoids undergoing spontaneous degeneration in tissue culture. Proc Soc Exp Biol Med 1953; 84: 570-73. Knotts FB, Cook ML, Stevens JG. Latent herpes simplex virus in the central nervous system of rabbits and mice. J Exp Med 1973; 138: 740-44.
4. Warren
KG, Devlin M, Gilden DH, Wroblewska Z, Brown SM, Subak-
Sharpe J, Koprowski H. Isolation of herpes simplex virus from human trigeminal ganglia including ganglia from one patient with multiple sclerosis. Lancet 1977; ii: 637-39. RJ, Graham DE, Neufeld BR. Analysis of repeating DNA sequences by reassociation. Methods Enzymol 1974, 29: 363-418.
5. Britten