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CYTOMEGALOVIRUS INFECTION AND PROGRESSION TO AIDS
681
CYTOMEGALOVIRUS INFECTION AND PROGRESSION TO AIDS
DEGREE OF SIDEROSIS JUDGED HISTOLOGICALLY AND AMOUNT OF BLOOD TRANSFUSED
SIR,-Dr Chavanet reports preliminary data (Aug 5, p 335) on acyclovir to potentially delay the onset of AIDS. Our own placebo-controlled trial of oral acyclovir 800 mg four times daily for the use of
HIV-positive individuals 400 x
with CD4
counts
between 200 and
106/1 is scheduled to begin in October. Two-year follow-up is
planned, and it will be interesting to see how the results compare with those from Dijon. In answer to Dr Morris (Aug 5, p 335), the mean annual factor VIII use did not differ between CMV-seropositive and CMVseronegative patients. These data were provided in our original text but not in the published version, and are consistent with our finding and that of Dr Bamass and colleagues (Aug 5, p 336) that the frequency of CMV infection in HIV-infected haemophiliacs is closely similar to that in the general population. Dr Bamass and colleagues’ failure to detect an association between CMV and AIDS could be explained by the fact that only 18 HIV-positive patients were available for investigation, and confounding variables, such as age and time since HIV seroconversion, were not controlled for. We find it difficult to accept that CMV antibody production and HIV disease progression result from coincidental T-cell compromise, since CMV antibody production was shown in the earliest available stored serum sample from 40 of 42 CMV seropositive patients, taken an average of more than five years before the study. Similar criticisms concerning number of patients, and ability to control for time elapsed since HIV seroconversion can be made about Dr Rugman and colleagues’ results (Sept 9, p 631). In addition, CDC stage III should not be regarded as progression of HIV disease. Although it may be true that there was no significant difference between the (32microglobulin values seen in groups of CMV-seropositive and CMV-seronegative patients, the trend was in the direction suggested in our original article (3 99 5’ 14 fg/ml, p=0-067). We feel that these results certainly do not exclude an association between CMV and Pmicroglobulin but should encourage clinicians with larger cohorts of patients to do similar
investigations. We agree with Dr Bamass et al that studies of active CMV infection should be done, and favour detection of CMV excretion rather than IgM estimation, since this latter technique is insensitive, even in patients with unimpaired immune function. The Medical Research Council has declined three requests (in 1987,1988, and 1989) to fund such studies in our cohort, and we have now applied elsewhere for funding.
Royal Free Hospital, London NW3 2QG
A. WEBSTER J. E. GRUNDY C. A. LEE V. C. EMERY D. G. COOK P. B. A. KERNOFF P. D. GRIFFITHS
p<0001
(x2 test).
these had been given more than 10 units. 14 patients had histological iron scores of 1/2, and of these 10 had been transfused with 4-41 units (mean 20). The relation between iron deposition and transfusion record is summarised in the table. In our cases clinically important consequences of iron overload have not been observed. Histologically, 1 case out of the 7 with scores of 3/4 showed mild portal fibrosis, but none showed portal linking or more advanced disease. This is scarcely surprising given the short duration of the siderosis. However the clinical consequences of longer-term acquired transfusional iron overload in non-thalassaemic adults have been clearly describedthe pattern of organ involvement resembling that in idiopathic haemochromatosis. While other more immediate problems may beset the HIVpositive patient on zidovudine therapy, our observations suggest that patients receiving large transfusions rapidly develop significant iron overload, which, with longer survival, may become clinically
important. We thank Mrs B. Jackson, department of haematology, Royal Free Hospital, London, for the liver iron measurements, and Dr A. J. Pinching and Dr B. Peters for allowing us to study their patients.
Departments of Histopathology and Immunology, St Mary’s Hospital, London W2 1NY
ROGER LINDLEY JACKIE PARKIN SPYROS DURAKIS ROBERT GOLDIN
1. Walker RJ, Miller, JPG, Dymock IW, Shilkin KB, Williams R. Relationship of hepatic iron concentration to histochemical grading and to total chelatable body iron in conditions associated with iron overload. Gut 1971; 12: 1011-14. 2. Barry M. Liver iron concentration, stainable iron, and total body storage iron. Gut
1974; 15: 411-15. R, Dluhy R, et al. Clinical consequences of acquired transfusional iron overload in adults. N Engl J Med 1981; 304: 319-24.
3. Schafer A, Cheron
REDUCED SWEATING IN ADULTS WITH GROWTH HORMONE DEFICIENCY
SIR,-Up to 50% of patients infected with HIV and treated with zidovudine acquire anaemia necessitating blood transfusion. While reviewing liver biopsy material from HIV-positive patients at St Mary’s Hospital we noted heavy iron deposition in some. This correlates directly with the transfusion history. In 74 liver biopsy specimens iron deposition was graded 0-41 on Perl’s stained sections, without knowledge of the transfusion history. This grading system correlates well with measurements of liver iron content.2 Seven patients had scores of 3 or 4, corresponding to significant iron deposition. Iron was present in hepatocytes, Kupffer cells, and biliary epithelium. All 7 were on zidovudine and had received between 29 and 59 units of blood (mean 44). They had been on zidovudine for between 12 and 19 months and had been receiving transfusion for between 11and 15 months. In 3 cases there was sufficient tissue for measurement of liver iron, which was 906, 1079, and 1575 ng per 100 mg dry weight
SIR,-Increased growth hormone (GH) production in acromegaly is known to be associated with increased sweat production1 yet little interest has been paid to sweating in GH deficiency. We find that some GH-deficient patients have dry skin and reduced sweat production and report here on sweat production in GH-deficient adults during a placebo-controlled trial of GH. 22 adults with GH deficiency (8 women, 14 men; mean age 24 years, range 18-39) were included in the study but 1 withdrew before completion of the investigation. The clinical data are given elsewhereGH deficiency had been diagnosed in childhood. All patients had discontinued GH treatment at least 6 months before the study. In this double-blind, crossover study2 the treatment periods lasted 4 months with a 4 month washout in between. GH (’Norditropin’; Novo-Nordisk) was given at a dose of 2 IU/m2 subcutaneously at 2000 hours daily. Serum IGF-1(insulin growth factor-1) was measured by RIA. 30 healthy volunteers (11 women, 19 men; mean age 28 years, range 16-40) served as controls. At the end of each treatment period the patients were asked if their sweating ability had decreased, remained unchanged, or increased compared with the previous period and if any change had
(normal range 35-126). Of the 53 patients with no liver iron deposition as judged histologically, only 10 had received any transfusion, and only 2 of
been associated with an alteration in comfort. Sweat secretion was measured by a pilocarpine test at room temperature. Sweating was induced on the flexor side of the forearm
IRON DEPOSITION IN LIVER IN ZIDOVUDINE-RELATED TRANSFUSION-DEPENDENT ANAEMIA
CYTOMEGALOVIRUS INFECTION AND PROGRESSION TO AIDS
DEGREE OF SIDEROSIS JUDGED HISTOLOGICALLY AND AMOUNT OF BLOOD TRANSFUSED
SIR,-Dr Chavanet reports preliminary data (Aug 5, p 335) on acyclovir to potentially delay the onset of AIDS. Our own placebo-controlled trial of oral acyclovir 800 mg four times daily for the use of
HIV-positive individuals 400 x
with CD4
counts
between 200 and
106/1 is scheduled to begin in October. Two-year follow-up is
planned, and it will be interesting to see how the results compare with those from Dijon. In answer to Dr Morris (Aug 5, p 335), the mean annual factor VIII use did not differ between CMV-seropositive and CMVseronegative patients. These data were provided in our original text but not in the published version, and are consistent with our finding and that of Dr Bamass and colleagues (Aug 5, p 336) that the frequency of CMV infection in HIV-infected haemophiliacs is closely similar to that in the general population. Dr Bamass and colleagues’ failure to detect an association between CMV and AIDS could be explained by the fact that only 18 HIV-positive patients were available for investigation, and confounding variables, such as age and time since HIV seroconversion, were not controlled for. We find it difficult to accept that CMV antibody production and HIV disease progression result from coincidental T-cell compromise, since CMV antibody production was shown in the earliest available stored serum sample from 40 of 42 CMV seropositive patients, taken an average of more than five years before the study. Similar criticisms concerning number of patients, and ability to control for time elapsed since HIV seroconversion can be made about Dr Rugman and colleagues’ results (Sept 9, p 631). In addition, CDC stage III should not be regarded as progression of HIV disease. Although it may be true that there was no significant difference between the (32microglobulin values seen in groups of CMV-seropositive and CMV-seronegative patients, the trend was in the direction suggested in our original article (3 99 5’ 14 fg/ml, p=0-067). We feel that these results certainly do not exclude an association between CMV and Pmicroglobulin but should encourage clinicians with larger cohorts of patients to do similar
investigations. We agree with Dr Bamass et al that studies of active CMV infection should be done, and favour detection of CMV excretion rather than IgM estimation, since this latter technique is insensitive, even in patients with unimpaired immune function. The Medical Research Council has declined three requests (in 1987,1988, and 1989) to fund such studies in our cohort, and we have now applied elsewhere for funding.
Royal Free Hospital, London NW3 2QG
A. WEBSTER J. E. GRUNDY C. A. LEE V. C. EMERY D. G. COOK P. B. A. KERNOFF P. D. GRIFFITHS
p<0001
(x2 test).
these had been given more than 10 units. 14 patients had histological iron scores of 1/2, and of these 10 had been transfused with 4-41 units (mean 20). The relation between iron deposition and transfusion record is summarised in the table. In our cases clinically important consequences of iron overload have not been observed. Histologically, 1 case out of the 7 with scores of 3/4 showed mild portal fibrosis, but none showed portal linking or more advanced disease. This is scarcely surprising given the short duration of the siderosis. However the clinical consequences of longer-term acquired transfusional iron overload in non-thalassaemic adults have been clearly describedthe pattern of organ involvement resembling that in idiopathic haemochromatosis. While other more immediate problems may beset the HIVpositive patient on zidovudine therapy, our observations suggest that patients receiving large transfusions rapidly develop significant iron overload, which, with longer survival, may become clinically
important. We thank Mrs B. Jackson, department of haematology, Royal Free Hospital, London, for the liver iron measurements, and Dr A. J. Pinching and Dr B. Peters for allowing us to study their patients.
Departments of Histopathology and Immunology, St Mary’s Hospital, London W2 1NY
ROGER LINDLEY JACKIE PARKIN SPYROS DURAKIS ROBERT GOLDIN
1. Walker RJ, Miller, JPG, Dymock IW, Shilkin KB, Williams R. Relationship of hepatic iron concentration to histochemical grading and to total chelatable body iron in conditions associated with iron overload. Gut 1971; 12: 1011-14. 2. Barry M. Liver iron concentration, stainable iron, and total body storage iron. Gut
1974; 15: 411-15. R, Dluhy R, et al. Clinical consequences of acquired transfusional iron overload in adults. N Engl J Med 1981; 304: 319-24.
3. Schafer A, Cheron
REDUCED SWEATING IN ADULTS WITH GROWTH HORMONE DEFICIENCY
SIR,-Up to 50% of patients infected with HIV and treated with zidovudine acquire anaemia necessitating blood transfusion. While reviewing liver biopsy material from HIV-positive patients at St Mary’s Hospital we noted heavy iron deposition in some. This correlates directly with the transfusion history. In 74 liver biopsy specimens iron deposition was graded 0-41 on Perl’s stained sections, without knowledge of the transfusion history. This grading system correlates well with measurements of liver iron content.2 Seven patients had scores of 3 or 4, corresponding to significant iron deposition. Iron was present in hepatocytes, Kupffer cells, and biliary epithelium. All 7 were on zidovudine and had received between 29 and 59 units of blood (mean 44). They had been on zidovudine for between 12 and 19 months and had been receiving transfusion for between 11and 15 months. In 3 cases there was sufficient tissue for measurement of liver iron, which was 906, 1079, and 1575 ng per 100 mg dry weight
SIR,-Increased growth hormone (GH) production in acromegaly is known to be associated with increased sweat production1 yet little interest has been paid to sweating in GH deficiency. We find that some GH-deficient patients have dry skin and reduced sweat production and report here on sweat production in GH-deficient adults during a placebo-controlled trial of GH. 22 adults with GH deficiency (8 women, 14 men; mean age 24 years, range 18-39) were included in the study but 1 withdrew before completion of the investigation. The clinical data are given elsewhereGH deficiency had been diagnosed in childhood. All patients had discontinued GH treatment at least 6 months before the study. In this double-blind, crossover study2 the treatment periods lasted 4 months with a 4 month washout in between. GH (’Norditropin’; Novo-Nordisk) was given at a dose of 2 IU/m2 subcutaneously at 2000 hours daily. Serum IGF-1(insulin growth factor-1) was measured by RIA. 30 healthy volunteers (11 women, 19 men; mean age 28 years, range 16-40) served as controls. At the end of each treatment period the patients were asked if their sweating ability had decreased, remained unchanged, or increased compared with the previous period and if any change had
(normal range 35-126). Of the 53 patients with no liver iron deposition as judged histologically, only 10 had received any transfusion, and only 2 of
been associated with an alteration in comfort. Sweat secretion was measured by a pilocarpine test at room temperature. Sweating was induced on the flexor side of the forearm
IRON DEPOSITION IN LIVER IN ZIDOVUDINE-RELATED TRANSFUSION-DEPENDENT ANAEMIA