1048
cryoglogulin depleted sera gave similar results, incubations of strips with patients’ sera were completed at 37°C to avoid cryoprecipitation. Samples from 14 patients (48%) reacted with two (n 3) or more (n = 11) of the four antigens on the strip, and were classified as positive. Sera from 14 of the remaining 15 patients reacted strongly with the c22 (core) antigen of HCV. This reactivity could be due to rheumatoid factors three out of eight sera from patients with rheumatoid arthritis reacted with c22. 11 of 14 HCV-antibody positive patients had serological evidence of hepatitis B virus (HBV) infection (antiHBc positivity). Among the 15 HCV-antibody negative patients, 8 were antiHBc positive. Chronic active hepatitis or cirrhosis was diagnosed in 13 of 14 HCV-antibody positive patients, in 5 of 8 HCV-antibody negative and antiHBc-positive patients, and in only 1 of 7 patients negative for both HCV and antiHBc antibodies. There was a significant association between chronic liver disease and both HCV (with or without HBV) (p=00024) and HBV infection (p=00052, Fisher’s exact test). These data support an association between HCV, HBV, and mixed cryoglobulinaemia. Furthermore, these
could be an avoidable cause of death and brain damage. It is therefore important to record details of the thermal environment when investigating SID and HSE.
RIBA =
viruses may account for most associated with this syndrome.’
cases
1. Levo Y, Gorevic PD, Kassab MJ, Zucker-Framklin D, Framklin EC. The association
hepatitis B virus and essential mixed cryoglobulinemia.
N Engl J
Med
1977; 296: 1501-04. 2. Pascual M, Perrin L, Giostra E, Schifferli JA. Hepatitis C virus in patients with cryoglobulinemia type II. J Infect Dis 1990, 162: 596-60. 3. Theilmann L, Blazek M, Goeser T, et al. False-positive anti-HCV tests in rheumatoid arthritis. Lancet 1990; 335: 1346. 4.
Montagnino G. Reappraisal of the clinical Semin Immunopathol 1988; 10: 1-19
expression of mixed
cryoglobulinemia.
Haemorrhagic shock encephalopathy and sudden infant death SIR,-Dr Trounce and colleagues’ report (Jan 26, p 202) of simultaneous haemorrhagic shock encephalopathy (HSE) and sudden infant death (SID) in two sets of twins supports a previous suggestion that the two conditions might sometimes be causally linked through overheating.! Trounce et al state that their cases "were not excessively covered in clothes or bedding" but do not provide details of these or of ambient temperature. This information has been obtained for one of their babies with HSE (case 1).). She was dressed in a vest, a one-piece baby suit, socks, and nappy, put to sleep in a cot warmed with a hot bottle, and was covered by a sheet, 3 layers of blanket, and a quilt. The night was warm and humid for December with relative humidity 90% and outside temperature 11°C; the temperature in the bedroom, which was unheated, was probably about 13°C? The baby’s total insulation was about 10-5 tog. Although this is within the normal range2 it is well over the theoretical ideal for ambient temperature. Her mother described the baby as "red-hot like fire" when she found her. There had been recent contact with chickenpox and the combination of fever and warm environment might have led to extreme hyperpyrexia. Unfortunately, no details of thermal environment could be obtained for Trounce and colleagues’ second baby, but he was described as "very hot" when found. Trounce et al propose a deficiency of cell-stress proteins, unmasked by various factors including overheating, as a causal link between the two conditions. I suggest that overheating itself may be the primary causal link, and that it might act in two ways. Some overheated babies may die quickly and quietly and present as SID; the disturbance of respiration observed in well-warmed babies4.5 suggests that the mode of death may be apnoea. Others might continue to breathe but become so hot that they incur the widespread tissue damage of heatstroke, with which the clinical and pathological features of HSE correspond.6 A very high temperature is commonly found in HSE, and where it is not the baby might have already cooled. Elucidation of this issue is important because here was
C. J. BACON
Northallerton, North Yorkshire DL6 1JG, UK
1. Bacon C, Scott D, Jones P. Heatstroke in well-wrapped infants. Lancet 1979; 422-25 2. Bacon CJ, Bell SA, Clulow EE, Beattie A. How mothers keep their babies warm. Arch Dis Child (in press). 3. Bacon CJ. The thermal environment of sleeping babies. In: David TJ, ed. Recent advances in paediatrics, no 9. Edinburgh: Churchill Livingstone, 1990 123-36 4. Gozal D, Colin AA, Daskalovic VI, Jaffe M. Environmental overheating as a cause of transient respiratory chemoreceptor dysfunction in an infant. Pediatrics 1988, 82:
738-40.
Y, Fleming P, McCabe R, Levene M. The effect of environmental temperature sleep in infants. Pediatr Rev Commun 1990; 4: 246. 6. Wadlington WB, Tucker AL, Fly F, Freen MC. Heatstroke in infancy. Am JDis Child 1976; 130: 1250-51. 5. Azaz
on
Spontaneous abortion after intrauterine
of chronic liver disease
Departments of Internal Medicine 3, M. CASATO G. TALIANI Gastroenterology, and Tropical Diseases L. P. PUCILLO F. GOFFREDO University of Rome, 00185 Rome, Italy B. LAGANÀ L. BONOMO
between
Friarage Hospital,
insemination SiR,—Dr Barros and colleagues (Feb 2, p 302) express concern of spontaneous abortions after inseminations (IUI). We compared direct intraperitoneal insemination (DIPI) with IUI, both being combined with hormonally induced ovulation, in the treatment of couples who were infertile because of male subfertility, endometriosis, or unexplained infertility.! 124 couples were randomised to either DIPI or IUI, for three consecutive cycles, if necessary. The women received clomiphene citrate 100 mg on cycle days 3-7, human menopausal gonadotropin 150 IU on cycle days 8-10, and human chorionic gonadotropin (hCG) 5000-10 000 IU when the leading follicle was 17 mm in diameter, as measured by ultrasound. Insemination was done 1 day after hCG injection. 15 pregnancies resulted from 174 DIPI cycles and 19 from 152 IUI cycles. The number of pregnancies did not differ between the two treatments. There were five spontaneous abortions in both groups, and three ectopic pregnancies in the DIPI group and two in the IUI group. The total number of pregnancies was close to that of Barros et al both with DIPI (15 vs 11) and IUI (19 vs 22). The conception rates per couple in 3 cycles in our study were 23-8% in the DIPI group and 31.1% in the IUI group, compared with Barros and colleagues’ findings of 24-5% and 40% in an average of 3-3 cycles. We did not detect any significant difference in spontaneous abortions between the DIPI (33%) and IUI (26%) groups. Since the completion of our multicentre study! we have used DIPI only when the uterine cavity was inaccessible by the insemination catheter. We have 3 DIPI pregnancies with 2 normal deliveries and 1 pregnancy beyond 13 weeks, and 41 pregnancies from IUI, 11 (27%) of which resulted in first-trimester abortion. We believe that the high abortion rate in both DIPI and IUI groups is related to infertility problems, and not the technique of insemination. The apparent differences in the outcomes of pregnancies between Barros and colleagues’ and our’ reports may be attributable to the small number of cases and differences in the indications for insemination. Therefore it is important to gain more experience with both insemination techniques. about the intrauterine
high frequency
Infertility Clinic of the Finnish Population and Family Welfare Federation, 00100 Helsinki, Finland
PEKKA LAHTEENMAKI OUTI HOVATTA
O, Kurunmaki H, Tiitinen A, Lahteenmaki P, Koskimies AI Direct intraperitoneal or intrauterine insemination and superovulation in infertility treatment: a randomized study. Fertil Steril 1990; 54: 339
1. Hovatta
CORRECTION Alcohol and mortality-In this letter by Prof A. G. Shaper Apnl 13. 911) the second sentence in the third paragraph should have read "BBhen the ’sick men’ are separated from the healthy men, the small reduction m total mortality (11-12%) among drinkers of 1-2 drinks per day compared with non-drinkers is present in both groups". p
cryoglogulin depleted sera gave similar results, incubations of strips with patients’ sera were completed at 37°C to avoid cryoprecipitation. Samples from 14 patients (48%) reacted with two (n 3) or more (n = 11) of the four antigens on the strip, and were classified as positive. Sera from 14 of the remaining 15 patients reacted strongly with the c22 (core) antigen of HCV. This reactivity could be due to rheumatoid factors three out of eight sera from patients with rheumatoid arthritis reacted with c22. 11 of 14 HCV-antibody positive patients had serological evidence of hepatitis B virus (HBV) infection (antiHBc positivity). Among the 15 HCV-antibody negative patients, 8 were antiHBc positive. Chronic active hepatitis or cirrhosis was diagnosed in 13 of 14 HCV-antibody positive patients, in 5 of 8 HCV-antibody negative and antiHBc-positive patients, and in only 1 of 7 patients negative for both HCV and antiHBc antibodies. There was a significant association between chronic liver disease and both HCV (with or without HBV) (p=00024) and HBV infection (p=00052, Fisher’s exact test). These data support an association between HCV, HBV, and mixed cryoglobulinaemia. Furthermore, these
could be an avoidable cause of death and brain damage. It is therefore important to record details of the thermal environment when investigating SID and HSE.
RIBA =
viruses may account for most associated with this syndrome.’
cases
1. Levo Y, Gorevic PD, Kassab MJ, Zucker-Framklin D, Framklin EC. The association
hepatitis B virus and essential mixed cryoglobulinemia.
N Engl J
Med
1977; 296: 1501-04. 2. Pascual M, Perrin L, Giostra E, Schifferli JA. Hepatitis C virus in patients with cryoglobulinemia type II. J Infect Dis 1990, 162: 596-60. 3. Theilmann L, Blazek M, Goeser T, et al. False-positive anti-HCV tests in rheumatoid arthritis. Lancet 1990; 335: 1346. 4.
Montagnino G. Reappraisal of the clinical Semin Immunopathol 1988; 10: 1-19
expression of mixed
cryoglobulinemia.
Haemorrhagic shock encephalopathy and sudden infant death SIR,-Dr Trounce and colleagues’ report (Jan 26, p 202) of simultaneous haemorrhagic shock encephalopathy (HSE) and sudden infant death (SID) in two sets of twins supports a previous suggestion that the two conditions might sometimes be causally linked through overheating.! Trounce et al state that their cases "were not excessively covered in clothes or bedding" but do not provide details of these or of ambient temperature. This information has been obtained for one of their babies with HSE (case 1).). She was dressed in a vest, a one-piece baby suit, socks, and nappy, put to sleep in a cot warmed with a hot bottle, and was covered by a sheet, 3 layers of blanket, and a quilt. The night was warm and humid for December with relative humidity 90% and outside temperature 11°C; the temperature in the bedroom, which was unheated, was probably about 13°C? The baby’s total insulation was about 10-5 tog. Although this is within the normal range2 it is well over the theoretical ideal for ambient temperature. Her mother described the baby as "red-hot like fire" when she found her. There had been recent contact with chickenpox and the combination of fever and warm environment might have led to extreme hyperpyrexia. Unfortunately, no details of thermal environment could be obtained for Trounce and colleagues’ second baby, but he was described as "very hot" when found. Trounce et al propose a deficiency of cell-stress proteins, unmasked by various factors including overheating, as a causal link between the two conditions. I suggest that overheating itself may be the primary causal link, and that it might act in two ways. Some overheated babies may die quickly and quietly and present as SID; the disturbance of respiration observed in well-warmed babies4.5 suggests that the mode of death may be apnoea. Others might continue to breathe but become so hot that they incur the widespread tissue damage of heatstroke, with which the clinical and pathological features of HSE correspond.6 A very high temperature is commonly found in HSE, and where it is not the baby might have already cooled. Elucidation of this issue is important because here was
C. J. BACON
Northallerton, North Yorkshire DL6 1JG, UK
1. Bacon C, Scott D, Jones P. Heatstroke in well-wrapped infants. Lancet 1979; 422-25 2. Bacon CJ, Bell SA, Clulow EE, Beattie A. How mothers keep their babies warm. Arch Dis Child (in press). 3. Bacon CJ. The thermal environment of sleeping babies. In: David TJ, ed. Recent advances in paediatrics, no 9. Edinburgh: Churchill Livingstone, 1990 123-36 4. Gozal D, Colin AA, Daskalovic VI, Jaffe M. Environmental overheating as a cause of transient respiratory chemoreceptor dysfunction in an infant. Pediatrics 1988, 82:
738-40.
Y, Fleming P, McCabe R, Levene M. The effect of environmental temperature sleep in infants. Pediatr Rev Commun 1990; 4: 246. 6. Wadlington WB, Tucker AL, Fly F, Freen MC. Heatstroke in infancy. Am JDis Child 1976; 130: 1250-51. 5. Azaz
on
Spontaneous abortion after intrauterine
of chronic liver disease
Departments of Internal Medicine 3, M. CASATO G. TALIANI Gastroenterology, and Tropical Diseases L. P. PUCILLO F. GOFFREDO University of Rome, 00185 Rome, Italy B. LAGANÀ L. BONOMO
between
Friarage Hospital,
insemination SiR,—Dr Barros and colleagues (Feb 2, p 302) express concern of spontaneous abortions after inseminations (IUI). We compared direct intraperitoneal insemination (DIPI) with IUI, both being combined with hormonally induced ovulation, in the treatment of couples who were infertile because of male subfertility, endometriosis, or unexplained infertility.! 124 couples were randomised to either DIPI or IUI, for three consecutive cycles, if necessary. The women received clomiphene citrate 100 mg on cycle days 3-7, human menopausal gonadotropin 150 IU on cycle days 8-10, and human chorionic gonadotropin (hCG) 5000-10 000 IU when the leading follicle was 17 mm in diameter, as measured by ultrasound. Insemination was done 1 day after hCG injection. 15 pregnancies resulted from 174 DIPI cycles and 19 from 152 IUI cycles. The number of pregnancies did not differ between the two treatments. There were five spontaneous abortions in both groups, and three ectopic pregnancies in the DIPI group and two in the IUI group. The total number of pregnancies was close to that of Barros et al both with DIPI (15 vs 11) and IUI (19 vs 22). The conception rates per couple in 3 cycles in our study were 23-8% in the DIPI group and 31.1% in the IUI group, compared with Barros and colleagues’ findings of 24-5% and 40% in an average of 3-3 cycles. We did not detect any significant difference in spontaneous abortions between the DIPI (33%) and IUI (26%) groups. Since the completion of our multicentre study! we have used DIPI only when the uterine cavity was inaccessible by the insemination catheter. We have 3 DIPI pregnancies with 2 normal deliveries and 1 pregnancy beyond 13 weeks, and 41 pregnancies from IUI, 11 (27%) of which resulted in first-trimester abortion. We believe that the high abortion rate in both DIPI and IUI groups is related to infertility problems, and not the technique of insemination. The apparent differences in the outcomes of pregnancies between Barros and colleagues’ and our’ reports may be attributable to the small number of cases and differences in the indications for insemination. Therefore it is important to gain more experience with both insemination techniques. about the intrauterine
high frequency
Infertility Clinic of the Finnish Population and Family Welfare Federation, 00100 Helsinki, Finland
PEKKA LAHTEENMAKI OUTI HOVATTA
O, Kurunmaki H, Tiitinen A, Lahteenmaki P, Koskimies AI Direct intraperitoneal or intrauterine insemination and superovulation in infertility treatment: a randomized study. Fertil Steril 1990; 54: 339
1. Hovatta
CORRECTION Alcohol and mortality-In this letter by Prof A. G. Shaper Apnl 13. 911) the second sentence in the third paragraph should have read "BBhen the ’sick men’ are separated from the healthy men, the small reduction m total mortality (11-12%) among drinkers of 1-2 drinks per day compared with non-drinkers is present in both groups". p
