- Email: [email protected]
Accelerated decline in cervical cancer mortality in England and Wales
towards universal vaccine could be offered move
B immunisation the both blood and organ donor
to
groups. *Mark Zuckerman, John Wardle, Ken Mutton, Richard Tedder Virology Department, University College London Medical School, London Wl, *Public Health Laboratory and Department of Medical Microbiology, King’s College School of Medicine and Dentistry, Dulwich Hospital, London SE22 8QF, UK; Pathology Department, Noble’s Isle of Man Hospital, Douglas, Isle of Man; and Public Health Laboratory, Fazakerley Hospital, Liverpool 1
Zuckerman MA, Hawkins AE, Briggs M, et al. Investigation of hepatitis B virus transmission in a health care setting: application of direct sequence analysis. J Infect Dis 1995; 172: 1080-83.
Sex chromosomal abnormalities and
intracytoplasmic
sperm
injection
SiR-In’t Veld and colleagues (Sept 16, p 773) suggest a preponderance of sex chromosomal abnormalities in pregnancies after intracytoplasmic sperm injection (ICSI), because they had detected abnormal cytogenetic results in four singleton and one twin pregnancies in a total of fifteen procedures of transabdominal chorionic villus sampling or amniocentesis. Our experience differs from theirs. Of our first 228 ICSI cases, 61 patients became pregnant; only four had a miscarriage (6-5%); 57 delivered 69 severe children-53 after ICSI because of and four after injection of oligoasthenoteratozoospermia from with obstructive testicular spermatozoa patients azoospermia. All pregnancies and children were evaluated in a prospective follow-up study. The women had been advised to have prenatal diagnosis. Seven (10%) amniocenteses were done and showed normal chromosomes. Reports for the children revealed only three minor malformations-a double thumb in one and double toes in twins. In none of the 69 newborn babies were there chromosomal abnormalities. Thus chromosomal abnormality and malformation rates were much lower in our series than those reported by the 2
Belgian groups.’ We postulate that this difference might be attributable to a modified ICSI technique: the Belgian ICSI pioneering group and others use polyvinylpyrrolidone (PVP) a viscous solution in a concentration of 1 g/10 mL in HEPES-buffered Earle’s medium to slow down the movement of the motile spermatozoon, enabling aspiration into the injecting pipette. We have always avoided the use of PVP. According to Harari et aP immobilisation of motile spermatozoon is achieved mechanically by crushing its tail between the bottom of the petri dish and the tip of the injection pipette. Edwards and Steirteghem4 postulate that a possible connection with anomalies attributed to ICSI may be caused by a disordered calcium discharge. A 10% PVP solution contains 5 mmol/L calcium, whereas we inject spermatozoa in culture medium with a calcium concentration of 1-7 mmol/L. However, the mechanism of how PVP, a synthetic substance, could cause chromosomal abnormalities remains hypothetical. Several groups are also now using the PVP-free ICSI technique.
in mosaic Klinefelter’s syndrome. Fertil Steril 1995; 63: 182-84. Edwards RG, Steirteghem AV. Intracytoplasmic sperm injections (ICSI) and human fertilization: does calcium hold the key to success? Hum Reprod 1993; 8: 988-89.
intracytoplasmic sperm injection
hepatitis
4
Accelerated decline in cervical cancer mortality in England and Wales SiR-Age-standardised mortality rates for cervical cancer in England and Wales have been falling since records began in 1950. However, the rate of fall in mortality in recent years is greater than ever before. Throughout the 1970s, over 2000 women died every year of cervical cancer. By 1990 the death toll had fallen to 1781. In 1993 there were 1485 deaths and the provisional number for 1994 is 1369 (Office of Population Censuses and Surveys, series DH2, unpublished). The annual percentage change in agestandardised mortality fell on average by between 1% and 2% per year between 1960 and 1988. Since then the fall in mortality has accelerated strikingly and is now around 7% per year.
The full picture is more complicated. Strong cohort effects mean that although the overall mortality rate has fallen steadily, certain age-specific rates have increased.’ A thorough examination of incidence and mortality rates for cervical cancer and discussion of the extent to which screening has played a part in the observed trends is beyond the scope of this letter. However, in the past, the rate of cervical cancer mortality in each birth cohort increased with age until 59 years and then remained roughly level until age 79. Recent data show a different trend (figure). In each birth cohort from 1920 to 1954, mortality has fallen over the past 5 years. Thus, for instance, women born between 1950 and 1954 had a lower rate of mortality at ages 40-44, than at ages 35-39. Such a decrease has not occurred before. Cytological screening is designed to detect preinvasive lesions. Even when early occult invasive cancer is found, it is likely that if left undiagnosed until clinically apparent such a cancer would not have killed the patient for at least 3 years. Thus the effect of screening on mortality will not be seen for at least 3 years and its benefit may continue for 15 years or more. It is reasonable, therefore, to assume that the accelerated reductions in mortality in 1993 and 1994 are at
*Wilfried Feichtinger, Andreas Obruca, Maureen Brunner Sterilitatsbetreuung, A-1130 Vienna, Austria
Institut für
1
2
3
Steriteghem AV, Liu J, Nagy H, et al. Microinsemination. In: Hedon B, Bringer J, Mares P, eds. Fertility and sterility: a current overview (Proceedings of the 15th world congress on fertility and sterility. Montpellier, France: L Parthenon Publ, 1995: 395-404. Liebaers I, Bonduelle M, Legein J, et al. Follow-up of children born after intracytoplasmic sperm injection. In: Hedon B, Bringer J, Mares P, eds. Fertility and sterility: a current overview (Proceedings of the 15th world congress on fertility and sterility. Montpellier, France: L Parthenon Publ, 1995: 409-12. Harari O, Bourne H, Baker G, et al.
1566
Figure: Age-specific mortality High fertilization
rate
with
and Wales, 1950-1994
rates
by birth cohort, England
least partly due to the striking increase of coverage achieved by the national screening programme between 1988 and 1992Y If the falls in mortality in 1993 and 1994 are indeed attributable to screening, then we can expect further substantial falls in 1995 and 1996, and we are well on target to meet the challenge of fewer than 1000 deaths from cervical cancer by the year 2000. *Peter Sasieni, Jack
Cuzick, Elaine Farmery
*Department of Mathematics, Statistics, and Epidemiology, Imperial Cancer Research Fund, PO Box 123, London WC2A 3PX, UK; and Health Commission for Wiltshire and Bath, Devizes, Wiltshire
1 Sasieni, P. Trends
in
cervical
cancer
mortality. Lancet 1991; 338:
818-19.
Department of Health. Cervical cytology 1992-93: summary information from form KC53, England. London: Department of Health (SD2B), 1994. 3 Farmery E, Gray JAM. Report of the first five years of the NHS cervical screening programme. Oxford: National Co-ordinating Network, 1994. 2
Inhaled steroids and psoriasis
Mark Harries St Mark’s NHS Trust, Middlesex HA1 3UJ, UK
cap
polyposis
SiR-Cap polyposis is rare.’-3 We report a patient with cap polyposis who had been treated for ulcerative colitis for 7 years. woman was admitted to our hospital in with May, 1995, suspected osteoporosis. Persistent mucoid diarrhoea started in 1988, and she was diagnosed elsewhere as having ulcerative colitis in 1989. She had been treated with 10 mg oral prednisolone and 40 mg prednisolone enema daily for 10 months, then topical steroids were reduced to 30 mg per day and continued for almost 6 years. Mucoid diarrhoea appeared again several months before she came to our hospital. Serum total protein was 3-9 g/dL and albumin 2-4 g/dL. Serum IgG, IgA, and IgM levels were also decreased (174 mg/dL, 61 mg/dL, and 61 mg/dL). Scintigraphy using 99m technetium-labelled human albumin indicated protein loss from her descending colon. A considerable amount of immunoglobulins was detected in mucous discharge (IgG 102 mg/dL, IgA 69 mg/dL, and IgM 13 mg/dL). Colonoscopy showed sessile polyposis with a remarkable quantity of mucus attached to the surface, from the rectum to the distal descending colon with patchy normal intervening mucosa. Our first impression was of a protein-losing enteropathy with ulcerative colitis; however, the biopsy specimen showed no crypt atrophy and a hyperplastic epithelium with the surface. of the towards infolding epithelium, particularly filled with There was acute cells were mucus. Epithelial The muscularis inflammation mainly towards the surface. mucosae was disrupted and occasional smooth muscle fibres were present in the mucosa. She was diagnosed as having cap polyposis. As mucosal ischaemia has been suggested for the pathogenesis of cap polyposis,2 mucosal blood flow was
54-year-old
*Nobuhide
Oshitani, Yoshinori Moriyama, Takayuki Matsumoto, Kenzo Kobayashi, Atsuo Kitano *Third Department of Internal Medicine, Osaka City University Medical School, Osaka 545, Japan; Department of Internal Medicine, Jyuso Municipal Hospital, Osaka
2
3
Williams GT, Bussey HJR, Morson BC. Inflammatory ’cap’ polyps of the large intestine. Br J Surg 1985; 72 (suppl): S133. Campbell AP, Cobb CA, Chapman RWG, et al. Cap polyposis—an unusual cause of diarrhoea. Gut 1993; 34: 562-64. Géhénot M, Colombel J-F, Wolschies E, et al. Cap polyposis occurring in the postoperative course of pelvic surgery. Gut 1994; 35: 1670-72.
English
as
she is wrote
SiR-Francis Crick has written that "There is no form of more difficult to understand and more tedious to read than the average scientific paper"’ which bears out the argument in your Oct 21 editorial. Having edited three medical or scientific journals over the years, I support your lament about the poor state of written English in most of the medical (and scientific) press. There are several contributory factors, for some of which editors have only themselves to blame. I agree that when they meet, medical editors are much more likely to discuss subjects other than the clarity of the papers that they publish. There are a number of fashionable topics floating around and journalology seems certain to have its own journal before very much longer. The role of the statistician seems to have become overly influential, editors apparently considering that p values and t tests are more descriptive than words. I very much regret that editors are more likely these days to consult Bradford Hill than Fowler (although if they consulted Bradford Hill solely for matters of style, one would have no complaints at all). It is to the statisticians that we owe the awful device of the structured abstract which, as I understand it, was devised to satisfy the requirements of those who only read the abstracts of papers dredged up for them by their computer. We have even had the spectacle of an author decrying the use of "Whimsical titles" which "may leave the readers bewildered about the broad category under which the contents of a paper belong". Readers in this case refers to those who are attempting "partial text electronic coverage".2 If this is the kind of English to which browsing electronic data bases leads, the sooner they are banned, the better. The increased use of computers as a substitute for a trip to the library does nothing to encourage authors to try to express themselves well, but editors might improve the situation if they allowed authors to break free of the IMRAD (Introduction, Methods and Materials, Results, and Discussion) convention in which papers are presented. A more informal style of writing, with the use of the active voice rather than the passive, is likely to allow authors to present their work in a more readable and interesting way, and probably describe the train of events that lead up to the prose
Department of Respiratory Medicine, Northwick Park Hospital, Northwick Park and
A
We thank Dr D P Jewell for clinical advice and Dr B F Warren for histopathological review.
1
SIR-A patient presented with relapse of her psoriasis which had been in remission for a number of years. She attributed this to a change in her asthma medication from budesonide Turbohaler to fluticasone Accuhaler. The budesonide was reinstituted and the psoriasis cleared. Does this observation reflect a difference in the absorption pattern of the two drugs from the lung or does it infer the efficacy of inhaled budesonide as a treatment for psoriasis?
Protein-losing enteropathy from
measured with laser doppler. No difference was noted between the affected and non-affected mucosa. Cap polyposis affects both sexes over a wide age range (17-82 years).’ Aetiology is unknown, although mucosal prolapse and abnormal rectosigmoid motility’2 or infection3 may contribute to the pathological appearances. 1,2 Our patient had constipation for a long time before diarrhoea started. The muscularisation in the biopsy specimen indicated the presence of some degree of mucosal prolapse in this patient. It is suggested that persistent mechanical stimulation due to mucosal prolapse might lead to hyperplasia of the mucosa, leading to hypersecretion of serum proteins into the lumen surface.
1567
B immunisation the both blood and organ donor
to
groups. *Mark Zuckerman, John Wardle, Ken Mutton, Richard Tedder Virology Department, University College London Medical School, London Wl, *Public Health Laboratory and Department of Medical Microbiology, King’s College School of Medicine and Dentistry, Dulwich Hospital, London SE22 8QF, UK; Pathology Department, Noble’s Isle of Man Hospital, Douglas, Isle of Man; and Public Health Laboratory, Fazakerley Hospital, Liverpool 1
Zuckerman MA, Hawkins AE, Briggs M, et al. Investigation of hepatitis B virus transmission in a health care setting: application of direct sequence analysis. J Infect Dis 1995; 172: 1080-83.
Sex chromosomal abnormalities and
intracytoplasmic
sperm
injection
SiR-In’t Veld and colleagues (Sept 16, p 773) suggest a preponderance of sex chromosomal abnormalities in pregnancies after intracytoplasmic sperm injection (ICSI), because they had detected abnormal cytogenetic results in four singleton and one twin pregnancies in a total of fifteen procedures of transabdominal chorionic villus sampling or amniocentesis. Our experience differs from theirs. Of our first 228 ICSI cases, 61 patients became pregnant; only four had a miscarriage (6-5%); 57 delivered 69 severe children-53 after ICSI because of and four after injection of oligoasthenoteratozoospermia from with obstructive testicular spermatozoa patients azoospermia. All pregnancies and children were evaluated in a prospective follow-up study. The women had been advised to have prenatal diagnosis. Seven (10%) amniocenteses were done and showed normal chromosomes. Reports for the children revealed only three minor malformations-a double thumb in one and double toes in twins. In none of the 69 newborn babies were there chromosomal abnormalities. Thus chromosomal abnormality and malformation rates were much lower in our series than those reported by the 2
Belgian groups.’ We postulate that this difference might be attributable to a modified ICSI technique: the Belgian ICSI pioneering group and others use polyvinylpyrrolidone (PVP) a viscous solution in a concentration of 1 g/10 mL in HEPES-buffered Earle’s medium to slow down the movement of the motile spermatozoon, enabling aspiration into the injecting pipette. We have always avoided the use of PVP. According to Harari et aP immobilisation of motile spermatozoon is achieved mechanically by crushing its tail between the bottom of the petri dish and the tip of the injection pipette. Edwards and Steirteghem4 postulate that a possible connection with anomalies attributed to ICSI may be caused by a disordered calcium discharge. A 10% PVP solution contains 5 mmol/L calcium, whereas we inject spermatozoa in culture medium with a calcium concentration of 1-7 mmol/L. However, the mechanism of how PVP, a synthetic substance, could cause chromosomal abnormalities remains hypothetical. Several groups are also now using the PVP-free ICSI technique.
in mosaic Klinefelter’s syndrome. Fertil Steril 1995; 63: 182-84. Edwards RG, Steirteghem AV. Intracytoplasmic sperm injections (ICSI) and human fertilization: does calcium hold the key to success? Hum Reprod 1993; 8: 988-89.
intracytoplasmic sperm injection
hepatitis
4
Accelerated decline in cervical cancer mortality in England and Wales SiR-Age-standardised mortality rates for cervical cancer in England and Wales have been falling since records began in 1950. However, the rate of fall in mortality in recent years is greater than ever before. Throughout the 1970s, over 2000 women died every year of cervical cancer. By 1990 the death toll had fallen to 1781. In 1993 there were 1485 deaths and the provisional number for 1994 is 1369 (Office of Population Censuses and Surveys, series DH2, unpublished). The annual percentage change in agestandardised mortality fell on average by between 1% and 2% per year between 1960 and 1988. Since then the fall in mortality has accelerated strikingly and is now around 7% per year.
The full picture is more complicated. Strong cohort effects mean that although the overall mortality rate has fallen steadily, certain age-specific rates have increased.’ A thorough examination of incidence and mortality rates for cervical cancer and discussion of the extent to which screening has played a part in the observed trends is beyond the scope of this letter. However, in the past, the rate of cervical cancer mortality in each birth cohort increased with age until 59 years and then remained roughly level until age 79. Recent data show a different trend (figure). In each birth cohort from 1920 to 1954, mortality has fallen over the past 5 years. Thus, for instance, women born between 1950 and 1954 had a lower rate of mortality at ages 40-44, than at ages 35-39. Such a decrease has not occurred before. Cytological screening is designed to detect preinvasive lesions. Even when early occult invasive cancer is found, it is likely that if left undiagnosed until clinically apparent such a cancer would not have killed the patient for at least 3 years. Thus the effect of screening on mortality will not be seen for at least 3 years and its benefit may continue for 15 years or more. It is reasonable, therefore, to assume that the accelerated reductions in mortality in 1993 and 1994 are at
*Wilfried Feichtinger, Andreas Obruca, Maureen Brunner Sterilitatsbetreuung, A-1130 Vienna, Austria
Institut für
1
2
3
Steriteghem AV, Liu J, Nagy H, et al. Microinsemination. In: Hedon B, Bringer J, Mares P, eds. Fertility and sterility: a current overview (Proceedings of the 15th world congress on fertility and sterility. Montpellier, France: L Parthenon Publ, 1995: 395-404. Liebaers I, Bonduelle M, Legein J, et al. Follow-up of children born after intracytoplasmic sperm injection. In: Hedon B, Bringer J, Mares P, eds. Fertility and sterility: a current overview (Proceedings of the 15th world congress on fertility and sterility. Montpellier, France: L Parthenon Publ, 1995: 409-12. Harari O, Bourne H, Baker G, et al.
1566
Figure: Age-specific mortality High fertilization
rate
with
and Wales, 1950-1994
rates
by birth cohort, England
least partly due to the striking increase of coverage achieved by the national screening programme between 1988 and 1992Y If the falls in mortality in 1993 and 1994 are indeed attributable to screening, then we can expect further substantial falls in 1995 and 1996, and we are well on target to meet the challenge of fewer than 1000 deaths from cervical cancer by the year 2000. *Peter Sasieni, Jack
Cuzick, Elaine Farmery
*Department of Mathematics, Statistics, and Epidemiology, Imperial Cancer Research Fund, PO Box 123, London WC2A 3PX, UK; and Health Commission for Wiltshire and Bath, Devizes, Wiltshire
1 Sasieni, P. Trends
in
cervical
cancer
mortality. Lancet 1991; 338:
818-19.
Department of Health. Cervical cytology 1992-93: summary information from form KC53, England. London: Department of Health (SD2B), 1994. 3 Farmery E, Gray JAM. Report of the first five years of the NHS cervical screening programme. Oxford: National Co-ordinating Network, 1994. 2
Inhaled steroids and psoriasis
Mark Harries St Mark’s NHS Trust, Middlesex HA1 3UJ, UK
cap
polyposis
SiR-Cap polyposis is rare.’-3 We report a patient with cap polyposis who had been treated for ulcerative colitis for 7 years. woman was admitted to our hospital in with May, 1995, suspected osteoporosis. Persistent mucoid diarrhoea started in 1988, and she was diagnosed elsewhere as having ulcerative colitis in 1989. She had been treated with 10 mg oral prednisolone and 40 mg prednisolone enema daily for 10 months, then topical steroids were reduced to 30 mg per day and continued for almost 6 years. Mucoid diarrhoea appeared again several months before she came to our hospital. Serum total protein was 3-9 g/dL and albumin 2-4 g/dL. Serum IgG, IgA, and IgM levels were also decreased (174 mg/dL, 61 mg/dL, and 61 mg/dL). Scintigraphy using 99m technetium-labelled human albumin indicated protein loss from her descending colon. A considerable amount of immunoglobulins was detected in mucous discharge (IgG 102 mg/dL, IgA 69 mg/dL, and IgM 13 mg/dL). Colonoscopy showed sessile polyposis with a remarkable quantity of mucus attached to the surface, from the rectum to the distal descending colon with patchy normal intervening mucosa. Our first impression was of a protein-losing enteropathy with ulcerative colitis; however, the biopsy specimen showed no crypt atrophy and a hyperplastic epithelium with the surface. of the towards infolding epithelium, particularly filled with There was acute cells were mucus. Epithelial The muscularis inflammation mainly towards the surface. mucosae was disrupted and occasional smooth muscle fibres were present in the mucosa. She was diagnosed as having cap polyposis. As mucosal ischaemia has been suggested for the pathogenesis of cap polyposis,2 mucosal blood flow was
54-year-old
*Nobuhide
Oshitani, Yoshinori Moriyama, Takayuki Matsumoto, Kenzo Kobayashi, Atsuo Kitano *Third Department of Internal Medicine, Osaka City University Medical School, Osaka 545, Japan; Department of Internal Medicine, Jyuso Municipal Hospital, Osaka
2
3
Williams GT, Bussey HJR, Morson BC. Inflammatory ’cap’ polyps of the large intestine. Br J Surg 1985; 72 (suppl): S133. Campbell AP, Cobb CA, Chapman RWG, et al. Cap polyposis—an unusual cause of diarrhoea. Gut 1993; 34: 562-64. Géhénot M, Colombel J-F, Wolschies E, et al. Cap polyposis occurring in the postoperative course of pelvic surgery. Gut 1994; 35: 1670-72.
English
as
she is wrote
SiR-Francis Crick has written that "There is no form of more difficult to understand and more tedious to read than the average scientific paper"’ which bears out the argument in your Oct 21 editorial. Having edited three medical or scientific journals over the years, I support your lament about the poor state of written English in most of the medical (and scientific) press. There are several contributory factors, for some of which editors have only themselves to blame. I agree that when they meet, medical editors are much more likely to discuss subjects other than the clarity of the papers that they publish. There are a number of fashionable topics floating around and journalology seems certain to have its own journal before very much longer. The role of the statistician seems to have become overly influential, editors apparently considering that p values and t tests are more descriptive than words. I very much regret that editors are more likely these days to consult Bradford Hill than Fowler (although if they consulted Bradford Hill solely for matters of style, one would have no complaints at all). It is to the statisticians that we owe the awful device of the structured abstract which, as I understand it, was devised to satisfy the requirements of those who only read the abstracts of papers dredged up for them by their computer. We have even had the spectacle of an author decrying the use of "Whimsical titles" which "may leave the readers bewildered about the broad category under which the contents of a paper belong". Readers in this case refers to those who are attempting "partial text electronic coverage".2 If this is the kind of English to which browsing electronic data bases leads, the sooner they are banned, the better. The increased use of computers as a substitute for a trip to the library does nothing to encourage authors to try to express themselves well, but editors might improve the situation if they allowed authors to break free of the IMRAD (Introduction, Methods and Materials, Results, and Discussion) convention in which papers are presented. A more informal style of writing, with the use of the active voice rather than the passive, is likely to allow authors to present their work in a more readable and interesting way, and probably describe the train of events that lead up to the prose
Department of Respiratory Medicine, Northwick Park Hospital, Northwick Park and
A
We thank Dr D P Jewell for clinical advice and Dr B F Warren for histopathological review.
1
SIR-A patient presented with relapse of her psoriasis which had been in remission for a number of years. She attributed this to a change in her asthma medication from budesonide Turbohaler to fluticasone Accuhaler. The budesonide was reinstituted and the psoriasis cleared. Does this observation reflect a difference in the absorption pattern of the two drugs from the lung or does it infer the efficacy of inhaled budesonide as a treatment for psoriasis?
Protein-losing enteropathy from
measured with laser doppler. No difference was noted between the affected and non-affected mucosa. Cap polyposis affects both sexes over a wide age range (17-82 years).’ Aetiology is unknown, although mucosal prolapse and abnormal rectosigmoid motility’2 or infection3 may contribute to the pathological appearances. 1,2 Our patient had constipation for a long time before diarrhoea started. The muscularisation in the biopsy specimen indicated the presence of some degree of mucosal prolapse in this patient. It is suggested that persistent mechanical stimulation due to mucosal prolapse might lead to hyperplasia of the mucosa, leading to hypersecretion of serum proteins into the lumen surface.
1567