BRITISH MEDICAL JOURNAL
5 FEBRUARY 1977
377
thickened. The collagenous structures of the pedantry, where Dr J A Farfor (15 January, lamina propria were normal in all the material p 173) now joins her. examined. The Oxford English Dictionary gives the We can only conclude that the beclo- following meanings of "localise": to identify methasone dipropionate aerosol had a bene- with a particular locality (1870 usage quoted); ficial effect, especially upon the oedema and to attribute (in thought or statement) to a eosinophilic infiltration. No adverse effects on particular place or locality; to find or invent a structure were seen. locality for (1816-1879 usages quoted); as S S CHATTERJEE well as the older sense, to restrict or confine W Y NASSAR to a particular place or area (1798-1880 usages Wythenshawe Hospital, quoted). Dr Farfor's special brickbat for Manchester A G BUTLER neurologists seems in this instance undeserved. D POYNTER To write of "localising signs," "localising a lesion," or "cerebral localisation" has lexicoMedical Division, Allen and Hanburys Research Ltd, graphic respectability as well as being well Ware, Herts accepted and perfectly understood. In certain more arcane areas of neurology, wherein the expert perhaps fancies himself Postcoital contraception safe from challenge, criticism is merited. For example, your leading article (15 January, SIR,-My colleague Dr C L Brewer (15 p 127) on unusual forms of epilepsy endorses January, p 169) is within his rights to ask for a the misuse of the learned word "quiritarian" precise definition of abortion and contracep- in the context of crying epilepsy. tion. I define abortion as the deliberate according to the OED, concerns "Quiritarian", the laws of the destruction of the embryo once it is embedded Quirites (that is, the citizens of ancient Rome), in the uterus. The absolutist on the abortion means legal as opposed to equitable, and has issue, until he is sure that an intrauterine nothing to do with crying. The confusion is device never works by destroying an embedded with the unrelated rarity "quiritation", whose embryo, must logically eschew this technique, only quoted usage, dated suggests advising his patient as to his ethical objections. complaint or lament rather 1634, than physical She may then seek other advice once she has weeping. the facts. The same leading article tacitly but wrongly However, to insist that those who advise accepts "cursive" to denote the act of running, an IUD with the motive of contraception mis-spells "dacryocystic" as "dacrocystic"; cannot therefore object to, say, intrauterine and with its "no rigid semilogical framework Derby Chest Clinic, saline aimed at the destruction of a moving could embrace all epileptic phenomena" Derby 27-week fetus is, in my view, stretching his 'Brown, H M, Storey, G, and George, W H S, British argument. With further stretching it could makes a most intriguing Freudian slip. Medical Journal, 1972, 1, 585. 2 Brown, H M, and Storey, G, British Medical Journal, be carried to absurdity in the rubella-early P WILSON
Research Ltd, examined our biopsy material from six patients with allergic rhinitis continuously treated with BDA eight puffs every day for from 21 to 31 years. In all cases there was evidence of a thickened basement membrane with a high collagen content, as seen in asthmatic bronchi. The lamina propria showed no evidence of any cellular infiltration. Nothing was recorded that was not seen in allergic rhinitis, and cellular infiltration and oedema appeared lessened. In no specimens were changes seen indicative of adverse effects attributable to BDA. Considering the incessant "blasting" of the nose four times a day for years with a very potent corticosteroid, these findings are almost a pleasant surprise. It seems likely that the respiratory mucosa, with its powers of rapid regeneration, behaves differently from the skin, where the effects of constant steroid usage are well known. In view of our long-term experience in Derby it would appear that anxiety regarding long-term side effects is groundless. Suspension of treatment for one month in 12, as suggested, would certainly demonstrate whether there is a continuing need for the treatment but would do no more than that. Finally, the drug should be referred to as "beclomethasone dipropionate" not "beclomethasone," which, as detailed in your leading article itself, is an inactive metabolite of BDA. H M BROWN
1973, 3, 3Brown, H Journal, 4Brown, H 4, 331.
161. M, and Storey, G, Postgraduate Medical 1975, 51, suppl 4, p 59. M, and Storey, G, Clinical Allergy, 1974,
SIR,-Your leading article (25 December, p 1522) prompts us to provide a preliminary report of certain investigations carried out on patients receiving intranasal beclomethasone dipropionate. That fears have been expressed with regard to the safety of the aerosol when used in the nose leads to only one rational approach-namely, to examine the nasal mucosa in treated patients. This we have done both macroscopically and microscopically. Seven patients suffering from allergic rhinitis were examined both before and after treatment at a level of 50 tlg/nostril, four times a day. The course lasted 3-5 months. Punch biopsy specimens were taken from the inferior turbinate, fixed in formol saline, and stained with haematoxylin and eosin as well as van Gieson's stain. Before treatment the nasal passages showed typical congestive changes which were relieved by the aerosol. The pretreatment biopsy specimens showed changes typical of allergic rhinitis. Hyperplastic and squamous changes were seen in the epithelium, the basement membrane was in every case thickened, six patients showed oedematous changes in the lamina propria, and in the same six this region was infiltrated by eosinophils. In every case the distribution and structure of collagenous tissue as determined by van Gieson's stain was normal. After treatment no changes were seen in the epithelium or in the basement membrane. Five out of the six patients previously showing oedema and eosinophilia no longer displayed these features but in all cases the basement membrane remained
pregnancy dilemma: why not deliver the child, examine it carefully, and then if imperfect kill it with a silver hammer? Unthinkable even if logical. Still, Dr Brewer has a point and (with me) no doubt he will sympathise with Pope John and his advisers in their support for family spacing only by the avoidance of the fertile days-aesthetically admirable but, alas, not always effective. How absurd the Catholic Church would now look if 10 years ago it had blessed the IUD only to find that it may operate not only by preventing the embedding of the zygote but by destroying it in situ-by definition an abortion! The future may settle the debate with hormones which convert the endometrium to a non-receptive state so that a fetus is never embedded in the womb. Even better, we may develop a male hormone which prevents sperm from penetrating the ovum. Meantime, motive is important: contraception is not abortion and our abortionists should not dress up as delayed contraceptors.
HUGH CAMERON MCLAREN Birmingham Maternity Hospital, Birmingham
***This correspondence is
now closed-ED,
BMJ.
"Locate" and "localise" SIR,-Minerva (13 November, p 1206) does well to enjoin contributors to use short words rather than long and not to use them loosely. A pity therefore that her concern for the accurate usage of the words "locate" and "localise" has led her into the bog of sterile
Department of Surgical Neurology, Morriston Hospital, Swansea
***Minerva is repentant and, such is the power of fashionable usage, awaits with resignation the day when a neurosurgeon will report on the localisation of localised cerebral tumours.-ED, BMJ. Hip fractures up to date
SIR,-Mr P A Ring (11 December p 1429) gives an excellent survey ofthe present position of this subject as a whole, but there are two points relating specifically to displaced subcapital fractures-still the problem-children of the group-which he has omitted to recognise. Firstly, when internal fixation is the method used Mr Ring rightly recognises that the key to success lies in good reduction complemented by fixation strong enough to maintain that reduction until union occurs and at the same time permit early postoperative weight-bearing in the elderly patient. However, a recent long-term survey by Barnes and his colleagues' of over 1500 subcapital fractures treated by intemal fixation of various types in 10 different centres (by far the most comprehensive review yet published) makes it absolutely clear that the trifin nail fails to satisfy these criteria for the inherently unstable displaced fracture. Fifty per cent of this group failed to unite with trifin nailing, however well executed, compared with over 80% union recorded with Garden crossed screwing or triangle pinning-methods mentioned by Mr Ring as too complex to be justified. While this may be so when the operations are left to
378
BRITISH MEDICAL JOURNAL
registrars or inexperienced surgeons, since precision is required within narrower limits than for trifin nailing, it is certainly not true in centres where these methods are employed by surgeons willing to devote the necessary time and effort to master a slightly more difficult, but very much more efficient technical procedure. Writing in the BMJ as long ago as 1969 Barnes2 described the trifin nail as the "least effective method in common use" and stated that it should be restricted to the undisplaced or impacted subcapital fracture. Secondly, Mr Ring states that "no method of internal fixation, however secure, can overcome the problem of the avascular femoral head." This is not necessarily so provided good reduction is also present. Garden3 has examined the long-term results of a consecutive series of 323 healed displaced subcapital fractures and shown that, with scarcely an exception, the fate of the femoral head is directly related to the quality of reduction and its maintenance until union is present. From his findings the fact emerges that anatomically reduced fractures, whatever their initial degree of displacement, will not only unite if securely held but will also normally escape the late secondary changes usually attributed to avascular necrosis. It is still insufficiently appreciated that these late secondary changes (now usually described as "late segmental collapse"), which appear after union and most commonly not until the second or third postoperative year, usually constitute a mild and comparatively easily manageable complication in the majority of the elderly patients affected, most of whom are able to continue to cope with life's demands and retain their activity without the need for further surgery. Of 53 patients with united displaced subcapital fractures treated by triangle pinning4 who survived a three-year follow-up, 21 showed some radiological evidence of collapse, but only four of these patients had sufficient disability to require secondary surgery, while in the remaining 17 symptoms were either slight or absent altogether. A similar picture of late segmental collapse emerges from the Barnes survey already mentioned.' EDWARD SMYTH Brook, Isle of Wight
'Barnes, R, et al, Journal of Bone and Joint Surgery, 1976, 58B, 2. 'Barnes, R, British Medical_Journal, 1969, 2, 575. 8 Garden, R S, Journal of Bone and Joint Surgery, 1971, 53B, 183. 'Smyth, E H J, and Shah, V M, Injury, 1974, 5, 197.
SIR,-Dr G K Morris and Professor J R A Mitchell (8 January, p 108) state that in the management of hip fractures "prophylactic anticoagulation is tedious and not without complications, but it will prevent pulmonary embolism." Undoubtedly, the efficacy of oral anticoagulants in preventing pulmonary embolism is proved.' 2 However, it is perhaps the complications that deter 970%' of orthopaedic surgeons from routine use of these drugs.3 Firstly, anticoagulant therapy carries its own mortality even in elective hip surgery in carefully screened cases.4 Secondly, the morbidity from postoperative wound bleeding and haematoma formation is increased' 2 4-6 when oral anticoagulants are used. The wound haematoma is viewed with particular dismay by the orthopaedic surgeon because of the risk of consequent "deep" sepsis involving the
metal implant.4 Infection of the implant is an unmitigated disaster which causes the failure of the operation and can itself produce a significant death rate. In a recent review of 85 patients undergoing operation at this hospital for femoral neck fractures there were six cases of postoperative deep sepsis and each of these patients died within three months.' This series is too small to be conclusive, but then there is no information at all about infection in either of the two major publications which advocate the use of anticoagulants. Until there is there is unlikely to be any wider acceptance of a method with these potential hazards and which is also "tedious."
5 FEBRUARY 1977
in the majority of patients, it fails to relieve neuralgia in herpes zoster. P A M WALDEN E S NEWLANDS J C COLEMAN M H N TATTERSALL K D BAGSHAWE Department of Medical Oncology and Microbiology, Charing Cross Hospital, London W6 1 Juel-Jensen, B, Journal of Antimicrobial Chemotherapy, 1976, 2, 261. 'Keeney, R E, and Buchanan, R A, Annals of the New York Academy of Sciences, 1975, 255, 185. 3Johnson, M T, Luby, J P, and Buchanan, R A, Journal of Infectious Diseases, 1975, 131, 225.
JAMES R LOUDON G MCGARRITY Western Infirmary,
Glasgow
ISevitt, S, and Gallagher, N G, Lancet, 1959, 2, 981. 2 Morris, G K, and Mitchell, J R A, Lancet, 1976, 2, 869. 3 Morris, G K, and Mitchell, J R A, Lancet, 1976, 2, 867. 4 Crawford, W J, Hillman, F, and Charnley, J, Centre for Hip Surgery, Wrightington Hospital, Publications No 14, 1968. 5 Hamilton, H W, et al, Journal of Bone and Joint Surgery, 1970, 52B, 268. Salzman, E W, and Harris, W H, Journal of Bone and Joint Surgery, 1976, 58A, 903. 7 Waddell, G, personal communication.
Chemotherapy for varicella-zoster infections
SIR,-We would like to add our experience of using adenine arabinoside (ara-A) in herpes simplex and herpes zoster infections to those commented on in your leading article (18 December, p 1466). Juel-Jensen' reported a good clinical response in two out of three cases with herpes zoster infections. During the past two years we have treated seven patients with this drug administered by intravenous infusion in a dose of 10 mg/kg/ day over a five-day period.2 All of these patients were suffering from some form of malignant disease and four were receiving cytotoxic chemotherapy when they developed their infections. Five developed disseminated zoster, two of whom had panencephalitis. Two further patients had herpes simplex infections, one with severe ophthalmitis. In all cases the diagnosis was confirmed virologically by direct electron microscopy of vesicle fluid and by virus isolation. Latterly indirect immunofluorescence techniques have been used to demonstrate herpes simplex or varicella-zoster antigen in cells from the base of the patient's lesion. A response was defined as the arrest of progressive disease with no new lesions and resolution of fever. Four of the five patients with herpes zoster, including one of those with panencephalitis, responded to treatment. The fifth patient, with progressive disease on treatment, failed to respond even when the dose of ara-A was doubled to 20 mg/kg/-day. Of the two patients with herpes simplex, the one with ophthalmitis responded, while the other, with multiple facial lesions, failed to respond. Myelosuppression occurred in three of these patients and four became drowsy during the infusion of ara-A. Gastrointestinal disturbance was minimal. Severe neuralgia occurred in two patients with herpes zoster and ara-A failed to relieve these symptoms. Our experience with ara-A lends support to the findings of other workers that, although effective in preventing dissemination of disease
Low-dose progestogens and ectopic pregnancy
SIR,-We were most interested in the communication from Drs P Liukko and R Erkkola (20 November, p 1257) on the relative risk of ectopic pregnancy with the different progestogens (D-norgestrel, norethisterone, and lynoestrenol). Although structurally similar progestogens have varying effects on the female reproductive tract, the observed difference in the incidence of ectopic pregnancy for these three closely related 19-norsteroids seems particularly marked and far more pronounced than their relative contraceptive efficiency as indicated by the Pearl index quoted by these authors. We should like to inquire if all three groups in this study were comparable for characteristics that influence the risk of pregnancy with continuous low-dose progestogens and for factors that might favour the development of an ectopic pregnancy. For example, was the form of hormone administration similar in all three groups-that is, were the tablets given in bottles or day-marked packs ? In this context it is interesting to note that for tablets given in bottles it has been found that only 400° of patients follow this form of regimen conscientiously.' Were all members of the study of the same ethnic group and comparable in stature and weight ? In relation to such considerations it has been observed2 that effective contraception was achieved in Mexican women by a smaller dose of hormones administered on the sequential regimen than was needed for the larger British female patient. Equally important, were all the women of comparable age, married, and able to have unrestricted intercourse ? Were they of proved fertility, having previously conceived with ease or was there any possibility of subfertility from a previous history of appendicitis, pelvic infection, or pelvic operations, factors which might not only prevent conception but favour ectopic pregnancy if conception did occur ? If this marked difference in the risk of ectopic pregnancy is valid then it indicates an impressive disparity of action between three closely related progestogens. It implies either (a) that lynoestrenol has a particularly efficient action on the cervical mucus, largely preventing any form of conception occurring, whereas norgestrel and norethisterone achieve their contraceptive effect principally by acting on the endometrium, thereby preventing intrauterine but not extrauterine pregnancy, or (b) that norgestrel and norethisterone, but not lynoestrenol, significantly affect tubal function and delay the passage of the fertilised ovum through the fallopian tube, thus favouring tubal or even ovarian3 implantation. Such
5 FEBRUARY 1977
377
thickened. The collagenous structures of the pedantry, where Dr J A Farfor (15 January, lamina propria were normal in all the material p 173) now joins her. examined. The Oxford English Dictionary gives the We can only conclude that the beclo- following meanings of "localise": to identify methasone dipropionate aerosol had a bene- with a particular locality (1870 usage quoted); ficial effect, especially upon the oedema and to attribute (in thought or statement) to a eosinophilic infiltration. No adverse effects on particular place or locality; to find or invent a structure were seen. locality for (1816-1879 usages quoted); as S S CHATTERJEE well as the older sense, to restrict or confine W Y NASSAR to a particular place or area (1798-1880 usages Wythenshawe Hospital, quoted). Dr Farfor's special brickbat for Manchester A G BUTLER neurologists seems in this instance undeserved. D POYNTER To write of "localising signs," "localising a lesion," or "cerebral localisation" has lexicoMedical Division, Allen and Hanburys Research Ltd, graphic respectability as well as being well Ware, Herts accepted and perfectly understood. In certain more arcane areas of neurology, wherein the expert perhaps fancies himself Postcoital contraception safe from challenge, criticism is merited. For example, your leading article (15 January, SIR,-My colleague Dr C L Brewer (15 p 127) on unusual forms of epilepsy endorses January, p 169) is within his rights to ask for a the misuse of the learned word "quiritarian" precise definition of abortion and contracep- in the context of crying epilepsy. tion. I define abortion as the deliberate according to the OED, concerns "Quiritarian", the laws of the destruction of the embryo once it is embedded Quirites (that is, the citizens of ancient Rome), in the uterus. The absolutist on the abortion means legal as opposed to equitable, and has issue, until he is sure that an intrauterine nothing to do with crying. The confusion is device never works by destroying an embedded with the unrelated rarity "quiritation", whose embryo, must logically eschew this technique, only quoted usage, dated suggests advising his patient as to his ethical objections. complaint or lament rather 1634, than physical She may then seek other advice once she has weeping. the facts. The same leading article tacitly but wrongly However, to insist that those who advise accepts "cursive" to denote the act of running, an IUD with the motive of contraception mis-spells "dacryocystic" as "dacrocystic"; cannot therefore object to, say, intrauterine and with its "no rigid semilogical framework Derby Chest Clinic, saline aimed at the destruction of a moving could embrace all epileptic phenomena" Derby 27-week fetus is, in my view, stretching his 'Brown, H M, Storey, G, and George, W H S, British argument. With further stretching it could makes a most intriguing Freudian slip. Medical Journal, 1972, 1, 585. 2 Brown, H M, and Storey, G, British Medical Journal, be carried to absurdity in the rubella-early P WILSON
Research Ltd, examined our biopsy material from six patients with allergic rhinitis continuously treated with BDA eight puffs every day for from 21 to 31 years. In all cases there was evidence of a thickened basement membrane with a high collagen content, as seen in asthmatic bronchi. The lamina propria showed no evidence of any cellular infiltration. Nothing was recorded that was not seen in allergic rhinitis, and cellular infiltration and oedema appeared lessened. In no specimens were changes seen indicative of adverse effects attributable to BDA. Considering the incessant "blasting" of the nose four times a day for years with a very potent corticosteroid, these findings are almost a pleasant surprise. It seems likely that the respiratory mucosa, with its powers of rapid regeneration, behaves differently from the skin, where the effects of constant steroid usage are well known. In view of our long-term experience in Derby it would appear that anxiety regarding long-term side effects is groundless. Suspension of treatment for one month in 12, as suggested, would certainly demonstrate whether there is a continuing need for the treatment but would do no more than that. Finally, the drug should be referred to as "beclomethasone dipropionate" not "beclomethasone," which, as detailed in your leading article itself, is an inactive metabolite of BDA. H M BROWN
1973, 3, 3Brown, H Journal, 4Brown, H 4, 331.
161. M, and Storey, G, Postgraduate Medical 1975, 51, suppl 4, p 59. M, and Storey, G, Clinical Allergy, 1974,
SIR,-Your leading article (25 December, p 1522) prompts us to provide a preliminary report of certain investigations carried out on patients receiving intranasal beclomethasone dipropionate. That fears have been expressed with regard to the safety of the aerosol when used in the nose leads to only one rational approach-namely, to examine the nasal mucosa in treated patients. This we have done both macroscopically and microscopically. Seven patients suffering from allergic rhinitis were examined both before and after treatment at a level of 50 tlg/nostril, four times a day. The course lasted 3-5 months. Punch biopsy specimens were taken from the inferior turbinate, fixed in formol saline, and stained with haematoxylin and eosin as well as van Gieson's stain. Before treatment the nasal passages showed typical congestive changes which were relieved by the aerosol. The pretreatment biopsy specimens showed changes typical of allergic rhinitis. Hyperplastic and squamous changes were seen in the epithelium, the basement membrane was in every case thickened, six patients showed oedematous changes in the lamina propria, and in the same six this region was infiltrated by eosinophils. In every case the distribution and structure of collagenous tissue as determined by van Gieson's stain was normal. After treatment no changes were seen in the epithelium or in the basement membrane. Five out of the six patients previously showing oedema and eosinophilia no longer displayed these features but in all cases the basement membrane remained
pregnancy dilemma: why not deliver the child, examine it carefully, and then if imperfect kill it with a silver hammer? Unthinkable even if logical. Still, Dr Brewer has a point and (with me) no doubt he will sympathise with Pope John and his advisers in their support for family spacing only by the avoidance of the fertile days-aesthetically admirable but, alas, not always effective. How absurd the Catholic Church would now look if 10 years ago it had blessed the IUD only to find that it may operate not only by preventing the embedding of the zygote but by destroying it in situ-by definition an abortion! The future may settle the debate with hormones which convert the endometrium to a non-receptive state so that a fetus is never embedded in the womb. Even better, we may develop a male hormone which prevents sperm from penetrating the ovum. Meantime, motive is important: contraception is not abortion and our abortionists should not dress up as delayed contraceptors.
HUGH CAMERON MCLAREN Birmingham Maternity Hospital, Birmingham
***This correspondence is
now closed-ED,
BMJ.
"Locate" and "localise" SIR,-Minerva (13 November, p 1206) does well to enjoin contributors to use short words rather than long and not to use them loosely. A pity therefore that her concern for the accurate usage of the words "locate" and "localise" has led her into the bog of sterile
Department of Surgical Neurology, Morriston Hospital, Swansea
***Minerva is repentant and, such is the power of fashionable usage, awaits with resignation the day when a neurosurgeon will report on the localisation of localised cerebral tumours.-ED, BMJ. Hip fractures up to date
SIR,-Mr P A Ring (11 December p 1429) gives an excellent survey ofthe present position of this subject as a whole, but there are two points relating specifically to displaced subcapital fractures-still the problem-children of the group-which he has omitted to recognise. Firstly, when internal fixation is the method used Mr Ring rightly recognises that the key to success lies in good reduction complemented by fixation strong enough to maintain that reduction until union occurs and at the same time permit early postoperative weight-bearing in the elderly patient. However, a recent long-term survey by Barnes and his colleagues' of over 1500 subcapital fractures treated by intemal fixation of various types in 10 different centres (by far the most comprehensive review yet published) makes it absolutely clear that the trifin nail fails to satisfy these criteria for the inherently unstable displaced fracture. Fifty per cent of this group failed to unite with trifin nailing, however well executed, compared with over 80% union recorded with Garden crossed screwing or triangle pinning-methods mentioned by Mr Ring as too complex to be justified. While this may be so when the operations are left to
378
BRITISH MEDICAL JOURNAL
registrars or inexperienced surgeons, since precision is required within narrower limits than for trifin nailing, it is certainly not true in centres where these methods are employed by surgeons willing to devote the necessary time and effort to master a slightly more difficult, but very much more efficient technical procedure. Writing in the BMJ as long ago as 1969 Barnes2 described the trifin nail as the "least effective method in common use" and stated that it should be restricted to the undisplaced or impacted subcapital fracture. Secondly, Mr Ring states that "no method of internal fixation, however secure, can overcome the problem of the avascular femoral head." This is not necessarily so provided good reduction is also present. Garden3 has examined the long-term results of a consecutive series of 323 healed displaced subcapital fractures and shown that, with scarcely an exception, the fate of the femoral head is directly related to the quality of reduction and its maintenance until union is present. From his findings the fact emerges that anatomically reduced fractures, whatever their initial degree of displacement, will not only unite if securely held but will also normally escape the late secondary changes usually attributed to avascular necrosis. It is still insufficiently appreciated that these late secondary changes (now usually described as "late segmental collapse"), which appear after union and most commonly not until the second or third postoperative year, usually constitute a mild and comparatively easily manageable complication in the majority of the elderly patients affected, most of whom are able to continue to cope with life's demands and retain their activity without the need for further surgery. Of 53 patients with united displaced subcapital fractures treated by triangle pinning4 who survived a three-year follow-up, 21 showed some radiological evidence of collapse, but only four of these patients had sufficient disability to require secondary surgery, while in the remaining 17 symptoms were either slight or absent altogether. A similar picture of late segmental collapse emerges from the Barnes survey already mentioned.' EDWARD SMYTH Brook, Isle of Wight
'Barnes, R, et al, Journal of Bone and Joint Surgery, 1976, 58B, 2. 'Barnes, R, British Medical_Journal, 1969, 2, 575. 8 Garden, R S, Journal of Bone and Joint Surgery, 1971, 53B, 183. 'Smyth, E H J, and Shah, V M, Injury, 1974, 5, 197.
SIR,-Dr G K Morris and Professor J R A Mitchell (8 January, p 108) state that in the management of hip fractures "prophylactic anticoagulation is tedious and not without complications, but it will prevent pulmonary embolism." Undoubtedly, the efficacy of oral anticoagulants in preventing pulmonary embolism is proved.' 2 However, it is perhaps the complications that deter 970%' of orthopaedic surgeons from routine use of these drugs.3 Firstly, anticoagulant therapy carries its own mortality even in elective hip surgery in carefully screened cases.4 Secondly, the morbidity from postoperative wound bleeding and haematoma formation is increased' 2 4-6 when oral anticoagulants are used. The wound haematoma is viewed with particular dismay by the orthopaedic surgeon because of the risk of consequent "deep" sepsis involving the
metal implant.4 Infection of the implant is an unmitigated disaster which causes the failure of the operation and can itself produce a significant death rate. In a recent review of 85 patients undergoing operation at this hospital for femoral neck fractures there were six cases of postoperative deep sepsis and each of these patients died within three months.' This series is too small to be conclusive, but then there is no information at all about infection in either of the two major publications which advocate the use of anticoagulants. Until there is there is unlikely to be any wider acceptance of a method with these potential hazards and which is also "tedious."
5 FEBRUARY 1977
in the majority of patients, it fails to relieve neuralgia in herpes zoster. P A M WALDEN E S NEWLANDS J C COLEMAN M H N TATTERSALL K D BAGSHAWE Department of Medical Oncology and Microbiology, Charing Cross Hospital, London W6 1 Juel-Jensen, B, Journal of Antimicrobial Chemotherapy, 1976, 2, 261. 'Keeney, R E, and Buchanan, R A, Annals of the New York Academy of Sciences, 1975, 255, 185. 3Johnson, M T, Luby, J P, and Buchanan, R A, Journal of Infectious Diseases, 1975, 131, 225.
JAMES R LOUDON G MCGARRITY Western Infirmary,
Glasgow
ISevitt, S, and Gallagher, N G, Lancet, 1959, 2, 981. 2 Morris, G K, and Mitchell, J R A, Lancet, 1976, 2, 869. 3 Morris, G K, and Mitchell, J R A, Lancet, 1976, 2, 867. 4 Crawford, W J, Hillman, F, and Charnley, J, Centre for Hip Surgery, Wrightington Hospital, Publications No 14, 1968. 5 Hamilton, H W, et al, Journal of Bone and Joint Surgery, 1970, 52B, 268. Salzman, E W, and Harris, W H, Journal of Bone and Joint Surgery, 1976, 58A, 903. 7 Waddell, G, personal communication.
Chemotherapy for varicella-zoster infections
SIR,-We would like to add our experience of using adenine arabinoside (ara-A) in herpes simplex and herpes zoster infections to those commented on in your leading article (18 December, p 1466). Juel-Jensen' reported a good clinical response in two out of three cases with herpes zoster infections. During the past two years we have treated seven patients with this drug administered by intravenous infusion in a dose of 10 mg/kg/ day over a five-day period.2 All of these patients were suffering from some form of malignant disease and four were receiving cytotoxic chemotherapy when they developed their infections. Five developed disseminated zoster, two of whom had panencephalitis. Two further patients had herpes simplex infections, one with severe ophthalmitis. In all cases the diagnosis was confirmed virologically by direct electron microscopy of vesicle fluid and by virus isolation. Latterly indirect immunofluorescence techniques have been used to demonstrate herpes simplex or varicella-zoster antigen in cells from the base of the patient's lesion. A response was defined as the arrest of progressive disease with no new lesions and resolution of fever. Four of the five patients with herpes zoster, including one of those with panencephalitis, responded to treatment. The fifth patient, with progressive disease on treatment, failed to respond even when the dose of ara-A was doubled to 20 mg/kg/-day. Of the two patients with herpes simplex, the one with ophthalmitis responded, while the other, with multiple facial lesions, failed to respond. Myelosuppression occurred in three of these patients and four became drowsy during the infusion of ara-A. Gastrointestinal disturbance was minimal. Severe neuralgia occurred in two patients with herpes zoster and ara-A failed to relieve these symptoms. Our experience with ara-A lends support to the findings of other workers that, although effective in preventing dissemination of disease
Low-dose progestogens and ectopic pregnancy
SIR,-We were most interested in the communication from Drs P Liukko and R Erkkola (20 November, p 1257) on the relative risk of ectopic pregnancy with the different progestogens (D-norgestrel, norethisterone, and lynoestrenol). Although structurally similar progestogens have varying effects on the female reproductive tract, the observed difference in the incidence of ectopic pregnancy for these three closely related 19-norsteroids seems particularly marked and far more pronounced than their relative contraceptive efficiency as indicated by the Pearl index quoted by these authors. We should like to inquire if all three groups in this study were comparable for characteristics that influence the risk of pregnancy with continuous low-dose progestogens and for factors that might favour the development of an ectopic pregnancy. For example, was the form of hormone administration similar in all three groups-that is, were the tablets given in bottles or day-marked packs ? In this context it is interesting to note that for tablets given in bottles it has been found that only 400° of patients follow this form of regimen conscientiously.' Were all members of the study of the same ethnic group and comparable in stature and weight ? In relation to such considerations it has been observed2 that effective contraception was achieved in Mexican women by a smaller dose of hormones administered on the sequential regimen than was needed for the larger British female patient. Equally important, were all the women of comparable age, married, and able to have unrestricted intercourse ? Were they of proved fertility, having previously conceived with ease or was there any possibility of subfertility from a previous history of appendicitis, pelvic infection, or pelvic operations, factors which might not only prevent conception but favour ectopic pregnancy if conception did occur ? If this marked difference in the risk of ectopic pregnancy is valid then it indicates an impressive disparity of action between three closely related progestogens. It implies either (a) that lynoestrenol has a particularly efficient action on the cervical mucus, largely preventing any form of conception occurring, whereas norgestrel and norethisterone achieve their contraceptive effect principally by acting on the endometrium, thereby preventing intrauterine but not extrauterine pregnancy, or (b) that norgestrel and norethisterone, but not lynoestrenol, significantly affect tubal function and delay the passage of the fertilised ovum through the fallopian tube, thus favouring tubal or even ovarian3 implantation. Such
