- Email: [email protected]
Loss of aura in lamotrigine-treated epilepsy
THE LANCET 4
5
Frohm M, Agerberh B, Ahangari G, et al. The expression of the gene coding for the antibacterial peptide LL-37 is induced in human keratinocytes during inflammatory disorders. J Biol Chem 1997; 272: 15258–63. Harder J, Bartels J, Christophers E, Scroder JM. A peptide antibiotic from human skin. Nature 1997; 387: 861.
Centre for Cutaneous Research, St Bartholomew’s & The Royal London Hospital School of Medicine & Dentistry, London E1 2AJ, UK (A G Quinn); and Magainin Pharmaceuticals Inc, Plymouth Meeting, Pennsylvania, USA
Management of pelvic floor dysfunction Charles W Nager, Devinder Kumar, Margie A Kahn, Stuart L Stanton
For patients with combinations of urinary incontinence, faecal incontinence, abnormal faecal evacuation, and pelvic organ prolapse, a focused organ system approach by urologists, gynaecologists, or colorectal surgeons reflects historical and anatomical divisions, but fails to recognise the interrelations of the pelvic floor organs and leads to partial and fragmented care. Childbirth causes denervation and muscle trauma to the pelvic floor and the urinary and anal sphincters.1 This leads to pelvic organ prolapse which includes cystourethroceles, uterine or vault prolapse, enteroceles, rectoceles, and rectal prolapse. These injuries are rarely isolated. Surgical repair of one compartment may lead to deterioration in other compartments.2 There is emerging opinion that a multidisciplinary approach to the whole pelvis is indicated,3 yet practical solutions to resolve this fragmented care have not been published. After August, 1994, patients referred to the urogynaecologist (SLS) with colorectal complaints or patients referred to the colorectal surgeon (DK) with urinary or prolapse complaints were given an appointment in a monthly pelvic floor clinic after appropriate investigations. Typical investigations were a cystometrogram and uroflowmetry for urinary incontinence, anorectal physiology, and endoanal ultrasound for faecal incontinence, scintigraphic defaecography for impaired faecal evacuation,4 and pelvic fluoroscopy for complex prolapse. New patients in the clinic were interviewed, examined, discussed, and managed jointly by the urogynaecologist and the colorectal surgeon. We report an audit of the first 34 months of the pelvic floor service. 123 patient notes of the 137 new patients seen by the pelvic floor service from August, 1994, until May, 1997, were reviewed. Patients tended to be older (mean age 55 years, range 26–84) and postmenopausal (74%). The median parity and median number of vaginal births was 2 (range 0–8). 200 previous gynaecological, urogynaecological, or colorectal operations had been performed (mean 1·6, range 0–6) in these 123 patients. Chief complaints could be categorised as colorectal (46%), urinary (31%), and prolapse-related (23%). Faecal incontinence (20%), urge urinary incontinence (16%), impaired faecal emptying (13%), posterior vaginal prolapse (9%), and stress urinary incontinence (8%) were the commonest main symptoms. 260 diagnoses were made in 123 patients (mean 2·1 diagnoses per patient). The most common diagnoses were impaired faecal evacuation with rectocele (34% of patients), detrusor instability (27% of patients), genuine stress incontinence of urine (25% of patients), external anal sphincter defect (24% of patients), and symptomatic posterior vaginal wall prolapse (19% of patients). 35% of patients were managed conservatively, 25% had a colorectal procedure, 18% had a urogynaecological procedure, and 20% required a combined surgical procedure by the urogynaecologist and colorectal surgeon. In total, 86
Vol 350 • December 13, 1997
Procedure
Number
Combined urogynaecology and colorectal External anal sphincter repair and colposuspension External anal sphincter and hysteropexy Rectocolpopexy Rectocolpopexy and colposuspension Rectopexy and colposuspension Transanal rectocele repair and colposuspension Transanal rectocele repair and vaginal hysterectomy Transanal rectocele repair and anterior colporrhaphy Miscellaneous Total
6 1 3 3 2 4 1 1 3 24
Colorectal Transanal rectocele repair External anal sphincter repair Miscellaneous Total
21 4 6 31
Urogynaecological Colpopexy Colposuspension Hysterectomy Posterior colporrhaphy Anterior colporrhaphy Miscellaneous Total
4 5 9 8 2 3 31
If more than two surgical procedures were done in the same patient at the same operation, then only the two most major procedures are included in the table. Miscellaneous procedures included slings, sling removals, periurethral or anal sphincter collagen injections, colon resection, postanal repair, and a Delorme’s procedure.
Surgical procedures by the pelvic floor service
different surgical procedures were performed in 77 patients (table). The pelvic floor service was established to develop a model to improve patient care, advance science, and train clinicians in new skills and knowledge for the complex pelvic floor problems that cross disciplines. Many patients were able to have a single examination and a single consultation. 20% of patients required combined procedures and avoided the anaesthetic risk and recuperative time of two separate procedures. We suggest that a pelvic floor service model which includes surgeons knowledgeable in gynaecology, urology, and colorectal surgery may improve patient care, convenience, and physician training. 1 2
3
4
Swash M, Snooks SJ, Henry MM. Unifying concept of pelvic floor disorders and incontinence. J R Soc Med 1985; 78: 906–11. Wiskind AK, Creighton SM, Stanton SL. The incidence of genital prolapse after the Burch colposuspension. Am J Obstet Gynecol 1992; 167: 399–405. Wall LL, DeLancey JOL. The politics of prolapse: a revisionist approach to disorders of the pelvic floor in women. Perspect Biol Med 1991; 34: 486–96. Hutchinson R, Mostafa AB, Grant EA, et al. Scintigraphic defecography: quantitative and dynamic assessment of anorectal function. Dis Colon Rectum 1993; 36; 1132–38.
Urogynaecology Unit, St George’s Hospital, London SW17 0QT, UK (C W Nager)
Loss of aura in lamotrigine-treated epilepsy Dirk Deleu, Yolande Hanssens
Lamotrigine is licensed for partial and generalised tonicclonic seizures.1 Its efficacy compares with that of carbamazepine in newly diagnosed and refractory epileptic patients.2 We report three patients who experienced loss of aura after switching from conventional antiepileptic therapy to lamotrigine. Features common to all cases included a long history of idiopathic epilepsy (5–13 years) in patients who had a normal neurological examination and normal brain computed tomography scan. All patients had been refractory
1751
THE LANCET
1 2
3
Deleu D, Hanssens Y. New challenges in the treatment of epilepsy. Saudi Med J 1996; 17: 428–36. Brodie MJ, Richens A, Yuen AWC. Double-blind comparison of lamotrigine and carbamazepine in newly diagnosed epilepsy. Lancet 1995; 345: 476–79. Goa KL, Ross SR, Chrisp P. Lamotrigine. A review of its pharmacological properties and clinical efficacy in epilepsy. Drugs 1993; 46: 152–76.
Departments of Clinical Neuropharmacology and Neurology, College of Medicine, Sultan Qaboos University, PO Box 35, Al Khod, Muscat-123, Sultanate of Oman (Dirk Deleu); and Drug Information Services, Pharmacy Department, Sultan Qaboos Hospital, Sultan of Oman
Half-life of truth in surgical literature John C Hall, Cameron Platell
The hypothetico-deductive model of Karl Popper contends that “An assertion is true if it corresponds to, or agrees with, the facts”.1 Because “the facts” change over time, truth is relative. In this view of events, science progresses via a series of theories (paradigms) that are held to be true until they are replaced by a better approximation of reality.2 It follows that some “truths” will last longer than others. We decided to estimate the half-life of dogma relating to the practice of surgery.
1752
80 95% CI of regression line
Positive responses (%)
to conventional antiepileptic therapies for the last 3–12 years. An 18-year-old woman had primary generalised tonicclonic seizures for which she was unsuccessfully treated with carbamazepine and phenytoin. Before each seizure she experienced irritability and tremulousness which gave her warning of a fit. Changing the treatment to lamotrigine (200 mg per day) did not affect the seizure frequency, but fits now presented without aura—and this resulted in frequent injuries. A 26-year-old man had complex partial seizures with frequent generalisation, poorly controlled by carbamazepine and valproate alone and in combination. Seizures were typically preceded by an abnormal epigastric sensation accompanied by an anxious feeling. After changing therapy to lamotrigine (150 mg per day) seizure frequency decreased by 40% but seizures were no longer preceded by aura. A 31-year-old man had complex partial and secondary generalised tonic-clonic seizures. Conventional antiepileptic therapies (phenobarbitone, phenytoin, valproate, carbamazepine) alone and in combination had all been tried without satisfactory seizure control. Vertigo was invariably the warning manifestation of his seizures. After switching the treatment to lamotrigine (200 mg per day) there was no change in seizure frequency; however the seizures were no longer preceded by aura—so that he sustained two serious injuries. All three patients were given lamotrigine in monotherapy and in doses as recommended by the manufacturer. Lamotrigine suppresses seizures by presynaptic inhibition via voltage-sensitive sodium channels, thereby preventing the release of excitatory neurotransmitters.3 Evidence that loss of aura was lamotrigine-specific is provided by the fact that the same patients had aura with other agents that affect sodium channels, suggesting that lamotrigine exerts additional mechanisms of action. Aura, particularly in patients with refractory seizures, can be an important warning sign for an epileptic patient. Therefore, we recommend that practitioners should inform their patients about the possibility of loss of aura when prescribing or switching to lamotrigine.
60 40 20 0 1930
1940
1950
1960 1970 Year
1980
1990
2000
Regression analysis of combined responses of assessors Score (%)=(date⫻0·747)⫺1422·4.
The journal Surgery Gynecology and Obstetrics had a section entitled International Surgical Abstracts that concluded at the end of 1994. We obtained copies of all of the abstracts for the even numbered months for each fifth year after 1935. The first 20 abstracts about general surgery from each of the 13 review periods were selected for study. The one sentence from each abstract that best summarised the conclusion was copied to a database. Editing of these sentences was restricted to the rephrasing of outdated terminology and the elimination of redundant words. The form, which contained the 260 selected sentences in a random order, was assessed by seven general surgeons. They were asked to mark each question as being either true or false. We explored the relation between time and the number of positive responses from the questionnaire using scatter plots and regression analyses. The linear model detailed in the figure was found to be most appropriate (R2=0·86, p<0·001). It suggests that the rate of loss of truth is 0·75% per year and that the estimated half-life of truth for clinical statements in the surgical literature is 45 years. This seems appropriate; 45 years ago it was suggested that: prefrontal lobotomy usefully altered patients’ reactions so that “no anxiety, fear, or concern over their impending death from cancer was manifest”3; “in primary malignant hypertension the malignant phase may disappear” after lumbodorsal sympathectomy4; and, the detection of a gastric ulcer was “a strong indication for immediate operation”.5 Extrapolation of the regression line can be used to hypothesise that the current era of surgery extends between 1904 and 2038. From an historical perspective, 1904 is a reasonable estimate of the commencement of the era of “open” surgery. Gauze masks and rubber gloves had just been introduced into operating theatres and abdominal surgery gained public respectability in the UK in 1902 when Edward VII’s coronation was delayed by the need to drain his appendiceal abscess. More contentious is extrapolation of the regression line to predict the future. However, a nexus point for the present era of surgery in the second quartile of the next century is consistent with the current trend towards the ascendancy of minimally invasive procedures and medical treatments over open surgery. 1 2 3 4 5
Popper KR. The myth of framework: in defence of science and rationality. London & New York: Routledge, 1994: 174. Polanyi M. Science, faith and society. Chicago and London: The University of Chicago Press, 1946. Dynes JB, Poppen JL. Lobotomy for intractable pain. JAMA 1949; 140: 15–19. Harland JC, D’Abreu F. Lumbodorsal sympathectomy in severe hypertension. BMJ 1949; 32: 1019–24. Ingelfinger FJ, Sanchez GC. Indications for surgery of the upper gastrointestinal tract. N Engl J Med 1950; 250: 445–52.
University Department of Surgery, Royal Perth Hospital, Perth WA 6000, Australia (J Hall); and Freemantle Hospital, Western Australia
Vol 350 • December 13, 1997
5
Frohm M, Agerberh B, Ahangari G, et al. The expression of the gene coding for the antibacterial peptide LL-37 is induced in human keratinocytes during inflammatory disorders. J Biol Chem 1997; 272: 15258–63. Harder J, Bartels J, Christophers E, Scroder JM. A peptide antibiotic from human skin. Nature 1997; 387: 861.
Centre for Cutaneous Research, St Bartholomew’s & The Royal London Hospital School of Medicine & Dentistry, London E1 2AJ, UK (A G Quinn); and Magainin Pharmaceuticals Inc, Plymouth Meeting, Pennsylvania, USA
Management of pelvic floor dysfunction Charles W Nager, Devinder Kumar, Margie A Kahn, Stuart L Stanton
For patients with combinations of urinary incontinence, faecal incontinence, abnormal faecal evacuation, and pelvic organ prolapse, a focused organ system approach by urologists, gynaecologists, or colorectal surgeons reflects historical and anatomical divisions, but fails to recognise the interrelations of the pelvic floor organs and leads to partial and fragmented care. Childbirth causes denervation and muscle trauma to the pelvic floor and the urinary and anal sphincters.1 This leads to pelvic organ prolapse which includes cystourethroceles, uterine or vault prolapse, enteroceles, rectoceles, and rectal prolapse. These injuries are rarely isolated. Surgical repair of one compartment may lead to deterioration in other compartments.2 There is emerging opinion that a multidisciplinary approach to the whole pelvis is indicated,3 yet practical solutions to resolve this fragmented care have not been published. After August, 1994, patients referred to the urogynaecologist (SLS) with colorectal complaints or patients referred to the colorectal surgeon (DK) with urinary or prolapse complaints were given an appointment in a monthly pelvic floor clinic after appropriate investigations. Typical investigations were a cystometrogram and uroflowmetry for urinary incontinence, anorectal physiology, and endoanal ultrasound for faecal incontinence, scintigraphic defaecography for impaired faecal evacuation,4 and pelvic fluoroscopy for complex prolapse. New patients in the clinic were interviewed, examined, discussed, and managed jointly by the urogynaecologist and the colorectal surgeon. We report an audit of the first 34 months of the pelvic floor service. 123 patient notes of the 137 new patients seen by the pelvic floor service from August, 1994, until May, 1997, were reviewed. Patients tended to be older (mean age 55 years, range 26–84) and postmenopausal (74%). The median parity and median number of vaginal births was 2 (range 0–8). 200 previous gynaecological, urogynaecological, or colorectal operations had been performed (mean 1·6, range 0–6) in these 123 patients. Chief complaints could be categorised as colorectal (46%), urinary (31%), and prolapse-related (23%). Faecal incontinence (20%), urge urinary incontinence (16%), impaired faecal emptying (13%), posterior vaginal prolapse (9%), and stress urinary incontinence (8%) were the commonest main symptoms. 260 diagnoses were made in 123 patients (mean 2·1 diagnoses per patient). The most common diagnoses were impaired faecal evacuation with rectocele (34% of patients), detrusor instability (27% of patients), genuine stress incontinence of urine (25% of patients), external anal sphincter defect (24% of patients), and symptomatic posterior vaginal wall prolapse (19% of patients). 35% of patients were managed conservatively, 25% had a colorectal procedure, 18% had a urogynaecological procedure, and 20% required a combined surgical procedure by the urogynaecologist and colorectal surgeon. In total, 86
Vol 350 • December 13, 1997
Procedure
Number
Combined urogynaecology and colorectal External anal sphincter repair and colposuspension External anal sphincter and hysteropexy Rectocolpopexy Rectocolpopexy and colposuspension Rectopexy and colposuspension Transanal rectocele repair and colposuspension Transanal rectocele repair and vaginal hysterectomy Transanal rectocele repair and anterior colporrhaphy Miscellaneous Total
6 1 3 3 2 4 1 1 3 24
Colorectal Transanal rectocele repair External anal sphincter repair Miscellaneous Total
21 4 6 31
Urogynaecological Colpopexy Colposuspension Hysterectomy Posterior colporrhaphy Anterior colporrhaphy Miscellaneous Total
4 5 9 8 2 3 31
If more than two surgical procedures were done in the same patient at the same operation, then only the two most major procedures are included in the table. Miscellaneous procedures included slings, sling removals, periurethral or anal sphincter collagen injections, colon resection, postanal repair, and a Delorme’s procedure.
Surgical procedures by the pelvic floor service
different surgical procedures were performed in 77 patients (table). The pelvic floor service was established to develop a model to improve patient care, advance science, and train clinicians in new skills and knowledge for the complex pelvic floor problems that cross disciplines. Many patients were able to have a single examination and a single consultation. 20% of patients required combined procedures and avoided the anaesthetic risk and recuperative time of two separate procedures. We suggest that a pelvic floor service model which includes surgeons knowledgeable in gynaecology, urology, and colorectal surgery may improve patient care, convenience, and physician training. 1 2
3
4
Swash M, Snooks SJ, Henry MM. Unifying concept of pelvic floor disorders and incontinence. J R Soc Med 1985; 78: 906–11. Wiskind AK, Creighton SM, Stanton SL. The incidence of genital prolapse after the Burch colposuspension. Am J Obstet Gynecol 1992; 167: 399–405. Wall LL, DeLancey JOL. The politics of prolapse: a revisionist approach to disorders of the pelvic floor in women. Perspect Biol Med 1991; 34: 486–96. Hutchinson R, Mostafa AB, Grant EA, et al. Scintigraphic defecography: quantitative and dynamic assessment of anorectal function. Dis Colon Rectum 1993; 36; 1132–38.
Urogynaecology Unit, St George’s Hospital, London SW17 0QT, UK (C W Nager)
Loss of aura in lamotrigine-treated epilepsy Dirk Deleu, Yolande Hanssens
Lamotrigine is licensed for partial and generalised tonicclonic seizures.1 Its efficacy compares with that of carbamazepine in newly diagnosed and refractory epileptic patients.2 We report three patients who experienced loss of aura after switching from conventional antiepileptic therapy to lamotrigine. Features common to all cases included a long history of idiopathic epilepsy (5–13 years) in patients who had a normal neurological examination and normal brain computed tomography scan. All patients had been refractory
1751
THE LANCET
1 2
3
Deleu D, Hanssens Y. New challenges in the treatment of epilepsy. Saudi Med J 1996; 17: 428–36. Brodie MJ, Richens A, Yuen AWC. Double-blind comparison of lamotrigine and carbamazepine in newly diagnosed epilepsy. Lancet 1995; 345: 476–79. Goa KL, Ross SR, Chrisp P. Lamotrigine. A review of its pharmacological properties and clinical efficacy in epilepsy. Drugs 1993; 46: 152–76.
Departments of Clinical Neuropharmacology and Neurology, College of Medicine, Sultan Qaboos University, PO Box 35, Al Khod, Muscat-123, Sultanate of Oman (Dirk Deleu); and Drug Information Services, Pharmacy Department, Sultan Qaboos Hospital, Sultan of Oman
Half-life of truth in surgical literature John C Hall, Cameron Platell
The hypothetico-deductive model of Karl Popper contends that “An assertion is true if it corresponds to, or agrees with, the facts”.1 Because “the facts” change over time, truth is relative. In this view of events, science progresses via a series of theories (paradigms) that are held to be true until they are replaced by a better approximation of reality.2 It follows that some “truths” will last longer than others. We decided to estimate the half-life of dogma relating to the practice of surgery.
1752
80 95% CI of regression line
Positive responses (%)
to conventional antiepileptic therapies for the last 3–12 years. An 18-year-old woman had primary generalised tonicclonic seizures for which she was unsuccessfully treated with carbamazepine and phenytoin. Before each seizure she experienced irritability and tremulousness which gave her warning of a fit. Changing the treatment to lamotrigine (200 mg per day) did not affect the seizure frequency, but fits now presented without aura—and this resulted in frequent injuries. A 26-year-old man had complex partial seizures with frequent generalisation, poorly controlled by carbamazepine and valproate alone and in combination. Seizures were typically preceded by an abnormal epigastric sensation accompanied by an anxious feeling. After changing therapy to lamotrigine (150 mg per day) seizure frequency decreased by 40% but seizures were no longer preceded by aura. A 31-year-old man had complex partial and secondary generalised tonic-clonic seizures. Conventional antiepileptic therapies (phenobarbitone, phenytoin, valproate, carbamazepine) alone and in combination had all been tried without satisfactory seizure control. Vertigo was invariably the warning manifestation of his seizures. After switching the treatment to lamotrigine (200 mg per day) there was no change in seizure frequency; however the seizures were no longer preceded by aura—so that he sustained two serious injuries. All three patients were given lamotrigine in monotherapy and in doses as recommended by the manufacturer. Lamotrigine suppresses seizures by presynaptic inhibition via voltage-sensitive sodium channels, thereby preventing the release of excitatory neurotransmitters.3 Evidence that loss of aura was lamotrigine-specific is provided by the fact that the same patients had aura with other agents that affect sodium channels, suggesting that lamotrigine exerts additional mechanisms of action. Aura, particularly in patients with refractory seizures, can be an important warning sign for an epileptic patient. Therefore, we recommend that practitioners should inform their patients about the possibility of loss of aura when prescribing or switching to lamotrigine.
60 40 20 0 1930
1940
1950
1960 1970 Year
1980
1990
2000
Regression analysis of combined responses of assessors Score (%)=(date⫻0·747)⫺1422·4.
The journal Surgery Gynecology and Obstetrics had a section entitled International Surgical Abstracts that concluded at the end of 1994. We obtained copies of all of the abstracts for the even numbered months for each fifth year after 1935. The first 20 abstracts about general surgery from each of the 13 review periods were selected for study. The one sentence from each abstract that best summarised the conclusion was copied to a database. Editing of these sentences was restricted to the rephrasing of outdated terminology and the elimination of redundant words. The form, which contained the 260 selected sentences in a random order, was assessed by seven general surgeons. They were asked to mark each question as being either true or false. We explored the relation between time and the number of positive responses from the questionnaire using scatter plots and regression analyses. The linear model detailed in the figure was found to be most appropriate (R2=0·86, p<0·001). It suggests that the rate of loss of truth is 0·75% per year and that the estimated half-life of truth for clinical statements in the surgical literature is 45 years. This seems appropriate; 45 years ago it was suggested that: prefrontal lobotomy usefully altered patients’ reactions so that “no anxiety, fear, or concern over their impending death from cancer was manifest”3; “in primary malignant hypertension the malignant phase may disappear” after lumbodorsal sympathectomy4; and, the detection of a gastric ulcer was “a strong indication for immediate operation”.5 Extrapolation of the regression line can be used to hypothesise that the current era of surgery extends between 1904 and 2038. From an historical perspective, 1904 is a reasonable estimate of the commencement of the era of “open” surgery. Gauze masks and rubber gloves had just been introduced into operating theatres and abdominal surgery gained public respectability in the UK in 1902 when Edward VII’s coronation was delayed by the need to drain his appendiceal abscess. More contentious is extrapolation of the regression line to predict the future. However, a nexus point for the present era of surgery in the second quartile of the next century is consistent with the current trend towards the ascendancy of minimally invasive procedures and medical treatments over open surgery. 1 2 3 4 5
Popper KR. The myth of framework: in defence of science and rationality. London & New York: Routledge, 1994: 174. Polanyi M. Science, faith and society. Chicago and London: The University of Chicago Press, 1946. Dynes JB, Poppen JL. Lobotomy for intractable pain. JAMA 1949; 140: 15–19. Harland JC, D’Abreu F. Lumbodorsal sympathectomy in severe hypertension. BMJ 1949; 32: 1019–24. Ingelfinger FJ, Sanchez GC. Indications for surgery of the upper gastrointestinal tract. N Engl J Med 1950; 250: 445–52.
University Department of Surgery, Royal Perth Hospital, Perth WA 6000, Australia (J Hall); and Freemantle Hospital, Western Australia
Vol 350 • December 13, 1997