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INTERACTION BETWEEN METHOTREXATE AND NON-STEROIDAL ANTI-INFLAMMATORY DRUGS
557 REFLUX
SYMPTOMS, ENDOSCOPY FINDINGS, PENTAGASTRIN TEST, pH MEASUREMENTS, AND TREATMENT
*See text BAO=basal acid output; MAO = maximal acid output.
REFLUX OESOPHAGITIS IN ONE FAMILY
SiR,-The main factor in the development of reflux oesophagitis be failure of the antireflux barrier, but the cause of this failure is not clear. While studying patients with symptomatic gastro-oesophageal refluxl I encountered an interesting family,
INTERACTION BETWEEN METHOTREXATE AND NON-STEROIDAL ANTI-INFLAMMATORY DRUGS
SlR,—Dr Thyss and colleagues (Feb 1, p 256) draw attention
seems to
presented here. The whole family (father, mother, five sons, and two daughters) was examined by endoscopy and a pentagastrin test, and the sons and daughters also had pH measurements in the lower oesophagus. Symptoms reflecting reflux oesophagitis were scoredbefore these investigations were done and were rated as none, mild, moderate, or severe. Endoscopic findings were classified as normal, erosions, or stricture formation. pH was measured by standard acid test3 or by long-term monitoring, the total time the pH of the lowet 4 oesophagus was below 4 in 18 h being recorded 4 symptomless father had had a Billroth II gastric resection, thought to be for peptic ulcer disease, 25 years earlier. His five siblings have not had any operations on the stomach or oesophagus. The mother had slight reflux symptoms and her sister had been operated on for a sliding hiatal hernia; she had two brothers who had died of coronary heart disease. All five sons in this family had reflux symptoms and four had erosive oesophagitis (table). These four men and their 30-year-old sister were operated on, with good results at follow-up (mean, 16 months). Thus six out of seven siblings had symptoms of gastrooesophageal reflux and five had an abnormal antireflux barrier, as demonstrated by pH measurements. Of the three without erosive oesophagitis two were almost achlorhydric, which might explain the normal oesophageal mucosa.4In general, symptoms seem to correlate better with lower sphincter incompetence oeso 16hageal than with a sliding hiatal hernia. However, all seven siblings in this family had sliding hernias. The mother had no hernia, despite slight symptoms. I know of no other reports of gastro-oesophageal reflux disease or reflux oesophagitis being present so strikingly in one family.
mg/m2)
HELENA DALY
The
Second Department of Surgery,
University of Helsinki,
MARTTI MATIKAINEN*
Helsinki, Finland *Present address. Department of Clinical Sciences, Finland.
University of Tampere,
33101
Tampere,
1. Matikainen M. Studies 2
on
reflux
oesophagitis
and its
surgical
treatment.
Academic
dissertation, University of Helsinki, 1982. DeMeester TR, Johnson LF. The evaluation of objective
esophageal reflux and
their contribution
to
measurement of gastropatient management. Surg Clin N Am
1976, 56: 39-53 DJ. Assessment of distal esophageal function in patients with hiatal hernia and/or gastroesophageal reflux Ann Surg 1970; 172: 627-37. Matikainen M. Gastric acid secretion, oesophageal acid reflex and oesophagitis in patients with symptomatic gastro-oesophageal reflux. Scand J Gastroenterol 1981;
3 Skinner DB, Booth 4
16: 1043-48. 5.
Wankling VJ, Earrin WG, Lind JF. The gastro-esophageal sphincter in hiatus hernia.
Can J Surg 1965; 8: 6 Cohen
61-67
S, Harris LD Does hiatus hernia affect competence of the gastroesophageal sphincter? N Engl J Med 1971; 284: 1053-56.
to
methotrexate (MTX) toxicity precipitated by concurrent administration of ketoprofen. They suggest that this high-risk association may also apply to other non-steroidal anti-inflammatory drugs (NSAID). We have seen a patient treated with conventional for psoriasis who had acute toxicity after the dose MTX (15 administration of azapropazone.! The main features of this case were reversible bone marrow failure and oral and genital ulceration. We believe that the clearance of MTX was impaired by the azapropazone, either by inhibition of hepatic enzymes or by competition for renal tubular secretion. We therefore agree with Thyss et al. Geat caution is needed in using this group of drugs in patients receiving MTX, whether at high or conventional doses. severe
JOSEPH BOYLE Bristol Royal Infirmary, Bristol BS2 8HW
1.
Daly HM,
Scott GL, Boyle J, Roberts CJC Methotrexate Br J Dermatol (in press).
CLIVE ROBERTS GEOFFREY SCOTT toxicity precipitated by
azapropazone.
KOILOCYTE FREQUENCY AND PREVALENCE OF CERVICAL HUMAN PAPILLOMAVIRUS INFECTION
SIR,-Two letters in The Lancet ofJan 25 (p 205) drew attention to the geographical variation in the frequency of koilocytosis (Dr Boon and colleagues) and the prevalence of koilocytosis in colposcopic cervical biopsy specimens in Birmingham (Dr Byrne and
colleagues). In 1985 we examined 1147 colposcopically directed punch biopsy specimens from patients who had been referred for evaluation of abnormal cytology. The histological reports were by two consultant pathologists with a special interest in this field using previously reported criteria.! Among the 925 cases showing an abnormality, koilocytosis of varying degree was noted in 800 (86 -5%). This was four times higher than the 21 % reported by the Birmingham group. A higher prevalence of human papillomavirus (HPV) infection in our patients is supported by the detection of HPV type 16 DNA in 64% and HPV 6 DNA in 28% of 78 cases of cervical intraepithelial neoplasia (CIN) by DNA-DNA hybridisation.2Also, of the 925 cases studied in 1985, 305 (33 0%) were positive for HPV antigen. Although HPV antigen staining is less sensitive than DNA-DNA hybridisation technique in detecting HPV infection in the uterine cervix (unpublished), the prevalence of HPV antigen alone indicates a higher prevalence of HPV infection in patients in north London than in Birmingham. This would suggest a striking geographical variation in the prevalence of HPV infection, not only between countries, as pointed out by Boon et al, but also apparently between different areas of Britain. This may reflect differences in sexual behaviour, but may also indicate that we are witnessing the early stages of the
SYMPTOMS, ENDOSCOPY FINDINGS, PENTAGASTRIN TEST, pH MEASUREMENTS, AND TREATMENT
*See text BAO=basal acid output; MAO = maximal acid output.
REFLUX OESOPHAGITIS IN ONE FAMILY
SiR,-The main factor in the development of reflux oesophagitis be failure of the antireflux barrier, but the cause of this failure is not clear. While studying patients with symptomatic gastro-oesophageal refluxl I encountered an interesting family,
INTERACTION BETWEEN METHOTREXATE AND NON-STEROIDAL ANTI-INFLAMMATORY DRUGS
SlR,—Dr Thyss and colleagues (Feb 1, p 256) draw attention
seems to
presented here. The whole family (father, mother, five sons, and two daughters) was examined by endoscopy and a pentagastrin test, and the sons and daughters also had pH measurements in the lower oesophagus. Symptoms reflecting reflux oesophagitis were scoredbefore these investigations were done and were rated as none, mild, moderate, or severe. Endoscopic findings were classified as normal, erosions, or stricture formation. pH was measured by standard acid test3 or by long-term monitoring, the total time the pH of the lowet 4 oesophagus was below 4 in 18 h being recorded 4 symptomless father had had a Billroth II gastric resection, thought to be for peptic ulcer disease, 25 years earlier. His five siblings have not had any operations on the stomach or oesophagus. The mother had slight reflux symptoms and her sister had been operated on for a sliding hiatal hernia; she had two brothers who had died of coronary heart disease. All five sons in this family had reflux symptoms and four had erosive oesophagitis (table). These four men and their 30-year-old sister were operated on, with good results at follow-up (mean, 16 months). Thus six out of seven siblings had symptoms of gastrooesophageal reflux and five had an abnormal antireflux barrier, as demonstrated by pH measurements. Of the three without erosive oesophagitis two were almost achlorhydric, which might explain the normal oesophageal mucosa.4In general, symptoms seem to correlate better with lower sphincter incompetence oeso 16hageal than with a sliding hiatal hernia. However, all seven siblings in this family had sliding hernias. The mother had no hernia, despite slight symptoms. I know of no other reports of gastro-oesophageal reflux disease or reflux oesophagitis being present so strikingly in one family.
mg/m2)
HELENA DALY
The
Second Department of Surgery,
University of Helsinki,
MARTTI MATIKAINEN*
Helsinki, Finland *Present address. Department of Clinical Sciences, Finland.
University of Tampere,
33101
Tampere,
1. Matikainen M. Studies 2
on
reflux
oesophagitis
and its
surgical
treatment.
Academic
dissertation, University of Helsinki, 1982. DeMeester TR, Johnson LF. The evaluation of objective
esophageal reflux and
their contribution
to
measurement of gastropatient management. Surg Clin N Am
1976, 56: 39-53 DJ. Assessment of distal esophageal function in patients with hiatal hernia and/or gastroesophageal reflux Ann Surg 1970; 172: 627-37. Matikainen M. Gastric acid secretion, oesophageal acid reflex and oesophagitis in patients with symptomatic gastro-oesophageal reflux. Scand J Gastroenterol 1981;
3 Skinner DB, Booth 4
16: 1043-48. 5.
Wankling VJ, Earrin WG, Lind JF. The gastro-esophageal sphincter in hiatus hernia.
Can J Surg 1965; 8: 6 Cohen
61-67
S, Harris LD Does hiatus hernia affect competence of the gastroesophageal sphincter? N Engl J Med 1971; 284: 1053-56.
to
methotrexate (MTX) toxicity precipitated by concurrent administration of ketoprofen. They suggest that this high-risk association may also apply to other non-steroidal anti-inflammatory drugs (NSAID). We have seen a patient treated with conventional for psoriasis who had acute toxicity after the dose MTX (15 administration of azapropazone.! The main features of this case were reversible bone marrow failure and oral and genital ulceration. We believe that the clearance of MTX was impaired by the azapropazone, either by inhibition of hepatic enzymes or by competition for renal tubular secretion. We therefore agree with Thyss et al. Geat caution is needed in using this group of drugs in patients receiving MTX, whether at high or conventional doses. severe
JOSEPH BOYLE Bristol Royal Infirmary, Bristol BS2 8HW
1.
Daly HM,
Scott GL, Boyle J, Roberts CJC Methotrexate Br J Dermatol (in press).
CLIVE ROBERTS GEOFFREY SCOTT toxicity precipitated by
azapropazone.
KOILOCYTE FREQUENCY AND PREVALENCE OF CERVICAL HUMAN PAPILLOMAVIRUS INFECTION
SIR,-Two letters in The Lancet ofJan 25 (p 205) drew attention to the geographical variation in the frequency of koilocytosis (Dr Boon and colleagues) and the prevalence of koilocytosis in colposcopic cervical biopsy specimens in Birmingham (Dr Byrne and
colleagues). In 1985 we examined 1147 colposcopically directed punch biopsy specimens from patients who had been referred for evaluation of abnormal cytology. The histological reports were by two consultant pathologists with a special interest in this field using previously reported criteria.! Among the 925 cases showing an abnormality, koilocytosis of varying degree was noted in 800 (86 -5%). This was four times higher than the 21 % reported by the Birmingham group. A higher prevalence of human papillomavirus (HPV) infection in our patients is supported by the detection of HPV type 16 DNA in 64% and HPV 6 DNA in 28% of 78 cases of cervical intraepithelial neoplasia (CIN) by DNA-DNA hybridisation.2Also, of the 925 cases studied in 1985, 305 (33 0%) were positive for HPV antigen. Although HPV antigen staining is less sensitive than DNA-DNA hybridisation technique in detecting HPV infection in the uterine cervix (unpublished), the prevalence of HPV antigen alone indicates a higher prevalence of HPV infection in patients in north London than in Birmingham. This would suggest a striking geographical variation in the prevalence of HPV infection, not only between countries, as pointed out by Boon et al, but also apparently between different areas of Britain. This may reflect differences in sexual behaviour, but may also indicate that we are witnessing the early stages of the