- Email: [email protected]
CHANGING PATTERN OF DUODENAL ULCER?
857 While we accept that there are variations in MSAFP in diabetic pregnant women compared with normal pregnancy, we do not believe that this can be fully explained on the basis of either maternal weight or glycaemic control as suggested by Reece et al. Clinicians should interpret levels of MSAFP with caution in diabetic pregnant patients until further work has clarified the pathophysiology.
ELIGIBILITY OF DUODENAL ULCER PATIENTS FOR CLINICAL TRIALS
K. POWRIE DONALD W. M. PEARSON I. S. ROSS HAMISH W. SUTHERLAND
JAMES
Aberdeen Maternity Hospital, Aberdeen AB9 2ZA
1, Ross IS, Gibson PF A semi-automated method for the determination of glycosylated haemoglobin. Clin Chim Acta 1979; 98: 53-59.
DIHYDROERGOTAMINE AND THE PELVIC PAIN SYNDROME
SIR,-In a study of pelvic congestion and pain Mr Reginald and colleagues (Aug 15, p 351) state that dihydroergotamine (DHE) is a "selective venoconstrictor" and
a
"venoconstrictor that
tree.
DHE is a semi-synthetic derivative of ergot alkaloids. Its pharmacological actions are complex, acting on the cardiovascular system, both centrally and peripherally, and on the central nervous system, and DHE antagonists 5-hydroxytryptamine (5-HT). That such compounds have generalised effects on the arterial side of
the vascular tree is evident not least from the effects of chronic ergot poisoning. Hence it seems incorrect to view the possible action of DHE in the pelvic pain syndrome as confined to pelvic venous systems. Indeed antagonism of 5-HT may explain part of the observed analgesic effect. Intravenous DHE has also been used in persistent migraine and the arterial responses are essential to the relief of pain;3 might it be that in the pelvic pain syndrome the radiographic demonstration of pelvic varicosities is merely a sign of local disturbance of vaso/veno motor control, and that the action of DHE on the pelvic arterial tree contributes to the pain relief? Pelvic arteriography is more invasive than transmyometrial pelvic venography, and would be unlikely to meet with ethical approval. Hence the supposed action of DHE on the pelvic arterial tree will remain unproven. The central activities of DHE include antagonism at 5-HT and adrenergic receptors but also, paradoxically, agonism at adrenergic receptors.1 The possible interference with neurotransmission by DHE might be important in diseases with a psychosomatic basis. Reginald’s unit has previously outlined the importance of psychosomatic factors in the pelvic pain syndrome. Indeed
gynaecologists might contribute to the cycle of psychosomatic illness-if, in the investigation of chronic pelvic pain, vaginal assessment and laparoscopy are otherwise normal, then both doctor and patients may invoke psychosomatic factors to explain the pain. The demonstration of pelvic varicosities might help to break this cycle by providing evidence of an organic basis to the pain. D. P.
J. BARTON
AG, Goodman LS, Rall TW, Murad F, eds Goodman and Gilman’s the pharmacological basis of therapeutics. 7th ed. New York MacMillan, 1985. Reynolds JEF, ed. Ergot and ergot derivities. Martindale; the extra pharmacopoeia.
1 Gilman 2.
28th ed. London Pharmaceutical Press 1982 662-64. 3 Raskin NH. Repetitive intravenous dihydroergotamine 4
migraine. Neurology 1986; 36: 995-97. Pearce S, Knight C, Beard RW Pelvic pain: J Psychosom Obstet Gynecol 1982; 1: 12-17.
as
a common
those with medical
or
social contraindications
acts
selectively on the capicitance vessels", referring to an animal study. The implication is that DHE has little or no action on the arterial
National Maternity Hospital, Holles Street, Dublin 2, Ireland
*Bleedmg ulcers apart, reasons for exclusion were’ patients with many small ulcers, aphthous ulcers, or erosions, with combined duodenal and gastric ulcer, or with nearly healed ulcers; patients aged 70 or over; patients on H2-receptor antagonists, non-steroidal anti-mflammatory drugs, or steroids; patients with obstruction or requiring surgery; and
therapy for intractable
gynaecological problem.
CHANGING PATTERN OF DUODENAL ULCER?
SiR,—In the past two years we have noted a sharp fall in the number of duodenal ulcer patients eligible for entry into clinical trials. To see if this difficulty in recruitment was due to the well-recognised fall in incidencel-3we reviewed our endoscopy register from 1979 to the end of June, 1987 (table). There has been
significant decline in duodenal ulcers (expressed as a percentage of the total number of endoscopies). What has changed is the number of patients not meeting criteria for inclusion in clinical trials-in other words there has been a change not in the incidence of duodenal ulcer but in the pattern of presentation. Previously 20-30 patients were recruited every year for clinical trials. In the past twelve months only 11 patients have been recruited, insufficient for the continuation of a current trial. There has been a 10% rise in the number of bleeding duodenal ulcers in the past 2 years, affecting all age groups, and there have been increasing numbers in other exclusion clauses (table). Have other centres observed a change in the pattern of duodenal ulcer on presentation? no
Department of Surgery, Basingstoke District Hospital, Basingstoke RG24 9NA
D. J. SCHACHE F. I. TOVEY A. MASTERS A. STEBBING M. REES
1. Mulholland
MW, Debas HT. Chronic duodenal and gastric ulcer Surg Clins N Am 1987; 67: 489-507
2.
Sonnenberg A Changes in physician visits for gastric and duodenal ulcer in the United States during 1958-1984 as shown by national disease and therapeutic index
(NDTI). Dig Dis Sci 1987; 32: 1-7. 3. Hollander D, Tarnawaski A. Dietary essential fatty acids and the decline in peptic ulcer disease: a hypothesis. Gut 1986; 27: 239-42.
MODIFIED TRIMETHOPRIMSULPHAMETHOXAZOLE DOSES IN PNEUMOCYSTIS CARINII PNEUMONIA
SiR,—Bowden et all reported that the recommended regimen of trimethoprim (TMP) and sulphamethoxazole (SMZ) in AIDS (TMP 15-20 mg/kg and SMZ 75-100 mg/kg daily) would maintain TMP levels in the range 5-10 g/ml. The serum SMZ level increased with time and it was suggested that the high serum SMZ levels might contribute to the high frequency of side-effects of TMP-SMZ in AIDS. It was postulated that the administration of TMP and SMZ separately, in lower doses, and in a different ratio to that usually administered, might lead to a lower rate of side-effects. We have now studied IAIDS patients with Pneumocystis carinii pneumonia (PCP) who were alternately allocated to one of two treatment regimens. Regimen A was at TMP 20 mg/kg and SMZ 100 mg/kg per day if used orally, or TMP 15 mg/kg and SMZ 75 mg/kg per day if used intravenously. The daily dose was given in either 6-hourly or 8-hourly divided doses. Regimen B was the same as A for the first 48 h, then the dose of both drugs was halved and additional doses of TMP alone were given to maintain the daily dose of TMP at 15-20 mg/kg. Both groups were treated for 3 weeks. Serum was collected 1h after an oral dose, or 05 h after completion of a 1 h intravenous infusion. The TMP and SMZ serum levels were measured by high-pressure liquid serum
chromatography.2
ELIGIBILITY OF DUODENAL ULCER PATIENTS FOR CLINICAL TRIALS
K. POWRIE DONALD W. M. PEARSON I. S. ROSS HAMISH W. SUTHERLAND
JAMES
Aberdeen Maternity Hospital, Aberdeen AB9 2ZA
1, Ross IS, Gibson PF A semi-automated method for the determination of glycosylated haemoglobin. Clin Chim Acta 1979; 98: 53-59.
DIHYDROERGOTAMINE AND THE PELVIC PAIN SYNDROME
SIR,-In a study of pelvic congestion and pain Mr Reginald and colleagues (Aug 15, p 351) state that dihydroergotamine (DHE) is a "selective venoconstrictor" and
a
"venoconstrictor that
tree.
DHE is a semi-synthetic derivative of ergot alkaloids. Its pharmacological actions are complex, acting on the cardiovascular system, both centrally and peripherally, and on the central nervous system, and DHE antagonists 5-hydroxytryptamine (5-HT). That such compounds have generalised effects on the arterial side of
the vascular tree is evident not least from the effects of chronic ergot poisoning. Hence it seems incorrect to view the possible action of DHE in the pelvic pain syndrome as confined to pelvic venous systems. Indeed antagonism of 5-HT may explain part of the observed analgesic effect. Intravenous DHE has also been used in persistent migraine and the arterial responses are essential to the relief of pain;3 might it be that in the pelvic pain syndrome the radiographic demonstration of pelvic varicosities is merely a sign of local disturbance of vaso/veno motor control, and that the action of DHE on the pelvic arterial tree contributes to the pain relief? Pelvic arteriography is more invasive than transmyometrial pelvic venography, and would be unlikely to meet with ethical approval. Hence the supposed action of DHE on the pelvic arterial tree will remain unproven. The central activities of DHE include antagonism at 5-HT and adrenergic receptors but also, paradoxically, agonism at adrenergic receptors.1 The possible interference with neurotransmission by DHE might be important in diseases with a psychosomatic basis. Reginald’s unit has previously outlined the importance of psychosomatic factors in the pelvic pain syndrome. Indeed
gynaecologists might contribute to the cycle of psychosomatic illness-if, in the investigation of chronic pelvic pain, vaginal assessment and laparoscopy are otherwise normal, then both doctor and patients may invoke psychosomatic factors to explain the pain. The demonstration of pelvic varicosities might help to break this cycle by providing evidence of an organic basis to the pain. D. P.
J. BARTON
AG, Goodman LS, Rall TW, Murad F, eds Goodman and Gilman’s the pharmacological basis of therapeutics. 7th ed. New York MacMillan, 1985. Reynolds JEF, ed. Ergot and ergot derivities. Martindale; the extra pharmacopoeia.
1 Gilman 2.
28th ed. London Pharmaceutical Press 1982 662-64. 3 Raskin NH. Repetitive intravenous dihydroergotamine 4
migraine. Neurology 1986; 36: 995-97. Pearce S, Knight C, Beard RW Pelvic pain: J Psychosom Obstet Gynecol 1982; 1: 12-17.
as
a common
those with medical
or
social contraindications
acts
selectively on the capicitance vessels", referring to an animal study. The implication is that DHE has little or no action on the arterial
National Maternity Hospital, Holles Street, Dublin 2, Ireland
*Bleedmg ulcers apart, reasons for exclusion were’ patients with many small ulcers, aphthous ulcers, or erosions, with combined duodenal and gastric ulcer, or with nearly healed ulcers; patients aged 70 or over; patients on H2-receptor antagonists, non-steroidal anti-mflammatory drugs, or steroids; patients with obstruction or requiring surgery; and
therapy for intractable
gynaecological problem.
CHANGING PATTERN OF DUODENAL ULCER?
SiR,—In the past two years we have noted a sharp fall in the number of duodenal ulcer patients eligible for entry into clinical trials. To see if this difficulty in recruitment was due to the well-recognised fall in incidencel-3we reviewed our endoscopy register from 1979 to the end of June, 1987 (table). There has been
significant decline in duodenal ulcers (expressed as a percentage of the total number of endoscopies). What has changed is the number of patients not meeting criteria for inclusion in clinical trials-in other words there has been a change not in the incidence of duodenal ulcer but in the pattern of presentation. Previously 20-30 patients were recruited every year for clinical trials. In the past twelve months only 11 patients have been recruited, insufficient for the continuation of a current trial. There has been a 10% rise in the number of bleeding duodenal ulcers in the past 2 years, affecting all age groups, and there have been increasing numbers in other exclusion clauses (table). Have other centres observed a change in the pattern of duodenal ulcer on presentation? no
Department of Surgery, Basingstoke District Hospital, Basingstoke RG24 9NA
D. J. SCHACHE F. I. TOVEY A. MASTERS A. STEBBING M. REES
1. Mulholland
MW, Debas HT. Chronic duodenal and gastric ulcer Surg Clins N Am 1987; 67: 489-507
2.
Sonnenberg A Changes in physician visits for gastric and duodenal ulcer in the United States during 1958-1984 as shown by national disease and therapeutic index
(NDTI). Dig Dis Sci 1987; 32: 1-7. 3. Hollander D, Tarnawaski A. Dietary essential fatty acids and the decline in peptic ulcer disease: a hypothesis. Gut 1986; 27: 239-42.
MODIFIED TRIMETHOPRIMSULPHAMETHOXAZOLE DOSES IN PNEUMOCYSTIS CARINII PNEUMONIA
SiR,—Bowden et all reported that the recommended regimen of trimethoprim (TMP) and sulphamethoxazole (SMZ) in AIDS (TMP 15-20 mg/kg and SMZ 75-100 mg/kg daily) would maintain TMP levels in the range 5-10 g/ml. The serum SMZ level increased with time and it was suggested that the high serum SMZ levels might contribute to the high frequency of side-effects of TMP-SMZ in AIDS. It was postulated that the administration of TMP and SMZ separately, in lower doses, and in a different ratio to that usually administered, might lead to a lower rate of side-effects. We have now studied IAIDS patients with Pneumocystis carinii pneumonia (PCP) who were alternately allocated to one of two treatment regimens. Regimen A was at TMP 20 mg/kg and SMZ 100 mg/kg per day if used orally, or TMP 15 mg/kg and SMZ 75 mg/kg per day if used intravenously. The daily dose was given in either 6-hourly or 8-hourly divided doses. Regimen B was the same as A for the first 48 h, then the dose of both drugs was halved and additional doses of TMP alone were given to maintain the daily dose of TMP at 15-20 mg/kg. Both groups were treated for 3 weeks. Serum was collected 1h after an oral dose, or 05 h after completion of a 1 h intravenous infusion. The TMP and SMZ serum levels were measured by high-pressure liquid serum
chromatography.2