1059
transfusion requirements. 1-5 These findings are supported by observations in acute cases, showing clear evidence of mucosal injury with doses as low as 300 mg daily and probably less. For example, data from this unit for the effect of low-dose aspirin on gastric mucosa6 show: No of gastric erosions (median [interquartile Treatment Placebo
Aspirin 75 mg per day Aspirin 300 mg per day Enteric-coated aspirin 300 mg per day
[interquartile
range])**
0 (0-2) 1.5 (0-7) (NS) 18 (2-26) (p < 0.001) 0 (0-1) (NS)
sites. Steady-state plasma ondansetron concentrations compared well to those in cancer patients receiving intravenous infusions at the same rate (66-3 ng/ml in our patient vs 67-8 ng/mll). Continuous subcutaneous infusion is well tolerated in patients with advanced cancer, whether at home or as inpatients. The manufacturers do not recommend ondansetron via the subcutaneous route because of the acidic pH of the injection form (pH 3-5). However, the pH of subcutaneously administered drugs seems to be a poor predictor of skin reactions at injection sites, and low pH solutions may be well tolerated by tissues because of the slow rate (0-3-1’0 ml/h) of continuous subcutaneous infusion: Skin reactions Unusual Unusual Unusual Occasional Unusual Occasional Sources. Martindale, the Extra Pharmacopoeia, 29th ed, and C Regnard and A Davies A Guide to Symptom Relief in Advanced Cancer, 2nd ed (Manchester: Haigh and Holland, 1986)
Drug Hyoscine hydrobromidc Hyoscine butylbromide Haloperidol Cyclizine Metoclopramide Methotrimeprazme
*After 5 days of treatment
The level of mucosal injury due to aspirin 300 mg per day is to that with aspirin 2-4 g per day in similar studies? Furthermore, enteric coating reduced acute low-dose-aspirininduced gastric injury to placebo levels. Such protection by enteric coating is also seen at higher doses of aspirin. 7,8Thus, although such protection might not be afforded in chronic disease, we disagree with Baker and collegues’ assertion that enteric coating does not protect the stomach against aspirin injury. Indeed, we believe that the evidence shows that low-dose aspirin causes substantial gastric damage and that the best strategy to prevent this would be the use of enteric-coated preparations.
similar
Department of Therapeutics, University Hospital, Queen’s Medical Centre, Nottingham NG7 2UH, UK 1.
F. E. MURRAY A. T. COLE N. HUDSON C. J. HAWKEY
Steering Committee of the Physicians’ Health Study Research Group. Final report on the aspirin component of the ongoing physicians’ health study. N Engl J Med 1989;
321: 131-35. 2. Peto R, Gray R, Collins R. Randomised trial of prophylactic daily aspirin in British male doctors. Br Med J 1988; 296: 313-16. 3. UK-TIA Study Group. United Kingdom transient ischaemic attack (UK-TIA) aspirin trial: interim results. Br Med J 1988, 296: 316-20 4 The Dutch TIA Trial Study Group. A comparison of two doses of aspirin (30 mg vs 282 mg a day) in patients after a transient ischemic attack or minor ischemic stroke. N Engl J Med 1991; 325: 1261-66. 5. The SALT Collaborative Group. Swedish aspirin low-dose (SALT) of 75 mg aspirin as secondary prophylaxis after cerebrovascular ischemic events Lancet 1991; 338: 1345-49. 6. Hudson N, Cole AT, Murray FE, et al. Low dose aspirin: an unrecognised cause of gastric mucosal damage Gut 1991; 332: A1245. 7. Hawthorne AB, Hurst SM, Mahida YR, Cole AT, Hawkey CJ. Aspirin-induced gastric mucosal damage: prevention by enteric-coating of aspirin and relation to prostaglandin synthesis. Br J Clin Pharm 1992; 32: 77-83. 8. O’Laughlin JC, Hoftiezer JW, Ivey KJ. Effect of aspirin on the human stomach in normals, endoscopic comparison of damage produced one hour, 24 hours, and 2 weeks after administration Scand J Gastroenterol 1991; 16 (suppl 67): 211-14.
Subcutaneous ondansetron SIR,-Ondansetron has a place in the control of nausea and vomiting in patients on highly emetogenic chemotherapy. Dr Nicholson and colleagues (Feb 22, p 490) have used intravenous and oral ondansetron to alleviate nausea and vomiting associated with terminal disease, not chemotherapy, and in the same issue of The Lancet, Dr Rosenthal and co-workers (p 490) report the use of oral ondansetron in patients given radiotherapy to the whole abdomen. We describe the continuous subcutaneous administration of this drug to good effect in a patient with intractable nausea and vomiting unresponsive to other antiemetics. A 62-year-old man was referred with persistent nausea, vomiting, and hiccoughs due to a metastatic, poorly differentiated gastric adenocarcinoma. At gastrectomy 8 months earlier, hepatic and local lymph-node involvement was noted. At first his symptoms partly responded to subcutaneous cyclizine (in view of hepatic metastases) and hyoscine butylbromide (to reduce afferent loop motility) plus rectal domperidone. The number of vomits per 24 h fell from 16 to 4, accompanied by a reduction in nausea, and the patient was able to return home for short periods. On subsequent admissions, however, symptom control was not achieved with this regimen. A chemical cause for his vomiting having been excluded, a subcutaneous infusion of ondansetron was started at 1 mg/h. This reduced daily vomits to less than 3 and abolished the nausea and hiccoughs. There were no problems with the skin at the infusion
pH
3-5-6-5 3-7-5-5 3-0-3-8 3.2-4.7 3-0-50 3-0-5-0
Subcutaneous ondansetron, should its future cost allow, may be a useful addition to the palliative physician’s antiemetic armoury. We thank Mr P. V. Colthup, biochemical pharmacology department, Glaxo Group Research Ltd, for his assistance and for analysing plasma ondansetron concentrations.
PAULA M. MULVENNA CLAUD F. B. REGNARD
St Oswald’s Hospice, Gosforth NE3 1EE, UK
DB, Newlands ES, Rustin GJS, et al A phase I/II study of the 5-HT3 antagonist GR38032F in the antiemetic prophylaxis of patients receiving high dose cisplatin chemotherapy. Cancer Chemother Pharmacol 1990; 25: 291-94.
1. Smith
Transmission of HCV between spouses SIR,—The transmissibility of hepatitis C virus (HCV) between husband and wife is thought to be low.l-4 However, most of the evidence comes from serological tests for the clOO antibody. Tajima et al5 found a 50% risk of spouse transmission in Japanese couples when C gene-derived antibodies (anti-core) were measured. However, those couples were from an isolated town that was highly endemic for HCV infection and there was no evidence that infections had not been community acquired. In our study of transmission risk, 195 spouses of Japanese patients with HCV-related chronic liver disease were first screened for risk of HCV infection via routes other than contact with their viraemic wives or husbands: 19 had had blood transfusions or had premarital histories of jaundice or non-viral hepatitis. The remaining 176 spouses were tested for HCV-core antibody, HCV RNA, and clOO antibody. There were 82 cases of chronic hepatitis, 55 of liver cirrhosis, and 39 of hepatocellular carcinoma. They came from three prefectures in Japan (47 patients from Yamanashi, 37 from Fukushima, and 92 from Ibaragi). Anti-c100 was detected by an ELISA kit (Ortho); anti-core was measured by ELISA based on synthetic peptides.6,7 HCV genome RNA was determined only in spouses positive for clOO or core antibody by amplifying the 5’-untranslated region.8 We also determined the HCV genotype in some couples, with type-specific
primers.99 11spouses (6%) had clOO antibody (and 9 were also positive for anti-core), and of the clOO-seronegative spouses, 21 had core antibody (table). Of these 32, 14 (8% of all spouses) had serum HCV SEROLOGICAL STATUS OF SPOUSES
i
No
in
parentheses RNA positive
transfusion requirements. 1-5 These findings are supported by observations in acute cases, showing clear evidence of mucosal injury with doses as low as 300 mg daily and probably less. For example, data from this unit for the effect of low-dose aspirin on gastric mucosa6 show: No of gastric erosions (median [interquartile Treatment Placebo
Aspirin 75 mg per day Aspirin 300 mg per day Enteric-coated aspirin 300 mg per day
[interquartile
range])**
0 (0-2) 1.5 (0-7) (NS) 18 (2-26) (p < 0.001) 0 (0-1) (NS)
sites. Steady-state plasma ondansetron concentrations compared well to those in cancer patients receiving intravenous infusions at the same rate (66-3 ng/ml in our patient vs 67-8 ng/mll). Continuous subcutaneous infusion is well tolerated in patients with advanced cancer, whether at home or as inpatients. The manufacturers do not recommend ondansetron via the subcutaneous route because of the acidic pH of the injection form (pH 3-5). However, the pH of subcutaneously administered drugs seems to be a poor predictor of skin reactions at injection sites, and low pH solutions may be well tolerated by tissues because of the slow rate (0-3-1’0 ml/h) of continuous subcutaneous infusion: Skin reactions Unusual Unusual Unusual Occasional Unusual Occasional Sources. Martindale, the Extra Pharmacopoeia, 29th ed, and C Regnard and A Davies A Guide to Symptom Relief in Advanced Cancer, 2nd ed (Manchester: Haigh and Holland, 1986)
Drug Hyoscine hydrobromidc Hyoscine butylbromide Haloperidol Cyclizine Metoclopramide Methotrimeprazme
*After 5 days of treatment
The level of mucosal injury due to aspirin 300 mg per day is to that with aspirin 2-4 g per day in similar studies? Furthermore, enteric coating reduced acute low-dose-aspirininduced gastric injury to placebo levels. Such protection by enteric coating is also seen at higher doses of aspirin. 7,8Thus, although such protection might not be afforded in chronic disease, we disagree with Baker and collegues’ assertion that enteric coating does not protect the stomach against aspirin injury. Indeed, we believe that the evidence shows that low-dose aspirin causes substantial gastric damage and that the best strategy to prevent this would be the use of enteric-coated preparations.
similar
Department of Therapeutics, University Hospital, Queen’s Medical Centre, Nottingham NG7 2UH, UK 1.
F. E. MURRAY A. T. COLE N. HUDSON C. J. HAWKEY
Steering Committee of the Physicians’ Health Study Research Group. Final report on the aspirin component of the ongoing physicians’ health study. N Engl J Med 1989;
321: 131-35. 2. Peto R, Gray R, Collins R. Randomised trial of prophylactic daily aspirin in British male doctors. Br Med J 1988; 296: 313-16. 3. UK-TIA Study Group. United Kingdom transient ischaemic attack (UK-TIA) aspirin trial: interim results. Br Med J 1988, 296: 316-20 4 The Dutch TIA Trial Study Group. A comparison of two doses of aspirin (30 mg vs 282 mg a day) in patients after a transient ischemic attack or minor ischemic stroke. N Engl J Med 1991; 325: 1261-66. 5. The SALT Collaborative Group. Swedish aspirin low-dose (SALT) of 75 mg aspirin as secondary prophylaxis after cerebrovascular ischemic events Lancet 1991; 338: 1345-49. 6. Hudson N, Cole AT, Murray FE, et al. Low dose aspirin: an unrecognised cause of gastric mucosal damage Gut 1991; 332: A1245. 7. Hawthorne AB, Hurst SM, Mahida YR, Cole AT, Hawkey CJ. Aspirin-induced gastric mucosal damage: prevention by enteric-coating of aspirin and relation to prostaglandin synthesis. Br J Clin Pharm 1992; 32: 77-83. 8. O’Laughlin JC, Hoftiezer JW, Ivey KJ. Effect of aspirin on the human stomach in normals, endoscopic comparison of damage produced one hour, 24 hours, and 2 weeks after administration Scand J Gastroenterol 1991; 16 (suppl 67): 211-14.
Subcutaneous ondansetron SIR,-Ondansetron has a place in the control of nausea and vomiting in patients on highly emetogenic chemotherapy. Dr Nicholson and colleagues (Feb 22, p 490) have used intravenous and oral ondansetron to alleviate nausea and vomiting associated with terminal disease, not chemotherapy, and in the same issue of The Lancet, Dr Rosenthal and co-workers (p 490) report the use of oral ondansetron in patients given radiotherapy to the whole abdomen. We describe the continuous subcutaneous administration of this drug to good effect in a patient with intractable nausea and vomiting unresponsive to other antiemetics. A 62-year-old man was referred with persistent nausea, vomiting, and hiccoughs due to a metastatic, poorly differentiated gastric adenocarcinoma. At gastrectomy 8 months earlier, hepatic and local lymph-node involvement was noted. At first his symptoms partly responded to subcutaneous cyclizine (in view of hepatic metastases) and hyoscine butylbromide (to reduce afferent loop motility) plus rectal domperidone. The number of vomits per 24 h fell from 16 to 4, accompanied by a reduction in nausea, and the patient was able to return home for short periods. On subsequent admissions, however, symptom control was not achieved with this regimen. A chemical cause for his vomiting having been excluded, a subcutaneous infusion of ondansetron was started at 1 mg/h. This reduced daily vomits to less than 3 and abolished the nausea and hiccoughs. There were no problems with the skin at the infusion
pH
3-5-6-5 3-7-5-5 3-0-3-8 3.2-4.7 3-0-50 3-0-5-0
Subcutaneous ondansetron, should its future cost allow, may be a useful addition to the palliative physician’s antiemetic armoury. We thank Mr P. V. Colthup, biochemical pharmacology department, Glaxo Group Research Ltd, for his assistance and for analysing plasma ondansetron concentrations.
PAULA M. MULVENNA CLAUD F. B. REGNARD
St Oswald’s Hospice, Gosforth NE3 1EE, UK
DB, Newlands ES, Rustin GJS, et al A phase I/II study of the 5-HT3 antagonist GR38032F in the antiemetic prophylaxis of patients receiving high dose cisplatin chemotherapy. Cancer Chemother Pharmacol 1990; 25: 291-94.
1. Smith
Transmission of HCV between spouses SIR,—The transmissibility of hepatitis C virus (HCV) between husband and wife is thought to be low.l-4 However, most of the evidence comes from serological tests for the clOO antibody. Tajima et al5 found a 50% risk of spouse transmission in Japanese couples when C gene-derived antibodies (anti-core) were measured. However, those couples were from an isolated town that was highly endemic for HCV infection and there was no evidence that infections had not been community acquired. In our study of transmission risk, 195 spouses of Japanese patients with HCV-related chronic liver disease were first screened for risk of HCV infection via routes other than contact with their viraemic wives or husbands: 19 had had blood transfusions or had premarital histories of jaundice or non-viral hepatitis. The remaining 176 spouses were tested for HCV-core antibody, HCV RNA, and clOO antibody. There were 82 cases of chronic hepatitis, 55 of liver cirrhosis, and 39 of hepatocellular carcinoma. They came from three prefectures in Japan (47 patients from Yamanashi, 37 from Fukushima, and 92 from Ibaragi). Anti-c100 was detected by an ELISA kit (Ortho); anti-core was measured by ELISA based on synthetic peptides.6,7 HCV genome RNA was determined only in spouses positive for clOO or core antibody by amplifying the 5’-untranslated region.8 We also determined the HCV genotype in some couples, with type-specific
primers.99 11spouses (6%) had clOO antibody (and 9 were also positive for anti-core), and of the clOO-seronegative spouses, 21 had core antibody (table). Of these 32, 14 (8% of all spouses) had serum HCV SEROLOGICAL STATUS OF SPOUSES
i
No
in
parentheses RNA positive
