Clinical review of lansoprazole.

Lansoprazole is an inhibitor of gastric H+,K(+)-ATPase, commonly referred to as the 'proton pump'. The pharmacodynamic effect of proton pump inhibition is to reduce gastric acid secretion. Long experience with H2 antagonists and more recently proton pump inhibitors has demonstrated the value of reducing gastric acid secretion in conditions where acid plays a key role in the pathogenesis of gastrointestinal inflammation and ulceration. The pharmacokinetics, pharmacodynamics and clinical safety of lansoprazole are discussed elsewhere in this supplement, and so this review will focus upon the European and American experience of the efficacy of lansoprazole in the treatment of peptic ulceration and gastro-oesophageal reflux.

Mouse hemithoracic irradiation and its interaction with cytotoxic drugs.

Irradiation of the mouse right or left hemithorax at 14 or 18 Gy produced a dose-dependent rise in breathing rate 16 weeks after irradiation without significant mortality. The measurement of breathing rate changes following right hemithoracic irradiation combined with the maximally tolerated dose of cytotoxic drugs was assessed as a method for qualitatively detecting drug-irradiation interactions which either exacerbate pneumonitis or alter its time course. Cyclophosphamide at 100 mg/kg accentuated and accelerated the rise in breathing rate, culminating in early mortality. BCNU 30 mg/kg delayed the appearance of the radiation response. Busulphan 30 mg/kg appeared to be radioprotective, but this was shown to be due to the DMSO-containing vehicle. Doxorubicin 6 mg/kg had no effect when combined with right or left hemithoracic irradiation. Carboplatin 100 mg/kg, vindesine 4 mg/kg and vinblastine 4 mg/kg had no substantial effect upon the changes in breathing rate.

A semi-automated method for breathing rate measurement in the mouse.

A semi-automated system of breathing rate measurement for the assessment of lung damage in mice has been developed. Based on the plethysmographic method, a BBC B microcomputer plus Torch CPM examines four plethysmographs at any given time, looking for periods of quiet breathing and measuring the breathing rate during rest. This requires both machine code and Microsoft Basic programs, linked using Microsoft Link 80. The results correlated closely with results obtained using the well-validated measurement of chart recorder assessed breathing rate. Using the computer method, up to 40 animals could be examined per hour.

Inhaled thiol and phosphorothiol radioprotectors fail to protect the mouse lung.

Pretreatment with an inhaled aerosol of WR 2721, cysteamine or N-acetylcysteine failed to influence the development of radiation-induced lung damage at 14-16 weeks as assessed by a rise in breathing rate in the mouse. In contrast, intraperitoneal WR 2721 400 mg/kg and cysteamine 230 mg/kg were effective indicating that, unlike N-acetylcysteine, they are effective radioprotectors if correctly delivered.

Changing ethnic and social characteristics of patients admitted for self-poisoning in West London during 1971/2 and 1983/4.

The characteristics of adult patients admitted for self-poisoning to an inner London district general hospital were examined during 1971/72 and 1983/84. The incidence of self-poisoning halved over the 12 years, from 326 to 178 per 100,000. Although no West Indians were admitted in the first period, they comprised 7% of such admissions 12 years later. The West Indian population in the catchment area remained constant at around 6%. Amongst all patients admitted for self-poisoning, there was a fall in the number of patients diagnosed as depressed, having a personality disorder or admitting to prior psychiatric care, but an increase in alcoholism. Paracetamol became more common as a drug used in self-poisoning and barbiturates were taken less often. Only one patient died in the series. These results should stimulate more soundly based epidemiological studies on ethnic variation in self-poisoning, and on self-injury in inner-city areas.

The effect of low dose-rate and cyclophosphamide on the radiation tolerance of the mouse lung.

Mice were given cyclophosphamide 30 mg/kg intraperitoneally before thoracic irradiation at high dose-rate (HDR, 100 cGy/min) or low dose-rate (LDR, 5 cGy/min). The development of pneumonitis was monitored by regular measurement of breathing rate. Peak rises in breathing rate occurred around 4-9 weeks in those given cyclophosphamide before irradiation, and around 14-16 weeks in those given radiation alone, regardless of dose-rate. The dose reduction factor (DRF = LDR/HDR ratio) for LDR irradiation was congruent to 1.8 but LDR sparing was abolished (DRF congruent to 1.0) when cyclophosphamide was given before irradiation.

Detecting alcohol consumption as a cause of emergency general medical admissions.

In a general medical unit 27% of 104 admissions and 17% of bed occupancy were attributed to alcohol consumption, although only 10 of these 28 patients had classical alcohol-related conditions. Questioning on the amount of alcohol consumed was the most accurate method of screening for these patients. The brief MAST questionnaire, mean red cell volume, gamma-glutamyl transferase, aspartate transaminase and urate were all inadequate as screening tests. Only 13% of the admissions were defined as 'problem drinkers' on the brief MAST questionnaire, suggesting that harmful effects of alcohol are not confined to 'alcoholics'. Clinical suspicion and questions on the level of alcohol consumption are more efficient than questionnaire, biochemical or haematological screening tests in detecting alcohol-related medical problems.

Emesis due to cancer chemotherapy: results of a prospective, randomised, double-blind trial of varying doses of metoclopramide in the management of cis-platinum-induced vomiting.

A randomised, double-blind prospective trial was conducted to determine the relative anti-emetic efficacy of three dose levels of metoclopramide in cancer patients receiving combination chemotherapy including cis-platinum. With consecutive courses of chemotherapy, 60 patients received doses of either 3,5 or 10 mg/kg metoclopramide (50, 54 or 55 courses respectively) in a randomly assigned sequence. Major control of emesis (less than or equal to 2 vomits) was achieved in 38% of 159 patient treatments. There were no significant differences in either anti-emetic efficacy or the incidence of side-effects between the three doses used. It is concluded that while metoclopramide is an effective anti-emetic for patients receiving cisplatinum therapy, no advantage accrues to the use of doses in excess of 3 mg/kg (total dose).

Paraneoplastic hypercalcaemia in ovarian carcinoma.

Five patients were seen in whom a raised serum calcium concentration was associated with ovarian carcinoma (clear cell in two cases, cystadenocarcinoma in three). None showed evidence of metastases in bone. The hypercalcaemia occurred as a paraneoplastic phenomenon, but biochemical studies suggested the production of a parathyroid-hormone-like substance. One patient remained free of symptoms of her hypercalcaemia throughout. Paraneoplastic hypercalcaemia due to ovarian carcinoma may be more common than generally recognised and present as a life threatening condition requiring urgent treatment.

Topical silver sulphadiazine: side effects and urinary excretion.

Silver sulphadiazine has been used as a topical antimicrobial agent in a large group of children with burns and scalds. Four developed neutropenia and two an erythema multiforme rash which were thought to be due to sulphadiazine sensitivity. To assess the extent of sulphadiazine absorption in children, the urinary excretion was measured in a group of 8 patients with a mean area of injury of 13 per cent BSA. The mean urinary concentration of sulphadiazine was 31.8 mg/l.

Pseudoerythrocytosis in myeloma with associated peripheral neuropathy.

A number of unusual features have been described in patients who have peripheral neuropathy in association with plasma cell neoplasia. Amongst these features are raised haemoglobins and increased platelet counts. We have measured the red cell mass in one such patient and have shown that the raised haemoglobin was due to a pseudoerythrocytosis. Our patient is also of interest because of his youth being only 19 years old at presentation.