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Eating fish at least twice a week was associated with reduced disease activity in patients with rheumatoid arthritis (RA) in a study that found higher levels of joint swelling and tenderness in patients who ate fish less than once a month.1 Previous research has suggested that fish oil supplements containing high doses of omega 3 fatty acids can improve symptoms in patients with RA, but the effect of eating fish was not clear. Researchers carried out a cross sectional analysis …

Western medicine is increasingly interested in the problem of euthanasia. There are two main reasons for this. One is related to the fact that modern medicine has prolonged not only our lives but also our period of dying. Modern medicine supports hastening death through withholding life supporting treatment or giving high doses of pain relief to those who are dying. Is this morally different from euthanasia? The second reason is the increased emphasis on respect for the patient's autonomy. Doctors have to abide by all sorts of requests from their patients. It is only natural, therefore, to wonder whether we have good reasons to decline a patient's request for euthanasia. Public support for a system of euthanasia is high in Western countries. In surveys I conducted, as many as 63% of Norwegians, 79% of Swedes, and 68% of Germans thought that if a patient has an incurable disease and doesn't want to go on living, he or she should be allowed to receive a lethal injection (unpublished data). And yet, most doctors and politicians in most Western countries are strongly opposed to legalised euthanasia. Is there any plausible moral rationale behind their opposition?

Modern chemotherapy regimens for childhood cancers have a greater effect on the future fertility of boys than on that of girls, a study published in the Lancet Oncology has found.1 Most women who have survived childhood cancer have a good chance of conceiving, particularly if they try for a child when they are young, the results showed. In contrast, male survivors of childhood cancer are significantly less likely to father children, especially if they were treated with chemotherapy regimens containing high doses of commonly used alkylating drugs (cyclophosphamide, ifosfamide, procarbazine) and cisplatin. US researchers followed up 10 938 male and female cancer survivors who had been treated with 14 commonly used chemotherapy drugs at 27 institutions across the United States and Canada from …

Several dogs died in preclinical studies of the experimental drug that killed a human volunteer in a French trial, the French medical safety agency ANSM has confirmed. But the expert committee the agency established to review the trial’s conduct concluded that these deaths were to be expected in animal testing designed to establish a safe dose for human administration. The protocol for the first in human trial recorded that this “no observed adverse effect level” was determined for mice, rats, dogs, and monkeys. As part of these studies, ANSM said, “very high doses are administered to determine the maximum tolerated doses, which can …

The symptoms of many asthmatic patients are poorly controlled, and there are several reasons why this may be so. Doctors fail to find out about symptoms that asthmatic patients are experiencing. Doctors wrongly assume that regular use of bronchodilators in small doses is satisfactory treatment for asthma and that taking high doses of bronchodilator in an asthma attack may be dangerous. Doctors think that inhaled steroids may be dangerous and are reluctant to use them in effective doses. Doctors do not check that patients can use their inhalers properly and do not make enough use of large volume spacers, the best available method for giving inhaled asthma treatment. Doctors undermine patients' confidence in advice on treatment by failing to ensure that consistent advice is given and often make the management of asthma more troublesome for the patient than the symptoms of asthma.

Researchers have called for a large trial of low dose fish oils in people with drug resistant epilepsy, after finding that seizures fell by a third among participants in a small study. However, high doses were no better than placebo, the study found. Experimental research has shown that omega 3 fatty acids can cross the blood-brain barrier and reduce the excitability of brain cells that trigger seizures. But previous research looking at the effect of high dose fish oil on seizure frequency in people with drug …

High doses of the cholesterol lowering drug simvastatin over two years led to reduced brain shrinkage in people with secondary progressive multiple sclerosis when compared with placebo, a study has found, and the researchers have called for trials to investigate the drug’s effect on disability. Ten years ago clinical studies of 80 mg simvastatin in people with early multiple sclerosis showed significant reductions in brain lesions, but more recent studies of simvastatin and atorvastatin have produced mixed results. To investigate the potential of simvastatin in treating multiple sclerosis, researchers from University College London Hospitals and University College London randomly assigned …

Mrs Patell is a 64 year old woman with osteoarthritis of the right knee. A year ago, her general practitioner had recommended up to 4000 mg/day of paracetamol (acetominophen) for pain localised at the medial compartment of the knee. Mrs Patell had been taking the paracetamol but had forgotten that her general practitioner had mentioned that it should not be taken with alcohol. She has recently seen a newspaper article warning people about the risks of chronic use of analgesics. The article warns against liver damage when taking high doses of paracetamol in association with alcohol. After reading the newspaper article she became worried, because she enjoys a cocktail before dinner and shares a bottle of wine while eating with her husband. She knew she needed to take something; her pain was intolerable with lower doses and the pain also limits her abilities to help her husband with routine tasks around the house. This case is fictional but was developed from several real cases. …

We report two cases of cerebellar syndrome after treatment with deferiprone, a metal chelator used to treat iron overload in thalassaemia major. Case 1 —A 9 year old boy was treated for two years with 119 mg/kg/day deferiprone, but this dose was not sufficiently effective (increased ferritin and hepatic cytolysis were noted) and was increased to 238 mg/kg/day. Sixteen months later, the patient developed cerebellar syndrome (dizziness, axial hypotonia, nystagmus, diplopia) and obsessive compulsive disorder. Magnetic resonance imaging, electroencephalogram, and …

Papers p 28 Clinical review p 39 Although frank rickets is now uncommon, a steady (some think increasing) trickle of new cases remains, and many local studies have shown high prevalences of suboptimal plasma vitamin 25-OH cholecalciferol (

The recent editorial by Landis et al has added confusion rather than clarity to the issue of osteonecrosis of the jaw (ONJ) in association with the use of bisphosphonates.1 They do not distinguish between the use of very high doses of intravenous bisphosphonates (monthly pamidronate or zoledronate) to treat patients with malignancy, and the use of much lower doses of bisphosphonates (approximately 1/12 of the oncology dose) in the treatment of Paget's disease or osteoporosis. These two different uses of bisphosphonates have been associated with different risks …

Last week (5 June, p 1362) we presented the case of a 64 year old woman who was concerned about taking paracetamol (acetaminophen) after reading that it could cause liver damage when taken with alcohol at the high doses she required to control her knee pain. Her general practitioner had discussed with her the benefits and harms of paracetamol versus non-steroidal anti-inflammatory drugs, but she felt she needed more information and time before making a decision. Her general practitioner gave her a patient education decision aid package about paracetamol and non-steroidal anti-inflammatories for osteoarthritis.1 He told her that this material describes the best evidence available today about the benefits and harms of both drugs and would help …

EDITOR,--Johanna Adami and colleagues present evidence of an association between lymphoma and skin cancer, interpreting their findings as evidence of the role of immunosuppression induced by ultraviolet light in the pathogenesis of non-Hodgkin's lymphoma and leukaemia.1 There are, however, several reasons for believing that this conclusion may not be valid. According to the authors' line of reasoning, the incidence of lymphoma in countries where people are exposed to high doses of ultraviolet radiation should …

EDITOR,—Michael Farrell and colleagues note that for successful maintenance treatment of people dependent on opiates high doses of methadone are needed, and they recommend a dose of 70-120 mg a day.1 High doses are essential for people with chronic dependence, particularly long term injecting misusers, who may use more than one drug, but it is doubtful whether extended treatment with high doses is suitable for people who smoke heroin and who meet the criteria for substitute prescribing. When heroin is smoked or inhaled (rather than injected) the equivalent …

EDITOR—In their review of acupuncture, Vickers and Zollman1 state that systemic infection seems to be uncommon. When it occurs, however, it can be devastating, and the single reported fatality from acupuncture last year was due to streptococcal toxic shock-like syndrome.2 A 41 year old man who received acupuncture for shoulder pain collapsed three days later with rapidly spreading erythematous and necrotic change in the skin of the shoulder. Despite immediate extensive debridement and high doses of …

Editor—I was heartened to read Compston’s editorial calling for action on vitamin D deficiency.1 Another point should be made to encourage a more active role by the health service. The British National Formulary does not include a tablet containing vitamin D alone in reasonable dose. Prescribers can give a calcium and vitamin D mixture, which may be unpalatable and therefore impair compliance. Alternatively, a vitamin capsule can be prescribed containing many other vitamins. If a dose greater than minimal daily requirements is needed higher doses of unnecessary vitamins must also be given. Surely it should be easy to prescribe 500-1000 units of vitamin D daily without any other addition?

Inhaling steroids carries similar risks for developing glaucoma as taking them orally, Canadian researchers have established. They have shown that people with asthma who take high doses of inhaled steroids for more than three months are 44% more likely to develop glaucoma than non-users. Investigators from the Royal Victoria Hospital in Montreal, Canada, studied the relation between the use of inhaled and nasal steroids in 48 118 patients in the Quebec universal health insurance programme for elderly people. They found …

Does not reduce the rate of caesarean section In the late 1960s, faced with rising numbers of hospital deliveries and staff shortages, obstetricians in Dublin introduced a package of care for first labours that they called active management.1 This included special classes preparing women for labour, strict criteria for determining onset of labour, psychological support, and regular supervision of the delivery area by senior staff. None of these measures was controversial, but the package also included some revolutionary changes: routine amniotomy, early recourse to high doses of oxytocin under supervision of a midwife to accelerate slow labours, and an undertaking that labour would never last more than 12 hours. Previously, amniotomy and oxytocin had been used only selectively by senior medical staff, and it had been assumed that limiting the duration of labour would result in more caesarean deliveries. The Irish obstetricians thought otherwise, and in a series of influential reports claimed …

EDITOR,—Alice McGrath and Graham Jackson's survey of neuroleptic prescribing to residents of nursing homes in Glasgow1 has been given extensive coverage by the BBC. It was reported that the survey showed an alarmingly high level of neuroleptic prescribing, that 88% of patients received them inappropriately, and that significant numbers of residents were receiving high doses. These headlines were repeated regularly through 8 March on Radios 4 and 5. On reading McGrath and …

EDITOR,—In 1990, Gardner et al reported that relatively high doses of ionising radiation measured by film badges worn by men while employed at the Sellafield nuclear installation before the conception of their children were statistically associated with the incidence of leukaemia among these children.1 The authors suggested that this association was …

Clonidine failed to reduce the blood pressures of two patients with essential hypertension. On was given 5-4 mg/day and the other 6 mg/day, and their respective peak plasma clonidine concentrations were 26-2 ng/ml and 14-4 ng/ml. Several months after the end of clonidine treatment a single oral dose of 0-3 mg of clonidine produced maximum falls in blood pressure of 30/22 mm Hg and 88/41 mm Hg with peak plasma clonidine concentrations of 1-4 ng/ml and 0-9 ng/ml. Resistance to the hypotensive effect of high doses of clonidine may be due to stimulation of peripheral alpha-adrenoceptors causing vasoconstriction, which maintains a raised blood pressure.

Experience in treating 81 patients with severe bronchial infection with Pseudomonas aeruginosa is described. For those who were desperately ill high doses of intravenous carbenicillin (18g. or more daily) were successful, even when initial carbenicillin resistance was present. For those who were less desperately ill lower doses of carbenicillin together with high doses of gentamicin (given both intramuscularly and by aerosol) comprised the treatment of choice. Gentamicin alone or colistin gave little or no benefit and cannot be recommended.