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Biomedical subjects

J Haworth

Publications and source records attributed to J Haworth.

14 recordsLinked to original sources

A purchaser experience of managing new expensive drugs: interferon beta.

Interferon beta is a new and expensive drug for treating multiple sclerosis. One published trial has shown that it reduces the exacerbation rate in patients who have relapsing-remitting disease without important disability. This paper describes the development of a strategy for purchasing the drug in one region of England before its licensing. Purchasers felt unable to decline funding for this marginally effective drug and thereby undertake explicit rationing. To ensure prescribing was within the guidelines, a vast communication network had to be sustained with managers, general practitioners, neurologists, the Multiple Sclerosis Society, and professional advisers in all the purchasing authorities. The workload involved was considerable. The dilemma of rationing in a public service with a high political profile is demonstrated.

Attitude of Health Personnel

Asthma control and morbidity: a comparison of inhaler devices.

This study assessed the difference in efficacy and patient morbidity when asthma drug therapy was administered by either a dry powder device (DPD) or metered dose inhaler (MDI). It assessed 27 patients who had used an MDI for at least six months before transferring to a DPD because of inadequate inhaler technique. Documentary evidence was collected retrospectively from the medical records six months before and six months after the change and outcomes were measured by daily bronchodilator therapy, daily inhaled steroid therapy, frequency of night-time wakening due to asthma symptoms, and peak expiratory flow rates. Patient symptoms and asthma control were found to be improved by the correct delivery of medication via DPD compared with an MDI.

Asthma

The molecular basis for the two different clinical presentations of classical pyruvate carboxylase deficiency.

Eight cases of isolated human pyruvate carboxylase deficiency were examined from seven families. Although all patients presented with a chronic lacticacidemia, two particular patients presented with the added features of hyperammonemia, citrullinemia, and hyperlysinemia. When cultured skin fibroblasts from these patients were examined for their ability to synthesize [3H]biotin-containing proteins, it was found that the two patients who presented with hyperammonemia, citrullinemia, and hyperlysinemia did not synthesise a protein of the correct subunit molecular weight (Mr = 125 K daltons) corresponding to pyruvate carboxylase. In addition, when skin fibroblast proteins were labeled with [35S]methionine, cross-reacting material (CRM) corresponding to pyruvate carboxylase was immunoprecipitated by antipyruvate carboxylase antiserum in most patients, but again the two patients with the atypical presentation showed no CRM. We propose that the different clinical presentation of human pyruvate carboxylase deficiency is a manifestation of two different mutations in the pyruvate carboxylase gene, one that results in the synthesis of a relatively inactive pyruvate carboxylase protein CRM(+ve) and one that results in the lack of expression of the gene in the form of a recognizable protein CRM(-ve).

Biotin

Cultivation techniques for the erythrocytic stages of malaria parasites.

The study of the biochemistry, physiology, and immunology of plasmodia has been restricted by the difficulty of maintaining the parasites in isolation from the host. Some success has been achieved in cultivating them in vitro, using tissue cultures and chick embryo techniques to study exoerythrocytic states and the sporogonic cycle, but no completely successful method has been found for studying the asexual and sexual stages of plasmodia in circulating red blood cells. The relative slowness with which techniques for continuous in vitro cultivation have been developed is the result of inadequate knowledge of the biochemistry of the parasites and of the blood and its constituents. However, radioactive labelling techniques applied to P. knowlesi cultures are beginning to yield data of fundamental importance. Existing methods for the short-term in vitro cultivation of plasmodia are potentially very useful for analysing malarial antigens, for developing vaccines, and for screening and studying antimalarial drugs. Investigations of the physicochemical requirements for the in vitro preservation of red blood cells are required, and more emphasis should be given to the study of plasmodia with longer cycles. Differences between the metabolism of plasmodia in vivo and in vitro should be studied and the growth factors in normal plasma identified. Studies of the membrane of the parasites and of the red blood cells, of the immune response, and of extracellular methods for the cultivation of plasmodia should be extended.

Amino Acids