John D. Cash

Serum and urinary fibrin-fibrinogen degradation products in glomerulonephritis.

The serum and urine concentrations of fibrin/fibrinogen degradation products (F.D.P.) were estimated in 172 patients with glomerulonephritis. In each case the diagnosis was established on the basis of clinical, renal histological, and ultrastructural findings. Serum F.D.P. concentrations were often raised in all types of glomerulonephritis, though more consistently in active proliferative forms. The urinary concentration provided a reliable and sensitive index of activity, progression, and natural history in proliferative glomerulonephritis. In these forms the urinary F.D.P. content was thought to reflect predominantly lysis of intraglomerular fibrin deposits. In minimal lesion and membranous glomerulonephritis low but abnormal concentrations of urinary F.D.P. were consistently found. It is suggested that in these cases the products are derived from limited proteolysis of fibrinogen filtered through an abnormally permeable basement membrane. Daily measurement of urinary F.D.P. concentration is of potential value in the differential diagnosis of patients with glomerulonephritis and at the same time provides a sensitive assessment of the activity and natural history of proliferative disease.

Modification by drugs of urinary fibrin/fibrinogen degradation products in glomerulonephritis.

Treatment with indomethacin, aspirin, or prednisone has been shown to reduce urinary fibrin/fibrinogen degradation products (F.D.P.) in approximately two-thirds of patients with proliferative glomerulonephritis. This reduction which is dose-dependent for prednisone but not for indomethacin or aspirin in the range of doses used occurs within two to three days of beginning treatment and is thought to result from decreased intraglomerular fibrin deposition rather than alteration of glomerular permeability to F.D.P. In patients who responded in this manner treatment was associated with reductions in the degree of proteinuria and maintenance or improvement in renal function.

Urinary Excretion of Fibrinogen-related Materials, Complement, and Immunoglobulins in Proliferative Glomerulonephritis and after Renal Transplantation

Using a radial immunodiffusion technique we measured the urinary concentration of material related to complement (C3), IgM, and IgG along with fibrin-fibrinogen degradation products and heterophile (sheep) haemagglutinins in 15 patients with proliferative glomerulonephritis and in 10 patients after renal transplantation. There was a significant correlation between all variables measured, and serial studies showed that with the exception of IgG-related materials potentially useful information could be obtained on the detection of rejection and the response to treatment in both conditions. The significance of these observations is discussed.

Fresh frozen plasma: is it farewell?

Fresh frozen plasma (FFP) has been defined as the fluid portion of one unit of human whole blood that has been centrifuged, separated, and frozen solid to -18C (or colder) within 6 hours after collection. Single donor plasma units (SDFFP) may also substitute. Renewed interest in the production and clinical use of FFP began almost 15 years ago, largely because of concerns about the variable quality of the product, lack of precision in the indications for use and a remarkable increase in the demand [1,2]. A Consensus Meeting took place at the NIH to review data on clinical indications, associated hazards, evidence of efficacy, alternative therapies and directions for future research. The conclusions were subsequently published [3]. Those indications for which in 1984 FFP was recommended were: replacement of certain isolated coagulation factor deficiencies; reversal of warfarin; massive blood transfusion; management of immunodeficiencies and the treatment of thrombotic thrombocytopaenic purpura. The use of FFP as a volume expander, without a co-existing haemorrhagic diathesis, was not supported, as there were safer alternatives. In 1992 an update was published by the British Committee for Standards in Haematology [4], which took particular cognisance of the availability of new and virus inactivated blood products and studies published since the NIH consensus meeting. In the British Guideline the indications were listed as (1) definite and (2) those which were conditional on the presence of active bleeding. In addition, a list of clinical situations in which prescribing of FFP could not be justified was appended. The well known adverse effects of FFP include viral transmission, allergic complications and rare anaphylactic reactions. It has now become evident that contaminating red cells [5], white cells [6], and leucocyte antibodies [7] can also occur and recent animal studies have suggested a harmful effect when used in septic shock [8]. Notwithstanding these additional adverse effects the over-riding concern with the use of FFP is virus transmission. There was a view that the primary outcome of the NIH Consensus Meeting would be a fall in the use of FFP. This conclusion seemed most likely in US as there was evidence that almost 50% of the FFP transfused was as a volume expander [9]. Recent surveys have indicated that in the US the Consensus Meeting seems to have had little impact on the use of FFP [ lo]. There have been many exhortations on the abuse and appropriate use of FFP [11,12] and in some individual institutions when guidelines have been actively promulgated and subsequently audited a substantial fall in the use of FFP has been recorded [13,14]. Many believe that the demand for FFP is unlikely to change. It has therefore been concluded that it would be more appropriate to direct energies to developing a safer product. The safety parameter considered to be pre-eminent is a reduction in the opportunity for virus transmission. The options which have been directed towards this end are currently under intense scrutiny and include the exclusive use of the unpaid donor, of single donor plasma, holding regular units in quarantine until the subsequent donation is received and all laboratory tests shown to be negative and combining the single donor with the quarantine approach [15]. Finally there is a move to apply the technology of virus inactivation, developed for plasma fractionation, to FFP thus providing virus inactivated plasma (VIP). The options currently available for virus inactivation of plasma can be summarised as follows: Solvent-detergent treated plasma [16] * Pasteurised plasma [17] * Photochemically treated plasma [18] The solvent-detergent (1 o/o tri(n-butyl)phosphate(TnBP) and 1 % triton X-1 00) is incubated with pooled

Faulty blood bags. Reputation of English blood transfusion service has been unjustly damaged.

Reputation of English blood transfusion service has been unjustly damaged EDITOR,--I wish to comment on recent reports of faults in some of the blood bags used by the English National Blood Authority.1 Several of the points made have been misleading and may have given rise to inappropriate public and professional concern. Firstly, international and published experience confirms that minor defects in plastic blood bags occur infrequently but regularly and that virtually all such defects …

Sir John David Nunes NabarroEdoardo ParmaMary Veronica Porter (n£e Burdett-Smith)Anthony Watson PurdieRory SadlerNorah Patricia SherlockMichael Edward SkinnerMark SticklandJohn WallaceWilliam Derek WylieStuart Young

# Sir John David Nunes Nabarro {#article-title-2} ![][1] Former consultant physician Middlesex Hospital, 1954-81 ( b London 1915; q UCL 1938; MD, FRCS), d 28 April 1998. The son of a pathologist, he was an extremely good general physician combining clinical skills with a scientific approach. John quickly realised the possibilities for exploiting the development of radioimmunoassays for peptide hormones and techniques for measuring thyroid and steroid hormones. He trained a large number of endocrinologists, many of whom rose to positions of distinction in Britain and abroad. An incredible hard worker he set a pace that tested the juniors who were fortunate enough to work with him. He was pre-eminent in clinical endocrinology and made major contributions to the studies of the pituitary and the treatment of pituitary disease, to analysis of adrenal function and dysfunction, and to reproductive endocrinology. At the same time he made important contributions to the field of diabetes, particularly in the management of diabetic keto-acidosis and the use of oral hypoglycaemic agents and new insulins. When he retired he became director of the Institute of Clinical Sciences. John was chairman of the executive council of the British Diabetic Association—he persuaded the government to give free prescriptions for disposable syringes and blood glucose test strips—a senior vice president of the Royal College of Physicians, 1977-9, and chairman of the Joint Consultants Committee, 1979-82. This involved critical discussions with the Department of Health, and during his chairmanship important decisions were made about the training of junior doctors, not the least was persuading people that there had to be a closer balance between the numbers being trained and the opportunities at consultant level. One of his chief interests was philately, particularly of the Netherlands. He leaves a wife, Joan (also a doctor); two sons; and two daughters. # Edoardo Parma {#article-title-3} ![][2] General practitioner Milan ( b 1955; q Milan 1979), died from … [1]: /embed/graphic-1.gif [2]: /embed/graphic-2.gif

Haemophilia A and the blood transfusion service: a Scottish study.

The demand for blood products containing factor VIII for treating patients with haemophilia A in south-east Scotland was reviewed. From 1961 to 1975 the demand for fresh frozen plasma (FFP), cryoprecipitate (CP), and antihaemophilic factor (AHF) increased by seven and a half times, while total donations increased by only a third. Patients with severe haemophilia A treated at the regional haemophilia centre used about 85% of the factor VIII issued in 1971-4, most of which was used on demand. A patient with severe haemophilia A on unlimited ondemand home treatment would need about 500 units of factor VII/kg body weight/year, and a regional haemophilia centre, treating moderate and mild cases as well as severe ones, would use 15000 units/patient/year. Altogether about 50 million units of factor VIII will be needed each year in the UK. Although cryoprecipitate is much harder to store and administer than AHF, its yield from plasma may be far greater and its cost far smaller. Unless the blood transfusion services receive increased amounts of money and reappraise their functions and operation, it seems likely that they will have to rely increasingly on commercial (and costly) sources for the major plasma fractions.