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Biomedical subjects

D A Winfield

Publications and source records attributed to D A Winfield.

At least 19 recordsLinked to original sources

Efficacy of urate oxidase (uricozyme) in tumour lysis induced urate nephropathy.

Urate oxidase (uricozyme) is an enzyme of non-human origin capable of oxidizing human uric acid to allantoin, a highly soluble product at renal tubule pH. We report its efficacy in three patients with acute urate nephropathy due to tumour lysis in chronic lymphatic leukaemia and high grade lymphoma. Two patients had an additional obstructive nephropathy due to ureteric urate crystals. An intravenous infusion (100 units/kg in 50 ml saline over 30 min) was given for between two and five consecutive days. All patients showed a rapid fall in serum urate levels with associated diuresis, correction of metabolic disturbance and full resolution of uraemia within a week. The treatment was well tolerated and caused a rapid resolution of clinical symptoms in all cases. We review the literature relating to the use of this agent both in the treatment of hyperuricaemic acute renal failure and gouty arthritis.

Aged

An outbreak of rubella in British troops in Bosnia.

An outbreak of rubella in April 1996 involved four male British soldiers deployed to Bosnia-Herzegovina. All were helicopter ground crew who were members of the same unit and who periodically travelled to and worked at forward air refuelling stations in Bosnia. There was a potential for spread of the infection to adjacent British units, to troops of other nations in the peacekeeping force, and also to the local civilian population. The British force included 620 female personnel, some of whom may have been non-immune to rubella. One pregnant British servicewoman was repatriated to UK for her own protection. There was a potential health risk, including the possibility of congenital rubella syndrome, in the non-immune wives and partners of deployed male personnel, as a result of contact during the mid-tour home leave of the husbands or partners. The outbreak was monitored through a medical surveillance system known as ARRC 97, and was contained by prompt and rigorous control measures. This outbreak shows the importance of effective surveillance and of good microbiology laboratory support during military operations. The role of immunization against rubella during future military deployments is discussed.

Adult

G-CSF after peripheral blood stem cell transplantation in lymphoma patients significantly accelerated neutrophil recovery and shortened time in hospital: results of a randomized BNLI trial.

We have undertaken a prospective randomized study in 90 patients with relapsed or resistant lymphomas to assess the value of G-CSF (lenograstim) in the acceleration of myeloid recovery after peripheral blood stem cell transplantation (PBSCT). A common regimen of cyclophosphamide 1.5 g/m2 on day 1 and lenograstim 263 microg s.c. on days 2-10 with two aphereses on days 10 and 11 was used for stem cell mobilization. 77% of patients achieved an adequate PBSC collection in two harvests (> 2 x 10(8) MNC/kg or > 2 x 10(6) CD34+ cells/kg). 65 patients went on to receive high-dose BEAM chemotherapy and engraftment data was available for 62. 34 patients had been randomized to receive lenograstim 263 microg/d s.c. and 28 to no growth factor. The median time to ANC > 0.5 x 10(9)/l was 9 d in the lenograstim arm versus 12.5 d in the no-lenograstim arm (P=0.0001). This was associated with a median duration of time in hospital post PBSCT of 13 d in the lenograstim arm versus 15.5 d in the no-lenograstim arm (P=0.0002). Median days to platelet independence, platelet transfusions, incidence of infection and red cell transfusion were the same in both arms. These data indicate that lenograstim significantly accelerated myeloid recovery after PBSCT and shortened the duration of hospital stay.

Adult

Angiotropic lymphoma: report of a case with histiocytic features.

Angiotropic lymphoma, also known as intravascular lymphomatosis, is characterised by widespread intravascular proliferation of malignant lymphoid cells, usually without evidence of focal disease. A case of a 52 year old man referred for investigation of a two year history of pyrexia of unknown origin, skin rash and multiple organ failure is described. Angiotropic lymphoma was seen in gastric, colonic and skin biopsy specimens, and review of an earlier skin biopsy specimen showed similar morphological features. In contrast to previous cases which showed B or T cell differentiation, immunohistochemical examination was positive for histiocyte markers. Molecular studies showed no evidence of immunoglobulin heavy chain gene or T cell receptor gene rearrangement. The patient responded to combination chemotherapy, comprising cyclophosphamide, doxorubicin, etoposide, and prednisolone. This case highlights the fact that advanced lymphoma may be present without evidence of focal disease and that the diagnosis may be missed easily both clinically and histologically.

Antineoplastic Agents

A study of primary health care at Divulje Barracks, Split on Operation Resolute (Bosnia).

A study of primary health care was undertaken at Divulje Barracks, Split, during Operation Resolute, 1996. A total of 1581 patients were seen during weeks 3 to 10 of the operation (day "13' to "70'). The number of consultations was greater for the first half of this period than for the second, and there were two early epidemics, one of respiratory disease and the other of enteric disease. Occupational and road traffic accident injuries were more common in the first 6 weeks and then declined with time.

Bosnia and Herzegovina

Dermatological conditions in winter in primary health care on Operation Resolute (Bosnia).

The distribution of dermatological conditions has been studied in a total of 1822 consultations with British troops in a primary health care setting on Operation Resolute (Bosnia) between 1 January and 4 March 1996. Approximately one in eight (12%) of the consultations were for skin conditions; eczema was the most common complaint, but, taken as a whole, infections due to virus (excluding warts), fungus and bacteria made up 30%. The overall distribution of diseases was similar to that seen in British general practice.

Adult

Mental health problems on Operation Resolute (Bosnia).

Mental health problems have been studied in a total of 2201 consultations with British troops in a primary health care practice on Operation Resolute (Bosnia) from 1 January to 31 March 1996. About one in 40 (2.5%) of the consultations were for mental health problems; Post Traumatic Stress Disorder (PTSD), depressive disorder, and grief reaction were the most common disorders, followed by acute adjustment reaction and panic disorder. Most cases pre-dated deployment. The number of cases repatriated to the UK was 17, about 10% of the total number of patients repatriated from theatre in this period.

Bosnia and Herzegovina

Analysis of the colonization of unirradiated and irradiated SCID mice by human lymphoma and non-malignant lymphoid cells.

We have evaluated the severe combined immunodeficient (SCID) mouse as an in-vivo model for the study of non-Hodgkin's lymphomas (NHL). Characterization of the immune system of the animals in our SCID mouse colony was carried out to assess the numbers of lymphoid cells present, to determine natural killer (NK) cell activity as a function of age and to examine the histology of the lymphoid organs. In this study four human NHL established cell lines (Daudi, Namalwa, U937, MC116), lymphoma cells from four fresh NHL biopsies and normal peripheral blood mononuclear cells (PBMC) and bone marrow cells were investigated, after intraperitoneal injection into the mice. The presence of the human NHL cells in the peritoneum and spleen was assessed by FACS analysis. The colonization potential was investigated in a range of tissues by polymerase chain reaction (PCR) amplification of human repetitive sequences. These studies revealed clear differences in the abilities of the NHL cell types to colonize the SCID mice. Namalwa, Daudi and U937 cells demonstrated the highest efficiency of colonization and readily formed tumours, whereas MC116, the NHL biopsy cell populations and the non-malignant lymphoid cells showed little ability to survive and colonize other tissues in the SCID mice. Whole body irradiation of the SCID mice appeared to improve the survival of human PBMC, NHL biopsy cells and MC116 cells in the peritoneum, but had little effect on their colonization potential. The significance of these studies is discussed.

Animals

Comparison of protein synthesis profiles in chronic lymphocytic leukaemia cells and B-lymphocytes from peripheral blood, cord blood and tonsil.

2D-gel electrophoresis was used to investigate protein synthesis in leukaemic cells from a series of 15 chronic lymphocytic leukaemia (CLL) patients, and in non-malignant B-cell populations from different sources. The protein synthesis profiles of CD5+ B-cells from umbilical cord blood and from tonsil were determined, and the levels of expression of their proteins were observed to be similar to the CLL cells. The CD5- cells from cord blood resembled peripheral blood B-lymphocytes, and the protein synthesis profile of CD5- cells from tonsils was very complex. One protein was also identified which consistently appeared to be synthesised at a low level in CD5+ B-cells from tonsil but which was always more prominent in CLL cells and other non-malignant B-lymphocytes. On the basis of these data it is possible that the closest non-malignant counterpart to CLL is the CD5+ B-lymphocyte from cord blood.

Antigens, CD

2D-gel analysis of protein synthesis profiles of different stages of chronic lymphocytic leukaemia.

Protein synthesis profiles of leukaemic cells from 15 chronic lymphocytic leukaemia (CLL) patients were analysed by 2D-electrophoresis of 35S-methionine labelled proteins. This series of CLL included patients with stage A (7), B (4) and C (4) disease. Although the protein synthesis profiles were similar in all cases, some consistent differences were noted between the different stages. The levels of synthesis of three proteins (approximately 35 kD size) were of particular interest. Two of these were always expressed in stage C CLL but either infrequently or not at all in stage A or B CLL. By contrast a third protein was expressed at a much reduced level in stage C compared to stages A or B. This type of analysis could prove invaluable for identifying proteins whose expression was intimately associated with the evolution of CLL.

Electrophoresis, Gel, Two-Dimensional

2D-gel analysis of proteins in chronic lymphocytic leukemia cells and normal B-lymphocytes.

Protein synthesis was analysed in leukaemic cells from 10 chronic lymphocytic leukaemia (CLL) patients by 2D-gel electrophoresis of 14C-labelled proteins. There appeared to be only minor differences between each of the CLL samples, but there was evidence that the level of expression of a few of the proteins might have correlated to the stage of the disease. Comparison of the CLL samples to populations of normal B-lymphocytes demonstrated marked differences in protein synthesis between the leukaemic and non-malignant cells. We subsequently used the fluorescence activated cell sorter (FACs) to separate CD5+ from CD5- B-lymphocytes, but observed that the protein synthesis exhibited by these two populations was essentially the same, and both were very different to that observed in CLL cells. The significance of these observations with respect to the origins of CLL is discussed.

Antigens, CD

Investigation of BCL-2 gene rearrangements in a United Kingdom series of low and high grade non-Hodgkin's lymphomas.

Rearrangements of the BCL-2 gene are thought to be the most frequent genetic changes that occur in non-Hodgkin's lymphomas (NHL), and are particularly associated with follicular low grade disease. Wide variations in the frequency of these rearrangements have, however, been reported in studies of NHL series from different parts of the world. We were therefore interested to determine the frequency of BCL-2 gene rearrangements in the different grades of NHL from a U.K. series. We have done this by using a combination of Southern blot hybridization and polymerase chain reaction (PCR) analysis. The frequencies of rearrangements in our series were 9/20 (45%) in low grade follicular NHL, 1/8 (12.5%) in low grade lymphocytic and 5/19 (26%) in high grade NHL. However, estimation of the high grade value was complicated by the fact that a number of the high grade samples in our series were from patients who had transformed from low grade follicular disease. If the patients were ranked on the basis of whether they had a history of low grade follicular disease then the frequency of BCL-2 rearrangement remained the same 13/29 (45%), but was only 1/10 (10%) in high grade NHL with no history of follicular disease. The former figure was intermediate between those reported for the USA and Japan series, but the latter high grade figure was the lowest reported from any series. The significance of BCL-2 rearrangements in the evolution of both low and high grade NHL is discussed.

Base Sequence