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Biomedical subjects

S Blake

Publications and source records attributed to S Blake.

At least 37 records · Page 2Linked to original sources

Timer error and beam quality variation during "ramp-up" of a superficial X-ray therapy unit.

Superficial and orthovoltage therapy machines generally exhibit a "ramp-up region" during which the dose rate increases from zero to the steady state output. This can produce a significant dose deficit, which can be made up by adding a correction to the treatment time. This correction, which can be determined from the intercept of the dose versus time plot, takes no account of either the true duration of the ramp-up region or the beam quality variation while it takes place. A new method for investigating the ramp-up region is proposed, and the results are presented for a 100 kVp beam. Measurements of beam quality in terms of half value layer (HVL) have been made as a function of time. A change in HVL from an average of 2.9 mm aluminium in the ramp-up region to 3.1 mm for the steady state region has been observed. A significant random variation in the time between initiation of the radiation and the beginning of the ramp-up region was also observed which was traced to a time varying signal in the control system.

Aluminum↗

State funding of comprehensive primary medical care service programs for medically underserved populations.

OBJECTIVES: This study examined the availability of state funding for comprehensive primary care programs and the need for primary care subsidies for medically underserved communities. METHODS: A brief questionnaire was used to ask health agencies in all 50 states whether their state funded a program that met our definition of comprehensive primary medical care practice programs. An in-depth written survey instrument was then administered to the states with programs. RESULTS: Almost half of all states provide some funds for the development and/or operation of comprehensive primary medical care practices. Expenditures in most states were found to be relatively modest in comparison with both federal funding and the total level of unmet need for primary care. States that subsidize primary care practices tend to follow the model established under the federal health centers program. CONCLUSIONS: The findings suggest the continued viability of the health center model of care, as well as the presence of some state support for such a program. However, in light of limited state resources for the development and operation of comprehensive practices, a continued and significant federal effort is imperative.

Comprehensive Health Care↗

The in vivo and in vitro characterisation of an engineered human antibody to E-selectin.

BACKGROUND: E-selectin is an endothelial cell specific adhesion molecule that is believed to play an important role in the early stages of leukocyte extravasation. OBJECTIVES: Here we describe the construction and evaluation of an engineered human monoclonal antibody that blocks E-selectin function. RESULTS: SPLAT-1 is an engineered human monoclonal antibody that has a very similar affinity for E-selectin as its murine parent antibody. In vitro SPLAT-1 blocks the binding of human leukocytes to E-selectin and does not mediate antibody-dependent cellular cytotoxicity (ADCC) or complement-mediated lysis of endothelial cells. In vivo, SPLAT-1 inhibits the recruitment of leukocytes to cytokine-inflamed human skin grafted on to SCID mice and has a long circulating half-life in primates. It does not appear to provoke an immune response in primates even on repeat administration. CONCLUSIONS: SPLAT-1 has the characteristics of a antibody suitable for human therapy studies.

Animals↗

Serial changes in cardiac output during normal pregnancy: a Doppler ultrasound study.

OBJECTIVES: To determine the direction and magnitude of change in cardiac output (CO) during pregnancy. STUDY DESIGN: We performed serial measurements of CO on five occasions from 24 weeks gestation to term and once during the puerperium in 26 normal pregnancies (156 measurements) using Doppler ultrasound measurement of flow velocity profiles and aortic root cross sectional area. RESULTS: CO increased to 7.0 l/min by 32 weeks gestation, 49% above baseline values. It fell to 5.7 l/min by term, 21% above baseline. The peak in CO corresponded with an increase in heart rate to 91 beats/min, 32% above baseline. Stroke volume peaked at 36 weeks gestation, by which time CO had already begun to decline. CONCLUSIONS: CO increased in a linear fashion until 32 weeks gestation and then declined to term, but to a value still greater than the postpartum baseline. These findings have obvious management implications for patients with serious heart disease complicating pregnancy.

Blood Pressure↗

Comparison of different procedures for serotyping aquatic birnavirus.

The current classification of aquatic birnaviruses is based on seroneutralization assays with polyclonal antibodies. In this study a comparison of several procedures used for serotyping aquatic birnaviruses was made with 10 virus strains (4 reference strains from salmonids and 6 birnaviruses isolated from turbot [Scophthalmus maximus]). The relationships among the birnavirus strains were studied by seroneutralization assay with polyclonal antibodies and by immunodot assay with both polyclonal and monoclonal antibodies. The results were compared with a presumptive classification obtained from analysis of restriction enzyme patterns of cDNA products obtained by PCR amplification. No correlation was found among the results obtained by the different procedures. The seroneutralization and the immunodot assays with polyclonal antibodies were not useful in classifying these birnaviruses strains; however, patterns of reaction with monoclonal antibodies emphasized the individuality of the strains, particularly in the case of two strains (231 and 460) whose patterns did not correspond to established serotypes. The application of PCR and restriction enzyme analysis is a promising system for approaching the classification of this viral group on the basis of genomic differences and similarities. The variable results obtained in this comparison lead us to think that the current classification of aquatic birnavirus may not be the most accurate and there is a need for modification incorporating recent isolates, not only from salmonid species but also from marine fish.

Animals↗

Role of TNF alpha in the induction of antigen induced arthritis in the rabbit and the anti-arthritic effect of species specific TNF alpha neutralising monoclonal antibodies.

OBJECTIVE: To investigate the role of tumour necrosis factor alpha (TNF alpha) in the development of antigen induced arthritis (AIA) in rabbits. METHODS: Monoclonal antibodies to rabbit TNF alpha were developed in rats and were used to detect TNF alpha in synovial fluid by enzyme linked immunosorbent assay and to localise it in tissue sections of synovium and cartilage from rabbits up to 21 days after induction of AIA. An antibody which neutralised TNF alpha activity in vitro was injected into rabbits to block TNF alpha action in vivo in AIA. Joint swelling, leucocyte infiltration into synovium and proteoglycan loss from cartilage were measured and compared with a control group, which were injected with sterile saline. RESULTS: Monoclonal antibodies to purified rabbit TNF alpha were prepared in rats and two were selected which were able to neutralise rabbit TNF alpha in a cytotoxicity bioassay. TNF alpha was detected in significant concentrations (21.7 (SE 0.5) pg/ml) in the arthritic joint fluid of rabbits with AIA only at one day after induction and it was then also sparsely localised in cells of the synovium, but from day 3 onwards it was localised more strongly in the deep zone of articular cartilage. Injection of anti-TNF monoclonal antibody R6 over three days into rabbits with AIA reduced joint swelling and leucocyte infiltration into joint fluid and decreased the expression of CD11b and CD18 on cells in the joint fluid. However, there was no significant reduction in the loss of proteoglycan from articular cartilage, although the joint fluid at three days contained a lower glycosaminoglycan content. The antibody R6 gave most effect at a dose of 0.6 mg/kg and there was no increase in its effectiveness at a fivefold greater dose (3.0 mg/kg). Treatment over 10 days gave a more complete suppression of joint swelling, but did not result in any less proteoglycan loss from cartilage. Treatment for five days with a 16 day follow up gave a significant reduction in swelling for several days beyond the treatment, but the swelling then slowly returned, until by day 21 there was no significant difference in joint swelling and there was also no recovery of cartilage proteoglycan content. A rabbit anti-rat immunoglobulin response was detected at 21 days, which may have limited the long term effectiveness of the antibody. CONCLUSIONS: In AIA in rabbits, TNF alpha was only detected in synovial fluid at one day after induction and there was only limited cellular localisation of TNF alpha in synovium and cartilage from three days. However, neutralising TNF alpha with a monoclonal antibody was effective in suppressing inflammatory changes in the joint during the acute onset of AIA, but it had little effect on the loss of proteoglycan from cartilage. The results suggest that blocking inflammation and synovitis with anti-TNF alpha may be more easily achieved than preventing damage to articular cartilage.

Animals↗

Antifibrotic action of interleukin-1 receptor antagonist in lapine monoarticular arthritis.

OBJECTIVE: To determine if the administration of interleukin-1 receptor antagonist (IL-1ra) to animals with established antigen induced arthritis had any beneficial effects on the synovitis and cartilage destruction. METHODS: Antigen induced arthritis was induced in New Zealand White rabbits, and after two weeks IL-1ra was administered every six hours over a 72 hour period. Animals were then killed and joint tissues examined for the degree of synovitis, synovial fibrosis, and cartilage damage. RESULTS: The response of the arthritis to the treatment was minor in terms of joint swelling, leucocyte accumulation, or cartilage proteoglycan loss. However, the synovial fibrosis was not only halted by administration of IL-1ra, but reversed. The inflamed synovial linings of IL-1ra treated animals showed a significant loss of synovial collagen content and a reappearance of the synovial fat spaces which are prominent in the normal synovial lining. CONCLUSION: This study shows that IL-1ra has potent antifibrotic activity and suggests the use of this agent for the reversal of the fibroproliferative process which is so important in the pathology of rheumatoid arthritis.

Animals↗

Application of 3 techniques for diagnosing birnavirus infection in turbot.

Three procedures for avoiding viral amplification by cell culture were evaluated for the diagnosis of birnavirus infections of turbot (Scophthalmus maximus) tissues. Immunodot assay using monoclonal and polyclonal antibodies was not satisfactory as a detection system because of false positive reactions. Although immunofluorescent assay of liver and kidney smears was an adequate method for a rapid diagnosis of the infection, blood smears from infected fish did not show higher levels of fluorescence than those from uninfected fish. However, the detection of birnavirus by polymerase chain reaction (PCR) amplification directly in fish tissues was successful and seems to be a promising system for the diagnosis of fish birnavirus.

Animals↗

Therapeutic potential of cytokine manipulation.

Interleukin 1 is just one of a large, growing, collection of potent cytokines that are produced by a variety of cells and have a myriad of overlapping activities. Many of these cytokines have important pathophysiological actions in diseases ranging from rheumatoid arthritis to AIDS. Selective inhibition of the synthesis or of the action of specific cytokines may have therapeutic benefit. In this review, Brian Henderson and Simon Blake discuss the ways in which cytokine function could be manipulated pharmacologically for therapeutic benefit.

Animals↗

The prevention of the maternal manifestations of pre-eclampsia by intensive antihypertensive treatment.

The purpose of the study was to determine if reduction of pregnancy hypertension to normal prevented the clinical maternal manifestations of pre-eclampsia. Thirty-six women with hypertension, but without proteinuria, were allotted at random to a test group of 17 who received intensive treatment, and a control group of 19 who were managed according to routine methods by hospital staff unconnected with the study. The development of proteinuria was chosen as an indicator of pre-eclampsia. Proteinuria developed significantly more often in the control group (in six of the 19 women) than in the test group (in one of the 17 women).

Adult↗

Apex beat.

Explore the source record for details and available documents.

Heart Ventricles↗

Dietary protein intake modulates glomerular eicosanoid production in the rat.

The quantity of protein in the diet modulates glomerular function. To study the effect of dietary protein intake on glomerular eicosanoid production, rats were randomized to either a high- (40%) or low- (8.5%) protein isocaloric diet. Ten to fourteen days later glomeruli were isolated and incubated in the absence (basal) and presence (stimulated conditions) of arachidonic acid, and production rates of prostaglandin (PG) E2, PGF2 alpha, and thromboxane B2 (TxB2) were determined by direct radioimmunoassay. Under basal conditions, glomerular production of all three eicosanoids was significantly greater in rats ingesting the high-protein diet. Glomerular production of PGE2 and TxB2 was also greater in animals fed the high-protein diet in the presence of arachidonic acid, suggesting that glomerular cyclooxygenase activity was augmented. In contrast, ingestion of a high-protein diet was not associated with a significant increase in eicosanoid production by renal papillae or in TxB2 release by clotting blood. To investigate the potential role of the renin-angiotensin system in the dietary protein-induced modulation of glomerular eicosanoid production, rats ingesting a high- or low-protein diet were randomized to treatment with an angiotensin-converting enzyme inhibitor or no therapy. Enalapril attenuated the dietary protein-induced augmentation in glomerular eicosanoid production. This effect occurred only when administered in vivo, since the active metabolite enalapril did not alter PGE2 production by isolated glomeruli when added in vitro. Dietary protein intake also modulated glomerular eicosanoid production in three models of experimental renal disease in the rat (streptozotocin-induced diabetes mellitus, Heymann nephritis, and partial renal ablation).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗