A safe supply of blood and the knowledge, skill, and resources for the appropriate use of blood are essential for medical services. Many problems are faced in the development of transfusion services ...in low- or medium-income countries (LMICs). Unfortunately, in many countries, providing safe blood is made more difficult by a lack of blood donors and the high frequency of transfusion-transmissible infections. The problems are compounded by the frequent need for urgent life-saving transfusions. This article examines the problems in supply, safety, and use of blood and how they are being addressed in LMICs, predominantly focusing on sub-Saharan Africa.
Lymphoedema in Urological Cancer Okeke, A.A; Bates, D.O; Gillatt, D.A
European Urology,
2004, 2004-Jan, 2004-01-00, 20040101, Volume:
45, Issue:
1
Book Review, Journal Article
Peer reviewed
Objectives:
To review the evidence underlying the diagnosis, pathology and treatment of lymphoedema of the lower extremities and genitalia from or following the treatment for urological cancer, and ...to suggest possible underlying pathophysiological mechanisms that may explain its development.
Methods:
Reviews of the epidemiological, surgical, and scientific literature and personal experience of treatment of patients are used to build a picture of clinical setting and the physiological principles underlying lymphoedema of the leg.
Results:
Lymphoedema of the leg and genitals results in serious morbidity for the patient. The incidence is largely unknown, but varies according to the type and location of tumours and may be up to 50% in advanced stages of penile carcinoma, or following its treatment. Although the aetiology of the condition is either iatrogenic, or associated with malignancy, the underlying pathophysiology is not well understood.
Conclusions:
Recent studies in breast cancer related lymphoedema point to underlying vascular as well as lymphatic problems, but the parallels with lower limb lymphoedema are not known.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Vascular endothelial growth factor (VEGF) chronically increases microvascular permeability, compliance and vessel diameter.
To determine the signalling pathways by which VEGF exerts these effects, we ...investigated the role of Ca 2+ influx and mitogen-activated protein kinase (MAPK) phosphorylation on the increase in hydraulic conductivity ( L p ), diameter and compliance in mesenteric microvessels in the anaesthetised frog ( Rana species).
The VEGF-mediated chronically increased permeability was attenuated by co-perfusion of VEGF with 5 m m NiCl 2 , previously shown to inhibit Ca 2+ influx. MAPK phosphorylation inhibition by PD98059 did not affect the chronic increase in L p . To determine whether other agonists which increased Ca 2+ influx also chronically increased L p , the effect of ATP perfusion on chronic L p was measured. ATP perfusion also chronically increased L p . The chronic increase in L p was therefore dependent on an initial transient Ca 2+ influx, and not MAPK activation, and was not unique to VEGF stimulation.
Inhibition of Ca 2+ influx did not inhibit the increase in microvascular diameter or compliance brought about by VEGF. Both these increases were
inhibited by PD98059. The VEGF-mediated increase in compliance and diameter was therefore dependent on MAPK activation, not
on Ca 2+ influx.
The chronic increase in L p stimulated by VEGF perfusion 24 h previously was reduced when the vessel was perfused with 5 m m NiCl 2 . The sustained, high L p was therefore dependent on Ca 2+ influx.
The endothelial cell calcium concentration (Ca 2+ i ) of vessels previously perfused with VEGF or ATP, and with a chronically increased L p , was not significantly increased compared to Ca 2+ i of endothelial cells in vessels before agonist perfusion
These experiments show that VEGF acts through different pathways to stimulate increased permeability and compliance. The data
are consistent with the hypothesis that VEGF chronically increases L p through an acute stimulation of Ca 2+ influx, but increases compliance and diameter by acute stimulation of the MAPK signalling pathway. They also suggest that
the increase in L p is dependent on a sustained Ca 2+ influx, even though the endothelial Ca 2+ i is not raised.
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Functional status is associated with patient outcomes, but is rarely included in hospital readmission risk models. The objective of this study was to determine whether functional status is a better ...predictor of 30-day acute care readmission than traditionally investigated variables including demographics and comorbidities.
Retrospective database analysis between 2002 and 2011.
1158 US inpatient rehabilitation facilities.
4,199,002 inpatient rehabilitation facility admissions comprising patients from 16 impairment groups within the Uniform Data System for Medical Rehabilitation database.
Logistic regression models predicting 30-day readmission were developed based on age, gender, comorbidities (Elixhauser comorbidity index, Deyo-Charlson comorbidity index, and Medicare comorbidity tier system), and functional status Functional Independence Measure (FIM). We hypothesized that (1) function-based models would outperform demographic- and comorbidity-based models and (2) the addition of demographic and comorbidity data would not significantly enhance function-based models. For each impairment group, Function Only Models were compared against Demographic-Comorbidity Models and Function Plus Models (Function-Demographic-Comorbidity Models). The primary outcome was 30-day readmission, and the primary measure of model performance was the c-statistic.
All-cause 30-day readmission rate from inpatient rehabilitation facilities to acute care hospitals was 9.87%. C-statistics for the Function Only Models were 0.64 to 0.70. For all 16 impairment groups, the Function Only Model demonstrated better c-statistics than the Demographic-Comorbidity Models (c-statistic difference: 0.03-0.12). The best-performing Function Plus Models exhibited negligible improvements in model performance compared to Function Only Models, with c-statistic improvements of only 0.01 to 0.05.
Readmissions are currently used as a marker of hospital performance, with recent financial penalties to hospitals for excessive readmissions. Function-based readmission models outperform models based only on demographics and comorbidities. Readmission risk models would benefit from the inclusion of functional status as a primary predictor.
Aims Vascular endothelial growth factor-C (VEGF-C) has been shown to stimulate both angiogenesis and lymphangiogenesis in some but not all models where VEGF-C is over-expressed. Our aim was to ...investigate the interaction between lymphangiogenesis and angiogenesis in adult tissues regulated by VEGF-C and identify evidence of polarized growth of lymphatics driven by specialized cells at the tip of the growing sprout. Methods and results We used an adult model of lymphangiogenesis in the rat mesentery. The angiogenic effect of VEGF-C was markedly attenuated in the presence of a growing lymphatic network. Furthermore, we show that this growth of lymphatic vessels can occur both by recruitment of isolated lymphatic islands to a connected network and by filopodial sprouting. The latter is independent of polarized tip cell differentiation that can be generated all along lymphatic capillaries, independently of the proliferation status of the lymphatic endothelial cells. Conclusion These results both demonstrate a dependence of VEGF-C-mediated angiogenesis on lymphatic vascular networks and indicate that the mechanism of VEGF-C-mediated lymphangiogenesis is different from that of classical angiogenic mechanisms.
Vascular endothelial growth factor (VEGF) is anti-cytotoxic in podocytes. Moreover, it has been suggested that nephrin, a cell adhesion molecule of the podocyte slit diaphragm, can contribute to ...antiapoptotic mechanisms in these cells. We therefore investigated whether VEGF signals to reduce apoptosis and the role of nephrin in this survival mechanism. Flow cytometry showed that podocytes with nephrin mutations had a significantly greater proportion of apoptosis. Although VEGF reduced apoptosis in human conditionally immortalized podocytes wild-type (WT) by 18.1% of control (P < 0.001), it was unable to do so in nephrin-deficient human conditionally immortalized podocytes. Moreover, Western blotting and immunodetection with an anti-nephrin antibody showed that the phosphorylation of nephrin, compared with serum-starved WTs, was significantly increased (ratio of 3.36 +/- 1.2 to control, P < 0.05) by VEGF treatment and significantly reduced by treatment with a neutralizing VEGF monoclonal antibody (mAb) (ratio of 0.2 +/- 0.09 to control, P < 0.05). The AKT signaling pathway has been implicated in nephrin-mediated inhibition of apoptosis in transfected cells, but the role of this pathway has not previously been shown in podocytes. Surprisingly, exogenous VEGF decreased AKT/PKB phosphorylation in normal podocytes but increased it in nephrin-deficient podocytes. We suggest therefore that both exogenous and endogenous (podocyte derived) VEGF can stimulate the phosphorylation of nephrin and through this action may prevent podocyte apoptosis. However, the involvement of AKT in this survival response in normal human podocytes is not clear.
A new method for the determination of hydraulic conductivity in individually perfused microvessels in vivo is described. A
vessel is cannulated at both ends with glass micropipettes and the fluid ...filtration rate across the vessel wall measured from
the velocities of red cells when the pressure in the micropipettes is balanced. Hydraulic conductivity measured using this
double-cannulation method (2.6 (± 0.9) à 10 â7 cm s â1 cmH 2 O â1 ) was not significantly different from that measured using a previously described technique in the same vessel (2.4 (± 0.9)
à 10 â7 cm s â1 cmH 2 O â1 using the Landis-Michel method). Shear stress on the vessel wall was controlled by changing the difference between the inflow
and outflow pressures during periods of perfusion. The volume flow through the vessel, calculated from red cell velocity either
in the vessel or in the pipette, was linearly proportional to this pressure difference. Higher flow rates could only be calculated
from red cell velocities in the micropipette. There was no relationship between the imposed shear stress and intervening measurements
of hydraulic conductivity ( r = 0.029). This novel technique has advantages over the Landis-Michel method, which include the control of outflow resistance,
the measurement of shear stress under conditions of controlled pressure, the elimination of compression damage to the vessel
(since vessel occlusion is not necessary) and assessment of hydraulic conductivity over the same length of vessel throughout
the experiment. The measurement of solute concentrations by indwelling micropipette electrodes and the collection of perfusate
for analysis are other possibilities.
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