Blood Substitutes: Has the Right Solution Been Found?

The Lancet ◽  
1986 ◽  
Vol 327 (8483) ◽  
pp. 717-718
Keyword(s):  
1983 ◽  
Vol 245 (3) ◽  
pp. H519-H523 ◽  
Author(s):  
T. H. Goodin ◽  
W. P. Clarke ◽  
K. Taylor ◽  
R. Eccles ◽  
R. P. Geyer ◽  
...  

Physiological evaluation of new and potential blood replacement agents has not kept pace with the development of such agents. Current procedures involve partial or total blood replacement in the anesthetized animal. This introduces the variable of anesthesia and eliminates the ability to observe behavior changes during blood replacement. Clinically, many patients receive blood or will receive artificial agents while sedated or under anesthesia, whereas others will be conscious. It is essential that evaluative studies be performed on the awake animal using procedures that are nontraumatic and nonrestrictive. A technique for isovolumic exchange perfusion utilizing an indwelling, heparin-coated, double-lumen catheter in the right atrium of a conscious rat is described. This animal model system permits continuous pre- and postperfusion monitoring. Nearly total blood replacement with perfluorochemical blood substitutes causes no discerniable discomfort or adverse reactions in the animal. Such animals thrive and replace missing hematologic components in 1-3 wk. The technique described can, with minimal modification, be used for isovolumic exchange perfusion of larger animals.


Author(s):  
David Metcalfe ◽  
Harveer Dev

As a junior doctor, you are constantly pulled in different directions by multiple competing interests. These include those of your immediate bosses (possibly multiple consultants, a registrar, and an SHO), Educational Supervisors (Clinical Supervisor, Foundation Programme Director), fellow FY1 doctors, other healthcare professionals (nurses, physiotherapists), ancillary services (laboratory, radiology), patients’ relatives, representatives of the Trust (infection control, human resources, information technology), and many others. In amongst all of these is a patient, if not many, for whom all of these individuals are also working. It will not come as a surprise that Good Medical Practice (2013) states early on that you must ‘make the care of your patient your first concern’ and ‘treat patients as individuals and respect their dignity’. In addition, Good Medical Practice requires that you: ● listen to, and respond to, their concerns and preferences ● give patients the information they want or need in a way they can understand ● respect patients’ right to reach decisions with you about their treatment and care ● support patients in caring for themselves to improve and maintain their health. One challenge is when patients reach decisions that are contrary to the best available medical advice. The archetypal case in point is that of a Jehovah’s Witness at risk of life- threatening haemorrhage but refusing a blood transfusion. In such cases, remember that: ● you should never assume what someone’s beliefs are just because they come bearing a particular religious label. It is always right to ask the patient what they believe and what they will accept under different circumstances. For example, some Jehovah’s Witnesses will accept cell salvage and some blood substitutes ● seek advice early, particularly if the stakes are high (e.g. active bleeding). Your own seniors (SpR, consultant, etc.) and the on- call haematology team are good places to start. They may direct you to other resources that you might contact (with the patient’s consent) such as the Jehovah’s Witnesses’ Hospital Liaison Committee ● document all conversations (with the patient and colleagues) carefully ● ultimately, an adult patient with capacity has the right to refuse treatments— however much you disagree and even if this ultimately results in their death.


2007 ◽  
Vol 405 (3) ◽  
pp. 503-511 ◽  
Author(s):  
Seetharama A. Acharya ◽  
Vivek N. Acharya ◽  
Nirmala Devi Kanika ◽  
Amy G. Tsai ◽  
Marcos Intaglietta ◽  
...  

TetraPEGylated canine Hb, [SP (succinimidophenyl)-PEG5K]4-canine-Hb, with PEGylation at its four reactive cysteine residues (α111 and β93) has been prepared and characterized. The hydrodynamic volume and the molecular radius of (SP-PEG5K)4-canine-Hb are intermediate to those of di- and hexaPEGylated human Hb as expected. However, the COP (colloidal osmotic pressure) of tetraPEGylated canine Hb is closer to that of hexaPEGylated human Hb than to that of diPEGylated human Hb. The O2 affinity of tetraPEGylated canine Hb is higher than that of canine Hb and comparable with that of hexaPEGylated Hb. The O2 affinity of tetraPEGylated canine Hb is not responsive to the presence of DPG (diphosphoglycerate) or chloride, but it retains almost full response to L-35, an allosteric effector that interacts at the αα-end of the central cavity. The tetraPEGylated canine Hb is vasoinactive in hamster in 10% top load infusion studies. It is also essentially non-hypertensive in an extreme exchange haemodilution protocol in hamster just as di- and hexaPEGylated human Hb. The O2 delivery by tetraPEGylated canine Hb is comparable with that of hexaPEGylated Hb but not as efficient as diPEGylated Hb. These results demonstrate that PEGylation-induced solution properties of PEG [poly(ethylene glycol)]–Hb conjugates are dictated by the level and chemistry of PEGylation and the interplay of these plays a critical role in tissue oxygenation. The studies imply the need to establish the right level (and/or pattern) of PEGylation and O2 affinity of Hb–PEG adducts in designing O2-carrying plasma volume expanders, and this remains the primary challenge in the design of PEGylated Hb as blood substitutes.


Author(s):  
J. Anthony VanDuzer

SummaryRecently, there has been a proliferation of international agreements imposing minimum standards on states in respect of their treatment of foreign investors and allowing investors to initiate dispute settlement proceedings where a state violates these standards. Of greatest significance to Canada is Chapter 11 of the North American Free Trade Agreement, which provides both standards for state behaviour and the right to initiate binding arbitration. Since 1996, four cases have been brought under Chapter 11. This note describes the Chapter 11 process and suggests some of the issues that may arise as it is increasingly resorted to by investors.


2019 ◽  
Vol 42 ◽  
Author(s):  
Guido Gainotti

Abstract The target article carefully describes the memory system, centered on the temporal lobe that builds specific memory traces. It does not, however, mention the laterality effects that exist within this system. This commentary briefly surveys evidence showing that clear asymmetries exist within the temporal lobe structures subserving the core system and that the right temporal structures mainly underpin face familiarity feelings.


Author(s):  
J. Taft∅

It is well known that for reflections corresponding to large interplanar spacings (i.e., sin θ/λ small), the electron scattering amplitude, f, is sensitive to the ionicity and to the charge distribution around the atoms. We have used this in order to obtain information about the charge distribution in FeTi, which is a candidate for storage of hydrogen. Our goal is to study the changes in electron distribution in the presence of hydrogen, and also the ionicity of hydrogen in metals, but so far our study has been limited to pure FeTi. FeTi has the CsCl structure and thus Fe and Ti scatter with a phase difference of π into the 100-ref lections. Because Fe (Z = 26) is higher in the periodic system than Ti (Z = 22), an immediate “guess” would be that Fe has a larger scattering amplitude than Ti. However, relativistic Hartree-Fock calculations show that the opposite is the case for the 100-reflection. An explanation for this may be sought in the stronger localization of the d-electrons of the first row transition elements when moving to the right in the periodic table. The tabulated difference between fTi (100) and ffe (100) is small, however, and based on the values of the scattering amplitude for isolated atoms, the kinematical intensity of the 100-reflection is only 5.10-4 of the intensity of the 200-reflection.


Author(s):  
Russell L. Steere ◽  
Michael Moseley

A redesigned specimen holder and cap have made possible the freeze-etching of both fracture surfaces of a frozen fractured specimen. In principal, the procedure involves freezing a specimen between two specimen holders (as shown in A, Fig. 1, and the left side of Fig. 2). The aluminum specimen holders and brass cap are constructed so that the upper specimen holder can be forced loose, turned over, and pressed down firmly against the specimen stage to a position represented by B, Fig. 1, and the right side of Fig. 2.


Author(s):  
K.S. McCarty ◽  
N.R. Wallace ◽  
W. Litaker ◽  
S. Wells ◽  
G. Eisenbarth

The production of adrenocorticotropic hormone by non-pituitary carcinomas has been documented in several tumors, most frequently small cell carcinoma of the lung, islet cell carcinomas of the pancreas, thymomas and carcinoids. Electron microscopy of these tumors reveals typical membrane-limited "neurosecretory" granules. Confirmation of the granules as adrenocorticotropin (ACTH) requires the use of OsO4 as a primary fixative to give the characteristic cored granule appearance in conjunction with immunohistochemical demonstration of the hormone peptide. Because of the rarity of ectopic ACTH production by mammary carcinomas and the absence of appropriate ultrastructural studies in the two examples of such ectopic hormone production in the literature of which we are aware (1,2), we present biochemical and ultrastructural data from a carcinoma of the breast with apparent ACTH production.The patient had her primary tumor in the right breast in 1969. The tumor recurred as visceral and subcutaneous metastases in 1976 and again in 1977.


Author(s):  
Melinda L. Estes ◽  
Samuel M. Chou

Many muscle diseases show common pathological features although their etiology is different. In primary muscle diseases a characteristic finding is myofiber necrosis. The mechanism of myonecrosis is unknown. Polymyositis is a primary muscle disease characterized by acute and subacute degeneration as well as regeneration of muscle fibers coupled with an inflammatory infiltrate. We present a case of polymyositis with unusual ultrastructural features indicative of the basic pathogenetic process involved in myonecrosis.The patient is a 63-year-old white female with a one history of proximal limb weakness, weight loss and fatigue. Examination revealed mild proximal weakness and diminished deep tendon reflexes. Her creatine kinase was 1800 mU/ml (normal < 140 mU/ml) and electromyography was consistent with an inflammatory myopathy which was verified by light microscopy on biopsy muscle. Ultrastructural study of necrotizing myofiber, from the right vastus lateralis, showed: (1) degradation of the Z-lines with preservation of the adjacent Abands including M-lines and H-bands, (Fig. 1), (2) fracture of the sarcomeres at the I-bands with disappearance of the Z-lines, (Fig. 2), (3) fragmented sarcomeres without I-bands, engulfed by invading phagocytes, (Fig. 3, a & b ), and (4) mononuclear inflammatory cell infiltrate in the endomysium.


Sign in / Sign up

Export Citation Format

Share Document