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Properties of the principal anion-exchange mechanism in human neutrophils.

As part of our ongoing studies aimed at understanding the physiology of human neutrophil function, we have been investigating the nature of the principal anion-exchange mechanism in these cells. This countertransport system functions physiologically as a Cl-/HCO3- exchanger in intracellular pH regulation from alkalinization (Simchowitz and Roos, 1985). In summarizing the results of our work, it is worthwhile to keep in mind the well-defined properties of the classic inorganic anion-exchange carrier of red blood cells, as important differences between the two are evident. Inhibitor Profile In our original articles on Cl- movements (Simchowitz and De Weer, 1986; Simchowitz et al., 1986), we had identified CHC, which suppresses monocarboxylate transport in mitochondria (Halestrap and Denton, 1975), as a relatively weak inhibitor. Several structural analogues, including alpha-methylcinnamate and alpha-phenylcinnamate, exhibited enhanced activity against anion exchange. The most potent compound thus far identified was UK-5099, which was approximately 300-fold more active than CHC. The inhibitory effect of each member of this series of compounds was strictly competitive in nature: both the drug and Cl ions appeared to bind to the same external translocation site on the exchange carrier. The inhibition by several other unrelated agents (e.g., MK-473, niflumate, flufenamate, and NAP-taurine), all weak organic acids, was also of the competitive type, which suggests that these compounds bind to the carrier by virtue of their negatively charged carboxyl or sulfonic groups. In marked contrast to erythrocytes, the anion-exchange carrier of neutrophils is rather insensitive to the disulfonic stilbenes SITS and DIDS (Simchowitz and De Weer, 1986): little or no effect can be detected in 148 mM Cl-. However, under conditions of low external Cl- (5-35 mM), SITS can in fact be shown to interact weakly with the anion binding site of the exchange carrier. In a comparable vein, several other drugs, all of which have been reported to suppress Cl- fluxes in red cells (for reviews, see Sachs et al., 1975; Gunn, 1979; Knauf, 1979; Lowe and Lambert, 1983), were either completely inactive against anion exchange in neutrophils at a concentration of 1 mM or only marginally effective at doses several orders of magnitude greater than those required in red blood cells. This list included furosemide, picrylsulfonate, maleic anhydride, 5,5'-dithio-bis(2-nitrobenzoate), salicylate, 2-methoxy-5-nitrotropone, and aldrithiol.4+he external

Anion Exchange Resins↗

[Organizational structure of internal medicine in Chile].

Internal Medicine, as a comprehensive discipline, has become increasingly dismembered during the last decades due to several reasons, some of which are the growing complexities of its practice, its obstinate confinement to hospital-based practice, its generation of and subsequent disfunction from general internal medicine and the medical subspecialities. In Chile internal medicine is currently organized in three levels of patient care, each of anarchical and distortioned proportions. These levels do not constitute a fluent network of progressive patient care but rather an heterogeneous combination of ironclad compartments in search of their own autonomy. A few of the many problems and challenges that internal medicine faces in Chile are: (a) in primary care medicine, problem-solving abilities must be improved and programmed care must be privileged over free choice. Specialist in general medicine must be assigned to primary care and multiprofessional teams must be strengthened; (b) Secondary care is underdeveloped due to the waning prestige of internal medicine and waxing attractiveness of its subspecialities. Programmed formation of specialist in internal medicine has been so far rigorous and demanding, but excessive in number in relation to available post. This leads trained internist to practice as subspecialist, without having the adequate conditions for such a practice. To avoid this situation, the scope of internal medicine emergency wards, integral medicine clinics, and medical student teaching should be handed over to it; (c) Tertiary care is a task of subspecialist. It is not known how many subspecialist are required, or how many physicians are currently practicing as a subspecialist. Most of the currently practicing subspecialist are self-qualified or have received quick training through short rotations by not always well-qualified centers. Many are only former internal medicine residents. In this setting, it is not possible to devise a prospective plan of subespecialty training. To make internal medicine in Chile efficient and timely, its is necessary to restore and restructure a rational patient care network that will do away with the current red tape and waiting list as well as to allow the insertion of well-trained specialist in the corresponding levels of patient care.

Chile↗

[Automated data processing system at the National Center for Blood Transfusion].

1) Data processing of blood unit test result on Groupamatic with manual labelling listings:--according to unit numbers;--according to blood results. 2) Blood donor file (updating):--114 473 donors;--150 characters/standard donors;--250 characters/precious donors. 3) Automatic print-out of:--call-ups;--donor data cards;--national blood donor cards:--diplomas;--red cards of badges;--particular listings of blood donors for medical checking, calling up, selecting units with special characteristics;--general listings. 4) Automatic labelling of blood units, by reading the unit identification number, and by printing out the corresponding labels.

Autoanalysis↗

Drug-induced red cell dyscrasias.

Major advances have been made in recent years in our understanding of the pathogenetic mechanisms of drug-induced blood dyscrasias, particularly those involving the red cell. Among the latter, hemolytic anemia is the most common. Drug-induced red cell destruction may occur on an immune basis or through disruption by the drug of red cell metabolism. The immunological basis of drug-induced hemolysis is reviewed with emphasis on the clinical and laboratory manifestations, differential diagnosis and the major mechanisms involved. Drug-induced oxidative hemolysis both in normal individuals and in those with certain enzymopathies, notably glucose-6-phosphate dehydrogenase deficiency, is summarized. Drugs may also produce red cell dyscrasias by acting on the immature erythroid compartment. Some of these inhibit erythroid growth by as yet poorly understood mechanisms. Others exert more specific metabolic effects in erythroid precursors. These include drugs which interfere with DNA synthesis causing megaloblastic erythropoiesis and those which disrupt mitochondrial function and the synthesis of heme manifested by sideroblastic erythropoiesis. A brief consideration of heme biosynthesis and the action of drugs which are associated with sideroblastic anemia, including the antituberculous agents, lead, alcohol and chloramphenicol is presented. Finally, where pertinent, an updated listing of drugs involved in red cell dyscrasias is included.

Erythrocytes↗

Comparative studies on the structure and stability of fluorescent proteins EGFP, zFP506, mRFP1, "dimer2", and DsRed1.

To obtain more information about the structural properties and conformational stabilities of GFP-like fluorescent proteins, we have undertaken a systematic analysis of series of green and red fluorescent proteins with different association states. The list of studied proteins includes EGFP (green monomer), zFP506 (green tetramer), mRFP1 (red monomer), "dimer2" (red dimer), and DsRed1 (red tetramer). Fluorescent and absorbance parameters, near-UV and visible CD spectra, the accessibility of the chromophores and tryptophans to acrylamide quenching, and the resistance of these proteins to the guanidine hydrochloride unfolding and kinetics of the approaching of the unfolding equilibrium have been compared. Tetrameric zFP506 was shown to be dramatically more stable than the EGFP monomer, assuming that association might contribute to the protein conformational stability. This assumption is most likely valid even though the sequences OF GFP and zPF506 are only approximately 25% identical. Interestingly, red FPs possessed comparable conformational stabilities, where monomeric mRFP1 was the most stable species under the equilibrium conditions, whereas the tetrameric DsRed1 possessed the slowest unfolding kinetics. Furthermore, EGFP is shown to be considerably less stable than mRFP1, whereas tetrameric zFP506 is the most stable species analyzed in this study. This means that the quaternary structure, being an important stabilizing factor, does not represent the only circumstance dictating the dramatic variations between fluorescent proteins in their conformational stabilities.

Acrylamide↗

Regional variations in peer reviewed liver allocation under the MELD system.

The Model for End-Stage Liver Disease (MELD) is used to assign priority for liver transplantation candidates. The Organ Procurement and Transplantation Network (OPTN) approved recognized exceptional diagnoses (RED's) for which MELD fails to accurately measure priority. Centers can request increased MELD points in cases not recognized by this policy (non-RED's). Our aim was to compare regional practices to justify non-RED requests for MELD adjustments. The UNOS/OPTN database was queried to extract all adult cases for which a non-RED MELD adjustment was requested from 2/27/02 until 8/27/03. The data were stratified by region and justification. Data for 29,510 listings were available. 26,947 had complete diagnosis information. There were 827 non-RED requests of which 477 (57.7%) petitions were approved by the regional review boards (RRBs). The approval rate varied significantly among regions (range: 28-75%, p<0.0001). The most common non-RED's were complications of portal hypertension (48%). The percentage of patients listed with non-RED's varied significantly among regions (0.7-8.3 %, p<0.0001), as did the proportion of patients transplanted with non-RED's (2.1-31.9%, p<0.0001). Demographics did not differ among regions requesting non-REDs.Widespread regional variations exist in the handling of requests for non-REDs. These variations point to the need for reform to standard exception criteria.

Adult↗

Associations between alcohol use and PTSD symptoms among American Red Cross disaster relief workers responding to the 9/11/2001 attacks.

OBJECTIVE: This study examined associations between alcohol use and PTSD symptoms among Red Cross workers who responded to the 9/11/2001 attacks. METHOD: Participants were 779 Red Cross paid and volunteer staff that responded during the first three months to the September 11, 2001, attacks against the United States. Women made up 64% of the sample. The American Red Cross provided a mailing list of all paid and volunteer staff (N = 6055 with valid addresses) that participated in the disaster relief operations in response to the September 11, 2001, attacks. Participants were randomly assigned to receive one of four questionnaire packets. The present study is based on the fourth group, which received the alcohol questionnaires. RESULTS: Overall, traumatic stress symptoms and alcohol use were low. Hyperarousal and intrusion symptoms on the Impact of Events Scale-Revised (IES-R) were associated with alcohol consumption, hazardous alcohol consumption, and change in alcohol consumption when controlling for age, gender, and worksite. Positive associations between Intrusion and Avoidance scores and hazardous consumption were stronger for younger participants. Individuals who reported increasing or decreasing alcohol use had higher IES-R scores than did those who maintained their normal rate of alcohol consumption, though effects were stronger for increasing alcohol use. Associations between alcohol variables and avoidance symptoms were minimal. CONCLUSIONS: The results suggest that there is a functional relation between posttraumatic stress symptoms and alcohol consumption. The study indicates that efforts to cope with traumatic stress symptoms may manifest in either increases or decreases in alcohol consumption.

Adaptation, Psychological↗

The red blood cell as a biopsy tool.

During the past several years, there has been much emphasis on understanding the relationship between abnormalities in RBC metabolism and hereditary haemolytic anaemias. More recently, attention has focused on utilizing erythrocyte biochemical abnormalities in the diagnosis of systemic disorders not necessarily associated with altered RBC function. In this chapter, we have enumerated several non-erythrocytic clinical conditions clearly associated with altered RBC metabolic products or enzyme activity. Specifically, we have described the use of erythrocytes (1) to diagnose inborn errors of metabolism, (2) to assess many nutritional disorders, (3) to monitor hyperglycaemia in patients with diabetes mellitus, and (4) to discriminate between essential and non-essential hypertension. As Eric Ponder said many years ago (Ponder, 1948), 'I have been told that I tend to speak of the red cell as if it were a microcosm, as if an understanding of its nature and properties would include an understanding of nearly everything else in the cellular world. To some extent this is true.' When the list of conditions for which the red cell can be used as a biopsy tool is reassessed several years from now, most assuredly many new clinical conditions will be added to the diseases we have discussed. For example, our knowledge of normal membrane structure and function currently is in its infancy, yet it already appears that analysis of RBC membranes may be useful in detecting certain neurological disorders such as muscular dystrophy (Roses, Herbstreith and Appel, 1975). Needless to say, to the delight of Dr Eric Ponder, the utility of the erythrocyte as an investigative tool appears to be without limit.

Biopsy↗

[Waiting lists and reality. Revision of the waiting list for reduction of breast hyperplasia in health region 1].

The Red Cross Hospital is the only public hospital providing plastic surgical services for the Oslo population. The waiting list for reduction mammaplasty had become unacceptably long. Some women had been waiting for as long as 4.5 years. We therefore decided to reexamine all the 309 patients in question. Only 22% were cleared for operation. 19% were removed temporarily from the waiting list due to obesity (awaiting weight reduction). The remainder was found to be either mainly motivated or to be motivated for mainly oesthetic reasons and therefore not eligible for public health funding.

Adult↗

Detection of Kanji words in a rapid serial visual presentation task.

In 3 experiments, lists of 12 Kanji words were rapidly presented in the same position, and participants reported a red target word embedded in green distractor words. Two lists were used: same and different category. A tendency toward category priming was found at longer durations. Frequency of target localization indicated that participants familiar with Kanji had a greater tendency to report the word immediately preceding the target. These pretarget intrusion errors dominated the posttarget intrusion errors, when the luminance of red and green stimuli were equated (Experiment 2), and when the response was recall (Experiments 1 and 2) or recognition (Experiment 3). In contrast, participants unfamiliar with Kanji made posttarget intrusion errors as frequently as pretarget intrusion errors (Experiment 3), suggesting that knowledge of Kanji influences the integration of color and form codes in visual information processing.

Adult↗

The cost of psoriasis therapies: considerations for therapy selection.

PURPOSE: The purpose of this article is to provide a review of the cost of psoriasis therapies from two sources as well as compare the average wholesale price (AWP), as listed in the 2003 Drug Topics Red Book to that of a popular Internet pharmacy. METHODS: Prices of therapies were obtained two ways: the AWP was recorded from the 2003 Drug Topics Red Book. A range and average price per gram (or mL) were calculated based on the smallest size or quantity available. In addition, a price comparison was made to values as they were reported online at drugstore.com. Monthly cost estimates were based on average systemic dosing and for topicals, 18 g/month (for 1% body surface area [BSA] involvement). RESULTS: The prices of psoriatic treatment medications vary considerably--from the relatively inexpensive topical corticosteroids to the more costly biologic therapies. In the category of corticosteroids, a trend was evident between the overall price per gram of each class and the potency of each class. Class I and VI corticosteroids had an average price per gram (or mL) of dollars 2.08 (dollars 37/month/1% BSA) and dollars 0.86 (dollars 15/month/1% BSA), respectively. Nonsteroidal topical treatments had an average price per gram (or mL) dollars 2.18 (dollars 39/month/1% BSA). Systemic therapies have a wide range of costs. The total monthly expense, based on estimated average dosing, was calculated for methotrexate, acitretin, and cyclosporine and were dollars 78.60, dollars 400.50, and dollars 735.00, respectively. Biologic therapies designed for continuous use cost roughly dollars 1,300/month. DISCUSSION: There are numerous treatment options for psoriasis with a wide range of costs. In addition to significant challenges from a scientific perspective, psoriasis treatment is further complicated by the cost of the numerous medications. Prices reported in the AWP were similar in many instances to those listed at an Internet pharmacy. Many considerations should go into therapy selection for psoriasis and a comprehensive approach that includes cost will likely provide the best patient care.

Anti-Inflammatory Agents↗

Glutaraldehyde: its uptake by sporing and non-sporing bacteria, rubber, plastic and an endoscope.

Uptake of glutaraldehyde to bacterial spores, germinating and outgrowing spores, vegetative cells (sporing and non-sporing bacteria), various types of rubber, plastic and an endoscope was investigated. Escherichia coli NCTC 10418 exhibited greatest uptake, followed by Bacillus subtilis NCTC 8236 vegetative cells and Staphylococcus aureus NCTC 6571. Germinated and outgrowing B. subtilis spores adsorbed more glutaraldehyde than resting spores, but less than vegetative cells. Low concentrations of alkaline and acid glutaraldehyde increased the surface hydrophobicity and inhibited the germination of bacterial spores, the alkaline solution to a greater extent in both cases. Rubbers exhibited varying degrees of uptake and are listed in decreasing order of uptake: red rubber, fluorinated rubber (Vinescol), silicone rubber (Silescol), butyl rubber (Butyl XX). Polypropylene, the only plastic examined, was found not to adsorb any glutaraldehyde. The endoscope adsorbed more glutaraldehyde (per gram) than fluorinated rubber but less than red rubber. No damage was observed.

Aldehydes↗

Clinical efficacy and cost comparison of an amiloride-hydrochlorothiazide combination versus hydrochlorothiazide and wax-matrix potassium supplement in the treatment of essential hypertension.

To compare the clinical efficacy and cost of therapy with an amiloride-hydrochlorothiazide combination versus hydrochlorothiazide and a wax-matrix potassium supplement, we reviewed the medical records of 20 hypertensive men who had received both treatments. The review period included 5.9 +/- 0.9 (mean +/- SE) months on hydrochlorothiazide and wax-matrix potassium and 5.3 +/- 0.7 months after changeover to the amiloride-hydrochlorothiazide combination. Control of blood pressure, maintenance of serum potassium levels, and number of outpatient visits were similar before and after the change in therapy. The monthly cost of medication, based on the lowest listed price in the Drug Topics Red Book and also in the Red Book Update, was approximately 12% higher for the hydrochlorothiazide and wax-matrix potassium regimen than for the amiloride-hydrochlorothiazide combination, whereas the federal agency contract price for the latter was significantly higher. The change to the amiloride-hydrochlorothiazide combination reduced the mean number of tablets taken daily from 5.3 +/- 0.6 to 1.25 +/- 0.1, suggesting a more convenient therapeutic regimen.

Adult↗

Transfusion practice and nosocomial infection: assessing the evidence.

PURPOSE OF REVIEW: To evaluate recent literature describing the potential relation between transfusion practice in the intensive care unit and the subsequent risk for nosocomial infection. RECENT FINDINGS: Multiple studies have documented that patients in the intensive care unit often receive transfusions of packed red blood cells while in the intensive care unit. Although the safety of the blood supply has increased substantially over the last decade, nosocomial infection is emerging as an unappreciated potential consequence of transfusion. Research now suggests that transfusion alters the host's immune system. Clinically, this may lead to relative immunosuppression and result in nosocomial infection. Supporting this hypothesis, an association between infection and transfusion has been shown in various settings and for several different types of infections. In both postoperative and medical intensive care unit subjects, administration of packed red blood cell consistently raises the risk for infection. Similarly, transfusion rates correlate with two major nosocomial complications in the intensive care unit: pneumonia and bloodstream infection. Proof of causation remains elusive because of study design issues. Nonetheless, the weight of the evidence favors adding nosocomial infection to the list of potential risks related to packed red blood cell transfusion. SUMMARY: Packed red blood cell transfusion may substantially increase the risk for nosocomial infection. The likely link between transfusion practice and nosocomial infection should factor into the provider's decision when determining when to transfuse.

Bacteremia↗

Red blood cell-mediated microinjection: methodological considerations.

Red blood cell-mediated microinjection is a powerful approach to introducing proteins into the cytoplasm of cultured cells. In the course of our microinjection studies of intracellular protein degradation, we have encountered several potential problems with certain proteins. The microinjection procedure may be accompanied by denaturation of protein by radiolabeling procedures, binding of protein to red cell ghosts during loading, degradation of protein by the red cell ghost prior to microinjection, and adsorption of protein that leaks from red cell ghosts in the presence of fusogen to the fibroblast monolayer. We conclude with a list of points that must be considered prior to use of red cell-mediated microinjection to study a particular protein.

Cells, Cultured↗

Postpartum hemorrhage and transfusion of blood and blood components.

UNLABELLED: Postpartum hemorrhage (PPH) is one of the top 5 causes of maternal mortality in developed and developing countries. The incidence of PPH is 40% after vaginal delivery and 30% after cesarean section. Criteria for PPH are based on the amount of blood loss. In clinical obstetrics, exact measurement of blood loss is often difficult. The most important treatment of PPH is red blood cell (RBC) transfusion. In the past few years, increasing concern has arisen about this treatment. Despite the introduction of several new guidelines, transfusion criteria still vary widely between clinicians. The decision whether to prescribe RBC transfusion is mostly based on postpartum hemoglobin (Hb) values. RBC transfusion should be aimed to reduce morbidity and especially to improve health-related quality of life (HRQoL). In this review, etiology, epidemiology, treatment, and prevention of postpartum hemorrhage are described. Special attention is given to the role of RBC transfusion in the treatment of PPH and the effects of RBC transfusion on HRQoL. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to summarize the new guidelines related to transfusion criteria, explain the importance of reducing morbidity related to improving quality of life issues, and list infectious and noninfectious complications of a red blood cell transfusion.

Blood Transfusion↗

Effect of enzymes on and chemical modifications of high-frequency red cell antigens.

Enzyme or chemical modification of intact red cells results in the destruction of some blood group antigens. The pattern of reactions of an antibody with red cells treated with various proteinases, with sialidase, and with the disulfide bond-reducing agent 2-aminoethylisothiouronium bromide (AET) can aid in antibody identification. This information can prove particularly beneficial with antibodies to antigens of very high frequency, where antigen- negative cells may be difficult to obtain. Provided in this article is a table listing most of the authenticated high-frequency red cell antigens and the effect on those antigens of trypsin, chymotrypsin, a mixture of trypsin and chymotrypsin, papain, pronase, sialidase, and AET.

Journal Article↗