The effects of additive solution pH and metabolic rejuvenation on anaerobic storage of red cells

BACKGROUND: Red cell (RBC) storage can be extended to 9 weeks under anaerobic or alkaline conditions. Simultaneous use of these approaches has not provided additive benefit. Our objective was to determine whether anaerobic storage with acidified additive solution (AS) coupled with metabolic rejuvenation might further improve the benefits of anaerobic storage. STUDY DESIGN AND METHODS: RBC storage in AS with a pH value of 6.5, 7.4, or 8.3 in aerobic or anaerobic conditions was examined using a panel of in vitro biochemical and RBC markers. RBC rejuvenation during cold storage was also evaluated. A randomized crossover radiolabeled recovery study (eight subjects) evaluated anaerobic RBC storage using AS65 with cold rejuvenation for up to 16 weeks of storage. RESULTS: Adenosine triphosphate (ATP) and diphosphoglycerate acid (DPG) were better maintained in anaerobic storage than in aerobic storage. Acidic or neutral AS preserved ATP concentration better, while a neutral or basic pH AS favored maintenance of DPG levels at higher levels for a longer period. AS pH had less of an effect on exposure of phosphatidylserine (PS), vesicle protein release, and hemolysis. Rejuvenation of RBCs during cold, anaerobic storage resulted in increases in ATP and DPG levels and a reversal of PS exposure. Anaerobic storage of RBCs in pH 6.5 AS rejuvenated at 7 weeks of storage yielded RBC 24‐hour recoveries of 77.3 ± 12.5 percent after 10 weeks' storage time. After a second rejuvenation at Week 11, six subjects' units demonstrated a recovery of 75.9 ± 7.3 percent at 12 weeks of storage. CONCLUSION: Extended RBC storage may be achieved using anaerobic conditions combined with low‐pH AS and rejuvenation during storage.     

Precision requirements for cost-effective operation of analytical processes

Current performance criteria for analytical methods are often based on recommendations developed many years ago. A common criterion for imprecision requires that two times the standard deviation (s) of the method be less than the allowable total error (TEa). Unfortunately, when this criterion is minimally satisfied, commonly used control procedures cannot achieve reliable detection of medically important errors. Studies of the power functions for statistical quality-control (QC) procedures show that the magnitude of medically important errors must be at least 3s to fall near the plateau of the power curves and be readily detected by current QC procedures. For methods that just meet the precision criterion 2s less than TEa, however, medically important errors will fall on the rising portion of the power curves and typically be detected less than half of the time. From a "reverse engineering" perspective, the 2s less than TEa criterion is inadequate because it does not allow for the known performance limitations (lack of sensitivity) of commonly used control procedures. A strong case can be made for using a criterion of at least '4s less than TEa, which calls for a twofold improvement in imprecision over, the current minimum requirements. This recommendation is consistent with current industrial guidelines for process capability and would lead to more reliable detection of medically important errors.     

Fasting plasma homocysteine levels in the insulin resistance syndrome: the Framingham offspring study

OBJECTIVE: Insulin resistance, associated metabolic abnormalities, and elevated homocysteine levels are risk factors for cardiovascular disease (CVD). We examined relationships between homocysteine levels and features of insulin resistance syndrome (IRS). RESEARCH DESIGN AND METHODS: We measured clinical characteristics, plasma levels of fasting homocysteine, folate, B vitamins, creatinine, and fasting and 2-h insulin and glucose levels after a 75-g oral glucose tolerance test in 2,214 subjects without CVD at the fifth examination (1991-1995) of the Framingham Offspring Study. After excluding 203 subjects with diabetes, the remaining 2,011 subjects were categorized as having none, one, two, or all three of the phenotypes of IRS: impaired glucose tolerance, hypertension, and/or a central metabolic syndrome (two or more traits: obesity, dyslipidemia, or hyperinsulinemia). In addition, in 1,592 subjects attending the sixth examination (1995-1998), we measured the urine albumin/creatinine ratio (UACR). Age-, sex-, creatinine-, vitamin-, and UACR-adjusted mean homocysteine levels or proportions with homocysteine >14 micromol/l in each phenotypic category and differences between categories were assessed with regression models. RESULTS: The mean age of the subjects was 54 years (range 28-82); 55% were women, 12.3% had hyperinsulinemia, and 15.9% had two or more of the IRS phenotypes. Adjusted mean homocysteine levels were higher comparing those with hyperinsulinemia (9.8 micromol/l) and those without (9.4 micromol/l, P = 0.04) and were higher among subjects with two or more IRS phenotypes (9.9 micromol/l) compared with those with 1 or no phenotype (9.3 micromol/l, P = 0.003). Mean UACR levels were also higher among subjects with two or more IRS phenotypes (7.2 mg/g) compared with those with 1 or no phenotype (5.5 mg/g, P = 0.007). CONCLUSIONS: Hyperhomocysteinemia and abnormal urinary albumin excretion are both associated with hyperinsulinemia and may partially account for increased risk of CVD associated with insulin resistance. Because hyperhomocysteinemia and microalbuminuria also reflect endothelial injury, these observations also support the hypothesis that endothelial dysfunction is associated with expression of the IRS.     

Receptors for complement of leukocytes

Sheep red blood cells sensitized by 7S, but not by 19S rabbit anti-Forssman antibodies, adhere and form rosettes on mouse macrophages and on a few monocytes and polymorphonuclear cells (PMN). When, however, C'' factors from mouse serum are added to the antigen-19S antibody complex (EAC''), rosettes are formed on most mouse peritoneal macrophages and PMN and on a few monocytes. In addition EAC'' also adheres to 10–25% of lymph node lymphocytes but not to thymus lymphocytes. EAC'' prepared with 7S anti-Forssman antibodies has identical properties. The adherence of red cells induces an increase in the membrane activity of the leukocytes and causes injury to the red cells which rapidly become deformed and fragmented. Adherence of EAC'' occurs at 37°C and is minimal at 4°C. Probably only the first four C'' components are involved in this phenomenon as mouse serum deficient in C''5 or rabbit serum, deficient in C''6 can be used as a source of C'' components. Treatment of EAC'' with EDTA does not modify its leukocyte-adherence properties. The adherence of EAC'' to the leukocytes is not inhibited in the presence of serum. The receptors for C'' on macrophages, PMN, and monocytes differ from those found on lymphocytes. Rosette formation by EAC'' on macrophages, PMN, and monocytes depends on divalent cations (Mg⁺⁺) and can be reversed by Na₃H EDTA, while adherence to lymphocytes is independent of these ions and occurs in the presence of 0.01 M Na₃H EDTA. Both types of receptors for C'' components are destroyed by trypsin treatment of the leukocytes, in contrast with the receptors for 7S antibodies on the same cells which persist after enzyme treatment.     

Effect of myoelectric signal processing on the relationship between muscle force and processed EMG

The relationship between the force generated by an isometrically contracting muscle and the associated myoelectric signal has been the subject of extensive investigation in the past and conflicting results were reported regarding this relationship. The objective of the present study was to investigate some of the sources that may lead to such conflicting results. Two possible sources were examined. The first was the variability in the force-EMG relationship resulting from processing the EMG signal with different EMG signal processing techniques and the second was the variability in the force-EMG relation obtained from repeated muscle contractions. The results of the study indicate that slight variations in the force-EMG relationships can be attributed to the selection of different processing techniques. However, the variability in the force-EMG relation, obtained by using different EMG signal processors, was found to be significantly smaller than the variability in this relationship obtained from repeated muscle contractions.     

Health status, sociodemographic factors, and the use of prescribed psychotropic drugs

The relations among sociodemographic factors, health status, and use of prescribed sleeping pills and tranquilizers are examined. The data are from the Rand Health Insurance Experiment, which has a random sample of the nonaged, noninstitutionalized, civilian population in six U.S. sites. Information on sociodemographic factors, health status, and the use of prescribed psychotropic drugs during the previous 3 months was obtained from self-report questionnaires collected at enrollment. Mental and physical health status have large independent and significant effects on the probability of use of both prescribed tranquilizers (P less than 0.0001) and sleeping pills (P less than 0.0001), whether or not we remove the effects of sociodemographic factors. For the probability of tranquilizer use, there is no significant interaction between gender and mental health or between mental health and physical health. Age and gender have large and significant effects on the use of prescribed psychotropic drugs even after controlling for differences in health status and other demographic factors. The effects of site and socioeconomic status are modest compared with the effects of health, age, and gender.     

Naturally Occurring Human Antiglobulins with Specificity for γE

Human sera have been examined for antibodies with specific reactivity for gammaE using the tanned cell hemagglutination test. Cells tanned with three different gammaE myeloma proteins provided a reproducible test system. Inhibition of agglutination reactions by gammaE proteins, but not by gammaG, gammaA, gammaM, or gammaD confirmed the specificity of these reactions. 8.5% of 304 serial serum samples obtained from miscellaneous hospitalized patients showed clear-cut anti-gamma-globulins with specificity for gammaE. In most of these instances no definite clinical history of concomitant allergic disorders could be obtained. 53% of 73 patients with well-established allergic disorders (hay fever, extrinsic asthma) showed serum anti-gamma-globulins with reactivity for gammaE. Some patients studied before and after desensitization to Bermuda grass allergen showed an increase in titer or a conversion from negative to positive reactions for anti-gammaE antibodies following several month courses of progressive desensitization. Gradient and gel filtration studies indicated that anti-gammaE globulins were 19S gammaM in all instances. No clear correlation was noted between quantitative serum gammaE levels and titer of anti-gammaE antibodies.19S serum fractions with anti-gammaE antibody activity did not release histamine from normal human peripheral blood leukocytes, whereas specific rabbit anti-gammaE antisera consistently induced leukocytic histamine release. Moreover, macroglobulin fractions with anti-gammaE activity did not block allergen-specific leukocyte histamine release induced by in vitro leukocyte challenge with allergens such as Bermuda grass and leukocytes from allergic donors. In some instances 19S human serum fractions with anti-gammaE activity appeared to potentiate histamine release when incubated concomitantly with specific allergen and leukocytes from allergic individuals.     

The sexual offender: Monster,victim, or everyman?

The nature of sexual offending is considered and it is concluded that offenders are more like other people than they are different. It is concluded that they are neither monsters nor victims and should, as a consequence, be treated like all other clients. Treatment implications are considered and it is suggested that we shift our focus away from a preoccupation with procedures and instead give attention to process features of treatment. Various therapist styles are discussed and it is proposed that a style that enhances the offender's self-esteem may be best. The value of this approach is outlined and tentative data are offered suggesting its value. Considerations for future developments are noted.Keynote address at the 14th Annual Research and Treatment Conference of the Association for the Treatment of Sexual Abusers, New Orleans, October 1995.