Risk factors for clinically important adverse events after protamine administration following cardiopulmonary bypass

OBJECTIVES: The purpose of this study was to determine risk factors for adverse events following protamine administration after cardiopulmonary bypass. BACKGROUND: Intravenous protamine administration is associated with a risk of severe systemic reactions. However, risk factors for these events have not been well delineated, thus hampering development of preventive strategies. METHODS: A case-control study nested within a cohort of consecutive patients undergoing surgery requiring cardiopulmonary bypass was performed. The primary case definition included those events (pulmonary hypertensive and systemic hypotensive) occurring within 10 min of protamine administration in the absence of other measurable causes of hemodynamic compromise. RESULTS: Comparing the 53 cases to the 223 control subjects, three risk factors were independently associated with events (multivariable odds ratio [95% confidence interval]): neutral protamine Hagedorn insulin use (8.18 [2.08, 32.2]); fish allergy (24.5 [1.24, 482.3]), and a history of nonprotamine medication allergy (2.97 [1.25, 7.07]). These risk factors demonstrated an increasingly strong association with progressively more specific case definitions. An estimated 39% of cardiopulmonary bypass patients had one or more of these risk factors. Prior intravenous protamine, central venous pressure prior to protamine, preoperative ejection fraction and the need for inotropes when coming off bypass did not exhibit statistically significant associations with events (all p > 0.15). Prior protamine allergy was associated specifically with an increased risk of pulmonary hypertension (multivariable odds ratio 189; 95% confidence interval 13, 2,856). CONCLUSIONS: Immunologic factors are important in predisposing individuals to protamine reactions, and a substantial proportion of patients are at considerably increased risk Strategies to reduce the risk of protamine-associated events are needed.     

Cancer therapy using bone-seeking isotopes

Bone pain is a common symptom in disseminated malignancy and may be difficult to manage effectively. Radiation is of proven benefit for pain palliation and there is growing interest in the therapeutic potential of bone-seeking radiopharmaceuticals. Clinical data relating to the use of phosphorus-32, strontium-89, samarium-153 EDTMP, rhenium-186 HEDP and tin-117m DTPA are reviewed in the context of the pathophysiology of metastatic bone pain. Possible mechanisms of action of palliative radiotherapy and, in particular, the theoretical role of early response genes are discussed. The application of Monte Carlo simulation to targeted radiotherapy for bone metastases may provide the basis for a clearer understanding of the microdosimetry and radiobiology of bone pain palliation and for reliable prediction of clinical response and toxicity.     

Tyrosinase stabilization by Tyrp1 (the brown locus protein)

Mammalian melanogenesis is regulated directly or indirectly by over 85 distinct loci. The Tyr/albino locus, in which mutations cause a lack of pigmentation, encodes tyrosinase (Tyr), the critical and rate-limiting melanogenic enzyme. Other melanogenic enzymes include Tyrp1 (or TRP1) and 3,4-dihydroxyphenylalanine-chrome tautomerase (Dct or TRP2) encoded at the Tyrp1/brown and Dct/slaty loci, respectively. Murine Tyrp1 can oxidize 5, 6-dihydroxyindole-2-carboxylic acid (DHICA) produced by Dct, but mutations in Tyrp1 also affect the catalytic functions of Tyr. All three enzymes are membrane-bound melanosomal proteins with similar structural features and are thought to interact within and stabilize a melanogenic complex. We have now further investigated the effect of a Tyrp1(b) mutation on Tyr stability. Pulse/chase labeling experiments show that Tyr is degraded more quickly in Tyrp1(b) mutant melanocytes than in melanocytes wild type at that locus. This reduced stability of Tyr can be partly rescued by infection with the wild type Tyrp1 gene, and this is accompanied by phenotypic rescue of infected melanocytes. In sum, these results suggest that, in addition to its catalytic function in oxidizing DHICA, Tyrp1 may play an important role in stabilizing Tyr, a second potential role in the regulation of melanin formation.     

Incidence of anemia in older people: an epidemiologic study in a well defined population

OBJECTIVE: To assess the incidence and clinical spectrum of anemia among older people. DESIGN: Inception cohort assembled and followed by medical records linkage until death or last clinical contact through January 1994. SETTING: Population-based study in Olmsted County, Minnesota. PARTICIPANTS: All 618 Olmsted County men and women aged 65 years or more with anemia by World Health Organization criteria that was first recognized in 1986. MEASUREMENTS: Age- and sex-adjusted incidence rates, corrected for prevalent anemia, and survival estimates using the Kaplan-Meier method, with calculation of standardized mortality ratios for specific causes of death. RESULTS: The corrected annual incidence of anemia rose with age, and rates were higher in men (90.3 per 1000; 95% CI, 79.2-101.4) than women (69.1 per 1000; 95% CI, 62.3-75.8). In 465 cases (75%), anemia was detected in conjunction with a hospitalization, but admission was due to anemia in only 57 instances. Half of the cases were caused by blood loss, two-thirds of these as a result of surgery. The cause of anemia was uncertain in 102 cases (16%). One-third of the patients were transfused with a median of 3 units each. Overall survival was worse than expected but was better among those with anemia caused by blood loss. Mortality attributable to malignancy, mental disorders, circulatory and respiratory diseases, ill-defined conditions, and injuries was significantly increased among these older patients with anemia. CONCLUSIONS: The incidence of anemia among older people is 4 to 6 times greater than that suspected clinically, rises with age, and is higher in men than in women. The apparent cause in half the cases is blood loss. Even mild anemia is associated with reduced survival, especially during the first year, but this could relate to underlying comorbid conditions.     

The use of the Kawabata Evaluation System for product development and quality control

The clothing manufacturing industry is an important user of the products of the dyeing and finishing industry. Major advances in Japan have shown that the use of mechanical property data can assist the dyer and finisher in providing products that are sufficiently consistent for their efficient conversion into clothes. The Kawabata Evaluation System for Fabrics (KES–F) can be used to provide appropriate information of use for quality control, product development and product specification. Current uses and applications are discussed.     

The national estimates approach to U.S. fire statistics

The development of the National Fire Incident Reporting System in the late 1970s made detailed, representative national fire statistics possible for the first time. However, calculation rules used to produce these statistics have varied among users. The authors present a detailed consensus procedure for such calculations and the supporting rationale.This article was co-written by Ms. Harwood in her official capacity, is in the public domain, and may be freely copied. The views expressed do not necessarily reflect the official views of the Commissioners of the Consumer Product Safety Commission.     

Fat metabolism in higher plants XLIX fatty acid biosynthesis by subcellular fractions of higher plants

A method is described for the rapid and comprehensive subcellular fraction-ation of plant tissue using a combination of differential and discontinuous Ficoll gradient centrifugation. The procedure has been used to study the synthesis of fatty acids from acetate-1-¹⁴C or malonyl CoA-1,3-¹⁴C, by fractions of germinating pea and lupin seeds and developing avocado fruit, castor bean and safflower seeds. Particle free supernatants of seeds synthesize fatty acids from¹⁴C-malonyl CoA in the presence of added cofactors. Since acetyl CoA carboxylase activity is absent the utilization of¹⁴C-acetate by these fractions is minimal. Other particulate fractions show different activities depending on seed types. Active fractions include the low speed particulate of pea and lupin, the pea microsomes, the avocado mesocarp chloroplasts, and the fat fractions of castor bean and safflower. Individual fractions produce characteristic patterns of acids; especially noteworthy is oleic acid biosynthesis by soluble enzymes of castor bean and safflower from¹⁴C-malonyl CoA. Some characteristics of the avocado supernatant, pea supernatant, and castor bean fat fraction synthesizing systems are compared. As a result of these studies, generalizations derived from work with mammalian or bacterial systems cannot be applied to higher plants. Presented in part at the AOCS Meeting, Houston, May 1971.     

An investigation into the high temperature strength and reinforcement of natural rubber

The failure criterion for amorphous polymers relating hysteresis at break with energy input to failure in tensile stress–strain tests was found to be obeyed only at very high or very low temperatures in natural rubber. Tensile results between about 80°C and 130°C show a high degree of scatter, and this behavior is attributed to the ability of natural rubber to crystallize at high strains. The modification of tensile properties by the addition of carbon black in natural rubber is also discussed and compared with published results from SBR. The effect of changing the degree of crosslinking on the failure properties in both dicumyl peroxide and sulfur-cured vulcanizates of natural rubber is also considered. It is found that differences in failure properties can be accounted for by the use of a crosslinking parameter from simple rubber elasticity theory in some of the failure equations.