Alteration of an intersubunit contact in hemoglobin variants: comparative study of modifications at position alpha 126 Asp (H9)

Four human hemoglobin variants have already been described at position alpha 126 (H9), which is normally occupied by an aspartate: Hb Montefiore (-->Tyr), Hb Tarrant (-->Asn), Hb Fukutomi (-->Val), Hb Sassari (-->His). An additional variant, Hb West One (alpha 126 (H9) Asp-->Gly) is herein described. Aspartate alpha 126 (H9) is involved in a set of hydrogen bonds and salt bridges located at the C-terminal portion of the alpha-chains and of the C-helix of the beta-chains, which are broken in the oxy conformer, providing one of the most important sources of the difference in free energy between the T- and R-state in hemoglobin. A comparative study of four of these alpha 126 Hb variants is presented. An identical degree of alteration of the oxygen binding properties (increased oxygen affinity and decreased cooperativity) was found in all cases, when measured under standard experimental conditions (pH 7.2, 0.1 M NaCl). In contrast, the effect of L345 (a derivative of bezafibrate, which is a specific alpha-chain binding effector) on oxygen binding to Hb differed from one variant to another. When a bulky Tyr or His residue occupied the alpha 126 (H9) position, little effect of L345 was observed. Conversely, when this position was occupied by a residue of smaller size (Gly or Asn), normal heterotropic effects were observed. Molecular graphic modelling indicates that two classes of three-dimensional structure modifications may occur.     

Glucose metabolism in photoreceptor outer segments. Its role in phototransduction and in NADPH-requiring reactions

Glucose metabolism in the photoreceptor rod outer segment produces both ATP (GTP) and NADPH to support phototransduction and NADPH-requiring processes in this organelle. Glycolysis in isolated bovine rod outer segments produces 44.0 +/- 6.4 nmol of ATP/min/mg of protein or 5.7 mM ATP/min. This rate of ATP production is more than sufficient to maintain the basal rate of cGMP synthesis (0.86 mM cGMP/min) in the dark requiring 1.7 mM ATP/min. Following photoexcitation, the 4.5-fold increase in the turnover of cGMP requires an ATP synthesis rate of up to 7.7 mM ATP/min (Ames, A., Walseth, T. F., Heyman, R. A., Barad, M., Graeff, R. M., and Goldberg, N. D. (1986) J. Biol. Chem. 261, 13034-13042). Under these conditions the rate of ATP production by glycolysis as measured in isolated rod outer segments is not sufficient for the regeneration of cGMP. Additional energy is most likely provided by the phosphocreatine shuttle which transports high energy phosphate groups in the form of creatine phosphate from the rod inner segment to the rod outer segment for conversion to ATP. The hexose monophosphate pathway in bovine rod outer segments can produce up to 39.8 +/- 2.2 nmol of NADPH/min/mg of protein. This rate of NADPH production is sufficient to support both the reduction of retinal to retinol (1.2 +/- 0.2 nmol of NADPH/min/mg of protein) following the photobleaching of rhodopsin and glutathione reduction (1.1 +/- 0.1 nmol of NADPH/min/mg of protein) for the protection of rod outer segments from oxidative damage. These studies provide insight into the contribution of anaerobic glycolysis and the hexose monophosphate pathway in providing energy and nucleotides for phototransduction and other outer segment processes.     

Assessing risk by hemodynamic profile in patients awaiting cardiac transplantation

A profile of hemodynamic abnormalities in patients listed for cardiac transplantation was related to survival during the first year after listing. After a patient is listed for cardiac transplantation, the waiting period for a suitable donor heart is often long; therefore, objective criteria to determine risk would be helpful in identifying the group at highest risk of dying before receiving a transplant. Several studies have suggested certain hemodynamic parameters to be related to a poor prognosis. However, no 1 variable has emerged as an adequate predictor of survival in patients awaiting cardiac transplantation. One-year outcomes were examined in 138 consecutive patients listed for cardiac transplantation, who were grouped according to a hemodynamic risk score (HRS) based on abnormalities in baseline measures of right atrial pressure, pulmonary artery systolic pressure, transpulmonary gradient, cardiac output, cardiac index and pulmonary vascular resistance. Right atrial pressure alone was the most significant predictor of survival (p < 0.05). Patients with a right atrial pressure > 12 mm Hg had a 47% 1-year survival as compared with the 68% survival for those with a right atrial pressure < 12 mm Hg. HRS was the next strongest predictor of survival. The 66% survival in group I (HRS = 0) and the 69% survival in group II (HRS = 1 to 3) were significantly (p < 0.03) higher than the 41% survival in group III (HRS = 4 to 6) at 1 year after listing. Differences in survival for the HRS groups could not be explained by left ventricular ejection fraction, left ventricular end-diastolic diameter or status at listing.(ABSTRACT TRUNCATED AT 250 WORDS)     

A transactional perspective on critical thinking

The quality of thinking has received much attention within the last decade. The scientific inquiry models introduced by Dewey, Dressel and Mayhew, and Watson-Glaser have been expanded to incorporate such aspects as reflection, development, attitude, skill, and knowledge domain. Dichotomies between critical and creative thinking have been eased. While this scholarship on thinking has been impressive, current pedagogy remains focused on scientific inquiry and on received knowledge. In nursing the learning paradigm has been similarly focused for the past 3 decades on a scientific inquiry model and received knowledge. The major cognitive approach to education and practice has been the nursing process, a linear problem-solving paradigm equivalent to the scientific method. This linear approach does not fully account for how nurses think and make judgments in clinical practice. The Transactional Model of Critical Thinking presented in this paper addresses the complexity of critical thinking in nursing. The model provides an educative and novel vision of thinking based on a transactional view of the individual, personal attributes, and the environment. Components and elements of the model are described and suggestions made for teaching-learning and for evaluation of critical thinking in nursing.     

Recalling the fundamental principles of the administration of injections: the correct procedure]

The present investigation was to identify the impact of recombinant human tumor necrosis factor-alpha (TNF-ALPHA) on alkaline phosphatase (ALP) activity of cultured human periodontal ligament fibroblasts (HPLF). It was found that, after treatment with TNF-alpha, HPLF in the experimental groups showed significantly lower ALP activity than in the blank control groups (P < 0.01). Further, the ALP activity was observed to decrease progressively with increasing TNF-alpha concentrations. These findings indicate that TNF-alpha possesses a remarkable concentration-dependent inhibitory effect on human periodontal ligament fibroblasts.     

The efficacy of diaspirin crosslinked hemoglobin solution resuscitation in a model of uncontrolled hemorrhage

Controversy exists whether early aggressive fluid therapy in the setting of uncontrolled hemorrhage worsens outcome by increasing blood loss from injured vessels. Since diaspirin crosslinked hemoglobin (DCLHb) is a vasoactive, oxygen-carrying solution, we compared the effects of DCLHb with other resuscitative fluids on blood loss, hemodynamics, and tissue oxygen delivery in a model of uncontrolled hemorrhage. Anesthetized rats (250-350 g) were subjected to a 50% tail transection and resuscitated 15 minutes later with 1:1 DCLHb, 3:1 lactated Ringer's solution (LR), 1:1 hypertonic saline (7.5% HTS), or 1:1 human serum albumin (8.3% HSA) based on initial volume of blood loss (average 4.7 +/- 0.3 mL/kg). An unresuscitated group served as a control. Cumulative blood loss was measured at 5 hours postresuscitation. By 15 minutes after tail transection, mean arterial pressure (MAP) decreased 19.2 +/- 3.8 mm Hg from the baseline value (102 +/- 5 mm Hg). The DCLHb solution restored and maintained MAP and subcutaneous tissue oxygen tension at baseline values better than all other resuscitative fluids. Although blood loss in DCLHb-treated animals was greater than in unresuscitated animals, it was no different from other resuscitative fluids and less than with HSA. There was no difference in 24-hour survival between all treatment groups. In conclusion, DCLHb elevates MAP but does not exacerbate blood loss or compromise tissue oxygen delivery compared with other resuscitative fluids in this model of uncontrolled hemorrhage.     

Psychological stress does not affect plasma catecholamines in subjects with cardiovascular disorder

Whereas the effects of cardiac transplantation on the catecholamine response to physical exercise have been studied previously, the impact on psychological stress is unknown. Here, the arterial catecholamine response to the Stroop test of patients with an orthotopic heart transplant (OHT) was compared with that in subjects who had received a coronary artery bypass graft (CABG) or who were in heart failure and destined for a heart transplant (HF). Subjects were tested whilst sitting and their usual drug therapy was maintained. The Stroop test increased subjects' subjective tension but did not affect arterial concentrations of adrenaline or noradrenaline in any group of subjects. Also, the concentration of both catecholamines was significantly higher in OHT and CABG subjects than in the HF group, but their relative concentration was unaffected by cardiovascular status or stress. It is concluded that the absolute concentrations of arterial catecholamines, but not their relative concentrations, depend on clinical status. Moreover, under these test conditions, subjects with a history of cardiovascular disorder do not show the normal catecholamine response to psychological stress.     

The role of advanced practice nurses in surgical services

Many of the changes in health care delivery systems have had detrimental effects on nurses; however, some of these same changes are providing opportunities for acute care advanced practice nurses. Advanced practice nurses ensure continuity of care, manage use of resources, and coordinate patient services, which often results in cost savings. This article describes how advanced practice nurses in the department of surgery at Memorial Health Care, Worcester, Mass, are caring for surgical patients with acute and chronic conditions.