Right ventricular function in adults with pulmonary hypertension with and without atrial septal defect

Using equilibrium (gated) radionuclide ventriculography, right ventricular (RV) function was studied in 22 adults with pulmonary hypertension and in 16 patients without evidence of cardiac disease. To assess the effect of volume overload on RV performance in pulmonary hypertension, RV ejection fractions were compared in patients with and without left-to-right shunts due to atrial septal defect (ASD). In addition, the effect of ASD repair on RV function was examined. In 14 patients with pulmonary hypertension without RV volume overload (group I), the RV ejection fraction (0.35 ± 0.11, mean ± standard deviation [SD]) was significantly lower than in the normal group (0.47 ± 0.11, p < 0.01). In 8 patients with left-to-right shunts due to ASD (group II) and with RV systolic pressures similar to those in group I, the mean RV ejection fraction (0.53 ± 0.15) was normal and was significantly higher than in group I (p < 0.01). Right ventricular end-diastolic volumes, estimated from combined radionuclide and hemodynamic data, were higher (p < 0.01) in group II patients (171 ± 70 ml/m²) than in group I patients (70 ± 13 ml/m²). In 5 patients who underwent isolated shunt repair, mean RV ejection fraction decreased postoperatively from 0.57 ± 0.17 to 0.40 ± 0.12 (p < 0.05). It is concluded that (1) pulmonary hypertension frequently causes a decrease in RV systolic function due to abnormal afterload; (2) in patients with RV volume overload due to left-to-right shunt, systolic function, as measured by the ejection fraction, remains normal despite pulmonary hypertension, possibly through the Starling mechanism; and (3) RV systolic function often decreases after repair of an ASD.     

Decreased expression of phospholipase C-beta 2 isozyme in human platelets with impaired function

Platelets from a patient with a mild inherited bleeding disorder and abnormal platelet aggregation and secretion show reduced generation of inositol 1,4,5-trisphosphate, mobilization of intracellular Ca2+, and phosphorylation of pleckstrin in response to several G protein mediated agonists, suggesting a possible defect at the level of phospholipase C (PLC) activation (see accompanying report). A procedure was developed that allows quantitation of platelet PLC isozymes. After fractionation of platelet extracts by high-performance liquid chromatography, 7 out of 10 known PLC isoforms were detected by immunoblot analysis. The amount of these isoforms in normal platelets decreased in the order PLC- gamma 2 > PLC-beta 2 > PLC-beta 3 > PLC-beta 1 > PLC-gamma 1 > PLC- delta 1 > PLC-beta 4. Compared with normal platelets, platelets from the patient contained approximately one-third the amount of PLC-beta 2, whereas PLC-beta 4 was increased threefold. These results suggest that the impaired platelet function in the patient in response to multiple G protein mediated agonists is attributable to a deficiency of PLC-beta 2. They document for the first time a specific PLC isozyme deficiency in human platelets and provide an unique opportunity to understand the role of different PLC isozymes in normal platelet function.     

Human platelet signaling defect characterized by impaired production of inositol-1,4,5-triphosphate and phosphatidic acid and diminished Pleckstrin phosphorylation: evidence for defective phospholipase C activation

Signal transduction on platelet activation involves phosphoinositide- specific phospholipase C (PLC)-mediated hydrolysis of phosphatidylinositides and formation of inositol-1,4,5-triphosphate [I(1,4,5)P3], which mediates Ca2+ mobilization, and diacylglycerol (DG), which activates protein kinase C (PKC) to phosphorylate a 47-kD protein (Pleckstrin). We studied these events in two related patients previously reported (Blood 74:664, 1989) to have abnormal aggregation and 14C-serotonin secretion, and impaired intracellular Ca2+ mobilization in response to several agonists. Thrombin-induced I(1,4,5)P3 and phosphatidic acid formation were diminished. Pleckstrin phosphorylation was impaired on activation with thrombin, platelet- activating factor, and ionophore A23187, but was normal with PKC activator 1,2-dioctonyl-sn-glycerol (DiC8). Ca2+ mobilization induced by guanosine triphosphate (GTP) analog guanosine 5'-0-(3 thiotriphosphate) (GTP gamma S) was diminished. Pretreatment with either A23187 or DiC8 did not correct the impaired adenine diphosphate- induced secretion; however, upon stimulation with A23187 plus DiC8, pleckstrin phosphorylation and secretion were normal, indicating that both PKC activation and Ca2+ mobilization are essential for normal secretion. We conclude that these patients have a unique inherited platelet defect in formation of two key intracellular mediators [I(1,4,5)P3 and DG] and in the responses mediated by them due to a defect in postreceptor mechanisms of PLC activation.     

Usefulness of Transesophageal Echocardiography in Diagnosing and Guiding Correct Placement of a Right Ventricular Assist Device Malpositioned in the Left Atrium

In this report, we describe how transesophageal echocardiography was used not only to diagnose incorrect cannula position of a right ventricular assist device in the left atrium through a patent foramen ovale, but also to guide and to confirm correct cannula placement.     

Life-expectancy projection by modelling and computer simulation (UKPDS 46)

A method is described for estimating the life-expectancy of cohorts of type 2 diabetic patients, based on computer simulation from a parametric model. The method can be used where non-parametric methods, such as the Kaplan-Meier estimate, fail due to lack of the data. The simulation algorithm combines observed and modelled information to estimate the life-expectancy implications of event rates observed within a study. The use of bootstrap methods to estimate confidence intervals is discussed. The methods are illustrated with results that have been previously published, without derivation, in a health economic analysis of tight blood pressure (BP) control in the UK Prospective Diabetes Study (UKPDS), and the application to other health economic analyses of UKPDS data is discussed.     

Acquired granular pool defect in stored platelets

Platelets stored as concentrates (PC) for 72 h at 22 degrees C develop a functional defect. Alterations in adenine nucleotides of platelets have been shown to affect platelet function. Adenine nucleotide content of platelets was measured before and after storage and a decrease of 27.1 /+- 1.7% (mean /+- SE) in ATP and 39.1 /+- 2.6% in ADP were found in 34 PC stored with final volume of 50 ml. In 11 PC with 30 ml volume. ATP and ADP decreased by 39.4 /+- 3.2% and 49.4 /+- 2.1%, respectively. The mean ATP to ADP ratio of stored platelets was significantly higher than of fresh platelets in both groups, suggesting a relatively greater decrease in granular than metabolic pool nucleotides. Levels of low affinity platelet factor 4 measured by radioimmunoassay in plasma from 0.86 /+- 0.08 microgram/ml in the fresh PC to 8.59 /+- 0.39 microgram/ml in stored PC, indicating a concomitant alpha-granular secretion. Labeling of metabolic pool with 14C-adenine revealed a mean decrease in the adenylate energy charge of 2.0 /+- 0.4% in 12 of 16 stored PC, with a lower ATP and higher hypoxanthine labeling in stored as compared to fresh platelets. These observations suggest that stored platelets develop an acquired defect in both dense and alpha granules and in their ability to maintain ATP homeostasis.     

Chaos and stability of the solar system

Over the last two decades, there has come about a recognition that chaotic dynamics is pervasive in the solar system. We now understand that the orbits of small members of the solar system-asteroids, comets, and interplanetary dust-are chaotic and undergo large changes on geological time scales. Are the major planets' orbits also chaotic? The answer is not straightforward, and the subtleties have prompted new questions.     

Anterior cruciate ligament injury about 20 years post‐treatment: A kinematic analysis of one‐leg hop

Reduced dynamic knee stability, often evaluated with one‐leg hops (OLHs), is reported after anterior cruciate ligament (ACL) injury. This may lead to long‐standing altered movement patterns, which are less investigated. 3D kinematics during OLH were explored in 70 persons 23 ± 2 years after ACL injury; 33 were treated with physiotherapy in combination with ACL reconstruction (ACL_R) and 37 with physiotherapy alone (ACL_PT). Comparisons were made to 33 matched controls. We analyzed (a) maximal knee joint angles and range of motion (flexion, abduction, rotation); (b) medio‐lateral position of the center of mass (COM) in relation to knee and ankle joint centers, during take‐off and landing phases. Unlike controls, ACL‐injured displayed leg asymmetries: less knee flexion and less internal rotation at take‐off and landing and more lateral COM related to knee and ankle joint of the injured leg at landing. Compared to controls, ACL_R had larger external rotation of the injured leg at landing. ACL_PT showed less knee flexion and larger external rotation at take‐off and landing, and larger knee abduction at Landing. COM was more medial in relation to the knee at take‐off and less laterally placed relative to the ankle at landing. ACL injury results in long‐term kinematic alterations during OLH, which are less evident for ACL_R.     

Improving postoperative pain management in subpectoral tissue expander implant reconstruction of the breast using an elastomeric pump

IntroductionPostoperative pain after breast surgery is one of the major factors contributing to delay in mobilisation and prolonged hospital stay. A retrospective analysis was performed of patients undergoing skin sparing mastectomy and insertion of a subpectoral implant. The aim was to determine whether the use of an elastomeric local anaesthetic pump improved pain control and length of stay.MethodsTwenty-five consecutive patients undergoing the above procedure were sited with an elastomeric local anaesthetic infusion pump intraoperatively, in addition to standard regular and pro re nata analgesia. The control group comprised 25 patients undergoing the same procedure in the same year who received standard analgesia alone. Visual analogue scale scores were recorded for the duration of inpatient stay, as was any further analgesic requirement.ResultsThe median age was 51 years (range: 26–75 years) in the intervention group and 50 years (range: 28–70 years) in the control group. The mean visual analogue scale score was 0.28 (standard deviation [SD]: 0.61) at 24 hours for the intervention group and 1.84 (SD: 0.37) for the control group (p<0.0001). The mean length of stay was 1.8 days (SD: 0.71 days) for the intervention group and 2.28 days (SD: 0.94 days) for the control group (p=0.15). There were no complications involving catheter placement, leakage or toxicity relating to use of the local anaesthetic.ConclusionsThere was significantly reduced pain with the use of the local anaesthetic infusion pump. The elastomeric pump is a step towards enhanced patient recovery after breast surgery in the case of skin sparing mastectomy and subpectoral tissue expander reconstruction.