Dopamine receptor DRD3 codes for trait aggression as Mendelian recessive.

The dopamine receptor gene DRD3 and in particular the single nucleotide polymorphism Ser9Gly has been extensively investigated and found to have potential association with a wide variety of conditions. These include essential tremor, unipolar and bipolar depression, as well as a loose association with schizophrenia. Evaluation of (1) these known associations with DRD3, (2) the recent finding of Costas and colleagues that a haplotype containing Ser-9 is associated with protection from schizophrenia, and (3) an extant trait model of personality, leads to the hypothesis that an allele DRD3/Ser codes for trait aggression by Mendelian recessive inheritance. The implications of this hypothesis are that (1) DRD3 is a pleiotropic gene having allelic polymorphism related to both behavior and disease, and (2) models of personality based on genetic traits hold promise. In the area of schizophrenia, the hypothesis implies that schizophrenic patients can be divided into two broad classes: those having genotype DRD3/Ser/Ser and those who lack this homozygosity. The hypothesis of the association of DRD3 with trait aggression could be readily evaluated by testing groups of healthy individuals by personality inventory focused on aggression and by biochemical assay of neurotransmitter levels.

Management of postcardiotomy hypertension by microcomputer-controlled administration of sodium nitroprusside.

Manual administration of sodium nitroprusside in patients who have undergone cardiac operations can be associated with wide swings in mean systemic arterial pressure. Moreover, it is necessary for constant attention to be paid in order to minimize these potentially catastrophic arterial pressure changes. A microcomputer-based controller was constructed in the belief that it might improve the accuracy of systemic arterial pressure control as well as relieve the clinical staff of a time-consuming task. Comparison was made of the effectiveness of manual control versus computer control of sodium nitroprusside infusion in two groups of patients with similar clinical characteristics. In the manual control group the mean systemic arterial pressure could be maintained within 5 mm Hg of the target pressure only half (52%) of the time. In the computer-controlled group the mean systemic arterial pressure was maintained within 5 mm Hg of the target pressure 94% of the time (p less than 0.005). Thus, computerized control of sodium nitroprusside infusion eliminated the need for an intensive care unit nurse to be "locked into" the task of making frequent adjustments of infusion rate. Of even greater importance, control of mean systemic arterial pressure was more precise.

Oxygen wash-in method for monitoring functional residual capacity.

Atelectasis, pulmonary edema, fibrosis, pneumothorax, and mucous plug airway obstruction all result in reduced lung volume. The oxygen (O2) wash-in method provides a way to monitor routinely the functional residual capacity (FRC) in the ICU without disconnecting the patient from the ventilator and without additional personnel or instrumentation. This method is a modification of an open-circuit nitrogen (N2) wash-out procedure and requires a computer-based respiratory monitoring system with a fast response O2 analyzer and respiratory flowmeter. FRC is computed after a 20% or greater change in the ventilator FIO2 setting. The accuracy and reproducibility of the method were evaluated using artificial lungs, normal subjects, and postcardiac surgery patients. FRC estimates by O2 wash-in and helium dilution were highly correlated, with r = 0.97 and a regression slope and zero intercept of 1.06 and -0.13, respectively. The FRC difference between 23 repeated trials in 18 postcardiac surgery patients was 70 +/- 160 ml (mean +/- SD).

Improved detection of adverse cardiovascular trends with the use of a two-variable computer alarm.

Assessment of preload and afterload of patients having undergone cardiac surgery is commonly done by the monitoring of mean arterial and left atrial pressures (MAP, LAP). In this ICU, a central computer has been in use to sample routinely the MAP and LAP every 10 min. This computer has been programmed to activate an alarm sequence if a routinely acquired value of MAP or LAP is found to be outside of preset ("trend") limits. The computer then initiates a repeat mode of sampling of MAP and LAP as 1 min intervals. If three consecutive repeated values of either variable remain outside of the preset limits, then the following occurs: 1) a plot of the trend of MAP and LAP over the preceding 3 h appears on the bedside video monitor, 2) a bedside light and audible chime are activated, and 3) the bedside keyboard is locked out to other functions until the alarm is reset. A study showed that this system can detect adverse trends appropriately, averaging only 1-2 false alarms/patient per 8-h shift.

Extracorporeal model for study of factors affecting thrombus formation.

Factors determining thrombus formation on a foreign surface were studied with the use of plastic flow chambers introduced into extracorporeal shunts. Silicone rubber shunts, joining the carotid artery and jugular vein, were implanted in dogs and remained patent for several weeks. The flow chamber geometry consisted of a 4.8 mm diameter straight tube having a 3.2 X 3.2 mm circumferential cavity in the wall. Chambers were introduced sequentially into the shunts for exposure times of 10 to 30 minutes and regulated blood flow rates of 100 to 400 ml/min. The dry weight of thrombus accumulated in the chamber (5 to 50 mg) was found to increase with exposure time up to 20 minutes and to decrease with increasing flow rate. Various components of the process of thrombus formation were altered by the administration of acetylsalicylic acid, heparin and lysozyme, used alone and in pairs. Heparin was found to be the most effective antithrombotic agent, dry weights of accumulated thrombus being on the order of 50 percent lower when compared to control values. The efficacy of heparin was found to be unaffected by the presence of aspirin and lysozyme, which themselves were not effective antithrombotic agents under the conditions of these experiments. The technique described here may provide a useful animal model for studying the influence of blood flow and different biomaterials on thrombus formation.