Adding precise nanoliter volume capabilities to liquid-handling automation for compound screening experimentation.

Miniaturizing experimental sample volumes to the nanoliter volume range is one of the most economical ways to perform mid- and high-throughput compound screening experiments. Existing automation platforms for nanoliter fluid handling can be bulky, expensive, and require periodic calibration to provide consistent liquid dispensing. In addition, even with frequent calibration, significant instrument-to-instrument variation in low-volume dispensing can occur between different instrument platforms. Many of these issues can be addressed by the use of PocketTips. PocketTips are tips with a defined internal pocket designed to hold specific nanoliter volumes of compound dissolved in dimethylsulfoxide. Although the overall liquid-handling process with PocketTips uses the aspirate/dispense features of the specific liquid-handling device being used, the dispensed nanoliter volume is solely based on the dimensions of the pocket of the PocketTip and thus, the liquid-handling device itself need not have nanoliter dispensing capabilities. In this report, we demonstrate the performance of PocketTips on different automation platforms. In addition, we used a cell-based ß-lactamase reporter assay system to demonstrate that compound delivery by PocketTips compares favorably with a standard compound addition technique.

QT dispersion in infants with apparent life-threatening events syndrome.

Apparent life-threatening event (ALTE) is a term used to define an event of unknown cause after an infant is found limp, cyanotic, bradycardic, and/or requires resuscitation. Eight to 15% of children with ALTE die of sudden infant death syndrome. Obstructive sleep apnea, bradycardia, gastroesophageal reflux, and laryngotracheal abnormalities are frequently associated with ALTE. Wide QT dispersion is associated with sudden death in heart failure and increased risk of ventricular fibrillation in acute myocardial infarction. Here, we assess QT dispersion in infants with ALTE and its correlation to clinical and electrocardiographic indices. The study included eighty nine infants (age 2.14 +/- 1.8 months, 46 males and 43 females) referred with ALTE to the pediatric emergency room and 18 controls (age 2.77 +/- 2.2 months) who underwent electrocardiogram assessment of QTmin, QTmax, QT dispersion (QT-D), and as well as QTmin, QTmax, and QT-D corrected for heart rate (QTcmin, QTcmax, QTC-D, respectively). All infants were referred at the usual diagnostic tests-the gastroesophageal reflux test, apnea monitoring, Holter ECG monitoring, electroencephalogram, and Doppler echocardiography. QT-D, QTc-D, and QTc-min were significantly greater in the ALTE group (p < 0.01). Greater QTc-D was found in males compared to females (p < 0.001). QT-D and QTc-D showed little or no correlation with age of infant or positivity of diagnostic tests. QTc has been found by multiple regression analysis to be the independent variable with the greatest impact on QTc-D (beta = -0.68, p < 0.001).

Empirical study on an inpatient psychogeriatric unit: biological treatment in patients with depressive illness.

A study of 112 psychogeriatric admissions identified seventy patients sufficiently depressed to require biologic treatment. Twenty-four patients completed a primary treatment trial with TCA's and seventeen with ECT. ECT proved to be more effective, (81.4% versus 62.5%), even though overtly psychotic and medically unstable patients preferentially received this treatment. The ECT response rate is comparable to other reports of its efficacy in the treatment of delusional depression. A higher morbidity rate of 27 percent in the TCA-treated group was observed. The authors conclude that ECT is a highly beneficial treatment modality for the carefully selected elderly patient with major depressive illness. They found that a higher number of ECT treatments than expected were required in their psychogeriatric patients, but did not find a higher morbidity other than increased confusion with more treatments. Careful repeated assessment of response to treatment combined with readiness for assertiveness, in spite of the advanced age of the patient, seem to be indicated. Conversely, excessive hesitance when caring for the elderly patient may lead to a premature termination of treatment, causing the patient to remain in a chronic mentally compromised state.

Empirical study on an inpatient psychogeriatric unit: diagnostic complexities.

Retrospective analysis of the phenomenology and the diagnostic process of 112 consecutive psychogeriatric admissions revealed the majority (61%) were suffering from affective illness. In 53 percent, the reason for admission was depression and 8 percent were in the manic phase of a bipolar disorder. Dementia was diagnosed in 32 percent, with a third of these patients having an associated depression. The remaining 7 percent had a schizophrenic or paranoid disorder. Ninety-two patients (82%) were found to have at least one coexisting medical and/or neurological disorder(s) requiring early intervention. Associated acute organic brain syndromes were common (18%) and often difficult to diagnose. The AOBS was at times the only sign of an underlying active medical condition. The diagnosis of this condition often required serial observations for fluctuations in mental status accompanied by appropriate laboratory investigations. These findings underscore the complexity of the diagnostic process in psychogeriatric patients suffering from concomitant medical and psychiatric disorders. High index of awareness is recommended for the need to search for coexisting delirium, which may be masked at times by the major psychiatric disorder.

Late-onset delusional depression: a distinct clinical entity?

A comparison of the prevalence of delusions was made between early-onset (less than age 60) and late-onset (greater than or equal to age 60) primary endogenous depressives. Depressives with onset after age 60 had delusions more frequently than those with earlier onset. Fourteen of 16 late-onset depressives but only 5 of 18 earlier onset patients were delusional (p less than .005). Within the early onset group, those with delusions tended to be older at index episode than those without delusions (.05 less than p less than .10). This correlation between age of onset of depression and the tendency to be delusional is of heuristic and possibly pathogenetic interest.

Psychiatric reactions during tricyclic treatment of the elderly reconsidered.

In a prospective study of all geriatric patients treated with tricyclic antidepressants over an 18-month period, a lower incidence of adverse psychiatric reactions than literature based on chart reviews has suggested was found. In only three of the 43 patients studied (7%) did a picture consistent with toxic delirium develop. None of the seven patients with senile dementia of the Alzheimer type suffered an adverse psychiatric reaction despite having achieved therapeutic blood levels of medication. Difficulties in determining the type and pathogenesis of untoward reactions that do occur as a source of error in establishing frequency are emphasized. The relationship of such reactions to the neurobiology of aging, the central anticholinergic syndrome, and the putative role of acetylcholine in contributing to the clinical picture of senile dementia of the Alzheimer type is discussed.