LC-MS/MS measurement of endogenous oxytocin in the posterior pituitary and CSF of macaques: A pilot study.

Oxytocin (OT) is a nanopeptide released into systemic circulation via the posterior pituitary (peripheral) and into the central nervous system via widespread OTergic pathways (central). Central OT plays a significant role in variety of functions from social and executive cognition to immune regulation. Many ongoing studies explore its therapeutic potential for variety of neuropsychiatric disorders. Measures of peripheral OT levels are most frequently used as an indicator of its concentration in the central nervous system in humans and animal models. In this study, LC-MS/MS was used to measure OT in pituitary samples collected from adult male macaque monkeys in order to explore the correlation between individual levels of OT in the CSF (central) and pituitary (peripheral). We quantified individual differences in the levels of OT in the pituitaries (44-151 ng/mg) and CSF (41-66 pg/mL) of these monkeys. A positive correlation between these two measures was identified. These preliminary results allow for future analyses to determine whether LC-MS/MS measures of peripheral OT can be used as markers of OT levels in the brain of nonhuman primates that serve as valuable models for many human neuropsychiatric disorders.

Labeled oxytocin administered via the intranasal route reaches the brain in rhesus macaques.

Oxytocin may have promise as a treatment for neuropsychiatric disorders. Its therapeutic effect may depend on its ability to enter the brain and bind to the oxytocin receptor. To date, the brain tissue penetrance of intranasal oxytocin has not been demonstrated. In this nonhuman primate study, we administer deuterated oxytocin intranasally and intravenously to rhesus macaques and measure, with mass spectrometry, concentrations of labeled (exogenously administered) and endogenous oxytocin in 12 brain regions two hours after oxytocin administration. Labeled oxytocin is quantified after intranasal (not intravenous) administration in brain regions (orbitofrontal cortex, striatum, brainstem, and thalamus) that lie in the trajectories of the olfactory and trigeminal nerves. These results suggest that intranasal administration bypasses the blood-brain barrier, delivering oxytocin to specific brain regions, such as the striatum, where oxytocin acts to impact motivated behaviors. Further, high concentrations of endogenous oxytocin are in regions that overlap with projection fields of oxytocinergic neurons.

Investigation of an outbreak of vancomycin-resistant Enterococcus faecium in a low prevalence university hospital.

BACKGROUND: Until 1995, there were no cases of vancomycin resistant enterococcus (VRE) identified at our university hospital. From May 1995 to August 1996, we investigated a cluster of 10 cases of phenotypic class Van B Enterococcus faecium. METHODS: Patients were matched with controls who were on the same unit for at least 7 days prior to the case developing VRE. Control patients were age and sex matched if possible, and had duration of hospitalization at least as long as the number of days it took the patient to become VRE positive. We analyzed 16 independent risk factors using Epi-info version 6. Environmental cultures were obtained in the MICU where 5 of the patients were located. All 10 patient isolates and environmental isolates were analyzed by pulsed field gel electrophoresis (PFGE). RESULTS: PFGE confirmed the genetic relatedness of all 10 patient isolates and environmental isolates. The VRE-positive group was more likely to be immunosuppressed and to have exposure to 3 physicians. In the MICU, significant, P < 0.05) risk factors for VRE were higher Apache scores, location adjacent to a VRE case, duration of vancomycin and amino-glycoside use, duration of invasive catheter use, and diarrhea. Among the VRE-positive environmental cultures was a blood pressure cuff wash that was used on several patients. CONCLUSION: We hypothesize that a VRE strain was introduced into our hospital environment and was spread by personnel or contaminated equipment. As a consequence of this study, a hospital-wide VRE policy was implemented.

New computer-based tools for empiric antibiotic decision support.

Since 1995 we have been developing a decision-support model, called Q-ID, which uses a series of infectious disease knowledge bases to make recommendations for empirical treatment or to check the appropriateness of current antibiotic therapy. From disease manifestations and risk factors, a differential diagnosis for the patient is generated by a diagnostic medical expert system. The resulting probability of each: disease is multiplied by the expected benefit in improved mortality and morbidity from optimal antibiotic treatment of each disease. To generate empirical treatment recommendations, site-specific data on sensitivity to antibiotics of each organism is used as an estimate of the likelihood of achieving maximum benefit for each disease on the patient's differential. Combining this data with drug and patient specific factors, the model recommends the antibiotic(s) most likely to produce the optimal benefit in this patient with the least risk and expense. In this paper the model is described, excerpts from each of the knowledge bases are presented, and performance of the model in a real case is shown for illustration.

Bacillus licheniformis bacteremia: five cases associated with indwelling central venous catheters.

Bacillus species are being more frequently recognized as pathogens in immunocompromised hosts or in patients with cancer and central venous catheters. Only nine cases of Bacillus licheniformis infection have been reported in the English-language literature since 1966. In a retrospective study we describe six patients and 17 episodes of B. licheniformis bacteremia over a 5-year span. All six patients had either a Hickman or a Broviac catheter in place for more than 3 months. Five of the six patients had multiple clinically significant episodes of bacteremia due to B. licheniformis. The six patients ranged in age from 4 years to 62 years. Two patients had leukemia or lymphoma and three patients had solid tumors, but only one patient was neutropenic. No deaths were related to B. licheniformis bacteremia. B. licheniformis should be considered as a potential pathogen in immunocompromised patients, especially when bacteremia is associated with the presence of long-term central venous catheters. Mortality due to B. licheniformis bacteremia is low, but recurrent bacteremia due to this organism causes significant morbidity and usually necessitates removal of the catheter.

Decline in inducibility of sustained ventricular tachycardia from two to twenty weeks after acute myocardial infarction.

To determine temporal evolution of sustained ventricular arrhythmias inducible after acute myocardial infarction (AMI), serial programmed ventricular stimulation (PVS) was performed in 27 patients 15 +/- 4 and 150 +/- 28 days after AMI. These patients did not have worsening of congestive heart failure or angina, coronary artery bypass surgery or spontaneous sustained ventricular tachycardia (VT) in the period between 2 PVS studies. During initial PVS, sustained VT or ventricular fibrillation (VF) was inducible in 17 patients (group I) and was not inducible in 10 (group II). Late PVS in group I induced sustained VT or VF in 8 patients (47%) and nonsustained VT or no VT in 9 (53%). A decrease in late inducibility of sustained VT/VF was greater for arrhythmias induced during initial PVS by triple extrastimuli and burst pacing than for those induced by double extrastimuli (88% vs 25%, p less than 0.04), but appeared to be unrelated to the morphologic characteristics or cycle length of the initially induced sustained VT or VF and to other clinical, hemodynamic or angiographic variables. During late PVS in 10 group II patients, sustained VT or VF remained noninducible in 9 (90% concordance); in 1 patient sustained VT was induced. During a mean follow-up of 14 +/- 5 months since late PVS, none of 27 patients had spontaneous sustained VT and 2 patients in group I died suddenly.(ABSTRACT TRUNCATED AT 250 WORDS)

The visual-preference technique in infancy: effect of number of stimuli presented upon experimental outcome.

To examine the effects of the number of stimuli presented when the visual-preference technique is used to measure attention in infancy, 2- and 4-month-old infants were randomly assigned to 1 of 3 experimental conditions. In the first condition, infants were shown 3 different checkerboards using the single-stimulus visual-preference methodology; in the second condition, 4 checkerboards; and in the third condition, 5 checkerboards. Infants in both the 3- and 4-pattern conditions were able to order the patterns as predicted by scaling theory. However, there was a significant decrease in the number of infants in the 5-pattern condition who could do so. The results are discussed in terms of both their methodological and theoretical implications.

Visual complexity in infancy: contour or numerosity?

To examine the relationship between visual attention in infancy and the stimulus variables of contour and numerosity, 2- and 4-month-old infants were placed in 3 experimental conditions. In the first condition, the patterns shown to the infants varied in amount of contour but had an equal number of elements; in the second, they varied in numerosity but had an equal amount of contour; and in the third, the patterns varied in both numerosity and contour. The results showed that contour and numerosity acting in tandem are responsible for the age-complexity shift observed in previous investigations of infant attention.

Differential responding as a function of auditory stimulus intensity without differential reinforcement.

Two groups of four rats each were trained to bar press on a variable-interval 2-min schedule. During training, either 3, 5, or 9 auditory stimuli of various intensities were randomly presented. A direct relationship between stimulus intensity and rate of responding was obtained, but it was more consistent in the group trained initially with three stimuli than for the group that started with nine stimuli. The results are related to the concept of stimulus intensity dynamism and the necessary conditions for the acquisition of stimulus control.

Auditory discrimination: a three-variable analysis of intensity effects.

The acquisition of auditory intensity discriminations in rats trained on multiple variable-interval extinction schedules was studied as a function of some of the variables that contribute to the speed of development of differential responding and the final level attained. The effects of three variables were isolated and studied in detail: (1) the decibel difference between the discriminative stimuli (intensity difference); (2) the intensity relationship between the stimuli (relative intensity); and (3) the position of the stimuli on the intensity continuum (absolute intensity). Each of the three variables generated orderly relationships and interacted with one another to produce complex effects upon differential responding.

Antecedent reinforcement contingencies in the stimulus control of an auditory discrimination.

In order to assess possible confounding of discriminative stimulus effects with those produced by the reinforcing stimulus, three groups of four rats each were trained for 45 hr on a variable-interval 1-min reinforcement program. Two groups were run on a multiple variable-interval extinction schedule in which the reinforcement stimulus (S(D)) and the nonreinforcement stimulus (S(Delta)) were two intensities of a 4-kHz (cps) tone separated by 40 or 10 db. The third group was run on a mixed schedule with a single intensity constantly present. The mixed-schedule animals showed no discrimination of the reinforcement program. Under the multiple schedule, the highest S(Delta) rates were obtained after S(D) intervals, regardless of the reinforcement availability in the S(D) interval. These local rate variations in S(Delta) were small in proportion to those produced by the S(D)versus S(Delta) intensities.