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Biomedical subjects

J L Falk

Publications and source records attributed to J L Falk.

At least 19 recordsLinked to original sources
PubMed1998

Schedule-induced polydipsic consumption of hypertonic NaCl solutions: effects of chlordiazepoxide.

Rats were exposed to daily, 3-h sessions of schedule-induced polydipsia (SIP) in which either water, hypertonic NaCl solution (1.5% or 2.2%), or concurrent water and 1.5% NaCl were available. Each condition was in effect for several, consecutive weeks. Presession subcutaneous injections of chlordiazepoxide (CDZP) produced dose-related increases in the polydipsic ingestion of both NaCl solutions but had smaller and less certain effects on water consumption. Under the concurrent-fluid presentation condition, CDZP primarily increased NaCl solution consumption. Conditions generating SIP may function to attenuate what might be viewed as the punishing effects of ingesting highly hypertonic NaCl solutions, thereby permitting the chronic self-administration of large, daily amounts. Like many benzodiazepines, CDZP can attenuate the effects of punishment and thereby also increase NaCl solution ingestion. The two sources of punishment attenuation may be additive, with both differentially effecting greater increases in hypertonic NaCl ingestion, compared to water, when both fluids are presented concurrently.

Animals↗
PubMed1997

Establishing preference for oral cocaine without an associative history with a reinforcer.

Using schedule-induced polydipsia (SIP), a stable, oral, preference for cocaine solution to water presented concurrently can be established by first presenting cocaine in a preferred vehicle, and subsequently fading the vehicle to water. The present study showed that rats exposed to a history of choosing 0.48 mg/ml cocaine in preference to concentrated lidocaine (2 mg/ml) under SIP conditions subsequently maintained this preference when the lidocaine concentration was progressively decreased to zero (water). Preference for lidocaine was tested by fixing it at 0.38 mg/ml (equimolar with 0.48 mg/ml cocaine) while subsequently increasing cocaine from 0.48 mg/ml to 2.5 mg/ml. Lidocaine preference did not occur, rather, preference for concentrated cocaine persisted. The results suggest that the avoidance of lidocaine solution may force the discrimination of the relation between high oral cocaine intake and its reinforcing effects, thereby instituting a stable preference for cocaine.

Administration, Oral↗
PubMed1997

Independent interaction of alprazolam and caffeine under chronic dose regimens on differential reinforcement of low-rate (DRL 45-s) performance.

In previous research, we found an independent interaction of alprazolam and caffeine in rats under acute dose regimens using two measures (reinforcement rate and shorter-response rate) of a differential reinforcement of low rate performance (DRL 45-s) in 3-h sessions. Applying the same behavioral endpoints, the present study investigated the alprazolam-caffeine interaction under chronic dose regimens. Both drugs were administered by the oral route. Acute alprazolam and caffeine dose-response curves (DRCs) were characterized and were then used to determine the maintenance dose for the respective chronic dose regimens. Both drugs decreased the reinforcement rate and increased the shorter-response rate in a dose-related fashion. An alprazolam DRC also was determined during chronic-caffeine, chronic-alprazolam, and concurrent chronic-caffeine-alprazolam dose regimens. Complete tolerance to caffeine-induced rate changes was observed on the second day. Incomplete tolerance occurred only at higher alprazolam doses (7-12.5 mg/kg). Cross tolerance was not found between alprazolam and caffeine. Upon discontinuation of both drugs, performance progressively returned to baseline. The four alprazolam DRCs as well as the effect-time profiles demonstrated that caffeine altered neither the magnitudes nor the patterns of alprazolam effects on the two rates under chronic dose regimens. The Pöch DRC method further confirmed the independent interaction of alprazolam and caffeine. Thus, the independence of the interaction held for both the acute and chronic dose regimens despite the development of tolerance in the latter regimens.

Alprazolam↗
PubMed1997

Schedule induction conditions not only exaggerate intake but also enhance drug solution choice.

In previous research, rats exposed to daily, 3 h sessions of schedule-induced polydipsia (SIP) self-administered high doses of cocaine orally. However, a strong and durable preference for cocaine solution to water requires training in addition to mere oral self-administration exposure. If cocaine is dissolved in a preferred vehicle solution, and the vehicle is subsequently faded to water, then a strong preference for cocaine remains. A similar preference can be instituted for lidocaine solution. Such preferences may develop because the gustatory property of a drug becomes associated with the preferred vehicle and remains to function as a durable conditioned reinforcer after vehicle fading. To determine if drug preference is solely a function of this posited conditioning mechanism, or whether it also depends upon the SIP condition, rats were exposed to daily, 3 h sessions of single-ration feeding, rather than the SIP condition. A preferred vehicle (glucose/saccharin solution) was slowly faded from a 0.19 mg/ml lidocaine solution, which was presented concurrently with a choice for water. Although a preference for lidocaine solution to water could be generated, it occurred for only 5 out of 9 rats, and the preference was relatively unstable. By contrast, in two previous studies using SIP, 26 out of 27 rats maintained a preference for lidocaine solution. Thus, SIP not only exaggerates the amount of drug solution ingested but also contributes to the fixation of the associative drug solution choice.

Animals↗
PubMed1997

Submersion injuries in children and adults.

Drowning and near drowning remain a common cause of childhood death and disability. Toddlers aged one through four drown in private swimming pools. Submersions greater than 10 minutes and lack of CPR at the scene or the need for greater than 20 minutes of resuscitation portends a poor prognosis. Management of respiratory failure without neurologic impairment has the most successful outcome. Prevention of drowning morbidity is dependent on constant parental supervision, and immediate and expert CPR.

Adolescent↗
PubMed1997

Cranial computed tomography in the emergency evaluation of adult patients without a recent history of head trauma: a prospective analysis.

OBJECTIVES: To examine the pattern of nontrauma cranial CT use in an urban ED, to identify the rate of significant CT abnormalities in this setting, and to develop criteria for restricting the ordering of CT scans. METHODS: A prospective, observational study of a case series of adults who underwent cranial CT scanning for nontraumatic cases was performed at the EDs of an urban teaching hospital and an affiliated community hospital with a combined annual census of 110,000. Clinically significant CT scans were defined as: 1) acute stroke, 2) CNS malignancy, 3) acute hydrocephalus, 4) intracranial bleeding, or 5) intracranial infection. X2 recursive partitioning was used to derive a decision rule to restrict ordering of CT scans. RESULTS: Only 61 (8%) of 806 CT scans revealed clinically significant abnormalities. The presence of any of the following: age > or = 60 years, focal neurologic deficit, headache with vomiting, or altered mental status, was 100% sensitive (95% CI: 94-100%) and 31% specific (95% CI: 28-33%) in detecting clinically significant CT scans. This set of features had positive and negative predictive values of 11% (95% CI: 8-13%) and 100% (95% CI: 98-100%), respectively. If these criteria had been used to restrict cranial CT use, 229 fewer patients (28%) would have had CT scans obtained and no clinically significant abnormalities would have been missed. CONCLUSION: Clinically significant CT abnormalities were uncommon in this study population, suggesting that current criteria for ordering nontrauma cranial CT scans may be too liberal. In this study, a set of clinical criteria was derived that may be useful at separating patients into high- and low-risk categories for clinically significant cranial CT abnormalities. Before these results are applied clinically, these criteria should be validated in larger, prospective studies.

Adult↗
PubMed1997

Do oral antibiotics prevent meningitis and serious bacterial infections in children with Streptococcus pneumoniae occult bacteremia? A meta-analysis.

OBJECTIVE: To determine whether oral antibiotics prevent meningitis and serious bacterial infections in children with Streptococcus pneumoniae occult bacteremia. DATA SOURCES: Using the Medline database, the English-language literature was searched for all publications concerning bacteremia, fever, or S pneumoniae from 1966 to April 1996. STUDY SELECTION: All studies that included a series of children with S pneumoniae occult bacteremia containing orally treated and untreated groups. Children were excluded from individual studies if they were immunocompromised, had a serious bacterial infection, underwent a lumbar puncture, or received parenteral antibiotics. DATA EXTRACTION: Three authors independently reviewed each article to determine the number of eligible children and the outcome of children meeting entry criteria. DATA SYNTHESIS: Eleven of 21 studies were excluded, leaving 10 evaluable studies with 656 total cases of S pneumoniae occult bacteremia identified. Patients who received oral antibiotics had fewer serious bacterial infections than untreated patients (3.3% vs 9.7%; pooled odds ratio, 0.35; 95% confidence interval, 0.17 to 0.73). Meningitis developed in 3 (0.8%) of 399 children in the oral antibiotic group and 7 (2.7%) of 257 untreated children (pooled odds ratio, 0.51; 95% confidence interval, 0.12 to 2.09). CONCLUSION: Although oral antibiotics modestly decreased the risk of serious bacterial infections in children with S pneumoniae occult bacteremia, there was insufficient evidence to conclude that oral antibiotics prevent meningitis. Published recommendations that oral antibiotics be administered to prevent serious bacterial infections in children with possible S pneumoniae occult bacteremia should be reevaluated in light of the lower risk of sequelae from S pneumoniae occult bacteremia and newer data concerning side effects from treatment.

Administration, Oral↗
PubMed1997

Differential reinforcement of low rate performance, pharmacokinetics and pharmacokinetic-pharmacodynamic modeling: independent interaction of alprazolam and caffeine.

To investigate the interaction between alprazolam and caffeine, performance on a differential reinforcement of low-rate behavior schedule and the respective pharmacokinetics (PK) were explored in concurrent studies. Alprazolam PK was not altered by caffeine, but alprazolam retarded caffeine absorption indirectly, as inferred by the lack of i.v. drug administration PK interaction, thereby decreasing serum methylxanthine concentrations. Inasmuch as alprazolam was more potent and short-lived than caffeine in decreasing the reinforcement rate (consonant with their respective t(1/2) values, 0.44 and 3.1 hr), the alprazolam/caffeine potency ratio decreased across the session time, which determined the expression of the combined effects. Thus, the decreased methylxanthine level yielded slightly less disruption in performance for the observed combined effect, compared to the expected calculated effect, only near the end of a session. The interaction was PK linked and mainly not distinguishable from independence as indicated by the Poch dose-response curve method and the integration of PK and pharmacodynamics. The sigmoid maximal effect-link pharmacodynamic model indicated that caffeine did not alter the concentration at half of the maximal effect value of alprazolam and suggested that the interaction is not competitive, but independent. Although the nature of the benzodiazepine-methylxanthine interaction has been controversial in other behavioral studies, as is the role of PK in determining behavior, this and our previous study make it evident that the interaction is independent not only across doses and routes of administration, but also with respect to two indices of differential reinforcement of low rate performance.

Alprazolam↗
PubMed1996

Conditions sufficient for the production of oral cocaine or lidocaine self-administration in preference to water.

Groups of rats were given a chronic history of drinking cocaine solutions of different concentrations in daily, 3-h schedule induced polydipsia sessions. Animals failed to develop a preference for cocaine solution to concurrently presented water. Schedule-induction conditions were maintained, and the animals were divided into separate groups, drinking either cocaine or lidocaine placed in a highly acceptable vehicle (glucose-saccharin solution). Animals preferred their respective drug solutions to concurrently presented water, and these preferences remained stable after the glucose-saccharin vehicle was gradually faded to water, leaving only cocaine or lidocaine, respectively, in the solution. Thus a stable preference for drug solution to water could be instituted in rats for either cocaine or lidocaine solution (putative reinforcing and nonreinforcing agents, respectively) given an appropriate associative history, with high intakes maintained by schedule-induction. Conditions sufficient for the initiation of an oral preference and high intake for a putatively reinforcing drug cannot be assumed to occur owing to the drug's reinforcing property in the absence of demonstrating the ineffectiveness of an appropriate negative control substance.

Administration, Oral↗
PubMed1996

Intravenous calcium chloride in the conversion of paroxysmal supraventricular tachycardia to normal sinus rhythm.

This brief report describes several cases of paroxysmal supraventricular tachycardia that converted promptly to normal sinus rhythm within 1 to 2 minutes of receiving intravenous calcium salts as pretreatment in anticipation of verapamil therapy. A review of calcium's hemodynamic and dromotropic effects suggests that this probably was due to electrophysiological effects rather than mere coincidence. Calcium raises blood pressure, which may reflexively increase cardiac parasympathetic tone, and also has a direct slowing effect on atrioventricular conduction. Adenosine remains the drug of choice in the treatment of paroxysmal supraventricular tachycardia. However, in addition to preventing hypotension when used as pretreatment to verapamil, intravenous calcium itself may terminate supraventricular tachycardia.

Adult↗
PubMed1996

Tolerance to the anxiolytic effects of the triazolobenzodiazepines triazolam and alprazolam, as measured by the ingestion of a hypertonic sodium chloride solution in rats.

Rats were adapted to a water-deprivation regimen that allowed daily 1-hr drinking sessions of a single fluid, either 1.5% NaCl solution or water. Oral, presession, acute doses of triazolam (0.05-1.6 mg/kg) or alprazolam (0.4-6.4 mg/kg) produced dose-related increases in session NaCl solution ingestion. The relative potencies found for these two drugs approximated their relative Ki values reported in the literature. The increased ingestion produced in this and other experiments by anxiolytic agents is presented as an alternative way of evaluating punishment attenuation, and hence anxiolytic activity. Chronic oral dosing (every 2nd day) with triazolam (0.2 mg/kg) or alprazolam (1.2 mg/kg) led, after several weeks, to partial, but surmountable, tolerance to the increased NaCl solution ingestion produced by these drugs, which was confirmed by a rightward shift in the dose-effect relations. During chronic dosing, no corresponding declines in the independently evaluated increases in water intake produced by these drugs occurred. Abrupt drug discontinuation produced a precipitous decrease in NaCl solution intake, with subsequent recovery. For triazolam, the initial discontinuation decrease in intake to below the original base line suggested the possible accrual of a mild physiological dependence under this moderate chronic dose regimen.

Alprazolam↗
PubMed1995

Stimulus control of addictive behavior: persistence in the presence and absence of a drug.

Rats were exposed daily to a food schedule-induced polydipsia condition, in which water and 0.16 mg/ml cocaine solution were available concurrently, with the cocaine solution indicated by a discriminative stimulus (SD) light. The cocaine solution was preferred, and the preference was maintained when the SD was gradually eliminated by fading its intensity. For a second group, if cocaine concentration was the stimulus gradually eliminated, preference for the resulting solution (water) indicated by the SD was stably maintained. For two additional groups, if either the light SD or the cocaine stimulus was removed abruptly rather than gradually, few animals retained preferences. These studies reveal the importance of establishing strong stimulus control for the initiation and persistence of drug abuse behavior.

Animals↗
PubMed1995

Oral and IP caffeine pharmacokinetics under a chronic food-limitation condition.

For food-limited rats, serum caffeine was proportional to IP caffeine doses (10-40 mg/kg) for Cmax and area under the curve [AUC(0-24 h)], whereas the three dimethylxanthine (DMX) metabolites of caffeine were disproportional over the dose range. Steady-state concentrations of caffeine and the three metabolites were evident at the 11th day of chronic, daily caffeine IP 20 mg/kg doses. Both caffeine and the three metabolites were dose proportional for Cmax and AUC(0-24 h) by schedule-induced oral caffeine self-administration within the dose range taken (9-38 mg/kg). These results contrast with the nonlinear kinetics of caffeine reported for rats under ad lib conditions. Elimination rate constants (Kel) remained the same for the two routes, but apparent volume of distribution (AVd) and clearance (Cl) were different. The order of the Kel values was caffeine > paraxanthine > theophylline > theobromine. The effects of linear vs. nonlinear caffeine pharmacokinetics may have distinct implications for the resulting pharmacodynamics.

Administration, Oral↗
PubMed1995

Dose-dependent surmountability of locomotor activity in caffeine tolerance.

For two chronic intraperitoneal caffeine dose regimens (10 and 80 mg/kg per day), tolerance developed rapidly (2-3 days) to the stimulatory effects of caffeine on locomotor activity. However, surmountability of the tolerant activity rate levels by caffeine administration was dose dependent: Activity rate was restored fully by acute caffeine administration for the 10 mg/kg per day series, but not for the 80 mg/kg per day series. The extent of tolerance was also dose-dependent: Tolerance was incomplete for the low-dose daily caffeine series but complete for the high-dose series. Upon discontinuation of daily caffeine dosing, activity rate decreased to the original baseline levels for both chronic series. Caffeine tolerance and the quantification of its surmountability may be explained by the pharmacokinetics of caffeine and the upregulation of adenosine receptors.

Animals↗
PubMed1995

Ethanol elimination rates in an ED population.

Knowledge of the rate of ethanol elimination is essential in the assessment of the intoxicated patient. Surprisingly little literature is available regarding ethanol elimination rates in emergency department (ED) patients; prior studies almost exclusively examined populations of alcoholics or normal controls. Consequently, this prospective observational study was undertaken to assess the rate of ethanol elimination in an ED population. Twenty-four consecutive adult ED patients clinically suspected of intoxication who had serum ethanol determinations drawn were enrolled. Patients underwent serial ethanol determinations via breathalyzer (Intoxilyzer 1400, CMI Inc., Owensboro, KY). Linear regression analysis of the plot of decrease in ethanol level over time was performed to determine the rate of ethanol elimination. Initial ethanol levels in the 24 patients ranged from 58 to 447 mg/dL (mean, 249 +/- 109 [SD] mg/dL). Patients were observed for a minimum of 2 and a maximum of 9 observations (mean, 3.9 +/- 1.7), over a period of 0.5 to 12.1 hours (mean, 4.4 +/-3.5 h). Clinical features of intoxication were poorly correlated with ethanol level (r < .5). The rate of ethanol elimination in the ED population was 19.6 mg/dL/h (r = .83; 95% confidence interval [CI], 16.9 to 22.3 mg/dL/h). Subgroup analysis found differences that were statistically significant but small. Multiple regression analysis showed that time was the major variable useful in predicting changes in ethanol level (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Reliability of infrared tympanic thermometry in the detection of rectal fever in children.

STUDY OBJECTIVE: Recently published clinical guidelines for the management of febrile children are based on studies that used rectal temperature data to stratify the risk of bacteremia and septic complications. Appropriate management decisions rely on accurate detection and categorization of fever. Accordingly, this study compared the newer infrared tympanic thermometry (ITT) to rectal thermometry in this regard. DESIGN: Prospective observational study. SETTING: Urban teaching hospital ED with annual census of 60,000. PARTICIPANTS: Consecutive children 6 months to 6 years old who had rectal temperatures measured. INTERVENTIONS: Triage nurses recorded rectal temperatures and bilateral ITT temperatures. Temperatures were correlated by Pearson correlation coefficients and compared using paired t tests with significance set at P < .01. Children were categorized by degree of fever using rectal temperature (afebrile, less than 100.4 degrees F; low fever, 100.4 to 102.9 degrees F; and high fever, more than 102.9 degrees F), and the accuracy of ITT in detecting fever and high fever was determined. RESULTS: Three hundred seventy patients were enrolled in the study. The mean age was 18.4 +/- 11.3 months; boys comprised 56% of patients. The mean temperatures were rectal, 101.0 +/- 2.0 degrees F; right tympanic membrane, 100.4 +/- 1.9 degrees F; and left tympanic membrane, 100.3 +/- 1.9 degrees F. The tympanic membrane temperatures were significantly lower than rectal readings (P << .001 for both right and left versus rectal). Rectal temperatures showed good correlation with both right and left tympanic membrane temperatures (r = .83 and .85, respectively). ITT was 76% sensitive and 92% specific in detecting fever of 100.4 degrees F or more (positive predictive value, 0.92; negative predictive value, 0.76). In the detection of high fever, ITT was only 57% sensitive but 98% specific (positive predictive value, 0.90; negative predictive value, 0.90). Rectal and TM temperatures differed by at least 0.5 degree F in 70% of the patients, 1.0 degree F in 41%, 2.0 degrees F in 12%, and 3.0 degrees F in 3%. CONCLUSION: Despite the statistical correlation between ITT and rectal temperatures, the modalities may yield significantly different temperatures. The poor sensitivity of ITT in detecting fever and high fever may result in clinically important miscategorizations of individual patients. Current clinical management that is based on the presence and height of fever may be adversely affected if ITT is used.

Child↗